Activity

The mechanisms regulating the disassembly of branched actin networks formed by the Arp2/3 complex still remain to be fully elucidated. In addition, the impact of Arp3 isoforms on the properties of Arp2/3 are also unexplored. We now demonstrate that Arp3 and Arp3B isocomplexes promote actin assembly equally efficiently but generate branched actin networks with different disassembly rates. Arp3B dissociates significantly faster than Arp3 from the network, and its depletion increases actin stability. This difference is due to the oxidation of Arp3B, but not Arp3, by the methionine monooxygenase MICAL2, which is recruited to the actin network by coronin 1C. Substitution of Arp3B Met293 by threonine, the corresponding residue in Arp3, increases actin network stability. Conversely, replacing Arp3 Thr293 with glutamine to mimic Met oxidation promotes disassembly. The ability of MICAL2 to enhance network disassembly also depends on cortactin. see more Our observations demonstrate that coronin 1C, cortactin, and MICAL2 act together to promote disassembly of branched actin networks by oxidizing Arp3B-containing Arp2/3 complexes.Memory B cells comprise a heterogenous group of cells that differ in origin and phenotype. During the early phases of the immune response, activated B cells can differentiate into IgM-expressing memory cells, short-lived plasma cells, or seed germinal centers (GCs). The memory compartment is subsequently enriched by B cells that have been through several rounds of division and selection in the GC. Here, we report on the use of an unbiased lineage-tracking approach to explore the origins and properties of memory B cell subsets in mice with an intact immune system. We find that activated B cells continue to differentiate into memory B cells throughout the immune response. When defined on the basis of their origins, the memory B cells originating from activated B cells or GCs differ in isotype and overall gene expression, somatic hypermutation, and their affinity for antigen.As indicated by its name, V-domain Ig suppressor of T cell activation (VISTA) is thought to serve primarily as an inhibitory protein that limits immune responses. VISTA antibodies can dampen the effects of several concomitantly elicited activation signals, including TCR and TLR activation, but it is currently unclear if VISTA agonism could singly affect immune cell biology. In this study, we discovered two novel VISTA antibodies and characterized their effects on human peripheral blood mononuclear cells by scRNA/CITE-seq. Both antibodies appeared to agonize VISTA in an Fc-functional manner to elicit transcriptional and functional changes in monocytes consistent with activation. We also used pentameric VISTA to identify Syndecan-2 and several heparan sulfate proteoglycan synthesis genes as novel regulators of VISTA interactions with monocytic cells, adding further evidence of bidirectional signaling. Together, our study highlights several novel aspects of VISTA biology that have yet to be uncovered in myeloid cells and serves as a foundation for future research.

Rheumatic heart disease (RHD), a sequela of rheumatic fever characterized by permanent heart valve damage, is the leading cause of cardiac surgery in Africa. However, its pathophysiologic characteristics and genetics are poorly understood. Understanding genetic susceptibility may aid in prevention, control, and interventions to eliminate RHD.

To identify common genetic loci associated with RHD susceptibility in Black African individuals.

This multicenter case-control genome-wide association study (GWAS), the Genetics of Rheumatic Heart Disease, examined more than 7 million genotyped and imputed single-nucleotide variations. The 4809 GWAS participants and 116 independent trio families were enrolled from 8 African countries between December 31, 2012, and March 31, 2018. All GWAS participants and trio probands were screened by use of echocardiography. Data analyses took place from May 15, 2017, until March 14, 2021.

Genetic associations with RHD.

This study included 4809 African participants (2548 RHD ity was estimated to be high at 0.49 (SE = 0.12; P = 3.28 × 10-5) in Black African individuals.

This study revealed a novel candidate susceptibility locus exclusive to Black African individuals and an important heritable component to RHD susceptibility in African individuals.

This study revealed a novel candidate susceptibility locus exclusive to Black African individuals and an important heritable component to RHD susceptibility in African individuals.Neonatal care has undergone important advances involving the technology for treatment and mo nitoring, the design of care spaces, the incorporation of support professionals, and, especially, the strengthening of an organizational model in networks with centers of different levels of care. Neona tal units should be located in centers with maternity services and, ideally, with pediatric ones of an equivalent level of care. This document defines the admission and transfer criteria according to the level of care and among the different levels, respectively. The evidence recommends an individual room design due to the associated benefits such as decreased occurrence and better control of health care-associated infections, improved breastfeeding, and better interaction with parents. The sugges ted room sizes favor the implementation of the family-centered care model. These recommendations establish the possibility of performing emergency surgical procedures in the neonatal unit and define the safety criteria of the physical plant. In addition, they define the human resources according to the level of care, recognizing the time dedicated to non-direct patient care activities, , and the re quirements of non-medical professionals such as psychologists, physical and respiratory therapists, occupational therapists, speech therapists, pharmacists, dietitians, and social workers. Neonatal care should be led by the neonatologist allowing the participation of general pediatricians with training and demonstrated experience in neonatal care. Midwives and neonatal nurses should have accredited formation in such area. The purpose of this document is to update the “Recommendations on the Organization, Characteristics and Operation of Neonatology Services or Units” to serve as an orien tation and guide for the design and management of neonatal care in public and private health care centers in the country.