Tubular Heads in Bacteriophages from Lactic Streptococci

Tubular bacteriophage heads were observed in the lysate of two phages from Streptococcus lactis obtained from single plaques without mutagenesis. The frequency of appearance of the tubular heads was 2.5 and 16%.     

A simplified key for identifying homofermentative Lactobacillus and Carnobacterium spp. from meat

Species of Lactobacillus and Carnobacterium from meat and meat products could be separated by a few biochemical characteristics; presence of meso -diaminopimelic acid in the cell wall, the isomers of lactic acid produced, production of citrulline from arginine and fermentation of some carbohydrates. This identification key was checked by DNA–DNA hybridizations studies.     

Mammalian-like differentiation of gastric cells in the shark Hexanchus griseus

Summary Gastric glands of submammalian vertebrates are formed by one single cell type known as the oxyntopeptic cell. This cell secretes both hydrochloric acid and pepsinogen. In mammals, this cell differentiates into an acid secreting cell and a pepsinogen secreting one. In the elasmobranch fish Hexanchus griseus we observed, by means of histological studies at the light-and electron-microscopic levels, two different cell types for the secretion of acid and zymogen. This organization represents an evolutionary divergence in a primitive animal, i.e., the appearance of a feature that is acquired much later in evolution, in mammals.     

A New Class of Small Molecule Inhibitor of BMP Signaling

Growth factor signaling pathways are tightly regulated by phosphorylation and include many important kinase targets of interest for drug discovery. Small molecule inhibitors of the bone morphogenetic protein (BMP) receptor kinase ALK2 (ACVR1) are needed urgently to treat the progressively debilitating musculoskeletal disease fibrodysplasia ossificans progressiva (FOP). Dorsomorphin analogues, first identified in zebrafish, remain the only BMP inhibitor chemotype reported to date. By screening an assay panel of 250 recombinant human kinases we identified a highly selective 2-aminopyridine-based inhibitor {"type":"entrez-nucleotide","attrs":{"text":"K02288","term_id":"191391"}}K02288 with in vitro activity against ALK2 at low nanomolar concentrations similar to the current lead compound LDN-193189. {"type":"entrez-nucleotide","attrs":{"text":"K02288","term_id":"191391"}}K02288 specifically inhibited the BMP-induced Smad pathway without affecting TGF-β signaling and induced dorsalization of zebrafish embryos. Comparison of the crystal structures of ALK2 with {"type":"entrez-nucleotide","attrs":{"text":"K02288","term_id":"191391"}}K02288 and LDN-193189 revealed additional contacts in the {"type":"entrez-nucleotide","attrs":{"text":"K02288","term_id":"191391"}}K02288 complex affording improved shape complementarity and identified the exposed phenol group for further optimization of pharmacokinetics. The discovery of a new chemical series provides an independent pharmacological tool to investigate BMP signaling and offers multiple opportunities for pre-clinical development.     

Evidence for the High Importance of Co-Morbid Factors in HFE C282Y/H63D Patients Cared by Phlebotomies: Results from an Observational Prospective Study

Despite type I haemochromatosis (HC) is mainly associated with the HFE C282Y/C282Y genotype, a second genotype -C282Y/H63D- has mostly been described in other patients. Its association with HC, apart from any associated co-morbid factors, remains unclear and complex to interpret for physicians. This study assesses the weight of this genotype and the role of co-morbid factors in the occurrence of iron overload. This prospective study included the C282Y/C282Y (n = 172) and C282Y/H63D (n = 58) patients enrolled in a phlebotomy program between 2004 and 2007 in a blood centre of western Brittany (Brest, France), where HC is frequent. We compared prevalence of these two genotypes, as well as patients’ profile regarding degree of iron overload and prevalence of co-morbid factors. First, we confirmed the obvious deficit of C282Y/H63D compound heterozygotes among patients cared by phlebotomies. This genotype was 3.0 times less frequent than the C282Y/C282Y genotype among those patients (18.9% vs. 56.0%) whereas it was 4.9 times more frequent in the general population (4.3% vs. 0.9%; p<0.0001). Despite a similar level of hyperferritinaemia, the C282Y/H63D patients who came to medical attention had a milder plasma iron overload, reflected by a lower transferrin saturation median (52.0% vs. 84.0%; p<0.0001). They also exhibited more frequently co-morbid factors, as heavy drinking (26.0% vs. 13.9%; p = 0.0454), overweight (66.7% vs. 39.4%; p = 0.0005) or both (21.3% vs. 2.6%; p<0.0001). Ultimately, they required a lower amount of iron removed to reach depletion (2.1 vs. 3.4 g; p<0.0001), clearly reflecting their lower tissue iron. This study confirms that H63D is a discrete genetic susceptibility factor whose expression is most visible in association with other co-factors. It highlights the importance of searching for co-morbidities in these diagnostic situations and of providing lifestyle and dietary advice.     

Low Birth Weight Is Strongly Associated with the Risk of Deep Infiltrating Endometriosis: Results of a 743 Case-Control Study

The influence of intrauterine environment on the risk of endometriosis is still controversial. Whether birth weight modifies the risk of endometriosis in adulthood remains an open question. For this purpose, we designed a case-control study involving 743 women operated on for benign gynecological indications from January 2004 to December 2011. Study group included 368 patients with histologically proven endometriosis: 54 superficial endometriosis (SUP), 79 endometriomas (OMA) and 235 deep infiltrating endometriosis (DIE). Control group included 375 patients without endometriosis as surgically checked. Mean birth weights were compared between patients and controls, according to endometriosis groups and rAFS stages. Mean birth weight was significantly lower for patients with endometriosis as compared to controls (3,119g ± 614 and 3,251g ± 557 respectively; p = 0.002). When compared to controls, patients with DIE had the lowest birth weight with a highly significant difference (3,103g ± 620, p = 0.002). In univariate analysis, patients with low birth weight (LBW), defined as a BW < 2,500g, had a higher risk of endometriosis, especially DIE, as compared to the reference group (OR = 1.5, 95%CI: 1.0-2.3 and OR = 1.7, 95%CI: 1.0-2.7, respectively). Multivariate analysis, adjusted on ethnicity and smoking status, showed the persistence of a significant association between endometriosis and LBW with a slight increase in the magnitude of the association (aOR = 1.7, 95%CI: 1.0-2.6 for endometriosis, aOR = 1.8; 95%CI: 1.1-2.9 for DIE). In conclusion, LBW is independently associated with the risk of endometriosis in our population. Among patients with LBW, the risk is almost two-times higher to develop DIE. This association could reflect common signaling pathways between endometriosis and fetal growth regulation. There is also the possibility of a role played by placental insufficiency on the development of the neonate’s pelvis and the occurrence of neonatal uterine bleeding that could have consequences on the risk of severe endometriosis.     

Lactococcus lactis AbiD1 abortive infection efficiency is drastically increased by a phage protein

Three genetically defined Actinobacillus pleuropneumoniae serotype 7 mutants with deletions in the small (tbpB), the large (tbpA), and both transferrin binding protein genes were constructed and examined in an aerosol infection model. Neither mutant caused clinical disease or could be reisolated, and no immune response could be detected 21 days after infection. This result clearly implies that each transferrin binding protein on its own is a virulence factor of A. pleuropneumoniae serotype 7.