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https://www.readbyqxmd.com/read/28806404/rig-i-and-il-6-are-negative-feedback-regulators-of-sting-induced-by-double-stranded-dna
#1
Xueling Wu, Jun Yang, Tao Na, Kehua Zhang, Andrew M Davidoff, Bao-Zhu Yuan, Youchun Wang
The stimulator of interferon genes (STING) protein has emerged as a critical signal transduction molecule in the innate immune response. Sustained activation of the STING signaling induced by cytosolic DNA has been considered to be the cause of a variety of autoimmune diseases characterized by uncontrolled inflammation. Therefore, it is important to understand the molecular basis of the regulation of STING signaling pathway. Here we demonstrate that the STING protein undergoes a proteasome-mediated degradation in human diploid cell (HDC) lines including MRC-5 following the transfection of double-stranded DNA (dsDNA)...
2017: PloS One
https://www.readbyqxmd.com/read/28799229/sitagliptin-mediated-preservation-of-endothelial-progenitor-cell-function-via-augmenting-autophagy-enhances-ischaemic-angiogenesis-in-diabetes
#2
Xiaozhen Dai, Jun Zeng, Xiaoqing Yan, Qian Lin, Kai Wang, Jing Chen, Feixia Shen, Xuemei Gu, Yuehui Wang, Jun Chen, Kejian Pan, Lu Cai, Kupper A Wintergerst, Yi Tan
Recently, the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin, a major anti-hyperglycaemic agent, has received substantial attention as a therapeutic target for cardiovascular diseases via enhancing the number of circulating endothelial progenitor cells (EPCs). However, the direct effects of sitagliptin on EPC function remain elusive. In this study, we evaluated the proangiogenic effects of sitagliptin on a diabetic hind limb ischaemia (HLI) model in vivo and on EPC culture in vitro. Treatment of db/db mice with sitagliptin (Januvia) after HLI surgery efficiently enhanced ischaemic angiogenesis and blood perfusion, which was accompanied by significant increases in circulating EPC numbers...
August 10, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28796254/sunitinib-induces-genomic-instability-of-renal-carcinoma-cells-through-affecting-the-interaction-of-lc3-ii-and-parp-1
#3
Siyuan Yan, Ling Liu, Fengxia Ren, Quan Gao, Shanshan Xu, Bolin Hou, Yange Wang, Xuejun Jiang, Yongsheng Che
Deficiency of autophagy has been linked to increase in nuclear instability, but the role of autophagy in regulating the formation and elimination of micronuclei, a diagnostic marker for genomic instability, is limited in mammalian cells. Utilizing immunostaining and subcellular fractionation, we found that either LC3-II or the phosphorylated Ulk1 localized in nuclei, and immunoprecipitation results showed that both LC3 and Unc-51-like kinase 1 (Ulk1) interacted with γ-H2AX, a marker for the DNA double-strand breaks (DSB)...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28780683/title-v-workforce-development-in-the-era-of-health-transformation
#4
Lewis Margolis, Amy Mullenix, Alexsandra A Apostolico, Lacy M Fehrenbach, Dorothy Cilenti
Purpose The National Maternal and Child Health Workforce Development Center at UNC Chapel Hill (the Center), funded by the Maternal and Child Health Bureau, provides Title V state/jurisdiction leaders and staff and partners from other sectors with opportunities to develop skills in quality improvement, systems mapping and analysis, change management, and strategies to enhance access to care to leverage and implement health transformation opportunities to improve the health of women and children. Description Since 2013, the Center has utilized a variety of learning platforms to reach state and jurisdiction Title V leaders...
August 5, 2017: Maternal and Child Health Journal
https://www.readbyqxmd.com/read/28780166/5-desmethylnobiletin-augments-synaptic-ach-levels-and-nicotinic-ach-receptor-activity-a-potential-candidate-for-alleviation-of-cholinergic-dysfunction
#5
Shalini Trivedi, Priyanka Maurya, Shreesh Raj Sammi, Madan Mohan Gupta, Rakesh Pandey
Cholinergic function is compromised in plethora of neurodegenerative disorders especially Alzheimer's disease. Increasing acetylcholine (ACh) levels has been the mainstay in majority of the therapeutic regimens, accepted for management of disease. The present study investigates the efficacy of 5-Desmethylnobiletin (DN), a polymethoxyflavone in augmenting cholinergic function using Caenorhabditis elegans as a model organism. The studies revealed significant elevation in cholinergic transmission mediated through increased levels of ACh and activity of nicotinic acetylcholine receptors (nAChR)...
August 3, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28777374/high-mobility-group-a1-protein-modulates-autophagy-in-cancer-cells
#6
Andrea Conte, Simona Paladino, Gaia Bianco, Dominga Fasano, Raffaele Gerlini, Mara Tornincasa, Maurizio Renna, Alfredo Fusco, Donatella Tramontano, Giovanna Maria Pierantoni
High Mobility Group A1 (HMGA1) is an architectural chromatin protein whose overexpression is a feature of malignant neoplasias with a causal role in cancer initiation and progression. HMGA1 promotes tumor growth by several mechanisms, including increase of cell proliferation and survival, impairment of DNA repair and induction of chromosome instability. Autophagy is a self-degradative process that, by providing energy sources and removing damaged organelles and misfolded proteins, allows cell survival under stress conditions...
August 4, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28772122/a-c1-c2-module-in-munc13-inhibits-calcium-dependent-neurotransmitter-release
#7
Francesco Michelassi, Haowen Liu, Zhitao Hu, Jeremy S Dittman
Almost all known forms of fast chemical synaptic transmission require the synaptic hub protein Munc13. This essential protein has also been implicated in mediating several forms of use-dependent plasticity, but the mechanisms by which it controls vesicle fusion and plasticity are not well understood. Using the C. elegans Munc13 ortholog UNC-13, we show that deletion of the C2B domain, the most highly conserved domain of Munc13, enhances calcium-dependent exocytosis downstream of vesicle priming, revealing a novel autoinhibitory role for the C2B...
August 2, 2017: Neuron
https://www.readbyqxmd.com/read/28767038/microtubule-dependent-ribosome-localization-in-c-elegans-neurons
#8
Kentaro Noma, Alexandr Goncharov, Mark H Ellisman, Yishi Jin
Subcellular localization of ribosomes defines the location and capacity for protein synthesis. Methods for in vivo visualizing ribosomes in multicellular organisms are desirable in mechanistic investigations of the cell biology of ribosome dynamics. Here, we developed an approach using split GFP for tissue-specific visualization of ribosomes in Caenorhabditis elegans. Labeled ribosomes are detected as fluorescent puncta in the axons and synaptic terminals of specific neuron types, correlating with ribosome distribution at the ultrastructural level...
August 2, 2017: ELife
https://www.readbyqxmd.com/read/28758335/discordant-rapid-hiv-tests-lessons-from-a-low-resource-community
#9
A A Adetunji, M A Kuti, R A Audu, S A Muyibi, M Imhansoloeva, O A Mosuro, E A Solanke, O M Akpa, A E Irabor, Mma Ladipo, B Berzins, K Robertson, A Ogunniyi, I F Adewole, B O Taiwo
OBJECTIVES: HIV rapid antibody tests are widely used in Africa, but dual testing sometimes produces discordant results. It is not clear if discordant rapid HIV tests should always heighten suspicion by frontline health workers that early HIV infection is present. Some studies have reported that discordant rapid tests have value for identifying early HIV infection in high HIV prevalence populations. It is not known if rapid test performance influenced this conclusion, or if this observation will hold true for low HIV prevalence populations...
July 31, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28747499/effects-of-the-inner-nuclear-membrane-proteins-sun1-unc-84a-and-sun2-unc-84b-on-the-early-steps-of-hiv-1-infection
#10
Torsten Schaller, Lorenzo Bulli, Darja Pollpeter, Gilberto Betancor, Juliane Kutzner, Luis Apolonia, Nikolas Herold, Robin Burk, Michael H Malim
Human immunodeficiency virus type 1 (HIV-1) infection of dividing and non-dividing cells involves regulatory interactions with the nuclear pore complex (NPC), followed by translocation to the nucleus and preferential integration into genomic areas in proximity to the inner nuclear membrane (INM). To identify host proteins that may contribute to these processes, we performed an overexpression screen of known membrane-associated NE proteins. We found that the integral transmembrane proteins SUN1/UNC84A and SUN2/UNC84B are potent or modest inhibitors of HIV-1 infection, respectively, and that suppression corresponds to defects in the accumulation of viral cDNA in the nucleus...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28741869/increased-baseline-runx2-caspase-3-and-p21-gene-expressions-in-the-peripheral-blood-of-disease-modifying-anti-rheumatic-drug-na%C3%A3-ve-rheumatoid-arthritis-patients-are-associated-with-improved-clinical-response-to-methotrexate-therapy
#11
Elena V Tchetina, Natalia V Demidova, Galina A Markova, Elena A Taskina, Svetlana I Glukhova, Dmitry E Karateev
OBJECTIVE: To investigate the potential of the baseline gene expression in the whole blood of disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis (RA) patients for predicting the response to methotrexate (MTX) treatment. METHODS: Twenty-six control subjects and 40 RA patients were examined. Clinical, immunological and radiographic parameters were assessed before and after 24 months of follow-up. The gene expressions in the whole blood were measured using real-time reverse transcription polymerase chain reaction...
July 25, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28729213/physical-exercise-increases-sestrin-2-protein-levels-and-induces-autophagy-in-the-skeletal-muscle-of-old-mice
#12
Luciene Lenhare, Barbara M Crisol, Vagner R R Silva, Carlos K Katashima, André V Cordeiro, Karina D Pereira, Augusto D Luchessi, Adelino S R da Silva, Dennys E Cintra, Leandro P Moura, José R Pauli, Eduardo R Ropelle
Sestrins and autophagy deficiencies are associated with several aging-related organic dysfunctions and metabolic disorders. Here we evaluate the effects of acute exercise on Sestrin 2 (Sesn2) protein content and autophagy markers in the skeletal muscle of experimental models of aging. Twenty-four months-old C57BL/6J male mice were submitted to a single bout of swimming exercise and the gastrocnemius muscle was evaluated by Western blot. Transcriptomic and phenotypic analysis were also performed by using strains of genetically-diverse BXD mice...
July 17, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28724767/integrity-of-the-linker-of-nucleoskeleton-and-cytoskeleton-is-required-for-efficient-herpesvirus-nuclear-egress
#13
Barbara G Klupp, Teresa Hellberg, Harald Granzow, Kati Franzke, Beatriz Dominguez Gonzalez, Rose Goodchild, Thomas C Mettenleiter
Herpesvirus capsids assemble in the nucleus while final virion maturation proceeds in the cytoplasm. This requires that newly formed nucleocapsids cross the nuclear envelope (NE), which occurs by budding at the inner nuclear membrane (INM), release of the primary enveloped virion into the perinuclear space (PNS), and subsequent rapid fusion with the outer nuclear membrane (ONM). During this process the NE remains intact, even at late stages of infection. In addition, the spacing between the INM and ONM is maintained, as is that between the primary virion envelope and nuclear membranes...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28716951/a-calcium-diacylglycerol-stimulated-protein-kinase-c-c-elegans-pkc-2-links-thermal-signals-to-learned-behavior-by-acting-in-a-sensory-neuron-and-intestinal-cells
#14
Marianne Land, Charles S Rubin
Ca(2+) and diacylglycerol (DAG) activated protein kinase C (cPKC) promotes learning and behavioral plasticity. However, knowledge of in vivo regulation and exact functions of cPKCs that affect behavior is limited. We show that PKC-2, a C. elegans cPKC, is essential for a complex behavior, thermotaxis. C. elegans memorizes a nutrient-associated cultivation temperature (Tc) and migrates along Tc within a 17-25°C gradient. pkc-2 gene disruption abrogated thermotaxis; a PKC-2 transgene, driven by endogenous pkc-2 promoters, restored thermotaxis behavior in pkc-2(-/-) animals...
July 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28708816/determination-of-the-minimal-clinically-important-difference-of-the-university-of-north-carolina-dry-eye-management-scale
#15
Christopher J Hwang, Reeves Ellis, Richard M Davis, Sue Tolleson-Rinehart
PURPOSE: To establish an initial estimation of the MCID of the University of North Carolina Dry Eye Management Scale (UNC DEMS) and assess its association with patient perceptions of symptom change. METHODS: Thirty-three patients (33.3% men, 67.7% women, mean age 60.5 yrs) with previous DEMS scores were recruited from a UNC ophthalmology clinic in spring 2014. We used anchor-based methods, categorizing important symptom change, to compare the change in the DEMS scores across visits to patient assessments of change; linear regression coefficients estimated the MCID...
September 2017: Cornea
https://www.readbyqxmd.com/read/28699918/ampk-activation-dependent-autophagy-compromises-oleanolic-acid-induced-cytotoxicity-in-human-bladder-cancer-cells
#16
Yarong Song, Peng Zhang, Yadong Sun, Xuechao Li, Lifeng Chen, Yajun Xiao, Yifei Xing
Autophagy is an evolutionarily conserved catabolic process in eukaryotic cells, which allows cells to overcome a wide array of of stresses and has recently been shown to result in drug resistance. This study examined the effect of autophagy on oleanolic acid (OA)-induced cytotoxicity against bladder cancer cells. Our study demonstrated that OA inhibited cell viability, proliferation, and induced apoptosis in bladder cancer lines T24 and EJ. Furthermore, OA induced autophagy in both cell lines by activating AMP-activated protein kinase (AMPK), inhibiting mechanistic target of rapamycin (mTOR) and promoting unc-51 like autophagy activating kinase 1 (ULK1)...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28694018/the-enu-3-protein-family-members-function-in-the-wnt-pathway-parallel-to-unc-6-netrin-to-promote-motor-neuron-axon-outgrowth-in-c-elegans
#17
Roxana Oriana Florica, Victoria Hipolito, Stephen Bautista, Homa Anvari, Chloe Rapp, Suzan El-Rass, Alimohammad Asgharian, Costin N Antonescu, Marie T Killeen
The axons of the DA and DB classes of motor neurons fail to reach the dorsal cord in the absence of the guidance cue UNC-6/Netrin or its receptor UNC-5 in C. elegans. However, the axonal processes usually exit their cell bodies in the ventral cord in the absence of both molecules. Strains lacking functional versions of UNC-6 or UNC-5 have a low level of DA and DB motor neuron axon outgrowth defects. We found that mutations in the genes for all six of the ENU-3 proteins function to enhance the outgrowth defects of the DA and DB axons in strains lacking either UNC-6 or UNC-5...
July 7, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28686223/regulation-of-autophagy-through-torc1-and-mtorc1
#18
REVIEW
Takeshi Noda
Autophagy is an intracellular protein-degradation process that is conserved across eukaryotes including yeast and humans. Under nutrient starvation conditions, intracellular proteins are transported to lysosomes and vacuoles via membranous structures known as autophagosomes, and are degraded. The various steps of autophagy are regulated by the target of rapamycin complex 1 (TORC1/mTORC1). In this review, a history of this regulation and recent advances in such regulation both in yeast and mammals will be discussed...
July 7, 2017: Biomolecules
https://www.readbyqxmd.com/read/28685860/exercise-mediated-modulation-of-autophagy-in-skeletal-muscle
#19
REVIEW
Marcos Martin-Rincon, David Morales-Alamo, Jose A L Calbet
Although exercise exerts multiple beneficial health effects, it may also damage cellular structures. Damaged elements are continuously degraded and its constituents recycled to produce renovated structures through a process called autophagy, which is essential for the adaptation to training. Autophagy is particularly active in skeletal muscle, where it can be evaluated by using specific molecular markers of activation (unc-51-like kinase 1 (ULK1) phosphorylation) and specific proteins indicating increased autophagosome content (increased total LC3, LC3-II, LC3-II/LC3-I ratio)...
July 7, 2017: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/28678595/the-unc-53-gene-negatively-regulates-rac-gtpases-to-inhibit-unc-5-activity-during-distal-tip-cell-migrations-in-c-elegans
#20
Amita Pandey, Vipul Yadav, Aditi Sharma, Jitendra P Khurana, Girdhar K Pandey
The unc-53/NAV2 gene encodes for an adaptor protein required for cell migrations along the anteroposterior (AP) axes of C. elegans. This study identifies unc-53 as a novel component of signaling pathways regulating distal tip cell (DTC) migrations along the AP and dorsoventral (DV) axes. unc-53 negatively regulates and functions downstream of ced-10/Rac pathway genes; ced-10/Rac and mig-2/RhoG, which are required for proper DTC migration. Moreover, unc-53 exhibits genetic interaction with abl-1 and unc-5, the two known negative regulators of ced-10/Rac signaling...
July 5, 2017: Cell Adhesion & Migration
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