Search

The authors introduce a new computational method, HapNe, for inferring the recent effective size of human populations. HapNe does not require high-quality genotype data, making it suitable for the study of ancient DNA samples.

Genome-wide ancient DNA data from individuals from the Middle Bronze Age to Iron Age documents large-scale movement of people from the European continent between 1300 and 800 bc that was probably responsible for spreading early Celtic languages to Britain.

The Cancer Genome Atlas Research Network reports an integrative analysis of more than 400 samples of clear cell renal cell carcinoma based on genomic, DNA methylation, RNA and proteomic characterisation; frequent mutations were identified in the PI(3)K/AKT pathway, suggesting this pathway might be a potential therapeutic target, among the findings is also a demonstration of metabolic remodelling which correlates with tumour stage and severity.

Cooling electrons into the microkelvin temperature range is of interest both for practical purposes and fundamental studies, but current demonstrations are limited to small, specific devices. Here, the authors achieve sub-millikelvin temperatures in a large-area, two-dimensional electron gas.

Climate warming increases evapotranspiration (ET) more in boreal peatlands than in forests. Observations show that peatland ET can exceed forest ET by up to 30%, indicating a stronger warming response in peatlands. Earth system models do not fully account for peatlands and hence may underestimate future boreal ET.

The genome of the grey short-tailed opossum Monodelphis domestica has been sequenced and analyzed, giving a first peek at a marsupial's genetic code. Of particular interest are the genetics of the immune system, which has been studied as a model for humans, and of the X chromosome for historical reasons.

Analysis of the results of a large clinical trial, EMPEROR-Preserved, shows that the SGLT2 inhibitor empagliflozin improves outcomes for heart failure patients with either mid-range (41–49%) or preserved (≥50%) ejection fraction, supporting the use of this drug for both categories of patients.

A mathematical framework to estimate the fitness of cancer driver mutations by integrating mutational bias, oncogenicity and immunogenicity finds fundamental trade-offs in cancer evolution.

Tracking data from 17 marine predator species in the Southern Ocean are used to identify Areas of Ecological Significance, the protection of which could help to mitigate increasing pressures on Southern Ocean ecosystems.

Cold exposure activates thermogenesis and fatty acid oxidation in brown fat, a process suppressed by Them1. Here, the authors show that cold induces Them1 phosphorylation and loss of puncta that suppress fatty acid use, leading to a diffuse localization and increased energy expenditure in mice.

Comprehensive analyses of 178 lung squamous cell carcinomas by The Cancer Genome Atlas project show that the tumour type is characterized by complex genomic alterations, with statistically recurrent mutations in 11 genes, including TP53 in nearly all samples; a potential therapeutic target is identified in most of the samples studied.

A biocompatible and biodegradable mesostructured form of silicon is used to make lipid-bilayer-supported bioelectric interfaces that can optically modulate the electrophysiology of single dorsal root ganglia neurons.

The Cancer Genome Atlas Network describe their multifaceted analyses of primary breast cancers, shedding light on breast cancer heterogeneity; although only three genes (TP53, PIK3CA and GATA3) are mutated at a frequency greater than 10% across all breast cancers, numerous subtype-associated and novel mutations were identified.

Both rare and common variants contribute to the aetiology of complex traits such as type 2 diabetes (T2D). Here, the authors examine the effect of coding variation on glycaemic traits and T2D, and identify low-frequency variation in GLP1Rsignificantly associated with these traits.

Despite observations from a hot-water-drilled access hole showing warm ocean waters beneath Thwaites Glacier Eastern Ice Shelf, the basal melt rate is strongly suppressed due to the low current speeds and strong density stratification.

As cryo-EM becomes commonplace in drug discovery, tools for automating small molecule structure determination are needed. Here, authors show a map-guided ligand modeling approach to building ligand structures at resolutions common in cryo-EM.

The Cancer Genome Atlas consortium reports on their genome-wide characterization of somatic alterations in colorectal cancer; in addition to revealing a remarkably consistent pattern of genomic alteration, with 24 genes being significantly mutated, the study identifies new targets for therapeutic intervention and suggests an important role for MYC-directed transcriptional activation and repression.

Only 7% of the 2245 estuaries, globally, that connect to the ocean only intermittently have been studied in past decades, with ecosystem services, climatic and human disturbances and management particularly neglected, according to a global meta-analysis of 271 published articles.

Single-cell whole-genome sequencing shows that 'foreground' cell-to-cell structural variation and alterations in copy number are associated with genomic diversity and evolution in triple-negative breast and high-grade serous ovarian cancers.

Nicholls and Brand present a bioenergetic critique of the futile creatine cycle as a mechanism for UCP1-independent diet-induced thermogenesis in brown adipose tissue.

Phytase is a high molecular weight acid phosphatase. The structure has an α/β-domain similar to that of rat acid phosphatase and an α-domain with a new fold.

Brown fat has a tremendous capacity to oxidize fatty acids and generate heat, owing to the presence of an 'uncoupling protein', UCP1. The fatty acids themselves are understood to activate UCP1, but Chouchani et al. now propose that oxidation of a critical cysteine residue on UCP1 is additionally required to sensitize the protein to fatty acids.

Whole-genome sequencing of human cancer cells in patient-derived mouse xenograft models indicates a key role for TP53 in determining the fitness landscape of polyclonal cancer cell populations.

Parallel patterning of atoms over a large surface would represent a major advance over current serial methods of single atom manipulation. Here, the authors explore a periodic instability from liquid alloy droplets for high-throughput atom printing.

The internal core antigen, p24, of HIV performs differing roles at various stages in the viral life cycle. The structure of the protein has now been solved allowing an informed view of its role in isolation and as a domain within the precursor virion structural protein Gag p55.

The three N-terminal zinc fingers of transcription factor IIIA bind in the DNA major groove. Substantial packing interfaces are formed between adjacent fingers, the linkers lose their intrinsic flexibility upon DNA binding, and several lysine side chains implicated in DNA recognition are dynamically disordered.

Protein tyrosine phosphatases (PTPs) are a family of signal transduction enzymes that dephosphorylate phosphotyrosine containing proteins. Structural and kinetic studies provide a molecular understanding of how these enzymes regulate a wide range of intracellular processes.

Inhibitor of mitochondrial transcription treatment leads to reduced oxidative phosphorylation capacity but increases fatty acid oxidation in the liver, leading to protection from obesity and related pathology.

Microcombs provide many opportunities for integration in optical communications systems. Here, the authors implement a soliton crystal microcomb as a tool to demonstrate more than 44 Tb/s communications with high spectral efficiency.