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Quantifying intact proviruses is key to understanding decreases in HIV reservoirs but results can differ depending on the method. To balance sensitivity and specificity of two assays, the authors use mathematical models and measurements of intact and defective proviruses to assess how misclassification can impact estimates of natural and therapeutic reservoir reduction.

Using data from the Tara Pacific expedition, this study reports the biogeography and the diversity of microbiomes collected from corals, fish and plankton in 99 reefs across the Pacific Ocean. The large richness of Pacific Ocean reef microorganisms, when extrapolated to all fish and corals of the Pacific, represents the current estimated total prokaryotic diversity for the entire Earth.

Integration of GWAS and single-cell transcriptomic data from the entire nervous system systematically identifies cell types underlying brain complex traits and provides insights into the etiology of Parkinson’s disease.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Epilepsies are common brain disorders and are classified based on clinical phenotyping, imaging and genetics. Here, the authors perform genome-wide association studies for 3 broad and 7 subtypes of epilepsy and identify 16 loci - 11 novel - that are further annotated by eQTL and partitioned heritability analyses.

Modeling analysis from the Global Dietary Database estimated that 70% of new global cases of type 2 diabetes are attributable to suboptimal intake of 11 dietary factors, with substantial differences in dietary risks across world regions and nations.

The development of asthma following eczema is known as the atopic march. Here the authors conduct a GWAS on affected children and identify two novel loci associated with the disease phenotype.

The synaptic vesicle protein 2 family are essential membrane proteins found in the brain that bind synaptotagmin and are targeted by anti-seizure medications. Structures reveal common features found in transport proteins, and the basis of ligand binding and selectivity.

International challenges have become the de facto standard for comparative assessment of image analysis algorithms. Here, the authors present the results of a biomedical image segmentation challenge, showing that a method capable of performing well on multiple tasks will generalize well to a previously unseen task.

Broadly neutralising anti-HIV-1 antibody (bNAb) administration in nonhuman primates has been shown to stimulate adaptive T cell-specific immunity, with infection prevention observed. In this work, the authors longitudinally analyse HIV-1 specific cellular immunity in HIV-1- infected individuals starting ART with or without adjunctive bNAb treatment.

Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn’s disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.

Witte et al show that previously acquired substitutions in the SARS-CoV-2 spike protein enable the acquisition of new antibody escape substitutions. New and old substitutions interact to enable escape from broadly neutralizing antibodies.

Philippe Froguel and colleagues report that common nonsynonymous variants in PCSK1, encoding a prohormone convertase, confer risk of obesity in individuals of European ancestry.

A clinical study shows that immunotherapy with anti-HIV-1 antibodies maintains prolonged viral suppression after anti-retroviral treatment is discontinued and affects the size and composition of the intact but not the defective proviral reservoir.

This study examines the impact of herbivorous insects on biogeochemical cycling within forests. From a global network of 74 plots within 40 mature, undisturbed broadleaved forests, they show that background levels of insect herbivory are sufficiently large to alter both ecosystem element cycling and influence terrestrial carbon cycling.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

Wobble uridine (U₃₄) tRNA modifications are important for the decoding of AA-ending codons. Here the authors show that while the U₃₄-codon content of mRNAs are predictive of changes in ribosome translation elongation, the resulting outcome in protein expression also relies on specific hydrophilic motifs-dependent protein aggregation and clearance.

Comparative analysis of inactive/active-state structures reveals molecular mechanistic maps of activation of the major GPCR classes. The findings and new approaches lay the foundation for targeted receptor-function studies and drugs with desired modalities.

Emerging SARS-CoV-2 mutants may escape neutralization by antibodies. Here, the authors use deep mutational scanning to identify mutations in the RBD that escape human monoclonal antibodies or convalescent plasmas.

By studying individuals along a spectrum of cardiometabolic disease and adjusting for effects of lifestyle and medication, this investigation identifies alterations of the metabolome and microbiome from dysmetabolic conditions, such as obesity and type 2 diabetes, to ischemic heart disease.

Individual memory antibodies selected over time by natural infection with SARS-CoV-2 have greater potency and breadth than antibodies elicited by vaccination, whereas the overall neutralizing potency of plasma is greater following vaccination.

Obenauf and colleagues report that acquired resistance to BRAF and MEK inhibitors in melanoma confers cross-resistance to immune checkpoint blockade by fostering a cancer cell–instructed, immune-evasive tumor microenvironment.

A third dose of an mRNA vaccine against SARS-CoV-2 results in an expanded B cell repertoire that produces antibodies with increased potency and breadth.

Pressure ridges, a characteristic feature of Arctic sea ice, play an important role in the ecosystem but pose challenges to shipping. Here the authors use aircraft measurements to document a decline in both the frequency and height of these pressure ridges in recent decades.

Follicular and marginal zone B (FoB and MZB, respectively) cells have divergent metabolic characteristics. Here the authors show that deficiency of glutamate cysteine ligase (Gclc), the enzyme for glutathione synthesis, differentially impacts FoB and MZB homeostasis, while specifically impeding FoB activation and downstream antiviral immunity.

A complex range of mutations within the SARS-CoV-2 spike protein is needed to escape polyclonal plasma neutralizing antibodies, and plasma from individuals who were first infected then vaccinated display the greatest resilience to escape mutations.

West and colleagues develop the Variant Database software tool for examination of changing Spike mutations in SARS-CoV-2 genomes. The authors use this to detect emerging lineages of SARS-CoV-2 in New York and report the rapid spread of the B.1.526 lineage in the city.

An analysis of 2,173 individuals from the MetaCardis cohort quantifies the individual and combinatorial effects of a range of drugs on host health, metabolome and gut microbiome in cardiometabolic disease.

The peripheral nervous system uses neuroimmune cardiovascular interfaces to assemble a structural artery–brain circuit, and therapeutic intervention in the artery–brain circuit attenuates atherosclerosis.

In a cohort of 87 individuals with COVID-19, the memory B cell response at 6.2 months after the onset of disease evolves in a manner that is consistent with the persistence of SARS-CoV-2 antigen.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

In a large cohort of patients who underwent aortic valve replacement, antibody responses to glycans present in bioprosthetic heart valves, notably galactose-α1,3-galactose and N-glycolylneuraminic acid, were implicated in valve calcification and deterioration.

The molecular mechanisms underlying contextual fear memory consolidation by sparse dentate gyrus (DG) neuronal populations remain unclear. Here using unbiased RNA sequencing of DG engram neurons the authors identify persistent transcriptome modifications during memory consolidation, in which CREB-dependent transcription features prominently

Identifying ligands which activate the specific effectors driving particular in vivo drug effects remains challenging. Here, the authors apply unsupervised clustering of pharmacodynamic parameters to classify GPCR ligands into different categories with similar signaling profiles and shared frequency of report of side effects.

Results of fine-mapping 94 inflammatory bowel disease loci using high-density genotyping in 67,852 individuals and several new fine-mapping methods.

Three-dimensional seismic data is used to reconstruct the flank collapse of Kolombo volcano in 1650, which led to a catastrophic tsunami event.

Manchado and colleagues combine CRISPR screening and transcriptomics to identify INPP5A as a dependency and therapeutic target in uveal melanoma driven by mutations in GNAQ/GNA11 and show that IP4 levels correlate with sensitivity to INPP5A loss.

A tethered macrocyclic peptide antibiotic class described here—which shows potent antibacterial activity against carbapenem-resistant Acinetobacter baumannii—blocks the transport of bacterial lipopolysaccharide from the inner membrane to its destination on the outer membrane through inhibition of the LptB₂FGC complex.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

How autophagy supports tumor cell metabolism is not fully clear. Here, the authors show that autophagy regulates lipid availability to support mitochondrial oxidative metabolism through mitochondria-endoplasmic reticulum contact sites, necessary for cell proliferation in AML.

A cross-sectional analysis of participants in the MetaCardis Body Mass Index Spectrum cohort finds that the higher prevalence of gut microbiota dysbiosis in individuals with obesity is not observed in those who take statin drugs.

A chemogenomic approach to explore activity of the free fatty acid receptor FFA2 independently of the related FFA3 shows that FFA2 in differentiated adipocytes and colonic crypt cells in mice is responsible for regulated lipolysis and GLP-1 release.

Peripheral macrophages located along motor axons react differently to neurodegeneration compared to CNS microglia in ALS mice. Modifying peripheral macrophages suppresses proinflammatory microglial responses, shifting them toward neuronal support.

Gut microbial metabolism of nutrients contributes to metabolic diseases, and the histidine metabolite imidazole propionate (ImP) is produced by type 2 diabetes (T2D) associated microbiome. Here the authors report that circulating ImP levels are increased in subjects with prediabetes or T2D in three European populations, and this increase associates with altered gut microbiota rather than dietary histidine.