Prediction of localization and interactions of apoptotic proteins

During apoptosis several mitochondrial proteins are released. Some of them participate in caspase-independent nuclear DNA degradation, especially apoptosis-inducing factor (AIF) and endonuclease G (endoG). Another interesting protein, which was expected to act similarly as AIF due to the high sequence homology with AIF is AIF-homologous mitochondrion-associated inducer of death (AMID). We studied the structure, cellular localization, and interactions of several proteins in silico and also in cells using fluorescent microscopy. We found the AMID protein to be cytoplasmic, most probably incorporated into the cytoplasmic side of the lipid membranes. Bioinformatic predictions were conducted to analyze the interactions of the studied proteins with each other and with other possible partners. We conducted molecular modeling of proteins with unknown 3D structures. These models were then refined by MolProbity server and employed in molecular docking simulations of interactions. Our results show data acquired using a combination of modern in silico methods and image analysis to understand the localization, interactions and functions of proteins AMID, AIF, endonuclease G, and other apoptosis-related proteins

How registry data are used to inform activities for stroke care quality improvement across 55 countries : A cross-sectional survey of Registry of Stroke Care Quality (RES-Q) hospitals

Background and purpose The Registry of Stroke Care Quality (RES-Q) is a worldwide quality improvement data platform that captures performance and quality measures, enabling standardized comparisons of hospital care. The aim of this study was to determine if, and how, RES-Q data are used to influence stroke quality improvement and identify the support and educational needs of clinicians using RES-Q data to improve stroke care. Methods A cross-sectional self-administered online survey was administered (October 2021–February 2022). Participants were RES-Q hospital local coordinators responsible for stroke data collection. Descriptive statistics are presented. Results Surveys were sent to 1463 hospitals in 74 countries; responses were received from 358 hospitals in 55 countries (response rate 25%). RES-Q data were used “always” or “often” to: develop quality improvement initiatives (n = 213, 60%); track stroke care quality over time (n = 207, 58%); improve local practice (n = 191, 53%); and benchmark against evidence-based policies, procedures and/or guidelines to identify practice gaps (n = 179, 50%). Formal training in the use of RES-Q tools and data were the most frequent support needs identified by respondents (n = 165, 46%). Over half “strongly agreed” or “agreed” that to support clinical practice change, education is needed on: (i) using data to identify evidence–practice gaps (n = 259, 72%) and change clinical practice (n = 263, 74%), and (ii) quality improvement science and methods (n = 255, 71%). Conclusion RES-Q data are used for monitoring stroke care performance. However, to facilitate their optimal use, effective quality improvement methods are needed. Educating staff in quality improvement science may develop competency and improve use of data in practice

Stage-specific roles of FGF2 signaling in human neural development

This study elucidated the stage-specific roles of FGF2 signaling during neural development using in-vitro human embryonic stem cell-based developmental modeling. We found that the dysregulation of FGF2 signaling prior to the onset of neural induction resulted in the malformation of neural rosettes (a neural tube-like structure), despite cells having undergone neural induction. The aberrant neural rosette formation may be attributed to the misplacement of ZO-1, which is a polarized tight junction protein and shown co-localized with FGF2/FGFR1 in the apical region of neural rosettes, subsequently led to abnormal neurogenesis. Moreover, the FGF2 signaling inhibition at the stage of neural rosettes caused a reduction in cell proliferation, an increase in numbers of cells with cell-cycle exit, and premature neurogenesis. These effects may be mediated by NUMB, to which expression was observed enriched in the apical region of neural rosettes after FGF2 signaling inhibition coinciding with the disappearance of PAX6+/Ki67+ neural stem cells and the emergence of MAP2+ neurons. Moreover, our results suggested that the hESC-based developmental system reserved a similar neural stem cell niche in vivo