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The depolarizing funny current contributing to cardiac pacemaking is upregulated in the myocardium of  failing and infarcted hearts, but whether the current is implied in disease mechanisms is unclear. Here the authors generate HCN4 transgenic mice and show that upregulation of funny current to the levels observed in human heart failure alters calcium homeostasis leading to cardiac remodelling and arrhythmia.

The female reproductive tract constitutes the ovary, fallopian tubes, uterus, and cervix, but it is challenging to engineer this systemin vitro. Here, the authors develop a microfluidic device (EVATAR) with reproductive tract and peripheral tissues to replicate hormone release of a 28-day menstrual cycle.

Clinical studies have suggested that the therapeutic potential of polyclonal convalescent plasma is highest in the first days of symptoms. Here, the authors present results from a pooled analysis of two clinical trials in COVID-19 outpatients that did not provide conclusive evidence in favor of convalescent plasma.

Numerical simulations of the exhumation of basin-filling river deposits suggest that ridge networks observed in Martian landscapes may represent erosional windows into sedimentary basins on Mars.

The transcription factor Foxp3 and Stat5 modulate lineage stability and function of regulatory T (Treg) cells to promote immune homeostasis. Here the authors show that O-GlcNAcylation of Foxp3 and Stat5, mediated by O-GlcNAc transferase (OGT), is essential for Treg-mediate immune balance, with Treg-specific deficiency of OGT leading to severe autoimmunity.

A sensitive method to analyze metagenomes, CATCH, enables detection and characterization of diverse viral sequences, including the 356 viruses known to infect humans.

Reconstructing the full shape of neurons is a major informatics challenge as it requires handling huge whole-brain imaging datasets. Here the authors present an open-source virtual reality annotation system for precise and efficient data production of neuronal shapes reconstructed from whole brains.

Organ-specific aging clocks for multiple brain and body systems show that the biological age of one organ system selectively influences the aging of multiple other systems via characteristic aging pathways.

Selection of COVID-19 mitigation measures requires balancing health outcomes with economic impacts. Here, the authors derive a system to set triggers for increasing mitigation measures to preserve healthcare capacity, and describe how it has been used to support public health decision making in Austin, Texas.

Cryo-EM analysis with DEER spectroscopy and molecular dynamics simulations of the ABC exporter BmrCD reveal dual-mode substrate binding in an ATP- and substrate-bound state.

Clean hydrogen could play a pivotal role in decarbonization but the paths for different sectors remain to be understood. Yang et al. present detailed scenarios to 2060 to explore options for using clean hydrogen in China’s economy for the sectors of industry and transport that are hard to abate.

Using whole-genome sequencing data from 1,739 individuals, the GenomeAsia 100K Project catalogues genetic variation, population structure and disease associations to facilitate genetic studies in Asian populations and increase representation in genetics studies worldwide.

This study examines the effect of four marine heatwaves in the Northeast Pacific on the distributions of 14 top predators, revealing a wide-array of predator responses both among and within heatwaves. Predator responses were highly predictable, demonstrating capacity for early warning systems of heatwave impacts, similar to weather forecasts.

A vast landscape of ‘undruggable’ cancer targets remains beyond the reach of conventional therapeutic agents. Recent advances in artificial intelligence (AI), however, are challenging this paradigm. Synthesizing insights from a Cancer Moonshot workshop, we argue that systemically addressing the undruggable target space with AI requires a new conceptual framework. We highlight the failure of current target taxonomies and the need for benchmarking datasets, and re-evaluate clinical validation for novel AI-driven modalities.

A population of cervical interneurons is identified that can regulate diaphragm function by modulating phrenic motor neurons; targeting this small population of neurons may be a functional strategy to restore breathing after traumatic spinal cord injury.

The pulsation spectra of intermediate-mass stars (so-called δ Scuti stars) have been challenging to analyse, but new observations of 60 such stars reveal remarkably regular sequences of high-frequency pulsation modes.

DNA single-strand breaks in neurons accumulate at high levelsin functional enhancers.

Double Asteroid Redirection Test (DART) mission impact on asteroid Dimophos resulted in an elliptical ejecta plume. Here, the authors show that this elliptical ejecta is due to the curvature of the asteroid and makes kinetic momentum transfer less efficient.

Myelination of peripheral axons by Schwann cells is essential for proper transmission of nerve signals but the underlying mechanisms are not completely understood. Here the authors show that metabolic changes are required to ensure Schwann cell differentiation and proper myelination, and involve the tumour suppressor Lkb1 in regulating this process.

New microgrid recordings on the human hippocampal surface reveal that oscillations travel in reversing directions. The route of travel at a given moment was related to behavior and topographic patterns of activity strength, suggesting directions may be biomarkers of hippocampal cognitive processes.

Conventionally fractionated external beam radiotherapy is an effective treatment for localized prostate cancer, but long treatment programmes result in a substantial burden to patients and the health-care system, which is particularly problematic in low-income and middle-income countries (LMICs) where health-care resources might be scarce and patient funds limited. Here, the authors discuss the outcomes and benefits of hypofractionation — in terms of both oncology and economics — and how it could be used to improve prostate cancer care in LMICs.

An array-based high-throughput approach, genetic interaction analysis technology for Escherichia coli (GIANT-coli), now allows comprehensive genetic interaction screens in bacteria. The method uses bacterial conjugation and robotic technology to generate double mutants on a genome-wide scale. In this issue another paper presents eSGA, a very similar approach.

Variable plant–soil biotic interactions influence the migration and fragmentation of tree species, and models will need to incorporate soil parameters to more accurately predict future species distributions.

The G-protein-coupled receptor GPR124, acting through the canonical Wnt pathway, is required for the maintenance of blood–brain barrier function in mouse models of stroke and glioblastoma.

A machine learning approach is presented to identify dominant patterns in disease progression in amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and Parkinson’s disease. The nonlinearity of ALS progression has important clinical implications.

COP21 led to a global commitment to decarbonization before 2100 to combat climate change, but leaves the timing and scale of mitigation efforts to individual countries. Here, the authors show that global carbon emissions need to peak within a decade to maintain realistic pathways for achieving the Paris Agreement.

Despite the need for new psychoactive drugs, there are few robust approaches for discovering novel neuroactive molecules. Development of a behavior-based high-throughput screen in zebrafish led to the discovery of molecules with neurological effects. Translating the complex behavioral phenotypes elicited by compounds into a simple barcode enabled identification of their mechanism of action.

What factors explain variation in the pace and trajectory of evolutionary divergence between lineages? Here, the authors show that a proxy measure for sexual selection intensity predicts both the rate and direction of plumage colour evolution in a diverse radiation of New World passerine birds.

T cell receptors are identified in large-scale screening of T cell repertoires cloned from primary human T cells.

The authors investigate the relationship between the volume of malignant tumours and their metabolic processes using a large dataset of patients with cancer. They find that cancers follow a superlinear metabolic scaling law, which implies that the proliferation of cancer cells accelerates with increasing volume.

Analyses of current coral reef growth rates in the tropical western Atlantic and Indian Ocean show that few reefs will have the capacity to track sea-level rise projections under Representative Concentration Pathway scenarios without sustained ecological recovery.

Fermi polarons are quasiparticles formed by impurities immersed in a Fermi gas. An experiment in an ultracold fermionic gas now shows how to control their properties with a tunable radio-frequency field.

Analysis of SARS-CoV-2 genomes from around the world show that following initial importation largely from India, Delta spread in England was driven first by inter-regional travel and then by local population mixing.

The detection of structural variants can be difficult with short-read sequencing technology, especially when variants are highly complex. Here, the authors use a MinION nanopore sequencer to analyse two patient genomes and develop NanoSV to map known and novel structural variants in long read data.

Kopal and colleagues built computational bridges between rare CNVs in a clinical dataset and their deep phenotypic profiling in ~40,000 UK Biobank participants. Results show that CNVs are associated with many organ systems across the entire body.

In some cases, hydrogen adsorption close to its boiling temperature shows unusually high monolayer capacities, but the microscopic nature of this adsorbate phase is not well understood. Now, H₂ adsorbed on a well-ordered mesoporous silica surface has been shown to form a 2D monolayer with very short H₂···H₂ intermolecular distances and a density more than twice that of bulk-solid H_2.

Expression of a single trehalose transgene in maize improves yield in field trials in both well-watered and drought conditions.

Some anesthetics despite being generally associated with sedation, can also increase brain activity—a phenomenon called paradoxical excitation. The authors identified dozens of compounds that generally decrease neuronal activity, but increase activity in the caudal hindbrain of zebrafish.

A revised date for the Laacher See eruption using measurements of subfossil trees shifts the chronology of European varved lakes relative to the Greenland ice core record, synchronizing the onset of the Younger Dryas across the North Atlantic–European sector.

Gut microbial dysbiosis in infancy is associated with childhood atopy and the development of asthma. Here, the authors show that gut microbiota perturbation is evident in the very earliest stages of postnatal life, continues throughout infancy, and can be partially rescued by Lactobacillus supplementation in high-risk for asthma infants.

Serial crystallography was developed for protein crystal data collection with X-ray free-electron lasers. Here the authors present several examples which show that serial crystallography using high-viscosity injectors can also be routinely employed for room-temperature data collection at synchrotrons.