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Girdhar et al. constructed chromosomal domains from prefrontal histone acetylation and methylation maps and discovered, in a large cohort of schizophrenia and bipolar brains, converging alignment by genetic risk, neuronal function and three-dimensional genomics.

Wzc is the master regulator of the biosynthesis and export of bacterial capsular polysaccharides and exopolysaccharides. Here, the authors report cryoEM structures of intermediate states and provide insights into phosphorylation and transmembrane signalling.

Ribozyme-based RNase MRP is an essential eukaryotic enzyme involved in the maturation of rRNA and is evolutionarily related to RNase P. Here, the authors present the 3.0 Å cryo-EM structure of the S. cerevisiae RNase MRP holoenzyme, a 450 kDa ribonucleoprotein complex and compare it with RNase P.

Septins are the key component of the cytoskeleton. Here, the authors show that Septin5 is assembled in microtubule-plasma membrane contact sites and mediates insulin secretion in pancreatic islet β-cells through cortical microtubule remodeling.

Conventional magnetic biosensing technologies have limited ability to detect magnetic field dimensionality. Here, the authors develop a platform which uses DNA hydrogels to spatially engineer a 3D magnetic response and demonstrate its use in the direct and programmable detection of RNA and protein biomarkers.

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.

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.

Estimates from the Global Dietary Database indicated that 2.2 million new type 2 diabetes and 1.2 million new cardiovascular disease cases were attributable to sugar-sweetened beverages worldwide in 2020, with the highest burdens in sub-Saharan Africa, Latin America and the Caribbean.

A seven-stage protocol enables differentiation of human embryonic stem cells into cells similar to pancreatic beta cells.

A 3.8-Å cryo-EM structure of a bacterial group IIA intron in complex with its intron-encoded protein reveals how the reverse transcriptase domain interacts with the mobile intron RNA as well as structural similarities with eukaryotic telomerase and spliceosomal components.

Staphylococcus pseudintermedius has a wide host-range in domesticated and wild animals, yet it has also been isolated as an opportunistic pathogen in human wounds. In this work, the authors genotypically analyse S. pseudintermedius isolates from veterinary diagnostic laboratories and medical care centres, alongside household surfaces and inhabitants.

Duy and Weise et al. combined human functional integrative genomics with mouse experimental biology to reveal a neuroprogenitor-based genetic subtype of human hydrocephalus with defective neurogenesis and altered brain–fluid biomechanics.

After infection with SARS-CoV-2 a diverse set of symptoms remain or develop longer term in a condition termed long-CoVID, yet an accurate and tractable model has remained elusive. Here the authors present a non-human primate model of long-CoVID and show persistent hyperglycemia following acute infection.

Developmental and epileptic encephalopathies are devastating neurological disorders. Here, the authors establish a cohort of patients with variants in the gene DENND5A and use human stem cells to discover a disease mechanism involving altered cell division.

Cross-neutralizing activity of monoclonal antibodies against poliovirus serotypes is less commonly reported. In this study, the authors use high-resolution cryo-EM to reveal that a cross-neutralizing human antibody neutralizes all three poliovirus serotypes by interacting with the receptor-binding region, called the canyon.

F₁F_o ATP synthase consists of two coupled rotary molecular motors: the soluble ATPase F₁ and the transmembrane F_o. Here, the authors present cryo-EM structures of E. coli ATP synthase in four discrete rotational sub-states at 3.1-3.4 Å resolution and observe a rotary sub-step of the F_o motor cring that reveals the mechanism of elastic coupling between the two rotary motors, which is essential for effective ATP synthesis.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

Functional interplay of sex hormones in estrogen receptor–positive breast cancer unveils the therapeutic potential of androgen receptor agonists.

The potential for enhanced sediment delivery to the Ganges-Brahmaputra delta exists, but it alone is insufficient to sustain the system. The delta may be resilient to climate change, but only in the absence of dam construction and water diversions.

Gene expression is precisely modulated with CRISPR interference and mismatched guide RNAs.

Here, the authors describe a new method to study how some proteins work together to control gene activity. They show that certain protein pairs can recognize new DNA sequences that they can’t recognize individually and control a wider range of genes.

In this study, the authors identify a mechanism for the distinct conformational preferences of tyrosine kinases vs serine/threonine kinases and suggest that the evolution of tyrosine kinase function can explain these conformational differences.

Shlien and colleagues report on 300 patients from the SickKids Cancer Sequencing program and identify clinically actionable variants in 56% of the patients by profiling somatic and germline data at multiple clinical time points.

Multiple variants of SARS-CoV-2 are inhibited by a trispecific DARPin.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

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.

Schizophrenia (SZ) is a severe psychiatric disorder; unfortunately, only ~1/3 of patients respond favorably to treatment. Here, the authors reveal hyperacetylation of histone H2A.Z in SZ neurons and postmortem SZ human brain tissues. They further show BRD4 is a reader of hyperacetylated H2A.Z and treatment with bromodomain inhibitor JQ1 largely rescues abnormal gene expression associated with SZ.

 A transcriptomic cell-type atlas of the whole adult mouse brain with ~5,300 clusters built from single-cell and spatial transcriptomic datasets with more than eight million cells reveals remarkable cell type diversity across the brain and unique cell type characteristics of different brain regions. 

Little is known about genes that regulate flowering time difference among winter wheat cultivars. Here, via map-based cloning, the authors show the role of an O-linked N-acetylglucosamine (O-GlcNAc) transferase TaOGT1 in regulating flowering time difference among winter wheat cultivars.

It is unclear why different antibiotics vary in their ability to shorten treatment of tuberculosis. Here, the authors show that a measure based on ribosomal RNA synthesis in Mycobacterium tuberculosis correlates with treatment shortening in culture, in mice and in human studies.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

Whole-genome sequencing and mutational signature analysis of 265 head and neck cancer samples collected from eight different countries provide insight into the vital contribution of tobacco smoke in disease etiology.

Vein of Galen malformations (VOGMs) are severe congenital brain arteriovenous malformations. Here the authors work to elucidate the pathogenesis of VOGMs by performing an integrated analysis of 310 VOGM proband family exomes and 336,326 human cerebrovasculature single-cell transcriptomes to identify mutations of key signaling regulators.

Berto et al. combine human intracranial brain oscillations recorded during mnemonic processing and measures of gene expression from brain tissue surgically removed from the same individuals to uncover gene expression patterns relevant to memory in humans.

Andrew Jackson, Peter Nürnberg and colleagues identify mutations in PLK4 and TUBGCP6 in individuals with microcephaly, primordial dwarfism, retinopathy and other congenital anomalies. These findings extend the spectrum of human phenotypes associated with centriole dysfunction.

Necrotizing enterocolitis (NEC) is one of the most lethal gastrointestinal emergencies in neonates needing precision treatment. Here the authors show that remote ischemic conditioning is a non-invasive therapeutic method that enhances blood flow in the intestine, reduces damage, and improves NEC outcome.

Here, the authors provide a 3.4 Å resolution structure of mature Zika virus (ZIKV) and identify two lipid moieties, coordinated by hydrophobic residues of the M and E transmembrane helices and between two helices of E protein, that play an essential role in the ZIKV assembly pathway.

Analysis of copy number alterations in 1,451 patient-derived xenografts (PDXs) and matched patient tumor samples shows strong conservation from patient tumors through late-passage PDXs and a lack of systematic copy number evolution driven by the mouse host.

In a cohort of patients with cerebral arachnoid cysts, multiomic analyses reveal de novo variants causing genetic neurodevelopmental conditions in up to 16% of cases, suggesting that surgery in these cases may not improve non-mass effect-related symptoms.