Biogeography of body size in terrestrial isopods (Crustacea: Oniscidea)

This study tries to unveil the contribution of climatic shift in shaping the extreme body size diversity in terrestrial isopods (Oniscidea). Trying to explain size variation at an interspecific level, we test five hypotheses: (1) Bergmann's Rule and the temperature‐size rule postulate large size in cold areas; (2) The metabolic cold adaptation theory postulates small animal sizes in cold environments; (3) The primary productivity hypothesis predicts size increase in resource‐rich areas; (4) The aridity resistance hypothesis predicts large size in arid regions; and (5). The acidosis hypothesis predicts smaller size with decreasing soil pH. Globally, Bergmann's rule and the aridity hypothesis are weakly supported. Among families and genera, results are variable and idiosyncratic. Conglobating species sizes provide weak support for the acidosis hypothesis. Overall, size is strongly affected by familial affiliation. Isopod size evolution seems to be mainly affected by phylogenetically constrained life‐history traits.     

Effect of periplasmic nitrate reductase on diauxic lag of Paracoccus pantotrophus

Paracoccus pantotrophus expresses two nitrate reductases—membrane bound nitrate reductase (Nar) and periplasmic nitrate reductase (Nap). In growth experiments with two denitrifying species (Paracoccus pantotrophus and Alcaligenes eutrophus) that have both Nap and Nar and two species (Pseudomonas denitrificans and Pseudomonas fluorescens) with Nar only, it was found that diauxic lag is shorter for bacteria that express Nap. In P. pantotrophus, napEDABC encodes the periplasmic nitrate reductase. To analyze the effect of Nap on diauxic lag, the nap operon was deleted from P. pantotrophus. The growth experiments with nap^? mutant resulted in increased diauxic lag when switched from aerobic to anoxic respiration, suggesting Nap is responsible for shorter lags and helps in adaptation to anoxic metabolism after transition from aerobic conditions. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009     

In Vivo Analysis of the Notch Receptor S1 Cleavage

A ligand-independent cleavage (S1) in the extracellular domain of the mammalian Notch receptor results in what is considered to be the canonical heterodimeric form of Notch on the cell surface. The in vivo consequences and significance of this cleavage on Drosophila Notch signaling remain unclear and contradictory. We determined the cleavage site in Drosophila and examined its in vivo function by a transgenic analysis of receptors that cannot be cleaved. Our results demonstrate a correlation between loss of cleavage and loss of in vivo function of the Notch receptor, supporting the notion that S1 cleavage is an in vivo mechanism of Notch signal control.     

Reducing the Activity and Secretion of Microbial Antioxidants Enhances the Immunogenicity of BCG

Background

In early clinical studies, the live tuberculosis vaccine Mycobacterium bovis BCG exhibited 80% protective efficacy against pulmonary tuberculosis (TB). Although BCG still exhibits reliable protection against TB meningitis and miliary TB in early childhood it has become less reliable in protecting against pulmonary TB. During decades of in vitro cultivation BCG not only lost some genes due to deletions of regions of the chromosome but also underwent gene duplication and other mutations resulting in increased antioxidant production.

Methodology/Principal Findings

To determine whether microbial antioxidants influence vaccine immunogenicity, we eliminated duplicated alleles encoding the oxidative stress sigma factor SigH in BCG Tice and reduced the activity and secretion of iron co-factored superoxide dismutase. We then used assays of gene expression and flow cytometry with intracellular cytokine staining to compare BCG-specific immune responses in mice after vaccination with BCG Tice or the modified BCG vaccine. Compared to BCG, the modified vaccine induced greater IL-12p40, RANTES, and IL-21 mRNA in the spleens of mice at three days post-immunization, more cytokine-producing CD8+ lymphocytes at the peak of the primary immune response, and more IL-2-producing CD4+ lymphocytes during the memory phase. The modified vaccine also induced stronger secondary CD4+ lymphocyte responses and greater clearance of challenge bacilli.

Conclusions/Significance

We conclude that antioxidants produced by BCG suppress host immune responses. These findings challenge the hypothesis that the failure of extensively cultivated BCG vaccines to prevent pulmonary tuberculosis is due to over-attenuation and suggest instead a new model in which BCG evolved to produce more immunity-suppressing antioxidants. By targeting these antioxidants it may be possible to restore BCG''s ability to protect against pulmonary TB.     

Inhibition of platelet aggregation and immunomodulation of NK lymphocytes by administration of ascorbic acid

Platelets aggregation around migrating tumor cells offers protection against the cytotoxic activity of the natural killers cells (NKC). The ascorbic acid in 3 x 10(-3) M concentration completely inhibited platelet aggregation, decreased thromboxane B2 levels, and inhibited the expression of platelet membranic receptor GpIIb/IIIa in non stimulated platelets, and increased the NKC cytotoxicity in an average rate of 105, 61, and 285% in the NKC/targets cells ratios 12.5:1, 25:1 and 50:1 respectively. The results suggest the role of ascorbic acid in increasing the susceptibility of tumor cells to NKC; the ascorbic acid could be used as part of a multidrug therapy to treat diseases which up to now have been treated only through chemotherapy.     

Physical forces may cause Hox gene collinearity in the primary and secondary axes of the developing vertebrates

The features of spatial and temporal Hox gene collinearity along the anteroposterior and secondary axes of vertebrate development have been extensively studied. However, the understanding of these features remains problematic. Some genetic engineering experiments were performed and the consequent modifications of the Hoxd gene expressions in the vertebrate limb and trunk were presented. A two-phases model was proposed to describe the above results but still many data cannot be explained. In the present work a different mechanism is put forward in order to deal with the above experiments. This alternative mechanism (coined biophysical model), is based on the hypothesis that physical forces decondense and 'loop out' the chromatin fiber causing the observed Hox gene collinearity phenomena at the early stages of axonal development. The two models are compared in detail. The biophysical model adequately explains the data even in cases where the results are characterized as unexpected. Furthermore, the biophysical model predicts that the Hox gene expressions are entangled in space and time and this coupling is compatible with the data of the early developmental stages. Additional experiments are proposed for a direct test of this model.     

OpenCyto: An Open Source Infrastructure for Scalable,Robust, Reproducible,and Automated,End-to-End Flow Cytometry Data Analysis

Flow cytometry is used increasingly in clinical research for cancer, immunology and vaccines. Technological advances in cytometry instrumentation are increasing the size and dimensionality of data sets, posing a challenge for traditional data management and analysis. Automated analysis methods, despite a general consensus of their importance to the future of the field, have been slow to gain widespread adoption. Here we present OpenCyto, a new BioConductor infrastructure and data analysis framework designed to lower the barrier of entry to automated flow data analysis algorithms by addressing key areas that we believe have held back wider adoption of automated approaches. OpenCyto supports end-to-end data analysis that is robust and reproducible while generating results that are easy to interpret. We have improved the existing, widely used core BioConductor flow cytometry infrastructure by allowing analysis to scale in a memory efficient manner to the large flow data sets that arise in clinical trials, and integrating domain-specific knowledge as part of the pipeline through the hierarchical relationships among cell populations. Pipelines are defined through a text-based csv file, limiting the need to write data-specific code, and are data agnostic to simplify repetitive analysis for core facilities. We demonstrate how to analyze two large cytometry data sets: an intracellular cytokine staining (ICS) data set from a published HIV vaccine trial focused on detecting rare, antigen-specific T-cell populations, where we identify a new subset of CD8 T-cells with a vaccine-regimen specific response that could not be identified through manual analysis, and a CyTOF T-cell phenotyping data set where a large staining panel and many cell populations are a challenge for traditional analysis. The substantial improvements to the core BioConductor flow cytometry packages give OpenCyto the potential for wide adoption. It can rapidly leverage new developments in computational cytometry and facilitate reproducible analysis in a unified environment.

This is a PLOS Computational Biology Software Article.

     

Risk-Cost Trade Off Considerations for Contaminated Sediment Disposal

Delays in dredging and inability to dredge the nation's harbors, due to the presence of contaminated sediments and the lack of environmentally acceptable disposal sites are interfering with shipping activities and hampering trade growth. The United States Government is committed to provide continuing support to the port industry's goals for enhancing economic growth while protecting, conserving and restoring natural resources within coastal aquatic lands. The government's commitment has resulted in the articulation of a national dredging policy in the Action Plan for Improvement of the Dredging Process in the United States. This national challenge calls for a systematic and consistent decision making approach to dredging and disposal including contaminated sediment management. In building an effective decision mak ing framework for costs, risk reduction and potential beneficial uses of the disposal material must be considered in identifying and evaluating environmentally acceptable and cost-effective disposal alternatives. A conceptual framework for applying a risk-cost trade off approach in making decisions regarding contaminated sediment disposal is presented and applied to a hypothetical disposal scenario involving three alternatives: deepwater confined disposal, nearshore fill or capping and, upland disposal. The approach entails the performance of sequential evaluations consisting of risk analysis, estimation of costs, integration of the results into a computational framework for trade-off analysis, and the application of decision analytical tools to build consensus among stakeholders and the general public in selecting a preferred alternative.     

Factors associated with the development of cross-reactive neutralizing antibodies during human immunodeficiency virus type 1 infection

The characterization of the cross-reactive, or heterologous, neutralizing antibody responses developed during human immunodeficiency virus type 1 (HIV-1) infection and the identification of factors associated with their generation are relevant to the development of an HIV vaccine. We report that in healthy HIV-positive, antiretroviral-naïve subjects, the breadth of plasma heterologous neutralizing antibody responses correlates with the time since infection, plasma viremia levels, and the binding avidity of anti-Env antibodies. Anti-CD4-binding site antibodies are responsible for the exceptionally broad cross-neutralizing antibody responses recorded only in rare plasma samples. However, in most cases examined, antibodies to the variable regions and to the CD4-binding site of Env modestly contributed in defining the overall breadth of these responses. Plasmas with broad cross-neutralizing antibody responses were identified that targeted the gp120 subunit, but their precise epitopes mapped outside the variable regions and the CD4-binding site. Finally, although several plasmas were identified with cross-neutralizing antibody responses that were not directed against gp120, only one plasma with a moderate breadth of heterologous neutralizing antibody responses contained cross-reactive neutralizing antibodies against the 4E10 epitope, which is within the gp41 transmembrane subunit. Overall, our study indicates that more than one pathway leads to the development of broad cross-reactive neutralizing antibodies during HIV infection and that the virus continuously escapes their action.