Designed Ankyrin Repeat Protein (DARPin) to target chimeric antigen receptor (CAR)-redirected T cells towards CD4+ T cells to reduce the latent HIV+ cell reservoir.

Chimeric Antigen Receptor (CAR)-redirected T cells show great efficacy in the patient-specific therapy of hematologic malignancies. Here, we demonstrate that a DARPin with specificity for CD4 specifically redirects and triggers the activation of CAR engineered T cells resulting in the depletion of CD4+ target cells aiming for elimination of the human immunodeficiency virus (HIV) reservoir.

Two-Year Effectiveness of a Controlled Trial With Physically Active Lessons on Behavioral Indicators of School Children.

Purpose: In this study, we evaluated the effectiveness of two years of an intervention with physically active lessons on indicators of sedentary behavior and physical activity measured objectively in elementary school children. Methods: A controlled clinical trial with cluster sampling was carried out in 2018 and 2019, with four classes of children in the 2nd year of elementary school. The intervention group classes received dynamic activities linked to the pedagogical content (n = 34) for 2 years. The indicators of sedentary behavior and physical activities were evaluated using ActivPal and ActiGraph GT3X accelerometers during the school shift. Crude and adjusted models of Generalized Estimation Equations with Bonferroni's post hoc were used to identify the differences between the groups (three evaluations in 2018 and two evaluations in 2019). Results: There was a reduction in stationary behavior (p = .01) and an increase in light physical activity (p = .044) during the two years. In the first year there were reductions in standing time (p = .044) and number of transitions (p ≤ .001), and an increase in walking time (p = .017). However, in the second year, the mean differences in percentage points were smaller than in the first year. No differences were found for sitting time as well as for moderate and vigorous physical activity. We observed a large effect size for all variables. Conclusions: The introduction of physically active lessons in the classroom reduced time in stationary behavior and increased time in light physical activity. However, the effects on behavior observed in the first year were not maintained in the second year of intervention.

Effects of two years of physically active lessons on cognitive indicators in children.

Our purpose was to evaluate the effect of physically active lessons (PAL) on the cognitive performance of children during two years of follow-up. Four classes (second grade of elementary school) were divided into two intervention classes (n = 34) and two control classes (n = 27). Evaluations were performed before the intervention (M1), after 3 (M2) and 9 (M3) months in the 1st year, and 14 (M4) and 18 (M5) months in the 2nd year. The intervention was based on PAL integrated with the curricular components, which stimulated the children to stand or move in the classroom. Cognitive performance was evaluated using three computerized tests for response inhibition, selective attention, and cognitive flexibility. The children in the intervention classes presented improved cognitive performance in the execution of all tasks along the two years follow-up, in both correct answers and time reactions, with exception of correct answers of visual search. For the intervention classes, in most of the tasks, the mean differences confidence interval of 95% did not include the 0 on the two last moments of evaluation, and in all cases, the mean differences of them between M1 versus M5 were significantly different with high values of effect size (cohen -d > 1). PAL promotes modest improvements in diverse cognitive functions in children.

Effects of Physically Active Lessons on Movement Behaviors, Cognitive, and Academic Performance in Elementary Schoolchildren: ERGUER/Aracaju Project.

BACKGROUND: To evaluate the effects of the introduction of physically active lessons on movement behaviors, cognitive, and academic performance in schoolchildren. METHODS: This was a cluster-controlled trial. A total of 61 students from the second year of elementary school in a public school in Brazil made up 2 intervention classes (n = 34) with the introduction of physically active lessons and 2 control classes (n = 27). Sedentary behavior, physical activity, cognitive, and academic performance were evaluated in 3 moments, which were compared using models of generalized estimating equations. RESULTS: The intervention was effective for reducing the standing time between the baseline and 3 months while increasing the walking time between baseline and 3 months and baseline and 9 months. There was a reduction in time in stationary activities and increased time in light physical activities between all moments. The intervention group increased their performance in the go/no go test, showing a smaller number of errors between the baseline and 3 months and baseline and 9 months, and a reduction in the test time between baseline and 3 months. No impact on students' academic performance was observed. CONCLUSION: Physically active lessons improve movement behaviors and cognitive functions among elementary schoolchildren.

Generation of three induced pluripotent cell lines (iPSCs) from an Aicardi-Goutières syndrome (AGS) patient harboring a deletion in the genomic locus of the sterile alpha motif and HD domain containing protein 1 (SAMHD1).

Aicardi-Goutières syndrome (AGS) is a hereditary early onset encephalopathy. AGS patients display variable clinical manifestations including intracranial calcification, cerebral atrophy, white matter abnormalities and characteristic leukocytosis as well as a constitutive upregulation of type I IFN production indicative of a type I interferonopathy. Seven genes (SAMHD1, TREX1, RNASEH2B, RNASEH2C, RNASEH2A, ADAR1, IFIH1) have been associated with the AGS phenotype, up to now. Here, we describe the generation of three induced pluripotent stem cell lines from a patient with a deletion of coding exons 14 and 15 of the SAMHD1 gene.

Induced pluripotent stem cell line (PEIi003-A) derived from an apparently healthy male individual.

Induced pluripotent stem cells (iPSCs) are a useful tool to investigate pathomechanistic and cellular processes due to their differentiation potential into different somatic cell types in vitro. Here, we have generated iPSCs from an apparently healthy male individual using an integration-free reprogramming method. The resulting iPSCs are pluripotent and display a normal karyotype. Furthermore, we demonstrate that this iPSC line can be differentiated into all three germ layers.

Induced pluripotent stem cells (iPSCs) derived from a renpenning syndrome patient with c.459_462delAGAG mutation in PQBP1 (PEIi001-A).

The Renpenning syndrome spectrum is a rare X-linked mental retardation syndrome characterized by intellectual disability, microcephaly, low stature, lean body and hypogonadism. Mutations in the polyglutamine tract binding protein 1 (PQBP1) locus are causative for disease. Here, we describe the generation of an iPSC line from a patient mutated in the polar amino acid-rich domain of PQBP1 resulting in a C-terminal truncated protein (c.459_462 delAGAG, type p.R153fs193X).

Dephosphorylation of the HIV-1 restriction factor SAMHD1 is mediated by PP2A-B55α holoenzymes during mitotic exit.

SAMHD1 is a critical restriction factor for HIV-1 in non-cycling cells and its antiviral activity is regulated by T592 phosphorylation. Here, we show that SAMHD1 dephosphorylation at T592 is controlled during the cell cycle, occurring during M/G1 transition in proliferating cells. Using several complementary proteomics and biochemical approaches, we identify the phosphatase PP2A-B55α responsible for rendering SAMHD1 antivirally active. SAMHD1 is specifically targeted by PP2A-B55α holoenzymes during mitotic exit, in line with observations that PP2A-B55α is a key mitotic exit phosphatase in mammalian cells. Strikingly, as HeLa or activated primary CD4+ T cells enter the G1 phase, pronounced reduction of RT products is observed upon HIV-1 infection dependent on the presence of dephosphorylated SAMHD1. Moreover, PP2A controls SAMHD1 pT592 level in non-cycling monocyte-derived macrophages (MDMs). Thus, the PP2A-B55α holoenzyme is a key regulator to switch on the antiviral activity of SAMHD1.