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https://www.readbyqxmd.com/read/27923209/recognition-of-ubiquitinated-nucleosomes
#1
REVIEW
Michael T Morgan, Cynthia Wolberger
Histone ubiquitination plays a non-degradative role in regulating transcription and the DNA damage response. A mechanistic understanding of this chromatin modification has lagged that of small histone modifications because of the technical challenges in preparing ubiquitinated nucleosomes. The recent structure of the DUB module of the SAGA coactivator complex bound to a nucleosome containing monoubiquitinated H2B has provided the first view of how specialized subunits target this enzyme to its substrate. Single particle electron microscopy of the intact SAGA coactivator suggests how the DUB module and histone acetyltransferase module engage a nucleosomal substrate...
December 3, 2016: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/27923190/a-two-photon-fluorescent-probe-for-biological-cu-%C3%A2-and-ppi-detection-in-aqueous-solution-and-in-vivo
#2
Mengmeng Guo, Pengyu Dong, Yan Feng, Xinguo Xi, Rong Shao, Xiaohe Tian, Buchang Zhang, Manzhou Zhu, Xiangming Meng
The first two-photon fluorescent probe (PC) for selectively detecting biological Cu (Ⅱ) and pyrophosphate (PPi) has been developed based on 7-substituted coumarin in this study. The probe presented excellent selective two-photon "on-off-on" detection signal for Cu(II) /PPi in aqueous solution. The two-photon detection ensemble (PCCu) can detect PPi released from DNA amplification after the polymerase chain reactions (PCR). The probe showed low cytotoxicity and good biocompatibility, and therefore can be applied for imaging Cu(II)/PPi in living cells under two-photon excitation...
November 30, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27923136/chromosome-segregation-reconstituting-the-kinetochore
#3
Frederick G Westhorpe, Aaron F Straight
Faithful chromosome segregation is accomplished by attachment of chromosomes to spindle microtubules using the kinetochore. In a major step forward in understanding the functional and structural complexity of kinetochores, a 21-subunit human centromere - kinetochore complex has been reconstituted entirely from purified components, recreating the connection between DNA and microtubule.
December 5, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27923135/crop-domestication-a-sneak-peek-into-the-midpoint-of-maize-evolution
#4
Garrett M Janzen, Matthew B Hufford
In a new study, DNA from a 5,310-year-old corn cob found in the Tehuacán Valley in Mexico was sequenced and compared to modern maize and its wild progenitor grasses. The sample was found to be an intermediate between modern maize and its wild relatives, suggesting a gradual, protracted domestication process.
December 5, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27923110/impact-of-oligonucleotide-structure-chemistry-and-delivery-method-on-in-vitro-cytotoxicity
#5
Maja M Janas, Yongfeng Jiang, Mark K Schlegel, Scott Waldron, Satya Kuchimanchi, Scott A Barros
Single-stranded (ss) 2'-fluoro (2'-F)-modified oligonucleotides (ONs) with a full phosphorothioate (PS) backbone have been reported to be cytotoxic and cause DNA double-strand breaks (DSBs) when transfected into HeLa cells. However, the molecular determinants of these effects have not been fully explored. In this study, we investigated the impact of ON structure, chemistry, delivery method, and cell type on in vitro cytotoxicity and DSBs. We found that ss PS-ONs were more cytotoxic than double-stranded (ds) PS-ONs, irrespective of the 2'-ribose chemistry, inclusive of the 2'-F modification...
December 6, 2016: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/27923103/noninvasive-microsurgery-using-aptamer-functionalized-magnetic-microdisks-for-tumor-cell-eradication
#6
Tatiana N Zamay, Galina S Zamay, Irina V Belyanina, Sergey S Zamay, Valery V Denisenko, Olga S Kolovskaya, Tatiana I Ivanchenko, Valentina L Grigorieva, Irina V Garanzha, Dmitry V Veprintsev, Yury E Glazyrin, Alexandr V Shabanov, Viktor Y Prinz, Vladimir A Seleznev, Alexey E Sokolov, Vladimir S Prokopenko, Petr D Kim, Ana Gargaun, Maxim V Berezovski, Anna S Zamay
Magnetomechanical cell disruption using nano- and microsized structures is a promising biomedical technology used for noninvasive elimination of diseased cells. It applies alternating magnetic field (AMF) for ferromagnetic microdisks making them oscillate and causing cell membrane disruption with cell death followed by apoptosis. In this study, we functionalized the magnetic microdisks with cell-binding DNA aptamers and guided the microdisks to recognize cancerous cells in a mouse tumor in vivo. Only 10 min of the treatment with a 100 Hz AMF was enough to eliminate cancer cells from a malignant tumor...
December 6, 2016: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/27923066/somatic-genomics-and-clinical-features-of-lung-adenocarcinoma-a-retrospective-study
#7
Jianxin Shi, Xing Hua, Bin Zhu, Sarangan Ravichandran, Mingyi Wang, Cu Nguyen, Seth A Brodie, Alessandro Palleschi, Marco Alloisio, Gianluca Pariscenti, Kristine Jones, Weiyin Zhou, Aaron J Bouk, Joseph Boland, Belynda Hicks, Adam Risch, Hunter Bennett, Brian T Luke, Lei Song, Jubao Duan, Pengyuan Liu, Takashi Kohno, Qingrong Chen, Daoud Meerzaman, Crystal Marconett, Ite Laird-Offringa, Ian Mills, Neil E Caporaso, Mitchell H Gail, Angela C Pesatori, Dario Consonni, Pier Alberto Bertazzi, Stephen J Chanock, Maria Teresa Landi
BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer and has a high risk of distant metastasis at every disease stage. We aimed to characterize the genomic landscape of LUAD and identify mutation signatures associated with tumor progression. METHODS AND FINDINGS: We performed an integrative genomic analysis, incorporating whole exome sequencing (WES), determination of DNA copy number and DNA methylation, and transcriptome sequencing for 101 LUAD samples from the Environment And Genetics in Lung cancer Etiology (EAGLE) study...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27923060/the-limitations-of-model-based-experimental-design-and-parameter-estimation-in-sloppy-systems
#8
Andrew White, Malachi Tolman, Howard D Thames, Hubert Rodney Withers, Kathy A Mason, Mark K Transtrum
We explore the relationship among experimental design, parameter estimation, and systematic error in sloppy models. We show that the approximate nature of mathematical models poses challenges for experimental design in sloppy models. In many models of complex biological processes it is unknown what are the relevant physical mechanisms that must be included to explain system behaviors. As a consequence, models are often overly complex, with many practically unidentifiable parameters. Furthermore, which mechanisms are relevant/irrelevant vary among experiments...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27923055/a-novel-rrm3-function-in-restricting-dna-replication-via-an-orc5-binding-domain-is-genetically-separable-from-rrm3-function-as-an-atpase-helicase-in-facilitating-fork-progression
#9
Salahuddin Syed, Claus Desler, Lene J Rasmussen, Kristina H Schmidt
In response to replication stress cells activate the intra-S checkpoint, induce DNA repair pathways, increase nucleotide levels, and inhibit origin firing. Here, we report that Rrm3 associates with a subset of replication origins and controls DNA synthesis during replication stress. The N-terminal domain required for control of DNA synthesis maps to residues 186-212 that are also critical for binding Orc5 of the origin recognition complex. Deletion of this domain is lethal to cells lacking the replication checkpoint mediator Mrc1 and leads to mutations upon exposure to the replication stressor hydroxyurea...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27923045/tumor-evolution-in-two-patients-with-basal-like-breast-cancer-a-retrospective-genomics-study-of-multiple-metastases
#10
Katherine A Hoadley, Marni B Siegel, Krishna L Kanchi, Christopher A Miller, Li Ding, Wei Zhao, Xiaping He, Joel S Parker, Michael C Wendl, Robert S Fulton, Ryan T Demeter, Richard K Wilson, Lisa A Carey, Charles M Perou, Elaine R Mardis
BACKGROUND: Metastasis is the main cause of cancer patient deaths and remains a poorly characterized process. It is still unclear when in tumor progression the ability to metastasize arises and whether this ability is inherent to the primary tumor or is acquired well after primary tumor formation. Next-generation sequencing and analytical methods to define clonal heterogeneity provide a means for identifying genetic events and the temporal relationships between these events in the primary and metastatic tumors within an individual...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27922905/scale-up-of-an-human-papillomavirus-testing-implementation-program-in-el-salvador
#11
Miriam Cremer, Mauricio Maza, Karla Alfaro, Mario Morales Velado, Juan Felix, Philip E Castle, Jane Kim, Julia C Gage
OBJECTIVE: The Cervical Cancer Prevention in El Salvador is a demonstration project to introduce a lower-cost human papillomavirus (HPV)-DNA test into a public sector project. Started in October 2012, The Cervical Cancer Prevention in El Salvador consists of 3 phases and will ultimately screen 30,000 women. Results of phase 2 of the project are presented. The objective of this project was to compare colposcopy and noncolposcopy-based management for HPV-positive women. MATERIAL AND METHODS: In phase 2, a total of 8,050 women, aged 30 to 49 years, were screened; 6,761 provided both self- and provider-collected specimens and 1,289 provided only provider-testing specimens...
December 6, 2016: Journal of Lower Genital Tract Disease
https://www.readbyqxmd.com/read/27922854/identification-of-hiv-infection-related-dna-methylation-sites-and-advanced-epigenetic-aging-in-hiv-treatment-na%C3%A3-ve-u-s-veterans
#12
Kristin N Nelson, Qin Hui, David Rimland, Ke Xu, Matthew S Freiberg, Amy C Justice, Vincent C Marconi, Yan V Sun
OBJECTIVE: HIV-positive individuals are at higher risk than healthy persons for aging-related diseases, including myocardial infarction and non-AIDS defining cancers. Recent evidence suggests that HIV infection may modulate changes in the host cell epigenome, and these changes represent a potential mechanism through which HIV infection accelerates aging. We assessed the difference in DNAm age, an aging marker involving multiple age-related CpG sites, among antiretroviral treatment (ART) naïve HIV-positive and HIV-negative individuals in a cohort of veterans from the Veterans Aging Cohort Study (VACS)...
December 5, 2016: AIDS
https://www.readbyqxmd.com/read/27922819/early-age-decline-in-dna-repair-capacity-in-the-liver-in-depth-profile-of-differential-gene-expression
#13
Avital Guedj, Anat Geiger-Maor, Eithan Galun, Hagai Amsalem, Jacob Rachmilewitz
Aging is associated with progressive decline in cell function and with increased damage to macromolecular components. DNA damage, in the form of double-strand breaks (DSBs), increases with age and in turn, contributes to the aging process and age-related diseases. DNA strand breaks triggers a set of highly orchestrated signaling events known as the DNA damage response (DDR), which coordinates DNA repair. However, whether the accumulation of DNA damage with age is a result of decreased repair capacity, remains to be determined...
November 30, 2016: Aging
https://www.readbyqxmd.com/read/27922817/ischemic-stroke-patients-are-biologically-older-than-their-chronological-age
#14
Carolina Soriano-Tárraga, Eva Giralt-Steinhauer, Marina Mola-Caminal, Rosa M Vivanco-Hidalgo, Angel Ois, Ana Rodríguez-Campello, Elisa Cuadrado-Godia, Sergi Sayols-Baixeras, Roberto Elosua, Jaume Roquer, Jordi Jiménez-Conde
Ischemic stroke is associated with aging. It is possible to predict chronological age by measuring age-related changes in DNA methylation from multiple CpG sites across the genome, known as biological age. The difference between biological age and actual chronological age would indicate an individual's level of aging. Our aim was to determine the biological age of ischemic stroke patients and compare their aging with controls of the same chronological age. A total of 123 individuals, 41 controls and 82 patients with ischemic stroke were paired by chronological age, ranging from 39 to 82 years...
August 25, 2016: Aging
https://www.readbyqxmd.com/read/27922802/urban-breeding-corvids-as-disseminators-of-ticks-and-emerging-tick-borne-pathogens
#15
Attila D Sándor, Zsuzsa Kalmár, Ioana Matei, Angela Monica Ionică, Ioan-Daniel Mărcuţan
Crows (Corvidae) are common city dwellers worldwide and are increasingly important subjects of epidemiology studies. Although their importance as hosts and transmitters of a number of zoonotic parasites and pathogens is well known, there are no studies on their importance as tick hosts. After mosquitoes, ticks are the most important vectors of zoonotic pathogens, especially for those causing emerging zoonotic diseases. Pathogenic bacteria, especially Borrelia spp., Rickettsia spp., and Anaplasma spp., vectored by ticks, are the cause for most vector-borne diseases in Europe...
December 6, 2016: Vector Borne and Zoonotic Diseases
https://www.readbyqxmd.com/read/27922685/5%C3%A2-bromo%C3%A2-3%C3%A2-3%C3%A2-hydroxyprop%C3%A2-1%C3%A2-ynyl-%C3%A2-2h%C3%A2-pyran%C3%A2-2%C3%A2-one-induces-apoptosis-in-t24-human-bladder-cancer-cells-through-mitochondria-dependent-signaling-pathways
#16
Guo-Qiang Yu, Zhong-Ling Dou, Zhao-Hui Jia
The present study was performed to investigate the effect of 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one (BHP) on the induction of apoptosis and cell cycle arrest in T24 human bladder carcinoma cells. An MTT assay was used to investigate the inhibition of cell proliferation. Flow cytometry was used to observe alterations in the cell cycle, generation of reactive oxygen species (ROS), alterations in mitochondrial membrane potential (MMP) and induction of apoptosis in the T24 cells following BHP treatment...
December 6, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27922679/repetitive-extragenic-palindromic-dna-sequences-from-brucella%C3%A2-melitensis-stimulate-toll-like-receptor-9-signaling-in-macrophages
#17
Hui Yu, Liyun Bai, Yaxian Zhang, Zhanli Wang, Yongchun Yu
Brucella DNA activates the host innate immune system via the intracellular Toll-like receptor 9 (TLR9). However, the Brucella DNA sequences which are responsible for these immunostimulatory effects remain to be elucidated. The present study demonstrated that repetitive extragenic palindromic (REPs) sequences present in Brucella DNA were able to stimulate macrophages through TLR9. The induction of interferon-α (IFN-α) production by Brucella REPs was detected in cultured RAW264.7 mouse macrophages as well as in Wistar rats...
December 6, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27922636/dna-methylation-and-substance-use-risk-a-prospective-genome-wide-study-spanning-gestation-to-adolescence
#18
C A M Cecil, E Walton, R G Smith, E Viding, E J McCrory, C L Relton, M Suderman, J-B Pingault, W McArdle, T R Gaunt, J Mill, E D Barker
Epigenetic processes have been implicated in addiction; yet, it remains unclear whether these represent a risk factor and/or a consequence of substance use. Here, we believe we conducted the first genome-wide, longitudinal study to investigate whether DNA methylation patterns in early life prospectively associate with substance use in adolescence. The sample comprised of 244 youth (51% female) from the Avon Longitudinal Study of Parents and Children (ALSPAC), with repeated assessments of DNA methylation (Illumina 450k array; cord blood at birth, whole blood at age 7) and substance use (tobacco, alcohol and cannabis use; age 14-18)...
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27922635/increased-plasma-levels-of-circulating-cell-free-mitochondrial-dna-in-suicide-attempters-associations-with-hpa-axis-hyperactivity
#19
D Lindqvist, J Fernström, C Grudet, L Ljunggren, L Träskman-Bendz, L Ohlsson, Å Westrin
Preclinical data suggest that chronic stress may cause cellular damage and mitochondrial dysfunction, potentially leading to the release of mitochondrial DNA (mtDNA) into the bloodstream. Major depressive disorder has been associated with an increased amount of mtDNA in leukocytes from saliva samples and blood; however, no previous studies have measured plasma levels of free-circulating mtDNA in a clinical psychiatric sample. In this study, free circulating mtDNA was quantified in plasma samples from 37 suicide attempters, who had undergone a dexamethasone suppression test (DST), and 37 healthy controls...
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27922628/a-chromosome-level-genome-assembly-of-the-asian-arowana-scleropages-formosus
#20
Jia Li, Chao Bian, Yinchang Hu, Xidong Mu, Xueyan Shen, Vydianathan Ravi, Inna S Kuznetsova, Ying Sun, Xinxin You, Ying Qiu, Xinhui Zhang, Hui Yu, Yu Huang, Pao Xu, Ruobo Gu, Junmin Xu, László Orbán, Byrappa Venkatesh, Qiong Shi
Asian arowana (Scleropages formosus), an ancient teleost belonging to the Order Osteoglossomorpha, has been a valuable ornamental fish with some varieties. However, its biological studies and breeding germplasm have been remarkably limited by the lack of a reference genome. To solve these problems, here we report high-quality genome sequences of three common varieties of Asian arowana (the golden, red and green arowana). We firstly generated a chromosome-level genome assembly of the golden arowana, on basis of the genetic linkage map constructed with the restriction site-associated DNA sequencing (RAD-seq)...
December 6, 2016: Scientific Data
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