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Organ trafficking

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https://www.readbyqxmd.com/read/27935765/gb3-binding-lectins-as-potential-carriers-for-transcellular-drug-delivery
#1
Stefan K Müller, Isabel Wilhelm, Thomas Schubert, Katharina Zittlau, Anne Imberty, Josef Madl, Thorsten Eierhoff, Roland Thuenauer, Winfried Römer
OBJECTIVES: Epithelial cell layers as well as endothelia forming the blood-brain barrier can drastically reduce the efficiency of drug targeting. Our goal was to investigate lectins recognizing the glycosphingolipid globotriaosylceramide (Gb3) for their potential as carriers for transcytotic drug delivery. METHODS: We utilized an in vitro model based on Madin-Darby canine kidney cells transfected with Gb3 synthase to characterize transcytosis of the Gb3-binding lectins LecA from Pseudomonas aeruginosa and the B-subunit of Shiga toxin (StxB)...
December 9, 2016: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/27933903/proteomic-identification-and-analysis-of-arginine-methylated-proteins-of-plasmodium-falciparum-at-asexual-blood-stages
#2
Mohammad Zeeshan, Inderjeet Kaur, Joseph Joy, Ekta Saini, Gourab Paul, Abhinav Kaushik, Surbhi Dabral, Asif Mohmmed, Dinesh Gupta, Pawan Malhotra
Plasmodium falciparum undergoes a tightly regulated developmental process in human erythrocytes, and recent studies suggest an important regulatory role of post-translational modifications (PTMs). As compared to Plasmodium phosphoproteome, little is known about other PTMs in the parasite. In the present study, we performed a global analysis of asexual blood stages of Plasmodium falciparum to identify arginine-methylated proteins. Using two different methyl arginine-specific antibodies we immunoprecipitated the arginine-methylated proteins from the stage-specific parasite lysates and identified 843 putative arginine methylated proteins by LC-MS/MS...
December 9, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27933048/clay-components-in-soil-dictate-environmental-stability-and-bioavailability-of-cervid-prions-in-mice
#3
A Christy Wyckoff, Sarah Kane, Krista Lockwood, Jeff Seligman, Brady Michel, Dana Hill, Aimee Ortega, Mihnea R Mangalea, Glenn C Telling, Michael W Miller, Kurt Vercauteren, Mark D Zabel
Chronic wasting disease (CWD) affects cervids and is the only known prion disease to affect free-ranging wildlife populations. CWD spread continues unabated, and exact mechanisms of its seemingly facile spread among deer and elk across landscapes in North America remain elusive. Here we confirm that naturally contaminated soil contains infectious CWD prions that can be transmitted to susceptible model organisms. We show that smectite clay content of soil potentiates prion binding capacity of different soil types from CWD endemic and non-endemic areas, likely contributing to environmental stability of bound prions...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27932950/amyloid-precursor-proteins-are-dynamically-trafficked-and-processed-during-neuronal-development
#4
Jenna M Ramaker, Robert S Cargill, Tracy L Swanson, Hanil Quirindongo, Marlène Cassar, Doris Kretzschmar, Philip F Copenhaver
Proteolytic processing of the Amyloid Precursor Protein (APP) produces beta-amyloid (Aβ) peptide fragments that accumulate in Alzheimer's Disease (AD), but APP may also regulate multiple aspects of neuronal development, albeit via mechanisms that are not well understood. APP is a member of a family of transmembrane glycoproteins expressed by all higher organisms, including two mammalian orthologs (APLP1 and APLP2) that have complicated investigations into the specific activities of APP. By comparison, insects express only a single APP-related protein (APP-Like, or APPL) that contains the same protein interaction domains identified in APP...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27925796/a-severe-asthma-disease-signature-from-gene-expression-profiling-of-peripheral-blood-from-u-biopred-cohorts
#5
Jeannette Bigler, Michael Boedigheimer, James P R Schofield, Paul J Skipp, Julie Corfield, Anthony Rowe, Ana R Sousa, Martin Timour, Lori Twehues, Xuguang Hu, Graham Roberts, Andrew A Welcher, Wen Yu, Kian F Chung, Ian M Adcock, Peter J Sterk, Ratko Djukanović
RATIONALE: Stratification of asthma at the molecular level, especially using accessible biospecimens, could greatly enable patient selection for targeted therapy. OBJECTIVES: To determine the value of blood to identify transcriptional differences between clinically defined asthmatic and non-asthmatic groups, identify potential patient subgroups based on gene expression, and explore biological pathways associated with identified differences. METHODS: Transcriptomics profiles were generated by microarray analysis of blood from 610 asthmatic and control participants in U-BIOPRED...
December 7, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27921095/journey-from-the-center-of-the-cell-the-intra-and-intercellular-transport-of-mrna
#6
Anna Kasprowicz-Maluśki, Wojciech Kwiatkowski, Alicja Starosta, Przemysław Wojtaszek
Transport and localized translation of mRNA is crucial for the proper spatiotemporal organization of proteins within cells. Distribution of RNAs to subcellular domains has recently emerged as a major mechanism for establishing functionally distinct compartments and structures in the cells. There is an emerging evidence that active transport of mRNA involves cytoskeleton and membrane trafficking pathways in fungi, plants and animals, suggesting that it is a common phenomenon among eukaryotes. The important highlights are that the RNA-binding proteins recognize the cargo mRNA and that RNPs are actively transported on the cytoskeletal tracks or co-transported with membranous compartments, such as the endoplasmic reticulum and endosomes...
December 6, 2016: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/27913668/cellular-functions-of-lrrk2-implicate-vesicular-trafficking-pathways-in-parkinson-s-disease
#7
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/27911810/in-vivo-bioluminescence-imaging-reveals-copper-deficiency-in-a-murine-model-of-nonalcoholic-fatty-liver-disease
#8
Marie C Heffern, Hyo Min Park, Ho Yu Au-Yeung, Genevieve C Van de Bittner, Cheri M Ackerman, Andreas Stahl, Christopher J Chang
Copper is a required metal nutrient for life, but global or local alterations in its homeostasis are linked to diseases spanning genetic and metabolic disorders to cancer and neurodegeneration. Technologies that enable longitudinal in vivo monitoring of dynamic copper pools can help meet the need to study the complex interplay between copper status, health, and disease in the same living organism over time. Here, we present the synthesis, characterization, and in vivo imaging applications of Copper-Caged Luciferin-1 (CCL-1), a bioluminescent reporter for tissue-specific copper visualization in living animals...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27908469/-ethics-and-kidney-transplants-with-living-donors
#9
Marie-France Mamzer Bruneel
The ethical debate surrounding transplant practices questions our societies. International recommendations set out numerous precautions which must be taken to ensure that donors act with their free will. While in most countries, including France, organ donation is a voluntary and non-commercial act, a black market exists in the world resulting in the trafficking of organs and tragic transplant tourism.
December 2016: Revue de L'infirmière
https://www.readbyqxmd.com/read/27905440/organization-and-functions-of-mglu-and-gabab-receptor-complexes
#10
Jean-Philippe Pin, Bernhard Bettler
The neurotransmitters glutamate and γ-aminobutyric acid (GABA) transmit synaptic signals by activating fast-acting ligand-gated ion channels and more slowly acting G-protein-coupled receptors (GPCRs). The GPCRs for these neurotransmitters, metabotropic glutamate (mGlu) and GABAB receptors, are atypical GPCRs with a large extracellular domain and a mandatory dimeric structure. Recent studies have revealed how these receptors are activated through multiple allosteric interactions between subunit domains. It emerges that the molecular complexity of these receptors is further increased through association with trafficking, effector and regulatory proteins...
December 1, 2016: Nature
https://www.readbyqxmd.com/read/27901125/rab14-specifies-the-apical-membrane-through-arf6-mediated-regulation-of-lipid-domains-and-cdc42
#11
Ruifeng Lu, Jean M Wilson
The generation of cell polarity is essential for the development of multi-cellular organisms as well as for the function of epithelial organs in the mature animal. Small GTPases regulate the establishment and maintenance of polarity through effects on cytoskeleton, membrane trafficking, and signaling. Using short-term 3-dimensional culture of MDCK cells, we find that the small GTPase Rab14 is required for apical membrane specification. Rab14 knockdown results in disruption of polarized lipid domains and failure of the Par/aPKC/Cdc42 polarity complex to localize to the apical membrane...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895414/hepatic-encephalopathy-ever-closer-to-its-big-bang
#12
EDITORIAL
Pablo A Souto, Ariel R Marcotegui, Lisandro Orbea, Juan Skerl, Juan Carlos Perazzo
Hepatic encephalopathy (HE) is a neuropsychiatric disorder that commonly complicates the course of patients with liver disease. Despite the fact that the syndrome was probably first recognized hundreds of years ago, the exact pathogenesis still remains unclear. Minimal hepatic encephalopathy (MHE) is the earliest form of HE and is estimated to affect more that 75% of patients with liver cirrhosis. It is characterized by cognitive impairment predominantly attention, reactiveness and integrative function with very subtle clinical manifestations...
November 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27895171/impairment-of-ccr6-and-cxcr3-th-cell-migration-in-hiv-1-infection-is-rescued-by-modulating-actin-polymerization
#13
Valentina Cecchinato, Enos Bernasconi, Roberto F Speck, Michele Proietti, Ulrike Sauermann, Gianluca D'Agostino, Gabriela Danelon, Tanja Rezzonico Jost, Fabio Grassi, Lorenzo Raeli, Franziska Schöni-Affolter, Christiane Stahl-Hennig, Mariagrazia Uguccioni
CD4(+) T cell repopulation of the gut is rarely achieved in HIV-1-infected individuals who are receiving clinically effective antiretroviral therapy. Alterations in the integrity of the mucosal barrier have been indicated as a cause for chronic immune activation and disease progression. In this study, we present evidence that persistent immune activation causes impairment of lymphocytes to respond to chemotactic stimuli, thus preventing their trafficking from the blood stream to peripheral organs. CCR6(+) and CXCR3(+) Th cells accumulate in the blood of aviremic HIV-1-infected patients on long-term antiretroviral therapy, and their frequency in the circulation positively correlates to levels of soluble CD14 in plasma, a marker of chronic immune activation...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27892730/delivery-of-therapeutic-rna-cleaving-oligodeoxyribonucleotides-deoxyribozymes-from-cell-culture-studies-to-clinical-trials
#14
Alesya A Fokina, Boris P Chelobanov, Masayuki Fujii, Dmitry A Stetsenko
Development of efficient in vivo delivery systems remains a major challenge en route to clinical application of antisense technology, including RNA-cleaving molecules such as deoxyribozymes (DNAzymes). The mechanisms of oligonucleotide uptake and trafficking are clearly dependent on cell type and the type of oligonucleotide analogue. It appears likely that each particular disease target would pose its own specific requirements for a delivery method. Areas covered. In this review we will discuss the available options for DNAzyme delivery in vitro and in vivo, outline various exogenous and endogenous strategies that have been, or are still being, developed and ascertain their applicability with emphasis on those methods that are currently being used in clinical trials...
November 28, 2016: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/27888388/cardiac-bin1-cbin1-is-a-regulator-of-cardiac-contractile-function-and-an-emerging-biomarker-of-heart-muscle-health
#15
REVIEW
Kang Zhou, Tingting Hong
In recent decades, a cardiomyocyte membrane scaffolding protein bridging integrator 1 (BIN1) has emerged as a critical multifunctional regulator of transverse-tubule (t-tubule) function and calcium signaling in cardiomyocytes. Encoded by a single gene with 20 exons that are alternatively spliced, more than ten BIN1 protein isoforms are expressed with tissue and disease specificity. The recently discovered cardiac alternatively spliced isoform BIN1 (cBIN1 or BIN1+13+17) plays a crucial role in organizing membrane microfolds within cardiac t-tubules...
November 23, 2016: Science China. Life Sciences
https://www.readbyqxmd.com/read/27883079/a-parasite-derived-68-mer-peptide-ameliorates-autoimmune-disease-in-murine-models-of-type-1-diabetes-and-multiple-sclerosis
#16
Maria E Lund, Judith Greer, Aakanksha Dixit, Raquel Alvarado, Padraig McCauley-Winter, Joyce To, Akane Tanaka, Andrew T Hutchinson, Mark W Robinson, Ann M Simpson, Bronwyn A O'Brien, John P Dalton, Sheila Donnelly
Helminth parasites secrete molecules that potently modulate the immune responses of their hosts and, therefore, have potential for the treatment of immune-mediated human diseases. FhHDM-1, a 68-mer peptide secreted by the helminth parasite Fasciola hepatica, ameliorated disease in two different murine models of autoimmunity, type 1 diabetes and relapsing-remitting immune-mediated demyelination. Unexpectedly, FhHDM-1 treatment did not affect the proliferation of auto-antigen specific T cells or their production of cytokines...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27882921/a-mutation-in-vps15-pik3r4-causes-a-ciliopathy-and-affects-ift20-release-from-the-cis-golgi
#17
Corinne Stoetzel, Séverine Bär, Johan-Owen De Craene, Sophie Scheidecker, Christelle Etard, Johana Chicher, Jennifer R Reck, Isabelle Perrault, Véronique Geoffroy, Kirsley Chennen, Uwe Strähle, Philippe Hammann, Sylvie Friant, Hélène Dollfus
Ciliopathies are a group of diseases that affect kidney and retina among other organs. Here, we identify a missense mutation in PIK3R4 (phosphoinositide 3-kinase regulatory subunit 4, named VPS15) in a family with a ciliopathy phenotype. Besides being required for trafficking and autophagy, we show that VPS15 regulates primary cilium length in human fibroblasts, as well as ciliary processes in zebrafish. Furthermore, we demonstrate its interaction with the golgin GM130 and its localization to the Golgi. The VPS15-R998Q patient mutation impairs Golgi trafficking functions in humanized yeast cells...
November 24, 2016: Nature Communications
https://www.readbyqxmd.com/read/27881733/lysosomal-trafficking-regulator-lyst-links-membrane-trafficking-to-toll-like-receptor-mediated-inflammatory-responses
#18
Andreas Westphal, Weijia Cheng, Jinbo Yu, Guntram Grassl, Martina Krautkrämer, Otto Holst, Niko Föger, Kyeong-Hee Lee
Subcellular compartmentalization of receptor signaling is an emerging principle in innate immunity. However, the functional integration of receptor signaling pathways into membrane trafficking routes and its physiological relevance for immune responses is still largely unclear. In this study, using Lyst-mutant beige mice, we show that lysosomal trafficking regulator Lyst links endolysosomal organization to the selective control of toll-like receptor 3 (TLR3)- and TLR4-mediated proinflammatory responses. Consequently, Lyst-mutant mice showed increased susceptibility to bacterial infection and were largely resistant to endotoxin-induced septic shock...
November 23, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27881675/the-intestinal-copper-exporter-cua-1-is-required-for-systemic-copper-homeostasis-in-caenorhabditis-elegans
#19
Haarin Chun, Anuj Kumar Sharma, Jaekwon Lee, Jefferson Chan, Shang Jia, Byung-Eun Kim
Copper (Cu) plays key catalytic and regulatory roles in biochemical processes essential for normal growth, development, and health. Defects in Cu metabolism cause Menkes and Wilson's disease, myeloneuropathy, and cardiovascular disease and are associated with other pathophysiological states. Consequently, it is critical to understand the mechanisms by which organisms control the acquisition, distribution, and utilization of Cu. The intestinal enterocyte is a key regulatory point for Cu absorption into the body, however the mechanisms by which intestinal cells transport Cu to maintain organismal Cu homeostasis are poorly understood...
November 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27879337/interactions-between-melanin-enzymes-and-their-atypical-recruitment-to-the-secretory-pathway-by-palmitoylation
#20
Srijana Upadhyay, Xinping Xu, Xiaorong Lin
: Melanins are biopolymers that confer coloration and protection to the host organism against biotic or abiotic insults. The level of protection offered by melanin depends on its biosynthesis and its subcellular localization. Previously, we discovered that Aspergillus fumigatus compartmentalizes melanization in endosomes by recruiting all melanin enzymes to the secretory pathway. Surprisingly, although two laccases involved in the late steps of melanization are conventional secretory proteins, the four enzymes involved in the early steps of melanization lack a signal peptide or a transmembrane domain and are thus considered "atypical" secretory proteins...
November 22, 2016: MBio
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