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Alternative polyadenylation is involved in plant responses to various stresses. Here, the authors show how a cis-natural antisense RNA promotes proximal polyadenylation of its cognate SlSPX5 gene in response to phosphate starvation in tomato.

Analyses of the nationally representative Indian Council of Medical Research–India Diabetes survey reported that Indian diets are characterized by high intakes of low-quality carbohydrates associated with 14–30% higher cardiometabolic risk, which can be reduced by substituting carbohydrates with protein.

Li et al. discovered that the cytotoxic synthetic small molecule BRD1732 is directly ubiquitinated in cells. Ubiquitination of BRD1732 is E3 ligase dependent and leads to inhibition of proteasomal degradation.

Clinical translation of cell products is impeded by the lack of clinically predictive potency assays. Here, the authors report a microfluidic system to evaluate patient-derived cells used in a clinical trial for osteoarthritis pain, and use the results and patient-matched clinical data to build prediction models, showing improved clinical prediction and higher correlative power with pain scores compared to 2D culture.

The α-cardiac actin M305L hypertrophic cardiomyopathy-causing mutation is located near residues that help confine tropomyosin to an inhibitory position along thin filaments. Here the authors assessed M305L actin in vivo, in vitro, and in silico to characterize emergent pathological properties and define the mechanistic basis of disease.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Global catastrophes such as nuclear war can generate soot that reduces the amount of light reaching the earth’s surface. Here the authors model how this kind of catastrophe would impact common crop growth, recommending increased crop diversity for agricultural resilience.

Analyses of epigenomic datasets spanning transitions from normal prostate epithelium to localized prostate cancer to metastases show that latent developmental programs are reactivated in metastatic disease and that prostate lineage-specific regulatory elements are strongly enriched for prostate cancer risk heritability.

Nematodes define a new role for sirtuins in lifespan extension, in which the sirtuin product nicotinamide is converted to a substrate for aldehyde oxidase; turnover of this enzyme generates hydrogen peroxide, causing upregulation of defense mechanisms that promote longevity.

Siddiqui et al. explore the role of islet-specific XBP1 expression in type 2 diabetes (T2D) and glycemic traits across diverse ancestries. XBP1 eQTL is associated with T2D, beta-cell function, HbA1c and drug response in East and South Asians in whom this variant is common and beta-cell dysfunction is a significant driver of early onset T2D.

Despite several decades of research that has revealed roles in the development and progression of many solid tumours, clinical translation of research targeting epithelial–mesenchymal transition (EMT) has thus far been limited. In this Review, the authors provide a summary of the role of EMT in cancer development and progression in the context of this lack of clinical translation, summarize the current status of direct or indirect EMT-modulating agents in clinical development, and highlight the major barriers to the development of EMT-related clinical interventions.

Nucleosome profiling from cell-free DNA (cfDNA) represents a potential approach for cancer detection and classification. Here, the authors develop Griffin, a computational framework for tumour subtype classification based on cfDNA nucleosome profiling that can work with ultra-low pass sequencing data.

Glaucoma is the most common cause of irreversible blindness worldwide. Here, the authors carry out a large meta-analysis of genetic data from individuals of European and Asian ancestry and identify 10 new loci associated with vertical cup-disc ratio, a key factor in the clinical assessment of patients with glaucoma.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Electrolytes play a critical role in designing next generation battery systems. Here, the authors developed a differentiable geometric deep-learning model for chemical mixtures and applied it in guiding a robot to design fast-charging battery electrolytes.

Biological determinants for developing post-acute sequelae of SARS-CoV-2 infection are largely unclear. Here, by comparing markers during acute infection in individuals who developed PASC with those who recovered, the authors found that early viral dynamics and immune responses might play a role in PASC pathogenesis.

Transancestral GWAS meta-analysis in 160,420 individuals identifies 139 loci associated with refractive error, including myopia. Newly identified genes implicate pathways involved in eye growth and light signaling cascades.

Transgene knock-ins into housekeeping genes lead to high efficiency of cell selection.

Prediabetes refers to individuals with blood glucose levels above the normal levels but below the thresholds for a diabetes mellitus diagnosis. In this Primer, Mohan and colleagues discuss the increasing prevalence of prediabetes, its pathophysiology and diagnosis as well as the importance of early intervention to improve adverse outcomes in patients.

Systematic sequencing of the genome of Saccharomyces cerevisiae has revealed thousands of new predicted genes and allowed analysis of long-range features of chromosomal organization. Generally, genes and predicted genes seem to be distributed evenly throughout the genome, having no overall preference for DNA strand. Apart from the smaller chromosomes, which can have substantially lower gene density in their telomeric regions^1–3, there is a consistent average of one open reading frame (ORF) approximately every two kilobases. However, one of the most surprising findings for a eukaryote with approximately 6,000 genes was the amount of apparent redundancy in its genome. This redundancy occurs both between individual ORFs and over more extensive chromosome regions, which have been duplicated preserving gene order and orientation^4–6. Here we report the entire nucleotide sequence of chromosome XIII, the sixth-largest S. cerevisiae chromosome, and demonstrate that its features and organization are consistent with those observed for other S. cerevisiae chromosomes. Analysis revealed 459 ORFs, 284 have not been identified previously. Both intra- and interchromosomal duplications of regions of this chromosome have occurred.

The composition of international scientific assessments influences their credibility. This study shows that membership nomination in the Millennium Ecosystem Assessment was driven by a group of core individuals based on prior institutional co-membership.

The yeast Saccharomyces cerevisiae is the pre-eminent organism for the study of basic functions of eukaryotic cells¹. All of the genes of this simple eukaryotic cell have recently been revealed by an international collaborative effort to determine the complete DNA sequence of its nuclear genome. Here we describe some of the features of chromosome XII.

Natural selection may favor traits underlying aging-related diseases if they benefit the young. Wang et al. find that oxidative activation of CaMKII provides physiological benefits critical to the initial and continued success of vertebrates but at the cost of disease, frailty, and shortened lifespan.

Tuberous sclerosis complex (TSC) is a multiorgan disease that can lead to hyperactive mTORC1 due to deficient TSC1 or TSC2 protein function. Here, the authors find that despite high mTORC1 activity, TFEB localizes to the nucleus and drives lysosomal gene expression via a non-canonical Rag-dependent mechanism.

Arginine methylation has been reported to regulate AKT-associated signalling. Here, the authors show that PRMT5-mediated arginine methylation promotes AKT activity and induces tumourigenesis.

Bifunctional ‘MoDE-A’ molecules, which contain ligands that bind to an extracellular protein and carbohydrate residues that recruit it to the asialoglycoprotein receptor, mediate cellular uptake and lysosomal turnover of target proteins.

A double-transgenic mouse model that enables monitoring or manipulation of dopamine and serotonin simultaneously in the brain’s nucleus accumbens shows that these neuromodulators have opponent roles in reward learning.

The reconstruction of dynamic, spatial fields from sparse sensor data is an important challenge in various fields of science and technology. Santos et al. introduce the Senseiver, a deep learning framework that reconstructs spatial fields from few observations using attention layers to encode and decode sparse data, enabling efficient inference.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

Here authors show that machine learning derives the degree of background retinal pigmentation with more nuance than self-described ethnicity. Retinal pigment scores are associated with genes linked to melanin and may improve algorithmic fairness.

Burrows, Denckla and colleagues performed a systematic review to evaluate the available evidence linking climate change to mental health outcomes.

The molecular and cellular causes of glaucoma are not well understood. Here, the authors integrate GWAS with genetic regulation and single cell expression from multiple eye tissues to identify genes and key cell types that affect glaucoma pathogenesis.

Malaria parasites obtain amino acids primarily from the host, but possess a gene encoding a putative asparagine synthetase. Here, the authors show that this enzyme is functional and that asparagine is crucial for the development of the parasite’s sexual stages in mosquitoes and liver stages in mice.

Sarcomatoid and rhabdoid tumours are highly aggressive forms of renal cell carcinoma that are also responsive to immunotherapy. In this study, the authors perform a comprehensive molecular characterization of these tumours discovering an enrichment of specific alterations and an inflamed phenotype.

Diabetes mellitus is a global health issue, yet huge regional disparities exist in its care, including in access to basic necessities such as insulin. In this Viewpoint, six experts from different regions discuss differences in access to insulin and other diabetes mellitus therapies as well as the key barriers in diabetes mellitus care accessibility and potential solutions.

Andrew Morris, Mark McCarthy, Michael Boehnke and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes, including 26,488 cases and 83,964 controls from populations of European, east Asian, south Asian and Mexican and Mexican American ancestry. They identify seven loci newly associated with type 2 diabetes and examine the genetic architecture of disease across populations.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.