SENP3 Promotes an Mff-Primed Bcl-x L -Drp1 Interaction Involved in Cell Death Following Ischemia

Dysregulation of the mitochondrial fission machinery has been linked to cell death following ischemia. Fission is largely dependent on recruitment of Dynamin-related protein 1 (Drp1) to the receptor Mitochondrial fission factor (Mff) located on the mitochondrial outer membrane (MOM). Drp1 is a target for SUMOylation and its deSUMOylation, mediated by the SUMO protease SENP3, enhances the Drp1-Mff interaction to promote cell death in an oxygen/glucose deprivation (OGD) model of ischemia. Another interacting partner for Drp1 is the Bcl-2 family member Bcl-x(L), an important protein in cell death and survival pathways. Here we demonstrate that preventing Drp1 SUMOylation by mutating its SUMO target lysines enhances the Drp1-Bcl-x(L) interaction in vivo and in vitro. Moreover, SENP3-mediated deSUMOylation of Drp1 promotes the Drp1-Bcl-x(L) interaction. Our data suggest that Mff primes Drp1 binding to Bcl-x(L) at the mitochondria and that Mff and Bcl-x(L) can interact directly, independent of Drp1, through their transmembrane domains. Importantly, SENP3 loss in cells subjected to OGD correlates with reduced Drp1-Bcl-x(L) interaction, whilst recovery of SENP3 levels in cells subjected to reoxygenation following OGD correlates with increased Drp1-Bcl-x(L) interaction. Expressing a Bcl-x(L) mutant with defective Drp1 binding reduces OGD plus reoxygenation-evoked cell death. Taken together, our results indicate that SENP3-mediated deSUMOlyation promotes an Mff-primed Drp1-Bcl-x(L) interaction that contributes to cell death following ischemia

Plasmid construction for development of recombinant tools that replace human liver in drug metabolism studies

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

A spatiotemporal framework for the joint risk assessments of urban flood and urban heat island

Urban Flood (UF) and Urban Heat Island (UHI) become prevalent “urban diseases” currently. Previous studies usually regarded UF and UHI as separate issues that requires respective concentration; however, UF and UHI are inextricably connected so that they should be considered together. Hence, this paper proposes a spatiotemporal framework to link UF and UHI by developing an Urban Flood Heat Island (UFHI) index, taking the Greater Bay Area (GBA) in China as the study case. Random Forest (RF) classifier and Urban-Rural Dichotomy were selected to compute the spatiotemporal distribution of UF susceptibility (UFS) and UHI intensity (UHII), respectively. Theil-Sen Median Slope, Mann-Kendall Test, and Hurst analysis were used to explore the spatiotemporal variation pattern of the UF-UHI joint risk. Spatial Durbin Model was used to compute the correlation between UFS and UHII. RF regressor was employed to quantify the contribution of the common driving factors. We found: (1) UFS and UHII are spatiotemporally correlated, thus UHII can be used as a control variable for the refined UFS assessments, (2) the areas with the UF-UHI joint risk of persistently significant increase (∼7.9 %) majorly distributed in the central region, (3) according to the contributions of factors, UF and UHI in the GBA could be effectively alleviated by breaking the continuous impervious surfaces by introducing blue-green structures. This study offers a new perspective for the effective alleviation of UF and UHI, which would be helpful for the sustainable development of cities in developing countries where human and material sources are limited

Research on the Principle of Residual Current Protection Technology Based on Transient Waveform Criterion

The paper uses a magnetic modulation current transformer method to detect transient waveform residual currents containing pulsating DC components and even smooth DC components. At the same time, it uses IIR-based digital low-pass filters to filter the collected signals, which improves Filtering accuracy. The software design is based on the floating-point DSP-TMS320F28335, which realizes the accurate sampling and analysis of the transient waveform residual current, and the transient waveform residual current detection meets the standard requirements

Efficient Whole-Cell Biotransformation for α‑Arbutin Production through the Engineering of Sucrose Phosphorylase Combined with Engineered Cell Modification

α-Arbutin is extensively used in cosmetic industries. The lack of highly active enzymes and the cytotoxicity of hydroquinone limit the biosynthesis of α-arbutin. In this study, a whole-cell biocatalytic approach based on enzyme engineering and engineered cell modification was identified as effective in enhancing α-arbutin production. First, a sucrose phosphorylase (SPase) mutant with higher enzyme activity was obtained by experimental screening. Next, to avoid the oxidation of hydroquinone, we established an anaerobic process to improve the robustness of the cells by knocking out lytC, sdpC, and skfA in Bacillus subtilis and overcoming the inhibitory effect of a high concentration of hydroquinone. Finally, the engineered strain was used for biotransformation in a 5 L fermenter with batch feeding for 24 h. The final yield of α-arbutin achieved was 129.6 g/L, which may provide a basis for the large-scale industrial production of α-arbutin

The Society for Translational Medicine: Clinical practice guidelines for the postoperative management of chest tube for patients undergoing lobectomy

The Society for Translational Medicine and The Chinese Society for Thoracic and Cardiovascular Surgery conducted a systematic review of the literature in an attempt to improve our understanding in the postoperative management of chest tubes of patients undergoing pulmonary lobectomy. Recommendations were produced and classified based on an internationally accepted GRADE system. The following recommendations were extracted in the present review: (I) chest tubes can be removed safely with daily pleural fluid of up to 450 mL (non-chylous and non-sanguinous), which may reduce chest tube duration and hospital length of stay (2B); (II) in rare instances, e.g., persistent abundant fluid production, the use of PrRP/B< 0.5 when evaluating fluid output to determine chest tube removal might be beneficial (2B); (III) it is recommended that one chest tube is adequate following pulmonary lobectomy, except for hemorrhage and space problems (2A); (IV) chest tube clearance by milking and stripping is not recommended after lung resection (2B); (V) chest tube suction is not necessary for patients undergoing lobectomy after first postoperative day (2A); (VI) regulated chest tube suction [-11 (-1.08 kPa) to -20 (1.96 kPa) cmH2O depending upon the type of lobectomy] is not superior to regulated seal [-2 (0.196 kPa) cmH2O] when electronic drainage systems are used after lobectomy by thoracotomy (2B); (VII) chest tube removal recommended at the end of expiration and may be slightly superior to removal at the end of inspiration (2A); (VIII) electronic drainage systems are recommended in the management of chest tube in patients undergoing lobectomy (2B)