Table of Contents
Research Articles
Inhibition of host NOX1 blocks tumor growth and enhances checkpoint inhibitor–based immunotherapyBlocking NOX1 with the novel small molecule inhibitor GKT771 inhibits tumor growth in mice by targeting tumor lymph/angiogenesis and promoting antitumor immune cells recruitment. GKT771 emerges as a novel and promising anticancer drug worth translating into the clinics.
Human organotypic brain slice culture: a novel framework for environmental research in neuro-oncologyTherapeutically resected, adult brain segments were maintained and characterized for an extended period to study glioblastoma progression and treatment in its almost natural environment.
Dietary restriction induces posttranscriptional regulation of longevity genesBy modulating posttranscriptional processes, including RNA editing, miRNA biogenesis, and intron retention, dietary restriction enacts some of its pro-longevity benefits in Caenorhabditis elegans through posttranscriptional regulation of gene expression.
The cancer cell proteome and transcriptome predicts sensitivity to targeted and cytotoxic drugsThis study shows that the proteomic and transcriptomic states of cancer cells are more predictive of drug sensitivity than genomic markers for most drugs, both within and across tumor types.
Systematic identification of recognition motifs for the hub protein LC8LC8 is a eukaryotic hub protein that interacts with multifarious partners; analysis of more than 100 binding/nonbinding sequences led to an algorithm that predicts LC8 partners with 78% accuracy.
Fibril-induced glutamine-/asparagine-rich prions recruit stress granule proteins in mammalian cellsThis study provides evidence that exogenous proteinaceous seeds can induce protein aggregates that sequester stress granule components independent of stress granule assembly.
Human DNA polymerase delta requires an iron–sulfur cluster for high-fidelity DNA synthesisThe iron–sulfur cluster in human DNA polymerase delta has an impact on DNA polymerase and exonuclease activities and can hence influence the fidelity of DNA synthesis.
Membrane curvature sensing of the lipid-anchored K-Ras small GTPaseProteolipid nanoassemblies of K-Ras and lipids in the plasma membrane sense changing membrane curvature architecture and convert mechanical perturbations to mitogenic signaling.
PRDM9 forms a trimer by interactions within the zinc finger arrayPRDM9 forms a trimer as a soluble protein and in complex with DNA mediated by the ZnF domain. Five ZnFs are already sufficient for multimerization and only one DNA molecule is complexed in the trimer.
Stromal fibroblasts induce metastatic tumor cell clusters via epithelial–mesenchymal plasticityThis study highlights the cellular and molecular mechanisms by which stromal fibroblasts enable human breast cancer cells to form tumor cell clusters and acquire highly invasive and metastatic traits.
The miRNA bantam regulates growth and tumorigenesis by repressing the cell cycle regulator tribblesThis work identifies the cell cycle regulator tribbles as a target of the miRNA bantam involved in the growth regulatory and oncogenic functions of bantam in Drosophila epithelia.
The early-acting glycosome biogenic protein Pex3 is essential for trypanosome viabilityThis study reports the identification of trypanosome Pex3, the master regulator of glycosome biogenesis. Trypanosome Pex3 is essential for glycosome assembly and trypanosome viability and is distinct from human Pex3.
XIAP controls RIPK2 signaling by preventing its deposition in speck-like structuresThis study provides evidence that the NOD1/2-associated kinase RIPK2 localizes to detergent insoluble cytosolic complexes upon activation and suggests novel regulatory mechanisms for RIPK2 signaling.
Subunit interactions and arrangements in the fission yeast Mis16–Mis18–Mis19 complexA structural study of the fission yeast Mis19 protein, required for centromere establishment, is presented together with data describing its interactions with functional partners Mis16 and Mis18.
Vinculin is critical for the robustness of the epithelial cell sheet paracellular barrier for ionsVinculin in the apical junctional complex maintains the paracellular barrier function specifically for ions, but not for large solutes, by buffering mechanical fluctuations.
Kinesin-8B controls basal body function and flagellum formation and is key to malaria transmissionThis comprehensive study describes the key role and real-time dynamics of Plasmodium kinesin-8B in microtubule-based basal body and axoneme assembly during flagellum (male gamete) formation and parasite transmission.
MITOL deletion in the brain impairs mitochondrial structure and ER tethering leading to oxidative stressMITOL deletion in mouse brain impairs the morphology and ER tethering of mitochondria, resulting in enhanced oxidative stress. This study suggests a relationship between morphological abnormalities of mitochondria and developmental disorder.
Ncl1-mediated metabolic rewiring critical during metabolic stressAccumulation of cysteine induces translational defects and metabolic rewiring that are abrogated by leucine in a transfer RNA (tRNA) methyltransferase NCL1-dependent manner in yeast.
GRP78 regulates CD44v membrane homeostasis and cell spreading in tamoxifen-resistant breast cancerEndoplasmic reticulum chaperone protein GRP78 interacts with CD44v and regulates F-actin integrity, cell adhesion, and cell spreading in breast cancer cells. Targeting cell surface GRP78 by antibodies can reduce CD44v expression.
KAP1 is an antiparallel dimer with a functional asymmetryThis study reveals the architecture of human KAP1 by integrating molecular modeling with small-angle X-ray scattering and single-molecule experiments. KAP1 dimers feature a structural asymmetry at the C-terminal domains that has functional implications for recruitment of HP1.
A molecule inducing androgen receptor degradation and selectively targeting prostate cancer cellsA new molecule induces AR sumoylation and degradation resulting in selective growth inhibition in AR-dependent prostate cancer cells, but its activity is blunted by interference with proteasomes.
Plasmalogen loss caused by remodeling deficiency in mitochondria31P NMR unveils cell type–dependent losses of plasmalogen in the chain remodeling–deficient brain, liver, kidney, and lymphoblast in association with aberrant mitochondrial function and morphology.
Heterozygous loss of function of IQSEC2/Iqsec2 leads to increased activated Arf6 and severe neurocognitive seizure phenotype in femalesWe show that the loss of Iqsec2 function in mice recapitulates key aspects of the human phenotype, irrespective of the X-inactivation status of the gene between species. Our understanding of the traditional X-chromosome inheritance with heterozygous female sparing needs revisiting.
Methods
De novo prediction of cell-type complexity in single-cell RNA-seq and tumor microenvironmentsThis study describes a computational method for determining statistical support to varying levels of heterogeneity provided by single-cell RNA-sequencing data with applications to tumor samples.
TAF-ChIP: an ultra-low input approach for genome-wide chromatin immunoprecipitation assayThe authors present a novel method for obtaining chromatin profiles from low cell numbers without prior nuclei isolation. The method is successfully implemented in generating epigenetic profile from 100 cells with high signal-to-noise ratio.
Targeted variant detection using unaligned RNA-Seq readsThis study introduces km, an approach leveraging k-mer decomposition to identify targeted mutations. It can detect single-base mutations, insertions and deletions, as well as fusions. An analysis of over 10,000 RNA-seq samples shows fast mutation detection via km.
Reconstructing B-cell receptor sequences from short-read single-cell RNA sequencing with BRAPeSBRAPeS is a software for B-cell receptor reconstruction in single cells from very short (25–30 bp) read lengths, which achieves similar success rates and accuracy as applying other methods on long reads.
