Search

The gH-associated tropism and entry (GATE) complex consists of glycoprotein H, UL116 and UL141. This complex is abundant on human cytomegalovirus virions and enables entry into human endothelial cells.

Current tools for single-cell spatial omics still face barriers with regard to incomplete molecular profiling, tissue loss, and probe failure. Here, the authors use machine learning for the imputation of protein abundance in tissue-based cyclic immunofluorescence, showing that the spatial context can improve the accuracy of the imputation outputs.

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.

Heterozygous mutations in the mechanoenzyme dynamin (DNM2) manifest as either a myopathy or a peripheral neuropathy. Here, the authors show antagonistic effects of these mutations and combining them, in mice, mitigates the phenotypic manifestations observed in individual mutants.

In this phase 1 trial, patients with heavily pretreated and refractory CD30⁺ lymphoma were safely treated with donor-cord-blood-derived NK cells that were precomplexed with the anti-CD30 and anti-CD16A bispecific antibody AFM13, showing encouraging preliminary clinical response rates.

All-carbon quaternary stereocenters are an important synthetic motif but are especially difficult to synthesize enantioselectively. Here, the authors demonstrate the organocatalytic regio- and enantioselective synthesis of valuable acyclic 1,4-dicarbonyl products with vinylated and arylated quaternary centers.

Licheva, Pflaum, Babic, Mancilla et al. show that low-affinity cargo–receptor interactions promote autophagy receptor mobility and condensation of the scaffold protein Atg11 to trigger initiation hub and phagophore formation.

Analyses reveal a previously undescribed transmembrane protein fold in the endoplasmic reticulum-based glucosyltransferase ALG6 and provide a structural basis for understanding the glucose transfer mechanism.

Flavivirus infection leads to a rearrangement of host cell ER membranes that creates an environment permissive to viral replication. The morphology of these membrane rearrangements is known, but the mechanisms involved are unclear. Here, atlastins—ER-resident membrane-bound GTPases of the dynamin family—are shown to be targeted by flaviviruses to establish their replication organelle and for virion maturation and secretion.

Toxicities limit combination of PARP inhibitors (PARPi) and chemotherapy in patients with germline BRCA1 and BRCA2 pathogenic variant (gBRCAm) breast cancer. Here, the authors report a preclinical study followed by a randomised phase II/III clinical trial investigating the addition of a gap between chemotherapy (carboplatin and paclitaxel) and PARPi (olaparib), in patients with early gBRCAm breast cancer.

An increase in stream temperature leads to a convergence of metabolic balance, overall decline in net ecosystem productivity, and higher CO₂ emissions from streams, according to analyses of temperature sensitivity of stream metabolism across six biomes.

Abeysundara, Rasnitsyn, Fong et al. report that the presence of leptomeningeal metastatic tumour cells leads to the recruitment and remodelling of fibroblasts, which, in turn, facilitate the colonization and outgrowth of medulloblastoma cells in the leptomeninges.

Autosomal dominant tubulointerstitial kidney disease (ADTKD) due to uromodulin mutations is a hereditary kidney disease causing renal fibrosis. Here, the authors show that mesencephalic astrocyte-derived neurotrophic factor can improve defective autophagy/mitophagy and decrease renal scarring in ADTKD.

Oblique line scan microscopy achieves nanoscale spatial and sub-millisecond temporal resolution across a large field of view, enabling improved and robust single-molecule biophysical measurements and single-molecule tracking in both cells and solution.

A correlated material SrVO₃ has been considered to be a Fermi liquid, however previous studies have been limited to disordered samples. Here the authors study transport in ultraclean films of SrVO₃, finding deviations from the Fermi liquid picture.

Adipogenesis associated Mth938 Domain Containing gene (AAMDC) is frequently amplified in the IntClus2 subgroup of ER + breast cancer. Here, the authors show that AAMDC drives tumourigenesis through activating PI3K-AKT-mTOR pathway for metabolic reprogramming.

Jeremy Reiter and colleagues show that Tctn1 is a component of a transition zone complex that regulates ciliogenesis and ciliary membrane composition. They also identify a likely causal mutation in TCTN1 in two siblings with Joubert syndrome.

A cell-based phenotypic screen identifying inhibitors of Notch signaling led to the discovery of NVS-ZP7-4, which blocks the activity of the zinc transporter SLC39a7 (ZIP7) and induces cell death through an ER stress mechanism.

Aromatase inhibitors are used to treat oestrogen-receptor-positive breast cancer. Here, the authors use genomic approaches to analyse tumours before and after neo-adjuvant treatment and find that treatment alters the clonal landscape of the tumours.

Zika virus (ZIKV) infection suppresses the induction of dendritic cell (DC)-derived immunity, but the underlying mechanistical insights are still lacking. Here the authors show, using in vitro systems profiling of DC transcriptome and epigenome, that ZIKV specifically alters SREBP2-related expression of inflammation- and metabolism-related genes to modulate DC functions.

Mitochondria depend on phospholipids supplied by the endoplasmic reticulum. Here, using biochemical assays and molecular dynamics simulations, authors identify VDAC as a scramblase-type lipid transporter that catalyze lipid entry.

Glutamine deprivation is currently being tested as a therapeutic strategy in cancer. Shanware et al.show that in cultured cells, glutamine deprivation stimulates IL-8 secretion by triggering endoplasmic reticulum stress, and suggest that the potential of this effect to influence tumour development should be examined.

Human cerebral organoids exhibit compositional and transcriptomic alterations in both neuronal and non-neuronal cells in the absence of UBE3A.

Synthetic Notch (SynNotch) receptors can be used to endow cells with custom sense-and-respond capabilities. Here, the authors introduce a fluorescein-binding SynNotch as a versatile tool for controlling gene expression responses to diverse stimuli via ligands based on fluorescein-conjugates.

The development of activated B cells into antibody-secreting cells (ASC) is a critical step for humoral immunity. Here the authors show, using adoptive transfers and single cell RNA sequencing, that commitment to ASC occurs soon following B cell activation, and is coordinated by specific transcriptome programs and proliferation kinetics.

A proteomic risk score for cardiorespiratory fitness, comprising as few as 21 proteins, is dynamic with exercise training and helps predict the risk of mortality and a range of cardiovascular, metabolic and neurological conditions.

Integration of pre-treatment tumour features in predictive models using machine learning could inform on response to therapy.

Here, the authors provide cryo-EM structures of mature and immature Spondweni virus, defining the furin recognition site at high resolution, and identifying a lipid that binds E upon capsid maturation and is also present in Zika and Dengue virions.

Genetic alteration can render tumor cells resistant to immune cell-mediated killing. Here based on a genome-wide CRISPR screening, the authors show that expression of CHMP2A confers tumor cell resistance to NK cell-mediated cytotoxicity, mechanistically involving CHMP2A-dependent regulation of extracellular vesicle secretion.

Opium poppy accumulates alkaloids in the specialized cytoplasm of laticifers known as latex. Here the authors show that the binding of alkaloids to the abundant major latex proteins triggers quaternary structural modification that mediates a functional role for protein aggregation.

PIEZO1 is a mechanosensitive ion channel. Here, authors identify PIEZO1 human mutations in Prune Belly Syndrome. At a single molecule level these mutations exhibit loss-of-function characteristics.

Regulated cell death is a key process in plant and animal development, but does it occur in parasitic protozoa? Jeremy Mottram and colleagues assess the evidence of regulated cell death in these organisms and propose that protozoan cell death should be classified as either necrotic or incidental.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

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.

Jung-Garcia et al. dissect the contributions of isoforms of the inner nuclear membrane protein LAP1 to nuclear envelope blebbing, constrained migration and invasion in melanoma cells.