88 research outputs found
MicroRNAs That Contribute to Coordinating the Immune Response in <i>Drosophila melanogaster</i>
No full textAbstract
Atilano et al. present a Drosophila post-infection survival screen that takes advantage of a library of miRNA mutant flies. Using genome wide microarray..
Small noncoding RNAs called microRNAs (miRNAs) have emerged as post-transcriptional regulators of gene expression related to host defenses. Here, we have used Drosophila melanogaster to explore the contribution of individual or clusters of miRNAs in countering systemic Candida albicans infection. From a total of 72 tested, we identify 6 miRNA allelic mutant backgrounds that modulate the survival response to infection and the ability to control pathogen number. These mutants also exhibit dysregulation of the Toll pathway target transcripts Drosomycin (Drs) and Immune-Induced Molecule 1 (IM1). These are characteristics of defects in Toll signaling, and consistent with this, we demonstrate dependency for one of the miRNA mutants on the NF-κΒ homolog Dif. We also quantify changes in the miRNA expression profile over time in response to three pathogen types, and identify 13 mature miRNA forms affected by pathogens that stimulate Toll signaling. To complement this, we provide a genome-wide map of potential NF-κB sites in proximity to miRNA genes. Finally, we demonstrate that systemic C. albicans infection contributes to a reduction in the total amount of branch-chained amino acids, which is miRNA-regulated. Overall, our data reveal a new layer of miRNA complexity regulating the fly response to systemic fungal infection.</jats:p
. 61 Año 21 (2014) mayo-agosto. Dimensión Antropológica
No full text- “[G]Ente es esta de que no se puede tomar entendimiento”: las cabriolas de Hernando de Soto ante Atahualpa en crónicas peruanas del XVI por Beatriz Carolina Peña. - La confrontación tlaxcalteca ante la Conquista por José Eduardo Contreras Martínez. - San Agustín victorioso: cantares y coplas de los santos ganaderos en la Tierra Caliente por Juan José Atilano Flores. - El sistema de cargos en la configuración de la clase obrera con orígenes rurales en la región de Cholula, Puebla por Guillermo Paleta Pérez. - El “voto bronca”, el ausentismo y las principales fuerzas políticas en las elecciones de 2001 en la provincia de Buenos Aires. Los casos de San Nicolás, La Matanza y General Pueyrredón por Sergio Blogna Tistuzza. - El agrarismo y la modernidad rural en Veracruz: la mirada fotográfica de Atanasio D. Vázquez (1925-1930) por Elissa J. Rashkin. - Carlos San Juan Victoria (coord.), El XX mexicano: lecturas de un siglo, México, Itaca, 2012 por Leticia Reina. - Félix Báez-Jorge, ¿Quiénes son aquí los dioses verdaderos? Religiosidad indígena y hagiografías populares, Xalapa, Universidad Veracruzana, 2013 por Isabel Lagarriga Attias. - Pilar Máynez (ed.), El mundo indígena desde la perspectiva actual. Vol. II. Aproximación multidisciplinaria, México, Grupo Destiempos (Dossiers), 2013 por Rodrigo Martínez Baracs
L-Rhamnosylation of Listeria monocytogenes Wall Teichoic Acids Promotes Resistance to Antimicrobial Peptides by Delaying Interaction with the Membrane.
No full textListeria monocytogenes is an opportunistic Gram-positive bacterial pathogen responsible for listeriosis, a human foodborne disease. Its cell wall is densely decorated with wall teichoic acids (WTAs), a class of anionic glycopolymers that play key roles in bacterial physiology, including protection against the activity of antimicrobial peptides (AMPs). In other Gram-positive pathogens, WTA modification by amine-containing groups such as D-alanine was largely correlated with resistance to AMPs. However, in L. monocytogenes, where WTA modification is achieved solely via glycosylation, WTA-associated mechanisms of AMP resistance were unknown. Here, we show that the L-rhamnosylation of L. monocytogenes WTAs relies not only on the rmlACBD locus, which encodes the biosynthetic pathway for L-rhamnose, but also on rmlT encoding a putative rhamnosyltransferase. We demonstrate that this WTA tailoring mechanism promotes resistance to AMPs, unveiling a novel link between WTA glycosylation and bacterial resistance to host defense peptides. Using in vitro binding assays, fluorescence-based techniques and electron microscopy, we show that the presence of L-rhamnosylated WTAs at the surface of L. monocytogenes delays the crossing of the cell wall by AMPs and postpones their contact with the listerial membrane. We propose that WTA L-rhamnosylation promotes L. monocytogenes survival by decreasing the cell wall permeability to AMPs, thus hindering their access and detrimental interaction with the plasma membrane. Strikingly, we reveal a key contribution of WTA L-rhamnosylation for L. monocytogenes virulence in a mouse model of infection
De ires y venires. Procesos migratorios en Guerrero. 6 Año 2 (2015) enero-febrero. Rutas de Campo. De ires y venires. Procesos migratorios en Guerrero
No full text- Aquí y allá por Enrique Serrano Carreto y Diego Prieto Hernández. - Presentación por Netzahualcóyotl Bustamante Santín. - De ires y venires. Procesos migratorios en Guerrero por Samuel L. Villela F. - Movimientos de población y rutas de intercambio en el Guerrero prehispánico por Rosa maría Reyna Robles. - La migración, una tradición prehispánica: la Montaña de Guerrero por Danièle Dehouve. - Trabajar y morir en el surco. El destino funesto de los jornaleros agrícolas de la Montaña de Guerrero por Abel Barrera Hernández e Isabel Margarita Nemecio. - El padre maíz y las vertientes de la transformación cultural. Los mixtecos migrantes de Cahuatache por Juan José Atilano Flores. - Presencia social de la población indígena en Acapulco por Beatriz Canabal Cristiani. - Migración, cohesión social e identidad étnica entre los nahuas de Acatlán, Guerrero, en la ciudad de México por Rosalba Díaz Vásquez. - Identidades en movimiento. La migración en el estado de Guerrero: el caso de los jornaleros agrícolas por Ramiro Arroyo Sepúlveda. - Enclave migratorio de nahuas oriundos de Chilacachapa, Guerrero, en la colonia Vista Hermosa, Distrito Federal por Olivia Leal Sorcia. - Vínculos, trayectorias y territorios migratorios de la agricultura en Morelos por Kim Sánchez Saldaña. - De migrantes temporales a asentados. Presencia de población indígena de la Montaña guerrerense en la región centro-oriente de Morelos por Adriana Saldaña Ramírez. - Migraciones indígenas del sur de México: viajeros y norteños nahuas por Martha García Ortega. - De Balsas y la Montaña a Chicago-Manhattan: “migradólares” y remesas culturales por Samuel L. Villela F. - Iniciativas y políticas públicas para migrantes guerrerenses 2011-2015: un recuento de esfuerzos institucionales por Netzahualcóyotl Bustamante Santín
Autophagic dysregulation triggers innate immune activation in glucocerebrosidase deficiency
No full textMutations in the GBA1 (glucosylceramidase beta 1) gene cause the most common lysosomal storage disorder, Gaucher disease (GD), characterized by the lysosomal accumulation of glucosylceramide and lysosomal dysfunction. Downstream of defects in lysosomal-autophagosome fusion, GD cells display autophagic dysfunction. Immune activation and inflammation are also known features of GD pathogenesis. However, the precise link between autophagy and immune activation, and the tissue-specific nature of these pathologies, are yet to be determined. Here we summarize our recent manuscript, which probes the role of autophagy in stimulating a chronic innate immune response in a Drosophila GD model. The gut-brain axis is increasingly being implicated in disease pathology, and accordingly, we demonstrated gastrointestinal dysfunction and gut microbiome dysbiosis in GD flies. Moreover, intestinal cells display lysosomal-autophagic defects like those seen in the GD fly brain. Stimulation of autophagy with rapamycin treatment is sufficient to lower NF-[Formula: see text]B signaling in the gut. Our research suggests that autophagic impairment in GD flies drives microbiome dysbiosis and chronic immune activation, with deleterious consequences on organismal health. We highlight pharmacological activation of autophagy, targeting tissues such as the gut, as a potential therapeutic strategy in GD.AbbreviationsAMP, antimicrobial peptide; DAMP, damage associated molecular pattern; GBA1, glucosylceramidase beta 1; LC3, microtubule-associated protein 1 light chain 3; MEGF10, multiple EGF like domains 10; mTOR, mammalian target of rapamycin; PGRP, peptidoglycan recognition protein receptor; TRIF, Toll/IL-1R domain-containing adaptor-inducing IFN-β
Autophagic dysregulation triggers innate immune activation in glucocerebrosidase deficiency
No full textMutations in the GBA1 (glucosylceramidase beta 1) gene cause the most common lysosomal storage disorder, Gaucher disease (GD), characterized by the lysosomal accumulation of glucosylceramide and lysosomal dysfunction. Downstream of defects in lysosomal-autophagosome fusion, GD cells display autophagic dysfunction. Immune activation and inflammation are also known features of GD pathogenesis. However, the precise link between autophagy and immune activation, and the tissue-specific nature of these pathologies, are yet to be determined. Here we summarize our recent manuscript, which probes the role of autophagy in stimulating a chronic innate immune response in a Drosophila GD model. The gut-brain axis is increasingly being implicated in disease pathology, and accordingly, we demonstrated gastrointestinal dysfunction and gut microbiome dysbiosis in GD flies. Moreover, intestinal cells display lysosomal-autophagic defects like those seen in the GD fly brain. Stimulation of autophagy with rapamycin treatment is sufficient to lower NF-κ
B signaling in the gut. Our research suggests that autophagic impairment in GD flies drives microbiome dysbiosis and chronic immune activation, with deleterious consequences on organismal health. We highlight pharmacological activation of autophagy, targeting tissues such as the gut, as a potential therapeutic strategy in GD
Lysosomal storage, impaired autophagy and innate immunity in Gaucher and Parkinson's diseases: insights for drug discovery
No full textImpairment of autophagic–lysosomal pathways is increasingly being implicated in Parkinson's disease (PD). GBA1 mutations cause the lysosomal storage disorder Gaucher disease (GD) and are the commonest known genetic risk factor for PD. GBA1 mutations have been shown to cause autophagic–lysosomal impairment. Defective autophagic degradation of unwanted cellular constituents is associated with several pathologies, including loss of normal protein homeostasis, particularly of α-synuclein, and innate immune dysfunction. The latter is observed both peripherally and centrally in PD and GD. Here, we will discuss the mechanistic links between autophagy and immune dysregulation, and the possible role of these pathologies in communication between the gut and brain in these disorders. Recent work in a fly model of neuronopathic GD (nGD) revealed intestinal autophagic defects leading to gastrointestinal dysfunction and immune activation. Rapamycin treatment partially reversed the autophagic block and reduced immune activity, in association with increased survival and improved locomotor performance. Alterations in the gut microbiome are a critical driver of neuroinflammation, and studies have revealed that eradication of the microbiome in nGD fly and mouse models of PD ameliorate brain inflammation. Following these observations, lysosomal–autophagic pathways, innate immune signalling and microbiome dysbiosis are discussed as potential therapeutic targets in PD and GD.
This article is part of a discussion meeting issue ‘Understanding the endo-lysosomal network in neurodegeneration’
A functional <i>rml</i> operon is required for glycosylation of <i>Lm</i> WTAs with l-rhamnose.
No full text<p>(<b>A</b>) Alcian blue-stained 20% polyacrylamide gel containing WTA extracts from logarithmic-phase cultures of different <i>Lm</i> strains. (<b>B–D</b>) HPAEC-PAD analyses of the sugar composition of the (B) WTA, (C) peptidoglycan and (D) cytoplasmic fractions isolated from the indicated <i>Lm</i> strains. Samples were hydrolyzed in 3 M HCl (2 h, 95°C), diluted with water and lyophilized before injection into the HPLC equipment. Standards for ribitol (Rib), l-rhamnose (Rha), glucosamine (GlcN), and muramic acid (Mur) were eluted under identical conditions to allow peak identification.</p
Genes encoding the l-rhamnose biosynthesis pathway are distributed in listeriae and other bacterial species.
No full text<p>Comparison of the genomic organization of the l-rhamnose pathway genes in the genus <i>Listeria</i> and other bacteria. The corresponding species and strains are indicated on the left (<i>Lmo</i>, <i>Listeria monocytogenes</i>; <i>Lin</i>, <i>Listeria innocua</i>; <i>Lse</i>, <i>Listeria seeligeri</i>; <i>Liv</i>, <i>Listeria ivanovii</i>; <i>Lwe</i>, <i>Listeria welshimeri</i>; <i>Smu</i>, <i>Streptococcus mutans</i>; <i>Mtu</i>, <i>Mycobacterium tuberculosis</i>; <i>Sen</i>, <i>Salmonella enterica</i> serovar Typhimurium; <i>Sfl</i>, <i>Shigella flexneri</i>; <i>Pae</i>, <i>Pseudomonas aeruginosa</i>) and listerial serotypes are indicated on the right. Genes are represented by boxed arrows and their names are provided for strain EGD-e. Operons are underlined by dashed arrows and homologs of the <i>rml</i> genes are shown with identical colors. Numbered gaps indicate the genetic distance (Mb, mega base pairs) between <i>rml</i> genes located far apart in the chromosome. Bacterial genomic sequences were obtained from NCBI database and chromosomal alignments assembled using Microbial Genomic context Viewer and Adobe Illustrator.</p
L-Rhamnosylation of Listeria monocytogenes Wall Teichoic Acids Promotes Resistance to Antimicrobial Peptides by Delaying Interaction with the Membrane
No full text- …
