Search

Longitudinal metatranscriptomics in a prospective cohort of 1,164 adults hospitalized for COVID-19 reveals that azithromycin offered no apparent anti-inflammatory benefit but enriched the respiratory microbiome with potential pathogens and antimicrobial resistance genes.

The mediobasal hypothalamus plays a central role in integrating nutritional and sex-related signals to regulate energy homeostasis. Here, through snRNA-seq of the mediobasal hypothalamus in female and male mice across nutritional states, authors show that Agrp neurons are nutrition-sensitive, DA neurons exhibit transcriptional differences in a sex-dependent manner, and KNDy neurons are responsive to both sex and nutrition.

The majority of human genes can produce multiple isoforms, but studying their functional relevance requires tools to target specific isoforms. Here, the authors develop a CRISPR-based exon-exon junction-targeting strategy to achieve isoform-specific RNA knockdown.

Off-target activation of nerve fibers is an ongoing problem in bioelectronic medicines such as vagus nerve stimulation. Here, the authors show that high-frequency stimulation can selectively block nerve fibers in the vagus nerve in swine models.

The authors describe the isolation and characterization of broadly cross-neutralizing monoclonal antibodies (mAbs) against diverse H5Nx viruses from individuals who received a monovalent H5N1 vaccine 15 years ago. They identify five mAbs that potently neutralized the majority of H5 clades and protected against lethal 2.3.4.4b H5N1 infection in mice.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

MGAT1 is a glycosyltransferase critical for the synthesis and maturation of complex N-glycans. Here, the authors show that MGAT1 modulation of CD73 glycosylation and function regulates tumor immune response in triple-negative breast cancer.

Records of the Asian monsoon have been extended to 640,000 years ago, and confirm both that the 100,000-year ice age cycle results from integral numbers of precessional cycles and that insolation influences the pacing of major millennial-scale climate events.

The variability in clinical outcomes of SARS-CoV-2 infection is partly due to deficiencies in production or response to type I interferons (IFN). Here, the authors describe a FIP200-dependent lysosomal degradation pathway, independent of canonical autophagy and type I IFN, that restricts SARS-CoV-2 replication, offering insights into critical COVID-19 pneumonia mechanisms.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Weatherbee, Weberling, Gantner et al. find contrasting requirements for BMP in the anterior signalling centre and pre-implantation epiblast between mice and humans. They further find that NOTCH may be indispensable for human epiblast survival.

Birds have evolved a unique sex chromosome dosage compensation mechanism involving the male-biased microRNA (miR-2954), which is essential for male survival by regulating the expression of dosage-sensitive Z-linked genes.

Lassa virus can cause haemorrhagic fever for which no specific treatment currently exists. Here the authors have cloned 113 monoclonal antibodies from the survivors of Lassa infection and show that the majority of neutralizing antibodies target a complex of GP1 and GP2 viral proteins.

Double Asteroid Redirection Test (DART) mission impact on asteroid Dimophos resulted in an elliptical ejecta plume. Here, the authors show that this elliptical ejecta is due to the curvature of the asteroid and makes kinetic momentum transfer less efficient.

Approaches have been devised to increase the discovery rate of intrabodies but often these yield results that aren’t functional in cells. Here the authors engineer and optimise an autonomous and disulphide-free human VH domain for intracellular expression, and they identify several VH domain binders against eIF4E.

InsP₃ 3-kinase phosphorylates 1,4,5-trisphosphate (InsP₃) specifically at its secondary 3-hydroxyl group to generate a tetrakisphosphate. Here, the authors used a combination of methods to survey InsP₃ 3-kinase ligand specificity and determined that IP3K specificity surpasses that of its natural substrate, allowing it to bind diverse ligands with a primary hydroxyl in the reactive position and based on a carbohydrate moiety.

Active fluids that consume local fuels to generate movements can be utilized to promote mixing in microfluidic devices. Here, Bate et al. show a transition from diffusion-like to superdiffusion-like behaviours with mixing efficacy depending on the Péclet number and spatial distribution of activities.

Exome-sequencing analyses of a large cohort of patients with type 2 diabetes and control individuals without diabetes from five ancestries are used to identify gene-level associations of rare variants that are associated with type 2 diabetes.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

Application of synthetic glycan (SG) preparations in gnotobiotic mice colonized with a defined bacterial community composed of members of the human gut microbiota identified a SG preparation that selectively altered the fitness of multiple bacteria.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Doan et al. show that loss of cardiac NAD⁺ is sufficient to drive metabolic derangements, hypertrophic remodeling and lethal arrhythmias in adult mouse hearts, despite maintenance of ejection fraction and bioenergetics.

Both rare and common variants contribute to the aetiology of complex traits such as type 2 diabetes (T2D). Here, the authors examine the effect of coding variation on glycaemic traits and T2D, and identify low-frequency variation in GLP1Rsignificantly associated with these traits.

Current approaches to detect allograft damages non-invasively are limited and do not differentiate between cellular mechanisms. Here, the authors show that the composition of cell-free DNA in blood samples can reveal cellular causes of allograft injury after liver transplant.

Arsenic trioxide and all-trans retinoic acid combination safely cures human acute promyelocytic leukemia. Here, the authors show that this combination has potent anticancer activity in triple negative breast cancer by cooperatively targeting Pin1, a master  regulator of oncogenic signaling networks, to eliminate cancer stem cells.

The risk of developing cancer increases with age. Here, the authors address the contribution of age-dependent accumulation of senescent cells within the tumour stroma compartment and show that senescent cells increase the infiltration of myeloid-derived suppressor cells that inhibit cytotoxic T-cells, thus facilitating tumour outgrowth.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Clinical and genetic evaluation of individuals with childhood-onset amyotrophic lateral sclerosis identifies a new monogenic cause for early-onset ALS and proposes a specific metabolic mechanism leading to motor neuron disease via sphingolipid excess.

Peripheral and central circuit adaptations can be flexibly coordinated in Drosophila, and such a modular circuit organization may facilitate the evolution of mate recognition systems by allowing novel sensory modalities to become linked to male arousal.

This study presents the assembly and analysis of the genome sequence of a female domestic Duroc pig and a comparison with the genomes of wild and domestic pigs from Europe and Asia; the results shed light on the evolutionary relationship between European and Asian wild boars.

A diverse, multidisciplinary panel of 386 experts in COVID-19 response from 112 countries provides health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

Derivation of human primordial germ cell-like cells (hPGCLCs) is critical for reproductive medicine. Here, authors report the induction of hPGCLCs in a bioengineered human pluripotent stem cell culture that mimics peri-implantation human development.

Buter et al. elucidated the biological function of the terpene nucleoside 1-TbAd, which is made abundantly by virulent but not avirulent Mycobacterium tuberculosis strains, and demonstrate that 1-TbAd regulates the pH and function of host macrophage endolysosomes.

Variable susceptibility to Salmonella infection across genetically similar mice from commercial vendors is due to differential colonization of the gut microbiome by endogenous Enterobacteriaceae.

Metastatic prostate cancer can be difficult to biopsy and characterise. Here, the authors use cell-free DNA methylation analysis to illustrate changes in hypermethylation in metastatic disease.

Infections induce activation of naïve T cells for protective immunity, but insights for this host-pathogen crosstalk are still missing. Here the authors show that infection-induced type I interferon (IFN-I) signaling promote the differentiation, expansion and functional maturation of naïve CD8 T cells, particularly for low affinity clones, to enhance anti-microbial immunity.

We leverage advances in integrated photonics to generate low-noise microwaves with an optical frequency division architecture that can be low power and chip integrated.

X-ray crystallography, cryo-EM and biochemical analysis provide insight into the assembly of the bacterial Gabija complex, an anti-phage system, and reveal how viruses can evade this defence mechanism.

H2AX phosphorylation is an early response to DNA damage and is mediated by the ATM/ATR kinases. By examining the genome-wide location of γ-H2A in wild type and mutant S. cerevisiae strains, loci that tend to engage ATR (Mec1) and ATM (Tel1) are identified as a route to mapping fragile sites in this genome.

Transcriptome and functional studies in human iPSC-derived neurons suggest that the phenotypic effects of NRXN1 deletions can occur through reduction in wild-type NRXN1α isoform levels and expression of mutant NRXN1α isoforms.

Genome-wide data from 166 East Asian individuals dating to between 6000 bc and ad 1000 and from 46 present-day groups provide insights into the histories of mixture and migration of human populations in East Asia.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

Chemical validation of new drug targets is urgently required to help develop new antimalarial therapies. Here, chemical proteomic tools and selective enzyme inhibitors are combined to study protein lipidation in human malaria parasites, leading to in vitro and in vivo validation of the enzyme N-myristoyltransferase as a drug target.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

MKL1 is a key transcriptional co-activator of actin cytoskeleton genes. Here the authors show that MKL1 activation in somatic cells reduces chromatin accessibility and hinders full reprogramming to pluripotency. Reduction of MKL1, disruption of actin cytoskeleton and its links to the nucleus relieve this repression.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.