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Journal of Clinical Investigation
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Lung-resident eosinophils have a homeostatic function in allergic disease

Eosinophil production is increased in allergic diseases, and the inflammatory, Th2-associated actions of these immune cells can cause pathogenic tissue damage. However, increasing evidence suggests that eosinophils may also play a non-inflammatory role in regulating homeostatic immune functions. Claire Mesnil, Stéfanie Raulier, and colleagues characterized a subset of lung-resident eosinophils that display a regulatory profile and can inhibit the pro-allergic function of allergen-loaded dendritic cells. Mice deficient for lung-resident eosinophils exhibited increased Th2 immunity in response to low doses of inhaled allergens, demonstrating a role for this subtype in the regulation of lung immune homeostasis. In the accompanying commentary, Marc Rothenberg discusses how the identification of this lung-resident population adds to our understanding of eosinophils as an immunoregulatory population.

RESEARCH ARTICLE: http://buff.ly/2bgIvZp
COMMENTARY: http://buff.ly/2bgHVee #allergy #immunology
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JCI INSIGHT: An imaging method to quantify dermal fat

Mammals contain two main varieties of fat: white adipose tissue (WAT), which is used to store energy, and brown adipose tissue (BAT), which is involved in the regulation of body temperature, particularly in infants. Dermal WAT (dWAT) is the layer of WAT is immediately adjacent to the dermis and is known to accumulate in response to ambient cold, hair growth, and exposure to bacteria in mice, but little is known about this tissue in humans. In this issue of JCI Insight, Caroline Alexander and her colleagues at the University of Wisconsin, Madison, report the development of a non-invasive MRI-based method to measure dWAT, total WAT volume, and BAT activation in mice and humans. Using this method, Alexander and colleagues demonstrated that dWAT, as well as visceral WAT and BAT, increase in genetically obese mice and mice fed a high-fat diet over several weeks. The accompanying image shows dWAT (top row) and visceral WAT (bottom row) accumulation in mice during a 5 week period of high-fat diet. Alexander and colleagues used their imaging technique on 10 healthy human subjects and determined that dWAT thickness was highly variable between subjects and weighed 8.8 kg on average. These studies demonstrate that this MRI-based method can be used to study multiple adipose depots, including dWAT, in both mice and humans.

RESEARCH ARTICLE: http://buff.ly/2b2IOTU #metabolism #obesity #UWMadison
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Ghrelin-cell β1-adrenergic receptors regulate ghrelin secretion to prevent hypoglycemia

The peptide hormone ghrelin is known to stimulate appetite and increase preference for calorie-dense foods. Ghrelin also increases blood glucose through multiple mechanisms, including modulation of insulin and glucagon secretion. Bharath Mani and coworkers at UT Southwestern Medical Center observed that activation of β1-adrenergic receptors (β1ARs) on ghrelin-producing cells drives ghrelin secretion during caloric restriction. Ghrelin cell-specific β1AR-deficient mice exhibited impairments in ghrelin secretion and exaggerated hypoglycemia upon caloric restriction, which was reversed by ghrelin administration. Inhibition of β1AR activity with beta blockers similarly reduced ghrelin secretion and increased the incidence of hypoglycemia in caloric-restricted adolescent wild-type mice. These findings highlight a critical role for β1AR signaling in ghrelin secretion and its requirement in the maintenance of blood glucose levels, indicating a potential therapeutic use for ghrelin replacement in treating beta blocker-induced hypoglycemia.

RESEARCH ARTICLE: http://buff.ly/2b2psVc #metabolism #endocrinology #UTSW
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A new batch of articles is now available online at
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Urea impairs insulin-producing cells in chronic kidney disease

Chronic kidney disease is characterized by a progressive inability to eliminate toxins from the bloodstream, which causes levels of urea and other toxic metabolites to increase. Although patients with chronic kidney disease often suffer from poor blood sugar regulation, the link between elevations in metabolite levels and glucose metabolism is not clear. In this issue of the <i>JCI</i>, researchers at the University of Montreal demonstrated that high levels of urea may compromise the function of insulin-producing pancreas cells and lead to impaired blood sugar regulation in chronic kidney disease. A team led by Vincent Poitout observed that insulin secretion was impaired in a mouse model of chronic kidney disease. Increasing urea levels in healthy mice led to similar reductions in insulin secretion as well as poor regulation of blood glucose levels. These findings point to a mechanism for blood sugar complications in chronic kidney disease that could potentially be targeted by preventative therapies.

RESEARCH ARTICLE: http://buff.ly/2aMTKVJ #kidneydisease #UMontreal
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A new batch of articles is now available online at
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AUTHOR’S TAKE: Vascular stiffness drives metabolic alterations in pulmonary hypertension

Pulmonary hypertension (PH) refers to a collection of vascular diseases that are characterized by increased arterial pressure in the lung, which can subsequently lead to heart failure and possibly death. It is not clear how PH develops or how early events in the disease correlate with later phenotypes. In this episode, Stephen Chan discusses work from his laboratory that links increased vascular stiffness to altered glutamine metabolism in the pathogenesis of PH. The results of this study provide important insight into the development of PH and identify metabolic pathways that have potential as therapeutic targets for PH.

VIDEO: http://buff.ly/2bMGGCB
ARTICLE: http://buff.ly/2bMG3cr
#pulmonology #hypertension
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Is vascular stiffness the same and arterial stiffness?
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Protein diluted diet improves glucose homeostasis through liver signaling pathways

Although high protein diets have been linked to an increased incidence of type 2 diabetes, it is not known whether decreasing protein intake is an effective strategy for lowering the risk of developing obesity-related metabolic disorders. Adriano Maida and coworkers demonstrated that very low protein diets can increase metabolic health by improving glucose homeostasis in mice and humans. In nutritional and genetic murine models of obesity, a protein-diluted diet prevented impairments in glucose homeostasis and promoted metabolic inefficiency by inducing the liver integrated stress response-driven nuclear protein 1 (NUPR1) and liver-derived fibroblast growth factor 21 (FGF21). These data indicate that stress response pathways in the liver may mediate the protective effects of low protein diets on obesity-related metabolic diseases.

RESEARCH ARTICLE: http://buff.ly/2b4smpq #metabolism #diabetes
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Angiopoietin and Tie signaling control blood vessel homeostasis

Blood vessel remodeling is a central feature of developmental angiogenesis and plays key roles in inflammation and tumor growth. These changes in blood vessels depend on complex signaling through angiopoietins (ANG) and Tie receptors. Emilia Korhonen, Anita Lampinen, and colleagues determined that Tie1 acts as an intermediate in determining the effects of ANG1 and ANG2 on Tie2 signaling. Tie1 deficiency impaired the agonist action of ANG2 on Tie2 under normal conditions, leading to decreased Tie2 phosphorylation that resembled its response to inflammatory states. Cleavage of Tie1’s ectodomain during inflammation was associated with the switch of ANG2 from Tie2 agonist to antagonist. In the accompanying commentary, Sarah Mueller and Christopher Kontos discuss context-dependent ANG2/Tie1 interactions in blood vessel remodeling.

RESEARCH ARTICLE: http://buff.ly/2b4Zx9C
COMMENTARY: http://buff.ly/2b4ZESB #inflammation #angiogenesis
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Angiopoietin and Tie signaling drive vascular remodeling in inflammation

ANG1 and ANG2 promote interactions between Tie1 and Tie2 that regulate changes in blood vessel structure, but the pathways that govern vessel stability or remodeling during inflammation are not well understood. Minah Kim and coworkers at UCSF investigated the mechanisms enabling ANG2 to activate or inhibit Tie2. In normal conditions, ANG2 activated Tie2 to promote stable enlargement of blood vessels. However, in an infection-induced inflammatory state, ANG2 acted as an antagonist that drove vascular remodeling. ANG2’s switch from Tie2 agonist to antagonist depended on cleavage of Tie1’s ectodomain during inflammation. In the accompanying commentary, Sarah Mueller and Christopher Kontos discuss ANG2/Tie1 interactions as an important control point in blood vessel remodeling under inflammatory conditions.

RESEARCH ARTICLE: http://buff.ly/2b4qUnn
COMMENTARY: http://buff.ly/2b4pYPN #inflammation #angiogenesis #UCSF
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JCI INSIGHT: Cell therapy promotes axon remyelination in a mouse model

Demyelinating diseases, such as multiple sclerosis and leukodystrophy, are characterized by damage to the protective myelin sheath that surrounds the axons of neurons. This demyelination can be caused by an autoimmune response or impaired myelin production by oligodendrocytes. A new report in JCI Insight from Arjun Saha and colleagues at Duke University demonstrates that a cell therapy product called DUOC-01 can accelerate remyelination of axons in mice treated with a demyelinating chemical agent. DUOC-01 cells, which are derived from banked umbilical cord blood, were transplanted into mice following toxic demyelination. DUOC-01 treatment resulted in faster remyelination (see the accompanying image) and promoted the differentiation of oligodendrocyte progenitor cells. These results suggest that a cord blood-derived cell product can promote neuronal repair and remyelination. Future clinical studies will be needed to determine if DUOC-01 cell therapy benefits patients with demyelinating diseases.

RESEARCH ARTICLE: http://buff.ly/2b2HWPl #multiplesclerosis #neuroscience #Duke
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Calpain-6 mediates atherogenic macrophage function

Atherosclerosis is a hardening of the arterial wall as the result of cholesterol accumulation. Macrophages deposit LDL-derived cholesterols via pinocytotis; therefore, preventing macrophage-mediated lipid deposition has potential to limit disease progression. In this episode, Takuro Miyazaki and colleagues reveal that elevation of calpain-6 in macrophages promotes atherogenic functions by disrupting CWC22/EJC/Rac1 signaling. Moreover, loss of calpain-6 in murine models was atheroprotective, suggesting that targeting this pathway has therapeutic potential for atherosclerosis.

AUTHOR’S TAKE: http://buff.ly/2bng8KL
RESEARCH ARTICLE: http://buff.ly/2bnfNI2 #cardiology #heartdisease
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In their circles
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Have them in circles
103 people
Xuanyang Li's profile photo
World Health Day, 7 April's profile photo
Jose Maria Franco Canton's profile photo
ibtisam ismail's profile photo
ICBio Clinical Research's profile photo
charles stevenson's profile photo
DEMOSTHENES BOUROS's profile photo
Parag Jhaveri's profile photo
biente dos's profile photo
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Premiere venue for discoveries in basic and clinical biomedical science.
Introduction
The Journal of Clinical Investigation (JCI) is a top-tier venue for discoveries in basic and clinical biomedical research that will advance the practice of medicine. Founded in 1924, the journal is published by the American Society for Clinical Investigation (ASCI) and has a 2015 Impact Factor of 12.575. Since 2012, the JCI has been headed by Dr. Howard A. Rockman, Editor, with an Editorial Board of peer scientists at Duke University Medical Center, the University of North Carolina, Duke-NUS, and the Sanford-Burnham Medical Research Institute. The JCI provides free access to all of its research articles.