• Gardner Conradsen posted an update 6 days, 2 hours ago

    Overall, our work supports the utility to apply personal genomic information for characterizing complex disease phenotypes.Mitochondrial dysfunction and iron (Fe) dyshomeostasis are invoked among the mechanisms contributing to muscle aging, possibly via a detrimental mitochondrial-iron feed-forward loop. We quantified the labile Fe pool, Fe isotopes, and the expression of mitochondrial Fe handling proteins in muscle biopsies obtained from young and older adults. The expression of key proteins of mitochondrial quality control (MQC) and the abundance of the mitochondrial DNA common deletion (mtDNA4977) were also assessed. An inverse association was found between total Fe and the heavier Fe isotope (56Fe), indicating an increase in labile Fe abundance in cells with greater Fe content. The highest levels of labile Fe were detected in old participants with a Short Physical Performance Battery (SPPB) score ≤ 7 (low-functioning, LF). Protein levels of mitoferrin and frataxin were, respectively, higher and lower in the LF group relative to young participants and older adults with SPPB scores ≥ 11 (high-functioning, HF). The mtDNA4977 relative abundance was greater in old than in young participants, regardless of SPPB category. Higher protein levels of Pink1 were detected in LF participants compared with young and HF groups. Finally, the ratio between lipidated and non-lipidated microtubule-associated protein 1A/1B-light chain 3 (i.e., LC3B II/I), as well as p62 protein expression was lower in old participants regardless of SPPB scores. Our findings indicate that cellular and mitochondrial Fe homeostasis is perturbed in the aged muscle (especially in LF older adults), as reflected by altered levels of mitoferrin and frataxin, which, together with MQC derangements, might contribute to loss of mtDNA stability.Synthetic biology is an advanced form of genetic manipulation that applies the principles of modularity and engineering design to reprogram cells by changing their DNA. Over the last decade, synthetic biology has begun to be applied to bacteria that naturally produce biomaterials, in order to boost material production, change material properties and to add new functionalities to the resulting material. Recent work has used synthetic biology to engineer several Komagataeibacter strains; bacteria that naturally secrete large amounts of the versatile and promising material bacterial cellulose (BC). In this review, we summarize how genetic engineering, metabolic engineering and now synthetic biology have been used in Komagataeibacter strains to alter BC, improve its production and begin to add new functionalities into this easy-to-grow material. As well as describing the milestone advances, we also look forward to what will come next from engineering bacterial cellulose by synthetic biology.Age-dependent alterations in the proteostasis network are crucial in the progress of prevalent neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, or amyotrophic lateral sclerosis, which are characterized by the presence of insoluble protein deposits in degenerating neurons. Because molecular chaperones deter misfolded protein aggregation, regulate functional phase separation, and even dissolve noxious aggregates, they are considered major sentinels impeding the molecular processes that lead to cell damage in the course of these diseases. Indeed, members of the chaperome, such as molecular chaperones and co-chaperones, are increasingly recognized as therapeutic targets for the development of treatments against degenerative proteinopathies. Chaperones must recognize diverse toxic clients of different orders (soluble proteins, biomolecular condensates, organized protein aggregates). It is therefore critical to understand the basis of the selective chaperone recognition to discern the mechanisms of action of chaperones in protein conformational diseases. This review aimed to define the selective interplay between chaperones and toxic client proteins and the basis for the protective role of these interactions. The presence and availability of chaperone recognition motifs in soluble proteins and in insoluble aggregates, both functional and pathogenic, are discussed. Finally, the formation of aberrant (pro-toxic) chaperone complexes will also be disclosed.The aim of this study was to conduct a community-based study with a view to construct a detailed analysis about metabolic syndrome and the related risk factors of the indigenous population. This was an observational, population-based and cross-sectional study that was conducted in remote villages of an indigenous community in northern Taiwan between 2010 and 2013. A total of 586 participants, 275 men and 311 women, were eligible for analysis. The participants underwent a questionnaire survey that included demographic and health behavior issues. An anthropometric assessment and measurements of blood pressure were carried out including serum biochemical variables. Forskolin cost Metabolic syndrome (MetS) was defined by following the criteria provided by the modified Adult Treatment Panel III (ATP III) criteria of the National Cholesterol Education Program (NCEP). Univariate and multiple logistic regressions were used to identify the risk factors for metabolic syndrome. The standardized prevalence rates of substance use (cigarette smoking, alcohol drinking and betel nut chewing) were significantly higher than the general population regardless of whether it was northern, central or southern Taiwan and this was especially the case with betel nut chewing in women. The prevalence rate of metabolic syndrome was 42.9% in the indigenous population with 41.3% in men and 44.4% in women, which was higher than for urban Taiwanese. In the multiple logistic regression models, we found that the significant associated factors for metabolic syndrome were older age, lower education level, high levels of uric acid, alanine transaminase (ALT), gamma-glutamyl transferase (γ-GT) and creatinine. A higher prevalence rate of metabolic syndrome and substance use were observed in the indigenous population compared with urban Taiwanese, especially in women.