Toward a humanized mouse model of Pneumocystis pneumonia.

Pneumocystis is an important opportunistic fungus that causes pneumonia in children and immunocompromised individuals. Recent genomic data show that divergence of major surface glycoproteins may confer speciation and host range selectivity. On the other hand, immune clearance between mice and humans is well correlated.

Mammary Adipose Tissue-Derived Lysophospholipids Promote Estrogen Receptor-Negative Mammary Epithelial Cell Proliferation.

Lysophosphatidic acid (LPA), acting in an autocrine or paracrine fashion through G protein-coupled receptors, has been implicated in many physiologic and pathologic processes, including cancer. LPA is converted from lysophosphatidylcholine (LPC) by the secreted phospholipase autotaxin (ATX). Although various cell types can produce ATX, adipocyte-derived ATX is believed to be the major source of circulating ATX and also to be the major regulator of plasma LPA levels.

Glucocorticoid receptor ChIP-sequencing of subcutaneous fat reveals modulation of inflammatory pathways.

Objective: To identify glucocorticoid receptor (GR)-associated chromatin sequences and target genes in primary human abdominal subcutaneous fat.

Methods: GR chromatin immunoprecipitation (ChIP)-sequencing (seq) methodology in subcutaneous human adipocytes treated ex vivo with dexamethasone (dex) was optimized to identify genome-wide dex-dependent GR-binding regions (GBRs). Gene expression analyses were performed in parallel ± dex treatment.

Aliphatic chain length by isotropic mixing (ALCHIM): determining composition of complex lipid samples by ¹H NMR spectroscopy.

Quantifying the amounts and types of lipids present in mixtures is important in fields as diverse as medicine, food science, and biochemistry. Nuclear magnetic resonance (NMR) spectroscopy can quantify the total amounts of saturated and unsaturated fatty acids in mixtures, but identifying the length of saturated fatty acid or the position of unsaturation by NMR is a daunting challenge. We have developed an NMR technique, aliphatic chain length by isotropic mixing, to address this problem.

Serum- and glucocorticoid-induced protein kinase 1 (SGK1) is regulated by store-operated Ca2+ entry and mediates cytoprotection against necrotic cell death.

Serum and glucocorticoid-regulated kinase 1 (SGK1) encodes a phosphatidylinositol 3-kinase-dependent serine/threonine kinase that is rapidly induced in response to cellular stressors and is an important cell survival signal. Previous studies have suggested that an increase in cytoplasmic Ca(2+) concentration ([Ca(2+)]c) is required for increased SGK1 expression, but the subcellular source of Ca(2+) regulating SGK1 transcription remains uncertain. Activation of endoplasmic reticulum stress (ERS) with thapsigargin (TG) increased SGK1 mRNA and protein expression in MDA-MB-231 cells.

Refeeding-induced brown adipose tissue glycogen hyper-accumulation in mice is mediated by insulin and catecholamines.

Brown adipose tissue (BAT) generates heat during adaptive thermogenesis through a combination of oxidative metabolism and uncoupling protein 1-mediated electron transport chain uncoupling, using both free-fatty acids and glucose as substrate. Previous rat-based work in 1942 showed that prolonged partial fasting followed by refeeding led to a dramatic, transient increase in glycogen stores in multiple fat depots. In the present study, the protocol was replicated in male CD1 mice, resulting in a 2000-fold increase in interscapular BAT (IBAT) glycogen levels within 4-12 hours (hr) of refeeding, with IBAT glycogen stores reaching levels comparable to fed liver glycogen.

Chronic social isolation is associated with metabolic gene expression changes specific to mammary adipose tissue.

Chronic social isolation is linked to increased mammary tumor growth in rodent models of breast cancer. In the C3(1)/SV40 T-antigen FVB/N (TAg) mouse model of "triple-negative" breast cancer, the heightened stress response elicited by social isolation has been associated with increased expression of metabolic genes in the mammary gland before invasive tumors develop (i.e.

Diminished autophagy limits cardiac injury in mouse models of type 1 diabetes.

Cardiac autophagy is inhibited in type 1 diabetes. However, it remains unknown if the reduced autophagy contributes to the pathogenesis of diabetic cardiomyopathy. We addressed this question using mouse models with gain- and loss-of-autophagy.

The influence of glucocorticoid signaling on tumor progression.

The diagnosis of cancer elicits a broad range of well-characterized stress-related biobehavioral responses. Recent studies also suggest that an individual's neuroendocrine stress response can influence tumor biology. One of the major physiological pathways altered by the response to unrelenting social stressors is the hypothalamic-pituitary-adrenal or HPA axis.

PCB 126 and other dioxin-like PCBs specifically suppress hepatic PEPCK expression via the aryl hydrocarbon receptor.

Dioxins and dioxin-like compounds encompass a group of structurally related heterocyclic compounds that bind to and activate the aryl hydrocarbon receptor (AhR). The prototypical dioxin is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a highly toxic industrial byproduct that incites numerous adverse physiological effects. Global commercial production of the structurally similar polychlorinated biphenyls (PCBs), however, commenced early in the 20(th) century and continued for decades; dioxin-like PCBs therefore contribute significantly to total dioxin-associated toxicity.

Transcription factor GATA4 inhibits doxorubicin-induced autophagy and cardiomyocyte death.

Doxorubicin (DOX) is a potent anti-tumor drug known to cause heart failure. The transcription factor GATA4 antagonizes DOX-induced cardiotoxicity. However, the protective mechanism remains obscure.

Escherichia coli O157:H7 requires colonizing partner to adhere and persist in a capillary flow cell.

Unlabelled: The ability of a strain of waterborne Escherichia coli O157:H7 to colonize a glass flow cell and develop microcolonies when grown alone and with Pseudomonas aeruginosa PAO1 was examined. When introduced alone, planktonic E. coil were unable to attach to the glass surface.

Regulation of Akt/PKB activity by P21-activated kinase in cardiomyocytes.

Akt/PKB is a critical regulator of cardiac function and morphology, and its activity is governed by dual phosphorylation at active loop (Thr308) by phosphoinositide-dependent protein kinase-1 (PDK1) and at carboxyl-terminal hydrophobic motif (Ser473) by a putative PDK2. P21-activated kinase-1 (Pak1) is a serine/threonine protein kinase implicated in the regulation of cardiac hypertrophy and contractility and was shown previously to activate Akt through an undefined mechanism. Here we report Pak1 as a potential PDK2 that is essential for Akt activity in cardiomyocytes.