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https://www.readbyqxmd.com/read/28109183/chloride-ion-transport-and-overexpression-of-tmem16a-in-a-guinea-pig-asthma-model
#1
Mitsuko Kondo, Mayoko Tsuji, Kaori Hara, Ken Arimura, Osamitsu Yagi, Etsuko Tagaya, Kiyoshi Takeyama, Jun Tamaoki
BACKGROUND: TMEM16A, a Ca-activated Cl channel, regulates various physiological functions such as mucin secretion. However, the role of TMEM16A in hypersecretion in asthma is not fully understood. OBJECTIVE: The aim of this study is to evaluate Cl ion transport via TMEM16A and determine the localization of TMEM16A in a guinea pig asthma model. METHODS: Guinea pigs were sensitized with OVA ip. on Day 1 and Day 8. On Day 22, we assessed OVA challenge-induced Cl ion transport in the sensitized tracheas ex vivo in an Ussing chamber, compared with the non-sensitized tracheas...
January 21, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28109174/%C3%AE-%C3%AE-nac-cooperates-with-sam37-to-mediate-early-stages-of-mitochondrial-protein-import
#2
J Carlos Ponce-Rojas, M Clara Avendaño-Monsalve, A Roberto Yañez-Falcón, Fabiola Jaimes-Miranda, Erika Garay, Francisco Torres-Quiroz, Alexander DeLuna, Soledad Funes
The mitochondrial proteome is mostly composed of nuclear-encoded proteins. Such polypeptides are synthesized with signals that guide their intracellular transport to the surface of the organelle and later within the different mitochondrial sub-compartments until they reach their functional destination. It has been suggested that NAC - a cytosolic chaperone which recognizes nascent chains on translationally active ribosomes - has a role in the import of nuclear-encoded mitochondrial proteins. However, the molecular mechanisms that regulate the NAC-mediated co-translational import are still not clear...
January 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28109119/serotonin-transporter-protects-the-placental-cells-against-apoptosis-in-caspase-3-independent-pathway
#3
Coedy Hadden, Tariq Fahmi, Anthonya Cooper, Alena V Savenka, Vladimir V Lupashin, Drucilla J Roberts, Luc Maroteaux, Sylvie Hauguel-de Mouzon, Fusun Kilic
Serotonin (5-HT) and its specific transporter, SERT play important roles in pregnancy. Using placentas dissected from 18d gestational SERT-knock out (KO), peripheral 5-HT (TPH1)-KO and wild-type (WT) mice, we explored the role of 5-HT and SERT in placental functions in detail. An abnormal thick band of fibrosis and necrosis under the giant cell layer in SERT-KO placentas appeared only moderately in TPH1-KO and minimally present in WT placentas. The majority of the changes were located at the junctional zone of the placentas in SERT...
January 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28109053/frogs-model-man-in-vivo-thyroid-hormone-signaling-during-development
#4
REVIEW
Laurent M Sachs, Daniel R Buchholz
Thyroid hormone (TH) signaling comprises TH transport across cell membranes, metabolism by deiodinases, and molecular mechanisms of gene regulation. Proper TH signaling is essential for normal perinatal development, most notably for neurogenesis and fetal growth. Knowledge of perinatal TH endocrinology needs improvement to provide better treatments for premature infants and endocrine diseases during gestation and to counteract effects of endocrine disrupting chemicals. Studies in amphibians have provided major insights to understand in-vivo mechanisms of TH signaling...
January 21, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28109051/shear-induced-platelet-aggregation-and-distribution-of-thrombogenesis-at-stenotic-vessels
#5
Hiroki Kamada, Yohsuke Imai, Masanori Nakamura, Takuji Ishikawa, Takami Yamaguchi
OBJECTIVE: Shear-induced platelet aggregation (SIPA), which is mediated by von Willebrand factor (vWF), is a key mechanism in arterial thrombosis under an abnormally high shear rate of blood flow. We investigated the influence of SIPA on thrombogenesis, focusing on alterations in blood flow at stenotic vessels. METHODS: We carried out a computer simulation of thrombogenesis in stenotic vessels at three different injury positions (i.e., upstream, apex, and downstream of the stenosis) to evaluate the effect of SIPA...
January 21, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28108917/quantitative-proteomics-analysis-reveals-the-tolerance-of-mirabilis-jalapa-l-to-petroleum-contamination
#6
Shuisen Chen, Hui Ma, Zhifu Guo, Yaping Feng, Jingwei Lin, Menghua Zhang, Ming Zhong
Petroleum is not only an important energy resource but is also a major soil pollutant. To gain better insight into the adaptability mechanism of Mirabilis jalapa to petroleum-contaminated soil, the protein profiles of M. jalapa root were investigated using label-free quantitative proteomics technique. After exposing to petroleum-contaminated soil for 24 h, 34 proteins significantly changed their protein abundance and most of the proteins increased in protein abundance (91.18%). Combined with gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses as well as data from previous studies, our results revealed that M...
January 20, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28108829/vascular-contractile-reactivity-in-hypotension-due-to-reduced-renal-reabsorption-of-na-and-restricted-dietary-na
#7
Saeed Alshahrani, Robert M Rapoport, Manoocher Soleimani
Reduced renal Na(+) reabsorption along with restricted dietary Na(+) depletes intravascular plasma volume which can then result in hypotension. Whether hypotension occurs and the magnitude of hypotension depends in part on compensatory angiotensin II-mediated increased vascular resistance. We investigated whether the ability of vascular resistance to mitigate the hypotension was compromised by decreased contractile reactivity. In vitro reactivity was investigated in aorta from mouse models of reduced renal Na(+) reabsorption and restricted dietary Na(+) associated with considerable hypotension and renin-angiotensin system activation: (1) the Na(+)-Cl(-)-Co-transporter (NCC) knockout (KO) with Na(+) restricted diet (0...
January 20, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28108666/antibiotic-induced-elevations-of-plasma-bile-acids-in-rats-independent-of-bsep-inhibition
#8
Yutai Li, Michael J Hafey, Hong Duong, Raymond Evers, Kyeongmi Cheon, Daniel J Holder, Alema Galijatovic-Idrizbegovic, Frank D Sistare, Warren E Glaab
Drug-induced liver injury (DILI) is a common toxicity observed in drug development and can lead to withdrawal of approved drugs from the market. To better understand the numerous mechanisms of DILI, recent efforts have focused on transporter inhibition, specifically liver canalicular bile salt export pump (Bsep) as one mechanism of DILI, and on the potential use of plasma bile acids as monitorable mechanism-based biomarkers of Bsep inhibition. To explore alternative mechanisms of bile acid increases in plasma, six antibiotic and two non-antibiotic drugs unlikely to be Bsep inhibitors were evaluated in rat studies...
January 20, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28108665/fasiglifam-tak-875-alters-bile-acid-homeostasis-in-rats-and-dogs-a-potential-cause-of-drug-induced-liver-injury
#9
Francis S Wolenski, Andy Z X Zhu, Mike Johnson, Shaoxia Yu, Yuu Moriya, Takuya Ebihara, Vilmos Csizmadia, Jessica Grieves, Martin Paton, Mingxiang Liao, Christopher Gemski, Liping Pan, Majid Vakilynejad, Yvonne P Dragan, Swapan K Chowdhury, Patrick J Kirby
Fasiglifam (TAK-875), a Free Fatty Acid Receptor 1 (FFAR1) agonist in development for the treatment of type 2 diabetes, was voluntarily terminated in phase 3 due to adverse liver effects. A mechanistic investigation described in this manuscript focused on the inhibition of bile acid (BA) transporters as a driver of the liver findings. TAK-875 was an in vitro inhibitor of multiple influx (NTCP and OATPs) and efflux (BSEP and MRPs) hepatobiliary BA transporters at micromolar concentrations. Repeat dose studies determined that TAK-875 caused a dose-dependent increase in serum total BA in rats and dogs...
January 20, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28108584/astrocytic-transporters-in-alzheimer-s-disease
#10
REVIEW
Chris Ugbode, Yuhan Hu, Benjamin Whalley, Chris Peers, Marcus Rattray, Mark L Dallas
Astrocytes play a fundamental role in maintaining the health and function of the central nervous system. Increasing evidence indicates that astrocytes undergo both cellular and molecular changes at an early stage in neurological diseases, including Alzheimer's disease (AD). These changes may reflect a change from a neuroprotective to a neurotoxic phenotype. Given the lack of current disease-modifying therapies for AD, astrocytes have become an interesting and viable target for therapeutic intervention. The astrocyte transport system covers a diverse array of proteins involved in metabolic support, neurotransmission and synaptic architecture...
February 1, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28108582/identification-of-a-novel-protein-kinase-that-affects-the-chronological-lifespan-in-fission-yeast
#11
Tatsuhiro Kurauchi, Aya Hashizume, Yuki Imai, Kanako Hayashi, Satoshi Tsubouchi, Kunio Ihara, Hokuto Ohtsuka, Hirofumi Aiba
Chronological lifespan is defined by how long a cell can survive in a non-dividing state. In yeast, it is measured by viability after entry into the stationary phase. To understand the regulatory mechanisms of chronological lifespan in Schizosaccharomyces pombe, it is necessary to identify and characterize novel factors involved in the regulation of chronological lifespan. To this end, we have screened for a long-lived mutant and identified that novel gene nnk1(+) that encodes an essential protein kinase is the determinant of chronological lifespan...
January 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28108572/use-of-ldl-receptor-targeting-peptide-vectors-for-in-vitro-and-in-vivo-cargo-transport-across-the-blood-brain-barrier
#12
Yves Molino, Marion David, Karine Varini, Françoise Jabès, Nicolas Gaudin, Aude Fortoul, Karima Bakloul, Maxime Masse, Anne Bernard, Lucile Drobecq, Pascaline Lécorché, Jamal Temsamani, Guillaume Jacquot, Michel Khrestchatisky
The blood-brain barrier (BBB) prevents the entry of many drugs into the brain and, thus, is a major obstacle in the treatment of CNS diseases. There is some evidence that the LDL receptor (LDLR) is expressed at the BBB and may participate in the transport of endogenous ligands from blood to brain, a process referred to as receptor-mediated transcytosis. We previously described a family of peptide vectors that were developed to target the LDLR. In the present study, in vitro BBB models that were derived from either wild-type and LDLR knockout animals (ldlr(-/-)) were used to validate the specific LDLR-dependent transcytosis of LDL via a nondegradative route...
January 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28108571/dynamical-theory-of-shear-bands-in-structural-glasses
#13
Apiwat Wisitsorasak, Peter G Wolynes
The heterogeneous elastoplastic deformation of structural glasses is explored using the framework of the random first-order transition theory of the glass transition along with an extended mode-coupling theory that includes activated events. The theory involves coupling the continuum elastic theory of strain transport with mobility generation and transport as described in the theory of glass aging and rejuvenation. Fluctuations that arise from the generation and transport of mobility, fictive temperature, and stress are treated explicitly...
January 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28108524/acbd5-and-vapb-mediate-membrane-associations-between-peroxisomes-and-the-er
#14
Joseph L Costello, Inês G Castro, Christian Hacker, Tina A Schrader, Jeremy Metz, Dagmar Zeuschner, Afsoon S Azadi, Luis F Godinho, Victor Costina, Peter Findeisen, Andreas Manner, Markus Islinger, Michael Schrader
Peroxisomes (POs) and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism and form tight structural associations, which were first observed in ultrastructural studies decades ago. PO-ER associations have been suggested to impact on a diverse number of physiological processes, including lipid metabolism, phospholipid exchange, metabolite transport, signaling, and PO biogenesis. Despite their fundamental importance to cell metabolism, the mechanisms by which regions of the ER become tethered to POs are unknown, in particular in mammalian cells...
January 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28108405/defects-of-the-vertebral-endplate-implications-for-disc-degeneration-depend-on-size
#15
Uruj Zehra, Luke Flower, Katharine Robson-Brown, Michael A Adams, Patricia Dolan
BACKGROUND CONTEXT: Bony vertebral endplates must be porous to allow metabolite transport into the disc, and yet strong to resist high intradiscal pressure. Endplate defects may therefore have nutritional and mechanical consequences for the disc, depending on their size and type. We hypothesise that broad, diffuse defects are more closely associated with disc decompression and degeneration than are focal Schmorl's node-type defects. PURPOSE: To determine how the size and type of endplate defects are related to decompression and degeneration in the adjacent intervertebral disc...
January 17, 2017: Spine Journal: Official Journal of the North American Spine Society
https://www.readbyqxmd.com/read/28108396/serotonin-5-ht4-receptors-modulate-the-development-of-glutamatergic-input-to-the-dorsal-raphe-nucleus
#16
Angela Chen, Katherine D Hubbert, Pasha F Foroudi, Vivian F Lu, Skirmantas Janušonis
The dorsal raphe nucleus (DRN) is a major serotonin (5-hydroxytryptamine, 5-HT)-producing region in the central nervous system. It receives glutamatergic inputs from several brain regions, which are reciprocally modulated by serotonergic signals. We investigated whether serotonin 5-HT4 receptors (5-HT4Rs) play a role in the development of glutamatergic control of the DRN, with an emphasis on cortical inputs. Double-label immunohistochemistry and confocal microscopy were used to quantify vesicular glutamate transporter 1 (vGluT1)-immunoreactive terminals in the DRN of mice with a null-mutation in the 5-HT4R gene...
January 17, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28108384/molecular-features-of-the-l-type-amino-acid-transporter-2-determine-different-import-and-export-profiles-for-thyroid-hormones-and-amino-acids
#17
Katrin M Hinz, Dominik Neef, Claudia Rutz, Jens Furkert, Josef Köhrle, Ralf Schülein, Gerd Krause
The L-type amino acid transporter 2 (LAT2) imports amino acids (AA) and also certain thyroid hormones (TH), e.g. 3,3'-T2 and T3, but not rT3 and T4. We utilized LAT2 mutations (Y130A, N133S, F242W) that increase 3,3'-T2 import and focus here on import and export capacity for AA, T4, T3, BCH and derivatives thereof to delineate molecular features. Transport studies and analysis of competitive inhibition of import by radiolabelled TH and AA were performed in Xenopus laevis oocytes. Only Y130A, a pocket widening mutation, enabled import for T4 and increased it for T3...
January 17, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28108329/exercise-increases-mitochondrial-complex-i-activity-and-drp1-expression-in-the-brains-of-aged-mice
#18
Aaron M Gusdon, Jason Callio, Giovanna DiStefano, Robert M O'Doherty, Bret H Goodpaster, Paul M Coen, Charleen T Chu
Exercise is known to have numerous beneficial effects. Recent studies indicate that exercise improves mitochondrial energetics not only in skeletal muscle but also in other tissues. While exercise elicits positive effects on memory, neurogenesis, and synaptic plasticity, the effects of exercise on brain mitochondrial energetics remain relatively unknown. Herein, we studied the effects of exercise training in old and young mice on brain mitochondrial energetics, in comparison to known effects on peripheral tissues that utilize fatty acid oxidation...
January 17, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28108216/the-phenomenon-of-atherosclerosis-reversal-and-regression-lessons-from-animal-models
#19
REVIEW
Dimitry A Chistiakov, Veronika A Myasoedova, Victor V Revin, Alexander N Orekhov, Yuri V Bobryshev
Studies in non-rodent and murine models showed that atherosclerosis can be reversed. Atherosclerosis progression induced by high-fat or cholesterol-rich diet can be reduced and reversed to plaque regression after switching to a normal diet or through administration of lipid-lowering agents. The similar process should exist in humans after implementation of lipid-lowering therapy and as a result of targeting of small rupture-prone plaques that are major contributors for acute atherosclerotic complications. Lowering of low density lipoprotein (LDL) cholesterol and the activation of reverse cholesterol transport lead to a decline in foam cell content, to the depletion of plaque lipid reservoirs, a decrease in lesional macrophage numbers through the activation of macrophage emigration and, probably, apoptosis, dampening plaque inflammation, and the induction of anti-inflammatory macrophages involved in clearance of the necrotic core and plaque healing...
January 17, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28108162/in-situ-degradation-of-soil-sorbed-17%C3%AE-estradiol-using-carboxymethyl-cellulose-stabilized-manganese-oxide-nanoparticles-column-studies
#20
Bing Han, Man Zhang, Dongye Zhao
This work tested a new remediation technology for in-situ degradation of estrogens by delivering a new class of stabilized manganese oxide (MnO2) nanoparticles in contaminated soils. The nanoparticles were prepared using a food-grade carboxymethyl cellulose (CMC) as a stabilizer, which was able to facilitate particle delivery into soil. The effectiveness of the technology was tested using 17β-estradiol (E2) as a model estrogen and three sandy loams (SL1, SL2, and SL3) as model soils. Column transport tests showed that the nanoparticles can be delivered in the three soils, though retention of the nanoparticles varied...
January 18, 2017: Environmental Pollution
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