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171.
Given a trade-off between offspring size and number, all mothers are predicted to produce the same optimal-sized offspring in a given environment. In many species, however, larger and/or older mothers produce bigger offspring. There are several hypotheses to explain this but they lack strong empirical support. In organisms with indeterminate growth, there is the additional problem that maternal size and age are positively correlated, so what are their relative roles in determining offspring size? To investigate this, we measured the natural relationship between maternal and offspring size in a wild population of Gambusia holbrooki (eastern mosquitofish), and experimentally disentangled the effects of maternal age and size on offspring size in the laboratory. In combination, our data indicate that the relationship between maternal and offspring size is nonlinear. Small mothers seem to produce larger than average offspring due to integer effects associated with very small broods. For extremely large mothers, which were only sampled in our wild data, these larger than average offspring may result from greater maternal resources or age effects. However, maternal age had no effect on offspring size or number in the laboratory experiment. Our results highlight the importance of sampling the full size–range of mothers when investigating maternal effects on offspring size. They also point to the difficulty of experimentally manipulating maternal size, because any change in size is invariably associated with a change in at least one factor affecting growth (be it temperature, food availability, or density) that might also have an indirect effect on offspring size.  相似文献   
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Background

Research investments are essential to address the burden of disease, however allocation of limited resources is poorly documented. We systematically reviewed the investments awarded by funding organisations to UK institutions and their global partners for infectious disease research.

Methodology/Principal Findings

Public and philanthropic investments for the period 1997 to 2010 were included. We categorised studies by infectious disease, cross-cutting theme, and by research and development value chain, reflecting the type of science. We identified 6165 funded studies, with a total research investment of UK £2.6 billion. Public organisations provided £1.4 billion (54.0%) of investments compared with £1.1 billion (42.4%) by philanthropic organisations. Global health studies represented an investment of £928 million (35.7%). The Wellcome Trust was the leading investor with £688 million (26.5%), closely followed by the UK Medical Research Council (MRC) with £673 million (25.9%). Funding over time was volatile, ranging from ∼£40 million to ∼£160 million per year for philanthropic organisations and ∼£30 million to ∼£230 million for public funders.

Conclusions/Significance

Infectious disease research funding requires global coordination and strategic long-term vision. Our analysis demonstrates the diversity and inconsistent patterns in investment, with volatility in annual funding amounts and limited investment for product development and clinical trials.  相似文献   
174.
Divergence dating studies, which combine temporal data from the fossil record with branch length data from molecular phylogenetic trees, represent a rapidly expanding approach to understanding the history of life. National Evolutionary Synthesis Center hosted the first Fossil Calibrations Working Group (3-6 March, 2011, Durham, NC, USA), bringing together palaeontologists, molecular evolutionists and bioinformatics experts to present perspectives from disciplines that generate, model and use fossil calibration data. Presentations and discussions focused on channels for interdisciplinary collaboration, best practices for justifying, reporting and using fossil calibrations and roadblocks to synthesis of palaeontological and molecular data. Bioinformatics solutions were proposed, with the primary objective being a new database for vetted fossil calibrations with linkages to existing resources, targeted for a 2012 launch.  相似文献   
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Platonova O  Akey IV  Head JF  Akey CW 《Biochemistry》2011,50(37):8078-8089
Human Npm2 is an ortholog of Xenopus nucleoplasmin (Np), a chaperone that binds histones. We have determined the crystal structure of a truncated Npm2-core at 1.9 ? resolution and show that the N-terminal domains of Npm2 and Np form similar pentamers. This allowed us to model an Npm2 decamer which may be formed by hydrogen bonds between quasi-conserved residues in the interface between two pentamers. Interestingly, the Npm2 pentamer lacks a prototypical A1-acidic tract in each of its subunits. This feature may be responsible for the inability of Npm2-core to bind histones. However, Npm2 with a large acidic tract in its C-terminal tail (Npm2-A2) is able to bind histones and form large complexes. Fluorescence resonance energy transfer experiments and biochemical analysis of loop mutations support the premise that nucleoplasmins form decamers when they bind H2A-H2B dimers and H3-H4 tetramers simultaneously. In the absence of histone tetramers, these chaperones bind H2A-H2B dimers with a single pentamer forming the central hub. When taken together, our data provide insights into the mechanism of histone binding by nucleoplasmins.  相似文献   
177.
We previously demonstrated that inhaling nitric oxide (NO) increases the oxygen affinity of sickle red blood cells (RBCs) in patients with sickle cell disease (SCD). Our recent studies found that NO lowered the P50 values of sickle hemoglobin (HbS) hemolysates but did not increase methemoglobin (metHb) levels, supporting the role of NO, but not metHb, in the oxygen affinity of HbS. Here we examine the mechanism by which NO increases HbS oxygen affinity. Because anti-sickling agents increase sickle RBC oxygen affinity, we first determined whether NO exhibits anti-sickling properties. The viscosity of HbS hemolysates, measured by falling ball assays, increased upon deoxygenation; NO treatment reduced the increment. Multiphoton microscopic analyses showed smaller HbS polymers in deoxygenated sickle RBCs and HbS hemolysates exposed to NO. These results suggest that NO inhibits HbS polymer formation and has anti-sickling properties. Furthermore, we found that HbS treated with NO exhibits an isoelectric point similar to that of HbA, suggesting that NO alters the electric charge of HbS. NO–HbS adducts had the same elution time as HbA upon high performance liquid chromatography analysis. This study demonstrates that NO may disrupt HbS polymers by abolishing the excess positive charge of HbS, resulting in increased oxygen affinity.  相似文献   
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Wildlife managers are urgently searching for improved sociodemographic population assessment methods to evaluate the effectiveness of implemented conservation activities. These need to be inexpensive, appropriate for a wide spectrum of species and straightforward to apply by local staff members with minimal training. Furthermore, conservation management would benefit from single approaches which cover many aspects of population assessment beyond only density estimates, to include for instance social and demographic structure, movement patterns, or species interactions. Remote camera traps have traditionally been used to measure species richness. Currently, there is a rapid move toward using remote camera trapping in density estimation, community ecology, and conservation management. Here, we demonstrate such comprehensive population assessment by linking remote video trapping, spatially explicit capture–recapture (SECR) techniques, and other methods. We apply it to three species: chimpanzees Pan troglodytes troglodytes, gorillas Gorilla gorilla gorilla, and forest elephants Loxodonta cyclotis in Loango National Park, Gabon. All three species exhibited considerable heterogeneity in capture probability at the sex or group level and density was estimated at 1.72, 1.2, and 1.37 individuals per km2 and male to female sex ratios were 1:2.1, 1:3.2, and 1:2 for chimpanzees, gorillas, and elephants, respectively. Association patterns revealed four, eight, and 18 independent social groups of chimpanzees, gorillas, and elephants, respectively: key information for both conservation management and studies on the species' ecology. Additionally, there was evidence of resident and nonresident elephants within the study area and intersexual variation in home range size among elephants but not chimpanzees. Our study highlights the potential of combining camera trapping and SECR methods in conducting detailed population assessments that go far beyond documenting species diversity patterns or estimating single species population size. Our study design is widely applicable to other species and spatial scales, and moderately trained staff members can collect and process the required data. Furthermore, assessments using the same method can be extended to include several other ecological, behavioral, and demographic aspects: fission and fusion dynamics and intergroup transfers, birth and mortality rates, species interactions, and ranging patterns.  相似文献   
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