Adding injury to insult: pathogen detection and responses.

Genomic approaches to the study of the expression of plant genes induced in response to disease and attack are now showing that there is an intimate association between pathogen perception and general stress detection.

The GENCODE pseudogene resource.

BACKGROUND: Pseudogenes have long been considered as nonfunctional genomic sequences. However, recent evidence suggests that many of them might have some form of biological activity, and the possibility of functionality has increased interest in their accurate annotation and integration with functional genomics data. RESULTS: As part of the GENCODE annotation of the human genome, we present the first genome-wide pseudogene assignment for protein-coding genes, based on both large-scale manual annotation and in silico pipelines. A key aspect of this coupled approach is that it allows us to identify pseudogenes in an unbiased fashion as well as untangle complex events through manual evaluation. We integrate the pseudogene annotations with the extensive ENCODE functional genomics information. In particular, we determine the expression level, transcription-factor and RNA polymerase II binding, and chromatin marks associated with each pseudogene. Based on their distribution, we develop simple statistical models for each type of activity, which we validate with large-scale RT-PCR-Seq experiments. Finally, we compare our pseudogenes with conservation and variation data from primate alignments and the 1000 Genomes project, producing lists of pseudogenes potentially under selection. CONCLUSIONS: At one extreme, some pseudogenes possess conventional characteristics of functionality; these may represent genes that have recently died. On the other hand, we find interesting patterns of partial activity, which may suggest that dead genes are being resurrected as functioning non-coding RNAs. The activity data of each pseudogene are stored in an associated resource, psiDR, which will be useful for the initial identification of potentially functional pseudogenes.

Plasminogen activator inhibitor-1 activity and 4G/5G polymorphism in hemodialysis

Introduction: Chronic insufficiency alters homeostasis, in part due to endothelial inflammation. Plasminogen activator inhibitor-1 (PAI-1) is increased in renal disease, contributing to vascular damage. We assessed PAI-1 activity and PAI-1 4G/5G polymorphism in hemodialysis (HD) subjects and any association between thrombotic vascular access (VA) events and PAI-1 polymorphism. Methods: Prospective, observational study in 36 HD patients: mean age: 66.6 +/- 12.5 yr, males n=26 (72%), time on HD: 28.71 +/- 22.45 months. Vascular accesses: 10 polytetrafluoroethylene grafts (PTFEG), 22 arteriovenous fistulae (AVF), four dual lumen catheters (CAT). Control group (CG): 40 subjects; mean age: 60.0 +/- 15 yrs, males n=30 (75%). Group A (GA): thrombotic events (n=12), and group B (GB): No events (n=24). Groups were no different according to age (69.2 +/- 9.12 vs. 65.3 +/- 14.5 yrs), gender (males: 7; 58.3% vs. 18; 81.8%), time on HD (26.1 +/- 14.7 vs. 30.1 +/- 38.7 months), causes of renal failure. Time to follow-up, for access thrombosis: 12 months. Results: PAI-1 levels in HD: 7.21 +/- 2.13 vs. CG: 0.42 +/- 0.27 U/ml (p < 0.000 1). PAI-1 4G/5G polymorphic variant distribution in HD: 5G/5G: 6 (17%),4G/5G: 23 (64%); 4G/4G: 7 (19%) and in CG: 5G/5G: 14 (35%); 4G/5G: 18 (45%); 4G/4G: 8 (20%). C-reactive protein (CRP) in HD: 24.5 +/- 15.2 mg/L vs. in CG 2.3 +/- 0.2 mg/L (p < 0.0001). PAI-1 4G/5G variants: GA: 5G/5G: 3; 4G/5G: 8; 4G/4G: 1; GB: 5G/5G: 3; 4G/5G: 15; 4G/4G: 6. Thrombosis occurred in 8/10 patients (80%) with PTFEG, 3/22 (9%) in AVF, and 1/4 (25%) in CAT. Among the eight PTFEG patients with thrombosis, seven were PAI 4G/5G. Conclusions: PAI-1 levels were elevated in HD patients, independent of their polymorphic variants, 4G/5G being the most prevalent variant. Our data suggest that in patients with PTFEG the 4G/5G variant might be associated with an increased thrombosis risk.

Efeito da alimentação de Schizaphis graminum com genótipos de sorgo no desenvolvimento do predador Cycloneda sanguinea

O pulgão Schizaphis graminum (Rondani) (Hemiptera: Aphididae) é uma das principais pragas do sorgo. O objetivo deste trabalho foi determinar o efeito da alimentação deste inseto com genótipos de sorgo resistentes e suscetíveis no desenvolvimento do predador Cycloneda sanguinea (Linnaeus) (Coleoptera: Coccinellidae). O pulgão foi criado em folhas dos genótipos de sorgo GR 11111 e TX 430 x GR 111, resistentes, GB 3B, de resistência moderada e BR 007B, suscetível ao hemíptero. As larvas de C. sanguinea foram alimentadas diariamente, ad libitum, com ninfas e adultos de S. graminum. A duração das fases de desenvolvimento e a sobrevivência de C. sanguinea não foram influenciadas pelo genótipo. Apenas a duração do quarto ínstar, da fase larval e do período de larva a adulto foram afetadas. O peso de larvas de segundo ínstar de C. sanguinea não foi afetado pelo genótipo. Nos demais ínstares e fase adulta, esse parâmetro foi diferenciado conforme o genótipo de sorgo utilizado como hospedeiro ao pulgão. Os genótipos resistentes GR 11111 e TX 430 x GR 111 não afetam adversamente o desenvolvimento e a fecundidade de C. sanguinea, durante uma geração. Estes genótipos demonstram compatibilidade com o predador e viabilizam o manejo de S. graminum na cultura do sorgo.

Roux-en-y Gastric Bypass is Superior to Gastric Banding in Non-superobese Patients. a Matched-case Study with Five-year Follow-up

Background: Roux-en-Y gastric bypass (RYGBP) and gastric banding (GB) are the two most popular bariatric procedures. Only few studies have compared their results and follow-up duration is usually limited to <3 years. Patients and Methods: Using our prospective bariatric database, we matched non-superobese GB to RYGBP patients for sex, age and BMI to RYGBP. Follow-up considered up to five years. Results: 442 patients were matched in 221 pairs. Mean age (38,6) and mean BMI (43) were identical. Overall operative morbidity was higher after RYGBP (17,2 versus 5,4 %, p<0,001), but major morbidity was similar (3,6 versus 2,2 %, p=0,57). More patients developed long-term complications after GB (43,9 % versus 19 %, p<0,001), and more required reoperations (24,4 % versus 12 %, p=0,001). After RYGBP, reoperations were mainly due to internal hernias (87 %), with no reversal, whereas 18,5 % of the GB patients required band removal. Even including only patients who retained their band, weight loss after RYGBP was better throughout the study period, with 5-year EBMIL of 77,6 % and 61,7 % (p<0,001) after RYGBP and GB respectively. RYGBP was associated with better food tolerance and greater improvement of the lipid profile. Conclusions: GB is associated with a smaller overall operative morbidity and similar major morbidity, but with more long-term complications, more reoperations, a significant number of reversal or conversion procedures, and reduced weight loss when compared with RYGBP. Five-year results of RYGBP are superior to GB and patients should be informed accordingly.

Impact of genetic polymorphisms in cytomegalovirus glycoprotein B on outcomes in solid organ transplant recipients with cytomegalovirus disease

Le cytomégalovirus (CMV) est le pathogène viral le plus important après transplantation d'organe. Le risque de développer une maladie à CMV chez les patients transplantés dépend d'une combinaison de facteurs de l'hôte et de facteurs viraux. Par exemple, il est bien établi que le status sérologique à CMV du donneur et du receveur est un facteur de risque très important pour développer une maladie à CMV, notamment chez le sous-groupe de patients donneurs positifs / receveurs négatifs (D+/R-). Par contre, il n'est pas complètement élucidé si des polymorphismes viraux spécifiques peuvent influencer l'évolution en la réponse thérapeutique chez des patients avec une infection à CMV. Nous avons évalué le rôle des différents génotypes de la glycoprotéine Β (gB) du CMV sur l'évolution clinique et virologique de la maladie à CMV chez des patients transplantés d'organe sous traitement antiviral.¦Pour ce faire, nous avons étudié 239 patients transplantés d'organe inclus dans une étude multicentrique évaluant deux médicaments antiviraux utilisés comme traitement de la maladie à CMV. Le génotypage de la gB du CMV a été réalisé en utilisant une PCR quantitative en temps réel au début du traitement antiviral. Les polymorphismes de la gB du CMV permettent la discrimination de quatre génotypes distincts (gBl, gB2, gB3 et gB4). Nous avons défini une infection mixte comme la présence simultanée de plus d'un génotype chez un patient avec maladie à CMV.¦La prévalence des différents génotypes de la gB a été 26% pour la gBl, 10% pour la gB2, 10% pour la gB3, et 5% pour la gB4, alors que les infections mixtes étaient présentes dans 49% des cas. Les patients D+/R+ présentaient plus fréquemment une infection mixte que les patients D+/R- (40% vs 12%, ρ <0.001). Les patients avec une infection mixte présentaient une médiane de la charge virale à CMV plus élevée et un temps d'éradication virale plus long comparé à des patients avec une infection par un génotype unique (p=0.005 et p=0.026, respectivement). Dans un modèle multivarié, les infections mixtes étaient un prédicteur important de l'échec de l'éradication de virus au jour 21 du début du traitement antiviral (rapport de côtes entre l'infection mixte vs. infection par un génotype unique = 2.66, intervalle de confiance à 95%= 1.31 à 5.38, p= 0.007). Aucun effet du génotype gB sur le développement d'une récidive clinique ou virologique de l'infection à CMV a été observé.¦Ces résultats indiquent qu'aucun génotype spécifique de la gB ne semble conférer un avantage de virulence au CMV. Cependant, les infections mixtes avec plusieurs génotypes de la gB sont associées à une charge virale plus élevée et à un retard de l'éradication virale suite au traitement antiviral.

Hepatitis C virus RNA replication requires a conserved structural motif within the transmembrane domain of the NS5B RNA-dependent RNA polymerase.

Hepatitis C virus (HCV) nonstructural protein 5B (NS5B), the viral RNA-dependent RNA polymerase (RdRp), is a tail-anchored protein with a highly conserved C-terminal transmembrane domain (TMD) that is required for the assembly of a functional replication complex. Here, we report that the TMD of the HCV RdRp can be functionally replaced by a newly identified analogous membrane anchor of the GB virus B (GBV-B) NS5B RdRp. Replicons with a chimeric RdRp consisting of the HCV catalytic domain and the GBV-B membrane anchor replicated with reduced efficiency. Compensatory amino acid changes at defined positions within the TMD improved the replication efficiency of these chimeras. These observations highlight a conserved structural motif within the TMD of the HCV NS5B RdRp that is required for RNA replication.

Foch et Douglas Haig à la gare Victoria [19 juillet 1919] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 55090

Maréchal Foch et Douglas Haig à la gare Victoria [19 juillet 1919] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 55091

[Soldats] français au défilé de la Victoire à Londres [19 juillet 1919] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 55092

[Soldats] américains au défilé de la Victoire à Londres [19 juillet 1919] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 55093