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Vaccination against one viral strain can result in cross-reactive antibodies against another viral strain. In this study, the vaccination of mice against the 2009 H1N1 virus is shown to protect mice from the 1918 Spanish influenza virus, which resulted in millions of deaths worldwide.

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.

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

The role of autoantibodies in bullous pemphigoid (BP) and their impact on keratinocytes and the response to BP pathology remains underexplored. By leveraging transcriptomics analysis and large-scale protein assays, here the authors identify keratinocyte MyD88 as a regulator of the pro-inflammatory response in BP, uncovering the role of keratinocytes in this disease pathology.

The Nr4a family of nuclear receptors has been implicated in thymocyte central tolerance via clonal deletion and regulatory T cell induction. Here the authors show, using mouse bone marrow chimeras, that Nr4a1 and Nr4a3 are also redundantly required for Bcl211/BIM induction and contribute to an anergy-like transcriptome in auto-reactive thymocytes.

Oxide heterostructures are attractive for their tuneable properties such as magnetism. Here, the authors find that SrTiO₃/SmTiO₃heterostructures with very high sheet carrier densities show quantum critical behaviour, sensitive also to variations in layer thickness.

The development of a new genetic tool to selectively deplete or modify group 2 innate lymphoid cells (ILC2s) addresses the debate regarding the non-redundant functions of this immune cell type.

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.

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 pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

McGavern and colleagues identified a CD8⁺ T cell population that expresses GZMK in ʽtau-richʼ brains, where it may play a protective role against neurodegeneration.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

This study identifies transcription factor 7-like 2 (TCF7L2) as a key regulator of hepatic metabolic zonation, and demonstrates that disruption to the transcriptional activity of TCF7L2 exacerbates the development of dietary-induced hepatic fibrosis.

Cryptosporidium infection can cause severe diarrhea with limited treatment options available. Here, Lunde et al. perform a drug repositioning screen with a library of benzoxaboroles and identify AN7973 as potent inhibitor of intracellular parasite development with good efficacy in murine and neonatal dairy calf disease models.

Systematic discovery of proteins interacting with low-abundance RNAs is challenging. Here, the authors develop an enhanced HyPro technology to identify proteins associated with compact RNA compartments and single RNA molecules, revealing early defects in ALS-linked mutant C9orf72 transcripts.

Using phenotypic screening followed by optimization of side activities, the authors here identify pyrazolopyrimidine phosphodiesterase (PDE) inhibitors as anti-cryptosporidial drug leads. Humanizing a Cryptosporidum PDE by CRISPR indicates they target the parasite enzyme.

Intricate color patterns are a defining aspect of morphological diversity in the Felidae. Here the authors apply morphological and single-cell gene expression analysis to fetal skin of domestic cats to identify when, where, and how, during fetal development, felid color patterns are established.

Orthogonal chimeric receptors containing intracellular domains for IL-4R, IL-20R, IL-22R and GCSFR reprogram T cells to promote distinct natural and synthetic cell states with functional and therapeutic implications.

Myelosuppressive injuries lead to chronic MAPK activation and impair blood reconstitution. Here, the authors show that chronic activation endothelial MAPK impairs hematopoietic stem cell (HSC) function through NFkB signaling, and that post-myelosuppressive HSC defects can be reversed by administration of Stem Cell Growth Factor SCGFa.

Staphylococcus epidermidis induces a potent, durable and specific antibody response that is conserved in humans and non-human primates, and which could be redirected against pathogens as a new form of topical vaccination.

How lung epithelial and endothelial cells develop into alveoli is a major knowledge gap, with implications for lung repair in preterm infants. Here, the authors establish a transcriptomic atlas of human neonatal lung disease, identifying semaphorins as pivotal mediators of organogenesis and injury.

Interactions between the immune system and adipose tissue contribute to the regulation of body weight, however, the underlying mechanisms remain incompletely understood. Here the authors dissect the role of two structurally and functionally similar immune mediators, BAFF and APRIL, in modifying diet-induced weight gain and adipocyte lipid handling.

LKB1 tumour suppressor gene is frequently mutated in lung adenocarcinoma. Here the authors show that in genetically engineered mouse models of lung cancer Lkb1 restoration induces growth arrest and drives neoplastic cells toward a more differentiated and less proliferative alveolar type II cell-like state via C/EBP-mediated reprogramming.

Riffelmacher et al. show that immunization with a live vaccine strain leads to the expansion of two memory-like mucosal-associated invariant T cell lineages with distinct metabolic needs, effector programmes and protective capacities.

A single-cell resolution image-based genome-wide CRISPR screen, analysed with deep learning and random forest models, identified host factors regulating Ebola virus infection at distinct stages in the viral life cycle.

Anandasabapathy and colleagues show that the inhibitory receptor PD-1 impacts the specification of tissue-resident memory T cells in the skin.

Chen et al. find that cerebellar Purkinje cells directly inhibit neurons in parabrachial nuclei that in turn influence many forebrain regions. This alternative output pathway could enable the cerebellum to regulate emotions, anxiety, aggression and affect.

Lundgren et al. show that in response to transient cold exposure, a distinct subpopulation of brown adipocytes carries out a lipogenic response involving production of acylcarnitines, which enables an improved thermogenic response to secondary cold exposure.

Here, the authors investigate the relationship between HUSH-MORC2 and DNA methylation in embryo-derived human neural progenitor cells, enhancing the understanding of the epigenetic control of repeats in somatic cells.

Senescent cells in fat and liver are shown to attract M1-like macrophages with increased expression of the NAD-consuming enzyme CD38, leading to their local accumulation and providing a mechanism for the age-associated decline in tissue NAD⁺ levels.

Mussels produce a dynamic bio-interface between their living tissue and their non-living byssus attachment, relevant for design of implant devices. Here, authors discover a mechanoresponsive protein that may mediate mechanosensing at the interface.

A hyper-stable de novo protein mimic of interleukin-2 computationally designed to not interact with a regulatory T-cell specific receptor subunit has improved therapeutic activity in mouse models of melanoma and colon cancer.

Through circuit dissection in juvenile, adolescent and adult mice, Klune, Goodpaster and colleagues reveal multiple developmental switches in mPFC–NAc and mPFC–BLA pathways that underlie developmental transitions in threat avoidance behavior.

Mitochondria contribute to metabolic adaptation in cells exposed to environmental challenges. Here, the authors identify a signaling cascade that regulates the lifespan of mitochondrial mutant animals grown on distinct diets.

The number of individuals in a given space influences animal interactions and network dynamics. Here the authors identify general rules underlying density dependence in animal networks and reveal some fundamental differences between spatial and social dynamics.

Using genetically engineered models, Genovese and colleagues study patterns of convergent evolution in renal cancer, and pinpoint dysregulation of interferon signaling as a means of adaptation to chromosomal instability in metastatic progression.

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.

Regulation of the actin cytoskeleton is essential for blood-brain barrier integrity and immune cell transmigration. Here, the authors show that the ion channel K2P2.1 regulates this process by shielding key signaling lipids and modulating actin dynamics.

Small CRISPR Cas9 proteins have potential in gene therapies but generally have poor editing efficiency or specificity and often recognize sub-optimal PAM sequences. Here the authors characterise four small nucleases and use protein engineering to create effective in vivo editors.

Here, the authors leverage whole-genome sequencing from >88,000 diverse individuals to uncover 18 BMI-related genetic signals, including novel variants in participants of African genetic ancestry, highlighting the value of diversity in genetic discovery.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Wnt signaling functions in tissue homeostasis and tumorigenesis. Here the authors show that ROR2, a Wnt receptor, plays roles not only in transducing Wnt signaling, but also in regulation of DNA damage response critical for stem cell maintenance.

Latorre-Muro et al. show that the cytosolic chaperone PPID drives insertion of the mitochondrial import receptor TOM70 into the mitochondrial outer membrane, thereby regulating body temperature, glucose homeostasis and body weight in obese mice.

Activation of ESCRT prevents potentially lethal outcomes of minor perturbations in lysosomal integrity. Here authors show that Ca2 + -activated scrambling of sphingomyelin and its cytosolic turnover drives lysosomal repair independently of ESCRT.