Mueller Matrix Fluorescence Spectroscopy for Probing Self-Assembled Peptide-Based Hybrid Supramolecular Structure and Orientation

Probing the assembly mechanism, orientation, shape, and structure function relationship of hybrid supramolecular materials is an outstanding challenge. In this regard, we have presented a novel method based on fluorescence spectroscopic Mueller matrix measurements and inverse analysis which can probe and quantify exclusive information on the molecular organization and orientation via a set of newly defined fluorescence anisotropy parameters, namely, fluorescence diattenuation and polarizance. A new dipeptide motif Boc-Xaa-Met-OMe (Xaa = Val/Leu) containing leucine, valine, and methionine forms a kink like structure and self-associates to form a twisted sheet like structure by multiple intermolecular N–H···O hydrogen bonds and finally grown to form supramolecular nanotubes having a diameter ca. 10 Å. Thus, the methionine sulfurs of peptide molecules are arranged helically along the tubes, work as a hot spot, and help to stabilize the electron deficient paint TB-NDI around the tube. The fluorescence Mueller matrix polarimetry and inverse analysis offers insight on the molecular organization and orientation of the achiral fluorescent dye molecules around the supramolecular nanotube from the chiral dipeptide. This method is promising for characterization of complex hybrid materials

FLJ25439, a novel cytokinesis-associated protein, induces tetraploidization and maintains chromosomal stability via enhancing expression of endoplasmic reticulum stress chaperones

<p>Investigation of the mechanisms leading to aneuploidy and polyploidy is critical to cancer research. Previous studies have provided strong evidence of the importance of tetraploidization as an early step in tumorigenesis. In cancer cells, tetraploid cells may contribute to abnormal mitotic progression, which may be associated with cytokinesis failure. Tetraploidy leads to genomic instability due to centrosome and chromosome over-replication. Until now, the mechanism by which cells maintain tetraploid status has been unknown. Here, we identified a novel D box-containing protein, FLJ25439, which displays a dynamic expression profile during mitosis/cytokinesis with the midbody as the most prominent associated structure. To understand the function of FLJ25439, we established stable cell lines overexpressing FLJ25439. FLJ25439-overexpression cells grew slower and displayed a tetraploid DNA content in comparison with diploid parental cells. They also showed aberrant mitosis and dysregulated expression of p53, pRb and p21, suggesting a defect in cell cycle progression. To explore the molecular mechanisms responsible for FLJ25439-induced tetraploidization, we conducted a comparative analysis of the global protein expression patterns of wild type and overexpressors using proteomics and bioinformatics approaches. Protein category profiling indicated that FLJ25439 is involved in pathways related to anti-apoptosis, protein folding, the cell cycle, and cytoskeleton regulation. Specifically, genotoxic-stress- and ER stress-related chaperone proteins greatly contributed to the FLJ25439 overexpression phenotypes. The results of this study pave the way to our further understanding of the role of this novel cytokinesis-related protein in protecting cells from environmental stress and tetraploid formation.</p

Table1_Early outcomes of moderate-to-high-risk pediatric congenital cardiac surgery and predictors of extracorporeal circulatory life support requirement.docx

BackgroundCardiopulmonary failure refractory to medical management after moderate-to-high-risk congenital cardiac surgery may necessitate mechanical support with veno-arterial extracorporeal membrane oxygenation (ECMO). On the extreme, ECMO can also be initiated in the setting of cardiac arrest (extracorporeal cardiopulmonary resuscitation, ECPR) unresponsive to conventional resuscitative measures.MethodsThis was a single-center retrospective cohort study of patients (n = 510) aged ResultsA total of 510 patients with a mean surgical age of 10.0 ± 13.4 months were included. Among them, 21 (4%) patients received postoperative ECMO—12 were initiated in the OR and 9 in the ICU. ECMO cannulation was associated with cardiopulmonary bypass duration, aortopulmonary shunt, residual severe mitral regurgitation, vaso-inotropic score, and postprocedural lactate (p DiscussionAlthough uncommon, postoperative ECMO in children after congenital cardiac surgery is associated with high mortality, especially in cases of ECPR. Patients with long cardiopulmonary bypass time, residual cardiac lesions, or increased vaso-inotropic requirement are at higher risk of receiving ECMO. Pre-emptive or early ECMO initiation before deterioration into cardiac arrest may improve survival.</p