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Dengue (DENV) and Zika (ZIKV) viruses normally display as smooth spherical particles, while DENV can also become bumpy-surfaced, resulting in immune evasion. Here, Morrone et al. report DENV and ZIKV infectious club-shaped particles (clubSP) that display distinct antibody binding properties.

Astarloa-Pando et al. provide an in-depth characterization of natural killer cell recovery following autologous hematopoietic stem cell transplantation in pediatric cancer. Findings reveal that natural killer cells temporarily adopt an activated, decidual-like phenotype influenced by cytokines such as IL-15 and TGF-β.

Induced pluripotent stem cell (iPSC) reprogramming is inherently inefficient. Here the authors identify 24 reprogramming roadblock genes through a CRISPR/Cas9-mediated genome-wide knockout screen including a KRAB-ZFP Zfp266, knockout of which consistently enhances murine iPSC generation.

Alveolar rhabdomyosarcoma is a clinically challenging disease due to the lack of druggable targets. Here the authors show preclinical evidence for ATR inhibitors as a therapeutic option for alveolar rhabdomyosarcoma.

Ultrasound-mediated blood-brain barrier opening has been exploited to improve drug delivery in the brain. Here the authors show that low-intensity pulsed ultrasound in combination with intravenous injection of microbubbles enhances the delivery of doxorubicin and anti-PD1 in gliomas, improving anti-tumor immune responses.

HERG channel inactivation is critical for normal heart rhythm. Authors determine structures of open and non-conducting states of HERG and identify a key role for S620 on the pore helix in coordinating transitions between open and inactivated states.

Here, Jacobsen et al show that Varicella zoster virus glycoprotein C binds interferon gamma and induces biased signalling through its receptor, leading to higher expression of adhesion molecules, more T cell adhesion and viral spread from epithelial cells.

During development of the peripheral ganglia, 50% of neurons die by apoptosis. This study finds that satellite glial cell precursors clear these neuronal corpses in developing dorsal root ganglia and identifies some of the molecular components involved in this phagocytosis.

Genome-wide association analyses identify 11 loci associated with native myocardial T1 time, a marker of interstitial fibrosis, providing insights into the pathways involved in myocardial fibrosis and myofibroblast cell state acquisition.

Pulendran and colleagues delineated the mechanisms underlying the nonspecific antiviral effects exerted by the BCG vaccine against SARS-CoV-2 and reveal a pivotal role for BCG-specific CD4⁺ T cells that produce interferon-γ in imprinting a persistent antiviral innate program in the lung, mediating heterologous viral protection.

The specification of positional values along the proximo-distal axis (shoulder to digits) of the vertebrate limb is an unresolved issue. By using heterochronic transplants of distal mesenchyme, the authors show that the zeugopod and autopod (elbow to digits) are progressively specified in an intrinsically timed manner.

Tamoxifen, widely used to modulate oestrogen receptor activity in breast cancer treatment, also regulates sphingolipid metabolism. Here the authors show that the latter activity of tamoxifen stimulates pro-inflammatory and antibacterial activities of human neutrophils.

In this study, a deep learning-based model of left atrial size in UK Biobank enabled genome-wide association studies in 35,049 healthy participants. Several lines of evidence, including the PITX2 locus, linked left atrial dysfunction to atrial fibrillation risk.

Analysis of individual-level patient records from Brazil reveals that the extensive shocks in COVID-19 mortality rates are associated with pre-pandemic geographic inequities as well as shortages in healthcare capacity during the pandemic.

The authors report that the ultrastructure and plasticity of excitatory synapses connecting dentate gyrus and CA3 of the hippocampus are severely compromised in a transchromosomic mouse model of Down syndrome. These alterations are accompanied by unstable information coding by CA3 and CA1 place cells, which may contribute to aspects of impaired cognition in the disease.

A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

Implantation of lung tissue into humanized mice enables in vivo study of the human immune response to pathogens.

Somatic mutations are identified from circulating cell-free DNA using a single-molecule-based lowpass whole-genome sequencing method. The regional distribution of mutations can identify a tumor-specific mutational profile in patients with cancer and can be used to monitor patients through treatment.

Xi et al. show that after influenza infection, hypoxia drives Notch signalling to expand Krt5⁺ basal-like cells in the lung. On HIF1α loss, epithelial progenitors directly differentiate into alveolar type II cells and promote functional regeneration.

Smad-interacting protein 1 (Sip1) is a transcriptional repressor that acts in the TGF-β signaling pathway. This study finds that Sip1 is involved in a feedback signaling mechanism in which newly generated postmitotic cells in neocortical layers instruct progenitor cells for proper cell-fate switch and proliferation.

Exercise has positive effects on the brain during aging. Here the authors show that in mice, platelet-released exerkine PF4 mediates the effects of exercise on the brain.

d-arginine and d-lysine are chemorepellent molecules sensed by a novel chemotaxis receptor in Vibrio cholerae that trigger a run-away response under adverse conditions.

Kielar and colleagues identified mutations in the microtubule-associated protein Eml1 in patients with severe cortical heterotopia. Using animal and cell models, the authors found that Eml1 inactivation alters spindle orientation in dividing neuronal progenitors during early corticogenesis, leading to their detachment from the ventricular zone, their accumulation in the intermediate zone and the subsequent development of subcortical heterotopia.

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.

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.

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.

Ageing is associated with deteriorating immune function and metabolic diseases. Here, the authors show that plasma levels of the stress-response protein MANF decline with age in various organisms and that MANF has beneficial effects on immune and metabolic function, particularly in the liver, in old mice.

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.

Some cancer patients first present with metastases where the ___location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

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.

Single-nucleus RNA-sequencing analyses of brain from humans, macaques, marmosets, mice and ferrets reveal diverse ways that interneuron populations have changed during evolution.

Patients with ovarium cancer frequently develop resistance to platinum chemotherapy and PARP inhibitors (PARPi). Here, the authors show that the combination of PARP and ATR inhibitors increases the therapeutic response in PARPi and platinum resistant ovarium cancer PDX models.

Stem cells exist in vitro in a spectrum of interconvertible pluripotent states. Here, authors show that pluripotency and self-renewal processes have a high level of regulatory complexity and suggest that genetic factors contribute to cell state transitions in human iPSC lines.

Unique microorganisms of a fossil river delta in the Atacama Desert unveil the current limits of life detection on Mars.

This paper reports integrative molecular analyses of urothelial bladder carcinoma at the DNA, RNA, and protein levels performed as part of The Cancer Genome Atlas project; recurrent mutations were found in 32 genes, including those involved in cell-cycle regulation, chromatin regulation and kinase signalling pathways; chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far.

Murre and colleagues identify a specific enhancer, E34, within the Igk locus that is required for chromatin remodeling and repositioning to promote Rag-mediated Igkv7-33 V_κ-J_κ gene recombination, needed for generation of anti-phosphorylcholine-specific antibodies. Mice lacking E34 are more susceptible to Streptococcus pneumoniae infections.

Here the authors show that sepsis and its resolution alter cancer susceptibility by epigenetically altering resident macrophages resulting in retention of T cells that increase antitumoral immunity.

Loss of PIK3R1 in ovarian cancer is a common event, which provides opportunities for therapeutic intervention. Here, the authors show that the STAT3 and AKT signaling pathways are activated upon PIK3R1 loss and that, in mice, inhibitors of these pathways could block tumorigenesis.

Brain cytoplasmic (BC1) RNA is a non-coding RNA that has been implicated in translational regulation, seizure, and anxiety. Here, the authors show that in the cortex, BC1 RNA is required for sensory deprivation-induced structural plasticity of dendritic spines, as well as for correct sensory learning and social behaviors.

The neocortex is responsible for higher level cognitive functions and long-range neural connections are critical for mediating these functions. Here, Srivatsa et al.show that axon guidance molecules downstream of transcription factors Stab2 and Ctip2 play a role in the establishment of cortical connections during mouse brain development.

Village cultures, where multiple stem cell lines are cultured in a single dish, provide an elegant solution for population-scale studies. Here, authors show the utility of village models – showing that expression heterogeneity is largely a result of line-specific effects and not village cultures.

Here, Gassen et al. show that S-phase kinase-associated protein 2 (SKP2) is responsible for lysine-48-linked poly-ubiquitination of beclin 1, resulting in its proteasomal degradation, and that inhibition of SKP2 enhances autophagy and reduces replication of MERS coronavirus.

Larionova et al. identify a mechanism by which acidification of the tumour microenvironment within the glioblastoma core induces the generation of an alternative splice isoform of ribosomal protein RPL22L1, which regulates cell stemness and increases tumour heterogeneity.

During pregnancy, maternal cells are transferred to the fetus, where they can reach the developing brain. In this study, the authors demonstrate that these maternal cells play an important role in neurodevelopment.

Activation of the non-canonical NF-κB signalling pathway by AZD5582 results in the induction of HIV and SIV RNA expression in the blood and tissues of antiretroviral-therapy-treated humanized mice and rhesus macaques.

Insight from the transcriptomes of 1,032 Saccharomyces cerevisiae natural isolates emphasizes the essential contribution of accessory genes to the species-level transcriptional landscape.