Oncogenic mutant KRAS inhibition through oxidation at cysteine 118.

Specific reactive oxygen species activate the GTPase Kirsten rat sarcoma virus (KRAS) by reacting with cysteine 118 (C118), leading to an electron transfer between C118 and nucleoside guanosine diphosphate (GDP), which causes the release of GDP. Here, we have mimicked permanent oxidation of human KRAS at C118 by replacing C118 with aspartic acid (C118D) in KRAS to show that oncogenic mutant KRAS is selectively inhibited via oxidation at C118, both in vitro and in vivo. Moreover, the combined treatment of hydrogen-peroxide-producing pro-oxidant paraquat and nitric-oxide-producing inhibitor N(ω)-nitro-l-arginine methyl ester selectively inhibits human mutant KRAS activity by inducing oxidization at C118.

Sex Differences in Gut Microbiota and Their Relation to Arterial Stiffness (MIVAS Study).

Background: Recent research highlights the potential role of sex-specific variations in cardiovascular disease. The gut microbiome has been shown to differ between the sexes in patients with cardiovascular risk factors.

Objectives: The main objective of this study is to analyze the differences between women and men in the relationship between gut microbiota and measures of arterial stiffness.

The blood pressure lowering effect of beetroot juice is impaired in periodontitis and recovered after periodontal treatment.

We have previously demonstrated that subgingival levels of nitrate-reducing bacteria, as well as the in vitro salivary nitrate reduction capacity (NRC), were diminished in periodontitis patients, increasing after periodontal treatment. However, it remains unclear if an impaired NRC in periodontitis can affect systemic health. To determine this, the effect of nitrate-rich beetroot juice (BRJ) on blood pressure was determined in 15 periodontitis patients before and 70 days after periodontal treatment (i.

Using High-Speed Videoendoscopy to Analyze Laryngeal Closure Parameters During Normal Swallow.

Objective: This pilot study was designed to test the tolerability of a lower scope position and feasibility of custom-designed MATLAB graphical user interface (GUI) used to analyze playback review of laryngeal high-speed videoendoscopy (laryngeal HSV) during healthy volitional dry swallows. We hypothesized this method would conceptually provide time resolution for glottic closure events compared with standard (30 frames per second, fps), and enable a means to measure timing, sequence, and duration of laryngeal movements during swallowing not otherwise visualized.

Methods: A total of 14 healthy adults (4 male, 22-80 years) participated.

A New Multi-Axial Functional Stress Analysis Assessing the Longevity of a Ti-6Al-4V Dental Implant Abutment Screw.

This study investigates the impact of tightening torque (preload) and the friction coefficient on stress generation and fatigue resistance of a Ti-6Al-4V abutment screw with an internal hexagonal connection under dynamic multi-axial masticatory loads in high-cycle fatigue (HCF) conditions. A three-dimensional model of the implant-abutment assembly was simulated using ANSYS Workbench 16.2 computer aided engineering software with chewing forces ranging from 300 N to 1000 N, evaluated over 1.