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The CD47/SIRPα axis is well known to mediate immune escape by promoting cancer resistance to phagocytosis. Here the authors show that low CD47-expressing prostate cancer cells still allow phagocytosis but the process is incomplete leading to the formation of macrophage:tumor hybrid cells with immune evasive and pro-metastatic properties.

PRDM9 is a PR domain containing histone methyl transferase which expression is normally restricted to the germline that has also been linked to a number of somatic cancers. Here the authors describe the identification of a small molecule that selectivity inhibits the methyltransferase activity of PRDM9 in biochemical and cellular assays

Mito-SEPs are small peptides that can modulate oxidative metabolism in mitochondria. Here the authors show that C15ORF48 encodes a mito-SEP, MOCCI, capable of altering mitochondria respiration to suppress inflammation, while C15ORF48 3’ untranslated region also contains a miRNA, miR-147b, that synergizes with MOCCI to modulate host anti-viral responses.

Sen et al. provide in-depth temporal multi-omic analyses with single-cell RNA-sequencing (scRNA-seq) profiles of nuclear factor kappa B (NF-κB)-regulated gene expression in B cells upon B cell receptor (BCR) activation. Their findings reveal distinct kinetic patterns of gene expression mediated by RelA and Rel and functional antagonism between the closely related NF-κB subunits.

By combining genome-wide clustered regularly interspaced short palindromic repeats with Cas9 screening and cryo-electron microscopy structure analysis, the authors identified transmembrane protein 63B as a lipid scramblase that detects structural changes in the lipid bilayer and scrambles lipids to regulate membrane lipid distributions.

Most people affected by Alcohol Use Disorder do not develop cirrhosis. Here, the authors show that induced pluripotent stem cell-derived hepatocytes from patients with Alcohol Cirrhosis, have impaired cell energy production and were more susceptible to oxidative stress, which is partially reversed by treatment with Aramchol.

HIC2 regulates the fetal-to-adult hemoglobin switch. It inactivates an enhancer of the BCL11A gene, a fetal globin repressor, by reducing chromatin accessibility and displacing the transcription factor GATA1.

Yanick Crow and colleagues report that biallelic mutations in SNORD118, which encodes the box C/D snoRNA U8, cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts. The mutations affect U8 expression, processing and protein binding and suggest a role for this snoRNA in cerebral vascular homeostasis.

The transcriptional regulator PRDM15 is expressed at low levels in normal tissues but overexpressed in B-cell lymphomas. Here, the authors show that PRDM15 depletion does not affect adult somatic cell homeostasis but leads to a metabolic crisis which impairs B-cell lymphomagenesis.

In a 15-year whole-ecosystem, single-factor experiment, stopping experimental mercury loading results in rapid decreases in methylmercury contamination of fish populations and almost complete recovery within the timeframe of the study.

The genetic characterisation of mixed phenotype acute leukemia (MPAL) remains limited. Here, single cell multi-omics analysis of 14 adult MPAL patients identifies a stem cell-like transcriptomic signature expressed by MPAL blasts that is indicative of high differentiation potential and gives rise to a gene set score MPAL95 that is predictive of survival.

The authors developed a platform for rapid identification of interacting plant immune receptors and pathogen avirulence proteins by library screening in protoplasts, then used it to identify new wheat stem rust Avr genes recognized by known wheat resistance genes.

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.

Depletion of BRD4 reduces the chromatin occupancy of NIPBL, resulting in aberrant genome folding. Loss of BRD4 impedes neural crest differentiation, which can be rescued by depletion of WAPL.

The anti-apoptotic protein Bcl-2 is selectively expressed in intestinal stem cells (ISCs). Here, the authors show that, in intestinal stem cells, Bcl-2 alleviates apoptotic priming induced by the loss of the tumour suppressor Apc in ISCs and that the absence of Bcl-2 or pharmacological blockade of Bcl-2 can inhibit the intestinal tumorigenesis driven by the Apc-loss.

Neuronal activity increases local cerebral blood flow (CBF) to satisfy metabolic demand, yet the role of astrocytes in this phenomenon is controversial. Here, the authors show that astrocytes amplify CBF only when neuronal activity is sustained.

Genomic and transcriptomic analysis of lung adenocarcinoma (LUAD) in Asia indicates that Asian LUADs have fewer mutations, lower driver prevalence and fewer copy number alterations than European LUADs.

A complex of suPAR and high-risk variants of APOL1 acting on integrin signaling in the kidney contributes to APOL1-associated chronic kidney disease.

Radiotracers used in human positron emission tomography studies need to be prepared according to current good manufacturing practice. Here we use the synthesis of [¹¹C]ER176 as an example to show the translation of an experimental radiosynthesis to a current good manufacturing practice process.

EGFR mutant lung adenocarcinoma (LUAD) exhibit diverse clinical outcomes in response to targeted therapies. Here the authors show that these LUADs involve a complex genomic landscape with high intratumor heterogeneity, providing insights into the evolutionary trajectory of oncogene-driven LUAD and potential mediators of EGFR TKI resistance.

A mouse study shows that non-neuronal epidermal Merkel cells aid fine-touch perception in the skin through their expression of the Piezo2 mechanosensitive cation channel which then actively tunes the response to touch in adjacent somatosensory neurons.

The critical effectors of MYC overexpression during lymphomagenesis in transgenic mice are defined.

Six WWE domain-containing proteins also contain domains with E3 ubiquitin ligase activity. We report structures, biophysical and biochemical assays for the discovery of novel WWE domain binders and their respective application.