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https://www.readbyqxmd.com/read/28549128/atad3-gene-cluster-deletions-cause-cerebellar-dysfunction-associated-with-altered-mitochondrial-dna-and-cholesterol-metabolism
#1
Radha Desai, Ann E Frazier, Romina Durigon, Harshil Patel, Aleck W Jones, Ilaria Dalla Rosa, Nicole J Lake, Alison G Compton, Hayley S Mountford, Elena J Tucker, Alice L R Mitchell, Deborah Jackson, Abdul Sesay, Miriam Di Re, Lambert P van den Heuvel, Derek Burke, David Francis, Sebastian Lunke, George McGillivray, Simone Mandelstam, Fanny Mochel, Boris Keren, Claude Jardel, Anne M Turner, P Ian Andrews, Jan Smeitink, Johannes N Spelbrink, Simon J Heales, Masakazu Kohda, Akira Ohtake, Kei Murayama, Yasushi Okazaki, Anne Lombès, Ian J Holt, David R Thorburn, Antonella Spinazzola
Although mitochondrial disorders are clinically heterogeneous, they frequently involve the central nervous system and are among the most common neurogenetic disorders. Identifying the causal genes has benefited enormously from advances in high-throughput sequencing technologies; however, once the defect is known, researchers face the challenge of deciphering the underlying disease mechanism. Here we characterize large biallelic deletions in the region encoding the ATAD3C, ATAD3B and ATAD3A genes. Although high homology complicates genomic analysis of the ATAD3 defects, they can be identified by targeted analysis of standard single nucleotide polymorphism array and whole exome sequencing data...
June 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28543362/commd1-a-multifunctional-regulatory-protein
#2
Mario Riera Romo
The COMMD Protein Family is highly conserved among multicellular eukaryotic organisms and many orthologs of human COMMD genes have been found in different species of plants, invertebrates, lower vertebrates and mammals. COMMD1 is the best characterized member of the family and is conserved among vertebrates. This protein represents a pleiotropic factor involved in the regulation of many cellular and physiological processes that include copper and cholesterol homeostasis, ionic transport, oxidative stress, protein aggregation, protein trafficking, NF-κB-mediated transcription, hypoxia induced transcription, DNA damage response and oncogenesis...
May 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28543308/exocytic-trafficking-pathways-in-plants-why-and-how-they-are-redirected
#3
REVIEW
Takehiko Kanazawa, Takashi Ueda
The membrane trafficking system is responsible for precise transportation and localization of proteins, lipids, and polysaccharides among single membrane-bound organelles, the plasma membrane, and the extracellular space. While the exocytic trafficking pathway is considered to be a default transport pathway in many organisms, including land plants, research has shown that evolutionary processes led to an increase in the number of machinery components involved in the plant exocytic pathway. This study provides an overview of the diversification of exocytic trafficking pathways in plants, which mediate the formation and maintenance of cell polarity, interaction with symbiotic and pathogenic microbes, and cytokinesis...
May 25, 2017: New Phytologist
https://www.readbyqxmd.com/read/28543168/a-new-tool-to-tackle-the-opioid-epidemic-description-utility-and-results-from-the-maine-diversion-alert-program
#4
Brian J Piper, Clare E Desrosiers, Harriet C Fisher, Kenneth L McCall, Stephanie D Nichols
STUDY OBJECTIVE: The opioid epidemic continues to impact the United States, and new strategies are needed to combat this epidemic. The objective of this study was to analyze 2015 drug arrest data from Maine's Diversion Alert program (diversionalert. org), compare arrest data between the first quarters of 2015 and 2016, and provide an analysis of the sex differences in the arrests as well as information about DA use. STUDY DESIGN: A population-based, descriptive study using data from the Maine Diversion Alert Program...
May 19, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28538737/lymphatic-endothelial-s1p-promotes-mitochondrial-function-and-survival-in-naive-t-cells
#5
Alejandra Mendoza, Victoria Fang, Cynthia Chen, Madhavika Serasinghe, Akanksha Verma, James Muller, V Sai Chaluvadi, Michael L Dustin, Timothy Hla, Olivier Elemento, Jerry E Chipuk, Susan R Schwab
Effective adaptive immune responses require a large repertoire of naive T cells that migrate throughout the body, rapidly identifying almost any foreign peptide. Because the production of T cells declines with age, naive T cells must be long-lived. However, it remains unclear how naive T cells survive for years while constantly travelling. The chemoattractant sphingosine 1-phosphate (S1P) guides T cell circulation among secondary lymphoid organs, including spleen, lymph nodes and Peyer's patches, where T cells search for antigens...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28537421/glutathione-glutaredoxins-and-iron
#6
Carsten Berndt, Christopher Horst Lillig
SIGNIFICANCE: Glutathione is the most abundant cellular low molecular weight thiol in the majority of organisms in all kingdoms of life. Therefore, functions of glutathione and disturbed regulation of its concentration are associated with numerous physiological and pathological situations. Recent advances: The function of glutathione as redox buffer or antioxidant is increasingly being questioned. New functions, especially functions connected to the cellular iron homeostasis were elucidated...
May 24, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28529840/adoptive-cell-therapy-with-tregs-to-improve-transplant-outcomes-the-promise-and-the-stumbling-blocks
#7
Mohamed B Ezzelarab, Angus W Thomson
The contribution of regulatory T cells (Treg) to the induction and maintenance of tolerance is well-recognized in rodents and may contribute to long-term human organ allograft survival. The therapeutic efficacy of adoptively-transferred Treg in promoting tolerance to organ allografts is well-recognized in mouse models. Early phase 1/2 clinical studies of Treg therapy have been conducted in patients with type-1 (autoimmune) diabetes and refractory Crohn's disease, and for inhibition of graft-versus-host disease following bone marrow transplantation with proven safety...
December 2016: Current Transplantation Reports
https://www.readbyqxmd.com/read/28529514/two-rab5-homologs-are-essential-for-the-development-and-pathogenicity-of-the-rice-blast-fungus-magnaporthe-oryzae
#8
Cheng D Yang, Xie Dang, Hua W Zheng, Xiao F Chen, Xiao L Lin, Dong M Zhang, Yakubu S Abubakar, Xin Chen, Guodong Lu, Zonghua Wang, Guangpu Li, Jie Zhou
The rice blast fungus, Magnaporthe oryzae, infects many economically important cereal crops, particularly rice. It has emerged as an important model organism for studying the growth, development, and pathogenesis of filamentous fungi. RabGTPases are important molecular switches in regulation of intracellular membrane trafficking in all eukaryotes. MoRab5A and MoRab5B are Rab5 homologs in M. oryzae, but their functions in the fungal development and pathogenicity are unknown. In this study, we have employed a genetic approach and demonstrated that both MoRab5A and MoRab5B are crucial for vegetative growth and development, conidiogenesis, melanin synthesis, vacuole fusion, endocytosis, sexual reproduction, and plant pathogenesis in M...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28526681/adoptive-transfer-of-phosphoantigen-specific-%C3%AE-%C3%AE-t-cell-subset-attenuates-mycobacterium-tuberculosis-infection-in-nonhuman-primates
#9
Arwa Qaqish, Dan Huang, Crystal Y Chen, Zhuoran Zhang, Richard Wang, Shengpu Li, Enzhuoa Yang, Yang Lu, Michelle H Larsen, William R Jacobs, Lixia Qian, James Frencher, Ling Shen, Zheng W Chen
The dominant Vγ2Vδ2 T cell subset recognizes phosphoantigen and exists only in humans and nonhuman primates. Despite the discovery of γδ T cells >30 y ago, a proof-of-concept study has not been done to prove the principle that the Vγ2Vδ2 T cell subset is protective against Mycobacterium tuberculosis and other infections. In this study, we used an adoptive cell-transfer strategy to define the protective role of Vγ2Vδ2 T cells in a primate tuberculosis (TB) model. Vγ2Vδ2 T cells for adoptive transfer displayed central/effector memory and mounted effector functions, including the production of anti-M...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28524754/arf-gtpase-interplay-with-rho-gtpases-in-regulation-of-the-actin-cytoskeleton
#10
Vikash Singh, Anthony C Davidson, Peter J Hume, Daniel Humphreys, Vassilis Koronakis
The Arf and Rho subfamilies of small GTPases are nucleotide-dependent molecular switches that act as master regulators of vesicular trafficking and the actin cytoskeleton organization. Small GTPases control cell processes with high fidelity by acting through distinct repertoires of binding partners called effectors. While we understand a great deal about how these GTPases act individually, relatively little is known about how they cooperate, especially in the control of effectors. This review highlights how Arf GTPases collaborate with Rac1 to regulate actin cytoskeleton dynamics at the membrane via recruiting and activating the Wave Regulatory Complex (WRC), a Rho effector that underpins lamellipodia formation and macropinocytosis...
May 19, 2017: Small GTPases
https://www.readbyqxmd.com/read/28521013/flagellin-peptide-flg22-gains-access-to-long-distance-trafficking-in-arabidopsis-via-its-receptor-fls2
#11
Joanna Jelenska, Sandra M Davern, Robert F Standaert, Saed Mirzadeh, Jean T Greenberg
Diverse pathogen-derived molecules, such as bacterial flagellin and its conserved peptide flg22, are recognized in plants via plasma membrane receptors and induce both local and systemic immune responses. The fate of such ligands was unknown: whether and by what mechanism(s) they enter plant cells and whether they are transported to distal tissues. We used biologically active fluorophore and radiolabeled peptides to establish that flg22 moves to distal organs with the closest vascular connections. Remarkably, entry into the plant cell via endocytosis together with the FLS2 receptor is needed for delivery to vascular tissue and long-distance transport of flg22...
March 1, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28512289/a-genetic-screen-in-combination-with-biochemical-analysis-in-saccharomyces-cerevisiae-indicates-that-phenazine-1-carboxylic-acid-is-harmful-to-vesicular-trafficking-and-autophagy
#12
Xiaolong Zhu, Yan Zeng, Xiu Zhao, Shenshen Zou, Ya-Wen He, Yongheng Liang
The environmentally friendly antibiotic phenazine-1-carboxylic acid (PCA) protects plants, mammals and humans effectively against various fungal pathogens. However, the mechanism by which PCA inhibits or kills fungal pathogens is not fully understood. We analyzed the effects of PCA on the growth of two fungal model organisms, Saccharomyces cerevisiae and Candida albicans, and found that PCA inhibited yeast growth in a dose-dependent manner which was inversely dependent on pH. In contrast, the commonly used antibiotic hygromycin B acted in a dose-dependent manner as pH increased...
May 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28506987/development-of-the-larval-lymphatic-system-in-the-zebrafish
#13
Hyun Min Jung, Daniel Castranova, Matthew R Swift, Van N Pham, Marina Venero Galanternik, Sumio Isogai, Matthew G Butler, Timothy S Mulligan, Brant M Weinstein
The lymphatic vascular system is a hierarchically organized complex network essential for tissue fluid homeostasis, immune trafficking, and absorption of dietary fats in the human body. Despite its importance, the assembly of the lymphatic network is still not fully understood. The zebrafish is a powerful model organism that enables study of lymphatic vessel development using high-resolution imaging and sophisticated genetic and experimental manipulation. Although several studies have described early lymphatic development in the fish, lymphatic development at later stages has not been completely elucidated...
May 15, 2017: Development
https://www.readbyqxmd.com/read/28495413/the-central-vacuole-of-the-diatom-phaeodactylum-tricornutum-identification-of-new-vacuolar-membrane-proteins-and-of-a-functional-di-leucine-based-targeting-motif
#14
Viktoria Schreiber, Josefine Dersch, Katharina Puzik, Oliver Bäcker, Xiaojuan Liu, Simone Stork, Julian Schulz, Thomas Heimerl, Andreas Klingl, Stefan Zauner, Uwe G Maier
Diatoms are unicellular organisms evolved by secondary endosymbiosis. Although studied in many aspects, the functions of vacuolar-like structures of these organisms are rarely investigated. One of these structures is a dominant central vacuole-like compartment with a marbled phenotype, which is supposed to represent a chrysolaminarin-storing and carbohydrate mobilization compartment. However, other functions as well as targeting of proteins to this compartment are not shown experimentally. In order to study trafficking of membrane proteins to the vacuolar membrane, we scanned the genome for intrinsic vacuolar membrane proteins and used one representative for targeting studies...
March 15, 2017: Protist
https://www.readbyqxmd.com/read/28490590/the-c-terminus-of-the-herpes-simplex-virus-pul25-protein-is-required-for-release-of-viral-genomes-from-capsids-bound-to-nuclear-pores
#15
Jamie B Huffman, Gina R Daniel, Erik Falck-Pedersen, Alexis Huet, Greg A Smith, James F Conway, Fred L Homa
The herpes simplex virus (HSV) capsid is released into the cytoplasm after fusion of viral and host membranes, whereupon dynein-dependent trafficking along microtubules targets it to the nuclear envelope. Binding of the capsid to the nuclear pore complex (NPC) is mediated by the capsid protein pUL25 and the capsid-tethered tegument protein pUL36. Temperature-sensitive mutants in both pUL25 and pUL36 dock at the NPC but fail to release DNA. The uncoating reaction has been difficult to study due to the rapid release of the genome once the capsid interacts with the nuclear pore...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28490503/entropic-forces-drive-self-organization-and-membrane-fusion-by-snare-proteins
#16
Hakhamanesh Mostafavi, Sathish Thiyagarajan, Benjamin S Stratton, Erdem Karatekin, Jason M Warner, James E Rothman, Ben O'Shaughnessy
SNARE proteins are the core of the cell's fusion machinery and mediate virtually all known intracellular membrane fusion reactions on which exocytosis and trafficking depend. Fusion is catalyzed when vesicle-associated v-SNAREs form trans-SNARE complexes ("SNAREpins") with target membrane-associated t-SNAREs, a zippering-like process releasing ∼65 kT per SNAREpin. Fusion requires several SNAREpins, but how they cooperate is unknown and reports of the number required vary widely. To capture the collective behavior on the long timescales of fusion, we developed a highly coarse-grained model that retains key biophysical SNARE properties such as the zippering energy landscape and the surface charge distribution...
May 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28487419/membrane-depolarization-activates-bk-channels-through-rock-mediated-%C3%AE-1-subunit-surface-trafficking-to-limit-vasoconstriction
#17
M Dennis Leo, Xue Zhai, Padmapriya Muralidharan, Korah P Kuruvilla, Simon Bulley, Frederick A Boop, Jonathan H Jaggar
Membrane depolarization of smooth muscle cells (myocytes) in the small arteries that regulate regional organ blood flow leads to vasoconstriction. Membrane depolarization also activates large-conductance calcium (Ca(2+))-activated potassium (BK) channels, which limits Ca(2+) channel activity that promotes vasoconstriction, thus leading to vasodilation. We showed that in human and rat arterial myocytes, membrane depolarization rapidly increased the cell surface abundance of auxiliary BK β1 subunits but not that of the pore-forming BKα channels...
May 9, 2017: Science Signaling
https://www.readbyqxmd.com/read/28485685/protein-palmitoylation-palmitoyltransferases-and-their-specificity
#18
Sabina Tabaczar, Aleksander Czogalla, Joanna Podkalicka, Agnieszka Biernatowska, Aleksander F Sikorski
A plethora of novel information has emerged over the past decade regarding protein lipidation. The reversible attachment of palmitic acid to cysteine residues, termed S-palmitoylation, has focused a special attention. This is mainly due to the unique role of this modification in the regulation of protein trafficking and function. A large family of protein acyltransferases (PATs) containing a conserved aspartate-histidine-histidine-cysteine motif use ping-pong kinetic mechanism to catalyze S-palmitoylation of a substrate protein...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28481649/new-perspectives-on-the-roles-of-abl-tyrosine-kinase-in-axon-patterning
#19
Ramakrishnan Kannan, Edward Giniger
The Abelson tyrosine kinase (Abl) lies at the heart of one of the small set of ubiquitous, conserved signal transduction pathways that do much of the work of development and physiology. Abl signaling is essential to epithelial integrity, motility of autonomous cells such as blood cells, and axon growth and guidance in the nervous system. However, though Abl was one of the first of these conserved signaling machines to be identified, it has been among the last to have its essential architecture elucidated. Here we will first discuss some of the challenges that long delayed the dissection of this pathway, and what they tell us about the special problems of investigating dynamic processes like motility...
May 8, 2017: Fly
https://www.readbyqxmd.com/read/28481347/membrane-curvature-regulates-ligand-specific-membrane-sorting-of-gpcrs-in-living-cells
#20
Kadla R Rosholm, Natascha Leijnse, Anna Mantsiou, Vadym Tkach, Søren L Pedersen, Volker F Wirth, Lene B Oddershede, Knud J Jensen, Karen L Martinez, Nikos S Hatzakis, Poul Martin Bendix, Andrew Callan-Jones, Dimitrios Stamou
The targeted spatial organization (sorting) of Gprotein-coupled receptors (GPCRs) is essential for their biological function and often takes place in highly curved membrane compartments such as filopodia, endocytic pits, trafficking vesicles or endosome tubules. However, the influence of geometrical membrane curvature on GPCR sorting remains unknown. Here we used fluorescence imaging to establish a quantitative correlation between membrane curvature and sorting of three prototypic class A GPCRs (the neuropeptide Y receptor Y2, the β1 adrenergic receptor and the β2 adrenergic receptor) in living cells...
May 8, 2017: Nature Chemical Biology
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