191 research outputs found

    Ferritin heavy chain Is the host factor responsible for HCV-Induced inhibition of apoB-100 production and is required for efficient viral infection

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    Hepatic fat export occurs by apolipoprotein B-100-containing lipoprotein production, whereas impaired production leads to liver steatosis. Hepatitis C virus (HCV) infection is associated to dysregulation of apoB-100 secretion and steatosis; however, the molecular mechanism by which HCV affects the apoB-100 secretion is not understood. Here, combining quantitative proteomics and computational biology, we propose ferritin heavy chain (Fth) as being the cellular determinant of apoB-100 production inhibition. By means of molecular analyses, we found that HCV nonstructural proteins and NS5A appear to be sufficient for inducing Fth up-regulation. Fth in turn was found to inhibit apoB-100 secretion leading to increased intracellular degradation via proteasome. Notably, intracellular Fth down-regulation by siRNA restores apoB-100 secretion. The inverse correlation between ferritin and plasma apoB-100 concentrations was also found in JFH-1 HCV cell culture systems (HCVcc) and HCV-infected patients. Finally, Fth expression was found to be required for robust HCV infection. These observations provide a further molecular explanation for the onset of liver steatosis and allow for hypothesizing on new therapeutic and antiviral strategies

    Tau Modulates VGluT1 Expression

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    Abstract Tau displacement from microtubules is the first step in the onset of tauopathies and is followed by toxic protein aggregation. However, other non-canonical functions of Tau might have a role in these pathologies. Here, we demonstrate that a small amount of Tau localizes in the nuclear compartment and accumulates in both the soluble and chromatin-bound fractions. We show that favoring Tau nuclear translocation and accumulation, by Tau overexpression or detachment from MTs, increases the expression of VGluT1, a disease-relevant gene directly involved in glutamatergic synaptic transmission. Remarkably, the P301L mutation, related to frontotemporal dementia FTDP-17, impairs this mechanism leading to a loss of function. Altogether, our results provide the demonstration of a direct physiological role of Tau on gene expression. Alterations of this mechanism may be at the basis of the onset of neurodegeneration

    household transmission and disease transmissibility of a large hav outbreak in lazio italy 2016 2017

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    Abstract A major outbreak of Hepatitis A Virus (HAV) has swept through Europe between mid-2016 and 2017, mainly within the community of men who have sex with men (MSM). Over the same period, about 1,000 outbreak-related cases of acute Hepatitis A (AHA) were recorded in Lazio region, Italy. We calibrated a Bayesian model to reconstruct likely transmission events within all 44 households where multiple infections were recorded, representing a total of 103 cases from the HAV outbreak in Lazio. Based on information on the observed times of symptom onset, we estimated for the probability distribution function of the HAV generation time and used it to compute the effective and instantaneous reproduction numbers for the considered outbreak from the overall epidemic curve (N = 998 cases). We estimated a mean generation time of 30.2 days (95%CI: 25.2-33.0) and an effective reproduction number of about 1.63 (95% CI: 1.35-1.94). Transmissibility peaked in January 2017, shortly before targeted awareness and vaccination campaigns were put in place by health authorities; however, transmission remained above the epidemic threshold until June 2017. Within households, children (0-15) and young adults (16-30) infected preferentially individuals of the same age class, whereas transmission within older age groups was substantially homogeneous. These results suggest that the implemented interventions were able to slow down HAV transmission, but not to bring it rapidly to a halt. According to our estimates of the HAV transmissibility, about 50% of the at-risk persons should be immunized to prevent similar outbreaks in the future. Our results also indicate spillover from community transmission to household members, suggesting the opportunity of vaccinating household contacts of cases to prevent further spread of the epidemics

    High-throughput sequencing of the paired human immunoglobulin heavy and light chain repertoire.

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    Each B-cell receptor consists of a pair of heavy and light chains. High-throughput sequencing can identify large numbers of heavy- and light-chain variable regions (VH and VL) in a given B-cell repertoire, but information about endogenous pairing of heavy and light chains is lost after bulk lysis of B-cell populations. Here we describe a way to retain this pairing information. In our approach, single B cells (>5 × 104 capacity per experiment) are deposited in a high-density microwell plate (125 pl/well) and lysed in situ. mRNA is then captured on magnetic beads, reverse transcribed and amplified by emulsion VH:VL linkage PCR. The linked transcripts are analyzed by Illumina high-throughput sequencing. We validated the fidelity of VH:VL pairs identified by this approach and used the method to sequence the repertoire of three human cell subsets-peripheral blood IgG+ B cells, peripheral plasmablasts isolated after tetanus toxoid immunization and memory B cells isolated after seasonal influenza vaccinatio

    Surgical site infection after caesarean section. Space for post-discharge surveillance improvements and reliable comparisons

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    Surgical site infections (SSI) after caesarean section (CS) represent a substantial health system concern. Surveying SSI has been associated with a reduction in SSI incidence. We report the findings of three (2008, 2011 and 2013) regional active SSI surveillances after CS in community hospital of the Latium region determining the incidence of SSI. Each CS was surveyed for SSI occurrence by trained staff up to 30 post-operative days, and association of SSI with relevant characteristics was assessed using binomial logistic regression. A total of 3,685 CS were included in the study. A complete 30 day post-operation follow-up was achieved in over 94% of procedures. Overall 145 SSI were observed (3.9% cumulative incidence) of which 131 (90.3%) were superficial and 14 (9.7%) complex (deep or organ/space) SSI; overall 129 SSI (of which 89.9% superficial) were diagnosed post-discharge. Only higher NNIS score was significantly associated with SSI occurrence in the regression analysis. Our work provides the first regional data on CS-associated SSI incidence, highlighting the need for a post-discharge surveillance which should assure 30 days post-operation to not miss data on complex SSI, as well as being less labour intensive

    El Taller Verde como fuente de aprendizaje e inclusión social

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    En la ciudad de Mar del Plata funciona el Centro de Día “La Casa del Ángel” cuyos concurrentes poseen discapacidad mental leve, moderada severa y/o motora. Este centro posee entre sus actividades el “Taller de Huerta”. Debido a las inclemencias climáticas y a la dificultad del trabajo al aire libre para este tipo de taller se decidió trabajar interdisciplinariamente entre el equipo terapéutico de la institución y la FCEyN (UNMdP) para solucionar estos inconvenientes. El proyecto se focaliza en la creación y adecuación de un espacio de capacitación denominado ¨TALLER VERDE¨, como lugar de: aprendizaje, fortalecimiento de autoestima, creación en hábitos de autoconsumo, seguridad alimentaria, salud humana, y entrenamiento en prácticas de formación para el auto emprendimiento e inserción social; generando así, un ámbito para aprender a emprender. La creación del TALLER VERDE implicó la adaptación de un espacio para el cultivo de especies hortícolas de plantas en condiciones de invernáculo, y el aprendizaje acerca de su cuidado y seguimiento. Realizar las tareas bajo cubierta facilita el trabajo sostenido a lo largo del año independizándolo de los cambios climáticos estacionales, brindándole a los concurrentes un ¨proyecto de vida¨ sostenible en el tiempo. En la primera etapa se aspira al autoconsumo de la producción hortícola para la elaboración de los alimentos que se proveen en el comedor institucional. Una vez adecuadas las condiciones del invernáculo para el cultivo y de las plantas durante el año, el trabajo consistirá en producir verduras para auto consumo, autoreproducir semilla y mantener las especies vegetales para luego colocar los productos en ferias locales, actividad que contribuirá para el desarrollo y sostenimiento del proyecto. Desde el punto de vista de la innovación, y a través del aporte del grupo de la FCEyN, el cultivo de las plantas implicará la formación acerca de sustratos, nutrientes y biopesticidas, especialmente seleccionados por sus condiciones de practicidad e inocuidad, tanto para el ambiente como la salud humana. Se pretende convertir al Taller-Verde en un espacio innovador y modelo para otros establecimientos, permitiendo generar una actividad educativa sostenida que integre el sentido del trabajo como constitutivo de la identidad personal, y como un elemento de gran potencialidad para generar lazos que integren la diversidad social conjuntamente con la naturaleza y con los productos de la tierra. El TALLER-VERDE constituirá un “laboratorio vivo” en el cual los concurrentes aprenderán, investigarán y experimentarán, desarrollando una cultura emprendedora, trabajando en equipo, planificando y proyectando.

    Group B streptococcal carriage, serotype distribution and antibiotic susceptibilities in pregnant women at the time of delivery in a refugee population on the Thai-Myanmar border

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    <p>Abstract</p> <p>Background</p> <p>Group B Streptococcus (GBS) is the leading cause of neonatal sepsis in the developed world. Little is known about its epidemiology in the developing world, where the majority of deaths from neonatal infections occur. Maternal carriage of GBS is a prerequisite for the development of early onset GBS neonatal sepsis but there is a paucity of carriage data published from the developing world, in particular South East Asia.</p> <p>Methods</p> <p>We undertook a cross sectional study over a 13 month period in a remote South East Asian setting on the Thai-Myanmar border. During labour, 549 mothers had a combined vaginal rectal swab taken for GBS culture. All swabs underwent both conventional culture as well as PCR for GBS detection. Cultured GBS isolates were serotyped by latex agglutination, those that were negative or had a weak positive reaction and those that were PCR positive but culture negative were additionally tested using multiplex PCR based on the detection of GBS capsular polysaccharide genes.</p> <p>Results</p> <p>The GBS carriage rate was 12.0% (95% CI: 9.4-15.0), with 8.6% positive by both culture and PCR and an additional 3.5% positive by PCR alone. Serotypes, Ia, Ib, II, III, IV, V, VI and VII were identified, with II the predominant serotype. All GBS isolates were susceptible to penicillin, ceftriaxone and vancomycin and 43/47 (91.5%) were susceptible to erythromycin and clindamycin.</p> <p>Conclusions</p> <p>GBS carriage is not uncommon in pregnant women living on the Thai-Myanmar border with a large range of serotypes represented.</p
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