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Steps are known to be important sites on the surface of heterogeneous catalysts. Now it is shown that the density of steps on a palladium surface can alter its stability, and thus reactivity, and is key to understanding the oscillatory behaviour of the CO oxidation reaction at atmospheric pressure.

Oncogene addiction is considered as a cancer cell-autonomous phenomenon, but can also influence the host immune system. Here the authors show that MYC-driven lymphomagenesis is associated with a block in the maturation and effector functions of natural killer cells as a mechanism of tumor escape from immunosurveillance.

Transcriptional adaptation upregulates UTRN in Duchenne muscular dystrophy (DMD) patients, as supported by several lines of evidence, including the use of splice-switching antisense oligonucleotides to induce the skipping of out-of-frame exons of the DMD gene.

A single dose of the anti-sporozoite monoclonal antibody CIS43LS can achieve durable, sterile protection against Plasmodium falciparum infection.

Tau aggregates are associated with several neurodegenerative disorders. In this work, I. Saha and colleagues show that valosin-containing protein (VCP) recruited to Tau fibrils disaggregates them. However, this process comes at a cost: it generates seeding-active Tau species as byproduct.

Pannexin 1 (PANX1) is a membrane channel mediating release of signaling molecules to the extracellular space. PANX1 can be activated by GPCRs. Here, the authors elucidate a non-canonical channel activation pathway by α1-adrenergic receptor that involves HDAC6- mediated lysine deacetylation of PANX1.

Sissoko et al. show that CENP-T local concentration regulates its ability to recruit the outer kinetochore, which may restrict complete kinetochore formation to regions with higher-order inner kinetochore assemblies.

Augsornworawat et al. perform single-nucleus multi-omics and integrated transcriptional and chromatin analysis to identify differences between human stem cell-derived and primary islets.

Here, the authors isolate and characterize a bispecific monomeric nanobody that induces dimerization of SARS-CoV-2 spike trimers, neutralizes variants of concerns as well as SARS-CoV, and inhibits SARS-CoV-2 infection in mice.

The authors develop a Vitamin K-dependent apoptotic reporter cell line for large-scale screening of enzymes associated with Vitamin K-dependent carboxylation and identify ferroptosis suppressor protein 1 (FSP1) as responsible for warfarin-resistant vitamin K reduction.

Clonal Vb2 usage is common among patients with mature T cell lymphoma. Here the authors report the generation of allogeneic CAR-T cells selectively targeting TCR Vb2+ on malignant T cells, with limited normal T cell destruction.

Much of the mammalian genome is derived from retroelements, a significant proportion of which are endogenous retroviruses (ERVs). ERVs are transcriptionally silenced during early embryogenesis by histone and DNA methylation, but the initiators of this process are largely unknown. Here, deletion of KAP1 is shown to lead to a marked upregulation of a range of ERVs in mouse embryonic stem cells and in early embryos.

A study finding an oestrogen-sensing signalling pathway that promotes melanoma metastasis only in female mice emphasizes the importance of recognizing sex-specific factors in cancer management.

The aspartate aminotransaminase GOT1 is important for maintaining redox balance. Here, the authors show that inhibition of GOT1 in pancreatic cancer cells leads to cell death via ferroptosis.

Current biological models for examining cancer immunobiology in a HIV infected context are lacking. Here the authors use a human-derived microphysiological model to represent the HIV immune system and assess the ability of transferred populations of NK cells in the targeting of tumours.

Microsporidia are obligate intracellular parasites that infect both humans and animals. Here, Dean et al. perform ancient gene reconstruction and functional assays to investigate the evolution and functional diversification of nucleotide transporters which are key to the parasite's intracellular lifestyle.

The liver-specific microRNA-122 is an essential proviral host factor of Hepatitis C virus replication. Here the authors show that microRNA-122 functions as an RNA chaperone that guides the formation of a functional internal ribosome entry site by preventing energetically more favorable secondary structures within the HCV RNA genome.

While prime editing is a promising technique, some genomic sites remain difficult to edit. Here the authors present fluoPEER, fluorescent prime editing and enrichment reporter, to rank the efficiency of pegRNAs and prime editor variants.

Cui et al. find that arginine depletion and inflammation reduces nuclear localization of arginyl-tRNA synthetase, which influences alternative splicing via condensate-like serine/arginine repetitive matrix protein 2, and regulates cellular metabolism and response to inflammation.

In this in vitro, in silico, and in vivo study Nguyen and colleagues show that specific and stable viral gene delivery of engineered prokaryotic voltage-gated sodium channels (BacNav) to cardiomyocytes can directly augment cardiac tissue excitability and conduction.

Clinical evidences have demonstrated limited efficacy of HER2-targeted therapies in patients with gastric cancer (GC). Here the authors show that survival benefit to anti-HER2 antibody Trastuzumab is reduced in GC patients with high levels of the caveolin-1 and that, in preclinical cancer models, antibody drug efficacy can be improved by modulating caveolin-1 levels with cholesterol-depleting drugs, statins.

Estimates from the Global Dietary Database indicated that 2.2 million new type 2 diabetes and 1.2 million new cardiovascular disease cases were attributable to sugar-sweetened beverages worldwide in 2020, with the highest burdens in sub-Saharan Africa, Latin America and the Caribbean.

Many current immunoassays require multiple washing, incubation and optimization steps. Here the authors present Ratiometric Plug-and-Play Immunodiagnostics (RAPPID), a generic assay platform that uses ratiometric bioluminescent detection to allow sandwich immunoassays to be performed directly in solution.

E2F transcription factors are regulators of cell division and cell fate decisions. Here the authors show that E2F4 is important for proliferation and survival of mouse ESCs, independent of the RB family, and that E2F4 interacts with chromatin regulators associated with gene activation.

SMARCB1/SNF5 is a tumour suppressor and component of the SWI/SNF chromatin remodeler. Here the authors show that, independent of chromatin remodelling activities, SNF5 acts to inhibit the pro-tumorigenic transcriptional program of MYC via control of RNA polymerase pause release at MYC target genes.

Ndeh et al. show that a genetic locus in the human gut bacterium, Bacteroides thetaiotaomicron, encodes a combination of glycosidases, a glycoprotease and a kinase enabling it to process and metabolise O-glycoproteins and the core mucin O-glycan sugar N-acetylgalactosamine.

The fusion of dead Cas9 with KRAB and the transcriptional repressor domain of the chromatin modifier MeCP2 leads to an efficient transcriptional silencer that can be applied to genome-scale screens and genetic circuits.

Cancer cells enriched in cholesterol in their plasma membrane impair T-cell-mediated cytotoxicity, which can be augmented by stiffening the cancer cells via cholesterol depletion, as shown in mouse models of adoptive T-cell immunotherapy.

The metabolic dependencies of androgen receptor (AR)-driven growth in prostate adenocarcinoma are largely unknown but could represent a therapeutic target when hormonal manipulations fail. Here the authors demonstrate that the mitochondrial pyruvate carrier (MPC) is transcriptionally regulated by AR and that MPC inhibition suppresses tumour growth in hormone-responsive and castrate-resistant conditions.

Transcriptional cell states can drive treatment resistance in cancer. Here, the authors develop ReSisTrace to predict cell states that are primed to resist ovarian cancer treatment and validate their findings using small molecule inhibitors.

Diehl et al. show that imbalance among nucleotide species is not sensed by canonical metabolic regulatory pathways, causing excessive cell growth despite a DNA replication block. ATR is needed to increase nucleotide availability in normal S phase.

White-tailed deer are a potential reservoir of SARS-CoV-2 variants.

Multiancestry genome-wide association analyses identify new risk loci for stroke and stroke subtypes. Fine mapping and bioinformatics analyses of these risk loci point to mechanisms not previously implicated in stroke pathophysiology.

Aberrant protein translation and uncontrolled lipid metabolism are hallmarks of cancer growth. Here, in diffuse large B-cell lymphoma, the authors show that fatty acid synthase increases USP11 interaction with and stability of eIF4B via PI3K-S6Kinase signaling, promoting oncogenic protein translation.

Various GPCRs display constitutive ligand-independent activity, but it remains unclear whether ligand-dependent and -independent conformations differ. Here the authors demonstrate the recognition and blocking of G protein recruitment of either the ligand-bound active, or the constitutively active apo-conformation of the viral GPCR US28 by different nanobodies that target similar intracellular loops of the receptor.

Bacterial symbionts of the Endozoicomonadaceae family are frequently found in marine animals but are poorly understood. Using data from the Tara Pacific expedition, this study of Endozoicomonadaceae ecology at an ocean basin-scale reveals that corals across the Pacific Ocean have different host-symbiont association strategies that are determined at the bacterial lineage level.

Calcium signalling downstream of VEGF is essential for VEGF-induced angiogenesis. Here Savage et al. show that Transmembrane Protein 33 (TMEM33) is required for angiogenesis and the endothelial calcium response to VEGF, revealing a function for TMEM33 in multicellular organisms.

Inflammation of brain endothelial cells is seen in neurodegenerative conditions and in aging. Here the authors examine the role of astrocytes in blood brain barrier function using an iPSC-derived cell co-culture model.

Barrett’s esophagus is a pro-oncogenic lesion in the proximal gastrointestinal tract, but with a distal colon-like morphology. Here the authors report that the distal HOX gene HOXA13 is expressed in Barrett’s esophagus and in single cells of the physiological esophagus, and may underlie the phenotypic aspects of metaplasia and increase proliferation.

Super enhancers are frequently involved in the dysregulation of gene expression in cancer. Here, in kidney cancer, a super enhancer is shown to drive the expression of KLF6, which alters the expression of lipid metabolism genes and promotes tumorigenesis.

Control of osteocyte differentiation is not well understood. Here the authors show that the miR-23 cluster represses the TGF-β signalling repressor Prdm16 in osteoblasts, thus enhancing osteocyte differentiation and a low bone mass phenotype.

Tumours acquire new vasculature through angiogenesis or through alternative pathways including the less understood vasculogenesis mimicry. Here the authors identify a vasculogenic mimicry-competent subpopulation of melanoma cells that expresses the vascular cell adhesion molecule PECAM1, but not VEGFR-2.

A dearth of adequate preclinical models to faithfully mimic diffuse large B-cell lymphoma has hampered the identification of driver genes. Here, the authors present a co-culture system that enables ex vivo expansion, viral transduction and transformation of primary human germinal center B cells.

FLT3 is commonly mutated in acute myeloid leukaemia and treatment with FLT3 inhibitors often ends with relapse. Here, the authors perform exome sequencing of samples from patients treated with the FLT3 inhibitor, crenolanib, to show that resistance occurs due to diverse molecular mechanisms, not primarily due to secondary FLT3 mutations.

The PNUTS-PP1 complex directly binds to RNA, and interacts with polymerase II and RNA processing factors to control transcriptional elongation rates and slow polymerase II after polyadenylation sites to promote termination. Using a genome-wide CRISPR screen, Devlin et al. identify this complex as a critical suppressor of herpesvirus KSHV gene expression. They further provide evidence that PNUTS-PP1 controls elongation both downstream and upstream of polyadenylation sites on specific viral genes.

The high degree of subtype plasticity in small cell lung cancer (SCLC) poses a therapeutic challenge. Here, the authors show that the non-neuroendocrine (non-NE) subtype of SCLC is sensitive to ferroptosis while the neuroendocrine (NE) subtype is vulnerable to TRX anti-oxidant pathway inhibition, and the combination of these two treatments in SCLC circumvents non-NE/NE subtype plasticity.

Mechanisms governing adaptation of breast cancer to the brain metastatic microenvironment are unclear. Here, the authors use RNA-sequencing and Drosophila screening to identify Rab11b-mediated endosomal recycling as a unique mechanism for adaptation to a challenging metastatic microenvironment, which can be exploited by repurposing statins.