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https://www.readbyqxmd.com/read/28335584/atrap-expression-in-brown-adipose-tissue-does-not-influence-the-development-of-diet-induced-metabolic-disorders-in-mice
#1
Kohji Ohki, Hiromichi Wakui, Kengo Azushima, Kazushi Uneda, Sona Haku, Ryu Kobayashi, Kotaro Haruhara, Sho Kinguchi, Miyuki Matsuda, Masato Ohsawa, Akinobu Maeda, Shintaro Minegishi, Tomoaki Ishigami, Yoshiyuki Toya, Akio Yamashita, Satoshi Umemura, Kouichi Tamura
Activation of tissue renin-angiotensin system (RAS), mainly mediated by an angiotensin II (Ang II) type 1 receptor (AT1R), plays an important role in the development of obesity-related metabolic disorders. We have shown that AT1R-associated protein (ATRAP), a specific binding protein of AT1R, functions as an endogenous inhibitor to prevent excessive activation of tissue RAS. In the present study, we newly generated ATRAP/Agtrap-floxed (ATRAP(fl/fl)) mice and adipose tissue-specific ATRAP downregulated (ATRAP(adipoq)) mice by the Cre/loxP system using Adipoq-Cre...
March 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28333962/different-regulation-of-limb-development-by-p63-transcript-variants
#2
Manabu Kawata, Yuki Taniguchi, Daisuke Mori, Fumiko Yano, Shinsuke Ohba, Ung-Il Chung, Tomomi Shimogori, Alea A Mills, Sakae Tanaka, Taku Saito
The apical ectodermal ridge (AER), located at the distal end of each limb bud, is a key signaling center which controls outgrowth and patterning of the proximal-distal axis of the limb through secretion of various molecules. Fibroblast growth factors (FGFs), particularly Fgf8 and Fgf4, are representative molecules produced by AER cells, and essential to maintain the AER and cell proliferation in the underlying mesenchyme, meanwhile Jag2-Notch pathway negatively regulates the AER and limb development. p63, a transcription factor of the p53 family, is expressed in the AER and indispensable for limb formation...
2017: PloS One
https://www.readbyqxmd.com/read/28324645/three-dimensional-analysis-of-somatic-mitochondrial-dynamics-in-fission-deficient-injured-motor-neurons-using-fib-sem
#3
Hiromi Tamada, Sumiko Kiryu-Seo, Hiroki Hosokawa, Keisuke Ohta, Naotada Ishihara, Masatoshi Nomura, Katsuyoshi Mihara, Kei-Ichiro Nakamura, Hiroshi Kiyama
Mitochondria undergo morphological changes through fusion and fission for their quality control, which are vital for neuronal function. In this study, we examined three-dimensional morphologies of mitochondria in motor neurons under normal, nerve injured, and nerve injured plus fission-impaired conditions using the focused ion beam/scanning electron microscopy (FIB/SEM), because the FIB/SEM technology is a powerful tool to demonstrate both 3D images of whole organelle and the intra-organellar structure simultaneously...
March 21, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28324064/bmp7-induces-uterine-receptivity-and-blastocyst-attachment
#4
Diana Monsivais, Caterina Clementi, Jia Peng, Paul T Fullerton, Renata Prunskaite-Hyyryläinen, Seppo Vainio, Martin M Matzuk
In women, the window of implantation is limited to a brief two- to three- day period characterized by optimal levels of circulating ovarian hormones and a receptive endometrium. Although the window of implantation is assumed to occur 8-10 days after ovulation in women, molecular markers of endometrial receptivity are necessary to determine optimal timing prior to embryo transfer. Previous studies showed that members of the bone morphogenetic protein (BMP) family are expressed in the uterus necessary for female fertility; however, the role of BMP7 during implantation and in late gestation is not known...
January 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28319140/role-of-muscle-il-6-in-gender-specific-metabolism-in-mice
#5
Amalia Molinero, Antonio Fernandez-Perez, Aina Mogas, Mercedes Giralt, Gemma Comes, Olaya Fernandez-Gayol, Mario Vallejo, Juan Hidalgo
The aim of the present work was to further explore the physiological roles of muscle-derived IL-6. Adult-floxed and conditional skeletal muscle IL-6 knock out male and female mice were used to study energy expenditure (indirect calorimetry at rest and during treadmill exercise, and body temperature cycle during the light phase) and energy intake (response to fast/refeeding). We also evaluated the responses to leptin and the activity of the insulin signalling pathway in skeletal muscle and liver by phosphorylation of Akt at Ser 473...
2017: PloS One
https://www.readbyqxmd.com/read/28314814/respiration-deficient-astrocytes-survive-as-glycolytic-cells-in-vivo
#6
Lotti M Supplie, Tim Düking, Graham Campbell, Francisca Diaz, Carlos T Moraes, Magdalena Götz, Bernd Hamprecht, Susann Boretius, Don Mahad, Klaus-Armin Nave
Neurons and glial cells exchange energy-rich metabolites and it has been suggested, originally based on in vitro data, that astrocytes provide lactate to glutamatergic synapses ("lactate shuttle"). Here, we have studied astrocytes that lack mitochondrial respiration in vitro and in vivo A novel mouse mutant (GLAST(CreERT2):Cox10(flox/flox) ) was generated, in which the administration of tamoxifen causes mutant astrocytes to fail in the assembly of mitochondrial cytochrome c oxidase (COX). Focussing on cerebellar Bergmann glial cells that exhibit the highest rate of Cre-mediated recombination, we find a normal density of viable astrocytes even one year after tamoxifen-induced Cox10 gene targeting...
March 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28298457/distinct-regulatory-effects-of-myeloid-cell-and-endothelial-cell-nox2-on-blood-pressure
#7
Can Martin Sag, Moritz Schnelle, Juqian Zhang, Colin E Murdoch, Sabine Kossmann, Andrea Protti, Celio X C Santos, Greta J Sawyer, Xiaohong Zhang, Heloise Mongue-Din, Daniel A Richards, Alison C Brewer, Oleksandra Prysyazhna, Lars S Maier, Philip Wenzel, Philip J Eaton, Ajay M Shah
Background -Hypertension due to increased renin angiotensin system (RAS) activation is associated with elevated reactive oxygen species (ROS) production. Previous studies implicate NADPH oxidase (Nox) proteins as important ROS sources during RAS activation, with different Nox isoforms being potentially involved. Among these, Nox2 is expressed in multiple cell types including endothelial cells, fibroblasts, immune cells and microglia. Blood pressure (BP) is regulated at central nervous system, renal and vascular levels but the cell-specific role of Nox2 in BP regulation is unknown...
March 15, 2017: Circulation
https://www.readbyqxmd.com/read/28293237/dc-derived-il-10-modulates-pro-inflammatory-cytokine-production-and-promotes-induction-of-cd4-il-10-regulatory-t-cells-during-plasmodium-yoelii-infection
#8
Katharina Loevenich, Kristina Ueffing, Simone Abel, Matthias Hose, Kai Matuschewski, Astrid M Westendorf, Jan Buer, Wiebke Hansen
The cytokine IL-10 plays a crucial role during malaria infection by counteracting the pro-inflammatory immune response. We and others demonstrated that Plasmodium yoelii infection results in enhanced IL-10 production in CD4(+) T cells accompanied by the induction of an immunosuppressive phenotype. However, it is unclear whether this is a direct effect caused by the parasite or an indirect consequence due to T cell activation by IL-10-producing antigen-presenting cells. Here, we demonstrate that CD11c(+)CD11b(+)CD8(-) dendritic cells (DCs) produce elevated levels of IL-10 after P...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28291223/liver-specific-deletion-of-the-plpp3-gene-alters-plasma-lipid-composition-and-worsens-atherosclerosis-in-apoe-mice
#9
Marco Busnelli, Stefano Manzini, Mika Hilvo, Cinzia Parolini, Giulia S Ganzetti, Federica Dellera, Kim Ekroos, Minna Jänis, Diana Escalante-Alcalde, Cesare R Sirtori, Reijo Laaksonen, Giulia Chiesa
The PLPP3 gene encodes for a ubiquitous enzyme that dephosphorylates several lipid substrates. Genome-wide association studies identified PLPP3 as a gene that plays a role in coronary artery disease susceptibility. The aim of the study was to investigate the effect of Plpp3 deletion on atherosclerosis development in mice. Because the constitutive deletion of Plpp3 in mice is lethal, conditional Plpp3 hepatocyte-specific null mice were generated by crossing floxed Plpp3 mice with animals expressing Cre recombinase under control of the albumin promoter...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28289711/the-volume-regulated-anion-channel-lrrc8-in-nodose-neurons-is-sensitive-to-acidic-ph
#10
Runping Wang, Yongjun Lu, Susheel Gunasekar, Yanhui Zhang, Christopher J Benson, Mark W Chapleau, Rajan Sah, François M Abboud
The leucine rich repeat containing protein 8A (LRRC8A), or SWELL1, is an essential component of the volume-regulated anion channel (VRAC) that is activated by cell swelling and ionic strength. We report here for the first time to our knowledge its expression in a primary cell culture of nodose ganglia neurons and its localization in the soma, neurites, and neuronal membrane. We show that this neuronal VRAC/SWELL1 senses low external pH (pHo) in addition to hypoosmolarity. A robust sustained chloride current is seen in 77% of isolated nodose neurons following brief exposures to extracellular acid pH...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28288121/a-genetic-system-to-study-plasmodium-falciparum-protein-function
#11
Jakob Birnbaum, Sven Flemming, Nick Reichard, Alexandra Blancke Soares, Paolo Mesén-Ramírez, Ernst Jonscher, Bärbel Bergmann, Tobias Spielmann
Current systems to study essential genes in the human malaria parasite Plasmodium falciparum are often inefficient and time intensive, and they depend on the genetic modification of the target locus, a process hindered by the low frequency of integration of episomal DNA into the genome. Here, we introduce a method, termed selection-linked integration (SLI), to rapidly select for genomic integration. SLI allowed us to functionally analyze targets at the gene and protein levels, thus permitting mislocalization of native proteins, a strategy known as knock sideways, floxing to induce diCre-based excision of genes and knocking in altered gene copies...
March 13, 2017: Nature Methods
https://www.readbyqxmd.com/read/28275690/intestinal-epithelial-specific-mtorc1-activation-enhances-intestinal-adaptation-after-small-bowel-resection
#12
Lauren Barron, Raphael C Sun, Bola Aladegbami, Christopher R Erwin, Brad W Warner, Jun Guo
BACKGROUND & AIMS: Intestinal adaptation is a compensatory response to the massive loss of small intestine after surgical resection. We investigated the role of intestinal epithelial cell-specific mammalian target of rapamycin complex 1 (i-mTORC1) in intestinal adaptation after massive small bowel resection (SBR). METHODS: We performed 50% proximal SBR on mice to study adaptation. To manipulate i-mTORC1 activity, Villin-Cre(ER) transgenic mice were crossed with tuberous sclerosis complex (TSC)1(flox/flox) or Raptor(flox/flox) mice to inducibly activate or inactivate i-mTORC1 activity with tamoxifen...
March 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28275162/leptin-signalling-in-agrp-neurons-modulates-puberty-onset-and-adult-fertility-in-mice
#13
Olivia K Egan, Megan A Inglis, Greg M Anderson
The hormone leptin indirectly communicates metabolic information to brain neurons that control reproduction, using GABAergic circuitry. Agouti-related peptide (AgRP) neurons in the arcuate nucleus are GABAergic, express leptin receptors (LepR) and are known to influence reproduction. This study tested whether leptin actions on AgRP neurons are required and sufficient for puberty onset and subsequent fertility. Firstly, Agrp-Cre and Lepr-flox mice were used to target deletion of LepR to AgRP neurons. AgRP-LepR knockout female mice exhibited mild obesity and adiposity as previously described, as well as a significant delay in the pubertal onset of estrous cycles compared to control animals...
March 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28271037/cholinergic-neurons-in-the-dorsomedial-hypothalamus-regulate-food-intake
#14
Jae Hoon Jeong, Dong Kun Lee, Young-Hwan Jo
OBJECTIVE: Central cholinergic neural circuits play a role in the regulation of feeding behavior. The dorsomedial hypothalamus (DMH) is considered the appetite-stimulating center and contains cholinergic neurons. Here, we study the role of DMH cholinergic neurons in the control of food intake. METHODS: To selectively stimulate DMH cholinergic neurons, we expressed stimulatory designer receptors exclusively activated by designer drugs (DREADDs) and channelrhodopsins in DMH cholinergic neurons by injection of adeno-associated virus (AAV) vectors into the DMH of choline acetyltransferase (ChAT)-IRES-Cre mice...
March 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28247981/hydrogen-treated-rutile-tio2-shell-in-graphite-core-structure-as-a-negative-electrode-for-high-performance-vanadium-flow-batteries
#15
Javier Vázquez Galván, Cristina Flox, Cristian Fabregas, Edgar Ventosa, Andres Parra, Teresa Andreu, Juan Ramon Morante
Hydrogen treated TiO2 as electrocatalyst has been demonstrated for high performance all-vanadium redox flow batteries (VRFB) as a simple and eco-friendly strategy, boosting the obtainable battery's capacity. GF@TiO2:H electrode performs an abrupt inhibition of the hydrogen-evolution reaction (HER), which is a critical barrier for operating at high rate for long-term cycling in VRFB. Significant improvements in charge-discharge and electron transfer processes towards V3+/V2+ reaction is achieved on the surface of reduced TiO2, as a consequence of the formation of oxygen-vacancies in the lattice structure and oxygen-functional groups...
March 1, 2017: ChemSusChem
https://www.readbyqxmd.com/read/28231307/differential-regulation-of-c5a-receptor-1-in-innate-immune-cells-during-the-allergic-asthma-effector-phase
#16
Fanny Ender, Anna V Wiese, Inken Schmudde, Jing Sun, Tillman Vollbrandt, Peter König, Yves Laumonnier, Jörg Köhl
C5a drives airway constriction and inflammation during the effector phase of allergic asthma, mainly through the activation of C5a receptor 1 (C5aR1). Yet, C5aR1 expression on myeloid and lymphoid cells during the allergic effector phase is ill-defined. Recently, we generated and characterized a floxed green fluorescent protein (GFP)-C5aR1 knock-in mouse. Here, we used this reporter strain to monitor C5aR1 expression in airway, pulmonary and lymph node cells during the effector phase of OVA-driven allergic asthma...
2017: PloS One
https://www.readbyqxmd.com/read/28223138/foxc1-and-foxc2-are-necessary-to-maintain-glomerular-podocytes
#17
Masaru Motojima, Tsutomu Kume, Taiji Matsusaka
Foxc1 and Foxc2 (Foxc1/2) are transcription factors involved in many biological processes. In adult kidneys, expression of Foxc1/2 is confined to the glomerular epithelial cells, i.e., podocytes. To bypass embryonic lethality of Foxc1/2 null mice, mice ubiquitously expressing inducible-Cre (ROSA26-CreER(T2)) or mice expressing Cre in podocytes (Nephrin-Cre) were mated with floxed-Foxc1 and floxed-Foxc2 mice. The CreER(T2) was activated in adult mice by administrations of tamoxifen. Eight weeks after tamoxifen treatment, ROSA26-CreER(T2); Foxc1(+/flox); Foxc2(flox/flox) mice developed microalbuminuria, while ROSA26-Cre ER(T2); Foxc1(flox/flox); Foxc2(+/flox) mice had no microalbuminuria...
March 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28213819/conditional-knockout-of-activin-like-kinase-1-alk-1-leads-to-heart-failure-without-maladaptive-remodeling
#18
Kevin J Morine, Xiaoying Qiao, Vikram Paruchuri, Mark J Aronovitz, Emily E Mackey, Lyanne Buiten, Jonathan Levine, Keshan Ughreja, Prerna Nepali, Robert M Blanton, Richard H Karas, S Paul Oh, Navin K Kapur
Activin like kinase-1 (AlK-1) mediates signaling via the transforming growth factor beta (TGFβ) family of ligands. AlK-1 activity promotes endothelial proliferation and migration. Reduced AlK-1 activity is associated with arteriovenous malformations. No studies have examined the effect of global AlK-1 deletion on indices of cardiac remodeling. We hypothesized that reduced levels of AlK-1 promote maladaptive cardiac remodeling. To test this hypothesis, we employed AlK-1 conditional knockout mice (cKO) harboring the ROSA26-CreER knock-in allele, whereby a single dose of intraperitoneal tamoxifen triggered ubiquitous Cre recombinase-mediated excision of floxed AlK-1 alleles...
February 17, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28210097/epac1-agonist-decreased-inflammatory-proteins-in-retinal-endothelial-cells-and-loss-of-epac1-increased-inflammatory-proteins-in-the-retinal-vasculature-of-mice
#19
Li Liu, Youde Jiang, Adam Chahine, Elizabeth Curtiss, Jena J Steinle
PURPOSE: Increased inflammatory mediator levels are reported in diabetic retinopathy. We previously reported that β-adrenergic receptor agonists reduced inflammatory mediators in the diabetic retina; however, these agents cannot be given systemically. Here, we investigated whether Epac1 is key to the protective effects of β-adrenergic receptor agonists. METHODS: We cultured primary human retinal endothelial cells (RECs) in normal (5 mM) or high (25 mM) glucose and treated them with an Epac1-specific agonist...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28191756/aberrant-transforming-growth-factor-%C3%AE-activation-recruits-mesenchymal-stem-cells-during-prostatic-hyperplasia
#20
Long Wang, Liang Xie, Francis Tintani, Hui Xie, Changjun Li, Zhuang Cui, Mei Wan, Xiongbing Zu, Lin Qi, Xu Cao
Benign prostatic hyperplasia (BPH) is the overgrowth of prostate tissues with high prevalence in older men. BPH pathogenesis is not completely understood, but it is believed to be a result of de novo overgrowth of prostatic stroma. In this study, we show that aberrant activation of transforming growth factor-β (TGF-β) mobilizes mesenchymal/stromal stem cells (MSCs) in circulating blood, which are recruited for the prostatic stromal hyperplasia. Elevated levels of active TGF-β were observed in both a phenylephrine-induced prostatic hyperplasia mouse model and human BPH tissues...
February 2017: Stem Cells Translational Medicine
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