Phylogenetic analysis of the tenascin gene family: evidence of origin early in the chordate lineage

Background  

Tenascins are a family of glycoproteins found primarily in the extracellular matrix of embryos where they help to regulate cell proliferation, adhesion and migration. In order to learn more about their origins and relationships to each other, as well as to clarify the nomenclature used to describe them, the tenascin genes of the urochordate Ciona intestinalis, the pufferfish Tetraodon nigroviridis and Takifugu rubripes and the frog Xenopus tropicalis were identified and their gene organization and predicted protein products compared with the previously characterized tenascins of amniotes.     

Mutual antagonism between IP3RII and miRNA-133a regulates calcium signals and cardiac hypertrophy

Inositol 1,4,5′-triphosphate receptor II (IP₃RII) calcium channel expression is increased in both hypertrophic failing human myocardium and experimentally induced models of the disease. The ectopic calcium released from these receptors induces pro-hypertrophic gene expression and may promote arrhythmias. Here, we show that IP₃RII expression was constitutively restrained by the muscle-specific miRNA, miR-133a. During the hypertrophic response to pressure overload or neurohormonal stimuli, miR-133a down-regulation permitted IP₃RII levels to increase, instigating pro-hypertrophic calcium signaling and concomitant pathological remodeling. Using a combination of in vivo and in vitro approaches, we demonstrated that IP₃-induced calcium release (IICR) initiated the hypertrophy-associated decrease in miR-133a. In this manner, hypertrophic stimuli that engage IICR set a feed-forward mechanism in motion whereby IICR decreased miR-133a expression, further augmenting IP₃RII levels and therefore pro-hypertrophic calcium release. Consequently, IICR can be considered as both an initiating event and a driving force for pathological remodeling.     

The Drosophila peptidoglycan recognition protein PGRP-LF blocks PGRP-LC and IMD/JNK pathway activation

Eukaryotic peptidoglycan recognition proteins (PGRPs) are related to bacterial amidases. In Drosophila, PGRPs bind peptidoglycan and function as central sensors and regulators of the innate immune response. PGRP-LC/PGRP-LE constitute the receptor complex in the immune deficiency (IMD) pathway, which is an innate immune cascade triggered upon Gram-negative bacterial infection. Here, we present the functional analysis of the nonamidase, membrane-associated PGRP-LF. We show that PGRP-LF acts as a specific negative regulator of the IMD pathway. Reduction of PGRP-LF levels, in the absence of infection, is sufficient to trigger IMD pathway activation. Furthermore, normal development is impaired in the absence of functional PGRP-LF, a phenotype mediated by the JNK pathway. Thus, PGRP-LF prevents constitutive activation of both the JNK and the IMD pathways. We propose a model in which PGRP-LF keeps the Drosophila IMD pathway silent by sequestering circulating peptidoglycan.     

Apport de l’injection intracaverneuse de Prostaglandine E1 lors de la premiere consultation de l’impuissant: à propos de 414 cas

The authors report their experience of 414 injections of prostaglandin E1 (prostine). The diagnostic orientation between functional or organic impotence was assessed through questionaires and more particularly on the presence or absence of nocturnal or morning erections. The prostine reconditioning and self injection use techniques are precised: 80% of positive responses with better results in the oldest patients, whatever their medical antecedents. No relation between positive response to prostaglandin E1 and normal nocturnal erections could be found. Patients still presenting erections can present good or bad responses. This confirms the results previously given only allow us to put in evidence the good functional and anatomic state of cavernous bodies, without any etiological orientation (not mentioning the cases in which these self-injections reveal the presence of deformation, bend or fibrosis). The acceptance of self injection is low (30%) as well as a regular and prolonged medical observance (only 15%). This work confirms the low rate of local complications after repeated injections and the low rate of prolonged erections or priapism during Test 1. However, these possibilities must incite to prudence as for the generalization of this kind of treatment, out of specialized centers.