Molecular sensors that detect holes in lysosomal membranes for rapid repair have been identified.

ADP-ribosylation is an important protein post-translational modification catalysed by a family of PARP enzymes in humans and is involved in DNA damage and immunity among other processes. While poly-AD...

The rapid, transient, and unpredictable nature of interactions between circulating cells and the endothelium challenges the investigation of these events under flow conditions. Here, we developed an i...

Most cytosolic and nuclear eukaryotic Fe-S proteins acquire their critical Fe-S cofactor by interacting with the cytosolic Fe-S cluster assembly targeting complex (CTC). Despite the critical roles the...

Cellular and environmental stress triggers the rapid and global reprogramming of gene transcription by coordinated recruitment of a limited number of key inducible transcription factors to cis-regulat...

The Legionella SidE effectors ubiquitinate host proteins independently of the canonical E1-E2 cascade. Here we engineer the SidE ligases to develop a modular proximity ligation approach for the identi...

Cytoplasmic pentapeptide repeat proteins (PRPs) protect bacterial DNA gyrase from quinolone antibiotics. While some secreted PRPs are essential upon quinolone exposure, their role in the regulation of...

Endothelial cell (EC) dysfunction is a critical driver of chronic vascular inflammation and atherosclerosis. However, the molecular details of EC state dynamics during vascular disease progression rem...

Cell fate decisions require tight regulation of gene expression. In planarians, highly regenerative flatworms, the mRNA modification N⁶-methyladenosine (m⁶A) modulates progenitor production and fate. ...

After damage from pathogenic, chemical or physical stress, endolysosomal membranes are repaired and resealed by the endosomal sorting complex required for transport (ESCRT) machinery, but how this mem...

The architecture of actin networks at the cell surface is regulated by local membrane topology. However, how actin nucleation can respond sensitively to the degree of membrane curvature remains incomp...

Alternative polyadenylation (APA) modulates gene expression by altering 3′ untranslated region (3′UTR) length. Although 3′UTR lengthening typically accompanies cell differentiation, we unexpectedly ob...

Bone fracture healing remains a significant challenge in orthopedics, as injury-responsive skeletal stem cell (SSC) populations and the regulatory mechanisms governing SSC activation during nonunion fracture repair remain poorly delineated. This study identifies zinc finger transcription factor basonuclin-2 (BNC2) as a skeletal fracture repair control factor in periosteal stem cells. BNC2 marks quiescent periosteal cells during homeostasis and is significantly upregulated upon injury in mice, driving endochondral ossification post-fracture via clonal expansion. Moreover, knockout of Bnc2 in Prx1-cre+ cells (not Ocn-cre+ osteoblasts or LepR-creER+ BMSCs) resulted in impaired fracture healing, suppressing SSC proliferation. Mechanistically, ATAC-seq revealed that BNC2 deletion reduced chromatin accessibility at promoter regions of proliferation genes, hindering transcriptional activation. Additionally, BNC2 regulates histone H3 acetylation by interacting with the NuRD complex. Pharmacologically inhibition of HDAC1/2 activity partially ameliorated the fracture repair defects observed in Prx1-cre; Bnc2f/f mice. Collectively, we identified BNC2+ cells as a rapidly expanding periosteal cell population inducing endochondral ossification niches during repair, providing potential therapeutic strategies for nonunion fractures.

Data detectives see validation in deal with U.S. government that penalizes Dana-Farber Cancer Institute for misrepresenting data in NIH grant applications

Oxidative stress is a major driver of cardiovascular disease; however, the fast changes in cellular metabolism caused by short-lived reactive oxygen species (ROS) remain ill-defined. Here, we characte...

Fat mass loss is a severe complication in cancer-associated cachexia, but its underlying mechanisms remain unclear. This study identifies the tumor-secreted chaperone clusterin (CLU) as a driver of wh...

Oxidative stress is a major driver of cardiovascular disease; however, the fast changes in cellular metabolism caused by short-lived reactive oxygen species (ROS) remain ill-defined. Here, we characte...