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Haematopoietic stem cell numbers are restricted at both systemic and local levels.

The ratio between the levels of two synaptic proteins in cerebrospinal fluid predicts future cognitive resilience versus decline among presymptomatic individuals and individuals with early Alzheimer’s disease harboring amyloid and tau pathology.

Acinetobacter baumannii is a major cause of hospital-acquired infections, yet its virulence factors, particularly lipooligosaccharides, are not well understood. Here, the authors synthesize A. baumannii lipid A(s) and their corresponding monophosphate derivatives, revealing that specific acylation patterns enhance immunological activity, as well as an inverted binding mode in the TLR4/MD-2 receptor complex.

Foetal haematopoiesis takes place in the liver before the bone marrow is seeded. Here the authors used imaging analysis and mouse genetics to look at nascent bone marrow formation and show that yolk-sac-derived myeloid cells promote haematopoiesis by promoting specification of a VCAM1⁺ sinusoidal colonisation niche.

NME3 is a member of NDPK family. Here, Chen et. al., discover that histidine phosphorylatable NME3 is required for hypoxia-induced mitophagy via PA-dependent interaction with Drp1, which is protected from MUL1-mediated ubiquitination for mitophagy.

Drug addiction is a chronic disorder and many sufferers experience relapses even after a period of successful abstinence. Here, the authors reveal a subset of neurons in the rat infralimbic cortex that suppresses relapse into cocaine or alcohol use by responding to drug-omission cues.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

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.

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

Transancestral GWAS meta-analysis in 160,420 individuals identifies 139 loci associated with refractive error, including myopia. Newly identified genes implicate pathways involved in eye growth and light signaling cascades.

The relationship between wound healing and cancer is intricate and complex. Here, the authors show that in breast cancer models an IL-6 driven co-expression of FAP and HO-1 in tumour-associated macrophages, similar to the wound healing response, facilitates migration and metastatic spread.

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.

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.

Many atmospheric pollutants including methane are removed by the hydroxyl radical. Southern-Hemisphere long-term measurements of radiocarbon monoxide and global model results indicate that this atmospheric self-cleansing capacity is strengthening.

The desmoplastic stroma constitutes part of the microenvironment in pancreatic ductal adenocarcinoma. Here the authors show that Class I HDACs regulate the pro-desmoplastic and pro-tumorigenic transcriptional programs to support stromal activation and tumour progression.

A systematic proteomic investigation of disease mediators secreted by pancreatic stellate cells identifies leukaemia inhibitory factor (LIF) as a key factor that acts on cancer cells, promoting tumour progression and chemoresistance.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

Hans van Bokhoven and colleagues report mutations in the ISPD gene as a cause of Walker-Warburg syndrome. Knockdown of ispd in zebrafish causes hydrocephalus, reduced eye size, muscle degeneration and α-dystroglycan hypoglycosylation.

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.

Here authors show that machine learning derives the degree of background retinal pigmentation with more nuance than self-described ethnicity. Retinal pigment scores are associated with genes linked to melanin and may improve algorithmic fairness.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

Characterization of the myotis bat morbillivirus shows that infection in human cells is restricted by innate immune responses in vitro and cross-neutralization by sera from measles, mumps and rubella vaccinees.

Direct elevation of heart rate using noninvasive optogenetics in mice influences anxiety-like behaviours in specific environmental contexts, and the posterior insular cortex is implicated in this integration of signals from the heart with environmental risk information.

Matthew Brown, Peter Donnelly and colleagues report results of a genome-wide association meta-analysis and follow-up study of ankylosing spondylitis. They identify three new risk variants and report a genetic interaction between ERAP1 and HLA-B27, implicating aberrant peptide handling in the pathophysiology of this disease.

The regulatory subunits (RI) of protein kinase A (PKA) form a disulfide bond in response to cellular hydrogen peroxide. Here the authors show that disulfide-activation of PKARIa regulates VEGF-induced angiogenesis in mice and may represent a new therapeutic target in diseases with abnormal angiogenesis.

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.

A horizon scan was used to explore possible impacts of robotics and automated systems on achieving the UN Sustainable Development Goals. Positive effects are likely. Iterative regulatory processes and continued dialogue could help avoid environmental damages and increases in inequality.

Bats are natural reservoirs for several zoonotic viruses including SARS-CoV-2 thus there is a need to better define bat antiviral responses. Here, Hashimi et al. profile antiviral responses to SARS-CoV-2 in bat intestinal organoids finding that interferon and regenerative responses where induced.

AGO2 binds to miRNAs to repress expression of cognate target mRNAs. Here the authors report that heterozygous AGO2 mutations result in defects in neurological development and impair RNA interference.

Embryonic stem-cell research is putting fresh strain on the already fractious relationship between science and religion. TonyReichhardt explores how faith is shaping the ever-changing landscape of bioethics.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Human population genomic studies, including whole‐genome sequencing, were undertaken to identify determinants of bone mineral density (BMD), a major predictor of osteoporotic fractures. Non‐coding variants with large effects on BMD and fractures were identified near the EN1 locus and mouse studies confirmed this gene has an important role in skeletal biology.