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Suicide genomics

Chiara Fabbri, Siegfried Kasper, Alexander Kautzky, Lucie Bartova, Markus Dold, Joseph Zohar, Daniel Souery, Stuart Montgomery, Diego Albani, Ilaria Raimondi, Dimitris Dikeos, Dan Rujescu, Rudolf Uher, Cathryn M Lewis, Julien Mendlewicz, Alessandro Serretti
BACKGROUND: Treatment-resistant depression (TRD) is the most problematic outcome of depression in terms of functional impairment, suicidal thoughts and decline in physical health.AimsTo investigate the genetic predictors of TRD using a genome-wide approach to contribute to the development of precision medicine. METHOD: A sample recruited by the European Group for the Study of Resistant Depression (GSRD) including 1148 patients with major depressive disorder (MDD) was characterised for the occurrence of TRD (lack of response to at least two adequate antidepressant treatments) and genotyped using the Infinium PsychArray...
November 23, 2018: British Journal of Psychiatry: the Journal of Mental Science
Qin Liang, Claudio Monetti, Maria V Shutova, Eric J Neely, Sabiha Hacibekiroglu, Huijuan Yang, Christopher Kim, Puzheng Zhang, Chengjin Li, Kristina Nagy, Maria Mileikovsky, Istvan Gyongy, Hoon-Ki Sung, Andras Nagy
Human pluripotent cell lines hold enormous promise for the development of cell-based therapies. Safety, however, is a crucial prerequisite condition for clinical applications. Numerous groups have attempted to eliminate potentially harmful cells through the use of suicide genes1 , but none has quantitatively defined the safety level of transplant therapies. Here, using genome-engineering strategies, we demonstrate the protection of a suicide system from inactivation in dividing cells. We created a transcriptional link between the suicide gene herpes simplex virus thymidine kinase (HSV-TK) and a cell-division gene (CDK1); this combination is designated the safe-cell system...
November 14, 2018: Nature
Ying-Jie Yang, Raghvendra Pratap Singh, Xin Lan, Cheng-Sheng Zhang, Yue-Zhong Li, Yi-Qiang Li, Duo-Hong Sheng
Myxococcus xanthus DK1622 is a rich source of novel secondary metabolites, and it is often used as an expression host of exogenous biosynthetic gene clusters. However, the frequency of obtaining large genome-deletion variants by using traditional strategies is low, and progenies generated by homologous recombination contain irregular deletions. The present study aims to develop an efficient genome-engineering system for this bacterium based on the Cre/loxP system. We first verified the functionality of the native cre system that was integrated into the chromosome with an inducible promoter P cuoA ...
November 6, 2018: Biomolecules
Marcus Sokolowski, Jerzy Wasserman, Danuta Wasserman
Suicidal behavior (SB) has a complex etiology involving different polygenic and environmental components. Here we used an excess of significant markers (ESM) test to study gene-level associations in previous genome-wide association studies (GWAS) SNP data from a family-based sample, having medically severe suicide attempt (SA) as main outcome in the offspring. In SA without major psychiatric disorders (N = 498), a screening of 5,316 genes across the genome suggested association 17 genes (at fdr < 0...
December 2018: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Santa S Naorem, Jin Han, Stephanie Y Zhang, Junyi Zhang, Lindsey B Graham, Angelou Song, Cameron V Smith, Fariha Rashid, Huatao Guo
BACKGROUND: Transposon mutagenesis is highly valuable for bacterial genetic and genomic studies. The transposons are usually delivered into host cells through conjugation or electroporation of a suicide plasmid. However, many bacterial species cannot be efficiently conjugated or transformed for transposon saturation mutagenesis. For this reason, temperature-sensitive (ts) plasmids have also been developed for transposon mutagenesis, but prolonged incubation at high temperatures to induce ts plasmid loss can be harmful to the hosts and lead to enrichment of mutants with adaptive genetic changes...
October 24, 2018: BMC Microbiology
Hilary Coon, Todd M Darlington, Emily DiBlasi, W Brandon Callor, Elliott Ferris, Alison Fraser, Zhe Yu, Nancy William, Sujan C Das, Sheila E Crowell, Danli Chen, John S Anderson, Michael Klein, Leslie Jerominski, Dale Cannon, Andrey Shabalin, Anna Docherty, Megan Williams, Ken R Smith, Brooks Keeshin, Amanda V Bakian, Erik Christensen, Qingqin S Li, Nicola J Camp, Douglas Gray
Suicide is the 10th leading cause of death in the United States. Although environment has undeniable impact, evidence suggests that genetic factors play a significant role in completed suicide. We linked a resource of ~ 4500 DNA samples from completed suicides obtained from the Utah Medical Examiner to genealogical records and medical records data available on over eight million individuals. This linking has resulted in the identification of high-risk extended families (7-9 generations) with significant familial risk of completed suicide...
October 23, 2018: Molecular Psychiatry
Jianli Wang, Wenjian Ma, Yuzhou Wang, Lin Lin, Tianyi Wang, Yuqian Wang, Ye Li, Xiaoyuan Wang
Pseudomonas putida KT2442, a natural producer of polyhydroxyalkanoate, spends a lot of energy and carbon sources to form flagella and pili; therefore, deleting the genes involved in the biosynthesis and assembly of flagella and pili might improve PHA productivity. In this study, two novel deletion systems were constructed in order to efficiently remove the 76 genes involved in the biosynthesis and assembly of flagella and pili in P. putida KT2442. Both systems combine suicide-plasmid-based homologous recombination and mutant lox site-specific recombination and involve three plasmids...
October 19, 2018: Applied Microbiology and Biotechnology
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, Lilah Rahn-Lee, Kristen N LeGault, 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...
November 15, 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...
November 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...
November 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
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