Comparative Genome Analysis of Uropathogenic Morganella morganii Strains

Morganella morganii is an opportunistic bacterial pathogen shown to cause a wide range of clinical and community-acquired infections. This study was aimed at sequencing and comparing the genomes of three M. morganii strains isolated from the urine samples of patients with community-acquired urinary tract infections. Draft genome sequencing was conducted using the Illumina HiSeq platform. The genomes of MM 1, MM 4, and MM 190 strains have a size of 3.82–3.97 Mb and a GC content of 50.9–51%. Protein-coding sequences (CDS) represent 96.1% of the genomes, RNAs are encoded by 2.7% of genes and pseudogenes account for 1.2% of the genomes. The pan-genome containes 4,038 CDS, of which 3,279 represent core genes. Six to ten prophages and 21–33 genomic islands were identified in the genomes of MM 1, MM 4, and MM 190. More than 30 genes encode capsular biosynthesis proteins, an average of 60 genes encode motility and chemotaxis proteins, and about 70 genes are associated with fimbrial biogenesis and adhesion. We determined that all strains contained urease gene cluster ureABCEFGD and had a urease activity. Both MM 4 and MM 190 strains are capable of hemolysis and their activity correlates well with a cytotoxicity level on T-24 bladder carcinoma cells. These activities were associated with expression of RTX toxin gene hlyA, which was introduced into the genomes by a phage similar to Salmonella phage 118970_sal4

Predictive risk factors before the onset of familial rheumatoid arthritis: the Tatarstan cohort study

BackgroundA familial history of rheumatoid arthritis (RA) predisposes an individual to develop RA. This study aimed at investigating factors associated with this conversion from the Tatarstan cohort.MethodsA total of 144 individuals, referred to as pre-RA and at risk for familial RA, were selected 2 years (range: 2–21 years) before conversion to RA and compared to non-converted 328 first-degree relatives (FDR) from RA as assessed after ≥2 years follow-up, and 355 healthy controls were also selected (HC). Preclinical parameters and socio-demographic/individual/HLA genetic factors were analyzed when data were available at the time of enrollment.ResultsAs compared to FDR and HC groups, pre-RA individuals were characterized before conversion to RA by the presence of arthralgia, severe morning symptoms, a lower educational level, and rural location. An association with the HLA-DRB1 SE risk factor was also retrieved with symmetrical arthralgia and passive smoking. On the contrary, alcohol consumption and childlessness in women were protective and associated with the HLA-DRB1*07:01 locus.ConclusionBefore RA onset, a combination of individual and genetic factors characterized those who are at risk of progressing to RA among those with familial RA relatives

A Novel Receptor Tyrosine Kinase Switch Promotes Gastrointestinal Stromal Tumor Drug Resistance

The fact that most gastrointestinal stromal tumors (GISTs) acquire resistance to imatinib (IM)-based targeted therapy remains the main driving force to identify novel molecular targets that are capable to increase GISTs sensitivity to the current therapeutic regimens. Secondary resistance to IM in GISTs typically occurs due to several mechanisms that include hemi- or homo-zygous deletion of the wild-type KIT allele, overexpression of focal adhesion kinase (FAK) and insulin-like growth factor receptor I (IGF-1R) amplification, BRAF mutation, a RTK switch (loss of c-KIT and gain of c-MET/AXL), etc. We established and characterized the IM-resistant GIST T-1 cell line (GIST T-1R) lacking secondary c-KIT mutations typical for the IM-resistant phenotype. The resistance to IM in GIST T-1R cells was due to RTK switch (loss of c-KIT/gain of FGFR2α). Indeed, we have found that FGFR inhibition reduced cellular viability, induced apoptosis and affected the growth kinetics of the IM-resistant GISTs in vitro. In contrast, IM-naive GIST T-1 parental cells were not susceptible to FGFR inhibition. Importantly, inhibition of FGF-signaling restored the susceptibility to IM in IM-resistant GISTs. Additionally, IM-resistant GISTs were less susceptible to certain chemotherapeutic agents as compared to parental IM-sensitive GIST cells. The chemoresistance in GIST T-1R cells is not due to overexpression of ABC-related transporter proteins and might be the result of upregulation of DNA damage signaling and repair (DDR) genes involved in DNA double-strand break (DSB) repair pathways (e.g., XRCC3, Rad51, etc.). Taken together, the established GIST T-1R cell subline might be used for in vitro and in vivo studies to examine the efficacy and prospective use of FGFR inhibitors for patients with IM-resistant, un-resectable and metastatic forms of GISTs with the type of RTK switch indicated above

Effect of the total fraction of

Intestinal microbes play a key role in the energy metabolism of broiler chickens, participate in the development of the gastrointestinal tract, including the regulation of intestinal epithelial proliferation, vitamin synthesis and ion absorption, fermentation of carbohydrates and proteins, biotransformation of bile acids, protection from pathogens and modulation of the immune system. Metagenomic analysis of the gastrointestinal microbiota allows to find approaches to improve the growth and productivity of chickens by introducing a diet based on beneficial bacterial strains or their secondary metabolites. In this paper, we studied the effect of the total fraction of Bacillus subtilis GM5 lipopeptides on the growth parameters and formation of bacterial communities in the caecum of cross Cobb 500 broiler chickens. It was found that the addition of bacillary lipopeptides to the feed resulted in an increase in chicken weight by 12.7% and a decrease in feed conversion by 6.36% compared to the control (P < 0.05). It was also shown that the introduction of a feed additive in the form of a lipopeptide fraction modulates the structure of the bacterial microbiota of the caecum of chickens. Thus, the proportion of classes Bacteroidia, Negativicutes, Betaproteobacteria, Epsilonproteobacteria, Deltaproteobacteria, Synergistia in the caecal microbiota of chickens of the experimental group increases, and the proportion of Clostridia, Methanobacteria decreases in comparison with the control

The novel HLA‐DQB1 allele, HLA‐DQB1 *04:72 , detected in a potential hematopoietic stem cell donor

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Draft genome sequence data and analysis of Brachybacterium sp. strain EE-P12 isolated from a laboratory-scale anaerobic reactor

The species of the genus Brachybacterium belonging to the family Dermabacteraceae within the phylum Actinobacteria are gram-positive, facultatively anaerobic or aerobic, nonmotile and nonsporeforming bacteria. Cells of Brachybacterium spp. vary in shape from coccoid forms (stationary phase) to rods (exponential phase). Brachybacterium species can be isolated from numerous sources such as poultry deep litter, human gut, soil, food products. Here we describe the draft genome sequence of Brachybacterium sp. EE-P12 that was isolated from a laboratory-scale anaerobic digester. The genome sequencing generated 3,964,988 bp, with a G+C content of 72.2%. This draft genome data has been deposited at DDBJ/ENA/GenBank under the accession number QXCP00000000 (https://www.ncbi.nlm.nih.gov/nuccore/QXCP00000000). Keywords: Draft genome, Actinobacteria, Brachybacterium sp., Chicken manure, Laboratory-scale biogas reacto