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Greda et al. show that sortilin and apolipoprotein E3 mediate import and utilization of long-chain fatty acids as a metabolic fuel in neurons after glucose restriction.

In patients with sporadic Alzheimer’s disease part of the Asp23 residues are isomerized to L-isoaspartate (L-isoAsp23). Here the authors present the MicroED structures of wild-type and L-isoAsp23 Aβ 20–34 amyloid fibrils that both form tightly packed cores and self-associate through two distinct interfaces with one of these interfaces being strengthened by the isoaspartyl modification.

What is the state of trust in scientists around the world? To answer this question, the authors surveyed 71,922 respondents in 68 countries and found that trust in scientists is moderately high.

PCSK9 regulates low density lipoprotein-cholesterol import and determines organ preference of metastatic pancreatic ductal adenocarcinoma, with PCSK9-low cells metastasizing to the liver and PCSK9-high cells preferring the lung.

Plasma extracellular vesicles contain quantifiable amounts of TDP-43 and full-length tau, allowing the accurate assessment of pathology in frontotemporal dementia, frontotemporal dementia spectrum disorders and amyotrophic lateral sclerosis.

The structurally different domains of a polycrystalline material may exhibit differing catalytic properties. Here, the authors directly visualize this phenomenon by observing the catalytic hydrogen oxidation that oscillates, simultaneously exhibiting different frequencies for structurally different rhodium domains.

In cancer, the impact on cellular fitness of copy-number gains affecting collaterally-amplified genes remains poorly understood compared to oncogenes. Here, the authors integrate genomic data from tumours and cell lines and identify a class of ‘Amplification-Related Gain Of Sensitivity’ (ARGOS) genes, with potential therapeutic applications.

Segments from TDP-43 LCD form irreversible steric zippers typical of amyloid fibrils and labile interactions found in reversible assemblies. Familial ALS mutations or a phosphorylation event can convert reversible to irreversible aggregates.

Literature produced inconsistent findings regarding the links between extreme weather events and climate policy support across regions, populations and events. This global study offers a holistic assessment of these relationships and highlights the role of subjective attribution.

Macrophages possess different G protein-coupled receptors such as the orphan receptor GPRC5B. Here the authors characterise the function of GPRC5B in macrophages in knockout mice showing that in the absence of GPRC5B there is increased inflammatory responses and macrophage activation because of reduced EP2-mediated anti-inflammatory effects.

Multi-ancestry genome-wide analyses identify new risk loci for age-related macular degeneration. Ancestry-specific analyses identify distinct effects at major risk loci, including smaller effect sizes for CFH risk alleles in haplotypes of African ancestry.

In a pivotal phase 2 trial, elranatamab, a bispecific antibody targeting B-cell maturation antigen (BCMA) and CD3, had a confirmed objective response rate of 61% in patients with relapsed or refractory multiple myeloma who had not previously received BCMA-directed therapy.

The endocardium lines the interior of the heart chambers and has been debated as a source of hematopoietic lineages. Here they show that the endocardium may act as a source of, and resident tissue for, hematopoietic stem and progenitor cells in zebrafish, providing evidence for diversity in origins and residences of hematopoietic cells.

Leonard Jahn et al. propose a probability-distributed equivalent circuit model that is capable of simulating open circuit voltage hysteresis and path dependency of rate capability in lithium-ion batteries with low computational cost.

A molecular mechanism for brain-specific angiogenesis operates under the control of Wnt7a/b ligands.

Whole-genome analysis of oestrogen-receptor-positive tumours in patients treated with aromatase inhibitors show that distinct phenotypes are associated with specific patterns of somatic mutations; however, most recurrent mutations are relatively infrequent so prospective clinical trials will require comprehensive sequencing and large study populations.

TOI-500 hosts at least four planets, the innermost of which is an Earth-sized ultra-short-period body with a density similar to Earth. The architecture of the TOI-500 system can be explained by a slow, secular, low-eccentricity migration scenario.

Iris Heid, Gonçalo Abecasis, Sudha Iyengar and colleagues report the results of a large genome-wide association meta-analysis of macular degeneration based on over 43,000 subjects. They identify 16 new risk loci, including some very rare coding variants.

Andrade et al. show that FOXO1 regulates mitochondrial metabolism to stimulate the production of the metabolite S-2HG to promote acquisition of a quiescent endothelial state.

Therapeutic application of hematopoietic stem cells requires a thorough understanding of their in situ differentiation pathways. Here they use single cell proteo-transcriptomic sequencing to identify human HSPC differentiation cues and an immunoregulatory function of CD273/PD-L2 on early HSPCs.

A short segment of α-synuclein called NACore (residues 68–78) is responsible for the formation of amyloid aggregates responsible for cytotoxicity in Parkinson disease; here the nanocrystal structure of this invisible-to-optical-microscopy segment is determined using micro-electron diffraction, offering insight into its function and simultaneously demonstrating the first use of micro-electron diffraction to solve a previously unknown protein structure.

Organismal ageing is driven by conserved biological processes. Here the authors build on a comparative RNA-seq analysis in three model organisms to demonstrate that the gene, bcat-1, which catalyses the degradation of branched-chain amino acids, regulates lifespan in worms.

Mass gathering events represent a risk for transmission of SARS-CoV-2. Here, the authors describe an experimental indoor test event in which individual contacts were measured and use aerosol and epidemiological modelling to evaluate transmission risks of different types of restrictions in the arena.

The production of nitric oxide (NO) is required for early stage embryo implantation into the uterus. Here the authors show that during differentiation of naive mouse ESCs, early production of endogenous NO leads to a mesendoderm differentiation commitment pathway by inhibiting the action of the transcriptional repressor Zeb1.

Structural analyses of fibrils formed by segments from human TDP-43 RRM2 reveal extensive packing and positional polymorphism.

Using intracranial electrocorticography and a series of motor tasks, a speech planning network that is central to natural language generation during social interaction is identified.

A class of enzymes known as alkyltransferase-like proteins (ATLs) can protect against alkylation damage to DNA. To gain insight into how this occurs, the structure of a yeast ATL has been solved in the presence and absence of damaged DNA, revealing that ATL flips the alkylated base out of the DNA helix, leaving the lesion to be acted on by proteins of the nucleotide excision repair pathway.

Ong et al. report how YAP/TAZ and mTORC1 signalling intersect in endothelial cells to regulate nutrient acquisition and vascular growth.

Terence Capellini, David Kingsley and colleagues use transgenic mice to show that a Gdf5 enhancer (termed GROW1) is required for normal bone length. They suggest that a common variant at the human GROW1 enhancer was under selection in human populations and also contributes to arthritis susceptibility.

Tetrahydrobiopterin (BH4) is an enzyme co-factor that is involved in the nervous system; it is shown here to also function in T cell activation and proliferation, with roles in autoimmunity, allergic inflammation and cancer.

A novel high-throughput sequencing kinetics approach is used to measure functional binding of the apparently nonspecific RNA-binding protein C5 to all possible sequence variants in its substrate binding site; C5 binds different substrate variants with affinities varying widely, and with a similar affinity distribution to that of highly specific nucleic-acid-binding proteins, but it does not bind its physiological RNA targets with the highest affinity.