Highlights d FUS multimer interacts dynamically with RNA, resulting in liquid-like condensates d ALS/FTD-linked FUS mutations in arginine lead to defective RNA binding d ALS/FTD-linked FUS mutations in glycine induce quick loss of condensate fluidity d Karyopherin-b2 reverses mutant defects and recovers wildtype FUS properties

No abstract

Bone marrow mesenchymal stem cells can be induced into neural cells by the human brain-derived neurotrophic factor gene in a RADA16-PRG functionalized self-assembling peptide hydrogel. This article is protected by copyright. All rights reserved.

Curcumin restores mice hind-limb function that has been reduced by SCI. This occurs by inhibition of TAK1/MKK6/p38MAPK via the TAK1 and NFκB pathways and inflammation. These results suggest the therapeutic potential for curcumin in the treatment of SCI.

No abstract

Human telomeres are protected by shelterin proteins, but how telomeres maintain a dynamic structure remains elusive. Here, we report an unexpected activity of POT1 in imparting conformational dynamics of the telomere overhang, even at a monomer level. Strikingly, such POT1-induced overhang dynamics is greatly enhanced when TRF2 engages with the telomere duplex. Interestingly, TRF2, but not TRF2ΔB, recruits POT1-bound overhangs to the telomere ds/ss junction and induces a discrete stepwise movement up and down the axis of telomere duplex. The same steps are observed regardless of the length of the POT1-bound overhang, suggesting a tightly regulated conformational dynamic coordinated by TRF2 and POT1. TPP1 and TIN2 which physically connect POT1 and TRF2 act to generate a smooth movement along the axis of the telomere duplex. Our results suggest a plausible mechanism wherein telomeres maintain a dynamic structure orchestrated by shelterin.

Neurodegenerative diseases are characterized by neuronal death and regenerative failure. However, gene regulatory programs governing how initial neuronal injuries lead to neuronal death remain poorly understood. In adult mice, optic nerve crush (ONC) injury, which severs all axons of retinal ganglion cells (RGCs), results in massive death of axotomized RGCs and regenerative failure of survivors. We performed an in vivo CRISPR/Cas9-based genome-wide screen of 1893 transcription factors (TFs) to seek repressors of RGC survival and axon regeneration following ONC. In parallel, we profiled the epigenetic and transcriptional landscapes of injured RGCs by ATAC-seq and RNA-seq to identify critical injury responsive TFs and their targets. Remarkably, these independent analyses converged on a set of four ATF/CEBP transcription factors: ATF3, ATF4, C/EBPg; and CHOP (Ddit3), as critical regulators of survival. Further studies indicate that these TFs contribute to two pro-death transcriptional programs: ATF3/CHOP preferentially regulate pathways activated by cytokines and innate immunity, whereas ATF4/C/EBPγ regulate pathways engaged by intrinsic neuronal stressors. Manipulation of these TFs also protects RGCs in an experimental model of glaucoma, a prevalent disease in which RGCs die. Together, our results reveal core transcription programs that transform an initial axonal insult into a degenerative result and suggest novel strategies for treating neurodegenerative diseases.

Heat-shock proteins (HSPs), one of the evolutionarily conserved protein families, are widely found in various organisms, and play important physiological functions. Nevertheless, HSPs have not been systematically analyzed in esophageal squamous cell carcinoma (ESCC). In this study, we applied the protein-protein interaction (PPI) network methodology to explore the characteristics of HSPs, and integrate their expression in ESCC. First, differentially expressed HSPs in ESCC were identified from our previous RNA-seq data. By constructing a specific PPI network, we found differentially expressed HSPs interacted with hundreds of neighboring proteins. Subcellular localization analyses demonstrated that HSPs and their interacting proteins distributed in multiple layers, from membrane to nucleus. Functional enrichment annotation analyses revealed known and potential functions for HSPs. KEGG pathway analyses identified four significant enrichment pathways. Moreover, three HSPs (DNAJC5B, HSPA1B, and HSPH1) could serve as promising targets for prognostic prediction in ESCC, suggesting these HSPs might play a significant role in the development of ESCC. These multiple bioinformatics analyses have provided a comprehensive view of the roles of heat-shock proteins in esophageal squamous cell carcinoma.