Nesprin-1 LINC complexes recruit microtubule cytoskeleton proteins and drive pathology in Lmna-mutant striated muscle.

Mutations in LMNA, the gene encoding A-type lamins, cause laminopathies-diseases of striated muscle and other tissues. The aetiology of laminopathies has been attributed to perturbation of chromatin organization or structural weakening of the nuclear envelope (NE) such that the nucleus becomes more prone to mechanical damage. The latter model requires a conduit for force transmission to the nucleus. NE-associated Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes are one such pathway. Using clustered regularly interspaced short palindromic repeats to disrupt the Nesprin-1 KASH (Klarsicht, ANC-1, Syne Homology) domain, we identified this LINC complex protein as the predominant NE anchor for microtubule cytoskeleton components, including nucleation activities and motor complexes, in mouse cardiomyocytes. Loss of Nesprin-1 LINC complexes resulted in loss of microtubule cytoskeleton proteins at the nucleus and changes in nuclear morphology and positioning in striated muscle cells, but with no overt physiological defects. Disrupting the KASH domain of Nesprin-1 suppresses Lmna-linked cardiac pathology, likely by reducing microtubule cytoskeleton activities at the nucleus. Nesprin-1 LINC complexes thus represent a potential therapeutic target for striated muscle laminopathies.

Carbon monoxide poisoning: a prediction model using meteorological factors and air pollutant.

BACKGROUND: While the influence of meteorology on carbon monoxide (CO) poisoning has been reported, few data are available on the association between air pollutants and the prediction of CO poisoning. Our objective is to explore meteorological and pollutant patterns associated with CO poisoning and to establish a predictive model. RESULTS: CO poisoning was found to be significantly associated with meteorological and pollutant patterns: low temperatures, low wind speeds, low air concentrations of sulfur dioxide (SO2) and ozone (O38h), and high daily temperature changes and ambient CO (r absolute value range: 0.079 to 0.232, all P values < 0.01). Based on the above factors, a predictive model was established: "logitPj = aj - 0.193 * temperature - 0.228 * wind speed + 0.221 * 24 h temperature change + 1.25 * CO - 0.0176 * SO2 + 0.0008 *O38h; j = 1, 2, 3, 4; a1 = -4.12, a2 = -2.93, a3 = -1.98, a4 = -0.92." The proposed prediction model based on combined factors showed better predictive capacity than a model using only meteorological factors as a predictor. CONCLUSION: Low temperatures, wind speed, and SO2 and high daily temperature changes, O38h, and CO are related to CO poisoning. Using both meteorological and pollutant factors as predictors could help facilitate the prevention of CO poisoning.

Chest Radiographs and CTs in the Era of COVID-19: Indications, Operational Safety Considerations and Alternative Imaging Practices.

Coronavirus disease-19 (COVID-19) is a pathogen that has shown an ability for sustained community transmission. To ensure utmost safety, radiology services will need to adapt to this disease in the coming months and possibly years ahead. This will include learning how to perform radiographs and CT in a safe and sustainable manner. Due to the risk of nosocomial spread of disease, the judicious use and implementation of strict infection protocols is paramount to limit healthcare worker and patient transmission. Between 28 January 2020 and 8 June 2020, our institution performed 12,034 radiographs and 178 CT scans for suspected or confirmed COVID-19 patients. As of 8 June 2020, there have been no documented instances of healthcare staff acquiring COVID-19 during the course of work. In this article, we present the indications and operational considerations used by our institution to safely image patients with suspected or confirmed COVID-19. Alternative practices for imaging radiographs are also discussed.

Effects of Bi-NTO complex on thermal behaviors, nonisothermal reaction kinetics and burning rates of NG/TEGDN/NC propellant.

A bismuth 3-nitro-1,2,4-triazol-5-one (Bi-NTO) complex was prepared and characterized, and its effects on the thermal behaviors, non-isothermal decomposition reaction kinetics, and burning rates of the double-base (DB) propellant containing the mixed ester of triethyleneglycol dinitrate (TEGDN) and nitroglycerin (NG) with Bi-NTO complex as a ballistic modifier were investigated by thermogravimetry and derivative thermogravimetry (TG-DTG), and differential scanning calorimetry (DSC). The results show that Bi-NTO complex can increase the decomposition heat by 140 J g(-1), and it can change the decomposition reaction mechanism function, the kinetic parameters and kinetic equation of the propellant under 0.1 MPa. Combustion experiment shows that Bi-NTO complex can increase the burning rate and reduce the pressure exponent of the NG/TEGDN/NC propellant effectively, with the increase of the catalysis efficiency by 40%.