Defects of WFS1-mediated peptide hormones secretion contribute to the manifestations of Wolfram syndrome.

Aims: The study aims to investigate whether WFS1 is involved in the regulation of the exportation and secretion of other peptide hormones, as well as to elucidate the precise molecular mechanisms underlying WS caused by pathogenic mutations in the WFS1 gene.

Materials And Methods: The plasma proteome from the WS patients (n = 2, male) and WFS1-deficient mice (n = 5, male) were analyzed using liquid-chromatography tandem mass spectrometry (LC-MS/MS), while age- and gender-matched healthy individuals and wildtype (WT) mice serve as controls. WFS1-deficient mice were intraperitoneally injected with IGF1 starting from 4 weeks of age.

Optimized AF4 combined with density cushion ultracentrifugation enables profiling of high-purity human blood extracellular vesicles.

Extracellular vesicles (EVs) have emerged as a promising tool for clinical liquid biopsy. However, the identification of EVs derived from blood samples is hindered by the presence of abundant plasma proteins, which impairs the downstream biochemical analysis of EV-associated proteins and nucleic acids. Here, we employed optimized asymmetric flow field-flow fractionation (AF4) combined with density cushion ultracentrifugation (UC) to obtain high-purity and intact EVs with very low lipoprotein contamination from human plasma and serum.

The tumor suppressor NF2 modulates TEAD4 stability and activity in Hippo signaling via direct interaction.

As an output effector of the Hippo signaling pathway, the TEAD transcription factor and co-activator YAP play crucial functions in promoting cell proliferation and organ size. The tumor suppressor NF2 has been shown to activate LATS1/2 kinases and interplay with the Hippo pathway to suppress the YAP-TEAD complex. However, whether and how NF2 could directly regulate TEAD remains unknown.

Long non-coding RNA LncCplx2 regulates glucose homeostasis and pancreatic β cell function.

Objective: Numerous studies have highlighted the role of clock genes in diabetes disease and pancreatic β cell functions. However, whether rhythmic long non-coding RNAs involve in this process is unknown.

Methods: RNA-seq and 3' rapid amplification of cDNA ends (RACE)-PCR were used to identify the rat LncCplx2 in pancreatic β cells.

CENP-I directly targets centromeric DNA to support CENP-A deposition and centromere maintenance.

The enrichment of histone H3 variant CENP-A is the epigenetic mark of centromere and initiates the assembly of the kinetochore at centromere. The kinetochore is a multi-subunit complex that ensures accurate attachment of microtubule centromere and faithful segregation of sister chromatids during mitosis. As a subunit of kinetochore, CENP-I localization at centromere also depends on CENP-A.

Rapid isolation and cryo-EM characterization of synaptic vesicles from mammalian brain.

Synaptic vesicles (SVs) store and release neurotransmitters at chemical synapses. Precise regulation of SV trafficking, exocytosis and endocytosis is crucial for neural transmission. Biochemical characterization of SVs, which is essential for research into neurotransmitter uptake and release, requires effective in vitro isolation methods.

The Dual Roles of MAGE-C2 in p53 Ubiquitination and Cell Proliferation Through E3 Ligases MDM2 and TRIM28.

The tumor suppressor p53 is critical for the maintenance of genome stability and protection against tumor malignant transformation, and its homeostasis is usually regulated by ubiquitination. MDM2 is a major E3 ligase of p53 ubiquitination, and its activity is enhanced by TRIM28. TRIM28 also independently ubiquitinates p53 as an E3 ligase activated by MAGE-C2.

The novel interaction mode among centromere sub-complex CENP-O/P/U/Q/R.

The kinetochore is essential for the accurate segregation of sister chromosome in the eukaryote cell. Among the kinetochore subunits, five proteins CENP-O/P/U/Q/R form a stable complex, referred to as CENP-O class, and are required for proper kinetochore function. Although the function and structure of yeast COMA complex (CENP-O/P/U/Q homologs) have been revealed extensively, the assembly mechanism and detail interactions among human CENP-O class are significantly different and remain largely unclear.

An electrogenerated chemiluminescence aptasensor for lysozyme based on the interaction between Ru(bpy) and cucurbit[8]uril.

Strong anodic Ru(bpy) electrogenerated chemiluminescence (ECL) was obtained at a cucurbil[8]uril (CB[8]) modified electrode in neutral conditions without the need of an additional coreactant. An ECL aptasensor was fabricated based on the strong ECL emission as well as the host-guest interaction between DNA and CB[8]. Firstly, amino group-terminated complementary DNA (DNA-NH ) was firmly immobilized on CB[8]/glass carbon electrode, which could further increase ECL intensity.

Multisite phosphorylation determines the formation of Ska-Ndc80 macro-complexes that are essential for chromosome segregation during mitosis.

The human Ska complex (Ska) localizing to both spindle microtubules and kinetochores is essential for proper chromosome segregation during mitosis. Although several mechanisms have been proposed to explain how Ska is recruited to kinetochores, it is still not fully understood. By analyzing Ska3 phosphorylation, we identified six critical Cdk1 sites, including the previously identified Thr358 and Thr360.

Structural insights into the intramolecular interactions of centromere protein CENP-I.

In mitosis, the accurate segregation of sister chromosomes relies on kinetochore, a multiple subunits complex assembled on centromere of each sister chromosome. As a core component of inner kinetochore, CENP-I plays important functions to mediate kinetochore assembly and supports the faithful chromosome segregation. The structures of the N-terminus and C-terminus of CENP-I homologs in complex with CENP-H/K have been reported, respectively.

The Tumor Suppressor Interferon Regulatory Factor 2 Binding Protein 2 Regulates Hippo Pathway in Liver Cancer by a Feedback Loop in Mice.

Background And Aims: The conserved Hippo pathway regulates organ size, tissue homeostasis, and tumorigenesis. Interferon regulatory factor 2 binding protein 2 (IRF2BP2) was originally identified as a transcriptional corepressor. However, the association between IRF2BP2 and the Hippo pathway remains largely unknown.

Structural analysis of fungal CENP-H/I/K homologs reveals a conserved assembly mechanism underlying proper chromosome alignment.

The kinetochore is a proteinaceous complex that is essential for proper chromosome segregation. As a core member of the inner kinetochore, defects of each subunit in the CENP-H/I/K complex cause dysfunction of kinetochore that leads to chromosome mis-segregation and cell death. However, how the CENP-H/I/K complex assembles and promotes kinetochore function are poorly understood.

Research progresses on the molecular structure of the Hippo signaling pathway components.

The Hippo signaling pathway has been identified to be involved in development and tissue homeostasis during the past decade, and is evolutionarily conserved from Drosophila to mammals. It transduces the signal through a series of protein-protein interaction and kinase cascades, to control the cell number and organ size by inhibiting cell proliferation and promoting apoptosis. Dysregulation of the Hippo signaling pathway is associated with tumorigenesis and cancers, so it is a crucial target for cancer therapy and regeneration medicine.