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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.

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

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).

Superior colliculus neurons develop the ability to integrate information from different senses postnatally based on experience with cross-modal events. In this Review, Steinet al. discuss how this experience-dependent process ensures that this multisensory circuit and the behaviours it mediates are adapted to the environment in which they will operate.

PARP inhibitor treatment triggers histone release from the chromatin in cancer cells; consequently, targeting the histone chaperone NASP renders cells vulnerable to PARP inhibition.

Photoredox transformations are achieved with infrared light by using triplet fusion upconversion that converts infrared into visible light, enabling the use of photoredox chemistry on larger scales and through barriers that are impenetrable by visible light.

Here, the authors use gene editing combined with Hi-C to show that cohesin acetylation restricts the length of chromatin loops through enhanced binding of cohesin to PDS5A.

Here, the authors determine the structural basis of how SGO1 protects centromeric cohesin from WAPL-mediated release until the kinetochores and the microtubules have formed functional attachments. In addition, they show that SGO1 and CTCF bind cohesin in a similar manner, suggesting a potential universal mechanism of cohesin control.

The link between 3D genome architecture and gene expression is still far from resolved. Here the authors show that loss of the CDK catalytic subunit of the Mediator complex results in heterochromatic silencing, which can be rescued by stabilization of cohesin on chromatin.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

The crystal structure of the SA2–SCC1 subunits of human cohesin in complex with CTCF reveals the molecular basis of the cohesin–CTCF interaction that enables the dynamic regulation of chromatin folding.

Zinc finger nucleases have an established role in genome editing. Here, the authors report a strategy for identifying zinc finger nucleases that discriminate between desired targets and provide genome-wide specificity.

Detailed analysis of an animal’s posture and gait can provide a rich resource for behavioural studies. Kain et al. apply the technology of real-time motion capture to Drosophila, allowing automatic classification of the behaviours of flies spontaneously roaming on a tracker ball.

Previous evidence has suggested that hippocampal place fields in rodents arise from the summation of input from entorhinal grid cells. Here the authors show that perturbing excitatory backprojections from the hippocampus to the entorhinal cortex causes a gradual firing rate–dependent loss of grid pattern and an emergence of head-directional tuning in grid cells of the medial entorhinal cortex.

Sperm use external cues to find the egg using ill-defined principles. Here the authors use holographic microscopy and optochemical tools to study sperm swimming in light-sculpted chemical 3D landscapes; they show that sperm translate the temporal stimulation pattern into multiple swimming behaviours to orient deterministically in a gradient.

Clones expressing variants of the X-chromosome-linked STAG2 gene only form lymphocytes in the absence of Stag2^WT clones. Interactions between epigenetic clones can thus modulate the impact of X-chromosome-linked genetic diversity in a cell-type-specific manner.

PTSD has been associated with DNA methylation of specific loci in the genome, but studies have been limited by small sample sizes. Here, the authors perform a meta-analysis of DNA methylation data from 10 different cohorts and identify CpGs in AHRR that are associated with PTSD.

Multi-contact 4C (MC-4C) sequencing analyzes multi-way conformations of individual alleles. MC-4C identifies the β-globin superenhancer as a hub that can accommodate two genes simultaneously and shows that CTCF-anchored loops collide in WAPL-depleted cells.

Lassa virus can cause haemorrhagic fever for which no specific treatment currently exists. Here the authors have cloned 113 monoclonal antibodies from the survivors of Lassa infection and show that the majority of neutralizing antibodies target a complex of GP1 and GP2 viral proteins.

The expression of each of the roughly 22,000 genes of the mouse genome has been mapped, at cellular resolution, across all major structures of the mouse brain, revealing that 80% of all genes appear to be expressed in the brain.

Enzymes that move along DNA, such as DNA and RNA polymerases, cause the DNA ahead of them to become supercoiled. This would lead to the DNA becoming overwound, were the stress not relieved by topoisomerases. Topoisomerase inhibitors have been used as antibacterial and anticancer drugs, but the structural basis for their activity has been unclear. Here, the crystal structures are presented of a topoisomerase on DNA, either alone or in the presence of a new type of antibiotic.

Serological analysis and infection outcomes of participants in the multi-center, prospectively enrolled OCTAVE cohort, comprising 2,686 participants with immune-suppressive diseases who recieved two COVID-19 vaccines, reveals specific clinical phenotypes that might benefit from specific COVID-19 therapeutic strategies.

RNA localization plays an important role in transcriptome regulation. The majority of TERT transcripts are detected in the nucleus and TUG1 lncRNAs in both the nucleus and cytoplasm. Here, the authors combine single-cell RNA imaging, antisense oligonucleotides and splicing analyses to show that retention of specific introns drives stable compartmentalization of TERT and TUG1 transcripts in the nucleus, and that splicing of TERT retained introns is mitotically regulated.

Processing within neural circuits in the retina extracts information about the direction of motion of images projected onto the retina. Vaney and colleagues describe the cellular components of this circuitry and outline our current understanding of the mechanisms that are involved in generating direction-selective responses in the retina.

Structural maintenance of chromosomes (SMC) complexes, which connect regulatory DNA elements, form chromatin loops and hold together sister chromatids, are required for accurate chromosome segregation and of control transcription, replication and DNA repair. It has recently become clear that SMC complexes also control nuclear organization by counteracting clustering between similar chromatin regions.

Krüppel-like factors are transcriptional regulators that function both as tumour suppressors and oncogenes through their control of p21 expression. This might be an important nodal point of cell control for other factors that have opposing functions in cancer.

Blocking the enzyme KMO with a small molecule reduces the levels of toxic tryptophan metabolites and reduces multiple extrapancreatic organ failure in a rat model of acute pancreatitis.

When an odour activates a fly′s antennae asymmetrically, more neurotransmitter is released from olfactory receptor neuron axon branches ipsilateral to the antenna than from contralateral branches. This causes ipsilateral central olfactory neurons to begin spiking earlier and at a higher rate than contralateral neurons, thereby enabling a walking fly to turn towards the odour.

Methane is an important greenhouse gas, responsible for about 20% of the warming induced by long-lived greenhouse gases since pre-industrial times. A compilation of observations and results from chemical transport, ecosystem and climate chemistry models suggests that a rise in wetland and fossil fuel emissions probably accounts for the renewed increase in global methane levels after 2006.