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Kilgore Hsu posted an update a month ago
e., no evidence of winner’s curse). Meta-regressions indicated consistent effects for neuroticism, openness, and conscientiousness across methods to assess dementia, dementia type, follow-up length, sample age, minority, country, and personality measures. The association of extraversion and agreeableness varied by country. Our findings indicate robust associations of neuroticism and conscientiousness with dementia risk.CsaA is known to function as a protein secretion chaperone in bacteria. Homologs of CsaA are also found in archaea while they are absent in eukaryotes. This paper presents the biophysical, biochemical analysis and crystallographic structure determination of CsaA from a thermoacidophilic archaeon Picrophilus torridus (PtCsaA). The PtCsaA appears to prevent the aggregation of heat denatured Bovine Carbonic Anhydrase II (BCAII). Differential denaturation of PtCsaA by guanidine hydrochloride (Gdn-HCl) and urea indicates the stabilization of the protein via salt bridges. Denaturant mediated decrease in 8-Anilinonaphthalene-1-sulfonic acid (ANS) binding and shift in wavelength signifies the partial unfolding of the protein molecule and exposure of hydrophobic patches to solvent on denaturation. The crystal structure of PtCsaA was solved to a resolution of 1.7 Å. The structure of PtCsaA appears to be similar to bacterial CsaA in architecture. Docking of a six amino acid peptide in the substrate binding pocket of PtCsaA suggests conservation in the substrate binding cavity. Residues involved in the formation of the binding cavity and hydrogen bonds responsible for the dimerization of PtCsaA were compared with those observed in the structure of Bacillus subtilis CsaA. The similarities and differences in electrostatic surface potential of the substrate binding cavities in bacterial CsaA and PtCsaA are discussed.The aggregation of proteins is of importance in fields ranging from protein homeostasis to disease. The light-sensing protein Vivid (VVD) regulates responses to blue-light illumination in the filamentous fungus Neurospora crassa. Consisting of a single light‑oxygen-voltage domain, VVD is characterized by cycling between dark and lit states that correspond to formation and disruption of a photoadduct between the flavin cofactor and the apoprotein. Recently, in vitro assays have shown that VVD undergoes self-oxidative damage and aggregation resulting from excessive blue-light illumination. To explore the aggregation process of VVD, here we study the kinetics of aggregation and how it is influenced by environmental factors such as initial protein concentration, temperature, and light. We found that the aggregation kinetics of VVD is consistent with a second-order reaction model involving kinetic control, where thermal decay from lit-VVD to dark-VVD is necessary for aggregation to proceed. The height of the energy barrier separating the lit and dark VVD states is measured as (80 ± 2) kJ mol-1. Application of the kinetic model to the observed dependence of aggregation vs. temperature allowed us to further estimate the energy involved in the nucleation of dark-VVD, (257 ± 24) kJ mol-1. Finally, we show that VVD aggregation levels increase as the time of blue light exposure is augmented, suggesting possible mechanisms for protein damage. These results demonstrate how aggregation of a photoreceptor depends not only on environmental factors but on the intrinsic response of the protein to illumination.The protozoan Trypanosoma cruzi is the causative agent of the neglected infectious illness Chagas disease. During its life cycle it differentiates into replicative and non-replicative life stages. Selleck EHT 1864 So far, T. cruzi cell division has been investigated by transcriptomics but not by proteomics approaches. Here we show the first quantitative proteome analysis of T. cruzi cell division. T. cruzi epimastigote cultures were subject to synchronization with hydroxyurea and harvested at different time points. Analysis by flow cytometry, bright field and fluorescence microscopy indicated that samples collected at 0 h, 2 h, 6 h and 14 h overrepresented G1, G1-S, S and M cell cycle phases, respectively. After trypsin digestion of these samples, the resulting peptides were labelled with iTRAQ and subjected to LC-MS/MS. Also, iTRAQ-labelled phosphopeptides were enriched with TiO2 to access the phosphoproteome. Overall, 597 protein groups and 94 phosphopeptides presented regulation with the most remarkable variation in abundance at 6 h (S-phase). Comparison of our proteomic data to previous transcriptome-wise analysis of epimastigote cell cycle showed 16 sequence entries in common, with the highest mRNA/protein correlation observed in transcripts with peak abundance in G1-phase. Our data revealed regulated proteins and phosphopeptides which play important roles in the control of cell division in other organisms and some of them were previously detected in the nucleus or associated with T. cruzi chromatin.Protein-protein interactions (PPIs) describe the direct physical contact of two proteins that usually results in specific biological functions or regulatory processes. The characterization and study of PPIs through the investigation of their pattern and principle have remained a question in biological studies. Various experimental and computational methods have been used for PPI studies, but most of them are based on the sequence similarity with current validated PPI participators or cellular localization patterns. Most methods ignore the fact that PPIs are defined by their specific biological functions. In this study, we constructed a novel rule-based computational method using gene ontology and KEGG pathway annotation of PPI participators that correspond to the complicated biological effects of PPIs. Our newly presented computational method identified a group of biological functions that are tightly associated with PPIs and provided a new function-based tool for PPI studies in a rule manner.
This study compared the structural and vascular intraretinal changes between epiretinal membrane and myopic traction maculopathy eyes.
An observational retrospective study of treatment-naïve epiretinal membrane and myopic traction maculopathy eyes was conducted to identify biomarkers of a 3 × 3 mm macular region centered on the fovea, using optical coherence tomography angiography.
The myopic traction maculopathy and epiretinal membrane groups comprised 27 and 32 eyes, respectively. In the myopic traction maculopathy group, the spherical equivalent was more myopic and the axial length was longer than in the epiretinal membrane group. Myopic traction maculopathy eyes had larger outer and smaller inner retinal volumes, larger area and perimeter of foveal avascular zones, greater circularity of foveal avascular zones, and smaller foveal vessel density in the superficial layer than epiretinal membrane eyes. Internal limiting membrane incompliance and staphyloma were significantly more in the myopic traction maculopathy group than in the epiretinal membrane group.