A Bacterial Toxin Perturbs Intracellular Amino Acid Balance To Induce Persistence.

Bacterial cells utilize toxin-antitoxin systems to inhibit self-reproduction, while maintaining viability, when faced with environmental challenges. The activation of the toxin is often coupled to the induction of cellular response pathways, such as the stringent response, in response to multiple stress conditions. Under these conditions, the cell enters a quiescent state referred to as dormancy or persistence.

A Localized Complex of Two Protein Oligomers Controls the Orientation of Cell Polarity.

Signaling hubs at bacterial cell poles establish cell polarity in the absence of membrane-bound compartments. In the asymmetrically dividing bacterium , cell polarity stems from the cell cycle-regulated localization and turnover of signaling protein complexes in these hubs, and yet the mechanisms that establish the identity of the two cell poles have not been established. Here, we recapitulate the tripartite assembly of a cell fate signaling complex that forms during the G-S transition.

A cell cycle kinase with tandem sensory PAS domains integrates cell fate cues.

All cells must integrate sensory information to coordinate developmental events in space and time. The bacterium Caulobacter crescentus uses two-component phospho-signalling to regulate spatially distinct cell cycle events through the master regulator CtrA. Here, we report that CckA, the histidine kinase upstream of CtrA, employs a tandem-PAS domain sensor to integrate two distinct spatiotemporal signals.

Bacterial scaffold directs pole-specific centromere segregation.

Bacteria use partitioning systems based on the ParA ATPase to actively mobilize and spatially organize molecular cargoes throughout the cytoplasm. The bacterium Caulobacter crescentus uses a ParA-based partitioning system to segregate newly replicated chromosomal centromeres to opposite cell poles. Here we demonstrate that the Caulobacter PopZ scaffold creates an organizing center at the cell pole that actively regulates polar centromere transport by the ParA partition system.

Structural map of a microRNA-122: hepatitis C virus complex.

MicroRNA-122 (miR-122) enhances hepatitis C virus (HCV) fitness via targeting two sites in the 5'-untranslated region (UTR) of HCV. We used selective 2'-hydroxyl acylation analyzed by primer extension to resolve the HCV 5'-UTR's RNA secondary structure in the presence of miR-122. Nearly all nucleotides in miR-122 are involved in targeting the second site, beyond classic seed base pairings.

Identification of an IFN-γ/mast cell axis in a mouse model of chronic asthma.

Asthma is considered a Th2 cell–associated disorder. Despite this, both the Th1 cell–associated cytokine IFN-γ and airway neutrophilia have been implicated in severe asthma. To investigate the relative contributions of different immune system components to the pathogenesis of asthma, we previously developed a model that exhibits several features of severe asthma in humans, including airway neutrophilia and increased lung IFN-γ.

Genome wide expression profiling of human peripheral blood mononuclear cells stimulated with BAY 50-4798, a novel T cell selective interleukin-2 analog.

BAY 50-4798, a novel, engineered form of interleukin (IL)-2, is a selective agonist for the high-affinity IL-2 receptor and induces the proliferation of activated human T cells with potency similar to recombinant IL-2 (rIL-2), but has reduced proliferative activity on natural killer cells and is associated with a diminished secondary cytokine cascade. In the current study, the transcriptional profiles of human peripheral blood mononuclear cells (PBMCs) stimulated in vitro with BAY 50-4798 and rIL-2 were compared using Affymetrix microarray technology in combination with Ingenuity Pathway Analysis (IPA) to determine whether there are quantitative or qualitative differences in the molecular networks activated by these IL-2 analogs. A total of 299 genes were differentially expressed in response to the two IL-2 analogs, with an increase in the number of differences over time.

Reduced secondary cytokine induction by BAY 50-4798, a high-affinity receptor-specific interleukin-2 analog.

Recombinant interleukin-2 (IL-2) (aldesleukin, Proleukin, Chiron, Emeryville, CA) is approved for treatment of cancer patients and under investigation in HIV-infected individuals. However, treatment with aldesleukin is associated with toxicity, which may be due to its elicitation of inflammatory mediators from cells that express the intermediate-affinity IL-2 receptor. BAY 50-4798, a novel IL-2 analog, is a selective agonist for the high-affinity receptor.

Keratinocyte growth factor and the transcription factors C/EBP alpha, C/EBP delta, and SREBP-1c regulate fatty acid synthesis in alveolar type II cells.

Strategies to stimulate endogenous surfactant production require a detailed understanding of the regulation of lipogenesis in alveolar type II cells. We developed culture conditions in which keratinocyte growth factor (KGF) stimulates fatty acid and phospholipid synthesis. KGF stimulated acetate incorporation into phosphatidylcholine, disaturated phosphatidylcholine, and phosphatidylglycerol more than 5% rat serum alone.