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https://www.readbyqxmd.com/read/29352755/a-mos1-transposase-in-vivo-assay-to-screen-new-hiv-1-integrase-inhibitors
#1
Mariana Cancian, Elgion L S Loreto
The integrase and transposase enzymes of retrovirus and transposons, respectively, share the catalytic DDE domain. In vitro assays showed that inhibitors of HIV-1 integrase generally inhibit the mariner Mos1 transposase. Using a Drosophila strain in which the mobilisation of the mariner element can be quantified by mosaic eyes, we showed that flies maintained in medium containing 210 µM to 4 mM of raltegravir, or 1 or 2 mM of dolutegravir, which are HIV-1 integrase inhibitor used in AIDS treatment, have 23-33% less somatic mobilisation in mosaic eyes when treated with raltegravir and 28-32% when treated with dolutegravir...
January 19, 2018: Genetica
https://www.readbyqxmd.com/read/29352745/negative-supercoiling-of-dna-by-gyrase-is-inhibited-in-salmonella-enterica-serovar-typhimurium-during-adaptation-to-acid-stress
#2
Aoife M Colgan, Heather J Quinn, Stefani C Kary, Lesley A Mitchenall, Anthony Maxwell, Andrew Ds Cameron, Charles J Dorman
DNA in intracellular Salmonella enterica serovar Typhimurium relaxes during growth in the acidified (pH 4 to 5) macrophage vacuole and DNA relaxation correlates with upregulation of Salmonella genes involved in adaptation to the macrophage environment. Bacterial ATP levels did not increase during adaptation to acid pH unless the bacterium was deficient in MgtC, a cytoplasmic-membrane-located inhibitor of proton-driven F1 F0 ATP synthase activity. Inhibiting ATP binding by DNA gyrase and topo IV with novobiocin enhanced the effect of low pH on DNA relaxation...
January 20, 2018: Molecular Microbiology
https://www.readbyqxmd.com/read/29352744/crystal-structure-of-adp-dependent-glucokinase-from-methanocaldococcus-jannaschii-in-complex-with-5-iodotubercidin-reveals-phosphoryl-transfer-mechanism
#3
Piotr Tokarz, Magdalena Wiśniewska, Marcin M Kamiński, Grzegorz Dubin, Przemysław Grudnik
ADP-dependent glucokinase (ADPGK) is an alternative novel glucose phosphorylating enzyme in a modified glycolysis pathway of hyperthermophilic Archaea. In contrast to classical ATP-dependent hexokinases, ADPGK utilizes ADP as a phosphoryl group donor. Here we present a crystal structure of archaeal ADPGK from Methanocaldococcus jannaschii in complex with an inhibitor, 5-iodotubercidin, D-glucose, inorganic phosphate and a magnesium ion. Detailed analysis of the architecture of the active site allowed for confirmation of the previously proposed phosphorylation mechanism and the crucial role of the invariant arginine residue (Arg197)...
January 20, 2018: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29352731/induced-cumulus-expansion-of-poor-quality-buffalo-cumulus-oocyte-complexes-by-interleukin-1beta-improves-their-developmental-ability
#4
Gaurav Kumar Chaubey, Sandeep Kumar, Manish Kumar, Parul Sarwalia, Arumugam Kumaresan, Sachinandan De, Rakesh Kumar, Tirtha Kumar Datta
The present study was conceived with the aim of modulating the cumulus expansion characteristics of poor quality (BCB-) buffalo oocyte complexes (COCs) in order to improve their fertilization outcomes. BCB- COCs were subjected to in vitro maturation (IVM) in presence of Interleukin - 1 beta (IL-1β) along with BCB- (control) and good quality (BCB +) COCs. Results were assessed morphologically, by scanning electron microscopy (SEM) and by expression analysis of cumulus expansion related genes. Also, numbers of zona pellucida bound spermatozoa were counted and development rates of oocytes were monitored under different groups...
January 20, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29352717/should-we-use-cell-of-origin-and-dual-protein-expression-in-treating-dlbcl
#5
REVIEW
Peter A Riedell, Sonali M Smith
Treatment outcomes in diffuse large B-cell lymphoma (DLBCL) following standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy is highly variable and dependent on a number of clinical, biologic, and genetic features. The identification of molecular heterogeneity via gene expression profiling dichotomizes patients based on the cell of origin (COO) model into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subsets, with ABC-DLBCL having a worse outcome...
December 24, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29352661/mechanistic-insights-into-the-genetics-of-affective-psychosis-from-prader-willi-syndrome
#6
REVIEW
Lucie C S Aman, Katherine E Manning, Joyce E Whittington, Anthony J Holland
Schizophrenia and bipolar disorder are common, severe, and disabling psychotic disorders, which are difficult to research. We argue that the genetically determined neurodevelopmental disorder Prader-Willi syndrome (PWS), which is associated with a high risk of affective psychotic illness, can provide a window into genetic mechanisms and associated neural pathways. People with PWS can all show non-psychotic psychopathology and problem behaviours, but the prevalence of psychotic illness differs markedly by genetic subtype; people with PWS due to chromosome 15 maternal uniparental disomy have higher prevalence of psychotic illness compared with patients with PWS due to 15q11-13 deletions of paternal origin...
January 15, 2018: Lancet Psychiatry
https://www.readbyqxmd.com/read/29352658/role-of-hypoxia-inducible-factor-1-in-the-development-of-renal-fibrosis-in-mouse-obstructed-kidney-special-references-to-hif-1-dependent-gene-expression-of-profibrogenic-molecules
#7
Kazuya Kabei, Yu Tateishi, Masakazu Nozaki, Masako Tanaka, Masayuki Shiota, Mayuko Osada-Oka, Shunji Nishide, Junji Uchida, Tatsuya Nakatani, Shuhei Tomita, Katsuyuki Miura
The aim of the study is to clarify the role of hypoxia-inducible factor-1 (HIF-1) in the development of renal fibrosis in mouse obstructive nephropathy. We used mice with floxed HIF-1α alleles and tamoxifen-inducible Cre/ERT2 recombinase under ubiquitin C promoter to induce global HIF-1α deletion. Following tamoxifen administration, mice were subjected to unilateral ureteral obstruction (UUO). At 3, 7 and 14 days after UUO, renal gene expression profiles and interstitial fibrosis were assessed. HIF-1 dependent up-regulation of prolyl hydroxylase 3 and glucose transporter-1 was observed in the obstructed kidney at 3 and 7 days but not at 14 days after UUO...
December 28, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29352562/cbs-mutations-are-good-predictors-for-b6-responsiveness-a-study-based-on-the-analysis-of-35-brazilian-classical-homocystinuria-patients
#8
Soraia Poloni, Fernanda Sperb-Ludwig, Taciane Borsatto, Giovana Weber Hoss, Maria Juliana R Doriqui, Emília K Embiruçu, Ney Boa-Sorte, Charles Marques, Chong A Kim, Carolina Fischinger Moura de Souza, Helio Rocha, Marcia Ribeiro, Carlos E Steiner, Carolina A Moreno, Pricila Bernardi, Eugenia Valadares, Osvaldo Artigalas, Gerson Carvalho, Hector Y C Wanderley, Johanna Kugele, Melanie Walter, Lorena Gallego-Villar, Henk J Blom, Ida Vanessa D Schwartz
BACKGROUND: Classical homocystinuria (HCU) is a monogenic disease caused by the deficient activity of cystathionine β-synthase (CβS). The objective of this study was to identify the CBS mutations in Brazilian patients with HCU. METHODS: gDNA samples were obtained for 35 patients (30 families) with biochemically confirmed diagnosis of HCU. All exons and exon-intron boundaries of CBS gene were sequenced. Gene expression analysis by qRT-PCR was performed in six patients...
January 20, 2018: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/29352444/activation-of-the-anti-aging-and-cognition-enhancing-gene-klotho-by-crispr-dcas9-transcriptional-effector-complex
#9
Ci-Di Chen, Ella Zeldich, Yuexuan Li, Andrea Yuste, Carmela R Abraham
Multiple lines of evidence show that the anti-aging and cognition-enhancing protein Klotho fosters neuronal survival, increases the anti-oxidative stress defense, and promotes remyelination of demyelinated axons. Thus, upregulation of the Klotho gene can potentially alleviate the symptoms and/or prevent the progression of age-associated neurodegenerative diseases such as Alzheimer's disease and demyelinating diseases such as multiple sclerosis. Here we used a CRISPR-dCas9 complex to investigate single-guide RNA (sgRNA) targeting the Klotho promoter region for efficient transcriptional activation of the Klotho gene...
January 19, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29352443/baculovirus-based-gene-silencing-of-humanin-for-the-treatment-of-pituitary-tumors
#10
María Florencia Gottardo, Matías L Pidre, Camila Zuccato, Antonela S Asad, Mercedes Imsen, Gabriela Jaita, Marianela Candolfi, Víctor Romanowski, Adriana Seilicovich
Pituitary tumors are the most common primary intracranial neoplasms. Humanin (HN) and Rattin (HNr), a rat homolog of HN, are short peptides with a cytoprotective action. In the present study, we aimed to evaluate whether endogenous HNr plays an antiapoptotic role in pituitary tumor cells. Thus, we used RNA interference based on short-hairpin RNA (shRNA) targeted to HNr (shHNr). A plasmid including the coding sequences for shHNr and dTomato fluorescent reporter gene was developed (pUC-shHNr). Transfection of somatolactotrope GH3 cells with pUC-shHNr increased apoptosis, suggesting that endogenous HNr plays a cytoprotective role in pituitary tumor cells...
January 19, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29352428/hnf4%C3%AE-is-involved-in-the-regulation-of-vertebrate-lc-pufa-biosynthesis-insights-into-the-regulatory-role-of-hnf4%C3%AE-on-expression-of-liver-fatty-acyl-desaturases-in-the-marine-teleost-siganus-canaliculatus
#11
Shuqi Wang, Junliang Chen, Danli Jiang, Qinghao Zhang, Cuihong You, Douglas R Tocher, Óscar Monroig, Yewei Dong, Yuanyou Li
Long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis is an important metabolic pathway in vertebrates, especially fish, considering they are the major source of n-3 LC-PUFA in the human diet. However, most fish have only limited capability for biosynthesis of LC-PUFA. The rabbitfish (Siganus canaliculatus) is able to synthesize LC-PUFA as it has all the key enzyme activities required including Δ6Δ5 Fads2, Δ4 Fads2, Elovl5, and Elovl4. We previously reported a direct interaction between the transcription factor Hnf4α and the promoter regions of Δ4 and Δ6Δ5 Fads2, which suggested that Hnf4α was involved in the transcriptional regulation of fads2 in rabbitfish...
January 19, 2018: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/29352424/cannabinoid-cb1-and-cb2%C3%A2-receptors-and-monoacylglycerol-lipase-gene-expression-alterations-in-the-basal-ganglia-of-patients-with-parkinson-s-disease
#12
Francisco Navarrete, M Salud García-Gutiérrez, Auxiliadora Aracil-Fernández, José L Lanciego, Jorge Manzanares
Previous studies suggest that the endocannabinoid system plays an important role in the neuropathological basis of Parkinson's disease (PD). This study was designed to detect potential alterations in the cannabinoid receptors CB1 (CB1r) and CB2 (A isoform, CB2Ar), and in monoacylglycerol lipase (MAGL) gene expression in the substantia nigra (SN) and putamen (PUT) of patients with PD. Immunohistochemical studies were performed to identify precise CB2r cellular localization in the SN of control and PD patients...
January 19, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29352321/inflammatory-linked-changes-in-cpg-island-methylation-of-three-opioid-peptide-genes-in-a-rat-model-for-pain
#13
Charlotte Louise Justine Jacobi, Christoph Stein
Expression of the opioid peptide genes proopiomelanocortin (Pomc), proenkephalin (Penk), and prodynorphin (Pdyn), in immune cells plays a key role in endogenous pain control. In a rat model of painful unilateral paw inflammation, we isolated cells from popliteal lymph nodes and evaluated the role of CpG island C5-methylation on the transcriptional activation of those genes. Using methylated DNA immunoprecipitation, we sorted gDNA into methylated (me) and non-me fractions and then determined the CpG island methylation status of each fraction via quantitative Real Time-PCR (qRT-PCR)...
2018: PloS One
https://www.readbyqxmd.com/read/29352308/high-efficiency-production-of-human-serum-albumin-in-the-posterior-silk-glands-of-transgenic-silkworms-bombyx-mori-l
#14
Qiujie Qian, Zhengying You, Lupeng Ye, Jiaqian Che, Yiran Wang, Shaohua Wang, Boxiong Zhong
Human serum albumin (HSA) is an important biological preparation with a variety of biological functions in clinical applications. In this study, the mRNA of a fusion transposase derived from the pESNT-PBase plasmid and a pBHSA plasmid containing the HSA gene under the control of a fibroin light chain (FL) promoter were co-injected into fertilized eggs. Fifty-six transgenic silkworm pedigrees expressing theexogenous recombinant HSA (rHSA) in the posterior silk glands (PSGs) with stable inheritance were successfully obtained...
2018: PloS One
https://www.readbyqxmd.com/read/29352300/5-aminosalicylic-acid-improves-lipid-profile-in-mice-fed-a-high-fat-cholesterol-diet-through-its-dual-effects-on-intestinal-ppar%C3%AE-and-ppar%C3%AE
#15
Zheng Wang, Debby Koonen, Marten Hofker, Zhijun Bao
Obesity is associated with a series of metabolic complications, including dyslipidemia and insulin resistance (IR) that lack effective therapies. In recent years, intestinal inflammation has been suggested to contribute to obesity related metabolic syndrome and targeting gut inflammation with 5-ASA improves diet induced IR, however, its role in dyslipidemia is unknown and has never been explored. In the present study, we reported for the first time that administration of 5-ASA for 12 weeks significantly improved lipid profile by repressing plasma triglycerides and free cholesterol levels in mice fed high-fat cholesterol diet (HFC)...
2018: PloS One
https://www.readbyqxmd.com/read/29352292/rna-seq-of-kaposi-s-sarcoma-reveals-alterations-in-glucose-and-lipid-metabolism
#16
For Yue Tso, Andrew V Kossenkov, Salum J Lidenge, Owen Ngalamika, John R Ngowi, Julius Mwaiselage, Jayamanna Wickramasinghe, Eun Hee Kwon, John T West, Paul M Lieberman, Charles Wood
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS). It is endemic in a number of sub-Saharan African countries with infection rate of >50%. The high prevalence of HIV-1 coupled with late presentation of advanced cancer staging make KS the leading cancer in the region with poor prognosis and high mortality. Disease markers and cellular functions associated with KS tumorigenesis remain ill-defined. Several studies have attempted to investigate changes of the gene profile with in vitro infection of monoculture models, which are not likely to reflect the cellular complexity of the in vivo lesion environment...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352289/electroacupuncture-at-guanyuan-cv-4-zusanli-st-36-and-baihui-du-20-regulate-the-aging-related-changes-in-gene-expression-profile-of-the-hippocampus-in-sub-acutely-aging-rats
#17
Jianmin Liu, Jing Liu, Guang'an Wang, Guangya Liu, Huanjiao Zhou, Yun Fan, Fengxia Liang, Hua Wang
To investigate the molecular mechanisms of sub-acutely aging and demonstrate the effect of electroacupuncture (EA) at the Guanyuan (CV 4), Zusanli (ST 36) and Baihui (DU 20) acupoint on the sub-acutely aging brain, cDNA microarrays and bioinformatics analyses were carried out. Thirty Sprague-Dawley (SD) male rats were selected and randomly divided into three groups: the control group (C), the sub-acutely aging model group (M) and the electroacupuncture group (M+EA). Sub-acutely aging model rats were obtained by D-galactose s...
2018: PloS One
https://www.readbyqxmd.com/read/29352281/differential-dna-methylation-and-transcription-profiles-in-date-palm-roots-exposed-to-salinity
#18
Ibtisam Al-Harrasi, Rashid Al-Yahyai, Mahmoud W Yaish
As a salt-adaptive plant, the date palm (Phoenix dactylifera L.) requires a suitable mechanism to adapt to the stress of saline soils. There is growing evidence that DNA methylation plays an important role in regulating gene expression in response to abiotic stresses, including salinity. Thus, the present study sought to examine the differential methylation status that occurs in the date palm genome when plants are exposed to salinity, and to identify salinity responsive genes that are regulated by DNA methylation...
2018: PloS One
https://www.readbyqxmd.com/read/29352272/nuclear-p53-mediated-repression-of-autophagy-involves-pink1-transcriptional-down-regulation
#19
Thomas Goiran, Eric Duplan, Lila Rouland, Wejdane El Manaa, Inger Lauritzen, Julie Dunys, Han You, Frédéric Checler, Cristine Alves da Costa
p53 is a transcription factor that is implicated in the control of both apoptotic and autophagic cell death. This tumor suppressor elicits both pro-autophagic and anti-autophagic phenotypes depending of its intracellular localization. The ability of p53 to repress autophagy has been exclusively associated to its cytoplasmic localization. Here, we show that transcriptional activity of p53 also contributes to autophagy down-regulation. Thus, nuclear p53 controls PINK1, a key protein involved in the control of mitophagy, by repressing its promoter activity, protein and mRNA levels, ex-vivo and in vivo...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352267/differential-susceptibility-of-striatal-hippocampal-and-cortical-neurons-to-caspase-6
#20
Anastasia Noël, Libin Zhou, Bénédicte Foveau, P Jesper Sjöström, Andréa C LeBlanc
Active cysteinyl protease Caspase-6 is associated with early Alzheimer and Huntington diseases. Higher entorhinal cortex and hippocampal Caspase-6 levels correlate with lower cognitive performance in aged humans. Caspase-6 induces axonal degeneration in human primary neuron cultures and causes inflammation and neurodegeneration in mouse hippocampus, and age-dependent memory impairment. To assess whether Caspase-6 causes damage to another neuronal system, a transgenic knock-in mouse overexpressing a self-activated form of Caspase-6 five-fold in the striatum, the area affected in Huntington disease, and 2...
January 19, 2018: Cell Death and Differentiation
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