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The use of antibodies against tumour necrosis factor (TNF) has markedly improved the treatment of Crohn's disease, but only certain patients respond to therapy. Here, Raja Atreya and colleagues have developed an approach using topical fluorescent antibodies to TNF and confocal laser endomicroscopy to evaluate the expression of transmembrane TNF (mTNF) in the intestinal mucosa of patients with active Crohn's disease in order to identify patients likely to respond to subsequent treatment with the anti-TNF therapy, adalimumab.

Structural, conformational and biochemical characterization of the AROM complex and its constituent shikimate pathway domains reveals how the complex balances compactness and conformational freedom, yet does not benefit from substrate channeling.

Muscle weakness has been associated with morbidity and mortality in older people. Here, the authors have investigated this trait further by performing a genome-wide meta-analysis of grip strength and Mendelian randomization to discover causal relationships between muscle weakness and other diseases.

A long-duration campaign to image the Sun’s middle corona—a region about 1.5–3 solar radii from the centre—reveals three dynamical processes that shape and restructure the middle corona. The dynamics can influence the global coronal structure and beyond.

Pre-existing antibodies against Cas9 proteins represent a potential issue for gene therapies, including those targeting the eye. Here the authors assess the presence of intraocular antibodies, and show that Cas9 antibodies were prevalent in human serum but not the eye, unless prior bacterial infection occurred.

Combining expansion microscopy with super-resolution radial fluctuations captures the morphology of single proteins.

Gaining access to medical data to train AI applications can present problems due to patient privacy or proprietary interests. A way forward can be privacy-preserving federated learning schemes. Kaissis, Ziller and colleagues demonstrate here their open source framework for privacy-preserving medical image analysis in a remote inference scenario.

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.

Genome-wide analyses identify variants associated with sinus node dysfunction, distal conduction disease and pacemaker implantation, implicating ion channel function, cardiac developmental programs and sarcomeric structure in bradyarrhythmia susceptibility.

Mitochondria have a pivotal role in the transport of dietary lipids in enterocytes, a finding that might have relevance to understanding the aberrant gastrointestinal function in patients with mitochondrial disorders.

Direct quantum state tomography—deducing the state of a system from measurements—is mostly unfeasible due to the exponential scaling of measurement number with system size. The authors present two new schemes, which scale linearly in this respect, and can be applied to a wide range of quantum states.

The ability to support the development of a premature fetus in the form of an extracorporeal system has had limited success. Here, the authors show that an extra-uterine device that mimics the intra-uterine environment can provide physiologic support for the extreme premature lamb fetus for four weeks.

Nona Sotoodehnia and colleagues report a meta-analysis of 14 genome-wide association studies for QRS interval, an electrocardiogram measurement of cardiac ventricular conduction. They identify 22 loci associated with QRS duration.

Analysis of genomic and clinical features of acute erythroid leukemia in comparison to other myeloid disorders supports its distinct classification, defines subgroups and suggests therapeutic vulnerabilities.

On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.

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.

A transancestral exome-wide association study for body-fat distribution identifies protein-coding variants that are significantly associated with waist-to-hip ratio adjusted for body mass index.

Transcriptional biosensors represent powerful tools for the screening of vast strain libraries, but the broad ligand specificity of some transcriptional regulators (TRs) can prohibit such applications. Here authors present the engineering of a LysG-based biosensor with a focused ligand specificity to isolate L-histidine-producing strains.

Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.

Despite their extensive use, the absolute dating of tree-ring chronologies has not hitherto been independently validated at the global scale. Here, the identification of distinct ¹⁴C excursions in 484 individual tree rings, enable the authors to confirm the dating of 44 dendrochronologies from five continents.

Here, the authors present a new method for isolating methanogenic archaea from human fecal samples and establish stable archaeal cultures yielding nine previously uncultivated strains, which upon further genomic and functional analyzes suggest may be potentially associated with gastrointestinal diseases.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

Circulating liver enzymes, like alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are highly heritable and predictive of disease. Here, the authors perform a genome-wide association study on ALT and AST, revealing a rare variant in SLC30A10 associated with elevated ALT and AST.

The molecular mechanisms underlying drug resistance in relapsed or refractory (rr) acute myeloid leukemia (AML) remain to be explored. Here, the use of bulk and single cell multi-omics and ex vivo drug profiling for 21 rrAML patients reveals mechanisms of resistance to the Bcl-2 inhibitor venetoclax and treatment vulnerabilities.

The authors show that political gatherings in the USA in 2021–2022 did not have any effect on COVID-19 case counts.

Anterior Uveitis is a common inflammatory eye disease that can result in vision loss. Here, the authors perform GWAS and whole-exome analyses of Anterior Uveitis to identify the underlying genetics of HLA-B*27 positive and negative forms of the disease.

Recent studies suggest that value-based choices involve communication between parietal and prefrontal cortices. Here the authors use a novel, non-invasive cortical manipulation technique to demonstrate a causal role for such communication in mediating accurate value-based, but not perceptual, choices.

Past genome-wide associate studies have identified hundreds of genetic loci that influence body size and shape when examined one trait at a time. Here, Jeff and colleagues develop an aggregate score of various body traits, and use meta-analysis to find new loci linked to body shape.

Patricia Munroe, Christopher Newton-Cheh, Andrew Morris and colleagues perform association studies in over 340,000 individuals of European ancestry and identify 66 loci, of which 17 are novel, involved in blood pressure regulation. The risk SNPs are enriched for cis-regulatory elements, particularly in vascular endothelial cells.

This meta-analysis of genome-wide association studies identifies four genetic loci associated with circulating leptin levels independent of adiposity. Examination in mouse adipose tissue explants provides functional support for the leptin-associated loci.

Cecilia Lindgren and colleagues report results of a large-scale genome-wide association study for waist-to-hip ratio, a measure of body fat distribution. They identify 13 new loci associated with this trait, several of which show stronger effects in women than in men.

John Chambers, Jaspal Kooner, Pim van der Harst, Shyong Tai, Paul Elliott, Jiang He, Norihiro Kato and colleagues performed a genome-wide association study of blood pressure phenotypes in individuals of European, East Asian and South Asian ancestry. They find trait-associated SNPs at 12 loci, some of which are associated with methylation at nearby CpG sites.

Erik Ingelsson and colleagues report a large-scale genome-wide meta-analysis for associations to the extremes of anthropometric traits, including body mass index, height, waist-to-hip ratio and clinical obesity. They identify four loci newly associated with height and seven loci newly associated with clinical obesity and find overlap in the genetic structure and distribution of variants identified for these extremes of the trait distributions and for the general population.

Polyaromatic hydrocarbons can be precisely manipulated to yield ever more complex and discrete graphene analogs, such as nanographenes. Here, the authors use azomethine ylide homocoupling to insert an antiaromatic pyrazine ring into the core of a nanographene, and characterize the molecule’s unique electronic character.

Christopher Newton-Cheh and colleagues report a genome-wide association study for blood pressure traits as part of the Global BPgen consortium. They report eight loci with replicated association to systolic and/or diastolic blood pressure, with each also showing association to hypertension.

The bulk photovoltaic effect (BPVE) has potential for the realization of high conversion efficiency optoelectronic devices. Here, the authors show that combined in-plane and out-of-plane charge polarizations in MoS₂/black phosphorus heterostructures can enhance the BPVE and reduce the extrinsic response times down to 2.2 ns.

Anna Köttgen and colleagues report genome-wide association studies for serum urate in over 140,000 individuals from the Global Urate Genetics Consortium (GUGC). They identify 18 loci newly associated with serum urate concentrations and confirm 10 known loci, characterize their associations with gout and include a network analysis suggesting a role for inhibins-activins pathways in regulating urate homeostasis.

Analysis of rare protein-truncating, damaging missense and copy number variants from exome sequencing of 63,237 individuals identifies 72 genes associated with autism spectrum disorder.

Stroke is a multifactorial disease influenced by genetic and environmental factors. Here, the authors apply exome-wide association analysis to find rare coding variants associated with stroke in a Pakistani cohort, finding a significant association of a variant in NOTCH3 that is highly enriched in South Asians.

Analysis of the kinase activity of 300 protein Ser/Thr kinases reveals that the substrate specificity of the kinome is substantially more diverse than expected and is driven extensively by negative selectivity

An adipocyte-selective product of the Clstn3 locus (CLSTN3β) facilitates the use of stored triglyceride by limiting lipid droplet (LD) expansion, defining a molecular mechanism that regulates LD form and function to facilitate lipid utilization in thermogenic adipocytes.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.