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HCMV rearranges the host cell to produce infectious virus but molecular details are still unclear. Here, the authors analyze the transcriptome of infected cells and show that HCMV turns on dormant neuronal genes through chromatin manipulation to achieve this goal.

During chronic but not acute inflammation, chromatin remodelling is influenced by nuclear autophagy through WSTF interaction with ATG8 in the nucleus, leading to WSTF nuclear export and its subsequent degradation.

A study demonstrates how experimental measurements of only the connectivity of a biological neural network can be used to predict neural responses across the fly visual system at single-neuron resolution using deep learning techniques.

Allelic variants for the HIV-1 co-receptors chemokine receptor 5 (CCR5) and CCR2, as well as the ligand for the co-receptor CXCR4, stromal-derived factor (SDF-1), have been associated with a delay in disease progression. We began this study to test whether polymorphisms in the CCRS regulatory regions influence the course of HIV-1 disease, as well as to examine the role of the previously identified allelic variants in 1,090 HIV-1 infected individuals. Here we describe the evolutionary relationships between the phenotypically important CCRS alleles, define precisely the CCR5 regulatory sequences that are linked to the CCR5-Δ32 and CCR2-64I polymorphisms, and identify genotypes associated with altered rates of HIV-1 disease progression. The disease-retarding effects of the CCR2-64I allele were found in African Americans but not in Caucasians, and the SDF1-3′A/3′A genotype was associated with an accelerated progression to death. In contrast, the CCR5-Δ32 allele and a CCR5 promoter mutation with which it is tightly linked were associated with limited disease-retarding effects. Collectively, these findings draw attention to a complex array of genetic determinants in the HIV-host interplay.

Clear cell renal cell carcinoma (ccRCC) usually metastasizes to the lungs. Here, the authors discover that SWI/SNF ATPase subunit SMARCA4 silencing of HLF regulates ccRCC lung metastasis by modulating the integration of collagen's mechanical cues with the actin cytoskeleton through leupaxin.

Interactions between Semaphorin-3A (SEMA3A) and Neuropilin-1 (NRP1) and Plexin-A1 and Plexin-A4 have been shown to affect T cell development. Here the authors investigate how these interactions affect CD8⁺ T cells in tumour immunity, showing that NRP-1, Plexin-A1 and Plexin-A4 are upregulated on T cells allowing tumour derived SEMA3A to inhibit CD8⁺ T cell migration and function.

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).

During segmentation of neurons in electron microscopy datasets, auxiliary learning via the prediction of local shape descriptors increases efficiency, which is important for the processing of datasets of ever-increasing size.

N⁶-methyladenosine (m⁶A) modification of mRNA regulates gene expression in eukaryotes. Here, Zeng et al. show that m⁶A modification of mRNAs contributes to protection against the pathogen Helicobacter pylori by downregulating a host protein that acts as receptor for the pathogen.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

A method, RARE-seq, for sensitive detection of cell-free RNAs in blood is demonstrated to have diverse clinical applications including diagnosing and characterizing human cancers, and tracking response to RNA therapeutics.

The commitment stage at which progenitors seed the thymus remains unclear. Jacobsen and colleagues show that the earliest progenitors in the neonatal thymus have combined myeloid, T lymphocyte and B lymphocyte potential but not megakaryocyte-erythroid potential.

This work integrates duplex sequencing with cost-effective Ultima sequencing to enhance the accuracy of whole-genome circulating cell-free DNA profiling.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

MoS₂ nanoparticles catalyze the extraction of heteroatom S in hydrocarbons by adsorption onto S vacancies. Here, the authors show that S vacancy properties are highly site sensitive and that adsorption of thiophene leads to self-generation of a more open double vacancy site.

The blood circulation time is important to the biomedical application of nanomaterials. Here, the authors explore the effect of protein corona formation on the blood residency of nanomaterials and show circulation times are governed by the dynamic remodelling of protein opsonins in vivo.

Malladi and colleagues show that inhibiting DRP1 limits mitochondrial plasticity, resulting in increased mitochondrial fusion, impaired fatty acid oxidation and reduced metastasis formation in breast cancer models.

Pycytominer is a user-friendly, open-source Python package that carries out key bioinformatics steps in image-based profiling.

Detection of circulating tumor DNA using MRD-EDGE, a machine-learning-guided single-nucleotide variant and copy-number variant detection platform for signal enrichment, enables monitoring of minimal residual disease and immunotherapy response in settings of low tumor burden.

A range of blood-based biomarkers have shown high specificity for Alzheimer’s disease (AD) pathophysiology with phosphorylated-tau (p-tau) being the most promising test. Here, the authors show the utility of plasma p-tau212 in autopsy-confirmed AD and memory clinic patient cohorts.

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.

A detailed whole-body model of the fruit fly, developed using a physics-based simulation and deep reinforcement learning, accurately replicates real fly behaviour.

Three electron microscopy datasets are combined to provide a complete connectomic description of the neural circuitry that makes up the neck connective in Drosophila, including the descending neurons, ascending neurons and sensory ascending neurons.

Although progress in the coverage of routine measles vaccination in children in low- and middle-income countries was made during 2000–2019, many countries remain far from the goal of 80% coverage in all districts by 2019.

The single-cell transcriptional profile of a human embryo between 16 and 19 days after fertilization reveals parallels and differences in gastrulation in humans as compared with mouse and non-human primate models.

This Review provides an overview of the main applications of single-port robotic surgery in urology, presenting emerging outcomes and discussing the transformative potential of this approach.

Chemoresistance and relapse are main limitations in the treatment of acute lymphoblastic leukemia (ALL). Here, the authors identify Quinacrine (QC) as a sensitizer for Cytarabine (AraC) and establish a QC-CASIN regimen to improve leukemia eradication in ALL.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

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.

Solvent shielding of the amide hydrogen bond donor through chemical modification or conformational control has been successfully utilized to impart membrane permeability to macrocyclic peptides. Here, the authors show that passive membrane permeability can also be conferred by masking the amide hydrogen bond acceptor through thioamide substitution, leading to improved pharmacological properties of peptide macrocycles.

The microbiota of the rhizosphere (roots) and phyllosphere (leaves) of healthy plants consist of taxonomically structured bacterial communities; here the majority of species representing the main bacterial phyla from these two organs were isolated and genomes of about 400 representative bacteria were sequenced; the resources of cultured bacteria, corresponding genomes and a gnotobiotic plant system enabled an examination of the taxonomic overlap and functional specialization between the rhizosphere and phyllosphere bacterial microbiota.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

Tumour thrombi (TT) are intravascular extensions of renal cell carcinomas (RCC) which often lead to distant metastases. Here the authors examine the determinants of vascular invasion and metastasis in a unique cohort of RCC patients with TT using multi-region genomics and in vivo models.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

Knottin is a cystine knot peptide. Here, the authors develop a knottin-based tracer for positron emission tomography and demonstrate its ability to detect cancer and idiopathic pulmonary fibrosis through selective binding to integrin αvβ₆.

The identity and lineage potential of the embryonic thymus-seeding progenitors that first seed the embryonic thymic rudiment is unclear. Jacobsen and colleagues find that these cells do not include multipotent stem cells or T cell–restricted progenitors but instead are lympho-myeloid progenitors.

Choi et al. highlight the centrality of glycolysis in squamous cell carcinoma, revealing the glycolysis-dampening tumour suppressor role of Sirt6, and identifying a subset of highly glycolytic tumour-propagating cells with elevated antioxidant capacity.

The authors demonstrate a multi-dimensional communication scheme that combines wavelength- and mode- multiplexing on photonic integrated circuits using foundry-compatible photonic inverse design and spectrally flattened microcombs