Acute influence of cigarette smoke in platelets, catecholamines and neurophysins in the normal conditions of daily life

Cigarette smoking is firmly linked to the occurrence of acute coronary events. In twenty-two healthy volunteers in normal conditions of daily life we studied the acute influence of smoking on the following parameters: beta-thromboglobulin, thromboxane B2, epinephrine, norepinephrine, estrogen-stimulated neurophysin, and nicotine-stimulated-neurophysin. Our results show that in our population and following our protocol, smoking did not induce platelet activation, thromboxane formation, catecholamine release or estrogen-stimulated-neurophysin secretion. However, smoking did provoke a significant increase of nicotine-stimulated-neurophysin (p<0.05) which reflects vasopressin increase and which might explain the high incidence of ischaemic accidents in cigarette smoking via the vasoactive properties of vasopressi

Review of the mechanisms of debris-flow impact against barriers

Our limited understanding of the mechanisms pertaining to the force exerted by debris flows on barriers makes it difficult to ascertain whether a design is inadequate, adequate, or over-designed. The main scientific challenge is because flow-type landslides impacting a rigid barrier is rarely captured in the field, and no systematic, physical experimental data is available to reveal the impact mechanisms. An important consideration in flow-structure interaction is that the impact dynamics can differ radically depending on the composition of the flow. Currently, no framework exists that can characterize the impact behavior for a wide range of flow compositions. This review paper examines recent works on debris-flow structure interactions and the limitations of commonly used approaches to estimate the impact load for the design of barriers. Key challenges faced in this area and outlook for further research are discussed

Human Female Genital Tract Infection by the Obligate Intracellular Bacterium Chlamydia trachomatis Elicits Robust Type 2 Immunity

While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms that regulate host response to this intracellular Gram-negative bacterium remain undefined. This investigation thus used peripheral blood mononuclear cells and endometrial tissue from women with or without Chlamydia genital tract infection to better define this response. Initial genome-wide microarray analysis revealed highly elevated expression of matrix metalloproteinase 10 and other molecules characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia-infected tissue. This result was corroborated in flow cytometry and immunohistochemistry studies that showed extant upper genital tract Chlamydia infection was associated with increased co-expression of CD200 receptor and CD206 (markers of alternative macrophage activation) by endometrial macrophages as well as increased expression of GATA-3 (the transcription factor regulating TH2 differentiation) by endometrial CD4+ T cells. Also among women with genital tract Chlamydia infection, peripheral CD3+ CD4+ and CD3+ CD4- cells that proliferated in response to ex vivo stimulation with inactivated chlamydial antigen secreted significantly more interleukin (IL)-4 than tumor necrosis factor, interferon-γ, or IL-17; findings that repeated in T cells isolated from these same women 1 and 4 months after infection had been eradicated. Our results thus newly reveal that genital infection by an obligate intracellular bacterium induces polarization towards Type 2 immunity, including Chlamydia-specific TH2 development. Based on these findings, we now speculate that Type 2 immunity was selected by evolution as the host response to C. trachomatis in the human female genital tract to control infection and minimize immunopathological damage to vital reproductive structures. © 2013 Vicetti Miguel et al

Principles of meiotic chromosome assembly revealed in S. cerevisiae

During meiotic prophase, chromosomes organise into a series of chromatin loops emanating from a proteinaceous axis, but the mechanisms of assembly remain unclear. Here we use Saccharomyces cerevisiae to explore how this elaborate three-dimensional chromosome organisation is linked to genomic sequence. As cells enter meiosis, we observe that strong cohesin-dependent grid-like Hi-C interaction patterns emerge, reminiscent of mammalian interphase organisation, but with distinct regulation. Meiotic patterns agree with simulations of loop extrusion with growth limited by barriers, in which a heterogeneous population of expanding loops develop along the chromosome. Importantly, CTCF, the factor that imposes similar features in mammalian interphase, is absent in S. cerevisiae, suggesting alternative mechanisms of barrier formation. While grid-like interactions emerge independently of meiotic chromosome synapsis, synapsis itself generates additional compaction that matures differentially according to telomere proximity and chromosome size. Collectively, our results elucidate fundamental principles of chromosome assembly and demonstrate the essential role of cohesin within this evolutionarily conserved process

Absolute quantification of cohesin, CTCF and their regulators in human cells.

The organisation of mammalian genomes into loops and topologically associating domains (TADs) contributes to chromatin structure, gene expression and recombination. TADs and many loops are formed by cohesin and positioned by CTCF. In proliferating cells, cohesin also mediates sister chromatid cohesion, which is essential for chromosome segregation. Current models of chromatin folding and cohesion are based on assumptions of how many cohesin and CTCF molecules organise the genome. Here we have measured absolute copy numbers and dynamics of cohesin, CTCF, NIPBL, WAPL and sororin by mass spectrometry, fluorescence-correlation spectroscopy and fluorescence recovery after photobleaching in HeLa cells. In G1-phase, there are similar to 250,000 nuclear cohesin complexes, of which similar to 160,000 are chromatin-bound. Comparison with chromatin immunoprecipitation-sequencing data implies that some genomic cohesin and CTCF enrichment sites are unoccupied in single cells at any one time. We discuss the implications of these findings for how cohesin can contribute to genome organisation and cohesion

A comparative evaluation of the efficacy of manual, magnetostrictive and piezoelectric ultrasonic instruments: an in vitro profilometric and SEM study

OBJECTIVES: The debridement of diseased root surface is usually performed by mechanical scaling and root planing using manual and power driven instruments. Many new designs in ultrasonic powered scaling tips have been developed. However, their effectiveness as compared to manual curettes has always been debatable. Thus, the objective of this in vitro study was to comparatively evaluate the efficacy of manual, magnetostrictive and piezoelectric ultrasonic instrumentation on periodontally involved extracted teeth using profilometer and scanning electron microscope (SEM). MATERIAL AND METHODS: 30 periodontally involved extracted human teeth were divided into 3 groups. The teeth were instrumented with hand and ultrasonic instruments resembling clinical application. In Group A all teeth were scaled with a new universal hand curette (Hu Friedy Gracey After Five Vision curette; Hu Friedy, Chicago, USA). In Group B Cavitron(TM) FSI - SLI(TM) ultrasonic device with focused spray slimline inserts (Dentsply International Inc., York, PA, USA) were used. In Group C teeth were scaled with an EMS piezoelectric ultrasonic device with prototype modified PS inserts. The surfaces were analyzed by a Precision profilometer to measure the surface roughness (Ra value in µm) consecutively before and after the instrumentation. The samples were examined under SEM at magnifications ranging from 17x to 300x and 600x. RESULTS: The mean Ra values (µm) before and after instrumentation in all the three groups A, B and C were tabulated. After statistically analyzing the data, no significant difference was observed in the three experimental groups. Though there was a decrease in the percentage reduction of Ra values consecutively from group A to C. CONCLUSION: Within the limits of the present study, given that the manual, magnetostrictive and piezoelectric ultrasonic instruments produce the same surface roughness, it can be concluded that their efficacy for creating a biologically compatible surface of periodontally diseased teeth is similar

SARS-CoV-2 infection and replication in human gastric organoids

COVID-19 typically manifests as a respiratory illness, but several clinical reports have described gastrointestinal symptoms. This is particularly true in children in whom gastrointestinal symptoms are frequent and viral shedding outlasts viral clearance from the respiratory system. These observations raise the question of whether the virus can replicate within the stomach. Here we generate gastric organoids from fetal, pediatric, and adult biopsies as in vitro models of SARS-CoV-2 infection. To facilitate infection, we induce reverse polarity in the gastric organoids. We find that the pediatric and late fetal gastric organoids are susceptible to infection with SARS-CoV-2, while viral replication is significantly lower in undifferentiated organoids of early fetal and adult origin. We demonstrate that adult gastric organoids are more susceptible to infection following differentiation. We perform transcriptomic analysis to reveal a moderate innate antiviral response and a lack of differentially expressed genes belonging to the interferon family. Collectively, we show that the virus can efficiently infect the gastric epithelium, suggesting that the stomach might have an active role in fecal-oral SARS-CoV-2 transmission

Development of an isoform-specific gene suppression system: the study of the human Pax-5B transcriptional element

The transcription factor Pax-5, is vital during B lymphocyte differentiation and is known to contribute to the oncogenesis of certain cancers. The Pax-5 locus generates multiple yet structurally related mRNA transcripts through the specific activation of alternative promoter regions and/or alternative splicing events which poses challenges in the study of specific isoform function. In this study, we investigated the function of a major Pax-5 transcript, Pax-5B using an enhanced version of the Hepatitis Delta Virus ribozyme (HDV Rz) suppression system that is specifically designed to recognize and cleave the human Pax-5B mRNA. The activity of these ribozymes resulted in the specific suppression of the Pax-5B transcripts without altering the transcript levels of other closely related Pax-5 isoforms mRNAs both in vitro and in an intracellular setting. Following stable transfection of the ribozymes into a model B cell line (REH), we showed that Pax-5B suppression led to an increase of CD19 mRNA and cell surface protein expression. In response to this Pax-5B specific deregulation, a marked increase in apoptotic activity compared to control cell lines was observed. These results suggest that Pax-5B has distinct roles in physiological processes in cell fate events during lymphocyte development