Human Cerebellar Development and Transcriptomics: Implications for Neurodevelopmental Disorders

Developmental abnormalities of the cerebellum are among the most recognized structural brain malformations in human prenatal imaging. Yet reliable information regarding their cause in humans is sparse, and few outcome studies are available to inform prognosis. We know very little about human cerebellar development, in stark contrast to the wealth of knowledge from decades of research on cerebellar developmental biology…
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The authors show that only a subset of the CD4+ T cells that are present in human melanoma actually are specific for tumor antigens and that there is another set of cells that are bystanders that don't recognize tumor cells. They are confident in their finding that the cells specific for tumor antigens have a particular "signature" of what genes and surface markers they express because several groups have independently validated similar findings using complementary methods. They then use this "signature" of CD4+ T cells that recognize tumor antigens to begin to ask questions about what these cells might be doing.
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BRCA1/BARD1 Is a Nucleosome Reader and Writer

Mutations in BRCA1 and BARD1 predispose carriers to breast and ovarian cancers. The BRCA1 and BARD1 proteins form a heterodimeric complex (BRCA1/BARD1) that regulates many biological processes, including transcription and DNA double-stranded break repair. These functions are mediated by the only known enzymatic activity of BRCA1/BARD1 in its capacity as an E3 ubiquitin ligase and its role as a central hub for many large protein complexes. But the…
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Familial Long-Read Sequencing Increases Yield of De Novo Mutations

Studies of de novo mutation (DNM) have typically excluded some of the most repetitive and complex regions of the genome because these regions cannot be unambiguously mapped with short-read sequencing data. To better understand the genome-wide pattern of DNM, we generated long-read sequence data from an autism parent-child quad with an affected female where no pathogenic variant had been discovered in short-read…
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One key barrier to curative therapies for HIV is the limited understanding of HIV persistence. HIV provirus integration sites (ISs) within BACH2 are common, and almost all sites mapped to date are located upstream of the start codon in the same transcriptional orientation as the gene. These unique features suggest the possibility of insertional mutagenesis at this location. Using CRISPR/Cas9-based homology-directed repair…
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The authors used single-cell RNA-sequencing to simultaneously study the transcriptomes of newly forming embryonic hematopoietic stem cells (HSCs)and HSC-supportive niche endothelial cells, generating a transcriptional atlas of HSC development and identifying ligand-receptor interactions regulating HSC development. They then applied this knowledge to rationally design a stromal cell-independent engineered niche sufficient to generate engrafting HSCs from embryonic hemogenic precursors in vitro.
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Multiple sclerosis (MS) is a demyelinating inflammatory disease of the CNS treated by diverse disease-modifying therapies that suppress the immune system. Severe acute respiratory syndrome coronavirus 2 mRNA vaccines have been very effective in immunocompetent individuals, but whether MS patients treated with modifying therapies are afforded the same protection is not known. This study determined that dimethyl fumarate caused a…
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Leiomyosarcoma (LMS) and liposarcoma (LPS) frequently express PD-L1 but are generally resistant to PD-1/PD-L1 inhibition (ICI). Trabectedin is FDA-approved for LMS and LPS. This study aimed to evaluate the safety and efficacy of trabectedin with anti-PD-L1 antibody avelumab in patients with advanced LMS and LPS. Patients and Methods: A single-arm, open-label, Phase 1/2 study tested avelumab with trabectedin for advanced…
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Effect of Lung Pericyte-Like Cell Ablation on the Bleomycin Model of Injury and Repair

The authors have previously showed that pericyte-like cells derived from the FoxD1-lineage contribute to myofibroblasts following bleomycin-induced lung injury. However, their functional significance in lung fibrosis remains unknown. In this study, they used a model of lung pericyte-like cell ablation to test the hypothesis that pericyte-like cell ablation attenuates lung fibrosis in bleomycin-induced lung injury. Methods: Lung fibrosis was induced…
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Bifurcation of cellular fates, a critical process in development, requires histone 3 lysine 27 methylation (H3K27me3) marks propagated by the polycomb repressive complex 2 (PRC2). However, precise chromatin loci of functional H3K27me3 marks are not yet known. Here, we identify critical PRC2 functional sites at high resolution. We fused a computationally designed protein, EED binder (EB), which competes with EZH2…
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