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Suicide genomics

Ching-Ning Huang, Wolfgang Liebl, Armin Ehrenreich
Background: Clostridium saccharobutylicum NCP 262 is a solventogenic bacterium that has been used for the industrial production of acetone, butanol, and ethanol. The lack of a genetic manipulation system for C. saccharobutylicum currently limits (i) the use of metabolic pathway engineering to improve the yield, titer, and productivity of n -butanol production by this microorganism, and (ii) functional genomics studies to better understand its physiology. Results: In this study, a marker-less deletion system was developed for C...
2018: Biotechnology for Biofuels
Domenico De Berardis, Michele Fornaro, Alessandro Valchera, Marilde Cavuto, Giampaolo Perna, Marco Di Nicola, Gianluca Serafini, Alessandro Carano, Maurizio Pompili, Federica Vellante, Laura Orsolini, Annastasia Fiengo, Antonio Ventriglio, Kim Yong-Ku, Giovanni Martinotti, Massimo Di Giannantonio, Carmine Tomasetti
Despite the continuous advancement in neurosciences as well as in the knowledge of human behaviors pathophysiology, currently suicide represents a puzzling challenge. The World Health Organization (WHO) has established that one million people die by suicide every year, with the impressive daily rate of a suicide every 40 s. The weightiest concern about suicidal behavior is how difficult it is for healthcare professionals to predict. However, recent evidence in genomic studies has pointed out the essential role that genetics could play in influencing person's suicide risk...
September 23, 2018: International Journal of Molecular Sciences
Carly R Grant, Kristen N LeGault, Lilah Rahn-Lee, Arash Komeili
Magnetosomes are complex bacterial organelles that serve as model systems for studying bacterial cell biology, biomineralization, and global iron cycling. Magnetosome biogenesis is primarily studied in two closely related Alphaproteobacteria of the genus Magnetospirillum that form cubooctahedral-shaped magnetite crystals within a lipid membrane. However, chemically and structurally distinct magnetic particles have been found in physiologically and phylogenetically diverse bacteria. Due to a lack of molecular genetic tools, the mechanistic diversity of magnetosome formation remains poorly understood...
September 7, 2018: Applied and Environmental Microbiology
Günther Muth
Actinomycetes are the most important producers of secondary metabolites for medical, agricultural and industrial applications. Efficient engineering of bacterial genomes to improve their biosynthetic capabilities largely depends on the available arsenal of tools and vectors. One of the most widely used vector systems for actinomycetes is derived from the Streptomyces ghanaensis DSM2932 plasmid pSG5. pSG5 is a broad host range multicopy plasmid replicating via a rolling circle mechanism. The unique feature of pSG5, which distinguishes it from other Streptomyces plasmids, is its naturally thermosensitive mode of replication...
September 6, 2018: Applied Microbiology and Biotechnology
Junqing Wang, Jian Peng, Han Fan, Xiang Xiu, Le Xue, Lei Wang, Jing Su, Xiaohui Yang, Ruiming Wang
Candida tropicalis can grow with alkanes or plant oils as the sole carbon source, and its industrial application thus has great potential. However, the choice of a suitable genetic operating system can effectively increase the speed of metabolic engineering. MazF functions as an mRNA interferase that preferentially cleaves single-stranded mRNAs at ACA sequences to inhibit protein synthesis, leading to cell growth arrest. Here, we constructed a suicide plasmid named pPICPJ-mazF that uses the mazF gene of Escherichia coli as a counterselectable marker for the markerless editing of C...
November 2018: Journal of Industrial Microbiology & Biotechnology
Ali Bani-Fatemi, Samia Tasmim, Kevin Z Wang, Jerry Warsh, Etienne Sibille, Vincenzo De Luca
BACKGROUND: Approximately 5% of patients with schizophrenia commit suicide, and 20% to 40% of them have at least one suicide attempt during their lifetime. Previous research has identified childhood trauma as a potential risk factor for suicide attempt in schizophrenia. The Psychiatric Genetics Consortium found 108 common genetic risk loci associated with schizophrenia. Moreover, familial, adoption, and twin studies suggested that suicidal behaviour is under genetic influence. OBJECTIVE: Our objective was to determine the effect of childhood trauma and schizophrenia polygenic risk in leading to suicide attempt, as well as to determine any interaction effect between the polygenic scores with childhood trauma...
August 25, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Filippo Corponi, Stefano Bonassi, Eduard Vieta, Diego Albani, Alessandra Frustaci, Giuseppe Ducci, Stefano Landi, Stefania Boccia, Alessandro Serretti, Chiara Fabbri
Shared genetic vulnerability between schizophrenia (SCZ) and bipolar disorder (BP) was demonstrated, but the genetic underpinnings of specific symptom domains are unclear. This study investigated which genes and gene sets may modulate specific psychopathological domains and if genome-wide significant loci previously associated with SCZ or BP may play a role. Genome-wide data were available in patients with SCZ (n = 226) or BP (n = 228). Phenotypes under investigation were depressive and positive symptoms severity, suicidal ideation, onset age and substance use disorder comorbidity...
August 24, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Nathan A Kimbrel, Melanie E Garrett, Michelle F Dennis, Michael A Hauser, Allison E Ashley-Koch, Jean C Beckham
Death by suicide and suicidal behavior are major concerns among U.S. military veterans; however, no genome-wide association studies (GWAS) studies of suicidal behavior have been conducted among U.S. military veterans to date, despite the elevated rate of suicidal behavior observed within this population. Accordingly, the primary objective of the present research was to conduct the first GWAS of suicide attempts and suicidal ideation in a large and well-characterized sample of U.S. military veterans. The gene most significantly associated (p = 9...
July 17, 2018: Psychiatry Research
Annette Erlangsen, Vivek Appadurai, Yunpeng Wang, Gustavo Turecki, Ole Mors, Thomas Werge, Preben B Mortensen, Anna Starnawska, Anders D Børglum, Andrew Schork, Ron Nudel, Marie Bækvad-Hansen, Jonas Bybjerg-Grauholm, David M Hougaard, Wesley K Thompson, Merete Nordentoft, Esben Agerbo
Family studies have shown an aggregation of suicidal behavior in families. Yet, molecular studies are needed to identify loci accounting for genetic heritability. We conducted a genome-wide association study and estimated single nucleotide polymorphisms (SNP) heritability for a suicide attempt. In a case-cohort study, national data on all individuals born in Denmark after 1981 and diagnosed with severe mental disorders prior to 2013 (n = 57,377) and individuals from the general population (n = 30,000) were obtained...
August 16, 2018: Molecular Psychiatry
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...
September 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...
September 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
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