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To control transposable elements, fruit flies rely on distinct genomic regions called piRNA clusters. Here, new piRNA clusters were identified across diverse Drosophila species, displaying a conserved and specialised role in the control of endogenous retroviruses in ovarian somatic cells.

A study generates a clinicogenomics dataset resource, MSK-CHORD, that combines natural language processing-derived clinical annotations with patient medical data from various sources to improve models of cancer outcome.

Piwi-interacting RNAs are small RNAs produced by processing of long precursor transcripts. Here the authors report that precursor cleavage typically occurs at positions corresponding to stop codons and that this pattern is conserved across mammals.

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.

It is unclear whether trait trade-offs and optimality principles observed at the individual level scale up to the ecosystem level. Here, the authors show that plant trait coordination principles also predict patterns between community-level traits and ecosystem-scale processes.

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.

Traumatic brain injury is associated with changes to the metabolome. Here the authors show that acute traumatic brain injury has distinctive serum metabolic patterns which may suggest protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.

Analyses of the relationships between temperature, moisture and seven key plant functional traits across the tundra and over time show that community height increased with warming across all sites, whereas other traits lagged behind predicted rates of change.

Viruses need host cell lipids for multiplication. Here, the authors use lipidomics to show that lipid remodeling by orthoflaviviruses includes distinct changes but also shared patterns, some of which are needed for efficient viral replication.

This study uses zinc-finger nucleases to target an inducible XIST transgene into chromosome 21 from trisomic Down’s syndrome pluripotent stem cells; the XIST RNA coats one copy of chromosome 21 and triggers whole chromosome silencing, suggesting the potential of this approach for studying chromosomal disorders such as Down’s syndrome and for research into gene therapies.

A predictive molecular model sheds light on serine proteases and Enterovirus capsids interaction leading to viral inactivation.

It is known that exercise influences many human traits, but not which tissues and genes are most important. This study connects transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular Transducers of Physical Activity Consortium with human data to identify traits with similar tissue specific gene expression signatures to exercise.

The host cell factor cyclophilin A (CypA) interacts with the HIV-1 capsid and regulates infectivity. Here the authors combine cryo-EM, solid-state NMR and all-atom MD simulations, identifying an interaction interface between CypA and the HIV capsid that stabilizes the viral capsid and regulates infectivity.

Pacing tools that support small animals and can serve as models for pathogenesis of cardiovascular diseases are currently not available. Here, the authors report a miniaturized wireless battery-free implantable multimodal and multisite pacemaker that provides unlimited stimulation to test subjects.

In situ and computational methods are used to investigate the nature of the dense liquid phase of calcium carbonate and its transformation to the amorphous phase that is common in biomineralization processes.

A set of enantioprobes—photoreactive, clickable fragment pairs differing only in absolute stereochemistry—have been used to provide a robust and streamlined chemical proteomic map of small-molecule/protein interactions in human cells. More than 170 stereoselective fragment–protein interactions were discovered and shown to occur at functional sites on proteins from diverse classes.

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.

Structural variants in more than 17,000 human genomes are mapped and characterized using whole-genome sequencing, showing how this type of variation contributes to rare deleterious coding and noncoding alleles.

Short hairpin RNAs, expressed from microRNA scaffold–containing vectors, efficiently silence gene expression in female germ cells as well as somatic cells in the fly. A genome-wide resource is being developed.

An adjuvanted SARS-CoV-2 spike-ferritin nanoparticle vaccine can elicit antibodies with relatively broad sarbecovirus activity in non-human primates. Here, the authors isolate and structurally characterize several monoclonal antibodies providing insights into the targeted epitopes and broad reactivity.

An extensive map of human DNase I hypersensitive sites, markers of regulatory DNA, in 125 diverse cell and tissue types is described; integration of this information with other ENCODE-generated data sets identifies new relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns.

Xie et al. characterize the translational dynamics of fibroblast conversion into induced cardiomyocytes (iCMs) and identify the protein Ybx1 as a critical barrier to iCM transdifferentiation. Ybx1 protein removal in mice with myocardial infarction enhanced iCM conversion and rescued cardiac dysfunction.

A functional interfacial material has been developed for soft integration of bioelectronic devices with biological tissues. This has been applied in battery-free optoelectronic systems for deep-brain optogenetics and subdermal phototherapy as well as wireless millimetre-scale pacemakers and flexible multielectrode epicardial arrays.

Single-cell gene expression analysis is challenging. This work describes a new droplet-based single cell RNA-seq platform capable of processing tens of thousands of cells across 8 independent samples in minutes, and demonstrates cellular subtypes and host–donor chimerism in transplant patients.

Protein lysine methyltransferases modulate the activities of chromatin and non-chromatin proteins by specific methylation of lysine side chains. A large-scale structure-based design approach has yielded a new chemical probe that potently and selectively inhibits G9a and GLP methyltransferases in cells.

Nanocrystal growth by oriented attachment remains poorly understood, despite being a prevalent pathway in geochemical, materials synthesis, and biomineral systems. Here, the authors show that zinc oxide nanocrystals grow by oriented attachment along the (001) plane driven by dipole-dipole interactions that align the particles at long distances prior to their collision and fusion.

A transcriptome-wide association study integrating genome-wide association data with expression data from brain, blood and adipose tissues identifies new candidate susceptibility genes for schizophrenia, providing a step toward understanding the underlying biology.

Neonatal cholestasis is a result of elevated bile acid levels, and is associated with mutations in genes regulating bile acid homeostasis. Here the authors identify mutations in the bile acid sensing farnesoid X receptor in four individuals with neonatal cholestasis from two unrelated families.

The increasing scale and scope of biomedical data is generating tremendous opportunities for improving health outcomes, but also raises new challenges ranging from data acquisition and storage to data analysis and utilization. To meet these challenges, the authors develop the Personal Health Dashboard, which provides an end-to-end solution for deep biomedical data analytics.

Keratinocytes require glucose for injury- or inflammation-driven but not homeostatic proliferation, and glucose-transport blockade blocks psoriasis-like pathology in experimental models.

A new microfluidic system makes it easy to identify rare cells that secrete or consume specific molecules

Bioproduct synthesis via reductive metabolism occurs with different efficiencies according to the availability of carbons, ATP and reducing agents. To maximize overall product synthesis efficiency, the authors develop a substrate cofeeding strategy, which circumvents catabolite repression and drives synergy in lipid synthesis from CO₂ using two microbes.

This is an issue edsumm for ng1946. Identification of the Palaeocene/Eocene thermal maximum in a marine sedimentary sequence.

The ion channel NALCN regulates cell shedding in mice and enhances metastasis in mouse models of cancer. Disseminated cells without oncogenic mutations form normal structures at secondary sites, suggesting that cell shedding is a physiological process that is hijacked during tumorigenesis.

This study explored single cells and single organelles to reveal unique molecular characteristics such as mutant peptides and modulation of diverse post-translational modifications that are inaccessible through DNA/RNA profiling.

The mechanism of oxygen redox in high-energy transition metal oxide cathodes is elusive. Here the authors illustrate the nature of the electron-hole states on oxide ions, offering insights for realizing reversible, high-voltage cathodes.

White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.

A UV-C source-sensor communication system combines phase-matched second-order processes in nonlinear optical crystals for generation of femtosecond UV-C laser pulses with fast-sensors based on two-dimensional semiconductors.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

Small-angle X-ray scattering (SAXS) combines the high tissue penetration of X-rays with specificity to periodic nanostructures. The authors use SAXS tensor tomography (SAXS-TT) on intact mouse and human brain tissue samples, to quantify myelin levels and determine myelin integrity, myelinated axon orientation, and fibre tracts non-destructively.

AMPK is involved in sensing of metabolic stress. The authors show that the autophagy initiator ULK1 phosphorylates β1-Ser108 on the regulatory β1-subunit, sensitizing AMPK to allosteric drugs, and activates signaling pathways that appear independent of Thr172 phosphorylation in the kinase activation loop.

Efficient statistical emulation of melting land ice under various climate scenarios to 2100 indicates a contribution from melting land ice to sea level increase of at least 13 centimetres sea level equivalent.

Mountain snowpack in the western United States has declined over the past three decades. Fyfeet al. show that this trend cannot be explained by natural variability alone and show that under a business-as-usual scenario a further loss of up to 60% in mountain snowpack is projected in the coming three decades.

The amyloid beta peptide can aggregate into insoluble plaques, which may indicate the onset of Alzheimer's disease. In a mouse model of Alzheimer's disease, Cao and colleagues report a phenotype of altered connectivity in the olfactory neuronal circuit that precedes amyloid plaque deposition.

Variations in the 17q21 locus are linked to asthma susceptibility and other autoimmune diseases. Here, the authors perform cell type-specific functional genomic analyses of asthma-risk SNPs, and show a genotype specific mechanism of differential gene regulation relevant to immune function.

Expression of a Huntington's-disease variant of huntingtin protein causes accumulation of the chaperone protein disulfide isomerase. This protein is the target of compounds obtained from screening for those that can alleviate cell death promoted by the mutant huntingtin, and represents a new connection between protein misfolding and cell death.

Integrating electrocatalytic H₂ production with biological H₂-fed systems for CO₂ upgrading requires H₂ generation to occur in biocompatible media—typically with neutral pH. Here, the authors design multi-site H₂ evolution catalysts that minimize the water dissociation barrier and promote hydride coupling in neutral media.

Yahara et al. show that yolk-sac macrophages, which are derived from erythromyeloid progenitors, produce neonatal osteoclasts that support bone homeostasis and repair and also provide long-lasting osteoclasts in adult bone.