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Transcriptomic and clinical data analyses from multiple cohorts of patients with cancer receiving immunotherapy find that PD-1 blockade potentiates tumor-specific IgG1 plasma cell responses that complement cellular immunity and contribute to clinical benefit.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Vertical transmission is thought to favour beneficial host–microbe interactions, but these may also be context dependent. Here Bruijning et al. show with a model that variable environments can select for bet-hedging by hosts via imperfect vertical transmission of microbes.

Krisai et al. compare brain structure and cognitive function in elderly patients with and without atrial fibrillation using brain MRI and cognitive testing. They find that atrial fibrillation is associated with more brain lesions and lower cognitive function, but the cognitive impairment occurs primarily through direct effects of the arrhythmia rather than through brain damage.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

CAR T cell therapies have been developed to treat paediatric diffuse intrinsic pontine glioma (DIPG), however, clinical efficacy remains limited. Here, the authors report that engineering B7-H3-targeting CAR T cells to express the chemokine receptor CXCR3-A enhances their trafficking and efficacy in DIPG preclinical models.

Political ecology aims to understand how politics and power influence both social and ecological dynamics. Conservation biologists and political ecologists tackle many of the same pressing environmental problems, but from quite different perspectives. In this Viewpoint, five political ecologists discuss their views on how the field can understand and tackle the biodiversity crisis.

Dendritic cells (DCs) induce infection-protective immune memory, which has yet to be exploited for cancer therapy. Here we show that type 1 DC vaccines quantitatively and qualitatively favors anti-tumor T cell memory that prevents cancer relapse.

Ying, Paulson and collagues have developed an open-source framework, Biolearn, to harmonize and systematically evaluate 39 aging biomarkers across diverse populations, enabling standardized validation and facilitating development of robust aging biomarkers.

The GREGoR consortium provides foundational resources and substrates for the future of rare disease genomics.

Caloric restriction improves Alzheimer’s Disease outcomes in mice, but this diet not only reduces calories, but imposes a prolonged fast between meals. Here, the authors show this fast is essential to improve Alzheimer’s pathology and cognition.

A pulse of ocean acidification is reconstructed from the boron isotope composition of fossilized oysters at the Triassic-Jurassic boundary, implicating ocean acidification from volcanic outgassing as a kill mechanism during the extinction event.

 A transcriptomic cell-type atlas of the whole adult mouse brain with ~5,300 clusters built from single-cell and spatial transcriptomic datasets with more than eight million cells reveals remarkable cell type diversity across the brain and unique cell type characteristics of different brain regions. 

An assessment of blue carbon strategies in Belize shows how quantifying fisheries, tourism and coastal risk co-benefits alongside carbon benefits can inform spatial and temporal target setting for nationally determined climate contributions that simultaneously provide societal benefits.

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.

The authors develop and characterise a selective Greatwall inhibitor, C-604, and show that its cytotoxicity stems from PP2A-B55α hyperactivation. They identify B55α and Greatwall levels as biomarkers of responses to Greatwall-targeted therapy.

Stromal cells are key players in immune cell homeostasis. Here, the authors decipher subset-specific human stromal responses in inflammatory bowel disease and suggest that intestinal PDGFRA⁺CD142^−/low fibroblasts guide monocyte transition to macrophages in human gut through GM-CSF.

Low-income urban communities are facing infrastructural inequities. This Perspective advocates for an agenda that aims at reorienting infrastructure research by bridging methodological divides, integrating fragmented datasets and actors, and centering engagement with affected communities.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Clarke, Hawkinson and colleagues study the contribution of glycogen accumulation in the onset and progression of lung cancer.

Progranulin deficiency causes untreatable neurodegenerative diseases. Here, the authors show that hematopoietic stem cell transplantation and optimized brain conditioning correct the disease phenotype in progranulin-deficient mice.

A workflow centred around base-specific in situ sequencing generates detailed maps of, and can phenotypically characterize, the unique set of subclones of cancers.

The latent HIV-1 reservoir is the key obstacle for curing HIV-1 infection, but the timepoint at which the HIV-1 reservoir is established is currently unclear. Here, Whitney et al. show in non-human primates that the SIV reservoir in CD4⁺ T cells is seeded within the first 2 days after infection.

The lymphotoxin (LT) system has several defined roles in the regulation of immunity as well as vascular and lymphatic biology, however its role in cancer is less understood. Here the authors show that regulatory T cell-derived LTα1β2 promotes LTβ receptor-nonclassical NFκB signaling in tumor cells and lymphatic endothelial cells, accelerating tumor growth and metastasis.

The vCA1-BA projection is enriched in shock responsive neurons, which are necessary for fear memory encoding and become correlated with a network of neurons during retrieval. Here the authors show that the magnitude of vCA1 correlated activity is proportional to memory strength and requires the shock response during encoding.

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

Lipophilic siRNA conjugates exert therapeutic activity in the mouse CNS.

An expert-elicitation process identifies current methodological barriers for monitoring terrestrial biodiversity, and how technological and procedural development of robotic and autonomous systems may contribute to overcoming these challenges.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

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.

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.

According to astrophysical and geological models, cosmic dust rich in bioessential elements could have accumulated on the surface of early Earth in arid environments (such as glaciers), potentially helping to foster the chemical origins of life.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

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.

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.

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.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

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.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Regulatory T cells (T_reg) develop in the thymus via two pathways including CD25⁻Foxp3^lo and CD25⁺Foxp3⁻ cells. Here, the authors show that lymphotoxin acts as an inhibitory checkpoint of thymic T_reg development, fine-tuning the Foxp3^lo precursor pathway by limiting IL-4 production in medullary thymic epithelial cells.

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.