5,092 research outputs found
Albumin activates the AKT signalling pathway and protects B-chronics lymphocytic leukemia cells from chlorambucil- and radiation-induced apoptosis
Assessing the apparent imbalance between geochemical and biochemical indicators of meso- and bathypelagic biological activity: What the @$#! is wrong with present calculations of carbon budgets?
Metabolic activity in the water column below the euphotic zone is ultimately fuelled by the vertical flux of organic material from the surface. Over time, the deep ocean is presumably at steady state, with sources and sinks balanced. But recently compiled global budgets and intensive local field studies suggest that estimates of metabolic activity in the dark ocean exceed the influx of organic substrates. This imbalance indicates either the existence of unaccounted sources of organic carbon or that metabolic activity in the dark ocean is being over-estimated. Budgets of organic carbon flux and metabolic activity in the dark ocean have uncertainties associated with environmental variability, measurement capabilities, conversion parameters, and processes that are not well sampled. We present these issues and quantify associated uncertainties where possible, using a Monte Carlo analysis of a published data set to determine the probability that the imbalance can be explained purely by uncertainties in measurements and conversion factors. A sensitivity analysis demonstrates that the bacterial growth efficiencies and assumed cell carbon contents have the greatest effects on the magnitude of the carbon imbalance. Two poorly quantified sources, lateral advection of particles and a population of slowly settling particles, are discussed as providing a means of closing regional carbon budgets. Finally, we make recommendations concerning future research directions to reduce important uncertainties and allow a better determination of the magnitude and causes of the unbalanced carbon budgets. (C) 2010 Elsevier Ltd. All rights reserved
Psychosocial adversity and socioeconomic position during childhood and epigenetic age: analysis of two prospective cohort studies
Psychosocial adversity in childhood (e.g. abuse) and low socioeconomic position (SEP) can have significant lasting effects on social and health outcomes. DNA methylation-based biomarkers are highly correlated with chronological age; departures of methylation-predicted age from chronological age can be used to define a measure of age acceleration, which may represent a potential biological mechanism linking environmental exposures to later health outcomes. Using data from two cohorts of women Avon Longitudinal Study of Parents and Children, (ALSPAC), N = 989 and MRC National Survey of Health and Development, NSHD, N = 773), we assessed associations of SEP, psychosocial adversity in childhood (parental physical or mental illness or death, parental separation, parental absence, sub-optimal maternal bonding, sexual, emotional and physical abuse and neglect) and a cumulative score of these psychosocial adversity measures, with DNA methylation age acceleration in adulthood (measured in peripheral blood at mean chronological ages 29 and 47 in ALSPAC and buccal cells at age 53 in NSHD). Sexual abuse was strongly associated with age acceleration in ALSPAC (sexual abuse data were not available in NSHD), e.g. at the 47-year time point sexual abuse associated with a 3.41 years higher DNA methylation age (95% CI 1.53 to 5.29) after adjusting for childhood and adulthood SEP. No associations were observed between low SEP, any other psychosocial adversity measure or the cumulative psychosocial adversity score and age acceleration. DNA methylation age acceleration is associated with sexual abuse, suggesting a potential mechanism linking sexual abuse with adverse outcomes. Replication studies with larger sample sizes are warranted
Wnt4 and LAP2alpha as pacemakers of Thymic Epithelial Senescence
Age-associated thymic involution has considerable physiological impact by inhibiting de novo T-cell selection. This impaired T-cell production leads to weakened immune responses. Yet the molecular mechanisms of thymic stromal adipose involution are not clear. Age-related alterations also occur in the murine thymus providing an excellent model system. In the present work structural and molecular changes of the murine thymic stroma were investigated during aging. We show that thymic epithelial senescence correlates with significant destruction of epithelial network followed by adipose involution. We also show in purified thymic epithelial cells the age-related down-regulation of Wnt4 (and subsequently FoxN1), and the prominent increase in LAP2α expression. These senescence-related changes of gene expression are strikingly similar to those observed during mesenchymal to pre-adipocyte differentiation of fibroblast cells suggesting similar molecular background in epithelial cells. For molecular level proof-of-principle stable LAP2α and Wnt4-over-expressing thymic epithelial cell lines were established. LAP2α over-expression provoked a surge of PPARγ expression, a transcription factor expressed in pre-adipocytes. In contrast, additional Wnt4 decreased the mRNA level of ADRP, a target gene of PPARγ. Murine embryonic thymic lobes have also been transfected with LAP2α- or Wnt4-encoding lentiviral vectors. As expected LAP2α over-expression increased, while additional Wnt4 secretion suppressed PPARγ expression. Based on these pioneer experiments we propose that decreased Wnt activity and increased LAP2α expression provide the molecular basis during thymic senescence. We suggest that these molecular changes trigger thymic epithelial senescence accompanied by adipose involution. This process may either occur directly where epithelium can trans-differentiate into pre-adipocytes; or indirectly where first epithelial to mesenchymal transition (EMT) occurs followed by subsequent pre-adipocyte differentiation. The latter version fits better with literature data and is supported by the observed histological and molecular level changes
Understanding disease control: influence of epidemiological and economic factors
We present a local spread model of disease transmission on a regular network
and compare different control options ranging from treating the whole
population to local control in a well-defined neighborhood of an infectious
individual. Comparison is based on a total cost of epidemic, including cost of
palliative treatment of ill individuals and preventive cost aimed at
vaccination or culling of susceptible individuals. Disease is characterized by
pre- symptomatic phase which makes detection and control difficult. Three
general strategies emerge, global preventive treatment, local treatment within
a neighborhood of certain size and only palliative treatment with no
prevention. The choice between the strategies depends on relative costs of
palliative and preventive treatment. The details of the local strategy and in
particular the size of the optimal treatment neighborhood weakly depends on
disease infectivity but strongly depends on other epidemiological factors. The
required extend of prevention is proportional to the size of the infection
neighborhood, but this relationship depends on time till detection and time
till treatment in a non-nonlinear (power) law. In addition, we show that the
optimal size of control neighborhood is highly sensitive to the relative cost,
particularly for inefficient detection and control application. These results
have important consequences for design of prevention strategies aiming at
emerging diseases for which parameters are not known in advance
Postcopulatory Sexual Selection Is Associated with Reduced Variation in Sperm Morphology
The evolutionary role of postcopulatory sexual selection in shaping male reproductive traits, including sperm morphology, is well documented in several taxa. However, previous studies have focused almost exclusively on the influence of sperm competition on variation among species. In this study we tested the hypothesis that intraspecific variation in sperm morphology is driven by the level of postcopulatory sexual selection in passerine birds.Using two proxy measures of sperm competition level, (i) relative testes size and (ii) extrapair paternity level, we found strong evidence that intermale variation in sperm morphology is negatively associated with the degree of postcopulatory sexual selection, independently of phylogeny.Our results show that the role of postcopulatory sexual selection in the evolution of sperm morphology extends to an intraspecific level, reducing the variation towards what might be a species-specific 'optimum' sperm phenotype. This finding suggests that while postcopulatory selection is generally directional (e.g., favouring longer sperm) across avian species, it also acts as a stabilising evolutionary force within species under intense selection, resulting in reduced variation in sperm morphology traits. We discuss some potential evolutionary mechanisms for this pattern
Proposals for evaluating the regularity of a scientist'sresearch output
Evaluating the career of individual scientists according to their scientific output is a common bibliometric problem. Two aspects are classically taken into account: overall productivity and overall diffusion/impact, which can be measured by a plethora of indicators that consider publications and/or citations separately or synthesise these two quantities into a single number (e.g. h-index). A secondary aspect, which is sometimes mentioned in the rules of competitive examinations for research position/promotion, is time regularity of one researcher's scientific output. Despite the fact that it is sometimes invoked, a clear definition of regularity is still lacking. We define it as the ability of generating an active and stable research output over time, in terms of both publications/ quantity and citations/diffusion. The goal of this paper is introducing three analysis tools to perform qualitative/quantitative evaluations on the regularity of one scientist's output in a simple and organic way. These tools are respectively (1) the PY/CY diagram, (2) the publication/citation Ferrers diagram and (3) a simplified procedure for comparing the research output of several scientists according to their publication and citation temporal distributions (Borda's ranking). Description of these tools is supported by several examples
El Niño Driven Changes in Global Fire 2015/16
This is the final version. Available on open access from Frontiers Media via the DOI in this recordData Availability Statement:
The JULES code used in these experiments is freely available on the JULES trunk from version 5.4 onward. The rose suite used for these experiments is u-bh074. Both the suite and the JULES code are available on the JULES FCM repository: https://code.metoffice.gov.uk/trac/jules (registration required). The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation, to any qualified researcher upon request.El Niño years are characterized by a high sea surface temperature anomaly in the Equatorial Pacific Ocean, which leads to unusually warm and dry conditions over many fire-prone regions globally. This can lead to an increase in burned area and emissions from fire activity, and socio-economic, and environmental losses. Previous studies using satellite observations to assess the impacts of the recent 2015/16 El Niño found an increase in burned area in some regions compared to La Niña years. Here, we use the dynamic land surface model JULES to assess how conditions differed as a result of the El Niño by comparing simulations driven by observations from the year 2015/16 with mean climatological drivers of temperature, precipitation, humidity, wind, air pressure, and short and long-wave radiation. We use JULES with the interactive fire module INFERNO to assess the effects on precipitation, temperature, burned area, and the associated impacts on the carbon sink globally and for three regions: South America, Africa, and Asia. We find that the model projects a variable response in precipitation, with some areas including northern South America, southern Africa and East Asia getting drier, and most areas globally seeing an increase in temperature. As a result, higher burned area is simulated with El Niño conditions in most regions, although there are areas of both increased and decreased burned area over Africa. South America shows the largest fire response with El Niño, with a 13% increase in burned area and emitted carbon, corresponding with the largest decrease in carbon uptake. Within South America, peak fire occurs from August to October across central-southern Brazil, and temperature is shown to be the main driver of the El Niño-induced increase in burned area during this period. Combined, our results indicate that although 2015/16 was not a peak year for global total burned area or fire emissions, the El Niño led to an overall increase of 4% in burned area and 5% in emissions compared to a “No El Niño” scenario for 2015/16, and contributed to a 4% reduction in the terrestrial carbon sink.Newton FundNatural Environment Research Council (NERC)São Paulo Research Foundation (FAPESP)Brazilian National Council for Scientific and Technological Development (CNPq)Inter-American Institute for Global Change Research (IAI
Non-supersymmetric heterotic model building
We investigate orbifold and smooth Calabi-Yau compactifications of the
non-supersymmetric heterotic SO(16)xSO(16) string. We focus on such Calabi-Yau
backgrounds in order to recycle commonly employed techniques, like index
theorems and cohomology theory, to determine both the fermionic and bosonic 4D
spectra. We argue that the N=0 theory never leads to tachyons on smooth
Calabi-Yaus in the large volume approximation. As twisted tachyons may arise on
certain singular orbifolds, we conjecture that such tachyonic states are lifted
in the full blow-up. We perform model searches on selected orbifold geometries.
In particular, we construct an explicit example of a Standard Model-like theory
with three generations and a single Higgs field.Comment: 1+30 pages latex, 11 tables; v2: references and minor revisions
added, matches version published in JHE
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