Preclinical Modeling of Metabolic Syndrome to Study the Pleiotropic Effects of Novel Antidiabetic Therapy Independent of Obesity

Background and Purpose: Cardiovascular-kidney-metabolic health reflects the interactions between metabolic risk factors, chronic kidney disease, and the cardiovascular system. A growing body of literature suggests that metabolic syndrome (MetS) in individuals of normal weight is associated with a high prevalence of cardiovascular diseases and an increased mortality. The aim of this study was to establish a non-invasive preclinical model of MetS in support of future research focusing on the effects of novel antidiabetic therapies beyond glucose reduction, independent of obesity. Experimental Approach: Eighteen healthy adult Beagle dogs were fed an isocaloric Western diet (WD) for ten weeks. Biospecimens were collected at baseline (BAS1) and after ten weeks of WD feeding (BAS2) for measurement of blood pressure (BP), serum chemistry, lipoprotein profiling, blood glucose, glucagon, insulin secretion, NT-proBNP, angiotensins, oxidative stress biomarkers, serum, urine, and fecal metabolomics. Differences between BAS1and BAS2 were analyzed using non-parametric Wilcoxon signed-rank testing. Key Results: The isocaloric WD model induced significant variations in several markers of MetS, including elevated BP, increased glucose concentrations, and reduced HDL-cholesterol. It also caused an increase in circulating NT-proBNP levels, a decrease in serum bicarbonate, and significant changes in general metabolism, lipids, and biogenic amines. Conclusions and Implications: Short-term, isocaloric feeding with a WD in dogs replicated key biological features of MetS while also causing low-grade metabolic acidosis and elevating natriuretic peptides. These findings support the use of the WD canine model for studying the metabolic effects of new antidiabetic therapies independent of obesity.This is a preprint from Mochel, Jonathan P., Jessica L. Ward, Thomas Blondel, Debosmita Kundu, Maria M. Merodio, Claudine Zemirline, Emilie Guillot et al. "Preclinical Modeling of Metabolic Syndrome to Study the Pleiotropic Effects of Novel Antidiabetic Therapy Independent of Obesity." (2024). doi: https://doi.org/10.21203/rs.3.rs-4235628/v1. Copyright 2024, The Authors. This work is licensed under a Creative Commons Attribution 4.0 International License

Communicating Information on Eruptions and Their Impacts from the Earliest Times Until the Late Twentieth Century

Volcanoes hold a fascination for human beings and, before they were recorded by literate observers, eruptions were portrayed in art, were recalled in legends and became incorporated into religious practices: being viewed as agents of punishment, bounty or intimidation depending upon their state of activity and the culture involved. In the Middle East the earliest depiction of an eruption is a wall painting dating from the Neolithic at Çatal Hüyük and the earliest record dates from the third millennium BCE. Knowledge of volcanoes increased over time. In some parts of the world knowledge of eruptions was passed down by oral transmission, but as far as written records were concerned, in the first century CE only 9 volcanoes in the Mediterranean region were recognised, together with Mount Cameroon in West Africa. In the next 1000 years the list grew by 17, some 14 of these volcanoes being in Japan. The first recorded eruptions in Indonesia occurred in 1000 and 1006, and volcanoes in newly settled Iceland increased the number to just 48 in 1380 CE. After this the list continued to increase, with important regions such as New Zealand and Hawaii only being added in the past 200 years. Only from 1900 did the rate of growth decline significantly (Simkin et al. 1981: 23; Simkin, 1993 Siebert et al. 2011; Simkin, 1993), but it is sobering to recall that in the twentieth century major eruptions have occurred from volcanoes that were considered inactive or extinct examples including: Mount Lamington - Papua New Guinea, 1951; Mount Arenal - Costa Rica, 1968 and Nyos - Cameroon, 1986. Although there are instances where the human impact of historical eruptions have been compiled - with examples including the 1883 eruption of Krakatau (Simkin and Fiske (1983) and 1943 -1952 eruption of Parícutin (Luhr and Simkin, 1993) - these are exceptions and there remains a significant gap in knowledge about both the short and long-term effects on societies of major eruptions which occurred before the 1980s. Following a broad review the chapter provides a discussion of the ways in which information has been collected, compiled and disseminated from the earliest times until the 1980s in two case study areas: the Azores Islands (Portugal) and southern Italy. In Italy information on eruptions stretches back to prehistoric times and has become progressively better known over more than 2,000 years of written history, yet even here there remain significant gaps in the record even for events that took place between 1900 and 1990. In contrast, located in the middle of the Atlantic, the Azores have been isolated for much of their history and illustrate the difficulties involved in using indigenous sources to compile, not only assessments of impact, but also at a more basic level a complete list of historical events with accurate dates

Settling-driven gravitational instabilities associated with volcanic clouds: new insights from experimental investigations

Downward propagating instabilities are often observed at the bottom of volcanic plumes and clouds. These instabilities generate fingers that enhance the sedimentation of fine ash. Despite their potential influence on tephra dispersal and deposition, their dynamics is not entirely understood, undermining the accuracy of volcanic ash transport and dispersal models. Here, we present new laboratory experiments that investigate the effects of particle size, composition and concentration on finger generation and dynamics. The experimental set-up consists of a Plexiglas tank equipped with a removable plastic sheet that separates two different layers. The lower layer is a solution of water and sugar, initially denser than the upper layer, which consists of water and particles. Particles in the experiments include glass beads as well as andesitic, rhyolitic and basaltic volcanic ash. During the experiments, we removed the horizontal plastic sheet separating the two fluids. Particles were illuminated with a laser and filmed with a HD camera; particle image velocimetry (PIV) is used to analyse finger dynamics. Results show that both the number and the downward advance speed of fingers increase with particle concentration in the upper layer, while finger speed increases with particle size but is independent of particle composition. An increase in particle concentration and turbulence is estimated to take place inside the fingers, which could promote aggregation in subaerial fallout events. Finally, finger number, finger speed and particle concentration were observed to decrease with time after the formation of fingers. A similar pattern could occur in volcanic clouds when the mass supply from the eruptive vent is reduced. Observed evolution of the experiments through time also indicates that there must be a threshold of fine ash concentration and mass eruption rate below which fingers do not form; this is also confirmed by field observations.Published395V. Dinamica dei processi eruttivi e post-eruttiviJCR Journa

Earthquakes, Volcanoes and God: Comparative Perspectives from Christianity and Islam

This paper asserts that both Christian and Islamic traditions of faith affect the ways in which people both try to make sense of, and respond to, disasters. This contention is supported by the results of empirical research, which demonstrates that differing Islamic and Christian perspectives on human suffering caused by disasters are neither as diverse, nor are they so intractable, as is commonly supposed. Today pastoral convergence between the two traditions may also be discerned, together with a general acceptance of the policies of both State agencies and Non-Governmental Organisations (NGOs) which are concerned with hazard relief and the propagation of policies of disaster risk reduction (DRR). Indeed some important disaster relief NGOs have emerged from Islamic and Christian faith communities and are supported by charitable donations

Evaluating explosive eruption risk at European volcanoes

No AbstractPublishedV-IX4.3. TTC - Scenari di pericolosità vulcanicaJCR Journalreserve

Evaluating explosive eruption risk at European volcanoes

No Abstrac

Revisiting Kelly Forks (10CW34):current and future research at a Western Stemmed Tradition occupation in the Nez Perce-Clearwater National Forest, Idaho, USA

The Kelly Forks Work Center Site (10CW34) is a deeply buried and stratified late Pleistocene to late Holocene aged archaeological site located on the North Fork Clearwater River in the Nez Perce-Clearwater National Forest, Idaho. Previous research suggested the site contained buried archaeological components associated with the Western Stemmed Tradition. Here, we report preliminary results of ongoing reinvestigation of the site to assess the stratigraphy, geochronology, archaeology, and traditional Nez Perce use of the Clearwater River drainage