Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C).

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, "burdenMC," which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.

Structure of the microtubule anchoring factor NEDD1 bound to the γ-tubulin ring complex.

The γ-tubulin ring complex (γ-TuRC) is an essential multiprotein assembly, in which γ-tubulin, GCP2-6, actin, MZT1 and MZT2 form an asymmetric cone-shaped structure that provides a template for microtubule nucleation. The γ-TuRC is recruited to microtubule organizing centers (MTOCs), such as centrosomes and pre-existing mitotic spindle microtubules, via the evolutionarily-conserved attachment factor NEDD1. NEDD1 contains an N-terminal WD40 domain that binds to microtubules, and a C-terminal domain that associates with the γ-TuRC.

ACK1 and BRK non-receptor tyrosine kinase deficiencies are associated with familial systemic lupus and involved in efferocytosis.

Systemic lupus erythematosus (SLE) is an autoimmune disease, the pathophysiology and genetic basis of which are incompletely understood. Using a forward genetic screen in multiplex families with SLE, we identified an association between SLE and compound heterozygous deleterious variants in the non-receptor tyrosine kinases (NRTKs) and . Experimental blockade of ACK1 or BRK increased circulating autoantibodies in vivo in mice and exacerbated glomerular IgG deposits in an SLE mouse model.

Liver X receptor unlinks intestinal regeneration and tumorigenesis.

Uncontrolled regeneration leads to neoplastic transformation. The intestinal epithelium requires precise regulation during continuous homeostatic and damage-induced tissue renewal to prevent neoplastic transformation, suggesting that pathways unlinking tumour growth from regenerative processes must exist. Here, by mining RNA-sequencing datasets from two intestinal damage models and using pharmacological, transcriptomics and genetic tools, we identified liver X receptor (LXR) pathway activation as a tissue adaptation to damage that reciprocally regulates intestinal regeneration and tumorigenesis.

Ecological diversification of sea catfishes is accompanied by genome-wide signatures of positive selection.

Habitat transitions have shaped the evolutionary trajectory of many clades. Sea catfishes (Ariidae) have repeatedly undergone ecological transitions, including colonizing freshwaters from marine environments, leading to an adaptive radiation in Australia and New Guinea alongside non-radiating freshwater lineages elsewhere. Here, we generate and analyze one long-read reference genome and 66 short-read whole genome assemblies, in conjunction with genomic data for 54 additional species.

Similar Kinetics of Pulmonary SARS-CoV-2 Load in Intensive Care Unit Patients with COVID-19 Pneumonia with or Without Autoantibodies Neutralizing Type I Interferons.

Purpose: The pathogenesis of life-threatening coronavirus disease 2019 (COVID-19) pneumonia in ICU patients can involve pre-existing auto-antibodies (auto-Abs) neutralizing type I interferons (IFNs). The impact of these auto-Abs on SARS-CoV-2 clearance in the lower respiratory tract (LRT) is unclear.

Methods: We performed a retrospective study in 99 ICU patients with COVID-19 pneumonia between March and May 2020.

A new stress test for ryanodine receptors.

JGP study (Steinz et al. https://doi.org/10.

Clinical benefit with tebentafusp in a patient with GNAQ mutant metastatic blue nevus-associated melanoma.

Melanoma arising in association with a blue nevus (BN) is rare but has molecular similarities to uveal melanoma (UM), including GNAQ/11 mutations. Tebentafusp was recently approved for UM based on improved overall survival in a phase 3 study. We hypothesized that tebentafusp may be active in BN-associated melanoma.

C. elegans PPEF-type phosphatase (Retinal degeneration C ortholog) functions in diverse classes of cilia to regulate nematode behaviors.

Primary (non-motile) cilia represent structurally and functionally diverse organelles whose roles as specialized cellular antenna are central to animal cell signaling pathways, sensory physiology and development. An ever-growing number of ciliary proteins, including those found in vertebrate photoreceptors, have been uncovered and linked to human disorders termed ciliopathies. Here, we demonstrate that an evolutionarily-conserved PPEF-family serine-threonine phosphatase, not functionally linked to cilia in any organism but associated with rhabdomeric (non-ciliary) photoreceptor degeneration in the Drosophila rdgC (retinal degeneration C) mutant, is a bona fide ciliary protein in C.

Exploring the Interplay Between Radioimmunoconjugates and Fcγ Receptors in Genetically Engineered Mouse Models of Cancer.

Fcγ receptors (FcγR) are responsible for many of the interactions between immunoglobulins (IgG) and immune cells. In biomedicine, this interplay is critical to the activity of several types of immunotherapeutics; however, relatively little is known about how FcγRs affect the in vivo performance of radiolabeled antibodies. A handful of recent preclinical studies suggest that binding by FcγR-and particularly FcγRI-can affect the pharmacokinetic profiles of Zr-labeled radioimmunoconjugates, but there are no extant studies in immunocompetent or genetically engineered mouse models of cancer.

A potential tool for marine biogeography: eDNA-dominant fish species differ among coastal habitats and by season concordant with gear-based assessments.

Effective ocean management asks for up-to-date knowledge of marine biogeography. Here we compare eDNA and gear-based assessments of marine fish populations using an approach that focuses on the commonest species. The protocol takes advantage of the "hollow curve" of species abundance distributions, with a minority of species comprising the great majority of individuals or biomass.

Aberrant zonal recycling of germinal center B cells impairs appropriate selection in lupus.

Autoimmune diseases such as lupus are characterized by polyclonal B cell activation, leading to the production of autoantibodies. The mechanism leading to B cell dysregulation is unclear; however, the defect may lie in selection within germinal centers (GCs). GC B cells cycle between proliferation and mutation in the dark zone and selection in the light zone (LZ).

The BAF complex enhances transcription through interaction with H3K56ac in the histone globular domain.

Histone post-translational modifications play pivotal roles in eukaryotic gene expression. To date, most studies have focused on modifications in unstructured histone N-terminal tail domains and their binding proteins. However, transcriptional regulation by chromatin-effector proteins that directly recognize modifications in histone globular domains has yet to be clearly demonstrated, despite the richness of their multiple modifications.

Tapping into the vocal learning and rhythmic synchronization hypothesis.

In this article, I present three main points that could benefit the "vocal learning and rhythmic synchronization hypothesis", encompassing neurogenetic mechanisms of gene expression transmission and single motor neuron function, classification of different behavioral motor phenotypes (e.g., spontaneous vs.

Mobile brain imaging in butoh dancers: from rehearsals to public performance.

Background: Dissecting the neurobiology of dance would shed light on a complex, yet ubiquitous, form of human communication. In this experiment, we sought to study, via mobile electroencephalography (EEG), the brain activity of five experienced dancers while dancing butoh, a postmodern dance that originated in Japan.

Results: We report the experimental design, methods, and practical execution of a highly interdisciplinary project that required the collaboration of dancers, engineers, neuroscientists, musicians, and multimedia artists, among others.

Cellular ATP demand creates metabolically distinct subpopulations of mitochondria.

Mitochondria serve a crucial role in cell growth and proliferation by supporting both ATP synthesis and the production of macromolecular precursors. Whereas oxidative phosphorylation (OXPHOS) depends mainly on the oxidation of intermediates from the tricarboxylic acid cycle, the mitochondrial production of proline and ornithine relies on reductive synthesis. How these competing metabolic pathways take place in the same organelle is not clear.

The structures of protein kinase A in complex with CFTR: Mechanisms of phosphorylation and noncatalytic activation.

Protein kinase A (PKA) is a key regulator of cellular functions by selectively phosphorylating numerous substrates, including ion channels, enzymes, and transcription factors. It has long served as a model system for understanding the eukaryotic kinases. Using cryoelectron microscopy, we present complex structures of the PKA catalytic subunit (PKA-C) bound to a full-length protein substrate, the cystic fibrosis transmembrane conductance regulator (CFTR)-an ion channel vital to human health.