221 research outputs found
Enforced Bcl-2 Expression Inhibits Antigen-mediated Clonal Elimination of Peripheral B Cells in an Antigen Doseâdependent Manner and Promotes Receptor Editing in Autoreactive, Immature B Cells
The mechanisms that establish immune tolerance in immature and mature B cells appear to be distinct. Membrane-bound autoantigen is thought to induce developmental arrest and receptor editing in immature B cells, whereas mature B cells have shortened lifespans when exposed to the same stimulus. In this study, we used EÎźâbcl-2-22 transgenic (Tg) mice to test the prediction that enforced expression of the Bcl-2 apoptotic inhibitor in B cells would rescue mature, but not immature, B cells from tolerance induction. To monitor tolerance to the natural membrane autoantigen H-2Kb, we bred 3â83Οδ (anti-Kk,b) Ig Tg mice to H-2b mice or to mice expressing transgene-driven Kb in the periphery. In 3â83Οδ/bcl-2 Tg mice, deletion of autoreactive B cells induced by peripheral Kb antigen expression in the liver (MT-Kb Tg) or epithelia (KerIV-Kb Tg), was partly or completely inhibited, respectively. Furthermore, Bcl-2 protected peritoneal B-2 B cells from deletion mediated by acute antigen exposure, but this protection could be overcome by higher antigen dose. In contrast to its ability to block peripheral self-tolerance, Bcl-2 overexpression failed to inhibit central tolerance induced by bone marrow antigen expression, but instead, enhanced the receptor editing process. These studies indicate that apoptosis plays distinct roles in central and peripheral B cell tolerance
Impaired fetal T cell development and perinatal lethality in mice lacking the cAMP response element binding protein
A Case Study Competition among Methods for Analyzing Large Spatial Data
The Gaussian process is an indispensable tool for spatial data analysts. The
onset of the "big data" era, however, has lead to the traditional Gaussian
process being computationally infeasible for modern spatial data. As such,
various alternatives to the full Gaussian process that are more amenable to
handling big spatial data have been proposed. These modern methods often
exploit low rank structures and/or multi-core and multi-threaded computing
environments to facilitate computation. This study provides, first, an
introductory overview of several methods for analyzing large spatial data.
Second, this study describes the results of a predictive competition among the
described methods as implemented by different groups with strong expertise in
the methodology. Specifically, each research group was provided with two
training datasets (one simulated and one observed) along with a set of
prediction locations. Each group then wrote their own implementation of their
method to produce predictions at the given location and each which was
subsequently run on a common computing environment. The methods were then
compared in terms of various predictive diagnostics. Supplementary materials
regarding implementation details of the methods and code are available for this
article online
Migration of epoxidized soybean oil (ESBO) and phthalates from twist closures into food and enforcement of the overall migration limit
Selection platforms for directed evolution in synthetic biology
Life on Earth is incredibly diverse. Yet, underneath that diversity, there are a number of constants and highly
conserved processes: all life is based on DNA and RNA; the genetic code is universal; biology is limited to a
small subset of potential chemistries. A vast amount of knowledge has been accrued through describing and
characterizing enzymes, biological processes and organisms. Nevertheless, much remains to be understood
about the natural world. One of the goals in Synthetic Biology is to recapitulate biological complexity from
simple systems made from biological molecules â gaining a deeper understanding of life in the process.
Directed evolution is a powerful tool in Synthetic Biology, able to bypass gaps in knowledge and capable of
engineering even the most highly conserved biological processes. It encompasses a range of methodologies
to create variation in a population and to select individual variants with the desired function â be it a ligand,
enzyme, pathway or even whole organisms. Here, we present some of the basic frameworks that underpin
all evolution platforms and review some of the recent contributions from directed evolution to synthetic
biology, in particular methods that have been used to engineer the Central Dogma and the genetic code
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