283 research outputs found

    Receptor chimeras demonstrate that the C-terminal domain of the human cytomegalovirus US27 gene product is necessary and sufficient for intracellular receptor localization

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    <p>Abstract</p> <p>Background</p> <p>Human cytomegalovirus (HCMV) is ubiquitous in the population but generally causes only mild or asymptomatic infection except in immune suppressed individuals. HCMV employs numerous strategies for manipulating infected cells, including mimicry of G-protein coupled receptors (GPCRs). The HCMV US27 gene product is a putative GPCR, yet no ligand or signaling has been identified for this receptor. In the present study, immunofluorescence microscopy was used to examine the cellular distribution of wild type US27, as well as US27 deletion mutants and chimeric receptors.</p> <p>Results</p> <p>In transiently transfected cells, wild type US27 was found primarily in intracellular compartments, in striking contrast to the cell surface distribution seen for the human cellular chemokine receptor CXCR3. When the N-terminal extracellular domains of the two receptors were swapped, no change in protein localization was observed. However, swapping of the C-terminal intracellular domains resulted in a significant change in receptor distribution. A chimera that contained US27 fused to the C-terminal intracellular tail of CXCR3 exhibited surface distribution similar to that of wild-type CXCR3. When the C-terminal domain of US27 was fused to CXCR3, this chimeric receptor (CXCR3/US27-CT) was found in the same intracellular pattern as wild-type US27. In addition, a US27 mutant lacking the C-terminus (US27ΔCT) failed to accumulate inside the cell and exhibited cell surface distribution. Co-localization with organelle-specific markers revealed that wild-type US27 was found predominantly in the Golgi apparatus and in endosomal compartments, whereas the US27/CXCR3-CT chimera, US27ΔCT and US27Δ348 mutants were not localized to endosomal compartments.</p> <p>Conclusions</p> <p>The results indicate that the C-terminal domain of the HCMV US27 protein, which contains a di-leucine endocytic sorting motif, is both necessary and sufficient for intracellular localization, which may also help explain why no cellular ligands have yet been identified for this viral receptor.</p

    Modelos de optimización aplicados al aprovechamiento de lactosuero en pymes de Santa Fe

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    El suero de leche es un subproducto de la fabricación de queso, es una fuente importante de nutrientes, pero aún hoy es subutilizado en muchas partes del mundo. El objetivo de este proyecto fue aplicar herramientas de Investigación Operativa para proponer soluciones sobre la localización de la planta centralizadora y el ruteo de recolección, de diseño de procesos de agregado de valor y de herramientas financieras para el análisis de costos y de rentabilidad. La propuesta desarrollada para alcanzar este objetivo se aplicó bajo la hipótesis de la conformación de una estructura asociativa con un grupo de PyMEs queseras de la Cuenca Central de Santa Fe, que aportarán un volumen diario aproximado de 530.000 litros de suero de queso a una planta centralizadora. Aplicando los modelos desarrollados, surge que la planta centralizadora se ubicará en el parque industrial de Rafaela, con un ruteo optimizado para minimizar el costo de transporte. Considerando los precios de venta internacionales, el potencial de crecimiento de los respectivos mercados, los niveles tecnológicos asociados y el aprovechamiento de los retenidos y permeados, se propone producir en dos líneas distintas tres derivados del suero: WPC80 (concentrado de proteínas de suero al 80%), Permeado de UF (para producción de lactosa), y D3011 (suero en polvo desmineralizado al 30%).EEA RafaelaFil: Paez, Roxana Beatriz. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Granata, V. Universidad Nacional en Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Carrera Ingeniería Industrial; ArgentinaFil: DeVito, M. Universidad Nacional en Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Carrera Ingeniería Industrial; ArgentinaFil: Karlen, Joselina. Instituto Nacional de Tecnología Industrial Lácteos; ArgentinaFil: Taverna, Miguel Angel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; Argentin

    On the spectrum of Farey and Gauss maps

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    In this paper we introduce Hilbert spaces of holomorphic functions given by generalized Borel and Laplace transforms which are left invariant by the transfer operators of the Farey map and its induced version, the Gauss map, respectively. By means of a suitable operator-valued power series we are able to study simultaneously the spectrum of both these operators along with the analytic properties of the associated dynamical zeta functions.Comment: 23 page

    A hippocampal circuit linking dorsal CA2 to ventral CA1 critical for social memory dynamics

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    Recent results suggest that social memory requires the dorsal hippocampal CA2 region as well as a subset of ventral CA1 neurons. However, it is unclear whether dorsal CA2 and ventral CA1 represent parallel or sequential circuits. Moreover, because evidence implicating CA2 in social memory comes largely from long-term inactivation experiments, the dynamic role of CA2 in social memory remains unclear. Here, we use pharmacogenetics and optogenetics in mice to acutely and reversibly silence dorsal CA2 and its projections to ventral hippocampus. We show that dorsal CA2 activity is critical for encoding, consolidation, and recall phases of social memory. Moreover, dorsal CA2 contributes to social memory by providing strong excitatory input to the same subregion of ventral CA1 that contains the subset of neurons implicated in social memory. Thus, our studies provide new insights into a dorsal CA2 to ventral CA1 circuit whose dynamic activity is necessary for social memory.We thank David H. Brann and the other members of the Siegelbaum laboratory for helpful discussions and João Cerqueira for critical input. This work was supported by R01 MH104602 and R01 MH106629 from the NIH (S.A.S.), by PD/BD/113700/2015 from the Portuguese Foundation for Science and Technology (T.M.) and by the European Molecular Biology Organization (A.O.)

    Development of a nursing intervention to facilitate optimal antiretroviral-treatment taking among people living with HIV

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    <p>Abstract</p> <p>Background</p> <p>Failure by a large portion of PLHIV to take optimally ARV treatment can have serious repercussions on their health. The absence of a systematic treatment-taking promotion program in Quebec prompted stakeholders to develop jointly a theory- and evidence-based nursing intervention to this end. This article describes the results of a collective effort by researchers, clinicians and PLHIV to share their knowledge and create an appropriate intervention.</p> <p>Methods</p> <p>Intervention mapping was used as the framework for developing the intervention. First, the target population and environmental conditions were analyzed and a literature review conducted to identify predictors of optimal treatment taking. The predictors to emerge were self-efficacy and attitudes. Performance objectives were subsequently defined and crossed-referenced with the predictors to develop a matrix of change objectives. Then, theories of self-efficacy and persuasion (the predictors to emerge from step 1), together with practical strategies derived from these theories, were used to design the intervention. Finally, the sequence and content of the intervention activities were defined and organized, and the documentary material designed.</p> <p>Results</p> <p>The intervention involves an intensive, personalized follow-up over four direct-contact sessions, each lasting 45–75 minutes. Individuals are engaged in a learning process that leads to the development of skills to motivate themselves to follow the therapeutic plan properly, to overcome situations that make taking the antiretroviral medication difficult, to cope with side-effects, to relate to people in their social circle, and to deal with health professionals.</p> <p>Conclusion</p> <p>The intervention was validated by various health professionals and pre-tested with four PLHIV. Preliminary results support the suitability and viability of the intervention. A randomized trial is currently underway to verify the effectiveness of the intervention in promoting optimal antiretroviral treatment taking.</p

    Inhibition of Nipah Virus Infection In Vivo: Targeting an Early Stage of Paramyxovirus Fusion Activation during Viral Entry

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    In the paramyxovirus cell entry process, receptor binding triggers conformational changes in the fusion protein (F) leading to viral and cellular membrane fusion. Peptides derived from C-terminal heptad repeat (HRC) regions in F have been shown to inhibit fusion by preventing formation of the fusogenic six-helix bundle. We recently showed that the addition of a cholesterol group to HRC peptides active against Nipah virus targets these peptides to the membrane where fusion occurs, dramatically increasing their antiviral effect. In this work, we report that unlike the untagged HRC peptides, which bind to the postulated extended intermediate state bridging the viral and cell membranes, the cholesterol tagged HRC-derived peptides interact with F before the fusion peptide inserts into the target cell membrane, thus capturing an earlier stage in the F-activation process. Furthermore, we show that cholesterol tagging renders these peptides active in vivo: the cholesterol-tagged peptides cross the blood brain barrier, and effectively prevent and treat in an established animal model what would otherwise be fatal Nipah virus encephalitis. The in vivo efficacy of cholesterol-tagged peptides, and in particular their ability to penetrate the CNS, suggests that they are promising candidates for the prevention or therapy of infection by Nipah and other lethal paramyxoviruses

    Research, education and capacity building priorities for violence, abuse and mental health in low- and middle-income countries: an international qualitative survey

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    Purpose Despite the World Health Organization and United Nations recognising violence, abuse and mental health as public health priorities, their intersection is under-studied in low- and middle-income countries (LMICs). International violence, abuse and mental health network (iVAMHN) members recognised the need to identify barriers and priorities to develop this field. Methods Informed by collaborative discussion between iVAMHN members, we conducted a pilot study using an online survey to identify research, education and capacity building priorities for violence, abuse and mental health in LMICs. We analysed free-text responses using thematic analysis. Results 35 senior (29%) and junior researchers (29%), non-government or voluntary sector staff (18%), health workers (11%), students (11%) and administrators (3%) completed the survey. Respondents worked in 24 LMICs, with 20% working in more than one country. Seventy-four percent of respondents worked in sub-Saharan Africa, 37% in Asia and smaller proportions in Latin America, Eastern Europe and the Middle East. Respondents described training, human resource, funding and sensitivity-related barriers to researching violence, abuse and mental health in LMICs and recommended a range of actions to build capacity, streamline research pathways, increase efficiency and foster collaborations and co-production. Conclusion The intersection between violence, abuse and mental health in LMICs is a priority for individuals with a range of expertise across health, social care and the voluntary sector. There is interest in and support for building a strong network of parties engaged in research, service evaluation, training and education in this field. Networks like iVAMHN can act as hubs, bringing together diverse stakeholders for collaboration, co-production and mutually beneficial exchange of knowledge and skills
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