Beta-amyloid pore linked to controlled calcium influx into the cell: A new paradigm for Alzheimer’s Disease

Author: Pannuzzo, Martina Description: Despite tremendous worldwide efforts, clinical trials assessing Alzheimer’s disease (AD)-related therapeutics have been relentlessly unsuccessful. Hence, there is an urgent need to challenge old hypotheses with novel paradigms. An emerging concept is that the amyloid-beta (AB) peptide, which was until recently deemed a major player in the cause of AD, may instead modulate synaptic plasticity and protect against excitotoxicity. The link between AB-mediated synaptic plasticity and AB trafficking is central for understanding AD pathogenesis and remains a perplexing relationship. The crossover between AB pathological and physiological…

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Energy metabolism in brown adipose tissue

Author: Wang, Zhichao; Wang, Qiong A.; Liu, Yong; Jiang, Lei Description: Brown adipose tissue (BAT) is well known to burn calories through uncoupled respiration, producing heat to maintain body temperature. This ‘calorie wasting’ feature makes BAT a special tissue, which can function as an ‘energy sink’ in mammals. While a combination of high energy intake and low energy expenditure is the leading cause of overweight and obesity in modern society, activating a safe ‘energy sink’ has been proposed as a promising obesity treatment strategy. Metabolically, lipids and glucose have been…

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Brown adipose tissue is associated with cardiometabolic health

Author: Becher, Tobias; Palanisamy, Srikanth; Kramer, Daniel J.; Eljalby, Mahmoud; Marx, Sarah J.; Wibmer, Andreas G.; Butler, Scott D.; Jiang, Caroline S.; Vaughan, Roger; Schoder, Heiko; Mark, Allyn; Cohen, Paul Description: White fat stores excess energy, whereas brown and beige fat are thermogenic and dissipate energy as heat. Thermogenic adipose tissues markedly improve glucose and lipid homeostasis in mouse models, although the extent to which brown adipose tissue (BAT) influences metabolic and cardiovascular disease in humans is unclear1,2. Here we retrospectively categorized 134,529 18F-fluorodeoxyglucose positron emission tomography-computed tomography scans from…

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Microbiota depletion promotes browning of white adipose tissue and reduces obesity

Author: Suarez-Zamorano, Nicolas; Fabbiano, Salvatore; Chevalier, Claire; Stojanovic, Ozren; Colin, Didier J.; Stevanovic, Ana; Veyrat-Durebex, Christelle; Tarallo, Valentina; Rigo, Dorothee; Germain, Stephane; Ilievska, Miroslava; Montet, Xavier; Seimbille, Yann; Hapfelmeier, Siegfried; Trajkovski, Mirko Description: Brown adipose tissue (BAT) promotes a lean and healthy phenotype and improves insulin sensitivity. In response to cold or exercise, brown fat cells also emerge in the white adipose tissue (WAT; also known as beige cells), a process known as browning. Here we show that the development of functional beige fat in the inguinal subcutaneous adipose tissue…

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Adipose tissue browning and metabolic health

Author: Bartelt, Alexander; Heeren, Joerg Description: Accumulation of excess white adipose tissue (WAT) has deleterious consequences for metabolic health. The activation of brown adipose tissue (BAT), the primary organ for heat production, confers beneficial effects on adiposity, insulin resistance and hyperlipidaemia, at least in mice. As the amount of metabolically active BAT seems to be particularly low in patients with obesity or diabetes mellitus who require immediate therapy, new avenues are needed to increase the capacity for adaptive thermogenesis. In this light, we review the findings that BAT in human…

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The endocrine role of brown adipose tissue: An update on actors and actions

Author: Gavalda-Navarro, Aleix; Villarroya, Joan; Cereijo, Ruben; Giralt, Marta; Villarroya, Francesc Description: In recent years, brown adipose tissue (BAT) has been recognized not only as a main site of non-shivering thermogenesis in mammals, but also as an endocrine organ. BAT secretes a myriad of regulatory factors. These so-called batokines exert local autocrine and paracrine effects, as well as endocrine actions targeting tissues and organs at a distance. The endocrine batokines include peptide factors, such as fibroblast growth factor-21 (FGF21), neuregulin-4 (NRG4), phospholipid transfer protein (PLTP), interleukin-6, adiponectin and myostatin, and…

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Greater Temperature and Precipitation Extremes Intensify Western U.S. Droughts, Wildfire Severity, and Sierra Nevada Tree Mortality

Author: Crockett, Joseph L.; Westerling, A. Leroy Description: Extensive drought in the western United States (WUS) during the twenty-first century and associated wildfire and tree mortality incidence has highlighted the potential for greater area of severity within widespread droughts. To place recent WUS droughts into a historical context, the authors analyzed gridded daily climate (temperature, precipitation, and climatic water deficit) data to identify and characterize the spatiotemporal evolution of the largest WUS droughts of the last 100 years, with an emphasis on severe cores within drought extents. Cores of droughts…

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Increasing precipitation volatility in twenty-first-century California

Author: Swain, Daniel L.; Langenbrunner, Baird; Neelin, J. David; Hall, Alex Description: Mediterranean climate regimes are particularly susceptible to rapid shifts between drought and flood–of which, California’s rapid transition from record multi-year dryness between 2012 and 2016 to extreme wetness during the 2016-2017 winter provides a dramatic example. Projected future changes in such dry-to-wet events, however, remain inadequately quantified, which we investigate here using the Community Earth System Model Large Ensemble of climate model simulations. Anthropogenic forcing is found to yield large twenty-first-century increases in the frequency of wet extremes,…

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Physical Understanding of Human-Induced Changes in U.S. Hot Droughts Using Equilibrium Climate Simulations

Author: Cheng, Linyin; Hoerling, Martin; Liu, Zhiyong; Eischeid, Jon Description: Although the link between droughts and heat waves is widely recognized, how climate change affects this link remains uncertain. Here we assess how, and by how much, human-induced climate change affects summertime hot drought compound events over the contiguous United States. Results are derived by comparing hot drought statistics in long simulations of a coupled climate model (CESM1) subjected to year-1850 and year-2000 radiative forcings. Within each climate state, a strong and nonlinear dependency of heat-wave intensity on drought severity…

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Precipitation variability increases in a warmer climate

Author: Pendergrass, Angeline G.; Knutti, Reto; Lehner, Flavio; Deser, Clara; Sanderson, Benjamin M. Description: Understanding changes in precipitation variability is essential for a complete explanation of the hydrologic cycle’s response to warming and its impacts. While changes in mean and extreme precipitation have been studied intensively, precipitation variability has received less attention, despite its theoretical and practical importance. Here, we show that precipitation variability in most climate models increases over a majority of global land area in response to warming (66% of land has a robust increase in variability of…

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