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https://www.readbyqxmd.com/read/28089905/nudix-type-motif-2-contributes-to-cancer-proliferation-through-the-regulation-of-rag-gtpase-mediated-mammalian-target-of-rapamycin-complex-1-localization
#1
Ohman Kwon, Dongoh Kwak, Sang Hoon Ha, Hyeona Jeon, Mangeun Park, Yeonho Chang, Pann-Ghill Suh, Sung Ho Ryu
Lysosomal localization of mammalian target of rapamycin complex 1 (mTORC1) is a critical step for activation of the molecule. Rag GTPases are essential for this translocation. Here, we demonstrate that Nudix-type motif 2 (NUDT2) is a novel positive regulator of mTORC1 activation. Activation of mTORC1 is impaired in NUDT2-silenced cells. Mechanistically, NUDT2 binds to Rag GTPase and controls mTORC1 translocation to the lysosomal membrane. Furthermore, NUDT2-dependent mTORC1 regulation is critical for proliferation of breast cancer cells, as NUDT2-silenced cells arrest in G0/G1 phases...
January 12, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28070494/pure-myopathy-with-enlarged-mitochondria-associated-to-a-new-mutation-in-mtnd2-gene
#2
Alice Zanolini, Ana Potic, Franco Carrara, Eleonora Lamantea, Daria Diodato, Flavia Blasevich, Silvia Marchet, Marina Mora, Francesco Pallotti, Lucia Morandi, Massimo Zeviani, Costanza Lamperti
To date, only few mutations in the mitochondrial DNA (mtDNA)-encoded ND2 subunit of Complex I have been reported, usually presenting a severe phenotype characterized by early onset encephalomyopathy and early death. In this report, we describe a new mutation in the MTND2 gene in a 21-year-old man with a mild myopathic phenotype characterized by exercise intolerance and increased plasma lactate at rest. Electromyography and brain NMR were normal, and no cardiac involvement was present. Muscle biopsy showed a massive presence of ragged red - COX-positive fibres, with enlarged mitochondria containing osmiophilic inclusions...
March 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28034779/a-mitochondrial-membrane-protein-is-a-target-for-rice-ragged-stunt-virus-in-its-insect-vector
#3
Hai-Jian Huang, Cheng-Wen Liu, Xiang Zhou, Chuan-Xi Zhang, Yan-Yuan Bao
Rice ragged stunt virus (RRSV; Reoviridae) is exclusively transmitted by the brown planthopper Nilaparvata lugens in a persistent-propagative manner. It is understood that RNA viral proliferation is associated with the intracellular membranes of the insect host cells. However, the molecular mechanisms of the interaction between the RRSV proliferation and the intracellular membranes remain essentially unknown. It will be of great interest to determine whether RRSV protein(s) directly interact with intracellular membrane components of its host cells...
February 2, 2017: Virus Research
https://www.readbyqxmd.com/read/28002842/efficacy-of-antibody-to-pnag-against-keratitis-caused-by-fungal-pathogens
#4
Ge Zhao, Tanweer S Zaidi, Cagla Bozkurt-Guzel, Tauqeer H Zaidi, James A Lederer, Gregory P Priebe, Gerald B Pier
Purpose: Developing immunotherapies for fungal eye infections is a high priority. We analyzed fungal pathogens for expression of the surface polysaccharide, poly-N-acetyl glucosamine (PNAG), and used a mouse model of ocular keratitis caused by Aspergillus flavus, A. fumigatus, or Fusarium solani to determine if PNAG was an immunotherapy target and requirements for ancillary cellular and molecular immune effectors. Methods: Enzyme-linked immunosorbent assay (ELISA) or immunofluorescence was used to detect PNAG on fungal cells...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27994173/transgenic-overexpression-of-baff-regulates-the-expression-of-immune-related-genes-in-zebrafish-danio-rerio
#5
Li Zhang, Chao Liu, Xin Zhou, Ying Xie, Libo Su, Qi Geng, Binghui Liu, Shufeng Liu
The B-cell activating factor (BAFF) is a member of tumour necrosis factor (TNF) superfamily that specifically regulates B lymphocyte proliferation and survival. Excess BAFF leads to overproduction of antibodies for secretion, anti-dsDNA antibodies and a lupus-like syndrome in mice. To investigate whether transgenic overexpression of the zebrafish BAFF leads to immunoglobulin changes and/or early maturing of the immune system, a Tol2-GFP-2A-BAFF/His recombinant plasmid was constructed by inserting a 2A peptide between the green fluorescent protein (GFP) and BAFF sequences...
December 2016: Journal of Genetics
https://www.readbyqxmd.com/read/27990351/epigenetic-profiling-reveals-a-developmental-decrease-in-promoter-accessibility-during-cortical-maturation-in-vivo
#6
Ishwariya Venkatesh, Matthew T Simpson, Denise M Coley, Murray G Blackmore
Axon regeneration in adult central nervous system (CNS) is limited in part by a developmental decline in the ability of injured neurons to re-express needed regeneration associated genes (RAGs). Adult CNS neurons may lack appropriate pro-regenerative transcription factors, or may display chromatin structure that restricts transcriptional access to RAGs. Here we performed epigenetic profiling around the promoter regions of key RAGs, and found progressive restriction across a time course of cortical maturation...
December 2016: Neuroepigenetics
https://www.readbyqxmd.com/read/27980781/critical-influence-of-the-thymus-on-peripheral-t-cell-homeostasis
#7
Pedro Henrique Oliveira Vianna, Fábio B Canto, Jeane S Nogueira, Caroline Fraga Cabral Gomes Nunes, Adriana César Bonomo, Rita Fucs
INTRODUCTION: A tight balance between regulatory CD4(+)Foxp3(+) (Treg) and conventional CD4(+)Foxp3(-) (Tconv) T cell subsets in the peripheral compartment, maintained stable throughout most of lifetime, is essential for preserving self-tolerance along with efficient immune responses. An excess of Treg cells, described for aged individuals, may critically contribute to their reported immunodeficiency. In this work, we investigated if quantitative changes in thymus emigration may alter the Treg/Tconv homeostasis regardless of the aging status of the peripheral compartment...
December 2016: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/27979968/rag-recombinase-as-a-selective-pressure-for-genome-evolution
#8
D Passagem-Santos, M Bonnet, D Sobral, I Trancoso, J G Silva, V M Barreto, A Athanasiadis, J Demengeot, J B Pereira-Leal
The RAG recombinase is a domesticated transposable element co-opted in jawed vertebrates to drive the process of the so-called V(D)J recombination, which is the hallmark of the adaptive immune system to produce antigen receptors. RAG targets, namely, the Recombination Signal Sequences (RSS), are rather long and degenerated sequences, which highlights the ability of the recombinase to interact with a wide range of target sequences, including outside of antigen receptor loci. The recognition of such cryptic targets by the recombinase threatens genome integrity by promoting aberrant DNA recombination, as observed in lymphoid malignancies...
December 14, 2016: Genome Biology and Evolution
https://www.readbyqxmd.com/read/27973733/new-insights-into-the-evolutionary-origins-of-the-rag-proteins-and-v-d-j-recombination
#9
REVIEW
Lina Marcela Carmona, David G Schatz
The adaptive immune system of jawed vertebrates relies on V(D)J recombination as one of the main processes to generate the diverse array of receptors necessary for the recognition of a wide range of pathogens. The DNA cleavage reaction necessary for the assembly of the antigen receptor genes from an array of potential gene segments is mediated by the Recombination Activating Gene proteins RAG1 and RAG2. The RAG proteins have been proposed to originate from a transposable element (TE) as they share mechanistic and structural similarities with several families of transposases and are themselves capable of mediating transposition...
December 14, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27931510/generation-of-equine-induced-pluripotent-stem-cells-and-analysis-of-their-therapeutic-potential-for-muscle-injuries
#10
Eun-Mi Lee, Ah-Young Kim, Eun-Joo Lee, Jin-Kyu Park, Se-Il Park, Ssang-Goo Cho, Hong Kyun Kim, Shin-Yoon Kim, Kyu-Shik Jeong
Horse health has become a major concern with the expansion of horse-related industries and sports; the importance of healthy muscles for horse performance and daily activities is undisputed. Here we generated equine-induced pluripotent stem cells (E-iPSCs) by reprogramming equine adipose-derived stem cells (E-ADSCs) into iPSCs using a polycistronic lentiviral vector encoding four transcription factors (i.e., Oct4, Sox2, Klf4, and c-Myc) and then examined their pluripotent characteristics. Subsequently, established E-iPSCs were transplanted into muscle-injured Rag/mdx mice...
November 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27924841/virus-altered-rice-attractiveness-to-planthoppers-is-mediated-by-volatiles-and-related-to-virus-titre-and-expression-of-defence-and-volatile-biosynthesis-genes
#11
Guanghua Lu, Tong Zhang, Yuange He, Guohui Zhou
Viruses may induce changes in plant hosts and vectors to enhance their transmission. The white-backed planthopper (WBPH) and brown planthopper (BPH) are vectors of Southern rice black-streaked dwarf virus (SRBSDV) and Rice ragged stunt virus (RRSV), respectively, which cause serious rice diseases. We herein describe the effects of SRBSDV and RRSV infections on host-selection behaviour of vector and non-vector planthoppers at different disease stages. The Y-tube olfactometer choice and free-choice tests indicated that SRBSDV and RRSV infections altered the attractiveness of rice plants to vector and non-vector planthoppers...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27918235/comprehensive-mapping-of-5-hydroxymethylcytosine-epigenetic-dynamics-in-axon-regeneration
#12
Yong-Hwee Eddie Loh, Andrew Koemeter-Cox, Mattéa Finelli, Li Shen, Roland H Friedel, Hongyan Zou
In contrast to central nervous system neurons, dorsal root ganglia (DRG) neurons can switch to a regenerative state after peripheral axotomy. In a screen for chromatin regulators of the regenerative responses in this conditioning lesion paradigm, we identified Tet methylcytosine dioxygenase 3 (Tet3) as upregulated in DRG neurons, along with increased 5-hydroxymethylcytosine (5 hmC). We generated genome-wide 5 hmC maps in adult DRG, which revealed that peripheral and central axotomy (leading to no regenerative effect) triggered differential 5 hmC changes that are associated with distinct signaling pathways...
December 5, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27907250/the-transcriptional-co-activator-bob1-is-associated-with-pathologic-b-cell-responses-in-autoimmune-tissue-inflammation
#13
Maria J Levels, Melissa N Van Tok, Tineke Cantaert, Juan D Cañete, Frans G M Kroese, Kristine Germar, Hergen Spits, Dominique L P Baeten, Nataliya G Yeremenko
OBJECTIVE: The molecular mechanisms steering abnormal B cell responses in autoimmune diseases remain poorly understood. In this study we aimed to identify molecular switches controlling pathological B cell responses in rheumatoid arthritis (RA). METHODS: Candidate molecules were identified by gene expression profiling of RA synovitis and validated by qPCR and immunohistochemistry. B cell-specific expression was confirmed by immunofluorescence, immunoblotting and flow cytometry...
December 1, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27890096/entrance-and-exit-wounds-of-high-velocity-bullet-an-autopsy-analysis-in-the-event-of-dispersing-the-mass-rally-in-bangkok-thailand-may-2010
#14
Vichan Peonim, Smith Srisont, Jitta Udnoon, Sompong Wongwichai, Arisa Thapon, Wisarn Worasuwannarak
Fatal mass casualties by high velocity bullets (HVBs) are rare events in peaceful countries. This study presents 27 forensic autopsy cases with 32 shots fired by 5.56×45mm. HVB (M-16 rifle bullets) during the dispersing the mass rally in Bangkok Thailand, May 2010. It was found that twenty-three (71.88%) typical entrance HVB wounds had round sizes less than the bullet diameters. Most entrance wounds had microtears but no collar abrasion since a HVB has a small streamlined spitzer tip and full metal jacket...
November 2016: Legal Medicine
https://www.readbyqxmd.com/read/27889897/growth-differentiation-factor-15-is-a-novel-diagnostic-biomarker-of-mitochondrial-diseases
#15
Xinbo Ji, Lizhen Zhao, Kunqian Ji, Yuying Zhao, Wei Li, Rui Zhang, Ying Hou, Jianqiang Lu, Chuanzhu Yan
The present study aimed to investigate whether serum growth differentiation factor 15 concentration is a valuable and reliable diagnostic biomarker of mitochondrial diseases. We examined consecutive patients with mitochondrial diseases, in comparison with patients with non-mitochondrial disease neuromuscular disorders and healthy controls. The serum concentrations of growth differentiation factor 15 were measured by ELISA, and compared with those of FGF21, lactate, and creatine kinase. We also evaluated the correlations between growth differentiation factor 15 concentrations and the Newcastle Mitochondrial Disease Adult Scale, numbers of ragged-red fibers, and COX-negative fibers in the biopsied muscles...
November 26, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27883081/v-d-j-recombination-process-and-the-pre-b-to-immature-b-cells-transition-are-altered-in-fanca-mice
#16
Thuy Vy Nguyen, Patrycja Pawlikowska, Virginie Firlej, Filippo Rosselli, Saïd Aoufouchi
B-lymphocytes in the bone marrow (BM) must generate a functional B-cell receptor and overcome the negative selection induced by reactivity with autoantigens. Two rounds of DNA recombination are required for the production of functional immunoglobulin heavy (Ig-HCs) and light (LCs) chains necessary for the continuation of B-lymphocyte development in the BM. Both rounds depend on the joint action of recombination activating gene-1 (RAG-1) and RAG-2 endonucleases with the DNA non-homologous end-joining pathway...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27883065/cycles-of-circadian-illuminance-are-sufficient-to-entrain-and-maintain-circadian-locomotor-rhythms-in-drosophila
#17
Eunjoo Cho, Ji Hye Oh, Euna Lee, Young Rag Do, Eun Young Kim
Light at night disrupts the circadian clock and causes serious health problems in the modern world. Here, we show that newly developed four-package light-emitting diodes (LEDs) can provide harmless lighting at night. To quantify the effects of light on the circadian clock, we employed the concept of circadian illuminance (CIL). CIL represents the amount of light weighted toward the wavelengths to which the circadian clock is most sensitive, whereas visual illuminance (VIL) represents the total amount of visible light...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27880903/mirnas-are-essential-for-the-regulation-of-the-pi3k-akt-foxo-pathway-and-receptor-editing-during-b%C3%A2-cell-maturation
#18
Maryaline Coffre, David Benhamou, David Rieß, Lili Blumenberg, Valentina Snetkova, Marcus J Hines, Tirtha Chakraborty, Sofia Bajwa, Kari Jensen, Mark M W Chong, Lelise Getu, Gregg J Silverman, Robert Blelloch, Dan R Littman, Dinis Calado, Doron Melamed, Jane A Skok, Klaus Rajewsky, Sergei B Koralov
B cell development is a tightly regulated process dependent on sequential rearrangements of immunoglobulin loci that encode the antigen receptor. To elucidate the role of microRNAs (miRNAs) in the orchestration of B cell development, we ablated all miRNAs at the earliest stage of B cell development by conditionally targeting the enzymes critical for RNAi in early B cell precursors. Absence of any one of these enzymes led to a block at the pro- to pre-B cell transition due to increased apoptosis and a failure of pre-B cells to proliferate...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27863852/the-rag-recombinase-beyond-breaking
#19
Chloé Lescale, Ludovic Deriano
DNA double-strand breaks (DSBs) are commonly seen as lesions that threaten genome integrity and contribute to cancer and aging processes. However, in the context of antigen receptor gene assembly, known as V(D)J recombination, DSBs are obligatory intermediates that allow the establishment of genetic diversity and adaptive immunity. V(D)J recombination is initiated when the lymphoid-restricted recombination-activating genes RAG1 and RAG2 are expressed and form a site-specific endonuclease (the RAG nuclease or RAG recombinase)...
November 15, 2016: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/27863423/cancer-cell-ccl5-mediates-bone-marrow-independent-angiogenesis-in-breast-cancer
#20
Michael John Sax, Christin Gasch, Vineel Rag Athota, Ruth Freeman, Parisa Rasighaemi, David Elton Westcott, Christopher John Day, Iva Nikolic, Benjamin Elsworth, Ming Wei, Kelly Rogers, Alexander Swarbrick, Vivek Mittal, Normand Pouliot, Albert Sleiman Mellick
It has recently been suggested that the chemokine receptor (CCR5) is required for bone marrow (BM) derived endothelial progenitor cell (EPC) mediated angiogenesis. Here we show that suppression of either cancer cell produced CCL5, or host CCR5 leads to distinctive vascular and tumor growth defects in breast cancer. Surprisingly, CCR5 restoration in the BM alone was not sufficient to rescue the wild type phenotype, suggesting that impaired tumor growth associated with inhibiting CCL5/CCR5 is not due to defects in EPC biology...
November 16, 2016: Oncotarget
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