275 research outputs found

    Light dark sectors through the Fermion portal

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    Abstract Pairs of Standard Model fermions form dimension-3 singlet operators that can couple to new dark sector states. This “fermion portal” is to be contrasted with the lower-dimensional Higgs, vector and neutrino singlet portals. We characterise its distinct phenomenology and place effective field theory bounds on this framework, focusing on the case of fermion portals to a pair of light dark sector fermions. We obtain current and projected limits on the dimension-6 effective operator scale from a variety of meson decay experiments, missing energy and long-lived particle searches at colliders, as well as astrophysical and cosmological bounds. The DarkEFT public code is made available for recasting these limits, which we illustrate with various examples including an integrated- out heavy dark photon.</jats:p

    Viral particles of the endogenous retrovirus ZAM from Drosophila melanogaster use a pre-existing endosome/exosome pathway for transfer to the oocyte

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    BACKGROUND: Retroviruses have evolved various mechanisms to optimize their transfer to new target cells via late endosomes. Here, we analyzed the transfer of ZAM, a retroelement from Drosophila melanogaster, from ovarian follicle cells to the oocyte at stage 9–10 of oogenesis, when an active yolk transfer is occurring between these two cell types. RESULTS: Combining genetic and microscopic approaches, we show that a functional secretory apparatus is required to tether ZAM to endosomal vesicles and to direct its transport to the apical side of follicle cells. There, ZAM egress requires an intact follicular epithelium communicating with the oocyte. When gap junctions are inhibited or yolk receptors mutated, ZAM particles fail to sort out the follicle cells. CONCLUSION: Overall, our results indicate that retrotransposons do not exclusively perform intracellular replication cycles but may usurp exosomal/endosomal traffic to be routed from one cell to another

    Correction for Tarallo et al., “Altered Fecal Small RNA Profiles in Colorectal Cancer Reflect Gut Microbiome Composition in Stool Samples”

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    Dysbiotic configurations of the human gut microbiota have been linked to colorectal cancer (CRC). Human small noncoding RNAs are also implicated in CRC, and recent findings suggest that their release in the gut lumen contributes to shape the gut microbiota. Bacterial small RNAs (bsRNAs) may also play a role in carcinogenesis, but their role has been less extensively explored. Here, we performed small RNA and shotgun sequencing on 80 stool specimens from patients with CRC or with adenomas and from healthy subjects collected in a cross-sectional study to evaluate their combined use as a predictive tool for disease detection. We observed considerable overlap and a correlation between metagenomic and bsRNA quantitative taxonomic profiles obtained from the two approaches. We identified a combined predictive signature composed of 32 features from human and microbial small RNAs and DNA-based microbiome able to accurately classify CRC samples separately from healthy and adenoma samples (area under the curve [AUC] = 0.87). In the present study, we report evidence that host-microbiome dysbiosis in CRC can also be observed by examination of altered small RNA stool profiles. Integrated analyses of the microbiome and small RNAs in the human stool may provide insights for designing more-accurate tools for diagnostic purposes.IMPORTANCE The characteristics of microbial small RNA transcription are largely unknown, while it is of primary importance for a better identification of molecules with functional activities in the gut niche under both healthy and disease conditions. By performing combined analyses of metagenomic and small RNA sequencing (sRNA-Seq) data, we characterized both the human and microbial small RNA contents of stool samples from healthy individuals and from patients with colorectal carcinoma or adenoma. With the integrative analyses of metagenomic and sRNA-Seq data, we identified a human and microbial small RNA signature which can be used to improve diagnosis of the disease. Our analysis of human and gut microbiome small RNA expression is relevant to generation of the first hypotheses about the potential molecular interactions occurring in the gut of CRC patients, and it can be the basis for further mechanistic studies and clinical test

    A Bayesian approach to detect QTL affecting a simulated binary and quantitative trait

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    Background - We analyzed simulated data from the 14th QTL-MAS workshop using a Bayesian approach implemented in the program iBay. The data contained individuals genotypes for 10,031 SNPs and phenotyped for a quantitative and a binary trait. Results - For the quantitative trait we mapped 8 out of 30 additive QTL, 1 out of 3 imprinted QTL and both epistatic pairs of QTL successfully. For the binary trait we mapped 11 out of 22 additive QTL successfully. Four out of 22 pleiotropic QTL were detected as such. Conclusions - The Bayesian variable selection method showed to be a successful method for genome-wide association. This method was reasonably fast using dense marker map

    Efficacy of Mesoglycan in Pain Control after Excisional Hemorrhoidectomy. A Pilot Comparative Prospective Multicenter Study

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    Introduction. Various pain management strategies for patients undergoing open excisional hemorrhoidectomy have been proposed, yet postoperative pain remains a frequent complaint. Objective. To determine whether mesoglycan (30 mg two vials i.m. once/day for the first 5 days postoperative, followed by 50 mg 1 oral tablet twice/day for 30 days) would reduce the edema of the mucocutaneous bridges and thus improve postoperative pain symptoms. Patients and Methods. For this prospective observational multicenter study, 101 patients undergoing excisional diathermy hemorrhoidectomy for III-IV degree hemorrhoidal disease were enrolled at 5 colorectal referral centers. Patients were assigned to receive either mesoglycan (study group SG) or a recommended oral dose of ketorolac tromethamine of 10 mg every 4-6 hours, not exceeding 40 mg per day and not exceeding 5 postoperative days according to the indications for short-term management of moderate/severe acute postoperative pain, plus stool softeners (control group CG). Results. Postoperative thrombosis (SG 1/48 versus CG 5/45) (p &lt; 0 001) and pain after rectal examination (p &lt; 0 001) were significantly reduced at 7-10 days after surgery in the mesoglycan-treated group, permitting a faster return to work (p &lt; 0 001); however, in the same group, the incidence of postoperative bleeding, considered relevant when needing a readmission or an unexpected outpatient visit, was higher, possibly owing to the drug's antithrombotic properties. Conclusions. The administration of mesoglycan after an open diathermy excisional hemorrhoidectomy can reduce postoperative thrombosis and pain at 7-10 days after surgery, permitting a faster return to normal activities

    Plan de negocio para evaluar la viabilidad de la implementaci?n de una cadena de sangucher?as de cerdo con tem?tica musical

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    En Lima existe una gran cantidad de estudiantes de educaci?n superior los cuales por su ritmo de vida buscan alternativas de alimentaci?n cercanas a su centro de estudios que puedan satisfacer sus necesidades las cuales abarcan no solamente el hambre sino tambi?n la necesidad de entretenimiento y sociabilizaci?n. Actualmente estas necesidades no son cubiertas por las cadenas de sangucher?as tradicionales las cuales optan por dirigirse a niveles socio-econ?micos AB, dejando un espacio para que las sangucher?as independientes, las cuales deben desarrollar una oferta de valor que pueda suplir estas necesidades. Observando esta oportunidad, la Porc?cola Don Lucho, productores de carne de cerdo, desea desarrollar una cadena sangucher?as la cual a trav?s de din?micas musicales pueda brindar entretenimiento es te p?blico objetivo, ofreciendo a su vez s?nguches con sabores especiales que puedan diferenciarlo de sus competidores

    Relationship Between Quorum Sensing and Secretion Systems

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    Quorum sensing (QS) is a communication mechanism between bacteria that allows specific processes to be controlled, such as biofilm formation, virulence factor expression, production of secondary metabolites and stress adaptation mechanisms such as bacterial competition systems including secretion systems (SS). These SS have an important role in bacterial communication. SS are ubiquitous; they are present in both Gram-negative and Gram-positive bacteria and in Mycobacterium sp. To date, 8 types of SS have been described (T1SS, T2SS, T3SS, T4SS, T5SS, T6SS, T7SS, and T9SS). They have global functions such as the transport of proteases, lipases, adhesins, heme-binding proteins, and amidases, and specific functions such as the synthesis of proteins in host cells, adaptation to the environment, the secretion of effectors to establish an infectious niche, transfer, absorption and release of DNA, translocation of effector proteins or DNA and autotransporter secretion. All of these functions can contribute to virulence and pathogenesis. In this review, we describe the known types of SS and discuss the ones that have been shown to be regulated by QS. Due to the large amount of information about this topic in some pathogens, we focus mainly on Pseudomonas aeruginosa and Vibrio spp

    CXCL1 can be regulated by IL-6 and promotes granulocyte adhesion to brain capillaries during bacterial toxin exposure and encephalomyelitis

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    <p>Abstract</p> <p>Background</p> <p>Granulocytes generally exert protective roles in the central nervous system (CNS), but recent studies suggest that they can be detrimental in experimental autoimmune encephalomyelitis (EAE), the most common model of multiple sclerosis. While the cytokines and adhesion molecules involved in granulocyte adhesion to the brain vasculature have started to be elucidated, the required chemokines remain undetermined.</p> <p>Methods</p> <p>CXCR2 ligand expression was examined in the CNS of mice suffering from EAE or exposed to bacterial toxins by quantitative RT-PCR and <it>in situ </it>hybridization. CXCL1 expression was analyzed in IL-6-treated endothelial cell cultures by quantitative RT-PCR and ELISA. Granulocytes were counted in the brain vasculature after treatment with a neutralizing anti-CXCL1 antibody using stereological techniques.</p> <p>Results</p> <p>CXCL1 was the most highly expressed ligand of the granulocyte receptor CXCR2 in the CNS of mice subjected to EAE or infused with lipopolysaccharide (LPS) or pertussis toxin (PTX), the latter being commonly used to induce EAE. IL-6 upregulated CXCL1 expression in brain endothelial cells by acting transcriptionally and mediated the stimulatory effect of PTX on CXCL1 expression. The anti-CXCL1 antibody reduced granulocyte adhesion to brain capillaries in the three conditions under study. Importantly, it attenuated EAE severity when given daily for a week during the effector phase of the disease.</p> <p>Conclusions</p> <p>This study identifies CXCL1 not only as a key regulator of granulocyte recruitment into the CNS, but also as a new potential target for the treatment of neuroinflammatory diseases such as multiple sclerosis.</p

    Identification of Multiple HPV Types on Spermatozoa from Human Sperm Donors

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    Human papillomaviruses (HPV) may cause sexually transmitted disease. High-risk types of HPV are involved in the development of cervical cell dysplasia, whereas low-risk types may cause genital condyloma. Despite the association between HPV and cancer, donor sperm need not be tested for HPV according to European regulations. Consequently, the potential health risk of HPV transmission by donor bank sperm has not been elucidated, nor is it known how HPV is associated with sperm. The presence of 35 types of HPV was examined on DNA from semen samples of 188 Danish sperm donors using a sensitive HPV array. To examine whether HPV was associated with the sperm, in situ hybridization were performed with HPV-6, HPV-16 and -18, and HPV-31-specific probes. The prevalence of HPV-positive sperm donors was 16.0% and in 66.7% of these individuals high-risk types of HPV were detected. In 5.3% of sperm donors, two or more HPV types were detected. Among all identified HPV types, 61.9% were high-risk types. In situ hybridization experiments identified HPV genomes particularly protruding from the equatorial segment and the tail of the sperm. Semen samples from more than one in seven healthy Danish donors contain HPV, most of them of high-risk types binding to the equatorial segment of the sperm cell. Most HPV-positive sperm showed decreased staining with DAPI, indicative of reduced content of DNA. Our data demonstrate that oncogenic HPV types are frequent in men
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