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Suicide genomics

Anne H Neddermeyer, Kjell Hultenby, Maruthibabu Paidikondala, Ryan M Schuchman, Mehdi R M Bidokhti
Background: Research on the biogenesis of tick-borne encephalitis virus (TBEV) would benefit gene therapy. Due to specific arrangements of genes along the TBEV genome, its viral-like particles (VLPs) could be exploited as shuttles to deliver their replicon, which carries therapeutic genes, to immune system cells. Objective: To develop a flaviviral vector for gene delivery as a part of gene therapy research that can be expressed in secretable VLP suicidal shuttles and provide abundant unique molecular and structural data supporting this gene therapy concept...
2018: Current Therapeutic Research, Clinical and Experimental
P-O Cheptou
Background and Aims: As a major evolutionary transition in seed plants, the evolution of plant mating systems has been much debated in evolutionary ecology. Over the last 10 years, well-established patterns of evolution have emerged. On the one hand, experimental studies have shown that self-fertilization is likely to evolve in a few generations (microevolution) as a response to rapid environmental change (e.g. pollinator decline), eventually rescuing a population. On the other, phylogenetic studies have demonstrated that repeated evolution towards self-fertilization (macroevolution) leads to a higher risk of lineage extinction and is thus likely to be disadvantageous in the long term...
July 20, 2018: Annals of Botany
Eugene Lin, Po-Hsiu Kuo, Yu-Li Liu, Younger W-Y Yu, Albert C Yang, Shih-Jen Tsai
In the wake of recent advances in scientific research, personalized medicine using deep learning techniques represents a new paradigm. In this work, our goal was to establish deep learning models which distinguish responders from non-responders, and also to predict possible antidepressant treatment outcomes in major depressive disorder (MDD). To uncover relationships between the responsiveness of antidepressant treatment and biomarkers, we developed a deep learning prediction approach resulting from the analysis of genetic and clinical factors such as single nucleotide polymorphisms (SNPs), age, sex, baseline Hamilton Rating Scale for Depression score, depressive episodes, marital status, and suicide attempt status of MDD patients...
2018: Frontiers in Psychiatry
A Wojtczyk-Miaskowska, B Schlichtholz
The maintenance of genomic integrity through the DNA repair processes is essential for proper cellular metabolism, growth, and development. DNA damage plays a key role in mutagenesis and the development of cancer. The cellular DNA damage response activates complex signaling pathways that may promote not only DNA repair and survival but also can trigger cell suicide. Exceptionally long-lived animals may allow explaining the mechanisms of healthy aging without cancer. One of the particular emphases of this review is the link between oxidative stress, DNA repair pathways, and longevity...
July 10, 2018: DNA Repair
Claire L McGrory, Karen M Ryan, Erik Kolshus, Martha Finnegan, Declan M McLoughlin
Sirtuins are a family of nicotinamide adenine dinucleotide (NAD+) dependent enzymes that regulate cellular functions through deacetylation of protein targets. They have roles in both the periphery and central nervous system and have been implicated in depression biology. A recent genome-wide association study has identified a locus for major depression in the Sirtuin1 gene (SIRT1) and lower blood levels of SIRT1 mRNA in patients with depression have also been observed in two studies. To our knowledge, no studies have examined the effect of treatment on SIRT1 levels in patients with depression...
July 12, 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Clement C Zai, Arun K Tiwari, Gwyneth C Zai, Vincenzo de Luca, Sajid A Shaikh, Nicole King, John Strauss, James L Kennedy, John B Vincent
Background: A number of genes have been implicated in recent genome-wide association studies of suicide attempt in bipolar disorder. More focused investigation of genes coding for protein targets of existing drugs may lead to drug repurposing for the treatment and/or prevention of suicide. Methods: We analyzed 2,457 DNA variants across 197 genes of interest to GlaxoSmithKline across the pipeline in our sample of European patients suffering from bipolar disorder ( N = 219)...
June 2018: Molecular Neuropsychiatry
Marine Ricordel, Johann Foloppe, Delphine Antoine, Annie Findeli, Juliette Kempf, Pascale Cordier, Aude Gerbaud, Benoit Grellier, Monika Lusky, Eric Quemeneur, Philippe Erbs
Oncolytic virus (OV) therapy has emerged as a promising approach for cancer treatment with the potential to be less toxic and more efficient than classic cancer therapies. Various types of OVs in clinical development, including Vaccinia virus (VACV)-derived OVs, have shown good safety profiles, but limited therapeutic efficacy as monotherapy in some cancer models. Many different methods have been employed to improve the oncolytic potency of OVs. In this study, we used a directed evolution process, pooling different strains of VACV, including Copenhagen, Western Reserve and Wyeth strains and the attenuated modified vaccinia virus Ankara (MVA), to generate a new recombinant poxvirus with increased oncolytic properties...
July 10, 2018: Cancers
MaFeng Liu, Yue Huang, JiaJun Liu, Francis Biville, DeKang Zhu, MingShu Wang, RenYong Jia, Shun Chen, XinXin Zhao, Qiao Yang, Ying Wu, Shaqiu Zhang, XiaoYue Chen, YunYa Liu, Ling Zhang, Yu You, YanLing Yu, AnChun Cheng
Riemerella anatipestifer (R. anatipestifer, RA) is an important bacterial pathogen of ducks and other birds; infection with RA causes high poultry mortality and heavy economic losses in the poultry industry. However, the pathogenesis of this bacterium is poorly understood, in part due to the lack of a suitable array of methods for genetic manipulation. In this study, we first examined the efficacy of the mutated pheS gene (pheS*) as a counterselectable marker in R. anatipestifer. A suicide vector carrying pheS*, pOES, was constructed and used for markerless deletion of the gene RA0C_2053 which encode a putative TonB-dependent receptor in RA ATCC11845...
June 27, 2018: Applied Microbiology and Biotechnology
Bin Xiong, Zhongkang Li, Li Liu, Dongdong Zhao, Xueli Zhang, Changhao Bi
Background: Ralstonia eutropha is an important bacterium for the study of polyhydroxyalkanoates (PHAs) synthesis and CO2 fixation, which makes it a potential strain for industrial PHA production and attractive host for CO2 conversion. Although the bacterium is not recalcitrant to genetic manipulation, current methods for genome editing based on group II introns or single crossover integration of a suicide plasmid are inefficient and time-consuming, which limits the genetic engineering of this organism...
2018: Biotechnology for Biofuels
Lisa Nonaka, Tatsuya Yamamoto, Fumito Maruyama, Yuu Hirose, Yuki Onishi, Takeshi Kobayashi, Satoru Suzuki, Nobuhiko Nomura, Michiaki Masuda, Hirokazu Yano
The capture of antimicrobial resistance genes (ARGs) by mobile genetic elements (MGEs) plays a critical role in resistance acquisition for human-associated bacteria. Although aquaculture environments are recognized as important reservoirs of ARGs, intra- and intercellular mobility of MGEs discovered in marine organisms is poorly characterized. Here, we show a new pattern of interspecies ARGs transfer involving a 'non-conjugative' integrative element. To identify active MGEs in a Vibrio ponticus isolate, we conducted whole-genome sequencing of a transconjugant obtained by mating between Escherichia coli and Vibrio ponticus...
2018: PloS One
R Tamouza, J Oliveira, B Etain, D Bengoufa, N Hamdani, C Manier, C Mariaselvam, A Sundaresh, F Bellivier, C Henry, J-P Kahn, R Krishnamoorthy, D Charron, M Leboyer
OBJECTIVE: Bipolar Disorder (BD) is characterized by deregulated adaptive immune processes. Recent genome-wide association studies (GWAS) implicate the major histocompatibility complex (MHC) region in BD. The present study investigates the potential influence of variations in human leukocyte antigen (HLA) on BD risk and/or clinical presentations. This may have relevance to the dysregulated inflammatory processes commonly found in BD. METHOD: DNAs from 475 BD patients and 195 healthy controls (HC) were genotyped for classical HLA class I and II loci...
June 4, 2018: Acta Psychiatrica Scandinavica
Xiao Wei Shi, Feng Zhang, Zhi Yan Li, Ai Li Lyu, Xiong Guo
A case-control study was conducted to investigate associations between organophosphate pesticide (OP) exposure, aggression, impulsivity, and attempted suicide. The purpose of this study was to explore whether genomic polymorphisms in the alpha 1(XI) collagen gene (COL11A1) were associated with the risk and severity of Kashin-Beck disease (KBD). Twenty-two single nucleotide polymorphisms (SNPs) in COL11A1 were genotyped in 274 KBD cases and 249 healthy controls using the Sequenom MassARRAY system. The expression of type XI collagen (COL11A) in the knee articular cartilage of 22 KBD patients and 21 controls was analyzed by immunohistochemistry...
April 2018: Biomedical and Environmental Sciences: BES
Naomi R Wray, Stephan Ripke, Manuel Mattheisen, Maciej Trzaskowski, Enda M Byrne, Abdel Abdellaoui, Mark J Adams, Esben Agerbo, Tracy M Air, Till M F Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan F T Beekman, Tim B Bigdeli, Elisabeth B Binder, Douglas R H Blackwood, Julien Bryois, Henriette N Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Toni-Kim Clarke, Jonathan I R Coleman, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E Crawford, Cheynna A Crowley, Hassan S Dashti, Gail Davies, Ian J Deary, Franziska Degenhardt, Eske M Derks, Nese Direk, Conor V Dolan, Erin C Dunn, Thalia C Eley, Nicholas Eriksson, Valentina Escott-Price, Farnush Hassan Farhadi Kiadeh, Hilary K Finucane, Andreas J Forstner, Josef Frank, Héléna A Gaspar, Michael Gill, Paola Giusti-Rodríguez, Fernando S Goes, Scott D Gordon, Jakob Grove, Lynsey S Hall, Eilis Hannon, Christine Søholm Hansen, Thomas F Hansen, Stefan Herms, Ian B Hickie, Per Hoffmann, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M Hougaard, Ming Hu, Craig L Hyde, Marcus Ising, Rick Jansen, Fulai Jin, Eric Jorgenson, James A Knowles, Isaac S Kohane, Julia Kraft, Warren W Kretzschmar, Jesper Krogh, Zoltán Kutalik, Jacqueline M Lane, Yihan Li, Yun Li, Penelope A Lind, Xiaoxiao Liu, Leina Lu, Donald J MacIntyre, Dean F MacKinnon, Robert M Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Peter McGuffin, Sarah E Medland, Divya Mehta, Christel M Middeldorp, Evelin Mihailov, Yuri Milaneschi, Lili Milani, Jonathan Mill, Francis M Mondimore, Grant W Montgomery, Sara Mostafavi, Niamh Mullins, Matthias Nauck, Bernard Ng, Michel G Nivard, Dale R Nyholt, Paul F O'Reilly, Hogni Oskarsson, Michael J Owen, Jodie N Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E Peterson, Erik Pettersson, Wouter J Peyrot, Giorgio Pistis, Danielle Posthuma, Shaun M Purcell, Jorge A Quiroz, Per Qvist, John P Rice, Brien P Riley, Margarita Rivera, Saira Saeed Mirza, Richa Saxena, Robert Schoevers, Eva C Schulte, Ling Shen, Jianxin Shi, Stanley I Shyn, Engilbert Sigurdsson, Grant B C Sinnamon, Johannes H Smit, Daniel J Smith, Hreinn Stefansson, Stacy Steinberg, Craig A Stockmeier, Fabian Streit, Jana Strohmaier, Katherine E Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A Thomson, Thorgeir E Thorgeirsson, Chao Tian, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G Uitterlinden, Daniel Umbricht, Sandra Van der Auwera, Albert M van Hemert, Alexander Viktorin, Peter M Visscher, Yunpeng Wang, Bradley T Webb, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Stephanie H Witt, Yang Wu, Hualin S Xi, Jian Yang, Futao Zhang, Volker Arolt, Bernhard T Baune, Klaus Berger, Dorret I Boomsma, Sven Cichon, Udo Dannlowski, E C J de Geus, J Raymond DePaulo, Enrico Domenici, Katharina Domschke, Tõnu Esko, Hans J Grabe, Steven P Hamilton, Caroline Hayward, Andrew C Heath, David A Hinds, Kenneth S Kendler, Stefan Kloiber, Glyn Lewis, Qingqin S Li, Susanne Lucae, Pamela F A Madden, Patrik K Magnusson, Nicholas G Martin, Andrew M McIntosh, Andres Metspalu, Ole Mors, Preben Bo Mortensen, Bertram Müller-Myhsok, Merete Nordentoft, Markus M Nöthen, Michael C O'Donovan, Sara A Paciga, Nancy L Pedersen, Brenda W J H Penninx, Roy H Perlis, David J Porteous, James B Potash, Martin Preisig, Marcella Rietschel, Catherine Schaefer, Thomas G Schulze, Jordan W Smoller, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Henry Völzke, Myrna M Weissman, Thomas Werge, Ashley R Winslow, Cathryn M Lewis, Douglas F Levinson, Gerome Breen, Anders D Børglum, Patrick F Sullivan
Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal...
May 2018: Nature Genetics
Philip D Harvey, Kelly Posner, Nallakkandi Rajeevan, Kseniya V Yershova, Mihaela Aslan, John Concato
OBJECTIVE: Using data from a Department of Veterans Affairs study of schizophrenia (SZ) and bipolar I disorder (BP), we evaluated lifetime risks for suicidal ideation and behavior. We were interested in the prevalence and correlates of these outcomes, in populations of patients with severe mental illness (SMI), who have not been compared directly in previous studies despite data on high risk in each group separately. METHOD: Data were collected on demographic factors, medical and psychiatric comorbidity, cognitive and functional status, and lifetime suicidal ideation or behavior in a study of veterans with SZ (N = 3942) or BP (N = 5414)...
July 2018: Journal of Psychiatric Research
Shenwei Zhang, Jee-Hwan Oh, Laura M Alexander, Mustafa Özçam, Jan-Peter van Pijkeren
The peptidoglycan composition in lactic acid bacteria dictates vancomycin resistance. Vancomycin binds relatively poorly to peptidoglycan ending in d-alanyl-d-lactate and binds with high affinity to peptidoglycan ending in d-alanyl-d-alanine (d-Ala-d-Ala), which results in vancomycin resistance and sensitivity, respectively. The enzyme responsible for generating these peptidoglycan precursors is dipeptide ligase (Ddl). A single amino acid in the Ddl active site, phenylalanine or tyrosine, determines depsipeptide or dipeptide activity, respectively...
July 1, 2018: Journal of Bacteriology
Qin Qin, Chen Ling, Yiqing Zhao, Tian Yang, Jin Yin, Yingying Guo, Guo Qiang Chen
Extremophiles are suitable chassis for developing the next generation industrial biotechnology (NGIB) due to their resistance to microbial contamination. However, engineering extremophiles are not an easy task. Halomonas, an industrially interesting halophile able to grow under unsterile and continuous conditions in large-scale processes, can only be engineered using suicide plasmid-mediated two-step homologous recombination which is very laborious and time-consuming (up to half a year). A convenient approach for the engineering of halophiles that can possibly be extended to other extremophiles is therefore urgently required...
May 2018: Metabolic Engineering
Sergi Papiol, Thomas G Schulze, Martin Alda
INTRODUCTION: Lithium remains the best-established long-term treatment for bipolar disorder because of its efficacy in maintaining periods of remission and reducing the risk of suicide. Not all patients successfully respond to lithium treatment, and the individual response, including the occurrence of side effects, is highly variable and not easy to predict. The genetic basis of lithium response is supported by the fact that the response clusters in families. Likewise, recent high-throughput genomic analyses have shed light on its genetic architecture...
March 26, 2018: Pharmacopsychiatry
Sandra Vuk Pisk, Tomislav Vuk, Ena Ivezić, Irena Jukić, Jasna Bingulac-Popović, Igor Filipčić
BACKGROUND: The prevalence of ABO alleles is different in different populations, and many studies have shown a correlation between the occurrences of some diseases and different genotypes of ABO blood groups. The aim of this study was to determine whether there is a significant association between psychiatric syndromes and ABO blood groups. MATERIALS AND METHODS: This case-control study involved 156 psychiatric patients and 303 healthy, unrelated, voluntary blood donors...
February 15, 2018: Blood Transfusion, Trasfusione del Sangue
Ashok Kumar, Satyabrata Bag, Bhabatosh Das
BACKGROUND: Genomic islands (GIs) are discrete segments of mobile DNA with defined boundaries, acquired in the bacterial genome from another organism by horizontal gene transfer during the course of evolution. GIs contribute significantly in virulence, disease development, antimicrobial resistance and metabolic process. OBJECTIVE: The present study focuses on the development of a vector based genetic tool carrying selectable and counter-selectable markers, in order to flag the GIs in the bacterial chromosome and monitor their stability in laboratory growth conditions...
February 22, 2018: Recent Patents on Biotechnology
Tiphaine Birien, Axel Thiel, Ghislaine Henneke, Didier Flament, Yann Moalic, Mohamed Jebbar
A gene disruption system for Thermococcus barophilus was developed using simvastatin (HMG-CoA reductase encoding gene) for positive selection and 5-Fluoroorotic acid (5-FOA), a pyrF gene for negative selection. Multiple gene mutants were constructed with this system, which offers the possibility of complementation in trans, but produces many false positives (<80%). To significantly reduce the rate of false positives, we used another counterselective marker, 6-methylpurine (6-MP), a toxic analog of adenine developed in Thermococcus kodakarensis , consistently correlated with the TK0664 gene (encoding a hypoxanthine-guanine phosphoribosyl-transferase)...
February 7, 2018: Genes
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