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https://www.readbyqxmd.com/read/27914072/identifying-bacterial-immune-evasion-proteins-using-phage-display
#1
Cindy Fevre, Lisette Scheepmaker, Pieter-Jan Haas
Methods aimed at identification of immune evasion proteins are mainly rely on in silico prediction of sequence, structural homology to known evasion proteins or use a proteomics driven approach. Although proven successful these methods are limited by a low efficiency and or lack of functional identification. Here we describe a high-throughput genomic strategy to functionally identify bacterial immune evasion proteins using phage display technology. Genomic bacterial DNA is randomly fragmented and ligated into a phage display vector that is used to create a phage display library expressing bacterial secreted and membrane bound proteins...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27913833/tight-repulsion-linkage-between-sr36-and-sr39-was-revealed-by-genetic-cytogenetic-and-molecular-analyses
#2
Bosco Chemayek, Urmil K Bansal, Naeela Qureshi, Peng Zhang, William W Wagoire, Harbans S Bariana
The shortening of Aegilops speltoides segment did not facilitate recombination between stem rust resistance genes Sr36 and Sr39 . Robustness of marker rwgs28 for marker-assisted selection of Sr39 was demonstrated. Stem rust resistance genes Sr39 and Sr36 were transferred from Aegilops speltoides and Triticum timopheevii, respectively, to chromosome 2B of wheat. Genetic stocks RL6082 and RWG1 carrying Sr39 on a large and a shortened Ae. speltoides segments, respectively, and the Sr36-carrying Australian wheat cultivar Cook were used in this study...
December 2, 2016: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
https://www.readbyqxmd.com/read/27913682/translational-regulation-of-mitochondrial-biogenesis
#3
REVIEW
Yi Zhang, Hong Xu
Mitochondria are generated by the expression of genes on both nuclear and mitochondrial genome. Mitochondrial biogenesis is highly plastic in response to cellular energy demand, developmental signals and environmental stimuli. Mechanistic target of rapamycin (mTOR) pathway regulates mitochondrial biogenesis to co-ordinate energy homeostasis with cell growth. The local translation of mitochondrial proteins on the outer membrane facilitates their efficient import and thereby allows prodigious mitochondrial biogenesis during rapid cell growth and proliferation...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27913617/evaluating-sequence-based-genomic-prediction-with-an-efficient-new-simulator
#4
Miguel Pérez-Enciso, Natalia Forneris, Gustavo de Los Campos, Andrés Legarra
The vast amount of sequence data to analyze complex traits is posing new challenges in terms of analysis and interpretation of the results. Although simulation is a fundamental tool to investigate the reliability of genomic analyses and to optimize experimental design, existing software cannot simulate complete genomes realistically. To remedy this, we have developed a new strategy (Sequence Based Virtual Breeding, SBVB) that consists of using real sequence data and simulating new offspring genomes and phenotypes in a very efficient and flexible manner...
December 2, 2016: Genetics
https://www.readbyqxmd.com/read/27913567/drug-repositioning-screens-identify-triamterene-as-a-selective-drug-for-the-treatment-of-dna-mismatch-repair-deficient-cells
#5
Delphine Guillotin, Philip Austin, Rumena Begum, Marta O Freitas, Ashirwad Merve, Tim Brend, Susan C Short, Silvia Marino, Sarah A Martin
PURPOSE: The DNA Mismatch repair (MMR) pathway is required for the maintenance of genome stability. Unsurprisingly, mutations in MMR genes occur in a wide range of different cancers. Studies thus far have largely focused on specific tumor types or MMR mutations, however it is becoming increasingly clear that a therapy targeting MMR-deficiency in general would be clinically very beneficial. EXPERIMENTAL DESIGN: Based on a drug-repositioning approach, we screened a large panel of cell lines with various MMR deficiencies from a range of different tumor types with a compound drug library of previously approved drugs...
December 2, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27913501/mutations-in-aml-prognostic-and-therapeutic-implications
#6
Courtney D DiNardo, Jorge E Cortes
Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the proliferation and aberrant differentiation of immature clonal myeloid cells. The prognosis of AML is variable, based on clinical features such as patient age, performance status, and comorbidities, as well as leukemia-specific genetic features including cytogenetics and molecular classification. The modern application of next-generation sequencing technology has uncovered marked heterogeneity and genomic complexity within AML, based on the presence or absence of cooperating mutations within functional categories such as epigenetic regulators, cell signaling and proliferation pathways, and master hematopoietic transcription factors...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913357/introducing-a-stable-bootstrap-validation-framework-for-reliable-genomic-signature-extraction
#7
Nikolaos-Kosmas Chlis, Ekaterini S Bei, Michael Zervakis
The application of machine learning methods for the identification of candidate genes responsible for phenotypes of interest, such as cancer, is a major challenge in the field of bioinformatics. These lists of genes are often called genomic signatures and their linkage to phenotype associations may form a significant step in discovering the causation between genotypes and phenotypes. Traditional methods that produce genomic signatures from DNA Microarray data tend to extract significantly different lists under relatively small variations of the training data...
November 29, 2016: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/27913139/estimating-heritable-genetic-contributions-to-innate-immune-and-endocrine-phenotypic-correlations-a-need-to-explore-repeatability
#8
REVIEW
Timothy J Greives, Ned A Dochtermann, Emily C Stewart
The immune system plays an important role in enhancing an individual's ability to survive in a world inhabited by pathogens and parasites. The innate immune system is regulated by processes encoded in an individual's genome, providing an avenue for selection to act on this system, as well as the phenotypic relationships generated between this system and other traits of interest. While relationships between innate immunity and endocrine traits (e.g. testosterone) have been reported often in the literature, these relationships are complex and may differ under varying environmental conditions...
November 29, 2016: Hormones and Behavior
https://www.readbyqxmd.com/read/27911958/advantages-of-an-improved-rhesus-macaque-genome-for-evolutionary-analyses
#9
Julien S Gradnigo, Abhishek Majumdar, Robert B Norgren, Etsuko N Moriyama
The rhesus macaque (Macaca mulatta) is widely used in molecular evolutionary analyses, particularly to identify genes under adaptive or unique evolution in the human lineage. For such studies, it is necessary to align nucleotide sequences of homologous protein-coding genes among multiple species. The validity of these analyses is dependent on high quality genomic data. However, for most mammalian species (other than humans and mice), only draft genomes are available. There has been concern that some results obtained from evolutionary analyses using draft genomes may not be correct...
2016: PloS One
https://www.readbyqxmd.com/read/27911848/global-analysis-of-genomic-instability-caused-by-dna-replication-stress-in-saccharomyces-cerevisiae
#10
Dao-Qiong Zheng, Ke Zhang, Xue-Chang Wu, Piotr A Mieczkowski, Thomas D Petes
DNA replication stress (DRS)-induced genomic instability is an important factor driving cancer development. To understand the mechanisms of DRS-associated genomic instability, we measured the rates of genomic alterations throughout the genome in a yeast strain with lowered expression of the replicative DNA polymerase δ. By a genetic test, we showed that most recombinogenic DNA lesions were introduced during S or G2 phase, presumably as a consequence of broken replication forks. We observed a high rate of chromosome loss, likely reflecting a reduced capacity of the low-polymerase strains to repair double-stranded DNA breaks (DSBs)...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911780/selective-sweep-suggests-transcriptional-regulation-may-underlie-plasmodium-vivax-resilience-to-malaria-control-measures-in-cambodia
#11
Christian M Parobek, Jessica T Lin, David L Saunders, Eric J Barnett, Chanthap Lon, Charlotte A Lanteri, Sujata Balasubramanian, Nicholas Brazeau, Derrick K DeConti, Deen L Garba, Steven R Meshnick, Michele D Spring, Char Meng Chuor, Jeffrey A Bailey, Jonathan J Juliano
Cambodia, in which both Plasmodium vivax and Plasmodium falciparum are endemic, has been the focus of numerous malaria-control interventions, resulting in a marked decline in overall malaria incidence. Despite this decline, the number of P vivax cases has actually increased. To understand better the factors underlying this resilience, we compared the genetic responses of the two species to recent selective pressures. We sequenced and studied the genomes of 70 P vivax and 80 P falciparum isolates collected between 2009 and 2013...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911745/the-role-of-epigenetic-mechanisms-in-the-regulation-of-gene-expression-in-the-nervous-system
#12
Justyna Cholewa-Waclaw, Adrian Bird, Melanie von Schimmelmann, Anne Schaefer, Huimei Yu, Hongjun Song, Ram Madabhushi, Li-Huei Tsai
Neuroepigenetics is a newly emerging field in neurobiology that addresses the epigenetic mechanism of gene expression regulation in various postmitotic neurons, both over time and in response to environmental stimuli. In addition to its fundamental contribution to our understanding of basic neuronal physiology, alterations in these neuroepigenetic mechanisms have been recently linked to numerous neurodevelopmental, psychiatric, and neurodegenerative disorders. This article provides a selective review of the role of DNA and histone modifications in neuronal signal-induced gene expression regulation, plasticity, and survival and how targeting these mechanisms could advance the development of future therapies...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27910942/improved-bi-allelic-modification-of-a-transcriptionally-silent-locus-in-patient-derived-ipsc-by-cas9-nickase
#13
Reto Eggenschwiler, Mohsen Moslem, Mariane Serra Fráguas, Melanie Galla, Oliver Papp, Maximilian Naujock, Ines Fonfara, Ingrid Gensch, Annabell Wähner, Abbas Beh-Pajooh, Claudio Mussolino, Marcel Tauscher, Doris Steinemann, Florian Wegner, Susanne Petri, Axel Schambach, Emmanuelle Charpentier, Toni Cathomen, Tobias Cantz
Homology directed repair (HDR)-based genome editing via selectable long flanking arm donors can be hampered by local transgene silencing at transcriptionally silent loci. Here, we report efficient bi-allelic modification of a silent locus in patient-derived hiPSC by using Cas9 nickase and a silencing-resistant donor construct that contains an excisable selection/counter-selection cassette. To identify the most active single guide RNA (sgRNA)/nickase combinations, we employed a lentiviral vector-based reporter assay to determine the HDR efficiencies in cella...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910927/novel-chemoimmunotherapeutic-strategy-for-hepatocellular-carcinoma-based-on-a-genome-wide-association-study
#14
Kaku Goto, Dorcas A Annan, Tomoko Morita, Wenwen Li, Ryosuke Muroyama, Yasuo Matsubara, Sayaka Ito, Ryo Nakagawa, Yasushi Tanoue, Masahisa Jinushi, Naoya Kato
Pharmacotherapeutic options are limited for hepatocellular carcinoma (HCC). Recently, we identified the anti-tumor ligand MHC class I polypeptide-related sequence A (MICA) gene as a susceptibility gene for hepatitis C virus-induced HCC in a genome-wide association study (GWAS). To prove the concept of HCC immunotherapy based on the results of a GWAS, in the present study, we searched for drugs that could restore MICA expression. A screen of the FDA-approved drug library identified the anti-cancer agent vorinostat as the strongest hit, suggesting histone deacetylase inhibitors (HDACis) as potent candidates...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910803/the-prognostic-and-predictive-value-of-tmprss2-erg-gene-fusion-and-erg-protein-expression-in-prostate-cancer-biopsies
#15
Kasper Drimer Berg
BACKGROUND: The clinical course of prostate carcinoma (PCa) is very heterogeneous. Consequently, a personalised approach for risk stratification and treatment planning is important. Recently, it has become evident that PCa, also at the genomic level, is heterogeneous. An early and common alteration is the gene fusion between the transmembrane protease serine 2 (TMPRSS2) gene and the v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) gene resulting in expression of the oncoprotein ERG...
December 2016: Danish Medical Journal
https://www.readbyqxmd.com/read/27910110/runs-of-homozygosity-current-knowledge-and-applications-in-livestock
#16
REVIEW
E Peripolli, D P Munari, M V G B Silva, A L F Lima, R Irgang, F Baldi
This review presents a broader approach to the implementation and study of runs of homozygosity (ROH) in animal populations, focusing on identifying and characterizing ROH and their practical implications. ROH are continuous homozygous segments that are common in individuals and populations. The ability of these homozygous segments to give insight into a population's genetic events makes them a useful tool that can provide information about the demographic evolution of a population over time. Furthermore, ROH provide useful information about the genetic relatedness among individuals, helping to minimize the inbreeding rate and also helping to expose deleterious variants in the genome...
December 1, 2016: Animal Genetics
https://www.readbyqxmd.com/read/27910017/fluorescence-in-situ-hybridization-probe-preparation
#17
Doron Tolomeo, Roscoe R Stanyon, Mariano Rocchi
The public human genome sequencing project utilized a hierarchical approach. A large number of BAC/PAC clones, with an insert size approximate from 50 kb to 300 kb, were identified and finely mapped with respect to the Sequence Tagged Site (STS) physical map and with respect to each other. A "golden path" of BACs, covering the entire human genome, was then selected and each clone was fully sequenced. The large number of remaining BACs was not fully sequenced, but the availability of the end sequence (~800-1000 bp) at each end allowed them to be very precisely mapped on the human genome...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27909440/introgressing-subgenome-components-from-brassica-rapa-and-b-carinata-to-b-juncea-for-broadening-its-genetic-base-and-exploring-intersubgenomic-heterosis
#18
Zili Wei, Meng Wang, Shihao Chang, Chao Wu, Peifa Liu, Jinling Meng, Jun Zou
Brassica juncea (A(j)A(j)B(j)B(j)), is an allotetraploid that arose from two diploid species, B. rapa (A(r)A(r)) and B. nigra (B(n)B(n)). It is an old oilseed crop with unique favorable traits, but the genetic improvement on this species is limited. We developed an approach to broaden its genetic base within several generations by intensive selection. The A(r) subgenome from the Asian oil crop B. rapa (A(r)A(r)) and the B(c) subgenome from the African oil crop B. carinata (B(c)B(c)C(c)C(c)) were combined in a synthesized allohexaploid (A(r)A(r)B(c)B(c)C(c)C(c)), which was crossed with traditional B...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27907911/genetic-variants-in-the-znf208-gene-are-associated-with-esophageal-cancer-in-a-chinese-han-population
#19
Huijie Wang, Jianzhong Yu, Yanling Guo, Zhengxing Zhang, Guoqi Liu, Jingjie Li, Xiyang Zhang, Tianbo Jin, Zhaoxia Wang
Previous studies showed an association between the ZNF208 gene and gastric cancer. In this study, we investigated the association between single nucleotide polymorphisms (SNPs) in ZNF208 and the risk of esophageal cancer in a Chinese Han population. We conducted a case-control study that included 386 cases and 495 controls. Five SNPs were selected from previous genome-wide association studies and genotyped using the Sequenom MassARRAY platform. Unconditional logistic regression was used to calculate odds ratios and 95% confidence intervals after adjustment for age and gender...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27907910/a-mononucleotide-repeat-in-prrt2-is-an-important-frequent-target-of-mismatch-repair-deficiency-in-cancer
#20
Inês Teles Alves, David Cano, René Böttcher, Hetty van der Korput, Winand Dinjens, Guido Jenster, Jan Trapman
The DNA mismatch repair (MMR) system corrects DNA replication mismatches thereby contributing to the maintenance of genomic stability. MMR deficiency has been observed in prostate cancer but its impact on the genomic landscape of these tumours is not known. In order to identify MMR associated mutations in prostate cancer we have performed whole genome sequencing of the MMR deficient PC346C prostate cancer cell line. We detected a total of 1196 mutations in PC346C which was 1.5-fold higher compared to a MMR proficient prostate cancer sample (G089)...
November 19, 2016: Oncotarget
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