Search

3D brain organoids have been used to investigate human brain development and pathology. Here the authors establish human ventral midbrain organoids coupled with single cell sequencing to study developing and mature dopamine neurons and use silk scaffolding to generate bioengineered brain organoids

Spinal cord injury (SCI) often leads to immune dysfunction, but mechanistic insights are still lacking. Here the authors show that SCI alters chemokine signaling and induces long, persisting defects in hematopoietic stem and progenitor cell migration, thereby entrapping them in the bone marrow and disrupting peripheral immune homeostasis.

Macrophages are critical regulators of adipose tissue homeostasis and function, though the mechanisms by which they impart these effects are unknown. Here, the authors show that Mir6236 is secreted by adipose tissue macrophages and regulates adipocyte insulin resistance and organismal metabolism during obesity.

Some individuals remain uninfected despite heavy exposure to tuberculosis. Using a household study in Indonesian living with tuberculosis patients, the authors here find that innate immune responses, not antibodies, correlate with protection against initial infection, particularly in individuals who have received the BCG vaccine.

Genomic analysis of Plasmodium DNA from 36 ancient individuals provides insight into the global distribution and spread of malaria-causing species during around 5,500 years of human history.

This study uses single-nucleus RNA sequencing to analyze lung tissue from 141 individuals with chronic obstructive pulmonary disease. Distinct patterns of spatially resolved changes in cell composition and cell states that correlate with clinical features are highlighted.

The combination of short-read sequence data, synthetic long reads and physical genome mapping allows for a phased de novo assembly of human genomes.

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.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

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.

Macrophages are pleiotropic and can have different functions and phenotypes. Here the authors show that a population of macrophages, previously described as pro-fibrotic, can be induced through Notch2 blockade and that in a mouse lung injury and fibrosis model this macrophage population does not promote inflammation or fibrosis.

Here, the authors show that SARS-CoV-2 infection causes gut microbiome dysbiosis and gut epithelial cell alterations in a mouse model, and correlate dysbiosis observed in COVID-19 patients with blood stream infections, matching reads of bacterial sequences from stool samples to organisms found in the blood.

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.

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.

Here, the authors report recent updates to the ENCODE data portal including a redesigned home page, an improved search interface, custom-designed pages highlighting biologically related datasets and an enhanced cart interface for data visualisation plus user-friendly data download options.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

Whether switching from low-molecular-weight heparin to direct oral anticoagulants (DOACs) in cancer-associated thrombosis patients is safe and effective is unknown. Here, the authors show that switching to DOACs reduced venous thromboembolism and mortality without increasing bleeding.

A risk score based on a 34-gene signature for outcome prediction in meningioma was developed and validated in large multi-institutional cohorts and showed better performance in discriminating postoperative menignioma outcomes compared with existing meningioma classification systems.

In thromboinflammation, early tissue plasminogen activator administration directly improves endothelial barrier function, prophylactic defibrotide and enoxaparin suppress microvascular thromboinflammation through endothelium-mediated mechanisms and combining enoxaparin with crizanlizumab reduces microvascular occlusion and protects endothelial function in sickle cell disease.

Recent reviewers suggest good books to refresh your mind this summer — from a cultural history of piracy to a scientific tour of the boulevards of Paris.

A survey of SARS-CoV-2 RBD antibodies identifies those with activity against diverse SARS-CoV-2 variants and SARS-related coronaviruses, highlighting epitopes and features to prioritize in antibody and vaccine development.

Yin Yang 1 (YY1) aids in the formation of enhancer–promoter (E–P) loops independently of cohesin. YY1 maintains a subset of E–P interactions in interphase and establishes an overlapping yet distinct set after mitotic exit.

Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.

Current action is insufficient to meet both the Paris Agreement and the Sustainable Development Goals. Integrated model-based analysis shows that strong interventions across many dimensions, together with ambitious lifestyle change, are needed to enable real progress towards the UN Agenda 2030.

The nutritional, economic and livelihood contributions provided by aquatic food systems are threatened by climate change. Building climate resilience requires systemic interventions that reduce social vulnerabilities.

The impact of rapidly falling costs of renewable energy and battery technology on long-term climate stabilization pathways is not well understood. Luderer et al. show that reduced renewable costs and climate policies will make electricity the cheapest energy carrier and can lead to electricity accounting for nearly two-thirds of global energy use by mid-century.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

Glycine sensing in the dorsal vagal complex (DVC) regulates hepatic glucose production in rodents. Here the authors show that pharmacological and molecular inhibition of glycine reuptake in the DVC potentiates NMDA receptors, and improves metabolic homeostasis in animal models of obesity and diabetes.

Genome-wide association meta-analysis of AAA identifies 121 independent risk loci and highlights potential therapeutic targets such as proprotein convertase, subtilisin/kexin-type 9 (PCSK9).

Sharks and rays are vital coral reef species. This study shows that nearly two thirds (59%) of the 134 coral-reef associated species are threatened with extinction. The main cause of their decline is found to be overfishing, both targeted and unintentional, and extinction risk is greater for larger species found in nations with higher fishing pressure and weaker governance.

A red blood cell haemostatic mechanism induced by dying ECs functions independently of platelets and fibrin.

Condensin-depleted mitotic chromosomes compartmentalize and form contacts among regulatory elements despite lacking transcription and most chromatin-associated factors. Heterochromatin protein 1 (HP1) proteins are surprisingly dispensable for compartmentalizing constitutive heterochromatin.

Using a gain-of-function method, this work identified 14 plant proteins that can repress gene expression via diverse epigenetic pathways, including DNA methylation, histone modifications and interference of RNA polymerase II transcription.

Using ethnically and geographically diverse metagenomic data, the authors identify microbiota alterations associated with inflammatory bowel disease (IBD). They discover universal IBD-associated bacteria, which serve as the basis for a multibacteria biomarker panel that could support a noninvasive tool for IBD diagnosis.

Cognitive function is associated with health and important life outcomes. Here, the authors perform a genome-wide association study for general cognitive function in 300,486 individuals and identify genetic loci that implicate neural and cell developmental pathways in this trait.

Progranulin deficiency causes untreatable neurodegenerative diseases. Here, the authors show that hematopoietic stem cell transplantation and optimized brain conditioning correct the disease phenotype in progranulin-deficient mice.

A synthetic proteome-scale strategy enables the identification of a diverse range of human proteins that can induce the degradation or stabilization of a target protein in a proximity-dependent way.

Glucagon has traditionally been thought to act exclusively on the liver to promote endogenous glucose production in that organ. Tony Lam and his colleagues now show that it also acts on the hypothalamus to inhibit glucose production through a neural relay to the liver and that under high fat–fed conditions in rats this pathway is inhibited. This resistance may further explain the hyperglycemia that exists during obesity and diabetes.

The most recent class of base editors utilize DddAtox, a deaminase domain that can act upon double-stranded DNA. Here the authors target DddAtox fragments and a FokI-based nickase to the human CIITA gene by fusing these domains to arrays of engineered zinc fingers; they also identify a variety of DddAtox orthologues.

The brain has a central role in the regulation of organismal energy homeostasis. Here the authors show that neurons in the mediobasal hypothalamus respond to fatty acids by generating neuronal signals, relayed to the liver viavagal nerves that mediate secretion of very-low-density lipoproteins.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Coastal and marine projects in the Global South can exacerbate existing contextual inequities, particularly in high-stakes locations found across all ocean basins and identified using current investment levels and a composite index of inequity.

Higher-order chromatin structure is temporarily disrupted during mitosis. Here the authors show that loss of the architectural factor CTCF results in failure to form structural loops and leads to inappropriate cis-regulatory contacts and alterations of compartmental interactions after mitosis. Furthermore, they show global 3D architecture is set up without transcription, but that transcription contributes to proper gene domain formation.

Observations of gravitational instability in the disk around AB Aurigae using deep observations of ¹³CO and C¹⁸O line emission provide evidence that giant protoplanets can be formed from collapsing fragments of vast spiral arms.

The distribution and uptake of siderophores across a meridional section of the eastern Pacific Ocean suggests that iron availability limits microbial metabolism in the upper mesopelagic in several large ocean basins.