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Language endangerment
Up to ninety percent of humanity's traditional languages and cultures are at risk and may disappear this century. While language endangerment has not achieved the publicity surrounding environmental change and biodiversity loss, it is just as serious, disastrously reducing the variety of human knowledge and thought. This book shows why it matters, why and how it happens, and what communities and scholars can do about it. David and Maya Bradley provide a new framework for investigating and documenting linguistic, social and other factors which contribute to languages shifting away from their cultural heritage. Illustrated with practical in-depth case studies and examples from the authors' own work in Asia and elsewhere, the book encourages communities to maintain or reclaim their traditional languages and cultures.
Book
Evolution of protein kinase substrate recognition at the active site
Protein kinases catalyse the phosphorylation of target proteins, controlling most cellular processes. The specificity of serine/threonine kinases is partly determined by interactions with a few residues near the phospho-acceptor residue, forming the so-called kinase-substrate motif. Kinases have been extensively duplicated throughout evolution, but little is known about when in time new target motifs have arisen. Here, we show that sequence variation occurring early in the evolution of kinases is dominated by changes in specificity-determining residues. We then analysed kinase specificity models, based on known target sites, observing that specificity has remained mostly unchanged for recent kinase duplications. Finally, analysis of phosphorylation data from a taxonomically broad set of 48 eukaryotic species indicates that most phosphorylation motifs are broadly distributed in eukaryotes but are not present in prokaryotes. Overall, our results suggest that the set of eukaryotes kinase motifs present today was acquired around the time of the eukaryotic last common ancestor and that early expansions of the protein kinase fold rapidly explored the space of possible target motifs.
Journal Article
Clusterin as a Potential Biomarker of Obesity-Related Alzheimer’s Disease Risk
Over 35% of the adult US population is obese. In turn, excess adiposity increases the risk of multiple complications including type 2 diabetes (T2D), insulin resistance, and cardiovascular disease; yet, obesity also independently heightens risk of Alzheimer’s Disease (AD), even after adjusting for other important confounding risk factors including blood pressure, sociodemographics, cholesterol levels, smoking status, and Apolipoprotein E (ApoE) genotype. Among patients over the age of 65 with dementia, 37% have coexisting diabetes, and an estimated 7.3% of cases of AD are directly attributable to midlife obesity. Clusterin, also known as apolipoprotein J (ApoJ), is a multifunctional glycoprotein that acts as a molecular chaperone, assisting folding of secreted proteins. Clusterin has been implicated in several physiological and pathological states, including AD, metabolic disease, and cardiovascular disease. Despite long-standing interest in elucidating clusterin’s relationship with amyloid beta (Aβ) aggregation/clearance and toxicity, significant knowledge gaps still exist. Altered clusterin expression and protein levels have been linked with cognitive and memory function, disrupted central nervous system lipid flux, as well as pathogenic brain structure; and its role in cardiometabolic disease suggests that it may be a link between insulin resistance, dyslipidemia, and AD. Here, we briefly highlight clusterin’s relevance to AD by presenting existing evidence linking clusterin to AD and cardiometabolic disease, and discussing its potential utility as a biomarker for AD in the presence of obesity-related metabolic disease.
Journal Article
Ancient Connections of Sinitic
Six main alternative linkage proposals which involve the Sino-Tibetan family, including Sinitic and other language families of the East Asian area (Miao-Yao, Altaic/Transeurasian, Austroasiatic, Tai-Kadai, Austronesian) are briefly outlined. Using the standard techniques of comparative linguistics, a remote linkage between the Sino-Tibetan languages, including Sinitic, the Yeniseian languages of Siberia, and the Na-Dene languages of northwest North America is demonstrated. This includes cognate core lexicon showing regular sound correspondences, morphological similarities of form and function, as well as similarities in social structure. The other proposals for linkages that connect Sinitic and other languages of the East Asian area appear not to be based on a genetic linguistic relationship but rather due to contact: millennia of loanwords from Sinitic into the languages of those families and some lexicon borrowed into Sinitic. More remains to be done to further document the status of the linkage between Sino-Tibetan and Dene-Yeniseian.
Journal Article
Clusterin and Its Role in Insulin Resistance and the Cardiometabolic Syndrome
The cardiometabolic syndrome involves a clustering of metabolic and cardiovascular factors which increase the risk of patients developing both Type 2 Diabetes Mellitus and cardio/cerebrovascular disease. Although the mechanistic underpinnings of this link remain uncertain, key factors include insulin resistance, excess visceral adiposity, atherogenic dyslipidemia, and endothelial dysfunction. Of these, a state of resistance to insulin action in overweight/obese patients appears to be central to the pathophysiologic process. Given the increasing prevalence of obesity-related Type 2 Diabetes, coupled with the fact that cardiovascular disease is the number one cause of mortality in this patient population, a more thorough understanding of the cardiometabolic syndrome and potential options to mitigate its risk is imperative. Inherent in the pathogenesis of insulin resistance is an underlying state of chronic inflammation, at least partly in response to excess adiposity. Within obese adipose tissue, an immunomodulatory shift occurs, involving a preponderance of pro-inflammatory immune cells and cytokines/adipokines, along with antigen presentation by adipocytes. Therefore, various adipokines differentially expressed by obese adipocytes may have a significant effect on cardiometabolism. Clusterin is a molecular chaperone that is widely produced by many tissues throughout the body, but is also preferentially overexpressed by obese compared lean adipocytes and relates strongly to multiple components of the cardiometabolic syndrome. Herein, we summarize the known and potential roles of circulating and adipocyte-specific clusterin in cardiometabolism and discuss potential further investigations to determine if clusterin is a viable target to attenuate both metabolic and cardiovascular disease.
Journal Article
Gender based lung cancer risks for symptomatic coronary artery disease patients undergone cardiac CT
We estimate the lifetime attributable risk (LAR) of lung cancer incidence in symptomatic Coronary Artery Disease (CAD) patients receiving enhanced Coronary Computed Tomography Angiography (CCTA) and the unenhanced Computed Tomography Calcium Scoring (CTCS) examination. Retrospective analysis has been made of CCTA and CTCS data collected for 87 confirmed CAD adult patients. Patient effective dose (E) and organ doses (ODs) were calculated using CT-EXPO. Statistical correlation and the differences between E and ODs in enhanced CCTA and unenhanced CTCS were calculated using the Pearson coefficient and Wilcoxon unpaired t-test. Following BEIR VII report guidance, organ-specific LARs for the cohort were estimated using the organ-equivalent dose-to-risk conversion factor for numbers of cases per 100,000 patients exposed to low doses of 0.1 Gy. Significant statistical difference (p<0.0001) is found between E obtained for CTCS and that of CCTA. The scan length was found to be greater in CCTA (17.5 ± 2.9 cm) compared to that for CTCS (15 ± 2 cm). More elevated values of dose were noted for the esophagus (4.2 ± 2.15 mSv) and thymus (9.6 ± 2.54 mSv) for both CTCS and CCTA. CTCS organ doses were lower than that of CCTA. Per 100,000 patients, female cumulative doses are seen to give rise to greater lung cancer LARs compared to that for males, albeit with risk varying significantly, noticeably greater for females, younger patients and combined CCTA and CTCS scans. While scan parameters and tube-modulation methods clearly contribute to patient dose, mAs offers by far the greater contribution.
Journal Article