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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.

The non-coding RNA RNU4-2, which is highly expressed in the developing human brain, is identified as a syndromic neurodevelopmental disorder gene, and, using RNA sequencing, 5′ splice-site use is shown to be systematically disrupted in individuals with RNU4-2 variants.

Microbial reduction of nitrous oxide to dinitrogen is considered negligible under acidic conditions. However, Guang He et al. show that a co-culture of two bacterial species derived from acidic tropical forest soil can reduce nitrous oxide at pH 4.5.

Patient-derived xenograft models (PDX) have been extensively used to study the molecular and clinical features of cancers. Here the authors present a cohort of 536 PDX models from 25 cancers, as well as their genomic and evolutionary profiles and their suitability for clinical trials.

Mouse models expressing liver apoE in the absence of brain apoE reveal detrimental effects of peripheral apoE4 associated with Alzheimer’s risk on cognition and amyloid pathology through compromising vascular integrity and function.

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

SEAMLESSM4T is a single machine translation tool that supports speech-to-speech translation, speech-to-text translation, text-to-speech translation, text-to-text translation and automatic speech recognition between up to 100 languages.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

Delivering genes to and across the brain vasculature efficiently and specifically across species remains challenging. Here, the authors show that endothelial-specific AAVs with serotype flexibility enable redosing and transform the brain vasculature into an in vivo biofactory in genetically diverse rodents. In primates, these vectors cross the blood-brain-barrier and show broad tropism.

Vaccines combat global influenza threats, relying on timely selection of optimal seed viruses. Here, authors introduce MAIVeSS, a machine learning assisted framework to streamline vaccine seed virus selection using genomic sequence, expediting seasonal flu vaccine production and supply.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Patient-derived xenografts provide a resource for basic and translational cancer research. Here, the authors generate multiple pediatric high-grade glioma xenografts, use omics technologies to show that they are representative of primary tumours and use them to assess therapeutic response.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

A study demonstrates that metabolic signalling and inflammatory cues associated with obesity selectively induce expression of PD-1 on tumour-associated macrophages to suppress anti-tumour immunity.

Results from a phase 1 clinical trial show that a broadly neutralizing, HIV-specific antibody is durably expressed in vivo from a viral vector, highlighting an alternate approach for the delivery of antibodies in humans.

Eitan et al. discovered genetic variants in the 3′UTR for the gene encoding IL-18 receptor that protect against ALS. The variant 3′UTR destabilizes the mRNA and dampens microglia NF-κB signaling and neurotoxicity, thus emphasizing the value of noncoding genetic association studies.

First-in-human trial of a self-assembling, ferritin nanoparticle-based influenza vaccine shows evidence that this new platform can elicit neutralizing and cross-reactive antibodies and has potential for further vaccine development.

A phase I trial of cerebellar deep brain stimulation to enhance chronic post-stroke motor rehabilitation supports the safety and feasibility of the approach while providing encouraging evidence of motor improvements.

Patients with stage 4 or unresectable stage 3 melanoma refractory to first-line anti-programmed death protein 1 (PD-1) or anti-programmed cell death 1 ligand 1 have longer progression-free survival when treated with a combination of anti-cytotoxic T-lymphocyte protein 4 (CTLA-4) and anti-PD-1 versus anti-CTLA-4 alone.

Crossing the blood–brain barrier in primates is a major obstacle to gene delivery in the brain. Here an adeno-associated virus variant (AAV.CAP-Mac) is identified and demonstrated for crossing the blood–brain barrier and delivering gene sequences to the brain of different non-human primates species.

The bacterium Helicobacter pylori, often found in the human stomach, can be classified into distinct subpopulations associated with the geographic origin of the host. Here, the authors provide insights into H. pylori population structure by collecting over 1,000 clinical strains from 50 countries and generating and analyzing high-quality bacterial genome sequences.

This study uses epi-retro-seq to link single-cell epigenomes and cell types to long-distance projections for neurons dissected from different regions projecting to different targets across the whole mouse brain.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

The early identification of metabolic disorders could improve or prevent overt disease. Here the authors show that the circulating concentration of hyocholic acid (HCA) species is decreased in the context of obesity and diabetes and increased after gastric bypass surgery in humans, and further that serum HCA species are predictive of metabolic outcomes in healthy individuals.

NOD-like receptor family pyrin domain-containing 6 (NLRP6) reduces colitis severity in a gut microbiome-dependent manner; however, in the context of murine intestinal graft-versus-host disease, NLRP6 exacerbates symptoms independently of gut microbiome composition and diversity, with NLRP6-deficient animals displaying protection against disease.

Vaccines against the WA1 SARS-CoV2 strain confer protection against other variants. However, the mechanisms underlying cross-protection are not fully understood. Here, the authors develop a method for rapid analysis of single B cells from patient samples and show that infection with a variant elicits convergent, public B cell responses to other variants.

Here, the authors integrate a photonic crystal, supporting photonic bound states in the continuum (BICs), with monolayer WSe₂, and leverage the high energy confinement of the BIC modes to demonstrate coherent directional dark exciton emission.

Using the lifespan brain chart and two large-scale cross-cultural consortia (ABIDE and CABIC), we disentangle the heterogeneity of brain morphology in ASD into two structural impairment pathways that could disrupt sensory to association functions.

Genome-wide analyses identify common variants associated with 11 distinct neuropathology endophenotypes, providing insights into the mechanisms underlying the genetic risk of Alzheimer’s disease and related dementias.

Caloric restriction is a common approach to weight reduction, however, weight regain is common. Here the authors report that caloric restriction reduces the abundance of Parabacteroides distasonis in the gut and alters serum bile acid (BA) profile, which contribute to weight regain in mice.

In two cohorts of patients with glioblastoma who received anti-PD-1, Sonabend and colleagues show that ERK1/2 phosphorylation, detected by immunohistochemistry, provides a biomarker for MAPK/ERK pathway activity and better survival on this therapy.

Here, in a cohort of mother-child dyads, the authors show that maternal prenatal social disadvantage and psychosocial stressors associate with distinct gut microbiome taxonomic and functional diversity in both the mothers and their four-month children.

Multi-cohort analysis of single cell and bulk transcriptional data combined with in vitro and in vivo experiments highlight the role of IL1R2+ myeloid cells on tissue injury during severe infection.

Ding and colleagues use bulk, single-cell and single-nucleus multi-omics together with spatial transcriptomics and multiplex imaging of clinical tumor samples to characterize gene expression and chromatin accessibility of breast cancer lineages.

Results from BALANCED, a phase 2a, multicenter, randomized controlled trial testing efruxifermin (a long-acting Fc-FGF21 fusion protein) over 16 weeks, demonstrated significant reductions in the hepatic fat fraction in patients with F1–F3 stage non-alcoholic steatohepatitis.

Thermal models predict that spreading velocity at mid-ocean rifts should influence the geometry of the underlying magma chamber. InSAR data from the slow-spreading Ethiopian Rift identify a shallow, elongated magma chamber—a feature usually associated with fast-spreading rifts—beneath the Erta Ale segment, implying that spreading velocity may not be so important after all.

Several studies show that APOE-ε4 coding variants are associated with Alzheimer’s disease (AD) risk. Here, Zhou et al. perform fine-mapping of the APOE region and find AD risk haplotypes with non-coding variants in the PVRL2 and APOC1 regions that are associated with relevant endophenotypes.

PD-L1 on tumor cells exerts an important dampening effect on T cells via their expression of PD-1. Miller and colleagues find that PD-L1 ‘back-signaling’ into T cells and macrophages can also dampen immune responses within the tumor microenvironment.

Emerging findings identify important roles for brain lipoprotein receptors in the control of whole-body energy homoeostasis. Here Lee et al. reveal that IDOL-mediated regulation of VLDLR abundance in neurons, but not in peripheral metabolic tissues, regulates food intake and energy expenditure.