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The role of normally silenced transposable elements (TEs) in tumorigenesis remains unclear. Here, the authors show that increased expression of TEs in both patients and mice with colitis or by DNA hypomethylating drugs elicits a viral mimicry response that suppresses tumorigenesis. This viral mimicry response inhibits the stemness of cancer initiating cells in a cell autonomous manner.

There is a need for an easy-to-use clinical tool, that could predict favorable early PSA response and subsequently enhance early risk stratification, as well as guide treatment planning. Here, the authors show that based on patient data from four phase III randomized trials, Nadir androgen receptor pathway inhibitor (APRI)- Derived Integrative Response (NADIR) model predicts favorable early PSA response to ≤0.2 ng/mL by 6 months in metastatic hormone sensitive prostate cancer (mHSPC) patients initiating treatment with an APRI.

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).

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

This study finds a decrease in severe hail across Europe under a high emissions scenario using km-scale climate model projections. However, very large hail remains a threat, particularly due to the emergence of tropical-like thunderstorms around the Mediterranean coasts.

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.

An ecosystem energetics approach, quantifying trophic energy flows across species, offers a unified framework for linking animal biodiversity loss to changes in ecosystem function and Earth system processes.

JWST data show that the exoplanet WASP-18b has thermally distinct regions of its dayside. The authors mapped the sizes of these regions, measured their temperatures and potentially identify water destruction in the hottest region.

The authors report non-adiabatic first principles molecular dynamics to show how an achiral molecule can be converted to a chiral one upon photoexcitation. These results demonstrate the possibility of asymmetric photochemistry starting from achiral reactants.

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.

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.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

To define the workings of cellular structures and molecules requires cutting-edge technology not only in biology and biochemistry, but also now in nanotechnology. Hayley M. Birch and Julie Clayton report.

InsP₃ 3-kinase phosphorylates 1,4,5-trisphosphate (InsP₃) specifically at its secondary 3-hydroxyl group to generate a tetrakisphosphate. Here, the authors used a combination of methods to survey InsP₃ 3-kinase ligand specificity and determined that IP3K specificity surpasses that of its natural substrate, allowing it to bind diverse ligands with a primary hydroxyl in the reactive position and based on a carbohydrate moiety.

A phase 2a trial of LM11A-31 in mild to moderate Alzheimer disease suggests that p75^NTR modulation is safe and attenuates measures of degeneration.

Antibody immunoprophylaxis for HIV-1 will require effective concentration of biologics at mucosal sites of exposure for effectivity. Here the authors show that infused Fc-modified VRC01LS antibody has increased levels in blood, in the female genital tract and male rectal tissue, compared to native antibody VRC01. VRC01LS is detectable for more than year at the sites of sexual HIV transmission.

The role of non-cancer cells infected by oncolytic viruses (OV) in cancer regression remains elusive. Here the authors engineer OV-sensitive and OV-resistant cancer cell lines and show that OV infection of non-cancer cells can elicit effective antitumour immunity via enhancing DC function and CD8⁺ T cell activation.

Analysis of colorectal cancer bulk gene expression data at the pathway level identifies a poor-prognosis subtype associated with cell differentiation. The subtypes are reproducible in single-cell data and offer biological insights beyond existing stratification strategies.

Epidemiological analyses coupled with immunological phenotyping suggest that humoral immunity induced by COVID-19 vaccines wanes more rapidly in individuals with severe obesity compared to individuals with a BMI within the normal range.

The dayside thermal emission spectrum and brightness temperature map of the ultra-hot Jupiter WASP-18b obtained from the NIRISS instrument on the JWST showed water emission features, an atmosphere consistent with solar metallicity, as well as a steep and symmetrical decrease in temperature towards the nightside.

High numbers of COVID-19-related deaths have been reported in the United States, but estimation of the true numbers of infections is challenging. Here, the authors estimate that on 1 June 2020, 3.7% of the US population was infected with SARS-CoV-2, and 0.01% was infectious, with wide variation by state.

The degree to which species tolerate human disturbance contributes to shape human-wildlife coexistence. Here, the authors identify key predictors of avian tolerance of humans across 842 bird species from open tropical ecosystems.

Automated pathotyping of synovial tissue in arthritis is a major unmet need. Here, the authors develop and demonstrate the efficacy of an automated tissue and cellular pathotyping tool for inflammatory arthritis.

The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.

McNamara et al. show that ALPK3 is an M-band protein required for phosphorylation of sarcomeric proteins and components of the protein quality control apparatus. Further, the autophagy receptor sequestosome-1 requires ALPK3 activity for sarcomeric localization.

Thousands of recombinant antibodies enriched for specificity against defined targets are assembled in multivalent mixtures with enhanced therapeutic activity.

A phase 2 randomized controlled trial of ustekinumab in 72 adolescents with recent-onset type 1 diabetes showed that treatment was well tolerated and β-cell function was 49% higher in the intervention group compared to the placebo arm after 12 months.

The Nile River system is faced with challenges including increasing water demands, political tensions, and future climate and socio-economic uncertainties. Cooperative adaptive management can help increase synergies, balance trade-offs and bring various benefits to riparian countries.

Tumor organoids derived from the most common subtypes of primary liver cancer recapitulate the histologic and molecular features of the tissues of origin, even after long-term culture. These in vitro models, as well as those for colorectal cancer reported in Crespo et al. in a previous issue, are amenable for drug screening and allow the identification of therapeutic approaches with potential for cancer treatment.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Unprecedented floods and droughts bring new challenges for risk reduction, as is clear from this analysis of the drivers of changing impacts in many cases worldwide, with implications for efficient governance and investment in integrated management.

CAR T cells targeting PSMA and engineered to be resistant to immunosuppressive TGFβ signaling exhibit dose-dependent toxicity and expansion following infusion, with some transient antitumor activity, in patients with metastatic castration-resistant prostate cancer

The authors report a mechanistic basis for intestinal polyp formation in patients with hereditary mixed polyposis syndrome that involves the aberrant epithelial expression of morphogens and leads to the formation of ectopic intestinal crypts by progenitor cells outside the stem cell niche, a mechanism that seems to also be involved in human ectopic serrated polyps.

Infections in infants continue to be an important cause of morbidity and mortality worldwide. Understanding the immune mechanisms that operate in infants is necessary for the development of new approaches to improve the health of infants around the world.

Esophageal adenocarcinoma (EAC) has a poor 5-year survival rate and lacks robust preclinical models for use in research. Here, the authors show that newly derived organoids recapitulate the transcriptomic, genetic, and morphological landscape of the primary EAC tumors and provide a platform to test drug sensitivity and study tumor clonality.

Reported COVID-19 mortality rates have been relatively low in Syria, but there has been concern about overwhelmed health systems. Here, the authors use community mortality indicators and estimate that <3% of COVID-19 deaths in Damascus were reported as of 2 September 2020.

Genome sequence data from colorectal tumours show how adenomas progress to carcinomas on the fitness landscape.

A study using a mouse solid tumour model suggests that adjusting the dosing frequency of the PI3Kδ inhibitor AMG319 in the treatment of human cancers could decrease tumour growth with fewer adverse effects.

Changes in precipitation extremes are occurring under climate change, but how they will manifest on sub-daily timescales is uncertain. This study used a high-resolution model, typically used for weather forecasting, to simulate hourly rainfall in the UK in the year 2100. The results confirmed previous findings of winter rainfall intensification and found that short-duration rainfall intensified in summer, increasing the risk of flash flooding.

The abundance of persistent organic pollutants (POPs) in the Arctic atmosphere has decreased over recent decades owing to international restrictions and regulations. However, an analysis confirms that warming is remobilizing POPs into the atmosphere from sinks such as snow and ice, a process that will increase the risk of exposure to these toxic chemicals.

Extreme daily precipitation is thought to increase with warming at a rate of 6.5% per K. High-resolution simulations for the southern UK show this scaling for present conditions, but above 22 °C this scaling fails owing to changes in dynamics.

Increased volcanism-related phosphorus delivery to the Late Ordovician ocean helps explain widespread cooling and eutrophication-driven extinctions, as shown by a biogeochemical model incorporating volcanic ash phosphorus and carbon isotope records.

The epigenetic changes underlying the heterogeneity of RA disease presentation have been the subject of intense scrutiny. In this study, the authors use multiple single-cell sequencing datasets to define ‘chromatin superstates’ in patients with RA, which associate with distinct transcription factors and disease phenotypes.

Pilocytic astrocytoma is a low-grade pediatric glioma, characterized by a single BRAF rearrangement. Here, Reitman and colleagues use single-cell RNA sequencing to reveal molecular hallmarks of the disease that might be targeted therapeutically.

Human follicular helper T cells engaging in synaptic interactions with germinal centre B cells release dopamine stored in chromogranin B⁺ granules, causing rapid externalization of ICOS ligand, which in turn enhances CD40L delivery to the synaptic cleft and synaptic contact, and results in an accelerated response.

Nemazee and colleagues show that PLD3 and PLD4 are endolysosomal exonucleases that digest ingested nucleic acids and thereby prevent activation of endosomal TLRs. Mice that lack PLD3 and PLD4 develop autoinflammatory disease.