Finite mixture models are being used increasingly to model a wide variety of random phenomena for clustering, classification and density estimation.
is a powerful and popular package which allows ...modelling of data as a Gaussian finite mixture with different covariance structures and different numbers of mixture components, for a variety of purposes of analysis. Recently, version 5 of the package has been made available on CRAN. This updated version adds new covariance structures, dimension reduction capabilities for visualisation, model selection criteria, initialisation strategies for the EM algorithm, and bootstrap-based inference, making it a full-featured R package for data analysis via finite mixture modelling.
Breakthroughs in the longevity field over the past few decades have led to major shifts in how we attack the problem of aging. What have been the most important of these shifts in our perspectives, ...aims, and approaches that will likely guide future research?
The study reports on a meta-analysis of attempts to correct misinformation (k = 65). Results indicate that corrective messages have a moderate influence on belief in misinformation (r = .35); ...however, it is more difficult to correct for misinformation in the context of politics (r = .15) and marketing (r = .18) than health (r = .27). Correction of real-world misinformation is more challenging (r = .14), as opposed to constructed misinformation (r = .48). Rebuttals (r = .38) are more effective than forewarnings (r = .16), and appeals to coherence (r = .55) outperform fact-checking (r = .25), and appeals to credibility (r = .14).
Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass associated with significant functional impairment. In addition to a loss of skeletal muscle ...mass and function, many patients with cancer cachexia also experience cardiac atrophy, remodeling, and dysfunction, which in the field of cancer cachexia is described as cardiac cachexia. The cardiac alterations may be due to underlying heart disease, the cancer itself, or problems initiated by the cancer treatment and, unfortunately, remains largely underappreciated by clinicians and basic scientists. Despite recent major advances in the treatment of cancer, little progress has been made in the treatment of cardiac cachexia in cancer, and much of this is due to lack of information regarding the mechanisms. This review focuses on the cardiac atrophy associated with cancer cachexia, describing some of the known mechanisms and discussing the current and future therapeutic strategies to treat this condition. Above all else, improved awareness of the condition and an increased focus on identification of mechanisms and therapeutic targets will facilitate the eventual development of an effective treatment for cardiac atrophy in cancer cachexia.
Africa's Information Revolution was recently announced as the2016 prizewinner of the Royal Academy for Overseas Sciences - congratulations to the authorsJames T. Murphy and Padraig Carmody! Africa's ...Information Revolution presents an in-depth examination of the development and economic geographies accompanying the rapid diffusion of new ICTs in Sub-Saharan Africa. * Represents the first book-length comparative case study ICT diffusion in Africa of its kind * Confronts current information and communication technologies for development (ICT4D) discourse by providing a counter to largely optimistic mainstream perspectives on Africa's prospects for m- and e-development * Features comparative research based on more than 200 interviews with firms from a manufacturing and service industry in Tanzania and South Africa * Raises key insights regarding the structural challenges facing Africa even in the context of the continent's recent economic growth spurt * Combines perspectives from economic and development geography and science and technology studies to demonstrate the power of integrated conceptual-theoretical frameworks * Include maps, photos, diagrams and tables to highlight the concepts, field research settings, and key findings
The biology and behavior of adults differ substantially from those of developing animals, and cell-specific information is critical for deciphering the biology of multicellular animals. Thus, adult ...tissue-specific transcriptomic data are critical for understanding molecular mechanisms that control their phenotypes. We used adult cell-specific isolation to identify the transcriptomes of C. elegans' four major tissues (or "tissue-ome"), identifying ubiquitously expressed and tissue-specific "enriched" genes. These data newly reveal the hypodermis' metabolic character, suggest potential worm-human tissue orthologies, and identify tissue-specific changes in the Insulin/IGF-1 signaling pathway. Tissue-specific alternative splicing analysis identified a large set of collagen isoforms. Finally, we developed a machine learning-based prediction tool for 76 sub-tissue cell types, which we used to predict cellular expression differences in IIS/FOXO signaling, stage-specific TGF-β activity, and basal vs. memory-induced CREB transcription. Together, these data provide a rich resource for understanding the biology governing multicellular adult animals.
Women's reproductive cessation is the earliest sign of human aging and is caused by decreasing oocyte quality. Similarly, C. elegans' reproduction declines in mid-adulthood and is caused by oocyte ...quality decline. Aberrant mitochondrial morphology is a hallmark of age-related dysfunction, but the role of mitochondrial morphology and dynamics in reproductive aging is unclear. We examined the requirements for mitochondrial fusion and fission in oocytes of both wild-type worms and the long-lived, long-reproducing insulin-like receptor mutant daf-2. We find that normal reproduction requires both fusion and fission, but that daf-2 mutants utilize a shift towards fission, but not fusion, to extend their reproductive span and oocyte health. daf-2 mutant oocytes' mitochondria are punctate (fissioned) and this morphology is primed for mitophagy, as loss of the mitophagy regulator PINK-1 shortens daf-2's reproductive span. daf-2 mutants maintain oocyte mitochondria quality with age at least in part through a shift toward punctate mitochondrial morphology and subsequent mitophagy. Supporting this model, Urolithin A, a metabolite that promotes mitophagy, extends reproductive span in wild-type mothers-even in mid-reproduction-by maintaining youthful oocytes with age. Our data suggest that promotion of mitophagy may be an effective strategy to maintain oocyte health with age.
Interventions that delay ageing mobilize mechanisms that protect and repair cellular components, but it is unknown how these interventions might slow the functional decline of extracellular matrices, ...which are also damaged during ageing. Reduced insulin/IGF-1 signalling (rIIS) extends lifespan across the evolutionary spectrum, and in juvenile Caenorhabditis elegans also allows the transcription factor DAF-16/FOXO to induce development into dauer, a diapause that withstands harsh conditions. It has been suggested that rIIS delays C. elegans ageing through activation of dauer-related processes during adulthood, but some rIIS conditions confer robust lifespan extension unaccompanied by any dauer-like traits. Here we show that rIIS can promote C. elegans longevity through a program that is genetically distinct from the dauer pathway, and requires the Nrf (NF-E2-related factor) orthologue SKN-1 acting in parallel to DAF-16. SKN-1 is inhibited by IIS and has been broadly implicated in longevity, but is rendered dispensable for rIIS lifespan extension by even mild activity of dauer-related processes. When IIS is decreased under conditions that do not induce dauer traits, SKN-1 most prominently increases expression of collagens and other extracellular matrix genes. Diverse genetic, nutritional, and pharmacological pro-longevity interventions delay an age-related decline in collagen expression. These collagens mediate adulthood extracellular matrix remodelling, and are needed for ageing to be delayed by interventions that do not involve dauer traits. By genetically delineating a dauer-independent rIIS ageing pathway, our results show that IIS controls a broad set of protective mechanisms during C. elegans adulthood, and may facilitate elucidation of processes of general importance for longevity. The importance of collagen production in diverse anti-ageing interventions implies that extracellular matrix remodelling is a generally essential signature of longevity assurance, and that agents promoting extracellular matrix youthfulness may have systemic benefit.
Nutrients are necessary for life, as they are a crucial requirement for biological processes including reproduction, somatic growth, and tissue maintenance. Therefore, signaling systems involved in ...detecting and interpreting nutrient or energy levels-most notably, the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway, mechanistic target of rapamycin (mTOR), and adenosine monophosphate-activated protein kinase (AMPK)-play important roles in regulating physiological decisions to reproduce, grow, and age. In this review, we discuss the connections between reproductive senescence and somatic aging and give an overview of the involvement of nutrient-sensing pathways in controlling both reproductive function and lifespan. Although the molecular mechanisms that affect these processes can be influenced by distinct tissue-, temporal-, and pathway-specific signaling events, the progression of reproductive aging and somatic aging is systemically coordinated by integrated nutrient-sensing signaling pathways regulating somatic tissue maintenance in conjunction with reproductive capacity.
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