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Diversified renewable energy sources can enable the sustainable operation of multisector resource systems. An artificial intelligence-assisted multi-objective design framework, applied in Ghana, explores optimized management and investment strategies balancing hydropower, bioenergy, solar and wind energies, and their impacts.

This Perspective reviews tools developed over the past five years in the macromolecular modeling, docking and design software Rosetta.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Although the number of participants is important for phenotypic prediction accuracy in brain-wide association studies using functional MRI, scanning for at least 30 min offers the greatest cost effectiveness.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

Kumar et al. show that under glucose-depleted conditions, neurons can use fatty acids as an alternative source of energy to support synaptic function.

Design of a two-component protein array enables robust formation of complex large-scale ordered biologically active materials.

G protein-coupled receptors (GPCRs) enable cells to sense environmental cues and are indispensable for coordinating vital processes including quorum sensing, proliferation, and sexual reproduction. Here the authors, using heterologous GPCR expression and endogenous ligand production, enable synthetic mating in haploid yeast, and GPCR-mediated biosensing in diploid probiotic yeast.

precisION discovers, localizes and quantifies protein modifications within complex proteoform assemblies through data-driven analysis of native top-down mass spectra.

The impacts of climate change on agriculture differ regionally and will increase hunger globally. Reducing tariffs and other barriers to international trade would mitigate this, but trade integration requires a careful approach to avoid reducing domestic food security in food-exporting regions.

This work introduces a pedigree-derived benchmark for single-nucleotide variants, indels, structural variants and tandem repeats, offering a variant map to validate sequencing workflows or to support the development and evaluation of new variant callers.

Circulating tumor cells (CTCs) are clinically useful for detecting and monitoring cancer, but they are rare in blood. Here, the authors use a highthroughput microfluidic device to massively enrich CTCs from leukapheresis products to uncover single cell molecular features in prostate and other cancers.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

Understanding principles that govern protein association with extracellular vesicles should expand their potential as a therapeutic modality. Here, the authors show that by localizing proteins to the plasma membrane and lipid rafts, a variety of proteins can be preferentially loaded into extracellular vesicles.

Using RFdiffusion, a general method for targeting intrinsically disordered proteins and regions for protein design has been developed.

Predictive protein design and experiments are combined to develop anisotropic bifaceted protein nanomaterials using pseudosymmetric hetero-oligomeric building blocks.

IL-17a is an evolutionarily conserved cytokine with behavior-modulating roles in the central nervous system. Kipnis and colleagues characterize a population of meningeal γδ17 T cells that use IL-17a to elicit anxiety-like behavior through cortical glutamatergic neurons.

There are continuing questions on how much investments in land-based mitigation activities could deliver in terms of abatement. This study shows that annual investments of $2.4billion in the U.S. land could deliver abatement of around 80 MtCO2e/yr.

Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.

Deep learning methods have been used to design proteins that can neutralize the effects of three-finger toxins found in snake venom, which could lead to the development of safer and more accessible antivenom treatments.

Temporal changes in brain dynamics are linked with cognitive abilities, but neither their stability nor relationship to psychosis is clear. Here, authors describe the dynamic neural architecture in healthy controls and patients with psychosis and find that they are stable over time and can predict psychotic symptoms.

Examining drivers of the latitudinal biodiversity gradient in a global database of local tree species richness, the authors show that co-limitation by multiple environmental and anthropogenic factors causes steeper increases in richness with latitude in tropical versus temperate and boreal zones.

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).

This paper highlights the far-red chemigenetic H₂O₂ reporter oROS-HT₆₃₅, which enables detailed insights into intricate intracellular and intercellular H₂O₂ dynamics, along with their environmental interactants, through spatially resolved, multiplexed real-time H₂O₂ imaging.

Plant-parasitic nematodes have the potential to destroy crops globally, and limited options for managing nematode infestation are available. Here, the authors report the 1,3,4-oxadiazole thioether scaffold called Cyprocide that selectively kills nematodes including diverse species of plant-parasitic nematodes.

Human ADAR proteins are responsible for RNA editing, conversion of adenosine to inosine in double-stranded RNA. Here the authors report a previously unknown zinc ion-binding site in the catalytic domain of human ADAR1 using high throughput mutagenesis, biochemical assay and Rosetta-based protein structure modeling.

Citizen scientists around the globe are uniting to make aflatoxin a thing of the past

Andre Berndt and colleagues introduce a machine learning approach to enhance the biophysical characteristics of genetically encoded fluorescent indicators, deriving and testing in vitro new GCaMP mutations that surpass the performance of existing fast GCaMP indicators.

The organization of membrane proteins is critical to cellular function. Here the authors explore how computational protein design, MD simulation, and cell-free systems can be combined to elucidate how membrane-protein hydrophobic mismatch affects protein folding and organization in synthetic lipid membranes.

A de novo-designed protein that precisely assembles a chlorophyll dimer has been developed. The design matches the conformation of the native ‘special pair’ of chlorophylls that functions as the primary electron donor in natural photosynthetic reaction centers. In the designed protein, excitonically coupled chlorophylls participate in energy transfer. The proteins were also redesigned to assemble into 24-chlorophyll nanocages.

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.

Dynamics of type I interferon (IFN) following infection with SARS-CoV-2 are critical in determining disease severity in humans but have been difficult to model in mice. Here, infection of genetically diverse mice reveals how delayed or immediate IFN signaling coordinates antiviral immunity.

A study comparing the pattern of single-nucleotide variation between unique and duplicated regions of the human genome shows that mutation rate and interlocus gene conversion are elevated in duplicated regions.

Fluorescent protein reporters based on GFP exist, but have intrinsic disadvantages. Here the authors incorporate pH, Ca²⁺ and protein–protein interaction sensing modalities into de novo designed mini-fluorescence-activating proteins (mFAPs), with increased photostability and smaller size, which bind a range of DFHBI chromophore variants.

A study describes an approach using designed building blocks that are far more regular in geometry than natural proteins to construct modular multicomponent protein assemblies.

An approach to design proteins that can capture amyloidogenic protein regions present in, for example, tau and Aβ42 has now been developed. These designer proteins can inhibit the formation of pathogenic amyloid fibrils and protect cells from toxic species.

To survive and evade host responses, malaria parasites export several hundred proteins into the host cell on infection. A feature of these proteins is a conserved, pentameric motif that is cleaved by an unknown protease before export. This is one of two independent studies revealing the identity of the protease as plasmepsin V, an aspartic acid protease located in the endoplasmic reticulum. This enzyme is essential for parasite viability and is an attractive candidate for drug development.

Many cell capture systems exist but the characterisation and controlled release of single cells is a challenge. Here, the authors report on the development of a duel trigger release system using a combination of photo and electro triggers to allow for light based analysis without unwanted release.

Comparisons within the human pangenome establish that homologous regions on short arms of heterologous human acrocentric chromosomes actively recombine, leading to the high rate of Robertsonian translocation breakpoints in these regions.

The modification of enzymes to generate desired compounds by non-natural pathways is a useful route for the production of commodity chemicals. Here, the authors show two approaches—genome mining and computational enzyme design—to generate higher alcohols from sugar.

Mitochondria are able to maintain two competing metabolic pathways—oxidative phosphorylation and the reductive synthesis of proline and ornithine—by generating two mitochondrial subpopulations that are enriched in either pyrroline-5-carboxylate synthase or ATP synthase.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

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.

Constructing genome graphs directly from genome assemblies overcomes single-reference bias.

The authors report data from the emergency department AURORA study to characterize resilience in more detail than the absence of psychopathology after trauma.