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BACKGROUND. Persistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure. METHODS. The characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using next- generation sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq). RESULTS. PCs and TCs, before losing virological control, presented significantly lower total, intact, and defective proviruses compared with those of participants on antiretroviral therapy (ART). No differences were found in total and defective proviruses between PCs and TCs. However, intact provirus levels were lower in PCs compared with TCs; indeed the intact/defective HIV-DNA ratio was significantly higher in TCs. Clonally expanded intact proviruses were found only in PCs and located in centromeric satellite DNA or zinc-finger genes, both associated with heterochromatin features. In contrast, sampled intact proviruses were located in permissive genic euchromatic positions in TCs. CONCLUSIONS. These results suggest the need for, and can give guidance to, the design of future research to identify a distinct proviral landscape that may be associated with the persistent control of HIV-1 without ART. FUNDING. Instituto de Salud Carlos III (FI17/00186, FI19/00083, MV20/00057, PI18/01532, PI19/01127 and PI22/01796), Gilead Fellowships (GLD22/00147). NIH grants AI155171, AI116228, AI078799, HL134539, DA047034, MH134823, amfAR ARCHE and the Bill and Melinda Gates Foundation., Introduction Elite controllers (ECs) represent a small subset of people living with HIV-1 (PLHIV), less than 1%, who can maintain undetectable viral load in the absence of antiretroviral therapy (ART) [...]

Programmed cell death protein 1 (PD-1) is an immune checkpoint marker commonly expressed on memory T cells and enriched in latently HIV-infected [CD4.sup.+] T cells. We engineered an anti-PD-1 chimeric antigen receptor (CAR) to assess the impact of PD-1 depletion on viral reservoirs and rebound dynamics in SIVmac239-infected rhesus macaques (RMs). Adoptive transfer of anti-PD-1 CAR T cells was done in 2 SIV-naive and 4 SIV-infected RMs on antiretroviral therapy (ART). In 3 of 6 RMs, anti-PD-1 CAR T cells expanded and persisted for up to 100 days concomitant with the depletion of [PD- 1.sup.+] memory T cells in blood and tissues, including lymph node [CD4.sup.+] follicular helper T (TFH) cells. Loss of TFH cells was associated with depletion of detectable SIV RNA from the germinal center (GC). However, following CAR T infusion and ART interruption, there was a marked increase in SIV replication in extrafollicular portions of lymph nodes, a 2-log higher plasma viremia relative to controls, and accelerated disease progression associated with the depletion of [CD8.sup.+] memory T cells. These data indicate anti-PD-1 CAR T cells depleted [PD-1.sup.+] T cells, including GC TFH cells, and eradicated SIV from this immunological sanctuary., Introduction HIV infects cells of the immune system through interaction with CD4, CCR5, and CXCR4 and establishes long-lasting infections that develop into the acquired immunodeficiency syndrome if left untreated. With [...]

Rickettsioses are life-threatening vectorborne infections transmitted by several arthropods, such as ticks, lice, fleas, and mites (1,2). Rickettsial diseases are an emerging threat in Mexico, particularly in the northern regions, [...]

Highly pathogenic avian influenza (HPAI) A(H5N1) viruses grouped within hemagglutinin (HA) gene clade 2.3.4.4b are spreading globally and causing high mortality among domestic and wild birds (1). In addition, the [...]

Ultramafic ecosystems are renowned for high endemism and habitat specialization. However, most of our understanding of ultramafic plant ecology comes from Mediterranean and temperate climes, raising questions about the generalizability of plant responses to ultramafic soils. This is especially apparent in tropical ultramafic ecosystems which exhibit a wide range of endemism and differentiation between ultramafic and adjacent non-ultramafic soils. Our objectives were two-fold: 1) synthesize our understanding of tropical ultramafic plant ecology, paying particular attention to generalities that may explain variation in endemism and habitat specialization among tropical ultramafic ecosystems; and 2) define an interdisciplinary research agenda using tropical ultramafic ecosystems as a macroecological model. We demonstrate that tropical ultramafic floras are diverse and variable in plant form and function due to the interactive effects of biogeography, climate, and edaphic properties. The variable rates of endemism, specialization, and stress tolerance traits across tropical ultramafic ecosystems have implications for the management and conservation of these diverse systems. Los ecosistemas ultramaficos son reconocidos por su endemismo y especializacion del habitat. Sin embargo, la mayor parte de nuestra comprension de la ecologia vegetal ultramafica proviene de climas mediterraneos y templados, lo que plantea dudas sobre la generalizacion de las respuestas de las plantas a los suelos ultramaficos. Esto es especialmente evidente en los ecosistemas tropicales ultramaficos que exhiben una amplia gama de endemismo y diferenciacion entre suelos tropicales ultramaficos y no ultramaficos adyacentes. Nosotros teniamos dos objetivos: 1) sintetizar nuestra comprension actual de la ecologia de las plantas tropicales ultramaficas, prestando especial atencion a las generalidades que pueden explicar la variacion en el endemismo y la especializacion del habitat entre los ecosistemas tropicales ultramaficos; y 2) definir una agenda de investigacion interdisciplinaria utilizando ecosistemas ultramaficos tropicales como modelo macroecologico. Las floras tropicales ultramaficas son diversas y variables en la forma y funcion de las plantas debido a los efectos interactivos de la biogeografia, el clima y las propiedades edaficas. Las tasas variables de endemismo, especializacion y rasgos de tolerancia al estres en los ecosistemas tropicales ultramaficos tienen implicaciones para el manejo y conservacion de estos diversos sistemas. Keywords Edaphic * Endemism * Hyperaccumulator * Metallophyte * Serpentine * Unusual soil, Introduction Ultramafic (serpentine) soils have long attracted scientific attention due to their specialized flora and ecological and evolutionary implications. However, our understanding of ultramafic plant ecology remains dominated by research [...]

The demand of social skills interventions for people with ASD has grown in recent years. The main goal of this research was to study social skills: 'responding to interaction' and 'initiating interaction', and to capture whether there were differences between an initial and a final session in a program for children with ASD. Additionally, we aimed to compare social skills patterns according to the VIQ level. The sample (N = 20) was divided into 2 subgroups depending on whether the VIQ was > 90 or < 90. We employed a mixed methods approach based on a systematic observation of social behaviors. The observational design was nomothetic, follow-up, and multidimensional. Once we confirmed inter-observer reliability for the ad hoc observational instrument we performed descriptive statistics and polar coordinate analysis using LINCE software. The results show high intragroup and intergroup variability. In general, participants with VIQ 90 showed more complex patterns to initiate interactions. The polar coordinate technique was useful for detecting significant relationships between autism's social micro-behaviors. Results and information obtained through observational methodology could allow professionals to understand communication and interaction of participants., Author(s): Carlota Alcover [sup.1] , M. Ángeles Mairena [sup.2] , Jairo Rodríguez-Medina [sup.3] , Marcela Mezzatesta [sup.2] , Gemma Balañá [sup.2] , Neus Elias [sup.2] , Maria Elias [sup.2] , [...]

ASXL1 mutation frequently occurs in all forms of myeloid malignancies and is associated with aggressive disease and poor prognosis. ASXL1 recruits Polycomb repressive complex 2 (PRC2) to specific gene loci to repress transcription through trimethylation of histone H3 on lysine 27 (H3K27me3). ASXL1 alterations reduce H3K27me3 levels, which results in leukemogenic gene expression and the development of myeloid malignancies. Standard therapies for myeloid malignancies have limited efficacy when mutated ASXL1 is present. We discovered upregulation of lysine demethylase 6B (KDM6B), a demethylase for H3K27me3, in ASXLI-mutant leukemic cells, which further reduces H3K27me3 levels and facilitates myeloid transformation. Here, we demonstrated that heterozygous deletion of Kdm6b restored H3K27me3 levels and normalized dysregulated gene expression in [Asxl1.sup.Y588X]Tg hematopoietic stem/progenitor cells (HSPCs). Furthermore, heterozygous deletion of Kdm6b decreased the HSPC pool, restored their self-renewal capacity, prevented biased myeloid differentiation, and abrogated progression to myeloid malignancies in [Asxl1.sup.Y588X]Tg mice. Importantly, administration of GSK- J4, a KDM6B inhibitor, not only restored H3K27me3 levels but also reduced the disease burden in NSG mice xenografted with human ASXL1-mutant leukemic cells in vivo. This preclinical finding provides compelling evidence that targeting KDM6B may be a therapeutic strategy for myeloid malignancies with ASXL1 mutations., Introduction Additional sex combs-like 1 (ASXL1) is one of the most frequently mutated genes across the spectrum of myeloid malignancies, including chronic myelomonocytic leukemia (1, 2), myelodysplastic syndrome (MDS) (3, [...]