Remodeling of an in vitro microvessel exposed to cyclic mechanical stretch.

In the lung, vascular endothelial cells experience cyclic mechanical strain resulting from rhythmic breathing motions and intraluminal blood pressure. Mechanical stress creates evident physiological, morphological, biochemical, and gene expression changes in vascular endothelial cells. However, the exact mechanisms of the mechanical signal transduction into biological response remain to be clarified. Besides, the level of mechanical stress is difficult to determine due to the complexity of the local distension patterns in the lung and thus assumed to be the same as the one acting on the alveolar epithelium. Existing in vitro models used to investigate the effect of mechanical stretch on endothelial cells are usually limited to two-dimensional (2D) cell culture platforms, which poorly mimic the typical three-dimensional structure of the vessels. Therefore, the development of an advanced in vitro vasculature model that closely mimics the dynamic of the human lung vasculatures is highly needed. Here, we present the first study that investigates the interplay of the three-dimensional (3D) mechanical cyclic stretch and its magnitude with vascular endothelial growth factor (VEGF) stimulation on a 3D perfusable vasculature in vitro. We studied the effects of the cyclic strain on a perfusable 3D vasculature, either made of human lung microvascular endothelial cells or human umbilical vein endothelial cells embedded in a gel layer. The in vitro 3D vessels underwent both in-vivo-like longitudinal and circumferential deformations, simultaneously. Our results showed that the responses of the human lung microvascular endothelial cells and human umbilical vein endothelial cells to cyclic stretch were in good agreement. Although our 3D model was in agreement with 2D model in predicting a cytoskeletal remodeling in response to different magnitudes of cyclic stretch, however we observed several phenomena in 3D model that 2D model was unable to predict to. Angiogenic sprouting induced by VEGF decreased significantly in presence of cyclic stretch. Similarly, while treatment with VEGF increased vascular permeability, the cyclic stretch restored vascular barrier tightness and significantly decreased vascular permeability. One of the major findings of this study was that a 3D microvasculature can be exposed to a much higher mechanical cyclic stress level than reported in the literature without any dysfunction of its barrier. For higher magnitudes of the cyclic stretch, the applied longitudinal strain level was 14% and the associated circumferential strain reached the equivalent of 63%. In sharp contrast with our findings, such strain typically leads to the disruption of the endothelial barrier in a 2D stretching assay and is considered pathological. This highlights the importance of 3D modeling to investigate mechanobiology effects rather than using a simple endothelial monolayer which truly recapitulates the in vivo situation

Phenotypic and genotypic evaluation of ESBL- and AmpC-producing Escherichia coli isolated from chicken distributed in Birjand, East of Iran

The aims of the present study were to detect Escherichia coli in chicken distributed in Birjand, to investigate the prevalence of ESBL and AmpC beta-lactamases producers among them, and to identify their antibiotic resistance patterns. The study was conducted on 150 chicken samples, and the antimicrobial susceptibility patterns were determined by the Kirby–Bauer disk diffusion method. Phenotypic identification of ESBL and AmpC was performed by the combined disk test (CDT). The specific genes of ESBL and AmpC beta-lactamases were detected using two multiplex PCR (m-PCR) assays. According to our results, 116 out of 150 chicken samples were contaminated with E. coli . Moreover, the highest resistance of E. coli isolates was observed to trimethoprim/sulfamethoxazole (46%), ampicillin (40%), and amoxicillin (29.33%). In the molecular confirmation step, among 17 (11.33%) beta-lactamase producers, five samples contained the bla CTX-M14 gene (3.33%), two samples contained bla DHA (1.33%) and bla CTX-M3 gene (1.33%), and just one sample carried bla CMY-2 gene (0.66%). The bla SHV and bla TEM genes were not detected in any strains isolated from the chicken samples. This study showed the contamination of chicken with antibiotic-resistant E. coli . Therefore, it is recommended that veterinarians be more precautious in prescribing antibiotics

Antimicrobial Susceptibility Profile of Enterococcus Species Isolated from Companion Birds and Poultry in the Northeast of Iran

Enterococci are Gram-positive facultative anaerobic bacteria commonly found in the gastrointestinal tract of the mammals and birds. These cocci are isolated from urinary tract infections, bacteremia, endocarditis, and burn wounds in humans. The evolution of antibiotic-resistant enterococci raised a problem due to the possibility of the transmission of these organisms between poultry and human. Regarding this, the present study was conducted to evaluate the prevalence of Enterococcus species among companion birds and poultry in the Northeastern of Iran and determine the antibiotic susceptibility profile of enterococci. To this end, oral and cloacal swabs were collected from 150 caged birds. Antibiotic susceptibility profile was determined using the standard disk diffusion method. The results revealed that out of 150 samples, 56 (37.33%) cases contained enterococci. Most of the specimens (25.33%) were Enterococcus faecalis isolated from 6.66% of the samples. Additionally, 2.66% and 1.33% of the samples were contaminated with Enterococcus mundtii and Enterococcus gallinarum, respectively. Furthermore, Enterococcus malodoratus and Enterococcus raffinosus were isolated from 0.66% of the samples. The results revealed that all of the isolates of E. faecalis and E. faecium were resistant to more than five antimicrobial agents. Most of E. faecalis and E. faecium isolates showed resistance to Cefazolin, Tiamulin, Flumequine, and Cephalexin. Accordingly, the majority of the isolates had multidrug resistance to the tested antibiotics. In conclusion, the presence of multidrug-resistant enterococci in the birds living close to humans requires thorough observations due to the transmission of these organisms to humans

Poplar phyllosphere harbors disparate isoprene-degrading bacteria

The climate-active gas isoprene (2-methyl-1,3-butadiene) is released to the atmosphere in huge quantities, almost equaling that of methane, yet we know little about the biological cycling of isoprene in the environment. Although bacteria capable of growth on isoprene as the sole source of carbon and energy have previously been isolated from soils and sediments, no microbiological studies have targeted the major source of isoprene and examined the phyllosphere of isoprene-emitting trees for the presence of degraders of this abundant carbon source. Here, we identified isoprene-degrading bacteria in poplar tree-derived microcosms by DNA stable isotope probing. The genomes of isoprene-degrading taxa were reconstructed, putative isoprene metabolic genes were identified, and isoprene-related gene transcription was analyzed by shotgun metagenomics and metatranscriptomics. Gram-positive bacteria of the genus Rhodococcus proved to be the dominant isoprene degraders, as previously found in soil. However, a wider diversity of isoprene utilizers was also revealed, notably Variovorax, a genus not previously associated with this trait. This finding was confirmed by expression of the isoprene monooxygenase from Variovorax in a heterologous host. A Variovorax strain that could grow on isoprene as the sole carbon and energy source was isolated. Analysis of its genome confirmed that it contained isoprene metabolic genes with an identical layout and high similarity to those identified by DNA-stable isotope probing and metagenomics. This study provides evidence of a wide diversity of isoprene-degrading bacteria in the isoprene-emitting tree phyllosphere and greatly enhances our understanding of the biodegradation of this important metabolite and climate-active gas

Measurements of branching fraction ratios and CP-asymmetries in suppressed B^- -> D(-> K^+ pi^-)K^- and B^- -> D(-> K^+ pi^-)pi^- decays

We report the first reconstruction in hadron collisions of the suppressed decays B^- -> D(-> K^+ pi^-)K^- and B^- -> D(-> K^+ pi^-)pi^-, sensitive to the CKM phase gamma, using data from 7 fb^-1 of integrated luminosity collected by the CDF II detector at the Tevatron collider. We reconstruct a signal for the B^- -> D(-> K^+ pi^-)K^- suppressed mode with a significance of 3.2 standard deviations, and measure the ratios of the suppressed to favored branching fractions R(K) = [22.0 \pm 8.6(stat)\pm 2.6(syst)]\times 10^-3, R^+(K) = [42.6\pm 13.7(stat)\pm 2.8(syst)]\times 10^-3, R^-(K)= [3.8\pm 10.3(stat)\pm 2.7(syst]\times 10^-3, as well as the direct CP-violating asymmetry A(K) = -0.82\pm 0.44(stat)\pm 0.09(syst) of this mode. Corresponding quantities for B^- -> D(-> K^+ pi^-)pi^- decay are also reported.Comment: 8 pages, 1 figure, accepted by Phys.Rev.D Rapid Communications for Publicatio

Molecular genetic diagnosis of Glanzmann syndrome in Iranian population; Reporting novel and recurrent mutations

Background: Glanzmann thrombasthenia (GT) is a rare autosomal recessive abnormality of platelet aggregation with quantitative and/or qualitative abnormality of αIIbβ3 integrin. The αIIbβ3 is a platelet fibrinogen receptor, which is required for platelet aggregation, firm adhesion, and also spreading. The disease is more prevalent in the populations with a higher rate of consanguineous marriages as in some Middle Eastern populations including Iraq, Jordan, and Iran. Different types of mutations in ITGA2B and ITGB3 genes have been previously reported to cause the disease. Result: In this study, 16 patients with the clinical diagnosis of GT were studied. Direct sequencing of the exons and exon-intron boundaries of the above genes revealed mutations in 14 patients (detection rate: 87.5). Briefly, out of fifteen types of identified mutations, 14 were novel. Seven mutations in the ITGB3 gene included 4 missense c.2T > C, c.155 G > T, c. 538 G > A, c.1990 G > T, one nonsense mutation c.1303 G > T, a small deletion c.1656-1658delCTC and a deletion of one nucleotide c.401delA. Mutations in the ITGA2B were 8 different mutations consisting 2 missense c.286 T > A, c.842 C > T, 2 deletions c.1899 del T, c.189-319-236del, an insertion c.1071-1072insG and one splice site mutations c.409-3 C > G, one synonymous mutation that might alter the normal splicing process c.1392 A > G and a nonsense mutation c.1555 C > T. The causative mutation in 2 patients remained unknown. Using long-range PCR and sequencing, we found a rather large deletion. The break point of this deletion covers 319 nt from the last part of the first intron and 48 nt from the beginning of the second exon of ITGA2B gene. The deletion was also detected in two unrelated patients with the same ethnicity. In addition, in silico analyses of novel mutations were performed. Conclusion: There was no recurrent mutation in the studied population. This may be due to either small sample size or the heterogeneity of the studied population. © 2019 The Author(s)

Search for anomalous t t-bar production in the highly-boosted all-hadronic final state

A search is presented for a massive particle, generically referred to as a Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are sufficiently massive to produce highly Lorentz-boosted top quarks, which yield collimated decay products that are partially or fully merged into single jets. The analysis uses new methods to analyze jet substructure, providing suppression of the non-top multijet backgrounds. The analysis is based on a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits in the range of 1 pb are set on the product of the production cross section and branching fraction for a topcolor Z' modeled for several widths, as well as for a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any enhancement in t t-bar production beyond expectations of the standard model for t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version includes a minor typo correction that will be submitted as an erratu

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE