Table of Contents
Research Articles
- Macrophage Sult2b1 promotes pathological neovascularization in age-related macular degeneration
Sult2b1 deficiency attenuates pathologic neovascularization by inhibiting M2 macrophage polarization and promoting cholesterol efflux via the LXR–ABCA1/G1 pathway.
- Parenchymal border macrophages regulate tau pathology and tau-mediated neurodegeneration
Parenchymal border macrophages’ (PBMs) function impedes tau pathology and tau-mediated neurodegeneration, whereas tau pathology promotes PBM dysfunction associated with impaired CSF flow.
- SF3B1 mutation–mediated sensitization to H3B-8800 splicing inhibitor in chronic lymphocytic leukemia
Understanding the pathogenic mechanisms of SF3B1 mutation can help unravel their contribution in patients’ worse prognosis. The cytotoxic effects and delayed leukemic infiltration induced by H3B-8800 support the potential use of SF3B1 inhibitors as a novel therapy in CLL.
- Neuroprotective effects of hepatoma-derived growth factor in models of Huntington’s disease
This study demonstrates that hepatoma-derived growth factor improves distinct Huntington’s disease phenotypes in cell culture and genetic mouse models.
- A Msp1-containing complex removes orphaned proteins in the mitochondrial outer membrane of T. brucei
Disruption of mitochondrial outer membrane protein biogenesis triggers a pathway leading to proteasomal degradation of orphan outer membrane proteins mediated by Msp1 and three interacting proteins.
- Whole genome sequencing of drug resistance Mycobacterium tuberculosis from extra-pulmonary sites
The article summarizes the characteristics of patients with drug resistance extra-pulmonary tuberculosis (DR-EPTB) and gene mutations of drug resistant Mycobacterium tuberculosis (DR-TB) from the patients with EPTB in a municipality of southwest China.
- A novel antifolate suppresses growth of FPGS-deficient cells and overcomes methotrexate resistance
Mechanistic characterization of a novel, lipophilic antifolate that suppresses growth of FPGS-deficient cells that are linked to methotrexate resistance and relapse in cancer patients.
- Structural evidence for elastic tethers connecting separating chromosomes in crane-fly spermatocytes
Correlative live imaging with electron tomography provides evidence that physical filamentous connections extend between separating telomeres at all stages of anaphase.
- Tumor necrosis factor mediates USE1-independent FAT10ylation under inflammatory conditions
The finding of TNF-dependent FAT10ylation in the absence of USE1 identifies seven additional, so far unknown FAT10-reactive E2 conjugating enzymes.
- Allotopic expression of COX6 elucidates Atco-driven co-assembly of cytochrome oxidase and ATP synthase
Relocation of COX6 from nuclear to the mitochondrial genome helps unveil the role of Atco (Atp9–Cox6 complex) in coupling the biogenesis of cytochrome oxidase and ATP synthase in yeast mitochondria.
- c-JUN is a barrier in hESC to cardiomyocyte transition
The study reveals that knocking out c-JUN improves cardiomyocyte generation in humans by increasing chromatin accessibility and H3K4me3 modification on key genes regulating heart development. These findings shed new light on c-JUN's unexpected role in human cardiogenesis.
- p62 and NBR1 functions are dispensable for aggrephagy in mouse ESCs and ESC-derived neurons
This work shows a robust and stable aggrephagy regulation in mouse ESCs and ESC-derived neurons in absence of p62 and NBR1 functions.
- Incomplete activation of Alyref and Gabpb1 leads to preimplantation arrest in cloned mouse embryos
This study shows that failed activation of developmentally required Alyref and Gabpb1 genes leads to the arrest of cloned mouse embryos.
- Convergent evolution and B-cell recirculation in germinal centers in a human lymph node
The study characterizes an ongoing immune response by sequencing B-cells from 10 germinal centers and finds diverse clonal patterns and convergent evolution, indicating re-engagement and rediversification of B-cell clones across GCs.
- Unique activities of two overlapping PAX6 retinal enhancers
A unique combination of high-resolution imaging and single-cell RNA sequencing in zebrafish reveals cell type-specific activities of developmental eye enhancers.
- Grp78 is required for intestinal Kras-dependent glycolysis proliferation and adenomagenesis
Heterozygous deletion of Grp78 reduces Apc–Kras-driven colorectal adenomagenesis. Apc–Kras-mutated cells rely on GLUT1 transporter for glycolysis, which is inhibited by Grp78 heterozygosity.
- Cell–cell interactions during the formation of primordial follicles in humans
This study revealed the presence of multinucleated syncytia and intercellular bridges in ovarian cords and highlighted the role of cell–cell interactions during primordial follicle formation in humans.
- Polo-like kinase-1 mediates hepatitis C virus-induced cell migration, a drug target for liver cancer
This study identifies PLK1 as a novel protein that promotes liver cancer in people with hepatitis C. The findings suggest a novel drug target for patients with liver cancer to reduce cancer spread and improve survival.
- T cell differentiation drives the negative selection of pathogenic mitochondrial DNA variants
Fluorescently activated cell-sorting coupled with high-throughput single cell mtDNA sequencing reveals enhanced negative selection of pathogenic mtDNA variants in T cells, with more mature, memory cells exhibiting lower mutation levels than their naïve counterparts.
- LEF1 enhances β-catenin transactivation through IDR-dependent liquid–liquid phase separation
This research elucidates the correlation between liquid–liquid phase separation (LLPS) of LEF1 with β-catenin and their transcriptional activation function, offering a novel therapeutic approach for the treatment of colorectal cancer through LLPS.
- Alternative oxidase causes cell type- and tissue-specific responses in mutator mice
Expression of the alternative oxidase in mtDNA mutator mice improves their blood phenotype but enhances inflammatory and stress responses in skeletal muscle.
- A new ferrocene derivative blocks K-Ras localization and function by oxidative modification at His95
We report redox system regulates KRAS localization and activity via oxidation at His95 residue, and proposes a role of oncogenic K-Ras in the antioxidant-induced growth and metastasis of KRAS-driven cancers.
- The arginine methyltransferase PRMT5 promotes mucosal defense in the intestine
Arginine methyltransferase PRMT5 promotes select colonic goblet cell-associated gene programs and facilitates host defense against enteric pathogens.
- Inhibition of the SREBP pathway prevents SARS-CoV-2 replication and inflammasome activation
SARS-CoV-2 exploits host lipid metabolism for its replication and pathogenesis. Blocking SREBPs prevents SARS-CoV-2–induced lipid remodeling, virus replication, cell death, and inflammatory mediators, suggesting SREBP as a potential host-derived antiviral target.
- VDR is an essential regulator of hair follicle regression through the progression of cell death
This study investigates the role of VDR in the progression of catagen, and demonstrates that aberrant regression that ectopically prevents cell death impairs hair follicle regeneration, emphasizing the significance of regression in tissue homeostasis.
- Structure shows that the BIR2 domain of E3 ligase XIAP binds across the RIPK2 kinase dimer interface
The structure of RIPK2 kinase bound to the XIAP BIR2 domain reveals the essential role of the RIPK2 dimer in NOD2 signalling and explains the mechanism of anti-inflammatory drugs targeting this complex.
- Loss of the mitochondrial protein SPD-3 elevates PLK-1 levels and dysregulates mitotic events
In C. elegans a mutation in the mitochondria-localized protein SPD-3 leads to elevated levels of Polo-like kinase 1, causing abnormal chromosome positioning during mitosis.
- Chromatin in 3D distinguishes dMes-4/NSD and Hypb/dSet2 in protecting genes from H3K27me3 silencing
Histone KMTs of H3K36me maintains euchromatin by antagonizing H3K27me3 spreading and influencing 3D genome organization at TADs boundaries, thus participating in transcriptional program maintenance.
- Huntingtin loss in hepatocytes is associated with altered metabolism, adhesion, and liver zonation
Lifelong huntingtin loss in mouse hepatocytes is associated with altered metabolism, adhesion, and liver zonation which mimics the phenotypes caused by impaired B-catenin function.
- Comprehensive analysis of the lysine succinylome in fish oil-treated prostate cancer cells
Through a global lysine succinylation analysis of prostate cancer cells treated with fish oil, a significant number of lysine succinylation sites have been identified and FO-dependent GOT2 succinylation status may have a potential to inhibit building block generation.
- KIF16B drives MT1-MMP recycling in macrophages and promotes co-invasion of cancer cells
Recycling of the metalloproteinase MT1-MMP by the motor KIF16B regulates 3D invasion of macrophages, and also co-invasion of cancer cells, pointing to a role of KIF16B in the tumor microenvironment.
- Control of Paneth cell function by HuR regulates gut mucosal growth by altering stem cell activity
HuR stimulates the activity of intestinal stem cells by enhancing Paneth cell function via activation of mitochondrial metabolism, thus promoting renewal of the intestinal mucosa.
- Identification of new drugs to counteract anti-spike IgG-induced hyperinflammation in severe COVID-19
COVID-19 still poses a major health threat with worldwide ongoing hospitalizations and mortality. Aberrant antibody responses are a crucial cause of development of severe COVID-19 by inducing hyperinflammation, edema, and thrombus formation. Here, we identified entospletinib as a promising therapeutic candidate against severe COVID-19.
- MAST4 promotes primary ciliary resorption through phosphorylation of Tctex-1
The mechanism that underlies cilium resorption is not well understood. This study reveals the microtubule-associated serine/threonine kinase family member 4 (MAST4) is a novel kinase that promotes ciliary resorption by localizing ciliary base-phosphorylation of Tctex-1 at Thr94 and its downstream effectors.
Reviews
- Decoding the obesity–cancer connection: lessons from preclinical models of pancreatic adenocarcinoma
Preclinical models demonstrate that obesity reprograms the pretumor or tumor cell and its micro- and macro-environments to drive cancer development via altered cellular metabolism, hormone dysregulation, inflammation, and microbial dysbiosis.
- Molecular mechanisms underlying totipotency
A review article summarizing recent findings related to totipotency in mammals, encompassing topics such as the epigenome and gene regulation in early embryos, in vitro totipotent-like cells, and somatic nuclear transfer.
Methods
- A targeted sequencing extension for transcript genotyping in single-cell transcriptomics
We describe the targeted sequencing extension and provide two proof-of-concept examples of how it can assist with understanding the impact of genetic variants.
- High-quality single-cell transcriptomics from ovarian histological sections during folliculogenesis
Quantitative RNA-sequencing method for single cells isolated from alcohol- and formalin-fixed tissue sections discovers new relationships between histology and transcriptome during folliculogenesis.