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Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

The multipass membrane transporter MFSD6 localizes to the plasma membrane and acts as a host entry factor for enterovirus D68 (EV-D68) by binding directly to EV-D68 particles through its extracellular, third loop, offering a potential target to combat infections by this emerging pathogen.

Chromosomal instability occurs frequently in cancer, making it an attractive therapeutic target. Here, the authors identify KIF18A as a targetable vulnerability of cancer cells with chromosomal instability and target this using VLS-1272, a selective KIF18A inhibitor.

Second-generation oxidation boosts the production of anthropogenic organic aerosol, according to an analysis of urban haze in an experimental chamber.

Computationally designed genetically encoded proteins can be used to target surface proteins, thereby triggering endocytosis and subsequent intracellular degradation, activating signalling or increasing cellular uptake in specific tissues.

Village cultures, where multiple stem cell lines are cultured in a single dish, provide an elegant solution for population-scale studies. Here, authors show the utility of village models – showing that expression heterogeneity is largely a result of line-specific effects and not village cultures.

As synthetic biology expands, creating “drag-and-drop” regulatory tools that can achieve diverse regulatory outcomes are paramount. In this work, the Carbon Storage Regulatory Network of Escherichia coli is rewired to create synthetic post-transcriptional genetic circuits that leverage the native interactions and are composed to achieve complex bacterial computation.

The mechanisms of pathological astrocyte responses during multiple sclerosis remain unclear. Kadowaki et al. found in MS mouse models that CLEC16A suppresses astrocyte pathogenic activities related to mitochondria by boosting mitophagy.

Causality, the relationship between cause and effect, is a central concept in Einstein’s theory of relativity. Here, authors show that a causality analogue in energy-momentum space plays an important role in describing quasiparticle interactions in quantum matter.

It’s not always clear whether blood biomarkers are differentially expressed in the time course of viral infections. In this SARS-CoV-2 human challenge study, the authors identify distinct single-gene blood transcriptional biomarkers for early stages of infection or for symptomatic infection.

Infection with Omicron after vaccination produces cross-neutralizing antibodies to other variants of concern, whereas this induces a limited response to non-Omicron variants in unvaccinated individuals.

Authors perform an analysis of the patient data and risk factors to evaluate unfavorable outcomes and adverse events in adults with pulmonary tuberculosis treated with a 4-month rifapentine based regimen. Low rifapentine exposure was the most clinically significant risk factor for treatment failure and tuberculosis relapse.

The authors show that the lncRNA-derived microprotein SMIMP, which is shown to promote tumor formation, regulates cohesin core subunit binding to cis-regulatory elements and alters the expression of tumor-suppressive cell cycle regulators.

In this study, the authors show that they can induce the direct conversion of fibroblasts into nociceptor neurons via the expression of only five key transcription factors. They further confirm that these induced neurons are bona fide nociceptors by demonstrating that their expression profiles resemble that of their endogenous counterparts and show that they are responsive to common nociceptor agonists.

DeepPBS is a deep-learning model designed to predict the binding specificity of protein–DNA interactions using physicochemical and geometric contexts. DeepPBS functions across protein families and on experimentally determined as well as predicted protein–DNA complex structures.

A retrospective analysis using PCR testing, viral enrichment-based sequencing and agnostic metagenomic sequencing finds an association between adeno-associated virus type 2 and paediatric hepatitis of unknown cause.

Highly accurate antibody tests for SARS-CoV-2 are needed for surveillance in low-prevalence populations. Here, the authors find seroprevalence of less than 1% in two San Francisco Bay Area populations at the beginning of April, and that seroreactivity is generally predictive of in vitro neutralising activity.

The ATLAS Collaboration reports the observation of the electroweak production of two jets and a Z-boson pair. This process is related to vector-boson scattering and allows the nature of electroweak symmetry breaking to be probed.

Selvakumar, Clayton et al. use a porcine model of myocardial infarction and PSC-CM transplantation and identify atrial and pacemaker-like cardiomyocytes as the cause of engraftment arrhythmias and surface marker signatures to distinguish between arrhythmogenic and non-arrhythmogenic cardiomyocytes.

Results from this single-arm cohort of the BFAST trial showed that the clinical efficacy of entrectinib in patients with ROS1-positive NSCLC, selected using liquid biopsies, is consistent with that seen in previous reports where patients were selected using tissue-based testing methods.

The spatial architecture of the lung cancer microenvironment could influence the survival outlook and therapeutic options of patients. Here the authors find distinct patterns and composition of immune cells when comparing lung adenocarcinomas and lung squamous cell carcinomas, paving way for precision immune therapy according to histological subtype.

Designing an organic polymer photocatalyst for efficient hydrogen evolution in the near-infrared (NIR) light region is still a major challenge. The authors present here a series of polymer nanoparticles for a efficient hydrogen evolution under visible and NIR light irradiation, without combining or hybridizing with other materials.

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.

Efficient mitophagy is essential for neuronal health. A study now shows that loss of VPS13D in neurons impairs mitochondrial clearance, gasdermin E activation, mitochondrial DNA release and microglial STING signaling. This neuroimmune mechanism promotes microglial responses that lead to neuronal dysfunction and loss.

The three-dimensional structure of actively transcribing rotavirus particles reveals that the nascent mRNA transcripts generated within the core of the virion by endogenous transcriptase complexes are translocated through the intact capsid through a system of channels at the icosahedral five-fold axes.

The ATLAS Collaboration reports a measurement of the ratio of the decay rates of W bosons to τ leptons and muons, in agreement with universal lepton couplings as postulated in the standard model of particle physics.

The ATLAS experiment at the Large Hadron Collider reports a search for charged-lepton-flavour violation in decays of Z bosons into a τ lepton and an electron or muon of opposite charge.

Herpesvirus virions have an outer lipid membrane dotted with glycoproteins that enable fusion with cell membranes to initiate entry and establish infection. Here the authors elucidate the structural mechanism of a neutralizing antibody derived from a patient infected by the herpesvirus varicella-zoster virus and targeted to its fusogen, glycoprotein-B.

Tumor cell in the peritoneum are often exposed to shear forces generated by ascitic flow during metastasis. Here, the authors show that metastatic cancer stem cells tether more and roll slower than the non-metastatic counterparts, and that sialyl-Lewis^x -P-selectin axis mediates peritoneal metastasis.