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Metformin is under clinical trial for brain neuroprotection but how it may work is poorly understood. Here, the authors show that metformin helps myelin formation by human oligodendrocytes and improves mitochondrial action in all brain cells.

The transition from senior postdoc to early-stage investigator is a pivotal step in the careers of academic scientists. In this series, early-stage investigators reflect on their labs’ first publications and the journeys that led them there.

The authors timestamp the development of amyloid plaques in a mouse model of Alzheimer’s disease in order to examine how plaque age affects the surrounding brain tissue. This includes a growing loss of nearby synapses, an increase in toxicity, and an increase in structural aggregation.

Hypoimmune gene editing in human pluripotent stem cells (hPSCs) provides a promising platform for cellular therapies. Here, the authors report that CRISPR mediated deletion of ICAM-1 in hPSC-derived grafts reduces immune cell adhesion, dampens T cell activation, and protects against immune rejection.

Unlike humans, rodents do not accumulate the brain pigment neuromelanin in catecholamine neurons with age. The transgenic mouse model here presented accumulates neuromelanin and mimics the early physiopathology of Parkinson’s disease.

In this study, the authors present work showing shared and distinct predictive network features associated with internalizing and externalizing behaviors in children, adolescents and adults.

I’ve learnt to overcome some aspects of my social anxiety, but I hope sharing my experiences can help others recognize the difficulties faced by scientists like me.

In schistosomiasis-endemic regions, the cyclical nature of infection and treatment complicates understanding of host immune responses. Repeated controlled human Schistosoma mansoni infection, designed to reflect the reinfection cycles common in endemic areas, shows that repeated exposure induces mixed worm-specific CD4⁺ T cell responses similar to those seen in endemic infection.

Current tissue engineering strategies lack materials that promote angiogenesis. Here the authors develop a microfluidic in vitro model in which chemokine-guided endothelial cell sprouting into a tunable hydrogel is followed by the formation of perfusable lumens to determine the material properties that regulate angiogenesis.

Lynch, Brenner and colleagues find that tissue-resident γδ T cells reside in adipose tissues in both mice and humans. These cells play essential roles in regulating thermogenesis and supporting age-dependent increases in adipose-tissue regulatory T cell populations.

Lydia Makkubu reflects on the socio-cultural dimensions at work in the Third-World that affect the numbers of women scientists, and introduces interventions that may help improve the situation.

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.

It is difficult to balance the benefits of collaboration and competition, argues Lydia Murray.

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.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Metabolic enzymes of the tricarboxylic acid cycle, such as 2-oxoglutarate dehydrogenase, are differentially expressed in absorptive and secretory lineages, guiding cell fate establishment and offering insights for targeted regenerative therapies.

White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.

Experimental warming of the active layer in permafrost tundra increased ecosystem respiration ~30%. Shoulder-season warming caused rapid snow melt and 100-fold higher methane emissions. Warming promotes greenhouse gas emissions, potentially contributing to arctic amplification of climate change

Dietary quality is reported at the global, regional and national level across 185 countries. Though diet quality increased modestly since 1990 at the global level, in South Asia and Sub-Saharan Africa it did not improve. In some regions, children’s dietary quality is lower than that of adults.

An analysis based on data from the Global Dietary Database shows mean animal-sourced food intakes among children and adolescents increased modestly from 1990 to two portions per day in 2018, but remain low in sub-Saharan Africa, India and Bangladesh.

Here, the authors compared measurements between 34 laboratories from 19 countries, to quantify by mass spectrometry four ceramides of clinical relevance in human blood plasma Standard Reference Materials. The main goals were to evaluate concordance obtained in a large inter-laboratory trial and to report absolute concentrations of four circulating lipids in a publicly available standard.

In a multicenter research program coordinated by the International Mouse Phenotyping Consortium, Spielmann et al. analyze the cardiac function and structure in ~4,000 monogenic mutant mice and identify 705 mouse genes involved in cardiac function, 75% of which have not been previously linked to cardiac heritable disease in humans. Using the UK Biobank human data, the authors validate the link between cardiovascular disease and some of the newly identified genes to illustrate the resource value and potential of their mutant mouse collection.

Recent estimates of sugar-sweetened beverages (SSBs) intake are generally unavailable. Here the authors show a global SSBs intake of 2.7 servings/week in 2018 in adults (range: 0.7 South Asia, 7.8 Latin America/Caribbean); intakes were higher among males, younger, more educated, and urban adults.

The genome of the model fern species Ceratopteris richardii reveals a history of remarkably dynamic genome evolution, including rapid changes in genome content and structure following the most recent whole-genome duplication approximately 60 million years ago.

Aarno Palotie and colleagues present results of a large genome-wide association study of migraine. They identified significant associations at 38 distinct loci and found enrichment for genes expressed in vascular and smooth muscle tissues.

Metformin treatment was found to be associated with acute increases in the appetite-suppressing metabolite Lac-Phe in several human observational and interventional studies.

The p85 regulatory subunit of phosphoinositide 3-kinase (PI3K) exists in two major isoforms: p85-alpha and -beta. Here, the authors reveal that p85-beta has a unique nuclear activity where it regulates gene transcription and contributes to tumorigenesis.

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).

Studying the intestinal pathology of undernourished children in Zambia with persistent stunting reveals that adaptation to pathogen exposure in early life may explain why children with stunting do not respond well to nutrient supplementation.

Recognizing ovarian aging as a formal diagnosis — akin to how the field of obstetrics adopted the concept of ‘advanced maternal age’ — would transform reproductive medicine, public health and research into women’s health.

Assessment of the health risks of exposure to anthropogenic nanomaterials is crucial to maximize their potential applications. This double-blind, randomized controlled study in healthy humans evaluates the impact of inhalation of graphene oxide nanosheets on acute pulmonary and cardiovascular functions.

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.

Telomerase deficiency leads to age-related diseases and shortened lifespan, while inhibition of the mTOR pathway delays aging. Here, the authors show that inhibition of mTORC1 signaling shortens the lifespan of telomerase deficient mice.

Analyses of genomes from 914 children, adolescents, and young adults provide a comprehensive resource of genomic alterations across a spectrum of common childhood cancers.

Metabolism can influence gene expression through histone modifications. Using a mouse model of the inborn error of metabolism propionic acidaemia, Park et al. show how raised propionate levels produce epigenetic actions that impact cardiac function.

 A transcriptomic cell-type atlas of the whole adult mouse brain with ~5,300 clusters built from single-cell and spatial transcriptomic datasets with more than eight million cells reveals remarkable cell type diversity across the brain and unique cell type characteristics of different brain regions. 

Differential expression of inflammasome gene modules and inflammasome-activating metabolites correlates with interleukin-1β expression, hypertension, arterial stiffness and longevity in older individuals.