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Altered mechanosensation by application of capsaicin to the skin is thought to be spinally mediated. Here, the authors use Ca2+ imaging in spinal neurons and develop a cell profiling approach to identify populations involved in central sensitization.

The archaeological site Shinfa-Metema 1 in the lowlands of northwest Ethiopia provides early evidence of intensive riverine-based foraging aided by the likely adoption of the bow and arrow.

After spinal cord injury, lesion-remote astrocytes acquire heterogeneous, spatially restricted reactivity states that shape neuroinflammation, neural repair and neurological recovery.

The neural circuits that transmit cool signals remain not fully understood. Here, authors identify a spinal circuit in mice that transmits cool sensations from the skin to the brain, revealing a dedicated neural pathway for detecting innocuous cool temperatures.

Human immunodeficiency virus (HIV)-associated gut microbiome dysbiosis correlates with systemic immunodeficiency and opportunistic gut infections. Faecal microbiome transplantation from people living with HIV with high peripheral CD4⁺ T cell counts improved intestinal immunity and protection against Cryptosporidium parvum in mice.

New hominin fossils from the Grotte à Hominidés at Thomas Quarry I (ThI-GH) in Casablanca, Morocco, dated to around 773 thousand years ago are similar in age to Homo antecessor, yet are morphologically distinct.

The origin and dispersal of Homo erectus, a long-lived and geographically widespread human ancestor, are unclear despite a rich fossil record. Here, the authors reconstruct the face from a Homo erectus cranium from Gona, Ethiopia, dated to 1.5-1.6 million years ago, providing insights into the evolutionary transition from early Homo to H. erectus.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Uterine perivascular cells were identified as progenitors for endometrial re-epithelialization via mesenchymal-to-epithelial transition, whereby cellular quiescence and activation were mediated via Notch signaling and estrogen, respectively.

Replication-dependent histone mRNA decay involves the RNA helicase UPF1, the histone stem-loop binding protein SLBP and the exoribonuclease 3’hExo. Here, the authors present evidence for assembly of a degradosome-like complex involving the three proteins and delineate the mechanism that drives their concerted action to achieve histone mRNA decay.

Lo and colleagues report that double-positive thymocytes from neonates express less Zap70 and show reduced Ca^2⁺/NFAT signaling compared to double-positive thymocytes from older thymi. This diminished Ca^2⁺ signaling alters negative selection for self-reactive TCRs, resulting in a cell-intrinsic temporal window for regulatory T versus conventional T cell development in the thymus.

Astrocytes regulate synaptic transmission. Carlsen et al. report that spinal astrocytes activated by endocannabinoids inhibit excitatory synaptic transmission and, thereby, decrease tremor.

Ureaplasma parvum is often isolated from intrauterine infections, which are associated with 40% of preterm births. Here, Pavlidis et al. present a mouse model of ascending U. parvum infection that resembles human disease, and show that mild cervical damage promotes intrauterine infection, inflammation and preterm birth.

Evidence that a dry-season outbreak of malaria in Dire Dawa, Ethiopia is caused by Anopheles stephensi carrying Plasmodium falciparum with diagnostic and drug resistance mutations calls for heightened vector surveillance in both urban and rural settings.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Two populations of neurons with distinct anatomy and receptor expression that convey information from the spinal cord to the brain have different functional properties with respect to touch and pain.

This study demonstrates that orange carrot was selected during the Renaissance period, probably in western Europe, through the selection of three recessive genes that increased the provitamin A carotenoid (α- and β-carotene) content.

Type 1 diabetes is associated with homozygous expression of specific major histocompatibility complex class II beta chain polymorphisms. Here the authors show that the disease-protective effect of major histocompatibility complex class II heterozygosity is conferred by non-cognate thymocyte negative selection.

μ opioid receptors (MORs) expressed on primary afferent nociceptor neurons are responsible for two maladaptive side-effects of chronic opioid use: opioid tolerance and opioid-induced hyperalgesia (pain). A combination therapy of opioid receptor agonism plus peripheral-restricted MOR antagonism abrogates these side-effects while preserving opioid analgesia in rodent models of peri-operative and chronic pain.

This work describes an informatic framework to identify multi-allelic markers in the genome of the malaria-causing Plasmodium vivax parasite that can inform on familial relatedness between infections. Spatial and temporal transmission patterns are demonstrated with an example marker set.

Magen et al. discovered new miRNA-based biomarkers in the blood of patients with ALS. miR-181 levels alone or in combination with an established protein biomarker predict ALS severity and prognosis and might enhance the power of clinical trials.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Toxoplasma gondii secretion systems can be engineered to deliver multiple large therapeutic proteins to neurons in vitro and in vivo.

Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease.

A large literature has demonstrated the important role of spinal microglia in chronic pain processing. This paper demonstrates that microglia are required in male but not female mice. In female mice, a similar function appears to be subserved by adaptive immune cell, likely T lymphocytes.

Urinary albumin-to-creatinine ratio (UCAR) is associated with various clinical outcomes such as kidney disease and cardiovascular disease. Here, the authors report genome-wide meta-analysis in over 500,000 individuals and find 68 UACR loci, followed by statistical fine-mapping, gene prioritization and experimental validation in flies.

A trans-ancestry genome-wide association study of serum urate levels identifies 183 loci influencing this trait. Enrichment analyses, fine-mapping and colocalization with gene expression in 47 tissues implicate the kidney and liver as key target organs and prioritize potential causal genes.

Drugs that block calcium channels reduce pain, but they can cause unwanted side effects. Now, Rajesh Khanna and his colleagues show that a peptide that inhibits the interaction between a calcium channel and a protein called CRMP-2 that activates the channel can reduce pain in animals without the side effects of the channel blocker drugs.

Ruth Loos and colleagues report a meta-analysis of genome-wide association studies in 181,171 individuals identifying 14 new loci associated with heart rate and test these for association with cardiac conduction, rhythm disorders and cardiovascular disease. Their experimental studies in Drosophila melanogaster and zebrafish models provide support for a role for 20 candidate genes at 11 of these loci in regulation of heart rate.

In the phase 2 HUDSON study, patients with advanced non-small-cell lung cancer received anti-PD-L1 combined with biomarker-guided therapy targeting ATR kinase, PARP, STAT3 or CD73, leading to encouraging clinical benefit in response to combination of the ATR kinase inhibitor ceralasertib with durvalumab.

GEMIN5, an RNA-binding protein, is required for formation of small nuclear ribonucleoproteins. Here, the authors identify loss of function mutations in GEMIN5 that are associated with a human neurodevelopmental disorder.

A genome-wide association study meta-analysis combined with multiomics data of osteoarthritis identifies 700 effector genes as well as biological processes with a convergent involvement of multiple effector genes; 10% of these genes express the target of approved drugs.

The HOX gene cluster is responsible for anteroposterior axis patterning in an evolutionarily conserved manner. Here they examine HOX gene expression in human embryos and show that neural-crest derivatives retain the anatomical HOX code of their origin while also adopting the code of their destination.

A set of neurons in the peri-locus coeruleus region controls arousal and avoidance states, providing an understanding of the neurobiological basis of arousal and exploratory behaviours.

Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

Pain and itch are very distinct sensations that rely on both overlapping and orthogonal mechanisms in primary sensory afferents and in the spinal cord. In this article, Bautista, Wilson and Hoon review recent advances in our understanding of the molecular, cellular and circuit basis of acute and chronic itch in the peripheral and central nervous systems.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

The dynamic of plasma heating in solar flares can be effectively derived from observations of optical hydrogen H-α line emissions. Here the authors report the observation of a C1.5 class flare that produced two H-α ribbons, interpreted combining radiative models affected by an electron beam.

Geospatial estimates of child growth failure in Africa provide a baseline for measuring progress and a precision public health platform to target interventions to those populations with the greatest need.

ABCC9 encodes the SUR2 subunit of K_ATP channels and dominant genetic variants in ABCC9 have been associated with cardiac phenotypes. Here, the authors report recessive ABCC9 mutations in individuals with mild intellectual disability, myopathy and cardiac systolic dysfunction which is associated with loss of K_ATP channel function.

Impairment of cognitive function is a common feature of many neurodevelopmental disorders. Systems genetics analysis in the brain uncovered a convergent gene network for both cognition and neurodevelopmental disorders. As the network does not recapitulate known pathways, this finding represents a new basis for understanding factors influencing normal and disordered cognition.