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https://www.readbyqxmd.com/read/28823121/characterization-of-the-porcine-nanog-5-flanking-region
#1
Azra Memon, Ki-Duk Song, Woon Kyu Lee
Objective: Nanog, a homeodomain protein, has been investigated in humans and mice using ESCs. Because of the limited availability of ESCs, few studies have reported the function and role of Nanog in porcine ESCs. Therefore, in this study, we investigated the location of the porcine Nanog chromosome and its basal promoter activity, which might have potential applications in development of ESs specific marker as well as understanding its operating systems in the porcine. Methods: To characterize the porcine Nanog promoter, the 5'-flanking region of Nanog was isolated from cells of mini-pig ears...
August 16, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28823044/diagnostic-implications-of-tert-promoter-mutation-status-in-diffuse-gliomas-in-a-routine-clinical-setting
#2
Ekkehard Hewer, Nadine Prebil, Sabina Berezowska, Marielena Gutt-Will, Philippe Schucht, Matthias S Dettmer, Erik Vassella
IDH (isocitrate dehydrogenase) gene mutations are present in most diffuse low-grade gliomas and define the clinico-pathological core of the respective morphologically defined entities. Conversely, according to the 2016 WHO classification, the majority of glioblastomas belong to the IDH-wildtype category, which is defined by exclusion. TERT (telomerase reverse transcriptase gene) promoter mutations have been suggested as a molecular marker for primary glioblastomas. We analyzed molecular, histopathological, and clinical profiles of a series of 110 consecutive diffuse gliomas (WHO grades II-IV) diagnosed at our institution, in which TERT promoter mutation analysis had been performed as part of diagnostic work-up...
August 19, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28822966/inhibitory-actions-of-the-nrg-1-erbb4-pathway-in-macrophages-during-tissue-fibrosis-in-heart-skin-and-lung
#3
Zarha Vermeulen, Anne-Sophie Hervent, Lindsey Dugaucquier, Leni Vandekerckhove, Miche Rombouts, Matthias Beyens, Dorien M Schrijvers, Guido R Y De Meyer, Stuart Maudsley, Gilles W De Keulenaer, Vincent Fm Segers
The neuregulin-1 (NRG-1)/ErbB system is an endothelium-controlled paracrine system modulating cardiac performance and adaptation. Recent studies indicate that NRG-1 has anti-fibrotic effects in the left ventricle (LV), which were explained by direct actions on cardiac fibroblasts. However, the NRG-1/ErbB system also regulates the function of macrophages. In this study, we hypothesized that the anti-fibrotic effect of NRG-1 in the heart is at least partially mediated through inhibitory effects on macrophages...
August 19, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28822962/glucose-transporter-4-glut4-deficient-hearts-develop-maladaptive-hypertrophy-in-response-to-physiologic-or-pathologic-stresses
#4
Adam Raymond Wende, Jaetaek Kim, William Holland, Benjamin E Wayment, Brian T O'Neill, Joseph Tuinei, Manoja K Brahma, Mark E Pepin, Mark A McCrory, Ivan Luptak, Ganesh V Halade, Sheldon E Litwin, E Dale Abel
Pathological cardiac hypertrophy may be associated with reduced expression of the GLUT4 glucose transporter in contrast to exercise-induced cardiac hypertrophy, where GLUT4 levels are increased. However, mice with cardiac specific deletion of GLUT4 (G4H-/-) have normal cardiac function in the unstressed state. This study tested the hypothesis that cardiac GLUT4 is required for myocardial adaptations to hemodynamic demands. G4H-/- and control littermates (Con) were subjected to either a pathological model of left ventricular pressure overload (transverse aortic constriction; TAC) or a physiological model of endurance exercise (swim training)...
August 19, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28822954/the-variability-of-hepatitis-b-envelope-is-associated-with-hbs-antigen-persistence-in-either-chronic-or-acute-hbv-genotype-a-infection
#5
Marine Eschlimann, Brice Malvé, Aurélie Velay, Honorine Fenaux, Sibel Berger, Jean-Pol Frippiat, Fabien Zoulim, Mouni Bensenane, Jean-Pierre Bronowicki, François Goehringer, Thierry May, Hélène Jeulin, Evelyne Schvoerer
BACKGROUND: More than 240 million people are chronically infected by hepatitis B virus (HBV) worldwide. Envelope proteins play a crucial role in viral cellular entry and immune recognition. The loss of HBs antigen (HBsAg) correlated with a good clinical prognosis is rarely achieved with or without treatment (3-16%). OBJECTIVES: HBV envelope variability was investigated according to HBsAg persistence. STUDY DESIGN: The cohort consisted of 15 HBV genotype A-infected patients divided into "resolvers", with HBsAg clearance, and "non-resolvers", with HBsAg persistence and in subgroups: acute (n=5, AHBV) or chronic infection (n=4, CHBV) and HBV/HIV coinfection (n=6, CHBV/HIV)...
August 5, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28822888/apatinib-enhances-antitumour-activity-of-egfr-tkis-in-non-small-cell-lung-cancer-with-egfr-tki-resistance
#6
Fang Li, Tengjiao Zhu, Baoshan Cao, Jiadong Wang, Li Liang
BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)-rechallenged therapy for EGFR-mutant non-small cell lung cancer (NSCLC) patients who acquired resistance showed moderate efficacy. Considering the high interrelation between EGFR and vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) pathways, we firstly evaluated EGFR-TKI combined with apatinib (a highly selective VEGFR2 inhibitor) in EGFR-TKI-resistant model and patients...
August 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28822858/comparison-of-genome-engineering-using-the-crispr-cas9-system-in-c-glabrata-wild-type-and-lig4-strains
#7
Yuke Cen, Bea Timmermans, Ben Souffriau, Johan M Thevelein, Patrick Van Dijck
Candida glabrata is reported as the second most prevalent human opportunistic fungal pathogen in North America and is threatening patients all over the world. Its incidence is rising, while it has developed resistance to the most widely used antifungal drugs, necessitating new approaches based on better insight into the biology of the organism. Despite its close phylogenetic relationship with Saccharomyces cerevisiae, generating precise genomic alterations in this species is problematic. Previously we have shown that deletion of LIG4, which encodes an enzyme involved in Non-Homologous End Joining (NHEJ), strongly enhances the probability of obtaining correctly modified transformants...
August 16, 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/28822833/complete-knockout-of-estrogen-receptor-alpha-is-not-directly-protective-in-murine-lupus
#8
Jennifer L Scott, Jena R Wirth, Jackie Eudaly, Phil Ruiz, Melissa A Cunningham
Systemic lupus erythematosus (SLE) is a chronic and potentially severe autoimmune disease that disproportionately affects women. Despite a known role for hormonal factors impacting autoimmunity and disease pathogenesis, the specific mechanisms of action remain poorly understood. Our laboratory previously backcrossed "estrogen receptor alpha knockout (ERαKO)" mice onto the NZM2410 lupus prone background to generate NZM/ERαKO mice. This original ERαKO mouse, developed in the mid-1990s and utilized in hundreds of published studies, is not in fact ERα null...
August 16, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28822352/vibrio-vulnificus-martx-cytotoxin-causes-inactivation-of-phagocytosis-related-signaling-molecules-in-macrophages
#9
Chun-Liang Chen, Shu-Chun Chien, Tzeng-Horng Leu, Hans I-Chen Harn, Ming-Jer Tang, Lien-I Hor
BACKGROUND: Vibrio vulnificus is a marine bacterial species that causes opportunistic infections manifested by serious skin lesions and fulminant septicemia in humans. We have previously shown that the multifunctional autoprocessing repeats in toxin (MARTXVv1) of a biotype 1 V. vulnificus strain promotes survival of this organism in the host by preventing it from engulfment by the phagocytes. The purpose of this study was to further explore how MARTXVv1 inhibits phagocytosis of this microorganism by the macrophage...
August 19, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28821882/identification-of-a-short-sequence-in-the-hcmv-terminase-pul56-essential-for-interaction-with-pul89-subunit
#10
G Ligat, C Jacquet, S Chou, A Couvreux, S Alain, S Hantz
The human cytomegalovirus (HCMV) terminase complex consists of several components acting together to cleave viral DNA into unit length genomes and translocate them into capsids, a critical process in the production of infectious virions subsequent to DNA replication. Previous studies suggest that the carboxyl-terminal portion of the pUL56 subunit interacts with the pUL89 subunit. However, the specific interacting residues of pUL56 remain unknown. We identified a conserved sequence in the C-terminal moiety of pUL56 (671WMVVKYMGFF680)...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821659/stim1-regulates-somatic-ca-2-signals-and-intrinsic-firing-properties-of-cerebellar-purkinje-neurons
#11
Changhyeon Ryu, Dong Cheol Jang, Dayoon Jung, Yong Gyu Kim, Hyun Geun Shim, Hyun-Hee Ryu, Yong-Seok Lee, David J Linden, Paul F Worley, Sang Jeong Kim
Control of Ca(2+) flux between the cytosol and intracellular Ca(2+) stores is essential for maintaining normal cellular function. It has been well established in both neuronal and non-neuronal cells that stromal interaction molecule 1 (STIM1) initiates and regulates refilling Ca(2+) into the endoplasmic reticulum (ER). Here, we describe a novel, additional role for STIM1, regulation of free cytosolic Ca(2+) and consequent control of spike firing in neurons. Among central neurons, cerebellar Purkinje neurons express the highest level of STIM1 and they fire continuously in the absence of stimulation, making somatic Ca(2+) homeostasis of particular importance...
August 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821644/calpain-dependent-degradation-of-nucleoporins-contributes-to-motor-neuron-death-in-a-mouse-model-of-chronic-excitotoxicity
#12
Kaori Sugiyama, Tomomi Aida, Masatoshi Nomura, Ryoichi Takayanagi, Hanns U Zeilhofer, Kohichi Tanaka
Glutamate-mediated excitotoxicity induces neuronal death by altering various intracellular signaling pathways and is implicated as a common pathogenic pathway in many neurodegenerative diseases. In the case of motor neuron disease, there is significant evidence to suggest that overactivation of AMPA receptors due to deficiencies in the expression and function of glial glutamate transporter GLT1 and GLAST plays an important role in the mechanisms of neuronal death. However, a causal role for glial glutamate transporter dysfunction in motor neuron death remains unknown...
August 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821607/two-plant-derived-aporphinoid-alkaloids-exert-their-antifungal-activity-by-disrupting-mitochondrial-iron-sulfur-cluster-biosynthesis
#13
Siddharth K Tripathi, Tao Xu, Qin Feng, Bharathi Avula, Xiaomin Shi, Xuewen Pan, Melanie M Mask, Scott R Baerson, Melissa R Jacob, Ranga Rao Ravu, Shabana I Khan, Xing-Cong Li, Ikhlas A Khan, Alice M Clark, Ameeta K Agarwal
Eupolauridine and liriodenine are plant-derived aporphinoid alkaloids that exhibit potent inhibitory activity against the opportunistic fungal pathogens Candida albicans and Cryptococcus neoformans However, the molecular mechanism of this antifungal activity is unknown. In this study, we show that eupolauridine 9591 (E9591), a synthetic analog of eupolauridine, and liriodenine methiodide (LMT), a methiodide salt of liriodenine, mediate their antifungal activities by disrupting mitochondrial iron-sulfur (Fe-S) cluster synthesis...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821574/mosaic-loss-of-non-muscle-myosin-iia-and-iib-is-sufficient-to-induce-mammary-epithelial-proliferation
#14
Kim-Vy Nguyen-Ngoc, Vanesa L Silvestri, Dan Georgess, Amanda N Fairchild, Andrew J Ewald
The mammary epithelium elaborates through hormonally-regulated changes in proliferation, migration, and differentiation. Non-muscle myosin II (NMII) functions at the interface between contractility, adhesion, and signal transduction. It was therefore a plausible regulator of mammary morphogenesis. We tested the genetic requirement for NMIIA and NMIIB through deletion of the myosin heavy chains (NMHC) that confer specificity to the complex. Surprisingly, mosaic loss, but not ubiquitous loss, of NMHCIIA and IIB induced high levels of proliferation in 3D culture...
August 18, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28821557/selected-alkylating-agents-can-overcome-drug-tolerance-of-g0-like-tumor-cells-and-eradicate-brca1-deficient-mammary-tumors-in-mice
#15
Marina Pajic, Sohvi Blatter, Charlotte Guyader, Maaike Gonggrijp, Ariena Kersbergen, Aslı Küçükosmanoğlu, Wendy Sol, Rinske Drost, Jos Jonkers, Piet Borst, Sven Rottenberg
We aimed to characterize and target drug-tolerant BRCA1-deficient tumor cells that cause residual disease and subsequent tumor relapse.<br /><br />Experimental Design: We studied responses to various mono- and bifunctional alkylating agents in a genetically engineered mouse model for BRCA1/p53-mutant breast cancer. Due to the large intragenic deletion of the Brca1 gene, no restoration of BRCA1 function is possible, and therefore no BRCA1-dependent acquired resistance occurs. To characterize the cell cycle stage from which Brca1(-/-);p53(-/-) mammary tumors arise after cisplatin treatment, we introduced the fluorescent ubiquitination-based cell cycle indicator (FUCCI) construct into the tumor cells...
August 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28821551/coordinated-regulation-of-the-eii-man-and-frurki-operons-of-streptococcus-mutans-by-global-and-fructose-specific-pathways
#16
Lin Zeng, Brinta Chakraborty, Tanaz Farivar, Robert A Burne
The glucose/mannose-PTS permease EII(Man) encoded by manLMN in the dental caries pathogen Streptococcus mutans has a dominant influence on sugar-specific, CcpA-independent catabolite repression (CR). Mutations in manL affect energy metabolism and virulence-associated traits, including biofilm formation, acid tolerance and competence. Using promoter:reporter fusions, expression of the manLMN and the fruRKI operons, encoding a transcriptional regulator, a fructose-1-P kinase and a fructose-PTS permease EII(Fru), respectively, was monitored in response to carbohydrate source and in mutants lacking CcpA, FruR, and components of EII(Man) Expression of genes for EII(Man) and EII(Fru) was directly regulated by CcpA and CR, as evinced by in vivo and in vitro methods...
August 18, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28821279/genetic-deletion-of-mglu2-metabotropic-glutamate-receptors-improves-the-short-term-outcome-of-cerebral-transient-focal-ischemia
#17
Federica Mastroiacovo, Slavianka Moyanova, Milena Cannella, Anderson Gaglione, Remy Verhaeghe, Giovanna Bozza, Michele Madonna, Marta Motolese, Anna Traficante, Barbara Riozzi, Valeria Bruno, Giuseppe Battaglia, David Lodge, Ferdinando Nicoletti
We have recently shown that pharmacological blockade of mGlu2 metabotropic glutamate receptors protects vulnerable neurons in the 4-vessel occlusion model of transient global ischemia, whereas receptor activation amplifies neuronal death. This raised the possibility that endogenous activation of mGlu2 receptors contributes to the pathophysiology of ischemic neuronal damage. Here, we examined this possibility using two models of transient focal ischemia: (i) the monofilament model of middle cerebral artery occlusion (MCAO) in mice, and (ii) the model based on intracerebral infusion of endothelin-1 (Et-1) in rats...
August 18, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28821231/novel-mutations-in-pank2-and-pla2g6-genes-in-patients-with-neurodegenerative-disorders-two-case-reports
#18
Hassan Dastsooz, Hamid Nemati, Mohammad Ali Farazi Fard, Majid Fardaei, Mohammad Ali Faghihi
BACKGROUND: Neurodegeneration with brain iron accumulation (NBIA) is a genetically heterogeneous group of disorders associated with progressive impairment of movement, vision, and cognition. The disease is initially diagnosed on the basis of changes in brain magnetic resonance imaging which indicate an abnormal brain iron accumulation in the basal ganglia. However, the diagnosis of specific types should be based on both clinical findings and molecular genetic testing for genes associated with different types of NBIA, including PANK2, PLA2G6, C19orf12, FA2H, ATP13A2, WDR45, COASY, FTL, CP, and DCAF17...
August 18, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28820723/a-lncrna-fine-tunes-the-dynamics-of-a-cell-state-transition-involving-lin28-let-7-and-de-novo-dna-methylation
#19
Meng Amy Li, Paulo P Amaral, Priscilla Cheung, Jan H Bergmann, Masaki Kinoshita, Tüzer Kalkan, Meryem Ralser, Sam Robson, Ferdinand von Meyenn, Maike Paramor, Fengtang Yang, Caifu Chen, Jennifer Nichols, David L Spector, Tony Kouzarides, Lin He, Austin Smith
Execution of pluripotency requires progression from the naïve status represented by mouse embryonic stem cells (ESCs) to a state capacitated for lineage specification. This transition is coordinated at multiple levels. Non-coding RNAs may contribute to this regulatory orchestra. We identified a rodent-specific long non-coding RNA (lncRNA) linc1281, hereafter Ephemeron (Eprn), that modulates the dynamics of exit from naïve pluripotency. Eprn deletion delays the extinction of ESC identity, an effect associated with perduring Nanog expression...
August 18, 2017: ELife
https://www.readbyqxmd.com/read/28820682/case-report-a-case-of-plasmodium-falciparum-hrp2-and-hrp3-gene-mutation-in-bangladesh
#20
Maisha Khair Nima, Thomas Hougard, Mohammad Enayet Hossain, Mohammad Golam Kibria, Abu Naser Mohon, Fatema Tuj Johora, Rajibur Rahman, Rashidul Haque, Mohammad Shafiul Alam
Several species of Plasmodium are responsible for causing malaria in humans. Proper diagnoses are crucial to case management, because severity and treatment varies between species. Diagnoses can be made using rapid diagnostic tests (RDTs), which detect Plasmodium proteins. Plasmodium falciparum causes the most virulent cases of malaria, and P. falciparum histidine-rich protein 2 (PfHRP2) is a common target of falciparum malaria RDTs. Here we report a case in which a falciparum malaria patient in Bangladesh tested negative on PfHRP2-based RDTs...
August 7, 2017: American Journal of Tropical Medicine and Hygiene
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