Search

How an exploratory study of neoadjuvant immunotherapy saved patient lives.

Understanding asteroid materials is critical for determining deflection methods for planetary defense. Here the authors show, via experiments performed in High-Radiation to Materials facility at CERN, that iron-rich asteroid materials can absorb more energy without structural failure than standard material parameters would suggest.

In this study, Weber et al., investigate the long-term survival and integration of human stem cell-derived neural progenitors into the stroke-injured mouse brains. They report grafted cells integrate into host circuits and mediate repair through graft-host crosstalk via neurexin, neuregulin, neural cell adhesion molecules, and SLIT signalling pathways.

An analysis of rare genetic variants identifies three genes—MAP1A, ANO8 and ANK2—that have a role in attention deficit hyperactivity disorder (ADHD) and investigates the potential underlying biological mechanisms.

Tree longevity is thought to increase in harsh environments, but global evidence of drivers is lacking. Here, the authors find two different pathways for tree longevity: slow growth in resource limited environments and increasing tree stature and/or slow growth in competitive environments.

In this study, the authors uncover how diverse inhibitory interneurons in the amygdala flexibly contribute to fear and safety learning, revealing a key role for inhibition in emotional memory and adaptive circuit plasticity.

The study shows a double dissociation between static and dynamic face perception in 108 patients with focal lesions, providing direct causal evidence for a third visual pathway via the posterior superior temporal sulcus (pSTS).

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

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.

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.

Marine sponges host bacteria that produce diverse bioactive compounds. Here, the authors conduct a large-scale metagenomic, single-bacterial and biochemical study to reveal the untapped biosynthetic potential of ‘Entotheonella’ symbionts, a talented producer taxon from microbial dark matter.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

A proteotoxic stress response specific to exhausted T cells, governed by AKT signaling and accompanied by increased protein translation, represents a mechanistic vulnerability and a new therapeutic target to improve cancer immunotherapies.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Latin Americans trace their ancestry to the admixture of Native Americans, Europeans and Sub-Saharan Africans. Here, the authors develop a novel haplotype-based approach and analyse over 6,500 Latin Americans to infer the geographically-detailed genetic structure of this population.

Genome-wide association meta-analyses of attention-deficit/hyperactivity disorder symptom measures and clinical diagnoses identify new risk loci, highlight putative effector genes and yield improved polygenic risk scores.

17β-oestradiol establishes an anti-ferroptotic state in female kidney tubules.

The success of allogeneic hematopoietic stem cell transplantation for the treatment of haematological cancers is limited by the morbidity and mortality associated with graft-versus-host disease (GVHD). Here the authors show that the microbial metabolite desaminotyrosine contributes to graft-versus-leukemia responses while protecting against GVHD and promoting mTORC1 and STING-dependent intestinal regeneration.

Identity fusion has traditionally been associated with intergroup violence. However, across two studies we show that fusion can predict increased willingness to trust and cooperate with outgroups, if contextual perceptions are positive.

A single-phase chromium–molybdenum–silicon alloy is described that exhibits compression ductility at room temperature as well as resistance to oxidation, pesting, nitridation and scale spallation at temperatures up to at least 1,100 °C.

As Greenland’s huge calving glaciers melt, they pump sediment deep into biologically rich fjords. In this study, the quantity and path of this sediment is tracked and an empirical relationship is found between sediment and the amount of surface melt on the glacier.

The performance of inverted perovskite solar cells has been limited by non-radiative recombination at the perovskite surfaces. Here, authors employ phosphonic acids and piperazinium chloride for homogeneous passivation, achieving certified efficiency of 28.9% for 60 cm² perovskite-silicon tandems.

Wood density is an important plant trait. Data from 1.1 million forest inventory plots and 10,703 tree species show a latitudinal gradient in wood density, with temperature and soil moisture explaining variation at the global scale and disturbance also having a role at the local level.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

Myelin damage in multiple sclerosis can be detected up to 7 years before symptoms, with early immune pathway activation and a 21-protein panel showing promise for presymptomatic diagnosis.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Hegazy and colleagues demonstrate that epithelial oncostatin M receptor expression drives gut inflammation and tumor formation.

Our understanding of how post-translational modification—protein phosphorylation—impacts the complexity of eukaryotic signalling pathways is continuously expanding. Now, protein oligophosphorylation has been characterized as an additional phosphorylation mode. Structural and mass spectrometry methods revealed that NME1 catalysed its own oligophosphorylation, leading to altered protein–protein interactions.

This multi-omic longitudinal analysis of the healthy human peripheral immune system constructs the Human Immune Health Atlas and assembles data on immune cell composition and state changes with age, including responses to cytomegalovirus infection and influenza vaccination.

FcγRI binds immune complex (IC) to contribute to various autoimmune diseases, but a specific blocking antibody has not been reported. Here the authors characterize two anti-FcγRI antibodies that block and replace IC-binding to FcγRI in the context of patient-derived samples or a mouse immune thrombocytopenia model to implicate potential clinical translation.

Here, the authors realize in-situ, tunable up-conversion luminescence in a monolayer semiconductor via an optical cavity in the strong light-matter coupling regime, and demonstrate nonlinear up-conversion as an efficient injection scheme of exciton-polariton populations.

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.

Graphene systems have the potential to host Wigner crystal states at zero magnetic field. Here, the authors report transport signatures consistent with Wigner crystallization in AB-stacked bilayer graphene at both zero and finite magnetic fields.

The mechanisms that impact tumorigenesis during aging are incompletely understood. Here Shuldiner et al. show that in mice, aging represses KRAS-driven lung tumorigenesis and dampens the impact of inactivating many tumor suppressor genes, which may contribute to the deceleration in cancer incidence with extreme age in humans.

Integrating UV lasers is of interest for portable optical clocks and ion-based quantum computers, but material absorption has impeded progress. Here, authors demonstrate a violet integrated laser using UV-transparent materials with mW-level output, narrow linewidth and precise frequency control.

This work challenges the view of nucleation governing halide perovskite grain morphology, showing that most additives act post-nucleation by boosting ion mobility across grain boundaries, triggering grain coarsening, similar to post-processing effects.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.