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My lack of time and fresh perspective has made me a better, more focused scientist, says nutrition epidemiologist Lindsey Smith Taillie.

Mouse models expressing liver apoE in the absence of brain apoE reveal detrimental effects of peripheral apoE4 associated with Alzheimer’s risk on cognition and amyloid pathology through compromising vascular integrity and function.

Genome assemblies of two allotetraploid cotton germplasms, Jin668 and YZ1, reveal the regulatory mechanisms underlying somatic embryogenesis and plant regeneration, and provide potential for precise genome editing in cotton.

Mismatch between the ancestry of mitochondrial and nuclear genomes can drive somatic evolution during ageing. Analysis of around 1.2 million mitochodrial somatic mutations in young and old mice shows haplotype-specific mutational patterns and hotspots, and reversion mutations that re-align mito-nuclear ancestry during an organism’s lifespan.

Xianlong Zhang, Keith Lindsey and colleagues report a population genomic analysis of Upland cotton (Gossypium hirsutum) that identifies 93 potential domestication-sweep regions and 19 candidate loci for fiber-quality-related traits. Their analysis provides evidence for asymmetric subgenome selection for long white fibers in cultivated cotton.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

Over the past years, countries in Latin America and the Caribbean have seen a range of developments around climate mitigation and environmental policy. Nature Climate Change asked a selection of scientists from the region to share their thoughts on research questions and responses to climate change in their area of study.

Many low- and middle-income countries, including The Gambia, had low COVID-19 vaccination coverage during the emergence of the Delta and Omicron variants. Here, the authors perform a prospective household cohort study in the Gambia to investigate the dynamics of SARS-Cov-2 infection in this setting.

A proteomic risk score for cardiorespiratory fitness, comprising as few as 21 proteins, is dynamic with exercise training and helps predict the risk of mortality and a range of cardiovascular, metabolic and neurological conditions.

GIANT, a genetically informed brain atlas, integrates genetic heritability with neuroanatomy. It shows strong neuroanatomical validity and surpasses traditional atlases in discovery power for brain imaging genomics.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

We evaluated the use of chimeric antigen receptor-modified T cells targeting GD2 (GD2-CART) for H3K27M⁺ diffuse midline glioma (DMG), finding that intravenous administration of GD2-CART, followed by intracranial infusions, induced tumour regressions and neurological improvements in patients with H3K27M-mutant pontine or spinal DMG.

A targeted protein stabilization platform termed deubiquitinase-targeting chimera (DUBTAC) was developed based on heterobifunctional small molecules consisting of a deubiquitinase OTUB1 recruiter linked to a protein-targeting ligand.

Early life exposure to environmental stressors, including endocrine disrupting chemicals (EDCs), can impact health later in life. Here, the authors show that neonatal EDC exposure in rats causes epigenetic reprogramming in the liver, which is transcriptionally silent until animals are placed on a Western-style diet.

A high-resolution gene expression atlas of prenatal and postnatal brain development of rhesus monkey charts global transcriptional dynamics in relation to brain maturation, while comparative analysis reveals human-specific gene trajectories; candidate risk genes associated with human neurodevelopmental disorders tend to be co-expressed in disease-specific patterns in the developing monkey neocortex.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

The glaciers of Juneau Icefield, Alaska are reconstructed from 1770 to 2020 AD. Ice loss has accelerated dramatically, with a number of positive feedbacks now happening that accelerate ice loss and inhibit future stabilisation and regrowth.

Genome-wide ancient DNA data from individuals from the Middle Bronze Age to Iron Age documents large-scale movement of people from the European continent between 1300 and 800 bc that was probably responsible for spreading early Celtic languages to Britain.

Hypermutation and microsatellite burden determine responses and long-term survival following PD-1 blockade in children and young adults with refractory cancers resulting from germline DNA replication repair deficiency.

A phase I dose-escalation trial of GD2-CAR T cells in children and young adults with diffuse midline gliomas to assess the feasibility of manufacturing, safety and tolerability, and to preliminarily assess efficacy.

Here the authors identify 33 individuals with a dominant neurodevelopmental disorder due to heterozygous missense or loss-of-function variants in the gene encoding Densin-180, a scaffold protein present at postsynaptic sites in neurons of the central nervous system.

Dense calcium imaging combined with co-registered high-resolution electron microscopy reconstruction of the brain of the same mouse provide a functional connectomics map of tens of thousands of neurons of a region of the primary cortex and higher visual areas.

Cities offer higher wages and more opportunities for adults but provide limited upward income mobility for children. This study finds that movement around cities varies more among US students of different income levels than among students and adults. Students from higher-income families spend more time outside the home and explore more unique locations, suggesting urban income mobility echoes physical mobility.

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).

Black pepper (Piper nigrum) belongs to the long-isolated lineage of basal angiosperm and its fruit has been used for food spice and phytomedicines for thousands of years. Here, the authors assemble the reference genome of this species and analyze gene families associated with piperine biosynthesis.

Photophoretic optical trapping of cellulose particles and persistence of vision are used to produce real-space volumetric images that can be viewed from all angles, in geometries unachievable by holograms and light-field technologies.

Analysis of antibody responses to COVID-19 vaccines encoding variant-specific spike, with or without ancestral spike, suggests no loss of neutralization of the ancestral virus with variant-only vaccines, which may simplify future vaccine updates.

T cells that are activated by self-antigens in the periphery can migrate into the brain causing neuroinflammatory disease. Here the authors show that TBK1 is necessary for activated T-cell egress from the lymph node, and blocking TBK1 ameliorates autoimmunity in a mouse model of multiple sclerosis.

Pak et al. show that prolonged fasting is required for the effects of calorie restriction on insulin sensitivity, fuel utilization and ageing in mice.

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.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

Currently licensed COVID-19 vaccines are based on antigen sequences of early SARS-CoV-2 isolates, despite the prevalence of variants of concerns escaping vaccine-mediated protection. Using their updated yellow fever 17D vectored candidate, here, authors assess neutralising antibody responses against variants of concern, and demonstrate protection and reduced transmission in a hamster model.

Spatial metabolomics are used to describe the location and chemistry of small molecules involved in metabolic phenotypes. Here, Conroy et al. present a bioinformatic pipeline to analyze MALDI data and show that it can be used to identify actionable targets such as glycogen in fibrotic lungs of both human and mice.

Here, Reader et al. screen the Medicines for Malaria Venture Pandemic Response Box in parallel against Plasmodiumasexual and liver stage parasites, stage IV/V gametocytes, gametes, oocysts and as endectocides. They identify two potent transmission-blocking drugs: a histone demethylase inhibitor ML324 and the antitubercular SQ109.

Ageing is associated with clonal hematopoiesis of indeterminate potential (CHIP), which is linked to increased risks of hematological malignancies. Here the authors uncover an epigenetic mechanism through which mutant p53 drives clonal hematopoiesis through interaction with EZH2.

A study of multisystem inflammatory syndrome in children (MIS-C) shows maintenance of elevated levels of monocyte-activating pathogen-specific IgG not seen in children infected with SARS-CoV-2 who do not develop MIS-C.

The improved genome assemblies of allotetraploid cotton species Gossypium hirsutum and Gossypium barbadense provide insights into cotton evolution and inform the construction of introgression lines used to identify loci associated with fiber quality.

In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer’s disease, and functional analysis suggests it interacts with amyloid-beta.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Fifty-five percent of individuals vaccinated with an attenuated Plasmodium falciparum sporozoite vaccine remained without parasitemia after controlled human malaria infection one year later; immune correlate analysis in humans and non-human primates suggest a role for liver-resident T cells.

Comprehensive genomic and transcriptomics analyses of more than 1,300 cases of childhood T-lineage acute lymphoblastic leukaemia identify 15 distinct subtypes that are associated with specific outcomes.

The pathogenesis of biliary atresia remains poorly understood. Here, the authors report that maternal butyrate treatment alters the gut microbiome and glutamine/hypoxanthine metabolites similar to human subjects, and suppresses biliary atresia in newborn mice.