Wealth, health, HIV and the economics of hope

PubMed Central

Barnett, Tony; Weston, Mark

2012-01-01

HIV/AIDS primarily affects people of working age. Population susceptibility is poorly understood. This paper speculates that an operationally defined concept of hope may offer new ways of understanding its social epidemiology. Hope is directly linked to the future in as much as it determines the value people place on that future. Individual and communal levels of hope may vary, with consequent impacts on HIV transmission. HIV/AIDS in turn may reduce hope and thereby reduce societies’ future wellbeing. The paper concludes by offering recommendations for research, programming and policy. PMID:18641467

[Communication of scientific fraud].

PubMed

Zeitoun, Jean-David; Rouquette, Sébastien

2012-09-01

There is for a scientific journal several levels of communication depending of the degree of suspicion or certainty of a case of error or fraud. The task is increasingly difficult for journal editors as disclosed cases of fraud are more common and scientific communication on this topic is growing. Biomedical fraud is fairly little reported by the mainstream press and causes of this low interest are not currently well understood. The difficulty of processing this type of news for journalists appears to be one possible reason. The potentially numerous and significant consequences of fraud on health professionals are poorly documented. Though it is likely to cause a feeling of distrust and create controversy, the impact of fraud on the general public is poorly studied and appears multifactorial. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Interactions between demography and environmental effects are important determinants of population dynamics

PubMed Central

Gamelon, Marlène; Grøtan, Vidar; Nilsson, Anna L. K.; Engen, Steinar; Hurrell, James W.; Jerstad, Kurt; Phillips, Adam S.; Røstad, Ole W.; Slagsvold, Tore; Walseng, Bjørn; Stenseth, Nils C.; Sæther, Bernt-Erik

2017-01-01

Climate change will affect the population dynamics of many species, yet the consequences for the long-term persistence of populations are poorly understood. A major reason for this is that density-dependent feedback effects caused by fluctuations in population size are considered independent of stochastic variation in the environment. We show that an interplay between winter temperature and population density can influence the persistence of a small passerine population under global warming. Although warmer winters favor an increased mean population size, density-dependent feedback can cause the local population to be less buffered against occasional poor environmental conditions (cold winters). This shows that it is essential to go beyond the population size and explore climate effects on the full dynamics to elaborate targeted management actions. PMID:28164157

Serious mental illness and negative substance use consequences among adults on probation.

PubMed

Rossheim, Matthew E; Livingston, Melvin D; Lerch, Jennifer A; Taxman, Faye S; Walters, Scott T

2018-03-22

Adults on probation are at greater risk of both using substances and having a mental disorder compared to the general population. Several theories explain the relationship between substance use and poor mental health. However, the interaction between substance use, mental health, and substance-related consequences is not well understood. A better understanding of this relationship may help treatment programs become more responsive to people with serious mental illness (SMI). The current study used interview data from 313 adults on probation who reported recent substance use. We examined associations between SMI risk, substance use, and substance use consequences. A substantial proportion of the sample (37.5%) screened at risk of having a SMI. Adjusting for type and amount of substance use, those who screened at risk of having a SMI reported more negative substance use consequences. Significant interaction effects were observed between use of alcohol or opiates and SMI risk. Alcohol use was associated with more negative substance use consequences among those at risk of SMI, while opiate use was associated with more consequences among those not at risk. Programs are sorely needed to identify and treat adults with comorbid substance use and mental health symptoms, particularly for adults in the justice system. Clinicians should carefully consider how mental health may interact with substance use to exacerbate consequences.

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

Intraspecific Variation among Social Insect Colonies: Persistent Regional and Colony-Level Differences in Fire Ant Foraging Behavior

PubMed Central

Bockoven, Alison A.; Wilder, Shawn M.; Eubanks, Micky D.

2015-01-01

Individuals vary within a species in many ecologically important ways, but the causes and consequences of such variation are often poorly understood. Foraging behavior is among the most profitable and risky activities in which organisms engage and is expected to be under strong selection. Among social insects there is evidence that within-colony variation in traits such as foraging behavior can increase colony fitness, but variation between colonies and the potential consequences of such variation are poorly documented. In this study, we tested natural populations of the red imported fire ant, Solenopsis invicta, for the existence of colony and regional variation in foraging behavior and tested the persistence of this variation over time and across foraging habitats. We also reared single-lineage colonies in standardized environments to explore the contribution of colony lineage. Fire ants from natural populations exhibited significant and persistent colony and regional-level variation in foraging behaviors such as extra-nest activity, exploration, and discovery of and recruitment to resources. Moreover, colony-level variation in extra-nest activity was significantly correlated with colony growth, suggesting that this variation has fitness consequences. Lineage of the colony had a significant effect on extra-nest activity and exploratory activity and explained approximately half of the variation observed in foraging behaviors, suggesting a heritable component to colony-level variation in behavior. PMID:26197456

Moyamoya Vasculopathy in PHACE Syndrome: Six New Cases and Review of the Literature.

PubMed

Tortora, Domenico; Severino, Mariasavina; Accogli, Andrea; Martinetti, Carola; Vercellino, Nadia; Capra, Valeria; Rossi, Andrea; Pavanello, Marco

2017-12-01

PHACE syndrome (Posterior fossa malformations, large cervicofacial infantile Hemangiomas, Arterial anomalies, aortic coarctation and Cardiac abnormalities, and Eye abnormalities) is a neurocutaneous disorder including posterior fossa malformations, hemangiomas, arterial lesions, cardiac defects, and eye abnormalities. PHACE arteriopathies may be progressive and recently have been categorized based on the risk of acute ischemic stroke, increasing attention to the potentially devastating consequences of cerebrovascular complications in this syndrome. In contrast, the natural history of arteriopathy in PHACE syndrome remains poorly understood. At the moment, there are no established surgical guidelines for high-risk vasculopathies, including quasi-moyamoya, in this syndrome. We described the clinicoradiologic features of a small series of 6 patients with PHACE syndrome and quasi-moyamoya (5 female, age range 4 months to 12 years), focusing on the clinical course and surgical outcome of 3 children who were treated with encephaloduroarteriosynangiosis and encephalomyosynangiosis. In addition, we reviewed the radiologic, clinical, and surgical aspects of moyamoya vasculopathy in PHACE syndrome, providing information on 15 additional published cases. Although the natural history of arteriopathy in PHACE syndrome is poorly understood, patients with high-risk vasculopathies, such as quasi-moyamoya disease, may benefit of revascularization by using encephaloduroarteriosynangiosis and encephalomyosynangiosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Transfusion-related immunomodulation: review of the literature and implications for pediatric critical illness.

PubMed

Muszynski, Jennifer A; Spinella, Philip C; Cholette, Jill M; Acker, Jason P; Hall, Mark W; Juffermans, Nicole P; Kelly, Daniel P; Blumberg, Neil; Nicol, Kathleen; Liedel, Jennifer; Doctor, Allan; Remy, Kenneth E; Tucci, Marisa; Lacroix, Jacques; Norris, Philip J

2017-01-01

Transfusion-related immunomodulation (TRIM) in the intensive care unit (ICU) is difficult to define and likely represents a complicated set of physiologic responses to transfusion, including both proinflammatory and immunosuppressive effects. Similarly, the immunologic response to critical illness in both adults and children is highly complex and is characterized by both acute inflammation and acquired immune suppression. How transfusion may contribute to or perpetuate these phenotypes in the ICU is poorly understood, despite the fact that transfusion is common in critically ill patients. Both hyperinflammation and severe immune suppression are associated with poor outcomes from critical illness, underscoring the need to understand potential immunologic consequences of blood product transfusion. In this review we outline the dynamic immunologic response to critical illness, provide clinical evidence in support of immunomodulatory effects of blood product transfusion, review preclinical and translational studies to date of TRIM, and provide insight into future research directions. © 2016 AABB.

The Effects of Performance Fatigability on Postural Control and Rehabilitation in the Older Patient

PubMed Central

Hassan, Mahdi; Bugnariu, Nicoleta

2016-01-01

Fatigue is common in older adults and has a significant effect on quality of life. Despite the high prevalence of fatigue in older individuals, several aspects are poorly understood. It is important to differentiate subjective fatigue complaints from fatigability of motor performance because the two are independent constructs with potentially distinct consequences on mobility. Performance fatigability is the magnitude of change in a performance criterion over a given time of task performance. Performance fatigability is a compulsory element of any strength training program, yet strength training is an important component of rehabilitation programs for older adults. The consequences of fatigability for older adults suggest that acute exercise of various types may result in acute impairments in postural control. The effects of performance fatigability on postural control in older adults are evaluated here to aid the rehabilitation clinician in making recommendations for evaluation of fall risks and exercise prescription. PMID:28154794

The Effects of Performance Fatigability on Postural Control and Rehabilitation in the Older Patient.

PubMed

Papa, Evan V; Hassan, Mahdi; Bugnariu, Nicoleta

2016-09-01

Fatigue is common in older adults and has a significant effect on quality of life. Despite the high prevalence of fatigue in older individuals, several aspects are poorly understood. It is important to differentiate subjective fatigue complaints from fatigability of motor performance because the two are independent constructs with potentially distinct consequences on mobility. Performance fatigability is the magnitude of change in a performance criterion over a given time of task performance. Performance fatigability is a compulsory element of any strength training program, yet strength training is an important component of rehabilitation programs for older adults. The consequences of fatigability for older adults suggest that acute exercise of various types may result in acute impairments in postural control. The effects of performance fatigability on postural control in older adults are evaluated here to aid the rehabilitation clinician in making recommendations for evaluation of fall risks and exercise prescription.

Bushmeat hunting and extinction risk to the world's mammals

PubMed Central

Abernethy, Katharine; Betts, Matthew G.; Chapron, Guillaume; Dirzo, Rodolfo; Galetti, Mauro; Levi, Taal; Lindsey, Peter A.; Macdonald, David W.; Machovina, Brian; Peres, Carlos A.; Wallach, Arian D.

2016-01-01

Terrestrial mammals are experiencing a massive collapse in their population sizes and geographical ranges around the world, but many of the drivers, patterns and consequences of this decline remain poorly understood. Here we provide an analysis showing that bushmeat hunting for mostly food and medicinal products is driving a global crisis whereby 301 terrestrial mammal species are threatened with extinction. Nearly all of these threatened species occur in developing countries where major coexisting threats include deforestation, agricultural expansion, human encroachment and competition with livestock. The unrelenting decline of mammals suggests many vital ecological and socio-economic services that these species provide will be lost, potentially changing ecosystems irrevocably. We discuss options and current obstacles to achieving effective conservation, alongside consequences of failure to stem such anthropogenic mammalian extirpation. We propose a multi-pronged conservation strategy to help save threatened mammals from immediate extinction and avoid a collapse of food security for hundreds of millions of people. PMID:27853564

Analysis of high quality superconducting resonators: consequences for TLS properties in amorphous oxides

NASA Astrophysics Data System (ADS)

Burnett, J.; Faoro, L.; Lindström, T.

2016-04-01

1/f noise caused by microscopic two-level systems (TLS) is known to be very detrimental to the performance of superconducting quantum devices but the nature of these TLS is still poorly understood. Recent experiments with superconducting resonators indicates that interaction between TLS in the oxide at the film-substrate interface is not negligible. Here we present data on the loss and 1/f frequency noise from two different Nb resonators with and without Pt capping and discuss what conclusions can be drawn regarding the properties of TLS in amorphous oxides. We also estimate the concentration and dipole moment of the TLS.

Functional Polymorphisms in Dopaminergic Genes Modulate Neurobehavioral and Neurophysiological Consequences of Sleep Deprivation.

PubMed

Holst, Sebastian C; Müller, Thomas; Valomon, Amandine; Seebauer, Britta; Berger, Wolfgang; Landolt, Hans-Peter

2017-04-10

Sleep deprivation impairs cognitive performance and reliably alters brain activation in wakefulness and sleep. Nevertheless, the molecular regulators of prolonged wakefulness remain poorly understood. Evidence from genetic, behavioral, pharmacologic and imaging studies suggest that dopaminergic signaling contributes to the behavioral and electroencephalographic (EEG) consequences of sleep loss, although direct human evidence thereof is missing. We tested whether dopamine neurotransmission regulate sustained attention and evolution of EEG power during prolonged wakefulness. Here, we studied the effects of functional genetic variation in the dopamine transporter (DAT1) and the dopamine D 2 receptor (DRD2) genes, on psychomotor performance and standardized waking EEG oscillations during 40 hours of wakefulness in 64 to 82 healthy volunteers. Sleep deprivation consistently enhanced sleepiness, lapses of attention and the theta-to-alpha power ratio (TAR) in the waking EEG. Importantly, DAT1 and DRD2 genotypes distinctly modulated sleep loss-induced changes in subjective sleepiness, PVT lapses and TAR, according to inverted U-shaped relationships. Together, the data suggest that genetically determined differences in DAT1 and DRD2 expression modulate functional consequences of sleep deprivation, supporting the hypothesis that striato-thalamo-cortical dopaminergic pathways modulate the neurobehavioral and neurophysiological consequences of sleep loss in humans.

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.

Effects of Plant Traits on Ecosystem and Regional Processes: a Conceptual Framework for Predicting the Consequences of Global Change

PubMed Central

CHAPIN, F. STUART

2003-01-01

Human activities are causing widespread changes in the species composition of natural and managed ecosystems, but the consequences of these changes are poorly understood. This paper presents a conceptual framework for predicting the ecosystem and regional consequences of changes in plant species composition. Changes in species composition have greatest ecological effects when they modify the ecological factors that directly control (and respond to) ecosystem processes. These interactive controls include: functional types of organisms present in the ecosystem; soil resources used by organisms to grow and reproduce; modulators such as microclimate that influence the activity of organisms; disturbance regime; and human activities. Plant traits related to size and growth rate are particularly important because they determine the productive capacity of vegetation and the rates of decomposition and nitrogen mineralization. Because the same plant traits affect most key processes in the cycling of carbon and nutrients, changes in plant traits tend to affect most biogeochemical cycling processes in parallel. Plant traits also have landscape and regional effects through their effects on water and energy exchange and disturbance regime. PMID:12588725

Seasonal infectious disease epidemiology

PubMed Central

Grassly, Nicholas C; Fraser, Christophe

2006-01-01

Seasonal change in the incidence of infectious diseases is a common phenomenon in both temperate and tropical climates. However, the mechanisms responsible for seasonal disease incidence, and the epidemiological consequences of seasonality, are poorly understood with rare exception. Standard epidemiological theory and concepts such as the basic reproductive number R0 no longer apply, and the implications for interventions that themselves may be periodic, such as pulse vaccination, have not been formally examined. This paper examines the causes and consequences of seasonality, and in so doing derives several new results concerning vaccination strategy and the interpretation of disease outbreak data. It begins with a brief review of published scientific studies in support of different causes of seasonality in infectious diseases of humans, identifying four principal mechanisms and their association with different routes of transmission. It then describes the consequences of seasonality for R0, disease outbreaks, endemic dynamics and persistence. Finally, a mathematical analysis of routine and pulse vaccination programmes for seasonal infections is presented. The synthesis of seasonal infectious disease epidemiology attempted by this paper highlights the need for further empirical and theoretical work. PMID:16959647

The contribution of aerobic and anaerobic respiration to intestinal colonization and virulence for Salmonella typhimurium in the chicken.

PubMed

Barrow, Paul Andrew; Berchieri, Angelo; Freitas Neto, Oliveiro Caetano de; Lovell, Margaret

2015-10-01

The basic mechanism whereby Salmonella serovars colonize the chicken intestine remains poorly understood. Previous studies have indicated that proton-translocating proteins utilizing oxygen as terminal electron acceptor do not appear to be of major importance in the gut of the newly hatched chicken and consequently they would be even less significant during intestinal colonization of more mature chickens where the complex gut microflora would trap most of the oxygen in the lumen. Consequently, alternative electron acceptors may be more significant or, in their absence, substrate-level phosphorylation may also be important to Salmonella serovars in this environment. To investigate this we constructed mutants of Salmonella enterica serovar Typhimurium defective in various aspects of oxidative or substrate-level phosphorylation to assess their role in colonization of the chicken intestine, assessed through faecal shedding, and virulence. Mutations affecting use of oxygen or alternative electron acceptors did not eliminate faecal shedding. By contrast mutations in either pta (phosphotransacetylase) or ackA (acetate kinase) abolished shedding. The pta but not the ackA mutation also abolished systemic virulence for chickens. An additional ldhA (lactate dehydrogenase) mutant also showed poor colonizing ability. We hypothesise that substrate-level phosphorylation may be more important than respiration using oxygen or alternative electron acceptors for colonization of the chicken caeca.

Transcriptional markers of sub-optimal nutrition in developing Apis mellifera nurse workers

PubMed Central

2014-01-01

Background Honey bees (Apis mellifera) contribute substantially to the worldwide economy and ecosystem health as pollinators. Pollen is essential to the bee’s diet, providing protein, lipids, and micronutrients. The dramatic shifts in physiology, anatomy, and behavior that accompany normal worker development are highly plastic and recent work demonstrates that development, particularly the transition from nurse to foraging roles, is greatly impacted by diet. However, the role that diet plays in the developmental transition of newly eclosed bees to nurse workers is poorly understood. To further understand honey bee nutrition and the role of diet in nurse development, we used a high-throughput screen of the transcriptome of 3 day and 8 day old worker bees fed either honey and stored pollen (rich diet) or honey alone (poor diet) within the hive. We employed a three factor (age, diet, age x diet) analysis of the transcriptome to determine whether diet affected nurse worker physiology and whether poor diet altered the developmental processes normally associated with aging. Results Substantial changes in gene expression occurred due to starvation. Diet-induced changes in gene transcription occurring in younger bees were largely a subset of those occurring in older bees, but certain signatures of starvation were only evident 8 day old workers. Of the 18,542 annotated transcripts in the A. mellifera genome, 150 transcripts exhibited differential expression due to poor diet at 3d of age compared with 17,226 transcripts that differed due to poor diet at 8d of age, and poor diet caused more frequent down-regulation of gene expression in younger bees compared to older bees. In addition, the age-related physiological changes that accompanied early adult development differed due to the diet these young adult bees were fed. More frequent down-regulation of gene expression was observed in developing bees fed a poor diet compared to those fed an adequate diet. Functional analyses also suggest that the physiological and developmental processes occurring in well-fed bees are vastly different than those occurring in pollen deprived bees. Our data support the hypothesis that poor diet causes normal age-related development to go awry. Conclusion Poor nutrition has major consequences for the expression of genes underlying the physiology and age-related development of nurse worker bees. More work is certainly needed to fully understand the consequences of starvation and the complex biology of nutrition and development in this system, but the genes identified in the present study provide a starting point for understanding the consequences of poor diet and for mitigating the economic costs of colony starvation. PMID:24529032

Release of Applied Mechanical Loading Stimulates Intercellular Calcium Waves in Drosophila Wing Discs.

PubMed

Narciso, Cody E; Contento, Nicholas M; Storey, Thomas J; Hoelzle, David J; Zartman, Jeremiah J

2017-07-25

Mechanical forces are critical but poorly understood inputs for organogenesis and wound healing. Calcium ions (Ca 2+ ) are critical second messengers in cells for integrating environmental and mechanical cues, but the regulation of Ca 2+ signaling is poorly understood in developing epithelial tissues. Here we report a chip-based regulated environment for microorgans that enables systematic investigations of the crosstalk between an organ's mechanical stress environment and biochemical signaling under genetic and chemical perturbations. This method enabled us to define the essential conditions for generating organ-scale intercellular Ca 2+ waves in Drosophila wing discs that are also observed in vivo during organ development. We discovered that mechanically induced intercellular Ca 2+ waves require fly extract growth serum as a chemical stimulus. Using the chip-based regulated environment for microorgans, we demonstrate that not the initial application but instead the release of mechanical loading is sufficient, but not necessary, to initiate intercellular Ca 2+ waves. The Ca 2+ response depends on the prestress intercellular Ca 2+ activity and not on the magnitude or duration of the mechanical stimulation applied. Mechanically induced intercellular Ca 2+ waves rely on IP 3 R-mediated Ca 2+ -induced Ca 2+ release and propagation through gap junctions. Thus, intercellular Ca 2+ waves in developing epithelia may be a consequence of stress dissipation during organ growth. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Functional duality of the cell wall.

PubMed

Latgé, Jean-Paul; Beauvais, Anne

2014-08-01

The polysaccharide cell wall is the extracellular armour of the fungal cell. Although essential in the protection of the fungal cell against aggressive external stresses, the biosynthesis of the polysaccharide core is poorly understood. For a long time it was considered that this cell wall skeleton was a fixed structure whose role was only to be sensed as non-self by the host and consequently trigger the defence response. It is now known that the cell wall polysaccharide composition and localization continuously change to adapt to their environment and that these modifications help the fungus to escape from the immune system. Moreover, cell wall polysaccharides could function as true virulence factors. Copyright © 2014 Elsevier Ltd. All rights reserved.

Exercising arrhythmias and sudden cardiac death in horses: Review of the literature and comparative aspects.

PubMed

Navas de Solis, C

2016-07-01

Arrhythmias are common in equine athletes during and immediately after exercise. Many of these rhythm variations are not clinically relevant. In horses, a link between different exercising arrhythmias and poor performance or between exercising arrhythmias and sudden cardiac death (SCD) is strongly suspected but not fully understood or proven. SCD during races or competitions is rare, but has catastrophic consequences for the safety of the human partner and public perceptions of welfare during equestrian sports. This review summarises current knowledge of equine exercise arrhythmias and their implications in SCD and compares existing principles and recommendations for equine subjects with those for human athletes. © 2016 EVJ Ltd.

Rethinking the Stalk Effect: A New Hypothesis Explaining Suprasellar Tumor-Induced Hyperprolactinemia

PubMed Central

Skinner, Donal C.

2009-01-01

The pars tuberalis is a distinct subdivision of the pituitary gland but its function remains poorly understood. Suprasellar tumors in this pars tuberalis region are frequently accompanied by hyperprolactinemia. As these tumors do not immunoreact for any of the established pituitary hormones, they are classified as non-secretory. It has been postulated that these suprasellar tumors induce hyperprolactinemia by compressing the pituitary stalk, resulting in impaired dopamine delivery to the pituitary and, consequently, disinhibition of the lactotropes. An alternative hypothesis proposed is that suprasellar tumors secrete a specific pars tuberalis factor that stimulates prolactin secretion. Hypothesized candidates are the preprotachykinin A derived tachykinins, substance P and/or neurokinin A. PMID:19028420

Relevance of Hypersexual Disorder to Family Medicine and Primary Care as a Complex Multidimensional Chronic Disease Construct

PubMed Central

Vrijhoef, Bert; De Maeseneer, Jan; Vansintejan, Johan; Devroey, Dirk

2013-01-01

Hypersexual disorder (HD) is not defined in a uniform way in the psychiatric literature. In the absence of solid evidence on prevalence, causes, empirically validated diagnostic criteria, instruments for diagnosis, consistent guidelines on treatment options, medical and psychosocial consequences, and type of caregivers that need to be involved, HD remains a controversial and relatively poorly understood chronic disease construct. The role of family medicine in the detection, treatment, and followup of HD is not well studied. The purpose of this paper is to describe the complexity of HD as a multidimensional chronic disease construct and its relevance to family medicine and primary care. PMID:24066230

Cheniere forest as stopover habitat for migrant landbirds: Immediate effects of Hurricane Rita: Chapter 6D in Science and the storms-the USGS response to the hurricanes of 2005

USGS Publications Warehouse

Barrow, Wylie; Chadwick, Paul; Couvillion, Brady R.; Doyle, Thomas; Faulkner, Stephen; Jeske, Clint; Michot, Tommy; Randall, Lori; Wells, Chris; Wilson, Scott

2007-01-01

It is not known whether en route fall migratory birds (August-October) are likely to suffer more from direct or secondary effects of hurricanes. On September 24, 2005, Hurricane Rita wreaked havoc on Louisiana's coast by toppling trees over vast areas and by stripping away microhabitats that harbor the invertebrates and produce the fruits upon which migrant landbirds depend (e.g., canopy foliage, vine tangles, epiphytes, leaf litter, and thickets of perennial plant species). Such transient effects of a hurricane on wildlife food resources are poorly understood, but these effects may have longterm consequences for some wildlife species.

The evolution of transcriptional regulation in eukaryotes

NASA Technical Reports Server (NTRS)

Wray, Gregory A.; Hahn, Matthew W.; Abouheif, Ehab; Balhoff, James P.; Pizer, Margaret; Rockman, Matthew V.; Romano, Laura A.

2003-01-01

Gene expression is central to the genotype-phenotype relationship in all organisms, and it is an important component of the genetic basis for evolutionary change in diverse aspects of phenotype. However, the evolution of transcriptional regulation remains understudied and poorly understood. Here we review the evolutionary dynamics of promoter, or cis-regulatory, sequences and the evolutionary mechanisms that shape them. Existing evidence indicates that populations harbor extensive genetic variation in promoter sequences, that a substantial fraction of this variation has consequences for both biochemical and organismal phenotype, and that some of this functional variation is sorted by selection. As with protein-coding sequences, rates and patterns of promoter sequence evolution differ considerably among loci and among clades for reasons that are not well understood. Studying the evolution of transcriptional regulation poses empirical and conceptual challenges beyond those typically encountered in analyses of coding sequence evolution: promoter organization is much less regular than that of coding sequences, and sequences required for the transcription of each locus reside at multiple other loci in the genome. Because of the strong context-dependence of transcriptional regulation, sequence inspection alone provides limited information about promoter function. Understanding the functional consequences of sequence differences among promoters generally requires biochemical and in vivo functional assays. Despite these challenges, important insights have already been gained into the evolution of transcriptional regulation, and the pace of discovery is accelerating.

Poor environmental tracking can make extinction risk insensitive to the colour of environmental noise

PubMed Central

van de Pol, Martijn; Vindenes, Yngvild; Sæther, Bernt-Erik; Engen, Steinar; Ens, Bruno J.; Oosterbeek, Kees; Tinbergen, Joost M.

2011-01-01

The relative importance of environmental colour for extinction risk compared with other aspects of environmental noise (mean and interannual variability) is poorly understood. Such knowledge is currently relevant, as climate change can cause the mean, variability and temporal autocorrelation of environmental variables to change. Here, we predict that the extinction risk of a shorebird population increases with the colour of a key environmental variable: winter temperature. However, the effect is weak compared with the impact of changes in the mean and interannual variability of temperature. Extinction risk was largely insensitive to noise colour, because demographic rates are poor in tracking the colour of the environment. We show that three mechanisms—which probably act in many species—can cause poor environmental tracking: (i) demographic rates that depend nonlinearly on environmental variables filter the noise colour, (ii) demographic rates typically depend on several environmental signals that do not change colour synchronously, and (iii) demographic stochasticity whitens the colour of demographic rates at low population size. We argue that the common practice of assuming perfect environmental tracking may result in overemphasizing the importance of noise colour for extinction risk. Consequently, ignoring environmental autocorrelation in population viability analysis could be less problematic than generally thought. PMID:21561978

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.

Desiccation stress and tolerance in green algae: consequences for ultrastructure, physiological and molecular mechanisms

PubMed Central

Holzinger, Andreas; Karsten, Ulf

2013-01-01

Although most green algae typically occur in aquatic ecosystems, many species also live partly or permanently under aeroterrestrial conditions, where the cells are exposed to the atmosphere and hence regularly experience dehydration. The ability of algal cells to survive in an air-dried state is termed desiccation tolerance. The mechanisms involved in desiccation tolerance of green algae are still poorly understood, and hence the aim of this review is to summarize recent findings on the effects of desiccation and osmotic water loss. Starting from structural changes, physiological, and biochemical consequences of desiccation will be addressed in different green-algal lineages. The available data clearly indicate a range of strategies, which are rather different in streptophycean and non-streptophycean green algae. While members of the Trebouxiophyceae exhibit effective water loss-prevention mechanisms based on the biosynthesis and accumulation of particular organic osmolytes such as polyols, these compounds are so far not reported in representatives of the Streptophyta. In members of the Streptophyta such as Klebsormidium, the most striking observation is the appearance of cross-walls in desiccated samples, which are strongly undulating, suggesting a high degree of mechanical flexibility. This aids in maintaining structural integrity in the dried state and allows the cell to maintain turgor pressure for a prolonged period of time during the dehydration process. Physiological strategies in aeroterrestrial green algae generally include a rapid reduction of photosynthesis during desiccation, but also a rather quick recovery after rewetting, whereas aquatic species are sensitive to drying. The underlying mechanisms such as the affected molecular components of the photosynthetic machinery are poorly understood in green algae. Therefore, modern approaches based on transcriptomics, proteomics, and/or metabolomics are urgently needed to better understand the molecular mechanisms involved in desiccation-stress physiology of these organisms. The very limited existing information is described in the present review. PMID:23986769

To boldly go: individual differences in boldness influence migratory tendency.

PubMed

Chapman, Ben B; Hulthén, Kaj; Blomqvist, David R; Hansson, Lars-Anders; Nilsson, Jan-Åke; Brodersen, Jakob; Anders Nilsson, P; Skov, Christian; Brönmark, Christer

2011-09-01

Partial migration, whereby only a fraction of the population migrates, is thought to be the most common type of migration in the animal kingdom, and can have important ecological and evolutionary consequences. Despite this, the factors that influence which individuals migrate and which remain resident are poorly understood. Recent work has shown that consistent individual differences in personality traits in animals can be ecologically important, but field studies integrating personality traits with migratory behaviour are extremely rare. In this study, we investigate the influence of individual boldness, an important personality trait, upon the migratory propensity of roach, a freshwater fish, over two consecutive migration seasons. We assay and individually tag 460 roach and show that boldness influences migratory propensity, with bold individuals being more likely to migrate than shy fish. Our data suggest that an extremely widespread personality trait in animals can have significant ecological consequences via influencing individual-level migratory behaviour. © 2011 Blackwell Publishing Ltd/CNRS.

How well do parental and peer relationships in adolescence predict health in adulthood?

PubMed

Landstedt, Evelina; Hammarström, Anne; Winefield, Helen

2015-07-01

Although health effects of social relationships are well-researched, long-term health consequences of adolescent family as well as peer relationships are poorly understood. The aim of the study was to explore the prospective importance of parental and peer social relationships in adolescence on internalising and functional somatic symptoms in adulthood. Data were drawn from four waves of the Northern Swedish Cohort Study, response rate 94.3%, N=1001. Outcome variables were internalising and functional somatic symptoms at the ages of 21, 30 and 42. Relationship variables at age 16 were poor parental contact and three indicators of poor peer relationships. Associations were assessed in multivariate ordinal logistic regressions with adjustment for confounders and baseline health. Results show that the main relationships-related predictors of adult internalising symptoms were self-rated poor peer relationships in terms of spending time alone during after-school hours and poor parental relationship. Functional somatic symptoms on the other hand were most strongly associated with poor parental contact and not being happy with classmates at age 16. The quality of parental and peer relationships in adolescence predicts adult mental and functional somatic health as much as 26 years later, even when accounting for confounders and adolescent symptomatology. This study extends past research by exploring how both adolescent parental and peer relationships (self-reported as well as teacher reported) predict adult self-reported health. © 2015 the Nordic Societies of Public Health.

Stalking. Part II: Victims' problems with the legal system and therapeutic considerations.

PubMed

Abrams, K M; Robinson, G E

1998-06-01

This paper is the second of 2 parts reviewing the topic of stalking. It focuses on victims difficulties with the legal system and the psychotherapeutic tasks for victims and therapists. Computerized literature searches were used to identify relevant papers from psychiatric and legal journals. Publications by victims' and women's organizations provided additional information. Victims suffer emotional consequences from being stalked. Additional stress is caused by the legal system's lack of understanding of the causes and consequences of stalking and inadequate and unenforced laws. The treatment of victims requires a comprehensive approach, including education, supportive psychotherapy, and discussion of practical measures. Therapists may overidentify with the patient's powerlessness or hesitate to take on a case out of fear of the stalker. Female therapists may protect themselves against the realization of their own vulnerability by blaming the victim, while male therapists may feel defensive or overprotective. Stalking is a crime with major mental health consequences which is often poorly understood by society. Therapists need to be aware of the victim's emotional reactions, the types of legal and practical supports available, and the possible biases of society. Further education and research should be encouraged.

Oxidative stress damages rRNA inside the ribosome and differentially affects the catalytic center

PubMed Central

Willi, Jessica; Küpfer, Pascal; Evéquoz, Damien; Fernandez, Guillermo; Polacek, Norbert

2018-01-01

Abstract Intracellular levels of reactive oxygen species (ROS) increase as a consequence of oxidative stress and represent a major source of damage to biomolecules. Due to its high cellular abundance RNA is more frequently the target for oxidative damage than DNA. Nevertheless the functional consequences of damage on stable RNA are poorly understood. Using a genome-wide approach, based on 8-oxo-guanosine immunoprecipitation, we present evidence that the most abundant non-coding RNA in a cell, the ribosomal RNA (rRNA), is target for oxidative nucleobase damage by ROS. Subjecting ribosomes to oxidative stress, we demonstrate that oxidized 23S rRNA inhibits the ribosome during protein biosynthesis. Placing single oxidized nucleobases at specific position within the ribosome's catalytic center by atomic mutagenesis resulted in markedly different functional outcomes. While some active site nucleobases tolerated oxidative damage well, oxidation at others had detrimental effects on protein synthesis by inhibiting different sub-steps of the ribosomal elongation cycle. Our data provide molecular insight into the biological consequences of RNA oxidation in one of the most central cellular enzymes and reveal mechanistic insight on the role of individual active site nucleobases during translation. PMID:29309687

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.

Reassessing Immune Control of Hepatitis A Virus

PubMed Central

Walker, Christopher M.; Feng, Zongdi; Lemon, Stanley M.

2015-01-01

There is renewed interest in hepatitis A virus (HAV) pathogenesis and immunity after 2–3 decades of limited progress. From a public health perspective, the average age at infection has increased in developing countries, resulting in more severe hepatitis that is poorly understood mechanistically. More fundamentally, there is interest in comparing immunity to HAV and hepatitis C virus (HCV): small, positive-strand RNA viruses with very different infection outcomes. Here, we review evidence that circulating HAV virions are cloaked in membranes, with consequences for induction of innate immunity and antibody-mediated neutralization. We also consider the contribution of CD4+ helper versus CD8+ cytotoxic T cells to antiviral immunity and liver injury, and present a model of non-cytotoxic immune control of HAV infection. PMID:25617494

Perception of effort in Exercise Science: Definition, measurement and perspectives.

PubMed

Pageaux, Benjamin

2016-11-01

Perception of effort, also known as perceived exertion or sense of effort, can be described as a cognitive feeling of work associated with voluntary actions. The aim of the present review is to provide an overview of what is perception of effort in Exercise Science. Due to the addition of sensations other than effort in its definition, the neurophysiology of perceived exertion remains poorly understood. As humans have the ability to dissociate effort from other sensations related to physical exercise, the need to use a narrower definition is emphasised. Consequently, a definition and some brief guidelines for its measurement are provided. Finally, an overview of the models present in the literature aiming to explain its neurophysiology, and some perspectives for future research are offered.

Does state boredom cause failures of attention? Examining the relations between trait boredom, state boredom, and sustained attention.

PubMed

Hunter, Andrew; Eastwood, John D

2016-08-10

Boredom is an important personal and social problem, but the phenomena itself remains poorly understood. Recent work has shown that boredom is highly related to attention, and that this relationship may be instrumental in revealing boredom's causes and consequences. In this paper, experimental findings on trait boredom, state boredom, and sustained attention performance are presented. We demonstrate that trait boredom uniquely predicts sustained attention performance, over and above depression and self-report attention problems. We also present exploratory findings consistent with the claim that attention failures may cause boredom and that sustained attention tasks may themselves be boring. Discussion of each of these findings, and potential ramifications for cognitive research as a whole, is included.

Transmission of the gut microbiota: spreading of health

PubMed Central

Browne, Hilary P.; Neville, B. Anne; Forster, Samuel C.; Lawley, Trevor D.

2018-01-01

Transmission of commensal intestinal bacteria between humans could promote health by establishing, maintaining and replenishing microbial diversity in the microbiota of an individual. Unlike pathogens, the routes of transmission for commensal bacteria remain unappreciated and poorly understood, despite the likely commonalities between both. Consequently, broad infection control measures that are designed to prevent pathogen transmission and infection, such as oversanitation and the overuse of antibiotics, may inadvertently affect human health by altering normal commensal transmission. In this Review, we discuss the mechanisms and factors that influence host-to-host transmission of the intestinal microbiota and examine how a better understanding of these processes will identify new approaches to nurture and restore transmission routes that are used by beneficial bacteria. PMID:28603278

Forest-climate interactions in fragmented tropical landscapes.

PubMed

Laurance, William F

2004-03-29

In the tropics, habitat fragmentation alters forest-climate interactions in diverse ways. On a local scale (less than 1 km), elevated desiccation and wind disturbance near fragment margins lead to sharply increased tree mortality, thus altering canopy-gap dynamics, plant community composition, biomass dynamics and carbon storage. Fragmented forests are also highly vulnerable to edge-related fires, especially in regions with periodic droughts or strong dry seasons. At landscape to regional scales (10-1000 km), habitat fragmentation may have complex effects on forest-climate interactions, with important consequences for atmospheric circulation, water cycling and precipitation. Positive feedbacks among deforestation, regional climate change and fire could pose a serious threat for some tropical forests, but the details of such interactions are poorly understood.

Variations in sleep characteristics and sleep-related impairment in at-risk college drinkers: a latent profile analysis.

PubMed

DeMartini, Kelly S; Fucito, Lisa M

2014-10-01

Sleep disturbance and heavy drinking increase risk of negative consequences in college students. Limited research exists on how they act synergistically, and the overall nature of sleep and sleep-related impairment in college student drinkers is poorly understood. A latent profile analysis was conducted on the sleep characteristics and daytime sleep-related consequences of college student drinkers who were at-risk based on Alcohol Use Disorders Identification Test-Consumption scores. Participants (N = 312, mean age = 18.90 (0.97) years) consumed a mean (SD) of 20.93 (13.04) drinks per week. Scores on the 10 items of the Sleep/Wake Behavior Problems Scale (SWPS) were the class indicators. Four classes best described the sleep and sleep-related consequences of at-risk college drinkers. Classes represented different gradients and types of sleep patterns and sleep-related impairment; nearly half the sample reported late bedtimes and daytime consequences of insufficient sleep. Subsequent validation analyses indicated that these classes were directly correspondent with severity of alcohol consumption, alcohol-related consequences illicit substance use, and perceived health. These findings indicate the presence of significant heterogeneity in college drinkers' sleep patterns and experiences of sleep-related impairment. Class differences significantly impact the level of alcohol and drug use and the consequences members experience. Greater alcohol use and sleep/wake problems are associated with increased risk for negative consequences for certain classes. These results suggest that college drinking interventions could benefit from the incorporation of sleep-related content and the value in adding brief alcohol assessments and interventions to other college health treatments.

The Affective Bases of Risk Perception: Negative Feelings and Stress Mediate the Relationship between Mental Imagery and Risk Perception.

PubMed

Sobkow, Agata; Traczyk, Jakub; Zaleskiewicz, Tomasz

2016-01-01

Recent research has documented that affect plays a crucial role in risk perception. When no information about numerical risk estimates is available (e.g., probability of loss or magnitude of consequences), people may rely on positive and negative affect toward perceived risk. However, determinants of affective reactions to risks are poorly understood. In a series of three experiments, we addressed the question of whether and to what degree mental imagery eliciting negative affect and stress influences risk perception. In each experiment, participants were instructed to visualize consequences of risk taking and to rate riskiness. In Experiment 1, participants who imagined negative risk consequences reported more negative affect and perceived risk as higher compared to the control condition. In Experiment 2, we found that this effect was driven by affect elicited by mental imagery rather than its vividness and intensity. In this study, imagining positive risk consequences led to lower perceived risk than visualizing negative risk consequences. Finally, we tested the hypothesis that negative affect related to higher perceived risk was caused by negative feelings of stress. In Experiment 3, we introduced risk-irrelevant stress to show that participants in the stress condition rated perceived risk as higher in comparison to the control condition. This experiment showed that higher ratings of perceived risk were influenced by psychological stress. Taken together, our results demonstrate that affect-laden mental imagery dramatically changes risk perception through negative affect (i.e., psychological stress).

The Affective Bases of Risk Perception: Negative Feelings and Stress Mediate the Relationship between Mental Imagery and Risk Perception

PubMed Central

Sobkow, Agata; Traczyk, Jakub; Zaleskiewicz, Tomasz

2016-01-01

Recent research has documented that affect plays a crucial role in risk perception. When no information about numerical risk estimates is available (e.g., probability of loss or magnitude of consequences), people may rely on positive and negative affect toward perceived risk. However, determinants of affective reactions to risks are poorly understood. In a series of three experiments, we addressed the question of whether and to what degree mental imagery eliciting negative affect and stress influences risk perception. In each experiment, participants were instructed to visualize consequences of risk taking and to rate riskiness. In Experiment 1, participants who imagined negative risk consequences reported more negative affect and perceived risk as higher compared to the control condition. In Experiment 2, we found that this effect was driven by affect elicited by mental imagery rather than its vividness and intensity. In this study, imagining positive risk consequences led to lower perceived risk than visualizing negative risk consequences. Finally, we tested the hypothesis that negative affect related to higher perceived risk was caused by negative feelings of stress. In Experiment 3, we introduced risk-irrelevant stress to show that participants in the stress condition rated perceived risk as higher in comparison to the control condition. This experiment showed that higher ratings of perceived risk were influenced by psychological stress. Taken together, our results demonstrate that affect-laden mental imagery dramatically changes risk perception through negative affect (i.e., psychological stress). PMID:27445901

Social Consequences of Alcohol Use among Urban Poor: A Cross-sectional Study in Kathmandu Valley.

PubMed

Thapa, P; Mishra, S R; Bista, B; Dhungana, R R; Adhikari, N; Soti, L; Puri, S; Aryal, K K

2015-01-01

Nepal is not an exception to alcohol use; urban poor are more prone than the general population. The question of social consequences of alcohol use among urban poor remains largely unanswered in Nepal. Study explored the alcohol linked social consequences among the urban poor of Kathmandu Valley. Taking 422 urban poor from four squatter settlements of Kathmandu Valley, a cross-sectional study was carried out. A series of univariate and bivariate analysis were performed in R version 3.1.2. Four out of 10 current drinkers (42.86%, 95% CI: 31.4-54.3) encountered various social consequences. The number one consequence hitting 23.19% drinkers was money loss. Male drinkers were 4.43 times (95% CI: 1.810.8) more likely to face social consequences than their female counterparts. Being male frequent drinker increased the odds of social consequence 3.80 times (95% CI:1.3-11.0) than that of female frequent drinker. A behaviour change communication campaign needs initiation; male populace and frequent drinkers being the target.

Reassessing immune control of hepatitis A virus.

PubMed

Walker, Christopher M; Feng, Zongdi; Lemon, Stanley M

2015-04-01

There is renewed interest in hepatitis A virus (HAV) pathogenesis and immunity after 2-3 decades of limited progress. From a public health perspective, the average age at infection has increased in developing countries, resulting in more severe hepatitis that is poorly understood mechanistically. More fundamentally, there is interest in comparing immunity to HAV and hepatitis C virus (HCV): small, positive-strand RNA viruses with very different infection outcomes. Here, we review evidence that circulating HAV virions are cloaked in membranes, with consequences for induction of innate immunity and antibody-mediated neutralization. We also consider the contribution of CD4+ helper versus CD8+ cytotoxic T cells to antiviral immunity and liver injury, and present a model of non-cytotoxic immune control of HAV infection. Copyright © 2015 Elsevier B.V. All rights reserved.

Polyelectrolyte Structure and Interactions in Model Cystic Fibrosis Sputum

NASA Astrophysics Data System (ADS)

Slimmer, Scott; Angelini, Thomas; Liang, Hongjun; Butler, John; Wong, Gerard C. L.

2002-03-01

Cystic fibrosis sputum is a complex fluid consisting of a number of components, including mucin (a glycoprotein), lysozyme (a cationic polypeptide), water, salt, as well as a high concentration of a number of anionic biological polyelectrolytes such as DNA and F-actin. The interactions governing these components are poorly understood, but may have important clinical consequences. For example, the formation of these biological polyelectrolytes into ordered gel phases may contribute significantly to the observed high viscosity of CF sputum. In this work, a number of model systems were created to simulate CF sputum in vitro, in order to elucidate the contributions of the different components. Preliminary results will be presented. This work was supported by NSF DMR-0071761, DOE DEFG02-91ER45439, the Beckman Young Investigator Program, and the Cystic Fibrosis Foundation.

Actin - Lysozyme Interactions in Model Cystic Fibrosis Sputum

NASA Astrophysics Data System (ADS)

Sanders, Lori; Slimmer, Scott; Angelini, Thomas; Wong, Gerard C. L.

2003-03-01

Cystic fibrosis sputum is a complex fluid consisting of mucin (a glycoprotein), lysozyme (a cationic polypeptide), water, salt, as well as a high concentration of a number of anionic biological polyelectrolytes such as DNA and F-actin. The interactions governing these components are poorly understood, but may have important clinical consequences. For example, the formation of these biological polyelectrolytes into ordered gel phases may contribute significantly to the observed high viscosity of CF sputum. In this work, a number of model systems containing actin, lysozyme, and KCl were created to simulate CF sputum in vitro. These model systems were studied using small angle x-ray scattering and confocal fluorescence microscopy. Preliminary results will be presented. This work was supported by NSF DMR-0071761, the Beckman Young Investigator Program, and the Cystic Fibrosis Foundation.

Social Information Links Individual Behavior to Population and Community Dynamics.

PubMed

Gil, Michael A; Hein, Andrew M; Spiegel, Orr; Baskett, Marissa L; Sih, Andrew

2018-05-07

When individual animals make decisions, they routinely use information produced intentionally or unintentionally by other individuals. Despite its prevalence and established fitness consequences, the effects of such social information on ecological dynamics remain poorly understood. Here, we synthesize results from ecology, evolutionary biology, and animal behavior to show how the use of social information can profoundly influence the dynamics of populations and communities. We combine recent theoretical and empirical results and introduce simple population models to illustrate how social information use can drive positive density-dependent growth of populations and communities (Allee effects). Furthermore, social information can shift the nature and strength of species interactions, change the outcome of competition, and potentially increase extinction risk in harvested populations and communities. Copyright © 2018 Elsevier Ltd. All rights reserved.

Electron temperature gradient scale at collisionless shocks.

PubMed

Schwartz, Steven J; Henley, Edmund; Mitchell, Jeremy; Krasnoselskikh, Vladimir

2011-11-18

Shock waves are ubiquitous in space and astrophysics. They transform directed flow energy into thermal energy and accelerate energetic particles. The energy repartition is a multiscale process related to the spatial and temporal structure of the electromagnetic fields within the shock layer. While large scale features of ion heating are known, the electron heating and smaller scale fields remain poorly understood. We determine for the first time the scale of the electron temperature gradient via electron distributions measured in situ by the Cluster spacecraft. Half of the electron heating coincides with a narrow layer several electron inertial lengths (c/ω(pe)) thick. Consequently, the nonlinear steepening is limited by wave dispersion. The dc electric field must also vary over these small scales, strongly influencing the efficiency of shocks as cosmic ray accelerators.

Postconcussion Syndrome: A Review.

PubMed

Barlow, Karen M

2016-01-01

Postconcussion syndrome is a symptom complex with a wide range of somatic, cognitive, sleep, and affective features, and is the most common consequence of traumatic brain injury. Between 14% and 29% of children with mild traumatic brain injury will continue to have postconcussion symptoms at 3 months, but the pathophysiological mechanisms driving this is poorly understood. The relative contribution of injury factors to postconcussion syndrome decreases over time and, instead, premorbid factors become important predictors of symptom persistence by 3 to 6 months postinjury. The differential diagnoses include headache disorder, cervical injury, anxiety, depression, somatization, vestibular dysfunction, and visual dysfunction. The long-term outcome for most children is good, although there is significant morbidity in the short term. Management strategies target problematic symptoms such as headaches, sleep and mood disturbances, and cognitive complaints. © The Author(s) 2014.

In vivo imaging of the pathophysiological changes and neutrophil dynamics in influenza virus-infected mouse lungs.

PubMed

Ueki, Hiroshi; Wang, I-Hsuan; Fukuyama, Satoshi; Katsura, Hiroaki; da Silva Lopes, Tiago Jose; Neumann, Gabriele; Kawaoka, Yoshihiro

2018-06-25

The pathophysiological changes that occur in lungs infected with influenza viruses are poorly understood. Here we established an in vivo imaging system that combines two-photon excitation microscopy and fluorescent influenza viruses of different pathogenicity. This approach allowed us to monitor and correlate several parameters and physiological changes including the spread of infection, pulmonary permeability, pulmonary perfusion speed, number of recruited neutrophils in infected lungs, and neutrophil motion in the lungs of live mice. Several physiological changes were larger and occurred earlier in mice infected with a highly pathogenic H5N1 influenza virus compared with those infected with a mouse-adapted human strain. These findings demonstrate the potential of our in vivo imaging system to provide novel information about the pathophysiological consequences of virus infections.

Female puberty acceleration by male odour in mice: neural pathway and behavioural consequences.

PubMed

Jouhanneau, Mélanie; Szymanski, Laura A; Keller, Matthieu

2014-08-01

In female mice, exposure to male chemosignals results in early puberty onset characterized by advanced vaginal opening and higher uterine weight. Evidence suggests that the male chemosignals responsible for acceleration of female puberty are androgen-dependent, but not all of the compounds that contribute to puberty acceleration have been identified. The male chemosignals are primarily detected and processed by the vomeronasal system including the vomeronasal organ, the accessory olfactory bulb and the medial amygdala. By contrast, the mechanism by which this olfactory information is integrated in the hypothalamus is poorly understood. In this context, the recent identification of the neuropeptide kisspeptin as a gatekeeper of puberty onset may provide a good candidate neuropeptide system for the transmission of chemosensory information to the gonadotrope axis.

Early-life stress origins of gastrointestinal disease: animal models, intestinal pathophysiology, and translational implications

PubMed Central

Pohl, Calvin S.; Medland, Julia E.

2015-01-01

Early-life stress and adversity are major risk factors in the onset and severity of gastrointestinal (GI) disease in humans later in life. The mechanisms by which early-life stress leads to increased GI disease susceptibility in adult life remain poorly understood. Animal models of early-life stress have provided a foundation from which to gain a more fundamental understanding of this important GI disease paradigm. This review focuses on animal models of early-life stress-induced GI disease, with a specific emphasis on translational aspects of each model to specific human GI disease states. Early postnatal development of major GI systems and the consequences of stress on their development are discussed in detail. Relevant translational differences between species and models are highlighted. PMID:26451004

Consequences of Growing Up Poor.

ERIC Educational Resources Information Center

Duncan, Greg J., Ed.; Brooks-Gunn, Jeanne, Ed.

The consequences and correlates of growing up poor as well as the mechanisms through which poverty influences children are explored. This book is organized with a primary focus on research findings and a secondary concern with policy implications. The chapters are: (1) "Poor Families, Poor Outcomes: The Well-Being of Children and Youth" (Jeanne…

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

Local peace and contemporary conflict: Constructing commonality and exclusion during war in Afghanistan.

PubMed

Karell, Daniel

2017-01-01

Despite the "local turn" in international peacekeeping and the emphasis on community-centered development during the recent wars in Afghanistan and Iraq, it remains poorly understood how local actors-both foreign and indigenous-shape local-level wartime settings. This article explores the processes and consequences of one military unit's efforts to "win hearts and minds" in Afghanistan during 2012-13. The first portion of the analysis examines original textual data with a novel methodological approach depicting the unit's perceptions of commonalities between itself and local actors. The second portion explores the consequences with data from original interviews with residents of southern Afghanistan in 2014-15. The findings suggest that achieving a local peace can be undermined by military and development actors' own perception of the local community. The article concludes with a discussion of how sociological studies of micro-settings between actors can contribute to research on conflict and wartime development, as well as how the sociological study of war can further develop by disaggregating conflict settings and tracing the social construction of wartime socio-political landscapes. Copyright © 2016 Elsevier Inc. All rights reserved.

Child maltreatment and pediatric asthma: a review of the literature.

PubMed

Schreier, Hannah M C; Chen, Edith; Miller, Gregory E

2016-01-01

Child maltreatment is a common problem with known adverse consequences, yet its contributions to the development and course of pediatric asthma are only poorly understood. This review first describes possible pathways connecting child maltreatment to pediatric asthma, including aspects of the physical home environment, health behaviors and disease management, and psychological consequences of child maltreatment. We subsequently review existing studies, which generally report an association between maltreatment experiences and asthma outcomes in childhood. However, this literature is in its early stages; there are only a handful studies, most of them rely on self-reports of both child maltreatment and asthma history, and none have investigated the physiological underpinnings of this association. Taken together, however, the studies are suggestive of child maltreatment playing a role in pediatric asthma incidence and expression that should be explored further. Existing data are sparse and do not allow for specific conclusions. However, the data are suggestive of child maltreatment influencing asthma risk and morbidity long before the adult years. Future research should focus on understanding how child maltreatment contributes to asthma disease risk and progression in this highly vulnerable population.

Overshadowing: a silver lining to a dark cloud in horse training.

PubMed

McLean, Andrew N

2008-01-01

Overshadowing is a process known in behavioral science that occurs when two stimuli of different strengths are applied simultaneously to a nonhuman animal. Typically, the stronger stimulus overshadows the weaker one, resulting in attenuation of the weaker stimulus. This phenomenon explains ways in which the decreased responsiveness and consequent conflict behaviors (and possibly learned helplessness and wastage) in some performance horses can result from the application of two concurrent aversive stimuli. Despite some adverse consequences in the context of ridden horses, overshadowing can have serendipitous benefits because it offers an efficient method of desensitization for certain stimuli that are sometimes highly aversive: the saddle/girth pressure, clippers, aerosols, and needles. Desensitization with concurrent overshadowing appears to be comparatively rapid, particularly with highly aversive stimuli, possibly because attentional mechanisms are diverted to the more salient stimulus. It is important to note that, following the overshadowing procedure, the effects appear to be retained when assessed on subsequent days. Using 4 examples, this article presents a preliminary exploration of the beneficial use of a poorly understood, underutilized--yet promising--phenomenon that warrants further investigation.

Effect of Phase Shift from Corals to Zoantharia on Reef Fish Assemblages

PubMed Central

Cruz, Igor C. S.; Loiola, Miguel; Albuquerque, Tiago; Reis, Rodrigo; de Anchieta C. C. Nunes, José; Reimer, James D.; Mizuyama, Masaru; Kikuchi, Ruy K. P.; Creed, Joel C.

2015-01-01

Consequences of reef phase shifts on fish communities remain poorly understood. Studies on the causes, effects and consequences of phase shifts on reef fish communities have only been considered for coral-to-macroalgae shifts. Therefore, there is a large information gap regarding the consequences of novel phase shifts and how these kinds of phase shifts impact on fish assemblages. This study aimed to compare the fish assemblages on reefs under normal conditions (relatively high cover of corals) to those which have shifted to a dominance of the zoantharian Palythoa cf. variabilis on coral reefs in Todos os Santos Bay (TSB), Brazilian eastern coast. We examined eight reefs, where we estimated cover of corals and P. cf. variabilis and coral reef fish richness, abundance and body size. Fish richness differed significantly between normal reefs (48 species) and phase-shift reefs (38 species), a 20% reduction in species. However there was no difference in fish abundance between normal and phase shift reefs. One fish species, Chaetodon striatus, was significantly less abundant on normal reefs. The differences in fish assemblages between different reef phases was due to differences in trophic groups of fish; on normal reefs carnivorous fishes were more abundant, while on phase shift reefs mobile invertivores dominated. PMID:25629532

“Culture Is So Interspersed”: Child-Minders' and Health Workers' Perceptions of Childhood Obesity in South Africa

PubMed Central

Saltzman, Jaclyn; Jarick Metcalfe, Jessica; Wiley, Angela

2017-01-01

Introduction. Forty-one million children globally are overweight or obese, with most rapid rate increases among low- and middle-income nations. Child-minders and health workers play a crucial role in obesity prevention efforts, but their perceptions of childhood obesity in low- and middle-income countries are poorly understood. This study aims to (1) explore child-minders and health workers' perceptions of the causes, consequences, potential strategies, and barriers for childhood obesity prevention and intervention in Cape Town, South Africa and (2) to provisionally test the fit of a socioecological framework to explain these perceptions. Methods. Twenty-one interviews were recorded, transcribed, and analyzed through analytic induction. Results. Participants identified multilevel factors and contexts, as well as potential consequences and priorities of interest in addressing childhood obesity. An adapted childhood obesity perceptions model was generated, which introduces an overarching cultural dimension embedded across levels of the socioecological framework. Conclusions. Culture plays a pivotal role in explaining obesogenic outcomes, and the results of this study demonstrate the need for further research investigating how obesity perceptions are shaped by cultural frames (e.g., social, political, and historical). Understanding the causes, consequences, and potential interventions to address obesity through a cultural lens is critical for promoting health in low- and middle-income nations. PMID:28367326

"Culture Is So Interspersed": Child-Minders' and Health Workers' Perceptions of Childhood Obesity in South Africa.

PubMed

Figueroa, Roger; Saltzman, Jaclyn; Jarick Metcalfe, Jessica; Wiley, Angela

2017-01-01

Introduction. Forty-one million children globally are overweight or obese, with most rapid rate increases among low- and middle-income nations. Child-minders and health workers play a crucial role in obesity prevention efforts, but their perceptions of childhood obesity in low- and middle-income countries are poorly understood. This study aims to (1) explore child-minders and health workers' perceptions of the causes, consequences, potential strategies, and barriers for childhood obesity prevention and intervention in Cape Town, South Africa and (2) to provisionally test the fit of a socioecological framework to explain these perceptions. Methods. Twenty-one interviews were recorded, transcribed, and analyzed through analytic induction. Results. Participants identified multilevel factors and contexts, as well as potential consequences and priorities of interest in addressing childhood obesity. An adapted childhood obesity perceptions model was generated, which introduces an overarching cultural dimension embedded across levels of the socioecological framework. Conclusions. Culture plays a pivotal role in explaining obesogenic outcomes, and the results of this study demonstrate the need for further research investigating how obesity perceptions are shaped by cultural frames (e.g., social, political, and historical). Understanding the causes, consequences, and potential interventions to address obesity through a cultural lens is critical for promoting health in low- and middle-income nations.

Fish stranding in freshwater systems: sources, consequences, and mitigation.

PubMed

Nagrodski, Alexander; Raby, Graham D; Hasler, Caleb T; Taylor, Mark K; Cooke, Steven J

2012-07-30

Fish can become stranded when water levels decrease, often rapidly, as a result of anthropogenic (e.g., canal drawdown, hydropeaking, vessel wakes) and natural (e.g., floods, drought, winter ice dynamics) events. We summarize existing research on stranding of fish in freshwater, discuss the sources, consequences, and mitigation options for stranding, and report current knowledge gaps. Our literature review revealed that ∼65.5% of relevant peer-reviewed articles were found to focus on stranding associated with hydropower operations and irrigation projects. In fact, anthropogenic sources of fish stranding represented 81.8% of available literature compared to only 19.9% attributed to natural fish stranding events. While fish mortality as a result of stranding is well documented, our analysis revealed that little is known about the sublethal and long-term consequences of stranding on growth and population dynamics. Furthermore, the contribution of stranding to annual mortality rates is poorly understood as are the potential ecosystem-scale impacts. Mitigation strategies available to deal with stranding include fish salvage, ramping rate limitations, and physical habitat works (e.g., to contour substrate to minimize stranding). However, a greater knowledge of the factors that cause fish stranding would promote the development and refinement of mitigation strategies that are economically and ecologically sustainable. Copyright © 2012 Elsevier Ltd. All rights reserved.

The recent history and population structure of five Mandarina snail species from subtropical Ogasawara (Bonin Islands, Japan).

PubMed

Davison, Angus; Chiba, Satoshi

2006-09-01

The effect of Pleistocene climate change on the organisms of tropical and subtropical regions is rather poorly understood. We therefore studied the land snail genus Mandarina (Bradybaenidae) of oceanic Ogasawara (Bonin Islands, Japan), with the aim of using population genetic data to understand their recent history. Our analysis of a mitochondrial 16S ribosomal RNA region from more than 600 snails in five ground-living species suggests that populations on the small islands of Mukoujima, Anejima, Imotojima and Meijima, as well as on the low-lying southern and central parts of Hahajima, have probably undergone recent bottlenecks followed by subsequent expansions. Except between the main island of Hahajima and Mukouijima, there is almost no evidence for gene flow among islands even though the islands were connected repeatedly by land bridges through the Pleistocene. Within islands the population structure is severe, suggestive of a long-term, low level of gene flow (F(ST) is frequently greater than 0.5 among geographically close populations). Finally, there is a marked genetic patchiness, meaning that genetically close populations are sometimes separated by genetically distant populations. These patterns could be a consequence of expansion from bottlenecks, low active dispersal and founder effects caused by rare long-distance migrants. Unfortunately, the exact nature of the refugia and bottlenecks remains unknown because the palaeoclimate of this region is poorly understood. Dating the population size changes is also challenging because the molecular clock is uncertain. We suggest, however, that arid conditions or deforestation induced by decreased atmospheric CO(2) may have been the main factor in determining population size.

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.

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.

The impact of sleep and psychiatric symptoms on alcohol consequences among young adults.

PubMed

Miller, Mary Beth; Van Reen, Eliza; Barker, David H; Roane, Brandy M; Borsari, Brian; McGeary, John E; Seifer, Ronald; Carskadon, Mary A

2017-03-01

Independent lines of research have documented links between psychiatric symptoms and poor sleep quality, psychiatric symptoms and alcohol use, and alcohol use and poor sleep quality. The current study examined the synergistic effect of poor sleep quality and psychiatric symptoms on alcohol-related consequences in heavy-drinking young adults. Matriculating college students reporting at least one heavy drinking episode over the first nine weeks of the semester (N=385, 52% female) were categorized as experiencing 'good' (n=280) versus 'poor' sleep quality (n=105) and screening 'positive' (n=203) or 'negative' (n=182) for a psychiatric disorder. Sleep quality was assessed using the Pittsburgh Sleep Quality Index; psychiatric diagnosis was assessed using the Psychiatric Diagnostic Screening Questionnaire; and alcohol-related consequences were assessed using the Brief Young Adult Alcohol Consequences Questionnaire. General linear models were used to examine the main effects and interaction between sleep quality and psychiatric symptoms on alcohol-related consequences. Sleep quality moderated the association between psychiatric screen and alcohol-related consequences among heavy-drinking college students, such that psychiatric symptoms were associated with more alcohol-related consequences in the context of poor sleep quality. The combination of poor sleep quality and psychiatric symptoms is associated with increased alcohol-related consequences among heavy-drinking college students. Given the significant interaction between these symptoms, healthcare providers are encouraged to screen for the presence of sleep and psychiatric disorders among heavy-drinking young adults and to provide empirically-supported treatments as appropriate. Copyright © 2016 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

Modelling fungal growth in heterogeneous soil: analyses of the effect of soil physical structure on fungal community dynamics

NASA Astrophysics Data System (ADS)

Falconer, R.; Radoslow, P.; Grinev, D.; Otten, W.

2009-04-01

Fungi play a pivital role in soil ecosystems contributing to plant productivity. The underlying soil physical and biological processes responsible for community dynamics are interrelated and, at present, poorly understood. If these complex processes can be understood then this knowledge can be managed with an aim to providing more sustainable agriculture. Our understanding of microbial dynamics in soil has long been hampered by a lack of a theoretical framework and difficulties in observation and quantification. We will demonstrate how the spatial and temporal dynamics of fungi in soil can be understood by linking mathematical modelling with novel techniques that visualise the complex structure of the soil. The combination of these techniques and mathematical models opens up new possibilities to understand how the physical structure of soil affects fungal colony dynamics and also how fungal dynamics affect soil structure. We will quantify, using X ray tomography, soil structure for a range of artificially prepared microcosms. We characterise the soil structures using soil metrics such as porosity, fractal dimension, and the connectivity of the pore volume. Furthermore we will use the individual based fungal colony growth model of Falconer et al. 2005, which is based on the physiological processes of fungi, to assess the effect of soil structure on microbial dynamics by qualifying biomass abundances and distributions. We demonstrate how soil structure can critically affect fungal species interactions with consequences for biological control and fungal biodiversity.

Chemoreception drives plastic consumption in a hard coral.

PubMed

Allen, Austin S; Seymour, Alexander C; Rittschof, Daniel

2017-11-15

The drivers behind microplastic (up to 5mm in diameter) consumption by animals are uncertain and impacts on foundational species are poorly understood. We investigated consumption of weathered, unfouled, biofouled, pre-production and microbe-free National Institute of Standards plastic by a scleractinian coral that relies on chemosensory cues for feeding. Experiment one found that corals ingested many plastic types while mostly ignoring organic-free sand, suggesting that plastic contains phagostimulents. Experiment two found that corals ingested more plastic that wasn't covered in a microbial biofilm than plastics that were biofilmed. Additionally, corals retained ~8% of ingested plastic for 24h or more and retained particles appeared stuck in corals, with consequences for energetics, pollutant toxicity and trophic transfer. The potential for chemoreception to drive plastic consumption in marine taxa has implications for conservation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Elevated arousal levels enhance contrast perception.

PubMed

Kim, Dongho; Lokey, Savannah; Ling, Sam

2017-02-01

Our state of arousal fluctuates from moment to moment-fluctuations that can have profound impacts on behavior. Arousal has been proposed to play a powerful, widespread role in the brain, influencing processes as far ranging as perception, memory, learning, and decision making. Although arousal clearly plays a critical role in modulating behavior, the mechanisms underlying this modulation remain poorly understood. To address this knowledge gap, we examined the modulatory role of arousal on one of the cornerstones of visual perception: contrast perception. Using a reward-driven paradigm to manipulate arousal state, we discovered that elevated arousal state substantially enhances visual sensitivity, incurring a multiplicative modulation of contrast response. Contrast defines vision, determining whether objects appear visible or invisible to us, and these results indicate that one of the consequences of decreased arousal state is an impaired ability to visually process our environment.

Revealing the role of phospholipase Cβ3 in the regulation of VEGF-induced vascular permeability

PubMed Central

Hoeppner, Luke H.; Phoenix, Kathryn N.; Clark, Karl J.; Bhattacharya, Resham; Gong, Xun; Sciuto, Tracey E.; Vohra, Pawan; Suresh, Sandip; Bhattacharya, Santanu; Dvorak, Ann M.; Ekker, Stephen C.; Dvorak, Harold F.; Claffey, Kevin P.

2012-01-01

VEGF induces vascular permeability (VP) in ischemic diseases and cancer, leading to many pathophysiological consequences. The molecular mechanisms by which VEGF acts to induce hyperpermeability are poorly understood and in vivo models that easily facilitate real-time, genetic studies of VP do not exist. In the present study, we report a heat-inducible VEGF transgenic zebrafish (Danio rerio) model through which VP can be monitored in real time. Using this approach with morpholino-mediated gene knock-down and knockout mice, we describe a novel role of phospholipase Cβ3 as a negative regulator of VEGF-mediated VP by regulating intracellular Ca2+ release. Our results suggest an important effect of PLCβ3 on VP and provide a new model with which to identify genetic regulators of VP crucial to several disease processes. PMID:22674805

Early-life stress origins of gastrointestinal disease: animal models, intestinal pathophysiology, and translational implications.

PubMed

Pohl, Calvin S; Medland, Julia E; Moeser, Adam J

2015-12-15

Early-life stress and adversity are major risk factors in the onset and severity of gastrointestinal (GI) disease in humans later in life. The mechanisms by which early-life stress leads to increased GI disease susceptibility in adult life remain poorly understood. Animal models of early-life stress have provided a foundation from which to gain a more fundamental understanding of this important GI disease paradigm. This review focuses on animal models of early-life stress-induced GI disease, with a specific emphasis on translational aspects of each model to specific human GI disease states. Early postnatal development of major GI systems and the consequences of stress on their development are discussed in detail. Relevant translational differences between species and models are highlighted. Copyright © 2015 the American Physiological Society.

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.

Why does starvation make bones fat?

PubMed Central

Devlin, Maureen J.

2011-01-01

Body fat, or adipose tissue, is a crucial energetic buffer against starvation in humans and other mammals, and reserves of white adipose tissue (WAT) rise and fall in parallel with food intake. Much less is known about the function of bone marrow adipose tissue (BMAT), which are fat cells found in bone marrow. BMAT mass actually increases during starvation, even as other fat depots are being mobilized for energy. Here I review the possible reasons for this poorly understood phenomenon. Is BMAT a passive filler that occupies spaces left by dying bone cells, a pathological consequence of suppressed bone formation, or potentially an adaptation for surviving starvation? To evaluate these possibilities, here I review what is known about the effects of starvation on the body, particularly the skeleton, and the mechanisms involved in storing and metabolizing BMAT during negative energy balance. PMID:21793093

Why does starvation make bones fat?

PubMed

Devlin, Maureen J

2011-01-01

Body fat, or adipose tissue, is a crucial energetic buffer against starvation in humans and other mammals, and reserves of white adipose tissue (WAT) rise and fall in parallel with food intake. Much less is known about the function of bone marrow adipose tissue (BMAT), which are fat cells found in bone marrow. BMAT mass actually increases during starvation, even as other fat depots are being mobilized for energy. This review considers several possible reasons for this poorly understood phenomenon. Is BMAT a passive filler that occupies spaces left by dying bone cells, a pathological consequence of suppressed bone formation, or potentially an adaptation for surviving starvation? These possibilities are evaluated in terms of the effects of starvation on the body, particularly the skeleton, and the mechanisms involved in storing and metabolizing BMAT during negative energy balance. Copyright © 2011 Wiley-Liss, Inc.

Artificial intelligence for breast cancer screening: Opportunity or hype?

PubMed

Houssami, Nehmat; Lee, Christoph I; Buist, Diana S M; Tao, Dacheng

2017-12-01

Interpretation of mammography for breast cancer (BC) screening can confer a mortality benefit through early BC detection, can miss a cancer that is present or fast growing, or can result in false-positives. Efforts to improve screening outcomes have mostly focused on intensifying imaging practices (double instead of single-reading, more frequent screens, or supplemental imaging) that may add substantial resource expenditures and harms associated with population screening. Less attention has been given to making mammography screening practice 'smarter' or more efficient. Artificial intelligence (AI) is capable of advanced learning using large complex datasets and has the potential to perform tasks such as image interpretation. With both highly-specific capabilities, and also possible un-intended (and poorly understood) consequences, this viewpoint considers the promise and current reality of AI in BC detection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human–nature interactions and the consequences and drivers of provisioning wildlife

PubMed Central

Gaston, Kevin J.

2018-01-01

Many human populations are undergoing an extinction of experience, with a progressive decline in interactions with nature. This is a consequence both of a loss of opportunity for, and orientation towards, such experiences. The trend is of concern in part because interactions with nature can be good for human health and wellbeing. One potential means of redressing these losses is through the intentional provision of resources to increase wildlife populations in close proximity to people, thereby increasing the potential for positive human–nature experiences, and thence the array of benefits that can result. In this paper, we review the evidence that these resource subsidies have such a cascade of effects. In some Westernized countries, the scale of provision is extraordinarily high, and doubtless leads to both positive and negative impacts for wildlife. In turn, these impacts often lead to more frequent, reliable and closer human–nature interactions, with a greater variety of species. The consequences for human wellbeing remain poorly understood, although benefits documented in the context of human–nature interactions more broadly seem likely to apply. There are also some important feedback loops that need to be better characterized if resource provisioning is to contribute effectively towards averting the extinction of experience. This article is part of the theme issue ‘Anthropogenic resource subsidies and host–parasite dynamics in wildlife’. PMID:29531147

The role of objective cognitive dysfunction in subjective cognitive complaints after stroke.

PubMed

van Rijsbergen, M W A; Mark, R E; Kop, W J; de Kort, P L M; Sitskoorn, M M

2017-03-01

Objective cognitive performance (OCP) is often impaired in patients post-stroke but the consequences of OCP for patient-reported subjective cognitive complaints (SCC) are poorly understood. We performed a detailed analysis on the association between post-stroke OCP and SCC. Assessments of OCP and SCC were obtained in 208 patients 3 months after stroke. OCP was evaluated using conventional and ecologically valid neuropsychological tests. Levels of SCC were measured using the CheckList for Cognitive and Emotional (CLCE) consequences following stroke inventory. Multivariate hierarchical regression analyses were used to evaluate the association of OCP with CLCE scores adjusting for age, sex and intelligence quotient. Analyses were performed to examine the global extent of OCP dysfunction (based on the total number of impaired neuropsychological tests, i.e. objective cognitive impairment index) and for each OCP test separately using the raw neuropsychological (sub)test scores. The objective cognitive impairment index for global OCP was positively correlated with the CLCE score (Spearman's rho = 0.22, P = 0.003), which remained significant in multivariate adjusted models (β = 0.25, P = 0.01). Results for the separate neuropsychological tests indicated that only one task (the ecologically valid Rivermead Behavioural Memory Test) was independently associated with the CLCE in multivariate adjusted models (β = -0.34, P < 0.001). Objective neuropsychological test performance, as measured by the global dysfunction index or an ecologically valid memory task, was associated with SCC. These data suggest that cumulative deficits in multiple cognitive domains contribute to subjectively experienced poor cognitive abilities in daily life in patients post-stroke. © 2016 EAN.

Reliability of image-free navigation to monitor lower-limb alignment.

PubMed

Pearle, Andrew D; Goleski, Patrick; Musahl, Volker; Kendoff, Daniel

2009-02-01

Proper alignment of the mechanical axis of the lower limb is the principal goal of a high tibial osteotomy. A well-accepted and relevant technical specification is the coronal plane lower-limb alignment. Target values for coronal plane alignment after high tibial osteotomy include 2 degrees of overcorrection, while tolerances for this specification have been established as 2 degrees to 4 degrees. However, the role of axial plane and sagittal plane realignment after high tibial osteotomy is poorly understood; consequently, targets and tolerance for this technical specification remain undefined. This article reviews the literature concerning the reliability and precision of navigation in monitoring the clinically relevant specification of lower-limb alignment in high tibial osteotomy. We conclude that image-free navigation registration may be clinically useful for intraoperative monitoring of the coronal plane only. Only fair and poor results for the axial and sagittal planes can be obtained by image-free navigation systems. In the future, combined image-based data, such as those from radiographs, magnetic resonance imaging, and gait analysis, may be used to help to improve the accuracy and reproducibility of quantitative intraoperative monitoring of lower-limb alignment.

X-ray Scaling Relations of Early Type Galaxies

NASA Astrophysics Data System (ADS)

Kim, Dong-Woo

2015-08-01

We will review recent results of the X-ray scaling relations of early type galaxies. With high quality Chandra X-ray data, the properties (Lx and T) of hot ISM are accurately measured from gas-poor to gas-rich galaxies. We found a strong correlation between Lx(gas) and M(total) among ETGs with independently measured M(total), indicating that the total mass is the primary factor in regulating the amount of hot gas. We found a tight correlation between Lx(gas) and T(gas) among normal (non-cD), genuine (passively evolving, sigma-supported) ellipticals. This relation holds in a large range of Lx (several 1038 - a few 1041 erg/s). While this relation can be understood among gas-rich galaxies (Lx > 1040 erg/s) as a consequence of virialized gaseous halos in the dark matter potentials, the same tight relation is unexpected among gas-poor galaxies where the hot gas is in a wind/outflow state. We also found an interesting difference between cDs and giant Es, the former having an order of magnitude higher Lx(gas) with a similar T(gas). We will discuss the implications of our results by comparing with other observations of galaxies/groups and recent simulations.

[Ehlers-Danlos syndromes: we are all concerned].

PubMed

de Wazières, B; Plauchu, H; Boucand, M H

1998-10-17

EHLERS-DANLOS SYNDROMES (EDS): A heterogeneous group of hereditary conditions having in common a molecular anomaly of the extracellular matrix comprise EDS. Clinical and genetic features are used for classification and in some cases the molecular anomaly can be demonstrated. Six main types are recognized and termed classic, hypermobile, vascular, cyphoscoliotic, arthrochalasic and dermatosparaxis. Skin and joint signs predominate, visceral disease is fortunately rare. The skin is hyperelastic and heals poorly. Joint involvement may lead to luxations and early-onset osteoarthritis causing chronic pain. The prognosis is severe in certain types such as vascular EDS where arterial ruptures may be life-threatening. Patients with cyphoscoliotic EDS may become bedridden due to the scoliosis and muscular hypotrophy. Minor forms as well as rapidly fatal major forms often go undiagnosed or are identified late after a complication which could have been avoided. A multidisciplinary approach is needed as certain interventions, technical procedures or explorations may have catastrophic consequences. The creation of an EDS association would be helpful in federating specialists and allow global management. The gravity of certain forms, the poorly understood epidemiology and the progressive nature of EDS point to the need for a national registry.

Acoustic measurement and morphological features of organic sediment deposits in combined sewer networks.

PubMed

Carnacina, Iacopo; Larrarte, Frédérique; Leonardi, Nicoletta

2017-04-01

The performance of sewer networks has important consequences from an environmental and social point of view. Poor functioning can result in flood risk and pollution at a large scale. Sediment deposits forming in sewer trunks might severely compromise the sewer line by affecting the flow field, reducing cross-sectional areas, and increasing roughness coefficients. In spite of numerous efforts, the morphological features of these depositional environments remain poorly understood. The interface between water and sediment remains inefficiently identified and the estimation of the stock of deposit is frequently inaccurate. In part, this is due to technical issues connected to difficulties in collecting accurate field measurements without disrupting existing morphologies. In this paper, results from an extensive field campaign are presented; during the campaign a new survey methodology based on acoustic techniques has been tested. Furthermore, a new algorithm for the detection of the soil-water interface, and therefore for the correct esteem of sediment stocks is proposed. Finally, results in regard to bed topography, and morphological features at two different field sites are presented and reveal that a large variability in bed forms is present along sewer networks. Copyright © 2017 Elsevier Ltd. All rights reserved.

The role of the uplift of the Qinghai-Tibetan Plateau for the evolution of Tibetan biotas.

PubMed

Favre, Adrien; Päckert, Martin; Pauls, Steffen U; Jähnig, Sonja C; Uhl, Dieter; Michalak, Ingo; Muellner-Riehl, Alexandra N

2015-02-01

Biodiversity is unevenly distributed on Earth and hotspots of biodiversity are often associated with areas that have undergone orogenic activity during recent geological history (i.e. tens of millions of years). Understanding the underlying processes that have driven the accumulation of species in some areas and not in others may help guide prioritization in conservation and may facilitate forecasts on ecosystem services under future climate conditions. Consequently, the study of the origin and evolution of biodiversity in mountain systems has motivated growing scientific interest. Despite an increasing number of studies, the origin and evolution of diversity hotspots associated with the Qinghai-Tibetan Plateau (QTP) remains poorly understood. We review literature related to the diversification of organisms linked to the uplift of the QTP. To promote hypothesis-based research, we provide a geological and palaeoclimatic scenario for the region of the QTP and argue that further studies would benefit from providing a complete set of complementary analyses (molecular dating, biogeographic, and diversification rates analyses) to test for a link between organismic diversification and past geological and climatic changes in this region. In general, we found that the contribution of biological interchange between the QTP and other hotspots of biodiversity has not been sufficiently studied to date. Finally, we suggest that the biological consequences of the uplift of the QTP would be best understood using a meta-analysis approach, encompassing studies on a variety of organisms (plants and animals) from diverse habitats (forests, meadows, rivers), and thermal belts (montane, subalpine, alpine, nival). Since the species diversity in the QTP region is better documented for some organismic groups than for others, we suggest that baseline taxonomic work should be promoted. © 2014 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.

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

PubMed

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

2014-10-01

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

Costs of mounting an immune response during pregnancy in a lizard.

PubMed

Meylan, Sandrine; Richard, Murielle; Bauer, Sophie; Haussy, Claudy; Miles, Donald

2013-01-01

Immune defenses are of great benefit to hosts, but reducing the impact of infection by mounting an immune response also entails costs. However, the physiological mechanisms that generate the costs of an immune response remain poorly understood. Moreover, the majority of studies investigating the consequences of an immune challenge in vertebrates have been conducted on mammals and birds. The aim of this study is to investigate the physiological costs of mounting an immune response during gestation in an ectothermic species. Indeed, because ectothermic species are unable to internally regulate their body temperature, the apportionment of resources to homeostatic activities in ectothermic species can differ from that in endothermic species. We conducted this study on the common lizard Zootoca vivipara. We investigated the costs of mounting an immune response by injecting females with sheep red blood cells and quantified the consequences to reproductive performance (litter mass and success) and physiological performance (standard metabolic rate, endurance, and phytohemagglutinin response). In addition, we measured basking behavior. Our analyses revealed that mounting an immune response affected litter mass, physiological performance, and basking behavior. Moreover, we demonstrated that the modulation of an immune challenge is impacted by intrinsic factors, such as body size and condition.

Sounding the Alarm: Health in the Anthropocene.

PubMed

Butler, Colin D

2016-06-30

There is growing scientific and public recognition that human actions, directly and indirectly, have profoundly changed the Earth system, in a still accelerating process, increasingly called the "Anthropocene". Planetary transformation, including of the atmosphere, climate, ecosystems and biodiversity, has enormous implications for human health, many of which are deeply disturbing, especially in low-income settings. A few health consequences of the Anthropocene have been partially recognized, including within environmental epidemiology, but their long-term consequences remain poorly understood and greatly under-rated. For example Syria could be a "sentinel" population, giving a glimpse to a much wider dystopian future. Health-Earth is a research network, co-founded in 2014, which seeks, with other groups, to catalyse a powerful curative response by the wider health community. This paper builds on a symposium presented by Health-Earth members at the 2015 conference of the International Society for Environmental Epidemiology. It reviews and synthesizes parts of the large literature relevant to the interaction between the changing Earth system and human health. It concludes that this topic should be prominent within future environmental epidemiology and public health. Created by our species, these challenges may be soluble, but solutions require far more understanding and resources than are currently being made available.

In Utero Alcohol Exposure, Epigenetic Changes, and Their Consequences

PubMed Central

Ungerer, Michelle; Knezovich, Jaysen; Ramsay, Michele

2013-01-01

Exposure to alcohol has serious consequences for the developing fetus, leading to a range of conditions collectively known as fetal alcohol spectrum disorders (FASD). Most importantly, alcohol exposure affects the development of the brain during critical periods of differentiation and growth, leading to cognitive and behavioral deficits. The molecular mechanisms and processes underlying the teratogenic effects of alcohol exposure remain poorly understood and are complex, because the specific effects depend on the timing, amount, and duration of exposure as well as genetic susceptibility. Accumulating evidence from studies on DNA methylation and histone modification that affect chromatin structure, as well as on the role of microRNAs in regulating mRNA levels supports the contribution of epigenetic mechanisms to the development of FASD. These epigenetic effects are difficult to study, however, because they often are cell-type specific and transient in nature. Rodent models play an important role in FASD research. Although recent studies using these models have yielded some insight into epigenetic mechanisms affecting brain development, they have generated more questions than they have provided definitive answers. Researchers are just beginning to explore the intertwined roles of different epigenetic mechanisms in neurogenesis and how this process is affected by exposure to alcohol, causing FASD. PMID:24313163

A preliminary spatial assessment of risk: Marine birds and chronic oil pollution on Canada's Pacific coast.

PubMed

Fox, C H; O'Hara, P D; Bertazzon, S; Morgan, K; Underwood, F E; Paquet, P C

2016-12-15

Chronic oil pollution poses substantial risks to marine birds and other marine wildlife worldwide. On Canada's Pacific coast, the negative ecological consequences to marine birds and marine ecosystems in general remain poorly understood. Using information relating to oil spill probability of occurrence, areas of overall importance to marine birds, and the at-sea distribution and density of 12 marine bird species and seven bird groups, including multiple Species at Risk, we undertook a spatial assessment of risk. Our results identify two main areas important to marine birds potentially at higher risk of exposure to oil. For individual bird species or species groups, those predicted to have elevated bird densities near the mainland and the northeast coast of Vancouver Island were identified as being at higher potential risk of exposure. Our results, however, should be considered preliminary. As with other anthropogenic stressors, in order to better understand and subsequently mitigate the consequences of chronic oil pollution on marine birds, improved information relating to marine birds and the occurrence of oil spills on Canada's Pacific coast is needed. Copyright © 2016 Elsevier B.V. All rights reserved.

Agricultural pesticide use and adverse birth outcomes in the San Joaquin Valley of California.

PubMed

Larsen, Ashley E; Gaines, Steven D; Deschênes, Olivier

2017-08-29

Virtually all agricultural communities worldwide are exposed to agricultural pesticides. Yet, the health consequences of such exposure are poorly understood, and the scientific literature remains ambiguous. Using individual birth and demographic characteristics for over 500 000 birth observations between 1997-2011 in the agriculturally dominated San Joaquin Valley, California, we statistically investigate if residential agricultural pesticide exposure during gestation, by trimester, and by toxicity influences birth weight, gestational length, or birth abnormalities. Overall, our analysis indicates that agricultural pesticide exposure increases adverse birth outcomes by 5-9%, but only among the population exposed to very high quantities of pesticides (e.g., top 5th percentile, i.e., ~4200 kg applied over gestation). Thus, policies and interventions targeting the extreme right tail of the pesticide distribution near human habitation could largely eliminate the adverse birth outcomes associated with agricultural pesticide exposure documented in this study.The health consequences of exposure to pesticides are uncertain and subject to much debate. Here, the effect of exposure during pregnancy is investigated in an agriculturally dominated residential area, showing that an increase in adverse birth outcomes is observed with very high levels of pesticide exposure.

Temperature-driven regime shifts in the dynamics of size-structured populations.

PubMed

Ohlberger, Jan; Edeline, Eric; Vøllestad, Leif Asbjørn; Stenseth, Nils C; Claessen, David

2011-02-01

Global warming impacts virtually all biota and ecosystems. Many of these impacts are mediated through direct effects of temperature on individual vital rates. Yet how this translates from the individual to the population level is still poorly understood, hampering the assessment of global warming impacts on population structure and dynamics. Here, we study the effects of temperature on intraspecific competition and cannibalism and the population dynamical consequences in a size-structured fish population. We use a physiologically structured consumer-resource model in which we explicitly model the temperature dependencies of the consumer vital rates and the resource population growth rate. Our model predicts that increased temperature decreases resource density despite higher resource growth rates, reflecting stronger intraspecific competition among consumers. At a critical temperature, the consumer population dynamics destabilize and shift from a stable equilibrium to competition-driven generation cycles that are dominated by recruits. As a consequence, maximum age decreases and the proportion of younger and smaller-sized fish increases. These model predictions support the hypothesis of decreasing mean body sizes due to increased temperatures. We conclude that in size-structured fish populations, global warming may increase competition, favor smaller size classes, and induce regime shifts that destabilize population and community dynamics.

Analysis of diffusion in curved surfaces and its application to tubular membranes

PubMed Central

Klaus, Colin James Stockdale; Raghunathan, Krishnan; DiBenedetto, Emmanuele; Kenworthy, Anne K.

2016-01-01

Diffusion of particles in curved surfaces is inherently complex compared with diffusion in a flat membrane, owing to the nonplanarity of the surface. The consequence of such nonplanar geometry on diffusion is poorly understood but is highly relevant in the case of cell membranes, which often adopt complex geometries. To address this question, we developed a new finite element approach to model diffusion on curved membrane surfaces based on solutions to Fick’s law of diffusion and used this to study the effects of geometry on the entry of surface-bound particles into tubules by diffusion. We show that variations in tubule radius and length can distinctly alter diffusion gradients in tubules over biologically relevant timescales. In addition, we show that tubular structures tend to retain concentration gradients for a longer time compared with a comparable flat surface. These findings indicate that sorting of particles along the surfaces of tubules can arise simply as a geometric consequence of the curvature without any specific contribution from the membrane environment. Our studies provide a framework for modeling diffusion in curved surfaces and suggest that biological regulation can emerge purely from membrane geometry. PMID:27733625

Ingested microscopic plastic translocates to the circulatory system of the mussel, Mytilus edulis (L).

PubMed

Browne, Mark A; Dissanayake, Awantha; Galloway, Tamara S; Lowe, David M; Thompson, Richard C

2008-07-01

Plastics debris is accumulating in the environment and is fragmenting into smaller pieces; as it does, the potential for ingestion by animals increases. The consequences of macroplastic debris for wildlife are well documented, however the impacts of microplastic (< 1 mm) are poorly understood. The mussel, Mytilus edulis, was used to investigate ingestion, translocation, and accumulation of this debris. Initial experiments showed that upon ingestion, microplastic accumulated in the gut. Mussels were subsequently exposed to treatments containing seawater and microplastic (3.0 or 9.6 microm). After transfer to clean conditions, microplastic was tracked in the hemolymph. Particles translocated from the gut to the circulatory system within 3 days and persisted for over 48 days. Abundance of microplastic was greatest after 12 days and declined thereafter. Smaller particles were more abundant than larger particles and our data indicate as plastic fragments into smaller particles, the potential for accumulation in the tissues of an organism increases. The short-term pulse exposure used here did not result in significant biological effects. However, plastics are exceedingly durable and so further work using a wider range of organisms, polymers, and periods of exposure will be required to establish the biological consequences of this debris.

The neural bases of feeling understood and not understood

PubMed Central

Torre, Jared B.; Eisenberger, Naomi I.

2014-01-01

Past research suggests that feeling understood enhances both personal and social well-being. However, little research has examined the neurobiological bases of feeling understood and not understood. We addressed these gaps by experimentally inducing felt understanding and not understanding as participants underwent functional magnetic resonance imaging. The results demonstrated that feeling understood activated neural regions previously associated with reward and social connection (i.e. ventral striatum and middle insula), while not feeling understood activated neural regions previously associated with negative affect (i.e. anterior insula). Both feeling understood and not feeling understood activated different components of the mentalizing system (feeling understood: precuneus and temporoparietal junction; not feeling understood: dorsomedial prefrontal cortex). Neural responses were associated with subsequent feelings of social connection and disconnection and were modulated by individual differences in rejection sensitivity. Thus, this study provides insight into the psychological processes underlying feeling understood (or not) and may suggest new avenues for targeted interventions that amplify the benefits of feeling understood or buffer individuals from the harmful consequences of not feeling understood. PMID:24396002

Protocols to Evaluate Cigarette Smoke-Induced Lung Inflammation and Pathology in Mice.

PubMed

Vlahos, Ross; Bozinovski, Steven

2018-01-01

Cigarette smoking is a major cause of chronic obstructive pulmonary disease (COPD). Inhalation of cigarette smoke causes inflammation of the airways, airway wall remodelling, mucus hypersecretion and progressive airflow limitation. Much of the disease burden and health care utilisation in COPD is associated with the management of its comorbidities and infectious (viral and bacterial) exacerbations (AECOPD). Comorbidities, in particular skeletal muscle wasting, cardiovascular disease and lung cancer markedly impact on disease morbidity, progression and mortality. The mechanisms and mediators underlying COPD and its comorbidities are poorly understood and current COPD therapy is relatively ineffective. Many researchers have used animal modelling systems to explore the mechanisms underlying COPD, AECOPD and comorbidities of COPD with the goal of identifying novel therapeutic targets. Here we describe a mouse model that we have developed to define the cellular, molecular and pathological consequences of cigarette smoke exposure and the development of comorbidities of COPD.

Ocean acidification changes the male fitness landscape.

PubMed

Campbell, Anna L; Levitan, Don R; Hosken, David J; Lewis, Ceri

2016-08-17

Sperm competition is extremely common in many ecologically important marine taxa. Ocean acidification (OA) is driving rapid changes to the marine environments in which freely spawned sperm operate, yet the consequences of OA on sperm performance are poorly understood in the context of sperm competition. Here, we investigated the impacts of OA (+1000 μatm pCO2) on sperm competitiveness for the sea urchin Paracentrotus lividus. Males with faster sperm had greater competitive fertilisation success in both seawater conditions. Similarly, males with more motile sperm had greater sperm competitiveness, but only under current pCO2 levels. Under OA the strength of this association was significantly reduced and there were male sperm performance rank changes under OA, such that the best males in current conditions are not necessarily best under OA. Therefore OA will likely change the male fitness landscape, providing a mechanism by which environmental change alters the genetic landscape of marine species.

Ocean acidification changes the male fitness landscape

NASA Astrophysics Data System (ADS)

Campbell, Anna L.; Levitan, Don R.; Hosken, David J.; Lewis, Ceri

2016-08-01

Sperm competition is extremely common in many ecologically important marine taxa. Ocean acidification (OA) is driving rapid changes to the marine environments in which freely spawned sperm operate, yet the consequences of OA on sperm performance are poorly understood in the context of sperm competition. Here, we investigated the impacts of OA (+1000 μatm pCO2) on sperm competitiveness for the sea urchin Paracentrotus lividus. Males with faster sperm had greater competitive fertilisation success in both seawater conditions. Similarly, males with more motile sperm had greater sperm competitiveness, but only under current pCO2 levels. Under OA the strength of this association was significantly reduced and there were male sperm performance rank changes under OA, such that the best males in current conditions are not necessarily best under OA. Therefore OA will likely change the male fitness landscape, providing a mechanism by which environmental change alters the genetic landscape of marine species.

Extinction order and altered community structure rapidly disrupt ecosystem functioning.

PubMed

Larsen, Trond H; Williams, Neal M; Kremen, Claire

2005-05-01

By causing extinctions and altering community structure, anthropogenic disturbances can disrupt processes that maintain ecosystem integrity. However, the relationship between community structure and ecosystem functioning in natural systems is poorly understood. Here we show that habitat loss appeared to disrupt ecosystem functioning by affecting extinction order, species richness and abundance. We studied pollination by bees in a mosaic of agricultural and natural habitats in California and dung burial by dung beetles on recently created islands in Venezuela. We found that large-bodied bee and beetle species tended to be both most extinction-prone and most functionally efficient, contributing to rapid functional loss. Simulations confirmed that extinction order led to greater disruption of function than predicted by random species loss. Total abundance declined with richness and also appeared to contribute to loss of function. We demonstrate conceptually and empirically how the non-random response of communities to disturbance can have unexpectedly large functional consequences.

Posterior cingulate cortex mediates outcome-contingent allocation of behavior

PubMed Central

Hayden, Benjamin Y.; Nair, Amrita C.; McCoy, Allison N.; Platt, Michael L.

2008-01-01

SUMMARY Adaptive decision making requires selecting an action and then monitoring its consequences to improve future decisions. The neuronal mechanisms supporting action evaluation and subsequent behavioral modification, however, remain poorly understood. To investigate the contribution of posterior cingulate cortex (CGp) to these processes, we recorded activity of single neurons in monkeys performing a gambling task in which the reward outcome of each choice strongly influenced subsequent choices. We found that CGp neurons signaled reward outcomes in a nonlinear fashion, and that outcome-contingent modulations in firing rate persisted into subsequent trials. Moreover, firing rate on any one trial predicted switching to the alternative option on the next trial. Finally, microstimulation in CGp following risky choices promoted a preference reversal for the safe option on the following trial. Collectively, these results demonstrate that CGp directly contributes to the evaluative processes that support dynamic changes in decision making in volatile environments. PMID:18940585

Potential increase in coastal wetland vulnerability to sea-level rise suggested by considering hydrodynamic attenuation effects

PubMed Central

Rodríguez, José F.; Saco, Patricia M.; Sandi, Steven; Saintilan, Neil; Riccardi, Gerardo

2017-01-01

The future of coastal wetlands and their ecological value depend on their capacity to adapt to the interacting effects of human impacts and sea-level rise. Even though extensive wetland loss due to submergence is a possible scenario, its magnitude is highly uncertain due to limited understanding of hydrodynamic and bio-geomorphic interactions over time. In particular, the effect of man-made drainage modifications on hydrodynamic attenuation and consequent wetland evolution is poorly understood. Predictions are further complicated by the presence of a number of vegetation types that change over time and also contribute to flow attenuation. Here, we show that flow attenuation affects wetland vegetation by modifying its wetting-drying regime and inundation depth, increasing its vulnerability to sea-level rise. Our simulations for an Australian subtropical wetland predict much faster wetland loss than commonly used models that do not consider flow attenuation. PMID:28703130

A high-contrast imaging survey of nearby red supergiants

NASA Astrophysics Data System (ADS)

Scicluna, Peter; Siebenmorgen, Ralf; Blommaert, Joris; Kemper, Francisca; Wesson, Roger; Wolf, Sebastian

2017-11-01

Mass-loss in cool supergiants remains poorly understood, but is one of the key elements in their evolution towards exploding as supernovae. Some show evidence of asymmetric mass loss, discrete mass-ejections and outbursts, with seemingly little to distinguish them from more quiescent cases. To explore the prevalence of discrete ejections and companions we have conducted a high-constrast survey using near-infrared imaging and optical polarimetric imaging of nearby southern and equatorial red supergiants, using the extreme adaptive optics instrument SPHERE, which was designed to image planets around nearby stars. We present the initial results of this survey, including the detection of large (500 nm) dust grains in the ejecta of VY CMa and a candidate dusty torus aligned with the maser ring of VX Sgr. We briefly speculate on the consequences for our understanding of mass loss in these extreme stars.

Celiac disease and non-celiac gluten sensitivity

PubMed Central

Lebwohl, Benjamin; Ludvigsson, Jonas F

2015-01-01

Celiac disease is a multisystem immune based disorder that is triggered by the ingestion of gluten in genetically susceptible individuals. The prevalence of celiac disease has risen in recent decades and is currently about 1% in most Western populations. The reason for this rise is unknown, although environmental factors related to the hygiene hypothesis are suspected. The pathophysiology of celiac disease involves both the innate and adaptive immune response to dietary gluten. Clinical features are diverse and include gastrointestinal symptoms, metabolic bone disease, infertility, and many other manifestations. Although a gluten-free diet is effective in most patients, this diet can be burdensome and can limit quality of life; consequently, non-dietary therapies are at various stages of development. This review also covers non-celiac gluten sensitivity. The pathophysiology of this clinical phenotype is poorly understood, but it is a cause of increasing interest in gluten-free diets in the general population. PMID:26438584

Predator personality structures prey communities and trophic cascades.

PubMed

Start, Denon; Gilbert, Benjamin

2017-03-01

Intraspecific variation is central to our understanding of evolution and population ecology, yet its consequences for community ecology are poorly understood. Animal personality - consistent individual differences in suites of behaviours - may be particularly important for trophic dynamics, where predator personality can determine activity rates and patterns of attack. We used mesocosms with aquatic food webs in which the top predator (dragonfly nymphs) varied in activity and subsequent attack rates on zooplankton, and tested the effects of predator personality. We found support for four hypotheses: (1) active predators disproportionately reduce the abundance of prey, (2) active predators select for predator-resistant prey species, (3) active predators strengthen trophic cascades (increase phytoplankton abundance) and (4) active predators are more likely to cannibalise one another, weakening all other trends when at high densities. These results suggest that intraspecific variation in predator personality is an important determinant of prey abundance, community composition and trophic cascades. © 2017 John Wiley & Sons Ltd/CNRS.

Baleen whales host a unique gut microbiome with similarities to both carnivores and herbivores.

PubMed

Sanders, Jon G; Beichman, Annabel C; Roman, Joe; Scott, Jarrod J; Emerson, David; McCarthy, James J; Girguis, Peter R

2015-09-22

Mammals host gut microbiomes of immense physiological consequence, but the determinants of diversity in these communities remain poorly understood. Diet appears to be the dominant factor, but host phylogeny also seems to be an important, if unpredictable, correlate. Here we show that baleen whales, which prey on animals (fish and crustaceans), harbor unique gut microbiomes with surprising parallels in functional capacity and higher level taxonomy to those of terrestrial herbivores. These similarities likely reflect a shared role for fermentative metabolisms despite a shift in primary carbon sources from plant-derived to animal-derived polysaccharides, such as chitin. In contrast, protein catabolism and essential amino acid synthesis pathways in baleen whale microbiomes more closely resemble those of terrestrial carnivores. Our results demonstrate that functional attributes of the microbiome can vary independently even given an animal-derived diet, illustrating how diet and evolutionary history combine to shape microbial diversity in the mammalian gut.

Baleen whales host a unique gut microbiome with similarities to both carnivores and herbivores

PubMed Central

Sanders, Jon G.; Beichman, Annabel C.; Roman, Joe; Scott, Jarrod J.; Emerson, David; McCarthy, James J.; Girguis, Peter R.

2015-01-01

Mammals host gut microbiomes of immense physiological consequence, but the determinants of diversity in these communities remain poorly understood. Diet appears to be the dominant factor, but host phylogeny also seems to be an important, if unpredictable, correlate. Here we show that baleen whales, which prey on animals (fish and crustaceans), harbor unique gut microbiomes with surprising parallels in functional capacity and higher level taxonomy to those of terrestrial herbivores. These similarities likely reflect a shared role for fermentative metabolisms despite a shift in primary carbon sources from plant-derived to animal-derived polysaccharides, such as chitin. In contrast, protein catabolism and essential amino acid synthesis pathways in baleen whale microbiomes more closely resemble those of terrestrial carnivores. Our results demonstrate that functional attributes of the microbiome can vary independently even given an animal-derived diet, illustrating how diet and evolutionary history combine to shape microbial diversity in the mammalian gut. PMID:26393325

Normative brain size variation and brain shape diversity in humans.

PubMed

Reardon, P K; Seidlitz, Jakob; Vandekar, Simon; Liu, Siyuan; Patel, Raihaan; Park, Min Tae M; Alexander-Bloch, Aaron; Clasen, Liv S; Blumenthal, Jonathan D; Lalonde, Francois M; Giedd, Jay N; Gur, Ruben C; Gur, Raquel E; Lerch, Jason P; Chakravarty, M Mallar; Satterthwaite, Theodore D; Shinohara, Russell T; Raznahan, Armin

2018-06-15

Brain size variation over primate evolution and human development is associated with shifts in the proportions of different brain regions. Individual brain size can vary almost twofold among typically developing humans, but the consequences of this for brain organization remain poorly understood. Using in vivo neuroimaging data from more than 3000 individuals, we find that larger human brains show greater areal expansion in distributed frontoparietal cortical networks and related subcortical regions than in limbic, sensory, and motor systems. This areal redistribution recapitulates cortical remodeling across evolution, manifests by early childhood in humans, and is linked to multiple markers of heightened metabolic cost and neuronal connectivity. Thus, human brain shape is systematically coupled to naturally occurring variations in brain size through a scaling map that integrates spatiotemporally diverse aspects of neurobiology. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Export of Strongly Diluted Greenland Meltwater From a Major Glacial Fjord

NASA Astrophysics Data System (ADS)

Beaird, Nicholas L.; Straneo, Fiammetta; Jenkins, William

2018-05-01

The Greenland Ice Sheet has been, and will continue, losing mass at an accelerating rate. The influence of this anomalous meltwater discharge on the regional and large-scale ocean could be considerable but remains poorly understood. This uncertainty is in part a consequence of challenges in observing water mass transformation and meltwater spreading in coastal Greenland. Here we use tracer observations that enable unprecedented quantification of the export, mixing, and vertical distribution of meltwaters leaving one of Greenland's major glacial fjords. We find that the primarily subsurface meltwater input results in the upwelling of the deep fjord waters and an export of a meltwater/deepwater mixture that is 30 times larger than the initial meltwater release. Using these tracer data, the vertical structure of Greenland's summer meltwater export is defined for the first time showing that half the meltwater export occurs below 65 m.

Neural Substrates of Counterfactual Emotions After Risky Decisions in Late Adolescents and Young Adults.

PubMed

Rodrigo, María José; Padrón, Iván; de Vega, Manuel; Ferstl, Evelyn

2018-03-01

Adolescents' neural substrates of emotional reactions to the consequences of risky decisions are poorly understood. In this functional magnetic resonance imaging study, 30 late adolescents and 30 young adults made risky and neutral decisions in social scenarios and received valenced outcomes. Negative outcomes in risky decisions eliciting regret, as compared with negative outcomes in neutral decisions eliciting disappointment, activated executive control (orbitofrontal cortex) and self-relevance regions (middle temporal gyrus [MTG], posterior cingulate cortex, and precuneus) for both age groups. Young adults showed more activation than adolescents in regret and disappointment as compared with relief and elation conditions in the avoidance (insula), action monitoring (inferior frontal gyrus, pre-SMA, and caudate), and social-cognition regions (superior temporal sulcus and MTG). These late socio-emotional developments may pave the way for more adaptive decision-making behavior in social contexts. © 2018 Society for Research on Adolescence.

Chicxulub impact basin: Gravity characteristics and implications for basin morphology and deep structure

NASA Technical Reports Server (NTRS)

Sharpton, Virgil L.; Burke, Kevin; Hall, Stuart A.; Lee, Scott; Marin, Luis E.; Suarez, Gerardo; Quezada-Muneton, Juan Manuel; Urrutia-Fucugauchi, Jaime

1993-01-01

The K-T-aged Chicxulub Impact Structure is buried beneath the Tertiary carbonate rocks of the Northern Yucatan Platform. Consequently its morphology and structure are poorly understood. Reprocessed Bouguer (onshore) and Free Air (offshore) gravity data over Northern Yucatan reveal that Chicxulub may be a 200-km-diameter multi-ring impact basin with at least three concentric basin rings. The positions of these rings follow the square root of 2 spacing rule derived empirically from analysis of multi-ring basins on other planets indicating that these rings probably correspond to now-buried topographic basin rings. A forward model of the gravity data along a radial transect from the southwest margin of the structure indicates that the Chicxulub gravity signature is compatible with this interpretation. We estimate the basin rim diameter to be 204 +/- 16 km and the central peak ring diameter (D) is 104 +/- 6 km.

TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling

PubMed Central

Jin, Jin; Xiao, Yichuan; Chang, Jae-Hoon; Yu, Jiayi; Hu, Hongbo; Starr, Robyn; Brittain, George C.; Chang, Mikyoung; Cheng, Xuhong; Sun, Shao-Cong

2012-01-01

Immunoglobulin (Ig) class switching is crucial for generating antibody diversity in humoral immunity and, if deregulated, also has severe pathological consequences. How the magnitude of Ig isotype switching is controlled is still poorly understood. Here we identify TANK-binding kinase 1 (TBK1) as a pivotal negative regulator of IgA class switching. B cell-specific TBK1 ablation in mice resulted in uncontrolled production of IgA and development of nephropathy-like disease symptoms. TBK1 negatively regulated IgA class switching by attenuating noncanonical NF-κB signaling, an action that involved TBK1-mediated phosphorylation and subsequent degradation of the NF-κB-inducing kinase. These findings establish TBK1 as a pivotal negative regulator of the noncanonical NF-κB pathway and highlight a unique mechanism that controls IgA production. PMID:23023393

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

Ma, Xiang; Zhang, Shuai; Jiao, Fang

Two-step nucleation pathways in which disordered, amorphous, or dense liquid states precede appearance of crystalline phases have been reported for a wide range of materials, but the dynamics of such pathways are poorly understood. Moreover, whether these pathways are general features of crystallizing systems or a consequence of system-specific structural details that select for direct vs two-step processes is unknown. Using atomic force microscopy to directly observe crystallization of sequence-defined polymers, we show that crystallization pathways are indeed sequence dependent. When a short hydrophobic region is added to a sequence that directly forms crystalline particles, crystallization instead follows a two-stepmore » pathway that begins with creation of disordered clusters of 10-20 molecules and is characterized by highly non-linear crystallization kinetics in which clusters transform into ordered structures that then enter the growth phase. The results shed new light on non-classical crystallization mechanisms and have implications for design of self-assembling polymer systems.« less

Current Concepts of Hyperinflammation in Chronic Granulomatous Disease

PubMed Central

Rieber, Nikolaus; Hector, Andreas; Kuijpers, Taco; Roos, Dirk; Hartl, Dominik

2012-01-01

Chronic granulomatous disease (CGD) is the most common inherited disorder of phagocytic functions, caused by genetic defects in the leukocyte nicotinamide dinucleotide phosphate (NADPH) oxidase. Consequently, CGD phagocytes are impaired in destroying phagocytosed microorganisms, rendering the patients susceptible to bacterial and fungal infections. Besides this immunodeficiency, CGD patients suffer from various autoinflammatory symptoms, such as granuloma formation in the skin or urinary tract and Crohn-like colitis. Owing to improved antimicrobial treatment strategies, the majority of CGD patients reaches adulthood, yet the autoinflammatory manifestations become more prominent by lack of causative treatment options. The underlying pathomechanisms driving hyperinflammatory reactions in CGD are poorly understood, but recent studies implicate reduced neutrophil apoptosis and efferocytosis, dysbalanced innate immune receptors, altered T-cell surface redox levels, induction of Th17 cells, the enzyme indolamine-2,3-dioxygenase (IDO), impaired Nrf2 activity, and inflammasome activation. Here we discuss immunological mechanisms of hyperinflammation and their potential therapeutic implications in CGD. PMID:21808651

The sixth mass coextinction: are most endangered species parasites and mutualists?

PubMed

Dunn, Robert R; Harris, Nyeema C; Colwell, Robert K; Koh, Lian Pin; Sodhi, Navjot S

2009-09-07

The effects of species declines and extinction on biotic interactions remain poorly understood. The loss of a species is expected to result in the loss of other species that depend on it (coextinction), leading to cascading effects across trophic levels. Such effects are likely to be most severe in mutualistic and parasitic interactions. Indeed, models suggest that coextinction may be the most common form of biodiversity loss. Paradoxically, few historical or contemporary coextinction events have actually been recorded. We review the current knowledge of coextinction by: (i) considering plausible explanations for the discrepancy between predicted and observed coextinction rates; (ii) exploring the potential consequences of coextinctions; (iii) discussing the interactions and synergies between coextinction and other drivers of species loss, particularly climate change; and (iv) suggesting the way forward for understanding the phenomenon of coextinction, which may well be the most insidious threat to global biodiversity.

Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity.

PubMed

Marusyk, Andriy; Tabassum, Doris P; Altrock, Philipp M; Almendro, Vanessa; Michor, Franziska; Polyak, Kornelia

2014-10-02

Cancers arise through a process of somatic evolution that can result in substantial sub-clonal heterogeneity within tumours. The mechanisms responsible for the coexistence of distinct sub-clones and the biological consequences of this coexistence remain poorly understood. Here we used a mouse xenograft model to investigate the impact of sub-clonal heterogeneity on tumour phenotypes and the competitive expansion of individual clones. We found that tumour growth can be driven by a minor cell subpopulation, which enhances the proliferation of all cells within a tumour by overcoming environmental constraints and yet can be outcompeted by faster proliferating competitors, resulting in tumour collapse. We developed a mathematical modelling framework to identify the rules underlying the generation of intra-tumour clonal heterogeneity. We found that non-cell-autonomous driving of tumour growth, together with clonal interference, stabilizes sub-clonal heterogeneity, thereby enabling inter-clonal interactions that can lead to new phenotypic traits.

High School Dropout in Proximal Context: The Triggering Role of Stressful Life Events.

PubMed

Dupéré, Véronique; Dion, Eric; Leventhal, Tama; Archambault, Isabelle; Crosnoe, Robert; Janosz, Michel

2018-03-01

Adolescents who drop out of high school experience enduring negative consequences across many domains. Yet, the circumstances triggering their departure are poorly understood. This study examined the precipitating role of recent psychosocial stressors by comparing three groups of Canadian high school students (52% boys; M age  = 16.3 years; N = 545): recent dropouts, matched at-risk students who remain in school, and average students. Results indicate that in comparison with the two other groups, dropouts were over three times more likely to have experienced recent acute stressors rated as severe by independent coders. These stressors occurred across a variety of domains. Considering the circumstances in which youth decide to drop out has implications for future research and for policy and practice. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

The temperature-ballast hypothesis explains carbon export efficiency observations in the Southern Ocean

NASA Astrophysics Data System (ADS)

Britten, Gregory L.; Wakamatsu, Lael; Primeau, François W.

2017-02-01

Carbon export from the Southern Ocean exerts a strong control on the ocean carbon sink, yet recent observations from the region demonstrate poorly understood relationships in which carbon export efficiency is weakly related to temperature. These observations conflict with traditional theory where export efficiency increases in colder waters. A recently proposed "temperature-ballast hypothesis" suggests an explanatory mechanism where the effect of temperature-dependent respiration is masked by variation in particle-ballast as upwelling waters move northward from Antarctica. We use observations and statistical models to test this mechanism and find positive support for the hypothesized temperature-ballast interactions. Best fitting models indicate a significant relation between export efficiency and silica-ballast while simultaneously revealing the expected inverse effect of temperature once ballast is accounted for. These findings reconcile model predictions, metabolic theory, and carbon export observations in the Southern Ocean and have consequences for how the ocean carbon sink responds to climate change.

Unexpected Complication after Caudal Epidural Steroid Injection: Hiccup

PubMed Central

Kaydu, Ayhan; Kılıç, Ebru Tarıkçı; Gökçek, Erhan; Akdemir, Mehmet Salim

2017-01-01

Persistent hiccup is uncommon, and the mechanism is poorly understood. We present the case of a 43-year-old male patient referred to the Algology department due to chronic back pain who developed what we believe a rare case of persistent hiccup secondary to caudal epidural steroid injection (CESI). The causes of hiccup are many and include electrolyte derangement, nutritional deficiencies, gastrointestinal disorders and instrumentation, cardiovascular disorders, renal impairment, central nervous system disorders, and drugs; however, the cause may be unknown. CESI is one of the treatments of back pain, in addition to various other modalities including surgical interventions. CESI has gained rapid and widespread acceptance for the treatment of lumbar and lower extremity pain. However, there are only a few well-designed, randomized, controlled studies on the effectiveness of steroid injections. Consequently, side effects should be considered. We aimed to present a persistent hiccup after CESI for chronic low back pain. PMID:28928587

An Update on Maternal Use of Antiepileptic Medications in Pregnancy and Neurodevelopment Outcomes

PubMed Central

Gerard, Elizabeth E.; Meador, Kimford J.

2015-01-01

Antiepileptic drugs (AEDs) are prescribed commonly to women of childbearing age. In utero exposure to some AEDs can have significant cognitive and behavioral consequences for the unborn child. Recently, prospective studies of women taking AEDs during pregnancy have added significantly to our understanding of cognitive and behavioral teratogenic risks posed by fetal AED exposure. Valproate is clearly associated with impaired cognitive development as well as an increased risk of disorders such as autism and autism spectrum disorder. Exposure to carbamazepine, lamotrigine, levetiracetam, or phenytoin monotherapy is associated with more favorable cognitive and behavioral outcomes than valproate, but more data are required to clarify if these AEDs have more subtle effects on cognition and behavior. There are insufficient data on the developmental effects of other AEDs in humans. Further, the underlying mechanisms of cognitive teratogenesis are poorly understood, including the genetic factors that affect susceptibility to AEDs. PMID:27617120

Influences of innate immunity, autophagy, and fibroblast activation in the pathogenesis of lung fibrosis

PubMed Central

O'Dwyer, David N.; Ashley, Shanna L.

2016-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by accumulation of extracellular matrix (ECM) and impaired gas exchange. The pathobiological mechanisms that account for disease progression are poorly understood but likely involve alterations in innate inflammatory cells, epithelial cells, and fibroblasts. Thus we seek to review the most recent literature highlighting the complex roles of neutrophils and macrophages as both promoters of fibrosis and defenders against infection. With respect to epithelial cells and fibroblasts, we review the data suggesting that defective autophagy promotes the fibrogenic potential of both cell types and discuss new evidence related to matrix metalloproteinases, growth factors, and cellular metabolism in the form of lactic acid generation that may have consequences for promoting fibrogenesis. We discuss potential cross talk between innate and structural cell types and also highlight literature that may help explain the limitations of current IPF therapies. PMID:27474089

Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart.

PubMed

Xu, Wenjing; Barrientos, Tomasa; Mao, Lan; Rockman, Howard A; Sauve, Anthony A; Andrews, Nancy C

2015-10-20

Both iron overload and iron deficiency have been associated with cardiomyopathy and heart failure, but cardiac iron utilization is incompletely understood. We hypothesized that the transferrin receptor (Tfr1) might play a role in cardiac iron uptake and used gene targeting to examine the role of Tfr1 in vivo. Surprisingly, we found that decreased iron, due to inactivation of Tfr1, was associated with severe cardiac consequences. Mice lacking Tfr1 in the heart died in the second week of life and had cardiomegaly, poor cardiac function, failure of mitochondrial respiration, and ineffective mitophagy. The phenotype could only be rescued by aggressive iron therapy, but it was ameliorated by administration of nicotinamide riboside, an NAD precursor. Our findings underscore the importance of both Tfr1 and iron in the heart, and may inform therapy for patients with heart failure. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Lamin-B in systemic inflammation, tissue homeostasis, and aging.

PubMed

Chen, Haiyang; Zheng, Xiaobin; Zheng, Yixian

2015-01-01

Gradual loss of tissue function (or homeostasis) is a natural process of aging and is believed to cause many age-associated diseases. In human epidemiology studies, the low-grade and chronic systemic inflammation in elderly has been correlated with the development of aging related pathologies. Although it is suspected that tissue decline is related to systemic inflammation, the cause and consequence of these aging phenomena are poorly understood. By studying the Drosophila fat body and gut, we have uncovered a mechanism by which lamin-B loss in the fat body upon aging induces age-associated systemic inflammation. This chronic inflammation results in the repression of gut local immune response, which in turn leads to the over-proliferation and mis-differentiation of the intestinal stem cells, thereby resulting in gut hyperplasia. Here we discuss the implications and remaining questions in light of our published findings and new observations.

Compaction behavior of out-of-autoclave prepreg materials

NASA Astrophysics Data System (ADS)

Serrano, Léonard; Olivier, Philippe; Cinquin, Jacques

2017-10-01

The main challenges with composite parts manufacturing are related to the curing means, mainly autoclaves, the length of their cycles and their operating costs. In order to decrease this dependency, out of autoclave materials have been considered as a solution for high production rate parts such as spars, flaps, etc… However, most out-of-autoclave process do not possess the same maturity as their counterpart, especially concerning part quality1. Some pre-cure processes such as compaction and ply lay-up are usually less of a concern for autoclave manufacturing: the pressure applied during the cycle participates to reduce the potential defects (porosity caused by a poor quality lay-up, bad compaction, entrapped air or humidity…). For out-of-autoclave parts, those are crucial steps which may have many consequences on the final quality of the laminate2. In order to avoid this quality loss, those steps must be well understood.

Potential increase in coastal wetland vulnerability to sea-level rise suggested by considering hydrodynamic attenuation effects

NASA Astrophysics Data System (ADS)

Rodríguez, José F.; Saco, Patricia M.; Sandi, Steven; Saintilan, Neil; Riccardi, Gerardo

2017-07-01

The future of coastal wetlands and their ecological value depend on their capacity to adapt to the interacting effects of human impacts and sea-level rise. Even though extensive wetland loss due to submergence is a possible scenario, its magnitude is highly uncertain due to limited understanding of hydrodynamic and bio-geomorphic interactions over time. In particular, the effect of man-made drainage modifications on hydrodynamic attenuation and consequent wetland evolution is poorly understood. Predictions are further complicated by the presence of a number of vegetation types that change over time and also contribute to flow attenuation. Here, we show that flow attenuation affects wetland vegetation by modifying its wetting-drying regime and inundation depth, increasing its vulnerability to sea-level rise. Our simulations for an Australian subtropical wetland predict much faster wetland loss than commonly used models that do not consider flow attenuation.

Osmotic pressure induced tensile forces in tendon collagen

NASA Astrophysics Data System (ADS)

Masic, Admir; Bertinetti, Luca; Schuetz, Roman; Chang, Shu-Wei; Metzger, Till Hartmut; Buehler, Markus J.; Fratzl, Peter

2015-01-01

Water is an important component of collagen in tendons, but its role for the function of this load-carrying protein structure is poorly understood. Here we use a combination of multi-scale experimentation and computation to show that water is an integral part of the collagen molecule, which changes conformation upon water removal. The consequence is a shortening of the molecule that translates into tensile stresses in the range of several to almost 100 MPa, largely surpassing those of about 0.3 MPa generated by contractile muscles. Although a complete drying of collagen would be relevant for technical applications, such as the fabrication of leather or parchment, stresses comparable to muscle contraction already occur at small osmotic pressures common in biological environments. We suggest, therefore, that water-generated tensile stresses may play a role in living collagen-based materials such as tendon or bone.

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.

Influences of innate immunity, autophagy, and fibroblast activation in the pathogenesis of lung fibrosis.

PubMed

O'Dwyer, David N; Ashley, Shanna L; Moore, Bethany B

2016-09-01

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by accumulation of extracellular matrix (ECM) and impaired gas exchange. The pathobiological mechanisms that account for disease progression are poorly understood but likely involve alterations in innate inflammatory cells, epithelial cells, and fibroblasts. Thus we seek to review the most recent literature highlighting the complex roles of neutrophils and macrophages as both promoters of fibrosis and defenders against infection. With respect to epithelial cells and fibroblasts, we review the data suggesting that defective autophagy promotes the fibrogenic potential of both cell types and discuss new evidence related to matrix metalloproteinases, growth factors, and cellular metabolism in the form of lactic acid generation that may have consequences for promoting fibrogenesis. We discuss potential cross talk between innate and structural cell types and also highlight literature that may help explain the limitations of current IPF therapies. Copyright © 2016 the American Physiological Society.

The mechanism of linkage-specific ubiquitin chain elongation by a single-subunit E2

PubMed Central

Wickliffe, Katherine E.; Lorenz, Sonja; Wemmer, David E.; Kuriyan, John; Rape, Michael

2011-01-01

Ubiquitin chains of different topologies trigger distinct functional consequences, including protein degradation and reorganization of complexes. The assembly of most ubiquitin chains is promoted by E2s, yet how these enzymes achieve linkage specificity is poorly understood. We have discovered that the K11-specific Ube2S orients the donor ubiquitin through an essential non-covalent interaction that occurs in addition to the thioester bond at the E2 active site. The E2-donor ubiquitin complex transiently recognizes the acceptor ubiquitin, primarily through electrostatic interactions. The recognition of the acceptor ubiquitin surface around Lys11, but not around other lysines, generates a catalytically competent active site, which is composed of residues of both Ube2S and ubiquitin. Our studies suggest that monomeric E2s promote linkage-specific ubiquitin chain formation through substrate-assisted catalysis. PMID:21376237

The Relationship between Frequently Used Glucose-Lowering Agents and Gut Microbiota in Type 2 Diabetes Mellitus.

PubMed

Lv, You; Zhao, Xue; Guo, Weiying; Gao, Ying; Yang, Shuo; Li, Zhuo; Wang, Guixia

2018-01-01

Metabolic diseases, especially diabetes mellitus, have become global health issues. The etiology of diabetes mellitus can be attributed to genetic and/or environmental factors. Current evidence suggests the association of gut microbiota with metabolic diseases. However, the effects of glucose-lowering agents on gut microbiota are poorly understood. Several studies revealed that these agents affect the composition and diversity of gut microbiota and consequently improve glucose metabolism and energy balance. Possible underlying mechanisms include affecting gene expression, lowering levels of inflammatory cytokines, and regulating the production of short-chain fatty acids. In addition, gut microbiota may alleviate adverse effects caused by glucose-lowering agents, and this can be especially beneficial in diabetic patients who experience severe gastrointestinal side effects and have to discontinue these agents. In conclusion, gut microbiota may provide a novel viewpoint for the treatment of patients with diabetes mellitus.

Feeding periodicity, diet composition, and food consumption of subyearling rainbow trout in winter

USGS Publications Warehouse

Johnson, James H.; Chalupnicki, Marc; Abbett, Ross

2016-01-01

Although winter is a critically important period for stream salmonids, aspects of the ecology of several species are poorly understood. Consequently, we examined the diel feeding ecology of subyearling rainbow trout (Oncorhynchus mykiss) during winter in a central New York stream. Rainbow trout diet was significantly different during each 4-h interval and also differed from the drift and benthos. Feeding was significantly greater during darkness (i.e. 20:00 h – 04:00 h) than during daylight hours (i.e. 08:00 h – 16:00 h), peaking at 20:00 h. Daily food consumption (1.9 mg) and daily ration (3.4 %) during winter were substantially lower than previously reported for subyearling rainbow trout in the same stream during summer. These findings provide important new insights into the winter feeding ecology of juvenile rainbow trout in streams.

Neurobehavioral Consequences of Prenatal Exposure to Smoking at 6 to 8 Months of Age

ERIC Educational Resources Information Center

Willoughby, Michael; Greenberg, Mark; Blair, Clancy; Stifter, Cynthia

2007-01-01

Between 400,000 and 800,000 infants are born in the United States each year to women who smoked cigarettes during their pregnancy. Whereas the physical health consequences to infants of prenatal exposure to smoking are well established, the early neurobehavioral consequences are less well understood. This study investigated the neurobehavioral…

The neural bases of feeling understood and not understood.

PubMed

Morelli, Sylvia A; Torre, Jared B; Eisenberger, Naomi I

2014-12-01

Past research suggests that feeling understood enhances both personal and social well-being. However, little research has examined the neurobiological bases of feeling understood and not understood. We addressed these gaps by experimentally inducing felt understanding and not understanding as participants underwent functional magnetic resonance imaging. The results demonstrated that feeling understood activated neural regions previously associated with reward and social connection (i.e. ventral striatum and middle insula), while not feeling understood activated neural regions previously associated with negative affect (i.e. anterior insula). Both feeling understood and not feeling understood activated different components of the mentalizing system (feeling understood: precuneus and temporoparietal junction; not feeling understood: dorsomedial prefrontal cortex). Neural responses were associated with subsequent feelings of social connection and disconnection and were modulated by individual differences in rejection sensitivity. Thus, this study provides insight into the psychological processes underlying feeling understood (or not) and may suggest new avenues for targeted interventions that amplify the benefits of feeling understood or buffer individuals from the harmful consequences of not feeling understood. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Mental health, sleep quality, drinking motives, and alcohol-related consequences: a path-analytic model.

PubMed

Kenney, Shannon R; Lac, Andrew; Labrie, Joseph W; Hummer, Justin F; Pham, Andy

2013-11-01

Poor mental health, sleep problems, drinking motivations, and high-risk drinking are prevalent among college students. However, research designed to explicate the interrelationships among these health risk behaviors is lacking. This study was designed to assess the direct and indirect influences of poor mental health (a latent factor consisting of depression, anxiety, and stress) to alcohol use and alcohol-related consequences through the mediators of global sleep quality and drinking motives in a comprehensive model. Participants were 1,044 heavy-drinking college students (66.3% female) who completed online surveys. A hybrid structural equation model tested hypotheses involving relations leading from poor mental health to drinking motives and poorer global sleep quality to drinking outcomes. Results showed that poor mental health significantly predicted all four subscales of drinking motivations (social, coping, conformity, and enhancement) as well as poor sleep. Most of the drinking motives and poor sleep were found to explain alcohol use and negative alcohol consequences. Poor sleep predicted alcohol consequences, even after controlling for all other variables in the model. The hypothesized mediational pathways were examined with tests of indirect effects. This is the first study to assess concomitantly the relationships among three vital health-related domains (mental health, sleep behavior, and alcohol risk) in college students. Findings offer important implications for college personnel and interventionists interested in reducing alcohol risk by focusing on alleviating mental health problems and poor sleep quality.

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…

African, male attitudes on female genital mutilation: an Australian survey.

PubMed

Shahid, Usama; Rane, Ajay

2017-11-01

Female genital mutilation (FGM) is a traditional practice where female genital organs are altered for non-medical reasons. The custom is outlawed in Australia and associated with an array of medical consequences. Due to the recent influx of migrants from regions endemic to FGM, the practice is becoming a growing concern locally. This federal government funded study aimed to elicit the poorly understood perceptions that young, Sub-Saharan African, migrant males residing in Townsville, Australia have on FGM. Through piloted questionnaires we found that amongst the 67 participants, 23.9% believed that FGM should be allowed under Australian Law. The independent predictors of supportive attitudes in favour of FGM were having resided in Australia for five or less years (p = .016, 95% CI 0.99-8.09) and coming from a basic educational background (high school or TAFE) (p = .003, 95% CI 1.3-12.4). This study also found that participant perceptions on FGM were amenable to change through educational interventional strategies. Impact statement Female genital mutilation (FGM) is a traditional practice where female genital organs are altered for non-medical reasons. The role that males play in the continuation of this outlawed practice remains poorly understood. No research has ever been conducted in Australia looking at the perception that young, migrant males have on FGM. Several European-based studies have examined the perceptions of older, poorly educated, migrant male cohorts. Generally, these studies show that the attitudinal support for FGM and intention to practice remains relatively high amongst these cohorts. This study examined the attitudes of a young, Sub-Saharan African, migrant, male cohort residing in Australia. This adds to the literature base by establishing the perceptions and associated socio-demographic variables of this unique and influential subset of the migrant population. This directly facilitates the development of interventional strategies against FGM by highlighting those most likely to have an attitudinal support in favour of FGM. Consequentially, this 'at risk' group can be more effectively focussed on interventional programmes and be further investigated in larger scale studies.

Biogeographical disparity in the functional diversity and redundancy of corals.

PubMed

McWilliam, Mike; Hoogenboom, Mia O; Baird, Andrew H; Kuo, Chao-Yang; Madin, Joshua S; Hughes, Terry P

2018-03-20

Corals are major contributors to a range of key ecosystem functions on tropical reefs, including calcification, photosynthesis, nutrient cycling, and the provision of habitat structure. The abundance of corals is declining at multiple scales, and the species composition of assemblages is responding to escalating human pressures, including anthropogenic global warming. An urgent challenge is to understand the functional consequences of these shifts in abundance and composition in different biogeographical contexts. While global patterns of coral species richness are well known, the biogeography of coral functions in provinces and domains with high and low redundancy is poorly understood. Here, we quantify the functional traits of all currently recognized zooxanthellate coral species ( n = 821) in both the Indo-Pacific and Atlantic domains to examine the relationships between species richness and the diversity and redundancy of functional trait space. We find that trait diversity is remarkably conserved (>75% of the global total) along latitudinal and longitudinal gradients in species richness, falling away only in species-poor provinces ( n < 200), such as the Persian Gulf (52% of the global total), Hawaii (37%), the Caribbean (26%), and the East-Pacific (20%), where redundancy is also diminished. In the more species-poor provinces, large and ecologically important areas of trait space are empty, or occupied by just a few, highly distinctive species. These striking biogeographical differences in redundancy could affect the resilience of critical reef functions and highlight the vulnerability of relatively depauperate, peripheral locations, which are often a low priority for targeted conservation efforts.

Integrated genomic analyses identify KDM1A's role in cell proliferation via modulating E2F signaling activity and associate with poor clinical outcome in oral cancer.

PubMed

Narayanan, Sathiya Pandi; Singh, Smriti; Gupta, Amit; Yadav, Sandhya; Singh, Shree Ram; Shukla, Sanjeev

2015-10-28

The histone demethylase KDM1A specifically demethylates lysine residues and its deregulation has been implicated in the initiation and progression of various cancers. However, KDM1A's molecular role and its pathological consequences, and prognostic significance in oral cancer remain less understood. In the present study, we sought to investigate the expression of KDM1A and its downstream role in oral cancer pathogenesis. By comparing mRNA expression profiles, we identified an elevated KDM1A expression in oral tumors when compared to normal oral tissues. In silico pathway prediction identified the association between KDM1A and E2F1 signaling in oral cancer. Pathway scanning, functional annotation analysis and In vitro assays showed the KDM1A's involvement in oral cancer cell proliferation and the cell cycle. Moreover, real time PCR and luciferase assays confirmed KDM1A's role in regulation of E2F1 signaling activity in oral cancer. Elevated KDM1A expression is associated with poor clinical outcome in oral cancer. Our data indicate that deregulated KDM1A expression is positively associated with proliferative phenotype of oral cancer and confers poor clinical outcome. These cumulative data suggest that KDM1A might be a potential diagnostic and therapeutic target for oral cancer. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Smoking and educational status in Africans].

PubMed

Kouassi, B; Kpebo, O D; Horo, K; N'Gom, A; Godé, C; Ahui, B; Koffi, N; Aka-Danguy, E

2010-03-01

Tobacco smoking is a scourge that continues to increase in developing countries despite its known consequences. Is the population of the Ivory Coast sufficiently informed about the consequences of smoking? For this reason, we decided to evaluate the knowledge of the effects of smoking among the people of Abidjan. To evaluate the knowledge of the effects of smoking in the population of Abidjan. To relate this knowledge to the educational level and smoking status. We evaluated knowledge about smoking and its consequences as a function of educational level and smoking status in the population of Abidjan over the age of 15 years. This was undertaken in 3 months, from November 2005 to January 2006, in the two busiest communes in Abidjan. The minimum number of persons required was 1152 but, in fact, we interviewed 1409. The prevalence of smoking was 36.5% with a predominance of males (sex ratio = 3:11). They were mainly young with a mean age of 27.44 years. This population's main sources of information on the ill effects of smoking were the mass media. In general, the subjects did not have a good understanding of smoking and its consequences. With regard to the diseases related to smoking, bronchial carcinoma and cardiovascular disorders were the best known, in 53.1 and 18.1%, respectively. With regard to the components of tobacco, nicotine was the best known (92.6%). Knowledge was related to the level of education: the subjects of a higher educational level were the most knowledgeable about the consequences of smoking. As a result, these subjects were less attached to smoking than the less educated. The consequences of smoking are poorly understood by the general population. With regard to the level of education, the better educated had a better understanding of the effects of smoking and were also those who smoked the least. Copyright 2010. Published by Elsevier Masson SAS.

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…

Money is Brain: Financial Barriers and Consequences for Canadian Stroke Patients.

PubMed

Ganesh, Aravind; King-Shier, Kathryn; Manns, Braden J; Hill, Michael D; Campbell, David J T

2017-03-01

Stroke patients of lower socioeconomic status have worse outcomes. It remains poorly understood whether this is due to illness severity or personal or health system barriers. We explored the experiences of stroke patients with financial barriers in a qualitative descriptive pilot study, seeking to capture perceived challenges that interfere with their poststroke health and recovery. We interviewed six adults with a history of stroke and financial barriers in Alberta, Canada, inquiring about their: (1) experiences after stroke; (2) experience of financial barriers; (3) perceived reasons for financial barriers; (4) health consequences of financial barriers; and (5) mechanisms for coping with financial barriers. Two reviewers analyzed data using inductive thematic analysis. The participants developed new or worsened financial circumstances as a consequence of stroke-related disability. Poststroke impairments and financial barriers took a toll on their mental health. They struggled to access several aspects of long-term poststroke care, including allied health professional services, medications, and proper nutrition. They described opportunity costs and tradeoffs when accessing health services. In several cases, they were unaware of health resources available to them and were hesitant to disclose their struggles to their physicians and even their families. Some patients with financial barriers perceive challenges to accessing various aspects of poststroke care. They may have inadequate knowledge of resources available to them and may not disclose their concerns to their health care team. This suggests that providers themselves might consider asking stroke patients about financial barriers to optimize their long-term poststroke care.

Ford Class Aircraft Carrier: Poor Outcomes Are the Predictable Consequences of the Prevalent Acquisition Culture

DTIC Science & Technology

2015-10-01

FORD CLASS AIRCRAFT CARRIER Poor Outcomes Are the Predictable Consequences of the Prevalent Acquisition Culture...2. REPORT TYPE 3. DATES COVERED 00-00-2015 to 00-00-2015 4. TITLE AND SUBTITLE Ford Class Aircraft Carrier: Poor Outcomes Are the Predictable...This Study The Navy set ambitious goals for the Ford -class program, including an array of new technologies and design features that were intended

Domestic violence and its associated factors among married women of a village development committee of rural Nepal.

PubMed

Sapkota, Diksha; Bhattarai, Sailesh; Baral, Dharanidhar; Pokharel, Paras K

2016-03-19

Violence against women is a global public health problem occurring in multitude of contexts and domestic violence is considered to be the most pervasive one. Poor enforcement of policies, limitation of researches and expertise in this field largely accounts for persistence of this problem and nature of domestic violence and its associated factors are poorly understood. This research aimed to estimate the magnitude of different forms of domestic violence and identify its associated factors. Community based cross sectional study was conducted among 355 married women of reproductive age group of Kusheshwor, Sindhuli, Nepal. The questionnaire adapted from the World Health Organization Multi-Country Study was used for the face to face interviews. Occurrence of current domestic violence was used as outcome variable in logistic regression. Descriptive and multivariate analysis were performed in order to assess the magnitude of domestic violence and to identify its associated factors respectively. Self-reported lifetime prevalence of physical violence was 29.6% and past year prevalence was 15.2%, while corresponding figures for sexual violence were 6.8 and 2.3%, and for psychological violence were 31.0 and 18.3%. Lifetime domestic violence was 38.6% while in past 12 months, prevalence was 23.1%. Furthermore, 12.4% of women were experiencing all forms of violence concurrently. Women with controlling husband and having poor mental health were found to be at higher risk of domestic violence. Domestic violence is still rampant in our society with several forms of violence occurring together. In a country like Nepal, differentials power in relationship and poor mental health was found to be positively associated with violent episodes. This study highlights the infringement of women rights which can be the cause for serious public health consequences.

Frequent Infection of Human Cancer Xenografts with Murine Endogenous Retroviruses in Vivo

PubMed Central

Naseer, Asif; Terry, Anne; Gilroy, Kathryn; Kilbey, Anna; Watts, Ciorsdaidh; Mackay, Nancy; Bell, Margaret; Mason, Susan; Blyth, Karen; Cameron, Ewan; Neil, James C.

2015-01-01

Infection of human cancer xenografts in mice with murine leukemia viruses (MLVs) is a long-standing observation, but the likelihood of infection in vivo and its biological consequences are poorly understood. We therefore conducted a prospective study in commonly used xenograft recipient strains. From BALB/c nude mice engrafted with MCF7 human mammary carcinoma cells, we isolated a virus that was virtually identical to Bxv1, a locus encoding replication-competent xenotropic MLV (XMLV). XMLV was detected in 9/17 (53%) independently isolated explants. XMLV was not found in primary leukemias or in THP1 leukemia cells grown in Bxv1-negative NSG (NOD/SCID/γCnull) mice, although MCF7 explants harbored replication-defective MLV proviruses. To assess the significance of infection for xenograft behavior in vivo, we examined changes in growth and global transcription in MCF7 and the highly susceptible Raji Burkitt lymphoma cell line chronically infected with XMLV. Raji cells showed a stronger transcriptional response that included up-regulation of chemokines and effectors of innate antiviral immunity. In conclusion, the risk of de novo XMLV infection of xenografts is high in Bxv1 positive mice, while infection can have positive or negative effects on xenograft growth potential with significant consequences for interpretation of many xenograft studies. PMID:25912714

Stress exposure in early post-natal life reduces telomere length: an experimental demonstration in a long-lived seabird

PubMed Central

Herborn, Katherine A.; Heidinger, Britt J.; Boner, Winnie; Noguera, Jose C.; Adam, Aileen; Daunt, Francis; Monaghan, Pat

2014-01-01

Exposure to stressors early in life is associated with faster ageing and reduced longevity. One important mechanism that could underlie these late life effects is increased telomere loss. Telomere length in early post-natal life is an important predictor of subsequent lifespan, but the factors underpinning its variability are poorly understood. Recent human studies have linked stress exposure to increased telomere loss. These studies have of necessity been non-experimental and are consequently subjected to several confounding factors; also, being based on leucocyte populations, where cell composition is variable and some telomere restoration can occur, the extent to which these effects extend beyond the immune system has been questioned. In this study, we experimentally manipulated stress exposure early in post-natal life in nestling European shags (Phalacrocorax aristotelis) in the wild and examined the effect on telomere length in erythrocytes. Our results show that greater stress exposure during early post-natal life increases telomere loss at this life-history stage, and that such an effect is not confined to immune cells. The delayed effects of increased telomere attrition in early life could therefore give rise to a ‘time bomb’ that reduces longevity in the absence of any obvious phenotypic consequences early in life. PMID:24648221

Spatiotemporal characterization of mTOR kinase activity following kainic acid induced status epilepticus and analysis of rat brain response to chronic rapamycin treatment.

PubMed

Macias, Matylda; Blazejczyk, Magdalena; Kazmierska, Paulina; Caban, Bartosz; Skalecka, Agnieszka; Tarkowski, Bartosz; Rodo, Anna; Konopacki, Jan; Jaworski, Jacek

2013-01-01

Mammalian target of rapamycin (mTOR) is a protein kinase that senses nutrient availability, trophic factors support, cellular energy level, cellular stress, and neurotransmitters and adjusts cellular metabolism accordingly. Adequate mTOR activity is needed for development as well as proper physiology of mature neurons. Consequently, changes in mTOR activity are often observed in neuropathology. Recently, several groups reported that seizures increase mammalian target of rapamycin (mTOR) kinase activity, and such increased activity in genetic models can contribute to spontaneous seizures. However, the current knowledge about the spatiotemporal pattern of mTOR activation induced by proconvulsive agents is rather rudimentary. Also consequences of insufficient mTOR activity on a status epilepticus are poorly understood. Here, we systematically investigated these two issues. We showed that mTOR signaling was activated by kainic acid (KA)-induced status epilepticus through several brain areas, including the hippocampus and cortex as well as revealed two waves of mTOR activation: an early wave (2 h) that occurs in neurons and a late wave that predominantly occurs in astrocytes. Unexpectedly, we found that pretreatment with rapamycin, a potent mTOR inhibitor, gradually (i) sensitized animals to KA treatment and (ii) induced gross anatomical changes in the brain.

Sounding the Alarm: Health in the Anthropocene

PubMed Central

Butler, Colin D.

2016-01-01

There is growing scientific and public recognition that human actions, directly and indirectly, have profoundly changed the Earth system, in a still accelerating process, increasingly called the “Anthropocene”. Planetary transformation, including of the atmosphere, climate, ecosystems and biodiversity, has enormous implications for human health, many of which are deeply disturbing, especially in low-income settings. A few health consequences of the Anthropocene have been partially recognized, including within environmental epidemiology, but their long-term consequences remain poorly understood and greatly under-rated. For example Syria could be a “sentinel” population, giving a glimpse to a much wider dystopian future. Health-Earth is a research network, co-founded in 2014, which seeks, with other groups, to catalyse a powerful curative response by the wider health community. This paper builds on a symposium presented by Health-Earth members at the 2015 conference of the International Society for Environmental Epidemiology. It reviews and synthesizes parts of the large literature relevant to the interaction between the changing Earth system and human health. It concludes that this topic should be prominent within future environmental epidemiology and public health. Created by our species, these challenges may be soluble, but solutions require far more understanding and resources than are currently being made available. PMID:27376314

Treeline proximity alters an alpine plant-herbivore interaction.

PubMed

Illerbrun, Kurt; Roland, Jens

2011-05-01

Rising treeline threatens the size and contiguity of alpine meadows worldwide. As trees encroach into previously open habitat, the movement and population dynamics of above-treeline alpine species may be disrupted. This process is well documented in studies of the Rocky Mountain apollo butterfly (Parnassius smintheus). However, subtler consequences of treeline rise remain poorly understood. In this study, we examine whether treeline proximity affects feeding behaviour of P. smintheus larvae, due to altered habitat affecting the distribution and availability of their host plant, lance-leaved stonecrop (Sedum lanceolatum). Understanding differential larval exploitation of food resources in relation to the treeline is an important step in predicting the consequences of continued treeline rise. Parnassius smintheus larvae feed more intensively on S. lanceolatum away from the treeline despite the relative paucity of hosts in these areas, and despite higher fitness penalties associated with the plant's herbivory-induced chemical defenses. Sedum lanceolatum growing near the treeline is less attractive, and therefore represents a less significant resource for P. smintheus larvae than its abundance might imply. If treeline rise continues, we suggest that this pattern of altered resource exploitation may represent a mechanism by which larvae are adversely affected even while adult movement among and within meadows appears sufficient for maintaining population health, and total host availability seems ample.

Thermal plasticity of growth and development varies adaptively among alternative developmental pathways.

PubMed

Kivelä, Sami M; Svensson, Beatrice; Tiwe, Alma; Gotthard, Karl

2015-09-01

Polyphenism, the expression of discrete alternative phenotypes, is often a consequence of a developmental switch. Physiological changes induced by a developmental switch potentially affect reaction norms, but the evolution and existence of alternative reaction norms remains poorly understood. Here, we demonstrate that, in the butterfly Pieris napi (Lepidoptera: Pieridae), thermal reaction norms of several life history traits vary adaptively among switch-induced alternative developmental pathways of diapause and direct development. The switch was affected both by photoperiod and temperature, ambient temperature during late development having the potential to override earlier photoperiodic cues. Directly developing larvae had higher development and growth rates than diapausing ones across the studied thermal gradient. Reaction norm shapes also differed between the alternative developmental pathways, indicating pathway-specific selection on thermal sensitivity. Relative mass increments decreased linearly with increasing temperature and were higher under direct development than diapause. Contrary to predictions, population phenology did not explain trait variation or thermal sensitivity, but our experimental design probably lacks power for finding subtle phenology effects. We demonstrate adaptive differentiation in thermal reaction norms among alternative phenotypes, and suggest that the consequences of an environmentally dependent developmental switch primarily drive the evolution of alternative thermal reaction norms in P. napi. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

translin Is Required for Metabolic Regulation of Sleep.

PubMed

Murakami, Kazuma; Yurgel, Maria E; Stahl, Bethany A; Masek, Pavel; Mehta, Aradhana; Heidker, Rebecca; Bollinger, Wesley; Gingras, Robert M; Kim, Young-Joon; Ja, William W; Suter, Beat; DiAngelo, Justin R; Keene, Alex C

2016-04-04

Dysregulation of sleep or feeding has enormous health consequences. In humans, acute sleep loss is associated with increased appetite and insulin insensitivity, while chronically sleep-deprived individuals are more likely to develop obesity, metabolic syndrome, type II diabetes, and cardiovascular disease. Conversely, metabolic state potently modulates sleep and circadian behavior; yet, the molecular basis for sleep-metabolism interactions remains poorly understood. Here, we describe the identification of translin (trsn), a highly conserved RNA/DNA binding protein, as essential for starvation-induced sleep suppression. Strikingly, trsn does not appear to regulate energy stores, free glucose levels, or feeding behavior suggesting the sleep phenotype of trsn mutant flies is not a consequence of general metabolic dysfunction or blunted response to starvation. While broadly expressed in all neurons, trsn is transcriptionally upregulated in the heads of flies in response to starvation. Spatially restricted rescue or targeted knockdown localizes trsn function to neurons that produce the tachykinin family neuropeptide Leucokinin. Manipulation of neural activity in Leucokinin neurons revealed these neurons to be required for starvation-induced sleep suppression. Taken together, these findings establish trsn as an essential integrator of sleep and metabolic state, with implications for understanding the neural mechanism underlying sleep disruption in response to environmental perturbation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ecological responses to el Niño-induced surface fires in central Brazilian Amazonia: management implications for flammable tropical forests.

PubMed Central

Barlow, Jos; Peres, Carlos A

2004-01-01

Over the past 20 years the combined effects of El Niño-induced droughts and land-use change have dramatically increased the frequency of fire in humid tropical forests. Despite the potential for rapid ecosystem alteration and the current prevalence of wildfire disturbance, the consequences of such fires for tropical forest biodiversity remain poorly understood. We provide a pan-tropical review of the current state of knowledge of these fires, and include data from a study in a seasonally dry terra firme forest of central Brazilian Amazonia. Overall, this study supports predictions that rates of tree mortality and changes in forest structure are strongly linked to burn severity. The potential consequences for biomass loss and carbon emissions are explored. Despite the paucity of data on faunal responses to tropical forest fires, some trends are becoming apparent; for example, large canopy frugivores and understorey insectivorous birds appear to be highly sensitive to changes in forest structure and composition during the first 3 years after fires. Finally, we appraise the management implications of fires and evaluate the viability of techniques and legislation that can be used to reduce forest flammability, prevent anthropogenic ignition sources from coming into contact with flammable forests and aid the post-fire recovery process. PMID:15212091

Drought and flooding have distinct effects on herbivore-induced responses and resistance in Solanum dulcamara.

PubMed

Nguyen, Duy; D'Agostino, Nunzio; Tytgat, Tom O G; Sun, Pulu; Lortzing, Tobias; Visser, Eric J W; Cristescu, Simona M; Steppuhn, Anke; Mariani, Celestina; van Dam, Nicole M; Rieu, Ivo

2016-07-01

In the field, biotic and abiotic stresses frequently co-occur. As a consequence, common molecular signalling pathways governing adaptive responses to individual stresses can interact, resulting in compromised phenotypes. How plant signalling pathways interact under combined stresses is poorly understood. To assess this, we studied the consequence of drought and soil flooding on resistance of Solanum dulcamara to Spodoptera exigua and their effects on hormonal and transcriptomic profiles. The results showed that S. exigua larvae performed less well on drought-stressed plants than on well-watered and flooded plants. Both drought and insect feeding increased abscisic acid and jasmonic acid (JA) levels, whereas flooding did not induce JA accumulation. RNA sequencing analyses corroborated this pattern: drought and herbivory induced many biological processes that were repressed by flooding. When applied in combination, drought and herbivory had an additive effect on specific processes involved in secondary metabolism and defence responses, including protease inhibitor activity. In conclusion, drought and flooding have distinct effects on herbivore-induced responses and resistance. Especially, the interaction between abscisic acid and JA signalling may be important to optimize plant responses to combined drought and insect herbivory, making drought-stressed plants more resistant to insects than well-watered and flooded plants. © 2016 John Wiley & Sons Ltd.

[Primary versus secondary stereotypic movements].

PubMed

Fernandez Alvarez, E

2004-02-01

Stereotypic movements are repetitive patterns of movements whose physiopathology and relations to other neurobehavioural disorders are still only poorly understood. In this paper our aim is to distinguish between primary stereotypic movements, which are the sole manifestation of an anomaly, while the complementary examinations, except for those involving molecular genetics, are normal; associated stereotypic movements, when they meet primary disorder criteria but there are other coexisting independent neurological signs, that is to say, they are neither the cause nor the consequence of the movement disorder; and secondary stereotypic movements, when they are the consequence of a lesion or acquired neurological dysfunction. Examples of primary stereotypic movements include episodes of parasomnia, such as head rocking, in subjects who are otherwise normal, and stereotypic movements due to emotional disorders, severe environmental deprivation or in institutionalised infants. Examples of associated stereotypic movements are those observed in Rett syndrome, in subjects with sensory defects or with mental retardation due to a variety of causes. And as instances of secondary stereotypic movements we have those that can be seen in infinite like syndrome caused by congenital cerebellar lesions. The purpose of the classification is to lay the foundations for the identification of new syndromes, which would without a doubt facilitate research into their physiopathology, their aetiology and the possible therapeutic attitude to be adopted.

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

Bonnefont, J.P.; Cepanec, C.; Leroux, J.P.

Carnitine palmitoyltransferase (CPT) II deficiency, an inherited disorder of mitochondrial long-chain fatty-acid (LCFA) oxidation, results in two distinct clinical act phenotypes, namely, an adult (muscular) form and an infantile (hepatocardiomuscular) form. The rationale of this phenotypic heterogeneity is poorly understood. The adult form of the disease is commonly ascribed to the Ser-113-Leu substitution in CPT II. Only few data are available regarding the molecular basis of the infantile form of the disease. We report herein a homozygous A-2399-C transversion predicting a Tyr-628-Ser substitution in a CPT II-deficient infant. In vitro expression of mutant cDNA in COS-1 cells demonstrated the responsibilitymore » of this mutation for the disease. Metabolic consequences of the Ser-113-Leu and Tyr-628-Ser substitutions were studied in fibroblasts. The Tyr-628-Ser substitution (infantile form) resulted in a 10% CPT II residual activity, markedly impairing LCFA oxidation, whereas the Ser-113-Leu substitution (adult form) resulted in a 20% CPT II residual activity, without consequence on LCFA oxidation. These data show that CPT II activity has to be reduced below a critical threshold in order for LCFA oxidation in fibroblasts to be impaired. The hypothesis that this critical threshold differs among tissues could provide a basis to explain phenotypic heterogeneity of CPT II deficiency. 32 refs., 5 figs.« less

Proteogenomics connects somatic mutations to signalling in breast cancer.

PubMed

Mertins, Philipp; Mani, D R; Ruggles, Kelly V; Gillette, Michael A; Clauser, Karl R; Wang, Pei; Wang, Xianlong; Qiao, Jana W; Cao, Song; Petralia, Francesca; Kawaler, Emily; Mundt, Filip; Krug, Karsten; Tu, Zhidong; Lei, Jonathan T; Gatza, Michael L; Wilkerson, Matthew; Perou, Charles M; Yellapantula, Venkata; Huang, Kuan-lin; Lin, Chenwei; McLellan, Michael D; Yan, Ping; Davies, Sherri R; Townsend, R Reid; Skates, Steven J; Wang, Jing; Zhang, Bing; Kinsinger, Christopher R; Mesri, Mehdi; Rodriguez, Henry; Ding, Li; Paulovich, Amanda G; Fenyö, David; Ellis, Matthew J; Carr, Steven A

2016-06-02

Somatic mutations have been extensively characterized in breast cancer, but the effects of these genetic alterations on the proteomic landscape remain poorly understood. Here we describe quantitative mass-spectrometry-based proteomic and phosphoproteomic analyses of 105 genomically annotated breast cancers, of which 77 provided high-quality data. Integrated analyses provided insights into the somatic cancer genome including the consequences of chromosomal loss, such as the 5q deletion characteristic of basal-like breast cancer. Interrogation of the 5q trans-effects against the Library of Integrated Network-based Cellular Signatures, connected loss of CETN3 and SKP1 to elevated expression of epidermal growth factor receptor (EGFR), and SKP1 loss also to increased SRC tyrosine kinase. Global proteomic data confirmed a stromal-enriched group of proteins in addition to basal and luminal clusters, and pathway analysis of the phosphoproteome identified a G-protein-coupled receptor cluster that was not readily identified at the mRNA level. In addition to ERBB2, other amplicon-associated highly phosphorylated kinases were identified, including CDK12, PAK1, PTK2, RIPK2 and TLK2. We demonstrate that proteogenomic analysis of breast cancer elucidates the functional consequences of somatic mutations, narrows candidate nominations for driver genes within large deletions and amplified regions, and identifies therapeutic targets.

Spatiotemporal Characterization of mTOR Kinase Activity Following Kainic Acid Induced Status Epilepticus and Analysis of Rat Brain Response to Chronic Rapamycin Treatment

PubMed Central

Macias, Matylda; Blazejczyk, Magdalena; Kazmierska, Paulina; Caban, Bartosz; Skalecka, Agnieszka; Tarkowski, Bartosz; Rodo, Anna; Konopacki, Jan; Jaworski, Jacek

2013-01-01

Mammalian target of rapamycin (mTOR) is a protein kinase that senses nutrient availability, trophic factors support, cellular energy level, cellular stress, and neurotransmitters and adjusts cellular metabolism accordingly. Adequate mTOR activity is needed for development as well as proper physiology of mature neurons. Consequently, changes in mTOR activity are often observed in neuropathology. Recently, several groups reported that seizures increase mammalian target of rapamycin (mTOR) kinase activity, and such increased activity in genetic models can contribute to spontaneous seizures. However, the current knowledge about the spatiotemporal pattern of mTOR activation induced by proconvulsive agents is rather rudimentary. Also consequences of insufficient mTOR activity on a status epilepticus are poorly understood. Here, we systematically investigated these two issues. We showed that mTOR signaling was activated by kainic acid (KA)-induced status epilepticus through several brain areas, including the hippocampus and cortex as well as revealed two waves of mTOR activation: an early wave (2 h) that occurs in neurons and a late wave that predominantly occurs in astrocytes. Unexpectedly, we found that pretreatment with rapamycin, a potent mTOR inhibitor, gradually (i) sensitized animals to KA treatment and (ii) induced gross anatomical changes in the brain. PMID:23724051

The long-term evolution of multilocus traits under frequency-dependent disruptive selection.

PubMed

van Doorn, G Sander; Dieckmann, Ulf

2006-11-01

Frequency-dependent disruptive selection is widely recognized as an important source of genetic variation. Its evolutionary consequences have been extensively studied using phenotypic evolutionary models, based on quantitative genetics, game theory, or adaptive dynamics. However, the genetic assumptions underlying these approaches are highly idealized and, even worse, predict different consequences of frequency-dependent disruptive selection. Population genetic models, by contrast, enable genotypic evolutionary models, but traditionally assume constant fitness values. Only a minority of these models thus addresses frequency-dependent selection, and only a few of these do so in a multilocus context. An inherent limitation of these remaining studies is that they only investigate the short-term maintenance of genetic variation. Consequently, the long-term evolution of multilocus characters under frequency-dependent disruptive selection remains poorly understood. We aim to bridge this gap between phenotypic and genotypic models by studying a multilocus version of Levene's soft-selection model. Individual-based simulations and deterministic approximations based on adaptive dynamics theory provide insights into the underlying evolutionary dynamics. Our analysis uncovers a general pattern of polymorphism formation and collapse, likely to apply to a wide variety of genetic systems: after convergence to a fitness minimum and the subsequent establishment of genetic polymorphism at multiple loci, genetic variation becomes increasingly concentrated on a few loci, until eventually only a single polymorphic locus remains. This evolutionary process combines features observed in quantitative genetics and adaptive dynamics models, and it can be explained as a consequence of changes in the selection regime that are inherent to frequency-dependent disruptive selection. Our findings demonstrate that the potential of frequency-dependent disruptive selection to maintain polygenic variation is considerably smaller than previously expected.

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…

The Power of the Rhythm of Tree Stems

NASA Astrophysics Data System (ADS)

Steppe, K.

2015-12-01

On annual and monthly scales, a remarkable close relationship has been shown between net ecosystem productivity (NEP) measured by eddy covariance and stem diameter variations (SDV) measured with automated point dendrometers in a Swiss subalpine Norway spruce forest (Zweifel et al. 2010). Causality for the close NEP-SDV relationship is poorly understood, but radial stem growth has been suggested to play a crucial role. Despite its huge ecological implications, and being 'hot' in anatomical, ecophysiologial, and ecological disciplines, radial stem growth in trees remains poorly understood (Steppe et al. 2015). While high-resolution SDV mirror a source of tree physiological information, unambiguous interpretation of dendrometer readings is more complicated than it appears at first sight, with a great potential still waiting to be discovered (De Swaef et al. 2015, Zweifel 2015). Also an integrative framework to assess impacts of climate on stem growth is still lacking, although such a theory is very much needed to predict annual tree growth patterns as well as future production and carbon sequestration potential of forests (Steppe et al. 2015). In this keynote lecture, I will present the major fluxes and pools of water and carbon inside a stem segment of a tree. I will examine diel dynamics in radial stem growth from underlying water and carbon mechanisms under wet and dry conditions, distinguishing between known patterns and processes, and more speculative ones. Discussions will be based on observations in the different research disciplines, but also result from mechanistic plant models aiming at integration. Based on this, I will show missing pieces that might be critical to build an integrative theory to understand causes and consequences of tree stem growth. Addressing these key-missing pieces of information may help improving quantification of terrestrial ecosystem carbon uptake and storage. ReferencesDe Swaef et al. (2015) Tree Physiology (in press). Steppe et al. (2015) Trends in Plant Science 20: 335-343. Zweifel et al. (2010) New Phytologist 187: 819-830. Zweifel (2015) Plant, Cell & Environment (in press).

Increased global transcription activity as a mechanism of replication stress in cancer

PubMed Central

Kotsantis, Panagiotis; Silva, Lara Marques; Irmscher, Sarah; Jones, Rebecca M.; Folkes, Lisa; Gromak, Natalia; Petermann, Eva

2016-01-01

Cancer is a disease associated with genomic instability that often results from oncogene activation. This in turn leads to hyperproliferation and replication stress. However, the molecular mechanisms that underlie oncogene-induced replication stress are still poorly understood. Oncogenes such as HRASV12 promote proliferation by upregulating general transcription factors to stimulate RNA synthesis. Here we investigate whether this increase in transcription underlies oncogene-induced replication stress. We show that in cells overexpressing HRASV12, elevated expression of the general transcription factor TATA-box binding protein (TBP) leads to increased RNA synthesis, which together with R-loop accumulation results in replication fork slowing and DNA damage. Furthermore, overexpression of TBP alone causes the hallmarks of oncogene-induced replication stress, including replication fork slowing, DNA damage and senescence. Consequently, we reveal that increased transcription can be a mechanism of oncogene-induced DNA damage, providing a molecular link between upregulation of the transcription machinery and genomic instability in cancer. PMID:27725641

Increased global transcription activity as a mechanism of replication stress in cancer.

PubMed

Kotsantis, Panagiotis; Silva, Lara Marques; Irmscher, Sarah; Jones, Rebecca M; Folkes, Lisa; Gromak, Natalia; Petermann, Eva

2016-10-11

Cancer is a disease associated with genomic instability that often results from oncogene activation. This in turn leads to hyperproliferation and replication stress. However, the molecular mechanisms that underlie oncogene-induced replication stress are still poorly understood. Oncogenes such as HRAS V12 promote proliferation by upregulating general transcription factors to stimulate RNA synthesis. Here we investigate whether this increase in transcription underlies oncogene-induced replication stress. We show that in cells overexpressing HRAS V12 , elevated expression of the general transcription factor TATA-box binding protein (TBP) leads to increased RNA synthesis, which together with R-loop accumulation results in replication fork slowing and DNA damage. Furthermore, overexpression of TBP alone causes the hallmarks of oncogene-induced replication stress, including replication fork slowing, DNA damage and senescence. Consequently, we reveal that increased transcription can be a mechanism of oncogene-induced DNA damage, providing a molecular link between upregulation of the transcription machinery and genomic instability in cancer.

Modelling the role of groundwater hydro-refugia in East African hominin evolution and dispersal

PubMed Central

Cuthbert, M. O.; Gleeson, T.; Reynolds, S. C.; Bennett, M. R.; Newton, A. C.; McCormack, C. J.; Ashley, G. M.

2017-01-01

Water is a fundamental resource, yet its spatiotemporal availability in East Africa is poorly understood. This is the area where most hominin first occurrences are located, and consequently the potential role of water in hominin evolution and dispersal remains unresolved. Here, we show that hundreds of springs currently distributed across East Africa could function as persistent groundwater hydro-refugia through orbital-scale climate cycles. Groundwater buffers climate variability according to spatially variable groundwater response times determined by geology and topography. Using an agent-based model, grounded on the present day landscape, we show that groundwater availability would have been critical to supporting isolated networks of hydro-refugia during dry periods when potable surface water was scarce. This may have facilitated unexpected variations in isolation and dispersal of hominin populations in the past. Our results therefore provide a new environmental framework in which to understand how patterns of taxonomic diversity in hominins may have developed. PMID:28556825

Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia.

PubMed

Shlush, Liran I; Zandi, Sasan; Mitchell, Amanda; Chen, Weihsu Claire; Brandwein, Joseph M; Gupta, Vikas; Kennedy, James A; Schimmer, Aaron D; Schuh, Andre C; Yee, Karen W; McLeod, Jessica L; Doedens, Monica; Medeiros, Jessie J F; Marke, Rene; Kim, Hyeoung Joon; Lee, Kwon; McPherson, John D; Hudson, Thomas J; Brown, Andrew M K; Yousif, Fouad; Trinh, Quang M; Stein, Lincoln D; Minden, Mark D; Wang, Jean C Y; Dick, John E

2014-02-20

In acute myeloid leukaemia (AML), the cell of origin, nature and biological consequences of initiating lesions, and order of subsequent mutations remain poorly understood, as AML is typically diagnosed without observation of a pre-leukaemic phase. Here, highly purified haematopoietic stem cells (HSCs), progenitor and mature cell fractions from the blood of AML patients were found to contain recurrent DNMT3A mutations (DNMT3A(mut)) at high allele frequency, but without coincident NPM1 mutations (NPM1c) present in AML blasts. DNMT3A(mut)-bearing HSCs showed a multilineage repopulation advantage over non-mutated HSCs in xenografts, establishing their identity as pre-leukaemic HSCs. Pre-leukaemic HSCs were found in remission samples, indicating that they survive chemotherapy. Therefore DNMT3A(mut) arises early in AML evolution, probably in HSCs, leading to a clonally expanded pool of pre-leukaemic HSCs from which AML evolves. Our findings provide a paradigm for the detection and treatment of pre-leukaemic clones before the acquisition of additional genetic lesions engenders greater therapeutic resistance.

Assortative mating among animals of captive and wild origin following experimental conservation releases

PubMed Central

Slade, Brendan; Parrott, Marissa L.; Paproth, Aleisha; Magrath, Michael J. L.; Gillespie, Graeme R.; Jessop, Tim S.

2014-01-01

Captive breeding is a high profile management tool used for conserving threatened species. However, the inevitable consequence of generations in captivity is broad scale and often-rapid phenotypic divergence between captive and wild individuals, through environmental differences and genetic processes. Although poorly understood, mate choice preference is one of the changes that may occur in captivity that could have important implications for the reintroduction success of captive-bred animals. We bred wild-caught house mice for three generations to examine mating patterns and reproductive outcomes when these animals were simultaneously released into multiple outdoor enclosures with wild conspecifics. At release, there were significant differences in phenotypic (e.g. body mass) and genetic measures (e.g. Gst and F) between captive-bred and wild adult mice. Furthermore, 83% of offspring produced post-release were of same source parentage, inferring pronounced assortative mating. Our findings suggest that captive breeding may affect mating preferences, with potentially adverse implications for the success of threatened species reintroduction programmes. PMID:25411380

Chicxulub Impact Melts: Geochemical Signatures of Target Lithology Mixing and Post-Impact Hydrothermal Fluid Processes

NASA Technical Reports Server (NTRS)

Kring, David A.; Zurcher, Lukas; Horz, Freidrich; Mertzmann, Stanley A.

2004-01-01

Impact melts within complex impact craters are generally homogeneous, unless they differentiated, contain immiscible melt components, or were hydrothermally altered while cooling. The details of these processes, however, and their chemical consequences, are poorly understood. The best opportunity to unravel them may lie with the Chicxulub impact structure, because it is the world s most pristine (albeit buried) large impact crater. The Chicxulub Scientific Drilling Project recovered approx. 100 meters of impactites in a continuous core from the Yaxcopoil-1 (YAX-1) borehole. This dramatically increased the amount of melt available for analyses, which was previously limited to two small samples N17 and N19) recovered from the Yucatan-6 (Y-6) borehole and one sample (N10) recovered from the Chicxulub-1 (C-1) borehole. In this study, we describe the chemical compositions of six melt samples over an approx. 40 m section of the core and compare them to previous melt samples from the Y-6 and C-1 boreholes.

Disaster-related exposures and health effects among US Coast Guard responders to Hurricanes Katrina and Rita: a cross-sectional study.

PubMed

Rusiecki, Jennifer A; Thomas, Dana L; Chen, Ligong; Funk, Renée; McKibben, Jodi; Dayton, Melburn R

2014-08-01

Disaster responders work among poorly characterized physical and psychological hazards with little understood regarding health consequences of their work. A survey administered to 2834 US Coast Guard responders to Hurricanes Katrina and Rita provided data on exposures and health effects. Prevalence odds ratios (PORs) evaluated associations between baseline characteristics, missions, exposures, and health effects. Most frequent exposures were animal/insect vector (n = 1309; 46%) and floodwater (n = 817; 29%). Most frequent health effects were sunburn (n = 1119; 39%) and heat stress (n = 810; 30%). Significant positive associations were for mold exposure and sinus infection (POR = 10.39); carbon monoxide and confusion (POR = 6.27); lack of sleep and slips, trips, falls (POR = 3.34) and depression (POR = 3.01); being a Gulf-state responder and depression (POR = 3.22). Increasing protection for disaster responders requires provisions for adequate sleep, personal protective equipment, and access to medical and psychological support.

Modelling the role of groundwater hydro-refugia in East African hominin evolution and dispersal

NASA Astrophysics Data System (ADS)

Cuthbert, M. O.; Gleeson, T.; Reynolds, S. C.; Bennett, M. R.; Newton, A. C.; McCormack, C. J.; Ashley, G. M.

2017-05-01

Water is a fundamental resource, yet its spatiotemporal availability in East Africa is poorly understood. This is the area where most hominin first occurrences are located, and consequently the potential role of water in hominin evolution and dispersal remains unresolved. Here, we show that hundreds of springs currently distributed across East Africa could function as persistent groundwater hydro-refugia through orbital-scale climate cycles. Groundwater buffers climate variability according to spatially variable groundwater response times determined by geology and topography. Using an agent-based model, grounded on the present day landscape, we show that groundwater availability would have been critical to supporting isolated networks of hydro-refugia during dry periods when potable surface water was scarce. This may have facilitated unexpected variations in isolation and dispersal of hominin populations in the past. Our results therefore provide a new environmental framework in which to understand how patterns of taxonomic diversity in hominins may have developed.

Notch3 marks clonogenic mammary luminal progenitor cells in vivo.

PubMed

Lafkas, Daniel; Rodilla, Veronica; Huyghe, Mathilde; Mourao, Larissa; Kiaris, Hippokratis; Fre, Silvia

2013-10-14

The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive "triple negative" human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2(SAT) transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells.

The Vicious Cycle of Myostatin Signaling in Sarcopenic Obesity: Myostatin Role in Skeletal Muscle Growth, Insulin Signaling and Implications for Clinical Trials.

PubMed

Consitt, L A; Clark, B C

2018-01-01

The age-related loss of skeletal muscle (sarcopenia) is a major health concern as it is associated with physical disability, metabolic impairments, and increased mortality. The coexistence of sarcopenia with obesity, termed 'sarcopenic obesity', contributes to skeletal muscle insulin resistance and the development of type 2 diabetes, a disease prevalent with advancing age. Despite this knowledge, the mechanisms contributing to sarcopenic obesity remain poorly understood, preventing the development of targeted therapeutics. This article will discuss the clinical and physiological consequences of sarcopenic obesity and propose myostatin as a potential candidate contributing to this condition. A special emphasis will be placed on examining the role of myostatin signaling in impairing both skeletal muscle growth and insulin signaling. In addition, the role of myostatin in regulating muscle-to fat cross talk, further exacerbating metabolic dysfunction in the elderly, will be highlighted. Lastly, we discuss how this knowledge has implications for the design of myostatin-inhibitor clinical trials.

Feedbacks between climate change and biosphere integrity

NASA Astrophysics Data System (ADS)

Lade, Steven; Anderies, J. Marty; Donges, Jonathan; Steffen, Will; Rockström, Johan; Richardson, Katherine; Cornell, Sarah; Norberg, Jon; Fetzer, Ingo

2017-04-01

The terrestrial and marine biospheres sink substantial fractions of human fossil fuel emissions. How the biosphere's capacity to sink carbon depends on biodiversity and other measures of biosphere integrity is however poorly understood. Here, we (1): review assumptions from literature regarding the relationships between the carbon cycle and the terrestrial and marine biospheres; and (2) explore the consequences of these different assumptions for climate feedbacks using the stylised carbon cycle model PB-INT. We find that: terrestrial biodiversity loss could significantly dampen climate-carbon cycle feedbacks; direct biodiversity effects, if they exist, could rival temperature increases from low-emission trajectories; and the response of the marine biosphere is critical for longer term climate change. Simple, low-dimensional climate models such as PB-INT can help assess the importance of still unknown or controversial earth system processes such as biodiversity loss for climate feedbacks. This study constitutes the first detailed study of the interactions between climate change and biosphere integrity, two of the 'planetary boundaries'.

Alternative Polyadenylation Regulates CELF1/CUGBP1 Target Transcripts Following T Cell Activation

PubMed Central

Beisang, Daniel; Reilly, Cavan; Bohjanen, Paul R.

2014-01-01

Alternative polyadenylation (APA) is an evolutionarily conserved mechanism for regulating gene expression. Transcript 3′ end shortening through changes in polyadenylation site usage occurs following T cell activation, but the consequences of APA on gene expression are poorly understood. We previously showed that GU-rich elements (GREs) found in the 3′ untranslated regions of select transcripts mediate rapid mRNA decay by recruiting the protein CELF1/CUGBP1. Using a global RNA sequencing approach, we found that a network of CELF1 target transcripts involved in cell division underwent preferential 3′ end shortening via APA following T cell activation, resulting in decreased inclusion of CELF1 binding sites and increased transcript expression. We present a model whereby CELF1 regulates APA site selection following T cell activation through reversible binding to nearby GRE sequences. These findings provide insight into the role of APA in controlling cellular proliferation during biological processes such as development, oncogenesis and T cell activation PMID:25123787

An empirical analysis of public and private medical practice in Australia.

PubMed

Cheng, Terence C; Joyce, Catherine M; Scott, Anthony

2013-06-01

The combination of public and private medical practice is widespread in many health systems and has important consequences for health care cost and quality. However, its forms and prevalence vary widely and are poorly understood. This paper examines factors associated with public and private sector work by medical specialists using a nationally representative sample of Australian doctors. We find considerable variations in the practice patterns, remuneration contracts and professional arrangements across doctors in different work sectors. Both specialists in mixed practice and private practice differ from public sector specialists with regard to their annual earnings, sources of income, maternity and other leave taken and number of practice locations. Public sector specialists are likely to be younger, to be international medical graduates, devote a higher percentage of time to education and research, and are more likely to do after hours and on-call work compared with private sector specialists. Gender and total hours worked do not differ between doctors across the different practice types. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Food that makes you different: the stigma experienced by adolescents with celiac disease.

PubMed

Olsson, Cecilia; Lyon, Phil; Hörnell, Agneta; Ivarsson, Anneli; Sydner, Ylva Mattsson

2009-07-01

For adolescents with celiac disease (CD), a gluten-free diet (GFD) is crucial for health, but compliance is problematic and noncompliance is common even among those aware of the risks. To better understand their lives with the disease, Swedish CD adolescents were invited to take part in focus group discussions. Data were analyzed for recurrent stigma-related themes across the groups. Adolescents described an awareness of being different from others that was produced by meal appearance and the poor availability of gluten-free food. The GFD often required discussions and special requests, so eating in public had the effect of making an invisible condition visible, and thereby creating a context for felt or enacted stigma. Maintaining invisibility avoided negative consequences of stigma, and other strategies were used to reduce the costs of visibility. The results of the study show that the GFD can produce stigma experiences in adolescence, and that dietary compliance (or lack thereof) can be understood in terms of dealing with GFD concealment and disclosure.

The mechanisms mediating the effects of poverty on children's intellectual development.

PubMed

Guo, G; Harris, K M

2000-11-01

Although adverse consequences of poverty for children are documented widely, little is understood about the mechanisms through which the effects of poverty disadvantage young children. In this analysis we investigate multiple mechanisms through which poverty affects a child's intellectual development. Using data from the NLSY and structural equation models, we have constructed five latent factors (cognitive stimulation, parenting style, physical environment, child's ill health at birth, and ill health in childhood) and have allowed these factors, along with child care, to mediate the effects of poverty and other exogenous variables. We produce two main findings. First, the influence of family poverty on children's intellectual development is mediated completely by the intervening mechanisms measured by our latent factors. Second, our analysis points to cognitive stimulation in the home, and (to a lesser extent) to parenting style, physical environment of the home, and poor child health at birth, as mediating factors that are affected by lack of income and that influence children's intellectual development.

Chemokine guided angiogenesis directs coronary vasculature formation in zebrafish

PubMed Central

Harrison, Michael R.M.; Bussmann, Jeroen; Huang, Ying; Zhao, Long; Osorio, Arthela; Burns, C. Geoffrey; Burns, Caroline E.; Sucov, Henry M.; Siekmann, Arndt F.; Lien, Ching-Ling

2015-01-01

SUMMARY Interruption of coronary blood supply severely impairs heart function with often-fatal consequences for heart disease patients. However the formation and maturation of these coronary vessels is not fully understood. Here we provide a detailed analysis of coronary vessel development in zebrafish. We observe that coronary vessels form in zebrafish by angiogenic sprouting of arterial cells derived from the endocardium at the atrioventricular canal. Endothelial cells express the CXC-motif chemokine receptor Cxcr4a and migrate to vascularize the ventricle under the guidance of the myocardium-expressed ligand Cxcl12b. cxcr4a mutant zebrafish fail to form a vascular network, whereas ectopic expression of Cxcl12b ligand induces coronary vessel formation. Importantly, cxcr4a mutant zebrafish fail to undergo heart regeneration following injury. Our results suggest that chemokine-signaling has an essential role in coronary vessel formation by directing migration of endocardium-derived endothelial cells. Poorly developed vasculature in cxcr4a mutants likely underlies decreased regenerative potential in adults. PMID:26017769

Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging.

PubMed

Soreq, Lilach; Rose, Jamie; Soreq, Eyal; Hardy, John; Trabzuni, Daniah; Cookson, Mark R; Smith, Colin; Ryten, Mina; Patani, Rickie; Ule, Jernej

2017-01-10

Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in age from 16 to 106 years. We show that astrocyte- and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional expression patterns upon aging, particularly in the hippocampus and substantia nigra, while the expression of microglia- and endothelial-specific genes increase in all brain regions. In line with these changes, high-resolution immunohistochemistry demonstrated decreased numbers of oligodendrocytes and of neuronal subpopulations in the aging brain cortex. Finally, glial-specific genes predict age with greater precision than neuron-specific genes, thus highlighting the need for greater mechanistic understanding of neuron-glia interactions in aging and late-life diseases. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Baleen whales host a unique gut microbiome with similarities to both carnivores and herbivores

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

Sanders, Jon G.; Beichman, Annabel C.; Roman, Joe

Mammals host gut microbiomes of immense physiological consequence, but the determinants of diversity in these communities remain poorly understood. Diet appears to be the dominant factor, but host phylogeny also seems to be an important, if unpredictable, correlate. Here we show that baleen whales, which prey on animals (fish and crustaceans), harbor unique gut microbiomes with surprising parallels in functional capacity and higher level taxonomy to those of terrestrial herbivores. These similarities likely reflect a shared role for fermentative metabolisms despite a shift in primary carbon sources from plant-derived to animal-derived polysaccharides, such as chitin. In contrast, protein catabolism andmore » essential amino acid synthesis pathways in baleen whale microbiomes more closely resemble those of terrestrial carnivores. Our results demonstrate that functional attributes of the microbiome can vary independently even given an animal-derived diet, illustrating how diet and evolutionary history combine to shape microbial diversity in the mammalian gut.« less

Disentangling complex parasite interactions: Protection against cerebral malaria by one helminth species is jeopardized by co-infection with another.

PubMed

Abbate, Jessica L; Ezenwa, Vanessa O; Guégan, Jean-François; Choisy, Marc; Nacher, Mathieu; Roche, Benjamin

2018-05-01

Multi-species interactions can often have non-intuitive consequences. However, the study of parasite interactions has rarely gone beyond the effects of pairwise combinations of species, and the outcomes of multi-parasite interactions are poorly understood. We investigated the effects of co-infection by four gastrointestinal helminth species on the development of cerebral malaria among Plasmodium falciparum-infected patients. We characterized associations among the helminth parasite infra-community, and then tested for independent (direct) and co-infection dependent (indirect) effects of helminths on cerebral malaria risk. We found that infection by Ascaris lumbricoides and Trichuris trichiura were both associated with direct reductions in cerebral malaria risk. However, the benefit of T. trichiura infection was halved in the presence of hookworm, revealing a strong indirect effect. Our study suggests that the outcome of interactions between two parasite species can be significantly modified by a third, emphasizing the critical role that parasite community interactions play in shaping infection outcomes.

Artificial light pollution increases nocturnal vigilance in peahens

PubMed Central

Chisholm, Sarah; Byerley, Sydney D; Coy, Jeanee R.; Aziz, Aisyah; Wolf, Jamie A.; Gnerlich, Amanda C.

2015-01-01

Artificial light pollution is drastically changing the sensory environments of animals. Even though many animals are now living in these changed environments, the effect light pollution has on animal behavior is poorly understood. We investigated the effect of light pollution on nocturnal vigilance in peahens (Pavo cristatus). Captive peahens were exposed to either artificial lighting or natural lighting at night. We employed a novel method to record their vigilance behavior by attaching accelerometers to their heads and continuously monitoring their large head movements. We found that light pollution significantly increases nocturnal vigilance in peahens. Furthermore, the birds faced a trade-off between vigilance and sleep at night: peahens that were more vigilant spent less time sleeping. Given the choice, peahens preferred to roost away from high levels of artificial lighting but showed no preference for roosting without artificial lighting or with low levels of artificial lighting. Our study demonstrates that light pollution can have a substantial impact on animal behavior that can potentially result in fitness consequences. PMID:26339552

Aerobic scope fails to explain the detrimental effects on growth resulting from warming and elevated CO2 in Atlantic halibut.

PubMed

Gräns, Albin; Jutfelt, Fredrik; Sandblom, Erik; Jönsson, Elisabeth; Wiklander, Kerstin; Seth, Henrik; Olsson, Catharina; Dupont, Sam; Ortega-Martinez, Olga; Einarsdottir, Ingibjörg; Björnsson, Björn Thrandur; Sundell, Kristina; Axelsson, Michael

2014-03-01

As a consequence of increasing atmospheric CO2, the world's oceans are becoming warmer and more acidic. Whilst the ecological effects of these changes are poorly understood, it has been suggested that fish performance including growth will be reduced mainly as a result of limitations in oxygen transport capacity. Contrary to the predictions given by the oxygen- and capacity-limited thermal tolerance hypothesis, we show that aerobic scope and cardiac performance of Atlantic halibut (Hippoglossus hippoglossus) increase following 14-16 weeks exposure to elevated temperatures and even more so in combination with CO2-acidified seawater. However, the increase does not translate into improved growth, demonstrating that oxygen uptake is not the limiting factor for growth performance at high temperatures. Instead, long-term exposure to CO2-acidified seawater reduces growth at temperatures that are frequently encountered by this species in nature, indicating that elevated atmospheric CO2 levels may have serious implications on fish populations in the future.

Robust gap repair in the contractile ring ensures timely completion of cytokinesis

PubMed Central

Maiato, Helder; Pinto, Inês Mendes; Rubinstein, Boris

2016-01-01

Cytokinesis in animal cells requires the constriction of an actomyosin contractile ring, whose architecture and mechanism remain poorly understood. We use laser microsurgery to explore the biophysical properties of constricting rings in Caenorhabditis elegans embryos. Laser cutting causes rings to snap open. However, instead of disintegrating, ring topology recovers and constriction proceeds. In response to severing, a finite gap forms and is repaired by recruitment of new material in an actin polymerization–dependent manner. An open ring is able to constrict, and rings repair from successive cuts. After gap repair, an increase in constriction velocity allows cytokinesis to complete at the same time as controls. Our analysis demonstrates that tension in the ring increases while net cortical tension at the site of ingression decreases throughout constriction and suggests that cytokinesis is accomplished by contractile modules that assemble and contract autonomously, enabling local repair of the actomyosin network. Consequently, cytokinesis is a highly robust process impervious to discontinuities in contractile ring structure. PMID:27974482

Different requirements of functional telomeres in neural stem cells and terminally differentiated neurons.

PubMed

Lobanova, Anastasia; She, Robert; Pieraut, Simon; Clapp, Charlie; Maximov, Anton; Denchi, Eros Lazzerini

2017-04-01

Telomeres have been studied extensively in peripheral tissues, but their relevance in the nervous system remains poorly understood. Here, we examine the roles of telomeres at distinct stages of murine brain development by using lineage-specific genetic ablation of TRF2, an essential component of the shelterin complex that protects chromosome ends from the DNA damage response machinery. We found that functional telomeres are required for embryonic and adult neurogenesis, but their uncapping has surprisingly no detectable consequences on terminally differentiated neurons. Conditional knockout of TRF2 in post-mitotic immature neurons had virtually no detectable effect on circuit assembly, neuronal gene expression, and the behavior of adult animals despite triggering massive end-to-end chromosome fusions across the brain. These results suggest that telomeres are dispensable in terminally differentiated neurons and provide mechanistic insight into cognitive abnormalities associated with aberrant telomere length in humans. © 2017 Lobanova et al.; Published by Cold Spring Harbor Laboratory Press.

Speed over efficiency: locusts select body temperatures that favour growth rate over efficient nutrient utilization

PubMed Central

Miller, Gabriel A.; Clissold, Fiona J.; Mayntz, David; Simpson, Stephen J.

2009-01-01

Ectotherms have evolved preferences for particular body temperatures, but the nutritional and life-history consequences of such temperature preferences are not well understood. We measured thermal preferences in Locusta migratoria (migratory locusts) and used a multi-factorial experimental design to investigate relationships between growth/development and macronutrient utilization (conversion of ingesta to body mass) as a function of temperature. A range of macronutrient intake values for insects at 26, 32 and 38°C was achieved by offering individuals high-protein diets, high-carbohydrate diets or a choice between both. Locusts placed in a thermal gradient selected temperatures near 38°C, maximizing rates of weight gain; however, this enhanced growth rate came at the cost of poor protein and carbohydrate utilization. Protein and carbohydrate were equally digested across temperature treatments, but once digested both macronutrients were converted to growth most efficiently at the intermediate temperature (32°C). Body temperature preference thus yielded maximal growth rates at the expense of efficient nutrient utilization. PMID:19625322

Measurement of alcohol craving.

PubMed

Kavanagh, David J; Statham, Dixie J; Feeney, Gerald F X; Young, Ross McD; May, Jon; Andrade, Jackie; Connor, Jason P

2013-02-01

Despite considerable research activity and application in treatment, the construct of craving remains poorly understood. We propose that cravings and urges are cognitive-emotional events in time, characterised by frequency, duration, intensity and salience. Commonly used measures of alcohol craving are reviewed, and their strengths and weaknesses identified. Most measures confound craving with behaviours, or with separable cognitive phenomena such as expectancies, intentions, or perceived behavioural control. These confounds have limited our advances in understanding the determinants and consequences of craving. Based on the criteria applied in this review, among the better performing multi-item measures are the Penn Alcohol Craving Scale and Obsessive subscale of the Obsessive-Compulsive Drinking Scale. Optimal assessment strategies are likely to involve daily assessments of peak intensity of cravings, desires or urges and of the frequency and duration of craving episodes. Of particular interest are measures of intensity at times when individuals are at risk of drinking or of other functional impacts from craving. Copyright © 2012 Elsevier Ltd. All rights reserved.

A quantitative framework for whole-body coordination reveals specific deficits in freely walking ataxic mice

PubMed Central

Machado, Ana S; Darmohray, Dana M; Fayad, João; Marques, Hugo G; Carey, Megan R

2015-01-01

The coordination of movement across the body is a fundamental, yet poorly understood aspect of motor control. Mutant mice with cerebellar circuit defects exhibit characteristic impairments in locomotor coordination; however, the fundamental features of this gait ataxia have not been effectively isolated. Here we describe a novel system (LocoMouse) for analyzing limb, head, and tail kinematics of freely walking mice. Analysis of visibly ataxic Purkinje cell degeneration (pcd) mice reveals that while differences in the forward motion of individual paws are fully accounted for by changes in walking speed and body size, more complex 3D trajectories and, especially, inter-limb and whole-body coordination are specifically impaired. Moreover, the coordination deficits in pcd are consistent with a failure to predict and compensate for the consequences of movement across the body. These results isolate specific impairments in whole-body coordination in mice and provide a quantitative framework for understanding cerebellar contributions to coordinated locomotion. DOI: http://dx.doi.org/10.7554/eLife.07892.001 PMID:26433022

Lake seasonality across the Tibetan Plateau and their varying relationship with regional mass changes and local hydrology

NASA Astrophysics Data System (ADS)

Lei, Yanbin; Yao, Tandong; Yang, Kun; Sheng, Yongwei; Kleinherenbrink, Marcel; Yi, Shuang; Bird, Broxton W.; Zhang, Xiaowen; Zhu, La; Zhang, Guoqing

2017-01-01

The recent growth and deepening of inland lakes in the Tibetan Plateau (TP) may be a salient indicator of the consequences of climate change. The seasonal dynamics of these lakes is poorly understood despite this being potentially crucial for disentangling contributions from glacier melt and precipitation, which are all sensitive to climate, to lake water budget. Using in situ observations, satellite altimetry and gravimetry data, we identified two patterns of lake level seasonality. In the central, northern, and northeastern TP, lake levels are characterized by considerable increases during warm seasons and decreases during cold seasons, which is consistent with regional mass changes related to monsoon precipitation and evaporation. In the northwestern TP, however, lake levels exhibit dramatic increases during both warm and cold seasons, which deviate from regional mass changes. This appears to be more connected with high spring snowfall and large summer glacier melt. The variable lake level response to different drivers indicates heterogeneous sensitivity to climate change between the northwestern TP and other regions.

Time to flourish: the relationship of temporal perspective to well-being and wisdom across adulthood.

PubMed

Webster, Jeffrey Dean; Bohlmeijer, Ernst T; Westerhof, Gerben J

2014-01-01

Despite the centrality of time to the aging process, the well-being consequences of different temporal orientations for optimal aging are poorly understood. We investigate one underexamined area of temporal orientation, namely a balanced time perspective, in a large, lifespan sample from the Netherlands. Participants consisted of 512 Dutch adults ranging in age from 17 to 92 years (Mage = 46.46, SD = 21.37), including 186 male and 326 females. Participants completed a measure of balanced time perspective, mental health, and wisdom. RESULTS indicated that a balanced time perspective uniquely predicted both mental health and wisdom even after controlling for demographic, physical health, and personality variables. Younger adults tended to be more future-oriented relative to older adults while older adults tended to be more past-oriented relative to younger adults. Further, both midlife and younger adults were more likely to have a balanced time perspective relative to older adults. A balanced time perspective is associated with higher well-being and wisdom across the adult age span.

Peripartum Cardiomyopathy: Moving Towards a More Central Role of Genetics#

PubMed Central

Cemin, Roberto; Janardhanan, Rajesh; Donazzan, Luca; Daves, Massimo

2013-01-01

Peripartum cardiomyopathy (PCM) is a relatively rare disease with potentially devasting consequences requiring prompt identification and correct treatment. Overall prognosis is good in majority of the cases, although some patients may progress to irreversible heart failure. Early diagnosis is important and effective treatment reduces mortality rates and increases the chance of complete recovery of ventricular systolic function. The aetiology and pathogenesis seems to be multifactorial and poorly understood, with the available literature rather conflicting. In recent years, there has been increased interest in the role played by genetic predisposition in the development of PCM. It probably develops as a result of a complex interaction of pregnancy-associated factors and genetic factors and recently there have been many observations pointing out the central role played by a genetic predisposition. The direct and indirect observations on genetic susceptibility may offer new insights into the pathogenesis of PCM. However, larger studies are needed before advising routine genetic testing in these patients. PMID:23909634

Inducible defenses in prey intensify predator cannibalism.

PubMed

Kishida, Osamu; Trussell, Geoffrey C; Nishimura, Kinya; Ohgushi, Takayuki

2009-11-01

Trophic cascades are often a potent force in ecological communities, but abiotic and biotic heterogeneity can diffuse their influence. For example, inducible defenses in many species create variation in prey edibility, and size-structured interactions, such as cannibalism, can shift predator diets away from heterospecific prey. Although both factors diffuse cascade strength by adding heterogeneity to trophic interactions, the consequences of their interactioh remain poorly understood. We show that inducible defenses in tadpole prey greatly intensify cannibalism in predatory larval salamanders. The likelihood of cannibalism was also strongly influenced by asymmetries in salamander size that appear to be most important in the presence of defended prey. Hence, variation in prey edibility and the size structure of the predator may synergistically affect predator-prey population dynamics by reducing prey mortality and increasing predator mortality via cannibalism. We also suggest that the indirect effects of prey defenses may shape the evolution of predator traits that determine diet breadth and how trophic dynamics unfold in natural systems.

STEF/TIAM2-mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap.

PubMed

Woroniuk, Anna; Porter, Andrew; White, Gavin; Newman, Daniel T; Diamantopoulou, Zoi; Waring, Thomas; Rooney, Claire; Strathdee, Douglas; Marston, Daniel J; Hahn, Klaus M; Sansom, Owen J; Zech, Tobias; Malliri, Angeliki

2018-05-29

The perinuclear actin cap is an important cytoskeletal structure that regulates nuclear morphology and re-orientation during front-rear polarisation. The mechanisms regulating the actin cap are currently poorly understood. Here, we demonstrate that STEF/TIAM2, a Rac1 selective guanine nucleotide exchange factor, localises at the nuclear envelope, co-localising with the key perinuclear proteins Nesprin-2G and Non-muscle myosin IIB (NMMIIB), where it regulates perinuclear Rac1 activity. We show that STEF depletion reduces apical perinuclear actin cables (a phenotype rescued by targeting active Rac1 to the nuclear envelope), increases nuclear height and impairs nuclear re-orientation. STEF down-regulation also reduces perinuclear pMLC and decreases myosin-generated tension at the nuclear envelope, suggesting that STEF-mediated Rac1 activity regulates NMMIIB activity to promote stabilisation of the perinuclear actin cap. Finally, STEF depletion decreases nuclear stiffness and reduces expression of TAZ-regulated genes, indicating an alteration in mechanosensing pathways as a consequence of disruption of the actin cap.

The Xenopus Tgfbi is required for embryogenesis through regulation of canonical Wnt signalling.

PubMed

Wang, Feng; Hu, Wanzhou; Xian, Jian; Ohnuma, Shin-ichi; Brenton, James D

2013-07-01

Tgfbi, a fasciclin family extracellular matrix protein, has various roles in human diseases from corneal dystrophies to cancer. However, the molecular mechanisms that underlie its functions are poorly understood. Here, we studied the role of Tgfbi during Xenopus embryogenesis. During gastrulation and immediately after, Xtgfbi is expressed at developmentally important signaling centers including the dorsal marginal zone, notochord and floorplate. Xtgfbi knockdown by anti-sense morpholinos causes defective organizer induction, patterning and differentiation of muscle, neuron and neural crests, similar to suppression of canonical Wnt signaling. In Xenopus embryos and animal caps as well as DLD-1 cells, we show that Tgfbi is strongly required for the full activation of the canonical Wnt pathway by promoting phosphorylation of GSK3β and consequently enhancing the stabilization and nuclear localization of β-catenin. Further analysis shows that Tgfbi is likely to promote GSK3β phosphorylation through integrin-linked kinase. Copyright © 2013 Elsevier Inc. All rights reserved.

Anisotropic forces from spatially constrained focal adhesions mediate contact guidance directed cell migration

PubMed Central

Ray, Arja; Lee, Oscar; Win, Zaw; Edwards, Rachel M.; Alford, Patrick W.; Kim, Deok-Ho; Provenzano, Paolo P.

2017-01-01

Directed migration by contact guidance is a poorly understood yet vital phenomenon, particularly for carcinoma cell invasion on aligned collagen fibres. We demonstrate that for single cells, aligned architectures providing contact guidance cues induce constrained focal adhesion maturation and associated F-actin alignment, consequently orchestrating anisotropic traction stresses that drive cell orientation and directional migration. Consistent with this understanding, relaxing spatial constraints to adhesion maturation either through reduction in substrate alignment density or reduction in adhesion size diminishes the contact guidance response. While such interactions allow single mesenchymal-like cells to spontaneously ‘sense' and follow topographic alignment, intercellular interactions within epithelial clusters temper anisotropic cell–substratum forces, resulting in substantially lower directional response. Overall, these results point to the control of contact guidance by a balance of cell–substratum and cell–cell interactions, modulated by cell phenotype-specific cytoskeletal arrangements. Thus, our findings elucidate how phenotypically diverse cells perceive ECM alignment at the molecular level. PMID:28401884

Copper control of bacterial nitrous oxide emission and its impact on vitamin B12-dependent metabolism

PubMed Central

Sullivan, Matthew J.; Gates, Andrew J.; Appia-Ayme, Corinne; Rowley, Gary; Richardson, David J.

2013-01-01

Global agricultural emissions of the greenhouse gas nitrous oxide (N2O) have increased by around 20% over the last 100 y, but regulation of these emissions and their impact on bacterial cellular metabolism are poorly understood. Denitrifying bacteria convert nitrate in soils to inert di-nitrogen gas (N2) via N2O and the biochemistry of this process has been studied extensively in Paracoccus denitrificans. Here we demonstrate that expression of the gene encoding the nitrous oxide reductase (NosZ), which converts N2O to N2, is regulated in response to the extracellular copper concentration. We show that elevated levels of N2O released as a consequence of decreased cellular NosZ activity lead to the bacterium switching from vitamin B12-dependent to vitamin B12-independent biosynthetic pathways, through the transcriptional modulation of genes controlled by vitamin B12 riboswitches. This inhibitory effect of N2O can be rescued by addition of exogenous vitamin B12. PMID:24248380

Shigella reroutes host cell central metabolism to obtain high-flux nutrient supply for vigorous intracellular growth.

PubMed

Kentner, David; Martano, Giuseppe; Callon, Morgane; Chiquet, Petra; Brodmann, Maj; Burton, Olga; Wahlander, Asa; Nanni, Paolo; Delmotte, Nathanaël; Grossmann, Jonas; Limenitakis, Julien; Schlapbach, Ralph; Kiefer, Patrick; Vorholt, Julia A; Hiller, Sebastian; Bumann, Dirk

2014-07-08

Shigella flexneri proliferate in infected human epithelial cells at exceptionally high rates. This vigorous growth has important consequences for rapid progression to life-threatening bloody diarrhea, but the underlying metabolic mechanisms remain poorly understood. Here, we used metabolomics, proteomics, and genetic experiments to determine host and Shigella metabolism during infection in a cell culture model. The data suggest that infected host cells maintain largely normal fluxes through glycolytic pathways, but the entire output of these pathways is captured by Shigella, most likely in the form of pyruvate. This striking strategy provides Shigella with an abundant favorable energy source, while preserving host cell ATP generation, energy charge maintenance, and survival, despite ongoing vigorous exploitation. Shigella uses a simple three-step pathway to metabolize pyruvate at high rates with acetate as an excreted waste product. The crucial role of this pathway for Shigella intracellular growth suggests targets for antimicrobial chemotherapy of this devastating disease.

Shigella reroutes host cell central metabolism to obtain high-flux nutrient supply for vigorous intracellular growth

PubMed Central

Kentner, David; Martano, Giuseppe; Callon, Morgane; Chiquet, Petra; Brodmann, Maj; Burton, Olga; Wahlander, Asa; Nanni, Paolo; Delmotte, Nathanaël; Grossmann, Jonas; Limenitakis, Julien; Schlapbach, Ralph; Kiefer, Patrick; Vorholt, Julia A.; Hiller, Sebastian; Bumann, Dirk

2014-01-01

Shigella flexneri proliferate in infected human epithelial cells at exceptionally high rates. This vigorous growth has important consequences for rapid progression to life-threatening bloody diarrhea, but the underlying metabolic mechanisms remain poorly understood. Here, we used metabolomics, proteomics, and genetic experiments to determine host and Shigella metabolism during infection in a cell culture model. The data suggest that infected host cells maintain largely normal fluxes through glycolytic pathways, but the entire output of these pathways is captured by Shigella, most likely in the form of pyruvate. This striking strategy provides Shigella with an abundant favorable energy source, while preserving host cell ATP generation, energy charge maintenance, and survival, despite ongoing vigorous exploitation. Shigella uses a simple three-step pathway to metabolize pyruvate at high rates with acetate as an excreted waste product. The crucial role of this pathway for Shigella intracellular growth suggests targets for antimicrobial chemotherapy of this devastating disease. PMID:24958876

Cardiac Cachexia: Perspectives for Prevention and Treatment.

PubMed

Okoshi, Marina Politi; Capalbo, Rafael Verardino; Romeiro, Fernando G; Okoshi, Katashi

2017-01-01

Cachexia is a prevalent pathological condition associated with chronic heart failure. Its occurrence predicts increased morbidity and mortality independent of important clinical variables such as age, ventricular function, or heart failure functional class. The clinical consequences of cachexia are dependent on both weight loss and systemic inflammation, which accompany cachexia development. Skeletal muscle wasting is an important component of cachexia; it often precedes cachexia development and predicts poor outcome in heart failure. Cachexia clinically affects several organs and systems. It is a multifactorial condition where underlying pathophysiological mechanisms are not completely understood making it difficult to develop specific prevention and treatment therapies. Preventive strategies have largely focused on muscle mass preservation. Different treatment options have been described, mostly in small clinical studies or experimental settings. These include nutritional support, neurohormonal blockade, reducing intestinal bacterial translocation, anemia and iron deficiency treatment, appetite stimulants, immunomodulatory agents, anabolic hormones, and physical exercise regimens. Currently, nonpharmacological therapy such as nutritional support and physical exercise are considered central to cachexia prevention and treatment.

Artificial light pollution increases nocturnal vigilance in peahens.

PubMed

Yorzinski, Jessica L; Chisholm, Sarah; Byerley, Sydney D; Coy, Jeanee R; Aziz, Aisyah; Wolf, Jamie A; Gnerlich, Amanda C

2015-01-01

Artificial light pollution is drastically changing the sensory environments of animals. Even though many animals are now living in these changed environments, the effect light pollution has on animal behavior is poorly understood. We investigated the effect of light pollution on nocturnal vigilance in peahens (Pavo cristatus). Captive peahens were exposed to either artificial lighting or natural lighting at night. We employed a novel method to record their vigilance behavior by attaching accelerometers to their heads and continuously monitoring their large head movements. We found that light pollution significantly increases nocturnal vigilance in peahens. Furthermore, the birds faced a trade-off between vigilance and sleep at night: peahens that were more vigilant spent less time sleeping. Given the choice, peahens preferred to roost away from high levels of artificial lighting but showed no preference for roosting without artificial lighting or with low levels of artificial lighting. Our study demonstrates that light pollution can have a substantial impact on animal behavior that can potentially result in fitness consequences.

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.

Baleen whales host a unique gut microbiome with similarities to both carnivores and herbivores

DOE PAGES

Sanders, Jon G.; Beichman, Annabel C.; Roman, Joe; ...

2015-09-22

Mammals host gut microbiomes of immense physiological consequence, but the determinants of diversity in these communities remain poorly understood. Diet appears to be the dominant factor, but host phylogeny also seems to be an important, if unpredictable, correlate. Here we show that baleen whales, which prey on animals (fish and crustaceans), harbor unique gut microbiomes with surprising parallels in functional capacity and higher level taxonomy to those of terrestrial herbivores. These similarities likely reflect a shared role for fermentative metabolisms despite a shift in primary carbon sources from plant-derived to animal-derived polysaccharides, such as chitin. In contrast, protein catabolism andmore » essential amino acid synthesis pathways in baleen whale microbiomes more closely resemble those of terrestrial carnivores. Our results demonstrate that functional attributes of the microbiome can vary independently even given an animal-derived diet, illustrating how diet and evolutionary history combine to shape microbial diversity in the mammalian gut.« less

The intellectual disability gene Kirrel3 regulates target-specific mossy fiber synapse development in the hippocampus.

PubMed

Martin, E Anne; Muralidhar, Shruti; Wang, Zhirong; Cervantes, Diégo Cordero; Basu, Raunak; Taylor, Matthew R; Hunter, Jennifer; Cutforth, Tyler; Wilke, Scott A; Ghosh, Anirvan; Williams, Megan E

2015-11-17

Synaptic target specificity, whereby neurons make distinct types of synapses with different target cells, is critical for brain function, yet the mechanisms driving it are poorly understood. In this study, we demonstrate Kirrel3 regulates target-specific synapse formation at hippocampal mossy fiber (MF) synapses, which connect dentate granule (DG) neurons to both CA3 and GABAergic neurons. Here, we show Kirrel3 is required for formation of MF filopodia; the structures that give rise to DG-GABA synapses and that regulate feed-forward inhibition of CA3 neurons. Consequently, loss of Kirrel3 robustly increases CA3 neuron activity in developing mice. Alterations in the Kirrel3 gene are repeatedly associated with intellectual disabilities, but the role of Kirrel3 at synapses remained largely unknown. Our findings demonstrate that subtle synaptic changes during development impact circuit function and provide the first insight toward understanding the cellular basis of Kirrel3-dependent neurodevelopmental disorders.

Notch3 marks clonogenic mammary luminal progenitor cells in vivo

PubMed Central

Lafkas, Daniel; Rodilla, Veronica; Huyghe, Mathilde; Mourao, Larissa; Kiaris, Hippokratis

2013-01-01

The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive “triple negative” human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2SAT transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells. PMID:24100291

YAP and TAZ regulate adherens junction dynamics and endothelial cell distribution during vascular development

PubMed Central

Neto, Filipa; Klaus-Bergmann, Alexandra; Ong, Yu Ting; Alt, Silvanus; Vion, Anne-Clémence; Szymborska, Anna; Carvalho, Joana R; Hollfinger, Irene; Bartels-Klein, Eireen; Franco, Claudio A

2018-01-01

Formation of blood vessel networks by sprouting angiogenesis is critical for tissue growth, homeostasis and regeneration. How endothelial cells arise in adequate numbers and arrange suitably to shape functional vascular networks is poorly understood. Here we show that YAP/TAZ promote stretch-induced proliferation and rearrangements of endothelial cells whilst preventing bleeding in developing vessels. Mechanistically, YAP/TAZ increase the turnover of VE-Cadherin and the formation of junction associated intermediate lamellipodia, promoting both cell migration and barrier function maintenance. This is achieved in part by lowering BMP signalling. Consequently, the loss of YAP/TAZ in the mouse leads to stunted sprouting with local aggregation as well as scarcity of endothelial cells, branching irregularities and junction defects. Forced nuclear activity of TAZ instead drives hypersprouting and vascular hyperplasia. We propose a new model in which YAP/TAZ integrate mechanical signals with BMP signaling to maintain junctional compliance and integrity whilst balancing endothelial cell rearrangements in angiogenic vessels. PMID:29400648

Molecular phylogeny and comparative morphology indicate that odontostomatids (Alveolata, Ciliophora) form a distinct class-level taxon related to Armophorea.

PubMed

Fernandes, Noemi M; Vizzoni, Vinicius F; Borges, Bárbara do N; A G Soares, Carlos; Silva-Neto, Inácio D da; S Paiva, Thiago da

2018-04-18

The odontostomatids are among the least studied ciliates, possibly due to their small sizes, restriction to anaerobic environments and difficulty in culturing. Consequently, their phylogenetic affinities to other ciliate taxa are still poorly understood. In the present study, we analyzed newly obtained ribosomal gene sequences of the odontostomatids Discomorphella pedroeneasi and Saprodinium dentatum, together with sequences from the literature, including Epalxella antiquorum and a large assemblage of ciliate sequences representing the major recognized classes. The results show that D. pedroeneasi and S. dentatum form a deep-diverging branch related to metopid and clevelandellid armophoreans, corroborating the old literature. However E. antiquorum clustered with the morphologically discrepant plagiopylids, indicating that either the complex odontostomatid body architecture evolved convergently, or the positioning of E. antiquorum as a plagiopylid is artifactual. A new ciliate class, Odontostomatea n. cl., is proposed based on molecular analyses and comparative morphology of odontostomatids with related taxa. Copyright © 2018. Published by Elsevier Inc.

[Lack of insight in schizophrenia: a review].

PubMed

Raffard, S; Bayard, S; Capdevielle, D; Garcia, F; Boulenger, J-P; Gely-Nargeot, M-C

2008-10-01

Relative to other psychiatric disorders, patients with schizophrenia are often unaware of the consequences of their disease and their need for treatment. These deficits in awareness referred in general in the English literature as "poor insight", have been the focus of many clinical studies over recent years. This phenomenon, which is considered as fundamental in clinical evaluations of schizophrenia, should be understood as a multidimensional process rather than a dichotomic phenomenon, as is presently the case. The links between insight deficits and responses to vocational rehabilitation efforts represent a major interest in research, including those related to medication compliance and clinical outcome. To conduct such studies, various evaluation tools have been developed, enabling the assessment of insight, of its time-course and of its components in psychosis and schizophrenia spectrum disorders. The Scale to Assess Unawareness of illness in Mental Disorders (SUMD) developed by Amador and Strauss appears to be the most frequently used scale for the evaluation of awareness of the disorder in schizophrenia. Although the model proposed by Amador and Strauss is considered as the privileged model in the multidimensional approach of insight, it corresponds only to a phenomenological analysis of this concept. In the second part of this article, we thus review the current models attempting to explain the lack of insight in schizophrenia. Four current explanatory models of lack of insight will be described as follows: resulting either from adaptation or defence mechanisms to environmental stressors, resulting from cognitive bias of data processing, resulting from neuropsychological functional deficits and resulting from metacognitive deficits. Several hypotheses concerning these deficits arise from clinical studies. Although coping, and defence mechanisms to the consequences and stigmatization of the disease were hardly studied, the fact that poor insight does not appear related to the severity of symptomatology or to the emotional state of the patients argue against this hypothesis. Conversely, a considerable body of literature emphasized how unawareness may result from cognitive deficits. Research in neuropsychology and cognitive psychology has provided consistent results concerning the link between deficit in executive functions, frontal lobe dysfunction and poor insight. Recent studies on bias in cognitive information treatment and social cognition theories currently open new prospects.

The Inverse Relation Between Risks and Benefits: The Role of Affect and Expertise.

PubMed

Sokolowska, Joanna; Sleboda, Patrycja

2015-07-01

Although risk and benefits of risky activities are positively correlated in the real world, empirical results indicate that people perceive them as negatively correlated. The common explanation is that confounding benefits and losses stems from affect. In this article, we address the issue that has not been clearly established in studies on the affect heuristic: to what extent boundary conditions, such as judgments' generality and expertise, influence the presence of the inverse relation in judgments of hazards. These conditions were examined in four studies in which respondents evaluated general or specific benefits and risks of "affect-rich" and "affect-poor" hazards (ranging from investments to applications of stem cell research). In line with previous research, affect is defined as good or bad feelings integral to a stimulus. In contrast to previous research, affect is considered as related both to personal feelings and to social controversies associated with a hazard. Expertise is related to personal knowledge (laypersons vs. experts) as well as to objective knowledge (targets well vs. poorly known to science). The direct comparison of the input from personal and objective ignorance into the inverse relation has not been investigated previously. It was found that affect invoked by a hazard guides general but not specific judgments of its benefits and risks. Technical expertise helps to avoid simplified evaluations of consequences as long as they are well known to science. For new, poorly understood hazards (e.g., stem cell research), expertise does not protect from the perception of the inverse relation between benefits and risks. © 2015 Society for Risk Analysis.

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)

Assessing tinnitus and prospective tinnitus therapeutics using a psychophysical animal model.

PubMed

Bauer, C A; Brozoski, T J

2001-03-01

Subjective tinnitus is a common and often debilitating disorder that is difficult to study because it is a perceptual state without an objective stimulus correlate. Studying tinnitus in humans is further complicated by the heterogeneity of tinnitus quality, severity, and associated hearing loss. As a consequence, the pathophysiology of tinnitus is poorly understood and treatments are often unsuccessful. In the present study, an animal psychophysical model was developed to reflect several features of tinnitus observed in humans. Chronic tinnitus was induced in rats by a single intense unilateral exposure to noise. The tinnitus was measured using a psychophysical procedure, which required the animals to discriminate between auditory test stimuli consisting of tones, noise, and 0 dB. Tinnitus was indicated by a frequency-specific shift in discrimination functions with respect to control subjects not exposed to noise. The psychophysical consequences of the noise exposure were best explained by a tinnitus hypothesis and could not be explained easily by other consequences of noise exposure such as hearing loss. The qualitative features of the tinnitus were determined and related to the duration of noise exposure and the associated cochlear trauma. The tinnitus was found to persist and intensify over 17 months of testing. Finally, the tinnitus was reversibly attenuated by treatment with gabapentin, a GABA agonist. It was concluded that this model reflected several features of human tinnitus, such as its tonality and persistence, and could be useful as a screen for potential therapeutics as well as a tool to help unravel the pathophysiology of the disorder of phantom auditory perception.

Ovarian steroids act as respiratory stimulant and antioxidant against the causes and consequences of sleep-apnea in women.

PubMed

Boukari, Ryma; Laouafa, Sofien; Ribon-Demars, Alexandra; Bairam, Aida; Joseph, Vincent

2017-05-01

Evidence supports the importance of ovarian hormones as potential tools against sleep apneas in women. On one hand, progesterone is largely acknowledged as being a respiratory stimulant that reduces the frequency of apneas, but the underlying mechanisms remain poorly understood. Recent studies in mice showed that the respiratory effects of progesterone are mediated by at least two classes of progesterone receptors, including the nuclear (nPR) and membrane receptors (mPR). Some of these receptors (nPR) have sex-specific effects on the frequency of apneas recorded during sleep in mice, while mPRβ acts in males as well as in females. Moreover, sleep apnea is a condition that induces an "oxidative stress" response in several tissues, and this contributes to the deleterious consequences of sleep apneas, including the development of hypertension. While estradiol is recognized as an antioxidant hormone, its potential protective role has remained mostly ignored in the field. We will review recent data supporting an antioxidant role of estradiol in female rats exposed to intermittent hypoxia, a reliable animal model of sleep apnea. Since estradiol has two main receptors (ERα and ERβ) we will discuss their relative implications, and present new data showing a key role for ERα to prevent the hypertension induced by intermittent hypoxia. Overall this review highlights the fact that ovarian hormones could potentially be used as efficient tools against the causes (i.e. instabilities of the respiratory control system) and consequences (oxidative stress) of sleep apnea. Copyright © 2017 Elsevier B.V. All rights reserved.

The evolution of CHROMOMETHYLASES and gene body DNA methylation in plants.

PubMed

Bewick, Adam J; Niederhuth, Chad E; Ji, Lexiang; Rohr, Nicholas A; Griffin, Patrick T; Leebens-Mack, Jim; Schmitz, Robert J

2017-05-01

The evolution of gene body methylation (gbM), its origins, and its functional consequences are poorly understood. By pairing the largest collection of transcriptomes (>1000) and methylomes (77) across Viridiplantae, we provide novel insights into the evolution of gbM and its relationship to CHROMOMETHYLASE (CMT) proteins. CMTs are evolutionary conserved DNA methyltransferases in Viridiplantae. Duplication events gave rise to what are now referred to as CMT1, 2 and 3. Independent losses of CMT1, 2, and 3 in eudicots, CMT2 and ZMET in monocots and monocots/commelinids, variation in copy number, and non-neutral evolution suggests overlapping or fluid functional evolution of this gene family. DNA methylation within genes is widespread and is found in all major taxonomic groups of Viridiplantae investigated. Genes enriched with methylated CGs (mCG) were also identified in species sister to angiosperms. The proportion of genes and DNA methylation patterns associated with gbM are restricted to angiosperms with a functional CMT3 or ortholog. However, mCG-enriched genes in the gymnosperm Pinus taeda shared some similarities with gbM genes in Amborella trichopoda. Additionally, gymnosperms and ferns share a CMT homolog closely related to CMT2 and 3. Hence, the dependency of gbM on a CMT most likely extends to all angiosperms and possibly gymnosperms and ferns. The resulting gene family phylogeny of CMT transcripts from the most diverse sampling of plants to date redefines our understanding of CMT evolution and its evolutionary consequences on DNA methylation. Future, functional tests of homologous and paralogous CMTs will uncover novel roles and consequences to the epigenome.

Dual temperature effects on oxygen isotopic ratio of shallow-water coral skeleton: Consequences on seasonal and interannual records

NASA Astrophysics Data System (ADS)

Juillet-Leclerc, A.; Reynaud, S.

2009-04-01

Oxygen isotopic ratio from coral skeleton is regarded for a long time as promising climate archives at seasonal scale. Although in isotopic disequilibrium relative to seawater, it is supposed to obey to the isotope thermometer. Indeed, coral oxygen isotopic records are strongly temperature dependent, but d18O-temperature calibrations derived from different corals are highly variable. The isotope thermometer assumption does not take into account vital effects due to biogenic origin of the mineral. Corals are animals living in symbiosis with algae (zooxanthellae). Interactions between symbiont photosynthesis and coral skeleton carbonation have been abundantly observed but they remain poorly understood and the effects of photosynthesis on coral growth and skeleton oxygen ratio are ignored. Coral cultured under two light conditions enabled to relate metabolic parameters and oxygen isotopic variability with photosynthetic activity. By examining responses provided by each colony they revealed that photosynthesis significantly affected d18O, by an opposite sense compared with the sole temperature influence. Since temperature and light changes are associated during seasonal variations, this complicates the interpretation of seasonal record. Additionally, this complexity is amplified because photosynthetic activity is also directly impacted by temperature variability. Thus, the annual isotopic amplitude due to the "physical" temperature influence is partly compensated through photosynthesis. Similar opposite effect is also shown by extension rate of the cultured colonies. First, we will examine and quantify consequences of photosynthesis on growth rate and oxygen isotopic signature, from cultured corals. Second, we will consider the consequences of this vital effect on data series, at seasonal and interannual time scales.

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...

Chromatin as active matter

NASA Astrophysics Data System (ADS)

Agrawal, Ankit; Ganai, Nirmalendu; Sengupta, Surajit; Menon, Gautam I.

2017-01-01

Active matter models describe a number of biophysical phenomena at the cell and tissue scale. Such models explore the macroscopic consequences of driving specific soft condensed matter systems of biological relevance out of equilibrium through ‘active’ processes. Here, we describe how active matter models can be used to study the large-scale properties of chromosomes contained within the nuclei of human cells in interphase. We show that polymer models for chromosomes that incorporate inhomogeneous activity reproduce many general, yet little understood, features of large-scale nuclear architecture. These include: (i) the spatial separation of gene-rich, low-density euchromatin, predominantly found towards the centre of the nucleus, vis a vis. gene-poor, denser heterochromatin, typically enriched in proximity to the nuclear periphery, (ii) the differential positioning of individual gene-rich and gene-poor chromosomes, (iii) the formation of chromosome territories, as well as (iv), the weak size-dependence of the positions of individual chromosome centres-of-mass relative to the nuclear centre that is seen in some cell types. Such structuring is induced purely by the combination of activity and confinement and is absent in thermal equilibrium. We systematically explore active matter models for chromosomes, discussing how our model can be generalized to study variations in chromosome positioning across different cell types. The approach and model we outline here represent a preliminary attempt towards a quantitative, first-principles description of the large-scale architecture of the cell nucleus.

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

FBW7 suppression leads to SOX9 stabilization and increased malignancy in medulloblastoma.

PubMed

Suryo Rahmanto, Aldwin; Savov, Vasil; Brunner, Andrä; Bolin, Sara; Weishaupt, Holger; Malyukova, Alena; Rosén, Gabriela; Čančer, Matko; Hutter, Sonja; Sundström, Anders; Kawauchi, Daisuke; Jones, David Tw; Spruck, Charles; Taylor, Michael D; Cho, Yoon-Jae; Pfister, Stefan M; Kool, Marcel; Korshunov, Andrey; Swartling, Fredrik J; Sangfelt, Olle

2016-10-17

SOX9 is a master transcription factor that regulates development and stem cell programs. However, its potential oncogenic activity and regulatory mechanisms that control SOX9 protein stability are poorly understood. Here, we show that SOX9 is a substrate of FBW7, a tumor suppressor, and a SCF (SKP1/CUL1/F-box)-type ubiquitin ligase. FBW7 recognizes a conserved degron surrounding threonine 236 (T236) in SOX9 that is phosphorylated by GSK3 kinase and consequently degraded by SCF FBW 7α Failure to degrade SOX9 promotes migration, metastasis, and treatment resistance in medulloblastoma, one of the most common childhood brain tumors. FBW7 is either mutated or downregulated in medulloblastoma, and in cases where FBW7 mRNA levels are low, SOX9 protein is significantly elevated and this phenotype is associated with metastasis at diagnosis and poor patient outcome. Transcriptional profiling of medulloblastoma cells expressing a degradation-resistant SOX9 mutant reveals activation of pro-metastatic genes and genes linked to cisplatin resistance. Finally, we show that pharmacological inhibition of PI3K/AKT/mTOR pathway activity destabilizes SOX9 in a GSK3/FBW7-dependent manner, rendering medulloblastoma cells sensitive to cytostatic treatment. © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

CXCL12 Chemokine Expression Suppresses Human Pancreatic Cancer Growth and Metastasis

PubMed Central

Roy, Ishan; Zimmerman, Noah P.; Mackinnon, A. Craig; Tsai, Susan; Evans, Douglas B.; Dwinell, Michael B.

2014-01-01

Pancreatic ductal adenocarcinoma is an unsolved health problem with nearly 75% of patients diagnosed with advanced disease and an overall 5-year survival rate near 5%. Despite the strong link between mortality and malignancy, the mechanisms behind pancreatic cancer dissemination and metastasis are poorly understood. Correlative pathological and cell culture analyses suggest the chemokine receptor CXCR4 plays a biological role in pancreatic cancer progression. In vivo roles for the CXCR4 ligand CXCL12 in pancreatic cancer malignancy were investigated. CXCR4 and CXCR7 were consistently expressed in normal and cancerous pancreatic ductal epithelium, established cell lines, and patient-derived primary cancer cells. Relative to healthy exocrine ducts, CXCL12 expression was pathologically repressed in pancreatic cancer tissue specimens and patient-derived cell lines. To test the functional consequences of CXCL12 silencing, pancreatic cancer cell lines stably expressingthe chemokine were engineered. Consistent with a role for CXCL12 as a tumor suppressor, cells producing the chemokine wereincreasingly adherent and migration deficient in vitro and poorly metastatic in vivo, compared to control cells. Further, CXCL12 reintroduction significantly reduced tumor growth in vitro, with significantly smaller tumors in vivo, leading to a pronounced survival advantage in a preclinical model. Together, these data demonstrate a functional tumor suppressive role for the normal expression of CXCL12 in pancreatic ducts, regulating both tumor growth andcellulardissemination to metastatic sites. PMID:24594697

Prevalence, Outcomes, and Management of Enteral Tube Feeding Intolerance: A Retrospective Cohort Study in a Tertiary Center.

PubMed

Wang, Kailun; McIlroy, Kerry; Plank, Lindsay D; Petrov, Max S; Windsor, John A

2017-08-01

Enteral tube feeding (ETF) is the most common form of artificial feeding in hospitalized patients, and the development of intolerance (ETFI) is the most common complication. This study aimed to determine the prevalence of ETFI, the clinical consequences, and the current management approach to ETFI in hospitalized adult patients. Adult patients receiving ETF were identified from a prospective database in the Nutrition Services at Auckland City Hospital. Further information was obtained by the review of clinical records for a 12-month period, up to December 2014. The prevalence of ETFI was 33% among 754 patients. ETFI more frequently occurred in the intensive care unit ( P < .05). Patients with ETFI were less likely to reach their feeding goal rate ( P < .01). Multivariate analysis showed that younger age, certain specialties, and acute mesenteric ischemia were independent predictors of ETFI ( P < .05). The management of ETFI was highly variable. Medication was the most common treatment, while changes in the feeding protocol such as reducing infusion rate and stopping and changing the route of ETF were also frequently attempted. ETFI is a frequent problem in adult hospitalized patients receiving ETF, and it is associated with poor clinical outcomes such as inadequate nutrition and complications of feeding. While the pathophysiology is poorly understood, there also appears to be no standard evidence-based treatment. Studies investigating the mechanisms and optimized management are therefore indicated.

Impacts of crop insurance on water withdrawals for irrigation

NASA Astrophysics Data System (ADS)

Deryugina, Tatyana; Konar, Megan

2017-12-01

Agricultural production remains particularly vulnerable to weather fluctuations and extreme events, such as droughts, floods, and heat waves. Crop insurance is a risk management tool developed to mitigate some of this weather risk and protect farmer income in times of poor production. However, crop insurance may have unintended consequences for water resources sustainability, as the vast majority of freshwater withdrawals go to agriculture. The causal impact of crop insurance on water use in agriculture remains poorly understood. Here, we determine the empirical relationship between crop insurance and irrigation water withdrawals in the United States. Importantly, we use an instrumental variables approach to establish causality. Our methodology exploits a major policy change in the crop insurance system - the 1994 Federal Crop Insurance Reform Act - which imposed crop insurance requirements on farmers. We find that a 1% increase in insured crop acreage leads to a 0.223% increase in irrigation withdrawals, with most coming from groundwater aquifers. We identify farmers growing more groundwater-fed cotton as an important mechanism contributing to increased withdrawals. A 1% increase in insured crop acreage leads to a 0.624% increase in cotton acreage, or 95,602 acres. These results demonstrate that crop insurance causally leads to more irrigation withdrawals. More broadly, this work underscores the importance of determining causality in the water-food nexus as we endeavor to achieve global food security and water resources sustainability.

A Model of Fatigue Following Traumatic Brain Injury.

PubMed

Ponsford, Jennie; Schönberger, Michael; Rajaratnam, Shantha M W

2015-01-01

Fatigue is one of the most frequent sequelae of traumatic brain injury (TBI), although its causes are poorly understood. This study investigated the interrelationships between fatigue and sleepiness, vigilance performance, depression, and anxiety, using a structural equation modeling approach. Seventy-two participants with moderate to severe TBI (78% males) were recruited a median of 305 days postinjury. They completed the Fatigue Severity Scale, a vigilance task, the Epworth Sleepiness Scale, and Hospital Anxiety and Depression Scale. A model of the interrelationships between the study variables was developed, tested, and modified with path analysis. The modified model had a good overall fit (χ2 = 1.3, P = .54; comparative fit index = 1.0; root-mean square error of approximation = 0.0; standardized root-mean square residual = 0.02). Most paths in this model were significant (P < .05). Fatigue predicted anxiety, depression, and daytime sleepiness. Depression predicted daytime sleepiness and poor vigilance, whereas anxiety tended to predict reduced daytime sleepiness. This model confirms the complexity of fatigue experience. It supports the hypothesis that fatigue after TBI is a cause, not a consequence, of anxiety, depression, and daytime sleepiness, which, in turn (especially depression), may exacerbate fatigue by affecting cognitive functioning. These findings suggest that to alleviate fatigue, it is important to address each of these factors. However, the findings need to be confirmed with a longitudinal research design.

From projected species distribution to food-web structure under climate change.

PubMed

Albouy, Camille; Velez, Laure; Coll, Marta; Colloca, Francesco; Le Loc'h, François; Mouillot, David; Gravel, Dominique

2014-03-01

Climate change is inducing deep modifications in species geographic ranges worldwide. However, the consequences of such changes on community structure are still poorly understood, particularly the impacts on food-web properties. Here, we propose a new framework, coupling species distribution and trophic models, to predict climate change impacts on food-web structure across the Mediterranean Sea. Sea surface temperature was used to determine the fish climate niches and their future distributions. Body size was used to infer trophic interactions between fish species. Our projections reveal that 54 fish species of 256 endemic and native species included in our analysis would disappear by 2080-2099 from the Mediterranean continental shelf. The number of feeding links between fish species would decrease on 73.4% of the continental shelf. However, the connectance of the overall fish web would increase on average, from 0.26 to 0.29, mainly due to a differential loss rate of feeding links and species richness. This result masks a systematic decrease in predator generality, estimated here as the number of prey species, from 30.0 to 25.4. Therefore, our study highlights large-scale impacts of climate change on marine food-web structure with potential deep consequences on ecosystem functioning. However, these impacts will likely be highly heterogeneous in space, challenging our current understanding of climate change impact on local marine ecosystems. © 2013 John Wiley & Sons Ltd.

Inflammation drives thrombosis after Salmonella infection via CLEC-2 on platelets

PubMed Central

Hitchcock, Jessica R.; Cook, Charlotte N.; Bobat, Saeeda; Ross, Ewan A.; Flores-Langarica, Adriana; Lowe, Kate L.; Khan, Mahmood; Dominguez-Medina, C. Coral; Lax, Sian; Carvalho-Gaspar, Manuela; Hubscher, Stefan; Rainger, G. Ed; Cobbold, Mark; Buckley, Christopher D.; Mitchell, Tim J.; Mitchell, Andrea; Jones, Nick D.; Van Rooijen, N.; Kirchhofer, Daniel; Henderson, Ian R.; Adams, David H.; Watson, Steve P.; Cunningham, Adam F.

2015-01-01

Thrombosis is a common, life-threatening consequence of systemic infection; however, the underlying mechanisms that drive the formation of infection-associated thrombi are poorly understood. Here, using a mouse model of systemic Salmonella Typhimurium infection, we determined that inflammation in tissues triggers thrombosis within vessels via ligation of C-type lectin–like receptor-2 (CLEC-2) on platelets by podoplanin exposed to the vasculature following breaching of the vessel wall. During infection, mice developed thrombi that persisted for weeks within the liver. Bacteria triggered but did not maintain this process, as thrombosis peaked at times when bacteremia was absent and bacteria in tissues were reduced by more than 90% from their peak levels. Thrombus development was triggered by an innate, TLR4-dependent inflammatory cascade that was independent of classical glycoprotein VI–mediated (GPVI-mediated) platelet activation. After infection, IFN-γ release enhanced the number of podoplanin-expressing monocytes and Kupffer cells in the hepatic parenchyma and perivascular sites and absence of TLR4, IFN-γ, or depletion of monocytic-lineage cells or CLEC-2 on platelets markedly inhibited the process. Together, our data indicate that infection-driven thrombosis follows local inflammation and upregulation of podoplanin and platelet activation. The identification of this pathway offers potential therapeutic opportunities to control the devastating consequences of infection-driven thrombosis without increasing the risk of bleeding. PMID:26571395

Glioblastoma progression is assisted by induction of immunosuppressive function of pericytes through interaction with tumor cells

PubMed Central

Valdor, Rut; García-Bernal, David; Bueno, Carlos; Ródenas, Mónica; Moraleda, José M.; Macian, Fernando; Martínez, Salvador

2017-01-01

The establishment of immune tolerance during Glioblastoma Multiforme (GBM) progression, is characterized by high levels expression of anti-inflammatory cytokines, which suppress the function of tumor assocciated myeloid cells, and the activation and expansion of tumor antigen specific T cells. However, the mechanisms underlying the failed anti-tumor immune response around the blood vessels during GBM, are poorly understood. The consequences of possible interactions between cancer cells and the perivascular compartment might affect the tumor growth. In this work we show for the first time that GBM cells induce immunomodulatory changes in pericytes in a cell interaction-dependent manner, acquiring an immunosuppresive function that possibly assists the evasion of the anti-tumor immune response and consequently participates in tumor growth promotion. Expression of high levels of anti-inflammatory cytokines was detected in vitro and in vivo in brain pericytes that interacted with GBM cells (GBC-PC). Furthermore, reduction of surface expression of co-stimulatory molecules and major histocompatibility complex molecules in GBC-PC correlated with a failure of antigen presentation to T cells and the acquisition of the ability to supress T cell responses. In vivo, orthotopic xenotransplant of human glioblastoma in an immunocompetent mouse model showed significant GBM cell proliferation and tumor growth after the establishment of interspecific immunotolerance that followed GMB interaction with pericytes. PMID:28978142

Living in the Here and Now: Interrelationships between Impulsivity, Mindfulness, and Alcohol Misuse

PubMed Central

Murphy, Cara; MacKillop, James

2013-01-01

Rationale Impulsivity and mindfulness both emphasize orientation to the present, and both have been linked to alcohol misuse, but the relationship between the two is not clearly understood. Objectives To examine the relationships between elements of impulsivity and mindfulness, and to examine both variables in relation to alcohol misuse. Method Young adults (N = 116) were assessed for alcohol use, mindfulness, and impulsivity using psychometrically validated measures. Results Numerous significant associations were present among the facets of impulsivity and mindfulness. The variable most substantially associated with alcohol misuse was Negative Urgency (NU; i.e., proneness to act out under conditions of negative affect). After controlling for other variables, Negative Urgency (NU), Positive Urgency (PU), and delay discounting (DD) were significantly related to alcohol consumption. When examining drinking related consequences, only Lack of Premeditation (LoP) and Negative Urgency (NU) were significant associated. Conclusions There was considerable overlap between some elements of impulsivity and mindfulness while the overlap was negligible for other facets. The associations between mindfulness and alcohol misuse were entirely a function of impulsivity. In particular, acting on impulses while experiencing negative affect was significantly associated with level of alcohol consumption and level of alcohol-related risk. Steep discounting of future rewards was associated with alcohol consumption while poor premeditation was associated with adverse drinking consequences. These findings illustrate the importance of jointly studying impulsivity when examining purported effects of mindfulness traits. PMID:22169883

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

PubMed Central

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

2012-01-01

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

Pressure Monitoring to Detect Fault Rupture Due to CO 2 Injection

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

Keating, Elizabeth; Dempsey, David; Pawar, Rajesh

The capacity for fault systems to be reactivated by fluid injection is well-known. In the context of CO 2 sequestration, however, the consequence of reactivated faults with respect to leakage and monitoring is poorly understood. Using multi-phase fluid flow simulations, this study addresses key questions concerning the likelihood of ruptures, the timing of consequent upward leakage of CO 2, and the effectiveness of pressure monitoring in the reservoir and overlying zones for rupture detection. A range of injection scenarios was simulated using random sampling of uncertain parameters. These include the assumed distance between the injector and the vulnerable fault zone,more » the critical overpressure required for the fault to rupture, reservoir permeability, and the CO 2 injection rate. We assumed a conservative scenario, in which if at any time during the five-year simulations the critical fault overpressure is exceeded, the fault permeability is assumed to instantaneously increase. For the purposes of conservatism we assume that CO 2 injection continues ‘blindly’ after fault rupture. We show that, despite this assumption, in most cases the CO 2 plume does not reach the base of the ruptured fault after 5 years. As a result, one possible implication of this result is that leak mitigation strategies such as pressure management have a reasonable chance of preventing a CO 2 leak.« less

Pressure Monitoring to Detect Fault Rupture Due to CO 2 Injection

DOE PAGES

Keating, Elizabeth; Dempsey, David; Pawar, Rajesh

2017-08-18

The capacity for fault systems to be reactivated by fluid injection is well-known. In the context of CO 2 sequestration, however, the consequence of reactivated faults with respect to leakage and monitoring is poorly understood. Using multi-phase fluid flow simulations, this study addresses key questions concerning the likelihood of ruptures, the timing of consequent upward leakage of CO 2, and the effectiveness of pressure monitoring in the reservoir and overlying zones for rupture detection. A range of injection scenarios was simulated using random sampling of uncertain parameters. These include the assumed distance between the injector and the vulnerable fault zone,more » the critical overpressure required for the fault to rupture, reservoir permeability, and the CO 2 injection rate. We assumed a conservative scenario, in which if at any time during the five-year simulations the critical fault overpressure is exceeded, the fault permeability is assumed to instantaneously increase. For the purposes of conservatism we assume that CO 2 injection continues ‘blindly’ after fault rupture. We show that, despite this assumption, in most cases the CO 2 plume does not reach the base of the ruptured fault after 5 years. As a result, one possible implication of this result is that leak mitigation strategies such as pressure management have a reasonable chance of preventing a CO 2 leak.« less

Methylphenidate disrupts cytoskeletal homeostasis and reduces membrane-associated lipid content in juvenile rat hippocampus.

PubMed

Schmitz, Felipe; Pierozan, Paula; Biasibetti-Brendler, Helena; Ferreira, Fernanda Silva; Dos Santos Petry, Fernanda; Trindade, Vera Maria Treis; Pessoa-Pureur, Regina; Wyse, Angela T S

2017-12-29

Although methylphenidate (MPH) is ubiquitously prescribed to children and adolescents, the consequences of chronic utilization of this psychostimulant are poorly understood. In this study, we investigated the effects of MPH on cytoskeletal homeostasis and lipid content in rat hippocampus. Wistar rats received intraperitoneal injections of MPH (2.0 mg/kg) or saline solution (controls), once a day, from the 15th to the 44th day of age. Results showed that MPH provoked hypophosphorylation of glial fibrillary acidic protein (GFAP) and reduced its immunocontent. Middle and high molecular weight neurofilament subunits (NF-M, NF-H) were hypophosphorylated by MPH on KSP repeat tail domains, while NFL, NFM and NFH immunocontents were not altered. MPH increased protein phosphatase 1 (PP1) and 2A (PP2A) immunocontents. MPH also decreased the total content of ganglioside and phospholipid, as well as the main brain gangliosides (GM1, GD1a, and GD1b) and the major brain phospholipids (sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine). Total cholesterol content was also reduced in the hippocampi of juvenile rats treated with MPH. These results provide evidence that disruptions of cytoskeletal and lipid homeostasis in hippocampus of juvenile rats are triggers by chronic MPH treatment and present a new basis for understanding the effects and consequences associated with chronic use of this psychostimulant during the development of the central nervous system.

Short-, Medium-, and Long-Term Consequences of Poor Infant Health: An Analysis Using Siblings and Twins

ERIC Educational Resources Information Center

Oreopoulos, Philip; Stabile, Mark; Walld, Randy; Roos, Leslie L.

2008-01-01

We use administrative data on a sample of births between 1978 and 1985 to investigate the short-, medium-, and long-term consequences of poor infant health. Our findings offer several advances to the existing literature on the effects of early infant health on subsequent health, education, and labor force attachment. First, we use a large sample…

Vertical Equity Consequences of Very High Cigarette Tax Increases: If the Poor Are the Ones Smoking, How Could Cigarette Tax Increases Be Progressive?

ERIC Educational Resources Information Center

Colman, Gregory J.; Remler, Dahlia K.

2008-01-01

Cigarette smoking is concentrated among low-income groups. Consequently, cigarette taxes are considered regressive. However, if poorer individuals are much more price sensitive than richer individuals, then tax increases would reduce smoking much more among the poor and their cigarette tax expenditures as a share of income would rise by much less…

Parental antagonism and parent–offspring co-adaptation interact to shape family life

PubMed Central

Meunier, Joël; Kölliker, Mathias

2012-01-01

The family is an arena for conflicts between offspring, mothers and fathers that need resolving to promote the evolution of parental care and the maintenance of family life. Co-adaptation is known to contribute to the resolution of parent–offspring conflict over parental care by selecting for combinations of offspring demand and parental supply that match to maximize the fitness of family members. However, multiple paternity and differences in the level of care provided by mothers and fathers can generate antagonistic selection on offspring demand (mediated, for example, by genomic imprinting) and possibly hamper co-adaptation. While parent–offspring co-adaptation and parental antagonism are commonly considered two major processes in the evolution of family life, their co-occurrence and the evolutionary consequences of their joint action are poorly understood. Here, we demonstrate the simultaneous and entangled effects of these two processes on outcomes of family interactions, using a series of breeding experiments in the European earwig, Forficula auricularia, an insect species with uniparental female care. As predicted from parental antagonism, we show that paternally inherited effects expressed in offspring influence both maternal care and maternal investment in future reproduction. However, and as expected from the entangled effects of parental antagonism and co-adaptation, these effects critically depended on postnatal interactions with caring females and maternally inherited effects expressed in offspring. Our results demonstrate that parent–offspring co-adaptation and parental antagonism are entangled key drivers in the evolution of family life that cannot be fully understood in isolation. PMID:22810433

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.

[Health consequences of smoking electronic cigarettes are poorly described].

PubMed

Tøttenborg, Sandra Søgaard; Holm, Astrid Ledgaard; Wibholm, Niels Christoffer; Lange, Peter

2014-09-01

Despite increasing popularity, health consequences of vaping (smoking electronic cigarettes, e-cigarettes) are poorly described. Few studies suggest that vaping has less deleterious effects on lung function than smoking conventional cigarettes. One large study found that e-cigarettes were as efficient as nicotine patches in smoking cessation. The long-term consequences of vaping are however unknown and while some experts are open towards e-cigarettes as a safer way of satisfying nicotine addiction, others worry that vaping in addition to presenting a health hazard may lead to an increased number of smokers of conventional cigarettes.

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 ...

Annual Research Review: Improved nutrition--pathway to resilience.

PubMed

Yousafzai, Aisha K; Rasheed, Muneera A; Bhutta, Zulfiqar A

2013-04-01

Early child nutritional deficiencies are prevalent in low- and middle-countries with consequences linked not only to poor survival and growth, but also to poor development outcomes. Children in disadvantaged communities face multiple risks for nutritional deficiencies, yet some children may be less susceptible or may recover more quickly from malnutrition. A greater understanding is needed about factors which moderate the effects of nutrition-related risks and foster resilience to protect against or ameliorate poor development outcomes. A literature review was undertaken from August to December 2011 and updated in August 2012. Key word searches using terms Nutrition, Malnutrition, Child Development, Responsive Care, Stimulation, Low and Middle Income Countries and Resilience were undertaken using PubMed and Psychinfo. Dietary adequacy is critical for growth and development, but current evidence indicates that nutrition supplementation alone is insufficient to foster resilience to protect against, mitigate, and recover from nutritional threats and to promote healthy development. The combination of nutrition interventions with stimulation and responsive care is necessary. Combined nutrition and psychosocial stimulation approaches can potentially work effectively together to promote protective factors and mitigate risks for poor cognitive, motor, social, and affective functioning helping children to adapt in times of adversity. However, there are gaps in our existing knowledge to combine nutrition and psychosocial stimulation interventions effectively and promote these interventions at scale. Research needs to address barriers at the level of family, community, programme, and policy which have prevented thus far the uptake of combined nutrition and psychosocial intervention strategies. Further investigations are needed on how to provide support to caregivers, enabling them to implement appropriate care for feeding and stimulation. Finally, the effect of combined interventions on pathways of care and protective mediators that foster resilience need to be better understood to determine focus areas for content of combined intervention curricula which help families in high-risk settings. © 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.

Contaminants of emerging concern in tributaries to the Laurentian Great Lakes: II. Biological consequences of exposure

PubMed Central

Brigham, Mark E.; Choy, Steven J.; Moore, Jeremy N.; Banda, Jo A.; Gefell, Daniel J.; Minarik, Thomas A.

2017-01-01

The Laurentian Great Lakes contain one fifth of the world’s surface freshwater and have been impacted by human activity since the Industrial Revolution. In addition to legacy contaminants, nitrification and invasive species, this aquatic ecosystem is also the recipient of Contaminants of Emerging Concern (CECs) with poorly understood biological consequences. In the current study, we documented the presence, concentrations, and biological effects of CECs across 27 field sites in six Great Lakes tributaries by examining over 2250 resident and caged sunfish (Lepomis ssp.) for a variety of morphological and physiological endpoints and related these results to CEC occurrence. CEC were ubiquitous across studies sites and their presence and concentrations in water and sediment were highest in effluent dominated rivers and downstream of municipal wastewater treatment plant discharges. However, even putative upstream reference sites were not free of CEC presence and fish at these sites exhibited biological effects consistent with CEC exposure. Only the Fox River exhibited consistent adverse biological effects, including increased relative liver size, greater prominence of hepatocyte vacuoles and increased plasma glucose concentrations. Canonical Redundancy Analysis revealed consistent patterns of biological consequences of CEC exposure across all six tributaries. Increasing plasma glucose concentrations, likely as a result of pollutant-induced metabolic stress, were associated with increased relative liver size and greater prominence of hepatocyte vacuoles. These indicators of pollutant exposure were inversely correlated with indicators of reproductive potential including smaller gonad size and less mature gametes. The current study highlights the need for greater integration of chemical and biological studies and suggests that CECs in the Laurentian Great Lakes Basin may adversely affect the reproductive potential of exposed fish populations. PMID:28953953

Genetic Disruption of 21-Hydroxylase in Zebrafish Causes Interrenal Hyperplasia.

PubMed

Eachus, Helen; Zaucker, Andreas; Oakes, James A; Griffin, Aliesha; Weger, Meltem; Güran, Tülay; Taylor, Angela; Harris, Abigail; Greenfield, Andy; Quanson, Jonathan L; Storbeck, Karl-Heinz; Cunliffe, Vincent T; Müller, Ferenc; Krone, Nils

2017-12-01

Congenital adrenal hyperplasia is a group of common inherited disorders leading to glucocorticoid deficiency. Most cases are caused by 21-hydroxylase deficiency (21OHD). The systemic consequences of imbalanced steroid hormone biosynthesis due to severe 21OHD remains poorly understood. Therefore, we developed a zebrafish model for 21OHD, which focuses on the impairment of glucocorticoid biosynthesis. A single 21-hydroxylase gene (cyp21a2) is annotated in the zebrafish genome based on sequence homology. Our in silico analysis of the 21-hydroxylase (Cyp21a2) protein sequence suggests a sufficient degree of similarity for the usage of zebrafish cyp21a2 to model aspects of human 21OHD in vivo. We determined the spatiotemporal expression patterns of cyp21a2 by whole-mount in situ hybridization and reverse transcription polymerase chain reaction throughout early development. Early cyp21a2 expression is restricted to the interrenal gland (zebrafish adrenal counterpart) and the brain. To further explore the in vivo consequences of 21OHD we created several cyp21a2 null-allele zebrafish lines by using a transcription activator-like effector nuclease genomic engineering strategy. Homozygous mutant zebrafish larvae showed an upregulation of the hypothalamic-pituitary-interrenal (HPI) axis and interrenal hyperplasia. Furthermore, Cyp21a2-deficient larvae had a typical steroid profile, with reduced concentrations of cortisol and increased concentrations of 17-hydroxyprogesterone and 21-deoxycortisol. Affected larvae showed an upregulation of the HPI axis and interrenal hyperplasia. Downregulation of the glucocorticoid-responsive genes pck1 and fkbp5 indicated systemic glucocorticoid deficiency. Our work demonstrates the crucial role of Cyp21a2 in glucocorticoid biosynthesis in zebrafish larvae and establishes an in vivo model allowing studies of systemic consequences of altered steroid hormone synthesis.

Contaminants of emerging concern in tributaries to the Laurentian Great Lakes: II. Biological consequences of exposure.

PubMed

Thomas, Linnea M; Jorgenson, Zachary G; Brigham, Mark E; Choy, Steven J; Moore, Jeremy N; Banda, Jo A; Gefell, Daniel J; Minarik, Thomas A; Schoenfuss, Heiko L

2017-01-01

The Laurentian Great Lakes contain one fifth of the world's surface freshwater and have been impacted by human activity since the Industrial Revolution. In addition to legacy contaminants, nitrification and invasive species, this aquatic ecosystem is also the recipient of Contaminants of Emerging Concern (CECs) with poorly understood biological consequences. In the current study, we documented the presence, concentrations, and biological effects of CECs across 27 field sites in six Great Lakes tributaries by examining over 2250 resident and caged sunfish (Lepomis ssp.) for a variety of morphological and physiological endpoints and related these results to CEC occurrence. CEC were ubiquitous across studies sites and their presence and concentrations in water and sediment were highest in effluent dominated rivers and downstream of municipal wastewater treatment plant discharges. However, even putative upstream reference sites were not free of CEC presence and fish at these sites exhibited biological effects consistent with CEC exposure. Only the Fox River exhibited consistent adverse biological effects, including increased relative liver size, greater prominence of hepatocyte vacuoles and increased plasma glucose concentrations. Canonical Redundancy Analysis revealed consistent patterns of biological consequences of CEC exposure across all six tributaries. Increasing plasma glucose concentrations, likely as a result of pollutant-induced metabolic stress, were associated with increased relative liver size and greater prominence of hepatocyte vacuoles. These indicators of pollutant exposure were inversely correlated with indicators of reproductive potential including smaller gonad size and less mature gametes. The current study highlights the need for greater integration of chemical and biological studies and suggests that CECs in the Laurentian Great Lakes Basin may adversely affect the reproductive potential of exposed fish populations.

Contaminants of emerging concern in tributaries to the Laurentian Great Lakes: II. Biological consequences of exposure

USGS Publications Warehouse

Thomas, Linnea M.; Jorgenson, Zachary G.; Brigham, Mark E.; Choy, Steven J.; Moore, Jeremy N.; Banda, Jo A.; Gefell, D.J.; Minarik, Thomas A.; Schoenfuss, Heiko L.

2017-01-01

The Laurentian Great Lakes contain one fifth of the world’s surface freshwater and have been impacted by human activity since the Industrial Revolution. In addition to legacy contaminants, nitrification and invasive species, this aquatic ecosystem is also the recipient of Contaminants of Emerging Concern (CECs) with poorly understood biological consequences. In the current study, we documented the presence, concentrations, and biological effects of CECs across 27 field sites in six Great Lakes tributaries by examining over 2250 resident and caged sunfish (Lepomis ssp.) for a variety of morphological and physiological endpoints and related these results to CEC occurrence. CEC were ubiquitous across studies sites and their presence and concentrations in water and sediment were highest in effluent dominated rivers and downstream of municipal wastewater treatment plant discharges. However, even putative upstream reference sites were not free of CEC presence and fish at these sites exhibited biological effects consistent with CEC exposure. Only the Fox River exhibited consistent adverse biological effects, including increased relative liver size, greater prominence of hepatocyte vacuoles and increased plasma glucose concentrations. Canonical Redundancy Analysis revealed consistent patterns of biological consequences of CEC exposure across all six tributaries. Increasing plasma glucose concentrations, likely as a result of pollutant-induced metabolic stress, were associated with increased relative liver size and greater prominence of hepatocyte vacuoles. These indicators of pollutant exposure were inversely correlated with indicators of reproductive potential including smaller gonad size and less mature gametes. The current study highlights the need for greater integration of chemical and biological studies and suggests that CECs in the Laurentian Great Lakes Basin may adversely affect the reproductive potential of exposed fish populations.

Understanding soil erosion impacts in temperate agroecosystems: bridging the gap between geomorphology and soil ecology

NASA Astrophysics Data System (ADS)

Baxter, C.; Rowan, J. S.; McKenzie, B. M.; Neilson, R.

2013-04-01

Soil is a key asset of natural capital, providing a myriad of goods and ecosystem services that sustain life through regulating, supporting and provisioning roles, delivered by chemical, physical and biological processes. One of the greatest threats to soil is accelerated erosion, which raises a natural process to unsustainable levels, and has downstream consequences (e.g. economic, environmental and social). Global intensification of agroecosystems is a major cause of soil erosion which, in light of predicted population growth and increased demand for food security, will continue or increase. Elevated erosion and transport is common in agroecosystems and presents a multi-disciplinary problem with direct physical impacts (e.g. soil loss), other less tangible impacts (e.g. loss of ecosystem productivity), and indirect downstream effects that necessitate an integrated approach to effectively address the problem. Climate is also likely to increase susceptibility of soil to erosion. Beyond physical response, the consequences of erosion on soil biota have hitherto been ignored, yet biota play a fundamental role in ecosystem service provision. To our knowledge few studies have addressed the gap between erosion and consequent impacts on soil biota. Transport and redistribution of soil biota by erosion is poorly understood, as is the concomitant impact on biodiversity and ability of soil to deliver the necessary range of ecosystem services to maintain function. To investigate impacts of erosion on soil biota a two-fold research approach is suggested. Physical processes involved in redistribution should be characterised and rates of transport and redistribution quantified. Similarly, cumulative and long-term impacts of biota erosion should be considered. Understanding these fundamental aspects will provide a basis upon which mitigation strategies can be considered.

Compared effects of missense mutations in Very-Long-Chain Acyl-CoA Dehydrogenase deficiency: Combined analysis by structural, functional and pharmacological approaches.

PubMed

Gobin-Limballe, Stéphanie; McAndrew, Ryan P; Djouadi, Fatima; Kim, Jung-Ja; Bastin, Jean

2010-05-01

Very-Long-Chain Acyl-CoA Dehydrogenase deficiency (VLCADD) is an autosomal recessive disorder considered as one of the more common ss-oxidation defects, possibly associated with neonatal cardiomyopathy, infantile hepatic coma, or adult-onset myopathy. Numerous gene missense mutations have been described in these VLCADD phenotypes, but only few of them have been structurally and functionally analyzed, and the molecular basis of disease variability is still poorly understood. To address this question, we first analyzed fourteen disease-causing amino acid changes using the recently described crystal structure of VLCAD. The predicted effects varied from the replacement of amino acid residues lining the substrate binding cavity, involved in holoenzyme-FAD interactions or in enzyme dimerisation, predicted to have severe functional consequences, up to amino acid substitutions outside key enzyme domains or lying on near enzyme surface, with predicted milder consequences. These data were combined with functional analysis of residual fatty acid oxidation (FAO) and VLCAD protein levels in patient cells harboring these mutations, before and after pharmacological stimulation by bezafibrate. Mutations identified as detrimental to the protein structure in the 3-D model were generally associated to profound FAO and VLCAD protein deficiencies in the patient cells, however, some mutations affecting FAD binding or monomer-monomer interactions allowed a partial response to bezafibrate. On the other hand, bezafibrate restored near-normal FAO rates in some mutations predicted to have milder consequences on enzyme structure. Overall, combination of structural, biochemical, and pharmacological analysis allowed assessment of the relative severity of individual mutations, with possible applications for disease management and therapeutic approach. Copyright 2010 Elsevier B.V. All rights reserved.

Examples of, reasons for, and consequences of the poor quality of wind data from ships for the marine boundary layer: Implications for remote sensing

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

Pierson, W.J. Jr.

1990-08-15

Wind reports by data buoys are used to demonstrate that these reports have in the past provided useful values for the synoptic scale winds and that at present these reports provide very reliable values for the synoptic scale winds. Past studies of wind reports by ships have revealed that the data are of poor quality, but the causes for this poor quality are not identified. Examples of the poor quality of wind data from ships are obtained by comparing ship reports with buoy reports and comparing reports of different kinds of ships with each other. These comparisons identify many differentmore » reasons for the poor quality of wind data from ships. Suggestions are made for improving the quality of ship data. The consequences of the poor quality of ship winds are described in terms of the effects on weather and wave forecasts. The implications for remotely sensed winds are discussed.« less

Genetic Patterns of Common-Bean Seed Acquisition and Early-Stage Adoption Among Farmer Groups in Western Uganda

PubMed Central

Wilkus, Erin L.; Berny Mier y Teran, Jorge C.; Mukankusi, Clare M.; Gepts, Paul

2018-01-01

Widespread adoption of new varieties can be valuable, especially where improved agricultural production technologies are hard to access. However, as farmers adopt new varieties, in situ population structure and genetic diversity of their seed holdings can change drastically. Consequences of adoption are still poorly understood due to a lack of crop genetic diversity assessments and detailed surveys of farmers' seed management practices. Common bean (Phaseolus vulgaris) is an excellent model for these types of studies, as it has a long history of cultivation among smallholder farmers, exhibits eco-geographic patterns of diversity (e.g., Andean vs. Mesoamerican gene-pools), and has been subjected to post-Columbian dispersal and recent introduction of improved cultivars. The Hoima district of western Uganda additionally provides an excellent social setting for evaluating consequences of adoption because access to improved varieties has varied across farmer groups in this production region. This study establishes a baseline understanding of the common bean diversity found among household producers in Uganda and compares the crop population structure, diversity and consequences of adoption of household producers with different adoption practices. Molecular diversity analysis, based on 4,955 single nucleotide polymorphism (SNP) markers, evaluated a total of 1,156 seed samples that included 196 household samples collected from household producers in the Hoima district, 19 breeder-selected varieties used in participatory breeding activities that had taken place prior to the study in the region, and a global bean germplasm collection. Households that had participated in regional participatory breeding efforts were more likely to adopt new varieties and, consequently, diversify their seed stocks than those that had not participated. Of the three farmer groups that participated in breeding efforts, households from the farmer group with the longest history of bean production were more likely to conserve “Seed Engufu”, a local “Calima”-type variety of the Andean bean gene pool, and, at the same time, introduce rare Mesoamerican gene pool varieties into household seed stocks. PMID:29868053

Anabolic steroids and cardiovascular risk.

PubMed

Angell, Peter; Chester, Neil; Green, Danny; Somauroo, John; Whyte, Greg; George, Keith

2012-02-01

Recent reports from needle exchange programmes and other public health initiatives have suggested growing use of anabolic steroids (AS) in the UK and other countries. Data indicate that AS use is not confined to body-builders or high-level sportsmen. Use has spread to professionals working in emergency services, casual fitness enthusiasts and subelite sportsmen and women. Although the precise health consequences of AS use is largely undefined, AS use represents a growing public health concern. Data regarding the consequences of AS use on cardiovascular health are limited to case studies and a modest number of small cohort studies. Numerous case studies have linked AS use with a variety of cardiovascular disease (CVD) events or endpoints, including myocardial infarction, stroke and death. Large-scale epidemiological studies to support these links are absent. Consequently, the impact of AS use upon known CVD risk factors has been studied in relatively small, case-series studies. Data relating AS use to elevated blood pressure, altered lipid profiles and ECG abnormalities have been reported, but are often limited in scope, and other studies have often produced equivocal outcomes. The use of AS has been linked to the appearance of concentric left ventricular hypertrophy as well as endothelial dysfunction but the data again remains controversial. The mechanisms responsible for the negative effect of AS on cardiovascular health are poorly understood, especially in humans. Possibilities include direct effects on myocytes and endothelial cells, reduced intracellular Ca2+ levels, increased release of apoptogenic factors, as well as increased collagen crosslinks between myocytes. New data relating AS use to cardiovascular health risks are emerging, as novel technologies are developed (especially in non-invasive imaging) that can assess physiological structure and function. Continued efforts to fully document the cardiovascular health consequences of AS use is important to provide a clear, accurate, public health message to the many groups now using AS for performance and image enhancement.

Genetic Patterns of Common-Bean Seed Acquisition and Early-Stage Adoption Among Farmer Groups in Western Uganda.

PubMed

Wilkus, Erin L; Berny Mier Y Teran, Jorge C; Mukankusi, Clare M; Gepts, Paul

2018-01-01

Widespread adoption of new varieties can be valuable, especially where improved agricultural production technologies are hard to access. However, as farmers adopt new varieties, in situ population structure and genetic diversity of their seed holdings can change drastically. Consequences of adoption are still poorly understood due to a lack of crop genetic diversity assessments and detailed surveys of farmers' seed management practices. Common bean ( Phaseolus vulgaris ) is an excellent model for these types of studies, as it has a long history of cultivation among smallholder farmers, exhibits eco-geographic patterns of diversity (e.g., Andean vs. Mesoamerican gene-pools), and has been subjected to post-Columbian dispersal and recent introduction of improved cultivars. The Hoima district of western Uganda additionally provides an excellent social setting for evaluating consequences of adoption because access to improved varieties has varied across farmer groups in this production region. This study establishes a baseline understanding of the common bean diversity found among household producers in Uganda and compares the crop population structure, diversity and consequences of adoption of household producers with different adoption practices. Molecular diversity analysis, based on 4,955 single nucleotide polymorphism (SNP) markers, evaluated a total of 1,156 seed samples that included 196 household samples collected from household producers in the Hoima district, 19 breeder-selected varieties used in participatory breeding activities that had taken place prior to the study in the region, and a global bean germplasm collection. Households that had participated in regional participatory breeding efforts were more likely to adopt new varieties and, consequently, diversify their seed stocks than those that had not participated. Of the three farmer groups that participated in breeding efforts, households from the farmer group with the longest history of bean production were more likely to conserve "Seed Engufu", a local "Calima"-type variety of the Andean bean gene pool, and, at the same time, introduce rare Mesoamerican gene pool varieties into household seed stocks.

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

Adolescent Sleepiness: Causes and Consequences.

PubMed

Hansen, Shana L; Capener, Dale; Daly, Christopher

2017-09-01

Insufficient sleep duration and poor sleep quality are common among adolescents. The multidimensional causes of insufficient sleep duration and poor sleep quality include biological, health-related, environmental, and lifestyle factors. The most common direct consequence of insufficient and/or poor sleep quality is excessive daytime sleepiness, which may contribute to poor academic performance, behavioral health problems, substance use, and drowsy driving. Evaluation of sleepiness includes a detailed sleep history and sleep diary, with polysomnography only required for the assessment of specific sleep disorders. Management involves encouraging healthy sleep practices such as having consistent bed and wake times, limiting caffeine and electronics at night before bed, and eliminating napping, in addition to treating any existing sleep or medical disorders. [Pediatr Ann. 2017;46(9):e340-e344.]. Copyright 2017, SLACK Incorporated.

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...

Excitotoxicity in the pathogenesis of neurological and psychiatric disorders: Therapeutic implications.

PubMed

Olloquequi, Jordi; Cornejo-Córdova, Elizabeth; Verdaguer, Ester; Soriano, Francesc X; Binvignat, Octavio; Auladell, Carme; Camins, Antoni

2018-03-01

Neurological and psychiatric disorders are leading contributors to the global disease burden, having a serious impact on the quality of life of both patients and their relatives. Although the molecular events underlying these heterogeneous diseases remain poorly understood, some studies have raised the idea of common mechanisms involved. In excitotoxicity, there is an excessive activation of glutamate receptors by excitatory amino acids, leading to neuronal damage. Thus, the excessive release of glutamate can lead to a dysregulation of Ca 2+ homeostasis, triggering the production of free radicals and oxidative stress, mitochondrial dysfunction and eventually cell death. Although there is a consensus in considering excitotoxicity as a hallmark in most neurodegenerative diseases, increasing evidence points to the relevant role of this pathological mechanism in other illnesses affecting the central nervous system. Consequently, antagonists of glutamate receptors are used in current treatments or in clinical trials in both neurological and psychiatric disorders. However, drugs modulating other aspects of the excitotoxic mechanism could be more beneficial. This review discusses how excitotoxicity is involved in the pathogenesis of different neurological and psychiatric disorders and the promising strategies targeting the excitotoxic insult.

Fip1 regulates mRNA alternative polyadenylation to promote stem cell self-renewal

PubMed Central

Lackford, Brad; Yao, Chengguo; Charles, Georgette M; Weng, Lingjie; Zheng, Xiaofeng; Choi, Eun-A; Xie, Xiaohui; Wan, Ji; Xing, Yi; Freudenberg, Johannes M; Yang, Pengyi; Jothi, Raja; Hu, Guang; Shi, Yongsheng

2014-01-01

mRNA alternative polyadenylation (APA) plays a critical role in post-transcriptional gene control and is highly regulated during development and disease. However, the regulatory mechanisms and functional consequences of APA remain poorly understood. Here, we show that an mRNA 3′ processing factor, Fip1, is essential for embryonic stem cell (ESC) self-renewal and somatic cell reprogramming. Fip1 promotes stem cell maintenance, in part, by activating the ESC-specific APA profiles to ensure the optimal expression of a specific set of genes, including critical self-renewal factors. Fip1 expression and the Fip1-dependent APA program change during ESC differentiation and are restored to an ESC-like state during somatic reprogramming. Mechanistically, we provide evidence that the specificity of Fip1-mediated APA regulation depends on multiple factors, including Fip1-RNA interactions and the distance between APA sites. Together, our data highlight the role for post-transcriptional control in stem cell self-renewal, provide mechanistic insight on APA regulation in development, and establish an important function for APA in cell fate specification. PMID:24596251

Strengthened effective connectivity underlies transfer of working memory training to tests of short-term memory and attention.

PubMed

Kundu, Bornali; Sutterer, David W; Emrich, Stephen M; Postle, Bradley R

2013-05-15

Although long considered a natively endowed and fixed trait, working memory (WM) ability has recently been shown to improve with intensive training. What remains controversial and poorly understood, however, are the neural bases of these training effects and the extent to which WM training gains transfer to other cognitive tasks. Here we present evidence from human electrophysiology (EEG) and simultaneous transcranial magnetic stimulation and EEG that the transfer of WM training to other cognitive tasks is supported by changes in task-related effective connectivity in frontoparietal and parieto-occipital networks that are engaged by both the trained and transfer tasks. One consequence of this effect is greater efficiency of stimulus processing, as evidenced by changes in EEG indices of individual differences in short-term memory capacity and in visual search performance. Transfer to search-related activity provides evidence that something more fundamental than task-specific strategy or stimulus-specific representations has been learned. Furthermore, these patterns of training and transfer highlight the role of common neural systems in determining individual differences in aspects of visuospatial cognition.

Drought Conditions Maximize the Impact of High-Frequency Flow Variations on Thermal Regimes and Biogeochemical Function in the Hyporheic Zone.

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

None, None

Anthropogenic activities, such as dam operations, often induce larger and more frequent stage fluctuations than those occurring in natural rivers. However, the long-term impact of such flow variations on thermal and biogeochemical dynamics of the associated hyporheic zone (HZ) is poorly understood. A heterogeneous, two-dimensional thermo-hydro-biogeochemical model revealed an important interaction between high-frequency flow variations and watershed-scale hydrology. High-frequency stage fluctuations had their strongest thermal and biogeochemical impacts when the mean river stage was low during fall and winter. An abnormally thin snowpack in 2015, however, created a low river stage during summer and early fall, whereby high frequency stagemore » fluctuations caused the HZ to be warmer than usual. This study provided the scientific basis to assess the potential ecological consequences of the high-frequency flow variations in a regulated river, as well as guidance on how to maximize the potential benefits—or minimize the drawbacks—of river regulation to river ecosystems.« less

New insights into the pathophysiology of post-stroke spasticity.

PubMed

Li, Sheng; Francisco, Gerard E

2015-01-01

Spasticity is one of many consequences after stroke. It is characterized by a velocity-dependent increase in resistance during passive stretch, resulting from hyperexcitability of the stretch reflex. The underlying mechanism of the hyperexcitable stretch reflex, however, remains poorly understood. Accumulated experimental evidence has supported supraspinal origins of spasticity, likely from an imbalance between descending inhibitory and facilitatory regulation of spinal stretch reflexes secondary to cortical disinhibition after stroke. The excitability of reticulospinal (RST) and vestibulospinal tracts (VSTs) has been assessed in stroke survivors with spasticity using non-invasive indirect measures. There are strong experimental findings that support the RST hyperexcitability as a prominent underlying mechanism of post-stroke spasticity. This mechanism can at least partly account for clinical features associated with spasticity and provide insightful guidance for clinical assessment and management of spasticity. However, the possible role of VST hyperexcitability cannot be ruled out from indirect measures. In vivo measure of individual brainstem nuclei in stroke survivors with spasticity using advanced fMRI techniques in the future is probably able to provide direct evidence of pathogenesis of post-stroke spasticity.

New insights into the pathophysiology of post-stroke spasticity

PubMed Central

Li, Sheng; Francisco, Gerard E.

2015-01-01

Spasticity is one of many consequences after stroke. It is characterized by a velocity-dependent increase in resistance during passive stretch, resulting from hyperexcitability of the stretch reflex. The underlying mechanism of the hyperexcitable stretch reflex, however, remains poorly understood. Accumulated experimental evidence has supported supraspinal origins of spasticity, likely from an imbalance between descending inhibitory and facilitatory regulation of spinal stretch reflexes secondary to cortical disinhibition after stroke. The excitability of reticulospinal (RST) and vestibulospinal tracts (VSTs) has been assessed in stroke survivors with spasticity using non-invasive indirect measures. There are strong experimental findings that support the RST hyperexcitability as a prominent underlying mechanism of post-stroke spasticity. This mechanism can at least partly account for clinical features associated with spasticity and provide insightful guidance for clinical assessment and management of spasticity. However, the possible role of VST hyperexcitability cannot be ruled out from indirect measures. In vivo measure of individual brainstem nuclei in stroke survivors with spasticity using advanced fMRI techniques in the future is probably able to provide direct evidence of pathogenesis of post-stroke spasticity. PMID:25914638

Sex chromosome aneuploidies.

PubMed

Skuse, David; Printzlau, Frida; Wolstencroft, Jeanne

2018-01-01

Sex chromosome aneuploidies comprise a relatively common group of chromosome disorders characterized by the loss or gain of one or more sex chromosomes. We discuss five of the better-known sex aneuploidies: Turner syndrome (XO), Klinefelter syndrome (XXY), trisomy X (XXX), XYY, and XXYY. Despite their prevalence in the general population, these disorders are underdiagnosed and the specific genetic mechanisms underlying their phenotypes are poorly understood. Although there is considerable variation between them in terms of associated functional impairment, each disorder has a characteristic physical, cognitive, and neurologic profile. The most common cause of sex chromosome aneuploidies is nondisjunction, which can occur during meiosis or during the early stages of postzygotic development. The loss or gain of genetic material can affect all daughter cells or it may be partial, leading to tissue mosaicism. In both typical and atypical sex chromosome karyotypes, there is random inactivation of all but one X chromosome. The mechanisms by which a phenotype results from sex chromosome aneuploidies are twofold: dosage imbalance arising from a small number of genes that escape inactivation, and their endocrinologic consequences. Copyright © 2018 Elsevier B.V. All rights reserved.

Activation of PTHrP-cAMP-CREB1 signaling following p53 loss is essential for osteosarcoma initiation and maintenance.

PubMed

Walia, Mannu K; Ho, Patricia Mw; Taylor, Scott; Ng, Alvin Jm; Gupte, Ankita; Chalk, Alistair M; Zannettino, Andrew Cw; Martin, T John; Walkley, Carl R

2016-04-12

Mutations in the P53 pathway are a hallmark of human cancer. The identification of pathways upon which p53-deficient cells depend could reveal therapeutic targets that may spare normal cells with intact p53. In contrast to P53 point mutations in other cancer, complete loss of P53 is a frequent event in osteosarcoma (OS), the most common cancer of bone. The consequences of p53 loss for osteoblastic cells and OS development are poorly understood. Here we use murine OS models to demonstrate that elevated Pthlh (Pthrp), cAMP levels and signalling via CREB1 are characteristic of both p53-deficient osteoblasts and OS. Normal osteoblasts survive depletion of both PTHrP and CREB1. In contrast, p53-deficient osteoblasts and OS depend upon continuous activation of this pathway and undergo proliferation arrest and apoptosis in the absence of PTHrP or CREB1. Our results identify the PTHrP-cAMP-CREB1 axis as an attractive pathway for therapeutic inhibition in OS.

An examination of the mechanisms for stable foam formation in activated sludge systems.

PubMed

Petrovski, Steve; Dyson, Zoe A; Quill, Eben S; McIlroy, Simon J; Tillett, Daniel; Seviour, Robert J

2011-02-01

Screening pure cultures of 65 mycolic acid producing bacteria (Mycolata) isolated mainly from activated sludge with a laboratory based foaming test revealed that not all foamed under the conditions used. However, for most, the data were generally consistent with the flotation theory as an explanation for foaming. Thus a stable foam required three components, air bubbles, surfactants and hydrophobic cells. With non-hydrophobic cells, an unstable foam was generated, and in the absence of surfactants, cells formed a greasy surface scum. Addition of surfactant converted a scumming population into one forming a stable foam. The ability to generate a foam depended on a threshold cell number, which varied between individual isolates and reduced markedly in the presence of surfactant. Consequently, the concept of a universal threshold applicable to all foaming Mycolata is not supported by these data. The role of surfactants in foaming is poorly understood, but evidence is presented for the first time that surfactin synthesised by Bacillus subtilis may be important. Copyright © 2010 Elsevier Ltd. All rights reserved.

Flushing History as a Hydrogeological Control on the Regional Distribution of Arsenic in Shallow Groundwater of the Bengal Basin

PubMed Central

2008-01-01

Whereas serious health consequences of widespread consumption of groundwater elevated in As have been documented in several South Asian countries, the mechanisms responsible for As mobilization in reducing aquifers remain poorly understood. We document here a previously unrecognized and consistent relationship between dissolved As concentrations in reducing groundwater and the phosphate-mobilizable As content of aquifer sediment for a set of precisely depth-matched samples from across Bangladesh. The relationship holds across nearly 3 orders of magnitude in As concentrations and suggests that regional as well as local patterns of dissolved As in shallow groundwater are set by the solid phase according to a remarkably constant ratio of ∼250 μg/L dissolved As per 1 mg/kg P-mobilizable As. We use this relationship in a simple model of groundwater recharge to propose that the distribution of groundwater As in shallow aquifers of the Bengal Basin could primarily reflect the different flushing histories of sand formations deposited in the region over the past several thousand years. PMID:18504954

Ecosystem responses to reduced and oxidised nitrogen inputs in European terrestrial habitats.

PubMed

Stevens, Carly J; Manning, Pete; van den Berg, Leon J L; de Graaf, Maaike C C; Wamelink, G W Wieger; Boxman, Andries W; Bleeker, Albert; Vergeer, Philippine; Arroniz-Crespo, Maria; Limpens, Juul; Lamers, Leon P M; Bobbink, Roland; Dorland, Edu

2011-03-01

While it is well established that ecosystems display strong responses to elevated nitrogen deposition, the importance of the ratio between the dominant forms of deposited nitrogen (NH(x) and NO(y)) in determining ecosystem response is poorly understood. As large changes in the ratio of oxidised and reduced nitrogen inputs are occurring, this oversight requires attention. One reason for this knowledge gap is that plants experience a different NH(x):NO(y) ratio in soil to that seen in atmospheric deposits because atmospheric inputs are modified by soil transformations, mediated by soil pH. Consequently species of neutral and alkaline habitats are less likely to encounter high NH(4)(+) concentrations than species from acid soils. We suggest that the response of vascular plant species to changing ratios of NH(x):NO(y) deposits will be driven primarily by a combination of soil pH and nitrification rates. Testing this hypothesis requires a combination of experimental and survey work in a range of systems. Copyright © 2010 Elsevier Ltd. All rights reserved.

TRPM7 controls mesenchymal features of breast cancer cells by tensional regulation of SOX4.

PubMed

Kuipers, Arthur J; Middelbeek, Jeroen; Vrenken, Kirsten; Pérez-González, Carlos; Poelmans, Geert; Klarenbeek, Jeffrey; Jalink, Kees; Trepat, Xavier; van Leeuwen, Frank N

2018-07-01

Mechanically induced signaling pathways are important drivers of tumor progression. However, if and how mechanical signals affect metastasis or therapy response remains poorly understood. We previously found that the channel-kinase TRPM7, a regulator of cellular tension implicated in mechano-sensory processes, is required for breast cancer metastasis in vitro and in vivo. Here, we show that TRPM7 contributes to maintaining a mesenchymal phenotype in breast cancer cells by tensional regulation of the EMT transcription factor SOX4. The functional consequences of SOX4 knockdown closely mirror those produced by TRPM7 knockdown. By traction force measurements, we demonstrate that TRPM7 reduces cytoskeletal tension through inhibition of myosin II activity. Moreover, we show that SOX4 expression and downstream mesenchymal markers are inversely regulated by cytoskeletal tension and matrix rigidity. Overall, our results identify SOX4 as a transcription factor that is uniquely sensitive to cellular tension and indicate that TRPM7 may contribute to breast cancer progression by tensional regulation of SOX4. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B

PubMed Central

Lee, Chih-Yung Sean; Lu, Tu

2017-01-01

Nanos RNA-binding proteins are required for germline development in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of primordial germ cells (PGCs) lacking the nanos homologs nos-1 and nos-2 in C. elegans. nos-1nos-2 PGCs fail to silence hundreds of transcripts normally expressed in oocytes. We find that this misregulation is due to both delayed turnover of maternal transcripts and inappropriate transcriptional activation. The latter appears to be an indirect consequence of delayed turnover of the maternally-inherited transcription factor LIN-15B, a synMuvB class transcription factor known to antagonize PRC2 activity. PRC2 is required for chromatin reprogramming in the germline, and the transcriptome of PGCs lacking PRC2 resembles that of nos-1nos-2 PGCs. Loss of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These findings suggest that Nanos promotes germ cell fate by downregulating maternal RNAs and proteins that would otherwise interfere with PRC2-dependent reprogramming of PGC chromatin. PMID:29111977

Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B.

PubMed

Lee, Chih-Yung Sean; Lu, Tu; Seydoux, Geraldine

2017-11-07

Nanos RNA-binding proteins are required for germline development in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of primordial germ cells (PGCs) lacking the nanos homologs nos-1 and nos-2 in C. elegans. nos-1nos-2 PGCs fail to silence hundreds of transcripts normally expressed in oocytes. We find that this misregulation is due to both delayed turnover of maternal transcripts and inappropriate transcriptional activation. The latter appears to be an indirect consequence of delayed turnover of the maternally-inherited transcription factor LIN-15B, a synMuvB class transcription factor known to antagonize PRC2 activity. PRC2 is required for chromatin reprogramming in the germline, and the transcriptome of PGCs lacking PRC2 resembles that of nos-1nos-2 PGCs. Loss of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These findings suggest that Nanos promotes germ cell fate by downregulating maternal RNAs and proteins that would otherwise interfere with PRC2-dependent reprogramming of PGC chromatin.

Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes.

PubMed

Kürten, Charlotte; Syrén, Per-Olof

2016-01-16

Enzyme catalysis evolved in an aqueous environment. The influence of solvent dynamics on catalysis is, however, currently poorly understood and usually neglected. The study of water dynamics in enzymes and the associated thermodynamical consequences is highly complex and has involved computer simulations, nuclear magnetic resonance (NMR) experiments, and calorimetry. Water tunnels that connect the active site with the surrounding solvent are key to solvent displacement and dynamics. The protocol herein allows for the engineering of these motifs for water transport, which affects specificity, activity and thermodynamics. By providing a biophysical framework founded on theory and experiments, the method presented herein can be used by researchers without previous expertise in computer modeling or biophysical chemistry. The method will advance our understanding of enzyme catalysis on the molecular level by measuring the enthalpic and entropic changes associated with catalysis by enzyme variants with obstructed water tunnels. The protocol can be used for the study of membrane-bound enzymes and other complex systems. This will enhance our understanding of the importance of solvent reorganization in catalysis as well as provide new catalytic strategies in protein design and engineering.

Localization of sclerotic-type chronic graft-vs-host disease to sites of skin injury: potential insight into the mechanism of isomorphic and isotopic responses.

PubMed

Martires, Kathryn J; Baird, Kristin; Citrin, Deborah E; Hakim, Fran T; Pavletic, Steven Z; Cowen, Edward W

2011-09-01

The mechanisms responsible for the variable manifestations of chronic cutaneous graft-vs-host disease (cGVHD) are poorly understood. Localization of sclerotic-type chronic graft-vs-host disease to sites of skin injury (isomorphic and isotopic responses), a recognized phenomenon in morphea, suggests a potential common pathway between cGVHD and other sclerotic skin conditions. Four cases of sclerotic-type cGVHD developed at the site of disparate skin injuries (ionizing radiotherapy, repeated needle sticks, central catheter site, and varicella-zoster virus infection). We review the spectrum of previously reported cases of sclerotic and nonsclerotic cGVHD relating to external forces on the skin. Localization of sclerotic-type cGVHD may occur after many types of skin injury, including UV and ionizing radiotherapy, needle sticks, viral infection, and pressure or friction. Recognition of this phenomenon may be helpful for the early diagnosis of sclerotic disease. Recent insights into the immunological consequences of minor skin injury may provide important clues to the underlying pathogenesis of cGVHD-mediated skin disease.

Work-role transition: from staff nurse to clinical nurse educator.

PubMed

Manning, Liz; Neville, Stephen

2009-07-01

This article presents the findings of a study describing Clinical Nurse Educators' experiences, as they recall their transition from staff nurse to the Clinical Nurse Educator role, within a New Zealand District Health Board. Nurse Educator roles influence clinical practice and professional development of nurses, and although designated as a senior role nationally, the complexities and size of the role are poorly understood. A qualitative descriptive methodology utilising transition theory as a conceptual framework underpinned the study. A sample of eight Clinical Nurse Educators from a New Zealand District Health Board were interviewed about their transition from experienced staff nurse to inexperienced senior nurse. Data were analysed using a general inductive approach. Participants found the Clinical Nurse Educator role was more complex than anticipated, with no preparation for the role and sub-optimal orientation periods being provided by the District Health Board. As a result, signs of stress were evident as the enormity of the role became apparent. Consequently, employers need to ensure that appropriate orientation programmes and mentorship are inherent in health care organisations.

Artificial Autopolyploidization Modifies the Tricarboxylic Acid Cycle and GABA Shunt in Arabidopsis thaliana Col-0

NASA Astrophysics Data System (ADS)

Vergara, Fredd; Kikuchi, Jun; Breuer, Christian

2016-05-01

Autopolyploidy is a process whereby the chromosome set is multiplied and it is a common phenomenon in angiosperms. Autopolyploidy is thought to be an important evolutionary force that has led to the formation of new plant species. Despite its relevance, the consequences of autopolyploidy in plant metabolism are poorly understood. This study compares the metabolic profiles of natural diploids and artificial autotetraploids of Arabidopsis thaliana Col-0. Different physiological parameters are compared between diploids and autotetraploids using nuclear magnetic resonance (NMR), elemental analysis (carbon:nitrogen balance) and quantitative real-time PCR (qRT-PCR). The main difference between diploid and autotetraploid A. thaliana Col-0 is observed in the concentration of metabolites related to the tricarboxylic acid cycle (TCA) and γ-amino butyric acid (GABA) shunt, as shown by multivariate statistical analysis of NMR spectra. qRT-PCR shows that genes related to the TCA and GABA shunt are also differentially expressed between diploids and autotetraploids following similar trends as their corresponding metabolites. Solid evidence is presented to demonstrate that autopolyploidy influences core plant metabolic processes.

A bacterial homolog of a eukaryotic inositol phosphate signaling enzyme mediates cross-kingdom dialog in the mammalian gut.

PubMed

Stentz, Régis; Osborne, Samantha; Horn, Nikki; Li, Arthur W H; Hautefort, Isabelle; Bongaerts, Roy; Rouyer, Marine; Bailey, Paul; Shears, Stephen B; Hemmings, Andrew M; Brearley, Charles A; Carding, Simon R

2014-02-27

Dietary InsP6 can modulate eukaryotic cell proliferation and has complex nutritive consequences, but its metabolism in the mammalian gastrointestinal tract is poorly understood. Therefore, we performed phylogenetic analyses of the gastrointestinal microbiome in order to search for candidate InsP6 phosphatases. We determined that prominent gut bacteria express homologs of the mammalian InsP6 phosphatase (MINPP) and characterized the enzyme from Bacteroides thetaiotaomicron (BtMinpp). We show that BtMinpp has exceptionally high catalytic activity, which we rationalize on the basis of mutagenesis studies and by determining its crystal structure at 1.9 Å resolution. We demonstrate that BtMinpp is packaged inside outer membrane vesicles (OMVs) protecting the enzyme from degradation by gastrointestinal proteases. Moreover, we uncover an example of cross-kingdom cell-to-cell signaling, showing that the BtMinpp-OMVs interact with intestinal epithelial cells to promote intracellular Ca(2+) signaling. Our characterization of BtMinpp offers several directions for understanding how the microbiome serves human gastrointestinal physiology. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

A Bacterial Homolog of a Eukaryotic Inositol Phosphate Signaling Enzyme Mediates Cross-kingdom Dialog in the Mammalian Gut

PubMed Central

Stentz, Régis; Osborne, Samantha; Horn, Nikki; Li, Arthur W.H.; Hautefort, Isabelle; Bongaerts, Roy; Rouyer, Marine; Bailey, Paul; Shears, Stephen B.; Hemmings, Andrew M.; Brearley, Charles A.; Carding, Simon R.

2014-01-01

Summary Dietary InsP6 can modulate eukaryotic cell proliferation and has complex nutritive consequences, but its metabolism in the mammalian gastrointestinal tract is poorly understood. Therefore, we performed phylogenetic analyses of the gastrointestinal microbiome in order to search for candidate InsP6 phosphatases. We determined that prominent gut bacteria express homologs of the mammalian InsP6 phosphatase (MINPP) and characterized the enzyme from Bacteroides thetaiotaomicron (BtMinpp). We show that BtMinpp has exceptionally high catalytic activity, which we rationalize on the basis of mutagenesis studies and by determining its crystal structure at 1.9 Å resolution. We demonstrate that BtMinpp is packaged inside outer membrane vesicles (OMVs) protecting the enzyme from degradation by gastrointestinal proteases. Moreover, we uncover an example of cross-kingdom cell-to-cell signaling, showing that the BtMinpp-OMVs interact with intestinal epithelial cells to promote intracellular Ca2+ signaling. Our characterization of BtMinpp offers several directions for understanding how the microbiome serves human gastrointestinal physiology. PMID:24529702

Bub1 autophosphorylation feeds back to regulate kinetochore docking and promote localized substrate phosphorylation

PubMed Central

Asghar, Adeel; Lajeunesse, Audrey; Dulla, Kalyan; Combes, Guillaume; Thebault, Philippe; Nigg, Erich A.; Elowe, Sabine

2015-01-01

During mitosis, Bub1 kinase phosphorylates histone H2A-T120 to promote centromere sister chromatid cohesion through recruitment of shugoshin (Sgo) proteins. The regulation and dynamics of H2A-T120 phosphorylation are poorly understood. Using quantitative phosphoproteomics we show that Bub1 is autophosphorylated at numerous sites. We confirm mitosis-specific autophosphorylation of a several residues and show that Bub1 activation is primed in interphase but fully achieved only in mitosis. Mutation of a single autophosphorylation site T589 alters kinetochore turnover of Bub1 and results in uniform H2A-T120 phosphorylation and Sgo recruitment along chromosome arms. Consequently, improper sister chromatid resolution and chromosome segregation errors are observed. Kinetochore tethering of Bub1-T589A refocuses H2A-T120 phosphorylation and Sgo1 to centromeres. Recruitment of the Bub1-Bub3-BubR1 axis to kinetochores has recently been extensively studied. Our data provide novel insight into the regulation and kinetochore residency of Bub1 and indicate that its localization is dynamic and tightly controlled through feedback autophosphorylation. PMID:26399325

Bub1 autophosphorylation feeds back to regulate kinetochore docking and promote localized substrate phosphorylation.

PubMed

Asghar, Adeel; Lajeunesse, Audrey; Dulla, Kalyan; Combes, Guillaume; Thebault, Philippe; Nigg, Erich A; Elowe, Sabine

2015-09-24

During mitosis, Bub1 kinase phosphorylates histone H2A-T120 to promote centromere sister chromatid cohesion through recruitment of shugoshin (Sgo) proteins. The regulation and dynamics of H2A-T120 phosphorylation are poorly understood. Using quantitative phosphoproteomics we show that Bub1 is autophosphorylated at numerous sites. We confirm mitosis-specific autophosphorylation of a several residues and show that Bub1 activation is primed in interphase but fully achieved only in mitosis. Mutation of a single autophosphorylation site T589 alters kinetochore turnover of Bub1 and results in uniform H2A-T120 phosphorylation and Sgo recruitment along chromosome arms. Consequently, improper sister chromatid resolution and chromosome segregation errors are observed. Kinetochore tethering of Bub1-T589A refocuses H2A-T120 phosphorylation and Sgo1 to centromeres. Recruitment of the Bub1-Bub3-BubR1 axis to kinetochores has recently been extensively studied. Our data provide novel insight into the regulation and kinetochore residency of Bub1 and indicate that its localization is dynamic and tightly controlled through feedback autophosphorylation.

On the value of aiming high: the causes and consequences of ambition.

PubMed

Judge, Timothy A; Kammeyer-Mueller, John D

2012-07-01

Ambition is a commonly mentioned but poorly understood concept in social science research. We sought to contribute to understanding of the concept by developing and testing a model in which ambition is a middle-level trait (Cantor, 1990)-predicted by more distal characteristics but, due to its teleological nature, more proximally situated to predict career success. A 7-decade longitudinal sample of 717 high-ability individuals from the Terman life-cycle study (Terman, Sears, Cronbach, & Sears, 1989) was used in the current study. Results indicated that ambition was predicted by individual differences-conscientiousness, extraversion, neuroticism, and general mental ability-and a socioeconomic background variable: parents' occupational prestige. Ambition, in turn, was positively related to educational attainment, occupation prestige, and income. Ambition had significant total effects with all of the endogenous variables except mortality. Overall, the results support the thesis that ambition is a middle-level trait-related to but distinct from more distal individual difference variables-that has meaningful effects on career success. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

BACE1 inhibition by microdose lithium formulation NP03 rescues memory loss and early stage amyloid neuropathology.

PubMed

Wilson, E N; Do Carmo, S; Iulita, M F; Hall, H; Ducatenzeiler, A; Marks, A R; Allard, S; Jia, D T; Windheim, J; Cuello, A C

2017-08-01

Lithium is first-line therapy for bipolar affective disorder and has recently been shown to have protective effects in populations at risk for Alzheimer's disease (AD). However, the mechanism underlying this protection is poorly understood and consequently limits its possible therapeutic application in AD. Moreover, conventional lithium formulations have a narrow therapeutic window and are associated with a severe side effect profile. Here we evaluated a novel microdose formulation of lithium, coded NP03, in a well-characterized rat model of progressive AD-like amyloid pathology. This formulation allows microdose lithium delivery to the brain in the absence of negative side effects. We found that NP03 rescued key initiating components of AD pathology, including inactivating GSK-3β, reducing BACE1 expression and activity, and reducing amyloid levels. Notably, NP03 rescued memory loss, impaired CRTC1 promoter binding of synaptic plasticity genes and hippocampal neurogenesis. These results raise the possibility that NP03 be of therapeutic value in the early or preclinical stages of AD.

Data integration aids understanding of butterfly-host plant networks

NASA Astrophysics Data System (ADS)

Muto-Fujita, Ai; Takemoto, Kazuhiro; Kanaya, Shigehiko; Nakazato, Takeru; Tokimatsu, Toshiaki; Matsumoto, Natsushi; Kono, Mayo; Chubachi, Yuko; Ozaki, Katsuhisa; Kotera, Masaaki

2017-03-01

Although host-plant selection is a central topic in ecology, its general underpinnings are poorly understood. Here, we performed a case study focusing on the publicly available data on Japanese butterflies. A combined statistical analysis of plant-herbivore relationships and taxonomy revealed that some butterfly subfamilies in different families feed on the same plant families, and the occurrence of this phenomenon more than just by chance, thus indicating the independent acquisition of adaptive phenotypes to the same hosts. We consequently integrated plant-herbivore and plant-compound relationship data and conducted a statistical analysis to identify compounds unique to host plants of specific butterfly families. Some of the identified plant compounds are known to attract certain butterfly groups while repelling others. The additional incorporation of insect-compound relationship data revealed potential metabolic processes that are related to host plant selection. Our results demonstrate that data integration enables the computational detection of compounds putatively involved in particular interspecies interactions and that further data enrichment and integration of genomic and transcriptomic data facilitates the unveiling of the molecular mechanisms involved in host plant selection.

Sociality and oxytocin and vasopressin in the brain of male and female dominant and subordinate mandarin voles.

PubMed

Qiao, Xufeng; Yan, Yating; Wu, Ruiyong; Tai, Fadao; Hao, Ping; Cao, Yan; Wang, Jianli

2014-02-01

The dominant-subordinate hierarchy in animals often needs to be established via agonistic encounters and consequently affects reproduction and survival. Differences in brain neuropeptides and sociality among dominant and subordinate males and females remain poorly understood. Here we explore neuropeptide levels and sociality during agonistic encounter tests in mandarin voles. We found that dominant mandarin voles engaged in higher levels of approaching, investigating, self-grooming and exploring behavior than subordinates. Dominant males habituated better to a stimulus vole than dominant females. Dominant males displayed significantly less oxytocin-immunoreactive neurons in the paraventricular nuclei and more vasopressin-immunoreactive neurons in the paraventricular nuclei, supraoptic nuclei, and the lateral and anterior hypothalamus than subordinates. Dominant females displayed significantly more vasopressin-immunoreactive neurons in the lateral hypothalamus and anterior hypothalamus than subordinates. Sex differences were found in the level of oxytocin and vasopressin. These results indicate that distinct parameters related to central nervous oxytocin and vasopressin are associated with behaviors during agonistic encounters in a sex-specific manner in mandarin voles.

Divided attention disrupts perceptual encoding during speech recognition.

PubMed

Mattys, Sven L; Palmer, Shekeila D

2015-03-01

Performing a secondary task while listening to speech has a detrimental effect on speech processing, but the locus of the disruption within the speech system is poorly understood. Recent research has shown that cognitive load imposed by a concurrent visual task increases dependency on lexical knowledge during speech processing, but it does not affect lexical activation per se. This suggests that "lexical drift" under cognitive load occurs either as a post-lexical bias at the decisional level or as a secondary consequence of reduced perceptual sensitivity. This study aimed to adjudicate between these alternatives using a forced-choice task that required listeners to identify noise-degraded spoken words with or without the addition of a concurrent visual task. Adding cognitive load increased the likelihood that listeners would select a word acoustically similar to the target even though its frequency was lower than that of the target. Thus, there was no evidence that cognitive load led to a high-frequency response bias. Rather, cognitive load seems to disrupt sublexical encoding, possibly by impairing perceptual acuity at the auditory periphery.

Induction of diapause and seasonal morphs in butterflies and other insects: knowns, unknowns and the challenge of integration

PubMed Central

Nylin, Sören

2013-01-01

The ‘choice’ of whether to enter diapause or to develop directly has profound effects on the life histories of insects, and may thus have cascading consequences such as seasonal morphs and other less obvious forms of seasonal plasticity. Present knowledge of the control of diapause and seasonal morphs at the physiological and molecular levels is briefly reviewed. Examples, mainly derived from personal research (primarily on butterflies), are given as a starting point with the aim of outlining areas of research that are still poorly understood. These include: the role of the direction of change in photoperiod; the role of factors such as temperature and diet in modifying the photoperiodic responses; and the role of sex, parental effects and sex linkage on photoperiodic control. More generally, there is still a limited understanding of how external cues and physiological pathways regulating various traits are interconnected via gene action to form a co-adapted complete phenotype that is adaptive in the wild despite environmental fluctuation and change. PMID:23894219

Facial contrast is a cue for perceiving health from the face.

PubMed

Russell, Richard; Porcheron, Aurélie; Sweda, Jennifer R; Jones, Alex L; Mauger, Emmanuelle; Morizot, Frederique

2016-09-01

How healthy someone appears has important social consequences. Yet the visual cues that determine perceived health remain poorly understood. Here we report evidence that facial contrast-the luminance and color contrast between internal facial features and the surrounding skin-is a cue for the perception of health from the face. Facial contrast was measured from a large sample of Caucasian female faces, and was found to predict ratings of perceived health. Most aspects of facial contrast were positively related to perceived health, meaning that faces with higher facial contrast appeared healthier. In 2 subsequent experiments, we manipulated facial contrast and found that participants perceived faces with increased facial contrast as appearing healthier than faces with decreased facial contrast. These results support the idea that facial contrast is a cue for perceived health. This finding adds to the growing knowledge about perceived health from the face, and helps to ground our understanding of perceived health in terms of lower-level perceptual features such as contrast. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

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

Wang, Jian; Krejci, Radovan; Giangrande, Scott

The nucleation of atmospheric vapours is an important source of new aerosol particles that can subsequently grow to form cloud condensation nuclei in the atmosphere. Most field studies of atmospheric aerosols over continents are influenced by atmospheric vapours of anthropogenic origin and, in consequence, aerosol processes in pristine, terrestrial environments remain poorly understood. The Amazon rainforest is one of the few continental regions where aerosol particles and their precursors can be studied under near-natural conditions, but the origin of small aerosol particles that grow into cloud condensation nuclei in the Amazon boundary layer remains unclear. Here we present aircraft- andmore » ground-based measurements under clean conditions during the wet season in the central Amazon basin. We find that high concentrations of small aerosol particles (with diameters of less than 50 nanometres) in the lower free troposphere are transported from the free troposphere into the boundary layer during precipitation events by strong convective downdrafts and weaker downward motions in the trailing stratiform region. Lastly, this rapid vertical transport can help to maintain the population of particles in the pristine Amazon boundary layer, and may therefore influence cloud properties and climate under natural conditions.« less

Caspase-2-mediated cleavage of Mdm2 creates p53-induced positive feedback loop

PubMed Central

Oliver, Trudy G.; Meylan, Etienne; Chang, Gregory P.; Xue, Wen; Burke, James R.; Humpton, Timothy J.; Hubbard, Diana; Bhutkar, Arjun; Jacks, Tyler

2011-01-01

SUMMARY Caspase-2 is an evolutionarily conserved caspase, yet its biological function and cleavage targets are poorly understood. Caspase-2 is activated by the p53 target gene product PIDD (also known as LRDD) in a complex called the Caspase-2-PIDDosome. We show that PIDD expression promotes growth arrest and chemotherapy resistance by a mechanism that depends on Caspase-2 and wild-type p53. PIDD-induced Caspase-2 directly cleaves the E3 ubiquitin ligase Mdm2 at Asp 367, leading to loss of the C-terminal RING domain responsible for p53 ubiquitination. As a consequence, N-terminally truncated Mdm2 binds p53 and promotes its stability. Upon DNA damage, p53 induction of the Caspase-2-PIDDosome creates a positive feedback loop that inhibits Mdm2 and reinforces p53 stability and activity, contributing to cell survival and drug resistance. These data establish Mdm2 as a cleavage target of Caspase-2 and provide insight into a mechanism of Mdm2 inhibition that impacts p53 dynamics upon genotoxic stress. PMID:21726810

Activity of Raphé Serotonergic Neurons Controls Emotional Behaviors.

PubMed

Teissier, Anne; Chemiakine, Alexei; Inbar, Benjamin; Bagchi, Sneha; Ray, Russell S; Palmiter, Richard D; Dymecki, Susan M; Moore, Holly; Ansorge, Mark S

2015-12-01

Despite the well-established role of serotonin signaling in mood regulation, causal relationships between serotonergic neuronal activity and behavior remain poorly understood. Using a pharmacogenetic approach, we find that selectively increasing serotonergic neuronal activity in wild-type mice is anxiogenic and reduces floating in the forced-swim test, whereas inhibition has no effect on the same measures. In a developmental mouse model of altered emotional behavior, increased anxiety and depression-like behaviors correlate with reduced dorsal raphé and increased median raphé serotonergic activity. These mice display blunted responses to serotonergic stimulation and behavioral rescues through serotonergic inhibition. Furthermore, we identify opposing consequences of dorsal versus median raphé serotonergic neuron inhibition on floating behavior, together suggesting that median raphé hyperactivity increases anxiety, whereas a low dorsal/median raphé serotonergic activity ratio increases depression-like behavior. Thus, we find a critical role of serotonergic neuronal activity in emotional regulation and uncover opposing roles of median and dorsal raphé function. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Data integration aids understanding of butterfly–host plant networks

PubMed Central

Muto-Fujita, Ai; Takemoto, Kazuhiro; Kanaya, Shigehiko; Nakazato, Takeru; Tokimatsu, Toshiaki; Matsumoto, Natsushi; Kono, Mayo; Chubachi, Yuko; Ozaki, Katsuhisa; Kotera, Masaaki

2017-01-01

Although host-plant selection is a central topic in ecology, its general underpinnings are poorly understood. Here, we performed a case study focusing on the publicly available data on Japanese butterflies. A combined statistical analysis of plant–herbivore relationships and taxonomy revealed that some butterfly subfamilies in different families feed on the same plant families, and the occurrence of this phenomenon more than just by chance, thus indicating the independent acquisition of adaptive phenotypes to the same hosts. We consequently integrated plant–herbivore and plant–compound relationship data and conducted a statistical analysis to identify compounds unique to host plants of specific butterfly families. Some of the identified plant compounds are known to attract certain butterfly groups while repelling others. The additional incorporation of insect–compound relationship data revealed potential metabolic processes that are related to host plant selection. Our results demonstrate that data integration enables the computational detection of compounds putatively involved in particular interspecies interactions and that further data enrichment and integration of genomic and transcriptomic data facilitates the unveiling of the molecular mechanisms involved in host plant selection. PMID:28262809

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

Older parents are less responsive to a stressor in a long-lived seabird: a mechanism for increased reproductive performance with age?

PubMed

Heidinger, Britt J; Nisbet, Ian C T; Ketterson, Ellen D

2006-09-07

In many taxa, reproductive performance increases throughout the lifespan and this may occur in part because older adults invest more in reproduction. The mechanisms that facilitate an increase in reproductive performance with age, however, are poorly understood. In response to stressors, vertebrates release glucocorticoids, which enhance survival but concurrently shift investment away from reproduction. Consequently, when the value of current reproduction is high relative to the value of future reproduction and survival, as it is in older adults, life history theory predicts that the stress response should be suppressed. In this study, we tested the hypothesis that older parents would respond less strongly to a stressor in a natural, breeding population of common terns (Sterna hirundo). Common terns are long-lived seabirds and reproductive performance is known to increase throughout the lifespan of this species. As predicted, the maximum level of glucocorticoids released in response to handling stress decreased significantly with age. We suggest that suppression of the stress response may be an important physiological mechanism that facilitates an increase in reproductive performance with age.

The neural substrates of improved phonological processing following successful treatment in a case of phonological alexia and agraphia

PubMed Central

DeMarco, Andrew T.; Wilson, Stephen M.; Rising, Kindle; Rapcsak, Steven Z.; Beeson, Pélagie M.

2018-01-01

Deficits in phonology are among the most common and persistent impairments in aphasia after left hemisphere stroke, and can have significant functional consequences for spoken and written language. While many individuals make considerable gains in response to treatment, the neural substrates supporting these improvements are poorly understood. To address this issue, we used BOLD fMRI to measure regional brain activation in an individual during pseudoword reading before and after treatment targeting phonological skills. After the first phase of treatment, significant improvement in pseudoword reading was associated with greater activation in residual regions of the left dorsal language network, as well as bilateral regions that support attention and cognitive effort outside of canonical language areas. Following a second treatment phase, behavioral gains were maintained, while brain activation returned to pre-treatment levels. In addition to revealing the neural support for improved phonological skills in the face of damage to critical brain regions, this case demonstrated that behavioral advances may ultimately be maintained without the need to sustain a marked increase in cognitive effort. PMID:29350575

Influence of the CCR-5/MIP-1 α Axis in the Pathogenesis of Rocio Virus Encephalitis in a Mouse Model

PubMed Central

Chávez, Juliana H.; França, Rafael F. O.; Oliveira, Carlo J. F.; de Aquino, Maria T. P.; Farias, Kleber J. S.; Machado, Paula R. L.; de Oliveira, Thelma F. M.; Yokosawa, Jonny; Soares, Edson G.; da Silva, João S.; da Fonseca, Benedito A. L.; Figueiredo, Luiz T. M.

2013-01-01

Rocio virus (ROCV) caused an outbreak of human encephalitis during the 1970s in Brazil and its immunopathogenesis remains poorly understood. CC-chemokine receptor 5 (CCR5) is a chemokine receptor that binds to macrophage inflammatory protein (MIP-1 α). Both molecules are associated with inflammatory cells migration during infections. In this study, we demonstrated the importance of the CCR5 and MIP-1 α, in the outcome of viral encephalitis of ROCV-infected mice. CCR5 and MIP-1 α knockout mice survived longer than wild-type (WT) ROCV-infected animals. In addition, knockout mice had reduced inflammation in the brain. Assessment of brain viral load showed mice virus detection five days post-infection in wild-type and CCR5−/− mice, while MIP-1 α−/− mice had lower viral loads seven days post-infection. Knockout mice required a higher lethal dose than wild-type mice as well. The CCR5/MIP-1 α axis may contribute to migration of infected cells to the brain and consequently affect the pathogenesis during ROCV infection. PMID:24080631

Turing-like structures in a functional model of cortical spreading depression

NASA Astrophysics Data System (ADS)

Verisokin, A. Yu.; Verveyko, D. V.; Postnov, D. E.

2017-12-01

Cortical spreading depression (CSD) along with migraine waves and spreading depolarization events with stroke or injures are the front-line examples of extreme physiological behaviors of the brain cortex which manifest themselves via the onset and spreading of localized areas of neuronal hyperactivity followed by their depression. While much is known about the physiological pathways involved, the dynamical mechanisms of the formation and evolution of complex spatiotemporal patterns during CSD are still poorly understood, in spite of the number of modeling studies that have been already performed. Recently we have proposed a relatively simple mathematical model of cortical spreading depression which counts the effects of neurovascular coupling and cerebral blood flow redistribution during CSD. In the present study, we address the main dynamical consequences of newly included pathways, namely, the changes in the formation and propagation speed of the CSD front and the pattern formation features in two dimensions. Our most notable finding is that the combination of vascular-mediated spatial coupling with local regulatory mechanisms results in the formation of stationary Turing-like patterns during a CSD event.

Snoring and obstructive sleep apnoea in children: why should we treat?

PubMed

Gozal, David; O'Brien, Louise M

2004-01-01

Frequent and loud snoring is a very frequent condition in prepubertal children affecting approximately 10% of all 2-8 year old children. If polysomnographical evaluations are performed in these snoring children, approximately 10% will be diagnosed with obstructive sleep apnoea (OSA). The pathophysiology of OSA in children is still poorly understood. Indeed, while adenotonsillar hypertrophy is certainly a major contributor to OSA, other factors need to be implicated for OSA to develop. In recent years, it has become apparent that OSA and snoring are not as innocuous as previously thought. Indeed, epidemiological and pre-post treatment analyses have identified substantial morbidities that primarily affect cardiovascular and neurobehavioural systems, namely pulmonary hypertension, systemic elevation of arterial blood pressure, nocturnal enuresis, reduced somatic growth, behavioural problems that resemble attention deficit-hyperactivity disorder, as well as learning and cognitive deficits. These problems are associated with marked increases in healthcare-related costs. More importantly, if timely diagnosis and intervention are not implemented, some of these morbid complications may not be completely reversible, leading to long-lasting residual consequences.

Dual leucine zipper kinase-dependent PERK activation contributes to neuronal degeneration following insult

PubMed Central

Larhammar, Martin; Huntwork-Rodriguez, Sarah; Jiang, Zhiyu; Solanoy, Hilda; Sengupta Ghosh, Arundhati; Wang, Bei; Kaminker, Joshua S; Huang, Kevin; Eastham-Anderson, Jeffrey; Siu, Michael; Modrusan, Zora; Farley, Madeline M; Tessier-Lavigne, Marc; Lewcock, Joseph W; Watkins, Trent A

2017-01-01

The PKR-like endoplasmic reticulum kinase (PERK) arm of the Integrated Stress Response (ISR) is implicated in neurodegenerative disease, although the regulators and consequences of PERK activation following neuronal injury are poorly understood. Here we show that PERK signaling is a component of the mouse MAP kinase neuronal stress response controlled by the Dual Leucine Zipper Kinase (DLK) and contributes to DLK-mediated neurodegeneration. We find that DLK-activating insults ranging from nerve injury to neurotrophin deprivation result in both c-Jun N-terminal Kinase (JNK) signaling and the PERK- and ISR-dependent upregulation of the Activating Transcription Factor 4 (ATF4). Disruption of PERK signaling delays neurodegeneration without reducing JNK signaling. Furthermore, DLK is both sufficient for PERK activation and necessary for engaging the ISR subsequent to JNK-mediated retrograde injury signaling. These findings identify DLK as a central regulator of not only JNK but also PERK stress signaling in neurons, with both pathways contributing to neurodegeneration. DOI: http://dx.doi.org/10.7554/eLife.20725.001 PMID:28440222

Current Progresses of Single Cell DNA Sequencing in Breast Cancer Research.

PubMed

Liu, Jianlin; Adhav, Ragini; Xu, Xiaoling

2017-01-01

Breast cancers display striking genetic and phenotypic diversities. To date, several hypotheses are raised to explain and understand the heterogeneity, including theories for cancer stem cell (CSC) and clonal evolution. According to the CSC theory, the most tumorigenic cells, while maintaining themselves through symmetric division, divide asymmetrically to generate non-CSCs with less tumorigenic and metastatic potential, although they can also dedifferentiate back to CSCs. Clonal evolution theory recapitulates that a tumor initially arises from a single cell, which then undergoes clonal expansion to a population of cancer cells. During tumorigenesis and evolution process, cancer cells undergo different degrees of genetic instability and consequently obtain varied genetic aberrations. Yet the heterogeneity in breast cancers is very complex, poorly understood and subjected to further investigation. In recent years, single cell sequencing (SCS) technology developed rapidly, providing a powerful new way to better understand the heterogeneity, which may lay foundations to some new strategies for breast cancer therapies. In this review, we will summarize development of SCS technologies and recent advances of SCS in breast cancer.

How hollow melanosomes affect iridescent colour production in birds

PubMed Central

Eliason, Chad M.; Bitton, Pierre-Paul; Shawkey, Matthew D.

2013-01-01

Developmental constraints and trade-offs can limit diversity, but organisms have repeatedly evolved morphological innovations that overcome these limits by expanding the range and functionality of traits. Iridescent colours in birds are commonly produced by melanin-containing organelles (melanosomes) organized into nanostructured arrays within feather barbules. Variation in array type (e.g. multilayers and photonic crystals, PCs) is known to have remarkable effects on plumage colour, but the optical consequences of variation in melanosome shape remain poorly understood. Here, we used a combination of spectrophotometric, experimental and theoretical methods to test how melanosome hollowness—a morphological innovation largely restricted to birds—affects feather colour. Optical analyses of hexagonal close-packed arrays of hollow melanosomes in two species, wild turkeys (Meleagris gallopavo) and violet-backed starlings (Cinnyricinclus leucogaster), indicated that they function as two-dimensional PCs. Incorporation of a larger dataset and optical modelling showed that, compared with solid melanosomes, hollow melanosomes allow birds to produce distinct colours with the same energetically favourable, close-packed configurations. These data suggest that a morphological novelty has, at least in part, allowed birds to achieve their vast morphological and colour diversity. PMID:23902909

Strengthened effective connectivity underlies transfer of working memory training to tests of short-term memory and attention

PubMed Central

Kundu, Bornali; Sutterer, David W.; Emrich, Stephen M.; Postle, Bradley R.

2013-01-01

Although long considered a natively endowed and fixed trait, working memory (WM) ability has recently been shown to improve with intensive training. What remains controversial and poorly understood, however, are the neural bases of these training effects, and the extent to which WM training gains transfer to other cognitive tasks. Here we present evidence from human electrophysiology (EEG) and simultaneous transcranial magnetic stimulation (TMS) and EEG that the transfer of WM training to other cognitive tasks is supported by changes in task-related effective connectivity in frontoparietal and parietooccipital networks that are engaged by both the trained and transfer tasks. One consequence of this effect is greater efficiency of stimulus processing, as evidenced by changes in EEG indices of individual differences in short-term memory capacity and in visual search performance. Transfer to search-related activity provides evidence that something more fundamental than task-specific strategy or stimulus-specific representations have been learned. Furthermore, these patterns of training and transfer highlight the role of common neural systems in determining individual differences in aspects of visuospatial cognition. PMID:23678114

BACE1 inhibition by microdose lithium formulation NP03 rescues memory loss and early stage amyloid neuropathology

PubMed Central

Wilson, E N; Do Carmo, S; Iulita, M F; Hall, H; Ducatenzeiler, A; Marks, A R; Allard, S; Jia, D T; Windheim, J; Cuello, A C

2017-01-01

Lithium is first-line therapy for bipolar affective disorder and has recently been shown to have protective effects in populations at risk for Alzheimer’s disease (AD). However, the mechanism underlying this protection is poorly understood and consequently limits its possible therapeutic application in AD. Moreover, conventional lithium formulations have a narrow therapeutic window and are associated with a severe side effect profile. Here we evaluated a novel microdose formulation of lithium, coded NP03, in a well-characterized rat model of progressive AD-like amyloid pathology. This formulation allows microdose lithium delivery to the brain in the absence of negative side effects. We found that NP03 rescued key initiating components of AD pathology, including inactivating GSK-3β, reducing BACE1 expression and activity, and reducing amyloid levels. Notably, NP03 rescued memory loss, impaired CRTC1 promoter binding of synaptic plasticity genes and hippocampal neurogenesis. These results raise the possibility that NP03 be of therapeutic value in the early or preclinical stages of AD. PMID:28763060

Biological consequences of the coaster brook trout restoration stocking program in Lake Superior tributaries with Pictured Rocks National Lakeshore

USGS Publications Warehouse

Leonard, Jill B.K.; Stott, Wendylee; Loope, Delora M.; Kusnierz, Paul C.; Sreenivasan, Ashwin

2013-01-01

The coaster Brook Trout Salvelinus fontinalis is a Lake Superior ecotype representing intraspecific variation that has been impacted by habitat loss and overfishing. Hatchery strains of Brook Trout derived from populations in Lake Superior were stocked into streams within Pictured Rocks National Lakeshore, Michigan, as part of an effort to rehabilitate adfluvial coaster Brook Trout. Wild and hatchery Brook Trout from three streams (Mosquito River, Hurricane River, and Sevenmile Creek) were examined for movement behavior, size, physiology, and reproductive success. Behavior and size of the stocked fish were similar to those of wild fish, and less than 15% of the stocked, tagged Brook Trout emigrated from the river into which they were stocked. There was little evidence of successful reproduction by stocked Brook Trout. Similar to the results of other studies, our findings suggest that the stocking of nonlocal Brook Trout strains where a local population already exists results in limited natural reproduction and should be avoided, particularly if the mechanisms governing the ecotype of interest are poorly understood.

Similarity increases altruistic punishment in humans

PubMed Central

Mussweiler, Thomas; Ockenfels, Axel

2013-01-01

Humans are attracted to similar others. As a consequence, social networks are homogeneous in sociodemographic, intrapersonal, and other characteristics—a principle called homophily. Despite abundant evidence showing the importance of interpersonal similarity and homophily for human relationships, their behavioral correlates and cognitive foundations are poorly understood. Here, we show that perceived similarity substantially increases altruistic punishment, a key mechanism underlying human cooperation. We induced (dis)similarity perception by manipulating basic cognitive mechanisms in an economic cooperation game that included a punishment phase. We found that similarity-focused participants were more willing to punish others’ uncooperative behavior. This influence of similarity is not explained by group identity, which has the opposite effect on altruistic punishment. Our findings demonstrate that pure similarity promotes reciprocity in ways known to encourage cooperation. At the same time, the increased willingness to punish norm violations among similarity-focused participants provides a rationale for why similar people are more likely to build stable social relationships. Finally, our findings show that altruistic punishment is differentially involved in encouraging cooperation under pure similarity vs. in-group conditions. PMID:24218611

Modeling postpartum depression in rats: theoretic and methodological issues

PubMed Central

Ming, LI; Shinn-Yi, CHOU

2016-01-01

The postpartum period is when a host of changes occur at molecular, cellular, physiological and behavioral levels to prepare female humans for the challenge of maternity. Alteration or prevention of these normal adaptions is thought to contribute to disruptions of emotion regulation, motivation and cognitive abilities that underlie postpartum mental disorders, such as postpartum depression. Despite the high incidence of this disorder, and the detrimental consequences for both mother and child, its etiology and related neurobiological mechanisms remain poorly understood, partially due to the lack of appropriate animal models. In recent decades, there have been a number of attempts to model postpartum depression disorder in rats. In the present review, we first describe clinical symptoms of postpartum depression and discuss known risk factors, including both genetic and environmental factors. Thereafter, we discuss various rat models that have been developed to capture various aspects of this disorder and knowledge gained from such attempts. In doing so, we focus on the theories behind each attempt and the methods used to achieve their goals. Finally, we point out several understudied areas in this field and make suggestions for future directions. PMID:27469254

The molecular structure and catalytic mechanism of a quorum-quenching N-acyl-L-homoserine lactone hydrolase

PubMed Central

Kim, Myung Hee; Choi, Won-Chan; Kang, Hye Ok; Lee, Jong Suk; Kang, Beom Sik; Kim, Kyung-Jin; Derewenda, Zygmunt S.; Oh, Tae-Kwang; Lee, Choong Hwan; Lee, Jung-Kee

2005-01-01

In many Gram-negative bacteria, including a number of pathogens such as Pseudomonas aeruginosa and Erwinia carotovora, virulence factor production and biofilm formation are linked to the quorum-sensing systems that use diffusible N-acyl-l-homoserine lactones (AHLs) as intercellular messenger molecules. A number of organisms also contain genes coding for lactonases that hydrolyze AHLs into inactive products, thereby blocking the quorum-sensing systems. Consequently, these enzymes attract intense interest for the development of antiinfection therapies. However, the catalytic mechanism of AHL-lactonase is poorly understood and subject to controversy. We here report a 2.0-Å resolution structure of the AHL-lactonase from Bacillus thuringiensis and a 1.7-Å crystal structure of its complex with l-homoserine lactone. Despite limited sequence similarity, the enzyme shows remarkable structural similarities to glyoxalase II and RNase Z proteins, members of the metallo-β-lactamase superfamily. We present experimental evidence that AHL-lactonase is a metalloenzyme containing two zinc ions involved in catalysis, and we propose a catalytic mechanism for bacterial metallo-AHL-lactonases. PMID:16314577

An extreme climatic event alters marine ecosystem structure in a global biodiversity hotspot

NASA Astrophysics Data System (ADS)

Wernberg, Thomas; Smale, Dan A.; Tuya, Fernando; Thomsen, Mads S.; Langlois, Timothy J.; de Bettignies, Thibaut; Bennett, Scott; Rousseaux, Cecile S.

2013-01-01

Extreme climatic events, such as heat waves, are predicted to increase in frequency and magnitude as a consequence of global warming but their ecological effects are poorly understood, particularly in marine ecosystems. In early 2011, the marine ecosystems along the west coast of Australia--a global hotspot of biodiversity and endemism--experienced the highest-magnitude warming event on record. Sea temperatures soared to unprecedented levels and warming anomalies of 2-4°C persisted for more than ten weeks along >2,000km of coastline. We show that biodiversity patterns of temperate seaweeds, sessile invertebrates and demersal fish were significantly different after the warming event, which led to a reduction in the abundance of habitat-forming seaweeds and a subsequent shift in community structure towards a depauperate state and a tropicalization of fish communities. We conclude that extreme climatic events are key drivers of biodiversity patterns and that the frequency and intensity of such episodes have major implications for predictive models of species distribution and ecosystem structure, which are largely based on gradual warming trends.

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.

Phospho-mimicking Atf1 mutants bypass the transcription activating function of the MAP kinase Sty1 of fission yeast.

PubMed

Sánchez-Mir, Laura; Salat-Canela, Clàudia; Paulo, Esther; Carmona, Mercè; Ayté, José; Oliva, Baldo; Hidalgo, Elena

2018-02-01

Stress-dependent activation of signaling cascades is often mediated by phosphorylation events, but the exact nature and role of these phosphorelays are frequently poorly understood. Here, we review which are the consequences of the stress-dependent phosphorylation of a transcription factor on gene activation. In fission yeast, the MAP kinase Sty1 is activated upon several environmental hazards and promotes cell adaptation and survival, greatly through activation of a gene program mediated by the transcription factor Atf1. Although described decades ago, the role of the phosphorylation of Atf1 by Sty1 is still a matter of debate. We present here a brief review of recent data, obtained through the characterization of several phosphorylation mutant derivatives of Atf1, demonstrating that Atf1 phosphorylation does not stabilize the factor nor stimulates its binding to DNA. Rather, it provides a structural platform of interaction with the transcriptional machinery. Based on these findings, future work will establish how this phosphorylated trans-activation domain promotes the massive gene expression shift allowing cellular adaptation to stress.

Sexual Patterns at Different Ages

ERIC Educational Resources Information Center

Kaplan, Helen S.; Sager, Clifford J.

1971-01-01

When not understood as normal consequences of growth and aging, sexual fluctuations can be the source of personal and marital distress. Discussed are sexual behavior norms as they change from infancy to old age. (Author/CJ)

Collective arrangements and social networks: Coping strategies for the poor households in the Great Ruaha Catchment in Tanzania

NASA Astrophysics Data System (ADS)

Kadigi, Reuben M. J.; Mdoe, N. S. Y.; Ashimogo, G. C.

Access to water and land resources underpins the socio-economic fabric of many societies in the Southern Africa region, which is characterized broadly as underdeveloped with widespread food insecurity, exacerbated by persistent droughts, erratic rainfalls and increasing human populations. The availability of land and water resources is increasingly diminishing and becoming a stumbling block to the development of the agrarian societies in the region. The poor households have in turn adopted new livelihood coping mechanisms but little research has been done to assess the effectiveness of these ‘instruments’. Consequently, the concepts of sustainable water resources management and agricultural development have remained elusive and poorly understood by policy makers as well as by water resources planners and managers. Recognizing this, a study was conducted between 2002 and 2005 under the RIPARWIN (Raising Irrigation Productivity and Releasing Water for Intersectoral Needs) project to assess the spatial dynamics of livelihood capital, vulnerability and coping strategies for the poor agrarian households in the Upper Great Ruaha River Catchment (GRRC) in Tanzania. The results of analysis showed an array of livelihood platforms and institutional contexts that act to shape the existing livelihood typologies in the GRRC. In addition, the results showed a gradual increase in household vulnerability from upstream to downstream, particularly in terms of access to physical and natural assets. Vulnerability was found to be directly associated with the number of dependants. The female-headed households were relatively more likely to be vulnerable than the male-headed households (cf. probabilities of 27% and 21%, respectively). The value of collective arrangements and drawing on social networks crosscut all social strata and ranked as the most common livelihood strategy. This suggests that the scope for reducing vulnerability among the poor households in the GRRC critically depends on the existing institutional arrangements and mechanisms. Of paramount importance is perhaps the need to facilitate the establishment and empowerment of water use associations and apex bodies. In the study area, this appears to be promising enough to build ‘strong’ institutional platforms through which water and land resources would be managed sustainably.

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...

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.

Consequences of plant phenolic compounds for productivity and health of ruminants.

PubMed

Waghorn, Garry C; McNabb, Warren C

2003-05-01

Plant phenolic compounds are diverse in structure but are characterised by hydroxylated aromatic rings (e.g. flavan-3-ols). They are categorised as secondary metabolites, and their function in plants is often poorly understood. Many plant phenolic compounds are polymerised into larger molecules such as the proanthocyanidins (PA; condensed tannins) and lignins. Only the lignins, PA, oestrogenic compounds and hydrolysable tannins will be considered here. Lignins slow the physical and microbial degradation of ingested feed, because of resilient covalent bonding with hemicellulose and cellulose, rather than any direct effects on the rumen per se. The PA are prevalent in browse and are expressed in the foliage of some legumes (e.g. Lotus spp.), but rarely in grasses. They reduce the nutritive value of poor-quality diets, but can also have substantial benefits for ruminant productivity and health when improved temperate forages are fed. Beneficial effects are dependent on the chemical and physical structure, and concentration of the PA in the diet, but they have been shown to improve live-weight gain, milk yield and protein concentration, and ovulation rate. They prevent bloat in cattle, reduce gastrointestinal nematode numbers, flystrike and CH4 production. Some phenolic compounds (e.g. coumestans) cause temporary infertility, whilst those produced by Fusarium fungi found in pasture, silage or stored grains can cause permanent infertility. The HT may be toxic because products of their metabolism can cause liver damage and other metabolic disorders.

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.

Demographic effects of extreme weather events: snow storms, breeding success, and population growth rate in a long-lived Antarctic seabird

PubMed Central

Descamps, Sébastien; Tarroux, Arnaud; Varpe, Øystein; Yoccoz, Nigel G; Tveraa, Torkild; Lorentsen, Svein-Håkon

2015-01-01

Weather extremes are one important element of ongoing climate change, but their impacts are poorly understood because they are, by definition, rare events. If the frequency and severity of extreme weather events increase, there is an urgent need to understand and predict the ecological consequences of such events. In this study, we aimed to quantify the effects of snow storms on nest survival in Antarctic petrels and assess whether snow storms are an important driver of annual breeding success and population growth rate. We used detailed data on daily individual nest survival in a year with frequent and heavy snow storms, and long term data on petrel productivity (i.e., number of chicks produced) at the colony level. Our results indicated that snow storms are an important determinant of nest survival and overall productivity. Snow storm events explained 30% of the daily nest survival within the 2011/2012 season and nearly 30% of the interannual variation in colony productivity in period 1985–2014. Snow storms are a key driver of Antarctic petrel breeding success, and potentially population dynamics. We also found state-dependent effects of snow storms and chicks in poor condition were more likely to die during a snow storm than chicks in good condition. This stresses the importance of considering interactions between individual heterogeneity and extreme weather events to understand both individual and population responses to climate change. PMID:25691959

Demographic effects of extreme weather events: snow storms, breeding success, and population growth rate in a long-lived Antarctic seabird.

PubMed

Descamps, Sébastien; Tarroux, Arnaud; Varpe, Øystein; Yoccoz, Nigel G; Tveraa, Torkild; Lorentsen, Svein-Håkon

2015-01-01

Weather extremes are one important element of ongoing climate change, but their impacts are poorly understood because they are, by definition, rare events. If the frequency and severity of extreme weather events increase, there is an urgent need to understand and predict the ecological consequences of such events. In this study, we aimed to quantify the effects of snow storms on nest survival in Antarctic petrels and assess whether snow storms are an important driver of annual breeding success and population growth rate. We used detailed data on daily individual nest survival in a year with frequent and heavy snow storms, and long term data on petrel productivity (i.e., number of chicks produced) at the colony level. Our results indicated that snow storms are an important determinant of nest survival and overall productivity. Snow storm events explained 30% of the daily nest survival within the 2011/2012 season and nearly 30% of the interannual variation in colony productivity in period 1985-2014. Snow storms are a key driver of Antarctic petrel breeding success, and potentially population dynamics. We also found state-dependent effects of snow storms and chicks in poor condition were more likely to die during a snow storm than chicks in good condition. This stresses the importance of considering interactions between individual heterogeneity and extreme weather events to understand both individual and population responses to climate change.

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.

Consequences of contextual factors on clinical reasoning in resident physicians.

PubMed

McBee, Elexis; Ratcliffe, Temple; Picho, Katherine; Artino, Anthony R; Schuwirth, Lambert; Kelly, William; Masel, Jennifer; van der Vleuten, Cees; Durning, Steven J

2015-12-01

Context specificity and the impact that contextual factors have on the complex process of clinical reasoning is poorly understood. Using situated cognition as the theoretical framework, our aim was to evaluate the verbalized clinical reasoning processes of resident physicians in order to describe what impact the presence of contextual factors have on their clinical reasoning. Participants viewed three video recorded clinical encounters portraying straightforward diagnoses in internal medicine with select patient contextual factors modified. After watching each video recording, participants completed a think-aloud protocol. Transcripts from the think-aloud protocols were analyzed using a constant comparative approach. After iterative coding, utterances were analyzed for emergent themes with utterances grouped into categories, themes and subthemes. Ten residents participated in the study with saturation reached during analysis. Participants universally acknowledged the presence of contextual factors in the video recordings. Four categories emerged as a consequence of the contextual factors: (1) emotional reactions (2) behavioral inferences (3) optimizing the doctor patient relationship and (4) difficulty with closure of the clinical encounter. The presence of contextual factors may impact clinical reasoning performance in resident physicians. When confronted with the presence of contextual factors in a clinical scenario, residents experienced difficulty with closure of the encounter, exhibited as diagnostic uncertainty. This finding raises important questions about the relationship between contextual factors and clinical reasoning activities and how this relationship might influence the cost effectiveness of care. This study also provides insight into how the phenomena of context specificity may be explained using situated cognition theory.

Disruptions of Host Immunity and Inflammation by Giardia Duodenalis: Potential Consequences for Co-Infections in the Gastro-Intestinal Tract

PubMed Central

Cotton, James A.; Amat, Christina B.; Buret, Andre G.

2015-01-01

Giardia duodenalis (syn. G. intestinalis, or G. lamblia) is a leading cause of waterborne diarrheal disease that infects hundreds of millions of people annually. Research on Giardia has greatly expanded within the last few years, and our understanding of the pathophysiology and immunology on this parasite is ever increasing. At peak infection, Giardia trophozoites induce pathophysiological responses that culminate in the development of diarrheal disease. However, human data has suggested that the intestinal mucosa of Giardia-infected individuals is devoid of signs of overt intestinal inflammation, an observation that is reproduced in animal models. Thus, our understanding of host inflammatory responses to the parasite remain incompletely understood and human studies and experimental data have produced conflicting results. It is now also apparent that certain Giardia infections contain mechanisms capable of modulating their host’s immune responses. As the oral route of Giardia infection is shared with many other gastrointestinal (GI) pathogens, co-infections may often occur, especially in places with poor sanitation and/or improper treatment of drinking water. Moreover, Giardia infections may modulate host immune responses and have been found to protect against the development of diarrheal disease in developing countries. The following review summarizes our current understanding of the immunomodulatory mechanisms of Giardia infections and their consequences for the host, and highlights areas for future research. Potential implications of these immunomodulatory effects during GI co-infection are also discussed. PMID:26569316

Analysis of diffusion in curved surfaces and its application to tubular membranes.

PubMed

Klaus, Colin James Stockdale; Raghunathan, Krishnan; DiBenedetto, Emmanuele; Kenworthy, Anne K

2016-12-01

Diffusion of particles in curved surfaces is inherently complex compared with diffusion in a flat membrane, owing to the nonplanarity of the surface. The consequence of such nonplanar geometry on diffusion is poorly understood but is highly relevant in the case of cell membranes, which often adopt complex geometries. To address this question, we developed a new finite element approach to model diffusion on curved membrane surfaces based on solutions to Fick's law of diffusion and used this to study the effects of geometry on the entry of surface-bound particles into tubules by diffusion. We show that variations in tubule radius and length can distinctly alter diffusion gradients in tubules over biologically relevant timescales. In addition, we show that tubular structures tend to retain concentration gradients for a longer time compared with a comparable flat surface. These findings indicate that sorting of particles along the surfaces of tubules can arise simply as a geometric consequence of the curvature without any specific contribution from the membrane environment. Our studies provide a framework for modeling diffusion in curved surfaces and suggest that biological regulation can emerge purely from membrane geometry. © 2016 Klaus, Raghunathan, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Stress and strain in the contractile and cytoskeletal filaments of airway smooth muscle.

PubMed

Deng, Linhong; Bosse, Ynuk; Brown, Nathan; Chin, Leslie Y M; Connolly, Sarah C; Fairbank, Nigel J; King, Greg G; Maksym, Geoffrey N; Paré, Peter D; Seow, Chun Y; Stephen, Newman L

2009-10-01

Stress and strain are omnipresent in the lung due to constant lung volume fluctuation associated with respiration, and they modulate the phenotype and function of all cells residing in the airways including the airway smooth muscle (ASM) cell. There is ample evidence that the ASM cell is very sensitive to its physical environment, and can alter its structure and/or function accordingly, resulting in either desired or undesired consequences. The forces that are either conferred to the ASM cell due to external stretching or generated inside the cell must be borne and transmitted inside the cytoskeleton (CSK). Thus, maintaining appropriate levels of stress and strain within the CSK is essential for maintaining normal function. Despite the importance, the mechanisms regulating/dysregulating ASM cytoskeletal filaments in response to stress and strain remained poorly understood until only recently. For example, it is now understood that ASM length and force are dynamically regulated, and both can adapt over a wide range of length, rendering ASM one of the most malleable living tissues. The malleability reflects the CSK's dynamic mechanical properties and plasticity, both of which strongly interact with the loading on the CSK, and all together ultimately determines airway narrowing in pathology. Here we review the latest advances in our understanding of stress and strain in ASM cells, including the organization of contractile and cytoskeletal filaments, range and adaptation of functional length, structural and functional changes of the cell in response to mechanical perturbation, ASM tone as a mediator of strain-induced responses, and the novel glassy dynamic behaviors of the CSK in relation to asthma pathophysiology.

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...

Child Poverty and Its Lasting Consequence. Low-Income Working Families. Paper 21

ERIC Educational Resources Information Center

Ratcliffe, Caroline; McKernan, Signe-Mary

2012-01-01

One in six newborns were born poor over the past 40 years, and nearly half remained poor half their childhoods. These persistently poor children are nearly 90 percent more likely than never-poor children to enter their 20s without completing high school and are four times more likely to give birth outside of marriage during their teenage years.…

A mixed-methods study of health worker migration from Jamaica.

PubMed

Tomblin Murphy, Gail; MacKenzie, Adrian; Waysome, Benjamin; Guy-Walker, Joan; Palmer, Rowena; Elliott Rose, Annette; Rigby, Janet; Labonté, Ronald; Bourgeault, Ivy Lynn

2016-06-30

This study sought to better understand the drivers of migration, its consequences, and the various strategies countries have employed to mitigate its negative impacts. The study was conducted in four countries-Jamaica, India, the Philippines, and South Africa-that have historically been 'sources' of health workers migrating to other countries. The aim of this paper is to present the findings from the Jamaica portion of the study. Data were collected using surveys of Jamaica's generalist and specialist physicians, nurses, midwives, and dental auxiliaries, as well as structured interviews with key informants representing government ministries, professional associations, regional health authorities, healthcare facilities, and educational institutions. Quantitative data were analyzed using descriptive statistics and regression models. Qualitative data were analyzed thematically. Multiple stakeholder engagement workshops were held across Jamaica to share and validate the study findings and discuss implications for the country. Migration of health workers from Jamaica continues to be prevalent. Its causes are numerous, long-standing, and systemic, and are largely based around differences in living and working conditions between Jamaica and 'destination' countries. There is minimal formal tracking of health worker migration from Jamaica, making scientific analysis of its consequences difficult. Although there is evidence of numerous national and international efforts to manage and mitigate the negative impacts of migration, there is little evidence of the implementation or effectiveness of such efforts. Potential additional strategies for better managing the migration of Jamaica's health workers include the use of information systems to formally monitor migration, updating the national cadre system for employment of health personnel, ensuring existing personnel management policies, such as bonding, are both clearly understood and equitably enforced, and providing greater formal and informal recognition of health personnel. Although historically common, migration of Jamaica's health workers is poorly monitored and understood. Improved management of the migration of Jamaica's health workers requires collaboration from stakeholders across multiple sectors. Indeed, participating stakeholders identified a wide range of potential strategies to better manage migration of Jamaica's health workers, the implementation and testing of which will have potential benefits to Jamaica as well as other 'source' countries.

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.

Universal public finance of tuberculosis treatment in India: an extended cost-effectiveness analysis.

PubMed

Verguet, Stéphane; Laxminarayan, Ramanan; Jamison, Dean T

2015-03-01

Universal public finance (UPF)-government financing of an intervention irrespective of who is receiving it-for a health intervention entails consequences in multiple domains. First, UPF increases intervention uptake and hence the extent of consequent health gains. Second, UPF generates financial consequences including the crowding out of private expenditures. Finally, UPF provides insurance either by covering catastrophic expenditures, which would otherwise throw households into poverty or by preventing diseases that cause them. This paper develops a method-extended cost-effectiveness analysis (ECEA)-for evaluating the consequences of UPF in each of these domains. It then illustrates ECEA with an evaluation of UPF for tuberculosis treatment in India. Using plausible values for key parameters, our base case ECEA concludes that the health gains and insurance value of UPF would accrue primarily to the poor. Reductions in out-of-pocket expenditures are more uniformly distributed across income quintiles. A variant on our base case suggests that lowering costs of borrowing for the poor could potentially achieve some of the health gains of UPF, but at the cost of leaving the poor more deeply in debt. © 2014 The Authors. Health Economics published by John Wiley Ltd.

Whistleblowing: what influences nurses' decisions on whether to report poor practice?

PubMed

Gallagher, Ann

Several recent high profile examples demonstrate that nurses fear and have reason to fear the consequences of reporting poor practice. This article examines the ethical issues surrounding whistleblowing, discussing in detail the reasons for and against reporting concerns about poor practice, and how nurses can be supported to do this.

Philosophical behaviorism: a review of things that happen because they should: a teleological approach to action, by Rowland Stout.

PubMed Central

Rachlin, H

1999-01-01

Mentalistic terms such as belief and desire have been rejected by behavior analysts because they are traditionally held to refer to unobservable events inside the organism. Behavior analysis has consequently been viewed by philosophers to be at best irrelevant to psychology, understood as a science of the mind. In this book, the philosopher Rowland Stout argues cogently that beliefs and desires (like operants such as rats' lever presses) are best understood in terms of an interaction over time between overt behavior and its overt consequences (a viewpoint called teleological behaviorism). This book is important because it identifies the science of the mind with the science of overt behavior and implies that the psychologists best equipped to study mental life are not those who purport to do so but those who focus on the experimental analysis of behavior. PMID:10503301

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).

Regime shifts in desert grasslands: patterns, mechanisms, and management

USDA-ARS?s Scientific Manuscript database

Transitions from semiarid grassland to shrubland states are among the most widely recognized examples of regime shifts in terrestrial ecosystems. Nonetheless, the processes causing grassland-shrubland transitions, and their consequences, are incompletely understood. We challenge several misconceptio...

Spatially Refined Aerosol Direct Radiative Focusing Efficiencies

EPA Science Inventory

Global aerosol direct radiative forcing (DRF) is an important metric for assessing potential climate impacts of future emissions changes. However, the radiative consequences of emissions perturbations are not readily quantified nor well understood at the level of detail necessary...

Spatially Refined Aerosol Direct Radiative Forcing Efficiencies

EPA Science Inventory

Global aerosol direct radiative forcing (DRF) is an important metric for assessing potential climate impacts of future emissions changes. However, the radiative consequences of emissions perturbations are not readily quantified nor well understood at the level of detail necessary...

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.

Consequences of variable reproduction for seedling recruitment in three neotropical tree species

Treesearch

Diane De Steven; S. Joesph Wright

2002-01-01

Variable seed production may have important consequences for recruitment but poorly documented for frugivore-dispersed tropical trees. Recruitment limitation may also may be a critical spatial process affectng forest dynamics, but it is rarely assessed at the scale of individual trees. Over an 11-yr period, we studied the consequences of variable seed production for...

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.

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)

Progress in Paralysis | NIH MedlinePlus the Magazine

MedlinePlus

... benefits from this research flowing to people with Parkinson's disease or other neurological disorders? The mechanism of dysfunction in spinal cord injury is not completely understood but is believed to be ... Parkinson's and some of the other neurological disorders. Consequently, ...

The Role of Training in Reducing Poverty: The Case of the Ultra-Poor in Bangladesh

ERIC Educational Resources Information Center

Khan, Mohammad Aktaruzzaman; Ali, Anees Janee

2014-01-01

Although microcredit is considered the main vehicle for increasing the income of the poor and alleviating poverty in Bangladesh, it is now well recognised that more than this is needed to reach the ultra poor in rural areas. Consequently, almost half of the Bangladesh population is in some way linked to non-governmental organizations' development…

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...

Decision-Making Alignment: Respecting Natural Consequences

ERIC Educational Resources Information Center

Quinby, Lee

2016-01-01

Many organizations have a tendency toward misalignment of "authority," "responsibility," and "accountability" that causes poor decision-making. There are natural consequences that result, similar to touching fire and getting burned. When those key elements are not properly aligned, the organization can experience…

The Relationship Between Perceived Hookup Attitudes and Negative Hookup Consequences: Do Perceived Attitudes of Close Friends Matter?

PubMed

Montes, Kevin S; Blanco, Lyzette; LaBrie, Joseph W

2017-01-01

Research suggests that the perceived hookup attitudes of close referents are generally a poor predictor of hookup behavior and likely a poor direct predictor of negative hookup consequences. The current study aimed to examine three intervening variables as mediators of the relationship between the perceived hookup attitudes of college students' close friends and negative hookup consequences (e.g., regret, embarrassment). Self-report data were collected from 589 heavy-drinking college students from three midsized universities. The results indicated that students' own attitudes toward hooking up, motivation to hook up, and self-reported number of hookup partners significantly mediated the relationship between the perceived hookup attitudes of close friends and negative hookup consequences. The perceived hookup attitudes of close friends were positively associated with participants' attitudes toward hooking up. Participants' attitudes toward hooking up were positively associated with social-sexual motivation to hook up. Elevated social-sexual motivation to hook up was positively associated with hooking up with multiple partners, with hooking up with multiple partners positively associated with negative hookup consequences. A better understanding of the predictors and mediators of negative hookup consequences has the potential to inform prevention and intervention efforts.

Poor maternal nutrition and accelerated postnatal growth induces an accelerated aging phenotype and oxidative stress in skeletal muscle of male rats

PubMed Central

Fernandez-Twinn, Denise S.; Chen, Jian Hua; Hargreaves, Iain P.; Neergheen, Viruna; Aiken, Catherine E.; Ozanne, Susan E.

2016-01-01

ABSTRACT ‘Developmental programming’, which occurs as a consequence of suboptimal in utero and early environments, can be associated with metabolic dysfunction in later life, including an increased incidence of cardiovascular disease and type 2 diabetes, and predisposition of older men to sarcopenia. However, the molecular mechanisms underpinning these associations are poorly understood. Many conditions associated with developmental programming are also known to be associated with the aging process. We therefore utilized our well-established rat model of low birth weight and accelerated postnatal catch-up growth (termed ‘recuperated’) in this study to establish the effects of suboptimal maternal nutrition on age-associated factors in skeletal muscle. We demonstrated accelerated telomere shortening (a robust marker of cellular aging) as evidenced by a reduced frequency of long telomeres (48.5-8.6 kb) and an increased frequency of short telomeres (4.2-1.3 kb) in vastus lateralis muscle from aged recuperated offspring compared to controls. This was associated with increased protein expression of the DNA-damage-repair marker 8-oxoguanine-glycosylase (OGG1) in recuperated offspring. Recuperated animals also demonstrated an oxidative stress phenotype, with decreased citrate synthase activity, increased electron-transport-complex activities of complex I, complex II-III and complex IV (all markers of functional mitochondria), and increased xanthine oxidase (XO), p67phox and nuclear-factor kappa-light-chain-enhancer of activated B-cells (NF-κB). Recuperated offspring also demonstrated increased antioxidant defense capacity, with increased protein expression of manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), catalase and heme oxygenase-1 (HO1), all of which are known targets of NF-κB and can be upregulated as a consequence of oxidative stress. Recuperated offspring also had a pro-inflammatory phenotype, as evidenced by increased tumor necrosis factor-α (TNFα) and interleukin-1β (IL1β) protein levels. Taken together, we demonstrate, for the first time to our knowledge, an accelerated aging phenotype in skeletal muscle in the context of developmental programming. These findings may pave the way for suitable interventions in at-risk populations. PMID:27585884

Feline drug metabolism and disposition: pharmacokinetic evidence for species differences and molecular mechanisms

PubMed Central

2013-01-01

Synopsis Although it is widely appreciated that cats respond differently to certain drugs when compared with other companion animal species, the causes of these differences are poorly understood. This review critically evaluates published evidence for altered drug effects in cats, focusing on pharmacokinetic differences between cats, dogs and humans, and the molecular mechanisms underlying these differences. Pharmacokinetic studies indicate that acetaminophen, propofol, carprofen, and acetylsalicylic acid (aspirin) are cleared significantly more slowly in cats versus dogs and humans. All of these drugs are metabolized by conjugation. Cats lack the major phenol UDP-glucuronosyltransferase (UGT) enzymes, including UGT1A6 and UGT1A9, that glucuronidate acetaminophen and propofol. Deficient glucuronidation may also explain slower carprofen clearance, although there is no direct evidence for this. However, poor aspirin clearance in cats appears to be mainly a consequence of slower glycine conjugation. Cats are also deficient in several other conjugation enzymes, including N-acetyltransferase (NAT) 2 and thiopurine methyltransferase (TMPT). NAT2 deficiency may be the reason cats are more prone to developing methemoglobinemia rather than hepatotoxicity from acetaminophen. TMPT deficiency may predispose cats to azathioprine toxicity. No evidence was found for slower elimination of drugs cleared by oxidation or unchanged into urine or bile. Piroxicam, an oxidized drug, was cleared much more rapidly in cats than humans and dogs, although the mechanism for this difference is unclear. More work is needed to better understand drug metabolism and disposition differences in cats, thereby enabling more rational prescribing of existing medications, and the development of safer drugs for this species. PMID:23890237

Understanding and Improving the Health of People Who Experience Incarceration: An Overview and Synthesis.

PubMed

Kinner, Stuart A; Young, Jesse T

2018-06-01

The world prison population is growing at a rate that exceeds the rate of population growth. This issue of Epidemiologic Reviews comprises articles in which researchers summarize what is known about some of the key health issues facing people in prison, particularly in relation to human immunodeficiency virus and other blood-borne viral infections. A key recurring theme is that addressing the health needs of people in prison is important to reducing health inequalities at the population level-that prisoner health is public health. The reviews also highlight some critical evidence gaps, notably the lack of evidence from low- and middle-income countries, and the limited number of longitudinal studies in which health behaviors, health outcomes, or health service experiences after release from prison are documented. Despite growing evidence of the poor health of detained adolescents, none of the included reviews considered this population. Further research on the health of young people who cycle through juvenile detention should be a priority. Despite a rapidly growing literature on the health of people who experience incarceration, some critical health issues remain poorly understood, and there has been insufficient attention devoted to co-occurring health conditions and the consequent need for coordinated care. Key populations in custodial settings remain understudied, limiting capacity to develop targeted, evidence-based responses to their health needs. The quality of many studies is suboptimal, and although rigorous, independent research in correctional settings can be challenging, it is not impossible and is critical to laying the groundwork for evidence-based reform.

Genetic diversity of Phytophthora infestans in the Northern Andean region.

PubMed

Cárdenas, Martha; Grajales, Alejandro; Sierra, Roberto; Rojas, Alejandro; González-Almario, Adriana; Vargas, Angela; Marín, Mauricio; Fermín, Gustavo; Lagos, Luz E; Grünwald, Niklaus J; Bernal, Adriana; Salazar, Camilo; Restrepo, Silvia

2011-02-09

Phytophthora infestans (Mont.) de Bary, the causal agent of potato late blight, is responsible for tremendous crop losses worldwide. Countries in the northern part of the Andes dedicate a large proportion of the highlands to the production of potato, and more recently, solanaceous fruits such as cape gooseberry (Physalis peruviana) and tree tomato (Solanum betaceum), all of which are hosts of this oomycete. In the Andean region, P. infestans populations have been well characterized in Ecuador and Peru, but are poorly understood in Colombia and Venezuela. To understand the P. infestans population structure in the Northern part of the Andes, four nuclear regions (ITS, Ras, β-tubulin and Avr3a) and one mitochondrial (Cox1) region were analyzed in isolates of P. infestans sampled from different hosts in Colombia and Venezuela. Low genetic diversity was found within this sample of P. infestans isolates from crops within several regions of Colombia and Venezuela, revealing the presence of clonal populations of the pathogen in this region. We detected low frequency heterozygotes, and their distribution patterns might be a consequence of a high migration rate among populations with poor effective gene flow. Consistent genetic differentiation exists among isolates from different regions. The results here suggest that in the Northern Andean region P. infestans is a clonal population with some within-clone variation. P. infestans populations in Venezuela reflect historic isolation that is being reinforced by a recent self-sufficiency of potato seeds. In summary, the P. infestans population is mainly shaped by migration and probably by the appearance of variants of key effectors such as Avr3a.

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…

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.

Defining Ebstein's malformation using three-dimensional echocardiography.

PubMed

Vettukattil, Joseph J; Bharucha, Tara; Anderson, Robert H

2007-12-01

Ebstein's malformation is difficult to visualise, for both the echocardiographer and the surgeon. The essence of the problem in Ebstein's malformation is the deviation of the hingepoints of the leaflets towards the junctions of the inlet and apical trabecular parts of the right ventricle. Three-dimensional echocardiography offers new insights into the morphology and function of malformed valves, and allows elucidation of all the features. It allows clear visualisation of the valve leaflets, showing the precise morphology of the valve leaflets, the extent of their formation, the level of their attachment, and their degree of coaptation. Visualisation of the mechanism of regurgitation or stenosis is possible, as is more accurate quantification of the regurgitant jet or jets. Subchordal apparatus may be seen more clearly using three-dimensional echocardiography, and their functional anatomy understood. The multiplanar review modality allows examination of the three-dimensional data set even in patients with sub-optimal echocardiographic imaging. Previously, much of this information could only be well-understood at the time of surgery or post mortem, meaning that the majority of the specimens fully examined were at the poorly functioning end of the spectrum. This information is of use in furthering our understanding of this complex lesion as it functions in vivo, and demonstrating which anatomical pathology is significant in producing functional and physiological consequences. It is also of use for the clinician in selecting which patients are amenable to surgical intervention, for either single or biventricular repair, and for the surgeon in planning how to approach the operation. Correlation between three-dimensional echocardiographic findings and surgical findings has already been established, but the effect of this enhanced anatomical knowledge on surgical planning and surgical outcome requires further investigation.

Size-resolved Chemical Composition of Cloud and Rain Water Collected during the Puerto Rico African Dust and Clouds Study (PRADACS) Campaign

NASA Astrophysics Data System (ADS)

Torres, E.; Valle Diaz, C. J.; Zurcher, F.; Lee, T.; Collett, J. L.; Fitzgerald, E.; Cuadra, L.; Prather, K. A.; Mayol-Bracero, O. L.

2011-12-01

The underlying physico-chemical processes of dust-aerosol interactions are poorly understood; even less understood is how aging impacts cloud properties and climate as the particles travel from Africa to the Caribbean region. Caribbean landmasses have tropical montane cloud forests (TMCFs) that are tightly coupled to the atmospheric hydrologic cycle. Small-scale shifts in temperature and precipitation could have serious ecological consequences. Therefore, this makes TMCFs an interesting ecosystem to see the effects African Dust (AD) might have on cloud formation and precipitation. As part of the Puerto Rico African Dust and Clouds Study (PRADACS) cloud and rain water samples for subsequent chemical analysis were collected at Pico del Este (PE) station in Luquillo, PR (1051 masl) during summer 2011. At PE, two cloud collectors (i.e., single stage (Aluminum version) and 2-stage (Teflon version) Caltech Active Strand Cloudwater Collector (CASCC)), and a rainwater collector were operated. Measurements such as the liquid water content (LWC), pH, conductivity., and composition of single particles using an aerosol time of flight mass spectrometer (ATOFMS) were performed. Preliminary results showed that days with the influence of African dust (AD), had LWC values that ranged from 300 to 500 mg/m3, pH values up to 5.7,, and conductivity up to 180 μS/cm. The ATOFMS showed titanium and iron ions, suggesting the presence of AD as well as, occasionally, sulfate and nitrate ions suggesting the influence of anthropogenic pollution. Results on the chemical composition and the physical properties of cloud, rainwater, and aerosol for the inorganic as well as the organic fraction and how these properties change for the different air masses observed will also be presented.

Symmetric vs. Asymmetric Stem Cell Divisions: An Adaptation against Cancer?

PubMed Central

Shahriyari, Leili; Komarova, Natalia L.

2013-01-01

Traditionally, it has been held that a central characteristic of stem cells is their ability to divide asymmetrically. Recent advances in inducible genetic labeling provided ample evidence that symmetric stem cell divisions play an important role in adult mammalian homeostasis. It is well understood that the two types of cell divisions differ in terms of the stem cells' flexibility to expand when needed. On the contrary, the implications of symmetric and asymmetric divisions for mutation accumulation are still poorly understood. In this paper we study a stochastic model of a renewing tissue, and address the optimization problem of tissue architecture in the context of mutant production. Specifically, we study the process of tumor suppressor gene inactivation which usually takes place as a consequence of two “hits”, and which is one of the most common patterns in carcinogenesis. We compare and contrast symmetric and asymmetric (and mixed) stem cell divisions, and focus on the rate at which double-hit mutants are generated. It turns out that symmetrically-dividing cells generate such mutants at a rate which is significantly lower than that of asymmetrically-dividing cells. This result holds whether single-hit (intermediate) mutants are disadvantageous, neutral, or advantageous. It is also independent on whether the carcinogenic double-hit mutants are produced only among the stem cells or also among more specialized cells. We argue that symmetric stem cell divisions in mammals could be an adaptation which helps delay the onset of cancers. We further investigate the question of the optimal fraction of stem cells in the tissue, and quantify the contribution of non-stem cells in mutant production. Our work provides a hypothesis to explain the observation that in mammalian cells, symmetric patterns of stem cell division seem to be very common. PMID:24204602

Human embryonic stem cells fail to activate CHK1 and commit to apoptosis in response to DNA replication stress.

PubMed

Desmarais, Joëlle A; Hoffmann, Michele J; Bingham, Gregg; Gagou, Mary E; Meuth, Mark; Andrews, Peter W

2012-07-01

Pluripotent cells of the early embryo, to which embryonic stem cells (ESCs) correspond, give rise to all the somatic cells of the developing fetus. Any defects that occur in their genome or epigenome would have devastating consequences. Genetic and epigenetic change in human ESCs appear to be an inevitable consequence of long-term culture, driven by selection of variant cells that have a higher propensity for self-renewal rather than either differentiation or death. Mechanisms underlying the potentially separate events of mutation and subsequent selection of variants are poorly understood. Here, we show that human ESCs and their malignant counterpart, embryonal carcinoma (EC) cells, both fail to activate critical S-phase checkpoints when exposed to DNA replication inhibitors and commit to apoptosis instead. Human ESCs and EC cells also fail to form replication protein A, γH2AX, or RAD51 foci or load topoisomerase (DNA) II binding protein 1 onto chromatin in response to replication inhibitors. Furthermore, direct measurements of single-stranded DNA (ssDNA) show that these cells fail to generate the ssDNA regions in response to replication stress that are necessary for the activation of checkpoints and the initiation of homologous recombination repair to protect replication fork integrity and restart DNA replication. Taken together, our data suggest that pluripotent cells control genome integrity by the elimination of damaged cells through apoptosis rather than DNA repair, and therefore, mutations or epigenetic modifications resulting in an imbalance in cell death control could lead to genetic instability. Copyright © 2012 AlphaMed Press.

Stiffness is more than just duration and severity: a qualitative exploration in people with rheumatoid arthritis

PubMed Central

Dures, Emma; Kirwan, John; Pollock, Jon; Baker, Gill; Edmunds, Avis; Hewlett, Sarah

2015-01-01

Objective. Stiffness is internationally recognized as an important indicator of inflammatory activity in RA but is poorly understood and difficult to measure. The aim of this study was to explore the experience of stiffness from the patient perspective. Methods. Semi-structured interviews conducted with 16 RA patients were analysed independently by researchers and pat.ient partners using inductive thematic analysis. Results. Six themes were identified. Part of having RA identified stiffness as a normal consequence of RA, perceived as associated with disease-related aspects such as fluctuating disease activity, other RA symptoms and disease duration. Local and widespread highlighted stiffness occurring not only in joints, but also over the whole body, being more widespread during the morning or flare. Linked to behaviour and environment illustrated factors that influence stiffness, including movement, medications and weather. Highly variable captured the fluctuating nature of stiffness within and between patients and in relation to temporality, duration and intensity. Impacts on daily life emphasized the effect of stiffness on a range of domains, including physical function, quality of life, psychological well-being, activities of daily living and participation in work and leisure activities. Requires self-management detailed self-management strategies targeting both the symptom and its consequences. Conclusion. Patients’ experiences of stiffness were varied, complex and not exclusive to the morning period. Importantly, stiffness was reported in terms of impact rather than the traditional measurement concepts of severity or duration. Based on these findings, further research is needed to develop a patient-centred measure that adequately reflects inflammatory activity. PMID:25231178

Gap junction communication between uterine stromal cells plays a critical role in pregnancy-associated neovascularization and embryo survival.

PubMed

Laws, Mary J; Taylor, Robert N; Sidell, Neil; DeMayo, Francesco J; Lydon, John P; Gutstein, David E; Bagchi, Milan K; Bagchi, Indrani C

2008-08-01

In the uterus, the formation of new maternal blood vessels in the stromal compartment at the time of embryonic implantation is critical for the establishment and maintenance of pregnancy. Although uterine angiogenesis is known to be influenced by the steroid hormones estrogen (E) and progesterone (P), the underlying molecular pathways remain poorly understood. Here, we report that the expression of connexin 43 (Cx43), a major gap junction protein, is markedly enhanced in response to E in uterine stromal cells surrounding the implanted embryo during the early phases of pregnancy. Conditional deletion of the Cx43 gene in these stromal cells and the consequent disruption of their gap junctions led to a striking impairment in the development of new blood vessels within the stromal compartment, resulting in the arrest of embryo growth and early pregnancy loss. Further analysis of this phenotypical defect revealed that loss of Cx43 expression resulted in aberrant differentiation of uterine stromal cells and impaired production of several key angiogenic factors, including the vascular endothelial growth factor (Vegf). Ablation of CX43 expression in human endometrial stromal cells in vitro led to similar findings. Collectively, these results uncovered a unique link between steroid hormone-regulated cell-cell communication within the pregnant uterus and the development of an elaborate vascular network that supports embryonic growth. Our study presents the first evidence that Cx43-type gap junctions play a critical and conserved role in modulating stromal differentiation, and regulate the consequent production of crucial paracrine signals that control uterine neovascularization during implantation.

Adolescent vulnerability to cardiovascular consequences of chronic social stress: Immediate and long-term effects of social isolation during adolescence.

PubMed

Cruz, Fábio C; Duarte, Josiane O; Leão, Rodrigo M; Hummel, Luiz F V; Planeta, Cleopatra S; Crestani, Carlos C

2016-01-01

It has been demonstrated that disruption of social bonds and perceived isolation (loneliness) are associated with an increased risk of cardiovascular morbidity and mortality. Adolescence is proposed as a period of vulnerability to stress. Nevertheless, the impact of chronic social stress during this ontogenic period in cardiovascular function is poorly understood. Therefore, the purpose of this study was to compare the impact in cardiovascular function of social isolation for 3 weeks in adolescent and adult male rats. Also, the long-term effects of social isolation during adolescence were investigated longitudinally. Social isolation reduced body weight in adolescent, but not in adult animals. Disruption of social bonds during adolescence increased arterial pressure without affecting heart rate and pulse pressure (PP). Nevertheless, social isolation in adulthood reduced systolic arterial pressure and increased diastolic arterial pressure, which in turn decreased PP without affecting mean arterial pressure. Cardiovascular changes in adolescents, but not adults, were followed by facilitation of both baroreflex sensitivity and vascular reactivity to the vasodilator agent acetylcholine. Vascular responsiveness to either the vasodilator agent sodium nitroprusside or the vasoconstrictor agent phenylephrine was not affected by social isolation. Except for the changes in body weight and baroreflex sensitivity, all alterations evoked by social isolation during adolescence were reversed in adulthood after moving animals from isolated to collective housing. These findings suggest a vulnerability of adolescents to the effects of chronic social isolation in cardiovascular function. However, results indicate minimal cardiovascular consequences in adulthood of disruption of social bonds during adolescence. © 2015 Wiley Periodicals, Inc.

Paternal Age Effect Mutations and Selfish Spermatogonial Selection: Causes and Consequences for Human Disease

PubMed Central

Goriely, Anne; Wilkie, Andrew O.M.

2012-01-01

Advanced paternal age has been associated with an increased risk for spontaneous congenital disorders and common complex diseases (such as some cancers, schizophrenia, and autism), but the mechanisms that mediate this effect have been poorly understood. A small group of disorders, including Apert syndrome (caused by FGFR2 mutations), achondroplasia, and thanatophoric dysplasia (FGFR3), and Costello syndrome (HRAS), which we collectively term “paternal age effect” (PAE) disorders, provides a good model to study the biological and molecular basis of this phenomenon. Recent evidence from direct quantification of PAE mutations in sperm and testes suggests that the common factor in the paternal age effect lies in the dysregulation of spermatogonial cell behavior, an effect mediated molecularly through the growth factor receptor-RAS signal transduction pathway. The data show that PAE mutations, although arising rarely, are positively selected and expand clonally in normal testes through a process akin to oncogenesis. This clonal expansion, which is likely to take place in the testes of all men, leads to the relative enrichment of mutant sperm over time—explaining the observed paternal age effect associated with these disorders—and in rare cases to the formation of testicular tumors. As regulation of RAS and other mediators of cellular proliferation and survival is important in many different biological contexts, for example during tumorigenesis, organ homeostasis and neurogenesis, the consequences of selfish mutations that hijack this process within the testis are likely to extend far beyond congenital skeletal disorders to include complex diseases, such as neurocognitive disorders and cancer predisposition. PMID:22325359

Anticipatory anxiety disrupts neural valuation during risky choice.

PubMed

Engelmann, Jan B; Meyer, Friederike; Fehr, Ernst; Ruff, Christian C

2015-02-18

Incidental negative emotions unrelated to the current task, such as background anxiety, can strongly influence decisions. This is most evident in psychiatric disorders associated with generalized emotional disturbances. However, the neural mechanisms by which incidental emotions may affect choices remain poorly understood. Here we study the effects of incidental anxiety on human risky decision making, focusing on both behavioral preferences and their underlying neural processes. Although observable choices remained stable across affective contexts with high and low incidental anxiety, we found a clear change in neural valuation signals: during high incidental anxiety, activity in ventromedial prefrontal cortex and ventral striatum showed a marked reduction in (1) neural coding of the expected subjective value (ESV) of risky options, (2) prediction of observed choices, (3) functional coupling with other areas of the valuation system, and (4) baseline activity. At the same time, activity in the anterior insula showed an increase in coding the negative ESV of risky lotteries, and this neural activity predicted whether the risky lotteries would be rejected. This pattern of results suggests that incidental anxiety can shift the focus of neural valuation from possible positive consequences to anticipated negative consequences of choice options. Moreover, our findings show that these changes in neural value coding can occur in the absence of changes in overt behavior. This suggest a possible pathway by which background anxiety may lead to the development of chronic reward desensitization and a maladaptive focus on negative cognitions, as prevalent in affective and anxiety disorders. Copyright © 2015 the authors 0270-6474/15/353085-15$15.00/0.

Role of the ubiquitin-proteasome system in brain ischemia: friend or foe?

PubMed

Caldeira, Margarida V; Salazar, Ivan L; Curcio, Michele; Canzoniero, Lorella M T; Duarte, Carlos B

2014-01-01

The ubiquitin-proteasome system (UPS) is a catalytic machinery that targets numerous cellular proteins for degradation, thus being essential to control a wide range of basic cellular processes and cell survival. Degradation of intracellular proteins via the UPS is a tightly regulated process initiated by tagging a target protein with a specific ubiquitin chain. Neurons are particularly vulnerable to any change in protein composition, and therefore the UPS is a key regulator of neuronal physiology. Alterations in UPS activity may induce pathological responses, ultimately leading to neuronal cell death. Brain ischemia triggers a complex series of biochemical and molecular mechanisms, such as an inflammatory response, an exacerbated production of misfolded and oxidized proteins, due to oxidative stress, and the breakdown of cellular integrity mainly mediated by excitotoxic glutamatergic signaling. Brain ischemia also damages protein degradation pathways which, together with the overproduction of damaged proteins and consequent upregulation of ubiquitin-conjugated proteins, contribute to the accumulation of ubiquitin-containing proteinaceous deposits. Despite recent advances, the factors leading to deposition of such aggregates after cerebral ischemic injury remain poorly understood. This review discusses the current knowledge on the role of the UPS in brain function and the molecular mechanisms contributing to UPS dysfunction in brain ischemia with consequent accumulation of ubiquitin-containing proteins. Chemical inhibitors of the proteasome and small molecule inhibitors of deubiquitinating enzymes, which promote the degradation of proteins by the proteasome, were both shown to provide neuroprotection in brain ischemia, and this apparent contradiction is also discussed in this review. Copyright © 2013 Elsevier Ltd. All rights reserved.

Influence of topography on debris flow development in Ichino-sawa subwatershed of Ohya-kuzure landslide, Japan

NASA Astrophysics Data System (ADS)

Tsunetaka, H.; Hotta, N.; Imaizumi, F.; Hayakawa, Y. S.

2015-12-01

Large sediment movements, such as deep-seated landslides, produce unstable sediment over the long term. Most of the unstable sediment in a mountain torrent is discharged via the development of debris flows through entrainment. Consequently, after a large sediment movement, debris flows have long-term effects on the watershed regime. However, the development of debris flows in mountain torrents is poorly understood, since the topography is more complicated than downstream. We compared temporal changes in topography to examine how topography affects the development of flows. The study site was the Ichino-sawa subwatershed in the Ohya-kuzure landslide, Japan. Unstable sediment has been produced continuously since the landslide occurred in 1707. Several topographic surveys using a terrestrial laser scanner (TLS) and aerial shoots by an unmanned aerial vehicle (UAV) were performed between November 2011 (TLS) or November 2014 (UAV) and August 2015. High-resolution digital elevation models were created from the TLS and UAV results to detect temporal topographic changes. Debris flow occurrences and rainfall were also monitored using interval cameras and rain gauges. Downstream, the deposit depth decreased after the debris flows. Upstream, more complex changes were detected due to surges in the debris flows, which not only induced entrainment, but were also deposited in the valley floor. Furthermore, sediment was supplied from the stream bank during the debris flows. Consequently, several debris flows of different magnitudes were observed, although the rainfall conditions did not differ significantly. The results imply that the magnitude of the debris flows was affected by successive sediment movement resulting from the changing of the topographic conditions.

Subjective Health Complaints in Individuals with Psoriasis and Psoriatic Arthritis: Associations with the Severity of the Skin Condition and Illness Perceptions - A Cross-Sectional Study.

PubMed

Nordbø, Emma Charlott Andersson; Aamodt, Geir; Ihlebæk, Camilla Martha

2017-06-01

High comorbidity has been reported among persons with psoriasis and psoriatic arthritis (PsA), but the occurrence of subjective health complaints (SHCs) in these patient groups is poorly understood. The study aimed to describe the prevalence of SHCs among individuals with psoriasis and PsA in Norway, and investigate whether the severity of their skin condition and their illness perceptions were associated with the number and severity of health complaints. Participants were recruited through the Psoriasis and Eczema Association of Norway (PEF) (n = 942). The participants answered a self-administered questionnaire covering subjective health complaints, the severity of their skin condition, and their illness perceptions measured with the Brief Illness Perception Questionnaire (BIPQ-R). The prevalence and severity of SHCs were high. Participants with PsA reported more complaints and higher severity of complaints compared with participants with psoriasis. In both groups, the severity of the skin condition was associated with the number and severity of SHCs. Cognitive illness perceptions (consequences) and emotional illness perceptions (emotional affect) were associated with SHCs in participants with psoriasis, whereas only cognitive illness perceptions (consequences and identity) were associated with SHCs in participants with PsA. The high prevalence and severity of SHCs among individuals with psoriasis and PsA were associated with the severity of the skin condition and illness perceptions. Somatic and cognitive sensitizations are proposed as possible mechanisms. The findings suggest that holistic approaches are essential when managing these patient groups in health care institutions and clinical practice.

Noradrenergic activation of the basolateral amygdala maintains hippocampus-dependent accuracy of remote memory.

PubMed

Atucha, Erika; Vukojevic, Vanja; Fornari, Raquel V; Ronzoni, Giacomo; Demougin, Philippe; Peter, Fabian; Atsak, Piray; Coolen, Marcel W; Papassotiropoulos, Andreas; McGaugh, James L; de Quervain, Dominique J-F; Roozendaal, Benno

2017-08-22

Emotional enhancement of memory by noradrenergic mechanisms is well-described, but the long-term consequences of such enhancement are poorly understood. Over time, memory traces are thought to undergo a neural reorganization, that is, a systems consolidation, during which they are, at least partly, transferred from the hippocampus to neocortical networks. This transfer is accompanied by a decrease in episodic detailedness. Here we investigated whether norepinephrine (NE) administration into the basolateral amygdala after training on an inhibitory avoidance discrimination task, comprising two distinct training contexts, alters systems consolidation dynamics to maintain episodic-like accuracy and hippocampus dependency of remote memory. At a 2-d retention test, both saline- and NE-treated rats accurately discriminated the training context in which they had received footshock. Hippocampal inactivation with muscimol before retention testing disrupted discrimination of the shock context in both treatment groups. At 28 d, saline-treated rats showed hippocampus-independent retrieval and lack of discrimination. In contrast, NE-treated rats continued to display accurate memory of the shock-context association. Hippocampal inactivation at this remote retention test blocked episodic-like accuracy and induced a general memory impairment. These findings suggest that the NE treatment altered systems consolidation dynamics by maintaining hippocampal involvement in the memory. This shift in systems consolidation was paralleled by time-regulated DNA methylation and transcriptional changes of memory-related genes, namely Reln and Pkm ζ, in the hippocampus and neocortex. The findings provide evidence suggesting that consolidation of emotional memories by noradrenergic mechanisms alters systems consolidation dynamics and, as a consequence, influences the maintenance of long-term episodic-like accuracy of memory.

Knowledge, group-based medical mistrust, future expectations, and perceived disadvantages of medical genetic testing: perspectives of Black African immigrants/refugees.

PubMed

Buseh, A; Kelber, S; Millon-Underwood, S; Stevens, P; Townsend, L

2014-01-01

Reasons for low participation of ethnic minorities in genetic studies are multifactorial and often poorly understood. Based on published literature, participation in genetic testing is low among Black African immigrants/refugees although they are purported to bear disproportionate disease burden. Thus, research involving Black African immigrant/refugee populations that examine their perspectives on participating in genetic studies is needed. This report examines and describes the knowledge of medical genetics, group-based medical mistrust, and future expectations of genetic research and the influence of these measures on the perceived disadvantages of genetic testing among Black African immigrants/refugees. Using a cross-sectional survey design, a nonprobability sample (n = 212) of Black African immigrants/refugees was administered a questionnaire. Participants ranged in age from 18 to 61 years (mean = 38.91, SD = 9.78). The questionnaire consisted of 5 instruments: (a) sociodemographic characteristics, (b) Knowledge of Medical Genetics scale, (c) Group-Based Medical Mistrust Scale, (d) Future Expectations/Anticipated Consequences of Genetics Research scale, and (e) Perceived Disadvantages of Genetic Testing scale. Participants were concerned that genetic research may result in scientists 'playing God,' interfering with the natural order of life. In multivariate analyses, the perceived disadvantages of genetic testing increased as medical mistrust and anticipated negative impacts of genetic testing increased. Increase in genetic knowledge contributed to a decrease in perceived disadvantages. Our findings suggest that recruitment of Black African immigrants/refugees in genetic studies should address potential low knowledge of genetics, concerns about medical mistrust, the expectations/anticipated consequences of genetic research, and the perceived disadvantages of genetic testing.

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

PubMed

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

2011-04-01

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

Tracking a Medically Important Spider: Climate Change, Ecological Niche Modeling, and the Brown Recluse (Loxosceles reclusa)

PubMed Central

Saupe, Erin E.; Papes, Monica; Selden, Paul A.; Vetter, Richard S.

2011-01-01

Most spiders use venom to paralyze their prey and are commonly feared for their potential to cause injury to humans. In North America, one species in particular, Loxosceles reclusa (brown recluse spider, Sicariidae), causes the majority of necrotic wounds induced by the Araneae. However, its distributional limitations are poorly understood and, as a result, medical professionals routinely misdiagnose brown recluse bites outside endemic areas, confusing putative spider bites for other serious conditions. To address the issue of brown recluse distribution, we employ ecological niche modeling to investigate the present and future distributional potential of this species. We delineate range boundaries and demonstrate that under future climate change scenarios, the spider's distribution may expand northward, invading previously unaffected regions of the USA. At present, the spider's range is centered in the USA, from Kansas east to Kentucky and from southern Iowa south to Louisiana. Newly influenced areas may include parts of Nebraska, Minnesota, Wisconsin, Michigan, South Dakota, Ohio, and Pennsylvania. These results illustrate a potential negative consequence of climate change on humans and will aid medical professionals in proper bite identification/treatment, potentially reducing bite misdiagnoses. PMID:21464985

Actions of Hydrogen Sulfide on Sodium Transport Processes across Native Distal Lung Epithelia (Xenopus laevis)

PubMed Central

Erb, Alexandra; Althaus, Mike

2014-01-01

Hydrogen sulfide (H2S) is well known as a highly toxic environmental chemical threat. Prolonged exposure to H2S can lead to the formation of pulmonary edema. However, the mechanisms of how H2S facilitates edema formation are poorly understood. Since edema formation can be enhanced by an impaired clearance of electrolytes and, consequently, fluid across the alveolar epithelium, it was questioned whether H2S may interfere with transepithelial electrolyte absorption. Electrolyte absorption was electrophysiologically measured across native distal lung preparations (Xenopus laevis) in Ussing chambers. The exposure of lung epithelia to H2S decreased net transepithelial electrolyte absorption. This was due to an impairment of amiloride-sensitive sodium transport. H2S inhibited the activity of the Na+/K+-ATPase as well as lidocaine-sensitive potassium channels located in the basolateral membrane of the epithelium. Inhibition of these transport molecules diminishes the electrochemical gradient which is necessary for transepithelial sodium absorption. Since sodium absorption osmotically facilitates alveolar fluid clearance, interference of H2S with the epithelial transport machinery provides a mechanism which enhances edema formation in H2S-exposed lungs. PMID:24960042

Population cycles and species diversity in dynamic Kill-the-Winner model of microbial ecosystems

NASA Astrophysics Data System (ADS)

Maslov, Sergei; Sneppen, Kim

2017-01-01

Determinants of species diversity in microbial ecosystems remain poorly understood. Bacteriophages are believed to increase the diversity by the virtue of Kill-the-Winner infection bias preventing the fastest growing organism from taking over the community. Phage-bacterial ecosystems are traditionally described in terms of the static equilibrium state of Lotka-Volterra equations in which bacterial growth is exactly balanced by losses due to phage predation. Here we consider a more dynamic scenario in which phage infections give rise to abrupt and severe collapses of bacterial populations whenever they become sufficiently large. As a consequence, each bacterial population in our model follows cyclic dynamics of exponential growth interrupted by sudden declines. The total population of all species fluctuates around the carrying capacity of the environment, making these cycles cryptic. While a subset of the slowest growing species in our model is always driven towards extinction, in general the overall ecosystem diversity remains high. The number of surviving species is inversely proportional to the variation in their growth rates but increases with the frequency and severity of phage-induced collapses. Thus counter-intuitively we predict that microbial communities exposed to more violent perturbations should have higher diversity.

Evidence for water-mediated mechanisms in coral–algal interactions

PubMed Central

Jorissen, Hendrikje; Skinner, Christina; Osinga, Ronald; de Beer, Dirk

2016-01-01

Although many coral reefs have shifted from coral-to-algal dominance, the consequence of such a transition for coral–algal interactions and their underlying mechanisms remain poorly understood. At the microscale, it is unclear how diffusive boundary layers (DBLs) and surface oxygen concentrations at the coral–algal interface vary with algal competitors and competitiveness. Using field observations and microsensor measurements in a flow chamber, we show that coral (massive Porites) interfaces with thick turf algae, macroalgae, and cyanobacteria, which are successful competitors against coral in the field, are characterized by a thick DBL and hypoxia at night. In contrast, coral interfaces with crustose coralline algae, conspecifics, and thin turf algae, which are poorer competitors, have a thin DBL and low hypoxia at night. Furthermore, DBL thickness and hypoxia at the interface with turf decreased with increasing flow speed, but not when thick turf was upstream. Our results support the importance of water-mediated transport mechanisms in coral–algal interactions. Shifts towards algal dominance, particularly dense assemblages, may lead to thicker DBLs, higher hypoxia, and higher concentrations of harmful metabolites and pathogens along coral borders, which in turn may facilitate algal overgrowth of live corals. These effects may be mediated by flow speed and orientation. PMID:27512146

Mechanism, Prevalence, and More Severe Neuropathy Phenotype of the Charcot-Marie-Tooth Type 1A Triplication

PubMed Central

Liu, Pengfei; Gelowani, Violet; Zhang, Feng; Drory, Vivian E.; Ben-Shachar, Shay; Roney, Erin; Medeiros, Adam C.; Moore, Rebecca J.; DiVincenzo, Christina; Burnette, William B.; Higgins, Joseph J.; Li, Jun; Orr-Urtreger, Avi; Lupski, James R.

2014-01-01

Copy-number variations cause genomic disorders. Triplications, unlike deletions and duplications, are poorly understood because of challenges in molecular identification, the choice of a proper model system for study, and awareness of their phenotypic consequences. We investigated the genomic disorder Charcot-Marie-Tooth disease type 1A (CMT1A), a dominant peripheral neuropathy caused by a 1.4 Mb recurrent duplication occurring by nonallelic homologous recombination. We identified CMT1A triplications in families in which the duplication segregates. The triplications arose de novo from maternally transmitted duplications and caused a more severe distal symmetric polyneuropathy phenotype. The recombination that generated the triplication occurred between sister chromatids on the duplication-bearing chromosome and could accompany gene conversions with the homologous chromosome. Diagnostic testing for CMT1A (n = 20,661 individuals) identified 13% (n = 2,752 individuals) with duplication and 0.024% (n = 5 individuals) with segmental tetrasomy, suggesting that triplications emerge from duplications at a rate as high as ∼1:550, which is more frequent than the rate of de novo duplication. We propose that individuals with duplications are predisposed to acquiring triplications and that the population prevalence of triplication is underascertained. PMID:24530202

Beyond blow-up in excitatory integrate and fire neuronal networks: Refractory period and spontaneous activity.

PubMed

Cáceres, María J; Perthame, Benoît

2014-06-07

The Network Noisy Leaky Integrate and Fire equation is among the simplest model allowing for a self-consistent description of neural networks and gives a rule to determine the probability to find a neuron at the potential v. However, its mathematical structure is still poorly understood and, concerning its solutions, very few results are available. In the midst of them, a recent result shows blow-up in finite time for fully excitatory networks. The intuitive explanation is that each firing neuron induces a discharge of the others; thus increases the activity and consequently the discharge rate of the full network. In order to better understand the details of the phenomena and show that the equation is more complex and fruitful than expected, we analyze further the model. We extend the finite time blow-up result to the case when neurons, after firing, enter a refractory state for a given period of time. We also show that spontaneous activity may occur when, additionally, randomness is included on the firing potential VF in regimes where blow-up occurs for a fixed value of VF. Copyright © 2014 Elsevier Ltd. All rights reserved.

Animal Models of Fibrotic Lung Disease

PubMed Central

Lawson, William E.; Oury, Tim D.; Sisson, Thomas H.; Raghavendran, Krishnan; Hogaboam, Cory M.

2013-01-01

Interstitial lung fibrosis can develop as a consequence of occupational or medical exposure, as a result of genetic defects, and after trauma or acute lung injury leading to fibroproliferative acute respiratory distress syndrome, or it can develop in an idiopathic manner. The pathogenesis of each form of lung fibrosis remains poorly understood. They each result in a progressive loss of lung function with increasing dyspnea, and most forms ultimately result in mortality. To better understand the pathogenesis of lung fibrotic disorders, multiple animal models have been developed. This review summarizes the common and emerging models of lung fibrosis to highlight their usefulness in understanding the cell–cell and soluble mediator interactions that drive fibrotic responses. Recent advances have allowed for the development of models to study targeted injuries of Type II alveolar epithelial cells, fibroblastic autonomous effects, and targeted genetic defects. Repetitive dosing in some models has more closely mimicked the pathology of human fibrotic lung disease. We also have a much better understanding of the fact that the aged lung has increased susceptibility to fibrosis. Each of the models reviewed in this report offers a powerful tool for studying some aspect of fibrotic lung disease. PMID:23526222

Improving understanding, promoting social inclusion, and fostering empowerment related to epilepsy: Epilepsy Foundation public awareness campaigns — 2001 through 2013☆

PubMed Central

Price, P.; Kobau, R.; Buelow, J.; Austin, J.; Lowenberg, K.

2015-01-01

It is a significant public health concern that epilepsy, the fourth most common neurological disorder in the United States, is generally poorly understood by both the public and those living with the condition. Lack of understanding may magnify the challenges faced by those with epilepsy, including limiting treatment opportunities, effective management of symptoms, and full participation in daily life activities. Insufficient awareness of epilepsy and appropriate seizure first aid among the public and professionals can result in insufficient treatment, inappropriate seizure response, physical restraint, social exclusion, or other negative consequences. To address the need for increased public education and awareness about epilepsy, the national Epilepsy Foundation, supported by the Centers for Disease Control and Prevention, has conducted yearly multifaceted public education and awareness campaigns designed to reach the broad population and targeted segments of the population including youth, young adults, racial/ethnic groups (i.e., African-, Hispanic-, and Asian-Americans), and people with epilepsy and their caregivers. Campaign channels have included traditional media, social media, and community opinion leaders and celebrity spokespersons. The key activities of these campaigns, conducted from 2001 to 2013, are summarized in this report. PMID:25726152

Autophagy in atherosclerosis: a cell survival and death phenomenon with therapeutic potential.

PubMed

Martinet, Wim; De Meyer, Guido R Y

2009-02-13

Autophagy is a reparative, life-sustaining process by which cytoplasmic components are sequestered in double-membrane vesicles and degraded on fusion with lysosomal compartments. A growing body of evidence suggests that autophagy is stimulated in advanced atherosclerotic plaques by oxidized lipids, inflammation, and metabolic stress conditions. However, despite the increasing interest in autophagy in various pathophysiological situations such as neurodegeneration, cancer, and cardiac myopathies, the process remains an underestimated and overlooked phenomenon in atherosclerosis. As a consequence, its role in plaque formation and stability is poorly understood. Most likely, autophagy safeguards plaque cells against cellular distress, in particular oxidative injury, by degrading damaged intracellular material. In this way, autophagy is antiapoptotic and contributes to cellular recovery in an adverse environment. An interesting observation is that basal autophagy can be intensified by specific drugs. Excessively stimulated autophagic activity is capable of destroying major proportions of the cytosol, leading finally to type II programmed cell death that lacks several hallmarks of apoptosis or necrosis. Because atherosclerosis is an inflammatory disorder of the arterial intima, pharmacological approaches could be developed to stabilize vulnerable, rupture-prone lesions through selective induction of macrophage autophagic death.

Activation of PTHrP-cAMP-CREB1 signaling following p53 loss is essential for osteosarcoma initiation and maintenance

PubMed Central

Walia, Mannu K; Ho, Patricia MW; Taylor, Scott; Ng, Alvin JM; Gupte, Ankita; Chalk, Alistair M; Zannettino, Andrew CW; Martin, T John; Walkley, Carl R

2016-01-01

Mutations in the P53 pathway are a hallmark of human cancer. The identification of pathways upon which p53-deficient cells depend could reveal therapeutic targets that may spare normal cells with intact p53. In contrast to P53 point mutations in other cancer, complete loss of P53 is a frequent event in osteosarcoma (OS), the most common cancer of bone. The consequences of p53 loss for osteoblastic cells and OS development are poorly understood. Here we use murine OS models to demonstrate that elevated Pthlh (Pthrp), cAMP levels and signalling via CREB1 are characteristic of both p53-deficient osteoblasts and OS. Normal osteoblasts survive depletion of both PTHrP and CREB1. In contrast, p53-deficient osteoblasts and OS depend upon continuous activation of this pathway and undergo proliferation arrest and apoptosis in the absence of PTHrP or CREB1. Our results identify the PTHrP-cAMP-CREB1 axis as an attractive pathway for therapeutic inhibition in OS. DOI: http://dx.doi.org/10.7554/eLife.13446.001 PMID:27070462

Centromere inactivation and epigenetic modifications of a plant chromosome with three functional centromeres.

PubMed

Zhang, Wenli; Friebe, Bernd; Gill, Bikram S; Jiang, Jiming

2010-10-01

A chromosome with two functional centromeres is cytologically unstable and can only be stabilized when one of the two centromeres becomes inactivated via poorly understood mechanisms. Here, we report a transmissible chromosome with multiple centromeres in wheat. This chromosome encompassed one large and two small domains containing the centromeric histone CENH3. The two small centromeres are in a close vicinity and often fused as a single centromere on metaphase chromosomes. This fused centromere contained approximately 30% of the CENH3 compared to the large centromere. An intact tricentric chromosome was transmitted to about 70% of the progenies, which was likely a consequence of the dominating pulling capacity of the large centromere during anaphases of meiosis. The tricentric chromosome showed characteristics typical to dicentric chromosomes, including chromosome breaks and centromere inactivation. Remarkably, inactivation was always associated with the small centromeres, indicating that small centromeres are less likely to survive than large ones in dicentric chromosomes. The inactivation of the small centromeres also coincided with changes of specific histone modifications, including H3K27me2 and H3K27me3, of the pericentromeric chromatin.

Molecular strategies of the Caenorhabditis elegans dauer larva to survive extreme desiccation.

PubMed

Erkut, Cihan; Vasilj, Andrej; Boland, Sebastian; Habermann, Bianca; Shevchenko, Andrej; Kurzchalia, Teymuras V

2013-01-01

Massive water loss is a serious challenge for terrestrial animals, which usually has fatal consequences. However, some organisms have developed means to survive this stress by entering an ametabolic state called anhydrobiosis. The molecular and cellular mechanisms underlying this phenomenon are poorly understood. We recently showed that Caenorhabditis elegans dauer larva, an arrested stage specialized for survival in adverse conditions, is resistant to severe desiccation. However, this requires a preconditioning step at a mild desiccative environment to prepare the organism for harsher desiccation conditions. A systems approach was used to identify factors that are activated during this preconditioning. Using microarray analysis, proteomics, and bioinformatics, genes, proteins, and biochemical pathways that are upregulated during this process were identified. These pathways were validated via reverse genetics by testing the desiccation tolerances of mutants. These data show that the desiccation response is activated by hygrosensation (sensing the desiccative environment) via head neurons. This leads to elimination of reactive oxygen species and xenobiotics, expression of heat shock and intrinsically disordered proteins, polyamine utilization, and induction of fatty acid desaturation pathway. Remarkably, this response is specific and involves a small number of functional pathways, which represent the generic toolkit for anhydrobiosis in plants and animals.

CO2 leakage-induced vegetation decline is primarily driven by decreased soil O2.

PubMed

Zhang, Xueyan; Ma, Xin; Zhao, Zhi; Wu, Yang; Li, Yue

2016-04-15

To assess the potential risks of carbon capture and storage (CCS), studies have focused on vegetation decline caused by leaking CO2. Excess soil CO2 caused by leakage can affect soil O2 concentrations and soil pH, but how these two factors affect plant development remains poorly understood. This hinders the selection of appropriate species to mitigate potential negative consequences of CCS. Through pot experiments, we simulated CO2 leakage to examine its effects on soil pH and soil O2 concentrations. We subsequently assessed how maize growth responded to these changes in soil pH and O2. Decreased soil O2 concentrations significantly reduced maize biomass, and explained 69% of the biomass variation under CO2 leakage conditions. In contrast, although leaked CO2 changed soil pH significantly (from 7.32 to 6.75), it remained within the optimum soil pH range for maize growth. This suggests that soil O2 concentration, not soil pH, influences plant growth in these conditions. Therefore, in case of potential CO2 leakage risks, hypoxia-tolerant species should be chosen to improve plant survival, growth, and yield. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evolution of the additive genetic variance–covariance matrix under continuous directional selection on a complex behavioural phenotype

PubMed Central

Careau, Vincent; Wolak, Matthew E.; Carter, Patrick A.; Garland, Theodore

2015-01-01

Given the pace at which human-induced environmental changes occur, a pressing challenge is to determine the speed with which selection can drive evolutionary change. A key determinant of adaptive response to multivariate phenotypic selection is the additive genetic variance–covariance matrix (G). Yet knowledge of G in a population experiencing new or altered selection is not sufficient to predict selection response because G itself evolves in ways that are poorly understood. We experimentally evaluated changes in G when closely related behavioural traits experience continuous directional selection. We applied the genetic covariance tensor approach to a large dataset (n = 17 328 individuals) from a replicated, 31-generation artificial selection experiment that bred mice for voluntary wheel running on days 5 and 6 of a 6-day test. Selection on this subset of G induced proportional changes across the matrix for all 6 days of running behaviour within the first four generations. The changes in G induced by selection resulted in a fourfold slower-than-predicted rate of response to selection. Thus, selection exacerbated constraints within G and limited future adaptive response, a phenomenon that could have profound consequences for populations facing rapid environmental change. PMID:26582016

Multisensory Self-Motion Compensation During Object Trajectory Judgments

PubMed Central

Dokka, Kalpana; MacNeilage, Paul R.; DeAngelis, Gregory C.; Angelaki, Dora E.

2015-01-01

Judging object trajectory during self-motion is a fundamental ability for mobile organisms interacting with their environment. This fundamental ability requires the nervous system to compensate for the visual consequences of self-motion in order to make accurate judgments, but the mechanisms of this compensation are poorly understood. We comprehensively examined both the accuracy and precision of observers' ability to judge object trajectory in the world when self-motion was defined by vestibular, visual, or combined visual–vestibular cues. Without decision feedback, subjects demonstrated no compensation for self-motion that was defined solely by vestibular cues, partial compensation (47%) for visually defined self-motion, and significantly greater compensation (58%) during combined visual–vestibular self-motion. With decision feedback, subjects learned to accurately judge object trajectory in the world, and this generalized to novel self-motion speeds. Across conditions, greater compensation for self-motion was associated with decreased precision of object trajectory judgments, indicating that self-motion compensation comes at the cost of reduced discriminability. Our findings suggest that the brain can flexibly represent object trajectory relative to either the observer or the world, but a world-centered representation comes at the cost of decreased precision due to the inclusion of noisy self-motion signals. PMID:24062317

The mammalian INO80 chromatin remodeling complex is required for replication stress recovery

PubMed Central

Vassileva, Ivelina; Yanakieva, Iskra; Peycheva, Michaela; Gospodinov, Anastas; Anachkova, Boyka

2014-01-01

A number of studies have implicated the yeast INO80 chromatin remodeling complex in DNA replication, but the function of the human INO80 complex during S phase remains poorly understood. Here, we have systematically investigated the involvement of the catalytic subunit of the human INO80 complex during unchallenged replication and under replication stress by following the effects of its depletion on cell survival, S-phase checkpoint activation, the fate of individual replication forks, and the consequences of fork collapse. We report that INO80 was specifically needed for efficient replication elongation, while it was not required for initiation of replication. In the absence of the Ino80 protein, cells became hypersensitive to hydroxyurea and displayed hyperactive ATR-Chk1 signaling. Using bulk and fiber labeling of DNA, we found that cells deficient for Ino80 and Arp8 had impaired replication restart after treatment with replication inhibitors and accumulated double-strand breaks as evidenced by the formation of γ-H2AX and Rad51 foci. These data indicate that under conditions of replication stress mammalian INO80 protects stalled forks from collapsing and allows their subsequent restart. PMID:25016522

Acidosis increases the susceptibility of respiratory epithelial cells to Pseudomonas aeruginosa-induced cytotoxicity.

PubMed

Torres, Iviana M; Demirdjian, Sally; Vargas, Jennifer; Goodale, Britton C; Berwin, Brent

2017-07-01

Bacterial infection can lead to acidosis of the local microenvironment, which is believed to exacerbate disease pathogenesis; however, the mechanisms by which changes in pH alter disease progression are poorly understood. We test the hypothesis that acidosis enhances respiratory epithelial cell death in response to infection with Pseudomonas aeruginosa Our findings support the idea that acidosis in the context of P. aeruginosa infection results in increased epithelial cell cytotoxicity due to ExoU intoxication. Importantly, enforced maintenance of neutral pH during P. aeruginosa infection demonstrates that cytotoxicity is dependent on the acidosis. Investigation of the underlying mechanisms revealed that host cell cytotoxicity correlated with increased bacterial survival during an acidic infection that was due to reduced bactericidal activity of host-derived antimicrobial peptides. These findings extend previous reports that the activities of antimicrobial peptides are pH-dependent and provide novel insights into the consequences of acidosis on infection-derived pathology. Therefore, this report provides the first evidence that physiological levels of acidosis increase the susceptibility of epithelial cells to acute Pseudomonas infection and demonstrates the benefit of maintaining pH homeostasis during a bacterial infection. Copyright © 2017 the American Physiological Society.

ABCB5 promotes melanoma metastasis through enhancing NF-κB p65 protein stability.

PubMed

Wang, Shenghao; Tang, Li; Lin, Junyu; Shen, Zhongliang; Yao, Yikun; Wang, Wei; Tao, Shuai; Gu, Chenjian; Ma, Jie; Xie, Youhua; Liu, Yanfeng

2017-10-07

Melanoma is the most aggressive type of skin cancer. Melanoma has an extremely poor prognosis because of its high potential for vascular invasion, metastasis and recurrence. The mechanism of melanoma metastasis is not well understood. ATP-binding cassette sub-family B member 5 (ABCB5) plays a key role in melanoma growth. However, it is uncertain what function ABCB5 may exert in melanoma metastasis. In this report, we for the first time demonstrate ABCB5 as a crucial factor that promotes melanoma metastasis. ABCB5 positive (ABCB5 + ) malignant melanoma initiating cells (MMICs) display a higher metastatic potential compared with ABCB5 negative (ABCB5 - ) melanoma subpopulation. Knockdown of ABCB5 expression reduces melanoma cell migration and invasion in vitro and melanoma pulmonary metastasis in tumor xenograft mice. ABCB5 and NF-κB p65 expression levels are positively correlated in both melanoma tissues and cell lines. Consequently, ABCB5 activates the NF-κB pathway by inhibiting p65 ubiquitination to enhance p65 protein stability. Our finding highlights ABCB5 as a novel pro-metastasis factor and provides a potential therapeutic target for melanoma. Copyright © 2017 Elsevier Inc. All rights reserved.

Incubation period and immune function: A comparative field study among coexisting birds

USGS Publications Warehouse

Palacios, M.G.; Martin, T.E.

2006-01-01

Developmental periods are integral components of life history strategies that can have important fitness consequences and vary enormously among organisms. However, the selection pressures and mechanisms causing variation in length of developmental periods are poorly understood. Particularly puzzling are prolonged developmental periods, because their selective advantage is unclear. Here we tested the hypotheses that immune function is stronger in species that are attacked at a higher rate by parasites and that prolonged embryonic development allows the development of this stronger immune system. Through a comparative field study among 12 coexisting passerine bird species, we show that species with higher blood parasite prevalence mounted stronger cellular immune responses than species with lower prevalence. These results provide support for the hypothesis that species facing greater selection pressure from parasites invest more in immune function. However, species with longer incubation periods mounted weaker cellular immune responses than species with shorter periods. Therefore, cellular immune responses do not support the hypothesis that longer development time enhances immunocompentence. Future studies should assess other components of the immune system and test alternative causes of variation in incubation periods among bird species. ?? Springer-Verlag 2005.

Heterostyly accelerates diversification via reduced extinction in primroses.

PubMed

de Vos, Jurriaan M; Hughes, Colin E; Schneeweiss, Gerald M; Moore, Brian R; Conti, Elena

2014-06-07

The exceptional species diversity of flowering plants, exceeding that of their sister group more than 250-fold, is especially evident in floral innovations, interactions with pollinators and sexual systems. Multiple theories, emphasizing flower-pollinator interactions, genetic effects of mating systems or high evolvability, predict that floral evolution profoundly affects angiosperm diversification. However, consequences for speciation and extinction dynamics remain poorly understood. Here, we investigate trajectories of species diversification focusing on heterostyly, a remarkable floral syndrome where outcrossing is enforced via cross-compatible floral morphs differing in placement of their respective sexual organs. Heterostyly evolved at least 20 times independently in angiosperms. Using Darwin's model for heterostyly, the primrose family, we show that heterostyly accelerates species diversification via decreasing extinction rates rather than increasing speciation rates, probably owing to avoidance of the negative genetic effects of selfing. However, impact of heterostyly appears to differ over short and long evolutionary time-scales: the accelerating effect of heterostyly on lineage diversification is manifest only over long evolutionary time-scales, whereas recent losses of heterostyly may prompt ephemeral bursts of speciation. Our results suggest that temporal or clade-specific conditions may ultimately determine the net effects of specific traits on patterns of species diversification.

Real-Time Observation of Human LINE-1 Retrotransposon Activity in Bacteria

NASA Astrophysics Data System (ADS)

Kaur, Davneet; Kuhlman, Thomas; Kuhlman Team; Nigel Goldenfeld Collaboration

Transposable elements (TEs) are fundamental building blocks of all genomes. Retrotransposable elements (RTEs) are one of the two primary classes of TEs that are ubiquitous in eukaryotes. They propagate through a copy-and-paste mechanism utilizing reverse-transcribed mRNA intermediates. This leads to disruption and dispersal of coding and control elements throughout the genome, and consequently TEs are thought to be a major driving force behind diversification. However, RTEs are absent in most prokaryotes including E. coli. and the reason for this remains an open question. Despite their prevalence, there still remain many unanswered questions about how `hot' or active L1 RTEs (L1Hs) function. In particular, their rates of activity and their effects upon their host are currently poorly understood and only roughly estimated within the limitations of available technology. To address these unanswered questions, we have constructed and released an L1H element in E. coli to quantify its rates of activity and physiological effects on its host. To overcome the technical limitations, we've designed fluorescent visualization and quantification techniques that make real time high resolution observations of retrotransposition events as they occur in living cells.

Culm Age and Rhizome Affects Night-Time Water Recharge in the Bamboo Phyllostachys pubescens

PubMed Central

Zhao, Xiuhua; Zhao, Ping; Zhang, Zhenzhen; Zhu, Liwei; Hu, Yanting; Ouyang, Lei; Ni, Guangyan; Ye, Qing

2017-01-01

Bamboo species—the only herbaceous trees—have unique structural and physiological characteristics that differ from those of other tree taxa. However, the role of night-time water use in bamboo is poorly understood and has rarely been investigated. We studied the day- and night-time sap flow response to culm age and rhizome structure in three age levels (juvenile, mature, and senescent) of Phyllostachys pubescens growing in the Nankun Mountain Natural Reserve, South China. We found that sap flow density and whole-tree hydraulic conductance decreased with culm age. After cutting of rhizome, the day-time sap flow and night-time water recharge decreased obviously. In addition, night-time water recharge accounted for the largest proportion (up to 30%) of total daily transpiration in normal senescent bamboos. Therefore, our study indicates that the connected rhizome system and night-time water recharge played a significant role in water compensation during the day and at night in bamboos. Night-time water recharge is especially critical to senescent bamboos, given their weaker transpiration due to the lower whole-tree hydraulic conductance, and consequently, they are more dependent on night-time water recharge for fulfilling their whole-day water consumption needs. PMID:29176989

Culm Age and Rhizome Affects Night-Time Water Recharge in the Bamboo Phyllostachys pubescens.

PubMed

Zhao, Xiuhua; Zhao, Ping; Zhang, Zhenzhen; Zhu, Liwei; Hu, Yanting; Ouyang, Lei; Ni, Guangyan; Ye, Qing

2017-01-01

Bamboo species-the only herbaceous trees-have unique structural and physiological characteristics that differ from those of other tree taxa. However, the role of night-time water use in bamboo is poorly understood and has rarely been investigated. We studied the day- and night-time sap flow response to culm age and rhizome structure in three age levels (juvenile, mature, and senescent) of Phyllostachys pubescens growing in the Nankun Mountain Natural Reserve, South China. We found that sap flow density and whole-tree hydraulic conductance decreased with culm age. After cutting of rhizome, the day-time sap flow and night-time water recharge decreased obviously. In addition, night-time water recharge accounted for the largest proportion (up to 30%) of total daily transpiration in normal senescent bamboos. Therefore, our study indicates that the connected rhizome system and night-time water recharge played a significant role in water compensation during the day and at night in bamboos. Night-time water recharge is especially critical to senescent bamboos, given their weaker transpiration due to the lower whole-tree hydraulic conductance, and consequently, they are more dependent on night-time water recharge for fulfilling their whole-day water consumption needs.

Signatures of selection acting on the innate immunity gene Toll-like receptor 2 (TLR2) during the evolutionary history of rodents.

PubMed

Tschirren, B; Råberg, L; Westerdahl, H

2011-06-01

Patterns of selection acting on immune defence genes have recently been the focus of considerable interest. Yet, when it comes to vertebrates, studies have mainly focused on the acquired branch of the immune system. Consequently, the direction and strength of selection acting on genes of the vertebrate innate immune defence remain poorly understood. Here, we present a molecular analysis of selection on an important receptor of the innate immune system of vertebrates, the Toll-like receptor 2 (TLR2), across 17 rodent species. Although purifying selection was the prevalent evolutionary force acting on most parts of the rodent TLR2, we found that codons in close proximity to pathogen-binding and TLR2-TLR1 heterodimerization sites have been subject to positive selection. This indicates that parasite-mediated selection is not restricted to acquired immune system genes like the major histocompatibility complex, but also affects innate defence genes. To obtain a comprehensive understanding of evolutionary processes in host-parasite systems, both innate and acquired immunity thus need to be considered. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

Geophagy in Northern Uganda: Perspectives from Consumers and Clinicians

PubMed Central

Huebl, Lena; Leick, Stephan; Guettl, Lukas; Akello, Grace; Kutalek, Ruth

2016-01-01

The etiology and health consequences of geophagy are still poorly understood. The consumed soil, individual motives, consumption habits, and the clinical perspective of geophagy in northern Uganda were examined. A total of 50 semistructured interviews (17 pregnant, eight nonpregnant women, 10 men, and 15 health-care professionals) were conducted. Our results suggest that geophagy is not limited to pregnancy and can also be found among nonpregnant women and men. During gestation, excessive amounts of various soil types are consumed and can replace food at times. Nonpregnant women and men consume less soil and stick to one type. When pregnant, craving and alleviating gastrointestinal upset are the main motives. In men, the main reasons for geophagy were craving, hypersalivation, and natural stimulants. If soil is craved, it can show similarities to a dependency syndrome. When picked up in childhood, geophagy is more likely to be continued throughout life. The consumption habits differ and thereby vary in their possible implications on health. Our findings suggest that men should be included in further studies. Especially nurses from the antenatal care are exposed to geophagists; however, no national guidelines exist for geophagy. Further research is necessary to create guidelines to be included in medical training and practice. PMID:27698274

Mechanisms of MDMA (Ecstasy)-Induced Oxidative Stress, Mitochondrial Dysfunction, and Organ Damage

PubMed Central

Song, Byoung-Joon; Moon, Kwan-Hoon; Upreti, Vijay V.; Eddington, Natalie D.; Lee, Insong J.

2010-01-01

Despite numerous reports about the acute and sub-chronic toxicities caused by MDMA (3,4-methylenedioxymethamphetamine, ecstasy), the underlying mechanism of organ damage is poorly understood. The aim of this review is to present an update of the mechanistic studies on MDMA-mediated organ damage partly caused by increased oxidative/nitrosative stress. Because of the extensive reviews on MDMA-mediated oxidative stress and tissue damage, we specifically focus on the mechanisms and consequences of oxidative-modifications of mitochondrial proteins, leading to mitochondrial dysfunction. We briefly describe a method to systematically identify oxidatively-modified mitochondrial proteins in control and MDMA-exposed rats by using biotin-N-maleimide (biotin-NM) as a sensitive probe for oxidized proteins. We also describe various applications and advantages of this Cys-targeted proteomics method and alternative approaches to overcome potential limitations of this method in studying oxidized proteins from MDMA-exposed tissues. Finally we discuss the mechanism of synergistic drug-interaction between MDMA and other abused substances including alcohol (ethanol) as well as application of this redox-based proteomics method in translational studies for developing effective preventive and therapeutic agents against MDMA-induced organ damage. PMID:20420575

Amazon boundary layer aerosol concentration sustained by vertical transport during rainfall

DOE PAGES

Wang, Jian; Krejci, Radovan; Giangrande, Scott; ...

2016-10-24

The nucleation of atmospheric vapours is an important source of new aerosol particles that can subsequently grow to form cloud condensation nuclei in the atmosphere. Most field studies of atmospheric aerosols over continents are influenced by atmospheric vapours of anthropogenic origin and, in consequence, aerosol processes in pristine, terrestrial environments remain poorly understood. The Amazon rainforest is one of the few continental regions where aerosol particles and their precursors can be studied under near-natural conditions, but the origin of small aerosol particles that grow into cloud condensation nuclei in the Amazon boundary layer remains unclear. Here we present aircraft- andmore » ground-based measurements under clean conditions during the wet season in the central Amazon basin. We find that high concentrations of small aerosol particles (with diameters of less than 50 nanometres) in the lower free troposphere are transported from the free troposphere into the boundary layer during precipitation events by strong convective downdrafts and weaker downward motions in the trailing stratiform region. Lastly, this rapid vertical transport can help to maintain the population of particles in the pristine Amazon boundary layer, and may therefore influence cloud properties and climate under natural conditions.« less

Allatostatin-A neurons inhibit feeding behavior in adult Drosophila.

PubMed

Hergarden, Anne Christina; Tayler, Timothy D; Anderson, David J

2012-03-06

How the brain translates changes in internal metabolic state or perceived food quality into alterations in feeding behavior remains poorly understood. Studies in Drosophila larvae have yielded information about neuropeptides and circuits that promote feeding, but a peptidergic neuron subset whose activation inhibits feeding in adult flies, without promoting metabolic changes that mimic the state of satiety, has not been identified. Using genetically based manipulations of neuronal activity, we show that activation of neurons (or neuroendocrine cells) expressing the neuropeptide allatostatin A (AstA) inhibits or limits several starvation-induced changes in feeding behavior in adult Drosophila, including increased food intake and enhanced behavioral responsiveness to sugar. Importantly, these effects on feeding behavior are observed in the absence of any measurable effects on metabolism or energy reserves, suggesting that AstA neuron activation is likely a consequence, not a cause, of metabolic changes that induce the state of satiety. These data suggest that activation of AstA-expressing neurons promotes food aversion and/or exerts an inhibitory influence on the motivation to feed and implicate these neurons and their associated circuitry in the mechanisms that translate the state of satiety into alterations in feeding behavior.

Allatostatin-A neurons inhibit feeding behavior in adult Drosophila

PubMed Central

Hergarden, Anne Christina; Tayler, Timothy D.; Anderson, David J.

2012-01-01

How the brain translates changes in internal metabolic state or perceived food quality into alterations in feeding behavior remains poorly understood. Studies in Drosophila larvae have yielded information about neuropeptides and circuits that promote feeding, but a peptidergic neuron subset whose activation inhibits feeding in adult flies, without promoting metabolic changes that mimic the state of satiety, has not been identified. Using genetically based manipulations of neuronal activity, we show that activation of neurons (or neuroendocrine cells) expressing the neuropeptide allatostatin A (AstA) inhibits or limits several starvation-induced changes in feeding behavior in adult Drosophila, including increased food intake and enhanced behavioral responsiveness to sugar. Importantly, these effects on feeding behavior are observed in the absence of any measurable effects on metabolism or energy reserves, suggesting that AstA neuron activation is likely a consequence, not a cause, of metabolic changes that induce the state of satiety. These data suggest that activation of AstA-expressing neurons promotes food aversion and/or exerts an inhibitory influence on the motivation to feed and implicate these neurons and their associated circuitry in the mechanisms that translate the state of satiety into alterations in feeding behavior. PMID:22345563

Omega-3 Free Fatty Acids Suppress Macrophage Inflammasome Activation by Inhibiting NF-κB Activation and Enhancing Autophagy

PubMed Central

Williams-Bey, Yolanda; Boularan, Cedric; Vural, Ali; Huang, Ning-Na; Hwang, Il-Young; Shan-Shi, Chong; Kehrl, John H.

2014-01-01

The omega-3 (ω3) fatty acid docosahexaenoic acid (DHA) can suppress inflammation, specifically IL-1β production through poorly understood molecular mechanisms. Here, we show that DHA reduces macrophage IL-1β production by limiting inflammasome activation. Exposure to DHA reduced IL-1β production by ligands that stimulate the NLRP3, AIM2, and NAIP5/NLRC4 inflammasomes. The inhibition required Free Fatty Acid Receptor (FFAR) 4 (also known as GPR120), a G-protein coupled receptor (GPR) known to bind DHA. The exposure of cells to DHA recruited the adapter protein β-arrestin1/2 to FFAR4, but not to a related lipid receptor. DHA treatment reduced the initial inflammasome priming step by suppressing the nuclear translocation of NF-κB. DHA also reduced IL-1β levels by enhancing autophagy in the cells. As a consequence macrophages derived from mice lacking the essential autophagy protein ATG7 were partially resistant to suppressive effects of DHA. Thus, DHA suppresses inflammasome activation by two distinct mechanisms, inhibiting the initial priming step and by augmenting autophagy, which limits inflammasome activity. PMID:24911523

Swallowing disorders in Parkinson's disease: impact of lingual pumping.

PubMed

Argolo, Natalie; Sampaio, Marília; Pinho, Patrícia; Melo, Ailton; Nóbrega, Ana Caline

2015-01-01

Lingual pumping (LP) is a repetitive, involuntary, anteroposterior movement of the tongue on the soft palate that is executed prior to transferring the food bolus to the pharynx, but we also observed LP when multiple swallows were taken. LP may be associated with rigidity and bradykinesia in patients with Parkinson's disease (PD). This phenomenon tends to be more prevalent in dysphagic PD patients, and its impact on swallowing dynamics remains poorly understood. To evaluate how LP interferes with the oral and pharyngeal phases of the swallowing of foods of different consistencies and volumes. We used videofluoroscopy to study the swallowing of 69 PD patients performing 10 swallows of barium mixed with foods of different consistencies and volumes. LP was associated with the unstable intra-oral organization of the bolus, the loss of bolus control, the pharyngeal retention of food and food entering the airway. This abnormal movement was also associated with a shorter oral transit time and was found to be more prevalent with food of thicker consistencies. LP is associated with swallowing incoordination and with food entering the airway. Preventive measures to minimise the pulmonary or nutritional consequences of this behaviour are necessary. © 2015 Royal College of Speech and Language Therapists.

The screening and management of pituitary dysfunction following traumatic brain injury in adults: British Neurotrauma Group guidance

PubMed Central

Tan, Chin Lik; Alavi, Seyed Alireza; Baldeweg, Stephanie E; Belli, Antonio; Carson, Alan; Feeney, Claire; Goldstone, Anthony P; Greenwood, Richard; Menon, David K; Simpson, Helen L; Toogood, Andrew A; Gurnell, Mark; Hutchinson, Peter J

2017-01-01

Pituitary dysfunction is a recognised, but potentially underdiagnosed complication of traumatic brain injury (TBI). Post-traumatic hypopituitarism (PTHP) can have major consequences for patients physically, psychologically, emotionally and socially, leading to reduced quality of life, depression and poor rehabilitation outcome. However, studies on the incidence of PTHP have yielded highly variable findings. The risk factors and pathophysiology of this condition are also not yet fully understood. There is currently no national consensus for the screening and detection of PTHP in patients with TBI, with practice likely varying significantly between centres. In view of this, a guidance development group consisting of expert clinicians involved in the care of patients with TBI, including neurosurgeons, neurologists, neurointensivists and endocrinologists, was convened to formulate national guidance with the aim of facilitating consistency and uniformity in the care of patients with TBI, and ensuring timely detection or exclusion of PTHP where appropriate. This article summarises the current literature on PTHP, and sets out guidance for the screening and management of pituitary dysfunction in adult patients with TBI. It is hoped that future research will lead to more definitive recommendations in the form of guidelines. PMID:28860331

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.

Contemporaneous Social Environment and the Architecture of Late-Life Gene Expression Profiles.

PubMed

Levine, Morgan E; Crimmins, Eileen M; Weir, David R; Cole, Steve W

2017-09-01

Environmental or social challenges can stimulate a cascade of coordinated physiological changes in stress response systems. Unfortunately, chronic activation of these adaptations under conditions such as low socioeconomic status (SES) can have negative consequences for long-term health. While there is substantial evidence tying low SES to increased disease risk and reduced life expectancy, the underlying biology remains poorly understood. Using pilot data on 120 older adults from the Health and Retirement Study (United States, 2002-2010), we examined the associations between SES and gene expression levels in adulthood, with particular focus on a gene expression program known as the conserved transcriptional response to adversity. We also used a bioinformatics-based approach to assess the activity of specific gene regulation pathways involved in inflammation, antiviral responses, and stress-related neuroendocrine signaling. We found that low SES was related to increased expression of conserved transcriptional response to adversity genes and distinct patterns of proinflammatory, antiviral, and stress signaling (e.g., sympathetic nervous system and hypothalamic-pituitary-adrenal axis) transcription factor activation. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Contrasting Ecosystem-Effects of Morphologically Similar Copepods

PubMed Central

Matthews, Blake; Hausch, Stephen; Winter, Christian; Suttle, Curtis A.; Shurin, Jonathan B.

2011-01-01

Organisms alter the biotic and abiotic conditions of ecosystems. They can modulate the availability of resources to other species (ecosystem engineering) and shape selection pressures on other organisms (niche construction). Very little is known about how the engineering effects of organisms vary among and within species, and, as a result, the ecosystem consequences of species diversification and phenotypic evolution are poorly understood. Here, using a common gardening experiment, we test whether morphologically similar species and populations of Diaptomidae copepods (Leptodiaptomus ashlandi, Hesperodiaptomus franciscanus, Skistodiaptomus oregonensis) have similar or different effects on the structure and function of freshwater ecosystems. We found that copepod species had contrasting effects on algal biomass, ammonium concentrations, and sedimentation rates, and that copepod populations had contrasting effects on prokaryote abundance, sedimentation rates, and gross primary productivity. The average size of ecosystem-effect contrasts between species was similar to those between populations, and was comparable to those between fish species and populations measured in previous common gardening experiments. Our results suggest that subtle morphological variation among and within species can cause multifarious and divergent ecosystem-effects. We conclude that using morphological trait variation to assess the functional similarity of organisms may underestimate the importance of species and population diversity for ecosystem functioning. PMID:22140432

Amazon boundary layer aerosol concentration sustained by vertical transport during rainfall

NASA Astrophysics Data System (ADS)

Wang, Jian; Krejci, Radovan; Giangrande, Scott; Kuang, Chongai; Barbosa, Henrique M. J.; Brito, Joel; Carbone, Samara; Chi, Xuguang; Comstock, Jennifer; Ditas, Florian; Lavric, Jost; Manninen, Hanna E.; Mei, Fan; Moran-Zuloaga, Daniel; Pöhlker, Christopher; Pöhlker, Mira L.; Saturno, Jorge; Schmid, Beat; Souza, Rodrigo A. F.; Springston, Stephen R.; Tomlinson, Jason M.; Toto, Tami; Walter, David; Wimmer, Daniela; Smith, James N.; Kulmala, Markku; Machado, Luiz A. T.; Artaxo, Paulo; Andreae, Meinrat O.; Petäjä, Tuukka; Martin, Scot T.

2016-11-01

The nucleation of atmospheric vapours is an important source of new aerosol particles that can subsequently grow to form cloud condensation nuclei in the atmosphere. Most field studies of atmospheric aerosols over continents are influenced by atmospheric vapours of anthropogenic origin (for example, ref. 2) and, in consequence, aerosol processes in pristine, terrestrial environments remain poorly understood. The Amazon rainforest is one of the few continental regions where aerosol particles and their precursors can be studied under near-natural conditions, but the origin of small aerosol particles that grow into cloud condensation nuclei in the Amazon boundary layer remains unclear. Here we present aircraft- and ground-based measurements under clean conditions during the wet season in the central Amazon basin. We find that high concentrations of small aerosol particles (with diameters of less than 50 nanometres) in the lower free troposphere are transported from the free troposphere into the boundary layer during precipitation events by strong convective downdrafts and weaker downward motions in the trailing stratiform region. This rapid vertical transport can help to maintain the population of particles in the pristine Amazon boundary layer, and may therefore influence cloud properties and climate under natural conditions.

Amazon boundary layer aerosol concentration sustained by vertical transport during rainfall.

PubMed

Wang, Jian; Krejci, Radovan; Giangrande, Scott; Kuang, Chongai; Barbosa, Henrique M J; Brito, Joel; Carbone, Samara; Chi, Xuguang; Comstock, Jennifer; Ditas, Florian; Lavric, Jost; Manninen, Hanna E; Mei, Fan; Moran-Zuloaga, Daniel; Pöhlker, Christopher; Pöhlker, Mira L; Saturno, Jorge; Schmid, Beat; Souza, Rodrigo A F; Springston, Stephen R; Tomlinson, Jason M; Toto, Tami; Walter, David; Wimmer, Daniela; Smith, James N; Kulmala, Markku; Machado, Luiz A T; Artaxo, Paulo; Andreae, Meinrat O; Petäjä, Tuukka; Martin, Scot T

2016-11-17

The nucleation of atmospheric vapours is an important source of new aerosol particles that can subsequently grow to form cloud condensation nuclei in the atmosphere. Most field studies of atmospheric aerosols over continents are influenced by atmospheric vapours of anthropogenic origin (for example, ref. 2) and, in consequence, aerosol processes in pristine, terrestrial environments remain poorly understood. The Amazon rainforest is one of the few continental regions where aerosol particles and their precursors can be studied under near-natural conditions, but the origin of small aerosol particles that grow into cloud condensation nuclei in the Amazon boundary layer remains unclear. Here we present aircraft- and ground-based measurements under clean conditions during the wet season in the central Amazon basin. We find that high concentrations of small aerosol particles (with diameters of less than 50 nanometres) in the lower free troposphere are transported from the free troposphere into the boundary layer during precipitation events by strong convective downdrafts and weaker downward motions in the trailing stratiform region. This rapid vertical transport can help to maintain the population of particles in the pristine Amazon boundary layer, and may therefore influence cloud properties and climate under natural conditions.

Rare species contribute disproportionately to the functional structure of species assemblages.

PubMed

Leitão, Rafael P; Zuanon, Jansen; Villéger, Sébastien; Williams, Stephen E; Baraloto, Christopher; Fortunel, Claire; Mendonça, Fernando P; Mouillot, David

2016-04-13

There is broad consensus that the diversity of functional traits within species assemblages drives several ecological processes. It is also widely recognized that rare species are the first to become extinct following human-induced disturbances. Surprisingly, however, the functional importance of rare species is still poorly understood, particularly in tropical species-rich assemblages where the majority of species are rare, and the rate of species extinction can be high. Here, we investigated the consequences of local and regional extinctions on the functional structure of species assemblages. We used three extensive datasets (stream fish from the Brazilian Amazon, rainforest trees from French Guiana, and birds from the Australian Wet Tropics) and built an integrative measure of species rarity versus commonness, combining local abundance, geographical range, and habitat breadth. Using different scenarios of species loss, we found a disproportionate impact of rare species extinction for the three groups, with significant reductions in levels of functional richness, specialization, and originality of assemblages, which may severely undermine the integrity of ecological processes. The whole breadth of functional abilities within species assemblages, which is disproportionately supported by rare species, is certainly critical in maintaining ecosystems particularly under the ongoing rapid environmental transitions. © 2016 The Author(s).

Improving understanding, promoting social inclusion, and fostering empowerment related to epilepsy: Epilepsy Foundation public awareness campaigns--2001 through 2013.

PubMed

Price, P; Kobau, R; Buelow, J; Austin, J; Lowenberg, K

2015-03-01

It is a significant public health concern that epilepsy, the fourth most common neurological disorder in the United States, is generally poorly understood by both the public and those living with the condition. Lack of understanding may magnify the challenges faced by those with epilepsy, including limiting treatment opportunities, effective management of symptoms, and full participation in daily life activities. Insufficient awareness of epilepsy and appropriate seizure first aid among the public and professionals can result in insufficient treatment, inappropriate seizure response, physical restraint, social exclusion, or other negative consequences. To address the need for increased public education and awareness about epilepsy, the national Epilepsy Foundation, supported by the Centers for Disease Control and Prevention, has conducted yearly multifaceted public education and awareness campaigns designed to reach the broad population and targeted segments of the population including youth, young adults, racial/ethnic groups (i.e., African-, Hispanic-, and Asian-Americans), and people with epilepsy and their caregivers. Campaign channels have included traditional media, social media, and community opinion leaders and celebrity spokespersons. The key activities of these campaigns, conducted from 2001 to 2013, are summarized in this report. Published by Elsevier Inc.

Irritable bowel syndrome: A microbiome-gut-brain axis disorder?

PubMed Central

Kennedy, Paul J; Cryan, John F; Dinan, Timothy G; Clarke, Gerard

2014-01-01

Irritable bowel syndrome (IBS) is an extremely prevalent but poorly understood gastrointestinal disorder. Consequently, there are no clear diagnostic markers to help diagnose the disorder and treatment options are limited to management of the symptoms. The concept of a dysregulated gut-brain axis has been adopted as a suitable model for the disorder. The gut microbiome may play an important role in the onset and exacerbation of symptoms in the disorder and has been extensively studied in this context. Although a causal role cannot yet be inferred from the clinical studies which have attempted to characterise the gut microbiota in IBS, they do confirm alterations in both community stability and diversity. Moreover, it has been reliably demonstrated that manipulation of the microbiota can influence the key symptoms, including abdominal pain and bowel habit, and other prominent features of IBS. A variety of strategies have been taken to study these interactions, including probiotics, antibiotics, faecal transplantations and the use of germ-free animals. There are clear mechanisms through which the microbiota can produce these effects, both humoral and neural. Taken together, these findings firmly establish the microbiota as a critical node in the gut-brain axis and one which is amenable to therapeutic interventions. PMID:25339800

On the complex non-linear interaction between bacteria and redox dynamics in sediments and its effects on water quality

NASA Astrophysics Data System (ADS)

Sanchez-Vila, X.; Rubol, S.; Fernandez-Garcia, D.

2011-12-01

Despite the fact that the prognoses on the availability of resources related to different climate scenarios have been already formulated, the complex hydrological and biogeochemical reactions taking place in different compartments in natural environmental media are poorly understood, especially regarding the interactions between water bodies, and the reactions taking place at soil-water interfaces. Amongst them, the inter-relationship between hydrology, chemistry and biology has important implications in natural (rivers, lakes) and man-made water facilities (lagoons, artificial recharge pounds, reservoirs, slow infiltration systems, etc). The consequences involve environment, economic, social and health-risk aspects. At the current stage, only limited explanations are available to understand the implications of these relationships on ecosystem services, water quality and water quantity. Therefore, there is an urgent need to seek a full understanding of these physical-biogeochemical processes in water-bodies, sediments and biota and its implications in ecological and health risk. We present a soil column experiment and a mathematical model which aim to study the mutual interplay between water and bacteria activity in porous media, the corresponding dynamics and the feedback on nutrient cycling by using a multidisciplinary approach.

Heterostyly accelerates diversification via reduced extinction in primroses

PubMed Central

de Vos, Jurriaan M.; Hughes, Colin E.; Schneeweiss, Gerald M.; Moore, Brian R.; Conti, Elena

2014-01-01

The exceptional species diversity of flowering plants, exceeding that of their sister group more than 250-fold, is especially evident in floral innovations, interactions with pollinators and sexual systems. Multiple theories, emphasizing flower–pollinator interactions, genetic effects of mating systems or high evolvability, predict that floral evolution profoundly affects angiosperm diversification. However, consequences for speciation and extinction dynamics remain poorly understood. Here, we investigate trajectories of species diversification focusing on heterostyly, a remarkable floral syndrome where outcrossing is enforced via cross-compatible floral morphs differing in placement of their respective sexual organs. Heterostyly evolved at least 20 times independently in angiosperms. Using Darwin's model for heterostyly, the primrose family, we show that heterostyly accelerates species diversification via decreasing extinction rates rather than increasing speciation rates, probably owing to avoidance of the negative genetic effects of selfing. However, impact of heterostyly appears to differ over short and long evolutionary time-scales: the accelerating effect of heterostyly on lineage diversification is manifest only over long evolutionary time-scales, whereas recent losses of heterostyly may prompt ephemeral bursts of speciation. Our results suggest that temporal or clade-specific conditions may ultimately determine the net effects of specific traits on patterns of species diversification. PMID:24759859

S-Nitrosation destabilizes glutathione transferase P1-1.

PubMed

Balchin, David; Stoychev, Stoyan H; Dirr, Heini W

2013-12-23

Protein S-nitrosation is a post-translational modification that regulates the function of more than 500 human proteins. Despite its apparent physiological significance, S-nitrosation is poorly understood at a molecular level. Here, we investigated the effect of S-nitrosation on the activity, structure, stability, and dynamics of human glutathione transferase P1-1 (GSTP1-1), an important detoxification enzyme ubiquitous in aerobes. S-Nitrosation at Cys47 and Cys101 reduces the activity of the enzyme by 94%. Circular dichroism spectroscopy, acrylamide quenching, and amide hydrogen-deuterium exchange mass spectrometry experiments indicate that the loss of activity is caused by the introduction of local disorder at the active site of GSTP1-1. Furthermore, the modification destabilizes domain 1 of GSTP1-1 against denaturation, smoothing the unfolding energy landscape of the protein and introducing a refolding defect. In contrast, S-nitrosation at Cys101 alone introduces a refolding defect in domain 1 but compensates by stabilizing the domain kinetically. These data elucidate the physical basis for the regulation of GSTP1-1 by S-nitrosation and provide general insight into the consequences of S-nitrosation on protein stability and dynamics.

The effect of maternal glucocorticoid levels on juvenile docility in yellow-bellied marmots.

PubMed

Petelle, Matthew B; Dang, Brian N; Blumstein, Daniel T

2017-03-01

Maternal effects can have significant and long-term consequences on offspring behavior and survival, while consistent individual differences (i.e., personality) can have profound impacts on individual fitness. Thus, both can influence population dynamics. However, the underlying mechanisms that determine variation in personality traits are poorly understood. Maternal effects are one potential mechanism that may explain personality variation. We capitalized on a long-term study of yellow-bellied marmots (Marmota flaviventris) to identify maternal effects on juvenile docility. To do so, we partitioned the variance in juvenile docility using a quantitative genetic modeling approach to isolate potential maternal effects. We also directly tested whether maternal stress, measured through fecal glucocorticoid metabolite levels during lactation of 82 mothers, was associated with offspring docility. Docility scores were estimated for 645 juveniles trapped between 2002 and 2012. We found an interaction between maternal glucocorticoid levels and dam age on juvenile docility. We also found significant maternal, litter, permanent environment, and year effects. These results suggest that a mother's life history stage interacts with stress to influence offspring personality. This early life influence can have long lasting effects on an individual's docility throughout life. Copyright © 2017 Elsevier Inc. All rights reserved.