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https://www.readbyqxmd.com/read/28646110/the-mcm2-7-interacting-domain-of-human-mini-chromosome-maintenance-10-mcm10-protein-is-important-for-stable-chromatin-association-and-origin-firing
#1
Masako Izumi, Takeshi Mizuno, Ken-Ichiro Yanagi, Kazuto Sugimura, Katsuzumi Okumura, Naoko Imamoto, Tomoko Abe, Fumio Hanaoka
The protein mini-chromosome maintenance 10 (Mcm10) was originally identified as an essential yeast protein in the maintenance of mini-chromosome plasmids. Subsequently, Mcm10 has been shown to be required for both initiation and elongation during chromosomal DNA replication. However, it is not fully understood how the multiple functions of Mcm10 are coordinated or how Mcm10 interacts with other factors at replication forks. Here, we identified and characterized the Mcm2-7-interacting domain in human Mcm10. The interaction with Mcm2-7 required the Mcm10 domain that contained amino acids 530-655, which overlapped with the domain required for the stable retention of Mcm10 on chromatin...
June 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28645708/identification-of-major-routes-of-hiv-transmission-throughout-mesoamerica
#2
Antoine Chaillon, Santiago Avila-Ríos, Joel O Wertheim, Ann Dennis, Claudia García-Morales, Daniela Tapia-Trejo, Carlos Mejía-Villatoro, Juan M Pascale, Guillermo Porras-Cortés, Carlos J Quant-Durán, Ivette Lorenzana, Rita I Meza, Elsa Y Palou, Marvin Manzanero, Rolando A Cedillos, Gustavo Reyes-Terán, Sanjay R Mehta
BACKGROUND: Migration and travel are major drivers of the spread of infectious diseases. Geographic proximity and a common language facilitate travel and migration in Mesoamerica, which in turn could affect the spread of HIV in the region. METHODS: 6092 HIV-1 subtype B partial pol sequences sampled from unique antiretroviral treatment-naïve individuals from Mexico (40.7%), Guatemala (24.4%), Honduras (19%), Panama (8.2%), Nicaragua (5.5%), Belize (1.4%), and El Salvador (0...
June 20, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28645368/fluorescence-based-reporters-for-detection-of-mutagenesis-in-e-coli
#3
Melissa Standley, Jennifer Allen, Layla Cervantes, Joshua Lilly, Manel Camps
Mutagenesis in model organisms following exposure to chemicals is used as an indicator of genotoxicity. Mutagenesis assays are also used to study mechanisms of DNA homeostasis. This chapter focuses on detection of mutagenesis in prokaryotes, which boils down to two approaches: reporter inactivation (forward mutation assay) and reversion of an inactivating mutation (reversion mutation assay). Both methods are labor intensive, involving visual screening, quantification of colonies on solid media, or determining a Poisson distribution in liquid culture...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28641146/early-development-and-predictors-of-morphological-awareness-disentangling-the-impact-of-decoding-skills-and-phonological-awareness
#4
Jeremy M Law, Pol Ghesquière
BACKGROUND: Morphological Awareness (MA) has been demonstrated to be influential on the reading outcomes of children and adults. Yet, little is known regarding MA's early development. AIM: The aim of this study is to better understand MA at different stages of development and its association with Phonological Awareness (PA) and reading. METHODS AND PROCEDURES: In a longitudinal design the development of MA was explored in a group of pre-reading children with a family risk of dyslexia and age-matched controls from kindergarten up to and including grade 2...
June 19, 2017: Research in Developmental Disabilities
https://www.readbyqxmd.com/read/28640874/risk-factors-are-different-for-deep-and-lobar-remote-hemorrhages-after-intravenous-thrombolysis
#5
Luis Prats-Sanchez, Alejandro Martínez-Domeño, Pol Camps-Renom, Raquel Delgado-Mederos, Daniel Guisado-Alonso, Rebeca Marín, Laura Dorado, Salvatore Rudilosso, Alejandra Gómez-González, Francisco Purroy, Manuel Gómez-Choco, David Cánovas, Dolores Cocho, Moises Garces, Sonia Abilleira, Joan Martí-Fàbregas
BACKGROUND AND PURPOSE: Remote parenchymal haemorrhage (rPH) after intravenous thrombolysis is defined as hemorrhages that appear in brain regions without visible ischemic damage, remote from the area of ischemia causing the initial stroke symptom. The pathophysiology of rPH is not clear and may be explained by different underlying mechanisms. We hypothesized that rPH may have different risk factors according to the bleeding location. We report the variables that we found associated with deep and lobar rPH after intravenous thrombolysis...
2017: PloS One
https://www.readbyqxmd.com/read/28640837/identification-and-prediction-of-alternative-transcription-start-sites-that-generate-rod-photoreceptor-specific-transcripts-from-ubiquitously-expressed-genes
#6
Evgenya Y Popova, Anna C Salzberg, Chen Yang, Samuel Shao-Min Zhang, Colin J Barnstable
Transcriptome complexity is substantially increased by the use of multiple transcription start sites for a given gene. By utilizing a rod photoreceptor-specific chromatin signature, and the RefSeq database of established transcription start sites, we have identified essentially all known rod photoreceptor genes as well as a group of novel genes that have a high probability of being expressed in rod photoreceptors. Approximately half of these novel rod genes are transcribed into multiple mRNA and/or protein isoforms through alternative transcriptional start sites (ATSS), only one of which has a rod-specific epigenetic signature and gives rise to a rod transcript...
2017: PloS One
https://www.readbyqxmd.com/read/28638477/triptolide-inhibits-the-ar-signaling-pathway-to-suppress-the-proliferation-of-enzalutamide-resistant-prostate-cancer-cells
#7
Yangyang Han, Weiwei Huang, Jiakuan Liu, Dandan Liu, Yangyan Cui, Ruimin Huang, Jun Yan, Ming Lei
Enzalutamide is a second-generation androgen receptor (AR) antagonist for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Unfortunately, AR dysfunction means that resistance to enzalutamide will eventually develop. Thus, novel agents are urgently needed to treat this devastating disease. Triptolide (TPL), a key active compound extracted from the Chinese herb Thunder God Vine (Tripterygium wilfordii Hook F.), possesses anti-cancer activity in human prostate cancer cells. However, the effects of TPL against CRPC cells and the underlying mechanism of any such effect are unknown...
2017: Theranostics
https://www.readbyqxmd.com/read/28636660/cellular-sensitivity-to-uv-irradiation-is-mediated-by-rna-polymerase-i-transcription
#8
Robin Assfalg, Marius Costel Alupei, Maximilian Wagner, Sylvia Koch, Omar Garcia Gonzalez, Adrian Schelling, Karin Scharffetter-Kochanek, Sebastian Iben
The nucleolus has long been considered to be a pure ribosome factory. However, over the last two decades it became clear that the nucleolus is involved in numerous other functions besides ribosome biogenesis. Our experiments indicate that the activity of RNA polymerase I (Pol I) transcription monitors the integrity of the DNA and influences the response to nucleolar stress as well as the rate of survival. Cells with a repressed ribosomal DNA (rDNA) transcription activity showed an increased and prolonged p53 stabilisation after UVC-irradiation...
2017: PloS One
https://www.readbyqxmd.com/read/28634352/differences-in-sequences-between-hbv-relaxed-circular-dna-and-covalently-closed-circular-dna
#9
Magda Rybicka, Anna Woziwodzka, Tomasz Romanowski, Piotr Stalke, Marcin Dręczewski, Krzysztof Piotr Bielawski
The hepatitis B virus (HBV) genome exists in two forms: circular covalently closed DNA (cccDNA) and relaxed circular DNA (RCDNA). Here, we investigated the presence of differences in the sequences of both forms in paired samples of serum and liver tissue. The serum and liver biopsy samples were collected at the same time from 67 chronically infected patients. The genotyping of the RCDNA and cccDNA was performed using mass spectrometry analysis. The HBV mutations located in the HBV pol (P) and the HBV basal core promoter/pre-core (BCP/PC) regions were included...
June 21, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28633435/mcm3ap-in-recessive-charcot-marie-tooth-neuropathy-and-mild-intellectual-disability
#10
Emil Ylikallio, Rosa Woldegebriel, Manuela Tumiati, Pirjo Isohanni, Monique M Ryan, Zornitza Stark, Maie Walsh, Sarah L Sawyer, Katrina M Bell, Alicia Oshlack, Paul J Lockhart, Mariia Shcherbii, Alejandro Estrada-Cuzcano, Derek Atkinson, Taila Hartley, Martine Tetreault, Inge Cuppen, W Ludo van der Pol, Ayse Candayan, Esra Battaloglu, Yesim Parman, Koen L I van Gassen, Marie-José H van den Boogaard, Kym M Boycott, Liisa Kauppi, Albena Jordanova, Tuula Lönnqvist, Henna Tyynismaa
Defects in mRNA export from the nucleus have been linked to various neurodegenerative disorders. We report mutations in the gene MCM3AP, encoding the germinal center associated nuclear protein (GANP), in nine affected individuals from five unrelated families. The variants were associated with severe childhood onset primarily axonal (four families) or demyelinating (one family) Charcot-Marie-Tooth neuropathy. Mild to moderate intellectual disability was present in seven of nine affected individuals. The affected individuals were either compound heterozygous or homozygous for different MCM3AP variants, which were predicted to cause depletion of GANP or affect conserved amino acids with likely importance for its function...
June 19, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28633434/psip1-p75-promotes-tumorigenicity-in-breast-cancer-cells-by-promoting-the-transcription-of-cell-cycle-genes
#11
Deepak K Singh, Omid Gholamalamdari, Mahdieh Jadaliha, Xiao Ling Li, Yo-Chuen Lin, Yang Zhang, Shuomeng Guang, Seyedsasan Hashemikhabir, Saumya Tiwari, Yuelin J Zhu, Abid Khan, Anu Thomas, Arindam Chakraborty, Virgilia Macias, Andre K Balla, Rohit Bhargava, Sarath Chandra Janga, Jian Ma, Supriya G Prasanth, Ashish Lal, Kannanganattu V Prasanth
Breast cancer (BC) is a highly heterogeneous disease, both at the pathological and molecular level, and several chromatin-associated proteins play crucial roles in breast cancer initiation and progression. Here, we demonstrate the role of PSIP1 (PC4 and SF2 interacting protein)/p75 (LEDGF) in breast cancer progression. PSIP1/p75, previously identified as a chromatin-adaptor protein, is found to be upregulated in basal-like/triple negative breast cancer (TNBC) patient samples and cell lines. Immunohistochemistry in tissue arrays showed elevated levels of PSIP1 in metastatic invasive ductal carcinoma...
June 17, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28631231/2-3-dideoxycytidine-protects-dopaminergic-neurons-in-a-mouse-model-of-parkinson-s-disease
#12
Jianyi Niu, Jing Xiong, Dan Hu, Fei Zeng, Shuke Nie, Shanping Mao, Tao Wang, Zhentao Zhang, Zhaohui Zhang
DNA polymerase-β (DNA pol-β) plays a crucial role in the pathogenesis of Parkinson's disease (PD). The aim of this study was to investigate the neuroprotective effects of a DNA polymerase-β inhibitor 2',3'-dideoxycytidine (DDC) in PD models. In the in vitro studies, primary cultured neurons were challenged with 1-methyl-4-phenylpyridinium ion (MPP(+)). The expression of DNA pol-β was assessed using western blot. The neuroprotective effect of DNA pol-β knockdown and DNA pol-β inhibitor DDC was determined using cell viability assay and caspase-3 activity assay...
June 19, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28630557/international-guidelines-on-human-rights-and-drug-control-a-tool-for-securing-women-s-rights-in-drug-control-policy
#13
Rebecca Schleifer, Luciana Pol
Discrimination and inequality shape women's experiences of drug use and in the drug trade and the impact of drug control efforts on them, with disproportionate burdens faced by poor and otherwise marginalized women. In recent years, UN member states and UN drug control and human rights entities have recognized this issue and made commitments to integrate a 'gender perspective' into drug control policies, with 'gender' limited to those conventionally deemed women. But the concept of gender in international law is broader, rooted in socially constructed and culturally determined norms and expectations around gender roles, sex, and sexuality...
June 2017: Health and Human Rights
https://www.readbyqxmd.com/read/28630251/valnoctamide-inhibits-cytomegalovirus-infection-in-developing-brain-and-attenuates-neurobehavioral-dysfunctions-and-brain-abnormalities
#14
Sara Ornaghi, Lawrence S Hsieh, Angélique Bordey, Patrizia Vergani, Michael J Paidas, Anthony N van den Pol
Cytomegalovirus (CMV) is the most common infectious cause of brain defects and neurological dysfunction in developing human babies. Due to the teratogenicity and toxicity of available CMV antivirals, treatment options during early development are markedly limited. Valnoctamide (VCD), a neuroactive mood stabilizer with no known teratogenic activity, was recently demonstrated to have anti-CMV potential. However, it is not known whether this can be translated into an efficacious therapeutic effect to improve CMV-induced adverse neurological outcomes...
June 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28628667/characterization-of-hiv-1-crf90_bf1-and-putative-novel-crfs_bf1-in-central-west-north-and-northeast-brazilian-regions
#15
Mônica Nogueira da Guarda Reis, Gonzalo Bello, Monick Lindenmeyer Guimarães, Mariane Martins Araújo Stefani
The Brazilian AIDS epidemic has been characterized by an increasing rate of BF1 recombinants and so far eight circulating recombinant forms/CRFs_BF1 have been described countrywide. In this study, pol sequences (protease/PR, reverse transcriptase/RT) of 87 BF1 mosaic isolates identified among 828 patients living in six Brazilian States from three geographic regions (Central West, North, Northeast) were analyzed. Phylogenetic and bootscan analyses were performed to investigate the evolutionary relationship and mosaic structure of BF1 isolates...
2017: PloS One
https://www.readbyqxmd.com/read/28626990/exhaled-breath-profiles-in-the-monitoring-of-loss-of-control-and-clinical-recovery-in-asthma
#16
Paul Brinkman, Marianne A van de Pol, Marije G Gerritsen, Lieuwe D Bos, Tamara Dekker, Barbara S Smids, Anirban Sinha, Christof J Majoor, Marlous M Sneeboer, Hugo H Knobel, Teunis J Vink, Frans H de Jongh, René Lutter, Peter J Sterk, Niki Fens
BACKGROUND: Asthma is a chronic inflammatory airway disease, associated with episodes of exacerbations. Therapy with inhaled corticosteroids (ICS) targets airway inflammation, which aims to maintain and restore asthma control. Clinical features are only modestly associated with airways inflammation. Therefore, we hypothesized that exhaled volatile metabolites identify longitudinal changes between clinically stable episodes and loss of asthma control. OBJECTIVES: To determine whether exhaled volatile organic compounds (VOCs) as measured by gas-chromatography / mass-spectrometry (GC/MS) and electronic nose (eNose) technology discriminate between clinically stable and unstable episodes of asthma...
June 19, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28626934/thermal-phsyiology-a-new-dimension-of-the-pace-of-life-syndrome
#17
C T Goulet, M B Thompson, M Michelangeli, B B M Wong, D G Chapple
1.Current syndrome research focuses primarily on behavior with few incorporating components of physiology. One such syndrome is the Pace-of-Life Syndrome (POLS) which describes covariation between behaviour, metabolism immunity, hormonal response, and life history traits. Despite the strong effect temperature has on behavior, thermal physiology has yet to be considered within this syndrome framework. 2.We proposed the POLS to be extended to include a new dimension, the cold-hot axis. Under this premise, it is predicted that thermal physiology and behavior would covary whereby individual positioning along the thermal continuum would coincide with that of the behavioral continuum...
June 19, 2017: Journal of Animal Ecology
https://www.readbyqxmd.com/read/28624568/towards-a-mechanistic-understanding-of-core-promoter-recognition-from-cryo-em-studies-of-human-tfiid
#18
REVIEW
Eva Nogales, Avinash B Patel, Robert K Louder
TFIID is a critical component of the eukaryotic transcription pre-initiation complex (PIC) required for the recruitment of RNA Pol II to the start site of protein-coding genes. Within the PIC, TFIID's role is to recognize and bind core promoter sequences and recruit the rest of the PIC components. Due to its size and its conformational complexity, TFIID poses a serious challenge for structural characterization. The small amounts of purified TFIID that can be obtained by present methods of purification from endogenous sources has limited structural studies to cryo-EM visualization, which requires very small amounts of sample...
June 15, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28624208/safe-and-efficient-silencing-with-a-pol-ii-but-not-a-pol-lii-promoter-expressing-an-artificial-mirna-targeting-human-huntingtin
#19
Edith L Pfister, Kathryn O Chase, Huaming Sun, Lori A Kennington, Faith Conroy, Emily Johnson, Rachael Miller, Florie Borel, Neil Aronin, Christian Mueller
Huntington's disease is a devastating, incurable neurodegenerative disease affecting up to 12 per 100,000 patients worldwide. The disease is caused by a mutation in the Huntingtin (Htt) gene. There is interest in reducing mutant Huntingtin by targeting it at the mRNA level, but the maximum tolerable dose and long-term effects of such a treatment are unknown. Using a self-complementary AAV9 vector, we delivered a mir-155-based artificial miRNA under the control of the chicken β-actin or human U6 promoter. In mouse brain, the artificial miRNA reduced the human huntingtin mRNA by 50%...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28624194/sustained-inhibition-of-hbv-replication-in%C3%A2-vivo-after-systemic-injection-of-aavs-encoding-artificial-antiviral-primary-micrornas
#20
Mohube Betty Maepa, Abdullah Ely, Wayne Grayson, Patrick Arbuthnot
Chronic infection with hepatitis B virus (HBV) remains a problem of global significance and improving available treatment is important to prevent life-threatening complications arising in persistently infected individuals. HBV is susceptible to silencing by exogenous artificial intermediates of the RNA interference (RNAi) pathway. However, toxicity of Pol III cassettes and short duration of silencing by effectors of the RNAi pathway may limit anti-HBV therapeutic utility. To advance RNAi-based HBV gene silencing, mono- and trimeric artificial primary microRNAs (pri-miRs) derived from pri-miR-31 were placed under control of the liver-specific modified murine transthyretin promoter...
June 16, 2017: Molecular Therapy. Nucleic Acids
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