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https://www.readbyqxmd.com/read/29346705/effect-of-dys-1-mutation-on-gene-expression-profile-in-space-flown-c-elegans
#1
Dan Xu, Ying Gao, Lin Guo, Chenggang Lin, Yeqing Sun
INTRODUCTION: Dystrophin-like dys-1 gene expression increases in the body-wall muscles of Caenorhabditis elegans (C. elegans) after spaceflight. Here, we utilized a dys-1(cx18) mutant to analyze the molecular adaptive responses of C. elegans to spaceflight. METHODS: DNA microarrays were performed to identify differentially expressed genes between wild-type and dys-1 mutant worms after spaceflight. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, predicted human diseases and screened out key genes for human muscle diseases with NextBio...
January 18, 2018: Muscle & Nerve
https://www.readbyqxmd.com/read/29342309/prognostic-power-of-a-tumor-differentiation-gene-signature-for-bladder-urothelial-carcinomas
#2
Qianxing Mo, Fotis Nikolos, Fengju Chen, Zoe Tramel, Yu-Cheng Lee, Kazukuni Hayashi, Jing Xiao, Jianjun Shen, Keith Syson Chan
Background: Muscle-invasive bladder cancers (MIBCs) cause approximately 150 000 deaths per year worldwide. Survival for MIBC patients is heterogeneous, with no clinically validated molecular markers that predict clinical outcome. Non-MIBCs (NMIBCs) generally have favorable outcome; however, a portion progress to MIBC. Hence, development of a prognostic tool that can guide decision-making is crucial for improving clinical management of bladder urothelial carcinomas. Methods: Tumor grade is defined by pathologic evaluation of tumor cell differentiation, and it often associates with clinical outcome...
January 12, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29335749/diversity-among-pou-transcription-factors-in-chromatin-recognition-and-cell-fate-reprogramming
#3
REVIEW
Vikas Malik, Dennis Zimmer, Ralf Jauch
The POU (Pit-Oct-Unc) protein family is an evolutionary ancient group of transcription factors (TFs) that bind specific DNA sequences to direct gene expression programs. The fundamental importance of POU TFs to orchestrate embryonic development and to direct cellular fate decisions is well established, but the molecular basis for this activity is insufficiently understood. POU TFs possess a bipartite 'two-in-one' DNA binding domain consisting of two independently folding structural units connected by a poorly conserved and flexible linker...
January 15, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29330382/sesn2-facilitates-mitophagy-by-helping-parkin-translocation-through-ulk1-mediated-beclin1-phosphorylation
#4
Ashish Kumar, Chandrima Shaha
Mitophagy, the selective degradation of mitochondria by autophagy, is crucial for the maintenance of healthy mitochondrial pool in cells. The critical event in mitophagy is the translocation of cytosolic Parkin, a ubiquitin ligase, to the surface of defective mitochondria. This study elucidates a novel role of SESN2/Sestrin2, a stress inducible protein, in mitochondrial translocation of PARK2/Parkin during mitophagy. The data demonstrates that SESN2 downregulation inhibits BECN1/Beclin1 and Parkin interaction, thereby preventing optimum mitochondrial accumulation of Parkin...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321955/the-central-domain-of-unc-45-chaperone-inhibits-the-myosin-power-stroke
#5
Paul J Bujalowski, Paul Nicholls, Eleno Garza, Andres F Oberhauser
The multidomain UNC-45B chaperone is crucial for the proper folding and function of sarcomeric myosin. We recently found that UNC-45B inhibits the translocation of actin by myosin. The main functions of the UCS and TPR domains are known but the role of the central domain remains obscure. Here, we show-using in vitro myosin motility and ATPase assays-that the central domain alone acts as an inhibitor of the myosin power stroke through a mechanism that allows ATP turnover. Hence, UNC-45B is a unique chaperone in which the TPR domain recruits Hsp90; the UCS domain possesses chaperone-like activities; and the central domain interacts with myosin and inhibits the actin translocation function of myosin...
January 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29314608/unc-120-srf-independently-controls-muscle-aging-and-lifespan-in-caenorhabditis-elegans
#6
Adeline Mergoud Dit Lamarche, Laurent Molin, Laura Pierson, Marie-Christine Mariol, Jean-Louis Bessereau, Kathrin Gieseler, Florence Solari
Aging is commonly defined as the loss of global homeostasis, which results from progressive alteration of all organs function. This model is currently challenged by recent data showing that interventions that extend lifespan do not always increase the overall fitness of the organism. These data suggest the existence of tissue-specific factors that regulate the pace of aging in a cell-autonomous manner. Here, we investigated aging of Caenorhabditis elegans striated muscles at the subcellular and the physiological level...
January 3, 2018: Aging Cell
https://www.readbyqxmd.com/read/29304491/influences-of-different-dietary-energy-level-on-sheep-testicular-development-associated-with-ampk-ulk1-autophagy-pathway
#7
Jing Pang, Fengzhe Li, Xu Feng, Hua Yang, Le Han, Yixuan Fan, Haitao Nie, Zhen Wang, Feng Wang, Yanli Zhang
Energy balance is an important feature for spermatozoa production in the testis. The 5'-AMP-activated protein kinase (AMPK) is a sensor of cell energy, has been implicated as a mediator between gonadal function and energy balance. Herein, we intended to determine the physiological effects of AMPK on testicular development in feed energy restricted and compensated pre-pubertal rams. Lambs had restricted feeding for 2 months and then provided compensatory feeding for another 3 months. Feed levels were 100%(control), 15% and 30% of energy restriction (ER) diets, respectively...
December 14, 2017: Theriogenology
https://www.readbyqxmd.com/read/29300818/improving-the-unc-passive-aerosol-sampler-model-based-on-comparison-with-commonly-used-aerosol-sampling-methods
#8
Mariam Shirdel, Britt M Andersson, Ingvar A Bergdahl, Johan N Sommar, Håkan Wingfors, Ingrid E Liljelind
Objectives: In an occupational environment, passive sampling could be an alternative to active sampling with pumps for sampling of dust. One passive sampler is the University of North Carolina passive aerosol sampler (UNC sampler). It is often analysed by microscopic imaging. Promising results have been shown for particles above 2.5 µm, but indicate large underestimations for PM2.5. The aim of this study was to evaluate, and possibly improve, the UNC sampler for stationary sampling in a working environment...
December 28, 2017: Annals of Work Exposures and Health
https://www.readbyqxmd.com/read/29300482/chemotext-a-publicly-available-web-server-for-mining-drug-target-disease-relationships-in-pubmed
#9
Stephen Joseph Capuzzi, Thomas Thornton, Kammy Liu, Nancy Baker, Wai In Lam, Colin O'Banion, Eugene N Muratov, Diane Pozefsky, Alexander Tropsha
Elucidation of the mechanistic relationships between drugs, their targets, and diseases is at the core of modern drug discovery research. Thousands of studies relevant to the drug-target-disease (DTD) triangle have been published and annotated in the Medline/PubMed database. Mining this database affords rapid identification of all published studies that confirm connections between vertices of this triangle or enable new inferences of such connections. To this end, we describe the development of Chemotext, a publicly-available Web server that mines the entire compendium of published literature in PubMed annotated by Medline Subject Heading (MeSH) terms...
January 4, 2018: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29261311/laser-ablated-u-atom-reactions-with-cn-2-to-form-unc-u-nc-2-and-u-nc-4-matrix-infrared-spectra-and-quantum-chemical-calculations
#10
Zongtang Fang, Edward B Garner, David A Dixon, Yu Gong, Lester Andrews, Benjamin K Liebov
Laser-ablated U atoms react with (CN)2 in excess argon and neon during co-deposition at 4 K to form UNC, U(NC)2, and U(NC)4 as the major uranium bearing products, which are identified from their matrix infrared spectra using cyanogen substituted with 13C and 15N and from quantum chemical calculations. The 12/13CN and C14/15N isotopic frequency ratios computed for the U(NC)1,2,4 molecules agree better with the observed values than those calculated for the U(CN)1,2,4 isomers. Multiplets using mixed isotopic cyanogens reveal the stoichiometries of these products, and the band positions and quantum chemical calculations confirm the isocyanide bonding arrangements, which are 14 and 51 kJ/mol more stable than the cyanide isomers for UNC and U(NC)2, respectively, and 62 kJ/mol for U(NC)4 in the isolated gas phase at the CCSD(T)/CBS level...
December 20, 2017: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/29259744/in-silico-hts-and-structure-based-optimization-of-indazole-derived-ulk1-inhibitors
#11
Spencer D Wood, Wayne Grant, Isabel Adrados, Jun Yong Choi, James M Alburger, Derek R Duckett, William R Roush
We present the outcome of an in silico high throughput screen (HTS) and optimization of a small molecule Unc-51-Like Kinase 1 (ULK1) inhibitor hit, SR-17398, with an indazole core. Docking studies guided design efforts that led to inhibitors with increased activity vs ULK1 (IC50 < 50 nM). The most advanced molecules in this inhibitor series (3a and 3g) hold promise for further development into selective ULK1 molecular probes to interrogate the biology of ULK1 and to assess whether selectively targeting autophagy is an effective anticancer strategy...
December 14, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29235522/an-optogenetic-arrhythmia-model-to-study-catecholaminergic-polymorphic-ventricular-tachycardia-mutations
#12
Elisabeth Fischer, Alexander Gottschalk, Christina Schüler
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a condition of abnormal heart rhythm (arrhythmia), induced by physical activity or stress. Mutations in ryanodine receptor 2 (RyR2), a Ca2+ release channel located in the sarcoplasmic reticulum (SR), or calsequestrin 2 (CASQ2), a SR Ca2+ binding protein, are linked to CPVT. For specific drug development and to study distinct arrhythmias, simple models are required to implement and analyze such mutations. Here, we introduced CPVT inducing mutations into the pharynx of Caenorhabditis elegans, which we previously established as an optogenetically paced heart model...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29233870/the-mammalian-ulk1-complex-and-autophagy-initiation
#13
REVIEW
Maria Zachari, Ian G Ganley
Autophagy is a vital lysosomal degradation pathway that serves as a quality control mechanism. It rids the cell of damaged, toxic or excess cellular components, which if left to persist could be detrimental to the cell. It also serves as a recycling pathway to maintain protein synthesis under starvation conditions. A key initial event in autophagy is formation of the autophagosome, a unique double-membrane organelle that engulfs the cytosolic cargo destined for degradation. This step is mediated by the serine/threonine protein kinase ULK1 (unc-51-like kinase 1), which functions in a complex with at least three protein partners: FIP200 (focal adhesion kinase family interacting protein of 200 kDa), ATG (autophagy-related protein) 13 (ATG13), and ATG101...
December 12, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/29233315/student-pharmacist-experiences-as-inpatient-psychiatry-medication-education-group-leaders-during-an-early-immersion-program
#14
Jacqueline E McLaughlin, Lindsey Kennedy, Shauna Garris, Suzanne C Harris, Ashley Hillman, Nicole R Pinelli, Denise H Rhoney
BACKGROUND AND PURPOSE: While research suggests that pharmacists generally hold positive attitudes toward consumers of psychiatric medications, they often feel less comfortable talking about these medications and providing services for patients with mental illness. The purpose of this program was to train second and third year student pharmacists as psychiatry medication education groups leaders and to examine resulting student self-efficacy and mental health stigma. EDUCATIONAL ACTIVITY AND SETTING: In partnership with the University of North Carolina (UNC) Eshelman School of Pharmacy, the inpatient psychiatry service at UNC Medical Center expanded weekly medication education groups with the help of trained student pharmacists...
September 2017: Currents in Pharmacy Teaching & Learning
https://www.readbyqxmd.com/read/29231144/qsar-of-natural-sesquiterpene-lactones-as-inhibitors-of-myb-dependent-gene-expression
#15
Gloria Castellano, Lucia Redondo, Francisco Torrens
Protein c-Myb is a therapeutic target. Some sesquiterpene lactones suppress Myb-dependent gene expression, which results in a mechanism for their potential anti-cancer activity. Database ChEMBL is representative of lactones for physicochemical and physiochemical properties. Data presented for 31 natural lactones are discussed in terms of quantitative structure-activity relationships, which objective is to predict inhibitors of Myb-induced gene expression. Several constitutional descriptors are related to structure-activity...
December 11, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29230855/a-role-for-autophagy-in-long-term-spatial-memory-formation-in-male-rodents
#16
Michael J Hylin, Jing Zhao, Karthikeyan Tangavelou, Natalia S Rozas, Kimberly N Hood, Jacalyn S MacGowan, Anthony N Moore, Pramod K Dash
A hallmark of long-term memory formation is the requirement for protein synthesis. Administration of protein synthesis inhibitors impairs long-term memory formation without influencing short-term memory. Rapamycin is a specific inhibitor of target of rapamycin complex 1 (TORC1) that has been shown to block protein synthesis and impair long-term memory. In addition to regulating protein synthesis, TORC1 also phosphorylates Unc-51-like autophagy activating kinase-1 (Ulk-1) to suppress autophagy. As autophagy can be activated by rapamycin (and rapamycin inhibits long-term memory), our aim was to test the hypothesis that autophagy inhibitors would enhance long-term memory...
December 12, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29230398/insulin-signaling-deficiency-produces-immobility-in-caenorhabditis-elegans-that-models-diminished-motivation-states-in-man-and-responds-to-antidepressants
#17
Julie Dagenhardt, Angeline Trinh, Halen Sumner, Jeffrey Scott, Eric Aamodt, Donard S Dwyer
Defects in insulin signaling have been reported in schizophrenia and major depressive disorder, which also share certain negative symptoms such as avolition, anhedonia, and apathy. These symptoms reflect diminished motivational states, which have been modeled in rodents as increased immobility in the forced swimming test. We have discovered that loss-of-function mutations in the insulin receptor (daf-2) and syntaxin (unc-64) genes in Caenorhabditis elegans, brief food deprivation, and exposure to DMSO produce immobility and avolition in non-dauer adults...
November 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/29229994/autophagy-induced-during-apoptosis-degrades-mitochondria-and-inhibits-type-i-interferon-secretion
#18
Lisa M Lindqvist, Daniel Frank, Kate McArthur, Toby A Dite, Michael Lazarou, Jonathan S Oakhill, Benjamin T Kile, David L Vaux
Cells undergoing Bax/Bak-mediated apoptosis exhibit signs of autophagy, but how it is activated and its significance is unknown. By directly activating Bax/Bak with BH3-only proteins or BH3 mimetic compounds, we demonstrate that mitochondrial damage correlated with a rapid increase in intracellular [AMP]/[ATP], phosphorylation of 5' AMP-activated protein kinase (AMPK), and activation of unc-51 like autophagy activating kinase 1 (ULK1). Consequently, autophagic flux was triggered early in the apoptotic pathway, as activation of the apoptosome and caspases were not necessary for its induction...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29226381/a-robust-and-powerful-two-step-testing-procedure-for-local-ancestry-adjusted-allelic-association-analysis-in-admixed-populations
#19
Qing Duan, Zheng Xu, Laura M Raffield, Suhua Chang, Di Wu, Ethan M Lange, Alex P Reiner, Yun Li
Genetic association studies in admixed populations allow us to gain deeper understanding of the genetic architecture of human diseases and traits. However, population stratification, complicated linkage disequilibrium (LD) patterns, and the complex interplay of allelic and ancestry effects on phenotypic traits pose challenges in such analyses. These issues may lead to detecting spurious associations and/or result in reduced statistical power. Fortunately, if handled appropriately, these same challenges provide unique opportunities for gene mapping...
December 10, 2017: Genetic Epidemiology
https://www.readbyqxmd.com/read/29223072/alteration-of-autophagy-related-proteins-in-peripheral-blood-mononuclear-cells-of-patients-with-parkinson-s-disease
#20
Yasuo Miki, Shuji Shimoyama, Tomoya Kon, Tatsuya Ueno, Ryo Hayakari, Kunikazu Tanji, Tomoh Matsumiya, Eiki Tsushima, Fumiaki Mori, Koichi Wakabayashi, Masahiko Tomiyama
Previous postmortem studies demonstrated dysregulation of autophagy in patients with Parkinson's disease (PD). To clarify whether this alteration reflects a fundamental aspect of PD or represents the final stage of autophagy dysregulation resulting from a long neurodegenerative process, we focused on basal autophagy in peripheral blood mononuclear cells (PBMCs) of PD patients (n = 35) and controls (n = 23). The whole-transcriptome assay revealed downregulation of mRNAs for 6 core regulators of autophagy (UNC-51-like kinase [ULK] 3, autophagy-related [Atg] 2A, Atg4B, Atg5, Atg16L1, and histone deacetylase 6)...
November 21, 2017: Neurobiology of Aging
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