448 research outputs found

    Spermatozoa, acts as an external cue and alters the cargo and production of the extracellular vesicles derived from oviductal epithelial cells in vitro

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    The oviduct provides optimum physiological and biochemical milieu essential for successful fertilization, early embryo development and facilitates functional maturation of spermatozoa. A study has revealed that spermatozoa alters the gene expression in bovine oviductal epithelial cells (BOECs) remotely via bio-active particles, thus acting as a cue to the oviduct prior to their arrival. However, very little attention has been paid to the question of whether spermatozoa could alter the cargo of extracellular vesicles (EVs) derived from BOECs. Therefore, the aim of this study was to investigate the alterations in small non-coding RNAs in EVs cargo derived from BOECs when incubated with spermatozoa in contact and non-contact co-culture models. After 4 h of incubation the EVs were isolated from the conditioned media, followed by small non-coding sequencing of the BOEC derived EVs. Our results revealed that EVs from both co-culture models contained distinct cargo in form of miRNA, fragmented mRNA versus control. The pathway enrichment analysis revealed that EV miRNA from direct co-culture were involved in the biological processes associated with phagocytosis, macroautophagy, placenta development, cellular responses to TNF and FGF. The mRNA fragments also varied within the different groups and mapped to the exonic regions of the transcriptome providing vital insights regarding the changes in cellular transcriptome on the arrival of spermatozoa. The findings of this study suggest that spermatozoa, in contact as well as remotely, alter the EV cargo of female reproductive tract epithelial cells which might be playing an essential role in pre and post-fertilization events

    Cancer - Cell survival guide

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62618/1/431035a.pd

    Il tensore energia-impulso per un fluido perfetto in relatività ristretta e generale

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    Con questo lavoro si vuole discutere la connessione esistente tra l' equazione di continuità e l'equazione del moto di un fluido perfetto in Relatività Ristretta e Generale. Dapprima forniremo una breve introduzione sulle basi della Relatività Ristretta , introducendo il tensore energia-impulso ed analizzando in maniera specifica tale tensore per un fluido perfetto, ricavandone le equazioni del moto. Forniremo un secondo esempio di tensore Energia-Impulso per la materia incoerente. Conclusa questa argomentazione ci concentreremo sulla Relatività Generale, analizzandone i principi che sono alla base e privilegiando tra questi il Principio di Covarianza Generale come linea guida per le argomentazioni logiche. In maniera analoga a quanto fatto per la Relatività Ristretta riprenderemo la discussione per il tensore energia-impulso per un fluido perfetto dal punto di vista della Relatività Generale , soffermandoci nel caso di equilibrio idrostatico. Sempre nel contesto della Relatività Generale verrà in ultima analisi discusso il concetto di fluido incoerente e moto geodetico. L'ultimo capitolo è dedicato ad una appendice matematica nel quale vengono ricordati alcuni risultati dell'analisi tensoriali utili nel seguire i calcoli effettuati

    Cellular, extracellular and extracellular vesicular miRNA profiles of pre-ovulatory follicles indicate signaling disturbances in polycystic ovaries

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    Cell-free RNAs have the potential to act as a means of gene expression regulation between cells and are therefore used as diagnostic markers describing the state of tissue environment. The origin and functions of such RNAs in human ovarian follicle, the environment of oocyte maturation, are unclear. The current study investigates the difference in the microRNA profiles of fertile women and polycystic ovary syndrome (PCOS) patients in three compartments from the same preovulatory follicle: mural granulosa cells (MGC), cell-free follicular fluid (FF), and extracellular vesicles (EV) of the FF by small RNA sequencing. In silico analysis was used for the prediction and over-representation of targeted pathways for the detected microRNAs. PCOS follicles were distinguished from normal tissue by the differential expression of 30 microRNAs in MGC and 10 microRNAs in FF (FDR < 0.1) that commonly regulate cytokine signaling pathways. The concentration of EV-s was higher in the FF of PCOS patients (p = 0.04) containing eight differentially expressed microRNAs (p < 0.05). In addition, we present the microRNA profiles of MGC, FF, and EV in the fertile follicle and demonstrate that microRNAs loaded into EVs target mRNAs of distinct signaling pathways in comparison to microRNAs in FF. To conclude, the three follicular compartments play distinct roles in the signaling disturbances associated with PCOS

    Clinical and genetic spectrum of SCN2A-associated episodic ataxia

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    Background: Pathogenic variants in SCN2A are associated with various neurological disorders including epilepsy, autism spectrum disorder and intellectual disability. Few reports have recently described SCN2A-associated episodic ataxia (EA). Our study identifies its broader clinical and genetic spectrum, and describes pharmacological approaches. Results: We report 21 patients with SCN2A-associated EA, of which 9 are unpublished cases. The large majority of patients present with epileptic seizures (18/21, 86%), often starting within the first three months of life (12/18, 67%). In contrast, onset of episodic ataxia ranged from 10 months to 14 years of age. The frequency of EA episodes ranged from brief, daily events up to 1-2 episodes per year each lasting several weeks. Potential triggers include minor head traumas and sleep deprivation. Cognitive outcome is favorable in most patients with normal or mildly impaired cognitive development in 17/21 patients (81%). No clear genotype-phenotype correlations were identified in this cohort. However, two mutational hotspots were identified, i.e. 7/21 patients (33%) harbor the identical pathogenic variant p.A263V, whereas 5/21 (24%) carry pathogenic variants that affect the S4 segment and its cytoplasmic loop within the domain IV. In addition, we identified six novel pathogenic variants in SCN2A. While acetazolamide was previously reported as beneficial in SCN2A-associated EA in one case, our data show a conflicting response in 8 additional patients treated with acetazolamide: three of them profited from acetazolamide treatment, while 5/8 did not. Conclusions: Our study describes the heterogeneous clinical spectrum of SCN2A-associated EA, identifies two mutational hotspots and shows positive effects of acetazolamide in about 50%. (C) 2019 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.Peer reviewe

    Towards a Social Trust-Aware Recommender for Teachers

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    Fazeli, S., Drachsler, H., Brouns, F., & Sloep, P. B. (2014). Towards a Social Trust-aware Recommender for Teachers. In N. Manouselis, H. Drachsler, K. Verbert & O. C. Santos (Eds.), Recommender Systems for Technology Enhanced Learning (pp. 177-194): Springer New York.Online communities and networked learning provide teachers with social learning opportunities, allowing them to interact and collaborate with others in order to develop their personal and professional skills. However, with the large number of learning resources produced everyday, teachers need to find out what are the most suitable ones for them. In this paper, we introduce recommender systems as a potential solution to this . The setting is the Open Discovery Space (ODS) project. Unfortunately, due to the sparsity of the educational datasets most educational recommender systems cannot make accurate recommendations. To overcome this problem, we propose to enhance a trust-based recommender algorithm with social data obtained from monitoring the activities of teachers within the ODS platform. In this article, we outline the re-quirements of the ODS recommender system based on experiences reported in related TEL recommender system studies. In addition, we provide empirical ev-idence from a survey study with stakeholders of the ODS project to support the requirements identified from a literature study. Finally, we present an agenda for further research intended to find out which recommender system should ul-timately be deployed in the ODS platform.NELLL, EU 7th framework Open Discovery Spac

    Rapid differential diagnosis of vaginal infections using gold nanoparticles coated with specific antibodies

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    Vaginal infections caused by bacteria, Candida and Trichomonas vaginalis, affect millions of women annually worldwide. Symptoms and signs have limited value in differential diagnosis of three causes of vaginitis. Current laboratory methods for differential diagnosis are either expensive or time consuming. Therefore, in this work, development of a method based on gold nanoparticles has been investigated for rapid diagnosis of vaginal infections. Specific antibodies against three main causes of vaginal infections were raised in rabbits. The antibodies were then purified and conjugated to gold nanoparticles and used in an agglutination test for detection of vaginal infections. Finally, sensitivity and specificity of this test for diagnosis of vaginal infections were estimated using culture method as gold standard. Purification of antibodies from sera was confirmed by electrophoresis. Construction of nanoparticles was proved by TEM and FT-IR methods. Conjugation of antibodies to gold nanoparticles was confirmed using XPS method. Sensitivity and specificity of gold nanoparticles for diagnosis of Candida species were 100%, for Gardnerella were 100% and 93%, and for T. vaginalis was 53.3% and 100%, respectively. Gold nanoparticle-based method is a simple, rapid, accurate, and cost-effective test for differential laboratory diagnosis of vaginal infection
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