Caracterización genómica de la integración in vitro del VIH-1 en células mononucleares de sangre periférica, macrófagos y células T de Jurkat

ResumenIntroducciónLa mayor parte del genoma celular es accesible a la integración retroviral; sin embargo, se propone que este proceso no es aleatorio y es dependiente de cada retrovirus.ObjetivosIdentificar y caracterizar las regiones del genoma humano en donde ocurre la integración del virus de la inmunodeficiencia humana de tipo 1 (VIH-1) en células mononucleares de sangre periférica, macrófagos y células T de Jurkat infectadas.Materiales y métodosSe seleccionaron 300 secuencias de ADN humano obtenidas por el método de ligación mediada por PCR, previamente depositadas en el GenBank. Utilizando el programa BLAST, sólo 264 de ellas se incluyeron en el estudio, pues se pudo obtener información sobre localización cromosómica, genes anotados, secuencias repetidas, número de islas CpG y tiempo medio de replicación, entre otras variables genómicas. Estas secuencias se exportaron a otras bases de datos.ResultadosEl 53% (140/264) de las integraciones se registraron en bandas G. El 70,45% de los provirus se localizaron en los genes humanos anotados, mientras que el restante lo hizo en elementos repetidos. En general, la selección del sitio de integración se relacionó con las características locales genómicas y estructurales de la cromatina, entre las que se incluyen secuencias Alu-Sx y L1, densidad génica y de islas CpG, remodelación de la cromatina y tiempo de replicación. Éstas influenciarían la interacción eficiente del complejo de preintegración con los genomas celulares.ConclusiónSe determinó que la integración del VIH-1 en los genomas celulares estudiados estaría condicionada por características diferenciales de la cromatina y por procesos epigenéticos que influirían la selección del sitio blanco de integración.AbstractIntroductionMost of the infected host cell genome is available for retroviral integration; however, it has been proposed that this process does not occur at random and depends upon each type of retrovirus.ObjectiveThe objective is to identify and characterize differences in human genome regions of peripheral blood mononuclear cells, macrophages and Jurkat T cells in which integration of HIV-1 occurs.Material and MethodsThree hundred human DNA genome sequences, previously deposited in the GenBank, were selected at random. Using program BLAST, only 264 of them were included in the study because relevant information about chromosomal position, associated genes, repetitive sequences, number of CpG islands and average replication time was available; these sequences were exported to other data bases for analysis.Results53% (140/264) of integrations were located on G bands. 70.45% of provirus was located in human genes and the rest was located in repetitive elements. In general the integration site selection was correlated with genomics and structural characteristics of cell chromatin including Alu-Sx and L1 sequences, gene and CpG island densities, remodeling of chromatin, and replication time. All of them would influence the efficient interaction between the pre-integration complex and target cell genomes.ConclusionIt was determined that HIV-1 integration in target cellular genomes would be conditioned by differential characteristics of associated chromatin and by epigenetic processes that would influence the selection of integration sites

Wnt and CDK-1 regulate cortical release of WRM-1/beta-catenin to control cell division orientation in early Caenorhabditis elegans embryos

In early Caenorhabditis elegans embryos, the Wingless/int (Wnt)- and Src-signaling pathways function in parallel to induce both the division orientation of the endomesoderm (EMS) blastomere and the endoderm fate of the posterior EMS daughter cell, called E. Here, we show that, in addition to its role in endoderm specification, the beta-catenin-related protein Worm armadillo 1 (WRM-1) also plays a role in controlling EMS division orientation. WRM-1 localizes to the cortex of cells in both embryos and larvae and is released from the cortex in a Wnt-responsive manner. We show that WRM-1 cortical release is disrupted in a hypomorphic cyclin-dependent protein kinase 1 (cdk-1) mutant and that WRM-1 lacking potential CDK-1 phosphoacceptor sites is retained at the cortex. In both cases, cortical WRM-1 interferes with EMS spindle rotation without affecting endoderm specification. Finally, we show that removal of WRM-1 from the cortex can restore WT division orientation, even when both Wnt- and Src-signaling pathways are compromised. Our findings are consistent with a model in which Wnt signaling and CDK-1 modify WRM-1 in a temporal and spatial manner to unmask an intrinsic polarity cue required for proper orientation of the EMS cell division axis

Linfoma cutáneo de células B tipo centro folicular con infiltración a médula ósea reporte de un caso

Los linfomas cutáneos primarios de células B constituyen cerca del 20-25% de todos los linfomas. Ellinfoma cutáneo primario de células B tipo centro folicular es el subtipo más frecuente y se manifiesta principalmente en pacientes adultos con una edad media de 58 años (1), la diseminación extra-cutánea es muy rara y se presenta con nódulos, tumores o placas solitarios o en grupo usualmente localizados en cabeza o tronco. Presentamos el caso de una paciente con un linfoma primario cutáneo tipo centro folicular con infiltración a médula ósea

High resting energy expenditure, less fat-free mass, and less muscle strength in HIV-infected children: a matched, cross-sectional study

Background and aimsMany improvements have been made in the treatment of human immunodeficiency virus (HIV) in pediatric patients; however, challenges remain in terms of achieving normal growth, body composition, and metabolism during treatment, etc. Current nutritional recommendations are based on studies performed in adults, with limited data on the HIV-infected pediatric population. Therefore, this study aimed to compare the resting energy expenditure (REE) of asymptomatic HIV-infected pediatric patients with healthy counterparts and to compare body composition, dietary intake, and physical activity between the two groups.MethodsThis was a cross-sectional study of asymptomatic HIV-infected children who were receiving antiretroviral therapy; the infected group was compared with the uninfected group, matched by age (± 6 months), sex, and body mass index (± 0.5 z-score). Participants were recruited between 2021 and 2022, as outpatients. In both groups, REE was determined by indirect calorimetry and body composition by bioelectrical impedance analysis and hand strength, measured using a hydraulic hand dynamometer.ResultsSeventy-eight participants were enrolled, where n = 39 HIV-infected children and n = 39 controls, with a mean age of 11.6 ± 3.4 years old. REE was significantly higher in the HIV group (1254.4 ± 334.7 kcal/day vs. 1124.7 ± 321 kcal/day, p = 0.013) than in the control group. Fat-free mass (FFM) was lower in the HIV group (28.2 ± 10.5 kg vs. 32 ± 11.2 kg, p = 0.001); this trend continued when the index skeletal muscle was evaluated (7.2 ± 1.2 vs. 7.6 ± 1.5, p = 0.04). The strength of the dominant hand was also lower in the HIV group (12 (8–18) kg vs. 20 (10.5–26) kg, p < 0.0001).ConclusionsChildren with asymptomatic HIV infection have higher REE than their uninfected peers. They also present decreased FFM, skeletal muscle mass index, and muscle strength. These parameters should be considered during nutritional assessment in this population to have a favorable impact on nutritional status and growth

Requirements for F-BAR Proteins TOCA-1 and TOCA-2 in Actin Dynamics and Membrane Trafficking during Caenorhabditis elegans Oocyte Growth and Embryonic Epidermal Morphogenesis

The TOCA family of F-BAR–containing proteins bind to and remodel lipid bilayers via their conserved F-BAR domains, and regulate actin dynamics via their N-Wasp binding SH3 domains. Thus, these proteins are predicted to play a pivotal role in coordinating membrane traffic with actin dynamics during cell migration and tissue morphogenesis. By combining genetic analysis in Caenorhabditis elegans with cellular biochemical experiments in mammalian cells, we showed that: i) loss of CeTOCA proteins reduced the efficiency of Clathrin-mediated endocytosis (CME) in oocytes. Genetic interference with CeTOCAs interacting proteins WSP-1 and WVE-1, and other components of the WVE-1 complex, produced a similar effect. Oocyte endocytosis defects correlated well with reduced egg production in these mutants. ii) CeTOCA proteins localize to cell–cell junctions and are required for proper embryonic morphogenesis, to position hypodermal cells and to organize junctional actin and the junction-associated protein AJM-1. iii) Double mutant analysis indicated that the toca genes act in the same pathway as the nematode homologue of N-WASP/WASP, wsp-1. Furthermore, mammalian TOCA-1 and C. elegans CeTOCAs physically associated with N-WASP and WSP-1 directly, or WAVE2 indirectly via ABI-1. Thus, we propose that TOCA proteins control tissues morphogenesis by coordinating Clathrin-dependent membrane trafficking with WAVE and N-WASP–dependent actin-dynamics

Phenology of Scramble Polygyny in a Wild Population of Chrysolemid Beetles: The Opportunity for and the Strength of Sexual Selection

Recent debate has highlighted the importance of estimating both the strength of sexual selection on phenotypic traits, and the opportunity for sexual selection. We describe seasonal fluctuations in mating dynamics of Leptinotarsa undecimlineata (Coleoptera: Chrysomelidae). We compared several estimates of the opportunity for, and the strength of, sexual selection and male precopulatory competition over the reproductive season. First, using a null model, we suggest that the ratio between observed values of the opportunity for sexual selections and their expected value under random mating results in unbiased estimates of the actual nonrandom mating behavior of the population. Second, we found that estimates for the whole reproductive season often misrepresent the actual value at any given time period. Third, mating differentials on male size and mobility, frequency of male fighting and three estimates of the opportunity for sexual selection provide contrasting but complementary information. More intense sexual selection associated to male mobility, but not to male size, was observed in periods with high opportunity for sexual selection and high frequency of male fights. Fourth, based on parameters of spatial and temporal aggregation of female receptivity, we describe the mating system of L. undecimlineata as a scramble mating polygyny in which the opportunity for sexual selection varies widely throughout the season, but the strength of sexual selection on male size remains fairly weak, while male mobility inversely covaries with mating success. We suggest that different estimates for the opportunity for, and intensity of, sexual selection should be applied in order to discriminate how different behavioral and demographic factors shape the reproductive dynamic of populations

The Global Alliance for Infections in Surgery : defining a model for antimicrobial stewardship-results from an international cross-sectional survey

Background: Antimicrobial Stewardship Programs (ASPs) have been promoted to optimize antimicrobial usage and patient outcomes, and to reduce the emergence of antimicrobial-resistant organisms. However, the best strategies for an ASP are not definitively established and are likely to vary based on local culture, policy, and routine clinical practice, and probably limited resources in middle-income countries. The aim of this study is to evaluate structures and resources of antimicrobial stewardship teams (ASTs) in surgical departments from different regions of the world. Methods: A cross-sectional web-based survey was conducted in 2016 on 173 physicians who participated in the AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections) project and on 658 international experts in the fields of ASPs, infection control, and infections in surgery. Results: The response rate was 19.4%. One hundred fifty-six (98.7%) participants stated their hospital had a multidisciplinary AST. The median number of physicians working inside the team was five [interquartile range 4-6]. An infectious disease specialist, a microbiologist and an infection control specialist were, respectively, present in 80.1, 76.3, and 67.9% of the ASTs. A surgeon was a component in 59.0% of cases and was significantly more likely to be present in university hospitals (89.5%, p <0.05) compared to community teaching (83.3%) and community hospitals (66.7%). Protocols for pre-operative prophylaxis and for antimicrobial treatment of surgical infections were respectively implemented in 96.2 and 82.3% of the hospitals. The majority of the surgical departments implemented both persuasive and restrictive interventions (72.8%). The most common types of interventions in surgical departments were dissemination of educational materials (62.5%), expert approval (61.0%), audit and feedback (55.1%), educational outreach (53.7%), and compulsory order forms (51.5%). Conclusion: The survey showed a heterogeneous organization of ASPs worldwide, demonstrating the necessity of a multidisciplinary and collaborative approach in the battle against antimicrobial resistance in surgical infections, and the importance of educational efforts towards this goal.Peer reviewe

The psychological science accelerator’s COVID-19 rapid-response dataset

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data