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https://www.readbyqxmd.com/read/27913668/cellular-functions-of-lrrk2-implicate-vesicular-trafficking-pathways-in-parkinson-s-disease
#1
REVIEW
Mark R Cookson
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene, associated with Parkinson's disease, have been shown to affect intracellular trafficking pathways in a variety of cells and organisms. An emerging theme is that LRRK2 can bind to multiple membranous structures in cells, and several recent studies have suggested that the Rab family of small GTPases might be important in controlling the recruitment of LRRK2 to specific cellular compartments. Once localized to membranes, LRRK2 then influences downstream events, evidenced by changes in the autophagy-lysosome pathway...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27910983/investigation-and-intervention-of-autophagy-to-guide-cancer-treatment-with-nanogels
#2
Xudong Zhang, Xin Liang, Jianjun Gu, Danfeng Chang, Jinxie Zhang, Zhaowei Chen, Yanqi Ye, Chao Wang, Wei Tao, Xiaowei Zeng, Gan Liu, Yongjun Zhang, Lin Mei, Zhen Gu
Cancer cells use autophagy to resist poor survival environmental conditions such as low PH, poor nutrients as well as chemical therapy. Nanogels have been used as efficient chemical drug carriers for cancer treatment. However, the effect of nanogels on autophagy is still unknown. Here, we used Rab proteins as the marker of multiple trafficking vesicles in endocytosis and LC3 as the marker of autophagy to investigate the intracellular trafficking network of Rhodamine B (Rho)-labeled nanogels. The nanogels were internalized by the cells through multiple protein dependent endocytosis and micropinocytosis...
December 2, 2016: Nanoscale
https://www.readbyqxmd.com/read/27905993/pregnant-women-s-perceptions-of-exposure-to-brominated-flame-retardants
#3
A Lane, C G Goodyer, F Rab, J M Ashley, S Sharma, A Hodgson, J Nisker
BACKGROUND: Recent media reports on human studies associating brominated flame retardants (BFRs) in household products in pregnancy with urogenital anomalies in boys and endocrine disruption in both sexes. We sought to explore the perceptions of pregnant women of brominated flame retardant (BFR) exposure, in light of recent media reports on the adverse health effects of BFR exposure prenatally. METHODS: Pregnant women were recruited for interviews through posters and pamphlets in prenatal clinics, prenatal fairs and community centres...
December 1, 2016: Reproductive Health
https://www.readbyqxmd.com/read/27905992/variable-sensitivity-to-complement-dependent-cytotoxicity-in-murine-models-of-neuromyelitis-optica
#4
Yiting Liu, Danielle E Harlow, Katherine S Given, Gregory P Owens, Wendy B Macklin, Jeffrey L Bennett
BACKGROUND: Studies of neuromyelitis optica (NMO), an autoimmune disease of the central nervous system (CNS), have demonstrated that autoantibodies against the water channel aquaporin-4 (AQP4) induce astrocyte damage through complement-dependent cytotoxicity (CDC). In developing experimental models of NMO using cells, tissues or animals from mice, co-administration of AQP4-IgG and normal human serum, which serves as the source of human complement (HC), is required. The sensitivity of mouse CNS cells to HC and CDC in these models is not known...
December 1, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27895719/drabal-novel-method-to-mine-large-high-throughput-screening-assays-using-bayesian-active-learning
#5
Othman Soufan, Wail Ba-Alawi, Moataz Afeef, Magbubah Essack, Panos Kalnis, Vladimir B Bajic
BACKGROUND: Mining high-throughput screening (HTS) assays is key for enhancing decisions in the area of drug repositioning and drug discovery. However, many challenges are encountered in the process of developing suitable and accurate methods for extracting useful information from these assays. Virtual screening and a wide variety of databases, methods and solutions proposed to-date, did not completely overcome these challenges. This study is based on a multi-label classification (MLC) technique for modeling correlations between several HTS assays, meaning that a single prediction represents a subset of assigned correlated labels instead of one label...
2016: Journal of Cheminformatics
https://www.readbyqxmd.com/read/27894104/proteomic-profiling-of-nci-60-extracellular-vesicles-uncovers-common-protein-cargo-and-cancer-type-specific-biomarkers
#6
Stephanie N Hurwitz, Mark A Rider, Joseph L Bundy, Xia Liu, Rakesh K Singh, David G Meckes
Packed with biological information, extracellular vesicles (EVs) offer exciting promise for biomarker discovery and applications in therapeutics and non-invasive diagnostics. Currently, our understanding of EV contents is confined by the limited cells from which vesicles have been characterized utilizing the same enrichment method. Using sixty cell lines from the National Cancer Institute (NCI-60), here we provide the largest proteomic profile of EVs in a single study, identifying 6,071 proteins with 213 common to all isolates...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27891416/effect-of-oral-iron-on-markers-of-oxidative-stress-and-antioxidant-status-in-children-with-iron-deficiency-anaemia
#7
Zeeba Zaka-Ur-Rab, Mohammad Adnan, Syed Moiz Ahmad, Najmul Islam
INTRODUCTION: Conflicting reports are available on the relationship of Iron Deficiency Anaemia (IDA) and iron therapy with oxidative stress. AIM: To study the levels of markers of oxidative stress and anti-oxidant status in children with IDA and to assess the effect of iron therapy on the same. MATERIALS AND METHODS: This prospective, single centre, hospital based study was a sub-study of a randomized controlled trial conducted in the Department of Paediatrics, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh in collaboration with the Department of Biochemistry (of the same institution) between October 2009 to February 2011...
October 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/27890989/the-burden-of-segregated-respiratory-diseases-in-india-and-the-quality-of-care-in-these-patients-results-from-the-asia-pacific-burden-of-respiratory-diseases-study
#8
Aloke Gopal Ghoshal, G D Ravindran, Paras Gangwal, Girish Rajadhyaksha, Sang-Heon Cho, Abdul Razak Bin Abdul Muttalif, Horng-Chyuan Lin, Sanguansak Thanaviratananich, Shalini Bagga, Rab Faruqi, Shiva Sajjan, Pradeep Shetty, Raeesuddin Syed, Kim K Hamrosi, De Yun Wang
BACKGROUND: Chronic respiratory diseases such as asthma, allergic rhinitis (AR), chronic obstructive pulmonary disease (COPD), and rhinosinusitis are becoming increasingly prevalent in the Asia-Pacific region. The Asia-Pacific Burden of Respiratory Diseases study examined the disease and economic burden of AR, asthma, COPD, and rhinosinusitis across the Asia-Pacific and more specifically India. OBJECTIVES: To estimate the proportion of adults receiving care for asthma, AR, COPD, and rhinosinusitis and assess the economic burden, both direct and indirect of these chronic respiratory disease...
November 2016: Lung India: Official Organ of Indian Chest Society
https://www.readbyqxmd.com/read/27888097/rab7a-regulates-cell-migration-through-rac1-and-vimentin
#9
Azzurra Margiotta, Cinzia Progida, Oddmund Bakke, Cecilia Bucci
Rab7a, a small GTPase of the Rab family, is localized to late endosomes and controls late endocytic trafficking. The discovery of several Rab7a interacting proteins revealed that Rab7a function is closely connected to cytoskeletal elements. Indeed, Rab7a recruits on vesicles RILP and FYCO that are responsible for the movement of Rab7a-positive vesicles and/or organelles on microtubule tracks, but also directly interacts with Rac1, a fundamental regulator of actin cytoskeleton, and with peripherin and vimentin, two intermediate filament proteins...
November 22, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27882103/identification-of-proteins-suppressing-the-functions-of-oncogenic-phosphatase-of-regenerating-liver-1-and-3
#10
Ju-Dong Lee, Haiyoung Jung, Sang-Hyun Min
The phosphatase of regenerating liver (PRL) family, including PRL-1, PRL-2, and PRL-3, comprises protein tyrosine phosphatases whose deregulation is associated with the tumorigenesis and metastasis of many types of cancer. However, the underlying mechanism is poorly understood. In this study, aiming to increase understanding of the molecular mechanisms underlying the functions of PRL-1 and PRL-3, a yeast two-hybrid system was employed to screen for their interacting proteins. Alignment with the NCBI BLAST database revealed 12 interactive proteins: Synaptic nuclear envelope protein 2, emerin, mannose 6-phosphate receptor-binding protein 1, low-density lipoprotein receptor-related protein 10, Rab acceptor 1, tumor protein D52-like 2, selectin P ligand (SELPLG), guanylate binding protein 1, transmembrane and ubiquitin-like domain-containing 2, NADH:ubiquinone oxidoreductase subunit B8, syndecan 4 and FK506-binding protein 8 (FKBP8)...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27881264/quality-of-life-and-economic-burden-of-respiratory-disease-in-asia-pacific-asia-pacific-burden-of-respiratory-diseases-study
#11
De Yun Wang, Aloke Gopal Ghoshal, Abdul Razak Bin Abdul Muttalif, Horng-Chyuan Lin, Sanguansak Thanaviratananich, Shalini Bagga, Rab Faruqi, Shiva Sajjan, Alan J M Brnabic, Francis C Dehle, Sang-Heon Cho
OBJECTIVES: Asia-Pacific Burden of Respiratory Diseases is a cross-sectional, observational study examining the burden of disease in adults with respiratory diseases across six countries. The aim of this study was to describe health care resource use (HCRU), work impairment, cost burden, and health-related quality of life (HRQOL) associated with respiratory disease in the Asia-Pacific. METHODS: Consecutive participants aged 18 years or older with a primary diagnosis of asthma, allergic rhinitis, chronic obstructive pulmonary disease, or rhinosinusitis were enrolled...
May 2016: Value in Health Regional Issues
https://www.readbyqxmd.com/read/27878588/the-impact-of-erdosteine-on-cisplatin-induced-ototoxicity-a-proteomics-approach
#12
Sofia Waissbluth, Delphine Garnier, Olubunmi V Akinpelu, Pezhman Salehi, Sam J Daniel
Cisplatin is a commonly used chemotherapeutic agent and causes serious side effects, including progressive and irreversible hearing loss. No treatment is currently available for cisplatin-induced ototoxicity. We have previously demonstrated that erdosteine, a potent antioxidant, partially protected the cochlea against cisplatin toxicity in vivo. The aims of this study were to (1) evaluate the protein profiles of the cochlea following cisplatin administration and (2) evaluate the impact of erdosteine on the protein profile using a proteomics-based approach...
November 23, 2016: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/27876895/multiple-crosstalk-between-tor-and-the-cell-integrity-mapk-signaling-pathway-in-fission-yeast
#13
Marisa Madrid, Beatriz Vázquez-Marín, Alejandro Franco, Teresa Soto, Jero Vicente-Soler, Mariano Gacto, José Cansado
In eukaryotic cells, the highly conserved Target of Rapamycin (TOR) and the Mitogen Activated Protein Kinase (MAPK) signaling pathways elicit adaptive responses to extra- and intracellular conditions by regulating essential cellular functions. However, the nature of the functional relationships between both pathways is not fully understood. In the fission yeast Schizosaccharomyces pombe the cell integrity MAPK pathway (CIP) regulates morphogenesis, cell wall structure and ionic homeostasis. We show that the Rab GTPase Ryh1, a TORC2 complex activator, cross-activates the CIP and its core member, the MAPK Pmk1, by two distinct mechanisms...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872253/gtpase-cross-talk-regulates-trappii-activation-of-rab11-homologues-during-vesicle-biogenesis
#14
Laura L Thomas, J Christopher Fromme
Rab guanosine triphosphatases (GTPases) control cellular trafficking pathways by regulating vesicle formation, transport, and tethering. Rab11 and its paralogs regulate multiple secretory and endocytic recycling pathways, yet the guanine nucleotide exchange factor (GEF) that activates Rab11 in most eukaryotic cells is unresolved. The large multisubunit transport protein particle (TRAPP) II complex has been proposed to act as a GEF for Rab11 based on genetic evidence, but conflicting biochemical experiments have created uncertainty regarding Rab11 activation...
November 21, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27866705/epileptic-encephalopathy-caused-by-mutations-in-the-guanine-nucleotide-exchange-factor-dennd5a
#15
Chanshuai Han, Reem Alkhater, Tawfiq Froukh, Arakel G Minassian, Melissa Galati, Rui Han Liu, Maryam Fotouhi, Julia Sommerfeld, Ayman J Alfrook, Christian Marshall, Susan Walker, Peter Bauer, Stephen W Scherer, Olaf Riess, Rebecca Buchert, Berge A Minassian, Peter S McPherson
Epileptic encephalopathies are a catastrophic group of epilepsies characterized by refractory seizures and cognitive arrest, often resulting from abnormal brain development. Here, we have identified an epileptic encephalopathy additionally featuring cerebral calcifications and coarse facial features caused by recessive loss-of-function mutations in DENND5A. DENND5A contains a DENN domain, an evolutionarily ancient enzymatic module conferring guanine nucleotide exchange factor (GEF) activity to multiple proteins serving as GEFs for Rabs, which are key regulators of membrane trafficking...
December 1, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27854154/small-gtpases-in-c-elegans-metabolism
#16
Daniel Z Bar, Chayki Charar, Yosef Gruenbaum
The mechanistic target of rapamycin (mTOR) is an evolutionary conserved protein with a serine/threonine kinase activity that regulates cell growth, proliferation, motility, survival, protein synthesis, autophagy and transcription. It is embedded in 2 large protein complexes: mTORC1 and mTORC2. Regulation of specific mTOR pathway functions depends on multiple GTPases, that act either as regulators of mTOR protein complexes, coupling energy availability with mTORC1 activity, or as downstream effectors of both mTORC1 and mTORC2...
November 17, 2016: Small GTPases
https://www.readbyqxmd.com/read/27852901/multivalent-rab-interactions-determine-tether-mediated-membrane-fusion
#17
Anna Lürick, Jieqiong Gao, Anne Kuhlee, Erdal Yavavli, Lars Langemeyer, Angela Perz, Stefan Raunser, Christian Ungermann
Membrane fusion at endomembranes requires crosstalk between Rab GTPases and tethers to drive SNARE-mediated lipid bilayer mixing. Several tethers have multiple Rab binding sites with largely untested function. Here, we dissected the lysosomal HOPS complex as a tethering complex with just two binding sites for the Rab7-like Ypt7 protein to determine their relevance for fusion. Using tethering and fusion assays combined with HOPS mutants we show that HOPS-dependent fusion requires both Rab binding sites, with Vps39 being the stronger Ypt7-interactor than Vps41...
November 16, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27852895/ras-and-rab-interactor-1-controls-neuronal-plasticity-by-coordinating-dendritic-filopodial-motility-and-ampa-receptor-turnover
#18
Zsófia Szíber, Hanna Liliom, Carlos O Oueslati Morales, Attila Ignácz, Anikó Erika Rátkai, Kornelia Ellwanger, Gisela Link, Attila Szűcs, Angelika Hausser, Katalin Schlett
Ras and Rab interactor 1 (RIN1) is predominantly expressed in the nervous system. RIN1 knockout animals have deficits in latent inhibition and fear extinction in the amygdala, suggesting a critical role for RIN1 in preventing the persistence of unpleasant memories. At the molecular level, RIN1 signals through Rab5 GTPases that control endocytosis of cell-surface receptors and Abl non-receptor tyrosine kinases that participate in actin cytoskeleton remodelling.Here, we report that RIN1 controls the plasticity of cultured mouse hippocampal neurons...
November 16, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27852828/emerging-biological-roles-of-cl-intracellular-channel-proteins
#19
REVIEW
Elisabetta Argenzio, Wouter H Moolenaar
Cl(-) intracellular channels (CLICs) are a family of six evolutionary conserved cytosolic proteins that exist in both soluble and membrane-associated forms; however, their functions have long been elusive. Soluble CLICs adopt a glutathione S-transferase (GST)-fold, can induce ion currents in artificial membranes and show oxidoreductase activity in vitro, but there is no convincing evidence of CLICs having such activities in vivo. Recent studies have revealed a role for CLIC proteins in Rho-regulated cortical actin dynamics as well as vesicular trafficking and integrin recycling, the latter of which are under the control of Rab GTPases...
November 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27846718/-rab-proteins-intracellular-transport-and-cancer
#20
R Černochová, M Nekulová, J Holčaková
BACKGROUND: Rab proteins are small monomeric enzymes which belong to the large Ras protein superfamily and allow hydrolysis of guanosine triphosphate (GTP) to guanosine (GDP). Up to now more than 60 proteins have been described that act primarily as regulators of intracellular transport. Rab GTPases are mostly located at the intracellular membranes, where they provide connections to motor proteins and to the cytoskeleton and control various steps of the traffic pathways including the formation and movement of vesicles or membrane fusion controlling secretion, endocytosis, recycling and degradation of proteins...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
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