Egelundkoch5263

Phosphorylation is among the most widely distributed mechanisms regulating the tunable structure and function of proteins in response to neuronal, hormonal and environmental signals. We demonstrate here that the low-voltage electrochemical reduction of histidine residues in reflectin A1, a protein that mediates the neuronal fine-tuning of colour reflected from skin cells for camouflage and communication in squids, acts as an in vitro surrogate for phosphorylation in vivo, driving the assembly previously shown to regulate its function. Using micro-drop voltammetry and a newly designed electrochemical cell integrated with an instrument measuring dynamic light scattering, we demonstrate selective reduction of the imidazolium side chains of histidine in monomers, oligopeptides and this complex protein in solution. The formal reduction potential of imidazolium proves readily distinguishable from those of hydronium and primary amines, allowing unequivocal confirmation of the direct and energetically selective deprotonation of histidine in the protein. The resulting 'electro-assembly' provides a new approach to probe, understand, and control the mechanisms that dynamically tune protein structure and function in normal physiology and disease. With its abilities to serve as a surrogate for phosphorylation and other mechanisms of charge neutralization, and to potentially isolate early intermediates in protein assembly, this method may be useful for analysing never-before-seen early intermediates in the phosphorylation-driven assembly of other proteins in normal physiology and disease.We examined the relationship between white matter hyperintensities (WMH) and cortical neurodegeneration in cerebral small vessel disease (CSVD) by investigating whether cortical thickness is a remote effect of WMH through structural fiber tract connectivity in a population at increased risk of CSVD. We measured cortical thickness on T1-weighted images and segmented WMH on FLAIR images in 930 participants of a population-based cohort study at baseline. DWI-derived whole-brain probabilistic tractography was used to define WMH connectivity to cortical regions. Linear mixed-effects models were applied to analyze the relationship between cortical thickness and connectivity to WMH. Factors associated with cortical thickness (age, sex, hemisphere, region, individual differences in cortical thickness) were added as covariates. Median age was 64 [IQR 46-76] years. Visual inspection of surface maps revealed distinct connectivity patterns of cortical regions to WMH. WMH connectivity to the cortex was associated with reduced cortical thickness (p = 0.009) after controlling for covariates. This association was found for periventricular WMH (p = 0.001) only. Our results indicate an association between WMH and cortical thickness via connecting fiber tracts. The results imply a mechanism of secondary neurodegeneration in cortical regions distant, yet connected to subcortical vascular lesions, which appears to be driven by periventricular WMH.The tree of life shows the relationship between all organisms based on their common ancestry. Until 1977, it comprised two major branches prokaryotes and eukaryotes. Work by Carl Woese and other microbiologists led to the recategorization of prokaryotes and the proposal of three primary domains Eukarya, Bacteria and Archaea. Microbiological, genetic and biochemical techniques were then needed to study the third domain of life. Haloferax volcanii, a halophilic species belonging to the phylum Euryarchaeota, has provided many useful tools to study Archaea, including easy culturing methods, genetic manipulation and phenotypic screening. This review will focus on DNA replication and DNA repair pathways in H. volcanii, how this work has advanced our knowledge of archaeal cellular biology, and how it may deepen our understanding of bacterial and eukaryotic processes.In asthma, progressive structural changes of the airway wall are collectively termed airway remodelling. Despite its deleterious effect on lung function, airway remodelling is incompletely understood. As one of the important causes leading to airway remodelling, here we discuss the significance of mechanical forces that are produced in the narrowed airway during asthma exacerbation, as a driving force of airway remodelling. We cover in vitro, ex vivo and in vivo work in this field, and discuss up-to-date literature supporting the idea that bronchoconstriction may be the missing link in a comprehensive understanding of airway remodelling in asthma.Background The triglyceride glucose (TyG) index has been proposed as a reliable surrogate marker for nonalcoholic fatty liver disease (NAFLD). Furthermore, NAFLD is strongly related with obesity. This study aimed to compare TyG index and its related parameters (TyG-waist circumference [WC] and TyG-body mass index [BMI]), comprising TyG and obesity markers, in predicting NAFLD and liver fibrosis in overweight/obese individuals without diabetes. Methods This was a cross-sectional study consisting of 184 overweight/obese people (96 with and 88 without NAFLD), 30-65 years of age. TyG, TyG-BMI, and TyG-WC were computed using the established formula. Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were determined by transient elastography (FibroScan). Results In correlation analyses, CAP and LSM were significantly associated with WC, BMI, TyG, TyG-BMI, and TyG-WC. Regression analyses highlighted TyG-WC as a significant predictor of NAFLD, with the highest standardized odds ratio (2.25, P  less then  0.001); while liver fibrosis was associated more strongly with TyG-BMI. In receiver operating characteristic (ROC) analysis, TyG-WC showed the largest area under the ROC curve (AUC) for detection of NAFLD (0.693, 95% confidence interval [CI] 0.617-0.769). However, TyG-BMI was a better discriminator of liver fibrosis (AUC 0.635, 95% CI 0.554-0.714). TyG-WC value of 876 (sensitivity 81.3%, specificity 52.3%) and TyG-BMI value of 259 (sensitivity 78.3%, specificity 51.3%) were the optimal cutoff points to predict NAFLD and liver fibrosis, respectively. Navitoclax Conclusions The results highlight the significant associations of TyG and its related indices with NAFLD, with TyG-WC being a better indicator. TyG-BMI and TyG-WC could reliably predict liver fibrosis in this population. These indices appear to be simple, practical, and affordable tools for screening NAFLD and liver fibrosis in clinical settings.