Search

Accurate non-invasive biomarkers to diagnose MASLD-related fibrosis are urgently needed. Here the authors show a disease mechanism-related blood-based biomarker panel consisting of three biomarkers which is able to accurately identify MASLD patients with mild or advanced hepatic fibrosis.

Fat distribution is associated with cardiometabolic disease, although it has been less well studied than overall obesity. In a multiancestry exome-sequencing study, the authors identified predicted loss-of-function mutations in INHBE associated with favorable fat distribution and protection from type 2 diabetes.

Greenland’s ice loss depends on propagation of mass loss from the marine glacier termini to the interior. An analysis of surface elevation change in 16 glacier catchments shows that the up-glacier extent of thinning is limited by glacier geometry.

Engineering new ligands that specifically target multiple G protein-coupled receptors with desired activity profiles requires time-consuming and expensive cycles of design-make-test-analyse work. Now it has been shown that limited experimental data can be used to train sophisticated machine learning models to accurately predict the activity of previously uncharacterized peptide ligand variants.

In a voter game, information gerrymandering can sway the outcome of the vote towards one party, even when both parties have equal sizes and each player has the same influence; and this effect can be exaggerated by strategically placed zealots or automated bots.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis that is activated by physiological regulators associated with health and longevity. Here, Steinberg and Carling provide an overview of the physiological functions of AMPK and discuss the potential of this enzyme as a therapeutic target across diverse disease areas. Pharmacological activation of AMPK and the associated drug development challenges are assessed.

This isoform-centric microglia genomic atlas includes 35,879 novel human microglia isoforms identified by long-read RNA sequencing. A multi-ancestry quantitative trait locus meta-analysis of known and novel isoforms in 555 samples from 391 donors finds associations with genetic risk loci in Alzheimer’s and Parkinson’s diseases.

TG2 functions as an eraser and exchanger of H3 monoaminylations, including histaminylation of Gln5 of histone H3.

A new method for measuring plant biodiversity based on spectral reflectance profiles captures variation in productivity comparable to that of taxonomic, functional and phylogenetic diversity.

Excessive lipid accumulation in hepatocytes causes fatty liver disease and liver failure. Here the authors show that ablation of Mitochondrial Fission Process 1 in hepatocytes in mice protects fatty liver disease and dysfunction caused by high fat diet.

Matye el al. show that coenzyme-A and glutathione deficiency in NAFLD limits fatty acid oxidation and antioxidant defence capacity. The nutrient sensing transcription factor EB induces autophagy–lysosome proteolysis and methionine cycle-transsulfuration to maintain hepatic cysteine, coenzyme-A and glutathione availability.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Using machine learning algorithms, this study estimates sea level rise and high tide flooding thresholds every 10 km along the United States’ coasts, complementing conventional linear-/point-based estimates and offering insights for ungauged areas.

The unfolded protein response (UPR) aims to relieve endoplasmic reticulum (ER) stress and restore protein homeostasis, but also contributes to disease. Here, Marciniak et al. assess small molecules that target ER stress and the UPR, highlighting those diseases in which the role of the UPR and its therapeutic modulation have been most well studied.

Evolutionary modelling and expert review are applied to integrate experimentally supported knowledge accumulated in the Gene Ontology knowledgebase to create a draft human gene ‘functionome’.

Novel peroxisome proliferator-activated receptor (PPAR) agonists are providing new opportunities in the management of metabolic and cardiovascular diseases. In this Review, Staels and colleagues discuss the physiological regulation and actions of the PPAR family and their modulation of the atherogenic lipid profile, atherosclerosis and cardiac remodelling.

In human societies, individuals who violate social norms may be punished by third-party observers who have not been harmed by the violator; this study suggests that a reason why the observers are willing to punish is to be seen as more trustworthy by the community.

The authors present the largest genome-wide association study to date for a rare Parkinsonian disorder, progressive supranuclear palsy (PSP). They include follow-up investigations of the identified susceptibility loci, functional consequences, and cell-specific pathologies, providing insights into genetic and molecular mechanisms underlying PSP.

Liver transplantation has progressed from an experimental procedure to routine operation since the first human liver transplantation in 1963. This Timeline article revisits the important milestones in the development of liver transplantation, discussing how the procedure has evolved over time and what challenges are still to overcome.

Maneix, Iakova and colleagues report that cyclophilin A is a chaperone for, and regulator of, intrinsically disordered proteins within haematopoietic stem and progenitor cells, with potential effects on ageing-like phenotypes and lineage commitment.

The current increasing rates of obesity are paralleled by a rise in the prevalence of chronic kidney disease. This Review outlines the potential mechanisms by which obesity might influence kidney function, but also presents evidence for the regulation of body weight by the kidney.

The CMS Collaboration reports evidence for off-shell Higgs boson contributions in the production of Z boson pairs, and measures the width of the Higgs boson, which is inversely related to its lifetime.

The CMS Collaboration reports the study of three simultaneous hard interactions between quarks and gluons in proton–proton collisions. This manifests through the concurrent production of three J/ψ mesons, which consist of a charm-quark–antiquark pair.

Surveys from 2,584 sites across the Indo-Pacific identify key climate, socioeconomic and environmental drivers associated with hard coral assemblages. This informs a strategic approach to protect, recover or transform coral reef management.

The most up-to-date combination of results on the properties of the Higgs boson is reported, which indicate that its properties are consistent with the standard model predictions, within the precision achieved to date.

Earth System Models are widely used for projecting future streamflow. The authors show that the models underestimate declines in global streamflow with climate change, indicating that a future water crisis could be more severe than previously estimated.

Climate change can exert a significant effect on the ozone recovery. Here, the authors show that the Arctic polar vortex shift associated with Arctic sea-ice loss could slow down ozone recovery over the Eurasian continent.