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Human and rodent supragranular pyramidal neurons differ in HCN channel-related properties. Comparison across primates reveals robust HCN1 expression and HCN channel-dependent physiology, with cell type dependent differences in macaques versus humans.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

An analysis of cell-type diversity in brain samples from a variety of mammalian species, both during development and in adult animals, reveals that the TAC3 initial class of striatal interneurons is conserved across placental mammals and is homologous to Th striatal interneurons in rodents.

A previously unsampled deep lineage in central Argentina was discovered that had distinctive genetic drift by 8,500 bp and persisted as the main Native American ancestry component in the region up to the present day.

Excessive complement C3 causes synaptic stripping and neurodegeneration. Here, the authors used the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis and single-cell RNA sequencing to show that C3 expression defines disease-associated reactive glia. C3 deletion abrogated these pro-inflammatory glia and protected neurons.

EPIC-seq predicts expression of individual genes from cell-free DNA.

Ni, Wei, Vona and colleagues use human brain organoids to dissect patient AIRIM variants associated with neurodevelopmental features. A subset of variants impaired ribosome production and protein synthesis, and delayed radial glial cell specification.

Bioleaching of rare earth elements using microorganisms offers an environmentally friendly alternative to thermochemical extraction. Here, Schmitz et al. generate a whole-genome knockout collection of mutants for one such microorganism, Gluconobacter oxydans, and identify genes affecting the production of acidic biolixiviant and thus bioleaching efficacy.

Whether Alzheimer’s disease originates in basal forebrain or entorhinal cortex remains highly debated. Here the authors use structural magnetic resonance data from a longitudinal sample of participants stratified by cerebrospinal biomarker and clinical diagnosis to show that tissue volume changes appear earlier in the basal forebrain than in the entorhinal cortex.

An analysis of 38 ancient genomes from the aurochs, the extinct ancestor of modern cattle, provides insight into the population ancestry and domestication of this species.

In this alternative approach to quantum computation, the all-electrical operation of two qubits, each encoded in three physical solid-state spin qubits, realizes swap-based universal quantum logic in an extensible physical architecture.

In extinct species including non-avian dinosaurs, bone density is shown to be a reliable indicator of aquatic behavioural adaptations, which emerged in spinosaurids during the Early Cretaceous.

Current biological models for examining cancer immunobiology in a HIV infected context are lacking. Here the authors use a human-derived microphysiological model to represent the HIV immune system and assess the ability of transferred populations of NK cells in the targeting of tumours.

A population epigenomic analysis of wild Arabidopsis thaliana accessions is presented, obtained by sequencing their whole genomes, methylomes and transcriptomes; thousands of DNA methylation variants are identified, some of which are associated with methylation quantitative trait loci.

Pertussis toxin is used extensively for perturbing Gαi/o pathways in the study of physiology and disease, but an equivalent inhibitor of Gαq signalling is not currently available to the research community. Here the authors characterize FR900359 as a specific Gq inhibitor and demonstrate its utility to dissect GPCR signalling and its potential to inhibit melanoma cells.

Post-fast refeeding increases intestinal stem cell function and tumour formation by augmenting protein synthesis via polyamine metabolism.

The onset of deep water export from the North Atlantic Ocean preceded the onset of Antarctic glaciation by about one million years, according to sediment geochemistry, and may have been triggered by tectonic changes in the Atlantic basin.

Examination of archaeological pottery residues and modern genes suggest that environmental conditions, subsistence economics and pathogen exposure may explain selection for lactase persistence better than prehistoric consumption of milk.

A20, encoded by TNFAIP3, is a negative-feedback inhibitor of NF-κB. Grey and colleagues identify natural human variants of TNFAIP3, which lower A20 activity and increase autoinflammatory responses. These alleles were inherited by descendants of Denisovans who crossed the Wallace Line to inhabit Oceania.

The scale and nature of energy investments under diverging technology and policy futures is of great importance to decision makers. Here, a multi-model study projects investment needs under countries’ nationally determined contributions and in pathways consistent with achieving the 2 °C and 1.5 °C targets as well as certain SDGs.

Estrogen promotes negative energy balance and preserves skeletal physiology. Here the authors show that loss of estrogen signalling after ablating estrogen receptor alpha (ERa) in specific hypothalamic neuronal populations leads to a marked sex-dependent increase in bone mass in female mice.

A tethered macrocyclic peptide antibiotic class described here—which shows potent antibacterial activity against carbapenem-resistant Acinetobacter baumannii—blocks the transport of bacterial lipopolysaccharide from the inner membrane to its destination on the outer membrane through inhibition of the LptB₂FGC complex.

Evolutionary modelling shows that an initial set of inhibitory neurons serving olfactory bulbs may have been repurposed to diversify the taxonomy of interneurons found in the expanded striata and cortices in primates.

Previously documented record values of the fusion triple product in the stellarator Wendelstein 7-X are shown to be evidence for reduced neoclassical energy transport in this optimized device.

Genome-scale screening of Gluconobacter oxydans B58 identifies genes and non-acid mechanisms involved in rare earth element bioleaching, providing insights into improving microbial recovery of critical minerals.

Analyses of 2,083 globally distributed group A Streptococcus (GAS) genomes enable the development of a compendium of all GAS vaccine antigen sequences, providing a platform for population-genomics-informed vaccine design.

The first week of life impacts health for all of life, but the mechanisms are little-understood. Here the authors extract multi-omic data from small volumes of blood to study the dynamic molecular changes during the first week of life, revealing a robust developmental trajectory common to different populations.

Data on de novo mutations in Arabidopsis thaliana reveal that mutations do not occur randomly; instead, epigenome-associated mutation bias reduces the occurrence of deleterious mutations.

Whole-ecosystem manipulations of Caribbean islands occupied by brown anoles, involving the addition of competitors (green anoles) and/or top predators (curly-tailed lizards), demonstrate that predator introductions can alter the ecological niches and destabilize the coexistence of competing prey species.

Climate change is spatially asymmetrical and so will alter the behaviour of generalist consumer species, affecting food webs in two ways. Movement into novel ecosystems will affect the topology of food webs, while changes within an ecosystem will affect interaction strengths.

Early stellarator designs suffered from high particle losses, an issue that can be addressed by optimization of the coils. Here the authors measure the magnetic field lines in the Wendelstein 7-X stellarator, confirming that the complicated design of the superconducting coils has been realized successfully.

Nonsense suppression, or reassigning stop codons to encode for other amino acids, offers a method for expanding the genetic code of proteins. Deletion of release factor 1 in an Escherichia coli strain enables the incorporation of non-natural amino acids into proteins at multiple sites.

Platypuses are monotremes and combine aspects of both reptilian and mammalian behaviour. An international consortium reports the genome sequence and analysis of Ornithorhynchus anatinus and as expected, parts of the genome look more like mammals, whereas other parts more like reptiles or even chickens.

Using insights from whole-genome screening, the mineral-dissolving microbe Gluconobacter oxydans was engineered by deleting the pstS gene and overexpressing mgdh, creating a strain that improves rare earth element extraction by up to 73%.

The Impact of Genomic Variation on Function Consortium is combining single-cell mapping, genomic perturbations and predictive modelling to investigate relationships between human genomic variation, genome function and phenotypes and will provide an open resource to the community.

Single-cell or single-nucleus RNA-sequencing experiments form a basis for biological insights about cell types and states, but they require orthogonal experiments to confirm the functional relevance of their findings. Here the authors discuss options to support such findings and their challenges.

As part of the Epigenome Roadmap Project, genome-wide maps of DNA methylation and transcriptomes together with genomic DNA sequencing of 18 different primary human tissue types from 4 individuals are presented; analysis reveals widespread differential methylation of CG sites between tissues, and the presence of non-CG methylation in adult tissues.

In this Perspective, a group representing a range of stakeholders makes the case for a set of five proposed globally applicable ethical guidelines for ancient human DNA research.

The COVID-19 pandemic spurred a wave of rapid and collaborative drug discovery efforts. This Perspective article summarizes scientific drivers and considerations behind such antiviral small-molecule discovery programmes and proposes strategies to accelerate future efforts.