TOpic: rare and special cases, the real "Strange cases"

Introduction: The bladder hernia represents approximately 1-3% of all inguinal hernias, where patients aged more than 50 years have a higher incidence (10%). Many factors contribute to the development of a bladder hernia, including the presence of a urinary outlet obstruction causing chronic bladder distention, the loss of bladder tone, pericystitis, the perivesical bladder fat protrusion and the obesity

A Systems Biology Approach Reveals the Endocrine Disrupting Potential of Aflatoxin B1

Background Aflatoxin B1 (AFB1) a mycotoxin produced by Aspergillus flavus and A. parasiticus is a potent carcinogen and causative agent of hepatocellular carcinoma (HCC). It is a food contaminant which presents a major risk to human health. AFB1 contamination poses a significant economic burden, as 25% of the world's food crops need to be destroyed annually. The mechanism of action (MOA) of aflatoxins remains to be fully elucidated. Recent findings suggest that AFB1 mediated endocrine disruption may occur in the population of regions with high contamination, even without evidence of direct dietary intake. Objective An integrative systems biology approach was undertaken to decipher the estrogenic component of the mechanism of action (MOA) of AFB1. Methods Molecular Docking and Molecular dynamics simulations were performed to examine the binding affinity of AFB1 and its metabolite aflatoxin Q1 (AFQ1) with the Estrogen Receptors (ERs). Differential gene expression (DGE), gene ontology (GO) and pathway analyses were carried out on hepatic transcriptomic data generated from in vivo AFB1 exposures. In parallel exposures to the synthetic estrogen ethinylestradiol (EE2) were examined for overlapping effects. Finally, protein–protein interaction (PPI) network analysis assessed the involvement of estrogen responsive targets (ERTs) associated with aflatoxin exposure. Results The free energies of binding affinity and estimated equilibrium dissociation constants (KD) demonstrated that AFB1 and AFQ1 can interact with the ERα and ERβ. DGE and GO analyses highlighted overlap in the responses between AFB1 and EE2 treatments with the activation of key processes involved in estrogenic signaling. PPI network analyses after AFBI exposure revealed a dynamic response to AFB1 treatments with the solid involvement of ERTs in regulatory networks. Conclusions This study revealed molecular interactions between aflatoxins (AFB1, AFQ1) and ERs in addition to overlap in differentially expressed genes and biological processes following AFB1 and EE2 exposures. The estrogenic components at the core of the PPI networks suggest that ER-mediated signaling pathways are a major component in the MOA of aflatoxins

Defining Global Gene Expression Changes of the Hypothalamic-Pituitary-Gonadal Axis in Female sGnRH-Antisense Transgenic Common Carp (Cyprinus carpio)

BACKGROUND: The hypothalamic-pituitary-gonadal (HPG) axis is critical in the development and regulation of reproduction in fish. The inhibition of neuropeptide gonadotropin-releasing hormone (GnRH) expression may diminish or severely hamper gonadal development due to it being the key regulator of the axis, and then provide a model for the comprehensive study of the expression patterns of genes with respect to the fish reproductive system. METHODOLOGY/PRINCIPAL FINDINGS: In a previous study we injected 342 fertilized eggs from the common carp (Cyprinus carpio) with a gene construct that expressed antisense sGnRH. Four years later, we found a total of 38 transgenic fish with abnormal or missing gonads. From this group we selected the 12 sterile females with abnormal ovaries in which we combined suppression subtractive hybridization (SSH) and cDNA microarray analysis to define changes in gene expression of the HPG axis in the present study. As a result, nine, 28, and 212 genes were separately identified as being differentially expressed in hypothalamus, pituitary, and ovary, of which 87 genes were novel. The number of down- and up-regulated genes was five and four (hypothalamus), 16 and 12 (pituitary), 119 and 93 (ovary), respectively. Functional analyses showed that these genes involved in several biological processes, such as biosynthesis, organogenesis, metabolism pathways, immune systems, transport links, and apoptosis. Within these categories, significant genes for neuropeptides, gonadotropins, metabolic, oogenesis and inflammatory factors were identified. CONCLUSIONS/SIGNIFICANCE: This study indicated the progressive scaling-up effect of hypothalamic sGnRH antisense on the pituitary and ovary receptors of female carp and provided comprehensive data with respect to global changes in gene expression throughout the HPG signaling pathway, contributing towards improving our understanding of the molecular mechanisms and regulative pathways in the reproductive system of teleost fish

Association of genomic domains in BRCA1 and BRCA2 with prostate cancer risk and aggressiveness

Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. Weevaluated whether PSVs inBRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 30 region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25-2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63-5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71-4.68; P = 0.00004) and elevated risk of Gleason 8+prostate cancer (HR = 4.95; 95% CI, 2.12-11.54; P = 0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. Significance: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.Peer reviewe

Combined searches for the production of supersymmetric top quark partners in proton–proton collisions at √s=13Te

A combination of searches for top squark pair production using proton–proton collision data at a center-of-mass energy of 13TeV at the CERN LHC, corresponding to an integrated luminosity of 137fb$^{-1}$ collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on the model, the combined result excludes a top squark mass up to 1325GeV for a massless neutralino, and a neutralino mass up to 700GeV for a top squark mass of 1150GeV. Top squarks with masses from 145 to 295GeV, for neutralino masses from 0 to 100GeV, with a mass difference between the top squark and the neutralino in a window of 30GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420GeV

Search for invisible decays of the Higgs boson produced via vector boson fusion in proton-proton collisions at s\sqrt{s} = 13 TeV

A search for invisible decays of the Higgs boson produced via vector boson fusion (VBF) has been performed with 101  fb$^{-1}$ of proton-proton collisions delivered by the LHC at $\sqrt{s}$ =13  TeV and collected by the CMS detector in 2017 and 2018. The sensitivity to the VBF production mechanism is enhanced by constructing two analysis categories, one based on missing transverse momentum and a second based on the properties of jets. In addition to control regions with Z and W boson candidate events, a highly populated control region, based on the production of a photon in association with jets, is used to constrain the dominant irreducible background from the invisible decay of a Z boson produced in association with jets. The results of this search are combined with all previous measurements in the VBF topology, based on data collected in 2012 (at $\sqrt{s}$ =8  TeV), 2015, and 2016, corresponding to integrated luminosities of 19.7, 2.3, and 36.3  fb$^{-1}$, respectively. The observed (expected) upper limit on the invisible branching fraction of the Higgs boson is found to be 0.18 (0.10) at the 95% confidence level, assuming the standard model production cross section. The results are also interpreted in the context of Higgs-portal models

Observation of the Bc+_\mathrm{c}^+ Meson in Pb-Pb and pp Collisions at sNN\sqrt{s_{\mathrm{NN}}} = 5.02 TeV and Measurement of its Nuclear Modification Factor

The B$_\mathrm{c}^+$ meson is observed for the first time in heavy ion collisions. Data from the CMS detector are used to study the production of the B$_\mathrm{c}^+$ meson in lead-lead (Pb-Pb) and proton-proton (pp) collisions at a center-of-mass energy per nucleon pair of $\sqrt{s_{\mathrm{NN}}}$ = 5.02 TeV , via the B$_\mathrm{c}^+$ → (J/ψ → μ$^+$μ$^−$)μ$^+$ν$_μ$ decay. The B$_\mathrm{c}^+$ nuclear modification factor, derived from the PbPb-to-pp ratio of production cross sections, is measured in two bins of the trimuon transverse momentum and of the PbPb collision centrality. The B$_\mathrm{c}^+$meson is shown to be less suppressed than quarkonia and most of the open heavy-flavor mesons, suggesting that effects of the hot and dense nuclear matter created in heavy ion collisions contribute to its production. This measurement sets forth a promising new probe of the interplay of suppression and enhancement mechanisms in the production of heavy-flavor mesons in the quark-gluon plasma