Essential role for interleukin-2 for CD4+CD25+ T regulatory cell development during the neonatal period

Although many aspects of CD4+CD25+ T regulatory (Treg) cell development remain largely unknown, signaling through the IL-2R represents one feature for the production of Treg cells. Therefore, the present study was undertaken to further define early developmental steps in the production of Treg cells, including a more precise view on the role of interleukin (IL)-2 in this process. After adoptive transfer of wild-type Treg cells into neonatal IL-2Rβ−/− mice, only a small fraction of donor Treg cells selectively seeded the lymph node (LN). These donor Treg cells underwent rapid and extensive IL-2–dependent proliferation, followed by subsequent trafficking to the spleen. Thus, IL-2 is essential for Treg cell proliferation in neonatal LN. The number and distribution of Treg cells in the periphery of normal neonatal mice closely paralleled that seen for IL-2Rβ−/− mice that received Treg cells. However, for normal neonates, blockade of IL-2 decreased Treg cells in both the thymus and LN. Therefore, two steps of Treg cell development depend upon IL-2 in neonatal mice, thymus production, and subsequent expansion in the LN

The emerging problem of bacterial resistance in cancer patients; proceedings of a workshop held by MASCC “Neutropenia, Infection and Myelosuppression” Study Group during the MASCC annual meeting held in Berlin on 27–29 June 2013

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Changes in academic research performance over time: A study of institutional accumulative advantage

This study examines changes in institutional research performance over time by analyzing data from four national surveys of the American professoriate conducted between 1969 and 1988. To assess whether groups of institutions may be accumulating advantage relative to others, research activities are compared across five Carnegie institution types. Weights are created to adjust for sampling differences and research output measures are standardized to adjust for variation by discipline. Findings show an overall strengthening of research emphasis reflected by a stronger orientation toward research (more faculty holding Ph.D.'s and having a primary interest in research) and higher research output (grant and publication performance). While Research-I universities have retained their initial (1969) advantage, they have not accumulated more. Meanwhile, Doctoral-Granting-I universities have gained strength relative to Research-II institutions. Research at Comprehensive-I was also up, but at a slower rate than the other Carnegie groups.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43603/1/11162_2004_Article_BF00992271.pd

Mapping the Environmental Fitness Landscape of a Synthetic Gene Circuit

Gene expression actualizes the organismal phenotypes encoded within the genome in an environment-dependent manner. Among all encoded phenotypes, cell population growth rate (fitness) is perhaps the most important, since it determines how well-adapted a genotype is in various environments. Traditional biological measurement techniques have revealed the connection between the environment and fitness based on the gene expression mean. Yet, recently it became clear that cells with identical genomes exposed to the same environment can differ dramatically from the population average in their gene expression and division rate (individual fitness). For cell populations with bimodal gene expression, this difference is particularly pronounced, and may involve stochastic transitions between two cellular states that form distinct sub-populations. Currently it remains unclear how a cell population's growth rate and its subpopulation fractions emerge from the molecular-level kinetics of gene networks and the division rates of single cells. To address this question we developed and quantitatively characterized an inducible, bistable synthetic gene circuit controlling the expression of a bifunctional antibiotic resistance gene in Saccharomyces cerevisiae. Following fitness and fluorescence measurements in two distinct environments (inducer alone and antibiotic alone), we applied a computational approach to predict cell population fitness and subpopulation fractions in the combination of these environments based on stochastic cellular movement in gene expression space and fitness space. We found that knowing the fitness and nongenetic (cellular) memory associated with specific gene expression states were necessary for predicting the overall fitness of cell populations in combined environments. We validated these predictions experimentally and identified environmental conditions that defined a “sweet spot” of drug resistance. These findings may provide a roadmap for connecting the molecular-level kinetics of gene networks to cell population fitness in well-defined environments, and may have important implications for phenotypic variability of drug resistance in natural settings

Undefined cellulase formulations hinder scientific reproducibility

In the shadow of a burgeoning biomass-to-fuels industry, biological conversion of lignocellulose to fermentable sugars in a cost-effective manner is key to the success of second-generation and advanced biofuel production. For the effective comparison of one cellulase preparation to another, cellulase assays are typically carried out with one or more engineered cellulase formulations or natural exoproteomes of known performance serving as positive controls. When these formulations have unknown composition, as is the case with several widely used commercial products, it becomes impossible to compare or reproduce work done today to work done in the future, where, for example, such preparations may not be available. Therefore, being a critical tenet of science publishing, experimental reproducibility is endangered by the continued use of these undisclosed products. We propose the introduction of standard procedures and materials to produce specific and reproducible cellulase formulations. These formulations are to serve as yardsticks to measure improvements and performance of new cellulase formulations

Plasma Micronutrient Concentrations Are Altered by Antiretroviral Therapy and Lipid-Based Nutrient Supplements in Lactating HIV-Infected Malawian Women

Background: Little is known about the influence of antiretroviral therapy with or without micronutrient supplementation on the micronutrient concentrations of HIV-infected lactating women in resource-constrained settings

Adherence to extended postpartum antiretrovirals is associated with decreased breast milk HIV-1 transmission

Estimate association between postpartum antiretroviral adherence and breastmilk HIV-1 transmissio

The Expanding Role of Natural Killer Cells in Type 1 Diabetes and Immunotherapy

Treatments for autoimmune diseases including type 1 diabetes (T1D) are aimed at resetting the immune system, especially its adaptive arm. The innate immune system is often ignored in the design of novel immune-based therapies. There is increasing evidence for multiple natural killer (NK) subpopulations, but their role is poorly understood in autoimmunity and likely is contributing to the controversial role reported for NKs. In this review, we will summarize NK subsets and their roles in tolerance, autoimmune diabetes, and immunotherapy