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https://www.readbyqxmd.com/read/27913417/development-of-an-improved-system-for-the-generation-of-knock-out-mutants-of-amycolatopsis-sp-atcc-39116
#1
Florian Meyer, Hilke Pupkes, Alexander Steinbüchel
The Gram-positive actinomycete Amycolatopsis sp. ATCC 39116 is used for the industrial production of natural vanillin. Previously, the only gene deletion performed in this strain targeted the gene vdh coding for a vanillin dehydrogenase. The generation of this mutant suffered from a high number of illegitimate recombinations and the low rate of homologous recombination. To alleviate this, we constructed an optimized deletion system based on a modified suicide vector. Thereby, we were able to enhance the rate of homologous integration from less than 1% of the analyzed clones to 20% or 50% depending on the targeted gene...
December 2, 2016: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/27910884/the-hha-tomb-toxin-antitoxin-system-shows-conditional-toxicity-and-promotes-persister-cell-formation-by-inhibiting-apoptosis-like-death-in-s-typhimurium
#2
Sangeeta Jaiswal, Prajita Paul, Chandrashekhar Padhi, Shilpa Ray, Daniel Ryan, Shantoshini Dash, Mrutyunjay Suar
Toxin-antitoxin (TA) modules are two component "addictive" genetic elements found on either plasmid or bacterial chromosome, sometimes on both. TA systems perform a wide range of functions like biofilm formation, persistence, programmed cell death, phage abortive infection etc. Salmonella has been reported to contain several such TA systems. However, the hemolysin expression modulating protein (Hha) and its adjacent uncharacterized hypothetical protein TomB (previously known as YbaJ), have not been listed as a TA module in Salmonella...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27907031/in-vitro-pre-clinical-validation-of-suicide-gene-modified-anti-cd33-redirected-chimeric-antigen-receptor-t-cells-for-acute-myeloid-leukemia
#3
Kentaro Minagawa, Muhammad O Jamil, Mustafa Al-Obaidi, Larisa Pereboeva, Donna Salzman, Harry P Erba, Lawrence S Lamb, Ravi Bhatia, Shin Mineishi, Antonio Di Stasi
BACKGROUND: Approximately fifty percent of patients with acute myeloid leukemia can be cured with current therapeutic strategies which include, standard dose chemotherapy for patients at standard risk of relapse as assessed by cytogenetic and molecular analysis, or high-dose chemotherapy with allogeneic hematopoietic stem cell transplant for high-risk patients. Despite allogeneic hematopoietic stem cell transplant about 25% of patients still succumb to disease relapse, therefore, novel strategies are needed to improve the outcome of patients with acute myeloid leukemia...
2016: PloS One
https://www.readbyqxmd.com/read/27895323/elevated-cyp2c19-expression-is-associated-with-depressive-symptoms-and-hippocampal-homeostasis-impairment
#4
M M Jukić, N Opel, J Ström, T Carrillo-Roa, S Miksys, M Novalen, A Renblom, S C Sim, E M Peñas-Lledó, P Courtet, A Llerena, B T Baune, D J de Quervain, A Papassotiropoulos, R F Tyndale, E B Binder, U Dannlowski, M Ingelman-Sundberg
The polymorphic CYP2C19 enzyme metabolizes psychoactive compounds and is expressed in the adult liver and fetal brain. Previously, we demonstrated that the absence of CYP2C19 is associated with lower levels of depressive symptoms in 1472 Swedes. Conversely, transgenic mice carrying the human CYP2C19 gene (2C19TG) have shown an anxious phenotype and decrease in hippocampal volume and adult neurogenesis. The aims of this study were to: (1) examine whether the 2C19TG findings could be translated to humans, (2) evaluate the usefulness of the 2C19TG strain as a tool for preclinical screening of new antidepressants and (3) provide an insight into the molecular underpinnings of the 2C19TG phenotype...
November 29, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27894372/affective-lability-mediates-the-association-between-childhood-trauma-and-suicide-attempts-mixed-episodes-and-co-morbid-anxiety-disorders-in-bipolar-disorders
#5
M Aas, C Henry, F Bellivier, M Lajnef, S Gard, J-P Kahn, T V Lagerberg, S R Aminoff, T Bjella, M Leboyer, O A Andreassen, I Melle, B Etain
BACKGROUND: Many studies have shown associations between a history of childhood trauma and more severe or complex clinical features of bipolar disorders (BD), including suicide attempts and earlier illness onset. However, the psychopathological mechanisms underlying these associations are still unknown. Here, we investigated whether affective lability mediates the relationship between childhood trauma and the severe clinical features of BD. METHOD: A total of 342 participants with BD were recruited from France and Norway...
November 29, 2016: Psychological Medicine
https://www.readbyqxmd.com/read/27874855/conditional-control-of-suicide-gene-expression-in-tumor-cells-with-theophylline-responsive-ribozyme
#6
Y Zhang, J Wang, H Cheng, Y Sun, M Liu, Z Wu, R Pei
Numerous synthetic RNA-based controls for integrating sensing switches with function devices have been demonstrated in a variety of organisms for gene regulatory. Although potential advantages of RNA-based genetic control strategies have been shown in clinical applications, successful extending these engineered systems into medical applications has seldom reported. Here, a synthetic RNA-based ribozyme system and its application in advancing rationally designed cellular therapy were described. The theophylline-responsive ribozyme-based device provided a powerful platform for suicide gene expression regulation in tumor cells...
November 22, 2016: Gene Therapy
https://www.readbyqxmd.com/read/27836463/understanding-epigenetic-architecture-of-suicide-neurobiology-a-critical-perspective
#7
REVIEW
Bhaskar Roy, Yogesh Dwivedi
Current understanding of environmental cross-talk with genetic makeup is found to be mediated through an epigenetic interface which is associated with prominent reversible and heritable changes at gene expression level. Recent emergence of epigenetic modulation in shaping the genetic information has become a key regulatory factor in answering the underlying complexities associated with several mental disorders. A comprehensive understanding of the pertinent changes in the epigenetic makeup of suicide phenotype exhibits a characteristic signature with the possibility of using it as a biomarker to help predict the risk factors associated with suicide...
November 9, 2016: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27825973/an-efficient-system-for-the-generation-of-marked-genetic-mutants-in-members-of-the-genus-burkholderia
#8
Sravanthi Shastri, Helena L Spiewak, Aderonke Sofoluwe, Vigdis A Eidsvaag, Atif H Asghar, Tyrone Pereira, Edward H Bull, Aaron T Butt, Mark S Thomas
To elucidate the function of a gene in bacteria it is vital that targeted gene inactivation (allelic replacement) can be achieved. Allelic replacement is often carried out by disruption of the gene of interest by insertion of an antibiotic-resistance marker followed by subsequent transfer of the mutant allele to the genome of the host organism in place of the wild-type gene. However, due to their intrinsic resistance to many antibiotics only selected antibiotic-resistance markers can be used in members of the genus Burkholderia, including the Burkholderia cepacia complex (Bcc)...
November 5, 2016: Plasmid
https://www.readbyqxmd.com/read/27820819/premature-adult-death-in-individuals-born-preterm-a-sibling-comparison-in-a-prospective-nationwide-follow-up-study
#9
Kari R Risnes, Kristine Pape, Johan H Bjørngaard, Dag Moster, Michael B Bracken, Pal R Romundstad
BACKGROUND: Close to one in ten individuals worldwide is born preterm, and it is important to understand patterns of long-term health and mortality in this group. This study assesses the relationship between gestational age at birth and early adult mortality both in a nationwide population and within sibships. The study adds to existing knowledge by addressing selected causes of death and by assessing the role of genetic and environmental factors shared by siblings. METHODS: Study population was all Norwegian men and women born from 1967 to 1997 followed using nation-wide registry linkage for mortality through 2011 when they were between 15 and 45 years of age...
2016: PloS One
https://www.readbyqxmd.com/read/27806711/prevalence-and-correlates-of-depression-and-anxiety-among-patients-with-hiv-on-follow-up-at-alert-hospital-addis-ababa-ethiopia
#10
Getachew Tesfaw, Getinet Ayano, Tadesse Awoke, Dawit Assefa, Zelalem Birhanu, Getenet Miheretie, Genet Abebe
BACKGROUND: Depression and anxiety disorders are common among people living with Human Immunodeficiency Virus than the non-infected individuals. The co-existence of these disorders are associated with barriers to treatment and worsening medical outcomes, including treatment resistance, increased risk for suicide, greater chance for recurrence and utilization of medical resources and/or increase morbidity and mortality. Therefore, assessing depression and anxiety among HIV patients has a pivotal role for further interventions...
November 2, 2016: BMC Psychiatry
https://www.readbyqxmd.com/read/27797688/cannabis-involvement-and-nonsuicidal-self-injury-a-discordant-twin-approach
#11
Lauren R Few, Julia D Grant, Elliot C Nelson, Timothy J Trull, Richard A Grucza, Kathleen K Bucholz, Karin J H Verweij, Nicholas G Martin, Dixie J Statham, Pamela A F Madden, Andrew C Heath, Michael T Lynskey, Arpana Agrawal
OBJECTIVE: Cannabis use, particularly at an early age, has been linked to suicidal thoughts and behavior, but minimal work has examined the association between cannabis use and lifetime nonsuicidal self-injury (NSSI). The current study aims to characterize the overlap between lifetime and early cannabis use and NSSI and to examine genetic and environmental mechanisms of this association. METHOD: Adult male and female twins from the Australian Twin Registry (N = 9,583) were used to examine the odds of NSSI associated with lifetime cannabis use and early cannabis use (i...
November 2016: Journal of Studies on Alcohol and Drugs
https://www.readbyqxmd.com/read/27791181/targeted-molecular-genetic-imaging-and-ligand-directed-therapy-in-aggressive-variant-prostate-cancer
#12
Fortunato Ferrara, Daniela I Staquicini, Wouter H P Driessen, Sara D'Angelo, Andrey S Dobroff, Marc Barry, Lesley C Lomo, Fernanda I Staquicini, Marina Cardó-Vila, Suren Soghomonyan, Mian M Alauddin, Leo G Flores, Marco A Arap, Richard C Lauer, Paul Mathew, Eleni Efstathiou, Ana M Aparicio, Patricia Troncoso, Nora M Navone, Christopher J Logothetis, Serena Marchiò, Juri G Gelovani, Richard L Sidman, Renata Pasqualini, Wadih Arap
Aggressive variant prostate cancers (AVPC) are a clinically defined group of tumors of heterogeneous morphologies, characterized by poor patient survival and for which limited diagnostic and treatment options are currently available. We show that the cell surface 78-kDa glucose-regulated protein (GRP78), a receptor that binds to phage-display-selected ligands, such as the SNTRVAP motif, is a candidate target in AVPC. We report the presence and accessibility of this receptor in clinical specimens from index patients...
October 24, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27781385/an-epigenetic-perspective-on-the-midwife-toad-experiments-of-paul-kammerer-1880-1926
#13
REVIEW
Alexander O Vargas, Quirin Krabichler, Carlos Guerrero-Bosagna
Paul Kammerer was the most outstanding neo-Lamarckian experimentalist of the early 20th century. He reported spectacular results in the midwife toad, including crosses of environmentally modified toads with normal toads, where acquired traits were inherited in Mendelian fashion. Accusations of fraud generated a great scandal, ending with Kammerer's suicide. Controversy reignited in the 1970s, when journalist Arthur Koestler argued against these accusations. Since then, others have argued that Kammerer's results, even if real, were not groundbreaking and could be explained by somatic plasticity, inadvertent selection, or conventional genetics...
October 26, 2016: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
https://www.readbyqxmd.com/read/27748930/mirnas-and-their-role-in-the-correlation-between-schizophrenia-and-cancer-review
#14
E Rizos, N Siafakas, E Skourti, C Papageorgiou, J Tsoporis, T H Parker, D I Christodoulou, D A Spandidos, E Katsantoni, V Zoumpourlis
Schizophrenia (SZ) and cancer (Ca) have a broad spectrum of clinical phenotypes and a complex biological background, implicating a large number of genetic and epigenetic factors. SZ is a chronic neurodevelopmental disorder signified by an increase in the expression of apoptotic molecular signals, whereas Ca is conversely characterized by an increase in appropriate molecular signaling that stimulates uncontrolled cell proliferation. The rather low risk of developing Ca in patients suffering from SZ is a hypothesis that is still under debate...
October 14, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27721799/genetic-association-studies-of-suicidal-behavior-a-review-of-the-past-10%C3%A2-years-progress-limitations-and-future-directions
#15
Bojan Mirkovic, Claudine Laurent, Marc-Antoine Podlipski, Thierry Frebourg, David Cohen, Priscille Gerardin
Suicidal behaviors (SBs), which range from suicidal ideation to suicide attempts and completed suicide, represent a fatal dimension of mental ill-health. The involvement of genetic risk factors in SB is supported by family, twin, and adoption studies. The aim of this paper is to review recent genetic association studies in SBs including (i) case-control studies, (ii) family-based association studies, and (iii) genome-wide association studies (GWAS). Various studies on genetic associations have tended to suggest that a number of genes [e...
2016: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/27703782/ketamine-stimulating-antidepressant-treatment
#16
Gin S Malhi, Yulisha Byrow, Frederick Cassidy, Andrea Cipriani, Koen Demyttenaere, Mark A Frye, Michael Gitlin, Sidney H Kennedy, Terence A Ketter, Raymond W Lam, Rupert McShane, Alex J Mitchell, Michael J Ostacher, Sakina J Rizvi, Michael E Thase, Mauricio Tohen
SUMMARY: The appeal of ketamine - in promptly ameliorating depressive symptoms even in those with non-response - has led to a dramatic increase in its off-label use. Initial promising results await robust corroboration and key questions remain, particularly concerning its long-term administration. It is, therefore, timely to review the opinions of mood disorder experts worldwide pertaining to ketamine's potential as an option for treating depression and provide a synthesis of perspectives - derived from evidence and clinical experience - and to consider strategies for future investigations...
May 2016: BJPsych Open
https://www.readbyqxmd.com/read/27690100/structure-evolution-and-functions-of-bacterial-type-iii-toxin-antitoxin-systems
#17
Nathalie Goeders, Ray Chai, Bihe Chen, Andrew Day, George P C Salmond
Toxin-antitoxin (TA) systems are small genetic modules that encode a toxin (that targets an essential cellular process) and an antitoxin that neutralises or suppresses the deleterious effect of the toxin. Based on the molecular nature of the toxin and antitoxin components, TA systems are categorised into different types. Type III TA systems, the focus of this review, are composed of a toxic endoribonuclease neutralised by a non-coding RNA antitoxin in a pseudoknotted configuration. Bioinformatic analysis shows that the Type III systems can be classified into subtypes...
2016: Toxins
https://www.readbyqxmd.com/read/27683660/filamentation-protects-candida-albicans-from-amphotericin-b-induced-programmed-cell-death-via-a-mechanism-involving-the-yeast-metacaspase-mca1
#18
David J Laprade, Melissa S Brown, Morgan L McCarthy, James J Ritch, Nicanor Austriaco
The budding yeast Candida albicans is one of the most significant fungal pathogens worldwide. It proliferates in two distinct cell types: blastopores and filaments. Only cells that are able to transform from one cell type into the other are virulent in mouse disease models. Programmed cell death is a controlled form of cell suicide that occurs when C. albicans cells are exposed to fungicidal drugs like amphotericin B and caspofungin, and to other stressful conditions. We now provide evidence that suggests that programmed cell death is cell-type specific in yeast: Filamentous C...
July 2016: Microbial Cell
https://www.readbyqxmd.com/read/27648504/national-initiative-to-prevent-suicide-nips-a-new-proposal-to-improve-the-understanding-and-prevention-of-suicide
#19
Sheldon H Preskorn
Suicide is a staggering, tragic, and growing cause of death in the United States. Despite a government-led 20-year effort, the suicide rate increased by 25% between 1999 and 2014. To prevent suicide, it is essential to understand the biological factors-genetic and epigenetic-and environmental factors that underlie it. To gain this increased understanding, the equivalent of the "War on Cancer" initiative is needed. The War on Cancer initiative, which began in the 1970s, has transformed the treatments and outcomes of cancer, and the same could occur with a similar initiative on suicide...
September 2016: Journal of Psychiatric Practice
https://www.readbyqxmd.com/read/27643478/a-genome-wide-association-study-of-emotion-dysregulation-evidence-for-interleukin-2-receptor-alpha
#20
Abigail Powers, Lynn Almli, Alicia Smith, Adriana Lori, Jen Leveille, Kerry J Ressler, Tanja Jovanovic, Bekh Bradley
Emotion dysregulation has been implicated as a risk factor for many psychiatric conditions. Therefore, examining genetic risk associated with emotion dysregulation could help inform cross-disorder risk more generally. A genome-wide association study (GWAS) of emotion dysregulation using single nucleotide polymorphism (SNP) array technology was conducted in a highly traumatized, minority, urban sample (N = 2600, males = 774). Post-hoc analyses examined associations between SNPs identified in the GWAS and current depression, posttraumatic stress disorder (PTSD), and history of suicide attempt...
December 2016: Journal of Psychiatric Research
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