Begomovirus quasispecies adapt to hosts by exploring different sequence space without changing their consensus sequences

Geminiviruses possess single-stranded circular DNA genomes that depend on cellular polymerases for replication in the host nucleus. In plant hosts, geminivirus populations behave as ensembles of mutant and recombinant genomes. This favours the emergence of new geminivirus strains able to produce new diseases or overcome the genetic resistance of cultivars. In warm and temperate areas several whitefly-transmitted geminiviruses of the genus Begomovirus cause the tomato yellow leaf curl disease (TYLCD) with important economic consequences. TYLCD is frequently controlled in commercial tomato production using the Ty-1 resistance gene. Over a 45 day period we studied the evolution of infectious clones from three TYLCD-associated begomoviruses: Tomato yellow leaf curl Sardinia virus, Tomato yellow leaf curl virus and the recombinant Tomato yellow leaf curl Axarquia virus. The evolution of their viral progeny was examined in susceptible tomato (ty1/ty1), resistant tomato (Ty1/ty1), common bean, and the wild reservoir Solanum nigrum. We found that in addition to affecting viral accumulation kinetics, the host influenced the sequence space explored by these begomoviruses. In tomato, viral dynamics was not influenced by the presence of the Ty-1 gene. Interestingly, positive adaptation of the coat protein gene was only observed in the common bean and S. nigrum, which correlates with these plants having viral quasispecies with the highest degree of complexity and heterogeneity. Our results underline the importance of analysing the mutant spectra of begomovirus infections, especially in wild reservoirs, which have the potential to give rise to large numbers of emergent variants in spite of the invariance of their consensus sequences.Junta de Andalucía proyecto: P10-CVI-6561. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

MicroRNAs and HIV-1 Infection: Antiviral Activities and Beyond

AbstractCellular microRNAs (miRNAs) are an important class of small, non-coding RNAs that bind to host mRNAs based on sequence complementarity and regulate protein expression. They play important roles in controlling key cellular processes including cellular inception, differentiation and death. While several viruses have been shown to encode for viral miRNAs, controversy persists over the expression of a functional miRNA encoded in the human immunodeficiency virus type 1 (HIV-1) genome. However, it has been reported that HIV-1 infectivity is influenced by cellular miRNAs. Either through directly targeting the viral genome or by targeting host cellular proteins required for successful virus replication, multiple cellular miRNAs seem to modulate HIV-1 infection and replication. Perhaps as a survival strategy, HIV-1 may modulate proteins in the miRNA biogenesis pathway to subvert miRNA-induced antiviral effects. Global expression profiles of cellular miRNAs have also identified alterations of specific miRNAs post-HIV-1 infection both in vitro and in vivo (in various infected patient cohorts), suggesting potential roles for miRNAs in pathogenesis and disease progression. However, little attention has been devoted in understanding the roles played by these miRNAs at a cellular level. In this manuscript, we review past and current findings pertaining to the field of miRNA and HIV-1 interplay. In addition, we suggest strategies to exploit miRNAs therapeutically for curbing HIV-1 infectivity, replication and latency since they hold an untapped potential that deserves further investigation

Effectiveness of online interventions in preventing depression: a protocol for systematic review and meta-analysis of randomised controlled trials

IntroductionAlthough evidence exists for the efficacy of psychosocial interventions in preventing depression, little is known about its prevention through online interventions. The objective of this study is to conduct a systematic review and meta-analysis of randomised controlled trials assessing the effectiveness of online interventions in preventing depression in heterogeneous populations.Methods and analysisWe will conduct a systematic review and meta-analysis of randomised controlled trials that will be identified through searches of PubMed, PsycINFO, WOS, Scopus, OpenGrey, Cochrane Central Register of Controlled Trials, ClinicalTrials. gov and Australia New Zealand Clinical Trials Register . We will also search the reference lists provided in relevant studies and reviews. Experts in the field will be contacted to obtain more references. Two independent reviewers will assess the eligibility criteria of all articles, extract data and determine their risk of bias (Cochrane Collaboration Tool). Baseline depression will be required to have been discarded through standardised interviews or validated self-reports with standard cut-off points. The outcomes will be the incidence of new cases of depression and/or the reduction of depressive symptoms as measured by validated instruments. Pooled standardised mean differences will be calculated using random-effect models. Heterogeneity and publication bias will be estimated. Predefined sensitivity and subgroup analyses will be performed. If heterogeneity is relevant, random-effect meta-regression will be performed

The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors

<p>Abstract</p> <p>Background</p> <p>HIV-1 infects macrophages and microglia in the brain and can cause neurological disorders in infected patients. We and others have shown that brain-derived envelope glycoproteins (Env) have lower CD4 dependence and higher avidity for CD4 than those from peripheral isolates, and we have also observed increased fusogenicity and reduced sensitivity to the fusion inhibitor T-1249. Due to the genetic differences between brain and spleen <it>env </it>from one individual throughout gp120 and in gp41's heptad repeat 2 (HR2), we investigated the viral determinants for the phenotypic differences by performing functional studies with chimeric and mutant Env.</p> <p>Results</p> <p>Chimeric Env showed that the V1/V2-C2-V3 region in brain's gp120 determines the low CD4 dependence and high avidity for CD4, as well as macrophage tropism and reduced sensitivity to the small molecule BMS-378806. Changes in brain gp41's HR2 region did not contribute to the increased fusogenicity or to the reduced sensitivity to T-1249, since a T-1249-based peptide containing residues found in brain's but not in spleen's HR2 had similar potency than T-1249 and interacted similarly with an immobilized heptad repeat 1-derived peptide in surface plasmon resonance analysis. However, the increased fusogenicity and reduced T-1249 sensitivity of brain and certain chimeric Env mostly correlated with the low CD4 dependence and high avidity for CD4 determined by brain's V1-V3 region. Remarkably, most but not all of these low CD4-dependent, macrophage tropic envelopes glycoproteins also had increased sensitivity to the novel allosteric entry inhibitor HNG-105. The gp120's C2 region asparagine 283 (N283) has been previously associated with macrophage tropism, brain infection, lower CD4 dependence and higher CD4 affinity. Therefore, we introduced the N283T mutation into an <it>env </it>clone from a brain-derived isolate and into a brain tissue-derived <it>env </it>clone, and the T283N change into a spleen-derived <it>env </it>from the same individual; however, we found that their phenotypes were not affected.</p> <p>Conclusion</p> <p>We have identified that the V1-V3 region of a brain-derived envelope glycoprotein seems to play a crucial role in determining not only the low CD4 dependence and increased macrophage tropism, but also the augmented fusogenicity and reduced sensitivity to T-1249 and BMS-378806. By contrast, increased sensitivity to HNG-105 mostly correlated with low CD4 dependence and macrophage tropism but was not determined by the presence of the brain's V1-V3 region, confirming that viral determinants of phenotypic changes in brain-derived envelope glycoproteins are likely complex and context-dependent.</p

The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors

<p>Abstract</p> <p>Background</p> <p>HIV-1 infects macrophages and microglia in the brain and can cause neurological disorders in infected patients. We and others have shown that brain-derived envelope glycoproteins (Env) have lower CD4 dependence and higher avidity for CD4 than those from peripheral isolates, and we have also observed increased fusogenicity and reduced sensitivity to the fusion inhibitor T-1249. Due to the genetic differences between brain and spleen <it>env </it>from one individual throughout gp120 and in gp41's heptad repeat 2 (HR2), we investigated the viral determinants for the phenotypic differences by performing functional studies with chimeric and mutant Env.</p> <p>Results</p> <p>Chimeric Env showed that the V1/V2-C2-V3 region in brain's gp120 determines the low CD4 dependence and high avidity for CD4, as well as macrophage tropism and reduced sensitivity to the small molecule BMS-378806. Changes in brain gp41's HR2 region did not contribute to the increased fusogenicity or to the reduced sensitivity to T-1249, since a T-1249-based peptide containing residues found in brain's but not in spleen's HR2 had similar potency than T-1249 and interacted similarly with an immobilized heptad repeat 1-derived peptide in surface plasmon resonance analysis. However, the increased fusogenicity and reduced T-1249 sensitivity of brain and certain chimeric Env mostly correlated with the low CD4 dependence and high avidity for CD4 determined by brain's V1-V3 region. Remarkably, most but not all of these low CD4-dependent, macrophage tropic envelopes glycoproteins also had increased sensitivity to the novel allosteric entry inhibitor HNG-105. The gp120's C2 region asparagine 283 (N283) has been previously associated with macrophage tropism, brain infection, lower CD4 dependence and higher CD4 affinity. Therefore, we introduced the N283T mutation into an <it>env </it>clone from a brain-derived isolate and into a brain tissue-derived <it>env </it>clone, and the T283N change into a spleen-derived <it>env </it>from the same individual; however, we found that their phenotypes were not affected.</p> <p>Conclusion</p> <p>We have identified that the V1-V3 region of a brain-derived envelope glycoprotein seems to play a crucial role in determining not only the low CD4 dependence and increased macrophage tropism, but also the augmented fusogenicity and reduced sensitivity to T-1249 and BMS-378806. By contrast, increased sensitivity to HNG-105 mostly correlated with low CD4 dependence and macrophage tropism but was not determined by the presence of the brain's V1-V3 region, confirming that viral determinants of phenotypic changes in brain-derived envelope glycoproteins are likely complex and context-dependent.</p

El derecho al trabajo y la estabilidad laboral en el marco de la pandemia covid-19, marzo – junio 2020.

El propósito de la investigación consistió en analizar la garantía del derecho al trabajo y la estabilidad laboral por parte del Estado salvadoreño en el marco de la pandemia COVID-19, en el sector formal e informal y sus afectaciones así como identificar las acciones que el Estado Salvadoreño tomó para minimizarlas. Si bien es cierto el estudio se centró principalmente en el Derecho al Trabajo y a la Estabilidad Laboral, la afectación causada por este fenómeno ha sido a nivel mundial y en diversidad de derechos humanos. La necesidad surgida a partir de le emergencia sanitaria acaecida y las vulneraciones a la estabilidad y el derecho laboral debido a las medidas tomadas por el gobierno de El Salvador, pretendiendo detener los contagios masivos en la población, permitió a las investigadoras retomar la población muestra, quienes solicitaron apoyo legal ante las suspensiones de contratos, los despidos en período de pandemia y la falta de medidas de seguridad dentro de los centros de trabajo, entre otras situaciones presentadas. Medidas que de forma preliminar supusieron un resguardo a la crisis, posteriormente se tornaron en afectaciones graves en la población y sus medios de subsistencia, poniéndolos en riesgo y hasta suspendiéndolos, al punto de la desesperación de las personas por garantizar a sus familias las necesidades básicas, los derechos a la alimentación, educación, entre otros, situación que permitió la intervención en relación con asesorías legales a la población que la requirió. Finalmente, la investigación de tipo documental permitió conocer la postura y pronunciamientos de organismos internacionales ante las medidas tomadas por los Estados e incluir comparativos entre diversos países, de tal manera que se recomiendan ideas para toma de decisiones más acertadas durante las crisis

Satisfação da gestante com a assistência ao parto e pós-parto e variáveis ​​associadas

[Abstract] Objective: To determine the level of satisfaction with childbirth and the postpartum period. Method: This is a longitudinal, observational study. Clinical variables of the patients and delivery were collected, and a descriptive and inferential analysis was performed. The validated state-trait anxiety inventory (STAI) and the satisfaction survey Care in Obstetrics Measure For Testing Satisfaction Scale (COMFORTS) in Spanish were used. Results: A total of 381 women was included in the study and grouped into satisfied vs. dissatisfied (94.54% vs. 5.46%). Women having given birth by eutocic delivery (p = 0.005), as well as those who had skin-to-skin time with their newborn (p = 0.012) after delivery, report more satisfaction. Mothers who were separated from their babies reported being less satisfied (p = 0.004), as did those who did not meet the expectations raised in the birth plan (p = 0.013). All the women with minimal anxiety are satisfied (p = 0.004), the same happening for those showing postpartum anxiety (p <0.001). Conclusion: The percentage of satisfied women is high; it is necessary to monitor childbirth and postpartum care, promoting good practices in childbirth care, as well as in women's emotional well-being.[Resumen] Objetivo: Determinar el grado de satisfacción en el parto y puerperio. Método: Estudio observacional longitudinal. Se recogieron variables clínicas de las pacientes y del parto, realizándose un análisis descriptivo e inferencial. Se utilizaron los cuestionarios validados de ansiedad estado y rasgo (STAI) y la encuesta de satisfacción Care in Obstetrics Measure For Testing Satisfaction Scale (COMFORTS) en Español. Resultados: Se incluyeron en el estudio 381 mujeres que se agruparon en satisfechas vs. no-satisfechas (94,54% vs. 5,46%). Las mujeres con un parto eutócico refieren estar más satisfechas (p=0,005), así como aquellas que realizaron piel con piel con su recién nacido (p=0,012). Las madres que se separaron de sus bebés refieren estar menos satisfechas (p=0,004), al igual que las que no cumplieron las expectativas reflejadas en el plan de nacimiento (p=0,013). El 100% de las mujeres con ansiedad mínima están satisfechas (p=0,004), de igual manera sucede con el grado de ansiedad estado postparto (p<0,001). Conclusión: El porcentaje de mujeres satisfechas es elevado, es necesario cuidar la atención al parto y puerperio, fomentando las buenas prácticas de atención al parto, así como el bienestar emocional de las mujeres.[Resumo] Objetivo: Determinar o grau de satisfação no parto e puerpério. Método: Estudo observacional longitudinal. Foram coletadas variáveis clínicas das pacientes e do parto, realizando-se análise descritiva e inferencial. Foram utilizados os questionários validados de ansiedade como traço e estado (STAI) e a pesquisa de satisfação da Care in Obstetrics Measure For Testing Satisfaction Scale (COMFORTS) em espanhol. Resultados: 381 mulheres foram incluídas no estudo, agrupadas em satisfeitas vs. não satisfeitas (94,54% vs. 5,46%). Mulheres com parto eutócico relataram estar mais satisfeitas (p = 0,005), assim como aquelas que realizaram contato pele-a-pele com o recém-nascido (p = 0,012). As mães que se separaram de seus bebês relataram estar menos satisfeitas (p = 0,004), assim como aquelas que não tiveram atendidas as expectativas refletidas no plano de parto (p = 0,013). 100% das mulheres com ansiedade mínima estão satisfeitas (p = 0,004), o mesmo ocorre com o grau de ansiedade pós-parto (p <0,001). Conclusão: O percentual de mulheres satisfeitas é alto, é necessário cuidar da assistência ao parto e puerpério, promovendo boas práticas na assistência ao parto, bem como o bem-estar emocional da mulher