The transcription factor Traffic jam orchestrates the somatic piRNA pathway in ovaries.

Unlabelled: Transposable elements (TEs) pose a threat to genome integrity, and the piRNA pathway in animal gonads plays a crucial role in silencing TE activity. While the transcriptional regulation of the piRNA pathway components in germ cells has been documented in mice and flies, the mechanisms orchestrating the transcriptional program of the somatic piRNA pathway in ovaries remains unresolved. Here, we demonstrate that Traffic jam (Tj), an orthologue of a large Maf transcription factor in mammals, is a master regulator of the piRNA pathway in ovarian somatic cells, playing a crucial role in maintaining TE silencing and genomic integrity in somatic tissues.

An Overview of the Influence of Breastfeeding on the Development of Inflammatory Bowel Disease.

The first 1000 days of life is a critical period that contributes significantly to the programming of an individual's future health. Among the many changes that occur during this period early in life, there is growing evidence that the establishment of healthy gut microbiota plays an important role in the prevention of both short- and long-term health problems. Numerous publications suggest that the quality of the gut microbiota colonisation depends on several dietary factors, including breastfeeding.

Reactivation of a somatic errantivirus and germline invasion in Drosophila ovaries.

Most Drosophila transposable elements are LTR retrotransposons, some of which belong to the genus Errantivirus and share structural and functional characteristics with vertebrate endogenous retroviruses. Like endogenous retroviruses, it is unclear whether errantiviruses retain some infectivity and transposition capacity. We created conditions where control of the Drosophila ZAM errantivirus through the piRNA pathway was abolished leading to its de novo reactivation in somatic gonadal cells.

The Class I HDAC Inhibitor, MS-275, Prevents Oxaliplatin-Induced Chronic Neuropathy and Potentiates Its Antiproliferative Activity in Mice.

Oxaliplatin, the first-line chemotherapeutic agent against colorectal cancer (CRC), induces peripheral neuropathies, which can lead to dose limitation and treatment discontinuation. Downregulation of potassium channels, which involves histone deacetylase (HDAC) activity, has been identified as an important tuner of acute oxaliplatin-induced hypersensitivity. MS-275, a class I histone deacetylase inhibitor (HDACi), prevents acute oxaliplatin-induced peripheral neuropathy (OIPN).

A polarized nucleus-cytoskeleton-ECM connection in migrating cardioblasts controls heart tube formation in Drosophila.

The formation of the cardiac tube is a remarkable example of complex morphogenetic processes conserved from invertebrates to humans. It involves coordinated collective migration of contralateral rows of cardiac cells. The molecular processes underlying the specification of cardioblasts (CBs) prior to migration are well established and significant advances have been made in understanding the process of lumen formation.

Gelsolin and dCryAB act downstream of muscle identity genes and contribute to preventing muscle splitting and branching in Drosophila.

A combinatorial code of identity transcription factors (iTFs) specifies the diversity of muscle types in Drosophila. We previously showed that two iTFs, Lms and Ap, play critical role in the identity of a subset of larval body wall muscles, the lateral transverse (LT) muscles. Intriguingly, a small portion of ap and lms mutants displays an increased number of LT muscles, a phenotype that recalls pathological split muscle fibers in human.

Predictive Value of the Residual SYNTAX Score in Patients With Cardiogenic Shock.

Background: In hemodynamically stable patients, complete revascularization (CR) following percutaneous coronary intervention (PCI) is associated with a better prognosis in chronic and acute coronary syndromes.

Objectives: This study sought to assess the extent, severity, and prognostic value of remaining coronary stenoses following PCI, by using the residual SYNTAX score (rSS), in patients with cardiogenic shock (CS) related to myocardial infarction (MI).

Methods: The CULPRIT-SHOCK (Culprit Lesion Only Percutaneous Coronary Intervention [PCI] Versus Multivessel PCI in Cardiogenic Shock) trial compared a multivessel PCI (MV-PCI) strategy with a culprit lesion-only PCI (CLO-PCI) strategy in patients with multivessel coronary artery disease who presented with MI-related CS.

Contribution of the Gut Microbiota in P28GST-Mediated Anti-Inflammatory Effects: Experimental and Clinical Insights.

An original immuno-regulatory strategy against inflammatory bowel diseases based on the use of 28 kDa glutathione S-transferase (P28GST), a unique schistosome protein, was recently proposed. Improvement of intestinal inflammation occurs through restoration of the immunological balance between pro-inflammatory T-helper 1 (Th1) responses and both T-helper 2 (Th2) and regulatory responses. However, detailed mechanisms explaining how P28GST prevents colitis and promotes gut homeostasis remain unknown.

Nucleotide-binding oligomerization domain 1 (NOD1) modulates liver ischemia reperfusion through the expression adhesion molecules.

Background & Aims: In liver transplantation, organ shortage leads to the use of marginal grafts that are more susceptible to ischemia-reperfusion (IR) injury. We identified nucleotide-binding oligomerization domain 1 (NOD1) as an important modulator of polymorphonuclear neutrophil (PMN)-induced liver injury, which occurs in IR. Herein, we aimed to elucidate the role of NOD1 in IR injury, particularly focusing on its effects on the endothelium and hepatocytes.

Peroxisome proliferator-activated receptor gamma (PPARγ) regulates lactase expression and activity in the gut.

Lactase (LCT) deficiency affects approximately 75% of the world's adult population and may lead to lactose malabsorption and intolerance. Currently, the regulation of LCT gene expression remains poorly known. Peroxisome proliferator activator receptorγ (PPARγ) is a key player in carbohydrate metabolism.

The Expression of the Short Isoform of Thymic Stromal Lymphopoietin in the Colon Is Regulated by the Nuclear Receptor Peroxisome Proliferator Activated Receptor-Gamma and Is Impaired during Ulcerative Colitis.

The etiology of inflammatory bowel diseases remains largely unknown. We previously demonstrated that the expression of the peroxisome proliferator activated receptor-gamma (PPARγ) is downregulated in colonic epithelial cells of patients with ulcerative colitis (UC). PPARγ is a nuclear receptor that modulates inflammation.

Novel PPARγ Modulator GED-0507-34 Levo Ameliorates Inflammation-driven Intestinal Fibrosis.

Background: Intestinal fibrosis is mainly associated with Crohn's disease and is defined as a progressive and excessive deposition of extracellular matrix components. No specific antifibrotic therapies are available. In this study, we evaluate the antifibrotic effect of a novel 5-ASA analog able to activate the peroxisome proliferator-activated receptor γ, named GED-0507-34 Levo.

TRAP-rc, Translating Ribosome Affinity Purification from Rare Cell Populations of Drosophila Embryos.

Measuring levels of mRNAs in the process of translation in individual cells provides information on the proteins involved in cellular functions at a given point in time. The protocol dubbed Translating Ribosome Affinity Purification (TRAP) is able to capture this mRNA translation process in a cell-type-specific manner. Based on the affinity purification of polysomes carrying a tagged ribosomal subunit, TRAP can be applied to translatome analyses in individual cells, making it possible to compare cell types during the course of developmental processes or to track disease development progress and the impact of potential therapies at molecular level.

Intestinal steroidogenesis.

Steroids are fundamental hormones that control a wide variety of physiological processes such as metabolism, immune functions, and sexual characteristics. Historically, steroid synthesis was considered a function restricted to the adrenals and the gonads. In the past 20 years, a significant number of studies have demonstrated that steroids could also be synthesized or metabolized by other organs.

Regulation of DNA methylation patterns by CK2-mediated phosphorylation of Dnmt3a.

DNA methylation is a central epigenetic modification that is established by de novo DNA methyltransferases. The mechanisms underlying the generation of genomic methylation patterns are still poorly understood. Using mass spectrometry and a phosphospecific Dnmt3a antibody, we demonstrate that CK2 phosphorylates endogenous Dnmt3a at two key residues located near its PWWP domain, thereby downregulating the ability of Dnmt3a to methylate DNA.

Intestinal steroidogenesis controls PPARγ expression in the colon and is impaired during ulcerative colitis.

Background And Aims: Immune tolerance breakdown during UC involves the peroxisome proliferator-activated receptor-γ (PPARγ), a key factor in mucosal homoeostasis and the therapeutic target of 5-aminosalycilates, which expression is impaired during UC. Here we assess the impact of glucocorticoids (GCs) on PPARγ expression, focusing especially on extra-adrenal cortisol production by colonic epithelial cells (CECs).

Methods: Activation of PPARγ in the colon was evaluated using transgenic mice for the luciferase gene under PPAR control (peroxisome proliferator response element-luciferase mice).

Switching invariant natural killer T (iNKT) cell response from anticancerous to anti-inflammatory effect: molecular bases.

Since the discovery in 1995 of α-galactosylceramide 1 (α-GalCer), also known as KRN7000,1 hundreds of compounds have been synthesized in order to activate invariant natural killer T (iNKT) cells. Such keen interest for this lymphocyte cell type is due to its ability to produce different cytokines that bias the immune response toward a Th1 or Th2 profile. Thus, an understanding of the immune polarization mechanism via iNKT activation may pave the way toward new therapeutics in various domains including cancer and infectious and autoimmune diseases.

Functional polymorphisms in the regulatory regions of the VNN1 gene are associated with susceptibility to inflammatory bowel diseases.

Background: Vanin-1 is an epithelial pantetheinase, which regulates intestinal inflammation in mouse. We investigated whether human VNN1 levels could be associated to the susceptibility to inflammatory bowel diseases (IBD) and explored the participation of PPARg to these processes.

Methods: We studied VNN1 expression in colon biopsies from IBD patients.

The 5-aminosalicylic acid antineoplastic effect in the intestine is mediated by PPARγ.

Epidemiological evidences suggested that 5-aminosalicylic acid (5-ASA) therapy may prevent the development of colorectal cancer in inflammatory bowel disease patients. Our aim is to investigate whether peroxisome proliferator-activated receptor-γ (PPARγ) mediates the antineoplastic effects of 5-ASA. HT-29 and Caco-2 cells were treated by 5-ASA, rosiglitazone (PPARγ ligand) or etoposide (anticarcinogenic drug).

PPAR-gamma in ulcerative colitis: a novel target for intervention.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor, originally described in adipose tissue, that controls the expression of a large number of regulatory genes in lipid metabolism and insulin sensitization. Well known by endocrinologists, thiazolidinediones (TZDs) are classical PPARγ synthetic agonists which were currently used as insulin-sensitizing agents in the treatment of type 2 diabetes. While the clinical benefits of TZDs in treating metabolic disorders have been clearly demonstrated, new studies performed in animal models of colitis and in patients with ulcerative colitis have also revealed the key roles of PPARγ activation in the regulation of inflammation and immune response, notably in the colon through epithelial cells.

Colonic inflammation in mice is improved by cigarette smoke through iNKT cells recruitment.

Cigarette smoke (CS) protects against intestinal inflammation during ulcerative colitis. Immunoregulatory mechanisms sustaining this effect remain unknown. The aim of this study was to assess the effects of CS on experimental colitis and to characterize the intestinal inflammatory response at the cellular and molecular levels.

In vivo imaging reveals selective PPAR activity in the skin of peroxisome proliferator-activated receptor responsive element-luciferase reporter mice.

Peroxisome proliferator-activated receptors (PPARs) have been revealed as key regulators of several skin disorders. This has led to a growing interest in the development of drugs targeting PPARs as therapeutics for skin diseases. To evaluate skin PPAR activity, we developed peroxisome proliferator responsive element-luciferase (PPRE-Luc) mice, a mouse model in which the luciferase gene expression is under the control of a PPAR-inducible promoter in all organs.

Drosophila fatty acid transport protein regulates rhodopsin-1 metabolism and is required for photoreceptor neuron survival.

Tight regulation of the visual response is essential for photoreceptor function and survival. Visual response dysregulation often leads to photoreceptor cell degeneration, but the causes of such cell death are not well understood. In this study, we investigated a fatty acid transport protein (fatp) null mutation that caused adult-onset and progressive photoreceptor cell death.

Visceral fat and gut inflammation.

The etiology of inflammatory bowel disease and, in particular, Crohn's disease involves a deregulated mucosal immune system under the influence of intestinal flora and environmental factors in genetically susceptible individuals. A new hypothesis has focused on mesenteric fat hypertrophy and the presence of ectopic fat surrounding inflamed bowel, the so-called creeping fat, which are hallmarks of Crohn's disease. Mesenteric adipose tissue is currently recognized as an active actor in immunity with a capacity for mediator secretion.