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https://www.readbyqxmd.com/read/29145636/localization-and-functional-characterization-of-the-p-asn965ser-n965s-abca4-variant-in-mice-reveal-pathogenic-mechanisms-underlying-stargardt-macular-degeneration
#1
Laurie L Molday, Daniel Wahl, Marinko Sarunic, Robert S Molday
ABCA4 is a member of the superfamily of ATP-binding cassette (ABC) proteins that transports N-retinylidene-phosphatidylethanolamine (N-Ret-PE) across outer segment disc membranes thereby facilitating the removal of potentially toxic retinoid compounds from photoreceptor cells. Mutations in the gene encoding ABCA4 are responsible for Stargardt disease (STGD1), an autosomal recessive retinal degenerative disease that causes severe vision loss. To define the molecular basis for STGD1 associated with the p.Asn965Ser (N965S) mutation in the Walker A motif of nucleotide binding domain 1 (NBD1), we generated a p...
November 14, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29144994/gene-pathways-associated-with-mitochondrial-function-oxidative-stress-and-telomere-length-are-differentially-expressed-in-the-liver-of-rats-fed-lifelong-on-virgin-olive-sunflower-or-fish-oils
#2
Alfonso Varela-Lopez, María Patricia Pérez-López, César Luis Ramirez-Tortosa, Maurizio Battino, Sergio Granados-Principal, María Del Carmen Ramirez-Tortosa, Julio José Ochoa, Laura Vera-Ramirez, Francesca Giampieri, José Luis Quiles
This study investigates the effect of lifelong intake of different fat sources rich in monounsaturated (virgin olive oil), n6 polyunsaturated (sunflower oil) or n3 polyunsaturated (fish oil) fatty acids in the aged liver. Male Wistar rats fed lifelong on diets differing in the fat source were killed at 6 and at 24 months of age. Liver histopathology, mitochondrial ultrastructure, biogenesis, oxidative stress, mitochondrial electron transport chain, relative telomere length and gene expression profiles were studied...
September 20, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29143921/dichloroacetate-induced-intracellular-acidification-in-glioblastoma-in-vivo-detection-using-aacid-cest-mri-at-9-4%C3%A2-tesla
#3
Mohammed Albatany, Alex Li, Susan Meakin, Robert Bartha
Intracellular pH (pHi) plays an important role in the maintenance of normal cell function, and is maintained within a narrow range by the activity of transporters located at the plasma membrane. Modulation of tumor pHi may influence proliferation, apoptosis, chemotherapy resistance, and thermosensitivity. Chemical exchange saturation transfer (CEST) is a novel MRI contrast mechanism that is dependent on cellular pH. Amine and amide concentration-independent detection (AACID) is a recently developed CEST contrast method that is intracellular pH (pHi) weighted...
November 16, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29143814/structural-basis-of-nucleotide-sugar-transport-across-the-golgi-membrane
#4
Joanne L Parker, Simon Newstead
Glycosylation is a fundamental cellular process that, in eukaryotes, occurs in the lumen of both the Golgi apparatus and the endoplasmic reticulum. Nucleotide sugar transporters (NSTs) are an essential component of the glycosylation pathway, providing the diverse range of substrates required for the glycosyltransferases. NSTs are linked to several developmental and immune disorders in humans, and in pathogenic microbes they have an important role in virulence. How NSTs recognize and transport activated monosaccharides, however, is currently unclear...
November 15, 2017: Nature
https://www.readbyqxmd.com/read/29143559/k-cl-co-transporter-2-kcc2-a-membrane-trafficking-perspective
#5
Bor Luen Tang
K(+)-Cl(-) co-transporter 2 (KCC2/SLC12A5) is a neuronal specific cation chloride co-transporter which is active under isotonic conditions, and thus a key regulator of intracellular Cl(-) levels. It also has an ion transporter-independent structural role in modulating the maturation and regulation of excitatory glutamatergic synapses. KCC2 levels are developmentally regulated, and a postnatal upregulation of KCC2 generates a low intracellular chloride concentration that allows the neurotransmitters γ-aminobutyric acid (GABA) and glycine to exert inhibitory neurotransmission through its Cl(-) permeating channel...
November 16, 2017: Molecular Membrane Biology
https://www.readbyqxmd.com/read/29143548/evaluation-on-the-thyroid-disrupting-mechanism-of-malathion-in-fischer-rat-thyroid-follicular-cell-line-frtl-5
#6
Jingyuan Xiong, Liantian Tian, Yongjie Qiu, Ding Sun, Hao Zhang, Mei Wu, Jintao Wang
Thyroid hormones are involved in many important physiological activities including regulation of energy metabolism, development of nervous system, maintenance of cerebral functions, and so on. Endocrine-disrupting chemicals (EDCs) that interfere with thyroid functions raise serious concerns due to their frequent misuse in areas where regulations are poorly implemented. In addition, chemicals that are originally regarded safe may now be considered as toxic with the development of life sciences. Malathion is an organophosphate insecticide that is widely applied and distributed in agricultural and residential settings...
November 16, 2017: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/29142405/antihyperglycemic-activity-of-caralluma-fimbriata-an-in-vitro-approach
#7
Shenai Ashwini, Roy Anitha
Background: An increase in prevalence of diabetes mellitus necessitates the need to develop new drugs for its effective management. Plants and their bioactive compounds are found to be an alternative therapeutic approach. Caralluma fimbriata, used in this study, is well known for its various biological effects. Objective: The present study was designed to investigate the antihyperglycemic effect of the ethanolic leaf extract of C. fimbriata. Materials and Methods: Different concentrations (1-1000 mg/mL) of the ethanolic leaf extract of C...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29142313/effects-of-exosome-on-the-activation-of-cd4-t-cells-in-rhesus-macaques-a-potential-application-for-hiv-latency-reactivation
#8
Xiaowu Hong, Blake Schouest, Huanbin Xu
Exosomes are small extracellular vesicles (EVs), released by a wide variety of cell types, carry donor origin-proteins, cytokines, and nucleic acids, transport these cargos to adjacent or distant specific recipient cells, and thereby regulate gene expression and activation of target cells. In this study, we isolated and identified exosomes in rhesus macaques, and investigated their effects on cell tropism and activation, especially their potential to reactivate HIV latency. The results indicated that plasma-derived exosomes preferentially fuse to TCR-activated T cells and autologous parent cells...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29142223/active-diffusion-and-advection-in-drosophila-oocytes-result-from-the-interplay-of-actin-and-microtubules
#9
Maik Drechsler, Fabio Giavazzi, Roberto Cerbino, Isabel M Palacios
Transport in cells occurs via a delicate interplay of passive and active processes, including diffusion, directed transport and advection. Despite progress in super-resolution microscopy, discriminating and quantifying these processes is a challenge, requiring tracking of rapidly moving, sub-diffraction objects in a crowded, noisy environment. Here we use differential dynamic microscopy with different contrast mechanisms to provide a thorough characterization of the dynamics in the Drosophila oocyte. We study the movement of vesicles and the elusive motion of a cytoplasmic F-actin mesh, a known regulator of cytoplasmic flows...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29142165/possible-mechanism-for-the-polychlorinated-bipheny-linduced-liver-selective-accumulation-of-thyroxine-in-rats
#10
Yoshihisa Kato, Aki Fujii, Koichi Haraguchi, Yukiko Fujii, Kazutaka Atobe, Tetsuya Endo, Osamu Kimura, Nobuyuki Koga, Chiho Ohta, Shizuo Yamada, Masakuni Degawa
We have previously reported that decrease in level of serum thyroxine T4 by Kanechor 500 (KC500) in rats would occur through the increase in hepatic T4 accumulation rather than the increase in hepatic T4-glucuronyl transferase activity. In the present study, to understand the mechanism underlying the KC500-mediated increase in hepatic T4 accumulation, we examined the relationship between the KC500-mediated changes in hepatic T4 accumulation and the expression levels of mRNAs of hepatic transporters including T4 transporters...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29142102/prolines-in-the-%C3%AE-helix-confer-the-structural-flexibility-and-functional-integrity-of-importin-%C3%AE
#11
Masahiro Kumeta, Hide A Konishi, Wanzhen Zhang, Sayuri Sakagami, Shige H Yoshimura
The karyopherin family of nuclear transport receptors is composed of a long array of amphiphilic α-helices and undergoes flexible conformational changes to pass through the hydrophobic crowding barrier of the nuclear pore. Here, we focused on the characteristic enrichment of prolines in the middle of the outer α-helices of importin β. When these prolines were substituted with alanine, nuclear transport activity was reduced drastically in vivo and in vitro, and caused a severe defect in mitotic progression...
November 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29142021/inf2-mediated-actin-polymerization-at-the-er-stimulates-mitochondrial-calcium-uptake-inner-membrane-constriction-and-division
#12
Rajarshi Chakrabarti, Wei-Ke Ji, Radu V Stan, Jaime de Juan Sanz, Timothy A Ryan, Henry N Higgs
Mitochondrial division requires division of both the inner and outer mitochondrial membranes (IMM and OMM, respectively). Interaction with endoplasmic reticulum (ER) promotes OMM division by recruitment of the dynamin Drp1, but effects on IMM division are not well characterized. We previously showed that actin polymerization through ER-bound inverted formin 2 (INF2) stimulates Drp1 recruitment in mammalian cells. Here, we show that INF2-mediated actin polymerization stimulates a second mitochondrial response independent of Drp1: a rise in mitochondrial matrix calcium through the mitochondrial calcium uniporter...
November 15, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29141908/two-distinct-regulatory-mechanisms-of-transcriptional-initiation-in-response-to-nutrient-signaling
#13
Jannatul Ferdoush, Rwik Sen, Amala Kaja, Priyanka Barman, Sukesh R Bhaumik
SAGA (Spt-Ada-Gcn5-Acetyltransferase) and TFIID (transcription factor IID) have been previously shown to facilitate the PIC (pre-initiation complex) formation at the promoters of two distinct sets of genes. Here, we demonstrate that TFIID and SAGA differentially participate in stimulation of the PIC formation (and hence transcriptional initiation) at the promoter of PHO84, a gene for high affinity inorganic phosphate (Pi) transporter for crucial cellular functions, in response to nutrient signaling. We show that transcriptional initiation of PHO84 occurs predominantly in the TFIID-dependent manner in the absence of Pi in the growth medium...
November 15, 2017: Genetics
https://www.readbyqxmd.com/read/29141646/physical-activity-and-the-environment-conceptual-review-and-framework-for-intervention-research
#14
REVIEW
Jenna Panter, Cornelia Guell, Rick Prins, David Ogilvie
BACKGROUND: Changing the physical environment is one way to promote physical activity and improve health, but evidence on intervention effectiveness is mixed. The theoretical perspectives and conceptual issues discussed or used in evaluative studies and related literature may contribute to these inconsistencies. We aimed to advance the intervention research agenda by systematically searching for and synthesising the literature pertaining to these wider conceptual issues. METHODS: We searched for editorials, commentaries, reviews, or primary qualitative or quantitative studies in multiple disciplines by electronic searches of key databases (MEDLINE and MEDLINE In-Process, Web of Science, Cochrane Reviews, ProQuest for dissertations, Health Evidence, EPPI-Centre, TRID and NICE) and snowballing...
November 15, 2017: International Journal of Behavioral Nutrition and Physical Activity
https://www.readbyqxmd.com/read/29141216/slc3a2-mediates-branched-chain-amino-acid-dependent-maintenance-of-regulatory-t-cells
#15
Kayo Ikeda, Makoto Kinoshita, Hisako Kayama, Shushi Nagamori, Pornparn Kongpracha, Eiji Umemoto, Ryu Okumura, Takashi Kurakawa, Mari Murakami, Norihisa Mikami, Yasunori Shintani, Satoko Ueno, Ayatoshi Andou, Morihiro Ito, Hideki Tsumura, Koji Yasutomo, Keiichi Ozono, Seiji Takashima, Shimon Sakaguchi, Yoshikatsu Kanai, Kiyoshi Takeda
Foxp3(+) regulatory T (Treg) cells, which suppress immune responses, are highly proliferative in vivo. However, it remains unclear how the active replication of Treg cells is maintained in vivo. Here, we show that branched-chain amino acids (BCAAs), including isoleucine, are required for maintenance of the proliferative state of Treg cells via the amino acid transporter Slc3a2-dependent metabolic reprogramming. Mice fed BCAA-reduced diets showed decreased numbers of Foxp3(+) Treg cells with defective in vivo proliferative capacity...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29140789/mechanism-and-dynamics-of-inpp5e-transport-into-and-inside-the-ciliary-compartment
#16
Stefanie Kristine Kösling, Eyad Kalawy Fansa, Stefano Maffini, Alfred Wittinghofer
The inositol polyphosphate 5´-phosphatase E (INPP5E) localizes to cilia. We showed that the carrier protein phosphodiesterase 6 delta subunit (PDE6δ) mediates the sorting of farnesylated INPP5E into cilia due to high affinity binding and release by Arl3 GTP. However, the dynamics of INPP5E transport into and inside the ciliary compartment are not fully understood. Here we first investigate the movement of INPP5E using live cell fluorescence microscopy and fluorescence recovery after photobleaching (FRAP) analysis...
August 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/29140741/comparative-in-vitro-study-of-11-c-methionine-and-11-c-deuterodeprenyl-uptake-in-three-human-glioma-cell-lines
#17
Elena Vasilskis, Ingrid Kreimerman, Silvia Olivera, Eduardo Savio, Henry Engler
AIM: To compare the uptake of (11)C-deuterodeprenyl ((11)C-DED) and (11)C-methionine ((11)C-MET) in three human glioma cell lines and study the relationship with glial fibrillary acid protein (GFAP) and monoamine oxidase B (MAO B) expression. (11)C-DED is used in positron emission tomography imaging as a marker of astrocytosis in various central nervous system pathologies. It binds irreversibly to MAO B, a glial dimeric enzyme with increased activity in some neurological pathologies. MATERIALS AND METHODS: Binding and internalization studies of (11)C-MET and (11)C-DED were performed in astrocytoma grade III, glioblastoma grade IV, and radio-resistant glioblastoma grade IV cells...
November 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29140707/grapefruit-flavonoid-naringenin-regulates-the-expression-of-lxr%C3%AE-in-thp-1-macrophages-by-modulating-amp-activated-protein-kinase
#18
Javier Saenz, Consuelo Santa-María, Maria Edith Reyes-Quiroz, Isabel Geniz, Juan Jiménez, Francisco Sobrino, Gonzalo Alba
The present work investigates the modulation of grapefruit flavonoid naringenin over Liver X Receptor alpha (LXRα) and its target genes in THP-1 macrophages, focusing on AMP-activated protein kinase (AMPK) implication. Naringenin induced LXRα at mRNA and protein levels besides influencing the expression of LXRα target genes ABCA1, ABCG1 (ATP-binding cassette A1 and G1), and SREBP1c (sterol response element binding protein 1c) in THP-1 macrophages. The increased LXRα mRNA and protein expression was reverted when AMPK was inhibited by its chemical inhibitor, compound C or by transfection with AMPK α1 and α2 siRNA...
November 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29140675/identification-of-novel-allosteric-modulators-of-glutamate-transporter-eaat2
#19
Sandhya Kortagere, Ole Valente Mortensen, Jingsheng Xia, William Lester, Yuhong Fang, Yellamelli V V Srikanth, Joseph M Salvino, Andreia Cristina Karklin Fontana
Dysfunction of excitatory amino acid transporters (EAATs) has been implicated in the pathogenesis of various neurological disorders, such as stroke, brain trauma, epilepsyand neurodegenerative diseases among others. EAAT2 is the main subtype responsible for glutamate clearance in the brain, having a key role in regulating transmission and preventing excitotoxicity. Therefore, compounds that increase the expression or activity of EAAT2 have therapeutic potential for neuroprotection. Previous studies identified molecular determinants for EAAT2 transport stimulation in a structural domain that lies at the interface of the rigid trimerization domain and the central substrate binding transport domain...
November 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29140396/a-2d-self-assembled-mos2-znin2s4-heterostructure-for-efficient-photocatalytic-hydrogen-evolution
#20
Weijia Li, Zhaoyong Lin, Guowei Yang
Semiconductor photocatalysis for hydrogen production is a promising route to address current energy demands. It is still a great challenge to spatially separate photogenerated electrons and holes in bulk photocatalysts because of the long carrier transport pathway from the bulk to the surface. 2D heterostructured photocatalysts with the type II band alignment can not only shorten the carrier transport pathway, but also create an electric field at the interface to suppress the carrier recombination. However, ultrathin and intimate-contact 2D heterostructured photocatalysts have rarely been achieved so far...
November 15, 2017: Nanoscale
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