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Sample records for originated gene depresses

  1. Genes, stress, and depression.

    Wurtman, Richard J

    2005-05-01

    A relationship between genetic makeup and susceptibility to major depressive disorder (MDD) has long been suspected on the basis of family and twin studies. A metaanalysis of reports on the basis of twin studies has estimated MDD's degree of heritability to be 0.33 (confidence interval, 0.26-0.39). Among families exhibiting an increased prevalence of MDD, risk of developing the illness was enhanced in members exposed to a highly stressful environment. Aberrant genes can predispose to depression in a number of ways, for example, by diminishing production of growth factors that act during brain development. An aberrant gene could also increase or decrease a neurotransmitter's release into synapses, its actions, or its duration of activity. The gene products of greatest interest at present are those involved in the synthesis and actions of serotonin; among them, the serotonin-uptake protein localized within the terminals and dendrites of serotonin-releasing neurons. It has been found that the Vmax of platelet serotonin uptake is low in some patients with MDD; also, Vmax is highly correlated in twins. Antidepressant drugs such as the selective serotonin reuptake inhibitors act on this uptake protein. The specific genetic locus causing serotonin uptake to be lower in some patients with major depression involves a polymorphic region (5-HTTLPR) in the promoter region of the gene for the uptake protein. The gene itself exists as several alleles, the short "S" allele and the long "L" allele. The S variant is associated with less, and the L variant with more, of the uptake protein. The effect of stressful life events on depressive symptoms in young adults was found to be significantly stronger among SS or SL subjects than among LL subjects. Neuroimaging studies showed that people with the SS or SL alleles exhibited a greater activation of the amygdala in response to fearful stimuli than those with LL. It has been reported recently that mutations in the gene that controls

  2. Depression and dementia of cerebrovascular origin

    Marmorato Paulo Germano

    2002-01-01

    Full Text Available We report the case of a patient who presented various psychiatric syndromes at the time of evaluation - partial complex epileptic seizures, personality change, and severe depression, which eventually progressed to dementia - resulting from multiple cerebral infarctions of probable neuro-angiopathic origin, of unknown etiology. Aspects related to depression following cerebrovascular accidents, as well as how cerebrovascular accidents can result in different disorders depending on the variables, are discussed based on the data from current literature.

  3. Clock genes in depression

    Christiansen, Sofie Laage; Bouzinova, Elena

    2017-01-01

    Data demonstrate that abnormal regulation of the circadian system can result in cardiovascular disease, metabolic syndrome, obesity, immune dysfunction, increased risk for cancer, reproductive complications, etc. It is highly individual among depressed patients and may be expressed as a phase...... in the brain and liver: expression of Per2 is sensitive to stress and changes in Bmal1 mostly associated with depressive behavior. The Per1 expression is sustainable in maintaining the circadian rhythm. A normalization of the expression patterns is likely to be essential for the recovery from the pathological...... state. Depression is a high prevalent disorder. The number of incidents is rising due to changes in lifestyle. The symptomatology is inconsistent and it is difficult to agree on one hypothesis. The disturbances of the 24 h circadian rhythm may be a factor in the development of major depressive disorder...

  4. Gene-environment interplay in depressive symptoms

    Petkus, A. J.; Beam, C. R.; Johnson, W.

    2017-01-01

    that genetic factors play a larger part in the association between depressive symptoms and physical illness for men than for women. For both sexes, across all ages, physical illness may similarly trigger social and health limitations that contribute to depressive symptoms.......Background Numerous factors influence late-life depressive symptoms in adults, many not thoroughly characterized. We addressed whether genetic and environmental influences on depressive symptoms differed by age, sex, and physical illness. Method The analysis sample included 24 436 twins aged 40......-90 years drawn from the Interplay of Genes and Environment across Multiple Studies (IGEMS) Consortium. Biometric analyses tested age, sex, and physical illness moderation of genetic and environmental variance in depressive symptoms. Results Women reported greater depressive symptoms than men. After age 60...

  5. Perceived discrimination and depressive symptoms among immigrant-origin adolescents.

    Tummala-Narra, Pratyusha; Claudius, Milena

    2013-07-01

    Although discrimination has been found to contribute to psychological distress among immigrant populations, there are few studies that have examined the relationship between racial and ethnic discrimination in the school setting among foreign-born immigrant and U.S.-born immigrant-origin adolescents. This study examined the relationship between perceived discrimination by adults and peers in the school setting and depressive symptoms in a sample (N = 95) of racial minority immigrant-origin adolescents (13 to 19 years of age) attending an urban high school. We examined the relation between perceived discrimination and depressive symptomology across gender and nativity status (foreign born vs. U.S. born), and the potential moderating role of ethnic identity and social support. Consistent with previous research, girls reported higher levels of depressive symptomology than boys, although the relationship between perceived discrimination and depressive symptoms was significant for both boys and girls. Perceived discrimination by adults and by peers at school was positively related to depressive symptoms for U.S.-born adolescents. For U.S.-born adolescents, ethnic identity mitigated the negative effects of perceived adult discrimination on depressive symptoms. However, ethnic identity did not moderate the relationship between perceived peer discrimination and depressive symptoms. Social support did not moderate the relationship between adult and peer discrimination and depressive symptoms for either foreign-born or U.S.-born adolescents. The findings support previous research concerning the immigrant paradox and highlight the importance of context in the relationship between perceived discrimination and mental health. Implications for future research and intervention are discussed. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  6. Natural gas geochemistry and its origins in Kuqa depression

    2008-01-01

    According to gas compositional and carbon isotopic measurement of 114 gas samples from the Kuqa depression,accumulation of the natural gases in the depression is dominated by hydrocarbon gases, with high gas dryness(C1/C1-4)at the middle and northern parts of the depression and low one towards east and west sides and southern part.The carbon isotopes of methane and its homologues are relatively enriched in 13 C,and the distributive range ofδ13C 1 ,δ13C 2 andδ13C 3 is-32‰―-36‰,-22‰―-24‰and-20‰―-22‰,respectively.In general,the carbon isotopes of gaseous alkanes become less negative with the increase of carbon numbers.Theδ13C CO2 value is less than-10‰in the Kuqa depression,indicating its organogenic origin.The distributive range of 3 He/ 4 He ratio is within n×10-8 and a decrease in 3 He/ 4 He ratio from north to south in the depression is observed.Based on the geochemical parameters of natural gas above,natural gas in the Kuqa depression is of characteristics of coal-type gas origin.The possible reasons for the partial reversal of stable carbon isotopes of gaseous alkanes involve the mixing of gases from one common source rock with different thermal maturity or from two separated source rock intervals of similar kerogen type,multistages accumulation of natural gas under high-temperature and over-pressure conditions,and sufficiency and diffusion of natural gas.

  7. Neural origins of psychosocial functioning impairments in major depression.

    Pulcu, Erdem; Elliott, Rebecca

    2015-09-01

    Major depressive disorder, a complex neuropsychiatric condition, is associated with psychosocial functioning impairments that could become chronic even after symptoms remit. Social functioning impairments in patients could also pose coping difficulties to individuals around them. In this Personal View, we trace the potential neurobiological origins of these impairments down to three candidate domains-namely, social perception and emotion processing, motivation and reward value processing, and social decision making. We argue that the neural basis of abnormalities in these domains could be detectable at different temporal stages during social interactions (eg, before and after decision stages), particularly within frontomesolimbic networks (ie, frontostriatal and amygdala-striatal circuitries). We review some of the experimental designs used to probe these circuits and suggest novel, integrative approaches. We propose that an understanding of the interactions between these domains could provide valuable insights for the clinical stratification of major depressive disorder subtypes and might inform future developments of novel treatment options in return. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. De novo origin of human protein-coding genes.

    Dong-Dong Wu

    2011-11-01

    Full Text Available The de novo origin of a new protein-coding gene from non-coding DNA is considered to be a very rare occurrence in genomes. Here we identify 60 new protein-coding genes that originated de novo on the human lineage since divergence from the chimpanzee. The functionality of these genes is supported by both transcriptional and proteomic evidence. RNA-seq data indicate that these genes have their highest expression levels in the cerebral cortex and testes, which might suggest that these genes contribute to phenotypic traits that are unique to humans, such as improved cognitive ability. Our results are inconsistent with the traditional view that the de novo origin of new genes is very rare, thus there should be greater appreciation of the importance of the de novo origination of genes.

  9. De Novo Origin of Human Protein-Coding Genes

    Wu, Dong-Dong; Irwin, David M.; Zhang, Ya-Ping

    2011-01-01

    The de novo origin of a new protein-coding gene from non-coding DNA is considered to be a very rare occurrence in genomes. Here we identify 60 new protein-coding genes that originated de novo on the human lineage since divergence from the chimpanzee. The functionality of these genes is supported by both transcriptional and proteomic evidence. RNA–seq data indicate that these genes have their highest expression levels in the cerebral cortex and testes, which might suggest that these genes contribute to phenotypic traits that are unique to humans, such as improved cognitive ability. Our results are inconsistent with the traditional view that the de novo origin of new genes is very rare, thus there should be greater appreciation of the importance of the de novo origination of genes. PMID:22102831

  10. Different stress-related gene expression in depression and suicide

    Zhao, J; Qi, X-R; Gao, S-F; Lu, J; van Wamelen, D J; Kamphuis, W; Bao, A-M; Swaab, D F

    OBJECTIVE: Suicide occurs in some, but not all depressed patients. So far, it remains unknown whether the studied stress-related candidate genes change in depression, suicide or both. The prefrontal cortex (PFC) is involved in, among other things, impulse control and inhibitory behavior and plays an

  11. Evolutionary origins of Brassicaceae specific genes in Arabidopsis thaliana

    2011-01-01

    Background All sequenced genomes contain a proportion of lineage-specific genes, which exhibit no sequence similarity to any genes outside the lineage. Despite their prevalence, the origins and functions of most lineage-specific genes remain largely unknown. As more genomes are sequenced opportunities for understanding evolutionary origins and functions of lineage-specific genes are increasing. Results This study provides a comprehensive analysis of the origins of lineage-specific genes (LSGs) in Arabidopsis thaliana that are restricted to the Brassicaceae family. In this study, lineage-specific genes within the nuclear (1761 genes) and mitochondrial (28 genes) genomes are identified. The evolutionary origins of two thirds of the lineage-specific genes within the Arabidopsis thaliana genome are also identified. Almost a quarter of lineage-specific genes originate from non-lineage-specific paralogs, while the origins of ~10% of lineage-specific genes are partly derived from DNA exapted from transposable elements (twice the proportion observed for non-lineage-specific genes). Lineage-specific genes are also enriched in genes that have overlapping CDS, which is consistent with such novel genes arising from overprinting. Over half of the subset of the 958 lineage-specific genes found only in Arabidopsis thaliana have alignments to intergenic regions in Arabidopsis lyrata, consistent with either de novo origination or differential gene loss and retention, with both evolutionary scenarios explaining the lineage-specific status of these genes. A smaller number of lineage-specific genes with an incomplete open reading frame across different Arabidopsis thaliana accessions are further identified as accession-specific genes, most likely of recent origin in Arabidopsis thaliana. Putative de novo origination for two of the Arabidopsis thaliana-only genes is identified via additional sequencing across accessions of Arabidopsis thaliana and closely related sister species

  12. Sleep Duration and Depressive Symptoms: A Gene-Environment Interaction

    Watson, Nathaniel F.; Harden, Kathryn Paige; Buchwald, Dedra; Vitiello, Michael V.; Pack, Allan I.; Strachan, Eric; Goldberg, Jack

    2014-01-01

    Objective: We used quantitative genetic models to assess whether sleep duration modifies genetic and environmental influences on depressive symptoms. Method: Participants were 1,788 adult twins from 894 same-sex twin pairs (192 male and 412 female monozygotic [MZ] pairs, and 81 male and 209 female dizygotic [DZ] pairs] from the University of Washington Twin Registry. Participants self-reported habitual sleep duration and depressive symptoms. Data were analyzed using quantitative genetic interaction models, which allowed the magnitude of additive genetic, shared environmental, and non-shared environmental influences on depressive symptoms to vary with sleep duration. Results: Within MZ twin pairs, the twin who reported longer sleep duration reported fewer depressive symptoms (ec = -0.17, SE = 0.06, P sleep duration interaction effect on depressive symptoms (a'c = 0.23, SE = 0.08, P sleep duration and depressive symptoms. Among individuals with sleep duration within the normal range (7-8.9 h/night), the total heritability (h2) of depressive symptoms was approximately 27%. However, among individuals with sleep duration within the low (sleep duration extremes (5 h/night: h2 = 53%; 10 h/night: h2 = 49%). Conclusion: Genetic contributions to depressive symptoms increase at both short and long sleep durations. Citation: Watson NF; Harden KP; Buchwald D; Vitiello MV; Pack AI; Stachan E; Goldberg J. Sleep duration and depressive symptoms: a gene-environment interaction. SLEEP 2014;37(2):351-358. PMID:24497663

  13. Huntingtin gene repeat size variations affect risk of lifetime depression.

    Gardiner, Sarah L; van Belzen, Martine J; Boogaard, Merel W; van Roon-Mom, Willeke M C; Rozing, Maarten P; van Hemert, Albert M; Smit, Johannes H; Beekman, Aartjan T F; van Grootheest, Gerard; Schoevers, Robert A; Oude Voshaar, Richard C; Roos, Raymund A C; Comijs, Hannie C; Penninx, Brenda W J H; van der Mast, Roos C; Aziz, N Ahmad

    2017-12-11

    Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect depression risk in the general population. Using binary logistic regression, we assessed the association between HTT CAG repeat size and depression risk in two well-characterized Dutch cohorts─the Netherlands Study of Depression and Anxiety and the Netherlands Study of Depression in Older Persons─including 2165 depressed and 1058 non-depressed persons. In both cohorts, separately as well as combined, there was a significant non-linear association between the risk of lifetime depression and HTT CAG repeat size in which both relatively short and relatively large alleles were associated with an increased risk of depression (β = -0.292 and β = 0.006 for the linear and the quadratic term, respectively; both P < 0.01 after adjustment for the effects of sex, age, and education level). The odds of lifetime depression were lowest in persons with a HTT CAG repeat size of 21 (odds ratio: 0.71, 95% confidence interval: 0.52 to 0.98) compared to the average odds in the total cohort. In conclusion, lifetime depression risk was higher with both relatively short and relatively large HTT CAG repeat sizes in the normal range. Our study provides important proof-of-principle that repeat polymorphisms can act as hitherto unappreciated but complex genetic modifiers of depression.

  14. Idioms of Distress Among Depressed White-Non-Mexican and Mexican-Origin Older Men.

    Apesoa-Varano, Ester Carolina; Barker, Judith C; Unutzer, Jurgen; Aguilar-Gaxiola, Sergio; Johnson, Megan Dwight; Tran, Cindy; Guarnaccia, Peter; Hinton, Ladson

    2015-09-01

    Older men are less likely than older women to receive depression treatment. Latino older men in particular have been found to have significantly lower rates of depression treatment than their white-non-Mexican (WNM) counterparts. Prior research has shown that men are less likely than women to express overt affect and/or report depression symptoms that may prompt primary care physicians' inquiry about depression. Previous studies have overlooked the idioms of distress common among older men. This study investigates: a) the range of idioms of distress that emerge in the narratives of depressed older men, and b) the use of these idioms among depressed WNM and Mexican-origin older men. The present report is based on qualitative data collected through the Men's Health and Aging Study (MeHAS), a mixed-method study of clinically depressed WNM and Mexican-origin older (65 and above) men recruited in primary care settings. Qualitative analysis of 77 interviews led to identification of idioms of distress and informed idiom categories. Study findings show that: a) both groups of men utilized a range of idioms of distress that met current DSM criteria for depression, b) both groups were also likely to utilize idioms that feel outside clinical depression criteria, and c) there were similarities as well as differences between WNM and Mexican-origin men. This study provides a larger vocabulary that clinicians might consider in recognizing depression and initiating depression care for older men from diverse ethnic backgrounds. This is important to improve depression care among older men in general and those of Mexican-origin in particular.

  15. Depressive symptoms in schizophrenia and dopamine and serotonin gene polymorphisms.

    Peitl, Vjekoslav; Štefanović, Mario; Karlović, Dalibor

    2017-07-03

    Although depressive symptoms seem to be frequent in schizophrenia they have received significantly less attention than other symptom domains. As impaired serotonergic and dopaminergic neurotransmission is implicated in the pathogenesis of depression and schizophrenia this study sought to investigate the putative association between several functional gene polymorphisms (SERT 5-HTTLPR, MAO-A VNTR, COMT Val158Met and DAT VNTR) and schizophrenia. Other objectives of this study were to closely examine schizophrenia symptom domains by performing factor analysis of the two most used instruments in this setting (Positive and negative syndrome scale - PANSS and Calgary depression rating scale - CDSS) and to examine the influence of investigated gene polymorphisms on the schizophrenia symptom domains, focusing on depressive scores. A total of 591 participants were included in the study (300 schizophrenic patients and 291 healthy volunteers). 192 (64%) of schizophrenic patients had significant depressive symptoms. Genotype distribution revealed no significant differences regarding all investigated polymorphisms except the separate gender analysis for MAO-A gene polymorphism which revealed significantly more allele 3 carriers in schizophrenic males. Factor analysis of the PANSS scale revealed the existence of five separate factors (symptom domains), while the CDSS scale revealed two distinct factors. Several investigated gene polymorphisms (mostly SERT and MAO-A, but also COMT) significantly influenced two factors from the PANSS (aggressive/impulsive and negative symptoms) and one from the CDSS scale (suicidality), respectively. Depressive symptoms in schizophrenic patients may be influenced by functional gene polymorphisms, especially those implicated in serotonergic neurotransmission. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Phylogenetic origin and diversification of RNAi pathway genes in insects

    Dowling, Daniel; Pauli, Thomas; Donath, Alexander

    2016-01-01

    RNAinterference (RNAi) refers tothe set ofmolecular processes foundin eukaryotic organisms in which smallRNAmolecules mediate the silencing or down-regulation of target genes. In insects, RNAi serves a number of functions, including regulation of endogenous genes, anti-viral defense, and defense...... against transposable elements. Despite being well studied in model organisms, such as Drosophila, the distribution of core RNAi pathway genes and their evolution in insects is not well understood. Here we present the most comprehensive overview of the distribution and diversity of core RNAi pathway genes...... across 100 insect species, encompassing all currently recognized insect orders. We inferred the phylogenetic origin of insect-specific RNAi pathway genes and also identified several hitherto unrecorded gene expansions using whole-body transcriptome data from the international 1KITE (1000 Insect...

  17. Huntingtin gene repeat size variations affect risk of lifetime depression

    Gardiner, Sarah L.; van Belzen, Martine J.; Boogaard, Merel W.

    2017-01-01

    Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect...

  18. Different stress-related gene expression in depression and suicide.

    Zhao, J; Qi, X-R; Gao, S-F; Lu, J; van Wamelen, D J; Kamphuis, W; Bao, A-M; Swaab, D F

    2015-09-01

    Suicide occurs in some, but not all depressed patients. So far, it remains unknown whether the studied stress-related candidate genes change in depression, suicide or both. The prefrontal cortex (PFC) is involved in, among other things, impulse control and inhibitory behavior and plays an important role in both suicide and depression. We have employed qPCR to study 124 anterior cingulate cortex (ACC) and dorsolateral PFC (DLPFC) brain samples, obtained from two brain banks, from: i) young depressed patients (average age 43 years) who committed suicide (MDD-S) and depressed patients who died from causes other than suicide (MDD-NS) and from ii) elderly depressed patients (average age 75 years) who did not commit suicide (DEP). Both cohorts were individually matched with non-psychiatric non-suicide control subjects. We determined the transcript levels of hypothalamic-pituitary-adrenal axis-regulating molecules (corticotropin-releasing hormone (CRH), CRH receptors, CRH binding protein, mineralocorticoid receptor/glucocorticoid receptor), transcription factors that regulate CRH expression, CRH-stimulating cytokines, chaperone proteins, retinoid signaling, brain-derived neurotrophic factor and tropomyosin-related kinase B, cytochrome proteins, nitric oxide synthase (NOS) and monoamines. In the MDD-S group, expression levels of CRH and neuronal NOS-interacting DHHC domain-containing protein with dendritic mRNA (NIDD) were increased. Other changes were only present in the DEP group, i.e. decreased NIDD, and increased and 5-hydroxytryptamine receptor 1A (5-HT1A) expression levels. Changes were found to be more pronounced in the anterior cingulate cortex than in the dorsolateral PFC. Depressed patients who committed suicide have different gene expression patterns than depressed patients who died of causes other than suicide. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Comparative genome analysis of PHB gene family reveals deep evolutionary origins and diverse gene function.

    Di, Chao; Xu, Wenying; Su, Zhen; Yuan, Joshua S

    2010-10-07

    PHB (Prohibitin) gene family is involved in a variety of functions important for different biological processes. PHB genes are ubiquitously present in divergent species from prokaryotes to eukaryotes. Human PHB genes have been found to be associated with various diseases. Recent studies by our group and others have shown diverse function of PHB genes in plants for development, senescence, defence, and others. Despite the importance of the PHB gene family, no comprehensive gene family analysis has been carried to evaluate the relatedness of PHB genes across different species. In order to better guide the gene function analysis and understand the evolution of the PHB gene family, we therefore carried out the comparative genome analysis of the PHB genes across different kingdoms. The relatedness, motif distribution, and intron/exon distribution all indicated that PHB genes is a relatively conserved gene family. The PHB genes can be classified into 5 classes and each class have a very deep evolutionary origin. The PHB genes within the class maintained the same motif patterns during the evolution. With Arabidopsis as the model species, we found that PHB gene intron/exon structure and domains are also conserved during the evolution. Despite being a conserved gene family, various gene duplication events led to the expansion of the PHB genes. Both segmental and tandem gene duplication were involved in Arabidopsis PHB gene family expansion. However, segmental duplication is predominant in Arabidopsis. Moreover, most of the duplicated genes experienced neofunctionalization. The results highlighted that PHB genes might be involved in important functions so that the duplicated genes are under the evolutionary pressure to derive new function. PHB gene family is a conserved gene family and accounts for diverse but important biological functions based on the similar molecular mechanisms. The highly diverse biological function indicated that more research needs to be carried out

  20. Recombination facilitates neofunctionalization of duplicate genes via originalization

    Huang Ren

    2010-06-01

    Full Text Available Abstract Background Recently originalization was proposed to be an effective way of duplicate-gene preservation, in which recombination provokes the high frequency of original (or wild-type allele on both duplicated loci. Because the high frequency of wild-type allele might drive the arising and accumulating of advantageous mutation, it is hypothesized that recombination might enlarge the probability of neofunctionalization (Pneo of duplicate genes. In this article this hypothesis has been tested theoretically. Results Results show that through originalization recombination might not only shorten mean time to neofunctionalizaiton, but also enlarge Pneo. Conclusions Therefore, recombination might facilitate neofunctionalization via originalization. Several extensive applications of these results on genomic evolution have been discussed: 1. Time to nonfunctionalization can be much longer than a few million generations expected before; 2. Homogenization on duplicated loci results from not only gene conversion, but also originalization; 3. Although the rate of advantageous mutation is much small compared with that of degenerative mutation, Pneo cannot be expected to be small.

  1. Origins of De Novo Genes in Human and Chimpanzee.

    Ruiz-Orera, Jorge; Hernandez-Rodriguez, Jessica; Chiva, Cristina; Sabidó, Eduard; Kondova, Ivanela; Bontrop, Ronald; Marqués-Bonet, Tomàs; Albà, M Mar

    2015-12-01

    The birth of new genes is an important motor of evolutionary innovation. Whereas many new genes arise by gene duplication, others originate at genomic regions that did not contain any genes or gene copies. Some of these newly expressed genes may acquire coding or non-coding functions and be preserved by natural selection. However, it is yet unclear which is the prevalence and underlying mechanisms of de novo gene emergence. In order to obtain a comprehensive view of this process, we have performed in-depth sequencing of the transcriptomes of four mammalian species--human, chimpanzee, macaque, and mouse--and subsequently compared the assembled transcripts and the corresponding syntenic genomic regions. This has resulted in the identification of over five thousand new multiexonic transcriptional events in human and/or chimpanzee that are not observed in the rest of species. Using comparative genomics, we show that the expression of these transcripts is associated with the gain of regulatory motifs upstream of the transcription start site (TSS) and of U1 snRNP sites downstream of the TSS. In general, these transcripts show little evidence of purifying selection, suggesting that many of them are not functional. However, we find signatures of selection in a subset of de novo genes which have evidence of protein translation. Taken together, the data support a model in which frequently-occurring new transcriptional events in the genome provide the raw material for the evolution of new proteins.

  2. Ethnic identity, perceived support, and depressive symptoms among racial minority immigrant-origin adolescents.

    Tummala-Narra, Pratyusha

    2015-01-01

    Although racial minority immigrant-origin adolescents compose a rapidly growing sector of the U.S. population, few studies have examined the role of contextual factors in mental health among these youth. The present study examined the relationship between ethnic identity and depressive symptoms, the relationship between perceived social support and depressive symptoms, and the relationship between sociodemographic factors (ethnicity, gender, and socioeconomic status) and depressive symptoms, among a culturally diverse group of adolescents. In addition, the potential moderating role of nativity status (U.S. born vs. foreign born) was examined in these associations. Participants were 9th and 10th graders (N = 341; 141 foreign born and 200 U.S. born, from Asian, Latino(a), and Afro-Caribbean backgrounds), attending an urban high school. Consistent with previous research, ethnic identity was negatively associated with depressive symptomatology in the overall sample. Nativity status did not moderate the relationship between ethnic identity and depressive symptoms. Among the sociodemographic factors examined, only gender was associated with depressive symptoms, with girls reporting higher levels of depressive symptoms compared with boys. Contrary to expectations, there were no differences in the degree of depressive symptomatology between U.S.-born and foreign-born adolescents, and perceived social support was not associated with fewer depressive symptoms. The findings suggest the importance of gender and ethnic identity in mental health and, more broadly, the complexity of social location in mental health outcomes among U.S.-born and foreign-born immigrant-origin adolescents. Implications for research and interventions with immigrant-origin adolescents are discussed.

  3. Familism Values, Family Time, and Mexican-Origin Young Adults’ Depressive Symptoms

    Zeiders, Katharine H.; Updegraff, Kimberly A.; Umaña-Taylor, Adriana J.; McHale, Susan M.; Padilla, Jenny

    2015-01-01

    Using longitudinal data across eight years, this study examined how parents’ familism values in early adolescence predicted youths’ depressive symptoms in young adulthood via youths’ familism values and family time. We examined these processes among 246 Mexican-origin families using interview and phone-diary data. Findings revealed that fathers’ familism values predicted male and female youths’ familism values in middle adolescence. For female youth only, fathers’ familism values also predicted youths’ family time in late adolescence. The link between family time and young adults’ depressive symptoms depended on parental acceptance and adolescent gender: Among female and male youth, family time predicted fewer depressive symptoms, but only when paternal acceptance was high. For female adolescents only, family time predicted fewer depressive symptoms when maternal acceptance was high but more depressive symptoms when maternal acceptance was low. Findings highlight family dynamics as the mechanisms through which familism values have implications for youths’ adjustment. PMID:26778855

  4. Major Depressive Disorder and Dysthymia at the Intersection of Nativity and Racial-Ethnic Origins.

    Szaflarski, Magdalena; Cubbins, Lisa A; Bauldry, Shawn; Meganathan, Karthikeyan; Klepinger, Daniel H; Somoza, Eugene

    2016-08-01

    Immigrants often have lower rates of depression than US-natives, but longitudinal assessments across multiple racial-ethnic groups are limited. This study examined the rates of prevalent, acquired, and persisting major depression and dysthymia by nativity and racial-ethnic origin while considering levels of acculturation, stress, and social ties. Data from the National Epidemiologic Survey on Alcohol and Related Conditions were used to model prevalence and 3-year incidence/persistence of major depression and dysthymia (DSM-IV diagnoses) using logistic regression. Substantive factors were assessed using standardized measures. The rates of major depression were lower for most immigrants, but differences were noted by race-ethnicity and outcome. Furthermore, immigrants had higher prevalence but not incidence of dysthymia. The associations between substantive factors and outcomes were mixed. This study describes and begins to explain immigrant trajectories of major depression and dysthymia over a 3-year period. The continuing research challenges and future directions are discussed.

  5. Differential gene expression in patients with subsyndromal symptomatic depression and major depressive disorder.

    Yang, Chengqing; Hu, Guoqin; Li, Zezhi; Wang, Qingzhong; Wang, Xuemei; Yuan, Chengmei; Wang, Zuowei; Hong, Wu; Lu, Weihong; Cao, Lan; Chen, Jun; Wang, Yong; Yu, Shunying; Zhou, Yimin; Yi, Zhenghui; Fang, Yiru

    2017-01-01

    Subsyndromal symptomatic depression (SSD) is a subtype of subthreshold depressive and can lead to significant psychosocial functional impairment. Although the pathogenesis of major depressive disorder (MDD) and SSD still remains poorly understood, a set of studies have found that many same genetic factors play important roles in the etiology of these two disorders. Nowadays, the differential gene expression between MDD and SSD is still unknown. In our previous study, we compared the expression profile and made the classification with the leukocytes by using whole-genome cRNA microarrays among drug-free first-episode subjects with SSD, MDD and matched healthy controls (8 subjects in each group), and finally determined 48 gene expression signatures. Based on these findings, we further clarify whether these genes mRNA was different expressed in peripheral blood in patients with SSD, MDD and healthy controls (60 subjects respectively). With the help of the quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR), we gained gene relative expression levels among the three groups. We found that there are three of the forty eight co-regulated genes had differential expression in peripheral blood among the three groups, which are CD84, STRN, CTNS gene (F = 3.528, p = 0.034; F = 3.382, p = 0.039; F = 3.801, p = 0.026, respectively) while there were no significant differences for other genes. CD84, STRN, CTNS gene may have significant value for performing diagnostic functions and classifying SSD, MDD and healthy controls.

  6. Elusive Origins of the Extra Genes in Aspergillus oryzae

    Khaldi, Nora; Wolfe, Kenneth H.

    2008-01-01

    The genome sequence of Aspergillus oryzae revealed unexpectedly that this species has approximately 20% more genes than its congeneric species A. nidulans and A. fumigatus. Where did these extra genes come from? Here, we evaluate several possible causes of the elevated gene number. Many gene families are expanded in A. oryzae relative to A. nidulans and A. fumigatus, but we find no evidence of ancient whole-genome duplication or other segmental duplications, either in A. oryzae or in the common ancestor of the genus Aspergillus. We show that the presence of divergent pairs of paralogs is a feature peculiar to A. oryzae and is not shared with A. nidulans or A. fumigatus. In phylogenetic trees that include paralog pairs from A. oryzae, we frequently find that one of the genes in a pair from A. oryzae has the expected orthologous relationship with A. nidulans, A. fumigatus and other species in the subphylum Eurotiomycetes, whereas the other A. oryzae gene falls outside this clade but still within the Ascomycota. We identified 456 such gene pairs in A. oryzae. Further phylogenetic analysis did not however indicate a single consistent evolutionary origin for the divergent members of these pairs. Approximately one-third of them showed phylogenies that are suggestive of horizontal gene transfer (HGT) from Sordariomycete species, and these genes are closer together in the A. oryzae genome than expected by chance, but no unique Sordariomycete donor species was identifiable. The postulated HGTs from Sordariomycetes still leave the majority of extra A. oryzae genes unaccounted for. One possible explanation for our observations is that A. oryzae might have been the recipient of many separate HGT events from diverse donors. PMID:18725939

  7. Elusive origins of the extra genes in Aspergillus oryzae.

    Nora Khaldi

    Full Text Available The genome sequence of Aspergillus oryzae revealed unexpectedly that this species has approximately 20% more genes than its congeneric species A. nidulans and A. fumigatus. Where did these extra genes come from? Here, we evaluate several possible causes of the elevated gene number. Many gene families are expanded in A. oryzae relative to A. nidulans and A. fumigatus, but we find no evidence of ancient whole-genome duplication or other segmental duplications, either in A. oryzae or in the common ancestor of the genus Aspergillus. We show that the presence of divergent pairs of paralogs is a feature peculiar to A. oryzae and is not shared with A. nidulans or A. fumigatus. In phylogenetic trees that include paralog pairs from A. oryzae, we frequently find that one of the genes in a pair from A. oryzae has the expected orthologous relationship with A. nidulans, A. fumigatus and other species in the subphylum Eurotiomycetes, whereas the other A. oryzae gene falls outside this clade but still within the Ascomycota. We identified 456 such gene pairs in A. oryzae. Further phylogenetic analysis did not however indicate a single consistent evolutionary origin for the divergent members of these pairs. Approximately one-third of them showed phylogenies that are suggestive of horizontal gene transfer (HGT from Sordariomycete species, and these genes are closer together in the A. oryzae genome than expected by chance, but no unique Sordariomycete donor species was identifiable. The postulated HGTs from Sordariomycetes still leave the majority of extra A. oryzae genes unaccounted for. One possible explanation for our observations is that A. oryzae might have been the recipient of many separate HGT events from diverse donors.

  8. Intrinsically bent DNA in replication origins and gene promoters.

    Gimenes, F; Takeda, K I; Fiorini, A; Gouveia, F S; Fernandez, M A

    2008-06-24

    Intrinsically bent DNA is an alternative conformation of the DNA molecule caused by the presence of dA/dT tracts, 2 to 6 bp long, in a helical turn phase DNA or with multiple intervals of 10 to 11 bp. Other than flexibility, intrinsic bending sites induce DNA curvature in particular chromosome regions such as replication origins and promoters. Intrinsically bent DNA sites are important in initiating DNA replication, and are sometimes found near to regions associated with the nuclear matrix. Many methods have been developed to localize bent sites, for example, circular permutation, computational analysis, and atomic force microscopy. This review discusses intrinsically bent DNA sites associated with replication origins and gene promoter regions in prokaryote and eukaryote cells. We also describe methods for identifying bent DNA sites for circular permutation and computational analysis.

  9. Depressive disorder and social stress in Pakistan compared to people of Pakistani origin in the UK.

    Husain, Nusrat; Chaudhry, Nasim; Tomenson, Barbara; Jackson, Judy; Gater, Richard; Creed, Francis

    2011-11-01

    Depressive disorder is more common in low to middle than high-income countries, but the reasons for this have not been explicitly defined. We compared the results of two population-based studies of people of Pakistani origin: one living in rural Pakistan and one in UK. Both samples were screened with the self-reporting questionnaire followed by research interview to determine depressive disorders and social stress. Logistic regression was used to compare the prevalence of depressive disorder in the two countries after adjustment for socio-demographic characteristics and social stress. The estimated prevalence of depression for men was 35.8% (95% CI 16.1-55.5) in Pakistan and 9% (5.0-13.0) in Manchester (pstress (both sexes). 35% of women in Pakistan and 71% of those in UK had received 8 years or more of education. Extremely poor housing and marked poverty were experienced by 36.1% of women in Pakistan and 0.6% of those in Manchester. In Pakistan, housing and poverty predominated as correlates of depression, whereas in Manchester it was marked difficulties in physical health and close relationships. The results suggest that the higher rate of depressive disorder amongst women in Pakistan compared to UK can be attributed to less education and frequent severe social difficulties. These differences have implications for treatment.

  10. [The brain and cytokines - the mutual origin of depression, obesity and cardiovascular diseases?].

    Ufnal, Marcin; Wolynczyk-Gmaj, Dorota

    2011-04-19

    Accumulating evidence points to a pivotal role of the brain in the regulation of the circulatory system and energy balance. It has also been found that common civilization diseases such as depression, obesity, hypertension, myocardial infarction or heart failure are accompanied by an increase in concentration of inflammatory mediators in the blood, cerebrospinal fluid and various tissues. Recent studies have revealed that inflammatory mediators that are synthesized peripherally or in the brain may affect the nervous regulation of animal body systems. For example, it has been found that non-specific pro-inflammatory stimuli as well as treatment with several cytokines may cause depressive behavior, disturbances in energy balance and alterations in the circulatory system. On the other hand, knockout of genes for pro-inflammatory cytokines or administration of anti-inflammatory mediators may normalize the pathological changes. In the present manuscript we will review studies that imply the common neuroinflammatory pathogenesis of cardiovascular diseases, depression and energy balance disorders.

  11. Mothers’ Trajectories of Depressive Symptoms Across Mexican-Origin Adolescent Daughters’ Transition to Parenthood

    Updegraff, Kimberly A.; Perez-Brena, Norma J.; Umaña-Taylor, Adriana J.; Jahromi, Laudan B.; Harvey-Mendoza, Elizabeth C.

    2013-01-01

    This study draws from a life-course perspective in examining trajectories of mothers’ depressive symptoms across their adolescent daughters’ adjustment to parenthood in 204 Mexican-origin families using latent class growth analysis. Four distinct trajectories were identified based on mothers’ depressive symptoms prior to the birth and 10 and 24 months postpartum. Two trajectories were characterized by stable levels of depressive symptoms but were differentiated in their levels of symptoms (i.e., High/Stable and Low/Stable). The remaining two trajectories were characterized by changes from pre- to post-birth, with one group exhibiting increases in depressive symptoms (i.e., Low/Post-Birth Increase) and the other group characterized by decreases in depressive symptoms (i.e., Low/Post-Birth Decrease). Consistent with a risk and resilience perspective, mothers with more disadvantaged socioeconomic circumstances and fewer intrapersonal resources (i.e., self-esteem, ethnic identity affirmation) were more likely to be members of the High/Stable group. In addition, daughters of mothers in the High/Stable group were more likely to have lower self-esteem as compared to daughters in the other three groups. Collectively, these findings suggested that the High/Stable group was at risk for adjustment difficulties from the third trimester to two years postpartum. In contrast, membership in the Low/Post-Birth Decrease trajectory group was associated with lower depressive symptoms and higher self-esteem for mothers and daughters. Findings point to the need to identify mothers who are at risk for depressive symptoms during their adolescent daughters’ pregnancy and offer prevention and intervention programs that reduce risks and enhance protective factors. PMID:23750520

  12. Clinical characteristics of inflammation-associated depression: Monocyte gene expression is age-related in major depressive disorder.

    Grosse, Laura; Carvalho, Livia A; Wijkhuijs, Annemarie J M; Bellingrath, Silja; Ruland, Tillmann; Ambrée, Oliver; Alferink, Judith; Ehring, Thomas; Drexhage, Hemmo A; Arolt, Volker

    2015-02-01

    Increased inflammatory activation might only be present in a subgroup of depressed individuals in which immune processes are especially relevant to disease development. We aimed to analyze demographic, depression, and trauma characteristics of major depressive disorder (MDD) patients with regard to inflammatory monocyte gene expression. Fifty-six naturalistically treated MDD patients (32 ± 12 years) and 57 healthy controls (HC; 31 ± 11 years) were analyzed by the Inventory of Depressive Symptomatology (IDS) and by the Childhood Trauma Questionnaire (CTQ). We determined the expression of 38 inflammatory and immune activation genes including the glucocorticoid receptor (GR)α and GRβ genes in purified CD14(+) monocytes using quantitative-polymerase chain reaction (RT-qPCR). Monocyte gene expression was age-dependent, particularly in MDD patients. Increased monocyte gene expression and decreased GRα/β ratio were only present in MDD patients aged ⩾ 28 years. Post hoc analyses of monocyte immune activation in patients depression (recurrent type, onset depression, onset ⩾15 years) - additionally characterized by the absence of panic symptoms - that exhibited a strongly reduced inflammatory monocyte activation compared to HC. In conclusion, monocyte immune activation was not uniformly raised in MDD patients but was increased only in patients of 28 years and older. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Altered expression pattern of clock genes in a rat model of depression

    Christiansen, Sofie; Bouzinova, Elena; Fahrenkrug, Jan

    2016-01-01

    BACKGROUND: Abnormalities in circadian rhythms may be causal factors in development of major depressive disorder. The biology underlying a causal relationship between circadian rhythm disturbances and depression is slowly being unraveled. Although there is no direct evidence of dysregulation...... of clock gene expression in depressive patients many studies have reported single-nucleotide polymorphisms in clock genes in these patients. METHODS: In the present study we investigated whether a depression-like state in rats associates with alternations of the diurnal expression of clock genes....... The validated chronic mild stress (CMS) animal model of depression was used to investigate rhythmic expression of three clock genes; Per1, Per2 and Bmal1. Brain and liver tissue was collected from 96 animals after 3.5 weeks of CMS (48 control and 48 depression-like rats) at 4 h sampling interval within 24 h. We...

  14. Anxiety and depressive disorders in elderly with chronic dizziness of vestibular origin

    Érica Toledo Piza Peluso

    2016-04-01

    Full Text Available ABSTRACT INTRODUCTION: Dizziness is one of the most prevalent symptoms in the elderly. Anxiety and depression are common in dizzy adult patients, but there is scarce information about comorbidity between vestibular disturbances and psychiatric disorders in the aged. OBJECTIVE: To assess the prevalence of anxiety and depression disorders in elderly with chronic dizziness of vestibular origin. METHODS: Transversal study that used the Brazilian version of the Composite International Diagnostic Interview 2.1 to assess anxiety and depressive disorders in elderly patients (≥60 years old with chronic dizziness. RESULTS: Most of the 44 patients included in the study were female (88.6% with a mean age of 71 years (±7.5, 68.1% had experienced dizziness for 1 year or more. The most prevalent diagnosis was benign paroxysmal positional vertigo (52.3%. The prevalence of generalized anxiety disorder and specific phobias during life were 29.5% and 22.7%, respectively, and, in the last 12 months, 18.2% and 15.9%. There was no patient with panic disorder, agoraphobia or social phobia. The prevalence of depressive disorder during life was 45.4%, and, in the last 12 months, were 11.3%. CONCLUSION: Aged patients with chronic dizziness had high prevalence of some mental disorders.

  15. A Developmental-Contextual Model of Depressive Symptoms in Mexican-Origin Female Adolescents

    Bámaca-Colbert, Mayra Y.; Umaña-Taylor, Adriana J.; Gayles, Jochebed G.

    2011-01-01

    The current study tested a developmental-contextual model of depressive symptomatology among early and middle adolescent Mexican-origin females and their mothers. The final sample was comprised of 271 dyads. We examined the interrelations among cultural (i.e., acculturation dissonance), developmental (i.e., pubertal development and autonomy expectation discrepancies), and interpersonal (i.e., mother-daughter conflict and maternal supportive parenting) factors in predicting adolescents’ depressive symptoms. For both early and middle adolescents, maternal support was negatively associated with mother-daughter conflict and depressive symptoms. Importantly, mother-daughter autonomy expectation discrepancies were positively associated with mother-daughter conflict, but this association was found only among early adolescents. Further, mother-daughter acculturation dissonance was positively associated with mother-daughter conflict, but only among middle adolescents. Findings call for concurrently examining the interface of developmental, relational, and cultural factors in predicting female adolescents’ depressive symptomatology and the potential differences by developmental stage (e.g., early vs. middle adolescence) PMID:21967564

  16. The effects of antenatal depression and antidepressant treatment on placental gene expression

    Jocelien DA Olivier

    2015-01-01

    Full Text Available The effects of antenatal depression and antidepressant treatment during pregnancy on both mother and child are vigorously studied, but the underlying biology for these effects is largely unknown. The placenta plays a crucial role in the growth and development of the fetus. We performed a gene expression study on the fetal side of the placenta to investigate gene expression patterns in mothers with antenatal depression and in mothers using antidepressant treatment during pregnancy.Placental samples from mothers with normal pregnancies, from mothers with antenatal depression, and from mothers using antidepressants were collected. We performed a pilot microarray study to investigate alterations in the gene expression and selected several genes from the microarray for biological validation with qPCR in a larger sample.In mothers with antenatal depression 108 genes were differentially expressed, whereas 109 genes were differentially expressed in those using antidepressants. Validation of the microarray revealed more robust gene expression differences in the seven genes picked for confirmation in antidepressant-treated women than in depressed women. Among the genes that were validated ROCK2 and C12orf39 were differentially expressed in both depressed and antidepressant-treated women, whereas ROCK1, GCC2, KTN1, and DNM1L were only differentially expressed in the antidepressant-treated women. In conclusion, antenatal depression and antidepressant exposure during pregnancy are associated with altered gene expression in the placenta. Findings on those genes picked for validation were more robust among antidepressant-treated women than in depressed women, possibly due to the fact that depression is a multifactorial condition with varying degrees of endocrine disruption. It remains to be established whether the alterations found in the gene expression of the placenta are found in the fetus as well.

  17. Is Low Self-Esteem a Risk Factor for Depression? Findings from a Longitudinal Study of Mexican-Origin Youth

    Orth, Ulrich; Robins, Richard W.; Widaman, Keith F.; Conger, Rand D.

    2014-01-01

    We examined the relation between low self-esteem and depression using longitudinal data from a sample of 674 Mexican-origin early adolescents who were assessed at age 10 and 12 years. Results supported the vulnerability model, which states that low self-esteem is a prospective risk factor for depression. Moreover, results suggested that the…

  18. The evolution of milk casein genes from tooth genes before the origin of mammals.

    Kawasaki, Kazuhiko; Lafont, Anne-Gaelle; Sire, Jean-Yves

    2011-07-01

    Caseins are among cardinal proteins that evolved in the lineage leading to mammals. In milk, caseins and calcium phosphate (CaP) form a huge complex called casein micelle. By forming the micelle, milk maintains high CaP concentrations, which help altricial mammalian neonates to grow bone and teeth. Two types of caseins are known. Ca-sensitive caseins (α(s)- and β-caseins) bind Ca but precipitate at high Ca concentrations, whereas Ca-insensitive casein (κ-casein) does not usually interact with Ca but instead stabilizes the micelle. Thus, it is thought that these two types of caseins are both necessary for stable micelle formation. Both types of caseins show high substitution rates, which make it difficult to elucidate the evolution of caseins. Yet, recent studies have revealed that all casein genes belong to the secretory calcium-binding phosphoprotein (SCPP) gene family that arose by gene duplication. In the present study, we investigated exon-intron structures and phylogenetic distributions of casein and other SCPP genes, particularly the odontogenic ameloblast-associated (ODAM) gene, the SCPP-Pro-Gln-rich 1 (SCPPPQ1) gene, and the follicular dendritic cell secreted peptide (FDCSP) gene. The results suggest that contemporary Ca-sensitive casein genes arose from a putative common ancestor, which we refer to as CSN1/2. The six putative exons comprising CSN1/2 are all found in SCPPPQ1, although ODAM also shares four of these exons. By contrast, the five exons of the Ca-insensitive casein gene are all reminiscent of FDCSP. The phylogenetic distribution of these genes suggests that both SCPPPQ1 and FDCSP arose from ODAM. We thus argue that all casein genes evolved from ODAM via two different pathways; Ca-sensitive casein genes likely originated directly from SCPPPQ1, whereas the Ca-insensitive casein genes directly differentiated from FDCSP. Further, expression of ODAM, SCPPPQ1, and FDCSP was detected in dental tissues, supporting the idea that both types of caseins

  19. Altered choroid plexus gene expression in major depressive disorder

    Cortney Ann Turner

    2014-04-01

    Full Text Available Given the emergent interest in biomarkers for mood disorders, we assessed gene expression in the choroid plexus, the region that produces cerebrospinal fluid (CSF, in individuals with major depressive disorder (MDD. Genes that are expressed in the choroid plexus (CP can be secreted into the CSF and may be potential biomarker candidates. Given that we have previously shown that fibroblast growth factor family members are differentially expressed in post-mortem brain of subjects with MDD and the CP is a known source of growth factors in the brain, we posed the question whether growth factor dysregulation would be found in the CP of subjects with MDD. We performed laser capture microscopy of the choroid plexus at the level of the hippocampus in subjects with MDD and psychiatrically normal controls. We then extracted, amplified, labeled and hybridized the cRNA to Illumina BeadChips to assess gene expression. In controls, the most highly abundant known transcript was transthyretin. Moreover, half of the 14 most highly expressed transcripts in controls encode ribosomal proteins. Using BeadStudio software, we identified 169 transcripts differentially expressed (p< 0.05 between control and MDD samples. Using pathway analysis we noted that the top network altered in subjects with MDD included multiple members of the transforming growth factor-beta (TGFβ pathway. Quantitative real-time PCR (qRT-PCR confirmed downregulation of several transcripts that interact with the extracellular matrix in subjects with MDD. These results suggest that there may be an altered cytoskeleton in the choroid plexus in MDD subjects that may lead to a disrupted blood-CSF-brain barrier.

  20. Association analyses of depression and genes in the hypothalamus-pituitary-adrenal axis

    Buttenschøn, Henriette Nørmølle; Krogh, Jesper; Nielsen, Marit Nyholm

    2017-01-01

    OBJECTIVE: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been reported in depression. The aim was to investigate the potential association between depression and seven genes regulating or interfering with the HPA axis, including the gene encoding angiotensin converting enzyme......) was investigated. RESULTS: After quality control, 68 genetic variants were left for analyses. Four of nine variants within ACE were nominally associated with depression and a gene-wise association was likewise observed. However, none of the SNPs located within AVP, CRH, CRHR1, CRHR2, FKBP5 or NC3C1 were associated...... with depression. One nominally significant interaction, most likely due to chance, was identified. CONCLUSION: The results indicate that ACE could be a potential candidate gene for depression....

  1. Comet 67p/Churyumov-Gerasimenko, possible origin of the depression Hatmehit

    Kossacki, Konrad J.; Czechowski, Leszek

    2018-05-01

    On the nucleus of comet 67P/Churyumov-Gerasimenko numerous pits and depressions of different sizes are identified. In the present work the origin of depression Hatmehit is investigated. We propose a mechanism that includes recession of the surface due to sub-dust sublimation together with formation of cavities. Recession of the surface is calculated taking into account the sub-dust sublimation of water ice with volatile organic components, formation of a strengthened ice-dust crust due to sintering of ice grains and the increase of the gas pressure in pores due to release of gaseous CO. Our simulations indicate, that the formation of a 300 m deep depression due to the sub-dust sublimation of ice can take as little as 50 orbital periods assuming that the heliocentric distance at perihelion is close to its present value (Ip. et al., 2016). When amorphous water ice is present at small depth the release of gaseous CO may cause either compression of low-strength material beneath the strengthened crust, or ejection of the crust. In both cases a cavity is formed and grows due to the sublimation of ice from the wall and the floor.

  2. Gene expression profiles associated with depression in patients with chronic hepatitis C (CH-C).

    Birerdinc, Aybike; Afendy, Arian; Stepanova, Maria; Younossi, Issah; Baranova, Ancha; Younossi, Zobair M

    2012-09-01

    The standard treatment for CH-C, pegylated interferon-α and ribavirin (PEG-IFN + RBV), is associated with depression. Recent studies have proposed a new role for cytokines in the pathogenesis of depression. We aimed to assess differential gene expression related to depression in CH-C patients treated with PEG-IFN + RBV. We included 67 CH-C patients being treated with PEG-IFN+RBV. Of the entire study cohort, 22% had pre-existing depression, while another 37% developed new depression in course of the treatment. Pretreatment blood samples were collected into PAXgene™ RNA tubes, the RNAs extracted from peripheral blood mononuclear cells (PBMCs) were used for one step RT-PCR to profile 160 mRNAs. Differentially expressed genes were separated into up- and down-regulated genes according to presence or absence of depression at baseline (pre-existing depression) or following the initiation of treatment (treatment-related depression). The mRNA expression profile associated with any depression and with treatment-related depression included four and six genes, respectively. Our data demonstrate a significant down-regulation of TGF-β1 and the shift of Th1-Th2 cytokine balance in the depression associated with IFN-based treatment of HCV infection. We propose that TGF-β1 plays an important role in the imbalance of Th1/Th2 in patients with CH-C and depression. With further validation, TGF-β1 and other components of Th1/Th2 regulation pathway may provide a future marker for CH-C patients predisposed to depression.

  3. Association between the epidermal growth factor gene and intelligence in major depression patients.

    Tian, Wen-min; Zhang, Ke-ran; Zhang, Juan; Shen, Yan; Xu, Qi

    2010-06-01

    To study the association between the epidermal growth factor (EGF) gene and intelligence in patients with major depression. Intelligence measurement using Wechsler Adult Intelligence Scale (WAIS) was performed on 120 unrelated patients with major depression and 46 control subjects. Blood was collected from all subjects for extraction of genomic DNA. Four single nucleotide polymorphisms (SNPs) in the EGF gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI- TOF-MS). Mean scores of both score lang and score task, two subtests in WAIS, differed significantly between major depression patients and controls (Pintelligence in patients with major depression. Genetic variation in the EGF gene may increase the susceptibility of major depression.

  4. Glucocorticoid Receptor Related Genes: Genotype And Brain Gene Expression Relationships To Suicide And Major Depressive Disorder

    Pantazatos, Spiro P.; Huang, Yung-yu; Rosoklija, Gorazd B.; Dwork, Andrew J.; Burke, Ainsley; Arango, Victoria; Oquendo, Maria A.; Mann, J. John

    2016-01-01

    Introduction We tested the relationship between genotype, gene expression and suicidal behavior and MDD in live subjects and postmortem samples for three genes, associated with the hypothalamic-pituitary-adrenal axis, suicidal behavior and major depressive disorder (MDD); FK506 binding protein 5 (FKBP5), Spindle and kinetochore-associated protein 2 (SKA2) and Glucocorticoid Receptor (NR3C1). Materials and Methods Single-nucleotide polymorphisms (SNPs) and haplotypes were tested for association with suicidal behavior and MDD in a live (N=277) and a postmortem sample (N=209). RNA-seq was used to examine gene and isoform-level brain expression postmortem (Brodmann Area 9) (N=59). Expression quantitative trait loci (eQTL) relationships were examined using a public database (UK Brain Expression Consortium). Results We identified a haplotype within the FKBP5 gene, present in 47% of the live subjects, that was associated with increased risk of suicide attempt (OR=1.58, t=6.03, p=0.014). Six SNPs on this gene, three SNPs on SKA2 and one near NR3C1 showed before-adjustment association with attempted suicide, and two SNPs of SKA2 with suicide death, but none stayed significant after adjustment for multiple testing. Only the SKA2 SNPs were related to expression in the prefrontal cortex. One NR3C1 transcript had lower expression in suicide relative to non-suicide sudden death cases (b=-0.48, SE=0.12, t=-4.02, adjusted p=0.004). Conclusion We have identified an association of FKBP5 haplotype with risk of suicide attempt and found an association between suicide and altered NR3C1 gene expression in the prefrontal cortex. Our findings further implicate hypothalamic pituitary axis dysfunction in suicidal behavior. PMID:27030168

  5. Origins of gene, genetic code, protein and life

    We have further presented the [GADV]-protein world hypothesis of the origin of life as well as a hypothesis of protein production, suggesting that proteins were originally produced by random peptide formation of amino acids restricted in specific amino acid compositions termed as GNC-, SNS- and GC-NSF(a)-0th order ...

  6. Origins of gene, genetic code, protein and life: comprehensive view ...

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    production, suggesting that proteins were originally produced by random peptide formation of amino acids restricted in specific amino acid compositions .... using random numbers by a computer, to confirm whether main chains of ...... world on the origin of life by the pseudo-replication of. [GADV]-proteins in the absence of ...

  7. Origins of gene, genetic code, protein and life

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    have concluded that newly-born genes are products of nonstop frames (NSF) ... research to determine tertiary structures of proteins such ... the present earth, is favourable for new genes to arise, if ..... NGG) in the universal genetic code table, cannot satisfy ..... which has been proposed to explain the development of life on.

  8. Evolutionary Origins of Cancer Driver Genes and Implications for Cancer Prognosis.

    Chu, Xin-Yi; Jiang, Ling-Han; Zhou, Xiong-Hui; Cui, Ze-Jia; Zhang, Hong-Yu

    2017-07-14

    The cancer atavistic theory suggests that carcinogenesis is a reverse evolution process. It is thus of great interest to explore the evolutionary origins of cancer driver genes and the relevant mechanisms underlying the carcinogenesis. Moreover, the evolutionary features of cancer driver genes could be helpful in selecting cancer biomarkers from high-throughput data. In this study, through analyzing the cancer endogenous molecular networks, we revealed that the subnetwork originating from eukaryota could control the unlimited proliferation of cancer cells, and the subnetwork originating from eumetazoa could recapitulate the other hallmarks of cancer. In addition, investigations based on multiple datasets revealed that cancer driver genes were enriched in genes originating from eukaryota, opisthokonta, and eumetazoa. These results have important implications for enhancing the robustness of cancer prognosis models through selecting the gene signatures by the gene age information.

  9. Acculturative and Enculturative Stress, Depressive Symptoms, and Maternal Warmth: Examining Within-Person Relations among Mexican-origin Adolescent Mothers

    Zeiders, Katharine H.; Umaña-Taylor, Adriana J.; Updegraff, Kimberly A.; Jahromi, Laudan B.

    2016-01-01

    Mexican-origin adolescent mothers face numerous social challenges during dual-cultural adaptation that are theorized to contribute to greater depressive symptoms. Alongside challenges, there are familial resources that may offer protection. As such, the current study examined the trajectories of depressive symptoms among 204 Mexican-origin adolescent mothers (Mage = 16.80, SD = 1.00) across a 4-year period (3rd trimester of pregnancy, and 10, 24, and 36 months postpartum). Further, we examined the within-person relations of two unique sources of stress experienced during the dual-cultural adaptation process, acculturative and enculturative stress, and youths’ depressive symptoms; we also tested whether adolescent mothers’ perceptions of warmth from their own mothers emerged as protective. Adolescent mothers reported a decline in depressive symptoms after the transition to parenthood. Acculturative and enculturative stress emerged as significant positive within-person predictors of depressive symptoms. Maternal warmth emerged as a protective factor in the relation between enculturative stressors and depressive symptoms; however, for acculturative stressors, the protective effect of maternal warmth only emerged for U.S.-born youth. Findings illustrate the multi-dimensionality of stress experienced during the cultural adaptation process and a potential mechanism for resilience among Mexican-origin adolescent mothers. PMID:25004391

  10. Moderation of Breastfeeding Effects on Adult Depression by Estrogen Receptor Gene Polymorphism

    Päivi Merjonen

    2012-01-01

    Full Text Available Breastfeeding is known to benefit both the mother’s and the child’s health. Our aim was to test the interactive effects between estrogen receptor 1 (ESR1 rs2234693 and breastfeeding when predicting the child’s later depression in adulthood. A sample of 1209 boys and girls from the Young Finns Study were followed from childhood over 27 years up to age 30–45 years. Adulthood depressive symptoms were self-reported by the participants using the Beck Depression Inventory. Breastfeeding as well as several possibly confounding factors was reported by the parents in childhood or adolescence. Breastfeeding tended to predict lower adult depression, while ESR1 rs2234693 was not associated with depression. A significant interaction between breastfeeding and ESR1 was found to predict participants’ depression (P=.004 so that C/C genotype carriers who had not been breastfed had higher risk of depression than T-allele carriers (40.5% versus 13.0% while there were no genotypic differences among those who had been breastfed. In sex-specific analysis, this interaction was evident only among women. We conclude that child’s genes and maternal behavior may interact in the development of child’s adult depression so that breastfeeding may buffer the inherited depression risk possibly associated with the C/C genotype of the ESR1 gene.

  11. Integrating social science and behavioral genetics: testing the origin of socioeconomic disparities in depression using a genetically informed design.

    Mezuk, Briana; Myers, John M; Kendler, Kenneth S

    2013-10-01

    We tested 3 hypotheses-social causation, social drift, and common cause-regarding the origin of socioeconomic disparities in major depression and determined whether the relationship between socioeconomic status (SES) and major depression varied by genetic liability for major depression. Data were from a sample of female twins in the baseline Virginia Adult Twin Study of Psychiatric and Substance Use Disorders interviewed between 1987 and 1989 (n = 2153). We used logistic regression and structural equation twin models to evaluate these 3 hypotheses. Consistent with the social causation hypothesis, education (odds ratio [OR] = 0.78; 95% confidence interval [CI] = 0.66, 0.93; P social mobility was associated with lower risk of depression. There was no evidence that childhood SES was related to development of major depression (OR = 0.98; 95% CI = 0.89, 1.09; P > .1). Consistent with a common genetic cause, there was a negative correlation between the genetic components of major depression and education (r(2) = -0.22). Co-twin control analyses indicated a protective effect of education and income on major depression even after accounting for genetic liability. This study utilized a genetically informed design to address how social position relates to major depression. Results generally supported the social causation model.

  12. Phylogenetic analysis of ferlin genes reveals ancient eukaryotic origins

    Lek Monkol

    2010-07-01

    Full Text Available Abstract Background The ferlin gene family possesses a rare and identifying feature consisting of multiple tandem C2 domains and a C-terminal transmembrane domain. Much currently remains unknown about the fundamental function of this gene family, however, mutations in its two most well-characterised members, dysferlin and otoferlin, have been implicated in human disease. The availability of genome sequences from a wide range of species makes it possible to explore the evolution of the ferlin family, providing contextual insight into characteristic features that define the ferlin gene family in its present form in humans. Results Ferlin genes were detected from all species of representative phyla, with two ferlin subgroups partitioned within the ferlin phylogenetic tree based on the presence or absence of a DysF domain. Invertebrates generally possessed two ferlin genes (one with DysF and one without, with six ferlin genes in most vertebrates (three DysF, three non-DysF. Expansion of the ferlin gene family is evident between the divergence of lamprey (jawless vertebrates and shark (cartilaginous fish. Common to almost all ferlins is an N-terminal C2-FerI-C2 sandwich, a FerB motif, and two C-terminal C2 domains (C2E and C2F adjacent to the transmembrane domain. Preservation of these structural elements throughout eukaryotic evolution suggests a fundamental role of these motifs for ferlin function. In contrast, DysF, C2DE, and FerA are optional, giving rise to subtle differences in domain topologies of ferlin genes. Despite conservation of multiple C2 domains in all ferlins, the C-terminal C2 domains (C2E and C2F displayed higher sequence conservation and greater conservation of putative calcium binding residues across paralogs and orthologs. Interestingly, the two most studied non-mammalian ferlins (Fer-1 and Misfire in model organisms C. elegans and D. melanogaster, present as outgroups in the phylogenetic analysis, with results suggesting

  13. Interdependence of cell growth and gene expression: origins and consequences.

    Scott, Matthew; Gunderson, Carl W; Mateescu, Eduard M; Zhang, Zhongge; Hwa, Terence

    2010-11-19

    In bacteria, the rate of cell proliferation and the level of gene expression are intimately intertwined. Elucidating these relations is important both for understanding the physiological functions of endogenous genetic circuits and for designing robust synthetic systems. We describe a phenomenological study that reveals intrinsic constraints governing the allocation of resources toward protein synthesis and other aspects of cell growth. A theory incorporating these constraints can accurately predict how cell proliferation and gene expression affect one another, quantitatively accounting for the effect of translation-inhibiting antibiotics on gene expression and the effect of gratuitous protein expression on cell growth. The use of such empirical relations, analogous to phenomenological laws, may facilitate our understanding and manipulation of complex biological systems before underlying regulatory circuits are elucidated.

  14. On the Origin of De Novo Genes in Arabidopsis thaliana Populations.

    Li, Zi-Wen; Chen, Xi; Wu, Qiong; Hagmann, Jörg; Han, Ting-Shen; Zou, Yu-Pan; Ge, Song; Guo, Ya-Long

    2016-08-03

    De novo genes, which originate from ancestral nongenic sequences, are one of the most important sources of protein-coding genes. This origination process is crucial for the adaptation of organisms. However, how de novo genes arise and become fixed in a population or species remains largely unknown. Here, we identified 782 de novo genes from the model plant Arabidopsis thaliana and divided them into three types based on the availability of translational evidence, transcriptional evidence, and neither transcriptional nor translational evidence for their origin. Importantly, by integrating multiple types of omics data, including data from genomes, epigenomes, transcriptomes, and translatomes, we found that epigenetic modifications (DNA methylation and histone modification) play an important role in the origination process of de novo genes. Intriguingly, using the transcriptomes and methylomes from the same population of 84 accessions, we found that de novo genes that are transcribed in approximately half of the total accessions within the population are highly methylated, with lower levels of transcription than those transcribed at other frequencies within the population. We hypothesized that, during the origin of de novo gene alleles, those neutralized to low expression states via DNA methylation have relatively high probabilities of spreading and becoming fixed in a population. Our results highlight the process underlying the origin of de novo genes at the population level, as well as the importance of DNA methylation in this process. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  15. Relationship between BMI and depression, according to the rs16139NPY gene

    Hamideh Pishva

    2017-06-01

    Full Text Available Objective: obesity and depression are likely to interact mutually which makes it unclear if obesity causes depression or it leads to obesity; and how the genotypes have a role in obesity and depression.Methods and Materials: This cross sectional study was conducted on a sample of 400 individuals from the participants in the third phase of the comprehensive Iranian Multicenter Osteoporosis Study (IMOS. Anthropometric measurements and depression were assessed. To investigate the NPY polymorphism, PCR-RFLP was used. Binary logistic regression model was employed to determine depression as the dependent factor and gene polymorphismResults: the frequency of NPY rs16139 was 6%. No significant association could be found between NPY genotypes and depression (p >0.05. Furthermore, the results suggest that those with central obesity seem an increased chance of developing depression (P=0.02.Conclusion: There is a significant relationship between obesity and depression and obesity is a possible cause of depression. Waist circumference and abdominal obesity as components of metabolic syndrome have the most important effects on depression.

  16. Qualitative cross-sectional study of the perceived causes of depression in South Asian origin women in Toronto

    Ekanayake, Samanthika; Ahmad, Farah

    2012-01-01

    Objective To explore how South Asian origin women in Toronto, Canada, understand and explain the causes of their depression. Design Cross-sectional in-depth qualitative interviews. Setting Outpatient service in Toronto, Ontario. Participants Ten women with symptoms of depression aged between 22 and 65 years of age. Seven were from India, two from Sri Lanka and one from Pakistan. Four were Muslim, three Hindu and three Catholic. Two participants had university degrees, one a high school diploma and seven had completed less than a high school education. Eight were married, one was unmarried and one a widow. Results Three main factors emerged from the participant narratives as the causes of depression: family and relationships, culture and migration and socioeconomic. The majority of the participants identified domestic abuse, marital problems and interpersonal problems in the family as the cause of their depression. Culture and migration and socioeconomic factors were considered contributory. None of our study participants reported spiritual, supernatural or religious factors as causes of depression. Conclusion A personal–social–cultural model emerged as the aetiological paradigm for depression. Given the perceived causation, psycho-social treatment methods may be more acceptable for South Asian origin women. PMID:22337816

  17. A rice gene of de novo origin negatively regulates pathogen-induced defense response.

    Wenfei Xiao

    Full Text Available How defense genes originated with the evolution of their specific pathogen-responsive traits remains an important problem. It is generally known that a form of duplication can generate new genes, suggesting that a new gene usually evolves from an ancestral gene. However, we show that a new defense gene in plants may evolve by de novo origination, resulting in sophisticated disease-resistant functions in rice. Analyses of gene evolution showed that this new gene, OsDR10, had homologs only in the closest relative, Leersia genus, but not other subfamilies of the grass family; therefore, it is a rice tribe-specific gene that may have originated de novo in the tribe. We further show that this gene may evolve a highly conservative rice-specific function that contributes to the regulation difference between rice and other plant species in response to pathogen infections. Biologic analyses including gene silencing, pathologic analysis, and mutant characterization by transformation showed that the OsDR10-suppressed plants enhanced resistance to a broad spectrum of Xanthomonas oryzae pv. oryzae strains, which cause bacterial blight disease. This enhanced disease resistance was accompanied by increased accumulation of endogenous salicylic acid (SA and suppressed accumulation of endogenous jasmonic acid (JA as well as modified expression of a subset of defense-responsive genes functioning both upstream and downstream of SA and JA. These data and analyses provide fresh insights into the new biologic and evolutionary processes of a de novo gene recruited rapidly.

  18. Altered gene synchrony suggests a combined hormone-mediated dysregulated state in major depression.

    Chris Gaiteri

    2010-04-01

    Full Text Available Coordinated gene transcript levels across tissues (denoted "gene synchrony" reflect converging influences of genetic, biochemical and environmental factors; hence they are informative of the biological state of an individual. So could brain gene synchrony also integrate the multiple factors engaged in neuropsychiatric disorders and reveal underlying pathologies? Using bootstrapped Pearson correlation for transcript levels for the same genes across distinct brain areas, we report robust gene transcript synchrony between the amygdala and cingulate cortex in the human postmortem brain of normal control subjects (n = 14; Control/Permutated data, p<0.000001. Coordinated expression was confirmed across distinct prefrontal cortex areas in a separate cohort (n = 19 subjects and affected different gene sets, potentially reflecting regional network- and function-dependent transcriptional programs. Genewise regional transcript coordination was independent of age-related changes and array technical parameters. Robust shifts in amygdala-cingulate gene synchrony were observed in subjects with major depressive disorder (MDD, denoted here "depression" (n = 14; MDD/Permutated data, p<0.000001, significantly affecting between 100 and 250 individual genes (10-30% false discovery rate. Biological networks and signal transduction pathways corresponding to the identified gene set suggested putative dysregulated functions for several hormone-type factors previously implicated in depression (insulin, interleukin-1, thyroid hormone, estradiol and glucocorticoids; p<0.01 for association with depression-related networks. In summary, we showed that coordinated gene expression across brain areas may represent a novel molecular probe for brain structure/function that is sensitive to disease condition, suggesting the presence of a distinct and integrated hormone-mediated corticolimbic homeostatic, although maladaptive and pathological, state in major depression.

  19. The GSK3B gene confers risk for both major depressive disorder and schizophrenia in the Han Chinese population.

    Chen, Jianhua; Wang, Meng; Waheed Khan, Raja Amjad; He, Kuanjun; Wang, Qingzhong; Li, Zhiqiang; Shen, Jiawei; Song, Zhijian; Li, Wenjin; Wen, Zujia; Jiang, Yiwen; Xu, Yifeng; Shi, Yongyong; Ji, Weidong

    2015-10-01

    Glycogen synthease kinase-3B is a key gene encoding a protein kinase which is abundant in brain, and is involved in signal transduction cascades of neuronal cell development and energy metabolism. Previous researches proposed GSK3B as a potential region for schizophrenia. To validate the susceptibility of GSK3B to major depressive disorder, and to investigate the overlapping risk conferred by GSK3B for mental disorders, we performed a large-scale case-control study, analyzed 6 tag single nucleotide polymorphisms using TaqMan® technology in 1,045 major depressive disorder patients, 1,235 schizophrenia patients and 1,235 normal controls of Han Chinese origin. We found rs334535 (Pallele=2.79E-03, Pgenotype=5.00E-03, OR=1.429) and rs2199503 (Pallele=0.020, Pgenotype= 0.040, OR=1.157) showed association with major depressive disorder before Bonferroni correction. rs6771023 (adjusted Pallele=1.64E-03, adjusted Pgenotype=6.00E-03, OR=0.701) and rs2199503 (adjusted Pallele=0.001, adjusted Pgenotype=0.002, OR=1.251) showed significant association with schizophrenia after Bonferroni correction. rs2199503 (adjusted Pallele=1.70E-03, adjusted Pgenotype=0.006, OR=1.208) remained to be significant in the combined cases of major depressive disorder and schizophrenia after Bonferroni correction. Further validations of our findings in samples with larger scale are suggested, and functional genomic study is needed to elucidate the role of GSK3B in signal pathway and psychiatric disorders. Our results provide evidence that the GSK3B gene could be a promising region which contains genetic risk for both major depressive disorder and schizophrenia in the Han Chinese population. The study on variants conferring overlapping risk for multiple psychiatric disorders could be tangible pathogenesis support and clinical or diagnostic references. Copyright © 2015. Published by Elsevier B.V.

  20. Gene-environment interplay in depressive symptoms: moderation by age, sex, and physical illness.

    Petkus, A J; Beam, C R; Johnson, W; Kaprio, J; Korhonen, T; McGue, M; Neiderhiser, J M; Pedersen, N L; Reynolds, C A; Gatz, M

    2017-07-01

    Numerous factors influence late-life depressive symptoms in adults, many not thoroughly characterized. We addressed whether genetic and environmental influences on depressive symptoms differed by age, sex, and physical illness. The analysis sample included 24 436 twins aged 40-90 years drawn from the Interplay of Genes and Environment across Multiple Studies (IGEMS) Consortium. Biometric analyses tested age, sex, and physical illness moderation of genetic and environmental variance in depressive symptoms. Women reported greater depressive symptoms than men. After age 60, there was an accelerating increase in depressive symptom scores with age, but this did not appreciably affect genetic and environmental variances. Overlap in genetic influences between physical illness and depressive symptoms was greater in men than in women. Additionally, in men extent of overlap was greater with worse physical illness (the genetic correlation ranged from near 0.00 for the least physical illness to nearly 0.60 with physical illness 2 s.d. above the mean). For men and women, the same environmental factors that influenced depressive symptoms also influenced physical illness. Findings suggested that genetic factors play a larger part in the association between depressive symptoms and physical illness for men than for women. For both sexes, across all ages, physical illness may similarly trigger social and health limitations that contribute to depressive symptoms.

  1. Origin of sphinx, a young chimeric RNA gene in Drosophila melanogaster

    Wang, Wen; Brunet, Frédéric G.; Nevo, Eviatar; Long, Manyuan

    2002-01-01

    Non-protein-coding RNA genes play an important role in various biological processes. How new RNA genes originated and whether this process is controlled by similar evolutionary mechanisms for the origin of protein-coding genes remains unclear. A young chimeric RNA gene that we term sphinx (spx) provides the first insight into the early stage of evolution of RNA genes. spx originated as an insertion of a retroposed sequence of the ATP synthase chain F gene at the cytological region 60DB since the divergence of Drosophila melanogaster from its sibling species 2–3 million years ago. This retrosequence, which is located at 102F on the fourth chromosome, recruited a nearby exon and intron, thereby evolving a chimeric gene structure. This molecular process suggests that the mechanism of exon shuffling, which can generate protein-coding genes, also plays a role in the origin of RNA genes. The subsequent evolutionary process of spx has been associated with a high nucleotide substitution rate, possibly driven by a continuous positive Darwinian selection for a novel function, as is shown in its sex- and development-specific alternative splicing. To test whether spx has adapted to different environments, we investigated its population genetic structure in the unique “Evolution Canyon” in Israel, revealing a similar haplotype structure in spx, and thus similar evolutionary forces operating on spx between environments. PMID:11904380

  2. Ecological Divergence and the Origins of Intrinsic Postmating Isolation with Gene Flow

    Aneil F. Agrawal

    2011-01-01

    Full Text Available The evolution of intrinsic postmating isolation has received much attention, both historically and in recent studies of speciation genes. Intrinsic isolation often stems from between-locus genetic incompatibilities, where alleles that function well within species are incompatible with one another when brought together in the genome of a hybrid. It can be difficult for such incompatibilities to originate when populations diverge with gene flow, because deleterious genotypic combinations will be created and then purged by selection. However, it has been argued that if genes underlying incompatibilities are themselves subject to divergent selection, then they might overcome gene flow to diverge between populations, resulting in the origin of incompatibilities. Nonetheless, there has been little explicit mathematical exploration of such scenarios for the origin of intrinsic incompatibilities during ecological speciation with gene flow. Here we explore theoretical models for the origin of intrinsic isolation where genes subject to divergent natural selection also affect intrinsic isolation, either directly or via linkage disequilibrium with other loci. Such genes indeed overcome gene flow, diverge between populations, and thus result in the evolution of intrinsic isolation. We also examine barriers to neutral gene flow. Surprisingly, we find that intrinsic isolation sometimes weakens this barrier, by impeding differentiation via ecologically based divergent selection.

  3. Depression

    ... in the winter. Depression is one part of bipolar disorder. There are effective treatments for depression, including antidepressants, talk therapy, or both. NIH: National Institute of Mental Health

  4. Origin of an unusual heavy oil from the Baiyinchagan depression, Erlian basin, northern China

    Haiping Huang [China University of Geosciences, Beijing (China); University of Newcastle, Newcastle upon Tyne (United Kingdom). School of Civil Engineering and Geosciences; Guangxi Jin [China University of Geosciences, Beijing (China); Exploration and Development Institute, Puyang (China); Changsong Lin; Yabin Zheng [China University of Geosciences, Beijing (China)

    2003-01-01

    A detailed organic geochemical analysis of six oil samples from the Baiyinchagan depression in the Erlian basin, Northern China, was carried out in order to evaluate their origin. The oils are reservoired at a very shallow depth (223-560 m subsurface) and their chemical and physical properties vary greatly, ranging from normal to extremely heavy oil. The preservation of non-biodegraded oil in such a shallow reservoir is possibly related with palaeo-pasteurization of the reservoir before uplift. Maturity difference is not the primary control on the chemical and physical properties of the oils and there is considerable geochemical evidence to suggest the additional influence of in-reservoir/post-accumulation processes such as biodegradation, water-washing and (possibly) evaporation. Whereas some oils appear to be less affected, others are moderately biodegraded up to level 4 on the [Peters and Moldowan, 1993] scale, with sterane distributions largely unaffected and 25-norhopanes undetected. Contrary to classical biodegradation, the unusual heavy oil shows little evidence of biodegradation from aliphatic components. Water-washing is suggested to be the primary process leading to its formation since the severe alteration of soluble aromatic hydrocarbons is observed. In addition, since the oils have been uplifted significantly after accumulation, evaporation and/or leakage to modify oil compositions cannot be ruled out. (author)

  5. Altered amygdalar resting-state connectivity in depression is explained by both genes and environment.

    Córdova-Palomera, Aldo; Tornador, Cristian; Falcón, Carles; Bargalló, Nuria; Nenadic, Igor; Deco, Gustavo; Fañanás, Lourdes

    2015-10-01

    Recent findings indicate that alterations of the amygdalar resting-state fMRI connectivity play an important role in the etiology of depression. While both depression and resting-state brain activity are shaped by genes and environment, the relative contribution of genetic and environmental factors mediating the relationship between amygdalar resting-state connectivity and depression remain largely unexplored. Likewise, novel neuroimaging research indicates that different mathematical representations of resting-state fMRI activity patterns are able to embed distinct information relevant to brain health and disease. The present study analyzed the influence of genes and environment on amygdalar resting-state fMRI connectivity, in relation to depression risk. High-resolution resting-state fMRI scans were analyzed to estimate functional connectivity patterns in a sample of 48 twins (24 monozygotic pairs) informative for depressive psychopathology (6 concordant, 8 discordant and 10 healthy control pairs). A graph-theoretical framework was employed to construct brain networks using two methods: (i) the conventional approach of filtered BOLD fMRI time-series and (ii) analytic components of this fMRI activity. Results using both methods indicate that depression risk is increased by environmental factors altering amygdalar connectivity. When analyzing the analytic components of the BOLD fMRI time-series, genetic factors altering the amygdala neural activity at rest show an important contribution to depression risk. Overall, these findings show that both genes and environment modify different patterns the amygdala resting-state connectivity to increase depression risk. The genetic relationship between amygdalar connectivity and depression may be better elicited by examining analytic components of the brain resting-state BOLD fMRI signals. © 2015 Wiley Periodicals, Inc.

  6. Is Low Self-Esteem a Risk Factor for Depression? Findings from a Longitudinal Study of Mexican-Origin Youth

    Orth, Ulrich; Robins, Richard W.; Widaman, Keith F.; Conger, Rand D.

    2013-01-01

    We examined the relation between low self-esteem and depression using longitudinal data from a sample of 674 Mexican-origin early adolescents who were assessed at age 10 and 12 years. Results supported the vulnerability model, which states that low self-esteem is a prospective risk factor for depression. Moreover, results suggested that the vulnerability effect of low self-esteem is driven, for the most part, by general evaluations of worth (i.e., global self-esteem), rather than by domain-specific evaluations of academic competence, physical appearance, and competence in peer relationships. The only domain-specific self-evaluation that showed a prospective effect on depression was honesty–trustworthiness. The vulnerability effect of low self-esteem held for male and female adolescents, for adolescents born in the United States vs. Mexico, and across different levels of pubertal status. Finally, the vulnerability effect held when we controlled for several theoretically relevant third variables (i.e., social support, maternal depression, stressful events, and relational victimization), and for interactive effects between self-esteem and the third variables. The present study contributes to an emerging understanding of the link between self-esteem and depression and provides much needed data on the antecedents of depression in ethnic minority populations. PMID:23895172

  7. Is low self-esteem a risk factor for depression? Findings from a longitudinal study of Mexican-origin youth.

    Orth, Ulrich; Robins, Richard W; Widaman, Keith F; Conger, Rand D

    2014-02-01

    We examined the relation between low self-esteem and depression using longitudinal data from a sample of 674 Mexican-origin early adolescents who were assessed at age 10 and 12 years. Results supported the vulnerability model, which states that low self-esteem is a prospective risk factor for depression. Moreover, results suggested that the vulnerability effect of low self-esteem is driven, for the most part, by general evaluations of worth (i.e., global self-esteem), rather than by domain-specific evaluations of academic competence, physical appearance, and competence in peer relationships. The only domain-specific self-evaluation that showed a prospective effect on depression was honesty-trustworthiness. The vulnerability effect of low self-esteem held for male and female adolescents, for adolescents born in the United States versus Mexico, and across different levels of pubertal status. Finally, the vulnerability effect held when we controlled for several theoretically relevant 3rd variables (i.e., social support, maternal depression, stressful events, and relational victimization) and for interactive effects between self-esteem and the 3rd variables. The present study contributes to an emerging understanding of the link between self-esteem and depression and provides much needed data on the antecedents of depression in ethnic minority populations.

  8. Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility.

    Bagot, Rosemary C; Cates, Hannah M; Purushothaman, Immanuel; Lorsch, Zachary S; Walker, Deena M; Wang, Junshi; Huang, Xiaojie; Schlüter, Oliver M; Maze, Ian; Peña, Catherine J; Heller, Elizabeth A; Issler, Orna; Wang, Minghui; Song, Won-Min; Stein, Jason L; Liu, Xiaochuan; Doyle, Marie A; Scobie, Kimberly N; Sun, Hao Sheng; Neve, Rachael L; Geschwind, Daniel; Dong, Yan; Shen, Li; Zhang, Bin; Nestler, Eric J

    2016-06-01

    Depression is a complex, heterogeneous disorder and a leading contributor to the global burden of disease. Most previous research has focused on individual brain regions and genes contributing to depression. However, emerging evidence in humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain regions drive depressive phenotypes. Here, we performed RNA sequencing on four brain regions from control animals and those susceptible or resilient to chronic social defeat stress at multiple time points. We employed an integrative network biology approach to identify transcriptional networks and key driver genes that regulate susceptibility to depressive-like symptoms. Further, we validated in vivo several key drivers and their associated transcriptional networks that regulate depression susceptibility and confirmed their functional significance at the levels of gene transcription, synaptic regulation, and behavior. Our study reveals novel transcriptional networks that control stress susceptibility and offers fundamentally new leads for antidepressant drug discovery. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Depression

    ... reasons why a woman may have depression: Family history . Women with a family history of depression may be more at risk. But depression can also happen in women who don’t have a family history of depression. Brain changes. The brains of people ...

  10. Is Low Self-Esteem a Risk Factor for Depression? Findings from a Longitudinal Study of Mexican-Origin Youth

    Orth, Ulrich; Robins, Richard W.; Widaman, Keith F.; Conger, Rand D.

    2013-01-01

    We examined the relation between low self-esteem and depression using longitudinal data from a sample of 674 Mexican-origin early adolescents who were assessed at age 10 and 12 years. Results supported the vulnerability model, which states that low self-esteem is a prospective risk factor for depression. Moreover, results suggested that the vulnerability effect of low self-esteem is driven, for the most part, by general evaluations of worth (i.e., global self-esteem), rather than by domain-sp...

  11. Early life trauma, depression and the glucocorticoid receptor gene--an epigenetic perspective.

    Smart, C; Strathdee, G; Watson, S; Murgatroyd, C; McAllister-Williams, R H

    2015-12-01

    Hopes to identify genetic susceptibility loci accounting for the heritability seen in unipolar depression have not been fully realized. Family history remains the 'gold standard' for both risk stratification and prognosis in complex phenotypes such as depression. Meanwhile, the physiological mechanisms underlying life-event triggers for depression remain opaque. Epigenetics, comprising heritable changes in gene expression other than alterations of the nucleotide sequence, may offer a way to deepen our understanding of the aetiology and pathophysiology of unipolar depression and optimize treatments. A heuristic target for exploring the relevance of epigenetic changes in unipolar depression is the hypothalamic-pituitary-adrenal (HPA) axis. The glucocorticoid receptor (GR) gene (NR3C1) has been found to be susceptible to epigenetic modification, specifically DNA methylation, in the context of environmental stress such as early life trauma, which is an established risk for depression later in life. In this paper we discuss the progress that has been made by studies that have investigated the relationship between depression, early trauma, the HPA axis and the NR3C1 gene. Difficulties with the design of these studies are also explored. Future efforts will need to comprehensively address epigenetic natural histories at the population, tissue, cell and gene levels. The complex interactions between the epigenome, genome and environment, as well as ongoing nosological difficulties, also pose significant challenges. The work that has been done so far is nevertheless encouraging and suggests potential mechanistic and biomarker roles for differential DNA methylation patterns in NR3C1 as well as novel therapeutic targets.

  12. Testing the predictive value of peripheral gene expression for nonremission following citalopram treatment for major depression.

    Guilloux, Jean-Philippe; Bassi, Sabrina; Ding, Ying; Walsh, Chris; Turecki, Gustavo; Tseng, George; Cyranowski, Jill M; Sibille, Etienne

    2015-02-01

    Major depressive disorder (MDD) in general, and anxious-depression in particular, are characterized by poor rates of remission with first-line treatments, contributing to the chronic illness burden suffered by many patients. Prospective research is needed to identify the biomarkers predicting nonremission prior to treatment initiation. We collected blood samples from a discovery cohort of 34 adult MDD patients with co-occurring anxiety and 33 matched, nondepressed controls at baseline and after 12 weeks (of citalopram plus psychotherapy treatment for the depressed cohort). Samples were processed on gene arrays and group differences in gene expression were investigated. Exploratory analyses suggest that at pretreatment baseline, nonremitting patients differ from controls with gene function and transcription factor analyses potentially related to elevated inflammation and immune activation. In a second phase, we applied an unbiased machine learning prediction model and corrected for model-selection bias. Results show that baseline gene expression predicted nonremission with 79.4% corrected accuracy with a 13-gene model. The same gene-only model predicted nonremission after 8 weeks of citalopram treatment with 76% corrected accuracy in an independent validation cohort of 63 MDD patients treated with citalopram at another institution. Together, these results demonstrate the potential, but also the limitations, of baseline peripheral blood-based gene expression to predict nonremission after citalopram treatment. These results not only support their use in future prediction tools but also suggest that increased accuracy may be obtained with the inclusion of additional predictors (eg, genetics and clinical scales).

  13. Birth origin differentially affects depressive-like behaviours: are captive-born cynomolgus monkeys more vulnerable to depression than their wild-born counterparts?

    Sandrine M J Camus

    Full Text Available BACKGROUND: Adverse early-life experience might lead to the expression of abnormal behaviours in animals and the predisposition to psychiatric disorder (e.g. major depressive disorder in Humans. Common breeding processes employ weaning and housing conditions different from what happens in the wild. METHODS: The present study, therefore, investigated whether birth origin impacts the possible existence of spontaneous atypical/abnormal behaviours displayed by 40 captive-born and 40 wild-born socially-housed cynomolgus macaques in farming conditions using an unbiased ethological scan-sampling analysis followed by multifactorial correspondence and hierarchical clustering analyses. RESULTS: We identified 10 distinct profiles (groups A to J that significantly differed on several behaviours, body postures, body orientations, distances between individuals and locations in the cage. Data suggest that 4 captive-born and 1 wild-born animals (groups G and J present depressive-like symptoms, unnatural early life events thereby increasing the risk of developing pathological symptoms. General differences were also highlighted between the captive- and wild-born populations, implying the expression of differential coping mechanisms in response to the same captive environment. CONCLUSIONS: Birth origin thus impacts the development of atypical ethologically-defined behavioural profiles, reminiscent of certain depressive-like symptoms. The use of unbiased behavioural observations might allow the identification of animal models of human mental/behavioural disorders and their most appropriate control groups.

  14. Place of origin associated with depressive symptoms in health professionals performing social health service in Ancash, Peru, 2015.

    Montesinos-Segura, Renee; Maticorena-Quevedo, Jesus; Chung-Delgado, Kocfa; Pereyra-Elías, Reneé; Taype-Rondan, Alvaro; Mayta-Tristán, Percy

    2018-05-01

    Health professionals performing their social health service (SHS) in rural communities could be at risk of developing depression. Moreover, those who migrate from farther places to perform their SHS could have an increased risk. The objective of this study was to evaluate the association between place of origin and the presence of depressive symptoms, in health professionals performing rural social health service (SHS) in Ancash, Peru. This was a cross-sectional study. During April 2015, a survey was applied to health professionals performing SHS in the Peruvian Ministry of Health (MINSA) facilities in Ancash. The main outcome was the presence of depressive symptoms, defined as a score ≥2 points in the Patient Health Questionnaire-2. The main exposure was the place of origin, defined as the place where the subjects completed their undergraduate professional studies (Ancash, Lima city or others). Poisson regressions with robust variance were performed to calculate crude and adjusted prevalence ratios (PR and aPR) and their 95% confidence interval (95%CI). From 573 health professionals performing their SHS in MINSA in Ancash, 347 were included in the study. The mean age was 27.2±4.5 years, 78.7% were women, and 14.7% scored positive for depressive symptoms. Those who had completed their undergraduate professional studies in Lima city had a higher prevalence of presence of depressive symptoms compared to those who did in Ancash (aPR=2.59, 95%CI=1.23-5.45). Those who completed their undergraduate professional studies in Lima had a higher prevalence of depressive symptoms than those who did in Ancash. Possible explanations include the difficulty in visiting family and friends, acculturation, and lack of Quechua language proficiency.

  15. Alterations in Gene Expression in Depression: Prospects for Personalize Patient Treatment.

    Donev, Rossen; Alawam, Khaled

    2015-01-01

    The number of people around the world suffering from depression has dramatically increased in last few decades. It has been predicted that by 2020 depression will become the second most common cause of disability. Furthermore, depression is often misdiagnosed and confused with other psychiatric disorders showing similar symptoms, i.e., anxiety and bipolar disorder, due to the fact that diagnosing is often carried out by medical workers who are not psychiatrically trained. These facts prompt us to prepare this review which focuses on alterations in gene expression in depression. We believe that an in-depth knowledge of molecular bases of behavior in depression and other mood disorders would be of a great benefit for the correct diagnosing of these disorders, as well as for prescribing a treatment that best suits each individual depending on expression alterations in depression-related genes. Therefore, the main aim of this review is to promote further translational research on the biochemistry of mood disorders and take the results further for the design of new targeted therapeutics that can be used for personalized treatment with minimal adverse effects. © 2015 Elsevier Inc. All rights reserved.

  16. Depression

    Kessing, Lars Veddel; Bukh, Jens Drachmann

    2014-01-01

    The prevalence of depression is not clearly established, but estimated to 3-4% in a Danish questionnaire study. Lifetime's prevalences of 12-17% are reported in other community samples. In the current diagnostic system depression is defined categorically and operationally. It has been argued......, that these diagnostic criteria represent an oversimplification, which has blurred the concept of depression. We suggest a greater emphasis on the depressed mood as the core symptom of depression, which may increase the specificity of the diagnosis. Furthermore, basic principles for the treatment of depression...

  17. Depression in early adolescence: Contributions from relational aggression and variation in the oxytocin receptor gene.

    Kushner, Shauna C; Herzhoff, Kathrin; Vrshek-Schallhorn, Suzanne; Tackett, Jennifer L

    2018-01-01

    Interpersonal stress arising from relational aggression (RA)-the intentional effort to harm others via rejection and exclusion-may increase risk for depression in youth. Biological vulnerabilities related to the hormone oxytocin, which affects social behavior and stress responses, may exacerbate this risk. In a community sample of 307 youth (52% female; age range = 10-14 years), we tested whether (1) the association between RA and subsequent depressive symptoms was mediated through social problems and (2) a single nucleotide polymorphism (rs53576) in the oxytocin receptor gene (OXTR) moderated this indirect association between RA and depression, where GG homozygotes are predicted to be more sensitive to the effects of social problems than A-allele carriers. Youth-reported RA and depressive symptoms were measured using a structured interview and a questionnaire, respectively. DNA was extracted from saliva collected with Oragene kits. Consistent with the interpersonal theory of depression, the association between relational aggression and subsequent depressive symptoms was mediated by social problems. This indirect effect was further moderated by rs53576 genotype, such that GG homozygotes showed a stronger mediation effect than A-carriers. These results suggest that rs53576 variants confer vulnerability for depression within the context of interpersonal risk factors, such that youth with the GG genotype may be particularly sensitive to the social consequences resulting from RA. © 2017 Wiley Periodicals, Inc.

  18. Relationship between mitochondrial gene rearrangements and stability of the origin of light strand replication

    Miguel M. Fonseca

    2008-01-01

    Full Text Available Mitochondrial gene rearrangements are much more frequent in vertebrates than initially thought. It has been suggested that the origin of light strand replication could have an important role in the process of gene rearrangements, but this hypothesis has never been tested before. We used amphibians to test the correlation between light-strand replication origin thermodynamic stability and the occurrence of gene rearrangements. The two variables were correlated in a non-phylogenetic approach, but when tested in a phylogenetically based comparative method the correlation was not significant, although species with unstable light-strand replication origins were much more likely to have undergone gene rearrangements. This indicates that within amphibians there are stable and unstable phylogenetic groups regarding mitochondrial gene order. The species analyzed showed variability in the thermodynamic stability of the secondary structure, in the length of its stem and loop, and several species did not present the 5’-GCCGG-3’ motif reported to be necessary for efficient mitochondrial DNA replication. Future studies should focus on the role of the light-strand replication origin in mitochondrial DNA replication and gene rearrangements mechanisms.

  19. Depressants

    ... For Teens / Depressants Print en español Depresores del sistema nervioso What They Are: Tranquilizers and other depressants ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on TeensHealth® is for ...

  20. Prefrontal alterations in GABAergic and glutamatergic gene expression in relation to depression and suicide.

    Zhao, Juan; Verwer, R.W.H.; Gao, S.; Qi, Xin-Rui; Lucassen, P.J.; Kessels, H.W.; Swaab, D.F.

    2018-01-01

    People that committed suicide were reported to have enhanced levels of gene transcripts for synaptic proteins in their prefrontal cortex (PFC). Given the close association of suicide with major depressive disorder (MDD), we here assessed whether these changes are related to suicide or rather to

  1. Prefrontal alterations in GABAergic and glutamatergic gene expression in relation to depression and suicide

    Zhao, J.; Verwer, R.W.H.; Gao, S.-F.; Qi, X.-R.; Lucassen, P.J.; Kessels, H.W.; Swaab, D.F.

    People that committed suicide were reported to have enhanced levels of gene transcripts for synaptic proteins in their prefrontal cortex (PFC). Given the close association of suicide with major depressive disorder (MDD), we here assessed whether these changes are related to suicide or rather to

  2. Origination of an X-linked testes chimeric gene by illegitimate recombination in Drosophila.

    J Roman Arguello

    2006-05-01

    Full Text Available The formation of chimeric gene structures provides important routes by which novel proteins and functions are introduced into genomes. Signatures of these events have been identified in organisms from wide phylogenic distributions. However, the ability to characterize the early phases of these evolutionary processes has been difficult due to the ancient age of the genes or to the limitations of strictly computational approaches. While examples involving retrotransposition exist, our understanding of chimeric genes originating via illegitimate recombination is limited to speculations based on ancient genes or transfection experiments. Here we report a case of a young chimeric gene that has originated by illegitimate recombination in Drosophila. This gene was created within the last 2-3 million years, prior to the speciation of Drosophila simulans, Drosophila sechellia, and Drosophila mauritiana. The duplication, which involved the Bällchen gene on Chromosome 3R, was partial, removing substantial 3' coding sequence. Subsequent to the duplication onto the X chromosome, intergenic sequence was recruited into the protein-coding region creating a chimeric peptide with approximately 33 new amino acid residues. In addition, a novel intron-containing 5' UTR and novel 3' UTR evolved. We further found that this new X-linked gene has evolved testes-specific expression. Following speciation of the D. simulans complex, this novel gene evolved lineage-specifically with evidence for positive selection acting along the D. simulans branch.

  3. Identification of imprinted genes subject to parent-of-origin specific expression in Arabidopsis thaliana seeds

    McKeown, Peter C

    2011-08-12

    Abstract Background Epigenetic regulation of gene dosage by genomic imprinting of some autosomal genes facilitates normal reproductive development in both mammals and flowering plants. While many imprinted genes have been identified and intensively studied in mammals, smaller numbers have been characterized in flowering plants, mostly in Arabidopsis thaliana. Identification of additional imprinted loci in flowering plants by genome-wide screening for parent-of-origin specific uniparental expression in seed tissues will facilitate our understanding of the origins and functions of imprinted genes in flowering plants. Results cDNA-AFLP can detect allele-specific expression that is parent-of-origin dependent for expressed genes in which restriction site polymorphisms exist in the transcripts derived from each allele. Using a genome-wide cDNA-AFLP screen surveying allele-specific expression of 4500 transcript-derived fragments, we report the identification of 52 maternally expressed genes (MEGs) displaying parent-of-origin dependent expression patterns in Arabidopsis siliques containing F1 hybrid seeds (3, 4 and 5 days after pollination). We identified these MEGs by developing a bioinformatics tool (GenFrag) which can directly determine the identities of transcript-derived fragments from (i) their size and (ii) which selective nucleotides were added to the primers used to generate them. Hence, GenFrag facilitates increased throughput for genome-wide cDNA-AFLP fragment analyses. The 52 MEGs we identified were further filtered for high expression levels in the endosperm relative to the seed coat to identify the candidate genes most likely representing novel imprinted genes expressed in the endosperm of Arabidopsis thaliana. Expression in seed tissues of the three top-ranked candidate genes, ATCDC48, PDE120 and MS5-like, was confirmed by Laser-Capture Microdissection and qRT-PCR analysis. Maternal-specific expression of these genes in Arabidopsis thaliana F1 seeds was

  4. Identification of imprinted genes subject to parent-of-origin specific expression in Arabidopsis thaliana seeds

    Wennblom Trevor J

    2011-08-01

    Full Text Available Abstract Background Epigenetic regulation of gene dosage by genomic imprinting of some autosomal genes facilitates normal reproductive development in both mammals and flowering plants. While many imprinted genes have been identified and intensively studied in mammals, smaller numbers have been characterized in flowering plants, mostly in Arabidopsis thaliana. Identification of additional imprinted loci in flowering plants by genome-wide screening for parent-of-origin specific uniparental expression in seed tissues will facilitate our understanding of the origins and functions of imprinted genes in flowering plants. Results cDNA-AFLP can detect allele-specific expression that is parent-of-origin dependent for expressed genes in which restriction site polymorphisms exist in the transcripts derived from each allele. Using a genome-wide cDNA-AFLP screen surveying allele-specific expression of 4500 transcript-derived fragments, we report the identification of 52 maternally expressed genes (MEGs displaying parent-of-origin dependent expression patterns in Arabidopsis siliques containing F1 hybrid seeds (3, 4 and 5 days after pollination. We identified these MEGs by developing a bioinformatics tool (GenFrag which can directly determine the identities of transcript-derived fragments from (i their size and (ii which selective nucleotides were added to the primers used to generate them. Hence, GenFrag facilitates increased throughput for genome-wide cDNA-AFLP fragment analyses. The 52 MEGs we identified were further filtered for high expression levels in the endosperm relative to the seed coat to identify the candidate genes most likely representing novel imprinted genes expressed in the endosperm of Arabidopsis thaliana. Expression in seed tissues of the three top-ranked candidate genes, ATCDC48, PDE120 and MS5-like, was confirmed by Laser-Capture Microdissection and qRT-PCR analysis. Maternal-specific expression of these genes in Arabidopsis thaliana F1

  5. TOMM40 rs2075650 May Represent a New Candidate Gene for Vulnerability to Major Depressive Disorder

    McFarquhar, Martyn; Elliott, Rebecca; McKie, Shane; Thomas, Emma; Downey, Darragh; Mekli, Krisztina; Toth, Zoltan G; Anderson, Ian M; Deakin, JF William; Juhasz, Gabriella

    2014-01-01

    Evidence suggests that depression is a risk factor for dementia; however, the relationship between the two conditions is not fully understood. A novel gene (TOMM40) has been consistently associated with Alzheimer's disease (AD), but has received no attention in depression. We conducted a three-level cross-sectional study to investigate the association of the TOMM40 rs2075650 SNP with depression. We recruited a community sample of 1220 participants (571 controls, 649 lifetime depression) to complete a psychiatric background questionnaire, the Brief Symptom Inventory, and Big Five Inventory at Level-1, 243 (102 controls, 97 remitted, 44 currently depressed) to complete a face-to-face clinical interview and neuropsychological testing at Level-2 and 58 (33 controls, 25 remitted) to complete an emotional face-processing task during fMRI at Level-3. Our results indicated that the TOMM40 rs2075650 G allele was a significant risk factor for lifetime depression (p=0.00006) and, in depressed subjects, was a significant predictor of low extraversion (p=0.009). Currently depressed risk allele carriers showed subtle executive dysfunction (p=0.004) and decreased positive memory bias (p=0.021) together with reduced activity in the posterior (p(FWE)=0.045) and anterior (p(FWE)=0.041) cingulate during sad face emotion processing. Our results suggest that TOMM40 rs2075650 may be a risk factor for the development of depression characterized by reduced extraversion, impaired executive function, and decreased positive emotional recall, and reduced top-down cortical control during sad emotion processing. PMID:24549102

  6. Depression

    Cizza, G; Ravn, Pernille; Chrousos, G P

    2001-01-01

    Existing studies of the relationship between depression and osteoporosis have been heterogeneous in their design and use of diagnostic instruments for depression, which might have contributed to the different results on the comorbidity of these two conditions. Nevertheless, these studies reveal...... a strong association between depression and osteoporosis. Endocrine factors such as depression-induced hypersecretion of corticotropin-releasing hormone and hypercortisolism, hypogonadism, growth hormone deficiency and increased concentration of circulating interleukin 6, might play a crucial role...... in the bone loss observed in subjects suffering from major depression....

  7. Saltatory Evolution of the Ectodermal Neural Cortex Gene Family at the Vertebrate Origin

    Feiner, Nathalie; Murakami, Yasunori; Breithut, Lisa; Mazan, Sylvie; Meyer, Axel; Kuraku, Shigehiro

    2013-01-01

    The ectodermal neural cortex (ENC) gene family, whose members are implicated in neurogenesis, is part of the kelch repeat superfamily. To date, ENC genes have been identified only in osteichthyans, although other kelch repeat-containing genes are prevalent throughout bilaterians. The lack of elaborate molecular phylogenetic analysis with exhaustive taxon sampling has obscured the possible link of the establishment of this gene family with vertebrate novelties. In this study, we identified ENC homologs in diverse vertebrates by means of database mining and polymerase chain reaction screens. Our analysis revealed that the ENC3 ortholog was lost in the basal eutherian lineage through single-gene deletion and that the triplication between ENC1, -2, and -3 occurred early in vertebrate evolution. Including our original data on the catshark and the zebrafish, our comparison revealed high conservation of the pleiotropic expression pattern of ENC1 and shuffling of expression domains between ENC1, -2, and -3. Compared with many other gene families including developmental key regulators, the ENC gene family is unique in that conventional molecular phylogenetic inference could identify no obvious invertebrate ortholog. This suggests a composite nature of the vertebrate-specific gene repertoire, consisting not only of de novo genes introduced at the vertebrate origin but also of long-standing genes with no apparent invertebrate orthologs. Some of the latter, including the ENC gene family, may be too rapidly evolving to provide sufficient phylogenetic signals marking orthology to their invertebrate counterparts. Such gene families that experienced saltatory evolution likely remain to be explored and might also have contributed to phenotypic evolution of vertebrates. PMID:23843192

  8. The diversity of antimicrobial resistance genes among staphylococci of animal origin.

    Wendlandt, Sarah; Feßler, Andrea T; Monecke, Stefan; Ehricht, Ralf; Schwarz, Stefan; Kadlec, Kristina

    2013-08-01

    Staphylococci of animal origin harbor a wide variety of resistance genes. So far, more than 40 different resistance genes have been identified in staphylococci from animals. This includes genes that confer resistance to virtually all classes of antimicrobial agents approved for use in animals, such as penicillins, cephalosporins, tetracyclines, macrolides, lincosamides, phenicols, aminoglycosides, aminocyclitols, pleuromutilins, and diaminopyrimidines. The gene products of some of these resistance genes confer resistance to only specific members of a class of antimicrobial agents, whereas others confer resistance to the entire class or even to members of different classes of antimicrobial agents. The resistance mechanisms specified by the resistance genes fall into three major categories: (i) enzymatic inactivation, (ii) active efflux, or (iii) protection/modification/replacement of the cellular target sites of the antimicrobial agents. Mobile genetic elements, in particular plasmids and transposons, play a major role as carriers of antimicrobial resistance genes in animal staphylococci. They facilitate the exchange of resistance genes with staphylococci of human origin but also with other Gram-positive bacteria. Copyright © 2013 Elsevier GmbH. All rights reserved.

  9. Polymorphism of the serotonin transporter gene (5-HTTLPR) in major depressive disorder patients in Malaysia.

    Mohamed Saini, Suriati; Muhamad Radzi, Azizah; Abdul Rahman, Abdul Hamid

    2012-06-01

    The serotonin transporter promoter (5-HTTLPR) is a potential susceptibility locus in the pathogenesis of major depressive disorder. However, data from Malaysia is lacking. The present study aimed to determine the association between the homozygous short variant of the serotonin transporter promoter gene (5-HTTLPR) with major depressive disorder. This is a candidate gene case-control association study. The sample consists of 55 major depressive disorder probands and 66 controls. They were Malaysian descents and were unrelated. The Axis I diagnosis was determined using Mini International Neuropsychiatric Interview (M.I.N.I.). The control group comprised healthy volunteers without personal psychiatric history and family history of mood disorders. Participants' blood was sent to the Institute Medical Research for genotyping. The present study failed to detect an association between 5-HTTLPR ss genotype with major depressive disorder (χ(2)  = 3.67, d.f. = 1, P = 0.055, odds ratio 0.25, 95% confidence interval = 0.07-1.94). Sub-analysis revealed that the frequency of l allele in healthy controls was higher (78.0%) than that of Caucasian and East Asian population. However, in view of the small sample size this study may be prone to type II error (and type I error). This preliminary study suggests that the homozygous short variant of the 5-HTTLPR did not appear to be a risk factor for increasing susceptibility to major depressive disorder. Copyright © 2012 Blackwell Publishing Asia Pty Ltd.

  10. The NVL gene confers risk for both major depressive disorder and schizophrenia in the Han Chinese population.

    Wang, Meng; Chen, Jianhua; He, Kuanjun; Wang, Qingzhong; Li, Zhiqiang; Shen, Jiawei; Wen, Zujia; Song, Zhijian; Xu, Yifeng; Shi, Yongyong

    2015-10-01

    NVL (nuclear VCP (valosin containing protein)/p97-Like), a member of the AAA-ATPase (ATPases associated with various cellular activities) family, encodes a novel hTERT (human telomerase reverse transcriptase)-interacting protein NVL2 which is a telomerase component essential for holoenzyme assembly. Previous researches have reported the impacts of telomerase activity on mental illness and the potential association between NVL and major depressive disorder. To validate the susceptibility of NVL to major depressive disorder, and to investigate the overlapping risk conferred by NVL for both major depressive disorder and schizophrenia, we analyzed 9 tag single nucleotide polymorphisms (tag SNPs) using TaqMan® technology, in 1045 major depressive disorder patients, 1235 schizophrenia patients and 1235 normal controls of Han Chinese origin. We found that rs10916583 (P(allele) = 0.020, P(genotype) = 0.028, OR = 1.156) and rs16846649 (adjusted P(allele) = 0.014, P(genotype) = 0.007, OR = 0.718) were associated with major depressive disorder, while rs10916583 (adjusted P(allele) = 1.08E-02, OR = 1.213), rs16846649 (adjusted P(allele) = 7.40E-06, adjusted P(genotype) = 8.07E-05, OR = 0.598) and rs10799541 (adjusted P(allele) = 8.10E-03, adjusted P(genotype) = 0.049, OR= 0.826) showed statistically significant association with schizophrenia after Bonferroni correction. Furthermore, rs10916583 (adjusted P(allele) = 9.00E-03, adjusted P(genotype) = 3.15E-02, OR = 1.187) and rs16846649 (adjusted P(allele) = 8.92E-06, adjusted P(genotype) = 8.84E-05, OR = 0.653) remained strongly associated with the analysis of combined cases of major depressive disorder and schizophrenia after Bonferroni correction. Our results indicated that the NVL gene may contain overlapping common genetic risk factors for major depressive disorder and schizophrenia in the Han Chinese population. The roles of NVL in telomerase biogenesis were also highlighted in psychiatric pathogenesis. The study on

  11. Origin,

    Artur de Vargas Giorgi

    2011-02-01

    Full Text Available This essay tightens the “origin” concept, its manifestation through puzzles and their relationship to techniques of reproduction. Contrary to the hegemonic critique of aesthetic and cultural objects – critique that, settled on the appearance and notions of identity, tradition, canon, etc., undervalues the reproductions of "originals" –, the aim is to deliver these objects from formal hierarchization dispositives, that is, release them of what is ideal and positively imposed, so that the reproducibility is potentiated as producer of singularities, of apparitions. The effort is to keep the undecided character of puzzles (bodies, texts, images in which the origin is manifest, so that the logic of the spectacle is reverted into sense opening, instance in which the aesthetic becomes a “performance” before contemporary complexity. With the reproducibility, an origin survives in passage: continually restored, but incomplete, present in trace, in absence.

  12. Origin and distribution of epipolythiodioxopiperazine (ETP gene clusters in filamentous ascomycetes

    Gardiner Donald M

    2007-09-01

    Full Text Available Abstract Background Genes responsible for biosynthesis of fungal secondary metabolites are usually tightly clustered in the genome and co-regulated with metabolite production. Epipolythiodioxopiperazines (ETPs are a class of secondary metabolite toxins produced by disparate ascomycete fungi and implicated in several animal and plant diseases. Gene clusters responsible for their production have previously been defined in only two fungi. Fungal genome sequence data have been surveyed for the presence of putative ETP clusters and cluster data have been generated from several fungal taxa where genome sequences are not available. Phylogenetic analysis of cluster genes has been used to investigate the assembly and heredity of these gene clusters. Results Putative ETP gene clusters are present in 14 ascomycete taxa, but absent in numerous other ascomycetes examined. These clusters are discontinuously distributed in ascomycete lineages. Gene content is not absolutely fixed, however, common genes are identified and phylogenies of six of these are separately inferred. In each phylogeny almost all cluster genes form monophyletic clades with non-cluster fungal paralogues being the nearest outgroups. This relatedness of cluster genes suggests that a progenitor ETP gene cluster assembled within an ancestral taxon. Within each of the cluster clades, the cluster genes group together in consistent subclades, however, these relationships do not always reflect the phylogeny of ascomycetes. Micro-synteny of several of the genes within the clusters provides further support for these subclades. Conclusion ETP gene clusters appear to have a single origin and have been inherited relatively intact rather than assembling independently in the different ascomycete lineages. This progenitor cluster has given rise to a small number of distinct phylogenetic classes of clusters that are represented in a discontinuous pattern throughout ascomycetes. The disjunct heredity of

  13. The role of the potassium channel gene KCNK2 in major depressive disorder.

    Congiu, Chiara; Minelli, Alessandra; Bonvicini, Cristian; Bortolomasi, Marco; Sartori, Riccardo; Maj, Carlo; Scassellati, Catia; Maina, Giuseppe; Trabucchi, Luigi; Segala, Matilde; Gennarelli, Massimo

    2015-02-28

    Six single nucleotide polymorphisms (SNPs) of the KCNK2 gene were investigated for their association with major depressive disorder (MDD) and treatment efficacy in 590 MDD patients and 441 controls. The A homozygotes of rs10779646 were significantly more frequent in patients than controls whereas G allele of rs7549184 was associated with the presence of psychotic symptoms and the severity of disease. Evaluating the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) dataset, we confirmed our findings. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Testing bidirectional effects between cannabis use and depressive symptoms: moderation by the serotonin transporter gene.

    Otten, Roy; Engels, Rutger C M E

    2013-09-01

    Evidence for the assumption that cannabis use is associated with depression and depressive symptoms is inconsistent and mostly weak. It is likely that the mixed results are due to the fact that prior studies ignored the moderating effects of an individual's genetic vulnerability. The present study takes a first step in scrutinizing the relationship between cannabis use and depressive symptoms by taking a developmental molecular-genetic perspective. Specifically, we concentrated on changes in cannabis use and depressive symptoms over time in a simultaneous manner and differences herein for individuals with and without the short allele of the 5-hydroxytryptamine (serotonin) transporter gene-linked polymorphic region (5-HTTLPR) genotype. Data were from 310 adolescents over a period of 4 years. We used a parallel-process growth model, which allows co-development of cannabis use and depressive symptoms throughout adolescence, and the possible role of the 5-HTTLPR genotype in this process. We used data from the younger siblings of these adolescents in an attempt to replicate potential findings. The parallel-process growth model shows that cannabis use increases the risk for an increase in depressive symptoms over time but only in the presence of the short allele of the 5-HTTLPR genotype. This effect remained significant after controlling for covariates. We did not find conclusive support for the idea that depressive symptoms affect cannabis use. These findings were replicated in the sample of the younger siblings. The findings of the present study show first evidence that the links between cannabis use and depressive symptoms are conditional on the individual's genetic makeup. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.

  15. Depression

    Pouwer, Frans

    2017-01-01

    There is ample evidence that depression is000  a common comorbid health issue in people with type 1 or type 2 diabetes. Reviews have also concluded that depression in diabetes is associated with higher HbA1c levels, less optimal self-care behaviours, lower quality of life, incident vascular...... complications and higher mortality rates. However, longitudinal studies into the course of depression in people with type 1 diabetes remain scarce. In this issue of Diabetologia, Kampling and colleagues (doi: 10.1007/s00125-016-4123-0 ) report the 5 year trajectories of depression in adults with newly diagnosed...... type 1 diabetes (mean age, 28 years). Their baseline results showed that shortly after the diagnosis of type 1 diabetes a major depressive episode was diagnosed in approximately 6% of participants, while 8% suffered from an anxiety disorder. The longitudinal depression data showed that, in a 5 year...

  16. [Anxiety and polymorphism Val66Met of BDNF gene--predictors of depression severity in ischemic heart disease].

    Golimbet, V E; Volel', B A; Kopylov, F Iu; Dolzhikov, A V; Korovaitseva, G I; Kasparov, S V; Isaeva, M I

    2015-01-01

    In a framework of search for early predictors of depression in patients with ischemic heart disease (IHD) we studied effect of molecular-genetic factors (polymorphism of brain-derived neirotrophic factor--BDNF), personality traits (anxiety, neuroticism), IHD severity, and psychosocial stressors on manifestations of depression in men with verified diagnosis of IHD. Severity of depression was assessed by Hamilton Depression Rating Scale 21-item (HAMD 21), anxiety and neuroticism were evaluated by the Spielberger State-Trait Anxiety Inventory and "Big Five" questionnaire, respectively. It wa shown that personal anxiety and ValVal genotype of BDNF gene appeared to be predictors of moderate and severe depression.

  17. Hominoid-specific de novo protein-coding genes originating from long non-coding RNAs.

    Chen Xie

    2012-09-01

    Full Text Available Tinkering with pre-existing genes has long been known as a major way to create new genes. Recently, however, motherless protein-coding genes have been found to have emerged de novo from ancestral non-coding DNAs. How these genes originated is not well addressed to date. Here we identified 24 hominoid-specific de novo protein-coding genes with precise origination timing in vertebrate phylogeny. Strand-specific RNA-Seq analyses were performed in five rhesus macaque tissues (liver, prefrontal cortex, skeletal muscle, adipose, and testis, which were then integrated with public transcriptome data from human, chimpanzee, and rhesus macaque. On the basis of comparing the RNA expression profiles in the three species, we found that most of the hominoid-specific de novo protein-coding genes encoded polyadenylated non-coding RNAs in rhesus macaque or chimpanzee with a similar transcript structure and correlated tissue expression profile. According to the rule of parsimony, the majority of these hominoid-specific de novo protein-coding genes appear to have acquired a regulated transcript structure and expression profile before acquiring coding potential. Interestingly, although the expression profile was largely correlated, the coding genes in human often showed higher transcriptional abundance than their non-coding counterparts in rhesus macaque. The major findings we report in this manuscript are robust and insensitive to the parameters used in the identification and analysis of de novo genes. Our results suggest that at least a portion of long non-coding RNAs, especially those with active and regulated transcription, may serve as a birth pool for protein-coding genes, which are then further optimized at the transcriptional level.

  18. Mosaic origins of a complex chimeric mitochondrial gene in Silene vulgaris.

    Helena Storchova

    Full Text Available Chimeric genes are significant sources of evolutionary innovation that are normally created when portions of two or more protein coding regions fuse to form a new open reading frame. In plant mitochondria astonishingly high numbers of different novel chimeric genes have been reported, where they are generated through processes of rearrangement and recombination. Nonetheless, because most studies do not find or report nucleotide variation within the same chimeric gene, evolution after the origination of these chimeric genes remains unstudied. Here we identify two alleles of a complex chimera in Silene vulgaris that are divergent in nucleotide sequence, genomic position relative to other mitochondrial genes, and expression patterns. Structural patterns suggest a history partially influenced by gene conversion between the chimeric gene and functional copies of subunit 1 of the mitochondrial ATP synthase gene (atp1. We identified small repeat structures within the chimeras that are likely recombination sites allowing generation of the chimera. These results establish the potential for chimeric gene divergence in different plant mitochondrial lineages within the same species. This result contrasts with the absence of diversity within mitochondrial chimeras found in crop species.

  19. The YWHAE gene confers risk to major depressive disorder in the male group of Chinese Han population.

    Liu, Jie; Zhang, Hong-Xin; Li, Zhi-Qiang; Li, Tao; Li, Jun-Yan; Wang, Ti; Li, You; Feng, Guo-Yin; Shi, Yong-Yong; He, Lin

    2017-07-03

    Schizophrenia and major depressive disorder are two major psychiatric illnesses that may share specific genetic risk factors to a certain extent. Increasing evidence suggests that the two disorders might be more closely related than previously considered. To investigate whether YWHAE gene plays a significant role in major depressive disorder in Han Chinese population, we recruited 1135 unrelated major depressive disorder patients (485 males, 650 females) and 989 unrelated controls (296 males, 693 females) of Chinese Han origin. Eleven common SNPs were genotyped using TaqMan® technology. In male-group, the allele and genotype frequencies of rs34041110 differed significantly between patients and control (P allele =0.036486, OR[95%CI]: 1.249442(1.013988-1.539571); P genotype =0.045301). Also in this group, allele and genotype frequencies of rs1532976 differed significantly (P allele =0.013242, OR[95%CI]: 1.302007(1.056501-1.604563); genotype: P=0.039152). Haplotype-analyses showed that, in male-group, positive association with major depressive disorder was found for the A-A-C-G haplotype of rs3752826-rs2131431-rs1873827-rs12452627 (χ 2 =20.397, P=6.38E-06, OR[95%CI]: 7.442 [2.691-20.583]), its C-A-C-G haplotype (χ 2 =19.122, P=1.24E-05, OR and 95%CI: 0.402 [0.264-0.612]), its C-C-T-G haplotype (χ 2 =9.766, P=0.001785, OR[95%CI]: 5.654 [1.664-19.211]). In female-group, positive association was found for the A-A-C-G haplotype of rs3752826-rs2131431-rs1873827-rs12452627 (χ 2 =78.628, P=7.94E-19, OR[95%CI]: 50.043 [11.087-225.876]), its A-C-T-G haplotype (χ 2 =38.806, P=4.83E-10, OR[95%CI]: 0.053 [0.015-0.192]), the C-A-C-G haplotype (χ 2 =18.930, P=1.37E-05, OR[95%CI]: 0.526 [0.392-0.705]), and the C-C-T-G haplotype (χ 2 =38.668, P=5.18E-10, OR[95%CI]: 6.130 [3.207-11.716]). Our findings support YWHAE being a risk gene for Major Depressive Disorder in the Han Chinese population. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. The origins of cognitive vulnerability in early childhood: mechanisms linking early attachment to later depression.

    Morley, Tara E; Moran, Greg

    2011-11-01

    This paper examines the theory and research linking attachment relationships to cognitive vulnerability to depression and assesses evidence that early attachment experiences contribute to the development of these cognitive processes. Most research in this area has involved adult participants using self-report measures of both attachment and depressive vulnerabilities and thus cannot convincingly speak to the existence of such a developmental pathway. Several studies, however, have followed individuals from infancy and examined the emergence of self-esteem and responses to failure throughout childhood and adolescence. These studies suggest that early experiences in non-secure attachment relationships place an individual at-risk for developing a cognitive framework that increases their vulnerability to depression following stressful life events. The paper concludes with a discussion of how future research might best explore specific mechanisms through which distinct attachment relationships may lead to divergent developmental pathways sharing the common outcome of cognitive processes that place individuals at risk for depression. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Synergistic effect of 5-HT2A receptor gene and MAOA gene on the negative emotion of patients with depression.

    Guo, Huirong; Ren, Yuming; Zhao, Ning; Wang, Yali; Li, Shuying; Cui, He; Zhang, Sijia; Zhang, Jianhua

    2014-07-01

    To analyse the synergistic effect of polymorphism of the tandem repeat sequence u-VNTR of 5-hydroxytryptamine 2A (5-HT2A) receptor gene and monoamine oxidase A (MAOA) gene on the negative emotion in frontal lobe of patients with depression through functional magnetic resonance imaging (fMRI) technique. Functional magnetic resonance imaging scanning was performed for 72 patients with depression and 70 gender, age-matched healthy people with physical examination under negative emotion recognition task. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was adopted to analyse genotype. The superior, middle and inferior gyrus of bilateral frontal lobe was regarded as the brain region of interest, and then the difference of activation intensity in frontal lobe subregion between control groups and patient groups with different genotypes, and the interaction between the two kinds of polymorphism were compared. The activation intensity in right frontal middle gyrus of patients with CC genotype increased obviously compared with TT and TC genotype patient groups and TT genotype control group (Peffect of the two genotypes on the activation abnormality of negative emotion recognition in right frontal middle gyrus (F = 6·18, P = 0·029). The negative activation in right frontal middle gyrus of patients with CC+H genotypes increased most obviously (Peffect on the activity abnormality when recognizing negative emotion in right frontal middle gyrus of patients with depression. © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  2. Original article Depressive symptom clusters among the elderly: a longitudinal study of course and its correlates

    Aleksandra Kroemeke

    2014-11-01

    Full Text Available Background The longitudinal course of depressive symptoms among the elderly was examined over a one-month follow-up period. The aim of the study was to identify clusters of change as well as their correlates, including demographic variables and coping strategies (brooding, reflection, co-rumination, and positive reappraisal. Participants and procedure Two hundred and seventy-seven seniors (age 77.39 ±9.20 years, 67.50% women were assessed twice within one month with the 11-item version of the Centre for Epidemiological Studies Depression Scale. Demographic and clinical characteristics were measured at baseline together with coping strategies. Selected items from Ruminative Response Styles (brooding, reflection, the Co-Rumination Questionnaire (co-rumination, and mini-COPE (positive reframing were used. Results On the basis of a two-step cluster analysis, four clusters of depression course were recognized: low stable (n = 53, medium stable (n = 101, high increasing (n = 69, and very high stable (n = 54. Multinomial logistic regression analyses showed that higher number of diseases, higher brooding and lower positive reappraisal were associated with increased likelihood of belonging to the higher symptom groups. No significant gender effect was noted. Conclusions A non-clinical sample of older people appeared to be heterogeneous regarding symptoms of depression and its course. However, only 19.00% of participants reported a low level of depression. Strategies of coping with health concerns may play a significant role here, as brooding and positive reappraisal significantly differentiate between clusters of low stable and high stable symptoms, even after control for a proxy of objective health status.

  3. Depression

    Johansen, Jon O. J.

    2013-01-01

    Nyhederne er fulde af historier om depression. Overskrifter som: ’Danskerne propper sig med lykkepiller’ eller ‘depression er stadigvæk tabu’ går tit igen i dagspressen. Men hvor er nuancerne, og hvorfor gider vi læse de samme historier igen og igen? Måske er det fordi, vores egne forestillinger er...

  4. Restriction and Recruitment—Gene Duplication and the Origin and Evolution of Snake Venom Toxins

    Hargreaves, Adam D.; Swain, Martin T.; Hegarty, Matthew J.; Logan, Darren W.; Mulley, John F.

    2014-01-01

    Snake venom has been hypothesized to have originated and diversified through a process that involves duplication of genes encoding body proteins with subsequent recruitment of the copy to the venom gland, where natural selection acts to develop or increase toxicity. However, gene duplication is known to be a rare event in vertebrate genomes, and the recruitment of duplicated genes to a novel expression domain (neofunctionalization) is an even rarer process that requires the evolution of novel combinations of transcription factor binding sites in upstream regulatory regions. Therefore, although this hypothesis concerning the evolution of snake venom is very unlikely and should be regarded with caution, it is nonetheless often assumed to be established fact, hindering research into the true origins of snake venom toxins. To critically evaluate this hypothesis, we have generated transcriptomic data for body tissues and salivary and venom glands from five species of venomous and nonvenomous reptiles. Our comparative transcriptomic analysis of these data reveals that snake venom does not evolve through the hypothesized process of duplication and recruitment of genes encoding body proteins. Indeed, our results show that many proposed venom toxins are in fact expressed in a wide variety of body tissues, including the salivary gland of nonvenomous reptiles and that these genes have therefore been restricted to the venom gland following duplication, not recruited. Thus, snake venom evolves through the duplication and subfunctionalization of genes encoding existing salivary proteins. These results highlight the danger of the elegant and intuitive “just-so story” in evolutionary biology. PMID:25079342

  5. Identification of Differentially Expressed Genes between Original Breast Cancer and Xenograft Using Machine Learning Algorithms

    Deling Wang

    2018-03-01

    Full Text Available Breast cancer is one of the most common malignancies in women. Patient-derived tumor xenograft (PDX model is a cutting-edge approach for drug research on breast cancer. However, PDX still exhibits differences from original human tumors, thereby challenging the molecular understanding of tumorigenesis. In particular, gene expression changes after tissues are transplanted from human to mouse model. In this study, we propose a novel computational method by incorporating several machine learning algorithms, including Monte Carlo feature selection (MCFS, random forest (RF, and rough set-based rule learning, to identify genes with significant expression differences between PDX and original human tumors. First, 831 breast tumors, including 657 PDX and 174 human tumors, were collected. Based on MCFS and RF, 32 genes were then identified to be informative for the prediction of PDX and human tumors and can be used to construct a prediction model. The prediction model exhibits a Matthews coefficient correlation value of 0.777. Seven interpretable interactions within the informative gene were detected based on the rough set-based rule learning. Furthermore, the seven interpretable interactions can be well supported by previous experimental studies. Our study not only presents a method for identifying informative genes with differential expression but also provides insights into the mechanism through which gene expression changes after being transplanted from human tumor into mouse model. This work would be helpful for research and drug development for breast cancer.

  6. Identification of Differentially Expressed Genes between Original Breast Cancer and Xenograft Using Machine Learning Algorithms.

    Wang, Deling; Li, Jia-Rui; Zhang, Yu-Hang; Chen, Lei; Huang, Tao; Cai, Yu-Dong

    2018-03-12

    Breast cancer is one of the most common malignancies in women. Patient-derived tumor xenograft (PDX) model is a cutting-edge approach for drug research on breast cancer. However, PDX still exhibits differences from original human tumors, thereby challenging the molecular understanding of tumorigenesis. In particular, gene expression changes after tissues are transplanted from human to mouse model. In this study, we propose a novel computational method by incorporating several machine learning algorithms, including Monte Carlo feature selection (MCFS), random forest (RF), and rough set-based rule learning, to identify genes with significant expression differences between PDX and original human tumors. First, 831 breast tumors, including 657 PDX and 174 human tumors, were collected. Based on MCFS and RF, 32 genes were then identified to be informative for the prediction of PDX and human tumors and can be used to construct a prediction model. The prediction model exhibits a Matthews coefficient correlation value of 0.777. Seven interpretable interactions within the informative gene were detected based on the rough set-based rule learning. Furthermore, the seven interpretable interactions can be well supported by previous experimental studies. Our study not only presents a method for identifying informative genes with differential expression but also provides insights into the mechanism through which gene expression changes after being transplanted from human tumor into mouse model. This work would be helpful for research and drug development for breast cancer.

  7. Associations between a polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene, neuroticism and postpartum depression.

    Iliadis, S I; Comasco, E; Hellgren, C; Kollia, N; Sundström Poromaa, I; Skalkidou, A

    2017-01-01

    This study examined the association between a single nucleotide polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene and neuroticism, as well as the possible mediatory role of neuroticism in the association between the polymorphism and postpartum depressive symptoms. 769 women received questionnaires containing the Edinburgh Postnatal Depression Scale (EPDS) at six weeks postpartum and demographic data at pregnancy week 17 and 32 and at six weeks postpartum, as well as the Swedish universities Scales of Personality at pregnancy week 32. Linear regression models showed an association between the GG genotype and depressive symptoms. When neuroticism was introduced in the model, it was associated with EPDS score, whereas the association between the GG genotype and EPDS became borderline significant. A path analysis showed that neuroticism had a mediatory role in the association between the polymorphism and EPDS score. The use of the EPDS, which is a self-reporting instrument. Neuroticism was associated with the polymorphism and had a mediatory role in the association between the polymorphism and postpartum depression. This finding elucidates the genetic background of neuroticism and postpartum depression. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Gene expression signature of normal cell-of-origin predicts ovarian tumor outcomes.

    Melissa A Merritt

    Full Text Available The potential role of the cell-of-origin in determining the tumor phenotype has been raised, but not adequately examined. We hypothesized that distinct cells-of-origin may play a role in determining ovarian tumor phenotype and outcome. Here we describe a new cell culture medium for in vitro culture of paired normal human ovarian (OV and fallopian tube (FT epithelial cells from donors without cancer. While these cells have been cultured individually for short periods of time, to our knowledge this is the first long-term culture of both cell types from the same donors. Through analysis of the gene expression profiles of the cultured OV/FT cells we identified a normal cell-of-origin gene signature that classified primary ovarian cancers into OV-like and FT-like subgroups; this classification correlated with significant differences in clinical outcomes. The identification of a prognostically significant gene expression signature derived solely from normal untransformed cells is consistent with the hypothesis that the normal cell-of-origin may be a source of ovarian tumor heterogeneity and the associated differences in tumor outcome.

  9. Gene expression profiles help identify the Tissue of Origin for metastatic brain cancers

    VandenBerg Scott R

    2010-04-01

    Full Text Available Abstract Background Metastatic brain cancers are the most common intracranial tumor and occur in about 15% of all cancer patients. In up to 10% of these patients, the primary tumor tissue remains unknown, even after a time consuming and costly workup. The Pathwork® Tissue of Origin Test (Pathwork Diagnostics, Redwood City, CA, USA is a gene expression test to aid in the diagnosis of metastatic, poorly differentiated and undifferentiated tumors. It measures the expression pattern of 1,550 genes in these tumors and compares it to the expression pattern of a panel of 15 known tumor types. The purpose of this study was to evaluate the performance of the Tissue of Origin Test in the diagnosis of primary sites for metastatic brain cancer patients. Methods Fifteen fresh-frozen metastatic brain tumor specimens of known origins met specimen requirements. These specimens were entered into the study and processed using the Tissue of Origin Test. Results were compared to the known primary site and the agreement between the two results was assessed. Results Fourteen of the fifteen specimens produced microarray data files that passed all quality metrics. One originated from a tissue type that was off-panel. Among the remaining 13 cases, the Tissue of Origin Test accurately predicted the available diagnosis in 12/13 (92.3% cases. Discussion This study demonstrates the accuracy of the Tissue of Origin Test when applied to predict the tissue of origin of metastatic brain tumors. This test could be a very useful tool for pathologists as they classify metastatic brain cancers.

  10. Relational Security Moderates the Effect of Serotonin Transporter Gene Polymorphism (5-HTTLPR) on Stress Generation and Depression among Adolescents

    Starr, Lisa R.; Hammen, Constance; Brennan, Patricia A.; Najman, Jake M.

    2013-01-01

    Previous research demonstrates that carriers of the short allele of the serotonin transporter gene (5-HTTLPR) show both greater susceptibility to depression in response to stressful life events and higher rates of generation of stressful events in response to depression. The current study examines relational security (i.e., self-reported beliefs…

  11. How do people of South Asian origin understand and experience depression? A protocol for a systematic review of qualitative literature.

    Mooney, Roisin; Trivedi, Daksha; Sharma, Shivani

    2016-08-30

    Individuals from Black and Asian Minority Ethnic (BAME) groups are less likely to receive a diagnosis and to engage with treatment for depression. This review aims to draw on international literature to summarise what is known about how people specifically of South Asian origin, migrants and non-migrants, understand and experience depressive symptoms. The resulting evidence base will further inform practices aimed at encouraging help-seeking behaviour and treatment uptake. A systematic review and thematic synthesis of qualitative literature conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Using predefined inclusion and exclusion criteria, electronic searches will be conducted across 16 databases. Study quality will be assessed using the Critical Appraisal Skills Programme (CASP). Data will be extracted independently by 2 reviewers. Ethical approval is not required. A comprehensive evidence base of how people from South Asian backgrounds conceptualise and experience depression will better inform the design and delivery of mental health initiatives and advance directions for future research. Findings will be published in a peer-reviewed journal, and disseminated through existing networks for professionals, researchers, patients and the public. CRD42015026120. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  12. Identification of Acinetobacter baumannii of Human and Animal Origins by a Gene-Specific PCR.

    Hamouda, Ahmed

    2017-09-01

    Acinetobacter baumannii is a notorious nosocomial pathogen known for its ability to cause severe infections, especially in intensive care units. The identification of a conserved gene encoding a hypothetical protein in A. baumannii isolates but not in other Acinetobacter species during a comparative genomic analysis was reported. For the purpose of this study, we call this gene, A.b_hyp gene. The aim of this study was to report the results of screening for the presence of the A.b_hyp gene in a worldwide collection of well-characterized A. baumannii collected from clinical and animal specimens. A total of 83 clinical, animal, and type strains were used. These comprised 73 A. baumannii isolates of clinical (n = 60) and animal origin (n = 13), and ten type strains, including a positive control strain, A. baumannii ATCC 19606. All isolates were examined by PCR amplification of the A.b_hyp gene. The A.b_hyp gene was detected in 72 isolates (99%) of A. baumannii but one clinical isolate failed to produce an amplicon. The control strain, A. baumannii ATCC 19606, was also positive for this gene. No bands were detected in non-A. baumannii species and therefore the isolates are thought to be negative for the gene. No bands were detected in non-A. baumannii isolates and therefore they are thought to be negative for the gene. The PCR A.b_ hyp method provides evidence that detection of this gene can be used as a reliable, easy, and low-cost biomarker for A. baumannii identification.

  13. Concomitant duplications of opioid peptide and receptor genes before the origin of jawed vertebrates.

    Görel Sundström

    Full Text Available BACKGROUND: The opioid system is involved in reward and pain mechanisms and consists in mammals of four receptors and several peptides. The peptides are derived from four prepropeptide genes, PENK, PDYN, PNOC and POMC, encoding enkephalins, dynorphins, orphanin/nociceptin and beta-endorphin, respectively. Previously we have described how two rounds of genome doubling (2R before the origin of jawed vertebrates formed the receptor family. METHODOLOGY/PRINCIPAL FINDINGS: Opioid peptide gene family members were investigated using a combination of sequence-based phylogeny and chromosomal locations of the peptide genes in various vertebrates. Several adjacent gene families were investigated similarly. The results show that the ancestral peptide gene gave rise to two additional copies in the genome doublings. The fourth member was generated by a local gene duplication, as the genes encoding POMC and PNOC are located on the same chromosome in the chicken genome and all three teleost genomes that we have studied. A translocation has disrupted this synteny in mammals. The PDYN gene seems to have been lost in chicken, but not in zebra finch. Duplicates of some peptide genes have arisen in the teleost fishes. Within the prepropeptide precursors, peptides have been lost or gained in different lineages. CONCLUSIONS/SIGNIFICANCE: The ancestral peptide and receptor genes were located on the same chromosome and were thus duplicated concomitantly. However, subsequently genetic linkage has been lost. In conclusion, the system of opioid peptides and receptors was largely formed by the genome doublings that took place early in vertebrate evolution.

  14. The prevalence of gene duplications and their ancient origin in Rhodobacter sphaeroides 2.4.1

    Cho Hyuk

    2010-12-01

    Full Text Available Abstract Background Rhodobacter sphaeroides 2.4.1 is a metabolically versatile organism that belongs to α-3 subdivision of Proteobacteria. The present study was to identify the extent, history, and role of gene duplications in R. sphaeroides 2.4.1, an organism that possesses two chromosomes. Results A protein similarity search (BLASTP identified 1247 orfs (~29.4% of the total protein coding orfs that are present in 2 or more copies, 37.5% (234 gene-pairs of which exist in duplicate copies. The distribution of the duplicate gene-pairs in all Clusters of Orthologous Groups (COGs differed significantly when compared to the COG distribution across the whole genome. Location plots revealed clusters of gene duplications that possessed the same COG classification. Phylogenetic analyses were performed to determine a tree topology predicting either a Type-A or Type-B phylogenetic relationship. A Type-A phylogenetic relationship shows that a copy of the protein-pair matches more with an ortholog from a species closely related to R. sphaeroides while a Type-B relationship predicts the highest match between both copies of the R. sphaeroides protein-pair. The results revealed that ~77% of the proteins exhibited a Type-A phylogenetic relationship demonstrating the ancient origin of these gene duplications. Additional analyses on three other strains of R. sphaeroides revealed varying levels of gene loss and retention in these strains. Also, analyses on common gene pairs among the four strains revealed that these genes experience similar functional constraints and undergo purifying selection. Conclusions Although the results suggest that the level of gene duplication in organisms with complex genome structuring (more than one chromosome seems to be not markedly different from that in organisms with only a single chromosome, these duplications may have aided in genome reorganization in this group of eubacteria prior to the formation of R. sphaeroides as gene

  15. High Rate of Chimeric Gene Origination by Retroposition in Plant Genomes

    Wang, Wen; Zheng, Hongkung; Fan, Chuanzhu

    2006-01-01

    Retroposition is widely found to play essential roles in origination of new mammalian and other animal genes. However, the scarcity of retrogenes in plants has led to the assumption that plant genomes rarely evolve new gene duplicates by retroposition, despite abundant retrotransposons in plants......, confirming a previously observed role of retroelements in generating plant retrogenes. Substitution analyses revealed that the vast majority are subject to negative selection, suggesting, along with expression data and evidence of age, that they are likely functional retrogenes. In addition, 42...

  16. Gene-based interaction analysis shows GABAergic genes interacting with parenting in adolescent depressive symptoms

    Van Assche, Evelien; Moons, Tim; Cinar, Ozan; Viechtbauer, Wolfgang; Oldehinkel, Albertine J.; Van Leeuwen, Karla; Verschueren, Karine; Colpin, Hilde; Lambrechts, Diether; Van den Noortgate, Wim; Goossens, Luc; Claes, Stephan; van Winkel, Ruud

    2017-01-01

    BACKGROUND: Most gene-environment interaction studies (G × E) have focused on single candidate genes. This approach is criticized for its expectations of large effect sizes and occurrence of spurious results. We describe an approach that accounts for the polygenic nature of most psychiatric

  17. Gene expression in blood of children and adolescents: Mediation between childhood maltreatment and major depressive disorder.

    Spindola, Leticia Maria; Pan, Pedro Mario; Moretti, Patricia Natalia; Ota, Vanessa Kiyomi; Santoro, Marcos Leite; Cogo-Moreira, Hugo; Gadelha, Ary; Salum, Giovanni; Manfro, Gisele Gus; Mari, Jair Jesus; Brentani, Helena; Grassi-Oliveira, Rodrigo; Brietzke, Elisa; Miguel, Euripedes Constantino; Rohde, Luis Augusto; Sato, João Ricardo; Bressan, Rodrigo Affonseca; Belangero, Sintia Iole

    2017-09-01

    Investigating major depressive disorder (MDD) in childhood and adolescence can help reveal the relative contributions of genetic and environmental factors to MDD, since early stages of disease have less influence of illness exposure. Thus, we investigated the mRNA expression of 12 genes related to the hypothalamic-pituitary-adrenal (HPA) axis, inflammation, neurodevelopment and neurotransmission in the blood of children and adolescents with MDD and tested whether a history of childhood maltreatment (CM) affects MDD through gene expression. Whole-blood mRNA levels of 12 genes were compared among 20 children and adolescents with MDD diagnosis (MDD group), 49 participants without MDD diagnosis but with high levels of depressive symptoms (DS group), and 61 healthy controls (HC group). The differentially expressed genes were inserted in a mediation model in which CM, MDD, and gene expression were, respectively, the independent variable, outcome, and intermediary variable. NR3C1, TNF, TNFR1 and IL1B were expressed at significantly lower levels in the MDD group than in the other groups. CM history did not exert a significant direct effect on MDD. However, an indirect effect of the aggregate expression of the 4 genes mediated the relationship between CM and MDD. In the largest study investigating gene expression in children with MDD, we demonstrated that NR3C1, TNF, TNFR1 and IL1B expression levels are related to MDD and conjunctly mediate the effect of CM history on the risk of developing MDD. This supports a role of glucocorticoids and inflammation as potential effectors of environmental stress in MDD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. A tale of two maladies? Pathogenesis of depression with and without the Huntington’s disease gene mutation

    Xin eDu

    2013-07-01

    Full Text Available Huntington’s disease (HD is an autosomal dominant disorder caused by a tandem repeat expansion encoding an expanded tract of glutamines in the huntingtin protein. HD is progressive and manifests as psychiatric symptoms (including depression, cognitive deficits (culminating in dementia and motor abnormalities (including chorea. Having reached the 20th anniversary of the discovery of the ‘genetic stutter’ which causes HD, we still lack sophisticated insight into why so many HD patients exhibit affective disorders such as depression at very early stages, prior to overt appearance of motor deficits. In this review, we will focus on depression as the major psychiatric manifestation of HD, discuss potential mechanisms of pathogenesis identified from animal models, and compare depression in HD patients with that of the wider gene-negative population. The discovery of depressive-like behaviours as well as cellular and molecular correlates of depression in transgenic HD mice has added strong support to the hypothesis that the HD mutation adds significantly to the genetic load for depression. A key question is whether HD-associated depression differs from that in the general population. Whilst preclinical studies, clinical data and treatment responses suggest striking similarities, there are also some apparent differences. We discuss various molecular and cellular mechanisms which may contribute to depression in HD, and whether they may generalise to other depressive disorders. The autosomal dominant nature of HD and the existence of models with excellent construct validity provide a unique opportunity to understand the pathogenesis of depression and associated gene-environment interactions. Thus, understanding the pathogenesis of depression in HD may not only facilitate tailored therapeutic approaches for HD sufferers, but may also translate to the clinical depression which devastates the lives of so many people.

  19. Feather development genes and associated regulatory innovation predate the origin of Dinosauria.

    Lowe, Craig B; Clarke, Julia A; Baker, Allan J; Haussler, David; Edwards, Scott V

    2015-01-01

    The evolution of avian feathers has recently been illuminated by fossils and the identification of genes involved in feather patterning and morphogenesis. However, molecular studies have focused mainly on protein-coding genes. Using comparative genomics and more than 600,000 conserved regulatory elements, we show that patterns of genome evolution in the vicinity of feather genes are consistent with a major role for regulatory innovation in the evolution of feathers. Rates of innovation at feather regulatory elements exhibit an extended period of innovation with peaks in the ancestors of amniotes and archosaurs. We estimate that 86% of such regulatory elements and 100% of the nonkeratin feather gene set were present prior to the origin of Dinosauria. On the branch leading to modern birds, we detect a strong signal of regulatory innovation near insulin-like growth factor binding protein (IGFBP) 2 and IGFBP5, which have roles in body size reduction, and may represent a genomic signature for the miniaturization of dinosaurian body size preceding the origin of flight. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  20. GLUCOCORTICOID RECEPTOR-RELATED GENES: GENOTYPE AND BRAIN GENE EXPRESSION RELATIONSHIPS TO SUICIDE AND MAJOR DEPRESSIVE DISORDER.

    Yin, Honglei; Galfalvy, Hanga; Pantazatos, Spiro P; Huang, Yung-Yu; Rosoklija, Gorazd B; Dwork, Andrew J; Burke, Ainsley; Arango, Victoria; Oquendo, Maria A; Mann, J John

    2016-06-01

    We tested the relationship between genotype, gene expression and suicidal behavior and major depressive disorder (MDD) in live subjects and postmortem samples for three genes, associated with the hypothalamic-pituitary-adrenal axis, suicidal behavior, and MDD; FK506-binding protein 5 (FKBP5), Spindle and kinetochore-associated protein 2 (SKA2), and Glucocorticoid Receptor (NR3C1). Single-nucleotide polymorphisms (SNPs) and haplotypes were tested for association with suicidal behavior and MDD in a live (N = 277) and a postmortem sample (N = 209). RNA-seq was used to examine gene and isoform-level brain expression postmortem (Brodmann Area 9; N = 59). Expression quantitative trait loci (eQTL) relationships were examined using a public database (UK Brain Expression Consortium). We identified a haplotype within the FKBP5 gene, present in 47% of the live subjects, which was associated with increased risk of suicide attempt (OR = 1.58, t = 6.03, P = .014). Six SNPs on this gene, three SNPs on SKA2, and one near NR3C1 showed before-adjustment association with attempted suicide, and two SNPs of SKA2 with suicide death, but none stayed significant after adjustment for multiple testing. Only the SKA2 SNPs were related to expression in the prefrontal cortex (pFCTX). One NR3C1 transcript had lower expression in suicide relative to nonsuicide sudden death cases (b = -0.48, SE = 0.12, t = -4.02, adjusted P = .004). We have identified an association of FKBP5 haplotype with risk of suicide attempt and found an association between suicide and altered NR3C1 gene expression in the pFCTX. Our findings further implicate hypothalamic pituitary axis dysfunction in suicidal behavior. © 2016 Wiley Periodicals, Inc.

  1. Indications for potential parent-of-origin effects within the FTO gene.

    Xuanshi Liu

    Full Text Available Genome-Wide Association Studies (GWAS were successfully applied to discover associations with obesity. However, the GWAS design is usually based on unrelated individuals and inheritance information on the parental origin of the alleles is missing. Taking into account parent-of-origin may provide further insights into the genetic mechanisms contributing to obesity. We hypothesized that there may be variants within the robustly replicated fat mass and obesity associated (FTO gene that may confer different risk for obesity depending on transmission from mother or father. Genome-wide genotypes and pedigree information from the Sorbs population were used. Phased genotypes among 525 individuals were generated by AlphaImpute. Subsequently, 22 SNPs within FTO introns 1 to 3 were selected and parent-of-origin specific association analyses were performed using PLINK. Interestingly, we identified several SNPs conferring different genetic effects (P≤0.05 depending on parental origin--among them, rs1861868, rs1121980 and rs9939973 (all in intron 1. To confirm our findings, we investigated the selected variants in 705 German trios comprising an (extremely obese child or adolescent and both parents. Again, we observed evidence for POE effects in intron 2 and 3 (P≤0.05 as indicated by the parental asymmetry test. Our results suggest that the obesity risk transmitted by several FTO variants may depend on the parental origin of the allele. Larger family-based studies are warranted to replicate our findings.

  2. Antibody Heavy Chain Variable Domains of Different Germline Gene Origins Diversify through Different Paths

    Ufuk Kirik

    2017-11-01

    Full Text Available B cells produce antibodies, key effector molecules in health and disease. They mature their properties, including their affinity for antigen, through hypermutation events; processes that involve, e.g., base substitution, codon insertion and deletion, often in association with an isotype switch. Investigations of antibody evolution define modes whereby particular antibody responses are able to form, and such studies provide insight important for instance for development of efficient vaccines. Antibody evolution is also used in vitro for the design of antibodies with improved properties. To better understand the basic concepts of antibody evolution, we analyzed the mutational paths, both in terms of amino acid substitution and insertions and deletions, taken by antibodies of the IgG isotype. The analysis focused on the evolution of the heavy chain variable domain of sets of antibodies, each with an origin in 1 of 11 different germline genes representing six human heavy chain germline gene subgroups. Investigated genes were isolated from cells of human bone marrow, a major site of antibody production, and characterized by next-generation sequencing and an in-house bioinformatics pipeline. Apart from substitutions within the complementarity determining regions, multiple framework residues including those in protein cores were targets of extensive diversification. Diversity, both in terms of substitutions, and insertions and deletions, in antibodies is focused to different positions in the sequence in a germline gene-unique manner. Altogether, our findings create a framework for understanding patterns of evolution of antibodies from defined germline genes.

  3. Effect of tryptophan hydroxylase gene polymorphism on aggression in major depressive disorder and undifferentiated somatoform disorder.

    Koh, Kyung Bong; Kim, Chan Hyung; Choi, Eun Hee; Lee, Young-joon; Seo, Won Youl

    2012-05-01

    Aggression and anger have been linked with depression, and anger suppression has been linked with somatic symptoms of somatoform disorders. However, the relationship between aggression or anger and genes in patients with depression and somatoform disorders has not been clearly elucidated. The objective of this study was to examine the effect of serotonin-related gene polymorphism on aggression in depressive disorders and somatoform disorders. A serotonin-related polymorphic marker was assessed by using single nucleotide polymorphism (SNP) genotyping. 106 outpatients with major depressive disorder (MDD), 102 outpatients with undifferentiated somatoform disorder, and 133 healthy subjects were enrolled between October 2005 and May 2008. Diagnoses were made according to the Korean version of the Structured Clinical Interview Schedule for DSM-IV. The allele and genotype frequencies of tryptophan hydroxylase-1 (TPH1) A218C were compared between groups. The Hamilton Depression Rating Scale and the Aggression Questionnaire were used for psychological assessment. Each of the 2 disorder groups scored significantly higher on all the Aggression Questionnaire subscales and on the total Aggression Questionnaire score than the healthy subjects (P sex and age. However, no significant differences were found in TPH1 C allele and CC homozygote frequencies between the undifferentiated somatoform disorder patients and the healthy subjects. TPH1 CC homozygote in the MDD group scored significantly higher in terms of verbal aggression (P = .03) and total Aggression Questionnaire score (P = .04) than A-carrier genotypes, regardless of sex and age. However, no significant differences were found in the scores of all the Aggression Questionnaire subscales and the total Aggression Questionnaire score between TPH1 CC homozygote and A-carrier genotypes in the undifferentiated somatoform disorder group and the control group, respectively. Aggression in MDD patients is more susceptible to an

  4. DNA Methylation Analysis of the Angiotensin Converting Enzyme (ACE) Gene in Major Depression

    Zill, Peter; Baghai, Thomas C.; Schüle, Cornelius; Born, Christoph; Früstück, Clemens; Büttner, Andreas; Eisenmenger, Wolfgang; Varallo-Bedarida, Gabriella; Rupprecht, Rainer; Möller, Hans-Jürgen; Bondy, Brigitta

    2012-01-01

    Background The angiotensin converting enzyme (ACE) has been repeatedly discussed as susceptibility factor for major depression (MD) and the bi-directional relation between MD and cardiovascular disorders (CVD). In this context, functional polymorphisms of the ACE gene have been linked to depression, to antidepressant treatment response, to ACE serum concentrations, as well as to hypertension, myocardial infarction and CVD risk markers. The mostly investigated ACE Ins/Del polymorphism accounts for ∼40%–50% of the ACE serum concentration variance, the remaining half is probably determined by other genetic, environmental or epigenetic factors, but these are poorly understood. Materials and Methods The main aim of the present study was the analysis of the DNA methylation pattern in the regulatory region of the ACE gene in peripheral leukocytes of 81 MD patients and 81 healthy controls. Results We detected intensive DNA methylation within a recently described, functional important region of the ACE gene promoter including hypermethylation in depressed patients (p = 0.008) and a significant inverse correlation between the ACE serum concentration and ACE promoter methylation frequency in the total sample (p = 0.02). Furthermore, a significant inverse correlation between the concentrations of the inflammatory CVD risk markers ICAM-1, E-selectin and P-selectin and the degree of ACE promoter methylation in MD patients could be demonstrated (p = 0.01 - 0.04). Conclusion The results of the present study suggest that aberrations in ACE promoter DNA methylation may be an underlying cause of MD and probably a common pathogenic factor for the bi-directional relationship between MD and cardiovascular disorders. PMID:22808171

  5. DNA methylation analysis of the angiotensin converting enzyme (ACE gene in major depression.

    Peter Zill

    Full Text Available BACKGROUND: The angiotensin converting enzyme (ACE has been repeatedly discussed as susceptibility factor for major depression (MD and the bi-directional relation between MD and cardiovascular disorders (CVD. In this context, functional polymorphisms of the ACE gene have been linked to depression, to antidepressant treatment response, to ACE serum concentrations, as well as to hypertension, myocardial infarction and CVD risk markers. The mostly investigated ACE Ins/Del polymorphism accounts for ~40%-50% of the ACE serum concentration variance, the remaining half is probably determined by other genetic, environmental or epigenetic factors, but these are poorly understood. MATERIALS AND METHODS: The main aim of the present study was the analysis of the DNA methylation pattern in the regulatory region of the ACE gene in peripheral leukocytes of 81 MD patients and 81 healthy controls. RESULTS: We detected intensive DNA methylation within a recently described, functional important region of the ACE gene promoter including hypermethylation in depressed patients (p = 0.008 and a significant inverse correlation between the ACE serum concentration and ACE promoter methylation frequency in the total sample (p = 0.02. Furthermore, a significant inverse correlation between the concentrations of the inflammatory CVD risk markers ICAM-1, E-selectin and P-selectin and the degree of ACE promoter methylation in MD patients could be demonstrated (p = 0.01 - 0.04. CONCLUSION: The results of the present study suggest that aberrations in ACE promoter DNA methylation may be an underlying cause of MD and probably a common pathogenic factor for the bi-directional relationship between MD and cardiovascular disorders.

  6. TECTONIC VERSUS VOLCANIC ORIGIN OF THE SUMMIT DEPRESSION AT MEDICINE LAKE VOLCANO, CALIFORNIA

    Mark Leon Gwynn

    2010-05-01

    Medicine Lake Volcano is a Quaternary shield volcano located in a tectonically complex and active zone at the transition between the Basin and Range Province and the Cascade Range of the Pacific Province. The volcano is topped by a 7x12 km elliptical depression surrounded by a discontinuous constructional ring of basaltic to rhyolitic lava flows. This thesis explores the possibility that the depression may have formed due to regional extension (rift basin) or dextral shear (pull-apart basin) rather than through caldera collapse and examines the relationship between regional tectonics and localized volcanism. Existing data consisting of temperature and magnetotelluric surveys, alteration mineral studies, and core logging were compiled and supplemented with additional core logging, field observations, and fault striae studies in paleomagnetically oriented core samples. These results were then synthesized with regional fault data from existing maps and databases. Faulting patterns near the caldera, extension directions derived from fault striae P and T axes, and three-dimensional temperature and alteration mineral models are consistent with slip across arcuate ring faults related to magma chamber deflation during flank eruptions and/or a pyroclastic eruption at about 180 ka. These results are not consistent with a rift or pull-apart basin. Limited subsidence can be attributed to the relatively small volume of ash-flow tuff released by the only known major pyroclastic eruption and is inconsistent with the observed topographic relief. The additional relief can be explained by constructional volcanism. Striae from unoriented and oriented core, augmented by striae measurements in outcrop suggest that Walker Lane dextral shear, which can be reasonably projected from the southeast, has probably propagated into the Medicine Lake area. Most volcanic vents across Medicine Lake Volcano strike north-south, suggesting they are controlled by crustal weakness related to Basin and

  7. Tectonic versus volcanic origin of the summit depression at Medicine Lake Volcano, California

    Mark Leon Gwynn

    2010-05-01

    Medicine Lake Volcano is a Quaternary shield volcano located in a tectonically complex and active zone at the transition between the Basin and Range Province and the Cascade Range of the Pacific Province. The volcano is topped by a 7x12 km elliptical depression surrounded by a discontinuous constructional ring of basaltic to rhyolitic lava flows. This thesis explores the possibility that the depression may have formed due to regional extension (rift basin) or dextral shear (pull-apart basin) rather than through caldera collapse and examines the relationship between regional tectonics and localized volcanism. Existing data consisting of temperature and magnetotelluric surveys, alteration mineral studies, and core logging were compiled and supplemented with additional core logging, field observations, and fault striae studies in paleomagnetically oriented core samples. These results were then synthesized with regional fault data from existing maps and databases. Faulting patterns near the caldera, extension directions derived from fault striae P and T axes, and three-dimensional temperature and alteration mineral models are consistent with slip across arcuate ring faults related to magma chamber deflation during flank eruptions and/or a pyroclastic eruption at about 180 ka. These results are not consistent with a rift or pull-apart basin. Limited subsidence can be attributed to the relatively small volume of ash-flow tuff released by the only known major pyroclastic eruption and is inconsistent with the observed topographic relief. The additional relief can be explained by constructional volcanism. Striae from unoriented and oriented core, augmented by striae measurements in outcrop suggest that Walker Lane dextral shear, which can be reasonably projected from the southeast, has probably propagated into the Medicine Lake area. Most volcanic vents across Medicine Lake Volcano strike north-south, suggesting they are controlled by crustal weakness related to Basin and

  8. Gene expression deficits in pontine locus coeruleus astrocytes in men with major depressive disorder.

    Chandley, Michelle J; Szebeni, Katalin; Szebeni, Attila; Crawford, Jessica; Stockmeier, Craig A; Turecki, Gustavo; Miguel-Hidalgo, Jose Javier; Ordway, Gregory A

    2013-07-01

    Norepinephrine and glutamate are among several neurotransmitters implicated in the neuropathology of major depressive disorder (MDD). Glia deficits have also been demonstrated in people with MDD, and glia are critical modulators of central glutamatergic transmission. We studied glia in men with MDD in the region of the brain (locus coeruleus; LC) where noradrenergic neuronal cell bodies reside and receive glutamatergic input. The expression of 3 glutamate-related genes (SLC1A3, SLC1A2, GLUL) concentrated in glia and a glia gene (GFAP) were measured in postmortem tissues from men with MDD and from paired psychiatrically healthy controls. Initial gene expression analysis of RNA isolated from homogenized tissue (n = 9-10 pairs) containing the LC were followed by detailed analysis of gene expressions in astrocytes and oligodendrocytes (n = 6-7 pairs) laser captured from the LC region. We assessed protein changes in GFAP using immunohistochemistry and immunoblotting (n = 7-14 pairs). Astrocytes, but not oligodendrocytes, demonstrated robust reductions in the expression of SLC1A3 and SLC1A2, whereas GLUL expression was unchanged. GFAP expression was lower in astrocytes, and we confirmed reduced GFAP protein in the LC using immunostaining methods. Reduced expression of protein products of SLC1A3 and SLC1A2 could not be confirmed because of insufficient amounts of LC tissue for these assays. Whether gene expression abnormalities were associated with only MDD and not with suicide could not be confirmed because most of the decedents who had MDD died by suicide. Major depressive disorder is associated with unhealthy astrocytes in the noradrenergic LC, characterized here by a reduction in astrocyte glutamate transporter expression. These findings suggest that increased glutamatergic activity in the LC occurs in men with MDD.

  9. Unexpected detection of porcine rotavirus C strains carrying human origin VP6 gene.

    Kattoor, Jobin Jose; Saurabh, Sharad; Malik, Yashpal Singh; Sircar, Shubhankar; Dhama, Kuldeep; Ghosh, Souvik; Bányai, Krisztián; Kobayashi, Nobumichi; Singh, Raj Kumar

    2017-12-01

    Rotavirus C (RVC), a known etiological agent of diarrheal outbreaks, mainly inflicts swine population globally with sporadic incidence in human, cattle, ferret, mink and dog. To demonstrate the presence of RVC in Indian swine population and characterization of its selected structural (VP6) and non-structural (NSP4 and NSP5) genes. A total of 108 diarrheic samples from different regions of India were used. Isolated RNA was loaded onto polyacrylamide gel to screen for the presence of RVs through the identification of specific electrophoretic genomic migration pattern. To characterize the RVC strains, VP6 gene and NSP4 and NSP5 genes were amplified, sequenced and analyzed. Based on VP6 gene specific diagnostic RT-PCR, the presence of RVC was confirmed in 12.0% (13/108) piglet fecal specimens. The nucleotide sequence analysis of VP6 gene, encoding inner capsid protein, from selected porcine RVC (PoRVC) strains revealed more than 93% homologies to human RVC strains (HuRVC) of Eurasian origin. These strains were distant from hitherto reported PoRVCs and clustered with HuRVCs, owning I2 genotype. However, the two non-structural genes, i.e. NSP4 and NSP5, of these strains were found to be of swine type, signifying a re-assortment event that has occurred in the Indian swine population. The findings indicate the presence of human-like RVC in Indian pigs and division of RVC clade with I2 genotype into further sub-clades. To the best of our knowledge, this appears to be the first report of RVC in Indian swine population. Incidence of human-like RVC VP6 gene in swine supports its subsequent zoonotic prospective.

  10. Origin of melting point depression for rare gas solids confined in carbon pores

    Morishige, Kunimitsu; Kataoka, Takaaki

    2015-01-01

    To obtain insights into the mechanism of the melting-point depression of rare gas solids confined in crystalline carbon pores, we examined the freezing and melting behavior of Xe and Ar confined to the crystalline pores of ordered mesoporous carbons as well as compressed exfoliated graphite compared to the amorphous pores of ordered mesoporous silicas, by means of X-ray diffraction. For the Xe and Ar confined to the crystalline carbon pores, there was no appreciable thermal hysteresis between freezing and melting. Furthermore, the position of the main diffraction peak did not change appreciably on freezing and melting. This strongly suggests that the liquids confined in the carbon pores form a multilayered structure parallel to the smooth walls. For the Xe and Ar confined to the amorphous silica pores, on the other hand, the position of the main diffraction peak shifted into higher scattering angle on freezing suggested that the density of the confined solid is distinctly larger than for the confined liquid. Using compressed exfoliated graphite with carbon walls of higher crystallinity, we observed that three-dimensional (3D) microcrystals of Xe confined in the slit-shaped pores melted to leave the unmelted bilayers on the pore walls below the bulk triple point. The lattice spacing of the 3D microcrystals confined is larger by ∼0.7% than that of the bilayer next to the pore walls in the vicinity of the melting point

  11. Origin of melting point depression for rare gas solids confined in carbon pores

    Morishige, Kunimitsu, E-mail: morishi@chem.ous.ac.jp; Kataoka, Takaaki [Department of Chemistry, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005 (Japan)

    2015-07-21

    To obtain insights into the mechanism of the melting-point depression of rare gas solids confined in crystalline carbon pores, we examined the freezing and melting behavior of Xe and Ar confined to the crystalline pores of ordered mesoporous carbons as well as compressed exfoliated graphite compared to the amorphous pores of ordered mesoporous silicas, by means of X-ray diffraction. For the Xe and Ar confined to the crystalline carbon pores, there was no appreciable thermal hysteresis between freezing and melting. Furthermore, the position of the main diffraction peak did not change appreciably on freezing and melting. This strongly suggests that the liquids confined in the carbon pores form a multilayered structure parallel to the smooth walls. For the Xe and Ar confined to the amorphous silica pores, on the other hand, the position of the main diffraction peak shifted into higher scattering angle on freezing suggested that the density of the confined solid is distinctly larger than for the confined liquid. Using compressed exfoliated graphite with carbon walls of higher crystallinity, we observed that three-dimensional (3D) microcrystals of Xe confined in the slit-shaped pores melted to leave the unmelted bilayers on the pore walls below the bulk triple point. The lattice spacing of the 3D microcrystals confined is larger by ∼0.7% than that of the bilayer next to the pore walls in the vicinity of the melting point.

  12. Origin, timing, and gene expression profile of adventitious rooting in Arabidopsis hypocotyls and stems.

    Welander, Margareta; Geier, Thomas; Smolka, Anders; Ahlman, Annelie; Fan, Jing; Zhu, Li-Hua

    2014-02-01

    Adventitious root (AR) formation is indispensable for vegetative propagation, but difficult to achieve in many crops. Understanding its molecular mechanisms is thus important for such species. Here we aimed at developing a rooting protocol for direct AR formation in stems, locating cellular AR origins in stems and exploring molecular differences underlying adventitious rooting in hypocotyls and stems. In-vitro-grown hypocotyls or stems of wild-type and transgenic ecotype Columbia (Col-0) of Arabidopsis thaliana were rooted on rooting media. Anatomy of AR formation, qRT-PCR of some rooting-related genes and in situ GUS expression were carried out during rooting from hypocotyls and stems. We developed a rooting protocol for AR formation in stems and traced back root origins in stems by anatomical and in situ expression studies. Unlike rooting in hypocotyls, rooting in stems was slower, and AR origins were mainly from lateral parenchyma of vascular bundles and neighboring starch sheath cells as well as, to a lesser extent, from phloem cap and xylem parenchyma. Transcript levels of GH3-3, LBD16, LBD29, and LRP1 in hypocotyls and stems were similar, but transcript accumulation was delayed in stems. In situ expression signals of DR5::GUS, LBD16::GUS, LBD29::GUS, and rolB::GUS reporters in stems mainly occurred at the root initiation sites, suggesting their involvement in AR formation. We have developed an efficient rooting protocol using half-strength Lepoivre medium for studying AR formation in stems, traced back the cellular AR origins in stems, and correlated expression of rooting-related genes with root initiation sites.

  13. Oxytocin and Social Sensitivity: Gene Polymorphisms in Relation to Depressive Symptoms and Suicidal Ideation

    Robyn Jane McQuaid

    2016-07-01

    Full Text Available Although the neuropeptide oxytocin has been associated with enhanced prosocial behaviors, it has also been linked to aggression and mental health disorders. Thus, it was suggested that oxytocin might act by increasing the salience of social stimuli, irrespective of whether these are positive or negative, thus increasing vulnerability to negative mental health outcomes. The current study (N = 243, conducted among White university students, examined the relation of trauma, depressive symptoms including suicidal ideation in relation to a single nucleotide polymorphism (SNP within the oxytocin receptor gene (OXTR, rs53576, and a SNP on the CD38 gene that controls oxytocin release, rs3796863. Individuals with the polymorphism on both alleles (AA genotype of the CD38 SNP had previously been linked to elevated plasma oxytocin levels. Consistent with the social sensitivity perspective, however, in the current study, individuals carrying the AA genotype displayed elevated feelings of alienation from parents and peers as well as increased levels of suicidal ideation. Moreover, they tended to report elevated depressive symptoms compared to CC homozygotes. It was also observed that the CD38 genotype moderated the relation between trauma and suicidal ideation scores, such that high levels of trauma were associated with elevated suicidal ideation among all CD38 genotypes, but this relationship was stronger among individuals with the AA genotype. In contrast, there was no relationship between the OXTR SNP, rs53576, depression or suicidal ideation. These findings support a social sensitivity hypothesis of oxytocin, wherein the AA genotype of the CD38 SNP, which has been considered the ‘protective allele’ was associated with increased sensitivity and susceptibility to disturbed social relations and suicidal ideation.

  14. Gene-environment interaction in Major Depression: focus on experience-dependent biological systems

    Nicola eLopizzo

    2015-05-01

    Full Text Available Major Depressive Disorder (MDD is a multifactorial and polygenic disorder, where multiple and partially overlapping sets of susceptibility genes interact each other and with the environment, predisposing individuals to the development of the illness. Thus, MDD results from a complex interplay of vulnerability genes and environmental factors that act cumulatively throughout individual's lifetime. Among these environmental factors, stressful life experiences, especially those occurring early in life, have been suggested to exert a crucial impact on brain development, leading to permanent functional changes that may contribute to life long risk for mental health outcomes. In this review we will discuss how genetic variants (polymorphisms, SNPs within genes operating in neurobiological systems that mediate stress response and synaptic plasticity, can impact, by themselves, the vulnerability risk for MDD; we will also consider how this MDD risk can be further modulated when gene X environment interaction is taken into account. Finally, we will discuss the role of epigenetic mechanisms, and in particular of DNA methylation and miRNAs expression changes, in mediating the effect of the stress on the vulnerability risk to develop MDD. Taken together, in this review we aim to underlie the role of genetic and epigenetic processes involved in stress and neuroplasticity related biological systems on development of MDD after exposure to early life stress, thereby building the basis for future research and clinical interventions.

  15. Serotonin and Dopamine Gene Variation and Theory of Mind Decoding Accuracy in Major Depression: A Preliminary Investigation.

    Zahavi, Arielle Y; Sabbagh, Mark A; Washburn, Dustin; Mazurka, Raegan; Bagby, R Michael; Strauss, John; Kennedy, James L; Ravindran, Arun; Harkness, Kate L

    2016-01-01

    Theory of mind-the ability to decode and reason about others' mental states-is a universal human skill and forms the basis of social cognition. Theory of mind accuracy is impaired in clinical conditions evidencing social impairment, including major depressive disorder. The current study is a preliminary investigation of the association of polymorphisms of the serotonin transporter (SLC6A4), dopamine transporter (DAT1), dopamine receptor D4 (DRD4), and catechol-O-methyl transferase (COMT) genes with theory of mind decoding in a sample of adults with major depression. Ninety-six young adults (38 depressed, 58 non-depressed) completed the 'Reading the Mind in the Eyes task' and a non-mentalistic control task. Genetic associations were only found for the depressed group. Specifically, superior accuracy in decoding mental states of a positive valence was seen in those homozygous for the long allele of the serotonin transporter gene, 9-allele carriers of DAT1, and long-allele carriers of DRD4. In contrast, superior accuracy in decoding mental states of a negative valence was seen in short-allele carriers of the serotonin transporter gene and 10/10 homozygotes of DAT1. Results are discussed in terms of their implications for integrating social cognitive and neurobiological models of etiology in major depression.

  16. Serotonin and Dopamine Gene Variation and Theory of Mind Decoding Accuracy in Major Depression: A Preliminary Investigation.

    Arielle Y Zahavi

    Full Text Available Theory of mind-the ability to decode and reason about others' mental states-is a universal human skill and forms the basis of social cognition. Theory of mind accuracy is impaired in clinical conditions evidencing social impairment, including major depressive disorder. The current study is a preliminary investigation of the association of polymorphisms of the serotonin transporter (SLC6A4, dopamine transporter (DAT1, dopamine receptor D4 (DRD4, and catechol-O-methyl transferase (COMT genes with theory of mind decoding in a sample of adults with major depression. Ninety-six young adults (38 depressed, 58 non-depressed completed the 'Reading the Mind in the Eyes task' and a non-mentalistic control task. Genetic associations were only found for the depressed group. Specifically, superior accuracy in decoding mental states of a positive valence was seen in those homozygous for the long allele of the serotonin transporter gene, 9-allele carriers of DAT1, and long-allele carriers of DRD4. In contrast, superior accuracy in decoding mental states of a negative valence was seen in short-allele carriers of the serotonin transporter gene and 10/10 homozygotes of DAT1. Results are discussed in terms of their implications for integrating social cognitive and neurobiological models of etiology in major depression.

  17. DNA methylation profiles of the brain-derived neurotrophic factor (BDNF gene as a potent diagnostic biomarker in major depression.

    Manabu Fuchikami

    Full Text Available Major depression, because of its recurring and life-threatening nature, is one of the top 10 diseases for global disease burden. Major depression is still diagnosed on the basis of clinical symptoms in patients. The search for specific biological markers is of great importance to advance the method of diagnosis for depression. We examined the methylation profile of 2 CpG islands (I and IV at the promoters of the brain-derived neurotrophic factor (BDNF gene, which is well known to be involved in the pathophysiology of depression. We analyzed genomic DNA from peripheral blood of 20 Japanese patients with major depression and 18 healthy controls to identify an appropriate epigenetic biomarker to aid in the establishment of an objective system for the diagnosis of depression. Methylation rates at each CpG unit was measured using a MassArray® system (SEQUENOM, and 2-dimensional hierarchical clustering analyses were undertaken to determine the validity of these methylation profiles as a diagnostic biomarker. Analyses of the dendrogram from methylation profiles of CpG I, but not IV, demonstrated that classification of healthy controls and patients at the first branch completely matched the clinical diagnosis. Despite the small number of subjects, our results indicate that classification based on the DNA methylation profiles of CpG I of the BDNF gene may be a valuable diagnostic biomarker for major depression.

  18. Varicella-zoster virus (VZV) origin of DNA replication oriS influences origin-dependent DNA replication and flanking gene transcription.

    Khalil, Mohamed I; Sommer, Marvin H; Hay, John; Ruyechan, William T; Arvin, Ann M

    2015-07-01

    The VZV genome has two origins of DNA replication (oriS), each of which consists of an AT-rich sequence and three origin binding protein (OBP) sites called Box A, C and B. In these experiments, the mutation in the core sequence CGC of the Box A and C not only inhibited DNA replication but also inhibited both ORF62 and ORF63 expression in reporter gene assays. In contrast the Box B mutation did not influence DNA replication or flanking gene transcription. These results suggest that efficient DNA replication enhances ORF62 and ORF63 transcription. Recombinant viruses carrying these mutations in both sites and one with a deletion of the whole oriS were constructed. Surprisingly, the recombinant virus lacking both copies of oriS retained the capacity to replicate in melanoma and HELF cells suggesting that VZV has another origin of DNA replication. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Gene expression-based biological test for major depressive disorder: an advanced study

    Watanabe S

    2017-02-01

    Full Text Available Shin-ya Watanabe,1 Shusuke Numata,1 Jun-ichi Iga,2 Makoto Kinoshita,1 Hidehiro Umehara,1 Kazuo Ishii,3 Tetsuro Ohmori1 1Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 2Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Ehime, 3Department of Applied Biological Science, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan Purpose: Recently, we could distinguished patients with major depressive disorder (MDD from nonpsychiatric controls with high accuracy using a panel of five gene expression markers (ARHGAP24, HDAC5, PDGFC, PRNP, and SLC6A4 in leukocyte. In the present study, we examined whether this biological test is able to discriminate patients with MDD from those without MDD, including those with schizophrenia and bipolar disorder.Patients and methods: We measured messenger ribonucleic acid expression levels of the aforementioned five genes in peripheral leukocytes in 17 patients with schizophrenia and 36 patients with bipolar disorder using quantitative real-time polymerase chain reaction (PCR, and we combined these expression data with our previous expression data of 25 patients with MDD and 25 controls. Subsequently, a linear discriminant function was developed for use in discriminating between patients with MDD and without MDD.Results: This expression panel was able to segregate patients with MDD from those without MDD with a sensitivity and specificity of 64% and 67.9%, respectively.Conclusion: Further research to identify MDD-specific markers is needed to improve the performance of this biological test. Keywords: depressive disorder, biomarker, gene expression, schizophrenia, bipolar disorder

  20. When naked became armored: an eight-gene phylogeny reveals monophyletic origin of theca in dinoflagellates.

    Russell J S Orr

    Full Text Available The dinoflagellates are a diverse lineage of microbial eukaryotes. Dinoflagellate monophyly and their position within the group Alveolata are well established. However, phylogenetic relationships between dinoflagellate orders remain unresolved. To date, only a limited number of dinoflagellate studies have used a broad taxon sample with more than two concatenated markers. This lack of resolution makes it difficult to determine the evolution of major phenotypic characters such as morphological features or toxin production e.g. saxitoxin. Here we present an improved dinoflagellate phylogeny, based on eight genes, with the broadest taxon sampling to date. Fifty-five sequences for eight phylogenetic markers from nuclear and mitochondrial regions were amplified from 13 species, four orders, and concatenated phylogenetic inferences were conducted with orthologous sequences. Phylogenetic resolution is increased with addition of support for the deepest branches, though can be improved yet further. We show for the first time that the characteristic dinoflagellate thecal plates, cellulosic material that is present within the sub-cuticular alveoli, appears to have had a single origin. In addition, the monophyly of most dinoflagellate orders is confirmed: the Dinophysiales, the Gonyaulacales, the Prorocentrales, the Suessiales, and the Syndiniales. Our improved phylogeny, along with results of PCR to detect the sxtA gene in various lineages, allows us to suggest that this gene was probably acquired separately in Gymnodinium and the common ancestor of Alexandrium and Pyrodinium and subsequently lost in some descendent species of Alexandrium.

  1. When Naked Became Armored: An Eight-Gene Phylogeny Reveals Monophyletic Origin of Theca in Dinoflagellates

    Orr, Russell J. S.; Murray, Shauna A.; Stüken, Anke; Rhodes, Lesley; Jakobsen, Kjetill S.

    2012-01-01

    The dinoflagellates are a diverse lineage of microbial eukaryotes. Dinoflagellate monophyly and their position within the group Alveolata are well established. However, phylogenetic relationships between dinoflagellate orders remain unresolved. To date, only a limited number of dinoflagellate studies have used a broad taxon sample with more than two concatenated markers. This lack of resolution makes it difficult to determine the evolution of major phenotypic characters such as morphological features or toxin production e.g. saxitoxin. Here we present an improved dinoflagellate phylogeny, based on eight genes, with the broadest taxon sampling to date. Fifty-five sequences for eight phylogenetic markers from nuclear and mitochondrial regions were amplified from 13 species, four orders, and concatenated phylogenetic inferences were conducted with orthologous sequences. Phylogenetic resolution is increased with addition of support for the deepest branches, though can be improved yet further. We show for the first time that the characteristic dinoflagellate thecal plates, cellulosic material that is present within the sub-cuticular alveoli, appears to have had a single origin. In addition, the monophyly of most dinoflagellate orders is confirmed: the Dinophysiales, the Gonyaulacales, the Prorocentrales, the Suessiales, and the Syndiniales. Our improved phylogeny, along with results of PCR to detect the sxtA gene in various lineages, allows us to suggest that this gene was probably acquired separately in Gymnodinium and the common ancestor of Alexandrium and Pyrodinium and subsequently lost in some descendent species of Alexandrium. PMID:23185516

  2. [Characterisation of three polymorphisms of the tryptophan hydroxylase 2 gene in a sample of Colombian population with major depressive disorder].

    Martínez-Idárraga, Adriana; Riveros-Barrera, Irene; Sánchez, Ricardo; Jaramillo, Luis Eduardo; Calvo-Gómez, José Manuel; Yunis-Londoño, Juan José

    Identify whether rs11179000, rs136494 and rs4570625 polymorphisms of the tryptophan hydroxylase 2 gene, are associated with a major depressive disorder in a sample of the Colombian population. Case-control study was conducted in which a comparison was made between subjects diagnosed with major depressive disorder at some point in adulthood or active symptoms at the time of evaluation, and subjects with no psychiatric disease. Subjects were studied in the Department of Psychiatry, Faculty of Medicine and the Institute of Genetics at the National University of Colombia. Polymorphisms were genotyped using Taqman probes in real time PCR. As well as studying the association between major depressive disorder and these (single nucleotide polymorphisms (SNPs), the association with other factors previously associated with depression were also analysed. No statistically significant association between genotypic and allelic frequencies of each polymorphism and major depressive disorder was found. Association between sex and complication during pregnancy / childbirth and major depressive disorder was observed. Association between sex and complication during pregnancy / childbirth and major depressive disorder was observed. There was no association between any polymorphism and major depressive disorder. Copyright © 2016 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  3. Genetic moderation of the association between adolescent romantic involvement and depression: Contributions of serotonin transporter gene polymorphism, chronic stress, and family discord

    Starr, Lisa R.; Hammen, Constance

    2015-01-01

    Studies support a link between adolescent romantic involvement and depression. Adolescent romantic relationships may increase depression risk by introducing chronic stress, and genetic vulnerability to stress reactivity/emotion dysregulation may moderate these associations. We tested genetic moderation of longitudinal associations between adolescent romantic involvement and later depressive symptoms by a polymorphism in the serotonin transporter linked polymorphic region gene (5-HTTLPR), and ...

  4. Tyrosine receptor kinase B gene variants (NTRK2 variants) are associated with depressive disorders in temporal lobe epilepsy.

    Torres, Carolina Machado; Siebert, Marina; Bock, Hugo; Mota, Suelen Mandelli; Castan, Juliana Unis; Scornavacca, Francisco; de Castro, Luiza Amaral; Saraiva-Pereira, Maria Luiza; Bianchin, Marino Muxfeldt

    2017-06-01

    Psychiatric comorbidities are highly prevalent in epilepsy, adding an important burden to the disease and profoundly affecting the quality of life of these individuals. Patients with temporal lobe epilepsy (TLE) are especially at risk to develop depression and several lines of evidence suggest that the association of depression with epilepsy might be related to common biological substrates. In this study, we test whether NTRK2 allele variants are associated with mood disorders or depressive disorders in patients with TLE. An association study of 163 patients with TLE. The NTRK2 variants studied were rs1867283, rs10868235, rs1147198, rs11140800, rs1187286, rs2289656, rs1624327, rs1443445, rs3780645, and rs2378672. All patients were submitted to the Structured Clinical Interview for DSM-IV (SCID) and epilepsy patients with mood disorders or depressive disorders were compared to epilepsy patients without mood disorders or depressive disorders. In our TLE cohort, 76 patients (46.6%) showed mood disorders. After logistic regression, independent risk factors for mood disorders in TLE were female sex, presence of concomitant anxiety disorders, and genetic variations in rs1867283 and rs10868235 NTRK2 variants. Depressive disorders accounted for this results and independent variables associated with depressive disorders in TLE were female sex (OR=2.59; 95%CI=1.15-5.82; p=0.021), presence of concomitant anxiety disorders (OR=3.72; 95%CI=1.71-8.06; p=0.001) or psychotic disorders (OR=3.86; 95%CI=1.12-13.25; p=0.032), A/A genotype in the rs1867283 NTRK2 gene (OR=3.06; 95%CI=1.25-7.50; p=0.015) and C/C genotype in the rs10868235 NTRK2 gene (OR=3.54; 1.55-8.08; p=0.003). Similarly, these genotypes also remained independently and significantly associated with depressive disorders when patients with depressive disorders were compared to TLE patients without any psychiatric comorbidity. In the present study, female sex, presence of concomitant anxiety or psychotic disorders, and

  5. Avian endogenous provirus (ev-3) env gene sequencing: implication for pathogenic retrovirus origination.

    Tikhonenko, A T; Lomovskaya, O L

    1990-02-01

    The avian endogenous env gene product blocks the surface receptor and, as a result, cells become immune to related exogenous retroviruses. On the other hand, the same sequence can be included in the pathogenic retrovirus genome, as shown by oligonucleotide mapping. However, since the complete env gene sequence was not known, the comparison of genomic nucleotide sequences was not possible. Therefore an avian endogenous provirus with an intact env gene was cloned from a chicken gene bank and the regions coding for the C terminus of the gp85 and gp37 proteins were sequenced. Comparison of this sequence with those of other retroviruses proved that one of the pathogenic viruses associated with osteopetrosis is a cross between avian endogenous virus and Rous sarcoma virus. Retroviruses and, especially, endogenous retroviruses are traditionally of the most developed models of viral carcinogenesis. Many endogenous retroviruses are implicated in neoplastic transformation of the cell. For instance, endogenous mouse mammary tumor virus of some inbred lines appears to be the only causative agent in these mammary cancers. Other even nonpathogenic murine endogenous retroviruses are involved in the origination of MCF-type recombinant acute leukosis viruses. Some endogenous retroviruses are implicated in the transduction or activation of cellular protooncogenes. Our interest in endogenous viruses is based on their ability to make cells resistant to exogenous retroviruses. Expression of their major envelope glycoprotein leads to cellular surface receptor blockage and imparts immunity to infection by the related leukemia retroviruses. This problem is quite elaborated for chicken endogenous virus RAV-O (7-9).(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Origins and Domestication of Cultivated Banana Inferred from Chloroplast and Nuclear Genes

    Zhang, Cui; Wang, Xin-Feng; Shi, Feng-Xue; Chen, Wen-Na; Ge, Xue-Jun

    2013-01-01

    Background Cultivated bananas are large, vegetatively-propagated members of the genus Musa. More than 1,000 cultivars are grown worldwide and they are major economic and food resources in numerous developing countries. It has been suggested that cultivated bananas originated from the islands of Southeast Asia (ISEA) and have been developed through complex geodomestication pathways. However, the maternal and parental donors of most cultivars are unknown, and the pattern of nucleotide diversity in domesticated banana has not been fully resolved. Methodology/Principal Findings We studied the genetics of 16 cultivated and 18 wild Musa accessions using two single-copy nuclear (granule-bound starch synthase I, GBSS I, also known as Waxy, and alcohol dehydrogenase 1, Adh1) and two chloroplast (maturase K, matK, and the trnL-F gene cluster) genes. The results of phylogenetic analyses showed that all A-genome haplotypes of cultivated bananas were grouped together with those of ISEA subspecies of M. acuminata (A-genome). Similarly, the B- and S-genome haplotypes of cultivated bananas clustered with the wild species M. balbisiana (B-genome) and M. schizocarpa (S-genome), respectively. Notably, it has been shown that distinct haplotypes of each cultivar (A-genome group) were nested together to different ISEA subspecies M. acuminata. Analyses of nucleotide polymorphism in the Waxy and Adh1 genes revealed that, in comparison to the wild relatives, cultivated banana exhibited slightly lower nucleotide diversity both across all sites and specifically at silent sites. However, dramatically reduced nucleotide diversity was found at nonsynonymous sites for cultivated bananas. Conclusions/Significance Our study not only confirmed the origin of cultivated banana as arising from multiple intra- and inter-specific hybridization events, but also showed that cultivated banana may have not suffered a severe genetic bottleneck during the domestication process. Importantly, our findings

  7. Relationship between major depressive disorder and ACE gene I/D polymorphism in a Turkish population

    Sema Inanir

    2016-04-01

    Full Text Available Abstract Background Major depressive disorder (MDD is a complex disease and a significant health problem that is prevalent across the world. Angiotensin-converting enzyme (ACE has an important role in renin-angiotensin system (RAS and converts inactive angiotensin I to a potent vasopressor and aldosterone-stimulating peptide angiotensin II. Levels of ACE in plasma vary according to the insertion/deletion (I/D polymorphism of ACE gene. Objective The aim of the current study was to examine the influence ACE gene I/D variations on the risk of MDD. Methods In the present case-control study, we analyzed ACE I/D polymorphism in 346 MDD patients and 210 healthy subjects using polymerase chain reaction technique. Results Comparing the two groups, no significant difference was observed with regard to either genotype distributions or allele frequencies of the I/D polymorphism of ACE gene. Discussion Our findings suggest that the ACE I/D polymorphism is not associated with MDD in Turkish case-control study. Further studies are still needed.

  8. Gene environment interaction studies in depression and suicidal behavior: An update.

    Mandelli, Laura; Serretti, Alessandro

    2013-12-01

    Increasing evidence supports the involvement of both heritable and environmental risk factors in major depression (MD) and suicidal behavior (SB). Studies investigating gene-environment interaction (G × E) may be useful for elucidating the role of biological mechanisms in the risk for mental disorders. In the present paper, we review the literature regarding the interaction between genes modulating brain functions and stressful life events in the etiology of MD and SB and discuss their potential added benefit compared to genetic studies only. Within the context of G × E investigation, thus far, only a few reliable results have been obtained, although some genes have consistently shown interactive effects with environmental risk in MD and, to a lesser extent, in SB. Further investigation is required to disentangle the direct and mediated effects that are common or specific to MD and SB. Since traditional G × E studies overall suffer from important methodological limitations, further effort is required to develop novel methodological strategies with an interdisciplinary approach. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. How much gene flow is needed to avoid inbreeding depression in wild tiger populations?

    Kenney, John; Allendorf, Fred W; McDougal, Charles; Smith, James L D

    2014-08-22

    The number and size of tiger populations continue to decline owing to habitat loss, habitat fragmentation and poaching of tigers and their prey. As a result, tiger populations have become small and highly structured. Current populations have been isolated since the early 1970s or for approximately seven generations. The objective of this study is to explore how inbreeding may be affecting the persistence of remaining tiger populations and how dispersal, either natural or artificial, may reduce the potentially detrimental effect of inbreeding depression. We developed a tiger simulation model and used published levels of genetic load in mammals to simulate inbreeding depression. Following a 50 year period of population isolation, we introduced one to four dispersing male tigers per generation to explore how gene flow from nearby populations may reduce the negative impact of inbreeding depression. For the smallest populations, even four dispersing male tigers per generation did not increase population viability, and the likelihood of extinction is more than 90% within 30 years. Unless habitat connectivity is restored or animals are artificially introduced in the next 70 years, medium size wild populations are also likely to go extinct, with only four to five of the largest wild tiger populations likely to remain extant in this same period without intervention. To reduce the risk of local extinction, habitat connectivity must be pursued concurrently with efforts to increase population size (e.g. enhance habitat quality, increase habitat availability). It is critical that infrastructure development, dam construction and other similar projects are planned appropriately so that they do not erode the extent or quality of habitat for these populations so that they can truly serve as future source populations. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  10. Abelson Helper Integration Site-1 Gene Variants on Major Depressive Disorder and Bipolar Disorder

    Porcelli, Stefano; Han, Changsu; Lee, Soo-Jung; Patkar, Ashwin A.; Masand, Prakash S.; Balzarro, Beatrice; Alberti, Siegfried; De Ronchi, Diana; Serretti, Alessandro

    2014-01-01

    Objective The present study aimed to explore whether 4 single nucleotide polymorphisms (SNPs) within the AHI1 gene could be associated with major depressive disorder (MD) and bipolar disorder (BD), and whether they could predict clinical outcomes in mood disorders. Methods One hundred and eighty-four (184) patients with MD, 170 patients with BD and 170 healthy controls were genotyped for 4 AHI1 SNPs (rs11154801, rs7750586, rs9647635 and rs9321501). Baseline and final clinical measures for MD patients were assessed through the Hamilton Rating Scale for Depression (HAM-D). Allelic and genotypic frequencies in MD and BD subjects were compared with those of each disorder and healthy group using the χ2 statistics. Repeated measures ANOVA was used to test possible influences of SNPs on treatment efficacy. Results The rs9647635 A/A was more represented in subjects with BD as compared with MD and healthy subjects together. The rs9647635 A/A was also more presented in patients with MD than in healthy subjects. With regard to the allelic analysis, rs9647635 A allele was more represented in subjects with BD compared with healthy subjects, while it was not observed between patients with MD and healthy subjects. Conclusion Our findings provide potential evidence of an association between some variants of AHI1 and mood disorders susceptibility but not with clinical outcomes. However, we will need to do more adequately-powered and advanced association studies to draw any conclusion due to clear limitations. PMID:25395981

  11. Parent-of-origin dependent gene-specific knock down in mouse embryos

    Iqbal, Khursheed; Kues, Wilfried A.; Niemann, Heiner

    2007-01-01

    In mice hemizygous for the Oct4-GFP transgene, the F1 embryos show parent-of-origin dependent expression of the marker gene. F1 embryos with a maternally derived OG2 allele (OG2 mat /-) express GFP in the oocyte and during preimplantation development until the blastocyst stage indicating a maternal and embryonic expression pattern. F1-embryos with a paternally inherited OG2 allele (OG2 pat /-) express GFP from the 4- to 8-cell stage onwards showing only embryonic expression. This allows to study allele specific knock down of GFP expression. RNA interference (RNAi) was highly efficient in embryos with the paternally inherited GFP allele, whereas embryos with the maternally inherited GFP allele showed a delayed and less stringent suppression, indicating that the initial levels of the target transcript and the half life of the protein affect RNAi efficacy. RT-PCR analysis revealed only minimum of GFP mRNA. These results have implications for studies of gene silencing in mammalian embryos

  12. The origin of the p.E180 growth hormone receptor gene mutation.

    Ostrer, Harry

    2016-06-01

    Laron syndrome, an autosomal recessive condition of extreme short stature, is caused by the absence or dysfunction of the growth hormone receptor. A recurrent mutation in the GHR gene, p.E180, did not alter the encoded amino acid, but activated a cryptic splice acceptor resulting in a receptor protein with an 8-amino acid deletion in the extracellular domain. This mutation has been observed among Sephardic Jews and among individuals in Ecuador, Brazil and Chile, most notably in a large genetic isolate in Loja, Ecuador. A common origin has been postulated based on a shared genetic background of markers flanking this mutation, suggesting that the Lojanos (and others) may have Sephardic (Converso) Jewish ancestry. Analysis of the population structure of Lojanos based on genome-wide analysis demonstrated European, Sephardic Jewish and Native American ancestry in this group. X-autosomal comparison and monoallelic Y chromosomal and mitochondrial genetic analysis demonstrated gender-biased admixture between Native American women and European and Sephardic Jewish men. These findings are compatible with the co-occurrence of the Inquisition and the colonization of the Americas, including Converso Jews escaping the Inquisition in the Iberian Peninsula. Although not found among Lojanos, Converso Jews also brought founder mutations to contemporary Hispanic and Latino populations in the BRCA1 (c.68_69delAG) and BLM (c.2207_2212delATCTGAinsTAGATTC) genes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Chronic and Acute Stress, Gender, and Serotonin Transporter Gene-Environment Interactions Predicting Depression Symptoms in Youth

    Hammen, Constance; Brennan, Patricia A.; Keenan-Miller, Danielle; Hazel, Nicholas A.; Najman, Jake M.

    2010-01-01

    Background: Many recent studies of serotonin transporter gene by environment effects predicting depression have used stress assessments with undefined or poor psychometric methods, possibly contributing to wide variation in findings. The present study attempted to distinguish between effects of acute and chronic stress to predict depressive…

  14. Effect of childhood trauma on adult depression and neuroendocrine function: sex-specific moderation by CRH receptor 1 gene

    Christine Heim

    2009-11-01

    Full Text Available Variations of the corticotropin-releasing hormone receptor 1 (CRHR1 gene appear to moderate the development of depression after childhood trauma. Depression more frequently affects women than men. We examined sex differences in the effects of the CRHR1 gene on the relationship between childhood trauma and adult depression. Methods: We recruited 1,063 subjects from the waiting rooms of a public urban hospital. Childhood trauma exposure and symptoms of depression were assessed using dimensional rating scales. Subjects were genotyped for rs110402 within the CRHR1 gene. An independent sample of 78 subjects underwent clinical assessment, genotyping, and a dexamethasone/CRH test. The age range at recruitment was 18-77 years and 18-45, for the two studies respectively. Results: In the hospital sample, the protective effect of the rs110402 A-allele against developing depression after childhood trauma was observed in men (N=424, but not in women (N=635. In the second sample, the rs110402 A-allele was associated with decreased cortisol response in the dexamethasone/CRH test only in men. In A-allele carriers with childhood trauma exposure women exhibited increased cortisol response compared men; there were no sex differences in A-allele carriers without trauma exposure. This effect may, however, not be related to gender-differences per se, but to differences in the type of experienced abuse between men and women. CRHR x environment interactions in the hospital sample were observed with exposure to physical, but not sexual or emotional abuse. Physical abuse was the most common type of abuse in men in this cohort, while sexual abuse was most commonly suffered by women. Conclusion: Our results suggest that the CRHR1 gene may only moderate the effects of specific types of childhood trauma on depression. Gender differences in environmental exposures could thus be reflected in sex-specific CRHR1 x child abuse interactions.

  15. Effect of Childhood Trauma on Adult Depression and Neuroendocrine Function: Sex-Specific Moderation by CRH Receptor 1 Gene.

    Heim, Christine; Bradley, Bekh; Mletzko, Tanja C; Deveau, Todd C; Musselman, Dominique L; Nemeroff, Charles B; Ressler, Kerry J; Binder, Elisabeth B

    2009-01-01

    Variations of the corticotropin-releasing hormone receptor 1 (CRHR1) gene appear to moderate the development of depression after childhood trauma. Depression more frequently affects women than men. We examined sex differences in the effects of the CRHR1 gene on the relationship between childhood trauma and adult depression. We recruited 1,063 subjects from the waiting rooms of a public urban hospital. Childhood trauma exposure and symptoms of depression were assessed using dimensional rating scales. Subjects were genotyped for rs110402 within the CRHR1 gene. An independent sample of 78 subjects underwent clinical assessment, genotyping, and a dexamethasone/CRH test. The age range at recruitment was 18-77 years and 18-45, for the two studies respectively. In the hospital sample, the protective effect of the rs110402 A-allele against developing depression after childhood trauma was observed in men (N = 424), but not in women (N = 635). In the second sample, the rs110402 A-allele was associated with decreased cortisol response in the dexamethasone/CRH test only in men. In A-allele carriers with childhood trauma exposure women exhibited increased cortisol response compared men; there were no sex differences in A-allele carriers without trauma exposure. This effect may, however, not be related to gender differences per se, but to differences in the type of experienced abuse between men and women. CRHR x environment interactions in the hospital sample were observed with exposure to physical, but not sexual or emotional abuse. Physical abuse was the most common type of abuse in men in this cohort, while sexual abuse was most commonly suffered by women. Our results suggest that the CRHR1 gene may only moderate the effects of specific types of childhood trauma on depression. Gender differences in environmental exposures could thus be reflected in sex-specific CRHR1 x child abuse interactions.

  16. Hippocampal Gene Expression of Deiodinases 2 and 3 and Effects of 3,5-Diiodo-L-Thyronine T2 in Mouse Depression Paradigms

    Markova, Natalyia; Chernopiatko, Anton; Schroeter, Careen A.; Malin, Dmitry; Kubatiev, Aslan; Bachurin, Sergey; Costa-Nunes, João; Steinbusch, Harry M. W.; Strekalova, Tatyana

    2013-01-01

    Central thyroid hormone signaling is important in brain function/dysfunction, including affective disorders and depression. In contrast to 3,3′,5-triiodo-L-thyronine (T3), the role of 3,5-diiodo-L-thyronine (T2), which until recently was considered an inactive metabolite of T3, has not been studied in these pathologies. However, both T3 and T2 stimulate mitochondrial respiration, a factor counteracting the pathogenesis of depressive disorder, but the cellular origins in the CNS, mechanisms, and kinetics of the cellular action for these two hormones are distinct and independent of each other. Here, Illumina and RT PCR assays showed that hippocampal gene expression of deiodinases 2 and 3, enzymes involved in thyroid hormone regulation, is increased in resilience to stress-induced depressive syndrome and after antidepressant treatment in mice that might suggest elevated T2 and T3 turnover in these phenotypes. In a separate experiment, bolus administration of T2 at the doses 750 and 1500 mcg/kg but not 250 mcg/kg in naive mice reduced immobility in a two-day tail suspension test in various settings without changing locomotion or anxiety. This demonstrates an antidepressant-like effect of T2 that could be exploited clinically. In a wider context, the current study suggests important central functions of T2, whose biological role only lately is becoming to be elucidated. PMID:24386638

  17. Hippocampal Gene Expression of Deiodinases 2 and 3 and Effects of 3,5-Diiodo-L-Thyronine T2 in Mouse Depression Paradigms

    Natalyia Markova

    2013-01-01

    Full Text Available Central thyroid hormone signaling is important in brain function/dysfunction, including affective disorders and depression. In contrast to 3,3′,5-triiodo-L-thyronine (T3, the role of 3,5-diiodo-L-thyronine (T2, which until recently was considered an inactive metabolite of T3, has not been studied in these pathologies. However, both T3 and T2 stimulate mitochondrial respiration, a factor counteracting the pathogenesis of depressive disorder, but the cellular origins in the CNS, mechanisms, and kinetics of the cellular action for these two hormones are distinct and independent of each other. Here, Illumina and RT PCR assays showed that hippocampal gene expression of deiodinases 2 and 3, enzymes involved in thyroid hormone regulation, is increased in resilience to stress-induced depressive syndrome and after antidepressant treatment in mice that might suggest elevated T2 and T3 turnover in these phenotypes. In a separate experiment, bolus administration of T2 at the doses 750 and 1500 mcg/kg but not 250 mcg/kg in naive mice reduced immobility in a two-day tail suspension test in various settings without changing locomotion or anxiety. This demonstrates an antidepressant-like effect of T2 that could be exploited clinically. In a wider context, the current study suggests important central functions of T2, whose biological role only lately is becoming to be elucidated.

  18. Improved Sleep in Military Personnel is Associated with Changes in the Expression of Inflammatory Genes and Improvement in Depression Symptoms

    Whitney S. Livingston

    2015-04-01

    Full Text Available Study Objectives: Sleep disturbances are common in military personnel and are associated with increased risk for psychiatric morbidity, including posttraumatic stress disorder and depression, as well as inflammation. Improved sleep quality is linked to reductions in inflammatory bio-markers; however, the underlying mechanisms remain elusive. Methods: In this study we examine whole genome expression changes related to improved sleep in 68 military personnel diagnosed with insomnia. Subjects were classified into the following groups and then compared: improved sleep (n=46, or non-improved sleep (n=22 following three months of standard of care treatment for insomnia. Within subject differential expression was determined from microarray data using the Partek Genomics Suite analysis program and the interactive pathway analysis was used to determine key regulators of observed expression changes. Changes in symptoms of depression and posttraumatic stress disorder were also compared. Results: At baseline both groups were similar in demographics, clinical characteristics, and gene-expression profiles. The microarray data revealed that 217 coding genes were differentially expressed at the follow-up-period compared to baseline in the participants with improved sleep. Expression of inflammatory cytokines were reduced including IL-1β, IL-6, IL-8 and IL-13, with fold changes ranging from -3.19 to -2.1, and there were increases in the expression of inflammatory regulatory genes including toll-like receptors 1, 4, 7, and 8 in the improved sleep group. Interactive pathway analysis revealed 6 gene networks, including ubiquitin which was a major regulator in these gene-expression changes. The improved sleep group also had a significant reduction in the severity of depressive symptoms.Conclusions: Interventions that restore sleep likely reduce the expression of inflammatory genes, which relate to ubiquitin genes and relate to reductions in depressive symptoms.

  19. BDNF Val66Met polymorphism, life stress and depression: A meta-analysis of gene-environment interaction.

    Zhao, Mingzhe; Chen, Lu; Yang, Jiarun; Han, Dong; Fang, Deyu; Qiu, Xiaohui; Yang, Xiuxian; Qiao, Zhengxue; Ma, Jingsong; Wang, Lin; Jiang, Shixiang; Song, Xuejia; Zhou, Jiawei; Zhang, Jian; Chen, Mingqi; Qi, Dong; Yang, Yanjie; Pan, Hui

    2018-02-01

    Depression is thought to be multifactorial in etiology, including genetic and environmental components. While a number of gene-environment interaction studies have been carried out, meta-analyses are scarce. The present meta-analysis aimed to quantify evidence on the interaction between brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and stress in depression. Included were 31 peer-reviewed with a pooled total of 21060 participants published before October 2016 and literature searches were conducted using PubMed, Wolters Kluwer, Web of Science, EBSCO, Elsevier Science Direct and Baidu Scholar databases. The results indicated that the Met allele of BDNF Val66Met polymorphism significantly moderated the relationship between stress and depression (Z=2.666, p = 0.003). The results of subgroup analysis concluded that stressful life events and childhood adversity separately interacted with the Met allele of BDNF Val66Met polymorphism in depression (Z = 2.552, p = 0.005; Z = 1.775, p = 0.03). The results could be affected by errors or bias in primary studies which had small sample sizes with relatively lower statistic power. We could not estimate how strong the interaction effect between gene and environment was. We found evidence that supported the hypothesis that BDNF Val66Met polymorphism moderated the relationship between stress and depression, despite the fact that many included individual studies did not show this effect. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Diagnostic accuracy of the original 30-item and shortened versions of the Geriatric Depression Scale in nursing home patients

    Jongenelis, K; Eisses, AMH; Gerritsen, DL; Beekman, ATF; Kluiter, H; Ribbe, MW

    Objective To determine the diagnostic accuracy of the 30-item and shortened versions of the Geriatric Depression Scale (GDS) in diagnosing depression in older nursing home patients. Method Three hundred and thirty-three older nursing home patients participated in a prospective cross-sectional study

  1. Diagnostic accuracy of the original 30-item and shortened versions of the Geriatric Depression Scale in nursing home patients

    Jongenelis, K; Eisses, AMH; Gerritsen, DL; Beekman, ATF; Kluiter, H; Ribbe, MW

    2005-01-01

    Objective To determine the diagnostic accuracy of the 30-item and shortened versions of the Geriatric Depression Scale (GDS) in diagnosing depression in older nursing home patients. Method Three hundred and thirty-three older nursing home patients participated in a prospective cross-sectional study

  2. Identification of imprinted genes subject to parent-of-origin specific expression in Arabidopsis thaliana seeds.

    Mckeown, P.C.; Laouielle-Duprat, S.; Prins, J.C.P.; Wolff, de P.; Schmid, M.W.; Donoghue, M.T.; Fort, A.; Duszynska, D.; Comte, A.; Lao, N.T.; Wennblom, T.J.; Smant, G.; Köhler, C.; Grossniklaus, U.; Spillane, C.

    2011-01-01

    Background: Epigenetic regulation of gene dosage by genomic imprinting of some autosomal genes facilitates normal reproductive development in both mammals and flowering plants. While many imprinted genes have been identified and intensively studied in mammals, smaller numbers have been characterized

  3. Occurrence of the structural enterocin A, P, B, L50B genes in enterococci of different origin.

    Strompfová, Viola; Lauková, Andrea; Simonová, Monika; Marcináková, Miroslava

    2008-12-10

    Enterococci are well-known producers of antimicrobial peptides--bacteriocins (enterocins) and the number of characterized enterocins has been significantly increased. Recently, enterocins are of great interest for their potential as biopreservatives in food or feed while research on enterocins as alternative antimicrobials in humans and animals is only at the beginning. The present study provides a survey about the occurrence of enterocin structural genes A, P, B, L50B in a target of 427 strains of Enterococcus faecium (368) and Enterococcus faecalis (59) species from different sources (animal isolates, food and feed) performed by PCR method. Based on our results, 234 strains possessed one or more enterocin structural gene(s). The genes of enterocin P and enterocin A were the most frequently detected structural genes among the PCR positive strains (170 and 155 strains, respectively). Different frequency of the enterocin genes occurrence was detected in strains according to their origin; the strains from horses and silage showed the highest frequency of enterocin genes presence. All possible combinations of the tested genes occurred at least twice except the combination of the gene of enterocin B and L50B which possessed neither strain. The gene of enterocin A was exclusively detected among E. faecium strains, while the gene of enterocin P, B, L50B were detected in strains of both species E. faecium and E. faecalis. In conclusion, a high-frequency and variability of enterocin structural genes exists among enterococci of different origin what offers a big possibility to find effective bacteriocin-producing strains for their application in veterinary medicine.

  4. Phylogenetic and Genomic Analyses Resolve the Origin of Important Plant Genes Derived from Transposable Elements.

    Joly-Lopez, Zoé; Hoen, Douglas R; Blanchette, Mathieu; Bureau, Thomas E

    2016-08-01

    Once perceived as merely selfish, transposable elements (TEs) are now recognized as potent agents of adaptation. One way TEs contribute to evolution is through TE exaptation, a process whereby TEs, which persist by replicating in the genome, transform into novel host genes, which persist by conferring phenotypic benefits. Known exapted TEs (ETEs) contribute diverse and vital functions, and may facilitate punctuated equilibrium, yet little is known about this process. To better understand TE exaptation, we designed an approach to resolve the phylogenetic context and timing of exaptation events and subsequent patterns of ETE diversification. Starting with known ETEs, we search in diverse genomes for basal ETEs and closely related TEs, carefully curate the numerous candidate sequences, and infer detailed phylogenies. To distinguish TEs from ETEs, we also weigh several key genomic characteristics including repetitiveness, terminal repeats, pseudogenic features, and conserved domains. Applying this approach to the well-characterized plant ETEs MUG and FHY3, we show that each group is paraphyletic and we argue that this pattern demonstrates that each originated in not one but multiple exaptation events. These exaptations and subsequent ETE diversification occurred throughout angiosperm evolution including the crown group expansion, the angiosperm radiation, and the primitive evolution of angiosperms. In addition, we detect evidence of several putative novel ETE families. Our findings support the hypothesis that TE exaptation generates novel genes more frequently than is currently thought, often coinciding with key periods of evolution. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  5. TIMP2 gene polymorphism as a potential tool to infer Brazilian population origin

    da Silva RA

    2013-12-01

    Full Text Available Rodrigo Augusto da Silva,1 André Luis Shinohara,2 Denise Carleto Andia,1 Ariadne Letra,3 Regina Célia Peres,1 Ana Paula de Souza11Department of Morphology, Piracicaba Dental School, State University of Campinas, 2Oral Biology Program, Bauru Dental School, State University of São Paulo, São Paulo, Brazil; 3Department of Endodontics and Center for Craniofacial Research, School of Dentistry, University of Texas Health Science Center, Houston, TX, USAAbstract: Single nucleotide polymorphisms are genome variations that can be used as population-specific markers to infer genetic background and population origin. The Brazilian population is highly admixed due to immigration from several other populations. In particular, the state of São Paulo is recognized for the presence of Japanese individuals who seem likely to have contributed to a substantial proportion of ancestry in the modern Brazilian population. In the present study, we analyzed allele and genotype frequencies and associations of the –418G>C (rs8179090 single nucleotide polymorphism in the TIMP2 gene promoter in Brazilian and Japanese subjects, as well as in Japanese descendants from southeastern Brazil. The allele and genotype frequency analyses among groups demonstrated statistical significance (PC single nucleotide polymorphism of the TIMP2 gene, have a high probability of being Japanese or Japanese descendants. In addition to other genetic polymorphisms, the −418G>C TIMP2 polymorphism could be a population marker to assist in predicting Japanese ancestry, both in Japanese individuals and in admixed populations.Keywords: Brazilian, Japanese, polymorphism, allele, TIMP2

  6. Up-regulation of leucocytes genes implicated in telomere dysfunction and cellular senescence correlates with depression and anxiety severity scores.

    Jean-Raymond Teyssier

    Full Text Available BACKGROUND: Major depressive disorder (MDD is frequently associated with chronic medical illness responsible of increased disability and mortality. Inflammation and oxidative stress are considered to be the major mediators of the allostatic load, and has been shown to correlate with telomere erosion in the leucocytes of MDD patients, leading to the model of accelerated aging. However, the significance of telomere length as an exclusive biomarker of aging has been questioned on both methodological and biological grounds. Furthermore, telomeres significantly shorten only in patients with long lasting MDD. Sensitive and dynamic functional biomarkers of aging would be clinically useful to evaluate the somatic impact of MDD. METHODOLOGY: To address this issue we have measured in the blood leucocytes of MDD patients (N=17 and controls (N=16 the expression of two genes identified as robust biomarkers of human aging and telomere dysfunction: p16(INK4a and STMN1. We have also quantified the transcripts of genes involved in the repair of oxidative DNA damage at telomeres (OGG1, telomere regulation and elongation (TERT, and in the response to biopsychological stress (FOS and DUSP1. RESULTS: The OGG1, p16(INK4a, and STMN1 gene were significantly up-regulated (25 to 100% in the leucocytes of MDD patients. Expression of p16(INK4a and STMN1 was directly correlated with anxiety scores in the depression group, and that of p16(INK4a, STMN and TERT with the depression and anxiety scores in the combined sample (MDD plus controls. Furthermore, we identified a unique correlative pattern of gene expression in the leucocytes of MDD subjects. CONCLUSIONS: Expression of p16(INK4 and STMN1 is a promising biomarker for future epidemiological assessment of the somatic impact of depressive and anxious symptoms, at both clinical and subclinical level in both depressive patients and general population.

  7. Obesity genes and risk of major depressive disorder in a multiethnic population: a cross-sectional study.

    Samaan, Zainab; Lee, Yvonne K; Gerstein, Hertzel C; Engert, James C; Bosch, Jackie; Mohan, Viswanathan; Diaz, Rafael; Yusuf, Salim; Anand, Sonia S; Meyre, David

    2015-12-01

    Observational studies have shown a positive association between obesity (body mass index [BMI] ≥ 30 kg/m2) and depression. Around 120 obesity-associated loci have been identified, but genetic variants associated with depression remain elusive. Recently, our team reported that the fat mass and obesity-associated (FTO) gene rs9939609 obesity-risk variant is paradoxically inversely associated with the risk of depression. This finding raises the question as to whether other obesity-associated genetic variants are also associated with depression. Twenty-one obesity gene variants other than FTO were selected from a custom ∼50,000 single-nucleotide polymorphisms (SNPs) genotyping array (ITMAT-Broad-CARe array). Associations of these 21 SNPs and an unweighted genotype score with BMI and major depressive disorder (determined using the DSM-IV diagnostic criteria) were tested in 3,209 cases and 14,195 noncases, using baseline data collected from July 2001 to August 2003 from the multiethnic EpiDREAM study. Body mass index was positively associated with depression status (odds ratio [OR] = 1.02; 95% CI, 1.02-1.03 per BMI unit; P = 2.9 × 10(-12), adjusted for age, sex, and ethnicity). Six of 21 genetic variants (rs1514176 [TNN13K], rs2206734 [CDKAL1], rs11671664 [GIPR], rs2984618 [TAL1], rs3824755 [NT5C2], and rs7903146 [TCF7L2]) and the genotype score were significantly associated with BMI (1.47 × 10(-14) ≤ P ≤ .04). Of the 21 SNPs, TAL1 rs2984618 obesity-risk allele was associated with a higher risk of major depressive disorder (P = 1.79 × 10(-4), adjusted for age, sex, BMI, and ethnicity), and BDNF rs1401635 demonstrated significant ethnic-dependent association with major depressive disorder (OR = 0.88; 95% CI, 0.80-0.97; P = .01 in non-Europeans and OR = 1.11; 95% CI, 1.02-1.20; P = .02 in Europeans; Pinteraction = 2.73 × 10(-4)). The genotype score, calculated with or without FTO rs9939609, and adjusted for the same covariates, was not associated with

  8. Conversations with children about DNA and genes using an original children's book.

    Newcomb, Patricia; Hudlow, Rachel; Heilskov, Joan; Martinez, Cynthia Diane; Le, Heather

    2014-01-01

    The purpose of this evaluation was to compare parent and nurse use of an original children's book about deoxyribonucleic acid (DNA) function as a potential aid in the assent process in research. We also appraised parent's knowledge about DNA and the use of genetic testing results. We used mixed qualitative and quantitative methods. Parent-child dyads were recruited at an urban pediatric hospital. Knowledge of genetic concepts was assessed in adults with use of the Genetic Knowledge Index. Participants read the book What DNA Does with a nurse or alone and participated in interviews with investigators. The content of field notes from interviews was analyzed. Parent and child knowledge of DNA and gene function was generally poor but improved in most cases, particularly after reading with the nurse. The evaluated book is appropriate as a teaching aid in the child assent process in research or prior to genetic testing but should be presented by clinicians in most cases. Copyright © 2014 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.

  9. Differential Expression of FosB Proteins and Potential Target Genes in Select Brain Regions of Addiction and Depression Patients.

    Paula A Gajewski

    Full Text Available Chronic exposure to stress or drugs of abuse has been linked to altered gene expression throughout the body, and changes in gene expression in discrete brain regions are thought to underlie many psychiatric diseases, including major depressive disorder and drug addiction. Preclinical models of these disorders have provided evidence for mechanisms of this altered gene expression, including transcription factors, but evidence supporting a role for these factors in human patients has been slow to emerge. The transcription factor ΔFosB is induced in the prefrontal cortex (PFC and hippocampus (HPC of rodents in response to stress or cocaine, and its expression in these regions is thought to regulate their "top down" control of reward circuitry, including the nucleus accumbens (NAc. Here, we use biochemistry to examine the expression of the FosB family of transcription factors and their potential gene targets in PFC and HPC postmortem samples from depressed patients and cocaine addicts. We demonstrate that ΔFosB and other FosB isoforms are downregulated in the HPC but not the PFC in the brains of both depressed and addicted individuals. Further, we show that potential ΔFosB transcriptional targets, including GluA2, are also downregulated in the HPC but not PFC of cocaine addicts. Thus, we provide the first evidence of FosB gene expression in human HPC and PFC in these psychiatric disorders, and in light of recent findings demonstrating the critical role of HPC ΔFosB in rodent models of learning and memory, these data suggest that reduced ΔFosB in HPC could potentially underlie cognitive deficits accompanying chronic cocaine abuse or depression.

  10. A dual origin of the Xist gene from a protein-coding gene and a set of transposable elements.

    Eugeny A Elisaphenko

    2008-06-01

    Full Text Available X-chromosome inactivation, which occurs in female eutherian mammals is controlled by a complex X-linked locus termed the X-inactivation center (XIC. Previously it was proposed that genes of the XIC evolved, at least in part, as a result of pseudogenization of protein-coding genes. In this study we show that the key XIC gene Xist, which displays fragmentary homology to a protein-coding gene Lnx3, emerged de novo in early eutherians by integration of mobile elements which gave rise to simple tandem repeats. The Xist gene promoter region and four out of ten exons found in eutherians retain homology to exons of the Lnx3 gene. The remaining six Xist exons including those with simple tandem repeats detectable in their structure have similarity to different transposable elements. Integration of mobile elements into Xist accompanies the overall evolution of the gene and presumably continues in contemporary eutherian species. Additionally we showed that the combination of remnants of protein-coding sequences and mobile elements is not unique to the Xist gene and is found in other XIC genes producing non-coding nuclear RNA.

  11. Characterization of the neurohypophysial hormone gene loci in elephant shark and the Japanese lamprey: origin of the vertebrate neurohypophysial hormone genes

    Brenner Sydney

    2009-02-01

    Full Text Available Abstract Background Vasopressin and oxytocin are mammalian neurohypophysial hormones with distinct functions. Vasopressin is involved mainly in osmoregulation and oxytocin is involved primarily in parturition and lactation. Jawed vertebrates contain at least one homolog each of vasopressin and oxytocin, whereas only a vasopressin-family hormone, vasotocin, has been identified in jawless vertebrates. The genes encoding vasopressin and oxytocin are closely linked tail-to-tail in eutherian mammals whereas their homologs in chicken, Xenopus and coelacanth (vasotocin and mesotocin are linked tail-to-head. In contrast, their pufferfish homologs, vasotocin and isotocin, are located on the same strand of DNA with isotocin located upstream of vasotocin and separated by five genes. These differences in the arrangement of the two genes in different bony vertebrate lineages raise questions about their origin and ancestral arrangement. To trace the origin of these genes, we have sequenced BAC clones from the neurohypophysial gene loci in a cartilaginous fish, the elephant shark (Callorhinchus milii, and in a jawless vertebrate, the Japanese lamprey (Lethenteron japonicum. We have also analyzed the neurohypophysial hormone gene locus in an invertebrate chordate, the amphioxus (Branchiostoma floridae. Results The elephant shark neurohypophysial hormone genes encode vasotocin and oxytocin, and are linked tail-to-head like their homologs in coelacanth and non-eutherian tetrapods. Besides the hypothalamus, the two genes are also expressed in the ovary. In addition, the vasotocin gene is expressed in the kidney, rectal gland and intestine. These expression profiles indicate a paracrine role for the two hormones. The lamprey locus contains a single neurohypophysial hormone gene, the vasotocin. The synteny of genes in the lamprey locus is conserved in elephant shark, coelacanth and tetrapods but disrupted in teleost fishes. The amphioxus locus encodes a single

  12. Experimental heart failure causes depression-like behavior together with differential regulation of inflammatory and structural genes in the brain

    Anna eFrey

    2014-10-01

    Full Text Available Background-Depression and anxiety are common and independent outcome predictors in patients with chronic heart failure (CHF. However, it is unclear whether CHF causes depression. Thus, we investigated whether mice develop anxiety- and depression-like behavior after induction of ischemic CHF by myocardial infarction (MI.Methods and Results- In order to assess depression-like behavior, anhedonia was investigated by repeatedly testing sucrose preference for 8 weeks after coronary artery ligation or sham operation. Mice with large MI and increased left ventricular dimensions on echocardiography (termed CHF mice showed reduced preference for sucrose, indicating depression-like behavior. 6 weeks after MI, mice were tested for exploratory activity, anxiety-like behavior and cognitive function using the elevated plus maze (EPM, light-dark box (LDB, open field (OF and object recognition (OR tests. In the EPM and OF, CHF mice exhibited diminished exploratory behavior and motivation despite similar movement capability. In the OR, CHF mice had reduced preference for novelty and impaired short-term memory. On histology, CHF mice had unaltered overall cerebral morphology. However, analysis of gene expression by RNA-sequencing in prefrontal cortical, hippocampal, and left ventricular tissue revealed changes in genes related to inflammation and cofactors of neuronal signal transduction in CHF mice, with Nr4a1 being dysregulated both in prefrontal cortex and myocardium after MI. Conclusions-After induction of ischemic CHF, mice exhibited anhedonic behavior, decreased exploratory activity and interest in novelty, and cognitive impairment. Thus, ischemic CHF leads to distinct behavioral changes in mice analogous to symptoms observed in humans with CHF and comorbid depression.

  13. Ethnic identity in context of ethnic discrimination: When does gender and other-group orientation increase risk for depressive symptoms for immigrant-origin young adults?

    Thibeault, M Alexander; Stein, Gabriela L; Nelson-Gray, Rosemery O

    2018-04-01

    Ethnic discrimination increases risk for depressive symptoms, but less is known about factors that influence the impact of this cultural challenge on psychological adjustment for immigrant-origin college students. Sociocultural identity development is especially relevant during emerging adulthood. Studies examining exacerbating or buffering impacts of ethnic identity have yielded mixed results. The current study examines conditions under which one aspect of ethnic identity, affirmation/belonging, moderates the impact of perceived ethnic discrimination stress on depressive symptoms. This was expected to vary by other-group orientation and gender, in accordance with rejection sensitivity theory. A multicultural sample of 290 non-White immigrant-origin emerging adults (aged 18-25) from mixed cultural backgrounds and generational statuses attending a college in the Southeastern United States completed electronic self-report questionnaires. More robust support was provided for social identity theory rather than rejection sensitivity theory: stronger affirmation/belonging was inversely associated with depressive symptoms across the sample, with a notable buffering impact for women. Trend-level results indicated a protective effect for those endorsing stronger affirmation/belonging paired with greater other-group orientation. Additionally, women with weaker affirmation/belonging demonstrated greater increased depressive symptoms compared to men with weaker affirmation/belonging. For this sample, social identity theory was relevant to the impact of affirmation/belonging on the relation between ethnic discrimination and depressive symptoms contingent on other-group orientation and gender. This finding underscores the importance of examining ethnic identity in a nuanced manner. Implications for these results extend to college counseling centers, where inclusion of sociocultural identity in case conceptualization would be useful. (PsycINFO Database Record (c) 2018 APA, all

  14. Perinatal depression and DNA methylation of oxytocin-related genes: a study of mothers and their children.

    King, Leonora; Robins, Stephanie; Chen, Gang; Yerko, Volodymyr; Zhou, Yi; Nagy, Corina; Feeley, Nancy; Gold, Ian; Hayton, Barbara; Turecki, Gustavo; Zelkowitz, Phyllis

    2017-11-01

    The present study investigated the association of perinatal depression (PD) with differential methylation of 3 genomic regions among mother and child dyads: exon 3 within the oxytocin receptor (OXTR) gene and 2 intergenic regions (IGR) between the oxytocin (OXT) and vasopressin (AVP) genes. Maternal PD was assessed at 5 time-points during pregnancy and postpartum. Four groups were established based on Edinburgh Postnatal Depression Scale (EPDS) cut-off scores: no PD, prenatal or postpartum depressive symptoms only and persistent PD (depressive symptoms both prenatally and postpartum). Salivary DNA was collected from mothers and children at the final time-point, 2.9years postpartum. Mothers with persistent PD had significantly higher overall OXTR methylation than the other groups and this pattern extended to 16/22 individual CpG sites. For the IGR, only the region closer to the AVP gene (AVP IGR) showed significant differential methylation, with the persistent PD group displaying the lowest levels of methylation overall, but not for individual CpG sites. These results suggest that transient episodes of depression may not be associated with OXTR hypermethylation. Validation studies need to confirm the downstream biological effects of AVP IGR hypomethylation as it relates to persistent PD. Differential methylation of the OXTR and IGR regions was not observed among children exposed to maternal PD. The consequences of OXTR hypermethylation and AVP IGR hypomethylation found in mothers with persistent PDS may not only impact the OXT system, but may also compromise maternal behavior, potentially resulting in negative outcomes for the developing child. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Evolution and Origin of HRS, a Protein Interacting with Merlin, the Neurofibromatosis 2 Gene Product

    Leonid V. Omelyanchuk

    2009-10-01

    Full Text Available Hepatocyte growth factor receptor tyrosine kinase substrate (HRS is an endosomal protein required for trafficking receptor tyrosine kinases from the early endosome to the lysosome. HRS interacts with Merlin, the Neurofibromatosis 2 (NF2 gene product, and this interaction may be important for Merlin’s tumor suppressor activity. Understanding the evolution, origin, and structure of HRS may provide new insight into Merlin function. We show that HRS homologs are present across a wide range of Metazoa with the yeast Vps27 protein as their most distant ancestor. The phylogenetic tree of the HRS family coincides with species evolution and divergence, suggesting a unique function for HRS. Sequence alignment shows that various protein domains of HRS, including the VHS domain, the FYVE domain, the UIM domain, and the clathrin-binding domain, are conserved from yeast to multicellular organisms. The evolutionary transition from unicellular to multicellular organisms was accompanied by the appearance of a binding site for Merlin, which emerges in the early Metazoa after its separation from flatworms. In addition to the region responsible for growth suppression, the Merlin-binding and STAM-binding domains of HRS are conserved among multicellular organisms. The residue equivalent to tyrosine-377, which is phosphorylated in the human HRS protein, is highly conserved throughout the HRS family. Three additional conserved boxes lacking assigned functions are found in the HRS proteins of Metazoa. While boxes 1 and 3 may constitute the Eps-15- and Snx1-binding sites, respectively, box 2, containing the residue equivalent to tyrosine-377, is likely to be important for HRS phosphorylation. While several functional domains are conserved throughout the HRS family, the STAM-binding, Merlin-binding, and growth suppression domains evolved in the early Metazoa around the time the Merlin protein emerged. As these domains appear during the transition to multicellularity

  16. Functional and evolutionary analysis of alternatively spliced genes is consistent with an early eukaryotic origin of alternative splicing

    Penny David

    2007-10-01

    Full Text Available Abstract Background Alternative splicing has been reported in various eukaryotic groups including plants, apicomplexans, diatoms, amoebae, animals and fungi. However, whether widespread alternative splicing has evolved independently in the different eukaryotic groups or was inherited from their last common ancestor, and may therefore predate multicellularity, is still unknown. To better understand the origin and evolution of alternative splicing and its usage in diverse organisms, we studied alternative splicing in 12 eukaryotic species, comparing rates of alternative splicing across genes of different functional classes, cellular locations, intron/exon structures and evolutionary origins. Results For each species, we find that genes from most functional categories are alternatively spliced. Ancient genes (shared between animals, fungi and plants show high levels of alternative splicing. Genes with products expressed in the nucleus or plasma membrane are generally more alternatively spliced while those expressed in extracellular location show less alternative splicing. We find a clear correspondence between incidence of alternative splicing and intron number per gene both within and between genomes. In general, we find several similarities in patterns of alternative splicing across these diverse eukaryotes. Conclusion Along with previous studies indicating intron-rich genes with weak intron boundary consensus and complex spliceosomes in ancestral organisms, our results suggest that at least a simple form of alternative splicing may already have been present in the unicellular ancestor of plants, fungi and animals. A role for alternative splicing in the evolution of multicellularity then would largely have arisen by co-opting the preexisting process.

  17. Interaction between CRHR1 and BDNF genes increases the risk of recurrent major depressive disorder in Chinese population.

    Zheman Xiao

    Full Text Available BACKGROUND: An important etiological hypothesis about depression is stress has neurotoxic effects that damage the hippocampal cells. Corticotropin-releasing hormone (CRH regulates brain-derived neurotrophic factor (BDNF expression through influencing cAMP and Ca2+ signaling pathways during the course. The aim of this study is to examine the single and combined effects of CRH receptor 1 (CRHR1 and BDNF genes in recurrent major depressive disorder (MDD. METHODOLOGY/PRINCIPAL FINDING: The sample consists of 181 patients with recurrent MDD and 186 healthy controls. Whether genetic variations interaction between CRHR1 and BDNF genes might be associated with increased susceptibility to recurrent MDD was studied by using a gene-based association analysis of single-nucleotide polymorphisms (SNPs. CRHR1 gene (rs1876828, rs242939 and rs242941 and BDNF gene (rs6265 were identified in the samples of patients diagnosed with recurrent MDD and matched controls. Allelic association between CRHR1 rs242939 and recurrent MDD was found in our sample (allelic: p = 0.018, genotypic: p = 0.022 with an Odds Ratio 0.454 (95% CI 0.266-0.775. A global test of these four haplotypes showed a significant difference between recurrent MDD group and control group (chi-2 = 13.117, df = 3, P = 0.016. Furthermore, BDNF and CRHR1 interactions were found in the significant 2-locus, gene-gene interaction models (p = 0.05 using a generalized multifactor dimensionality reduction (GMDR method. CONCLUSION: Our results suggest that an interaction between CRHR1 and BDNF genes constitutes susceptibility to recurrent MDD.

  18. Convergent evolution of RFX transcription factors and ciliary genes predated the origin of metazoans

    Chen Nansheng

    2010-05-01

    Full Text Available Abstract Background Intraflagellar transport (IFT genes, which are critical for the development and function of cilia and flagella in metazoans, are tightly regulated by the Regulatory Factor X (RFX transcription factors (TFs. However, how and when their evolutionary relationship was established remains unknown. Results We have identified evidence suggesting that RFX TFs and IFT genes evolved independently and their evolution converged before the first appearance of metazoans. Both ciliary genes and RFX TFs exist in all metazoans as well as some unicellular eukaryotes. However, while RFX TFs and IFT genes are found simultaneously in all sequenced metazoan genomes, RFX TFs do not co-exist with IFT genes in most pre-metazoans and thus do not regulate them in these organisms. For example, neither the budding yeast nor the fission yeast possesses cilia although both have well-defined RFX TFs. Conversely, most unicellular eukaryotes, including the green alga Chlamydomonas reinhardtii, have typical cilia and well conserved IFT genes but lack RFX TFs. Outside of metazoans, RFX TFs and IFT genes co-exist only in choanoflagellates including M. brevicollis, and only one fungus Allomyces macrogynus of the 51 sequenced fungus genomes. M. brevicollis has two putative RFX genes and a full complement of ciliary genes. Conclusions The evolution of RFX TFs and IFT genes were independent in pre-metazoans. We propose that their convergence in evolution, or the acquired transcriptional regulation of IFT genes by RFX TFs, played a pivotal role in the establishment of metazoan.

  19. Origin and loss of nested LRRTM/α-catenin genes during vertebrate evolution.

    Pavel Uvarov

    Full Text Available Leucine-rich repeat transmembrane neuronal proteins (LRRTMs form in mammals a family of four postsynaptic adhesion proteins, which have been shown to bind neurexins and heparan sulphate proteoglycan (HSPG glypican on the presynaptic side. Mutations in the genes encoding LRRTMs and neurexins are implicated in human cognitive disorders such as schizophrenia and autism. Our analysis shows that in most jawed vertebrates, lrrtm1, lrrtm2, and lrrtm3 genes are nested on opposite strands of large conserved intron of α-catenin genes ctnna2, ctnna1, and ctnna3, respectively. No lrrtm genes could be found in tunicates or lancelets, while two lrrtm genes are found in the lamprey genome, one of which is adjacent to a single ctnna homolog. Based on similar highly positive net charge of lamprey LRRTMs and the HSPG-binding LRRTM3 and LRRTM4 proteins, we speculate that the ancestral LRRTM might have bound HSPG before acquiring neurexins as binding partners. Our model suggests that lrrtm gene translocated into the large ctnna intron in early vertebrates, and that subsequent duplications resulted in three lrrtm/ctnna gene pairs present in most jawed vertebrates. However, we detected three prominent exceptions: (1 the lrrtm3/ctnna3 gene structure is absent in the ray-finned fish genomes, (2 the genomes of clawed frogs contain ctnna1 but lack the corresponding nested (lrrtm2 gene, and (3 contain lrrtm3 gene in the syntenic position but lack the corresponding host (ctnna3 gene. We identified several other protein-coding nested gene structures of which either the host or the nested gene has presumably been lost in the frog or chicken lineages. Interestingly, majority of these nested genes comprise LRR domains.

  20. Ancient origin of placental expression in the growth hormone genes of anthropoid primates.

    Papper, Zack; Jameson, Natalie M; Romero, Roberto; Weckle, Amy L; Mittal, Pooja; Benirschke, Kurt; Santolaya-Forgas, Joaquin; Uddin, Monica; Haig, David; Goodman, Morris; Wildman, Derek E

    2009-10-06

    In anthropoid primates, growth hormone (GH) genes have undergone at least 2 independent locus expansions, one in platyrrhines (New World monkeys) and another in catarrhines (Old World monkeys and apes). In catarrhines, the GH cluster has a pituitary-expressed gene called GH1; the remaining GH genes include placental GHs and placental lactogens. Here, we provide cDNA sequence evidence that the platyrrhine GH cluster also includes at least 3 placenta expressed genes and phylogenetic evidence that placenta expressed anthropoid GH genes have undergone strong adaptive evolution, whereas pituitary-expressed GH genes have faced strict functional constraint. Our phylogenetic evidence also points to lineage-specific gene gain and loss in early placental mammalian evolution, with at least three copies of the GH gene present at the time of the last common ancestor (LCA) of primates, rodents, and laurasiatherians. Anthropoid primates and laurasiatherians share gene descendants of one of these three copies, whereas rodents and strepsirrhine primates each maintain a separate copy. Eight of the amino-acid replacements that occurred on the lineage leading to the LCA of extant anthropoids have been implicated in GH signaling at the maternal-fetal interface. Thus, placental expression of GH may have preceded the separate series of GH gene duplications that occurred in catarrhines and platyrrhines (i.e., the roles played by placenta-expressed GHs in human pregnancy may have a longer evolutionary history than previously appreciated).

  1. The genetic interacting landscape of 63 candidate genes in Major Depressive Disorder: an explorative study.

    Lekman, Magnus; Hössjer, Ola; Andrews, Peter; Källberg, Henrik; Uvehag, Daniel; Charney, Dennis; Manji, Husseini; Rush, John A; McMahon, Francis J; Moore, Jason H; Kockum, Ingrid

    2014-01-01

    Genetic contributions to major depressive disorder (MDD) are thought to result from multiple genes interacting with each other. Different procedures have been proposed to detect such interactions. Which approach is best for explaining the risk of developing disease is unclear. This study sought to elucidate the genetic interaction landscape in candidate genes for MDD by conducting a SNP-SNP interaction analysis using an exhaustive search through 3,704 SNP-markers in 1,732 cases and 1,783 controls provided from the GAIN MDD study. We used three different methods to detect interactions, two logistic regressions models (multiplicative and additive) and one data mining and machine learning (MDR) approach. Although none of the interaction survived correction for multiple comparisons, the results provide important information for future genetic interaction studies in complex disorders. Among the 0.5% most significant observations, none had been reported previously for risk to MDD. Within this group of interactions, less than 0.03% would have been detectable based on main effect approach or an a priori algorithm. We evaluated correlations among the three different models and conclude that all three algorithms detected the same interactions to a low degree. Although the top interactions had a surprisingly large effect size for MDD (e.g. additive dominant model Puncorrected = 9.10E-9 with attributable proportion (AP) value = 0.58 and multiplicative recessive model with Puncorrected = 6.95E-5 with odds ratio (OR estimated from β3) value = 4.99) the area under the curve (AUC) estimates were low (< 0.54). Moreover, the population attributable fraction (PAF) estimates were also low (< 0.15). We conclude that the top interactions on their own did not explain much of the genetic variance of MDD. The different statistical interaction methods we used in the present study did not identify the same pairs of interacting markers. Genetic interaction studies may uncover previously

  2. Heterogeneic dynamics of the structures of multiple gene clusters in two pathogenetically different lines originating from the same phytoplasma.

    Arashida, Ryo; Kakizawa, Shigeyuki; Hoshi, Ayaka; Ishii, Yoshiko; Jung, Hee-Young; Kagiwada, Satoshi; Yamaji, Yasuyuki; Oshima, Kenro; Namba, Shigetou

    2008-04-01

    Phytoplasmas are phloem-limited plant pathogens that are transmitted by insect vectors and are associated with diseases in hundreds of plant species. Despite their small sizes, phytoplasma genomes have repeat-rich sequences, which are due to several genes that are encoded as multiple copies. These multiple genes exist in a gene cluster, the potential mobile unit (PMU). PMUs are present at several distinct regions in the phytoplasma genome. The multicopy genes encoded by PMUs (herein named mobile unit genes [MUGs]) and similar genes elsewhere in the genome (herein named fundamental genes [FUGs]) are likely to have the same function based on their annotations. In this manuscript we show evidence that MUGs and FUGs do not cluster together within the same clade. Each MUG is in a cluster with a short branch length, suggesting that MUGs are recently diverged paralogs, whereas the origin of FUGs is different from that of MUGs. We also compared the genome structures around the lplA gene in two derivative lines of the 'Candidatus Phytoplasma asteris' OY strain, the severe-symptom line W (OY-W) and the mild-symptom line M (OY-M). The gene organizations of the nucleotide sequences upstream of the lplA genes of OY-W and OY-M were dramatically different. The tra5 insertion sequence, an element of PMUs, was found only in this region in OY-W. These results suggest that transposition of entire PMUs and PMU sections has occurred frequently in the OY phytoplasma genome. The difference in the pathogenicities of OY-W and OY-M might be caused by the duplication and transposition of PMUs, followed by genome rearrangement.

  3. Testing Models for the Contributions of Genes and Environment to Developmental Change in Adolescent Depression.

    Gillespie, Nathan A; Eaves, Lindon J; Maes, Hermine; Silberg, Judy L

    2015-07-01

    We tested two models to identify the genetic and environmental processes underlying longitudinal changes in depression among adolescents. The first assumes that observed changes in covariance structure result from the unfolding of inherent, random individual differences in the overall levels and rates of change in depression over time (random growth curves). The second assumes that observed changes are due to time-specific random effects (innovations) accumulating over time (autoregressive effects). We found little evidence of age-specific genetic effects or persistent genetic innovations. Instead, genetic effects are consistent with a gradual unfolding in the liability to depression and rates of change with increasing age. Likewise, the environment also creates significant individual differences in overall levels of depression and rates of change. However, there are also time-specific environmental experiences that persist with fidelity. The implications of these differing genetic and environmental mechanisms in the etiology of depression are considered.

  4. Origin of a function by tandem gene duplication limits the evolutionary capability of its sister copy.

    Hasselmann, Martin; Lechner, Sarah; Schulte, Christina; Beye, Martin

    2010-07-27

    The most remarkable outcome of a gene duplication event is the evolution of a novel function. Little information exists on how the rise of a novel function affects the evolution of its paralogous sister gene copy, however. We studied the evolution of the feminizer (fem) gene from which the gene complementary sex determiner (csd) recently derived by tandem duplication within the honey bee (Apis) lineage. Previous studies showed that fem retained its sex determination function, whereas the rise of csd established a new primary signal of sex determination. We observed a specific reduction of nonsynonymous to synonymous substitution ratios in Apis to non-Apis fem. We found a contrasting pattern at two other genetically linked genes, suggesting that hitchhiking effects to csd, the locus under balancing selection, is not the cause of this evolutionary pattern. We also excluded higher synonymous substitution rates by relative rate testing. These results imply that stronger purifying selection is operating at the fem gene in the presence of csd. We propose that csd's new function interferes with the function of Fem protein, resulting in molecular constraints and limited evolvability of fem in the Apis lineage. Elevated silent nucleotide polymorphism in fem relative to the genome-wide average suggests that genetic linkage to the csd gene maintained more nucleotide variation in today's population. Our findings provide evidence that csd functionally and genetically interferes with fem, suggesting that a newly evolved gene and its functions can limit the evolutionary capability of other genes in the genome.

  5. Evolution Analysis of the Aux/IAA Gene Family in Plants Shows Dual Origins and Variable Nuclear Localization Signals

    Wentao Wu

    2017-10-01

    Full Text Available The plant hormone auxin plays pivotal roles in many aspects of plant growth and development. The auxin/indole-3-acetic acid (Aux/IAA gene family encodes short-lived nuclear proteins acting on auxin perception and signaling, but the evolutionary history of this gene family remains to be elucidated. In this study, the Aux/IAA gene family in 17 plant species covering all major lineages of plants is identified and analyzed by using multiple bioinformatics methods. A total of 434 Aux/IAA genes was found among these plant species, and the gene copy number ranges from three (Physcomitrella patens to 63 (Glycine max. The phylogenetic analysis shows that the canonical Aux/IAA proteins can be generally divided into five major clades, and the origin of Aux/IAA proteins could be traced back to the common ancestor of land plants and green algae. Many truncated Aux/IAA proteins were found, and some of these truncated Aux/IAA proteins may be generated from the C-terminal truncation of auxin response factor (ARF proteins. Our results indicate that tandem and segmental duplications play dominant roles for the expansion of the Aux/IAA gene family mainly under purifying selection. The putative nuclear localization signals (NLSs in Aux/IAA proteins are conservative, and two kinds of new primordial bipartite NLSs in P. patens and Selaginella moellendorffii were discovered. Our findings not only give insights into the origin and expansion of the Aux/IAA gene family, but also provide a basis for understanding their functions during the course of evolution.

  6. Evolution Analysis of the Aux/IAA Gene Family in Plants Shows Dual Origins and Variable Nuclear Localization Signals.

    Wu, Wentao; Liu, Yaxue; Wang, Yuqian; Li, Huimin; Liu, Jiaxi; Tan, Jiaxin; He, Jiadai; Bai, Jingwen; Ma, Haoli

    2017-10-08

    The plant hormone auxin plays pivotal roles in many aspects of plant growth and development. The auxin/indole-3-acetic acid (Aux/IAA) gene family encodes short-lived nuclear proteins acting on auxin perception and signaling, but the evolutionary history of this gene family remains to be elucidated. In this study, the Aux/IAA gene family in 17 plant species covering all major lineages of plants is identified and analyzed by using multiple bioinformatics methods. A total of 434 Aux/IAA genes was found among these plant species, and the gene copy number ranges from three ( Physcomitrella patens ) to 63 ( Glycine max ). The phylogenetic analysis shows that the canonical Aux/IAA proteins can be generally divided into five major clades, and the origin of Aux/IAA proteins could be traced back to the common ancestor of land plants and green algae. Many truncated Aux/IAA proteins were found, and some of these truncated Aux/IAA proteins may be generated from the C-terminal truncation of auxin response factor (ARF) proteins. Our results indicate that tandem and segmental duplications play dominant roles for the expansion of the Aux/IAA gene family mainly under purifying selection. The putative nuclear localization signals (NLSs) in Aux/IAA proteins are conservative, and two kinds of new primordial bipartite NLSs in P. patens and Selaginella moellendorffii were discovered. Our findings not only give insights into the origin and expansion of the Aux/IAA gene family, but also provide a basis for understanding their functions during the course of evolution.

  7. Hybrid origin of Asian aspermic Fasciola flukes is confirmed by analyzing two single-copy genes, pepck and pold

    HAYASHI, Kei; ICHIKAWA-SEKI, Madoka; MOHANTA, Uday Kumar; SHORIKI, Takuya; CHAICHANASAK, Pannigan; ITAGAKI, Tadashi

    2017-01-01

    Nuclear gene markers, phosphoenolpyruvate carboxykinase (pepck) and DNA polymerase delta (pold), have been developed for precise discrimination of Fasciola flukes instead of internal transcribed spacer 1. In this study, these two genes of 730 Fasciola flukes from eight Asian countries were analyzed. The results were compared with their mitochondrial NADH dehydrogenase subunit 1 (nad1) lineages for obtaining a definitive evidence of the hybrid origin of aspermic Fasciola flukes. All the flukes categorized into the aspermic nad1 lineages possessed both the fragment patterns of F. hepatica and F. gigantica (mixed types) in pepck and/or pold. These findings provide clear evidence for the hybrid origin of aspermic Fasciola lineages and suggest that “aspermic Fasciola flukes” should hereafter be called “hybrid Fasciola flukes”. PMID:29187710

  8. A serotonin transporter gene polymorphism predicts peripartum depressive symptoms in an at-risk psychiatric cohort.

    Binder, Elisabeth B; Newport, D Jeffrey; Zach, Elizabeth B; Smith, Alicia K; Deveau, Todd C; Altshuler, Lori L; Cohen, Lee S; Stowe, Zachary N; Cubells, Joseph F

    2010-07-01

    Peripartum major depressive disorder (MDD) is a prevalent psychiatric disorder with potential detrimental consequences for both mother and child. Despite its enormous health care relevance, data regarding genetic predictors of peripartum depression are sparse. The aim of this study was to investigate associations of the serotonin-transporter linked polymorphic region (5-HTTLPR) genotype with peripartum MDD in an at-risk population. Two hundred and seventy four women with a prior history of MDD were genotyped for 5-HTTLPR and serially evaluated in late pregnancy (gestational weeks 31-40), early post-partum (week 1-8) and late post-partum (week 9-24) for diagnosis of a current major depressive episode (MDE) and depressive symptom severity. 5-HTTLPR S-allele carrier status predicted the occurrence of a MDE in the early post-partum period only (OR=5.13, p=0.017). This association persisted despite continued antidepressant treatment. The 5-HTTLPR genotype may be a clinically relevant predictor of early post-partum depression in an at-risk population. Peripartum major depressive disorder is a prevalent psychiatric disorder with potential detrimental consequences for both mother and child. Despite its enormous health care relevance, data regarding genetic predictors of peripartum depression are sparse. The aim of this study was to investigate associations of the serotonin-transporter linked polymorphic region (5-HTTLPR) genotype with peripartum MDD in an at-risk population. Copyright 2009 Elsevier Ltd. All rights reserved.

  9. Phylogenetic analysis of bacterial and archaeal arsC gene sequences suggests an ancient, common origin for arsenate reductase

    Dugas Sandra L

    2003-07-01

    Full Text Available Abstract Background The ars gene system provides arsenic resistance for a variety of microorganisms and can be chromosomal or plasmid-borne. The arsC gene, which codes for an arsenate reductase is essential for arsenate resistance and transforms arsenate into arsenite, which is extruded from the cell. A survey of GenBank shows that arsC appears to be phylogenetically widespread both in organisms with known arsenic resistance and those organisms that have been sequenced as part of whole genome projects. Results Phylogenetic analysis of aligned arsC sequences shows broad similarities to the established 16S rRNA phylogeny, with separation of bacterial, archaeal, and subsequently eukaryotic arsC genes. However, inconsistencies between arsC and 16S rRNA are apparent for some taxa. Cyanobacteria and some of the γ-Proteobacteria appear to possess arsC genes that are similar to those of Low GC Gram-positive Bacteria, and other isolated taxa possess arsC genes that would not be expected based on known evolutionary relationships. There is no clear separation of plasmid-borne and chromosomal arsC genes, although a number of the Enterobacteriales (γ-Proteobacteria possess similar plasmid-encoded arsC sequences. Conclusion The overall phylogeny of the arsenate reductases suggests a single, early origin of the arsC gene and subsequent sequence divergence to give the distinct arsC classes that exist today. Discrepancies between 16S rRNA and arsC phylogenies support the role of horizontal gene transfer (HGT in the evolution of arsenate reductases, with a number of instances of HGT early in bacterial arsC evolution. Plasmid-borne arsC genes are not monophyletic suggesting multiple cases of chromosomal-plasmid exchange and subsequent HGT. Overall, arsC phylogeny is complex and is likely the result of a number of evolutionary mechanisms.

  10. The sex-dependent role of the glucocorticoid receptor in depression: variations in the NR3C1 gene are associated with major depressive disorder in women but not in men.

    Sarubin, Nina; Hilbert, Sven; Naumann, Felix; Zill, Peter; Wimmer, Anna-Maria; Nothdurfter, Caroline; Rupprecht, Rainer; Baghai, Thomas C; Bühner, Markus; Schüle, Cornelius

    2017-03-01

    Genetic variations in the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) have been associated with maladaptive stress responses and major depressive disorder (MDD). In a case-control study design, we examined whether single nucleotide polymorphisms (SNPs) and haploid genotype (haplotype) associations of MR gene NR3C2, GR gene NR3C1 and genes of GR chaperone molecules FK506 binding protein 5 (FKBP5) and corticotrophin-releasing hormone receptor 1 (CRHR1) differed between healthy subjects (n = 634) and inpatients with major depressive disorder (n = 412). All analyses were conducted for women and men separately. After conservative correction of Type-I-error to obtain reliable p values, one SNP in the NR3C1 gene, namely rs6195, showed a significant association with the presence of a major depression (p = 0.048) in females. In contrast, NR3C2, FKBP5 and CRHR1 polymorphisms were not significantly associated with MDD. No haplotype effects could be identified. Our results support the notion of an association between variants of GR-related genes in women and the pathophysiology of depression: females suffering from MDD showed a more than three times higher frequency of the T/C polymorphism compared to controls, which thus seems to increase the vulnerability to depression in females.

  11. Origin and consequences of brain Toll-like receptor 4 pathway stimulation in an experimental model of depression

    Madrigal José LM

    2011-11-01

    Full Text Available Abstract Background There is a pressing need to identify novel pathophysiological pathways relevant to depression that can help to reveal targets for the development of new medications. Toll-like receptor 4 (TLR-4 has a regulatory role in the brain's response to stress. Psychological stress may compromise the intestinal barrier, and increased gastrointestinal permeability with translocation of lipopolysaccharide (LPS from Gram-negative bacteria may play a role in the pathophysiology of major depression. Methods Adult male Sprague-Dawley rats were subjected to chronic mild stress (CMS or CMS+intestinal antibiotic decontamination (CMS+ATB protocols. Levels of components of the TLR-4 signaling pathway, of LPS and of different inflammatory, oxidative/nitrosative and anti-inflammatory mediators were measured by RT-PCR, western blot and/or ELISA in brain prefrontal cortex. Behavioral despair was studied using Porsolt's test. Results CMS increased levels of TLR-4 and its co-receptor MD-2 in brain as well as LPS and LPS-binding protein in plasma. In addition, CMS also increased interleukin (IL-1β, COX-2, PGE2 and lipid peroxidation levels and reduced levels of the anti-inflammatory prostaglandin 15d-PGJ2 in brain tissue. Intestinal decontamination reduced brain levels of the pro-inflammatory parameters and increased 15d-PGJ2, however this did not affect depressive-like behavior induced by CMS. Conclusions Our results suggest that LPS from bacterial translocation is responsible, at least in part, for the TLR-4 activation found in brain after CMS, which leads to release of inflammatory mediators in the CNS. The use of Gram-negative antibiotics offers a potential therapeutic approach for the adjuvant treatment of depression.

  12. Gene-associated markers can assign origin in a weakly structured fish, Atlantic herring

    Bekkevold, Dorte; Helyar, Sarah J.; Limborg, Morten T.

    2015-01-01

    , there are relatively few examples in marine fish displaying accurate origin assignment. We synthesize data for 156 single-nucleotide polymorphisms typed in 1039 herring, Clupea harengus L., spanning the Northeast Atlantic to develop a tool that allows assignment of individual herring to their regional origin. We show......Regulations on the exploitation of populations of commercially important fish species and the ensuing consumer interest in sustainable products have increased the need to accurately identify the population of origin of fish and fish products. Although genomics-based tools have proven highly useful...... the method's suitability to address specific biological questions, as well as management applications. We analyse temporally replicated collections from two areas, the Skagerrak (n = 81, 84, 66) and the western Baltic (n = 52, 52). Both areas harbour heavily fished mixed-origin stocks, complicating...

  13. Selection of suitable housekeeping genes for real-time quantitative PCR in CD4(+ lymphocytes from asthmatics with or without depression.

    Ting Wang

    Full Text Available OBJECTIVE: No optimal housekeeping genes (HKGs have been identified for CD4(+ T cells from non-depressive asthmatic and depressive asthmatic adults for normalizing quantitative real-time PCR (qPCR assays. The aim of present study was to select appropriate HKGs for gene expression analysis in purified CD4(+ T cells from these asthmatics. METHODS: Three groups of subjects (Non-depressive asthmatic, NDA, n = 10, Depressive asthmatic, DA, n = 11, and Healthy control, HC, n = 10 respectively were studied. qPCR for 9 potential HKGs, namely RNA, 28S ribosomal 1 (RN28S1, ribosomal protein, large, P0 (RPLP0, actin, beta (ACTB, cyclophilin A (PPIA, glyceraldehyde-3-phosphate dehydrogenase (GAPDH, phosphoglycerate kinase 1 (PGK1, beta-2-microglobulin (B2M, glucuronidase, beta (GUSB and ribosomal protein L13a (RPL13A, was performed. Then the data were analyzed with three different applications namely BestKeeper, geNorm, and NormFinder. RESULTS: The analysis of gene expression data identified B2M and RPLP0 as the most stable reference genes and showed that the level of PPIA was significantly different among subjects of three groups when the two best HKGs identified were applied. Post-hoc analysis by Student-Newman-Keuls correction shows that depressive asthmatics and non-depressive asthmatics exhibited lower expression level of PPIA than healthy controls (p<0.05. CONCLUSIONS: B2M and RPLP0 were identified as the most optimal HKGs in gene expression studies involving human blood CD4(+ T cells derived from normal, depressive asthmatics and non-depressive asthmatics. The suitability of using the PPIA gene as the HKG for such studies was questioned due to its low expression in asthmatics.

  14. Altered Expression of Endoplasmic Reticulum Stress Associated Genes in Hippocampus of Learned Helpless Rats: Relevance to Depression Pathophysiology

    Matthew A. Timberlake

    2016-01-01

    Full Text Available The unfolded protein response (UPR is an evolutionarily conserved defensive mechanism that is used by cells to correct misfolded proteins that accumulate in the endoplasmic reticulum. These proteins are misfolded as a result of physical stress on a cell and initiate a host of downstream effects that govern processes ranging from inflammation to apoptosis. To examine whether UPR system plays a role in depression, we examined the expression of genes that are part of the three different pathways for UPR activation, namely GRP78, GRP94, ATF6, XBP-1, ATF4 and CHOP using an animal model system that distinguishes vulnerability (learned helpless, LH from resistance (non-learned helpless, NLH to develop depression. Rats were exposed to inescapable shock on day 1 and day 7 and were tested for escape latency on day 14. Rats not given shock but tested for escape latency were used as tested control (TC. Plasma corticosterone levels were measured. Expression levels of various UPR associated genes were determined in hippocampus using qPCR. We found that the corticosterone level was higher in LH rats compared with TC and NLH rats. Expression of GRP78, GRP94, ATF6 and XBP-1 were significantly upregulated in LH rats compared with TC or NLH rats, whereas NLH rats did not show such changes. Expression levels of ATF4 and CHOP showed trends towards upregulation but were not significantly altered in LH or NLH group. Our data show strong evidence of altered UPR system in depressed rats, which could be associated with development of depressive behavior.

  15. Molecular Pathways of Disturbed Sleep and Depression: Studies on Adenosine and Gene Expression Patterns

    Gass, Natalia

    2010-01-01

    Background: Adenosine is a potent sleep-promoting substance, and one of its targets is the basal forebrain. Fairly little is known about its mechanism of action in the basal forebrain and about the receptor subtype mediating its regulating effects on sleep homeostasis. Homeostatic deficiency might be one of the causes of the profoundly disturbed sleep pattern in major depressive disorder, which could explain the reduced amounts of delta-activity-rich stages 3 and 4. Since major depression has...

  16. Resequencing three candidate genes discovers seven potentially deleterious variants susceptibility to major depressive disorder and suicide attempts in Chinese.

    Rao, Shitao; Leung, Cherry She Ting; Lam, Macro Hb; Wing, Yun Kwok; Waye, Mary Miu Yee; Tsui, Stephen Kwok Wing

    2017-03-01

    To date almost 200 genes were found to be associated with major depressive disorder (MDD) or suicide attempts (SA), but very few genes were reported for their molecular mechanisms. This study aimed to find out whether there were common or rare variants in three candidate genes altering the risk for MDD and SA in Chinese. Three candidate genes (HOMER1, SLC6A4 and TEF) were chosen for resequencing analysis and association studies as they were reported to be involved in the etiology of MDD and SA. Following that, bioinformatics analyses were applied on those variants of interest. After resequencing analysis and alignment for the amplicons, a total of 34 common or rare variants were found in the randomly selected 36 Hong Kong Chinese patients with both MDD and SA. Among those, seven variants show potentially deleterious features. Rs60029191 and a rare variant located in regulatory region of the HOMER1 gene may affect the promoter activities through interacting with predicted transcription factors. Two missense mutations existed in the SLC6A4 coding regions were firstly reported in Hong Kong Chinese MDD and SA patients, and both of them could affect the transport efficiency of SLC6A4 to serotonin. Moreover, a common variant rs6354 located in the untranslated region of this gene may affect the expression level or exonic splicing of serotonin transporter. In addition, both of a most studied polymorphism rs738499 and a low-frequency variant in the promoter region of the TEF gene were found to be located in potential transcription factor binding sites, which may let the two variants be able to influence the promoter activities of the gene. This study elucidated the potentially molecular mechanisms of the three candidate genes altering the risk for MDD and SA. These findings implied that not only common variants but rare variants could make contributions to the genetic susceptibility to MDD and SA in Chinese. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Comparative genomic analysis of the Lipase3 gene family in five plant species reveals distinct evolutionary origins.

    Wang, Dan; Zhang, Lin; Hu, JunFeng; Gao, Dianshuai; Liu, Xin; Sha, Yan

    2018-04-01

    Lipases are physiologically important and ubiquitous enzymes that share a conserved domain and are classified into eight different families based on their amino acid sequences and fundamental biological properties. The Lipase3 family of lipases was reported to possess a canonical fold typical of α/β hydrolases and a typical catalytic triad, suggesting a distinct evolutionary origin for this family. Genes in the Lipase3 family do not have the same functions, but maintain the conserved Lipase3 domain. There have been extensive studies of Lipase3 structures and functions, but little is known about their evolutionary histories. In this study, all lipases within five plant species were identified, and their phylogenetic relationships and genetic properties were analyzed and used to group them into distinct evolutionary families. Each identified lipase family contained at least one dicot and monocot Lipase3 protein, indicating that the gene family was established before the split of dicots and monocots. Similar intron/exon numbers and predicted protein sequence lengths were found within individual groups. Twenty-four tandem Lipase3 gene duplications were identified, implying that the distinctive function of Lipase3 genes appears to be a consequence of translocation and neofunctionalization after gene duplication. The functional genes EDS1, PAD4, and SAG101 that are reportedly involved in pathogen response were all located in the same group. The nucleotide diversity (Dxy) and the ratio of nonsynonymous to synonymous nucleotide substitutions rates (Ka/Ks) of the three genes were significantly greater than the average across the genomes. We further observed evidence for selection maintaining diversity on three genes in the Toll-Interleukin-1 receptor type of nucleotide binding/leucine-rich repeat immune receptor (TIR-NBS LRR) immunity-response signaling pathway, indicating that they could be vulnerable to pathogen effectors.

  18. Sleep homeostatic pressure and PER3 VNTR gene polymorphism influence antidepressant response to sleep deprivation in bipolar depression.

    Dallaspezia, Sara; Locatelli, Clara; Lorenzi, Cristina; Pirovano, Adele; Colombo, Cristina; Benedetti, Francesco

    2016-03-01

    Combined Total sleep deprivation (TSD) and light therapy (LT) cause a rapid improvement in bipolar depression which has been hypothesized to be paralleled by changes in sleep homeostasis. Recent studies showed that bipolar patients had lower changes of EEG theta power after sleep and responders to antidepressant TSD+LT slept less and showed a lower increase of EEG theta power then non-responders. A polymorphism in PER3 gene has been associated with diurnal preference, sleep structure and homeostatic response to sleep deprivation in healthy subjects. We hypothesized that the individual variability in the homeostatic response to TSD could be a correlate of antidepressant response and be influenced by genetic factors. We administered three TSD+LT cycles to bipolar depressed patients. Severity of depression was rated on Hamilton Depression Rating Scale. Actigraphic recordings were performed in a group of patients. PER3 polymorphism influenced changes in total sleep time (F=2.24; p=0.024): while PER3(4/4) and PER3(4/5) patients showed a reduction in it after treatment, PER3(5/5) subjects showed an increase of about 40min, suggesting a higher homeostatic pressure. The same polymorphism influenced the change of depressive symptomatology during treatment (F=3.72; p=0.028). Sleep information was recorded till the day after the end of treatment: a longer period of observation could give more information about the possible maintenance of allostatic adaptation. A higher sleep homeostatic pressure reduced the antidepressant response to TSD+LT, while an allostatic adaptation to sleep loss was associated with better response. This process seems to be under genetic control. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Origin and Evolution of Nitrogen Fixation Genes on Symbiosis Islands and Plasmid in Bradyrhizobium

    Okubo, Takashi; Piromyou, Pongdet; Tittabutr, Panlada; Teaumroong, Neung; Minamisawa, Kiwamu

    2016-01-01

    The nitrogen fixation (nif) genes of nodule-forming Bradyrhizobium strains are generally located on symbiosis islands or symbiosis plasmids, suggesting that these genes have been transferred laterally. The nif genes of rhizobial and non-rhizobial Bradyrhizobium strains were compared in order to infer the evolutionary histories of nif genes. Based on all codon positions, the phylogenetic tree of concatenated nifD and nifK sequences showed that nifDK on symbiosis islands formed a different clade from nifDK on non-symbiotic loci (located outside of symbiosis islands and plasmids) with elongated branches; however, these genes were located in close proximity, when only the 1st and 2nd codon positions were analyzed. The guanine (G) and cytosine (C) content of the 3rd codon position of nifDK on symbiosis islands was lower than that on non-symbiotic loci. These results suggest that nif genes on symbiosis islands were derived from the non-symbiotic loci of Bradyrhizobium or closely related strains and have evolved toward a lower GC content with a higher substitution rate than the ancestral state. Meanwhile, nifDK on symbiosis plasmids clustered with nifDK on non-symbiotic loci in the tree representing all codon positions, and the GC content of symbiotic and non-symbiotic loci were similar. These results suggest that nif genes on symbiosis plasmids were derived from the non-symbiotic loci of Bradyrhizobium and have evolved with a similar evolutionary pattern and rate as the ancestral state. PMID:27431195

  20. Association analysis between mitogen-activated protein/extracellular signal-regulated kinase (MEK) gene polymorphisms and depressive disorder in the Han Chinese population.

    Hu, Yingyan; Hong, Wu; Smith, Alicia; Yu, Shunying; Li, Zezhi; Wang, Dongxiang; Yuan, Chengmei; Cao, Lan; Wu, Zhiguo; Huang, Jia; Fralick, Drew; Phillips, Michael Robert; Fang, Yiru

    2017-11-01

    Recent research findings suggest that BDNF and BDNF signaling pathways participate in the development of major depressive disorder. Mitogen-activated extracellular signal-regulated kinase (MEK) is the most important kinase in the extracellular signal-regulated kinase pathway, and the extracellular signal-regulated kinase pathway is the key signaling pathway of BDNF, so it may play a role in development of depressive disorder. The aim of this study is to investigate the association between polymorphisms of the MAP2K1 (also known as MEK) gene and depressive disorder. Three single nucleotide polymorphisms (SNPs), were significantly associated with depressive disorder: rs1549854 (p = 0.006), rs1432441 (p = 0.025), and rs7182853 (p = 0.039). When subdividing the sample by gender, two of the SNPs remained statistically associated with depressive disorder in females: rs1549854 (p = 0.013) and rs1432441 (p = 0.04). The rs1549854 and rs1432441 polymorphisms of the MAP2K1 gene may be associated with major depressive disorder, especially in females. This study is the first to report that the MAP2K1 gene may be a genetic marker for depressive disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Ancient Origin of the U2 Small Nuclear RNA Gene-Targeting Non-LTR Retrotransposons Utopia.

    Kojima, Kenji K; Jurka, Jerzy

    2015-01-01

    Most non-long terminal repeat (non-LTR) retrotransposons encoding a restriction-like endonuclease show target-specific integration into repetitive sequences such as ribosomal RNA genes and microsatellites. However, only a few target-specific lineages of non-LTR retrotransposons are distributed widely and no lineage is found across the eukaryotic kingdoms. Here we report the most widely distributed lineage of target sequence-specific non-LTR retrotransposons, designated Utopia. Utopia is found in three supergroups of eukaryotes: Amoebozoa, SAR, and Opisthokonta. Utopia is inserted into a specific site of U2 small nuclear RNA genes with different strength of specificity for each family. Utopia families from oomycetes and wasps show strong target specificity while only a small number of Utopia copies from reptiles are flanked with U2 snRNA genes. Oomycete Utopia families contain an "archaeal" RNase H domain upstream of reverse transcriptase (RT), which likely originated from a plant RNase H gene. Analysis of Utopia from oomycetes indicates that multiple lineages of Utopia have been maintained inside of U2 genes with few copy numbers. Phylogenetic analysis of RT suggests the monophyly of Utopia, and it likely dates back to the early evolution of eukaryotes.

  2. Investigation of Virulence Genes by PCR in Stapylococcus aureus Isolates Originated from Subclinical Bovine Mastitis in Turkey

    Murat Karahan, Mehmet Nuri Acik1* and Burhan Cetinkaya

    2011-06-01

    Full Text Available The aim of the present study was to characterize coagulase (coa positive Staphylococcus aureus strains (n=92 isolated from bovine subclinical mastitis in Turkey by PCR amplification of clumping factor A (clfA and protein A (spa genes. All the coa-positive S. aureus isolates were determined to harbor the genes encoding the IgG binding region (spa-IgG and the X region (spa-X of spa. On the other hand, 84 (91.3% isolates were positive for clfA gene. These three genes displayed size polymorphisms. It was concluded that spa gene polymorphisms for S. aureus, when used together with coa-PCR, can be proposed as good alternatives to conventional methods in typing S. aureus isolates of bovine origin which may provide valuable data for the development of effective control strategies against staphylococcal mastitis. The results of the present study showed that S. aureus isolates responsible for the mastitis cases in Turkey were genetically diverse.

  3. Carotenoid content and root color of cultivated carrot: a candidate-gene association study using an original broad unstructured population.

    Matthieu Jourdan

    Full Text Available Accumulated in large amounts in carrot, carotenoids are an important product quality attribute and therefore a major breeding trait. However, the knowledge of carotenoid accumulation genetic control in this root vegetable is still limited. In order to identify the genetic variants linked to this character, we performed an association mapping study with a candidate gene approach. We developed an original unstructured population with a broad genetic basis to avoid the pitfall of false positive detection due to population stratification. We genotyped 109 SNPs located in 17 candidate genes – mostly carotenoid biosynthesis genes – on 380 individuals, and tested the association with carotenoid contents and color components. Total carotenoids and β-carotene contents were significantly associated with genes zeaxanthin epoxydase (ZEP, phytoene desaturase (PDS and carotenoid isomerase (CRTISO while α-carotene was associated with CRTISO and plastid terminal oxidase (PTOX genes. Color components were associated most significantly with ZEP. Our results suggest the involvement of the couple PDS/PTOX and ZEP in carotenoid accumulation, as the result of the metabolic and catabolic activities respectively. This study brings new insights in the understanding of the carotenoid pathway in non-photosynthetic organs.

  4. Bone-associated gene evolution and the origin of flight in birds.

    Machado, João Paulo; Johnson, Warren E; Gilbert, M Thomas P; Zhang, Guojie; Jarvis, Erich D; O'Brien, Stephen J; Antunes, Agostinho

    2016-05-18

    Bones have been subjected to considerable selective pressure throughout vertebrate evolution, such as occurred during the adaptations associated with the development of powered flight. Powered flight evolved independently in two extant clades of vertebrates, birds and bats. While this trait provided advantages such as in aerial foraging habits, escape from predators or long-distance travels, it also imposed great challenges, namely in the bone structure. We performed comparative genomic analyses of 89 bone-associated genes from 47 avian genomes (including 45 new), 39 mammalian, and 20 reptilian genomes, and demonstrate that birds, after correcting for multiple testing, have an almost two-fold increase in the number of bone-associated genes with evidence of positive selection (~52.8 %) compared with mammals (~30.3 %). Most of the positive-selected genes in birds are linked with bone regulation and remodeling and thirteen have been linked with functional pathways relevant to powered flight, including bone metabolism, bone fusion, muscle development and hyperglycemia levels. Genes encoding proteins involved in bone resorption, such as TPP1, had a high number of sites under Darwinian selection in birds. Patterns of positive selection observed in bird ossification genes suggest that there was a period of intense selective pressure to improve flight efficiency that was closely linked with constraints on body size.

  5. Early Developmental and Evolutionary Origins of Gene Body DNA Methylation Patterns in Mammalian Placentas.

    Diane I Schroeder

    2015-08-01

    Full Text Available Over the last 20-80 million years the mammalian placenta has taken on a variety of morphologies through both divergent and convergent evolution. Recently we have shown that the human placenta genome has a unique epigenetic pattern of large partially methylated domains (PMDs and highly methylated domains (HMDs with gene body DNA methylation positively correlating with level of gene expression. In order to determine the evolutionary conservation of DNA methylation patterns and transcriptional regulatory programs in the placenta, we performed a genome-wide methylome (MethylC-seq analysis of human, rhesus macaque, squirrel monkey, mouse, dog, horse, and cow placentas as well as opossum extraembryonic membrane. We found that, similar to human placenta, mammalian placentas and opossum extraembryonic membrane have globally lower levels of methylation compared to somatic tissues. Higher relative gene body methylation was the conserved feature across all mammalian placentas, despite differences in PMD/HMDs and absolute methylation levels. Specifically, higher methylation over the bodies of genes involved in mitosis, vesicle-mediated transport, protein phosphorylation, and chromatin modification was observed compared with the rest of the genome. As in human placenta, higher methylation is associated with higher gene expression and is predictive of genic location across species. Analysis of DNA methylation in oocytes and preimplantation embryos shows a conserved pattern of gene body methylation similar to the placenta. Intriguingly, mouse and cow oocytes and mouse early embryos have PMD/HMDs but their placentas do not, suggesting that PMD/HMDs are a feature of early preimplantation methylation patterns that become lost during placental development in some species and following implantation of the embryo.

  6. Single-copy nuclear genes place haustorial Hydnoraceae within piperales and reveal a cretaceous origin of multiple parasitic angiosperm lineages.

    Julia Naumann

    Full Text Available Extreme haustorial parasites have long captured the interest of naturalists and scientists with their greatly reduced and highly specialized morphology. Along with the reduction or loss of photosynthesis, the plastid genome often decays as photosynthetic genes are released from selective constraint. This makes it challenging to use traditional plastid genes for parasitic plant phylogenetics, and has driven the search for alternative phylogenetic and molecular evolutionary markers. Thus, evolutionary studies, such as molecular clock-based age estimates, are not yet available for all parasitic lineages. In the present study, we extracted 14 nuclear single copy genes (nSCG from Illumina transcriptome data from one of the "strangest plants in the world", Hydnora visseri (Hydnoraceae. A ~15,000 character molecular dataset, based on all three genomic compartments, shows the utility of nSCG for reconstructing phylogenetic relationships in parasitic lineages. A relaxed molecular clock approach with the same multi-locus dataset, revealed an ancient age of ~91 MYA for Hydnoraceae. We then estimated the stem ages of all independently originated parasitic angiosperm lineages using a published dataset, which also revealed a Cretaceous origin for Balanophoraceae, Cynomoriaceae and Apodanthaceae. With the exception of Santalales, older parasite lineages tend to be more specialized with respect to trophic level and have lower species diversity. We thus propose the "temporal specialization hypothesis" (TSH implementing multiple independent specialization processes over time during parasitic angiosperm evolution.

  7. ORIGINAL ARTICLES Otosclerosis and TGF-β1 gene in black South ...

    2008-08-20

    Aug 20, 2008 ... conductive hearing loss among adult Caucasians.4 Theories about the aetiology of otosclerosis have been postulated but, despite extensive research, its origin remains unclear.1. Genetically, otosclerosis is considered to be a multifactorial and complex disease.1,2,5 During the embryonic formation of the.

  8. Ancient origin and gene mosaicism of the progenitor of Mycobacterium tuberculosis.

    M Cristina Gutierrez

    2005-09-01

    Full Text Available The highly successful human pathogen Mycobacterium tuberculosis has an extremely low level of genetic variation, which suggests that the entire population resulted from clonal expansion following an evolutionary bottleneck around 35,000 y ago. Here, we show that this population constitutes just the visible tip of a much broader progenitor species, whose extant representatives are human isolates of tubercle bacilli from East Africa. In these isolates, we detected incongruence among gene phylogenies as well as mosaic gene sequences, whose individual elements are retrieved in classical M. tuberculosis. Therefore, despite its apparent homogeneity, the M. tuberculosis genome appears to be a composite assembly resulting from horizontal gene transfer events predating clonal expansion. The amount of synonymous nucleotide variation in housekeeping genes suggests that tubercle bacilli were contemporaneous with early hominids in East Africa, and have thus been coevolving with their human host much longer than previously thought. These results open novel perspectives for unraveling the molecular bases of M. tuberculosis evolutionary success.

  9. A paradoxical association of an oxytocin receptor gene polymorphism: Early-life adversity and vulnerability to depression

    Robyn Jane McQuaid

    2013-07-01

    Full Text Available Several prosocial behaviors may be influenced by the hormone oxytocin. In line with this perspective, the oxytocin receptor (OXTR gene single nucleotide polymorphism (SNP, rs53576, has been associated with a broad range of social behaviors. In this regard, the G allele of the OXTR SNP has been accompanied by beneficial attributes such as increased empathy, optimism and trust. In the current study among university students (N = 288, it was shown that early-life maltreatment was associated with depressive symptoms, and that the OXTR genotype moderated this relationship, such that under high levels of childhood maltreatment, only individuals with GG/GA genotype demonstrated increased depressive symptomatology compared to those with the AA genotype. In addition, the role of distrust in mediating the relation between childhood maltreatment and depression seemed to be more important among G allele carriers compared to individuals with the AA genotype. Thus, a breach in trust (i.e. in the case of early-life abuse or neglect may have a more deleterious effect among G carriers, who have been characterized as more prosocial and attuned to social cues. The data suggested that G carriers of the OXTR might favor social sensitivity and thus might have been more vulnerable to the effects of early-life adversity.

  10. No Association of BDNF, COMT, MAOA, SLC6A3, and SLC6A4 Genes and Depressive Symptoms in a Sample of Healthy Colombian Subjects.

    González-Giraldo, Yeimy; Camargo, Andrés; López-León, Sandra; Forero, Diego A

    2015-01-01

    Background. Major depressive disorder (MDD) is the second cause of years lived with disability around the world. A large number of studies have been carried out to identify genetic risk factors for MDD and related endophenotypes, mainly in populations of European and Asian descent, with conflicting results. The main aim of the current study was to analyze the possible association of five candidate genes and depressive symptoms in a Colombian sample of healthy subjects. Methods and Materials. The Spanish adaptation of the Hospital Anxiety and Depression Scale (HADS) was applied to one hundred eighty-eight healthy Colombian subjects. Five functional polymorphisms were genotyped using PCR-based assays: BDNF-Val66Met (rs6265), COMT-Val158Met (rs4680), SLC6A4-HTTLPR (rs4795541), MAOA-uVNTR, and SLC6A3-VNTR (rs28363170). Result. We did not find significant associations with scores of depressive symptoms, derived from the HADS, for any of the five candidate genes (nominal p values >0.05). In addition, we did not find evidence of significant gene-gene interactions. Conclusion. This work is one of the first studies of candidate genes for depressive symptoms in a Latin American sample. Study of additional genetic and epigenetic variants, taking into account other pathophysiological theories, will help to identify novel candidates for MDD in populations around the world.

  11. Interaction between FKBP5 gene and childhood trauma on psychosis, depression and anxiety symptoms in a non-clinical sample.

    de Castro-Catala, Marta; Peña, Elionora; Kwapil, Thomas R; Papiol, Sergi; Sheinbaum, Tamara; Cristóbal-Narváez, Paula; Ballespí, Sergi; Barrantes-Vidal, Neus; Rosa, Araceli

    2017-11-01

    Childhood trauma has been associated with a heightened risk for presenting clinical and non-clinical psychopathology in adulthood. Genes related with the stress response, such as the FK506 binding protein 51 (FKBP5), are plausible candidates moderating the effects of childhood trauma on the emergence of such symptoms later on. The present study aimed to explore the moderating role of FKBP5 genetic variability on the association of different types of childhood trauma with subclinical psychosis, depression and anxiety in a non-clinical sample. Schizotypy, psychotic-like experiences, depression and anxiety symptoms and childhood trauma were assessed in 808 young adults. Two FKBP5 haplotypic blocks were detected: block 1 (rs3800373 - rs9296158 - rs1360780) and block 2 (rs9470080 - rs4713916). Subjects were classified in two groups according to whether they carried or not the risk haplotype previously described in the literature (block 1: CAT and block 2: TA). Linear regression analyses were used to study (i) the main effects of childhood trauma and FKBP5 haplotype blocks and (ii) their interaction effects on the mentioned forms of psychopathology. All childhood trauma scales, except sexual abuse, were associated with schizotypy, psychotic-like experiences, depression and anxiety symptoms. None of the analysed symptoms was associated with the main effects of FKBP5 genetic variability. However an interaction effect between block 1 and physical abuse was observed on anxiety, with lower scores in CAT carriers. This effect was driven by SNP 1 and 2. Moreover, an interaction effect between block 2 and physical abuse was identified on the variables tapping depressive and anxiety symptoms. Specifically, non-TA carrier subjects who were exposed to physical abuse were found to be at higher risk for depressive and anxiety symptoms. These effects were driven by SNP 5. No interaction effect was observed for the other variables. Our data suggest that exposure to childhood physical

  12. Sequence of the non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase from Nicotiana plumbaginifolia and phylogenetic origin of the gene family.

    Habenicht, A; Quesada, A; Cerff, R

    1997-10-01

    A cDNA-library has been constructed from Nicotiana plumbaginifolia seedlings, and the non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase (GapN, EC 1.2.1.9) was isolated by plaque hybridization using the cDNA from pea as a heterologous probe. The cDNA comprises the entire GapN coding region. A putative polyadenylation signal is identified. Phylogenetic analysis based on the deduced amino acid sequences revealed that the GapN gene family represents a separate ancient branch within the aldehyde dehydrogenase superfamily. It can be shown that the GapN gene family and other distinct branches of the superfamily have its phylogenetic origin before the separation of primary life-forms. This further demonstrates that already very early in evolution, a broad diversification of the aldehyde dehydrogenases led to the formation of the superfamily.

  13. Functional and evolutionary analysis of alternatively spliced genes is consistent with an early eukaryotic origin of alternative splicing

    Irimia, Manuel; Rukov, Jakob Lewin; Penny, David

    2007-01-01

    , and may therefore predate multicellularity, is still unknown. To better understand the origin and evolution of alternative splicing and its usage in diverse organisms, we studied alternative splicing in 12 eukaryotic species, comparing rates of alternative splicing across genes of different functional......, we find several similarities in patterns of alternative splicing across these diverse eukaryotes. CONCLUSION: Along with previous studies indicating intron-rich genes with weak intron boundary consensus and complex spliceosomes in ancestral organisms, our results suggest that at least a simple form...... of alternative splicing may already have been present in the unicellular ancestor of plants, fungi and animals. A role for alternative splicing in the evolution of multicellularity then would largely have arisen by co-opting the preexisting process....

  14. Gene expression profiling in chemoresistant variants of three cell lines of different origin

    Johnsson, Anders; Vallon-Christensson, Johan; Strand, Carina

    2005-01-01

    lines (K562 leukemia, MCF-7 breast cancer and S1 colon cancer) with acquired resistance against five cytostatic drugs; daunorubicin (DNR), doxorubicin (DOX), vincristine (VCR), etoposide (VP) and mitoxantrone (MX). RESULTS: The resistant cell lines clustered together based on their type of origin...... was also seen in, e.g., GSTs, topoisomerases, caveolins, annexins and CD44. CONCLUSION: These results will constitute a platform for further studies on specific pathways and biological processes involved in chemotherapy resistance....

  15. Gene expression analysis of zebrafish melanocytes, iridophores, and retinal pigmented epithelium reveals indicators of biological function and developmental origin.

    Charles W Higdon

    Full Text Available In order to facilitate understanding of pigment cell biology, we developed a method to concomitantly purify melanocytes, iridophores, and retinal pigmented epithelium from zebrafish, and analyzed their transcriptomes. Comparing expression data from these cell types and whole embryos allowed us to reveal gene expression co-enrichment in melanocytes and retinal pigmented epithelium, as well as in melanocytes and iridophores. We found 214 genes co-enriched in melanocytes and retinal pigmented epithelium, indicating the shared functions of melanin-producing cells. We found 62 genes significantly co-enriched in melanocytes and iridophores, illustrative of their shared developmental origins from the neural crest. This is also the first analysis of the iridophore transcriptome. Gene expression analysis for iridophores revealed extensive enrichment of specific enzymes to coordinate production of their guanine-based reflective pigment. We speculate the coordinated upregulation of specific enzymes from several metabolic pathways recycles the rate-limiting substrate for purine synthesis, phosphoribosyl pyrophosphate, thus constituting a guanine cycle. The purification procedure and expression analysis described here, along with the accompanying transcriptome-wide expression data, provide the first mRNA sequencing data for multiple purified zebrafish pigment cell types, and will be a useful resource for further studies of pigment cell biology.

  16. Geographic and Research Center Origins of Rice Resistance to Asian Planthoppers and Leafhoppers: Implications for Rice Breeding and Gene Deployment

    Finbarr G. Horgan

    2017-09-01

    Full Text Available This study examines aspects of virulence to resistant rice varieties among planthoppers and leafhoppers. Using a series of resistant varieties, brown planthopper, Nilaparvata lugens, virulence was assessed in seedlings and early-tillering plants at seven research centers in South and East Asia. Virulence of the whitebacked planthopper, Sogatella furcifera, in Taiwan and the Philippines was also assessed. Phylogenetic analysis of the varieties using single-nucleotide polymorphisms (SNPs indicated a clade of highly resistant varieties from South Asia with two further South Asian clades of moderate resistance. Greenhouse bioassays indicated that planthoppers can develop virulence against multiple resistance genes including genes introgressed from wild rice species. Nilaparvata lugens populations from Punjab (India and the Mekong Delta (Vietnam were highly virulent to a range of key resistance donors irrespective of variety origin. Sogatella furcifera populations were less virulent to donors than N. lugens; however, several genes for resistance to S. furcifera are now ineffective in East Asia. A clade of International Rice Research Institute (IRRI-bred varieties and breeding lines, without identified leafhopper-resistance genes, were highly resistant to the green leafhopper, Nephotettix virescens. Routine phenotyping during breeding programs likely maintains high levels of quantitative resistance to leafhoppers. We discuss these results in the light of breeding and deploying resistant rice in Asia.

  17. Rapid rise of the ESBL and mcr-1 genes in Escherichia coli of chicken origin in China, 2008-2014.

    Wu, Congming; Wang, Yingchao; Shi, Xiaomin; Wang, Shuang; Ren, Hongwei; Shen, Zhangqi; Wang, Yang; Lin, Juchun; Wang, Shaolin

    2018-03-14

    Extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) strains are emerging around the world as a source of resistance to β-lactam antibiotics such as ampicillin, cefotaxime, and ceftazidime. mcr-1 is a novel plasmid-mediated gene conferring resistance to colistin. The aim of this study was to investigate the prevalence of ESBL-EC mcr-1 of chicken origin in the different provinces of China during 2008-2014. Overall, 341 of 821 isolates were determined to be ESBL-EC strains, and the proportion of ESBL-positive strains almost doubled from 2008 to 2014. The findings of our study revealed regional differences, with significantly more ESBL-EC isolates from stockbreeding in concentrated poultry industry areas in Shandong than from the other four provinces. The ESBL type analysis showed that bla CTX-M was the most prevalent ESBL-encoding gene (92.7%). In total, twelve subtypes of CTX-M genes were detected, among which, bla CTX-M-55 (34.3%) and bla CTX-M-65 (17.9%) were the major identified genotypes. In addition, bla TEM and pAmpC genes were carried by 86.0% and 8.5% of isolates, respectively. In this study, we also observed 44 E. coli isolates with multiple ST types (ST46, ST1286, ST10, ST29, ST101, and ST354) carrying mcr-1, and the majority of mcr-1-carrying plasmids were IncI2. The whole-genome sequencing analysis indicated the co-existence of bla CTX-M and mcr-1 in ESBL-EC of both animal and human origin, and phylogenetic analysis further revealed their close relationship, especially several isolates sharing a small number of SNPs, which suggested the increasing trend of co-existence and transmission of ESBL and mcr-1 in both clinical medicine and veterinary medicine.

  18. New insights into the evolutionary origins of the recombination-activating gene proteins and V(D)J recombination.

    Carmona, Lina Marcela; Schatz, David G

    2017-06-01

    The adaptive immune system of jawed vertebrates relies on V(D)J recombination as one of the main processes to generate the diverse array of receptors necessary for the recognition of a wide range of pathogens. The DNA cleavage reaction necessary for the assembly of the antigen receptor genes from an array of potential gene segments is mediated by the recombination-activating gene proteins RAG1 and RAG2. The RAG proteins have been proposed to originate from a transposable element (TE) as they share mechanistic and structural similarities with several families of transposases and are themselves capable of mediating transposition. A number of RAG-like proteins and TEs with sequence similarity to RAG1 and RAG2 have been identified, but only recently has their function begun to be characterized, revealing mechanistic links to the vertebrate RAGs. Of particular significance is the discovery of ProtoRAG, a transposon superfamily found in the genome of the basal chordate amphioxus. ProtoRAG has many of the sequence and mechanistic features predicted for the ancestral RAG transposon and is likely to be an evolutionary relative of RAG1 and RAG2. In addition, early observations suggesting that RAG1 is able to mediate V(D)J recombination in the absence of RAG2 have been confirmed, implying independent evolutionary origins for the two RAG genes. Here, recent progress in identifying and characterizing RAG-like proteins and the TEs that encode them is summarized and a refined model for the evolution of V(D)J recombination and the RAG proteins is presented. © 2016 Federation of European Biochemical Societies.

  19. Yersinia enterocolitica of porcine origin: carriage of virulence genes and genotypic diversity.

    Tadesse, Daniel A; Bahnson, Peter B; Funk, Julie A; Morrow, W E Morgan; Abley, Melanie J; Ponte, Valeria A; Thakur, Siddhartha; Wittum, Thomas; DeGraves, Fred J; Rajala-Schultz, Paivi J; Gebreyes, Wondwossen A

    2013-01-01

    Yersinia enterocolitica is an important foodborne pathogen, and pigs are recognized as a major reservoir and potential source of pathogenic strains to humans. A total of 172 Y. enterocolitica recovered from conventional and antimicrobial-free pig production systems from different geographic regions (North Carolina, Ohio, Michigan, Wisconsin, and Iowa) were investigated to determine their pathogenic significance to humans. Phenotypic and genotypic diversity of the isolates was assessed using antibiogram, serogrouping, and amplified fragment length polymorphism (AFLP). Carriage of chromosomal and plasmid-borne virulence genes were investigated using polymerase chain reaction. A total of 12 antimicrobial resistance patterns were identified. More than two-thirds (67.4%) of Y. enterocolitica were pan-susceptible, and 27.9% were resistant against β-lactams. The most predominant serogroup was O:3 (43%), followed by O:5 (25.6%) and O:9 (4.1%). Twenty-two of 172 (12.8%) isolates were found to carry Yersinia adhesion A (yadA), a virulence gene encoded on the Yersinia virulence plasmid. Sixty-nine (40.1%) isolates were found to carry ail gene. The ystA and ystB genes were detected in 77% and 26.2% of the strains, respectively. AFLP genotyping of isolates showed wide genotypic diversity and were grouped into nine clades with an overall genotypic similarity of 66.8-99.3%. AFLP analysis revealed that isolates from the same production system showed clonal relatedness, while more than one genotype of Y. enterocolitica circulates within a farm.

  20. The interaction of combined effects of the BDNF and PRKCG genes and negative life events in major depressive disorder.

    Yang, Chunxia; Sun, Ning; Liu, Zhifen; Li, Xinrong; Xu, Yong; Zhang, Kerang

    2016-03-30

    Major depressive disorder (MDD) is a mental disorder that results from complex interplay between multiple and partially overlapping sets of susceptibility genes and environmental factors. The brain derived neurotrophic factor (BDNF) and Protein kinase C gamma type (PRKCG) are logical candidate genes in MDD. Among diverse environmental factors, negative life events have been suggested to exert a crucial impact on brain development. In the present study, we hypothesized that interactions between genetic variants in BDNF and PRKCG and negative life events may play an important role in the development of MDD. We recruited a total of 406 patients with MDD and 391 age- and gender-matched control subjects. Gene-environment interactions were analyzed using generalized multifactor dimensionality reduction (GMDR). Under a dominant model, we observed a significant three-way interaction among BDNF rs6265, PRKCG rs3745406, and negative life events. The gene-environment combination of PRKCG rs3745406 C allele, BDNF rs6265 G allele and high level of negative life events (C-G-HN) was significantly associated with MDD (OR, 5.97; 95% CI, 2.71-13.15). To our knowledge, this is the first report of evidence that the BDNF-PRKCG interaction may modify the relationship between negative life events and MDD in the Chinese population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. On slaves and genes: "origins" and "processes" in genetic studies of the Brazilian population.

    Calvo-González, Elena

    2014-01-01

    In this article I examine how contemporary geneticists investigating the history and configuration of the Brazilian population engage with other academic disciplines. To do so I use as a case study some articles published by geneticists researching the presence of hemoglobin S variants in Brazil, in which there is a clear pretension to contribute to the analysis of issues such as slavery or Brazil's ethnic identity. By contrasting these studies with contemporary works from history and the social science, the explanatory centrality of "origin" in the genetic studies analyzed is problematized, as is the lack of interaction with the epistemological characteristics of other areas of knowledge.

  2. The developmental origins of cognitive vulnerability to depression: temperament, parenting, and negative life events in childhood as contributors to negative cognitive style.

    Mezulis, Amy H; Hyde, Janet Shibley; Abramson, Lyn Y

    2006-11-01

    Cognitive models of depression have been well supported with adults, but the developmental origins of cognitive vulnerability are not well understood. The authors hypothesized that temperament, parenting, and negative life events in childhood would contribute to the development of cognitive style, with withdrawal negativity and negative parental feedback moderating the effects of negative life events to predict more depressogenic cognitive styles. These constructs were assessed in 289 children and their parents followed longitudinally from infancy to 5th grade; a subsample (n = 120) also participated in a behavioral task in which maternal feedback to child failure was observed. Results indicated that greater withdrawal negativity in interaction with negative life events was associated with more negative cognitive styles. Self-reported maternal anger expression and observed negative maternal feedback to child's failure significantly interacted with child's negative events to predict greater cognitive vulnerability. There was little evidence of paternal parenting predicting child negative cognitive style.

  3. The origin and evolution of Basigin(BSG) gene: A comparative genomic and phylogenetic analysis.

    Zhu, Xinyan; Wang, Shenglan; Shao, Mingjie; Yan, Jie; Liu, Fei

    2017-07-01

    Basigin (BSG), also known as extracellular matrix metalloproteinase inducer (EMMPRIN) or cluster of differentiation 147 (CD147), plays various fundamental roles in the intercellular recognition involved in immunologic phenomena, differentiation, and development. In this study, we aimed to compare the similarities and differences of BSG among organisms and explore possible evolutionary relationships based on the comparison result. We used the extensive BLAST tool to search the metazoan genomes, N-glycosylation sites, the transmembrane region and other functional sites. We then identified BSG homologs from genomic sequences and analyzed their phylogenetic relationships. We identified that BSG genes exist not only in the vertebrate metazoans but also in the invertebrate metazoans such as Amphioxus B. floridae, D. melanogaster, A. mellifera, S. japonicum, C. gigas, and T. patagoniensis. After sequence analysis, we confirmed that only vertebrate metazoans and Cephalochordate (amphioxus B. floridae) have the classic structure (a signal peptide, two Ig-like domains (IgC2 and IgI), a transmembrane region, and an intracellular domain). The invertebrate metazoans (excluding amphioxus B. floridae) lack the N-terminal signal peptides and IgC2 domain. We then generated a phylogenetic tree, genome organization comparison, and chromosomal disposition analysis based on the biological information obtained from the NCBI and Ensembl databases. Finally, we established the possible evolutionary scenario of the BSG gene, which showed the restricted exon rearrangement that has occurred during evolution, forming the present-day BSG gene. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. An original SERPINA3 gene cluster: Elucidation of genomic organization and gene expression in the Bos taurus 21q24 region

    Ouali Ahmed

    2008-04-01

    Full Text Available Abstract Background The superfamily of serine proteinase inhibitors (serpins is involved in numerous fundamental biological processes as inflammation, blood coagulation and apoptosis. Our interest is focused on the SERPINA3 sub-family. The major human plasma protease inhibitor, α1-antichymotrypsin, encoded by the SERPINA3 gene, is homologous to genes organized in clusters in several mammalian species. However, although there is a similar genic organization with a high degree of sequence conservation, the reactive-centre-loop domains, which are responsible for the protease specificity, show significant divergences. Results We provide additional information by analyzing the situation of SERPINA3 in the bovine genome. A cluster of eight genes and one pseudogene sharing a high degree of identity and the same structural organization was characterized. Bovine SERPINA3 genes were localized by radiation hybrid mapping on 21q24 and only spanned over 235 Kilobases. For all these genes, we propose a new nomenclature from SERPINA3-1 to SERPINA3-8. They share approximately 70% of identity with the human SERPINA3 homologue. In the cluster, we described an original sub-group of six members with an unexpected high degree of conservation for the reactive-centre-loop domain, suggesting a similar peptidase inhibitory pattern. Preliminary expression analyses of these bovSERPINA3s showed different tissue-specific patterns and diverse states of glycosylation and phosphorylation. Finally, in the context of phylogenetic analyses, we improved our knowledge on mammalian SERPINAs evolution. Conclusion Our experimental results update data of the bovine genome sequencing, substantially increase the bovSERPINA3 sub-family and enrich the phylogenetic tree of serpins. We provide new opportunities for future investigations to approach the biological functions of this unusual subset of serine proteinase inhibitors.

  5. DNA methylation perturbations in genes involved in polyunsaturated Fatty Acid biosynthesis associated with depression and suicide risk.

    Haghighi, Fatemeh; Galfalvy, Hanga; Chen, Sean; Huang, Yung-Yu; Cooper, Thomas B; Burke, Ainsley K; Oquendo, Maria A; Mann, J John; Sublette, M Elizabeth

    2015-01-01

    Polyunsaturated fatty acid (PUFA) status has been associated with neuropsychiatric disorders, including depression and risk of suicide. Long-chain PUFAs (LC-PUFAs) are obtained in the diet or produced by sequential desaturation and elongation of shorter-chain precursor fatty acids linoleic acid (LA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3). We compared DNA methylation patterns in genes involved in LC-PUFA biosynthesis in major depressive disorder (MDD) with (n = 22) and without (n = 39) history of suicide attempt, and age- and sex-matched healthy volunteers (n = 59). Plasma levels of selected PUFAs along the LC-PUFA biosynthesis pathway were determined by transesterification and gas chromatography. CpG methylation levels for the main human LC-PUFA biosynthetic genes, fatty acid desaturases 1 (Fads1) and 2 (Fads2), and elongation of very long-chain fatty acids protein 5 (Elovl5), were assayed by bisulfite pyrosequencing. Associations between PUFA levels and diagnosis or suicide attempt status did not survive correction for multiple testing. However, MDD diagnosis and suicide attempts were significantly associated with DNA methylation in Elovl5 gene regulatory regions. Also the relative roles of PUFA levels and DNA methylation with respect to diagnostic and suicide attempt status were determined by least absolute shrinkage and selection operator logistic regression analyses. We found that PUFA associations with suicide attempt status were explained by effects of Elovl5 DNA methylation within the regulatory regions. The observed link between plasma PUFA levels, DNA methylation, and suicide risk may have implications for modulation of disease-associated epigenetic marks by nutritional intervention.

  6. DNA methylation perturbations in genes involved in polyunsaturated fatty acid biosynthesis associated with depression and suicide risk

    Fatemeh eHaghighi

    2015-04-01

    Full Text Available Polyunsaturated fatty acid (PUFA status has been associated with neuropsychiatric disorders, including depression and risk of suicide. Long-chain PUFAs (LC-PUFAs are obtained in the diet or produced by sequential desaturation and elongation of shorter-chain precursor fatty acids linoleic acid (LA, 18:2n-6 and α-linolenic acid (ALA, 18:3n-3. We compared DNA methylation patterns in genes involved in LC-PUFA biosynthesis in major depressive disorder (MDD with (n=22 and without (n=39 history of suicide attempt, and age- and sex-matched healthy volunteers (n=59. Plasma levels of selected PUFAs along the LC-PUFA biosynthesis pathway were determined by transesterification and gas chromatography. CpG methylation levels for the main human LC-PUFA biosynthetic genes, fatty acid desaturases 1 (Fads1 and 2 (Fads2, and elongation of very long chain fatty acids protein 5 (Elovl5, were assayed by bisulfite pyrosequencing. Associations between PUFA levels and diagnosis or suicide attempt status did not survive correction for multiple testing. However, MDD diagnosis and suicide attempts were significantly associated with DNA methylation in Elovl5 gene regulatory regions. Also the relative roles of PUFA levels and DNA methylation with respect to diagnostic and suicide attempt status were determined by least absolute shrinkage and selection operator (LASSO logistic regression analyses. We found that PUFA associations with suicide attempt status were explained by effects of Elovl5 DNA methylation within the regulatory regions. The observed link between plasma PUFA levels, DNA methylation, and suicide risk may have implications for modulation of disease-associated epigenetic marks by nutritional intervention.

  7. Cell of origin associated classification of B-cell malignancies by gene signatures of the normal B-cell hierarchy.

    Johnsen, Hans Erik; Bergkvist, Kim Steve; Schmitz, Alexander; Kjeldsen, Malene Krag; Hansen, Steen Møller; Gaihede, Michael; Nørgaard, Martin Agge; Bæch, John; Grønholdt, Marie-Louise; Jensen, Frank Svendsen; Johansen, Preben; Bødker, Julie Støve; Bøgsted, Martin; Dybkær, Karen

    2014-06-01

    Recent findings have suggested biological classification of B-cell malignancies as exemplified by the "activated B-cell-like" (ABC), the "germinal-center B-cell-like" (GCB) and primary mediastinal B-cell lymphoma (PMBL) subtypes of diffuse large B-cell lymphoma and "recurrent translocation and cyclin D" (TC) classification of multiple myeloma. Biological classification of B-cell derived cancers may be refined by a direct and systematic strategy where identification and characterization of normal B-cell differentiation subsets are used to define the cancer cell of origin phenotype. Here we propose a strategy combining multiparametric flow cytometry, global gene expression profiling and biostatistical modeling to generate B-cell subset specific gene signatures from sorted normal human immature, naive, germinal centrocytes and centroblasts, post-germinal memory B-cells, plasmablasts and plasma cells from available lymphoid tissues including lymph nodes, tonsils, thymus, peripheral blood and bone marrow. This strategy will provide an accurate image of the stage of differentiation, which prospectively can be used to classify any B-cell malignancy and eventually purify tumor cells. This report briefly describes the current models of the normal B-cell subset differentiation in multiple tissues and the pathogenesis of malignancies originating from the normal germinal B-cell hierarchy.

  8. Analysis of single nucleotide polymorphisms of CRYGA and CRYGB genes in control population of western Indian origin

    Kapur Suman

    2009-01-01

    Full Text Available Aim: Polymorphisms in γ-crystallins ( CRYG can serve as markers for lens differentiation and eye disorders leading to cataract. Several investigators have reported the presence of sequence variations within crystallin genes, with or without apparent effects on the function of the proteins both in mice and humans. Delineation of these polymorphic sites may explain the differences observed in the susceptibility to cataract observed among various ethnic groups. An easier Restriction Fragment Length Polymorphism (RFLP-based method has been used to detect the frequency of four single nucleotide polymorphisms (SNPs in CRYGA / CRYGB genes in control subjects of western Indian origin. Materials and Methods: A total of 137 healthy volunteers from western India were studied. Examination was performed to exclude volunteers with any ocular defects. Polymerase chain reaction (PCR-RFLP based method was developed for genotyping of G198A (Intron A, T196C (Exon 3 of CRYGA and T47C (Promoter, G449T (Exon 2 of CRYGB genes. Results: The exonic SNPs in CRYGA and CRYGB were found to have an allele frequency 0.03 and 1.00 for ancestral allele respectively, while frequency of non-coding SNP in CRYGA was 0.72. Allele frequency of T90C of CRYGB varied significantly ( P = 0.02 among different age groups. An in-silico analysis reveals that this sequence variation in CRYGB promoter impacts the binding of two transcription factors, ACE2 (Member of CLB2 cluster and Progesterone Receptor (PR which may impact the expression of CRYGB gene. Conclusions: This study establishes baseline frequency data for four SNPs in CRYGA and CRYGB genes for future case control studies on the role of these SNPs in the genetic basis of cataract.

  9. Evolution and origin of merlin, the product of the Neurofibromatosis type 2 (NF2 tumor-suppressor gene

    Omelyanchuk Leonid V

    2005-12-01

    Full Text Available Abstract Background Merlin, the product of the Neurofibromatosis type 2 (NF2 tumor suppressor gene, belongs to the ezrin-radixin-moesin (ERM subgroup of the protein 4.1 superfamily, which links cell surface glycoproteins to the actin cytoskeleton. While merlin's functional activity has been examined in mammalian and Drosophila models, little is understood about its evolution, diversity, and overall distribution among different taxa. Results By combining bioinformatic and phylogenetic approaches, we demonstrate that merlin homologs are present across a wide range of metazoan lineages. While the phylogenetic tree shows a monophyletic origin of the ERM family, the origin of the merlin proteins is robustly separated from that of the ERM proteins. The derivation of merlin is thought to be in early metazoa. We have also observed the expansion of the ERM-like proteins within the vertebrate clade, which occurred after its separation from Urochordata (Ciona intestinalis. Amino acid sequence alignment reveals the absence of an actin-binding site in the C-terminal region of all merlin proteins from various species but the presence of a conserved internal binding site in the N-terminal domain of the merlin and ERM proteins. In addition, a more conserved pattern of amino acid residues is found in the region containing the so-called "Blue Box," although some amino acid substitutions in this region exist in the merlin sequences of worms, fish, and Ciona. Examination of sequence variability at functionally significant sites, including the serine-518 residue, the phosphorylation of which modulates merlin's intra-molecular association and function as a tumor suppressor, identifies several potentially important sites that are conserved among all merlin proteins but divergent in the ERM proteins. Secondary structure prediction reveals the presence of a conserved α-helical domain in the central to C-terminal region of the merlin proteins of various species. The

  10. Oxytocin and Social Sensitivity: Gene Polymorphisms in Relation to Depressive Symptoms and Suicidal Ideation

    McQuaid, Robyn J.; McInnis, Opal A.; Matheson, Kimberly; Anisman, Hymie

    2016-01-01

    Although the neuropeptide oxytocin has been associated with enhanced prosocial behaviors, it has also been linked to aggression and mental health disorders. Thus, it was suggested that oxytocin might act by increasing the salience of social stimuli, irrespective of whether these are positive or negative, thus increasing vulnerability to negative mental health outcomes. The current study (N = 243), conducted among White university students, examined the relation of trauma, depressive symptoms ...

  11. Origin of Aymaras from Bolivia and their relationship with other Amerindians according to HLA genes.

    Arnaiz-Villena, A; Siles, N; Moscoso, J; Zamora, J; Serrano-Vela, J I; Gomez-Casado, E; Castro, M J; Martinez-Laso, J

    2005-04-01

    Aymara Amerindians from the Titicaca Lake Andean highlands are studied for HLA-A, HLA-B, HLA-DRB1 and HLA-DQB1 gene frequencies. Genetic distances, neighbour-joining and correspondence analyses are performed by using other Amerindian and worldwide populations (15384 chromosomes are studied). The HLA genetic profile of Aymaras is different from neighbouring and language-related Quechuas (Incas). Both Quechuas and Aymaras seem to present an HLA-DRB1*0901 high frequency, which is present in a very low frequency or absent in Mesoamericans (Mazatecans, Mayans) and most studied Amerindians. Moreover, it is observed a closer relatedness of Aymaras with Amerindians from the Amazon Basin and Chaco lowlands, compared to Quechuans.

  12. [Study on genetic instability of nm23H1 gene in Chinese with original gallbladder tumor].

    Lu, Hai Ying; Zhang, Guo Qiang; Li, Ji Cheng

    2006-06-01

    The aim of this study was to examine the microsatellite instability (MSI) and loss of heterozygosity (LOH) of locus D17S396 on chromosome 17 and their influence on the expression of nm23H1 in gallbladder tumors, which may provide experimental basis for the tumor occurrence and metastasis. Techniques such as DNA extraction from formalin-fixed paraffin-embedded tissues, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), ordinary silver stain were used to study MSI and LOH of locus D17S396. Envision immunohistochemistry and Leica-Qwin computer imaging techniques were used to assess the expression of gene nm23H1. In our experiment, the frequency of genetic instability of malignant gallbladder tumors was 42.55%, which was higher than that of gallbladder adenomas, while there were no genetic instability occurred in chronic cholecystitis tissue. The frequency of LOH seemed higher with the deteriorism of gallbladder tumor. Among 47 gallbladder carcinomas, the frequency of LOH and MSI were different between different differentiation cases (P gallbladder carcinoma, gallbladder adenoma and chronic cholecystitis tissue were different (P gallbladder carcinomas, the positive frequency of nm23H1 protein in LOH positive group was lower than that of LOH negative group (P gallbladder tumor. Both MSI and LOH of nm23H1 gene controlled the development of gallbladder tumor independently in different paths. MSI may be an early stage molecule marker of gallbladder carcinoma. LOH may be molecule marker for the deteriorism of gallbladder tissue, which could inhibit the expression of nm23H1 in local tissue of gallbladder carcinoma and endow it with high aggressive and poor prognosis. Increasing the amount of nm23H1 protein expression could effectively restrain gallbladder carcinoma metastasis and improve prognosis of patients.

  13. Candidate genes and favoured loci: strategies for molecular genetic research into schizophrenia, manic depression, autism, alcoholism and Alzheimer's disease.

    Gurling, H

    1986-01-01

    It is argued that further research to achieve more detailed diagnostic systems in many psychiatric disorders is unlikely to be productive without taking genetic effects into account. Even when this is done, for example when carrying out segregation analysis to determine a mode of genetic transmission, mental illnesses often pose specific problems that preclude accurate analysis. Because techniques in molecular biology and genetics have made it possible to study gene effects in human disease systematically it should now be possible to specify the genes that are involved. When this has been achieved then a diagnostic system based on genetic causation can develop. This will have the advantage of helping to pinpoint environmental factors more accurately. Specific strategies will need to be adopted to overcome uncertain modes of inheritance, incomplete or non-penetrance of disease alleles and disease heterogeneity. Highly speculative hypotheses can be put forward for a locus causing Alzheimer's disease on a portion of the long arm of chromosome 21. For autism it is plausible that there is a disease locus at or near the fragile X site on the X chromosome. A locus for manic depression has been very tentatively mapped using DNA markers to chromosome 11 and in a small proportion of families DNA markers have also shown some evidence for X linkage. Schizophrenia does not seem to be associated with any favoured loci. Candidate genes for schizophrenia include those encoding dopamine, other neurotransmitter receptors or enzymes and various neuropeptides such as enkephalin and beta endorphin.

  14. Permuted tRNA genes of Cyanidioschyzon merolae, the origin of the tRNA molecule and the root of the Eukarya domain.

    Di Giulio, Massimo

    2008-08-07

    An evolutionary analysis is conducted on the permuted tRNA genes of Cyanidioschyzon merolae, in which the 5' half of the tRNA molecule is codified at the 3' end of the gene and its 3' half is codified at the 5' end. This analysis has shown that permuted genes cannot be considered as derived traits but seem to possess characteristics that suggest they are ancestral traits, i.e. they originated when tRNA molecule genes originated for the first time. In particular, if the hypothesis that permuted genes are a derived trait were true, then we should not have been able to observe that the most frequent class of permuted genes is that of the anticodon loop type, for the simple reason that this class would derive by random permutation from a class of non-permuted tRNA genes, which instead is the rarest. This would not explain the high frequency with which permuted tRNA genes with perfectly separate 5' and 3' halves were observed. Clearly the mechanism that produced this class of permuted genes would envisage the existence, in an advanced stage of evolution, of minigenes codifying for the 5' and 3' halves of tRNAs which were assembled in a permuted way at the origin of the tRNA molecule, thus producing a high frequency of permuted genes of the class here referred. Therefore, this evidence supports the hypothesis that the genes of the tRNA molecule were assembled by minigenes codifying for hairpin-like RNA molecules, as suggested by one model for the origin of tRNA [Di Giulio, M., 1992. On the origin of the transfer RNA molecule. J. Theor. Biol. 159, 199-214; Di Giulio, M., 1999. The non-monophyletic origin of tRNA molecule. J. Theor. Biol. 197, 403-414]. Moreover, the late assembly of the permuted genes of C. merolae, as well as their ancestrality, strengthens the hypothesis of the polyphyletic origins of these genes. Finally, on the basis of the uniqueness and the ancestrality of these permuted genes, I suggest that the root of the Eukarya domain is in the super

  15. A single-nucleotide polymorphism of human neuropeptide s gene originated from Europe shows decreased bioactivity.

    Cheng Deng

    Full Text Available Using accumulating SNP (Single-Nucleotide Polymorphism data, we performed a genome-wide search for polypeptide hormone ligands showing changes in the mature regions to elucidate genotype/phenotype diversity among various human populations. Neuropeptide S (NPS, a brain peptide hormone highly conserved in vertebrates, has diverse physiological effects on anxiety, fear, hyperactivity, food intake, and sleeping time through its cognate receptor-NPSR. Here, we report a SNP rs4751440 (L(6-NPS causing non-synonymous substitution on the 6(th position (V to L of the NPS mature peptide region. L(6-NPS has a higher allele frequency in Europeans than other populations and probably originated from European ancestors ~25,000 yrs ago based on haplotype analysis and Approximate Bayesian Computation. Functional analyses indicate that L(6-NPS exhibits a significant lower bioactivity than the wild type NPS, with ~20-fold higher EC50 values in the stimulation of NPSR. Additional evolutionary and mutagenesis studies further demonstrate the importance of the valine residue in the 6(th position for NPS functions. Given the known physiological roles of NPS receptor in inflammatory bowel diseases, asthma pathogenesis, macrophage immune responses, and brain functions, our study provides the basis to elucidate NPS evolution and signaling diversity among human populations.

  16. HLA genes in Madeira Island (Portugal) inferred from sequence-based typing: footprints from different origins.

    Spínola, Hélder; Bruges-Armas, Jácome; Mora, Marian Gantes; Middleton, Derek; Brehm, António

    2006-04-01

    Human leukocyte antigen (HLA)-A, HLA-B, and HLA-DRB1 polymorphisms were examined in Madeira Island populations. The data was obtained at high-resolution level, using sequence-based typing (SBT). The most frequent alleles at each loci were: A*020101 (24.6%), B*5101 (9.7%), B*440201 (9.2%), and DRB1*070101 (15.7%). The predominant three-loci haplotypes in Madeira were A*020101-B*510101-DRB1*130101 (2.7%) and A*010101-B*0801-DRB1*030101 (2.4%), previously found in north and central Portugal. The present study corroborates historical sources and other genetic studies that say Madeira were populated not only by Europeans, mostly Portuguese, but also sub-Saharan Africans due to slave trade. Comparison with other populations shows that Madeira experienced a stronger African influence due to slave trade than Portugal mainland and even the Azores archipelago. Despite this African genetic input, haplotype and allele frequencies were predominantly from European origin, mostly common to mainland Portugal.

  17. Genetic, Physical and Comparative Mapping of the Powdery Mildew Resistance Gene Pm21 Originating from Dasypyrum villosum

    Huagang He

    2017-11-01

    Full Text Available Pm21, originating from wheat wild relative Dasypyrum villosum, confers immunity to all known races of Blumeria graminis f. sp. tritici (Bgt and has been widely utilized in wheat breeding. However, little is known on the genetic basis of the Pm21 locus. In the present study, four seedling-susceptible D. villosum lines (DvSus-1 ∼ DvSus-4 were identified from different natural populations. Based on the collinearity among genomes of Brachypodium distachyon, Oryza, and Triticeae, a set of 25 gene-derived markers were developed declaring the polymorphisms between DvRes-1 carrying Pm21 and DvSus-1. Fine genetic mapping of Pm21 was conducted by using an extremely large F2 segregation population derived from the cross DvSus-1/DvRes-1. Then Pm21 was narrowed to a 0.01-cM genetic interval defined by the markers 6VS-08.4b and 6VS-10b. Three DNA markers, including a resistance gene analog marker, were confirmed to co-segregate with Pm21. Moreover, based on the susceptible deletion line Y18-S6 induced by ethyl methanesulfonate treatment conducted on Yangmai 18, Pm21 was physically mapped into a similar interval. Comparative analysis revealed that the orthologous regions of the interval carrying Pm21 were narrowed to a 112.5 kb genomic region harboring 18 genes in Brachypodium, and a 23.2 kb region harboring two genes in rice, respectively. This study provides a high-density integrated map of the Pm21 locus, which will contribute to map-based cloning of Pm21.

  18. Sequence variants of the DFNB31 gene among Usher syndrome patients of diverse origin

    Aller, Elena; Jaijo, Teresa; van Wijk, Erwin; Ebermann, Inga; Kersten, Ferry; García-García, Gema; Voesenek, Krysta; Aparisi, María José; Hoefsloot, Lies; Cremers, Cor; Díaz-Llopis, Manuel; Pennings, Ronald; Bolz, Hanno J.; Kremer, Hannie; Millán, José M.

    2010-01-01

    Purpose It has been demonstrated that mutations in deafness, autosomal recessive 31 (DFNB31), the gene encoding whirlin, is responsible for nonsyndromic hearing loss (NSHL; DFNB31) and Usher syndrome type II (USH2D). We screened DFNB31 in a large cohort of patients with different clinical subtypes of Usher syndrome (USH) to determine the prevalence of DFNB31 mutations among USH patients. Methods DFNB31 was screened in 149 USH2, 29 USH1, six atypical USH, and 11 unclassified USH patients from diverse ethnic backgrounds. Mutation detection was performed by direct sequencing of all coding exons. Results We identified 38 different variants among 195 patients. Most variants were clearly polymorphic, but at least two out of the 15 nonsynonymous variants (p.R350W and p.R882S) are predicted to impair whirlin structure and function, suggesting eventual pathogenicity. No putatively pathogenic mutation was found in the second allele of patients with these mutations. Conclusions DFNB31 is not a major cause of USH. PMID:20352026

  19. Social Isolation Stress Induces Anxious-Depressive-Like Behavior and Alterations of Neuroplasticity-Related Genes in Adult Male Mice

    Alessandro Ieraci

    2016-01-01

    Full Text Available Stress is a major risk factor in the onset of several neuropsychiatric disorders including anxiety and depression. Although several studies have shown that social isolation stress during postweaning period induces behavioral and brain molecular changes, the effects of social isolation on behavior during adulthood have been less characterized. Aim of this work was to investigate the relationship between the behavioral alterations and brain molecular changes induced by chronic social isolation stress in adult male mice. Plasma corticosterone levels and adrenal glands weight were also analyzed. Socially isolated (SI mice showed higher locomotor activity, spent less time in the open field center, and displayed higher immobility time in the tail suspension test compared to group-housed (GH mice. SI mice exhibited reduced plasma corticosterone levels and reduced difference between right and left adrenal glands. SI showed lower mRNA levels of the BDNF-7 splice variant, c-Fos, Arc, and Egr-1 in both hippocampus and prefrontal cortex compared to GH mice. Finally, SI mice exhibited selectively reduced mGluR1 and mGluR2 levels in the prefrontal cortex. Altogether, these results suggest that anxious- and depressive-like behavior induced by social isolation stress correlates with reduction of several neuroplasticity-related genes in the hippocampus and prefrontal cortex of adult male mice.

  20. Association between norepinephrine transporter gene (SLC6A2) polymorphisms and suicide in patients with major depressive disorder.

    Kim, Yong-Ku; Hwang, Jung-A; Lee, Heon-Jeong; Yoon, Ho-Kyoung; Ko, Young-Hoon; Lee, Bun-Hee; Jung, Han-Yong; Hahn, Sang-Woo; Na, Kyoung-Sae

    2014-04-01

    Although several studies have investigated possible associations between norepinephrine neurotransmitter transporter gene (SLC6A2) polymorphisms and depression, few studies have examined associations between SLC6A2 polymorphisms and suicide. Three single-nucleotide polymorphisms (rs2242446, rs28386840, and rs5569) were measured in 550 patients: 201 with major depressive disorder (MDD) and suicide attempt/s, 160 with MDD without suicide attempts, and 189 healthy controls. Analysis of single-nucleotide polymorphisms (SNPs) and haplotype was conducted for the three groups. Subsequently, multivariate logistic regression analysis adjusting for age and gender was conducted to identify independent influences of each SNP. A possible association between suicide lethality and SLC6A2 polymorphisms was also investigated. In the genotype and allele frequency analysis, there were significant differences in rs28386840 between suicidal MDD patients and healthy controls. In the haplotype analysis, TAA (rs2242446-rs28386840-rs5569, from left to right) was associated with suicide attempts in MDD, although the significance (p=0.043) disappeared after Bonferroni correction. There were no relationships between lethality scores and SLC6A2 polymorphisms in suicidal MDD. Modest sample size and a single type of neurotransmitter analyzed (norepinephrine) are the primary limitations. Our results suggest that SLC6A2 polymorphisms were associated with suicide risk in patients with MDD. Future studies are warranted to elucidate possible mechanisms by which SLC6A2 polymorphisms influence suicide risk. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Search for a gene predisposing to manic-depression on chromosome 21

    Byerley, W.; Holik, J.; Hoff, M.; Coon, H. [Univ. of Utah Medical Center, Salt Lake City, UT (United States)

    1995-06-19

    Six kindreds containing multiple cases of manic-depressive illness (MDI) were genotyped with seven highly polymorphic microsatellite loci used in the construction of an index map for chromosome 21. The kindreds were also genotyped with a microsatellite polymorphism for PFKL, a chromosome 21 locus that has shown suggestive linkage to MDI in one pedigree. Evidence of linkage was not found assuming either autosomal dominant or recessive inheritance. The nonparametric affected sib pair test did not yield significant evidence of linkage. 11 refs., 1 fig., 3 tabs.

  2. Major depression

    Depression - major; Depression - clinical; Clinical depression; Unipolar depression; Major depressive disorder ... providers do not know the exact causes of depression. It is believed that chemical changes in the ...

  3. Genome-wide comparative analysis reveals similar types of NBS genes in hybrid Citrus sinensis genome and original Citrus clementine genome and provides new insights into non-TIR NBS genes.

    Yunsheng Wang

    Full Text Available In this study, we identified and compared nucleotide-binding site (NBS domain-containing genes from three Citrus genomes (C. clementina, C. sinensis from USA and C. sinensis from China. Phylogenetic analysis of all Citrus NBS genes across these three genomes revealed that there are three approximately evenly numbered groups: one group contains the Toll-Interleukin receptor (TIR domain and two different Non-TIR groups in which most of proteins contain the Coiled Coil (CC domain. Motif analysis confirmed that the two groups of CC-containing NBS genes are from different evolutionary origins. We partitioned NBS genes into clades using NBS domain sequence distances and found most clades include NBS genes from all three Citrus genomes. This suggests that three Citrus genomes have similar numbers and types of NBS genes. We also mapped the re-sequenced reads of three pomelo and three mandarin genomes onto the C. sinensis genome. We found that most NBS genes of the hybrid C. sinensis genome have corresponding homologous genes in both pomelo and mandarin genomes. The homologous NBS genes in pomelo and mandarin suggest that the parental species of C. sinensis may contain similar types of NBS genes. This explains why the hybrid C. sinensis and original C. clementina have similar types of NBS genes in this study. Furthermore, we found that sequence variation amongst Citrus NBS genes were shaped by multiple independent and shared accelerated mutation accumulation events among different groups of NBS genes and in different Citrus genomes. Our comparative analyses yield valuable insight into the structure, organization and evolution of NBS genes in Citrus genomes. Furthermore, our comprehensive analysis showed that the non-TIR NBS genes can be divided into two groups that come from different evolutionary origins. This provides new insights into non-TIR genes, which have not received much attention.

  4. Conserved role of the Vsx genes supports a monophyletic origin for bilaterian visual systems.

    Erclik, Ted; Hartenstein, Volker; Lipshitz, Howard D; McInnes, Roderick R

    2008-09-09

    Components of the genetic network specifying eye development are conserved from flies to humans, but homologies between individual neuronal cell types have been difficult to identify. In the vertebrate retina, the homeodomain-containing transcription factor Chx10 is required for both progenitor cell proliferation and the development of the bipolar interneurons, which transmit visual signals from photoreceptors to ganglion cells. We show that dVsx1 and dVsx2, the two Drosophila homologs of Chx10, play a conserved role in visual-system development. DVSX1 is expressed in optic-lobe progenitor cells, and, in dVsx1 mutants, progenitor cell proliferation is defective, leading to hypocellularity. Subsequently, DVSX1 and DVSX2 are coexpressed in a subset of neurons in the medulla, including the transmedullary neurons that transmit visual information from photoreceptors to deeper layers of the visual system. In dVsx mutant adults, the optic lobe is reduced in size, and the medulla is small or absent. These results suggest that the progenitor cells and photoreceptor target neurons of the vertebrate retina and fly optic lobe are ancestrally related. Genetic and functional homology may extend to the neurons directly downstream of the bipolar and transmedullary neurons, the vertebrate ganglion cells and fly lobula projection neurons. Both cell types project to visual-processing centers in the brain, and both sequentially express the Math5/ATO and Brn3b/ACJ6 transcription factors during their development. Our findings support a monophyletic origin for the bilaterian visual system in which the last common ancestor of flies and vertebrates already contained a primordial visual system with photoreceptors, interneurons, and projection neurons.

  5. Independent Origin and Global Distribution of Distinct Plasmodium vivax Duffy Binding Protein Gene Duplications.

    Jessica B Hostetler

    2016-10-01

    Full Text Available Plasmodium vivax causes the majority of malaria episodes outside Africa, but remains a relatively understudied pathogen. The pathology of P. vivax infection depends critically on the parasite's ability to recognize and invade human erythrocytes. This invasion process involves an interaction between P. vivax Duffy Binding Protein (PvDBP in merozoites and the Duffy antigen receptor for chemokines (DARC on the erythrocyte surface. Whole-genome sequencing of clinical isolates recently established that some P. vivax genomes contain two copies of the PvDBP gene. The frequency of this duplication is particularly high in Madagascar, where there is also evidence for P. vivax infection in DARC-negative individuals. The functional significance and global prevalence of this duplication, and whether there are other copy number variations at the PvDBP locus, is unknown.Using whole-genome sequencing and PCR to study the PvDBP locus in P. vivax clinical isolates, we found that PvDBP duplication is widespread in Cambodia. The boundaries of the Cambodian PvDBP duplication differ from those previously identified in Madagascar, meaning that current molecular assays were unable to detect it. The Cambodian PvDBP duplication did not associate with parasite density or DARC genotype, and ranged in prevalence from 20% to 38% over four annual transmission seasons in Cambodia. This duplication was also present in P. vivax isolates from Brazil and Ethiopia, but not India.PvDBP duplications are much more widespread and complex than previously thought, and at least two distinct duplications are circulating globally. The same duplication boundaries were identified in parasites from three continents, and were found at high prevalence in human populations where DARC-negativity is essentially absent. It is therefore unlikely that PvDBP duplication is associated with infection of DARC-negative individuals, but functional tests will be required to confirm this hypothesis.

  6. Genetic moderation of the association between adolescent romantic involvement and depression: Contributions of serotonin transporter gene polymorphism, chronic stress, and family discord.

    Starr, Lisa R; Hammen, Constance

    2016-05-01

    Studies support a link between adolescent romantic involvement and depression. Adolescent romantic relationships may increase depression risk by introducing chronic stress, and genetic vulnerability to stress reactivity/emotion dysregulation may moderate these associations. We tested genetic moderation of longitudinal associations between adolescent romantic involvement and later depressive symptoms by a polymorphism in the serotonin transporter linked polymorphic region gene (5-HTTLPR) and examined contributory roles of chronic stress and family discord. Three hundred eighty-one youth participated at ages 15 and 20. The results indicated that 5-HTTLPR moderated the association between age 15 romantic involvement and age 20 depressive symptoms, with strongest effects for short homozygotes. Conditional process analysis revealed that chronic stress functioned as a moderated mediator of this association, fully accounting for the romantic involvement-depression link among short/short genotypes. Also, romantic involvement predicted later depressive symptoms most strongly among short-allele carriers with high family discord. The results have important implications for understanding the romantic involvement-depression link and the behavioral and emotional correlates of the 5-HTTLPR genotype.

  7. No Evidence for the Association between a Polymorphism in the PCLO Depression Candidate Gene with Memory Bias in Remitted Depressed Patients and Healthy Individuals

    Vrijsen, J.N.; Speckens, A.E.M.; Arias Vasquez, A.; Franke, B.; Becker, E.S.; Oostrom, I.I.H. van

    2014-01-01

    The PCLO rs2522833 candidate polymorphism for depression has been associated to monoaminergic neurotransmission. In healthy and currently depressed individuals, the polymorphism has been found to affect activation of brain areas during memory processing, but no direct association of PCLO with memory

  8. Cytokine responses in primary chicken embryo intestinal cells infected with Campylobacter jejuni strains of human and chicken origin and the expression of bacterial virulence-associated genes

    Li, Yiping; Ingmer, Hanne; Madsen, Mogens

    2008-01-01

    of the bacterial genes. We have investigated the invasiveness of primary chicken embryo intestinal cells (CEICs) by C. jejuni strains of human and chicken origins and the production of pro-inflammatory cytokines as well as the expression of the bacterial virulence-associated genes during co-cultivation. Results C......-free media from another co-cultivation experiment also increased the expression of the virulence-associated genes in the C. jejuni chicken isolate, indicating that the expression of bacterial genes is regulated by component(s) secreted upon co-cultivation of bacteria and CEICs. Conclusion We show that under...... in vitro culture condition C. jejuni strains of both human and chicken origins can invade avian host cells with a pro-inflammatory response and that the virulence-associated genes of C. jejuni may play a role in this process....

  9. Gene-environment interaction affects substance P and neurokinin A in the entorhinal cortex and periaqueductal grey in a genetic animal model of depression: implications for the pathophysiology of depression

    Husum, Henriette; Wörtwein, Gitta; Andersson, Weronika

    2008-01-01

    Evidence implies a role for corticotropin-releasing hormone (CRH) and tachykinins, e.g. substance P (SP) and neurokinin A (NKA) in the pathophysiology of depression. We have previously shown that SP- and NKA-like immunoreactivity (-LI) concentrations were altered in the frontal cortex and striatum...... of the congenitally 'depressed' Flinders Sensitive Line (FSL) compared to the Flinders Resistant Line (FRL) control rats. It is also known that environmental stress may affect brain levels of tachykinins. In view of these results we decided to superimpose maternal deprivation, an early life environmental stressor......, onto the genetically predisposed 'depressed' FSL rats and the FRL control rats and use this paradigm as a model of gene-environment interaction. The adult animals were sacrificed, adrenal glands and brains dissected out and SP-, NKA- and CRH-LI levels were determined in ten discrete brain regions...

  10. Fatty acid CoA ligase-4 gene polymorphism influences fatty acid metabolism in metabolic syndrome, but not in depression.

    Zeman, Miroslav; Vecka, Marek; Jáchymová, Marie; Jirák, Roman; Tvrzická, Eva; Stanková, Barbora; Zák, Ales

    2009-04-01

    The composition of polyunsaturated fatty acids (PUFAs) in cell membranes and body tissues is altered in metabolic syndrome (MetS) and depressive disorder (DD). Within the cell, fatty acid coenzyme A (CoA) ligases (FACLs) activate PUFAs by esterifying with CoA. The FACL4 isoform prefers PUFAs (arachidonic and eicosapentaenoic acid) as substrates, and the FACL4 gene is mapped to Xq23. We have analyzed the association between the common single nucleotide polymorphism (SNP) (rs1324805, C to T substitution) in the first intron of the FACL4 gene and MetS or DD. The study included 113 healthy subjects (54 Males/59 Females), 56 MetS patients (34M/22F) and 41 DD patients (7M/34F). In MetS group, T-carriers and patients with CC or C0 (CC/C0) genotype did not differ in the values of metabolic indices of MetS and M/F ratio. Nevertheless, in comparison with CC/C0, the T-allele carriers were characterized by enhanced unfavorable changes in fatty acid metabolism typical for MetS: higher content of dihomogammalinolenic acid (P phosphatidylcholine (PC) (P = 0.052), lower index of Delta5 desaturation (P insulin, conjugated dienes and index of insulin resistance, but showed no significant association with the studied SNP. The present study shows that the common SNP (C to T substitution) in the first intron of the FACL4 gene is associated with altered FA composition of plasma phosphatidylcholines in patients with MetS.

  11. Association of angiotensin-converting enzyme (ACE) gene polymorphism with elevated serum ACE activity and major depression in an Iranian population.

    Firouzabadi, Negar; Shafiei, Massoumeh; Bahramali, Ehsan; Ebrahimi, Soltan Ahmed; Bakhshandeh, Hooman; Tajik, Nader

    2012-12-30

    Genetic factors contribute substantially to the likelihood of developing major depressive disorder (MDD). The importance of renin-angiotensin system (RAS) elements in cognition and behaviour and their involvement in aetiology and treatment of depression imply that RAS gene polymorphism(s) associated with RAS overactivity might also be associated with depression. In the present study, genotype and allele frequencies of six common polymorphisms of genes encoding for RAS components were determined in DNAs extracted from venous blood of 191 depressed and 104 healthy individuals using polymerase chain reaction (PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and serum angiotensin-converting enzyme (ACE) activity was assayed using a high-performance liquid chromatography (HPLC) method. The results showed, for the first time, that GG genotype of ACE A2350G was significantly associated with MDD among Iranian participants (P=0.001; odds ratio (OR)=6.2; 95% confidence interval (CI)=2.1-18.3). Significant higher serum ACE activity (P=0.0001) as well as higher diastolic blood pressure (P=0.036) were observed in depressed patients compared to the healthy control group. Depressed patients carrying GG genotype of the A2350G polymorphism had a significantly higher serum ACE activity (P=0.02) than individuals with either AA or AG genotype. In conclusion, this study supports the hypothesis of RAS overactivity in depression in that the genotype associated with higher serum ACE activity in an Iranian population was also associated with MDD. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  12. Common genetic variation in the indoleamine-2,3-dioxygenase genes and antidepressant treatment outcome in major depressive disorder.

    Cutler, Jessica A; Rush, A John; McMahon, Francis J; Laje, Gonzalo

    2012-03-01

    The essential amino acid tryptophan is the precursor to serotonin, but it can also be metabolized into kynurenine through indoleamine-2,3-dioxygenase (IDO). Increased immune activation has long been associated with symptoms of depression and has been shown to upregulate the expression of IDO. The presence of additional IDO directs more tryptophan down the kynurenine pathway, leaving less available for synthesis of serotonin and its metabolites. Kynurenine can be metabolized through a series of enzymes to quinolinic acid, a potent N-methyl-D-aspartate receptor agonist with demonstrated neurotoxic effects. We tested the hypothesis that IDO plays a role in outcome of treatment with the selective serotonin reuptake inhibitor, citalopram. Patients consisted of 1953 participants enrolled in the Sequenced Treatment Alternatives to Relieve Depression study (STAR*D). Genotypes corresponding to 94 single nucleotide polymorphisms (SNPs) in the genes IDO1 and IDO2, which encode IDO and IDO2, were extracted from a larger genome-wide set and analyzed using single marker tests to look for association with previously defined response, remission and QIDS-C score change phenotypes, with adequate correction for racial stratification and multiple testing. One SNP, rs2929115, showed evidence of association with citalopram response (OR = 0.64, p = 0.0005) after experiment-wide correction for multiple testing. Another closely associated marker, rs2929116 (OR = 0.64, p = 0.0006) had an experiment-wide significant result. Both implicated SNPs are located between 26 kb and 28 kb downstream of IDO2. We conclude that common genetic variation in IDO1 and IDO2 may play a role in antidepressant treatment outcome. These results are modest in a genome-wide context and need to be replicated in an independent sample.

  13. Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment.

    Bull, S J

    2009-12-01

    Depression and fatigue are frequent side effects of interferon-alpha (IFN-alpha) treatment, and there is compelling evidence that the inflammatory response system (including interleukin-6, IL-6) and the serotonergic system is important in the pathophysiology of such symptoms. Functional polymorphisms in the promoter region of the IL-6 gene (rs1800795) and serotonin transporter gene (5-HTTLPR) have been identified as regulating these systems. The present study aimed to determine if these polymorphisms were associated with the development of depression and fatigue during IFN-alpha and ribavirin treatment. Ninety-eight Caucasian patients receiving pegylated IFN-alpha and ribavirin treatment for chronic hepatitis C virus at King\\'s College Hospital, London, and Emory University Hospital, Atlanta, participated in this prospective cohort study. Symptoms of depression and fatigue were measured before treatment and at weeks 4, 8, 12 and 24 during treatment. The \\'low IL-6\\' synthesizing genotype (CC) was associated with significantly fewer symptoms of depression (effect size = 0.7 at week 24; F = 9.4, d.f. = 436, P = 0.002). The \\'high transcription\\' serotonin transporter (5-HTT) genotype (LL) was also associated with significantly fewer symptoms of depression, but with a much smaller effect (effect size = 0.2 at week 24; F = 4.5, d.f. = 436, P = 0.03). Neither polymorphisms were associated with symptoms of fatigue (IL-6: F = 1.2, d.f. = 430, P = 0.2; 5-HTT: F = 0.5, d.f. = 430, P = 0.5). The smaller effects of the 5-HTT polymorphism on depression may be explained by an interaction between the genes (F = 5.0, d.f. = 434, P = 0.02): the \\'protective\\' effect of the 5-HTTLPR polymorphism was evident only in the presence of the \\'low IL-6\\' genotype (F = 5.4, d.f. = 64, P = 0.02), not in the presence of the \\'high IL-6\\' genotype (F = 2.2, d.f. = 369, P = 0.1). The association between the IL-6 polymorphism and reduced risk of depressive symptoms confirms the role

  14. Allotetraploid origin and divergence in Eleusine (Chloridoideae, Poaceae): evidence from low-copy nuclear gene phylogenies and a plastid gene chronogram.

    Liu, Qing; Triplett, Jimmy K; Wen, Jun; Peterson, Paul M

    2011-11-01

    Eleusine (Poaceae) is a small genus of the subfamily Chloridoideae exhibiting considerable morphological and ecological diversity in East Africa and the Americas. The interspecific phylogenetic relationships of Eleusine are investigated in order to identify its allotetraploid origin, and a chronogram is estimated to infer temporal relationships between palaeoenvironment changes and divergence of Eleusine in East Africa. Two low-copy nuclear (LCN) markers, Pepc4 and EF-1α, were analysed using parsimony, likelihood and Bayesian approaches. A chronogram of Eleusine was inferred from a combined data set of six plastid DNA markers (ndhA intron, ndhF, rps16-trnK, rps16 intron, rps3, and rpl32-trnL) using the Bayesian dating method. The monophyly of Eleusine is strongly supported by sequence data from two LCN markers. In the cpDNA phylogeny, three tetraploid species (E. africana, E. coracana and E. kigeziensis) share a common ancestor with the E. indica-E. tristachya clade, which is considered a source of maternal parents for allotetraploids. Two homoeologous loci are isolated from three tetraploid species in the Pepc4 phylogeny, and the maternal parents receive further support. The A-type EF-1α sequences possess three characters, i.e. a large number of variations of intron 2; clade E-A distantly diverged from clade E-B and other diploid species; and seven deletions in intron 2, implying a possible derivation through a gene duplication event. The crown age of Eleusine and the allotetraploid lineage are 3·89 million years ago (mya) and 1·40 mya, respectively. The molecular data support independent allotetraploid origins for E. kigeziensis and the E. africana-E. coracana clade. Both events may have involved diploids E. indica and E. tristachya as the maternal parents, but the paternal parents remain unidentified. The habitat-specific hypothesis is proposed to explain the divergence of Eleusine and its allotetraploid lineage.

  15. Origin of the CMS gene locus in rapeseed cybrid mitochondria: active and inactive recombination produces the complex CMS gene region in the mitochondrial genomes of Brassicaceae.

    Oshima, Masao; Kikuchi, Rie; Imamura, Jun; Handa, Hirokazu

    2010-01-01

    CMS (cytoplasmic male sterile) rapeseed is produced by asymmetrical somatic cell fusion between the Brassica napus cv. Westar and the Raphanus sativus Kosena CMS line (Kosena radish). The CMS rapeseed contains a CMS gene, orf125, which is derived from Kosena radish. Our sequence analyses revealed that the orf125 region in CMS rapeseed originated from recombination between the orf125/orfB region and the nad1C/ccmFN1 region by way of a 63 bp repeat. A precise sequence comparison among the related sequences in CMS rapeseed, Kosena radish and normal rapeseed showed that the orf125 region in CMS rapeseed consisted of the Kosena orf125/orfB region and the rapeseed nad1C/ccmFN1 region, even though Kosena radish had both the orf125/orfB region and the nad1C/ccmFN1 region in its mitochondrial genome. We also identified three tandem repeat sequences in the regions surrounding orf125, including a 63 bp repeat, which were involved in several recombination events. Interestingly, differences in the recombination activity for each repeat sequence were observed, even though these sequences were located adjacent to each other in the mitochondrial genome. We report results indicating that recombination events within the mitochondrial genomes are regulated at the level of specific repeat sequences depending on the cellular environment.

  16. Comparative genomic analysis of SET domain family reveals the origin, expansion, and putative function of the arthropod-specific SmydA genes as histone modifiers in insects.

    Jiang, Feng; Liu, Qing; Wang, Yanli; Zhang, Jie; Wang, Huimin; Song, Tianqi; Yang, Meiling; Wang, Xianhui; Kang, Le

    2017-06-01

    The SET domain is an evolutionarily conserved motif present in histone lysine methyltransferases, which are important in the regulation of chromatin and gene expression in animals. In this study, we searched for SET domain-containing genes (SET genes) in all of the 147 arthropod genomes sequenced at the time of carrying out this experiment to understand the evolutionary history by which SET domains have evolved in insects. Phylogenetic and ancestral state reconstruction analysis revealed an arthropod-specific SET gene family, named SmydA, that is ancestral to arthropod animals and specifically diversified during insect evolution. Considering that pseudogenization is the most probable fate of the new emerging gene copies, we provided experimental and evolutionary evidence to demonstrate their essential functions. Fluorescence in situ hybridization analysis and in vitro methyltransferase activity assays showed that the SmydA-2 gene was transcriptionally active and retained the original histone methylation activity. Expression knockdown by RNA interference significantly increased mortality, implying that the SmydA genes may be essential for insect survival. We further showed predominantly strong purifying selection on the SmydA gene family and a potential association between the regulation of gene expression and insect phenotypic plasticity by transcriptome analysis. Overall, these data suggest that the SmydA gene family retains essential functions that may possibly define novel regulatory pathways in insects. This work provides insights into the roles of lineage-specific domain duplication in insect evolution. © The Authors 2017. Published by Oxford University Press.

  17. Multiple genetic origins of histidine-rich protein 2 gene deletion in Plasmodium falciparum parasites from Peru

    Akinyi, Sheila; Hayden, Tonya; Gamboa, Dionicia; Torres, Katherine; Bendezu, Jorge; Abdallah, Joseph F.; Griffing, Sean M.; Quezada, Wilmer Marquiño; Arrospide, Nancy; De Oliveira, Alexandre Macedo; Lucas, Carmen; Magill, Alan J.; Bacon, David J.; Barnwell, John W.; Udhayakumar, Venkatachalam

    2013-01-01

    The majority of malaria rapid diagnostic tests (RDTs) detect Plasmodium falciparum histidine-rich protein 2 (PfHRP2), encoded by the pfhrp2 gene. Recently, P. falciparum isolates from Peru were found to lack pfhrp2 leading to false-negative RDT results. We hypothesized that pfhrp2-deleted parasites in Peru derived from a single genetic event. We evaluated the parasite population structure and pfhrp2 haplotype of samples collected between 1998 and 2005 using seven neutral and seven chromosome 8 microsatellite markers, respectively. Five distinct pfhrp2 haplotypes, corresponding to five neutral microsatellite-based clonal lineages, were detected in 1998-2001; pfhrp2 deletions occurred within four haplotypes. In 2003-2005, outcrossing among the parasite lineages resulted in eight population clusters that inherited the five pfhrp2 haplotypes seen previously and a new haplotype; pfhrp2 deletions occurred within four of these haplotypes. These findings indicate that the genetic origin of pfhrp2 deletion in Peru was not a single event, but likely occurred multiple times. PMID:24077522

  18. Identification of a novel vga(E) gene variant that confers resistance to pleuromutilins, lincosamides and streptogramin A antibiotics in staphylococci of porcine origin.

    Li, Jun; Li, Beibei; Wendlandt, Sarah; Schwarz, Stefan; Wang, Yang; Wu, Congming; Ma, Zhiyong; Shen, Jianzhong

    2014-04-01

    To investigate the genetic basis of pleuromutilin resistance in coagulase-negative staphylococci of porcine origin that do not carry known pleuromutilin resistance genes and to determine the localization and genetic environment of the identified resistance gene. Plasmid DNA of two pleuromutilin-resistant Staphylococcus cohnii and Staphylococcus simulans isolates was transformed into Staphylococcus aureus RN4220. The identified resistance plasmids were sequenced completely. The candidate gene for pleuromutilin resistance was cloned into shuttle vector pAM401. S. aureus RN4220 transformants carrying this recombinant shuttle vector were tested for their MICs. S. cohnii isolate SA-7 and S. simulans isolate SSI1 carried the same plasmid of 5584 bp, designated pSA-7. A variant of the vga(E) gene was detected, which encodes a 524 amino acid ATP-binding cassette protein. The variant gene shared 85.7% nucleotide sequence identity and the variant protein 85.3% amino acid sequence identity with the original vga(E) gene and Vga(E) protein, respectively. The Vga(E) variant conferred cross-resistance to pleuromutilins, lincosamides and streptogramin A antibiotics. Plasmid pSA-7 showed an organization similar to that of the apmA-carrying plasmid pKKS49 from methicillin-resistant S. aureus and the dfrK-carrying plasmid pKKS966 from Staphylococcus hyicus. Sequence comparisons suggested that recombination events may have played a role in the acquisition of this vga(E) variant. A novel vga(E) gene variant was identified, which was located on a small plasmid and was not associated with the transposon Tn6133 [in contrast to the original vga(E) gene]. The plasmid location may enable its further dissemination to other staphylococci and possibly also to other bacteria.

  19. Asymmetrical expression of BDNF and NTRK3 genes in frontoparietal cortex of stress-resilient rats in an animal model of depression.

    Farhang, Sara; Barar, Jaleh; Fakhari, Ali; Mesgariabbasi, Mehran; Khani, Sajjad; Omidi, Yadollah; Farnam, Alireza

    2014-09-01

    The current study is based on the "approach-withdrawal" theory of emotional regulation and lateralization of brain function in rodents, which has little been studied. The aim was to indentify asymmetry in hemispheric genes expression during depression. Depressive-like symptoms were induced in rats using chronic mild stress protocol. The sucrose consumption test was performed to identify the anhedonic and stress-resilient rats. After decapitation, RNA was extracted from frontotemporal cortex of both hemispheres of anhedonic and stress-resilient rats. The pattern of gene expression in these samples was compared with controls by real-time polymerase chain reaction. A linear mixed model analysis of variance was fitted to the data to estimate the effect of rat line. From the total of 30 rats in the experimental group, five rats were identified to be anhedonic and five were stress-resilient, according to the result of sucrose-consumption test. BDNF and NTRK-3 were expressed at significantly lower levels in the right hemisphere of anhedonic rats compared with stress-resilient rats. No significant difference was found between left hemispheres. Hemispheric asymmetry in the level of gene expression was only observed for the BDNF gene in stress-resilient rats, upregulated in right hemisphere compared with the left. Expression of NTRK3, HTR2A, COMT, and SERT was not lateralized. There was no significant asymmetry between hemispheres of anhedonic rats. This study supports the evidence for the role of genes responsible for neural plasticity in pathophysiology of depression, emphasizing probable hemispheric asymmetry at level of gene expression. Copyright © 2014 Wiley Periodicals, Inc.

  20. Serotonin Transporter Gene 5-HTTLPR Polymorphism as a Protective Factor Against the Progression of Post-Stroke Depression.

    Zhao, Qiang; Guo, Yi; Yang, Dong; Yang, Tiansong; Meng, Xianghui

    2016-04-01

    Polymorphisms in the 5-HTT and BDNF genes are shown to affect their function at the molecular and serum level. Prior work has tried to correlate the polymorphisms with post-stroke depression (PSD), the results nevertheless remain indefinitive. A plausible reason accounting for the uncertainty relates to the small sample of each published trial. In this study, we have performed a comprehensive meta-analysis in order to evaluate the effects of 5-HTT and BDNF polymorphisms (5-HTTLPR, STin2 VNTR, 5-HTR2a 102 T/C, Val66Met) on genetic risk of PSD. Human case-control trials were identified by computer-assisted and manual searches. The article search was performed until October 2014. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the fixed effects meta-analysis to measure the effects 5-HTT and BDNF polymorphisms exerted on PSD. We also performed test of heterogeneity, test of publication bias, and sensitivity analysis to examine the reliability and stability of combined effects. 5-HTTLPR was clearly associated with genetic risk of PSD. The association seemed to be more pronounced in the homozygous model (OR = 0.34, 95% CI = 0.23-0.51, P(Q-test) = 0.63). Both the heterozygous model and the recessive model showed 50% decreased risk of PSD (OR = 0.50, 95% CI = 0.37-0.67, P(Q-test) = 0.91; OR = 0.50, 95% CI = 0.36-0.70, P(Q-test) = 0.43, respectively). Such significant association was also detected for Caucasian and Asian. These results were reliable and stable based on related analyses. Taken together, 5-HTTLPR polymorphism of the 5-HTT gene seems to protect against the occurrence of PSD. Small sample size for the polymorphisms within 5-HTT and BDNF genes may have caused underestimated associations, and a larger study is required to further assess the relations.

  1. Recent long-distance transgene flow into wild populations conforms to historical patterns of gene flow in cotton (Gossypium hirsutum) at its centre of origin.

    Wegier, A; Piñeyro-Nelson, A; Alarcón, J; Gálvez-Mariscal, A; Alvarez-Buylla, E R; Piñero, D

    2011-10-01

    Over 95% of the currently cultivated cotton was domesticated from Gossypium hirsutum, which originated and diversified in Mexico. Demographic and genetic studies of this species at its centre of origin and diversification are lacking, although they are critical for cotton conservation and breeding. We investigated the actual and potential distribution of wild cotton populations, as well as the contribution of historical and recent gene flow in shaping cotton genetic diversity and structure. We evaluated historical gene flow using chloroplast microsatellites and recent gene flow through the assessment of transgene presence in wild cotton populations, exploiting the fact that genetically modified cotton has been planted in the North of Mexico since 1996. Assessment of geographic structure through Bayesian spatial analysis, BAPS and Genetic Algorithm for Rule-set Production (GARP), suggests that G. hirsutum seems to conform to a metapopulation scheme, with eight distinct metapopulations. Despite evidence for long-distance gene flow, genetic variation among the metapopulations of G. hirsutum is high (He = 0.894 ± 0.01). We identified 46 different haplotypes, 78% of which are unique to a particular metapopulation, in contrast to a single haplotype detected in cotton cultivars. Recent gene flow was also detected (m = 66/270 = 0.24), with four out of eight metapopulations having transgenes. We discuss the implications of the data presented here with respect to the conservation and future breeding of cotton populations and genetic diversity at its centre of crop origin. © 2011 Blackwell Publishing Ltd.

  2. Evolutionary reversion of editing sites of ndh genes suggests their origin in the Permian-Triassic, before the increase of atmospheric CO2

    Mercedes eMartin

    2015-07-01

    Full Text Available The plastid ndh genes have hovered frequently on the edge of dispensability. They are absent in the plastid DNA of many algae and certain higher plants and present editing sites requiring C-to-U corrections of primary transcripts. The evolutionary origin of editing sites and their loss due to C-to-T reversions at the DNA level are unknown and must be related to the dispensability of the ndh genes in specific environments. In order to better understand the evolution of ndh gene editing sites, we have created expandable data banks with the 12 editing sites of the ndhB gene (600 GenBank sequences and both editing sites of the ndhF gene (1,600 GenBank sequences. Since their origin via T-to-C mutations that probably occurred between 300 and 200 Myr BP (Permian-Triassic, ndh editing sites have undergone independent and random C-to-T reversions in the different angiosperm lineages. Some of these reversions appear early in angiosperm diversification. Old C-to-T reversions can be traced back to radiation steps that gave origin to main classes, orders and some families.

  3. Orígenes del Fútbol en Barcelona (1892-1903. | Origins of Fooball in Barcelona (1892-1903.

    Xavier Torrebadella Flix

    2012-01-01

    Full Text Available This article shows some unpublished data that seek to clarify the origins of football in Spain and particularly in Barcelona. Apart from the influence of the English colony in the dissemination of football, the background of school sport is described and evaluated. It is provided data about football in Barcelona which reveal that before the constitution of the Football Club Barcelona, often considered the first team of the city, there were ten associations that practiced this sport. It emphasizes the importance of the British colony, gyms and sports clubs of Barcelona from 1892 to 1903, to generate the enabling environment that made ​​the modern sport of football triumph, stimulating in turn the context Regenerationism and the emergence of associations sports from the early twentieth century. The research method has focused on historical analysis techniques, with the treatment of the original documentary sources and complemented with historicist indirect sources.ResumenEn este artículo se presentan algunos datos inéditos que pretenden esclarecer los orígenes del fútbol en España y más concretamente en Barcelona. Aparte de la influencia que ejerce la colonia inglesa en la divulgación del fútbol, se describen y se valoran los antecedentes del deporte escolar. Sobre el fútbol en Barcelona se aportan datos que revelan que antes de la constitución del Fútbol Club Barcelona, considerado frecuentemente como el primer equipo de fútbol de la ciudad, existieron una decena de asociaciones que practicaron este deporte. Se acentúa la importancia que tuvo la colonia inglesa, los gimnasios y las sociedades deportivas de Barcelona entre 1892 y 1903, para generar el ambiente favorable que hizo que el fútbol triunfase como deporte moderno, estimulando a su vez el contexto regeneracionista y la emergencia del asociacionismo deportivo de principios del siglo XX. El método de investigación se ha centrado en técnicas de análisis histórico en

  4. Culture as a mediator of gene-environment interaction: Cultural consonance, childhood adversity, a 2A serotonin receptor polymorphism, and depression in urban Brazil.

    Dressler, William W; Balieiro, Mauro C; Ferreira de Araújo, Luiza; Silva, Wilson A; Ernesto Dos Santos, José

    2016-07-01

    Research on gene-environment interaction was facilitated by breakthroughs in molecular biology in the late 20th century, especially in the study of mental health. There is a reliable interaction between candidate genes for depression and childhood adversity in relation to mental health outcomes. The aim of this paper is to explore the role of culture in this process in an urban community in Brazil. The specific cultural factor examined is cultural consonance, or the degree to which individuals are able to successfully incorporate salient cultural models into their own beliefs and behaviors. It was hypothesized that cultural consonance in family life would mediate the interaction of genotype and childhood adversity. In a study of 402 adult Brazilians from diverse socioeconomic backgrounds, conducted from 2011 to 2014, the interaction of reported childhood adversity and a polymorphism in the 2A serotonin receptor was associated with higher depressive symptoms. Further analysis showed that the gene-environment interaction was mediated by cultural consonance in family life, and that these effects were more pronounced in lower social class neighborhoods. The findings reinforce the role of the serotonergic system in the regulation of stress response and learning and memory, and how these processes in turn interact with environmental events and circumstances. Furthermore, these results suggest that gene-environment interaction models should incorporate a wider range of environmental experience and more complex pathways to better understand how genes and the environment combine to influence mental health outcomes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. A horizontal gene transfer at the origin of phenylpropanoid metabolism: a key adaptation of plants to land.

    Emiliani, Giovanni; Fondi, Marco; Fani, Renato; Gribaldo, Simonetta

    2009-02-16

    The pioneering ancestor of land plants that conquered terrestrial habitats around 500 million years ago had to face dramatic stresses including UV radiation, desiccation, and microbial attack. This drove a number of adaptations, among which the emergence of the phenylpropanoid pathway was crucial, leading to essential compounds such as flavonoids and lignin. However, the origin of this specific land plant secondary metabolism has not been clarified. We have performed an extensive analysis of the taxonomic distribution and phylogeny of Phenylalanine Ammonia Lyase (PAL), which catalyses the first and essential step of the general phenylpropanoid pathway, leading from phenylalanine to p-Coumaric acid and p-Coumaroyl-CoA, the entry points of the flavonoids and lignin routes. We obtained robust evidence that the ancestor of land plants acquired a PAL via horizontal gene transfer (HGT) during symbioses with soil bacteria and fungi that are known to have established very early during the first steps of land colonization. This horizontally acquired PAL represented then the basis for further development of the phenylpropanoid pathway and plant radiation on terrestrial environments. Our results highlight a possible crucial role of HGT from soil bacteria in the path leading to land colonization by plants and their subsequent evolution. The few functional characterizations of sediment/soil bacterial PAL (production of secondary metabolites with powerful antimicrobial activity or production of pigments) suggest that the initial advantage of this horizontally acquired PAL in the ancestor of land plants might have been either defense against an already developed microbial community and/or protection against UV.

  6. A horizontal gene transfer at the origin of phenylpropanoid metabolism: a key adaptation of plants to land

    Gribaldo Simonetta

    2009-02-01

    Full Text Available Abstract Background The pioneering ancestor of land plants that conquered terrestrial habitats around 500 million years ago had to face dramatic stresses including UV radiation, desiccation, and microbial attack. This drove a number of adaptations, among which the emergence of the phenylpropanoid pathway was crucial, leading to essential compounds such as flavonoids and lignin. However, the origin of this specific land plant secondary metabolism has not been clarified. Results We have performed an extensive analysis of the taxonomic distribution and phylogeny of Phenylalanine Ammonia Lyase (PAL, which catalyses the first and essential step of the general phenylpropanoid pathway, leading from phenylalanine to p-Coumaric acid and p-Coumaroyl-CoA, the entry points of the flavonoids and lignin routes. We obtained robust evidence that the ancestor of land plants acquired a PAL via horizontal gene transfer (HGT during symbioses with soil bacteria and fungi that are known to have established very early during the first steps of land colonization. This horizontally acquired PAL represented then the basis for further development of the phenylpropanoid pathway and plant radiation on terrestrial environments. Conclusion Our results highlight a possible crucial role of HGT from soil bacteria in the path leading to land colonization by plants and their subsequent evolution. The few functional characterizations of sediment/soil bacterial PAL (production of secondary metabolites with powerful antimicrobial activity or production of pigments suggest that the initial advantage of this horizontally acquired PAL in the ancestor of land plants might have been either defense against an already developed microbial community and/or protection against UV. Reviewers This article was reviewed by Purificación López-García, Janet Siefert, and Eugene Koonin.

  7. A putatively functional polymorphism in the HTR2C gene is associated with depressive symptoms in white females reporting significant life stress.

    Beverly H Brummett

    Full Text Available Psychosocial stress is well known to be positively associated with subsequent depressive symptoms. Cortisol response to stress may be one of a number of biological mechanisms that links psychological stress to depressive symptoms, although the precise causal pathway remains unclear. Activity of the x-linked serotonin 5-HTR2C receptor has also been shown to be associated with depression and with clinical response to antidepressant medications. We recently demonstrated that variation in a single nucleotide polymorphism on the HTR2C gene, rs6318 (Ser23Cys, is associated with different cortisol release and short-term changes in affect in response to a series of stress tasks in the laboratory. Based on this observation, we decided to examine whether rs6318 might moderate the association between psychosocial stress and subsequent depressive symptoms. In the present study we use cross-sectional data from a large population-based sample of young adult White men (N = 2,366 and White women (N = 2,712 in the United States to test this moderation hypothesis. Specifically, we hypothesized that the association between self-reported stressful life events and depressive symptoms would be stronger among homozygous Ser23 C females and hemizygous Ser23 C males than among Cys23 G carriers. In separate within-sex analyses a genotype-by-life stress interaction was observed for women (p = .022 but not for men (p = .471. Homozygous Ser23 C women who reported high levels of life stress had depressive symptom scores that were about 0.3 standard deviations higher than female Cys23 G carriers with similarly high stress levels. In contrast, no appreciable difference in depressive symptoms was observed between genotypes at lower levels of stress. Our findings support prior work that suggests a functional SNP on the HTR2C gene may confer an increased risk for depressive symptoms in White women with a history of significant life stress.

  8. Depression (Major Depressive Disorder)

    ... generally miserable or unhappy without really knowing why. Depression symptoms in children and teens Common signs and ... in normal activities, and avoidance of social interaction. Depression symptoms in older adults Depression is not a ...

  9. A canonical discriminant analysis to study the association between milk fatty acids of ruminal origin and milk fat depression in dairy cows.

    Conte, G; Dimauro, C; Serra, A; Macciotta, N P P; Mele, M

    2018-04-04

    Although milk fat depression (MFD) has been observed and described since the beginning of the last century, all the molecular and biochemical mechanisms involved are still not completely understood. Some fatty acids (FA) originating during rumen biohydrogenation have been proposed as causative elements of MFD. However, contradictory results were obtained when studying the effect of single FA on MFD. An alternative could be the simultaneous evaluation of the effect of many FA using a multivariate approach. The aim of this study was to evaluate the relationship between individual milk FA of ruminal origin and MFD using canonical discriminant analysis, a multivariate technique able to distinguish 2 or more groups on the basis of a pool of variables. In a commercial dairy herd, a diet containing 26% starch on a DM basis induced an unintentional MFD syndrome in 14 cows out of 40. Milk yielded by these 14 animals showed a fat content lower than 50% of the ordinary value, whereas milk production and protein content were normal. The remaining 26 cows secreted typical milk fat content and therefore were considered the control group, even though they ate the same diet. The stepwise discriminant analysis selected 14 milk FA of ruminal origin most able to distinguish the 2 groups. This restricted pool of FA was used, as variables, in a run of the canonical discriminant analysis that was able to significantly discriminate between the 2 groups. Out of the 14 FA, 5 conjugated linoleic acid isomers (C18:2 trans-10,trans-12, C18:2 trans-8,trans-10, C18:2 trans-11,cis-13, C18:2 cis-9,cis-11, C18:2 cis-10,cis-12) and C15:0 iso were more related to the control group, whereas C18:2 trans-10,cis-12, C16:1 trans-6-7, C16:1 trans-9, C18:1 trans-6-8, C18:1 trans-9, C18:1 trans-10, C18:1 cis-11, and C18:3n-3 were positively associated with the MFD group, allowing a complete discrimination. On the basis of these results, we can conclude that (1) the shift of ruminal biohydrogenation from C18

  10. Gene expression in aminergic and peptidergic cells during aggression and defeat: relevance to violence, depression and drug abuse.

    Miczek, Klaus A; Nikulina, Ella M; Takahashi, Aki; Covington, Herbert E; Yap, Jasmine J; Boyson, Christopher O; Shimamoto, Akiko; de Almeida, Rosa M M

    2011-11-01

    In this review, we examine how experiences in social confrontations alter gene expression in mesocorticolimbic cells. The focus is on the target of attack and threat due to the prominent role of social defeat stress in the study of coping mechanisms and victimization. The initial operational definition of the socially defeated mouse by Ginsburg and Allee (1942) enabled the characterization of key endocrine, cardiovascular, and metabolic events during the initial response to an aggressive opponent and during the ensuing adaptations. Brief episodes of social defeat stress induce an augmented response to stimulant challenge as reflected by increased locomotion and increased extracellular dopamine (DA) in the nucleus accumbens (NAC). Cells in the ventral tegmental area (VTA) that project to the NAC were more active as indicated by increased expression of c-fos and Fos-immunoreactivity and BDNF. Intermittent episodes of social defeat stress result in increased mRNA for MOR in brainstem and limbic structures. These behavioral and neurobiological indices of sensitization persist for several months after the stress experience. The episodically defeated rats also self-administered intravenous cocaine during continuous access for 24 h ("binge"). By contrast, continuous social stress, particularly in the form of social subordination stress, leads to reduced appetite, compromised endocrine activities, and cardiovascular and metabolic abnormalities, and prefer sweets less as index of anhedonia. Cocaine challenges in subordinate rats result in a blunted psychomotor stimulant response and a reduced DA release in NAC. Subordinate rats self-administer cocaine less during continuous access conditions. These contrasting patterns of social stress result from continuous vs. intermittent exposure to social stress, suggesting divergent neuroadaptations for increased vulnerability to cocaine self-administration vs. deteriorated reward mechanisms characteristic of depressive-like profiles.

  11. Using paleogenomics to study the evolution of gene families: origin and duplication history of the relaxin family hormones and their receptors.

    Sergey Yegorov

    Full Text Available Recent progress in the analysis of whole genome sequencing data has resulted in the emergence of paleogenomics, a field devoted to the reconstruction of ancestral genomes. Ancestral karyotype reconstructions have been used primarily to illustrate the dynamic nature of genome evolution. In this paper, we demonstrate how they can also be used to study individual gene families by examining the evolutionary history of relaxin hormones (RLN/INSL and relaxin family peptide receptors (RXFP. Relaxin family hormones are members of the insulin superfamily, and are implicated in the regulation of a variety of primarily reproductive and neuroendocrine processes. Their receptors are G-protein coupled receptors (GPCR's and include members of two distinct evolutionary groups, an unusual characteristic. Although several studies have tried to elucidate the origins of the relaxin peptide family, the evolutionary origin of their receptors and the mechanisms driving the diversification of the RLN/INSL-RXFP signaling systems in non-placental vertebrates has remained elusive. Here we show that the numerous vertebrate RLN/INSL and RXFP genes are products of an ancestral receptor-ligand system that originally consisted of three genes, two of which apparently trace their origins to invertebrates. Subsequently, diversification of the system was driven primarily by whole genome duplications (WGD, 2R and 3R followed by almost complete retention of the ligand duplicates in most vertebrates but massive loss of receptor genes in tetrapods. Interestingly, the majority of 3R duplicates retained in teleosts are potentially involved in neuroendocrine regulation. Furthermore, we infer that the ancestral AncRxfp3/4 receptor may have been syntenically linked to the AncRln-like ligand in the pre-2R genome, and show that syntenic linkages among ligands and receptors have changed dynamically in different lineages. This study ultimately shows the broad utility, with some caveats, of

  12. Genomic regression of claw keratin, taste receptor and light-associated genes provides insights into biology and evolutionary origins of snakes.

    Emerling, Christopher A

    2017-10-01

    Regressive evolution of anatomical traits often corresponds with the regression of genomic loci underlying such characters. As such, studying patterns of gene loss can be instrumental in addressing questions of gene function, resolving conflicting results from anatomical studies, and understanding the evolutionary history of clades. The evolutionary origins of snakes involved the regression of a number of anatomical traits, including limbs, taste buds and the visual system, and by analyzing serpent genomes, I was able to test three hypotheses associated with the regression of these features. The first concerns two keratins that are putatively specific to claws. Both genes that encode these keratins are pseudogenized/deleted in snake genomes, providing additional evidence of claw-specificity. The second hypothesis is that snakes lack taste buds, an issue complicated by conflicting results in the literature. I found evidence that different snakes have lost one or more taste receptors, but all snakes examined retained at least one gustatory channel. The final hypothesis addressed is that the earliest snakes were adapted to a dim light niche. I found evidence of deleted and pseudogenized genes with light-associated functions in snakes, demonstrating a pattern of gene loss similar to other dim light-adapted clades. Molecular dating estimates suggest that dim light adaptation preceded the loss of limbs, providing some bearing on interpretations of the ecological origins of snakes. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Origin and diversification of leucine-rich repeat receptor-like protein kinase (LRR-RLK) genes in plants

    Liu, Ping-Li; Du, Liang; Huang, Yuan; Gao, Shu-Min; Yu, Meng

    2017-01-01

    Background Leucine-rich repeat receptor-like protein kinases (LRR-RLKs) are the largest group of receptor-like kinases in plants and play crucial roles in development and stress responses. The evolutionary relationships among LRR-RLK genes have been investigated in flowering plants; however, no comprehensive studies have been performed for these genes in more ancestral groups. The subfamily classification of LRR-RLK genes in plants, the evolutionary history and driving force for the evolution...

  14. Variation in the oxytocin receptor gene is associated with increased risk for anxiety, stress and depression in individuals with a history of exposure to early life stress.

    Myers, Amanda J; Williams, Leanne; Gatt, Justine M; McAuley-Clark, Erica Z; Dobson-Stone, Carol; Schofield, Peter R; Nemeroff, Charles B

    2014-12-01

    Oxytocin is a neuropeptide that is involved in the regulation of mood, anxiety and social biology. Genetic variation in the oxytocin receptor gene (OXTR) has been implicated in anxiety, depression and related stress phenotypes. It is not yet known whether OXTR interacts with other risk factors such as early life trauma to heighten the severity of experienced anxiety and depression. In this study, we examined genotypes in 653 individuals and tested whether SNP variation in OXTR correlates with severity of features of self-reported experience on the Depression Anxiety and Stress Scale (DASS), and whether this correlation is enhanced when early life trauma is taken into account. We also assessed the effects of OXTR SNPs on RNA expression levels in two separate brain tissue cohorts totaling 365 samples. A significant effect of OXTR genotype on DASS anxiety, stress and depression scores was found and ELS events, in combination with several different OXTR SNPs, were significantly associated with differences in DASS scores with one SNP (rs139832701) showing significant association or a trend towards association for all three measures. Several OXTR SNPs were correlated with alterations in OXTR RNA expression and rs3831817 replicated across both sets of tissues. These results support the hypothesis that the oxytocin system plays a role in the pathophysiology of mood and anxiety disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Association of glucocorticoid and type 1 corticotropin-releasing hormone receptors gene variants and risk for depression during pregnancy and post-partum.

    Engineer, Neelam; Darwin, Lucy; Nishigandh, Deole; Ngianga-Bakwin, Kandala; Smith, Steve C; Grammatopoulos, Dimitris K

    2013-09-01

    Women with postnatal depression (PND) appear to have abnormal hypothalamic pituitary adrenal (HPA) axis responses to stress, which might involve a genetic variability component. We investigated association of genetic variants in the glucocorticoid receptor (GR, NR3C1) and corticotropin releasing hormone receptor 1 (CRHR1) genes with increased risk for PND. Two hundred pregnant women were recruited prospectively and PND risk was assessed by the Edinburgh Postnatal Depression Scale (EPDS) during pregnancy and again 2-8 weeks post-natally (CW-GAPND study). The BclI and ER22/23EK single nucleotide polymorphisms (SNPs) of the GR and the haplotype-tagged rs1876828, rs242939 and rs242941 SNPs of the CRHR1 associated with genetic risk to depressive disorders were genotyped. A cut-off score of 10 was used to detect increased risk of PND. Association analysis was carried out in 140 patients that completed the study protocol. The BclI and rs242939 SNPs were over-represented in women with postnatal EPDS score ≥10 with significant allele association (p = 0.011 and depression during pregnancy and postpartum. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Depression of p53-independent Akt survival signals in human oral cancer cells bearing mutated p53 gene after exposure to high-LET radiation

    Nakagawa, Yosuke [Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Takahashi, Akihisa [Advanced Scientific Research Leader Development Unit, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Kajihara, Atsuhisa; Yamakawa, Nobuhiro; Imai, Yuichiro [Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Ota, Ichiro; Okamoto, Noritomo [Department of Otorhinolaryngology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Mori, Eiichiro [Department of Radiation Oncology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Noda, Taichi [Department of Dermatology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Furusawa, Yoshiya [Heavy-ion Radiobiology Research Group, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Kirita, Tadaaki [Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Ohnishi, Takeo, E-mail: tohnishi@naramed-u.ac.jp [Department of Radiation Oncology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer High-LET radiation induces efficiently apoptosis regardless of p53 gene status. Black-Right-Pointing-Pointer We examined whether high-LET radiation depresses the Akt-survival signals. Black-Right-Pointing-Pointer High-LET radiation depresses of survival signals even in the mp53 cancer cells. Black-Right-Pointing-Pointer High-LET radiation activates Caspase-9 through depression of survival signals. Black-Right-Pointing-Pointer High-LET radiation suppresses cell growth through depression of survival signals. -- Abstract: Although mutations and deletions in the p53 tumor suppressor gene lead to resistance to low linear energy transfer (LET) radiation, high-LET radiation efficiently induces cell lethality and apoptosis regardless of the p53 gene status in cancer cells. Recently, it has been suggested that the induction of p53-independent apoptosis takes place through the activation of Caspase-9 which results in the cleavage of Caspase-3 and poly (ADP-ribose) polymerase (PARP). This study was designed to examine if high-LET radiation depresses serine/threonine protein kinase B (PKB, also known as Akt) and Akt-related proteins. Human gingival cancer cells (Ca9-22 cells) harboring a mutated p53 (mp53) gene were irradiated with 2 Gy of X-rays or Fe-ion beams. The cellular contents of Akt-related proteins participating in cell survival signaling were analyzed with Western Blotting 1, 2, 3 and 6 h after irradiation. Cell cycle distributions after irradiation were assayed with flow cytometric analysis. Akt-related protein levels decreased when cells were irradiated with high-LET radiation. High-LET radiation increased G{sub 2}/M phase arrests and suppressed the progression of the cell cycle much more efficiently when compared to low-LET radiation. These results suggest that high-LET radiation enhances apoptosis through the activation of Caspase-3 and Caspase-9, and suppresses cell growth by suppressing Akt-related signaling, even in mp

  17. Interaction between early-life stress and FKBP5 gene variants in major depressive disorder and post-traumatic stress disorder: A systematic review and meta-analysis.

    Wang, Qingzhong; Shelton, Richard C; Dwivedi, Yogesh

    2018-01-01

    Gene-environment interaction contributes to the risks of psychiatric disorders. Interactions between FKBP5 gene variants and early-life stress may enhance the risk not only for mood disorder, but also for a number of other behavioral phenotypes. The aim of the present study was to review and conduct a meta-analysis on the results from published studies examining interaction between FKBP5 gene variants and early-life stress and their associations with stress-related disorders such as major depression and PTSD. A literature search was conducted using PsychINFO and PubMed databases until May 2017. A total of 14 studies with a pooled total of 15109 participants met the inclusion criteria, the results of which were combined and a meta-analysis was performed using the differences in correlations as the effect measure. Based on literature, rs1360780, rs3800373, and rs9470080 SNPs were selected within the FKBP5 gene and systematic review was conducted. Based on the Comprehensive Meta-Analysis software, no publication bias was detected. Sensitivity analysis and credibility of meta-analysis results also indicated that the analyses were stable. The meta-analysis showed that individuals who carry T allele of rs1360780, C-allele of rs3800373 or T-allele of rs9470080 exposed to early-life trauma had higher risks for depression or PTSD. The effects of ethnicity, age, sex, and different stress measures were not examined due to limited sample size. These results provide strong evidence of interactions between FKBP5 genotypes and early-life stress, which could pose a significant risk factor for stress-associated disorders such as major depression and PTSD. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. The dopamine D4 receptor gene, birth weight, maternal depression, maternal attention, and the prediction of disorganized attachment at 36 months of age: A prospective gene×environment analysis.

    Graffi, Justin; Moss, Ellen; Jolicoeur-Martineau, Alexia; Moss, Gal; Lecompte, Vanessa; Pascuzzo, Katherine; Babineau, Vanessa; Gordon-Green, Cathryn; Mileva-Seitz, Viara R; Minde, Klaus; Sassi, Roberto; Steiner, Meir; Kennedy, James L; Gaudreau, Helene; Levitan, Robert; Meaney, Michael J; Wazana, Ashley

    2018-02-01

    Efforts to understand the developmental pathways for disorganized attachment reflect the importance of disorganized attachment on the prediction of future psychopathology. The inconsistent findings on the prediction of disorganized attachment from the dopamine D4 receptor (DRD4) gene, birth weight, and maternal depression as well as the evidence supporting the contribution of early maternal care, suggest the importance of exploring a gene by environment model. Our sample is from the Maternal Adversity, Vulnerability, and Neurodevelopment project; consisting of 655 mother-child dyads. Birth weight was cross-referenced with normative data to calculate birth weight percentile. Infant DRD4 genotype was obtained with buccal swabs and categorized according to the presence of the 7-repeat allele. Maternal depression was assessed with the Center for Epidemiologic Studies Depression Scale at the prenatal, 6-, 12-, and 24-month assessments. Maternal attention was measured at 6-months using a videotaped session of a 20-min non-feeding interaction. Attachment was assessed at 36-months using the Strange Situation Procedure. The presence of the DRD4 7-repeat allele was associated with less disorganized attachment, β=-1.11, OR=0.33, p=0.0008. Maternal looking away frequency showed significant interactions with maternal depression at the prenatal assessment, β=0.003, OR=1.003, p=0.023, and at 24 months, β=0.004, OR=1.004, p=0.021, as at both time points, women suffering from depression and with frequent looking away behavior had an increased probability of disorganized attachment in their child, while those with less looking away behavior had a decreased probability of disorganized attachment in their child at 36 months. Our models support the contribution of biological and multiple environmental factors in the complex prediction of disorganized attachment at 36 months. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Deep evolutionary comparison of gene expression identifies parallel recruitment of trans-factors in two independent origins of C4 photosynthesis.

    Sylvain Aubry

    2014-06-01

    Full Text Available With at least 60 independent origins spanning monocotyledons and dicotyledons, the C4 photosynthetic pathway represents one of the most remarkable examples of convergent evolution. The recurrent evolution of this highly complex trait involving alterations to leaf anatomy, cell biology and biochemistry allows an increase in productivity by ∼ 50% in tropical and subtropical areas. The extent to which separate lineages of C4 plants use the same genetic networks to maintain C4 photosynthesis is unknown. We developed a new informatics framework to enable deep evolutionary comparison of gene expression in species lacking reference genomes. We exploited this to compare gene expression in species representing two independent C4 lineages (Cleome gynandra and Zea mays whose last common ancestor diverged ∼ 140 million years ago. We define a cohort of 3,335 genes that represent conserved components of leaf and photosynthetic development in these species. Furthermore, we show that genes encoding proteins of the C4 cycle are recruited into networks defined by photosynthesis-related genes. Despite the wide evolutionary separation and independent origins of the C4 phenotype, we report that these species use homologous transcription factors to both induce C4 photosynthesis and to maintain the cell specific gene expression required for the pathway to operate. We define a core molecular signature associated with leaf and photosynthetic maturation that is likely shared by angiosperm species derived from the last common ancestor of the monocotyledons and dicotyledons. We show that deep evolutionary comparisons of gene expression can reveal novel insight into the molecular convergence of highly complex phenotypes and that parallel evolution of trans-factors underpins the repeated appearance of C4 photosynthesis. Thus, exploitation of extant natural variation associated with complex traits can be used to identify regulators. Moreover, the transcription factors

  20. Deep evolutionary comparison of gene expression identifies parallel recruitment of trans-factors in two independent origins of C4 photosynthesis.

    Aubry, Sylvain; Kelly, Steven; Kümpers, Britta M C; Smith-Unna, Richard D; Hibberd, Julian M

    2014-06-01

    With at least 60 independent origins spanning monocotyledons and dicotyledons, the C4 photosynthetic pathway represents one of the most remarkable examples of convergent evolution. The recurrent evolution of this highly complex trait involving alterations to leaf anatomy, cell biology and biochemistry allows an increase in productivity by ∼ 50% in tropical and subtropical areas. The extent to which separate lineages of C4 plants use the same genetic networks to maintain C4 photosynthesis is unknown. We developed a new informatics framework to enable deep evolutionary comparison of gene expression in species lacking reference genomes. We exploited this to compare gene expression in species representing two independent C4 lineages (Cleome gynandra and Zea mays) whose last common ancestor diverged ∼ 140 million years ago. We define a cohort of 3,335 genes that represent conserved components of leaf and photosynthetic development in these species. Furthermore, we show that genes encoding proteins of the C4 cycle are recruited into networks defined by photosynthesis-related genes. Despite the wide evolutionary separation and independent origins of the C4 phenotype, we report that these species use homologous transcription factors to both induce C4 photosynthesis and to maintain the cell specific gene expression required for the pathway to operate. We define a core molecular signature associated with leaf and photosynthetic maturation that is likely shared by angiosperm species derived from the last common ancestor of the monocotyledons and dicotyledons. We show that deep evolutionary comparisons of gene expression can reveal novel insight into the molecular convergence of highly complex phenotypes and that parallel evolution of trans-factors underpins the repeated appearance of C4 photosynthesis. Thus, exploitation of extant natural variation associated with complex traits can be used to identify regulators. Moreover, the transcription factors that are shared by

  1. Stress-induced activation of the brainstem Bcl-xL gene expression in rats treated with fluoxetine: correlations with serotonin metabolism and depressive-like behavior.

    Shishkina, Galina T; Kalinina, Tatyana S; Berezova, Inna V; Dygalo, Nikolay N

    2012-01-01

    Mechanisms underlying stress-induced depression and antidepressant drug action were shown to involve alterations in serotonergic (5-HT) neurotransmission and expression of genes coding for proteins associated with neurotrophic signaling pathways and cell-survival in the hippocampus and cortex. Expression of these genes in the brainstem containing 5-HT neurons may also be related to vulnerability or resilience to stress-related psychopathology. Here we investigated 5-HT markers and expression of genes for Brain-Derived Neurotrophic Factor (BDNF) and apoptotic proteins in the brainstem in relation to swim stress-induced behavioral despair. We found that anti-apoptotic Bcl-xL gene is sensitive to stress during the course of fluoxetine administration. Responsiveness of this gene to stress appeared concomitantly with an antidepressant-like effect of fluoxetine in the forced swim test. Bcl-xL transcript levels showed negative correlations with duration of immobility in the test and 5-HT turnover in the brainstem. In contrast, BDNF and pro-apoptotic protein Bax mRNA levels were unchanged by either fluoxetine or stress, suggesting specificity of Bcl-xL gene responses to these treatments. We also found that the levels of mRNAs for tryptophan hydroxylase-2 (TPH2) and 5-HT transporter (5-HTT) were significantly down-regulated following prolonged treatment with fluoxetine, but were not affected by stress. Unlike TPH2 and 5-HTT, 5-HT1A receptor mRNA levels were not altered by fluoxetine but significantly increased in response to swim stress. These data show that long-term fluoxetine treatment leads to changes in 5-HT and Bcl-xL responses to stress associated with antidepressant-like effects of the drug. This article is part of a Special Issue entitled 'Anxiety and Depression'. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. From mutation identification to therapy: discovery and origins of the first approved gene therapy in the Western world

    Kastelein, John J. P.; Ross, Colin J. D.; Hayden, Michael R.

    2013-01-01

    On November 2, 2012, Glybera® (alipogene tipovarvec) was the first human gene therapy to receive long awaited market approval in the Western world. This important milestone is expected to open the door to additional gene therapies for the treatment of many diseases in the future. The development of

  3. Serotonin transporter gene promoter polymorphisms modify the association between paroxetine serotonin transporter occupancy and clinical response in major depressive disorder

    Ruhé, Henricus G.; Ooteman, Wendy; Booij, Jan; Michel, Martin C.; Moeton, Martina; Baas, Frank; Schene, Aart H.

    2009-01-01

    BACKGROUND: In major depressive disorder, selective serotonin reuptake inhibitors target the serotonin transporter (SERT). Their response rates (30-50%) are modified by SERT promotor polymorphisms (5-HTTLPR). OBJECTIVES: To quantify the relationship between SERT occupancy and response, and whether

  4. Does prior traumatization affect the treatment outcome of CBT for panic disorder? The potential role of the MAOA gene and depression symptoms.

    Trautmann, Sebastian; Richter, Jan; Muehlhan, Markus; Höfler, Michael; Wittchen, Hans-Ulrich; Domschke, Katharina; Ströhle, Andreas; Hamm, Alfons O; Weber, Heike; Kircher, Tilo; Arolt, Volker; Gerlach, Alexander L; Alpers, Georg W; Fydrich, Thomas; Lang, Thomas; Reif, Andreas

    2017-07-15

    Although cognitive behavioral therapy (CBT) is highly effective in the treatment of anxiety disorders, many patients still do not benefit. This study investigates whether a history of traumatic event experience is negatively associated with outcomes of CBT for panic disorder. The moderating role of the monoamine oxidase A (MAOA) gene and depression symptoms as well as the association between trauma history and fear reactivity as a potential mechanism are further analyzed. We conducted a post-hoc analysis of 172 male and 60 female patients with panic disorder treated with CBT in a multi-center study. Treatment outcome was assessed at post-treatment using self-report and clinician rating scales. Fear reactivity before treatment was assessed via heart rate and self-reported anxiety during a behavioral avoidance test. Among females, we did not find any differences in treatment response between traumatized and non-traumatized individuals or any two-way interaction trauma history × MAOA genotype. There was a significant three-way interaction trauma history × MAOA genotype × depression symptoms on all treatment outcomes indicating that in traumatized female patients carrying the low-activity allele, treatment effect sizes decreased with increasing depression symptoms at baseline. No such effects were observed for males. In conclusion, we found no evidence for a differential treatment response in traumatized and non-traumatized individuals. There is preliminary evidence for poorer treatment outcomes in a subgroup of female traumatized individuals carrying the low-active variant of the MAOA gene. These patients also report more symptoms of depression symptomatology and exhibit a dampened fear response before treatment which warrants further investigation.

  5. Major depression in China-to-US immigrants and US-born Chinese Americans: testing a hypothesis from culture-gene co-evolutionary theory of mental disorders.

    Tan, Tony Xing

    2014-01-01

    In this study, the culture-gene co-evolutionary theory of mental disorders was used to test the hypothesis that major depression was less prevalent in China-to-US immigrants who migrated to the US as adults than in US-born adult Chinese Americans. Data from the Collaborative Psychiatric Epidemiology Surveys (CPES) were extracted for secondary data analyses on the rates of major depression disorder (MDD) and major depressive episode (MDE) in the two groups. Findings showed that for life time MDD, the rates for China-to-US immigrant and US-born Chinese were 5.3% and 7.9% for men and 8.5% and 33.1% for women. For 12-month MDD, the corresponding rates were 2.2% and 3.4% for men, and 4.7% and 12.6% for women. For life time MDE, the corresponding rates were 6.8% and 8.8% for men; for women the rates were 8.5% and 33.1%. For 12-month MDE, the rates were 2.2% and 4.4% for men; the rates were 4.7% and 12.6% for women. Controlling for age, education level, income, BMI, marital status, and income-to-needs ratio, China-to-US immigrant women remained less likely to have life time major depression than US-born Chinese American women. While the study has the strength of utilizing nationally representative datasets, the approach is limited as the data sources lack the capacity to investigate how the strength of connection with the collectivist culture might be related to major depression in the immigrant group. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Genetic moderation of child maltreatment effects on depression and internalizing symptoms by 5-HTTLPR, BDNF, NET, and CRHR1 genes in African-American children

    Cicchetti, Dante; Rogosch, Fred A.

    2014-01-01

    Genetic moderation of the effects of child maltreatment on depression and internalizing symptoms was investigated in a sample of low-income maltreated and nonmaltreated African-American children (N = 1,096). Lifetime child maltreatment experiences were independently coded from Child Protective Services records and maternal report. Child depression and internalizing problems were assessed in the context of a summer research camp by self-report (Children’s Depression Inventory, CDI) and adult counselor-report (Teacher Report Form, TRF). DNA was obtained from buccal cell or saliva samples and genotyped for polymorphisms of the following genes: 5-HTTLPR, BDNF, NET, and CRHR1. ANCOVAs with age and gender as covariates were conducted, with maltreatment status and respective polymorphism as main effects and their GxE interactions. Maltreatment consistently was associated with higher CDI and TRF symptoms. Results for child self-report symptoms indicated a GxE interaction for BDNF and maltreatment. Additionally, BDNF and tri-allelic 5-HTTLPR interacted with child maltreatment in a GxGxE interaction. Analyses for counselor-report of child anxiety/depression symptoms on the TRF indicated moderation of child maltreatment effects by tri-allelic 5-HTTLPR. These effects were elaborated based on variation in developmental timing of maltreatment experiences. NET was found to further moderate the GxE interaction of 5-HTTLPR and maltreatment status revealing a GxGxE interaction. This GxGxE was extended by consideration of variation in maltreatment subtype experiences. Finally, GxGxE effects were observed for the co-action of BDNF and the CRHR1 haplotype. The findings illustrate the variable influence of specific genotypes in GxE interactions based on variation in maltreatment experiences and the importance of a multi-genic approach for understanding influences on depression and internalizing symptoms among African-American children. PMID:25422957

  7. The Interacting Effect of the BDNF Val66Met Polymorphism and Stressful Life Events on Adolescent Depression Is Not an Artifact of Gene-Environment Correlation: Evidence from a Longitudinal Twin Study

    Chen, Jie; Li, Xinying; McGue, Matt

    2013-01-01

    Background: Confounding introduced by gene-environment correlation (rGE) may prevent one from observing a true gene-environment interaction (G × E) effect on psychopathology. The present study investigated the interacting effect of the BDNF Val66Met polymorphism and stressful life events (SLEs) on adolescent depression while controlling for the…

  8. Comprehensive search for intra- and inter-specific sequence polymorphisms among coding envelope genes of retroviral origin found in the human genome: genes and pseudogenes

    Vasilescu Alexandre

    2005-09-01

    Full Text Available Abstract Background The human genome carries a high load of proviral-like sequences, called Human Endogenous Retroviruses (HERVs, which are the genomic traces of ancient infections by active retroviruses. These elements are in most cases defective, but open reading frames can still be found for the retroviral envelope gene, with sixteen such genes identified so far. Several of them are conserved during primate evolution, having possibly been co-opted by their host for a physiological role. Results To characterize further their status, we presently sequenced 12 of these genes from a panel of 91 Caucasian individuals. Genomic analyses reveal strong sequence conservation (only two non synonymous Single Nucleotide Polymorphisms [SNPs] for the two HERV-W and HERV-FRD envelope genes, i.e. for the two genes specifically expressed in the placenta and possibly involved in syncytiotrophoblast formation. We further show – using an ex vivo fusion assay for each allelic form – that none of these SNPs impairs the fusogenic function. The other envelope proteins disclose variable polymorphisms, with the occurrence of a stop codon and/or frameshift for most – but not all – of them. Moreover, the sequence conservation analysis of the orthologous genes that can be found in primates shows that three env genes have been maintained in a fully coding state throughout evolution including envW and envFRD. Conclusion Altogether, the present study strongly suggests that some but not all envelope encoding sequences are bona fide genes. It also provides new tools to elucidate the possible role of endogenous envelope proteins as susceptibility factors in a number of pathologies where HERVs have been suspected to be involved.

  9. The interleukin 1 beta (IL1B) gene is associated with failure to achieve remission and impaired emotion processing in major depression.

    Baune, Bernhard T; Dannlowski, Udo; Domschke, Katharina; Janssen, Debbie G A; Jordan, Margaret A; Ohrmann, Patricia; Bauer, Jochen; Biros, Erik; Arolt, Volker; Kugel, Harald; Baxter, Alan G; Suslow, Thomas

    2010-03-15

    Accumulating evidence suggests the involvement of inflammatory processes and cytokines in particular in the pathophysiology of major depression (MDD) and resistance to antidepressant treatment. Furthermore, amygdala and anterior cingulate cortex (ACC) responsiveness to emotional stimuli has been suggested as a predictor of treatment response. This study investigated the association between genetic variants of the interleukin 1 beta (IL1B) gene and amygdala and ACC responsiveness to emotional stimuli and response to antidepressant treatment. In this analysis, 256 Caucasian patients with MDD (145 women, 111 men) were genotyped for variants rs16944, rs1143643, and rs1143634 in the IL1B gene (2q14). Response to antidepressant treatment over 6 weeks was defined as remission (50% decrease on Hamilton Rating Scale for Depression-21-question). Brain activity under visual presentation of emotional faces was assessed in a subsample of 32 depressed patients by means of functional magnetic resonance imaging at 3 T. Pharmacogenetic analyses show significant associations of the GG genotypes of single nucleotide polymorphisms (SNPs) rs16944 (odds ratio = 1.74; 95% confidence interval 1.2-4.3) and rs1143643 (odds ratio = 3.1; 95% confidence interval 1.3-7.8) (compared with the AA genotype) with nonremission after 6 weeks. The imaging analyses show that the number of G-alleles in both SNPs (rs16944 and rs1143643) was associated with reduced responsiveness of the amygdala and ACC to emotional stimulation. The present study suggests a negative effect of the IL1B gene on pharmacological response and amygdala and ACC function involving the same genotypes of two SNPs (rs16944, rs116343), which taken together increase the risk of nonremission over 6 weeks of antidepressant treatment in MDD. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  10. Methylation of the leukocyte glucocorticoid receptor gene promoter in adults: associations with early adversity and depressive, anxiety and substance-use disorders.

    Tyrka, A R; Parade, S H; Welch, E S; Ridout, K K; Price, L H; Marsit, C; Philip, N S; Carpenter, L L

    2016-07-05

    Early adversity increases risk for developing psychopathology. Epigenetic modification of stress reactivity genes is a likely mechanism contributing to this risk. The glucocorticoid receptor (GR) gene is of particular interest because of the regulatory role of the GR in hypothalamic-pituitary-adrenal (HPA) axis function. Mounting evidence suggests that early adversity is associated with GR promoter methylation and gene expression. Few studies have examined links between GR promoter methylation and psychopathology, and findings to date have been mixed. Healthy adult participants (N=340) who were free of psychotropic medications reported on their childhood experiences of maltreatment and parental death and desertion. Lifetime depressive and anxiety disorders and past substance-use disorders were assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Methylation of exon 1F of the GR gene (NR3C1) was examined in leukocyte DNA via pyrosequencing. On a separate day, a subset of the participants (n=231) completed the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test. Childhood adversity and a history of past substance-use disorder and current or past depressive or anxiety disorders were associated with lower levels of NR3C1 promoter methylation across the region as a whole and at individual CpG sites (Pdisorder. GR promoter methylation was linked to altered cortisol responses to the Dex/CRH test (Pdepressive, anxiety and substance-use disorders in adults. This finding stands in contrast to our prior work, but is consistent with emerging findings, suggesting complexity in the regulation of this gene.

  11. Depression - resources

    Resources - depression ... Depression is a medical condition. If you think you may be depressed, see a health care provider. ... following organizations are good sources of information on depression : American Psychological Association -- www.apa.org/topics/depression/ ...

  12. Depression (Major Depressive Disorder)

    ... your mood. Chronic pain causes a number of problems that can lead to depression, such as trouble sleeping and stress. Disabling pain can cause low self-esteem due to work, legal or financial issues. Depression ...

  13. Variation in fumonisin and ochratoxin production associated with differences in biosynthetic gene content in Aspergillus niger and A. welwitschiae isolates from multiple crop and geographic origins

    Antonia Susca

    2016-09-01

    Full Text Available The fungi Aspergillus niger and A. welwitschiae are morphologically indistinguishable species used for industrial fermentation and for food and beverage production. The fungi also occur widely on food crops. Concerns about their safety have arisen with the discovery that some isolates of both species produce fumonisin (FB and ochratoxin A (OTA mycotoxins. Here, we examined FB and OTA production as well as the presence of genes responsible for synthesis of the mycotoxins in a collection of 92 A. niger/A. welwitschiae isolates from multiple crop and geographic origins. The results indicate that i isolates of both species differed in ability to produce the mycotoxins; ii FB-nonproducing isolates of A. niger had an intact fumonisin biosynthetic gene (fum cluster; iii FB-nonproducing isolates of A. welwitschiae exhibited multiple patterns of fum gene deletion; and iv OTA-nonproducing isolates of both species lacked the ochratoxin A biosynthetic gene (ota cluster. Analysis of genome sequence data revealed a single pattern of ota gene deletion in the two species. Phylogenetic analysis suggest that the simplest explanation for this is that ota cluster deletion occurred in a common ancestor of A. niger and A. welwitschiae, and subsequently both the intact and deleted cluster were retained as alternate alleles during divergence of the ancestor into descendent species. Finally, comparison of results from this and previous studies indicate that a majority of A. niger isolates and a minority of A. welwitschiae isolates can produce FBs, whereas a minority of isolates of both species produce OTA. The comparison also suggested that the relative abundance of each species and frequency of FB/OTA-producing isolates can vary with crop and/or geographic origin.

  14. The moderating role of an oxytocin receptor gene polymorphism in the relation between unsupportive social interactions and coping profiles: Implications for depression

    Opal Arilla Mcinnis

    2015-08-01

    Full Text Available Oxytocin is a hormone that is thought to influence prosocial behaviors and may be important in modulating responses to both positive and negative social interactions. Indeed, a single nucleotide polymorphism (SNP of the oxytocin receptor gene (OXTR has been associated with decreased trust, empathy, optimism and social support seeking, which are important components of coping with stressors. In the current study, conducted among undergraduate students (N=225, it was shown that parental and peer social support was related to fewer depressive symptoms through elevated problem-focused coping and lower emotion-focused coping, and these effects were independent of the OXTR polymorphism. Unsupportive social interactions from parents were associated with more severe depressive symptoms through the greater use of emotion-focused coping, and this relation was moderated by the OXTR genotype. Specifically, individuals who carried the polymorphism on one or both of their alleles demonstrated increased emotion-focused coping following unsupportive responses compared to those without the polymorphism. Likewise, lower problem-focused coping mediated the relation between parental and peer unsupportive responses to depressive symptoms, but this mediated relation was only evident among carriers of the polymorphism. These findings suggest that carrying this OXTR polymorphism might favor disadvantageous coping styles in the face of negative social interactions, which in turn are linked to poor mood. Regardless of genotype, parental and peer social support are fundamental in determining stress-related coping and well-being.

  15. Reverted glutathione S-transferase-like genes that influence flower color intensity of carnation (Dianthus caryophyllus L.) originated from excision of a transposable element.

    Momose, Masaki; Itoh, Yoshio; Umemoto, Naoyuki; Nakayama, Masayoshi; Ozeki, Yoshihiro

    2013-12-01

    A glutathione S-transferase-like gene, DcGSTF2, is responsible for carnation (Dianthus caryophyllus L.) flower color intensity. Two defective genes, DcGSTF2mu with a nonsense mutation and DcGSTF2-dTac1 containing a transposable element dTac1, have been characterized in detail in this report. dTac1 is an active element that produces reverted functional genes by excision of the element. A pale-pink cultivar 'Daisy' carries both defective genes, whereas a spontaneous deep-colored mutant 'Daisy-VPR' lost the element from DcGSTF2-dTac1. This finding confirmed that dTac1 is active and that the resulting reverted gene, DcGSTF2rev1, missing the element is responsible for this color change. Crosses between the pale-colored cultivar '06-LA' and a deep-colored cultivar 'Spectrum' produced segregating progeny. Only the deep-colored progeny had DcGSTF2rev2 derived from the 'Spectrum' parent, whereas progeny with pale-colored flowers had defective forms from both parents, DcGSTF2mu and DcGSTF2-dTac1. Thus, DcGSTF2rev2 had functional activity and likely originated from excision of dTac1 since there was a footprint sequence at the vacated site of the dTac1 insertion. Characterizing the DcGSTF2 genes in several cultivars revealed that the two functional genes, DcGSTF2rev1 and DcGSTF2rev2, have been used for some time in carnation breeding with the latter in use for more than half a century.

  16. Evidence for the bacterial origin of genes encoding fermentation enzymes of the amitochondriate protozoan parasite Entamoeba histolytica.

    Rosenthal, B; Mai, Z; Caplivski, D; Ghosh, S; de la Vega, H; Graf, T; Samuelson, J

    1997-06-01

    Entamoeba histolytica is an amitochondriate protozoan parasite with numerous bacterium-like fermentation enzymes including the pyruvate:ferredoxin oxidoreductase (POR), ferredoxin (FD), and alcohol dehydrogenase E (ADHE). The goal of this study was to determine whether the genes encoding these cytosolic E. histolytica fermentation enzymes might derive from a bacterium by horizontal transfer, as has previously been suggested for E. histolytica genes encoding heat shock protein 60, nicotinamide nucleotide transhydrogenase, and superoxide dismutase. In this study, the E. histolytica por gene and the adhE gene of a second amitochondriate protozoan parasite, Giardia lamblia, were sequenced, and their phylogenetic positions were estimated in relation to POR, ADHE, and FD cloned from eukaryotic and eubacterial organisms. The E. histolytica por gene encodes a 1,620-amino-acid peptide that contained conserved iron-sulfur- and thiamine pyrophosphate-binding sites. The predicted E. histolytica POR showed fewer positional identities to the POR of G. lamblia (34%) than to the POR of the enterobacterium Klebsiella pneumoniae (49%), the cyanobacterium Anabaena sp. (44%), and the protozoan Trichomonas vaginalis (46%), which targets its POR to anaerobic organelles called hydrogenosomes. Maximum-likelihood, neighbor-joining, and parsimony analyses also suggested as less likely E. histolytica POR sharing more recent common ancestry with G. lamblia POR than with POR of bacteria and the T. vaginalis hydrogenosome. The G. lamblia adhE encodes an 888-amino-acid fusion peptide with an aldehyde dehydrogenase at its amino half and an iron-dependent (class 3) ADH at its carboxy half. The predicted G. lamblia ADHE showed extensive positional identities to ADHE of Escherichia coli (49%), Clostridium acetobutylicum (44%), and E. histolytica (43%) and lesser identities to the class 3 ADH of eubacteria and yeast (19 to 36%). Phylogenetic analyses inferred a closer relationship of the E

  17. Phylogenetic relationships among domesticated and wild species of Cucurbita (Cucurbitaceae) inferred from a mitochondrial gene: Implications for crop plant evolution and areas of origin.

    Sanjur, Oris I; Piperno, Dolores R; Andres, Thomas C; Wessel-Beaver, Linda

    2002-01-08

    We have investigated the phylogenetic relationships among six wild and six domesticated taxa of Cucurbita using as a marker an intron region from the mitochondrial nad1 gene. Our study represents one of the first successful uses of a mtDNA gene in resolving inter- and intraspecific taxonomic relationships in Angiosperms and yields several important insights into the origins of domesticated Cucurbita. First, our data suggest at least six independent domestication events from distinct wild ancestors. Second, Cucurbita argyrosperma likely was domesticated from a wild Mexican gourd, Cucurbita sororia, probably in the same region of southwest Mexico that gave rise to maize. Third, the wild ancestor of Cucurbita moschata is still unknown, but mtDNA data combined with other sources of information suggest that it will probably be found in lowland northern South America. Fourth, Cucurbita andreana is supported as the wild progenitor of Cucurbita maxima, but humid lowland regions of Bolivia in addition to warmer temperate zones in South America from where C. andreana was originally described should possibly be considered as an area of origin for C. maxima. Fifth, our data support other molecular results that indicate two separate domestications in the Cucurbita pepo complex. The potential zone of domestication for one of the domesticated subspecies, C. pepo subsp. ovifera, includes eastern North America and should be extended to northeastern Mexico. The wild ancestor of the other domesticated subspecies, C. pepo subsp. pepo, is undiscovered but is closely related to C. pepo subsp. fraterna and possibly will be found in southern Mexico.

  18. Exploration of gene-environment interactions, maternal effects and parent of origin effects in the etiology of hypospadias

    Zanden, L.F.M. van der; Galesloot, T.E.; Feitz, W.F.J.; Brouwers, M.M.; Shi, M.; Knoers, N.V.; Franke, B.; Roeleveld, N.; Rooij, I.A.L.M. van

    2012-01-01

    PURPOSE: Hypospadias is a common congenital malformation of the male external genitalia. Association studies for single nucleotide polymorphisms in genes encoding steroid 5alpha-reductase, estrogen receptors 1 and 2, and activating transcription factor 3 have been equivocal. We examined whether

  19. Extensive evolutionary changes in regulatory element activity during human origins are associated with altered gene expression and positive selection.

    Yoichiro Shibata

    2012-06-01

    Full Text Available Understanding the molecular basis for phenotypic differences between humans and other primates remains an outstanding challenge. Mutations in non-coding regulatory DNA that alter gene expression have been hypothesized as a key driver of these phenotypic differences. This has been supported by differential gene expression analyses in general, but not by the identification of specific regulatory elements responsible for changes in transcription and phenotype. To identify the genetic source of regulatory differences, we mapped DNaseI hypersensitive (DHS sites, which mark all types of active gene regulatory elements, genome-wide in the same cell type isolated from human, chimpanzee, and macaque. Most DHS sites were conserved among all three species, as expected based on their central role in regulating transcription. However, we found evidence that several hundred DHS sites were gained or lost on the lineages leading to modern human and chimpanzee. Species-specific DHS site gains are enriched near differentially expressed genes, are positively correlated with increased transcription, show evidence of branch-specific positive selection, and overlap with active chromatin marks. Species-specific sequence differences in transcription factor motifs found within these DHS sites are linked with species-specific changes in chromatin accessibility. Together, these indicate that the regulatory elements identified here are genetic contributors to transcriptional and phenotypic differences among primate species.

  20. Application of pulsed-magnetic field enhances non-viral gene delivery in primary cells from different origins

    Kamau Chapman, Sarah W. [Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstr. 190, 8057 Zurich (Switzerland); Hassa, Paul O. [Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstr. 190, 8057 Zurich (Switzerland); European Molecular Biology Laboratory (EMBL) Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg (Germany); Koch-Schneidemann, Sabine; Rechenberg, Brigitte von [Musculoskeletal Research Unit, Equine Hospital, Vetsuisse Faculty Zurich, University of Zurich, Winterthurerstr. 260, 8057 Zurich (Switzerland); Hofmann-Amtenbrink, Margarethe [MatSearch, Chemin Jean Pavillard 14, 1009 Pully (Switzerland); Steitz, Benedikt; Petri-Fink, Alke; Hofmann, Heinrich [Laboratory of Powder Technology, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne (Switzerland); Hottiger, Michael O. [Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstr. 190, 8057 Zurich (Switzerland)], E-mail: hottiger@vetbio.uzh.ch

    2008-04-15

    Primary cell lines are more difficult to transfect when compared to immortalized/transformed cell lines, and hence new techniques are required to enhance the transfection efficiency in these cells. We isolated and established primary cultures of synoviocytes, chondrocytes, osteoblasts, melanocytes, macrophages, lung fibroblasts, and embryonic fibroblasts. These cells differed in several properties, and hence were a good representative sample of cells that would be targeted for expression and delivery of therapeutic genes in vivo. The efficiency of gene delivery in all these cells was enhanced using polyethylenimine-coated polyMAG magnetic nanoparticles, and the rates (17-84.2%) surpassed those previously achieved using other methods, especially in cells that are difficult to transfect. The application of permanent and pulsating magnetic fields significantly enhanced the transfection efficiencies in synoviocytes, chondrocytes, osteoblasts, melanocytes and lung fibroblasts, within 5 min of exposure to these magnetic fields. This is an added advantage for future in vivo applications, where rapid gene delivery is required before systemic clearance or filtration of the gene vectors occurs.

  1. The apoptosis linked gene ALG-2 is dysregulated in tumors of various origin and contributes to cancer cell viability

    la Cour, Jonas; Høj, Berit Rahbek; Mollerup, Jens

    2008-01-01

    microarrays we analysed the expression of ALG-2 in 7371 tumor tissue samples of various origin as well as in 749 normal tissue samples. Most notably, ALG-2 was upregulated in mesenchymal tumors. No correlation was found between ALG-2 staining intensity and survival of patients with lung, breast or colon...... cancer. siRNA mediated ALG-2 downregulation led to a significant reduction in viability of HeLa cells indicating that ALG-2 may contribute to tumor development and expansion....

  2. More about the Viking hypothesis of origin of the delta32 mutation in the CCR5 gene conferring resistance to HIV-1 infection.

    Lucotte, Gérard; Dieterlen, Florent

    2003-11-01

    The chemokine receptor CCR5 constitutes the major coreceptor for the HIV-1, because a mutant allele of the CCR5 gene named delta32 was shown to provide to homozygotes a strong resistance against infection. In the present study the frequency of the delta32 allele was collected in 36 European populations and in Cyprus, and the highest allele frequencies were found in Nordic countries. We constructed an allele map of delta32 frequencies in Europe; the map is in accordance to the Vikings hypothesis of the origin of the mutation and his dissemination during the eighth to the tenth centuries.

  3. Absence of Wdr13 Gene Predisposes Mice to Mild Social Isolation – Chronic Stress, Leading to Depression-Like Phenotype Associated With Differential Expression of Synaptic Proteins

    Mitra, Shiladitya; Sameer Kumar, Ghantasala S.; Jyothi Lakshmi, B.; Thakur, Suman; Kumar, Satish

    2018-01-01

    We earlier reported that the male mice lacking the Wdr13 gene (Wdr13-/0) showed mild anxiety, better memory retention, and up-regulation of synaptic proteins in the hippocampus. With increasing evidences from parallel studies in our laboratory about the possible role of Wdr13 in stress response, we investigated its role in brain. We observed that Wdr13 transcript gets up-regulated in the hippocampus of the wild-type mice exposed to stress. To further dissect its function, we analyzed the behavioral and molecular phenotypes of Wdr13-/0 mice when subjected to mild chronic psychological stress, namely; mild (attenuated) social isolation. We employed iTRAQ based quantitative proteomics, real time PCR and western blotting to investigate molecular changes. Three weeks of social isolation predisposed Wdr13-/0 mice to anhedonia, heightened anxiety-measured by Open field test (OFT), increased behavior despair- measured by Forced swim test (FST) and reduced dendritic branching along with decreased spine density of hippocampal CA1 neurons as compared to wild-type counterparts. This depression-like-phenotype was however ameliorated when treated with anti-depressant imipramine. Molecular analysis revealed that out of 1002 quantified proteins [1% False discovery rate (FDR), at-least two unique peptides], strikingly, a significant proportion of synaptic proteins including, SYN1, CAMK2A, and RAB3A were down-regulated in the socially isolated Wdr13-/0 mice as compared to its wild-type counterparts. This was in contrast to the elevated levels of these proteins in non-stressed mutants as compared to the controls. We hypothesized that a de-regulated transcription factor upstream of the synaptic genes might be responsible for the observed phenotype. Indeed, in the socially isolated Wdr13-/0 mice, there was an up-regulation of GATA1 – a transcription factor that negatively regulates synaptic genes and has been associated with Major Depression (MD) in humans. The present study

  4. The majority of atypical cpb2 genes in Clostridium perfringens isolates of different domestic animal origin are expressed.

    Kircanski, Jasmina; Parreira, Valeria R; Whiteside, Samantha; Pei, Yanlong; Prescott, John F

    2012-10-12

    This study examined the prevalence and expression of the "consensus" and the "atypical"cpb2 genes in Clostridium perfringens isolates from cattle, chickens, dogs, goats, horses, pigs and sheep using polymerase chain reaction (PCR), sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by Western blotting. Almost all porcine isolates (12/14) carried and expressed the consensus form of cpb2 but, when present in 108 non-porcine isolates, the gene was usually the atypical form (40 atypical versus 9 consensus). Western blotting showed expression in 30 of 40 (75%) atypical cpb2-positive isolates, considerably more frequently than reported previously. CPB2 was expressed by almost all (20/21) the consensus cpb2-positive isolates, regardless of source. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Evolutionary origin of Rosaceae-specific active non-autonomous hAT elements and their contribution to gene regulation and genomic structural variation.

    Wang, Lu; Peng, Qian; Zhao, Jianbo; Ren, Fei; Zhou, Hui; Wang, Wei; Liao, Liao; Owiti, Albert; Jiang, Quan; Han, Yuepeng

    2016-05-01

    Transposable elements account for approximately 30 % of the Prunus genome; however, their evolutionary origin and functionality remain largely unclear. In this study, we identified a hAT transposon family, termed Moshan, in Prunus. The Moshan elements consist of three types, aMoshan, tMoshan, and mMoshan. The aMoshan and tMoshan types contain intact or truncated transposase genes, respectively, while the mMoshan type is miniature inverted-repeat transposable element (MITE). The Moshan transposons are unique to Rosaceae, and the copy numbers of different Moshan types are significantly correlated. Sequence homology analysis reveals that the mMoshan MITEs are direct deletion derivatives of the tMoshan progenitors, and one kind of mMoshan containing a MuDR-derived fragment were amplified predominately in the peach genome. The mMoshan sequences contain cis-regulatory elements that can enhance gene expression up to 100-fold. The mMoshan MITEs can serve as potential sources of micro and long noncoding RNAs. Whole-genome re-sequencing analysis indicates that mMoshan elements are highly active, and an insertion into S-haplotype-specific F-box gene was reported to cause the breakdown of self-incompatibility in sour cherry. Taken together, all these results suggest that the mMoshan elements play important roles in regulating gene expression and driving genomic structural variation in Prunus.

  6. Origin of the diversity in DNA recognition domains in phasevarion associated modA genes of pathogenic Neisseria and Haemophilus influenzae.

    Gawthorne, Jayde A; Beatson, Scott A; Srikhanta, Yogitha N; Fox, Kate L; Jennings, Michael P

    2012-01-01

    Phase variable restriction-modification (R-M) systems have been identified in a range of pathogenic bacteria. In some it has been demonstrated that the random switching of the mod (DNA methyltransferase) gene mediates the coordinated expression of multiple genes and constitutes a phasevarion (phase variable regulon). ModA of Neisseria and Haemophilus influenzae contain a highly variable, DNA recognition domain (DRD) that defines the target sequence that is modified by methylation and is used to define modA alleles. 18 distinct modA alleles have been identified in H. influenzae and the pathogenic Neisseria. To determine the origin of DRD variability, the 18 modA DRDs were used to search the available databases for similar sequences. Significant matches were identified between several modA alleles and mod gene from distinct bacterial species, indicating one source of the DRD variability was via horizontal gene transfer. Comparison of DRD sequences revealed significant mosaicism, indicating exchange between the Neisseria and H. influenzae modA alleles. Regions of high inter- and intra-allele similarity indicate that some modA alleles had undergone recombination more frequently than others, generating further diversity. Furthermore, the DRD from some modA alleles, such as modA12, have been transferred en bloc to replace the DRD from different modA alleles.

  7. Diverse effects of lead nitrate on the proliferation, differentiation, and gene expression of stem cells isolated from a dental origin.

    Abdullah, Mariam; Rahman, Fazliny Abd; Gnanasegaran, Nareshwaran; Govindasamy, Vijayendran; Abu Kasim, Noor Hayaty; Musa, Sabri

    2014-01-01

    Lead (Pb(2+)) exposure continues to be a significant public health problem. Therefore, it is vital to have a continuous epidemiological dataset for a better understanding of Pb(2+) toxicity. In the present study, we have exposed stem cells isolated from deciduous and permanent teeth, periodontal ligament, and bone marrow to five different types of Pb(2+) concentrations (160, 80, 40, 20, and 10 µM) for 24 hours to identify the adverse effects of Pb(2+) on the proliferation, differentiation, and gene expression on these cell lines. We found that Pb(2+) treatment altered the morphology and adhesion of the cells in a dose-dependent manner. There were no significant changes in terms of cell surface phenotypes. Cells exposed to Pb(2+) continued to differentiate into chondrogenesis and adipogenesis, and a severe downregulation was observed in osteogenesis. Gene expression studies revealed a constant expression of key markers associated with stemness (Oct 4, Rex 1) and DNA repair enzyme markers, but downregulation occurred with some ectoderm and endoderm markers, demonstrating an irregular and untimely differentiation trail. Our study revealed for the first time that Pb(2+) exposure not only affects the phenotypic characteristics but also induces significant alteration in the differentiation and gene expression in the cells.

  8. Diverse Effects of Lead Nitrate on the Proliferation, Differentiation, and Gene Expression of Stem Cells Isolated from a Dental Origin

    Mariam Abdullah

    2014-01-01

    Full Text Available Lead (Pb2+ exposure continues to be a significant public health problem. Therefore, it is vital to have a continuous epidemiological dataset for a better understanding of Pb2+ toxicity. In the present study, we have exposed stem cells isolated from deciduous and permanent teeth, periodontal ligament, and bone marrow to five different types of Pb2+ concentrations (160, 80, 40, 20, and 10 µM for 24 hours to identify the adverse effects of Pb2+ on the proliferation, differentiation, and gene expression on these cell lines. We found that Pb2+ treatment altered the morphology and adhesion of the cells in a dose-dependent manner. There were no significant changes in terms of cell surface phenotypes. Cells exposed to Pb2+ continued to differentiate into chondrogenesis and adipogenesis, and a severe downregulation was observed in osteogenesis. Gene expression studies revealed a constant expression of key markers associated with stemness (Oct 4, Rex 1 and DNA repair enzyme markers, but downregulation occurred with some ectoderm and endoderm markers, demonstrating an irregular and untimely differentiation trail. Our study revealed for the first time that Pb2+ exposure not only affects the phenotypic characteristics but also induces significant alteration in the differentiation and gene expression in the cells.

  9. Origin, evolution, and population genetics of the selfish Segregation Distorter gene duplication in European and African populations of Drosophila melanogaster.

    Brand, Cara L; Larracuente, Amanda M; Presgraves, Daven C

    2015-05-01

    Meiotic drive elements are a special class of evolutionarily "selfish genes" that subvert Mendelian segregation to gain preferential transmission at the expense of homologous loci. Many drive elements appear to be maintained in populations as stable polymorphisms, their equilibrium frequencies determined by the balance between drive (increasing frequency) and selection (decreasing frequency). Here we show that a classic, seemingly balanced, drive system is instead characterized by frequent evolutionary turnover giving rise to dynamic, rather than stable, equilibrium frequencies. The autosomal Segregation Distorter (SD) system of the fruit fly Drosophila melanogaster is a selfish coadapted meiotic drive gene complex in which the major driver corresponds to a partial duplication of the gene Ran-GTPase activating protein (RanGAP). SD chromosomes segregate at similar, low frequencies of 1-5% in natural populations worldwide, consistent with a balanced polymorphism. Surprisingly, our population genetic analyses reveal evidence for parallel, independent selective sweeps of different SD chromosomes in populations on different continents. These findings suggest that, rather than persisting at a single stable equilibrium, SD chromosomes turn over frequently within populations. © 2015 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

  10. Application of GP IIIa gene Taq I polymorphism to determination of carrier status in Glanzmann's thrombasthenia families of Chinese origin

    Ruan Changgeng; Gu Jianmin; Wang Xiaodong; Chu Xiaohong; Pan Junliang; Wu Qingyu

    1992-08-01

    Glanzmann's thrombasthenia is a bleeding disorder caused by qualitative and/or quantitative defects of platelet membrane glycoprotein (GP) Ii b /III a complex. The disease is inherited in an autosomal recessive manner. The use of cDNA probes to study restriction fragment length polymorphisms (RFLPs) in GPIII a gene is reported. A Taq I polymorphism was identified and this RFLP consisted of variant bands of 6.5 kb/4.0 and 2.5 kb with a frequency of 0.46/0.54 in Chinese population. The Taq I polymorphism was further localized by polymerase chain reaction (PCR) method to exon VIII of the GPIII a gene. In two Glanzmann's thrombasthenia families, the Taq I RFLP studied with both Southern blotting and PCR methods identified defective GPIII a gene inherited by patients, and determined the genotype of asymptomatic subjects. Analysis of this Taq I polymorphism by PCR method should be potentially useful in future for the carrier detection and prenatal diagnosis in Glanzmann's thrombasthenia families

  11. Multiple Origins of Mutations in the mdr1 Gene--A Putative Marker of Chloroquine Resistance in P. vivax.

    Mette L Schousboe

    2015-11-01

    Full Text Available Chloroquine combined with primaquine has been the recommended antimalarial treatment of Plasmodium vivax malaria infections for six decades but the efficacy of this treatment regimen is threatened by chloroquine resistance (CQR. Single nucleotide polymorphisms (SNPs in the multidrug resistance gene, Pvmdr1 are putative determinants of CQR but the extent of their emergence at population level remains to be explored.In this study we describe the prevalence of SNPs in the Pvmdr1 among samples collected in seven P. vivax endemic countries and we looked for molecular evidence of drug selection by characterising polymorphism at microsatellite (MS loci flanking the Pvmdr1 gene.We examined the prevalence of SNPs in the Pvmdr1 gene among 267 samples collected from Pakistan, Afghanistan, Sri Lanka, Nepal, Sudan, São Tomé and Ecuador. We measured and diversity in four microsatellite (MS markers flanking the Pvmdr1 gene to look evidence of selection on mutant alleles.SNP polymorphism in the Pvmdr1 gene was largely confined to codons T958M, Y976F and F1076L. Only 2.4% of samples were wildtype at all three codons (TYF, n = 5, 13.3% (n = 28 of the samples were single mutant MYF, 63.0% of samples (n = 133 were double mutant MYL, and 21.3% (n = 45 were triple mutant MFL. Clear geographic differences in the prevalence of these Pvmdr mutation combinations were observed. Significant linkage disequilibrium (LD between Pvmdr1 and MS alleles was found in populations sampled in Ecuador, Nepal and Sri Lanka, while significant LD between Pvmdr1 and the combined 4 MS locus haplotype was only seen in Ecuador and Sri Lanka. When combining the 5 loci, high level diversity, measured as expected heterozygosity (He, was seen in the complete sample set (He = 0.99, while He estimates for individual loci ranged from 0.00-0.93. Although Pvmdr1 haplotypes were not consistently associated with specific flanking MS alleles, there was significant differentiation between geographic

  12. Conditions of formation and dispersal of Frasnian complex of reef origin of the marginal zone of the Umetovsko-Linevski depression

    Batanova, G.P.; Benderovich, L.Yu.

    1982-01-01

    A classification is made of the organogenic structures of the upper Frasnian age dispersed in the marginal zone of the Umetovsko-Linevskiy depression. Morphological characteristics are provided for each type of structure. Features of their structure and type of formation are covered. A link is examined between the facial and paleogeographic situations determining the dispersal of zones of different types of structures, and their link to paleostructures. The effect of the subsequent movements on morphology and the volume of hydrocarbon traps in the reef structures is noted.

  13. Gene expression associated with suicide attempts in US veterans (Open Access)

    2017-09-05

    depression , bipolar disorder, alcohol use disorder9 and intermittent explosive disorder.8 However, because suicide attempts occur in the context of many... suicidal ideation in a genome wide associa- tion study of depressed inpatients.25 These results provide partial replication of gene expression...OPEN ORIGINAL ARTICLE Gene expression associated with suicide attempts in US veterans JD Flory1,2,7, D Donohue3,7, S Muhie3, R Yang4, SA Miller3, R

  14. Fine physical and genetic mapping of powdery mildew resistance gene MlIW172 originating from wild emmer (Triticum dicoccoides.

    Shuhong Ouyang

    Full Text Available Powdery mildew, caused by Blumeria graminis f. sp. tritici, is one of the most important wheat diseases in the world. In this study, a single dominant powdery mildew resistance gene MlIW172 was identified in the IW172 wild emmer accession and mapped to the distal region of chromosome arm 7AL (bin7AL-16-0.86-0.90 via molecular marker analysis. MlIW172 was closely linked with the RFLP probe Xpsr680-derived STS marker Xmag2185 and the EST markers BE405531 and BE637476. This suggested that MlIW172 might be allelic to the Pm1 locus or a new locus closely linked to Pm1. By screening genomic BAC library of durum wheat cv. Langdon and 7AL-specific BAC library of hexaploid wheat cv. Chinese Spring, and after analyzing genome scaffolds of Triticum urartu containing the marker sequences, additional markers were developed to construct a fine genetic linkage map on the MlIW172 locus region and to delineate the resistance gene within a 0.48 cM interval. Comparative genetics analyses using ESTs and RFLP probe sequences flanking the MlIW172 region against other grass species revealed a general co-linearity in this region with the orthologous genomic regions of rice chromosome 6, Brachypodium chromosome 1, and sorghum chromosome 10. However, orthologous resistance gene-like RGA sequences were only present in wheat and Brachypodium. The BAC contigs and sequence scaffolds that we have developed provide a framework for the physical mapping and map-based cloning of MlIW172.

  15. Identification of Ohnolog Genes Originating from Whole Genome Duplication in Early Vertebrates, Based on Synteny Comparison across Multiple Genomes.

    Singh, Param Priya; Arora, Jatin; Isambert, Hervé

    2015-07-01

    Whole genome duplications (WGD) have now been firmly established in all major eukaryotic kingdoms. In particular, all vertebrates descend from two rounds of WGDs, that occurred in their jawless ancestor some 500 MY ago. Paralogs retained from WGD, also coined 'ohnologs' after Susumu Ohno, have been shown to be typically associated with development, signaling and gene regulation. Ohnologs, which amount to about 20 to 35% of genes in the human genome, have also been shown to be prone to dominant deleterious mutations and frequently implicated in cancer and genetic diseases. Hence, identifying ohnologs is central to better understand the evolution of vertebrates and their susceptibility to genetic diseases. Early computational analyses to identify vertebrate ohnologs relied on content-based synteny comparisons between the human genome and a single invertebrate outgroup genome or within the human genome itself. These approaches are thus limited by lineage specific rearrangements in individual genomes. We report, in this study, the identification of vertebrate ohnologs based on the quantitative assessment and integration of synteny conservation between six amniote vertebrates and six invertebrate outgroups. Such a synteny comparison across multiple genomes is shown to enhance the statistical power of ohnolog identification in vertebrates compared to earlier approaches, by overcoming lineage specific genome rearrangements. Ohnolog gene families can be browsed and downloaded for three statistical confidence levels or recompiled for specific, user-defined, significance criteria at http://ohnologs.curie.fr/. In the light of the importance of WGD on the genetic makeup of vertebrates, our analysis provides a useful resource for researchers interested in gaining further insights on vertebrate evolution and genetic diseases.

  16. [ROLE OF SLC2A9 AND ABCG2 GENE POLYMORPHISMS IN ORIGIN OF HYPERURICEMIA AND GOUT].

    Fadieieva, A; Prystupa, L; Pogorelova, O; Kirichenko, N; Dudchenko, I

    2016-03-01

    The polymorphisms V253I, Q126X, Q141K of SLC2A9 and ABCG2 genes were characterized. GCA и GTC haplotypes of Q126X and Q141K variants can be predictors of gout. The relationship of these polymorphisms with hyperuricaemia according to gender, metabolic syndrome components, with the response to allopurinol was analyzed. It has been established that Q141K polymorphism can directly modulate BCRP-mediated allopurinol and oxypurinol efflux, the K allele is associated with a lower reduction in serum uric acid in response to allopurinol treatment.

  17. Phylogenetic relationships among domesticated and wild species of Cucurbita (Cucurbitaceae) inferred from a mitochondrial gene: Implications for crop plant evolution and areas of origin

    Sanjur, Oris I.; Piperno, Dolores R.; Andres, Thomas C.; Wessel-Beaver, Linda

    2002-01-01

    We have investigated the phylogenetic relationships among six wild and six domesticated taxa of Cucurbita using as a marker an intron region from the mitochondrial nad1 gene. Our study represents one of the first successful uses of a mtDNA gene in resolving inter- and intraspecific taxonomic relationships in Angiosperms and yields several important insights into the origins of domesticated Cucurbita. First, our data suggest at least six independent domestication events from distinct wild ancestors. Second, Cucurbita argyrosperma likely was domesticated from a wild Mexican gourd, Cucurbita sororia, probably in the same region of southwest Mexico that gave rise to maize. Third, the wild ancestor of Cucurbita moschata is still unknown, but mtDNA data combined with other sources of information suggest that it will probably be found in lowland northern South America. Fourth, Cucurbita andreana is supported as the wild progenitor of Cucurbita maxima, but humid lowland regions of Bolivia in addition to warmer temperate zones in South America from where C. andreana was originally described should possibly be considered as an area of origin for C. maxima. Fifth, our data support other molecular results that indicate two separate domestications in the Cucurbita pepo complex. The potential zone of domestication for one of the domesticated subspecies, C. pepo subsp. ovifera, includes eastern North America and should be extended to northeastern Mexico. The wild ancestor of the other domesticated subspecies, C. pepo subsp. pepo, is undiscovered but is closely related to C. pepo subsp. fraterna and possibly will be found in southern Mexico. PMID:11782554

  18. Aegilops tauschii Accessions with Geographically Diverse Origin Show Differences in Chromosome Organization and Polymorphism of Molecular Markers Linked to Leaf Rust and Powdery Mildew Resistance Genes.

    Majka, Maciej; Kwiatek, Michał T; Majka, Joanna; Wiśniewska, Halina

    2017-01-01

    Aegilops tauschii (2n = 2x = 14) is a diploid wild species which is reported as a donor of the D-genome of cultivated bread wheat. The main goal of this study was to examine the differences and similarities in chromosomes organization among accessions of Ae. tauschii with geographically diversed origin, which is believed as a potential source of genes, especially determining resistance to fungal diseases (i.e., leaf rust and powdery mildew) for breeding of cereals. We established and compared the fluorescence in situ hybridization patterns of 21 accessions of Ae. tauschii using various repetitive sequences mainly from the BAC library of wheat cultivar Chinese Spring. Results obtained for Ae. tauschii chromosomes revealed many similarities between analyzed accessions, however, some hybridization patterns were specific for accessions, which become from cognate regions of the World. The most noticeable differences were observed for accessions from China which were characterized by presence of distinct signals of pTa-535 in the interstitial region of chromosome 3D, less intensity of pTa-86 signals in chromosome 2D, as well as lack of additional signals of pTa-86 in chromosomes 1D, 5D, or 6D. Ae. tauschii of Chinese origin appeared homogeneous and separate from landraces that originated in western Asia. Ae. tauschii chromosomes showed similar hybridization patterns to wheat D-genome chromosomes, but some differences were also observed among both species. What is more, we identified reciprocal translocation between short arm of chromosome 1D and long arm of chromosome 7D in accession with Iranian origin. High polymorphism between analyzed accessions and extensive allelic variation were revealed using molecular markers associated with resistance genes. Majority of the markers localized in chromosomes 1D and 2D showed the diversity of banding patterns between accessions. Obtained results imply, that there is a moderate or high level of polymorphism in the genome of Ae

  19. In silico reversal of repeat-induced point mutation (RIP identifies the origins of repeat families and uncovers obscured duplicated genes

    Hane James K

    2010-11-01

    Full Text Available Abstract Background Repeat-induced point mutation (RIP is a fungal genome defence mechanism guarding against transposon invasion. RIP mutates the sequence of repeated DNA and over time renders the affected regions unrecognisable by similarity search tools such as BLAST. Results DeRIP is a new software tool developed to predict the original sequence of a RIP-mutated region prior to the occurrence of RIP. In this study, we apply deRIP to the genome of the wheat pathogen Stagonospora nodorum SN15 and predict the origin of several previously uncharacterised classes of repetitive DNA. Conclusions Five new classes of transposon repeats and four classes of endogenous gene repeats were identified after deRIP. The deRIP process is a new tool for fungal genomics that facilitates the identification and understanding of the role and origin of fungal repetitive DNA. DeRIP is open-source and is available as part of the RIPCAL suite at http://www.sourceforge.net/projects/ripcal.

  20. Adhesion of human and animal escherichia coli strains in association with their virulence-associated genes and phylogenetic origins

    Fr̈mmel, Ulrike; R̈diger, Stefan; B̈hm, Alexander

    2013-01-01

    for the occurrence of 44 VAGs using a novel multiplex PCR microbead assay (MPMA) and for adhesion to four epithelial cell lines using a new adhesion assay. We correlated data for the definition of new adhesion genes. inVAGs were identified only sporadically, particularly in roe deer (Capreolus capreolus...... to cells, host, and tissue, though it was also unspecific. Occurrence of the following VAGs was associated with a higher rate of adhesion to one or more cell lines: afa-dra, daaD, tsh, vat, ibeA, fyuA, mat, sfa-foc, malX, pic, irp2, and papC. In summary, we established new screening methods which enabled...

  1. Cord blood gene expression supports that prenatal exposure to perfluoroalkyl substances causes depressed immune functionality in early childhood.

    Pennings, Jeroen L A; Jennen, Danyel G J; Nygaard, Unni C; Namork, Ellen; Haug, Line S; van Loveren, Henk; Granum, Berit

    2016-01-01

    Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a class of synthetic compounds that have widespread use in consumer and industrial applications. PFAS are considered environmental pollutants that have various toxic properties, including effects on the immune system. Recent human studies indicate that prenatal exposure to PFAS leads to suppressed immune responses in early childhood. In this study, data from the Norwegian BraMat cohort was used to investigate transcriptomics profiles in neonatal cord blood and their association with maternal PFAS exposure, anti-rubella antibody levels at 3 years of age and the number of common cold episodes until 3 years. Genes associated with PFAS exposure showed enrichment for immunological and developmental functions. The analyses identified a toxicogenomics profile of 52 PFAS exposure-associated genes that were in common with genes associated with rubella titers and/or common cold episodes. This gene set contains several immunomodulatory genes (CYTL1, IL27) as well as other immune-associated genes (e.g. EMR4P, SHC4, ADORA2A). In addition, this study identified PPARD as a PFAS toxicogenomics marker. These markers can serve as the basis for further mechanistic or epidemiological studies. This study provides a transcriptomics connection between prenatal PFAS exposure and impaired immune function in early childhood and supports current views on PPAR- and NF-κB-mediated modes of action. The findings add to the available evidence that PFAS exposure is immunotoxic in humans and support regulatory policies to phase out these substances.

  2. The vertebrate Hox gene regulatory network for hindbrain segmentation: Evolution and diversification: Coupling of a Hox gene regulatory network to hindbrain segmentation is an ancient trait originating at the base of vertebrates.

    Parker, Hugo J; Bronner, Marianne E; Krumlauf, Robb

    2016-06-01

    Hindbrain development is orchestrated by a vertebrate gene regulatory network that generates segmental patterning along the anterior-posterior axis via Hox genes. Here, we review analyses of vertebrate and invertebrate chordate models that inform upon the evolutionary origin and diversification of this network. Evidence from the sea lamprey reveals that the hindbrain regulatory network generates rhombomeric compartments with segmental Hox expression and an underlying Hox code. We infer that this basal feature was present in ancestral vertebrates and, as an evolutionarily constrained developmental state, is fundamentally important for patterning of the vertebrate hindbrain across diverse lineages. Despite the common ground plan, vertebrates exhibit neuroanatomical diversity in lineage-specific patterns, with different vertebrates revealing variations of Hox expression in the hindbrain that could underlie this diversification. Invertebrate chordates lack hindbrain segmentation but exhibit some conserved aspects of this network, with retinoic acid signaling playing a role in establishing nested domains of Hox expression. © 2016 WILEY Periodicals, Inc.

  3. Interactions between the vascular endothelial growth factor gene polymorphism and life events in susceptibility to major depressive disorder in a Chinese population.

    Han, Dong; Qiao, Zhengxue; Chen, Lu; Qiu, Xiaohui; Fang, Deyu; Yang, Xiuxian; Ma, Jingsong; Chen, Mingqi; Yang, Jiarun; Wang, Lin; Zhu, Xiongzhao; Zhang, Congpei; Yang, Yanjie; Pan, Hui

    2017-08-01

    Recent studies suggest that vascular endothelial growth factor (VEGF) is involved in the development of major depressive disorder. The aim of this study is to investigate the interaction between vascular endothelial growth factor (VEGF) polymorphism (+405G/C, rs2010963) and negative life events in the pathogenesis of major depressive disorder (MDD). DNA genotyping was performed on peripheral blood leukocytes in 274 patients with MDD and 273 age-and sex-matched controls. The frequency and severity of negative life events were assessed by the Life Events Scale (LES). A logistics method was employed to assess the gene-environment interaction (G×E). Differences in rs2010963 genotype distributions were observed between MDD patients and controls. Significant G×E interactions between allelic variation of rs2010963 and negative life events were observed. Individuals carrying the C alleles were susceptible to MDD only when exposed to high-negative life events. These results indicate that interactions between the VEGF rs2010963 polymorphism and environment increases the risk of developing MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Chemistry and origin of deep ground water in crystalline rocks; Kemi och genes av djupa grundvatten i kristallint berg

    Lagerblad, B [Swedish Cement and Concrete Research Inst., Stockholm (Sweden)

    1995-11-01

    This report discusses the interactions between water and crystalline rocks and its consequences for the chemical composition of the water. It also treats how flows of different types of water are modified by the rock, and the possible consequences for the ground water near a nuclear waste repository. The focus of the work is the changes in composition that ground water gets at deep levels in the rock. Data from Finnsjoen and Aespoe in Sweden show higher salinity in deep rock, which has been interpreted as a result of marine inflow of water during glaciation. Data from other, deeper boreholes in Finland, Canada, Russia, England and Sweden show that the increasing salinity is a rule and very high at great depths, higher than marine water can produce. Therefore, the deep waters from Finnsjoen and Aespoe are probably very old, and the high salinity a result from geological processes. Differing cation and isotopic composition than seawater also indicate geologic water. Differing theories on the origin of the ground water should be regarded in the safety analysis for a repository. 36 refs, 3 figs, 1 tab.

  5. Comparative Analysis of WUSCHEL-Related Homeobox Genes Revealed Their Parent-of-Origin and Cell Type-Specific Expression Pattern During Early Embryogenesis in Tobacco

    Xuemei Zhou

    2018-03-01

    Full Text Available WUSCHEL-related homeobox (WOX gene is a plant-specific clade of homeobox transcription factors. Increasing evidences reveal that WOXs play critical roles in early embryogenesis, which involves zygote development, initiation of zygote division, and apical or basal cell lineage establishment. However, how WOXs regulate these developmental events remains largely unknown, and even detailed expression pattern in gametes and early proembryos is not yet available. Here, 13 WOX family genes were identified in Nicotiana tabacum genome. Comparative analysis of 13 WOX family genes with their homologs in Arabidopsis thaliana reveals relatively conserved expression pattern of WUS and WOX5 in shoot/root apical meristem. Whereas variations were also found, e.g., lacking homolog of WOX8 (a marker for suspensor cell in tobacco genome and the expression of WOX2/WOX9 in both apical cell and basal cell. Transient transcriptional activity analysis revealed that WOXs in WUS clade have repressive activities for their target's transcription, whereas WOXs in ancient and intermediate clade have activation activities, giving a molecular basis for the phylogenetic classification of tobacco WOXs into three major clades. Expression pattern analysis revealed that some WOXs (e.g., WOX 13a expressed in both male and female gametes and some WOXs (e.g., WOX 11 and WOX 13b displayed the characteristics of parent-of-origin genes. Interestingly, some WOXs (e.g., WOX2 and WOX9, which are essential for early embryo patterning, were de novo transcribed in zygote, indicating relevant mechanism for embryo pattern formation is only established in zygote right after fertilization and not carried in by gametes. We also found that most WOXs displayed a stage-specific and cell type-specific expression pattern. Taken together, this work provides a detailed landscape of WOXs in tobacco during fertilization and early embryogenesis, which will facilitate the understanding of their specific roles

  6. Immediate Early Genes Anchor a Biological Pathway of Proteins Required for Memory Formation, Long-Term Depression and Risk for Schizophrenia

    Ketan K. Marballi

    2018-02-01

    Full Text Available While the causes of myriad medical and infectious illnesses have been identified, the etiologies of neuropsychiatric illnesses remain elusive. This is due to two major obstacles. First, the risk for neuropsychiatric disorders, such as schizophrenia, is determined by both genetic and environmental factors. Second, numerous genes influence susceptibility for these illnesses. Genome-wide association studies have identified at least 108 genomic loci for schizophrenia, and more are expected to be published shortly. In addition, numerous biological processes contribute to the neuropathology underlying schizophrenia. These include immune dysfunction, synaptic and myelination deficits, vascular abnormalities, growth factor disruption, and N-methyl-D-aspartate receptor (NMDAR hypofunction. However, the field of psychiatric genetics lacks a unifying model to explain how environment may interact with numerous genes to influence these various biological processes and cause schizophrenia. Here we describe a biological cascade of proteins that are activated in response to environmental stimuli such as stress, a schizophrenia risk factor. The central proteins in this pathway are critical mediators of memory formation and a particular form of hippocampal synaptic plasticity, long-term depression (LTD. Each of these proteins is also implicated in schizophrenia risk. In fact, the pathway includes four genes that map to the 108 loci associated with schizophrenia: GRIN2A, nuclear factor of activated T-cells (NFATc3, early growth response 1 (EGR1 and NGFI-A Binding Protein 2 (NAB2; each of which contains the “Index single nucleotide polymorphism (SNP” (most SNP at its respective locus. Environmental stimuli activate this biological pathway in neurons, resulting in induction of EGR immediate early genes: EGR1, EGR3 and NAB2. We hypothesize that dysfunction in any of the genes in this pathway disrupts the normal activation of Egrs in response to stress. This may

  7. Immediate Early Genes Anchor a Biological Pathway of Proteins Required for Memory Formation, Long-Term Depression and Risk for Schizophrenia

    Marballi, Ketan K.; Gallitano, Amelia L.

    2018-01-01

    While the causes of myriad medical and infectious illnesses have been identified, the etiologies of neuropsychiatric illnesses remain elusive. This is due to two major obstacles. First, the risk for neuropsychiatric disorders, such as schizophrenia, is determined by both genetic and environmental factors. Second, numerous genes influence susceptibility for these illnesses. Genome-wide association studies have identified at least 108 genomic loci for schizophrenia, and more are expected to be published shortly. In addition, numerous biological processes contribute to the neuropathology underlying schizophrenia. These include immune dysfunction, synaptic and myelination deficits, vascular abnormalities, growth factor disruption, and N-methyl-D-aspartate receptor (NMDAR) hypofunction. However, the field of psychiatric genetics lacks a unifying model to explain how environment may interact with numerous genes to influence these various biological processes and cause schizophrenia. Here we describe a biological cascade of proteins that are activated in response to environmental stimuli such as stress, a schizophrenia risk factor. The central proteins in this pathway are critical mediators of memory formation and a particular form of hippocampal synaptic plasticity, long-term depression (LTD). Each of these proteins is also implicated in schizophrenia risk. In fact, the pathway includes four genes that map to the 108 loci associated with schizophrenia: GRIN2A, nuclear factor of activated T-cells (NFATc3), early growth response 1 (EGR1) and NGFI-A Binding Protein 2 (NAB2); each of which contains the “Index single nucleotide polymorphism (SNP)” (most SNP) at its respective locus. Environmental stimuli activate this biological pathway in neurons, resulting in induction of EGR immediate early genes: EGR1, EGR3 and NAB2. We hypothesize that dysfunction in any of the genes in this pathway disrupts the normal activation of Egrs in response to stress. This may result in

  8. Origin of Bolivian Quechua Amerindians: their relationship with other American Indians and Asians according to HLA genes.

    Martinez-Laso, Jorge; Siles, Nancy; Moscoso, Juan; Zamora, Jorge; Serrano-Vela, Juan I; R-A-Cachafeiro, Juan I; Castro, Maria J; Serrano-Rios, Manuel; Arnaiz-Villena, Antonio

    2006-01-01

    The Incas were Quechua-speaking people who settled down near Cuzco (Peru). They had an empire ranging from Ecuador to Chile, when Spanish conquerors seized their kingdom around 1532 AD. Nowadays, Quechua-speaking people inhabits Colombia, Ecuador, Bolivia, Peru and Argentina; however, Quechua language was imposed by both Incas and Spaniards to many non-Quechua speaking communities. We have taken a sample of Quechuan Bolivian blood donors from La Paz (Titicaca Lake region) where Inca-Quechuas themselves believed that came from. This group was compared with 6892 individuals from 68 different world populations regarding HLA/DNA allele frequencies distribution. Genetic distances, dendrograms and correspondence analyses were carried out in order to establish relationships among populations. The main conclusions are: (1) DRB1 and -DQB1 haplotypes shared with Asians are found in Quechuas and are not observed in other (Mesoamerican) Amerindians. (2) Aymara-speaking people from the same Titicaca Lake (La Paz) area shows close genetic distances with Quechuas in one dimension results (genetic distances); however, their HLA gene frequency distribution differs according to Neighbor-Joining (NJ) trees and correspondence analysis (multidimensional and more reliable analyses). Also, the common high frequency Asian and Athabascan HLA-DRB1*0901 allele is found in Quechuas in a significant frequency. Quechuas are clearly included within the Amerindian group.

  9. Reduced expression of glucocorticoid-inducible genes GILZ and SGK-1: high IL-6 levels are associated with reduced hippocampal volumes in major depressive disorder.

    Frodl, T

    2012-01-01

    Neuroplasticity may have a core role in the pathophysiology of major depressive disorder (MDD), a concept supported by experimental studies that found that excessive cortisol secretion and\\/or excessive production of inflammatory cytokines impairs neuronal plasticity and neurogenesis in the hippocampus. The objective of this study was to examine how changes in the glucocorticoid and inflammatory systems may affect hippocampal volumes in MDD. A multimodal approach with structural neuroimaging of hippocampus and amygdala, measurement of peripheral inflammatory proteins interleukin (IL)-6 and C-reactive protein (CRP), glucocorticoid receptor (GR) mRNA expression, and expression of glucocorticoid-inducible genes (glucocorticoid-inducible genes Leucin Zipper (GILZ) and glucocorticoid-inducible kinase-1 (SGK-1)) was used in 40 patients with MDD and 43 healthy controls (HC). Patients with MDD showed smaller hippocampal volumes and increased inflammatory proteins IL-6 and CRP compared with HC. Childhood maltreatment was associated with increased CRP. Patients with MDD, who had less expression of the glucocorticoid-inducible genes GILZ or SGK-1 had smaller hippocampal volumes. Regression analysis showed a strong positive effect of GILZ and SGK-1 mRNA expression, and further inverse effects of IL-6 concentration, on hippocampal volumes. These findings suggest that childhood maltreatment, peripheral inflammatory and glucocorticoid markers and hippocampal volume are interrelated factors in the pathophysiology of MDD. Glucocorticoid-inducible genes GILZ and SGK-1 might be promising candidate markers for hippocampal volume changes relevant for diseases like MDD. Further studies need to explore the possible clinical usefulness of such a blood biomarker, for example, for diagnosis or prediction of therapy response.

  10. Expression of cagA, virB/D Complex and/or vacA Genes in Helicobacter pylori Strains Originating from Patients with Gastric Diseases.

    Andrzej Szkaradkiewicz

    Full Text Available In order to better understand pathogenicity of Helicobacter pylori, particularly in the context of its carcinogenic activity, we analysed expression of virulence genes: cagA, virB/D complex (virB4, virB7, virB8, virB9, virB10, virB11, virD4 and vacA in strains of the pathogen originating from persons with gastric diseases. The studies were conducted on 42 strains of H. pylori isolated from patients with histological diagnosis of non-atrophic gastritis-NAG (group 1, including subgroup 1 containing cagA+ isolates and subgroup 2 containing cagA- strains, multifocal atrophic gastritis-MAG (group 2 and gastric adenocarcinoma-GC (group 3. Expression of H. pylori genes was studied using microarray technology. In group 1, in all strains of H. pylori cagA+ (subgroup 1 high expression of the gene as well as of virB/D was disclosed, accompanied by moderate expression of vacA. In strains of subgroup 2 a moderate expression of vacA was detected. All strains in groups 2 and 3 carried cagA gene but they differed in its expression: a high expression was detected in isolates of group 2 and its hyperexpression in strains of group 3 (hypervirulent strains. In both groups high expression of virB/D and vacA was disclosed. Our results indicate that chronic active gastritis may be induced by both cagA+ strains of H. pylori, manifesting high expression of virB/D complex but moderate activity of vacA, and cagA- strains with moderate expression of vacA gene. On the other hand, in progression of gastric pathology and carcinogenesis linked to H. pylori a significant role was played by hypervirulent strains, manifesting a very high expression of cagA and high activity of virB/D and vacA genes.

  11. Original Research

    A cross-sectional survey of adolescent depression in Malawi. Stanley Kutcher1,2 ..... depression in young people nor did they refer any student for mental health ... health problem and inappropriately treated, which has been previously ...

  12. Chronic high-dose creatine has opposing effects on depression-related gene expression and behavior in intact and sex hormone-treated gonadectomized male and female rats.

    Allen, Patricia J; DeBold, Joseph F; Rios, Maribel; Kanarek, Robin B

    2015-03-01

    Creatine is an antioxidant, neuromodulator and key regulator of energy metabolism shown to improve depressive symptoms in humans and animals, especially in females. To better understand the pharmacological effects of creatine, we examined its influence on depression-related hippocampal gene expression and behaviors in the presence and absence of sex steroids. Sham-operated and gonadectomized male and female rats were fed chow alone or chow blended with either 2% or 4% w/w creatine monohydrate for five weeks before forced swim, open field, and wire suspension tests, or seven weeks total. Before supplementation, males were chronically implanted with an empty or a testosterone-filled (T) capsule (10-mm surface release), and females were administered progesterone (P, 250 μg), estradiol benzoate (EB, 2.5 μg), EB+P, or sesame oil vehicle weekly. Relative to non-supplemented shams, all hippocampal plasticity-related mRNAs measured, including brain-derived neurotrophic factor (BDNF), tyrosine kinase B, doublecortin, calretinin, and calbindin, were downregulated in sham males given 4% creatine, and BDNF, doublecortin, and calbindin mRNAs were downregulated in sham females given 4% creatine. In contrast, combined 4% creatine+T in castrates prevented downregulation of BDNF, doublecortin, and calretinin mRNAs. Similarly, combined 4% creatine+EB+P in ovariectomized females attenuated downregulation of BDNF and calbindin mRNA levels. Moderate antidepressant and anxiolytic-like behaviors were observed in EB+P-treated ovariectomized females fed creatine, with similar trends in T-treated castrates fed creatine. Altogether, these data show that chronic, high-dose creatine has opposing effects on neuroplasticity-related genes and depressive behavior in intact and gonadectomized male and female rats. The dose and schedule of creatine used negatively impacted hippocampal neuronal integrity in otherwise healthy brains, possibly through negative compensatory changes in energy

  13. Unraveling the effect of genes and environment in the transmission of parental antisocial behavior to children’s conduct disturbance, depression, and hyperactivity

    Silberg, Judy L.; Maes, Hermine; Eaves, Lindon J.

    2011-01-01

    Background A critical issue in devising effective interventions for the treatment of children’s behavioral and emotional problems rests upon identifying genuine family environmental factors that place children at risk. In most twin and family studies, environmental factors are confounded with both direct genetic risk from parents and the indirect effect of genes influencing parents’ ability to provide an optimal rearing environment. The present study was undertaken to determine whether parental psychopathology, specifically parental antisocial behavior (ASP), is a genuine environmental risk factor for juvenile conduct disturbance, depression, and hyperactivity, or whether the association between parental ASP and children’s behavioral and emotional problems can be explained as a secondary consequence of the intergenerational transmission of genetic factors Methods An extended Children of Twins design (E-COT) comprised of data collected on 2,674 adult female and male twins, their spouses, and 2,454 of their children was used to test whether genetic and/or family environmental factors best accounted for the association between parental antisocial behavior children’s behavioral problems. An age matched sample of 2,826 juvenile twin pairs from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) was also included to examine developmental differences in gene expression by partitioning child specific transmissible effects from those effects that persist into adulthood. The fit of alternative models was evaluated using the statistical program Mx Results We found distinct patterns of transmission between parental antisocial behavior and juvenile conduct, depression, and hyperactivity. Genetic and family environmental factors accounted for the resemblance between parents’ ASP and children’s conduct disturbance. Family environmental factors alone explained the association between child depression and parental ASP, and the impact of parental ASP on

  14. Epidemiology of subtypes of depression

    Kessing, L V

    2007-01-01

    depression, dysthymia, and subsyndromal states; the association between stressful life events and depression appears to diminish with the number of depressive episodes. Finally, recent genetic findings are congruent with a model indicating that the majority of depressions develop in the interplay between...... genes and stressful experiences, whereas 'reactive' depressions and 'endogenous' depressions apparently exist at a lower prevalence. CONCLUSION: Further longitudinal, analytical, and genetic epidemiologic studies are needed to reveal which conditions are mild and transient, and which may be precursors......OBJECTIVE: There is a general clinical impression that depression differs qualitatively from non-depressive conditions, and that it can be identified as a categorical entity. In contrast, epidemiological studies support the view that depression is dynamic in nature and develops on a continuous...

  15. Colorectal carcinomas with microsatellite instability display a different pattern of target gene mutations according to large bowel site of origin

    Pinheiro, Manuela; Fragoso, Maria; Santos, Lúcio; Henrique, Rui; Lopes, Paula; Lopes, Carlos; Lothe, Ragnhild A; Teixeira, Manuel R; Ahlquist, Terje; Danielsen, Stine A; Lind, Guro E; Veiga, Isabel; Pinto, Carla; Costa, Vera; Afonso, Luís; Sousa, Olga

    2010-01-01

    Only a few studies have addressed the molecular pathways specifically involved in carcinogenesis of the distal colon and rectum. We aimed to identify potential differences among genetic alterations in distal colon and rectal carcinomas as compared to cancers arising elsewhere in the large bowel. Constitutional and tumor DNA from a test series of 37 patients with rectal and 25 patients with sigmoid carcinomas, previously analyzed for microsatellite instability (MSI), was studied for BAX, IGF2R, TGFBR2, MSH3, and MSH6 microsatellite sequence alterations, BRAF and KRAS mutations, and MLH1 promoter methylation. The findings were then compared with those of an independent validation series consisting of 36 MSI-H carcinomas with origin from each of the large bowel regions. Immunohistochemical and germline mutation analyses of the mismatch repair system were performed when appropriate. In the test series, IGFR2 and BAX mutations were present in one and two out of the six distal MSI-H carcinomas, respectively, and no mutations were detected in TGFBR2, MSH3, and MSH6. We confirmed these findings in the validation series, with TGFBR2 and MSH3 microsatellite mutations occurring less frequently in MSI-H rectal and sigmoid carcinomas than in MSI-H colon carcinomas elsewhere (P = 0.00005 and P = 0.0000005, respectively, when considering all MSI-carcinomas of both series). No MLH1 promoter methylation was observed in the MSI-H rectal and sigmoid carcinomas of both series, as compared to 53% found in MSI-H carcinomas from other locations (P = 0.004). KRAS and BRAF mutational frequencies were 19% and 43% in proximal carcinomas and 25% and 17% in rectal/sigmoid carcinomas, respectively. The mechanism and the pattern of genetic changes driving MSI-H carcinogenesis in distal colon and rectum appears to differ from that occurring elsewhere in the colon and further investigation is warranted both in patients with sporadic or hereditary disease

  16. The avian-origin PB1 gene segment facilitated replication and transmissibility of the H3N2/1968 pandemic influenza virus.

    Wendel, Isabel; Rubbenstroth, Dennis; Doedt, Jennifer; Kochs, Georg; Wilhelm, Jochen; Staeheli, Peter; Klenk, Hans-Dieter; Matrosovich, Mikhail

    2015-04-01

    The H2N2/1957 and H3N2/1968 pandemic influenza viruses emerged via the exchange of genomic RNA segments between human and avian viruses. The avian hemagglutinin (HA) allowed the hybrid viruses to escape preexisting immunity in the human population. Both pandemic viruses further received the PB1 gene segment from the avian parent (Y. Kawaoka, S. Krauss, and R. G. Webster, J Virol 63:4603-4608, 1989), but the biological significance of this observation was not understood. To assess whether the avian-origin PB1 segment provided pandemic viruses with some selective advantage, either on its own or via cooperation with the homologous HA segment, we modeled by reverse genetics the reassortment event that led to the emergence of the H3N2/1968 pandemic virus. Using seasonal H2N2 virus A/California/1/66 (Cal) as a surrogate precursor human virus and pandemic virus A/Hong Kong/1/68 (H3N2) (HK) as a source of avian-derived PB1 and HA gene segments, we generated four reassortant recombinant viruses and compared pairs of viruses which differed solely by the origin of PB1. Replacement of the PB1 segment of Cal by PB1 of HK facilitated viral polymerase activity, replication efficiency in human cells, and contact transmission in guinea pigs. A combination of PB1 and HA segments of HK did not enhance replicative fitness of the reassortant virus compared with the single-gene PB1 reassortant. Our data suggest that the avian PB1 segment of the 1968 pandemic virus served to enhance viral growth and transmissibility, likely by enhancing activity of the viral polymerase complex. Despite the high impact of influenza pandemics on human health, some mechanisms underlying the emergence of pandemic influenza viruses still are poorly understood. Thus, it was unclear why both H2N2/1957 and H3N2/1968 reassortant pandemic viruses contained, in addition to the avian HA, the PB1 gene segment of the avian parent. Here, we addressed this long-standing question by modeling the emergence of the H3N2

  17. Do mood symptoms subdivide the schizophrenia phenotype? : Association of the GMP6A gene with a depression subgroup

    Boks, Marco P M; Hoogendoorn, Mechteld; Jungerius, Bart J; Bakker, Steven C; Sommer, Iris E; Sinke, Richard J; Ophoff, Roel A; Kahn, René S

    2008-01-01

    Genetic studies of clinically defined subgroups of schizophrenia patients may reduce the phenotypic heterogeneity of schizophrenia and thus facilitate the identification of genes that confer risk to this disorder. Several latent class analyses have provided subgroups of psychotic disorders that show

  18. Preliminary evidence for an association between a dopamine D3 receptor gene variant and obsessive-compulsive personality disorder in patients with major depression.

    Light, Katrina J; Joyce, Peter R; Luty, Suzanne E; Mulder, Roger T; Frampton, Christropher M A; Joyce, Laura R M; Miller, Allison L; Kennedy, Martin A

    2006-06-05

    We have previously reported that the Ser9Gly dopamine D3 receptor (DRD3) polymorphism was associated with increased rates of obsessive-compulsive personality disorder (OCPD) symptomology. We tested the replicability of this association within a further two independent groups of individuals with a history of depression, from a clinical sample (n = 149) and a family study (n = 213). The data from the replication samples and the original sample, within which the association was found, were compiled within a meta-analysis. Although the independent samples did not replicate the original finding, the meta-analysis elucidated significant evidence supporting the association. An individual with Gly/Gly genotype is 2.4 (P = 0.017) times more likely to be diagnosed with OCPD. Male gender was also found to be a significant predictor of OCPD diagnosis (OR = 2.82, P = 0.001). An exploration of an association of DRD3 with Axis I anxiety disorder diagnoses and Temperament and Character Inventory (TCI) traits, in particular persistence, revealed no support for an association. We conclude that DRD3 may contribute to the development of OCPD.

  19. Gene-by-social-environment interaction (GxSE) between ADCYAP1R1 genotype and neighborhood crime predicts major depression symptoms in trauma-exposed women.

    Lowe, Sarah R; Pothen, John; Quinn, James W; Rundle, Andrew; Bradley, Bekh; Galea, Sandro; Ressler, Kerry J; Koenen, Karestan C

    2015-11-15

    Few studies have explored interactions between genes and social environmental exposures (GxSEs) for trauma-related psychopathology, including symptoms of posttraumatic stress (PTS) and major depression (MD). The extant literature suggests the possibility of a GxSE between the rs2267735 variant of the ADCYAP1R1 gene and neighborhood crime. The current study aimed to explore this possibility among a predominantly African American sample of trauma-exposed women. Female participants (N=1361) were recruited from a public hospital, and completed measures of PTS and MD symptoms and provided DNA samples. Participants' home addresses were mapped onto 300 neighborhoods (2010 census tracts), and data on crime within neighborhoods was collected. Multilevel models detected a significant GxSE between rs2267735 and neighborhood crime for MD symptoms (p=.01). Having two copies of the risk (C) allele was associated with higher MD symptoms for participants living in high-crime neighborhoods. At least six limitations are noteworthy: (1) low statistical power; (2) use of self-report symptom inventories; (3) lack of information on symptom onset; (4) homogeneous sample from a single metropolitan area; (5) non-specific index of crime; and (6) use of census tracts to define neighborhoods. The results provide further evidence of GxSEs for psychiatric outcomes among trauma-exposed populations. Further investigations of genetic factors for trauma-related psychopathology should include careful assessments of the social environment. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Original Researc Original Research

    RAGHAVENDRA

    Practices. Problems. Supervision. Primary School. *Corresponding Author: Asrat Dagnew. E-mail: asratboza@yahoo.com tructional support. The relevant and ... vision is one of indispensable system pment. Supervision is a system of that directly concerned on the aff members in a school or other. Original Research ...

  1. Original Research Original Research

    RAGHAVENDRA

    language in social interaction( Anto et al., 2012; Tessema et al., 2012). While such ..... 10 items on a five-point Likert scale originally developed by Benard et al. (2007). ..... self-confidence, and hold down their anxiety levels. In this study ...

  2. Gene

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  3. Step-wise and lineage-specific diversification of plant RNA polymerase genes and origin of the largest plant-specific subunits.

    Wang, Yaqiong; Ma, Hong

    2015-09-01

    Proteins often function as complexes, yet little is known about the evolution of dissimilar subunits of complexes. DNA-directed RNA polymerases (RNAPs) are multisubunit complexes, with distinct eukaryotic types for different classes of transcripts. In addition to Pol I-III, common in eukaryotes, plants have Pol IV and V for epigenetic regulation. Some RNAP subunits are specific to one type, whereas other subunits are shared by multiple types. We have conducted extensive phylogenetic and sequence analyses, and have placed RNAP gene duplication events in land plant history, thereby reconstructing the subunit compositions of the novel RNAPs during land plant evolution. We found that Pol IV/V have experienced step-wise duplication and diversification of various subunits, with increasingly distinctive subunit compositions. Also, lineage-specific duplications have further increased RNAP complexity with distinct copies in different plant families and varying divergence for subunits of different RNAPs. Further, the largest subunits of Pol IV/V probably originated from a gene fusion in the ancestral land plants. We propose a framework of plant RNAP evolution, providing an excellent model for protein complex evolution. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  4. Association of polymorphisms in 5-HTT (SLC6A4) and MAOA genes with measures of obesity in young adults of Portuguese origin.

    Dias, Helena; Muc, Magdalena; Padez, Cristina; Manco, Licínio

    2016-01-01

    To investigate the association of polymorphisms in SLC6A4 and MAOA genes with overweight (including obesity). Young adults (n = 535) of Portuguese origin were genotyped for the SLC6A4 polymorphisms 5-HTTLPR and STin2 and a MAOA VNTR. BMI and body fat percentage were measured and a questionnaire was used to assess individual's sport practicing habits. In whole study sample, haplotype-based analysis revealed significant association with overweight/obesity for the individual 5-HTTLPR/Stin2 haplotype L10 (p = 0.04). In men, the MAOA 3R genotype was nominally associated with body fat (p = 0.04). In inactive individuals, overweight/obesity was found significantly associated with 5-HTTLPR L-allele (p = 0.01) and nominally associated with STin2 10-allele (p = 0.03). A significant association was also found testing for all haplotype effects (χ(2 )= 8.7; p = 0.03). We found some evidences for the association of SLC6A4 and MAOA genes with measures of obesity. Our results suggest physical inactivity accentuates the influence of SLC6A4 polymorphisms on obesity risk.

  5. Mutation profile of all 49 exons of the human myosin VIIA gene, and haplotype analysis, in Usher 1B families from diverse origins.

    Adato, A; Weil, D; Kalinski, H; Pel-Or, Y; Ayadi, H; Petit, C; Korostishevsky, M; Bonne-Tamir, B

    1997-10-01

    Usher syndrome types I (USH1A-USH1E) are a group of autosomal recessive diseases characterized by profound congenital hearing loss, vestibular areflexia, and progressive visual loss due to retinitis pigmentosa. The human myosin VIIA gene, located on 11q14, has been shown to be responsible for Usher syndrome type 1B (USH1B). Haplotypes were constructed in 28 USH1 families by use of the following polymorphic markers spanning the USH1B locus: D11S787, D11S527, D11S1789, D11S906, D11S4186, and OMP. Affected individuals and members of their families from 12 different ethnic origins were screened for the presence of mutations in all 49 exons of the myosin VIIA gene. In 15 families myosin VIIA mutations were detected, verifying their classification as USH1B. All these mutations are novel, including three missense mutations, one premature stop codon, two splicing mutations, one frameshift, and one deletion of >2 kb comprising exons 47 and 48, a part of exon 49, and the introns between them. Three mutations were shared by more than one family, consistent with haplotype similarities. Altogether, 16 USH1B haplotypes were observed in the 15 families; most haplotypes were population specific. Several exonic and intronic polymorphisms were also detected. None of the 20 known USH1B mutations reported so far in other world populations were identified in our families.

  6. Origin of the Y genome in Elymus and its relationship to other genomes in Triticeae based on evidence from elongation factor G (EF-G) gene sequences.

    Sun, Genlou; Komatsuda, Takao

    2010-08-01

    It is well known that Elymus arose through hybridization between representatives of different genera. Cytogenetic analyses show that all its members include the St genome in combination with one or more of four other genomes, the H, Y, P, and W genomes. The origins of the H, P, and W genomes are known, but not for the Y genome. We analyzed the single copy nuclear gene coding for elongation factor G (EF-G) from 28 accessions of polyploid Elymus species and 45 accessions of diploid Triticeae species in order to investigate origin of the Y genome and its relationship to other genomes in the tribe Triticeae. Sequence comparisons among the St, H, Y, P, W, and E genomes detected genome-specific polymorphisms at 66 nucleotide positions. The St and Y genomes are relatively dissimilar. The phylogeny of the Y genome sequences was investigated for the first time. They were most similar to the W genome sequences. The Y genome sequences were placed in two different groups. These two groups were included in an unresolved clade that included the W and E sequences as well as sequences from many annual species. The H genomes sequences were in a clade with the F, P, and Ns genome sequences as sister groups. These two clades were more closely related to each other and to the L and Xp genomes than they were to the St genome sequences. These data support the hypothesis that the Y genome evolved in a diploid species and has a different origin from the St genome. Copyright 2010 Elsevier Inc. All rights reserved.

  7. Caregiver Depression

    ... will not sell or share your name. Caregiver Depression Tweet Bookmark this page | Email | Print Many caregivers ... depression See your doctor Treatment Coping Symptoms of depression Caregiving is hard — and can lead to feelings ...

  8. Depression FAQs

    Depression affects about 15 million American adults every year. Women are more likely to get depression than men. In general, about one out of every four women will get depression at some point in her life.

  9. Depression Screening

    ... Depression Screening Substance Abuse Screening Alcohol Use Screening Depression Screening (PHQ-9) - Instructions The following questions are ... this tool, there is also text-only version . Depression Screening - Manual Instructions The following questions are a ...

  10. Depression, osteoporosis, serotonin and cell membrane viscosity between biology and philosophical anthropology

    Gabrielli Fabio

    2011-03-01

    Full Text Available Abstract Due to the relationship between biology and culture, we believe that depression, understood as a cultural and existential phenomenon, has clear markers in molecular biology. We begin from an existential analysis of depression constituting the human condition and then shift to analysis of biological data confirming, according to our judgment, its original (ontological structure. In this way philosophy is involved at the anthropological level, in as much as it detects the underlying meanings of depression in the original biological-cultural horizon of human life. Considering the integration of knowledge it is the task of molecular biology to identify the aforementioned markers, to which the existential aspects of depression are linked to. In particular, recent works show the existence of a link between serotonin and osteoporosis as a result of a modified expression of the low-density lipoprotein receptor-related protein 5 gene. Moreover, it is believed that the hereditary or acquired involvement of tryptophan hydroxylase 2 (Tph2 or 5-hydroxytryptamine transporter (5-HTT is responsible for the reduced concentration of serotonin in the central nervous system, causing depression and affective disorders. This work studies the depression-osteoporosis relationship, with the aim of focusing on depressive disorders that concern the quantitative dynamic of platelet membrane viscosity and interactome cytoskeleton modifications (in particular Tubulin and Gsα protein as a possible condition of the involvement of the serotonin axis (gut, brain and platelet, not only in depression but also in connection with osteoporosis.

  11. [Primary headache and depression].

    Gesztelyi, Gyöngyi

    2004-11-28

    Primary headaches--mainly tension-type headache and migraine--affect a significant portion of the population. Depression is also highly prevalent. The co-existence of a primary headache and depression in the same patient therefore might be a coincidence due to the high prevalence of these conditions, but there might be a causal relationship between them, or headaches and depression might have a common background. This review of the literature summarizes the features of the relationship between primary headaches and depression. Depression is more prevalent in headache patients than in the headache-free population. Prospective epidemiological studies suggest a common genetic, biochemical or environmental background behind primary headaches and depression. This theory is supported by the role of the same neurotransmitter systems (mostly serotonin and dopamine) in headaches as well as in depression. Comorbid depression is associated with female gender, higher age, and higher frequency of headaches. Most depression inventories--questionnaires used to screen for the severity of depressive symptoms--contain transdiagnostic items, therefore their use in their original form is limited in organic diseases: due to the somatic items they might overestimate the severity of depression. When examining a headache patient special attention should be paid to the recognition of comorbid depression. The diagnosis of suspected mood disorder could be supported by using simple screening methods, such as the original or the abbreviated versions of standard depression inventories, but the final diagnosis of major depression needs psychiatric evaluation. Quality of life of the headache patient is affected not only by the characteristics of pain (frequency, duration, severity) but also by the disability caused by headache and the associating mood disorder. Recognizing coexisting mood disorder and disability helps to make the best treatment choice for the acute and preventive treatment of

  12. Sex Differences in the Expression of Depressive Responses on the Beck Depression Inventory

    Hammen, Constance L.; Padesky, Christine A.

    1977-01-01

    Although epidemiological data have documented sex differences in depression, the nature and origins of the differences are unclear. Depression in a large sample of young, unmarried college students was measured and described by the Beck Depression Inventory. Considers the consequences of sex differences in depressive responses, including…

  13. Depressive Disorder, Anxiety Disorder and Chronic Pain: Multiple Manifestations of a Common Clinical and Pathophysiological Core.

    Arango-Dávila, Cesar A; Rincón-Hoyos, Hernán G

    A high proportion of depressive disorders are accompanied by anxious manifestations, just as depression and anxiety often present with many painful manifestations, or conversely, painful manifestations cause or worsen depressive and anxious expressions. There is increasingly more evidence of the pathophysiological, and neurophysiological and technical imaging similarity of pain and depression. Narrative review of the pathophysiological and clinical aspects of depression and chronic pain comorbidity. Research articles are included that emphasise the most relevant elements related to understanding the pathophysiology of both manifestations. The pathological origin, physiology and clinical approach to these disorders have been more clearly established with the latest advances in biochemical and cellular techniques, as well as the advent of imaging technologies. This information is systematised with comprehensive images and clinical pictures. The recognition that the polymorphism of inflammation-related genes generates susceptibility to depressive manifestations and may modify the response to antidepressant treatments establishes that the inflammatory response is not only an aetiopathogenic component of pain, but also of stress and depression. Likewise, the similarity in approach with images corroborates not only the structural, but the functional and pathophysiological analogy between depression and chronic pain. Knowledge of depression-anxiety-chronic pain comorbidity is essential in the search for effective therapeutic interventions. Copyright © 2016 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  14. Original Research

    settings, and this limits access to effective mental healthcare for young people with depression. ... Methods. A sample of healthcare providers (N = 25) from community health clinics ... to youth referred from schools, it led to generally favourable clinical outcomes. ... A cross-sectional survey of adolescent depression in Malawi.

  15. Evidence for Broadening Criteria for Atypical Depression Which May Define a Reactive Depressive Disorder

    Brett Silverstein

    2015-01-01

    Full Text Available Objective. Arguing that additional symptoms should be added to the criteria for atypical depression. Method. Published research articles on atypical depression are reviewed. Results. (1 The original studies upon which the criteria for atypical depression were based cited fatigue, insomnia, pain, and loss of weight as characteristic symptoms. (2 Several studies of DSM depressive criteria found patients with atypical depression to exhibit high levels of insomnia, fatigue, and loss of appetite/weight. (3 Several studies have found atypical depression to be comorbid with headaches, bulimia, and body image issues. (4 Most probands who report atypical depression meet criteria for “somatic depression,” defined as depression associated with several of disordered eating, poor body image, headaches, fatigue, and insomnia. The gender difference in prevalence of atypical depression results from its overlap with somatic depression. Somatic depression is associated with psychosocial measures related to gender, linking it with the descriptions of atypical depression as “reactive” appearing in the studies upon which the original criteria for atypical depression were based. Conclusion. Insomnia, disordered eating, poor body image, and aches/pains should be added as criteria for atypical depression matching criteria for somatic depression defining a reactive depressive disorder possibly distinct from endogenous melancholic depression.

  16. Evidence for Broadening Criteria for Atypical Depression Which May Define a Reactive Depressive Disorder.

    Silverstein, Brett; Angst, Jules

    2015-01-01

    Objective. Arguing that additional symptoms should be added to the criteria for atypical depression. Method. Published research articles on atypical depression are reviewed. Results. (1) The original studies upon which the criteria for atypical depression were based cited fatigue, insomnia, pain, and loss of weight as characteristic symptoms. (2) Several studies of DSM depressive criteria found patients with atypical depression to exhibit high levels of insomnia, fatigue, and loss of appetite/weight. (3) Several studies have found atypical depression to be comorbid with headaches, bulimia, and body image issues. (4) Most probands who report atypical depression meet criteria for "somatic depression," defined as depression associated with several of disordered eating, poor body image, headaches, fatigue, and insomnia. The gender difference in prevalence of atypical depression results from its overlap with somatic depression. Somatic depression is associated with psychosocial measures related to gender, linking it with the descriptions of atypical depression as "reactive" appearing in the studies upon which the original criteria for atypical depression were based. Conclusion. Insomnia, disordered eating, poor body image, and aches/pains should be added as criteria for atypical depression matching criteria for somatic depression defining a reactive depressive disorder possibly distinct from endogenous melancholic depression.

  17. Fluoxetine normalizes disrupted light-induced entrainment, fragmented ultradian rhythms and altered hippocampal clock gene expression in an animal model of high trait anxiety- and depression-related behavior.

    Schaufler, Jörg; Ronovsky, Marianne; Savalli, Giorgia; Cabatic, Maureen; Sartori, Simone B; Singewald, Nicolas; Pollak, Daniela D

    2016-01-01

    Disturbances of circadian rhythms are a key symptom of mood and anxiety disorders. Selective serotonin reuptake inhibitors (SSRIs) - commonly used antidepressant drugs - also modulate aspects of circadian rhythmicity. However, their potential to restore circadian disturbances in depression remains to be investigated. The effects of the SSRI fluoxetine on genetically based, depression-related circadian disruptions at the behavioral and molecular level were examined using mice selectively bred for high anxiety-related and co-segregating depression-like behavior (HAB) and normal anxiety/depression behavior mice (NAB). The length of the circadian period was increased in fluoxetine-treated HAB as compared to NAB mice while the number of activity bouts and light-induced entrainment were comparable. No difference in hippocampal Cry2 expression, previously reported to be dysbalanced in untreated HAB mice, was observed, while Per2 and Per3 mRNA levels were higher in HAB mice under fluoxetine treatment. The present findings provide evidence that fluoxetine treatment normalizes disrupted circadian locomotor activity and clock gene expression in a genetic mouse model of high trait anxiety and depression. An interaction between the molecular mechanisms mediating the antidepressant response to fluoxetine and the endogenous regulation of circadian rhythms in genetically based mood and anxiety disorders is proposed.

  18. ORIGINAL ARTICLE

    Boaz

    use of antibiotic and appropriate methods of screening ESBL genes in routine laboratories in Niger is needed to control the. ESBL genes ... lactam antibiotics currently available and other ... data on the ESBLs gene characterization available.

  19. Acquisition through Horizontal Gene Transfer of Plasmid pSMA198 by Streptococcus macedonicus ACA-DC 198 Points towards the Dairy Origin of the Species

    Papadimitriou, Konstantinos; Anastasiou, Rania; Maistrou, Eleni; Plakas, Thomas; Papandreou, Nikos C.; Hamodrakas, Stavros J.; Ferreira, Stéphanie; Supply, Philip; Renault, Pierre; Pot, Bruno; Tsakalidou, Effie

    2015-01-01

    Background Streptococcus macedonicus is an intriguing streptococcal species whose most frequent source of isolation is fermented foods similarly to Streptococcus thermophilus. However, S. macedonicus is closely related to commensal opportunistic pathogens of the Streptococcus bovis/Streptococcus equinus complex. Methodology/Principal Findings We analyzed the pSMA198 plasmid isolated from the dairy strain Streptococcus macedonicus ACA-DC 198 in order to provide novel clues about the main ecological niche of this bacterium. pSMA198 belongs to the narrow host range pCI305/pWV02 family found primarily in lactococci and to the best of our knowledge it is the first such plasmid to be reported in streptococci. Comparative analysis of the pSMA198 sequence revealed a high degree of similarity with plasmids isolated from Lactococcus lactis strains deriving from milk or its products. Phylogenetic analysis of the pSMA198 Rep showed that the vast majority of closely related proteins derive from lactococcal dairy isolates. Additionally, cloning of the pSMA198 ori in L. lactis revealed a 100% stability of replication over 100 generations. Both pSMA198 and the chromosome of S. macedonicus exhibit a high percentage of potential pseudogenes, indicating that they have co-evolved under the same gene decay processes. We identified chromosomal regions in S. macedonicus that may have originated from pSMA198, also supporting a long co-existence of the two replicons. pSMA198 was also found in divergent biotypes of S. macedonicus and in strains isolated from dispersed geographic locations (e.g. Greece and Switzerland) showing that pSMA198’s acquisition is not a recent event. Conclusions/Significance Here we propose that S. macedonicus acquired plasmid pSMA198 from L. lactis via an ancestral genetic exchange event that took place most probably in milk or dairy products. We provide important evidence that point towards the dairy origin of this species. PMID:25584532

  20. Biochemical and Structural Insights into the Preference of Nairoviral DeISGylases for Interferon-Stimulated Gene Product 15 Originating from Certain Species

    Deaton, M. K.; Dzimianski, J. V.; Daczkowski, C. M.; Whitney, G. K.; Mank, N. J.; Parham, M. M.; Bergeron, E.; Pegan, S. D.; Perlman, S.

    2016-07-13

    ABSTRACT

    The regulation of the interferon type I (IFN-I) response has been shown to rely on posttranslational modification by ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15) to stabilize, or activate, a variety of IFN-I signaling and downstream effector proteins. Unlike Ub, which is almost perfectly conserved among eukaryotes, ISG15 is highly divergent, even among mammals. Since zoonotic viruses rely on viral proteins to recognize, or cleave, ISG15 conjugates in order to evade, or suppress, innate immunity, the impact of ISG15 biodiversity on deISGylating proteases of the ovarian tumor family (vOTU) from nairoviruses was evaluated. The enzymatic activities of vOTUs originating from the Crimean-Congo hemorrhagic fever virus, Erve virus, and Nairobi sheep disease virus were tested against ISG15s from humans, mice, shrews, sheep, bats, and camels, which are mammalian species known to be infected by nairoviruses. This along with investigation of binding by isothermal titration calorimetry illustrated significant differences in the abilities of nairovirus deISGylases to accommodate certain species of ISG15. To investigate the molecular underpinnings of species preferences of these vOTUs, a structure was determined to 2.5 Å for a complex of Erve virus vOTU protease and a mouse ISG15 domain. This structure revealed the molecular basis of Erve virus vOTU's preference for ISG15 over Ub and the first structural insight into a nonhuman ISG15. This structure also revealed key interactions, or lack thereof, surrounding three amino acids that may drive a viral deISgylase to prefer an ISG15 from one species over that of another.

    IMPORTANCEViral ovarian tumor domain proteases (vOTUs) are one of the two principal classes of viral proteases observed to reverse posttranslational modification of host proteins by ubiquitin and interferon-stimulated gene product 15 (ISG15), subsequently facilitating downregulation of

  1. ORIGINAL ARTICLES Depression and anxiety in multisomatoform ...

    2008-06-02

    Jun 2, 2008 ... disorder, with a prevalence of 8 - 10% in primary care.5,10. MSD is characterised ... Exclusion criteria included current or past bipolar mood disorder ... significant risk of suicide, concurrent cognitive behavioural therapy, or use ...

  2. The Role of the Val66Met Polymorphism of the Brain Derived Neurotrophic Factor Gene in Coping Strategies Relevant to Depressive Symptoms.

    Warren Caldwell

    Full Text Available Disturbances of brain derived neurotrophic factor (BDNF signalling have been implicated in the evolution of depression, which likely arises, in part, as a result of diminished synaptic plasticity. Predictably, given stressor involvement in depression, BDNF is affected by recent stressors as well as stressors such as neglect experienced in early life. The effects of early life maltreatment in altering BDNF signalling may be particularly apparent among those individuals with specific BDNF polymorphisms. We examined whether polymorphisms of the Val66Met genotype might be influential in moderating how early-life events play out with respect to later coping styles, cognitive flexibility and depressive features. Among male and female undergraduate students (N = 124, childhood neglect was highly related to subsequent depressive symptoms. This outcome was moderated by the BDNF polymorphism in the sense that depressive symptoms appeared higher in Met carriers who reported low levels of neglect than in those with the Val/Val allele. However, under conditions of high neglect depressive symptoms only increased in the Val/Val individuals. In effect, the Met polymorphism was associated with depressive features, but did not interact with early life neglect in predicting later depressive features. It was further observed that among the Val/Val individuals, the relationship between neglect and depression was mediated by emotion-focused styles and diminished perceived control, whereas this mediation was not apparent in Met carriers. In contrast to the more typical view regarding this polymorphism, the data are consistent with the perspective that in the presence of synaptic plasticity presumably associated with the Val/Val genotype, neglect allows for the emergence of specific appraisal and coping styles, which are tied to depression. In the case of the reduced degree of neuroplasticity expected in the Met carriers, early life adverse experiences are not tied

  3. , ORIGINAL ARTICLES

    rheumatic diseases associated with higher rates of depression ..... Halverson PB, Holmes Ss. Systemic lupus erythematosus: medical and nursing treabnents. .... Stress management and copipg research in the health care setting: an oven'iew.

  4. ORIGINAL ARTICLE

    User

    the Center for Epidemiological Studies Depression Scale (CES-D) for stress assessment and State ... Almost all the pregnant women had no complication in the current pregnancy ... mous biological, psychological and social challenges.

  5. Comparative transcriptome analyses of a late-maturing mandarin mutant and its original cultivar reveals gene expression profiling associated with citrus fruit maturation

    Lu Wang

    2017-05-01

    Full Text Available Characteristics of late maturity in fruit are good agronomic traits for extending the harvest period and marketing time. However, underlying molecular basis of the late-maturing mechanism in fruit is largely unknown. In this study, RNA sequencing (RNA-Seq technology was used to identify differentially expressed genes (DEGs related to late-maturing characteristics from a late-maturing mutant ‘Huawan Wuzishatangju’ (HWWZSTJ (Citrus reticulata Blanco and its original line ‘Wuzishatangju’ (WZSTJ. A total of approximately 17.0 Gb and 84.2 M paried-end reads were obtained. DEGs were significantly enriched in the pathway of photosynthesis, phenylpropanoid biosynthesis, carotenoid biosynthesis, chlorophyll and abscisic acid (ABA metabolism. Thirteen candidate transcripts related to chlorophyll metabolism, carotenoid biosynthesis and ABA metabolism were analyzed using real-time quantitative PCR (qPCR at all fruit maturing stages of HWWZSTJ and WZSTJ. Chlorophyllase (CLH and divinyl reductase (DVR from chlorophyll metabolism, phytoene synthase (PSY and capsanthin/capsorubin synthase (CCS from carotenoid biosynthesis, and abscisic acid 8′-hydroxylase (AB1 and 9-cis-epoxycarotenoid dioxygenase (NCED1 from ABA metabolism were cloned and analyzed. The expression pattern of NCED1 indicated its role in the late-maturing characteristics of HWWZSTJ. There were 270 consecutive bases missing in HWWZSTJ in comparison with full-length sequences of NCED1 cDNA from WZSTJ. Those results suggested that NCED1 might play an important role in the late maturity of HWWZSTJ. This study provides new information on complex process that results in the late maturity of Citrus fruit at the transcriptional level.

  6. Orígenes de la enseñanza de la Farmacia en Cuba Origin of Pharmacy teaching in Cuba

    Pilar Marchante Castellanos

    2006-12-01

    Full Text Available Aunque la Universidad cubana cuenta con casi tres siglos de existencia, hasta el momento no ha sido realizado un estudio que presente la historia de la carrera de Farmacia de manera cronológica y sistemática. El objetivo del presente trabajo ha sido comenzar la búsqueda de la información más antigua disponible para presentar, en apretada síntesis, los antecedentes y orígenes de la enseñanza universitaria de las Ciencias Farmacéuticas en Cuba tomando lo más significativo de la situación imperante en la Isla antes del surgimiento de su primera Universidad, en 1728. Adicionalmente, y mediante el análisis de la documentación existente, se logra precisar el año en que se incluyó, por primera vez, la carrera de Farmacia en esa Universidad.Havana University is almost three centuries-old; however, no study has been made so far in which the history of Pharmacy career has been chronologically and systematically presented. The objective of this paper was to look for the most ancient information available in order to present in a brief way the antecedents and origins of Pharmaceutical Sciences teaching at university in Cuba, taking the most significant aspects of the situation prevailing in the island before the emergence of the first university in 1728 as a basis. Additionally, through the analysis of existing documents of that time, it was possible to precise over the year when Pharmacy career was included in that first university.

  7. Pollen-Mediated Gene Flow in Maize: Implications for Isolation Requirements and Coexistence in Mexico, the Center of Origin of Maize.

    Baltazar, Baltazar M; Castro Espinoza, Luciano; Espinoza Banda, Armando; de la Fuente Martínez, Juan Manuel; Garzón Tiznado, José Antonio; González García, Juvencio; Gutiérrez, Marco Antonio; Guzmán Rodríguez, José Luis; Heredia Díaz, Oscar; Horak, Michael J; Madueño Martínez, Jesús Ignacio; Schapaugh, Adam W; Stojšin, Duška; Uribe Montes, Hugo Raúl; Zavala García, Francisco

    2015-01-01

    Mexico, the center of origin of maize (Zea mays L.), has taken actions to preserve the identity and diversity of maize landraces and wild relatives. Historically, spatial isolation has been used in seed production to maintain seed purity. Spatial isolation can also be a key component for a strategy to minimize pollen-mediated gene flow in Mexico between transgenic maize and sexually compatible plants of maize conventional hybrids, landraces, and wild relatives. The objective of this research was to generate field maize-to-maize outcrossing data to help guide coexistence discussions in Mexico. In this study, outcrossing rates were determined and modeled from eight locations in six northern states, which represent the most economically important areas for the cultivation of hybrid maize in Mexico. At each site, pollen source plots were planted with a yellow-kernel maize hybrid and surrounded by plots with a white-kernel conventional maize hybrid (pollen recipient) of the same maturity. Outcrossing rates were then quantified by assessing the number of yellow kernels harvested from white-kernel hybrid plots. The highest outcrossing values were observed near the pollen source (12.9% at 1 m distance). The outcrossing levels declined sharply to 4.6, 2.7, 1.4, 1.0, 0.9, 0.5, and 0.5% as the distance from the pollen source increased to 2, 4, 8, 12, 16, 20, and 25 m, respectively. At distances beyond 20 m outcrossing values at all locations were below 1%. These trends are consistent with studies conducted in other world regions. The results suggest that coexistence measures that have been implemented in other geographies, such as spatial isolation, would be successful in Mexico to minimize transgenic maize pollen flow to conventional maize hybrids, landraces and wild relatives.

  8. Closed depression topography Harps soil, revisited

    Accumulation of carbonates around depressions indicates past or present water and solute flow paths out and up from the depressions. The purpose of this study was to determine the pattern of surface carbonates in relation to landscape parameters, depressions, and original Harps map units. Surface ca...

  9. The influence of the rs6295 gene polymorphism on serotonin-1A receptor distribution investigated with PET in patients with major depression applying machine learning.

    Kautzky, A; James, G M; Philippe, C; Baldinger-Melich, P; Kraus, C; Kranz, G S; Vanicek, T; Gryglewski, G; Wadsak, W; Mitterhauser, M; Rujescu, D; Kasper, S; Lanzenberger, R

    2017-06-13

    Major depressive disorder (MDD) is the most common neuropsychiatric disease and despite extensive research, its genetic substrate is still not sufficiently understood. The common polymorphism rs6295 of the serotonin-1A receptor gene (HTR1A) is affecting the transcriptional regulation of the 5-HT 1A receptor and has been closely linked to MDD. Here, we used positron emission tomography (PET) exploiting advances in data mining and statistics by using machine learning in 62 healthy subjects and 19 patients with MDD, which were scanned with PET using the radioligand [carbonyl- 11 C]WAY-100635. All the subjects were genotyped for rs6295 and genotype was grouped in GG vs C allele carriers. Mixed model was applied in a ROI-based (region of interest) approach. ROI binding potential (BP ND ) was divided by dorsal raphe BP ND as a specific measure to highlight rs6295 effects (BP Div ). Mixed model produced an interaction effect of ROI and genotype in the patients' group but no effects in healthy controls. Differences of BP Div was demonstrated in seven ROIs; parahippocampus, hippocampus, fusiform gyrus, gyrus rectus, supplementary motor area, inferior frontal occipital gyrus and lingual gyrus. For classification of genotype, 'RandomForest' and Support Vector Machines were used, however, no model with sufficient predictive capability could be computed. Our results are in line with preclinical data, mouse model knockout studies as well as previous clinical analyses, demonstrating the two-pronged effect of the G allele on 5-HT 1A BP ND for, we believe, the first time. Future endeavors should address epigenetic effects and allosteric heteroreceptor complexes. Replication in larger samples of MDD patients is necessary to substantiate our findings.

  10. Depression (PDQ)

    ... Data Conducting Clinical Trials Statistical Tools and Data Terminology Resources NCI Data Catalog Cryo-EM NCI's Role ... that may also cause depression. There are many medical conditions that can cause depression. Medical conditions that ...

  11. Postpartum Depression

    ... do not need treatment. The symptoms of postpartum depression last longer and are more severe. You may ... treatment right away, often in the hospital. Postpartum depression can begin anytime within the first year after ...

  12. Depression Treatment

    ... 3286 After hours (404) 639-2888 Contact Media Depression Treatment Recommend on Facebook Tweet Share Compartir On ... How Do I Know if I Am Experiencing Depression? The following questions may help you determine if ...

  13. Teen Depression

    What is depression in teens? Teen depression is a serious medical illness. It's more than just a feeling of being sad or "blue" for a few days. It is ... trouble focusing and have no motivation or energy. Depression can make you feel like it is hard ...

  14. Association of functional polymorphisms from brain-derived neurotrophic factor and serotonin-related genes with depressive symptoms after a medical stressor in older adults.

    Kerri S Rawson

    Full Text Available Depressive symptoms are common in older adults after a disabling medical event and interfere with rehabilitation and recovery from the disability. This prospective study examined the role of genetic polymorphisms implicated in synaptic integrity and stress-associated depression as predictors of depressive symptoms after hip fracture. We recruited healthy comparisons from the community and participants with hip fracture after surgical fixation from Saint Louis, Missouri hospitals. We examined the valine (Val to methionine (Met polymorphism in brain-derived neurotrophic factor (BDNF, serotonin 1A receptor (5HT1a-rs6295 polymorphism, and the serotonin transporter-linked polymorphic region (5HTTLPR interaction with the rs25531 A to G single nucleotide polymorphism (5HTTLPR-rs25531 as predictors of depressive symptoms. We also examined whether depressive symptoms mediate the influence of BDNF genotype on functional recovery. Among 429 participants with hip fracture, BDNF Met/Met carriers developed significantly more depressive symptoms than Val/Val carriers during a four-week period after the fracture (p=.012. BDNF genotype also predicted functional recovery over the ensuing year, mediated by its effects on depressive symptoms (CI: 0.07-3.37. Unlike prior studies of stressful life events, the S' 5HTTLPR-rs25531 variant did not predict higher levels of depressive symptoms; instead, we report an exploratory finding of an epistatic effect between BDNF and 5HTTLPR-rs25531 whereby the compounded effects of two LA alleles and BDNF Met/Met genotype elevate risk of depressive symptoms after hip fracture (p=.006. No differences between 5HT1a genotypes were found. Our findings suggest plasticity-related genetic factors contribute to the neural mechanisms of mental and functional well-being after a disabling medical stressor.

  15. Triple-reassortant influenza A virus with H3 of human seasonal origin, NA of swine origin, and internal A(H1N1) pandemic 2009 genes is established in Danish pigs

    Krog, Jesper Schak; Hjulsager, Charlotte Kristiane; Larsen, Michael Albin

    2017-01-01

    This report describes a triple-reassortant influenza A virus with a HA that resembles H3 of human seasonal influenza from 2004 to 2005, N2 from influenza A virus already established in swine, and the internal gene cassette from A(H1N1)pdm09 has spread in Danish pig herds. The virus has been detec...

  16. DNA methylation differences at growth related genes correlate with birth weight: a molecular signature linked to developmental origins of adult disease?

    Turan Nahid

    2012-04-01

    Full Text Available Abstract Background Infant birth weight is a complex quantitative trait associated with both neonatal and long-term health outcomes. Numerous studies have been published in which candidate genes (IGF1, IGF2, IGF2R, IGF binding proteins, PHLDA2 and PLAGL1 have been associated with birth weight, but these studies are difficult to reproduce in man and large cohort studies are needed due to the large inter individual variance in transcription levels. Also, very little of the trait variance is explained. We decided to identify additional candidates without regard for what is known about the genes. We hypothesize that DNA methylation differences between individuals can serve as markers of gene "expression potential" at growth related genes throughout development and that these differences may correlate with birth weight better than single time point measures of gene expression. Methods We performed DNA methylation and transcript profiling on cord blood and placenta from newborns. We then used novel computational approaches to identify genes correlated with birth weight. Results We identified 23 genes whose methylation levels explain 70-87% of the variance in birth weight. Six of these (ANGPT4, APOE, CDK2, GRB10, OSBPL5 and REG1B are associated with growth phenotypes in human or mouse models. Gene expression profiling explained a much smaller fraction of variance in birth weight than did DNA methylation. We further show that two genes, the transcriptional repressor MSX1 and the growth factor receptor adaptor protein GRB10, are correlated with transcriptional control of at least seven genes reported to be involved in fetal or placental growth, suggesting that we have identified important networks in growth control. GRB10 methylation is also correlated with genes involved in reactive oxygen species signaling, stress signaling and oxygen sensing and more recent data implicate GRB10 in insulin signaling. Conclusions Single time point measurements of gene

  17. Deciphering the Origin, Evolution, and Physiological Function of the Subtelomeric Aryl-Alcohol Dehydrogenase Gene Family in the Yeast Saccharomyces cerevisiae.

    Yang, Dong-Dong; de Billerbeck, Gustavo M; Zhang, Jin-Jing; Rosenzweig, Frank; Francois, Jean-Marie

    2018-01-01

    Homology searches indicate that Saccharomyces cerevisiae strain BY4741 contains seven redundant genes that encode putative aryl-alcohol dehydrogenases (AAD). Yeast AAD genes are located in subtelomeric regions of different chromosomes, and their functional role(s) remain enigmatic. Here, we show that two of these genes, AAD4 and AAD14 , encode functional enzymes that reduce aliphatic and aryl-aldehydes concomitant with the oxidation of cofactor NADPH, and that Aad4p and Aad14p exhibit different substrate preference patterns. Other yeast AAD genes are undergoing pseudogenization. The 5' sequence of AAD15 has been deleted from the genome. Repair of an AAD3 missense mutation at the catalytically essential Tyr 73 residue did not result in a functional enzyme. However, ancestral-state reconstruction by fusing Aad6 with Aad16 and by N-terminal repair of Aad10 restores NADPH-dependent aryl-alcohol dehydrogenase activities. Phylogenetic analysis indicates that AAD genes are narrowly distributed in wood-saprophyte fungi and in yeast that occupy lignocellulosic niches. Because yeast AAD genes exhibit activity on veratraldehyde, cinnamaldehyde, and vanillin, they could serve to detoxify aryl-aldehydes released during lignin degradation. However, none of these compounds induce yeast AAD gene expression, and Aad activities do not relieve aryl-aldehyde growth inhibition. Our data suggest an ancestral role for AAD genes in lignin degradation that is degenerating as a result of yeast's domestication and use in brewing, baking, and other industrial applications. IMPORTANCE Functional characterization of hypothetical genes remains one of the chief tasks of the postgenomic era. Although the first Saccharomyces cerevisiae genome sequence was published over 20 years ago, 22% of its estimated 6,603 open reading frames (ORFs) remain unverified. One outstanding example of this category of genes is the enigmatic seven-member AAD family. Here, we demonstrate that proteins encoded by two

  18. Protective influences of N-acetylcysteine against alcohol abstinence-induced depression by regulating biochemical and GRIN2A, GRIN2B gene expression of NMDA receptor signaling pathway in rats.

    Yawalkar, Rutuja; Changotra, Harish; Gupta, Girdhari Lal

    2018-04-25

    Evidences have indicated a high degree of comorbidity of alcoholism and depression. N-acetylcysteine (NAC) has shown its clinical efficiency in the treatment of several psychiatric disorders and is identified as a multi-target acting drug. The ability of NAC to prevent alcohol abstinence-induced depression-like effects and underlying mechanism(s) have not been adequately addressed. This study was aimed to investigate the beneficial effects of NAC in the alcohol abstinence-induced depression developed following long-term voluntary alcohol intake. For evaluation of the effects of NAC, Sprague-Dawley rats were enabled to voluntary drinking of 4.5%, 7.5% and 9% v/v alcohol for fifteen days. NAC (25, 50, and 100 mg/kg) and fluoxetine (5 mg/kg) were injected intraperitoneally for three consecutive days during the alcohol abstinence period on the days 16, 17, 18. The behavioral studies were conducted employing forced swim test (FST), and tail suspension test (TST) on day 18 to determine the effects of N-acetylcysteine and fluoxetine in the ethanol withdrawal induced-depression. Blood alcohol concentration, alcohol biomarkers like SGPT, SGOT, ALP, GGT, and MCV were estimated by using commercially available kits. Serotonin concentrations were measured in the plasma, hippocampus and pre-frontal cortex using the rat ELISA kit. The expression of GRIN1, GRIN2A, GRIN2B genes for the N-methyl d-aspartate receptors (NMDAR) subunits in the hippocampus and the prefrontal cortex were also examined by reverse-transcription quantitative polymerase chain reaction. The results revealed that alcohol abstinence group depicted increased immobility time in FST and TST. Further, NAC exerted significant protective effect at the doses 50 mg/kg and 100 mg/kg, but 25 mg/kg showed insignificant protection against alcohol abstinence-induced depression. The increased level of biochemical parameters following ethanol abstinence were also reversed by NAC at the dose of 100 mg/kg. The

  19. Characterization of an artificial swine-origin influenza virus with the same gene combination as H1N1/2009 virus: a genesis clue of pandemic strain.

    Zhao, Xueli; Sun, Yipeng; Pu, Juan; Fan, Lihong; Shi, Weimin; Hu, Yanxin; Yang, Jun; Xu, Qi; Wang, Jingjing; Hou, Dongjun; Ma, Guangpeng; Liu, Jinhua

    2011-01-01

    Pandemic H1N1/2009 influenza virus, derived from a reassortment of avian, human, and swine influenza viruses, possesses a unique gene segment combination that had not been detected previously in animal and human populations. Whether such a gene combination could result in the pathogenicity and transmission as H1N1/2009 virus remains unclear. In the present study, we used reverse genetics to construct a reassortant virus (rH1N1) with the same gene combination as H1N1/2009 virus (NA and M genes from a Eurasian avian-like H1N1 swine virus and another six genes from a North American triple-reassortant H1N2 swine virus). Characterization of rH1N1 in mice showed that this virus had higher replicability and pathogenicity than those of the seasonal human H1N1 and Eurasian avian-like swine H1N1 viruses, but was similar to the H1N1/2009 and triple-reassortant H1N2 viruses. Experiments performed on guinea pigs showed that rH1N1 was not transmissible, whereas pandemic H1N1/2009 displayed efficient transmissibility. To further determine which gene segment played a key role in transmissibility, we constructed a series of reassortants derived from rH1N1 and H1N1/2009 viruses. Direct contact transmission studies demonstrated that the HA and NS genes contributed to the transmission of H1N1/2009 virus. Second, the HA gene of H1N1/2009 virus, when combined with the H1N1/2009 NA gene, conferred efficient contact transmission among guinea pigs. The present results reveal that not only gene segment reassortment but also amino acid mutation were needed for the generation of the pandemic influenza virus.

  20. Characterization of an artificial swine-origin influenza virus with the same gene combination as H1N1/2009 virus: a genesis clue of pandemic strain.

    Xueli Zhao

    Full Text Available Pandemic H1N1/2009 influenza virus, derived from a reassortment of avian, human, and swine influenza viruses, possesses a unique gene segment combination that had not been detected previously in animal and human populations. Whether such a gene combination could result in the pathogenicity and transmission as H1N1/2009 virus remains unclear. In the present study, we used reverse genetics to construct a reassortant virus (rH1N1 with the same gene combination as H1N1/2009 virus (NA and M genes from a Eurasian avian-like H1N1 swine virus and another six genes from a North American triple-reassortant H1N2 swine virus. Characterization of rH1N1 in mice showed that this virus had higher replicability and pathogenicity than those of the seasonal human H1N1 and Eurasian avian-like swine H1N1 viruses, but was similar to the H1N1/2009 and triple-reassortant H1N2 viruses. Experiments performed on guinea pigs showed that rH1N1 was not transmissible, whereas pandemic H1N1/2009 displayed efficient transmissibility. To further determine which gene segment played a key role in transmissibility, we constructed a series of reassortants derived from rH1N1 and H1N1/2009 viruses. Direct contact transmission studies demonstrated that the HA and NS genes contributed to the transmission of H1N1/2009 virus. Second, the HA gene of H1N1/2009 virus, when combined with the H1N1/2009 NA gene, conferred efficient contact transmission among guinea pigs. The present results reveal that not only gene segment reassortment but also amino acid mutation were needed for the generation of the pandemic influenza virus.

  1. A protein that binds to the P1 origin core and the oriC 13mer region in a methylation-specific fashion is the product of the host seqA gene.

    Brendler, T; Abeles, A; Austin, S

    1995-08-15

    The P1 plasmid replication origin P1oriR is controlled by methylation of four GATC adenine methylation sites within heptamer repeats. A comparable (13mer) region is present in the host origin, oriC. The two origins show comparable responses to methylation; negative control by recognition of hemimethylated DNA (sequestration) and a positive requirement for methylation for efficient function. We have isolated a host protein that recognizes the P1 origin region only when it is isolated from a strain proficient for adenine methylation. The substantially purified 22 kDa protein also binds to the 13mer region of oriC in a methylation-specific fashion. It proved to be the product of the seqA gene that acts in the negative control of oriC by sequestration. We conclude that the role of the SeqA protein in sequestration is to recognize the methylation state of P1oriR and oriC by direct DNA binding. Using synthetic substrates we show that SeqA binds exclusively to the hemimethylated forms of these origins forms that are the immediate products of replication in a methylation-proficient strain. We also show that the protein can recognize sequences with multiple GATC sites, irrespective of the surrounding sequence. The basis for origin specificity is primarily the persistence of hemimethylated forms that are over-represented in the natural. DNA preparations relative to controls.

  2. Structural analysis of the 5' flanking region of the β-globin gene in African sickle cell anemia patients: Further evidence for three origins of the sickle cell mutation in Africa

    Chebloune, Y.; Pagnier, J.; Trabuchet, G.; Faure, C.; Verdier, G.; Labie, D.; Nigon, V.

    1988-01-01

    Haplotype analysis of the β-globin gene cluster shows two regions of DNA characterized by nonrandom association of restriction site polymorphisms. These regions are separated by a variable segment containing the repeated sequences (ATTTT) n and (AT) x T y , which might be involved in recombinational events. Studies of haplotypes linked to the sickle cell gene in Africa provide strong argument for three origins of the mutation: Benin, Senegal, and the Central African Republic. The structure of the variable segment in the three African populations was studied by S1 nuclease mapping of genomic DNA, which allows a comparison of several samples. A 1080-base-pair DNA segment was sequenced for one sample from each population. S1 nuclease mapping confirmed the homogeneity of each population with regard to both (ATTTT) n and (AT) x T y repeats. The authors found three additional structures for (AT) x T y correlating with the geographic origin of the patients. Ten other nucleotide positions, 5' and 3' to the (AT) x T y copies, were found to be variable when compared to homologous sequences from human and monkey DNAs. These results allow us to propose an evolutionary scheme for the polymorphisms in the 5' flanking region of the β-globin gene. The results strongly support the hypothesis of three origins for the sickle mutation in Africa

  3. Molecular Adaptations to Social Defeat Stress and Induced Depression in Mice.

    Bondar, Natalya; Bryzgalov, Leonid; Ershov, Nikita; Gusev, Fedor; Reshetnikov, Vasiliy; Avgustinovich, Damira; Tenditnik, Mikhail; Rogaev, Evgeny; Merkulova, Tatiana

    2018-04-01

    Chronic stress is a risk factor for major depression. Social defeat stress is a well-validated murine model of depression. However, little is known about the gene activity dynamics during the development of a depression-like state. We analyzed the effects of social defeat stress of varying duration (10 and 30 days) on the behavioral patterns and prefrontal-cortex transcriptome of C57BL/6 mice. The 10-day exposure to social defeat stress resulted in a high level of social avoidance with no signs of depression-associated behavior. Most animals exposed to 30 days of social defeat stress demonstrated clear hallmarks of depression, including a higher level of social avoidance, increased immobility in the forced swimming test, and anhedonic behavior. The monitoring of transcriptome changes revealed widespread alterations in gene expression on the 10th day. Surprisingly, the expression of only a few genes were affected by the 30th day of stress, apparently due to a reversal of the majority of the early stress-induced changes to the original basal state. Moreover, we have found that glucocorticoid-sensitive genes are clearly stimulated targets on the 10th day of stress, but these genes stop responding to the elevated corticosterone level by the 30th day of stress. The majority of genes altered by the 30-day stress were downregulated, with the most relevant ones participating in chromatin modifications and neuroplasticity (e.g., guanine nucleotide exchange factors of the Rho-family of GTPases). Very different molecular responses occur during short-term and long-term social stress in mice. The early-stress response is associated with social avoidance and with upregulation and downregulation of many genes, including those related to signal transduction and cell adhesion pathways. Downregulation of a few genes, in particular, genes for histone-modifying methyltransferases, is a signature response to prolonged stress that induces symptoms of depression. Altogether, our data

  4. Original Misunderstanding

    Holtzman, Alexander

    2009-01-01

    Humorist Josh Billings quipped, "About the most originality that any writer can hope to achieve honestly is to steal with good judgment." Billings was harsh in his view of originality, but his critique reveals a tension faced by students every time they write a history paper. Research is the essence of any history paper. Especially in high school,…

  5. A novel deletion in the thyrotropin Beta-subunit gene identified by array comparative genomic hybridization analysis causes central congenital hypothyroidism in a boy originating from Turkey.

    Hermanns, Pia; Couch, Robert; Leonard, Norma; Klotz, Cherise; Pohlenz, Joachim

    2014-01-01

    Isolated central congenital hypothyroidism (ICCH) is rare but important. Most ICCH patients are diagnosed later, which results in severe growth failure and intellectual disability. We describe a boy with ICCH due to a large homozygous TSHβ gene deletion. A 51-day-old male Turkish infant, whose parents were first cousins, was admitted for evaluation of prolonged jaundice. His clinical appearance was compatible with hypothyroidism. Venous thyrotropin (TSH) was undetectably low, with a subsequent low free T4 and a low free T3, suggestive of central hypothyroidism. Using different PCR protocols, we could not amplify both coding exons of the boy's TSHβ gene, which suggested a deletion. An array comparative genomic hybridization (aCGH) using specific probes around the TSHβ gene locus showed him to be homozygous for a 6-kb deletion spanning all exons and parts of the 5' untranslated region of the gene. Infants who are clinically suspected of having hypothyroidism should be evaluated thoroughly, even if their TSH-based screening result is normal. In cases with ICCH and undetectably low TSH serum concentrations, a TSHβ gene deletion should be considered; aCGH should be performed when gene deletions are suspected. In such cases, PCR-based sequencing techniques give negative results.

  6. Genome evolution in an ancient bacteria-ant symbiosis: parallel gene loss among Blochmannia spanning the origin of the ant tribe Camponotini

    Laura E. Williams

    2015-04-01

    Full Text Available Stable associations between bacterial endosymbionts and insect hosts provide opportunities to explore genome evolution in the context of established mutualisms and assess the roles of selection and genetic drift across host lineages and habitats. Blochmannia, obligate endosymbionts of ants of the tribe Camponotini, have coevolved with their ant hosts for ∼40 MY. To investigate early events in Blochmannia genome evolution across this ant host tribe, we sequenced Blochmannia from two divergent host lineages, Colobopsis obliquus and Polyrhachis turneri, and compared them with four published genomes from Blochmannia of Camponotus sensu stricto. Reconstructed gene content of the last common ancestor (LCA of these six Blochmannia genomes is reduced (690 protein coding genes, consistent with rapid gene loss soon after establishment of the symbiosis. Differential gene loss among Blochmannia lineages has affected cellular functions and metabolic pathways, including DNA replication and repair, vitamin biosynthesis and membrane proteins. Blochmannia of P. turneri (i.e., B. turneri encodes an intact DnaA chromosomal replication initiation protein, demonstrating that loss of dnaA was not essential for establishment of the symbiosis. Based on gene content, B. obliquus and B. turneri are unable to provision hosts with riboflavin. Of the six sequenced Blochmannia, B. obliquus is the earliest diverging lineage (i.e., the sister group of other Blochmannia sampled and encodes the fewest protein-coding genes and the most pseudogenes. We identified 55 genes involved in parallel gene loss, including glutamine synthetase, which may participate in nitrogen recycling. Pathways for biosynthesis of coenzyme A, terpenoids and riboflavin were lost in multiple lineages, suggesting relaxed selection on the pathway after inactivation of one component. Analysis of Illumina read datasets did not detect evidence of plasmids encoding missing functions, nor the presence of

  7. Impulsive Internet Game Play Is Associated With Increased Functional Connectivity Between the Default Mode and Salience Networks in Depressed Patients With Short Allele of Serotonin Transporter Gene

    Ji Sun Hong

    2018-04-01

    Full Text Available Problematic Internet game play is often accompanied by major depressive disorder (MDD. Depression seems to be closely related to altered functional connectivity (FC within (and between the default mode network (DMN and salience network. In addition, serotonergic neurotransmission may regulate the symptoms of depression, including impulsivity, potentially by modulating the DMN. We hypothesized that altered connectivity between the DMN and salience network could mediate an association between the 5HTTLPR genotype and impulsivity in patients with depression. A total of 54 participants with problematic Internet game play and MDD completed the research protocol. We genotyped for 5HTTLPR and assessed the DMN FC using resting-state functional magnetic resonance imaging. The severity of Internet game play, depressive symptoms, anxiety, attention and impulsivity, and behavioral inhibition and activation were assessed using the Young Internet Addiction Scale (YIAS, Beck Depressive Inventory, Beck Anxiety Inventory (BAI, Korean Attention Deficit Hyperactivity Disorder scale, and the Behavioral Inhibition and Activation Scales (BIS-BAS, respectively. The SS allele was associated with increased FC within the DMN, including the middle prefrontal cortex (MPFC to the posterior cingulate cortex, and within the salience network, including the right supramarginal gyrus (SMG to the right rostral prefrontal cortex (RPFC, right anterior insular (AInsular to right SMG, anterior cingulate cortex (ACC to left RPFC, and left AInsular to right RPFC, and between the DMN and salience network, including the MPFC to the ACC. In addition, the FC from the MPFC to ACC positively correlated with the BIS and YIAS scores in the SS allele group. The SS allele of 5HTTLPR might modulate the FC within and between the DMN and salience network, which may ultimately be a risk factor for impulsive Internet game play in patients with MDD.

  8. Impulsive Internet Game Play Is Associated With Increased Functional Connectivity Between the Default Mode and Salience Networks in Depressed Patients With Short Allele of Serotonin Transporter Gene.

    Hong, Ji Sun; Kim, Sun Mi; Bae, Sujin; Han, Doug Hyun

    2018-01-01

    Problematic Internet game play is often accompanied by major depressive disorder (MDD). Depression seems to be closely related to altered functional connectivity (FC) within (and between) the default mode network (DMN) and salience network. In addition, serotonergic neurotransmission may regulate the symptoms of depression, including impulsivity, potentially by modulating the DMN. We hypothesized that altered connectivity between the DMN and salience network could mediate an association between the 5HTTLPR genotype and impulsivity in patients with depression. A total of 54 participants with problematic Internet game play and MDD completed the research protocol. We genotyped for 5HTTLPR and assessed the DMN FC using resting-state functional magnetic resonance imaging. The severity of Internet game play, depressive symptoms, anxiety, attention and impulsivity, and behavioral inhibition and activation were assessed using the Young Internet Addiction Scale (YIAS), Beck Depressive Inventory, Beck Anxiety Inventory (BAI), Korean Attention Deficit Hyperactivity Disorder scale, and the Behavioral Inhibition and Activation Scales (BIS-BAS), respectively. The SS allele was associated with increased FC within the DMN, including the middle prefrontal cortex (MPFC) to the posterior cingulate cortex, and within the salience network, including the right supramarginal gyrus (SMG) to the right rostral prefrontal cortex (RPFC), right anterior insular (AInsular) to right SMG, anterior cingulate cortex (ACC) to left RPFC, and left AInsular to right RPFC, and between the DMN and salience network, including the MPFC to the ACC. In addition, the FC from the MPFC to ACC positively correlated with the BIS and YIAS scores in the SS allele group. The SS allele of 5HTTLPR might modulate the FC within and between the DMN and salience network, which may ultimately be a risk factor for impulsive Internet game play in patients with MDD.

  9. Characterization of the IncA/C plasmid pSCEC2 from Escherichia coli of swine origin that harbours the multiresistance gene cfr.

    Zhang, Wan-Jiang; Xu, Xing-Ran; Schwarz, Stefan; Wang, Xiu-Mei; Dai, Lei; Zheng, Hua-Jun; Liu, Siguo

    2014-02-01

    To determine the complete nucleotide sequence of the multidrug resistance plasmid pSCEC2, isolated from a porcine Escherichia coli strain, and to analyse it with particular reference to the cfr gene region. Plasmid pSCEC2 was purified from its E. coli J53 transconjugant and then sequenced using the 454 GS-FLX System. After draft assembly, predicted gaps were closed by PCR with subsequent sequencing of the amplicons. Plasmid pSCEC2 is 135 615 bp in size and contains 200 open reading frames for proteins of ≥100 amino acids. Analysis of the sequence of pSCEC2 revealed two resistance gene segments. The 4.4 kb cfr-containing segment is flanked by two IS256 elements in the same orientation, which are believed to be involved in the dissemination of the rRNA methylase gene cfr. The other segment harbours the resistance genes floR, tet(A)-tetR, strA/strB and sul2, which have previously been found on other IncA/C plasmids. Except for these two resistance gene regions, the pSCEC2 backbone displayed >99% nucleotide sequence identity to that of other IncA/C family plasmids isolated in France, Chile and the USA. The cfr gene was identified on an IncA/C plasmid, which is well known for its broad host range and transfer and maintenance properties. The location on such a plasmid will further accelerate the dissemination of cfr and co-located resistance genes among different Gram-negative bacteria. The genetic context of cfr on plasmid pSCEC2 underlines the complexity of cfr transfer events and confirms the role that insertion sequences play in the spread of cfr.

  10. Depressive Disorders

    Brown, Jacqueline A.; Russell, Samantha; Rasor, Kaitlin

    2017-01-01

    Depression is among the most common mental disorders in the United States. Its diagnosis is often related to impairment of functioning across several domains, including how an individual thinks, feels, and participates in daily activities. Although depression has a relatively high prevalence among adults, the rate is alarmingly higher among…

  11. Postpartum Depression

    ... professionals for help. With support and treatment, new mothers with depression can go on to be healthy, happy parents. ... or two, talk to your doctor. A new mother who feels like giving up, who feels that life is not ... depression can last for several months or even longer ...

  12. The evolution and appearance of C3 duplications in fish originate an exclusive teleost c3 gene form with anti-inflammatory activity.

    Gabriel Forn-Cuní

    Full Text Available The complement system acts as a first line of defense and promotes organism homeostasis by modulating the fates of diverse physiological processes. Multiple copies of component genes have been previously identified in fish, suggesting a key role for this system in aquatic organisms. Herein, we confirm the presence of three different previously reported complement c3 genes (c3.1, c3.2, c3.3 and identify five additional c3 genes (c3.4, c3.5, c3.6, c3.7, c3.8 in the zebrafish genome. Additionally, we evaluate the mRNA expression levels of the different c3 genes during ontogeny and in different tissues under steady-state and inflammatory conditions. Furthermore, while reconciling the phylogenetic tree with the fish species tree, we uncovered an event of c3 duplication common to all teleost fishes that gave rise to an exclusive c3 paralog (c3.7 and c3.8. These paralogs showed a distinct ability to regulate neutrophil migration in response to injury compared with the other c3 genes and may play a role in maintaining the balance between inflammatory and homeostatic processes in zebrafish.

  13. Genome-wide comparative analysis reveals similar types of NBS genes in hybrid Citrus sinensis genome and original Citrus clementine genome and provides new insights into non-TIR NBS genes

    In this study, we identified and compared nucleotide-binding site (NBS) domain-containing genes from three Citrus genomes (C. clementina, C. sinensis from USA and C. sinensis from China). Phylogenetic analysis of all Citrus NBS genes across these three genomes revealed that there are three approxima...

  14. Original Article

    Administratör

    Original Article. Prevalence of Gall Bladder Stones among Type 2 Diabetic ... Increasing age, female gender, overweight, familial history of the disease and type 2 diabetes mellitus is all associated ... GBS development in diabetics. An Italian ...

  15. ORIGINAL ARTICLE

    User

    UDS Publishers Limited All Right Reserved 2026-6294. ORIGINAL ... Reproductive development and function in human and other ... sulting solution was filtered and left to stand for three days to ..... male rat brain and pituitary. Brain Res 164,.

  16. Original pedagogues

    Schmidt, Christina Haandbæk

    Original pedagogues Distention between competences and originality By Christina Haandbæk Schmidt, ph. d. student Aarhus University, Denmark This presentation concerns a Ph.D. project (Sept. 2012 –Sept. 2015) about pedagogues in day care facilities and their struggles to develop and retain...... shall argue that it is necessary for the pedagogues to know how they are constituted by the regimes of power on one side and on the other side are forced to create themselves. This knowledge could transform pedagogues into what I suggest calling ‘original pedagogues’, who have an authentic, ethic...... and professional autonomy in exercising judgment concerning pedagogical situations. To understand how pedagogues can struggle the distention between being competent and being original the project draws on both Michel Foucault and Charles Taylor as two incompatible theories on modern identity. The study...

  17. Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances.

    Wang, S.S.; Kamphuis, W.; Huitinga, I.; Zhou, J.N.; Swaab, D.F.

    2008-01-01

    Hyperactivity of corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus (PVN) of the hypothalamus is a prominent feature in depression and may be important in the etiology of this disease. The activity of the CRF neurons in the stress response is modulated by a number of factors

  18. Frequency and origin of haplotypes associated with the beta-globin gene cluster in individuals with trait and sickle cell anemia in the Atlantic and Pacific coastal regions of Colombia.

    Fong, Cristian; Lizarralde-Iragorri, María Alejandra; Rojas-Gallardo, Diana; Barreto, Guillermo

    2013-12-01

    Sickle cell anemia is a genetic disease with high prevalence in people of African descent. There are five typical haplotypes associated with this disease and the haplotypes associated with the beta-globin gene cluster have been used to establish the origin of African-descendant people in America. In this work, we determined the frequency and the origin of haplotypes associated with hemoglobin S in a sample of individuals with sickle cell anemia (HbSS) and sickle cell hemoglobin trait (HbAS) in coastal regions of Colombia. Blood samples from 71 HbAS and 79 HbSS individuals were obtained. Haplotypes were determined based on the presence of variable restriction sites within the β-globin gene cluster. On the Pacific coast of Colombia the most frequent haplotype was Benin, while on the Atlantic coast Bantu was marginally higher than Benin. Eight atypical haplotypes were observed on both coasts, being more diverse in the Atlantic than in the Pacific region. These results suggest a differential settlement of the coasts, dependent on where slaves were brought from, either from the Gulf of Guinea or from Angola, where the haplotype distributions are similar. Atypical haplotypes probably originated from point mutations that lost or gained a restriction site and/or by recombination events.

  19. Genetik og stressende livsbegivenheder interagerer ved depression

    Kessing, Lars Vedel; Bukh, Jens Otto Drachmann

    2013-01-01

    The aim of the present review was to present clinical aspects of recent research in genes, the experience of stressful life events and depression. 60-70% experience a moderate to severe stressful life event half a year prior to the first onset of depression, whereas later depressive episodes...... to a lesser extent are preceded by stressful life events. Clinical features do not differ between depressions with or without prior stressful life events. Certain genetic variations in the serotonin receptor system seem to increase the risk of developing depression in relation to experiencing stressful life...

  20. Depressive realism and clinical depression.

    Carson, Richard C; Hollon, Steven D; Shelton, Richard C

    2010-04-01

    Depressive realism suggests that depressed individuals make more accurate judgments of control than their nondepressed counterparts. However, most studies demonstrating this phenomenon were conducted in nonclinical samples. In this study, psychiatric patients who met criteria for major depressive disorder underestimated control in a contingent situation and were consistently more negative in their judgments than were nondepressed controls. Depressed patients were less likely than their nondepressed counterparts to overestimate control in a noncontingent situation, but largely because they perceived receiving less reinforcement. Depressed patients were no more likely to use the appropriate logical heuristic to generate their judgments of control than their nondepressed counterparts and each appeared to rely on different primitive heuristics. Depressed patients were consistently more negative than their nondepressed counterparts and when they did appear to be more "accurate" in their judgments of control (as in the noncontingent situation) it was largely because they applied the wrong heuristic to less accurate information. These findings do not support the notion of depressive realism and suggest that depressed patients distort their judgments in a characteristically negative fashion. 2009 Elsevier Ltd. All rights reserved.

  1. Polymorphisms of renin-angiotensin system and natriuretic peptide receptor A genes in patients of Greek origin with a history of myocardial infarction.

    Karayannis, George; Tsezou, Aspasia; Giannatou, Eirini; Papanikolaou, Vassilios; Giamouzis, Gregory; Triposkiadis, Filippos

    2010-11-01

    We assessed the association between (CA)n repeat polymorphism of angiotensinogen (AGT), 250 base pair (bp) insertion/deletion (I/D) of angiotensin-converting enzyme (ACE), tetranucleotide repeat polymorphism (TCTG)n of renin (REN), (CT)n repeat polymorphism of the natriuretic peptide receptor A (NPRA) genes, and the presence and extent of coronary artery disease (CAD) in Greek patients with a history of myocardial infarction (MI). A total of 158 post-MI patients referred for coronary angiography were compared with 144 controls. The SS genotype of the AGT gene was related with an increased risk for 3-vessel CAD (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.05-3.61; P = .041), whereas the SL genotype was related with a decreased risk (OR, 0.44; 95% CI, 0.22-0.87; P = .019). Moreover, there was a trend for the SL genotype of the REN gene toward increased risk for CAD. There was a significant association between (CA)n polymorphism of the AGT gene and the extent of CAD in Greek patients with a history of MI.

  2. Adrenocorticotropin-dependent precocious puberty of testicular origin in a boy with X-linked adrenal hypoplasia congenita due to a novel mutation in the DAX1 gene.

    Domenice, S; Latronico, A C; Brito, V N; Arnhold, I J; Kok, F; Mendonca, B B

    2001-09-01

    Primary adrenal insufficiency is a rare condition in pediatric age, and its association with precocious sexual development is very uncommon. We report a 2-yr-old Brazilian boy with DAX1 gene mutation whose first clinical manifestation was isosexual gonadotropin-independent precocious puberty. He presented with pubic hair, enlarged penis and testes, and advanced bone age. T levels were elevated, whereas basal and GnRH-stimulated LH levels were compatible with a prepubertal pattern. Chronic GnRH agonist therapy did not reduce T levels, supporting the diagnosis of gonadotropin-independent precocious puberty. Testotoxicosis was ruled out after normal sequencing of exon 11 of the LH receptor gene. At age 3 yr he developed clinical and hormonal features of severe primary adrenal insufficiency. The entire coding region of the DAX1 gene was analyzed through direct sequencing. A nucleotide G insertion between nucleotides 430 and 431 in exon 1, resulting in a novel frameshift mutation and a premature stop codon at position 71 of DAX-1, was identified. Surprisingly, steroid replacement therapy induced a clear decrease in testicular size and T levels to the prepubertal range. These findings suggest that chronic excessive ACTH levels resulting from adrenal insufficiency may stimulate Leydig cells and lead to gonadotropin-independent precocious puberty in some boys with DAX1 gene mutations.

  3. High sequence variations in the region containing genes encoding a cellular morphogenesis protein and the repressor of sexual development help to reveal origins of Aspergillus oryzae

    Aspergillus oryzae and Aspergillus flavus are closely related fungal species. The A. flavus population that produces numerous small sclerotia (S strain) and aflatoxin has a unique 1.5 kb deletion in the norB-cypA region of the aflatoxin gene cluster (the S genotype). Phylogenetic studies have indica...

  4. Depression in the Workplace

    ... You are here Home » Depression In The Workplace Depression In The Workplace Clinical depression has become one ... will die by suicide vi . Employees' Attitudes Towards Depression Often times a depressed employee will not seek ...

  5. Genetics Home Reference: depression

    ... Share: Email Facebook Twitter Home Health Conditions Depression Depression Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Depression (also known as major depression or major depressive ...

  6. The obesity gene, TMEM18, is of ancient origin, found in majority of neuronal cells in all major brain regions and associated with obesity in severely obese children

    Levine Allen S

    2010-04-01

    Full Text Available Abstract Background TMEM18 is a hypothalamic gene that has recently been linked to obesity and BMI in genome wide association studies. However, the functional properties of TMEM18 are obscure. Methods The evolutionary history of TMEM18 was inferred using phylogenetic and bioinformatic methods. The gene's expression profile was investigated with real-time PCR in a panel of rat and mouse tissues and with immunohistochemistry in the mouse brain. Also, gene expression changes were analyzed in three feeding-related mouse models: food deprivation, reward and diet-induced increase in body weight. Finally, we genotyped 502 severely obese and 527 healthy Swedish children for two SNPs near TMEM18 (rs6548238 and rs756131. Results TMEM18 was found to be remarkably conserved and present in species that diverged from the human lineage over 1500 million years ago. The TMEM18 gene was widely expressed and detected in the majority of cells in all major brain regions, but was more abundant in neurons than other cell types. We found no significant changes in the hypothalamic and brainstem expression in the feeding-related mouse models. There was a strong association for two SNPs (rs6548238 and rs756131 of the TMEM18 locus with an increased risk for obesity (p = 0.001 and p = 0.002. Conclusion We conclude that TMEM18 is involved in both adult and childhood obesity. It is one of the most conserved human obesity genes and it is found in the majority of all brain sites, including the hypothalamus and the brain stem, but it is not regulated in these regions in classical energy homeostatic models.

  7. Comparative analysis of mitochondrial genomes between the hau cytoplasmic male sterility (CMS) line and its iso-nuclear maintainer line in Brassica juncea to reveal the origin of the CMS-associated gene orf288.

    Heng, Shuangping; Wei, Chao; Jing, Bing; Wan, Zhengjie; Wen, Jing; Yi, Bin; Ma, Chaozhi; Tu, Jinxing; Fu, Tingdong; Shen, Jinxiong

    2014-04-30

    Cytoplasmic male sterility (CMS) is not only important for exploiting heterosis in crop plants, but also as a model for investigating nuclear-cytoplasmic interaction. CMS may be caused by mutations, rearrangement or recombination in the mitochondrial genome. Understanding the mitochondrial genome is often the first and key step in unraveling the molecular and genetic basis of CMS in plants. Comparative analysis of the mitochondrial genome of the hau CMS line and its maintainer line in B. juneca (Brassica juncea) may help show the origin of the CMS-associated gene orf288. Through next-generation sequencing, the B. juncea hau CMS mitochondrial genome was assembled into a single, circular-mapping molecule that is 247,903 bp in size and 45.08% in GC content. In addition to the CMS associated gene orf288, the genome contains 35 protein-encoding genes, 3 rRNAs, 25 tRNA genes and 29 ORFs of unknown function. The mitochondrial genome sizes of the maintainer line and another normal type line "J163-4" are both 219,863 bp and with GC content at 45.23%. The maintainer line has 36 genes with protein products, 3 rRNAs, 22 tRNA genes and 31 unidentified ORFs. Comparative analysis the mitochondrial genomes of the hau CMS line and its maintainer line allowed us to develop specific markers to separate the two lines at the seedling stage. We also confirmed that different mitotypes coexist substoichiometrically in hau CMS lines and its maintainer lines in B. juncea. The number of repeats larger than 100 bp in the hau CMS line (16 repeats) are nearly twice of those found in the maintainer line (9 repeats). Phylogenetic analysis of the CMS-associated gene orf288 and four other homologous sequences in Brassicaceae show that orf288 was clearly different from orf263 in Brassica tournefortii despite of strong similarity. The hau CMS mitochondrial genome was highly rearranged when compared with its iso-nuclear maintainer line mitochondrial genome. This study may be useful for studying the

  8. The ACE Gene Is Associated with Late-Life Major Depression and Age at Dementia Onset in a Population-Based Cohort.

    Zettergren, Anna; Kern, Silke; Gustafson, Deborah; Gudmundsson, Pia; Sigström, Robert; Östling, Svante; Eriksson, Elias; Zetterberg, Henrik; Blennow, Kaj; Skoog, Ingmar

    2017-02-01

    Depression and dementia in the elderly have been suggested to share similar risk factors and pathogenetic background, and recently the authors reported that the APOEɛ4 allele is a risk factor for both disorders in the general population. The aim of the present study was to examine the influence of the well-known polymorphisms rs1799752 in the angiotensin-converting enzyme (ACE) and rs5186 in the angiotensin receptor II type 1 (AGTR1) on late-life depression and dementia in a population-based Swedish cohort of older individuals followed over 12 years. In 2000-2001, 900 individuals underwent neuropsychiatric and neuropsychological examinations. Follow-up evaluations were performed in 2005-2006 and 2009-2010, and register data on dementia to 2012 were included. Cross-sectional associations between genotypes/alleles and depression and dementia at baseline and between genotypes/alleles and depression on at least one occasion during the study period and dementia onset to 2012 were investigated. As previously found for rs1799752 in ACE, rs5186 in AGTR1 was associated with dementia at baseline (OR: 3.25 [CI: 1.42-7.06], z = 2.90, p = 0.004). These associations became substantially weaker, or disappeared, when dementia onset to 2012 was included. For rs1799752 this could be explained by a significant association with age at onset (mean: 79.5 [SD: 6.45] years for risk-genotype carriers and 81.7 [SD: 7.12] years for carriers of other genotypes, b = -2.43, t = -2.38, df = 192, p = 0.02). When individuals with major depression on at least one occasion were analyzed, a significant association (OR: 2.14 [95% CI: 1.13-4.20], z = 2.28, p = 0.02), remaining after exclusion of dementia, with rs1799752 in ACE was found. In this population-based sample of older individuals, genetic variations in ACE seem to be important both for late-life major depression and dementia. Copyright © 2017 American Association for Geriatric Psychiatry. Published by

  9. A gene expression signature classifying telomerase and ALT immortalization reveals an hTERT regulatory network and suggests a mesenchymal stem cell origin for ALT

    Lafferty-Whyte, K; Cairney, C J; Will, M B

    2009-01-01

    Telomere length is maintained by two known mechanisms, the activation of telomerase or alternative lengthening of telomeres (ALT). The molecular mechanisms regulating the ALT phenotype are poorly understood and it is unknown how the decision of which pathway to activate is made at the cellular le......TERT in different tumour types and normal tissues. We also show evidence to suggest a novel mesenchymal stem cell origin for ALT immortalization in cell lines and mesenchymal tissues....

  10. Postpartum Depression

    Smith-Nielsen, Johanne

    Background: In three academic articles, this PhD thesis investigates maternal postpartum depression (PPD) as a risk factor for the infant-mother attachment and infant development. Previous studies have been contradictory with respect to the question of whether PPD can have long term effects...... on offspring. This may be due to not differing between when PPD is only occurring in the postpartum period and when effects are also due to ongoing or recurrent depression. However, it may also be due to viewing maternal depression as a unitary construct, and not considering underlying maternal psychological...... difficulties which may moderate potential adverse effects. The present thesis investigates two potential maternal moderators of risk:. Comorbid personality disorder and adult attachment insecurity. Moreover, the question of early environmental effects of PPD versus effects of later or ongoing depression...

  11. ZFP57 maintains the parent-of-origin-specific expression of the imprinted genes and differentially affects non-imprinted targets in mouse embryonic stem cells

    Riso, Vincenzo; Cammisa, Marco; Kukreja, Harpreet

    2016-01-01

    ZFP57 is necessary for maintaining repressive epigenetic modifications at Imprinting control regions (ICRs). In mouse embryonic stem cells (ESCs), ZFP57 binds ICRs (ICRBS) and many other loci (non-ICRBS). To address the role of ZFP57 on all its target sites, we performed high-throughput and multi......-locus analyses of inbred and hybrid mouse ESC lines carrying different gene knockouts. By using an allele-specific RNA-seq approach, we demonstrate that ZFP57 loss results in derepression of the imprinted allele of multiple genes in the imprinted clusters. We also find marked epigenetic differences between ICRBS...... the imprinted expression over long distances. At non-ICRBS, ZFP57 inactivation results in acquisition of epigenetic features that are characteristic of poised enhancers, suggesting that another function of ZFP57 in early embryogenesis is to repress cis-acting regulatory elements whose activity is not yet...

  12. Genotypic to expression profiling of bovine calcium channel, voltage-dependent, alpha-2/delta subunit 1 gene, and their association with bovine mastitis among Frieswal (HFX Sahiwal) crossbred cattle of Indian origin.

    Deb, Rajib; Singh, Umesh; Kumar, Sushil; Kumar, Arun; Singh, Rani; Sengar, Gyanendra; Mann, Sandeep; Sharma, Arjava

    2014-04-03

    Calcium channel, voltage-dependent, alpha-2/delta subunit 1 (CACNA2D1) gene is considered to be an important noncytokine candidate gene influencing mastitis. Scanty of reports are available until today regarding the role play of CACNA2D1 gene on the susceptibility of bovine mastitis. We interrogated the CACNA2D1 G519663A [A>G] SNP by PCR-RFLP among two hundreds Frieswal (HF X Sahiwal) crossbred cattle of Indian origin. Genotypic frequency of AA (51.5, n=101) was comparatively higher than AG (35, n=70) and GG (14.5, n=29). Association of Somatic cell score (SCS) with genotypes revealed that, GG genotypes showing lesser count (less susceptible to mastitis) compare to AA and AG. Relative expression of CACNA2D1 transcript (in milk samples) was significantly higher among GG than AG and AA. Further we have also isolated blood sample from the all groups and PBMCs were cultured from each blood sample as per the standard protocol. They were treated with Calcium channel blocker and the expression level of the CACNA2D1 gene was evaluated by Real Time PCR. Results show that expression level decline in each genotypic group after treatment and expression level of GG are again significantly higher than AA and AG. Thus, it may be concluded that GG genotypic animals are favorable for selecting disease resistant breeds.

  13. Origin and diversification of hindwingless Damaster ground beetles within the Japanese islands as deduced from mitochondrial ND5 gene sequences (Coleoptera, Carabidae).

    Su, Z H; Tominaga, O; Okamoto, M; Osawa, S

    1998-08-01

    Genealogical trees have been constructed using mitochondrial ND5 gene sequences of 78 Damaster (s. str.) specimens from all over the Japanese Islands. Eight lineages (called races in this paper) have been recognized. The races are tightly linked to geography with sharp distribution boundaries between them. The races and their distribution ranges do not coincide with those of classical morphology. Based on the observed distribution of the mitochondrial DNA haplotypes and the geohistorical data, we propose a diversification scenario of Damaster.

  14. Determination of enterotoxigenic Clostridium perfringens by detecting of the cpa and cpe genes in stool samples of human origin, associated to gastrointestinal disease

    Oropeza Barrios, Gletty

    2014-01-01

    A molecular methodology is provided to the Centro Nacional de Referencia de Bacteriologia (CNRB) of the Instituto Costarricense de Investigacion y Ensenanza en Nutricion y Salud. An opportune diagnosis is realized of enterotoxigenic Clostridium perfringens in stool samples of sporadic cases and cases associated to foodborne disease outbreaks. DNA extraction of the white microorganism was performed through the methodology implemented in the CNRB. The technique of polymerase chain reaction (PCR) were adapted and standardized to establish the identification of C. perfringens to species level and detection of cpe gene coding for enterotoxin. The sensitivity of the method was determined in a selective culture medium for C. perfringens (Tryptose sulfite cycloserine Agar). A detection limit of about 2,3 x 10 4 CFU/ml was reached for the cpe gene and at least 2,8 x 10 2 CFU/ml for the cpa gene. Retrospective analysis of 61 samples of diarrheal stool suspicious by C. perfringens is performed to evaluate the efficacy of the technique. Three outbreaks caused by C. perfringens were identified and a 10% of positivity in the samples were obtained analyzed during the period between July 2012-March 2014 [es

  15. The temperature-sensitive and attenuation phenotypes conferred by mutations in the influenza virus PB2, PB1, and NP genes are influenced by the species of origin of the PB2 gene in reassortant viruses derived from influenza A/California/07/2009 and A/WSN/33 viruses.

    Broadbent, Andrew J; Santos, Celia P; Godbout, Rachel A; Subbarao, Kanta

    2014-11-01

    Live attenuated influenza vaccines in the United States are derived from a human virus that is temperature sensitive (ts), characterized by restricted (≥ 100-fold) replication at 39 °C. The ts genetic signature (ts sig) has been mapped to 5 loci in 3 genes: PB1 (391 E, 581 G, and 661 T), PB2 (265 S), and NP (34 G). However, when transferred into avian and swine influenza viruses, only partial ts and attenuation phenotypes occur. To investigate the reason for this, we introduced the ts sig into the human origin virus A/WSN/33 (WSN), the avian-origin virus A/Vietnam/1203/04 (VN04), and the swine origin triple-reassortant 2009 pandemic H1N1 virus A/California/07/2009 (CA07), which contains gene segments from human, avian, and swine viruses. The VN04(ts sig) and CA07(ts sig) viruses replicated efficiently in Madin-Darby canine kidney (MDCK) cells at 39 °C, but the replication of WSN(ts sig) was restricted ≥ 100-fold compared to that at 33 °C. Reassortant CA07(ts sig) viruses were generated with individual polymerase gene segments from WSN, and vice versa. Only ts sig viruses with a PB2 gene segment derived from WSN were restricted in replication ≥ 100-fold at 39 °C. In ferrets, the CA07(ts sig) virus replicated in the upper and lower respiratory tract, but the replication of a reassortant CA07(ts sig) virus with a WSN PB2 gene was severely restricted in the lungs. Taken together, these data suggest that the origin of the PB2 gene segment influences the ts phenotype in vitro and attenuation in vivo. This could have implications for the design of novel live vaccines against animal origin influenza viruses. Live attenuated influenza vaccines (LAIVs) on temperature-sensitive (ts) backbones derived from animal origin influenza viruses are being sought for use in the poultry and swine industries and to protect people against animal origin influenza. However, inserting the ts genetic signature from a licensed LAIV backbone fails to fully attenuate these viruses. Our

  16. ORIGINAL ARTICLES

    ORIGINAL ARTICLES. Illnesses of Herod the Great. Francois P Retief, Johan F G Cilliers. Herod the Great, ldumean by birth, was king ofthe Jews from 40 to 4 BC. An able statesman, builder and warrior, he ruthlessly stamped out all perceived opposition to his rule. His last decade was characterised by vicious strife within ...

  17. ORIGINAL ARTICLES

    ORIGINAL ARTICLES. OCCUPATIONAL EXPOSURE OF. INTERNS TO BLOOD IN AN AREA. OF HIGH HIV SEROPREVALENCE. A S Karstaedt, L Pantanowitz. Objective. To determine the epidemiology of work-related exposure to blood among interns. Design. Interns were invited to complete anonymously a questionnaire ...

  18. ORIGINAL ARTICLES

    ORIGINAL ARTICLES. References. 1. McCarthy D, Amos A, Zimmet P. The rising global burden of diabetes and its complications: estimates and projections to the year 2010. Diabet Med 1997; 14: suppl 5, Sl-585. 2. Zgibor JC, Songer TJ, Kelsey SF, et al. The association of diabetes specialist care with health care practices ...

  19. ORIGINAL ARTICLES

    ORIGINAL ARTICLES. Cost to patients of obtaining treatment for HIV/AIDS in. South Africa. Sydney Rosen, Mpefe Ketlhapile, Ian Sanne, Mary Bachman DeSilva. Background. South Africa is providing antiretroviral (ARV) drugs for HIV I AIDS free of charge in order to increase access for poorer patients and promote ...

  20. ORIGINAL ARTICLES

    ORIGINAL ARTICLES could be chosen to link to action policy decisions. In the. Integrated Management of Childhood Illness (IMCI) programme, such a screening test would also remind the health provider to prescribe an iron tonic and to emphasise the importance of a balanced diet. A potential disadvantage of copper ...

  1. Original Article

    Arab Journal of Nephrology and Transplantation. 2013 Sep;6(3):153-60. Original Article. AJNT. Abstract. Introduction: Dense Deposit Disease (DDD) is a devastating renal disease that leads to renal failure within. 10 years of diagnosis in about half of affected patients. In this study, we evaluated the relative prevalence and.

  2. ORIGINAL ARTICLE

    User

    One of the concerns among mothers for delivery is labor pain. There are various ... Journal of Medical and Biomedical Sciences (2017) 6(2): 11-16. © UDS Publishers ... ORIGINAL ARTICLE ..... effective than a placebo during the first stage of.

  3. Original Article

    Pezhman Kharazm

    treatment in 32 patients who were admitted in Shohada-E-Tajrish hospital with final diagnosis of AMI from March 1996 to March 2002. ... of the patient and diagnostic studies and early surgical or non surgical intervention is the most ... operative diagnosis of etiology was based on presence of pulse at the origin of mesenteric.

  4. ORIGINAL ARTICLES

    ORIGINAL ARTICLES. References. 1. UNAIDS. Report on the Global HTV/AIDS Epidemic. Geneva: June 2000. 2. Connor E..\\1, Sperling RS, Gelber R. et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovu dine treatment. N Eng! J Med 1994; 331:1173-1180. 3. Undegren ML ...

  5. Original Research

    A facility based comparative cross-sectional study ... Health care delivery should consider the desire for children by men and .... Socio-Demographic Characteristics of the .... For substitution, children are an important part of marriage, current child needs sibling, original desires .... does not, the only way to avoid the risk of.

  6. ORIGINAL ARTICLE

    User

    source of blood supply whilst in developed countries VNRDs are the major source. This study de- termined and ... UDS Publishers Limited All Right Reserved 2026-6294. ORIGINAL ..... ferral rate of females in comparison to males as pre- .... nors at blood bank of a medical college,. Australia. Med J Armed Forces 61: 131- 4.

  7. ORIGINAL ARTICLES

    alternatives to conventional care (homoeopathy, chiropractic, acupuncture, etc.), and also recognise the groundswell of interest in and support for inclusion of benefits for services provided by traditional healers. The transition from the original, relatively restricted approach which was concerned with established, mainstream.

  8. Original contributions

    hefere

    Original contributions ... Results suggest that there is a significant positive ... psychological abuse, including economic abuse, intimidation, harassment, stalking, damage ... or maintaining the structure and function of the African home (Alio et al., 2011; Jewkes,. Levin ... Revictimisation occurs due to emotional violence and.

  9. Original Copies

    Sørensen, Tim Flohr

    2013-01-01

    of similarity by looking at artefactual similarity as the results of prototyping and as a production of simulacra. In this light, the concept of copying turns out to be more than simply a matter of trying to imitate an exotic or prestigious original, and it fundamentally raises the question how different a copy...

  10. ORIGINAL ARTICLE

    User

    there are racial and gender differences in the knowledge and awareness of HPV among Guyanese. The study aimed to ... UDS Publishers Limited All Right Reserved 2026-6294. ORIGINAL ... shown that, about 80.0% of women contracted HPV infection before ... 2010), age of initial sexual contact, and lack of symp- toms for ...

  11. Original Research

    2013-09-27

    Sep 27, 2013 ... DNA sequences were masked using CENSOR. The multiple sequence analysis revealed nine highly conserved regions of similarities in the 5'- flanking region of butyrophilin genes across species. Consensus putative transcription factor binding sites were identified using MatInspector and compared with ...

  12. The SKINT1-like gene is inactivated in hominoids but not in all primate species: implications for the origin of dendritic epidermal T cells.

    Rania Hassan Mohamed

    Full Text Available Dendritic epidermal T cells, which express an invariant Vγ5Vδ1 T-cell receptor and account for 95% of all resident T cells in the mouse epidermis, play a critical role in skin immune surveillance. These γδ T cells are generated by positive selection in the fetal thymus, after which they migrate to the skin. The development of dendritic epidermal T cells is critically dependent on the Skint1 gene expressed specifically in keratinocytes and thymic epithelial cells, suggesting an indispensable role for Skint1 in the selection machinery for specific intraepithelial lymphocytes. Phylogenetically, rodents have functional SKINT1 molecules, but humans and chimpanzees have a SKINT1-like (SKINT1L gene with multiple inactivating mutations. In the present study, we analyzed SKINT1L sequences in representative primate species and found that all hominoid species have a common inactivating mutation, but that Old World monkeys such as olive baboons, green monkeys, cynomolgus macaques and rhesus macaques have apparently functional SKINT1L sequences, indicating that SKINT1L was inactivated in a common ancestor of hominoids. Interestingly, the epidermis of cynomolgus macaques contained a population of dendritic-shaped γδ T cells expressing a semi-invariant Vγ10/Vδ1 T-cell receptor. However, this population of macaque T cells differed from rodent dendritic epidermal T cells in that their Vγ10/Vδ1 T-cell receptors displayed junctional diversity and expression of Vγ10 was not epidermis-specific. Therefore, macaques do not appear to have rodent-type dendritic epidermal T cells despite having apparently functional SKINT1L. Comprehensive bioinformatics analysis indicates that SKINT1L emerged in an ancestor of placental mammals but was inactivated or lost multiple times in mammalian evolution and that Skint1 arose by gene duplication in a rodent lineage, suggesting that authentic dendritic epidermal T cells are presumably unique to rodents.

  13. Depression: An Immuno-Inflammatory Cascade

    Vivek Sharma

    2016-06-01

    Full Text Available Major depressive disorder also known as clinical depression, unipolar depression or depression is associated with significant morbidity, mortality, high suicidal tendencies and deaths. Preclinical and clinical studies suggest that psychiatric illnesses like MDD, are associated with inflammatory processes. While it is unlikely that major depressive disorder is a primary and lsquo;inflammatory' disorder, there is now evidence to suggest that inflammation play a subtle role in the pathophysiology of major depressive disorder. The inflammation in depression cascade pin points to the origin from immune hyperactivity and thus a new theory that explains role of immune system mediated inflammation has been accepted and researched upon. widely. This theory states that depression is accompanied by altered immune function and activation of the inflammatory response system. This theory is strengthened form the fact that the current therapeutic options which mainly target neurotransmitters, are not effective in many patients and these patients has been found to be associated with elevated levels of inflammatory mediators specifically cytokines. It is reported more recently that other risk factors for depression, including psychosocial stress, psychological trauma, sleep disturbance and pain, also increases inflammatory processes. Thus the intervention in the immune system originated from inflammatory cytokines seems a therapeutically viable option in the field of depression research. [Archives Medical Review Journal 2016; 25(2.000: 223-240

  14. The role of clinical variables, neuropsychological performance and SLC6A4 and COMT gene polymorphisms on the prediction of early response to fluoxetine in major depressive disorder.

    Gudayol-Ferré, Esteve; Herrera-Guzmán, Ixchel; Camarena, Beatriz; Cortés-Penagos, Carlos; Herrera-Abarca, Jorge E; Martínez-Medina, Patricia; Cruz, David; Hernández, Sandra; Genis, Alma; Carrillo-Guerrero, Mariana Y; Avilés Reyes, Rubén; Guàrdia-Olmos, Joan

    2010-12-01

    Major depressive disorder (MDD) is treated with antidepressants, but only between 50% and 70% of the patients respond to the initial treatment. Several authors suggested different factors that could predict antidepressant response, including clinical, psychophysiological, neuropsychological, neuroimaging, and genetic variables. However, these different predictors present poor prognostic sensitivity and specificity by themselves. The aim of our work is to study the possible role of clinical variables, neuropsychological performance, and the 5HTTLPR, rs25531, and val108/58Met COMT polymorphisms in the prediction of the response to fluoxetine after 4weeks of treatment in a sample of patient with MDD. 64 patients with MDD were genotyped according to the above-mentioned polymorphisms, and were clinically and neuropsychologically assessed before a 4-week fluoxetine treatment. Fluoxetine response was assessed by using the Hamilton Depression Rating Scale. We carried out a binary logistic regression model for the potential predictive variables. Out of the clinical variables studied, only the number of anxiety disorders comorbid with MDD have predicted a poor response to the treatment. A combination of a good performance in variables of attention and low performance in planning could predict a good response to fluoxetine in patients with MDD. None of the genetic variables studied had predictive value in our model. The possible placebo effect has not been controlled. Our study is focused on response prediction but not in remission prediction. Our work suggests that the combination of the number of comorbid anxiety disorders, an attentional variable, and two planning variables makes it possible to correctly classify 82% of the depressed patients who responded to the treatment with fluoxetine, and 74% of the patients who did not respond to that treatment. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. A review of depression research in malaysia.

    Ng, C G

    2014-08-01

    Depression is a debilitating illness and has become a leading cause of morbidity globally. We aim to summarise the evidence available in regard to the prevalence, type of assessment tools used and treatment options for depression in Malaysia. Two hundred and forty seven articles related to depression were found in a search through a database dedicated to indexing all original data relevant to medicine published in Malaysia between the years 2000-2013. Fifty seven articles were selected and reviewed on the basis of clinical relevance and future research implications. Findings were summarised, categorised and presented according to prevalence of depression, depression in women, depression in clinical condition, assessment tools, and treatment of depression. The prevalence of depression in Malaysia was estimated to be between 8 and 12%. The figures were higher among women of low socio-economic background or those with comorbid medical condition. The common assessment tools used in Malaysia include Beck Depression Inventory (BDI), Depression, Anxiety and Stress Scale (DASS), Patient Health Questionnaire 9 (PHQ-9) and Hospital Anxiety and Depression Scale (HADS). They were translated into the Malay language and their psychometric properties were established. Both pharmacological treatment and psychotherapy were commonly used in Malaysia, and were highly recommended in local clinical practice guidelines. There are discrepancies in the reported rates of depression in Malaysia and this needs to be addressed. There were lack of studies looking into the depression among subgroups in Malaysia especially in the male population. There were several instruments available for assessment of depression in Malaysia but their suitability for the local setting need further research. Both pharmacotherapy and psychotherapy were recommended in the local treatment guideline in Malaysia. With the emergence of generic medication, we need to compare their clinical efficacy and tolerability

  16. Selegiline Ameliorates Depression-Like Behavior in Mice Lacking the CD157/BST1 Gene, a Risk Factor for Parkinson’s Disease

    Satoka Kasai

    2017-05-01

    Full Text Available Parkinson’s disease (PD, a neurodegenerative disorder, is accompanied by various non-motor symptoms including depression and anxiety, which may precede the onset of motor symptoms. Selegiline is an irreversible monoamine oxidase-B (MAO-B inhibitor, and is widely used in the treatment of PD and major depression. However, there are few reports about the effects of selegiline on non-motor symptoms in PD. The aim of this study was to explore the antidepressant and anxiolytic effects of selegiline, using CD157/BST1 knockout (CD157 KO mouse, a PD-related genetic model displaying depression and anxiety, compared with other antiparkinsonian drugs and an antidepressant, and was to investigate the effects of selegiline on biochemical parameters in emotion-related brain regions. A single administration of selegiline (1–10 mg/kg dose-dependently reduced immobility time in the forced swimming test (FST in CD157 KO mice, but not C57BL/6N wild-type (WT mice. At 10 mg/kg, but not 3 mg/kg, selegiline significantly increased climbing time in CD157 KO mice. A single administration of the antiparkinsonian drugs pramipexole (a dopamine (DA D2/D3 receptor agonist or rasagiline (another MAO-B inhibitor, and repeated injections of a noradrenergic and specific serotonergic antidepressant (NaSSA, mirtazapine, also decreased immobility time, but did not increase climbing time, in CD157 KO mice. The antidepressant-like effects of 10 mg/kg selegiline were comparable to those of 10 mg/kg rasagiline, and tended to be stronger than those of 1 mg/kg rasagiline. After the FST, CD157 KO mice showed decreases in striatal and hippocampal serotonin (5-HT content, cortical norepinephrine (NE content, and plasma corticosterone concentration. A single administration of selegiline at 10 mg/kg returned striatal 5-HT, cortical NE, and plasma corticosterone levels to those observed in WT mice. In the open field test (OFT, repeated administration of mirtazapine had anxiolytic effects

  17. Molecular pathways associated with stress resilience and drug resistance in the chronic mild stress rat model of depression: a gene expression study

    Bergström, Anders; Jayatissa, Magdalena Niepsuj; Andersen, Thomas Thykjær

    2007-01-01

    The current antidepressant drugs are ineffective in 30 to 40% of the treated patients; hence, the pathophysiology of the disease needs to be further elucidated. We used the chronic mild stress (CMS) paradigm to induce anhedonia, a core symptom of major depression, in rats. A fraction of the animals...... exposed to CMS is resistant to the development of anhedonia; they are CMS resilient. In the CMS-sensitive animals, the induced anhedonic state is reversed in 50% of the animals when treating with escitalopram, whereas the remaining animals are treatment resistant. We used the microarray and the real...

  18. A Combined Study of SLC6A15 Gene Polymorphism and the Resting-State Functional Magnetic Resonance Imaging in First-Episode Drug-Naive Major Depressive Disorder.

    Wang, Lijuan; Liu, Zhifen; Cao, Xiaohua; Li, Jianying; Zhang, Aixia; Sun, Ning; Yang, Chunxia; Zhang, Kerang

    2017-09-01

    The SLC6A15 gene has been identified as a novel candidate gene for major depressive disorder (MDD). However, the mechanism underlying the effects of how the SLC6A15 gene affects functional brain activity of patients with MDD remains unknown. In the present study, we investigated the effect of the SLC6A15 gene polymorphism, rs1545843, on resting-state brain function in MDD with the imaging genomic technology and the regional homogeneity (ReHo) method. Sixty-seven MDD patients and 44 healthy controls underwent functional magnetic resonance imaging scans and genotyping. The differences in ReHo between genotypes were initially tested using the student's t test. We then performed a 2 × 2 (genotypes × disease status) analysis of variance to identify the main effects of genotypes, disease status, and their interactions in MDD. MDD patients with A+ genotypes showed decreased ReHo in the medial cingulum compared with MDD patients with the GG genotype. This was in contrast to normal controls with A+ genotypes who showed increased ReHo in the posterior cingulum and the frontal, temporal, and parietal lobes and decreased ReHo in the left corpus callosum, compared with controls with the GG genotypes. The main effect of disease was found in the frontal, parietal, and temporal lobes. The main effect of genotypes was found in the left corpus callosum and the frontal lobe. There was no interaction between rs1545843 genotypes and disease status. We found that the left corpus callosum ReHo was positively correlated with total scores of the Hamilton Depression Scale (HAMD) (p = 0.021), so as was the left inferior parietal gyrus ReHo with cognitive disorder (p = 0.02). In addition, the right middle temporal gyrus had a negative correlation with retardation (p = 0.049). We observed an association between the SLC6A15 rs1545843 and resting-state brain function of the corpus callosum, cingulum and the frontal, parietal, and temporal lobes in MDD patients, which may be

  19. Reformulating the Depression Model of Learned Hopelessness for Academic Outcomes

    Au, Raymond C. P.; Watkins, David; Hattie, John; Alexander, Patricia

    2009-01-01

    This review explores developments in the construct of learned hopelessness, which originated in the clinical literature dealing with depression. In that context, the model developed by Abramson, Metalsky, and Alloy [Abramson, L. Y., Metalsky, G. I., & Alloy, L. B. (1989). "Hopelessness depression: A theory-based subtype of depression."…

  20. The impact of Cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6 genes on suicide attempt and suicide risk-a European multicentre study on treatment-resistant major depressive disorder.

    Höfer, Peter; Schosser, Alexandra; Calati, Raffaella; Serretti, Alessandro; Massat, Isabelle; Kocabas, Neslihan Aygun; Konstantinidis, Anastasios; Linotte, Sylvie; Mendlewicz, Julien; Souery, Daniel; Zohar, Joseph; Juven-Wetzler, Alzbeta; Montgomery, Stuart; Kasper, Siegfried

    2013-08-01

    Recently published data have reported associations between cytochrome P450 metabolizer status and suicidality. The aim of our study was to investigate the role of genetic polymorphisms of the cytochrome P450 genes on suicide risk and/or a personal history of suicide attempts. Two hundred forty-three major depressive disorder patients were collected in the context of a European multicentre resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. Suicidality was assessed using the Mini International Neuropsychiatric Interview and the Hamilton Rating Scale for Depression (HAM-D). Treatment response was defined as HAM-D ≤ 17 and remission as HAM-D ≤ 7 after 4 weeks of treatment with antidepressants at adequate dose. Genotyping was performed for all relevant variations of the CYP1A2 gene (*1A, *1F, *1C, *1 J, *1 K), the CYP2C9 gene (*2, *3), the CYP2C19 gene (*2, *17) and the CYP2D6 gene (*3, *4, *5, *6, *9, *19, *XN). No association between both suicide risk and personal history of suicide attempts, and the above mentioned metabolic profiles were found after multiple testing corrections. In conclusion, the investigated cytochrome gene polymorphisms do not seem to be associated with suicide risk and/or a personal history of suicide attempts, though methodological and sample size limitations do not allow definitive conclusions.

  1. FRAS1-related extracellular matrix 3 (FREM3) single-nucleotide polymorphism effects on gene expression, amygdala reactivity and perceptual processing speed: An accelerated aging pathway of depression risk

    Nikolova, Yuliya S.; Iruku, Swetha P.; Lin, Chien-Wei; Conley, Emily Drabant; Puralewski, Rachel; French, Beverly; Hariri, Ahmad R.; Sibille, Etienne

    2015-01-01

    The A allele of the FRAS1-related extracellular matrix protein 3 (FREM3) rs7676614 single nucleotide polymorphism (SNP) was linked to major depressive disorder (MDD) in an early genome-wide association study (GWAS), and to symptoms of psychomotor retardation in a follow-up investigation. In line with significant overlap between age- and depression-related molecular pathways, parallel work has shown that FREM3 expression in postmortem human brain decreases with age. Here, we probe the effect of rs7676614 on amygdala reactivity and perceptual processing speed, both of which are altered in depression and aging. Amygdala reactivity was assessed using a face-matching BOLD fMRI paradigm in 365 Caucasian participants in the Duke Neurogenetics Study (DNS) (192 women, mean age 19.7 ± 1.2). Perceptual processing speed was indexed by reaction times in the same task and the Trail Making Test (TMT). The effect of rs7676614 on FREM3 mRNA brain expression levels was probed in a postmortem cohort of 169 Caucasian individuals (44 women, mean age 50.8 ± 14.9). The A allele of rs7676614 was associated with blunted amygdala reactivity to faces, slower reaction times in the face-matching condition (p < 0.04), as well as marginally slower performance on TMT Part B (p = 0.056). In the postmortem cohort, the T allele of rs6537170 (proxy for the rs7676614 A allele), was associated with trend-level reductions in gene expression in Brodmann areas 11 and 47 (p = 0.066), reminiscent of patterns characteristic of older age. The low-expressing allele of another FREM3 SNP (rs1391187) was similarly associated with reduced amygdala reactivity and slower TMT Part B speed, in addition to reduced BA47 activity and extraversion (p < 0.05). Together, these results suggest common genetic variation associated with reduced FREM3 expression may confer risk for a subtype of depression characterized by reduced reactivity to environmental stimuli and slower perceptual processing speed, possibly suggestive of

  2. Depression and Multiple Sclerosis

    ... Symptoms Depression Share this page Facebook Twitter Email Depression Depression Fatigue Walking (Gait) Difficulties Numbness or Tingling ... away from addictive substances such as alcohol. Clinical depression It’s important to distinguish between mild, everyday “blues” — ...

  3. Depression in Older Adults

    ... here Home » Depression In Older Adults: More Facts Depression In Older Adults: More Facts Depression affects more ... combination of both. [8] Older Adult Attitudes Toward Depression: According to a Mental Health America survey [9] ...

  4. Older Adults and Depression

    ... find more information? Reprints Share Older Adults and Depression Download PDF Download ePub Order a free hardcopy ... depression need treatment to feel better. Types of Depression There are several types of depression. The most ...

  5. Depression and Caregiving

    ... FCA - A A + A You are here Home Depression and Caregiving Order this publication Printer-friendly version ... a more serious depression over time. Symptoms of Depression People experience depression in different ways. Some may ...

  6. Depression and Suicide Risk

    ... due to another medical disorder Relationship Between Depression & Suicide: 1. Depression is the psychiatric diagnosis most commonly associated with ... of patients with treated depression eventually die by suicide. xiv 4. Depression is present in at least 50 percent of ...

  7. Original Thinking

    Ashok Natarajan

    2012-04-01

    Full Text Available History that comes to us as a chronology of events is really a collective existence that is evolving through several stages to develop Individuality in all members of the society. The human community, nation states, linguistic groups, local castes and classes, and families are the intermediate stages in development of the Individual. The social process moves through phases of survival, growth, development and evolution. In the process it organizes the consciousness of its members at successive levels from social external manners, formed behavior, value-based character and personality to culminate in the development of Individuality. Through this process, society evolves from physicality to Mentality. The power of accomplishment in society and its members develops progressively through stages of skill, capacity, talent, and ability. Original thinking is made possible by the prior development of thinking that organizes facts into information. The immediate result of the last world war was a shift in reliance from physical force and action to mental conception and mental activity on a global scale. At such times no problem need defy solution, if only humanity recognizes the occasion for thinking and Original Thinking. The apparently insoluble problems we confront are an opportunity to formulate a comprehensive theory of social evolution. The immediate possibility is to devise complete solutions to all existing problems, if only we use the right method of thought development.

  8. Detection of Rare G3P[19] Porcine Rotavirus Strains in Chiang Mai, Thailand, Provides Evidence for Origin of the VP4 Genes of Mc323 and Mc345 Human Rotaviruses▿

    Maneekarn, Niwat; Khamrin, Pattara; Chan-it, Wisoot; Peerakome, Supatra; Sukchai, Sujin; Pringprao, Kidsadagon; Ushijima, Hiroshi

    2006-01-01

    Among 175 fecal specimens collected from diarrheic piglets during a surveillance of porcine rotavirus (PoRV) strains in Chiang Mai, Thailand, 39 (22.3%) were positive for group A rotaviruses. Of these, 33.3% (13 of 39) belonged to G3P[19], which was a rare P genotype seldom reported. Interestingly, their VP4 nucleotide sequences were most closely related to human P[19] strains (Mc323 and Mc345) isolated in 1989 from the same geographical area where these PoRV strains were isolated. These P[19] PoRV strains were also closely related to another human P[19] strain (RMC321), isolated from India in 1990. The VP4 sequence identities with human P[19] were 95.4% to 97.4%, while those to a porcine P[19] strain (4F) were only 87.6 to 89.1%. Phylogenetic analysis of the VP4 gene revealed that PoRV P[19] strains clustered with human P[19] strains in a monophyletic branch separated from strain 4F. Analysis of the VP7 gene confirmed that these strains belonged to the G3 genotype and shared 97.7% to 98.3% nucleotide identities with other G3 PoRV strains circulating in the regions. This close genetic relationship was also reflected in the phylogenetic analysis of their VP7 genes. Altogether, the findings provided peculiar evidence that supported the porcine origin of VP4 genes of Mc323 and Mc345 human rotaviruses. PMID:16988014

  9. Genetic and biological characterization of three poultry-origin H5N6 avian influenza viruses with all internal genes from genotype S H9N2 viruses.

    Liu, Kaituo; Gu, Min; Hu, Shunlin; Gao, Ruyi; Li, Juan; Shi, Liwei; Sun, Wenqi; Liu, Dong; Gao, Zhao; Xu, Xiulong; Hu, Jiao; Wang, Xiaoquan; Liu, Xiaowen; Chen, Sujuan; Peng, Daxin; Jiao, Xinan; Liu, Xiufan

    2018-04-01

    During surveillance for avian influenza viruses, three H5N6 viruses were isolated in chickens obtained from live bird markets in eastern China, between January 2015 and April 2016. Sequence analysis revealed a high genomic homology between these poultry isolates and recent human H5N6 variants whose internal genes were derived from genotype S H9N2 avian influenza viruses. Glycan binding assays revealed that all avian H5N6 viruses were capable of binding to both human-type SAα-2,6Gal receptors and avian-type SAα-2,3Gal receptors. Their biological characteristics were further studied in BALB/c mice, specific-pathogen-free chickens, and mallard ducks. All three isolates had low pathogenicity in mice but were highly pathogenic to chickens, as evidenced by 100% mortality 36-120 hours post infection at a low dose of 10 3.0 EID 50 and through effective contact transmission. Moreover, all three poultry H5N6 isolates caused asymptomatic infections in ducks, which may serve as a reservoir host for their maintenance and dissemination; these migrating waterfowl could cause a potential global pandemic. Our study suggests that continuous epidemiological surveillance in poultry should be implemented for the early prevention of future influenza outbreaks.

  10. The biosynthetic origin of irregular monoterpenes in Lavandula: isolation and biochemical characterization of a novel cis-prenyl diphosphate synthase gene, lavandulyl diphosphate synthase.

    Demissie, Zerihun A; Erland, Lauren A E; Rheault, Mark R; Mahmoud, Soheil S

    2013-03-01

    Lavender essential oils are constituted predominantly of regular monoterpenes, for example linalool, 1,8-cineole, and camphor. However, they also contain irregular monoterpenes including lavandulol and lavandulyl acetate. Although the majority of genes responsible for the production of regular monoterpenes in lavenders are now known, enzymes (including lavandulyl diphosphate synthase (LPPS)) catalyzing the biosynthesis of irregular monoterpenes in these plants have not been described. Here, we report the isolation and functional characterization of a novel cis-prenyl diphosphate synthase cDNA, termed Lavandula x intermedia lavandulyl diphosphate synthase (LiLPPS), through a homology-based cloning strategy. The LiLPPS ORF, encoding for a 305-amino acid long protein, was expressed in Escherichia coli, and the recombinant protein was purified by nickel-nitrilotriacetic acid affinity chromatography. The approximately 34.5-kDa bacterially produced protein specifically catalyzed the head-to-middle condensation of two dimethylallyl diphosphate units to LPP in vitro with apparent Km and kcat values of 208 ± 12 μm and 0.1 s(-1), respectively. LiLPPS is a homodimeric enzyme with a sigmoidal saturation curve and Hill coefficient of 2.7, suggesting a positive co-operative interaction among its catalytic sites. LiLPPS could be used to modulate the production of lavandulol and its derivatives in plants through metabolic engineering.

  11. Molecular analysis of HEXA gene in Argentinean patients affected with Tay-Sachs disease: possible common origin of the prevalent c.459+5A>G mutation.

    Zampieri, Stefania; Montalvo, Annalisa; Blanco, Mariana; Zanin, Irene; Amartino, Hernan; Vlahovicek, Kristian; Szlago, Marina; Schenone, Andrea; Pittis, Gabriela; Bembi, Bruno; Dardis, Andrea

    2012-05-15

    Tay-Sachs disease (TSD) is a recessively inherited disorder caused by the deficient activity of hexosaminidase A due to mutations in the HEXA gene. Up to date there is no information regarding the molecular genetics of TSD in Argentinean patients. In the present study we have studied 17 Argentinean families affected by TSD, including 20 patients with the acute infantile form and 3 with the sub-acute form. Overall, we identified 14 different mutations accounting for 100% of the studied alleles. Eight mutations were novel: 5 were single base changes leading to drastic residue changes or truncated proteins, 2 were small deletions and one was an intronic mutation that may cause a splicing defect. Although the spectrum of mutations was highly heterogeneous, a high frequency of the c.459+5G>A mutation, previously described in different populations was found among the studied cohort. Haplotype analysis suggested that in these families the c.459+5G>A mutation might have arisen by a single mutational event. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Postpartum Depression

    ... or guilty. These emotions can affect a woman’s self-esteem and how she deals with stress. Fatigue—Many ... FAQs Exercise After Pregnancy (FAQ131) Depression (FAQ106) Patient Education FAQs Resources & Publications Committee Opinions Practice Bulletins Patient ...

  13. Origin of the polycomb repressive complex 2 and gene silencing by an E(z) homolog in the unicellular alga Chlamydomonas.

    Shaver, Scott; Casas-Mollano, J Armando; Cerny, Ronald L; Cerutti, Heriberto

    2010-05-16

    Polycomb group proteins play an essential role in the maintenance of cell identity and the regulation of development in both animals and plants. The Polycomb Repressive Complex 2 (PRC2) is involved in the establishment of transcriptionally silent chromatin states, in part through its ability to methylate lysine 27 of histone H3 by the Enhancer of zeste [E(z)] subunit. The absence of PRC2 in unicellular model fungi and its function in the repression of genes vital for the development of higher eukaryotes led to the proposal that this complex may have evolved together with the emergence of multicellularity. However, we report here on the widespread presence of PRC2 core subunits in unicellular eukaryotes from the Opisthokonta, Chromalveolata and Archaeplastida supergroups. To gain insight on the role of PRC2 in single celled organisms, we characterized an E(z) homolog, EZH, in the green alga Chlamydomonas reinhardtii. RNAi-mediated suppression of EZH led to defects in the silencing of transgenes and retrotransposons as well as to a global increase in histone post-translational modifications associated with transcriptional activity, such as trimethylation of histone H3 lysine 4 and acetylation of histone H4. On the basis of the parsimony principle, our findings suggest that PRC2 appeared early in eukaryotic evolution, even perhaps in the last unicellular common ancestor of eukaryotes. One of the ancestral roles of PCR2 may have been in defense responses against intragenomic parasites such as transposable elements, prior to being co-opted for lineage specific functions like developmental regulation in multicellular eukaryotes.

  14. High sequence variations in the region containing genes encoding a cellular morphogenesis protein and the repressor of sexual development help to reveal origins of Aspergillus oryzae.

    Chang, Perng-Kuang; Scharfenstein, Leslie L; Solorzano, Cesar D; Abbas, Hamed K; Hua, Sui-Sheng T; Jones, Walker A; Zablotowicz, Robert M

    2015-05-04

    Aspergillus oryzae and Aspergillus flavus are closely related fungal species. The A. flavus morphotype that produces numerous small sclerotia (S strain) and aflatoxin has a unique 1.5 kb deletion in the norB-cypA region of the aflatoxin gene cluster (i.e. the S genotype). Phylogenetic studies have indicated that an isolate of the nonaflatoxigenic A. flavus with the S genotype is the ancestor of A. oryzae. Genome sequence comparison between A. flavus NRRL3357, which produces large sclerotia (L strain), and S-strain A. flavus 70S identified a region (samA-rosA) that was highly variable in the two morphotypes. A third type of samA-rosA region was found in A. oryzae RIB40. The three samA-rosA types were later revealed to be commonly present in A. flavus L-strain populations. Of the 182 L-strain A. flavus field isolates examined, 46%, 15% and 39% had the samA-rosA type of NRRL3357, 70S and RIB40, respectively. The three types also were found in 18 S-strain A. flavus isolates with different proportions. For A. oryzae, however, the majority (80%) of the 16 strains examined had the RIB40 type and none had the NRRL3357 type. The results suggested that A. oryzae strains in the current culture collections were mostly derived from the samA-rosA/RIB40 lineage of the nonaflatoxigenic A. flavus with the S genotype. Published by Elsevier B.V.

  15. Quench origins

    Devred, A.

    1990-03-01

    In this paper, I shall discuss the quench origins. I shall first establish a method of classification and introduce the notions of conductor-limited and energy-deposited quenches. Next the paper will be devoted to the study of conductor-limited quenches, and I shall introduce the notions of plateau and of fraction of short sample. Also the paper will be devoted to the study of energy-deposited quenches, and I shall introduce the notions of training and of minimum energy deposit; I shall then review the possible causes of energy release. Lastly, I shall introduce the notion of operating margin, and I shall indicate how to optimize the operating margin in order to limit the risk of premature quenching. 112 refs., 14 figs

  16. A Novel Therapeutic Frame for Treating Depression in Group Treating Depression Downhill

    Valery Krupnik

    2014-01-01

    We describe an original protocol Treating Depression Downhill (TDD) that was designed as a specific therapy for depression. Evolutionary theories of depression served as a basis for its development. We discuss the rationale for using evolutionary theory and describe the structure and integrative nature of TDD. We then present an observation on TDD’s application to group therapy of active duty military personnel. In the...

  17. Sekuen Nukleotida Gene Shiga like toxin-2 dari Isolat Lokal Escherichia coli O157:H7 asal Hewan dan Manusia (NUCLEOTIDES SQUENCES OF SHIGA-LIKE TOXIN 2 GENES OF ESCHERICHIA COLI O157:H7 LOCAL ISOLATES ORIGINATED FROM ANIMALS AND HUMAN

    I Wayan Suardana

    2017-04-01

    Full Text Available Animals/livestock, especially cattle, are known as the main reservoir of Escherichia coli O157: H7. As the only one of zoonotic E. coli, the pathogenicity of these bacteria is determined by its ability to produce one or more very potent cytotoxin known as Shiga-like toxin (Stx or verocytotoxin, particularly of the Stx2 type that is closely related to the incidence of hemolytic uremic syndrome (HUS in humans. This study analyzed the nucleotide sequences of stx2 gene between isolates from animals and humans in an effort to assess the potential zoonoses of the agent. The research activity was initiated by cultivating 20 isolates of E. coli O157:H7 collection based on result in the previous study i.e. 2 isolates originated from cattle feces, 2 isolates originated from beef, 2 isolates originated from chicken feces, 2 isolates originated from human feces, and 12 non-clinical isolates originated from human fecal who were suffering with renal failure. All isolates were confirmed on selective medium Sorbitol MacConkey Agar (SMAC followed by testing on aglutination O157 latex test, and H7 antisera. Molecular analysis of stx2 gene covering open reading frame (ORF of the stx2 gene was performed using the primer which was designed by researcher i.e. Stx2 (F/Stx2 (R. The results showed, there were 2 isolates i.e. KL-48 (2 originated from human feces and SM-25 (1 originated from cattle feces were positive for carrying a stx2 gene, which was marked by the 1587 bp PCR product. Analysis of sequencing showed both isolates had identical to stx2 nucleotide squences with E. phaga 933 as well as E. coli ATCC 933. These results indicate the both local isolates are potential as zoonotic agents with clinical effects similar to E. phaga 933 and E. coli ATCC 43894. ABSTRAK Hewan ternak khususnya sapi, dikenal sebagai reservoir utama Escherichia coli O157:H7. Sebagai satu-satunya serotipe E. coli yang bersifat zoonosis, patogenitas bakteri ini ditentukan oleh kemampuannya

  18. Life stress and family history for depression: the moderating role of past depressive episodes.

    Monroe, Scott M; Slavich, George M; Gotlib, Ian H

    2014-02-01

    Three of the most consistently reported and powerful predictors of depression are a recent major life event, a positive family history for depression, and a personal history of past depressive episodes. Little research, however, has evaluated the inter-relations among these predictors in depressed samples. Such information is descriptively valuable and potentially etiologically informative. In the present article we summarize the existing literature and test four predictions in a sample of 62 clinically depressed individuals: (1) participants who experienced a major life event prior to onset would be less likely than participants who did not experience a major life event to have a positive family history for depression; (2) participants with a recent major life event would have fewer lifetime episodes of depression than would participants without; (3) participants with a positive family history for depression would have more lifetime episodes of depression than would participants with a negative family history for depression; and (4) we would obtain a 3-way interaction in which participants with a positive family history and without a major life event would have the most lifetime episodes, whereas participants with a negative family history and a major life event would have the fewest lifetime episodes. The first three predictions were confirmed, and the fourth prediction partially confirmed. These novel findings begin to elucidate the complex relations among these three prominent risk factors for depression, and point to avenues of research that may help illuminate the origins of depressive episodes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Archaeal origin of tubulin

    Yutin Natalya

    2012-03-01

    Full Text Available Abstract Tubulins are a family of GTPases that are key components of the cytoskeleton in all eukaryotes and are distantly related to the FtsZ GTPase that is involved in cell division in most bacteria and many archaea. Among prokaryotes, bona fide tubulins have been identified only in bacteria of the genus Prosthecobacter. These bacterial tubulin genes appear to have been horizontally transferred from eukaryotes. Here we describe tubulins encoded in the genomes of thaumarchaeota of the genus Nitrosoarchaeum that we denote artubulins Phylogenetic analysis results are compatible with the origin of eukaryotic tubulins from artubulins. These findings expand the emerging picture of the origin of key components of eukaryotic functional systems from ancestral forms that are scattered among the extant archaea. Reviewers This article was reviewed by Gáspár Jékely and J. Peter Gogarten.

  20. Epstein-Barr virus latent gene sequences as geographical markers of viral origin: unique EBNA3 gene signatures identify Japanese viruses as distinct members of the Asian virus family.

    Sawada, Akihisa; Croom-Carter, Deborah; Kondo, Osamu; Yasui, Masahiro; Koyama-Sato, Maho; Inoue, Masami; Kawa, Keisei; Rickinson, Alan B; Tierney, Rosemary J

    2011-05-01

    Polymorphisms in Epstein-Barr virus (EBV) latent genes can identify virus strains from different human populations and individual strains within a population. An Asian EBV signature has been defined almost exclusively from Chinese viruses, with little information from other Asian countries. Here we sequenced polymorphic regions of the EBNA1, 2, 3A, 3B, 3C and LMP1 genes of 31 Japanese strains from control donors and EBV-associated T/NK-cell lymphoproliferative disease (T/NK-LPD) patients. Though identical to Chinese strains in their dominant EBNA1 and LMP1 alleles, Japanese viruses were subtly different at other loci. Thus, while Chinese viruses mainly fall into two families with strongly linked 'Wu' or 'Li' alleles at EBNA2 and EBNA3A/B/C, Japanese viruses all have the consensus Wu EBNA2 allele but fall into two families at EBNA3A/B/C. One family has variant Li-like sequences at EBNA3A and 3B and the consensus Li sequence at EBNA3C; the other family has variant Wu-like sequences at EBNA3A, variants of a low frequency Chinese allele 'Sp' at EBNA3B and a consensus Sp sequence at EBNA3C. Thus, EBNA3A/B/C allelotypes clearly distinguish Japanese from Chinese strains. Interestingly, most Japanese viruses also lack those immune-escape mutations in the HLA-A11 epitope-encoding region of EBNA3B that are so characteristic of viruses from the highly A11-positive Chinese population. Control donor-derived and T/NK-LPD-derived strains were similarly distributed across allelotypes and, by using allelic polymorphisms to track virus strains in patients pre- and post-haematopoietic stem-cell transplant, we show that a single strain can induce both T/NK-LPD and B-cell-lymphoproliferative disease in the same patient.

  1. Multiple origins of the phenol reaction negative phenotype in foxtail millet, Setaria italica (L.) P. Beauv., were caused by independent loss-of-function mutations of the polyphenol oxidase (Si7PPO) gene during domestication.

    Inoue, Takahiko; Yuo, Takahisa; Ohta, Takeshi; Hitomi, Eriko; Ichitani, Katsuyuki; Kawase, Makoto; Taketa, Shin; Fukunaga, Kenji

    2015-08-01

    frequencies of ca. 25-67 % and those with negative Phr were broadly found in Europe and Asia. The stop codon type was found in 285 accessions and was broadly distributed in Europe and Asia, whereas the TE-1 insertion type was found in 99 accessions from Europe and Asia but was not found in India. The 6-bp duplication type was found in only 8 accessions from Nansei Islands (Okinawa Prefecture) of Japan. We also analyzed Phr in the wild ancestor and concluded that the negative Phr type was likely to have originated after domestication of foxtail millet. It was also implied that negative Phr of foxtail millet arose by multiple independent loss of function of PPO gene through dispersal because of some advantages under some environmental conditions and human selection as in rice and barley.

  2. Anxiety- and depression-like behavior in mice lacking the CD157/BST1 gene, a risk factor for Parkinson’s disease

    Olga eLopatina

    2014-04-01

    Full Text Available CD157, known as bone marrow stromal cell antigen-1, is a glycosylphosphatidylinositol-anchored ADP-ribosyl cyclase that supports the survival and function of B-lymphocytes and hematopoietic or intestinal stem cells. Although CD157/Bst1 is a risk locus in Parkinson’s disease (PD, little is known about the function of CD157 in the nervous system and contribution to PD progression. Here, we show that no apparent motor dysfunction was observed in young knockout (CD157-/- male mice under less aging-related effects on behaviors. CD157-/- mice exhibited anxiety-related and depression-like behaviors compared with wild-type mice. These behaviors were rescued through treatment with anti-psychiatric drugs and oxytocin. CD157 was weakly expressed in the amygdala and c-Fos immunoreactivity was less evident in CD157-/- mice than in wild-type mice. These results demonstrate for the first time that CD157 plays a role as a neuro-regulator and suggest a potential role in pre-motor symptoms in PD.

  3. Family Conflict Interacts with Genetic Liability in Predicting Childhood and Adolescent Depression

    Rice, Frances; Harold, Gordon T.; Shelton, Katherine H.; Thapar, Anita

    2006-01-01

    Objective: To test for gene-environment interaction with depressive symptoms and family conflict. Specifically, to first examine whether the influence of family conflict in predicting depressive symptoms is increased in individuals at genetic risk of depression. Second, to test whether the genetic component of variance in depressive symptoms…

  4. Citation bias and selective focus on positive findings in the literature on the serotonin transporter gene (5-HTTLPR), life stress and depression.

    de Vries, Y A; Roest, A M; Franzen, M; Munafò, M R; Bastiaansen, J A

    2016-10-01

    Caspi et al.'s 2003 report that 5-HTTLPR genotype moderates the influence of life stress on depression has been highly influential but remains contentious. We examined whether the evidence base for the 5-HTTLPR-stress interaction has been distorted by citation bias and a selective focus on positive findings. A total of 73 primary studies were coded for study outcomes and focus on positive findings in the abstract. Citation rates were compared between studies with positive and negative results, both within this network of primary studies and in Web of Science. In addition, the impact of focus on citation rates was examined. In all, 24 (33%) studies were coded as positive, but these received 48% of within-network and 68% of Web of Science citations. The 38 (52%) negative studies received 42 and 23% of citations, respectively, while the 11 (15%) unclear studies received 10 and 9%. Of the negative studies, the 16 studies without a positive focus (42%) received 47% of within-network citations and 32% of Web of Science citations, while the 13 (34%) studies with a positive focus received 39 and 51%, respectively, and the nine (24%) studies with a partially positive focus received 14 and 17%. Negative studies received fewer citations than positive studies. Furthermore, over half of the negative studies had a (partially) positive focus, and Web of Science citation rates were higher for these studies. Thus, discussion of the 5-HTTLPR-stress interaction is more positive than warranted. This study exemplifies how evidence-base-distorting mechanisms undermine the authenticity of research findings.

  5. Helping your teen with depression

    Teen depression - helping; Teen depression - talk therapy; Teen depression - medicine ... teen the most. The most effective treatments for depression are: Talk therapy Antidepressant medicines If your teen ...

  6. IGF-1 deficiency in a critical period early in life influences the vascular aging phenotype in mice by altering miRNA-mediated post-transcriptional gene regulation: implications for the developmental origins of health and disease hypothesis.

    Tarantini, Stefano; Giles, Cory B; Wren, Jonathan D; Ashpole, Nicole M; Valcarcel-Ares, M Noa; Wei, Jeanne Y; Sonntag, William E; Ungvari, Zoltan; Csiszar, Anna

    2016-08-01

    Epidemiological findings support the concept of Developmental Origins of Health and Disease, suggesting that early-life hormonal influences during a sensitive period of development have a fundamental impact on vascular health later in life. The endocrine changes that occur during development are highly conserved across mammalian species and include dramatic increases in circulating IGF-1 levels during adolescence. The present study was designed to characterize the effect of developmental IGF-1 deficiency on the vascular aging phenotype. To achieve that goal, early-onset endocrine IGF-1 deficiency was induced in mice by knockdown of IGF-1 in the liver using Cre-lox technology (Igf1 f/f mice crossed with mice expressing albumin-driven Cre recombinase). This model exhibits low-circulating IGF-1 levels during the peripubertal phase of development, which is critical for the biology of aging. Due to the emergence of miRNAs as important regulators of the vascular aging phenotype, the effect of early-life IGF-1 deficiency on miRNA expression profile in the aorta was examined in animals at 27 months of age. We found that developmental IGF-1 deficiency elicits persisting late-life changes in miRNA expression in the vasculature, which significantly differed from those in mice with adult-onset IGF-1 deficiency (TBG-Cre-AAV8-mediated knockdown of IGF-1 at 5 month of age in Igf1 f/f mice). Using a novel computational approach, we identified miRNA target genes that are co-expressed with IGF-1 and associate with aging and vascular pathophysiology. We found that among the predicted targets, the expression of multiple extracellular matrix-related genes, including collagen-encoding genes, were downregulated in mice with developmental IGF-1 deficiency. Collectively, IGF-1 deficiency during a critical period during early in life results in persistent changes in post-transcriptional miRNA-mediated control of genes critical targets for vascular health, which likely contribute to the

  7. A Novel Therapeutic Frame for Treating Depression in Group Treating Depression Downhill

    Valery Krupnik

    2014-02-01

    Full Text Available We describe an original protocol Treating Depression Downhill (TDD that was designed as a specific therapy for depression. Evolutionary theories of depression served as a basis for its development. We discuss the rationale for using evolutionary theory and describe the structure and integrative nature of TDD. We then present an observation on TDD’s application to group therapy of active duty military personnel. In the described sample, TDD demonstrated effectiveness and specificity for depression, differentiating it from anxiety and personality disorders.

  8. Influences of Biological and Adoptive Mothers’ Depression and Antisocial Behavior on Adoptees’ Early Behavior Trajectories

    Kerr, David C. R.; Leve, Leslie D.; Harold, Gordon T.; Natsuaki, Misaki; Neiderhiser, Jenae M.; Shaw, Daniel S.; Reiss, David

    2013-01-01

    Research clearly demonstrates that parents pass risk for depression and antisocial behavior on to their children. However, most research confounds genetic and environmental mechanisms by studying genetically related individuals. Furthermore, most studies focus on either depression or antisocial behavior in parents or children, despite evidence of co-occurrence and shared etiology, and few consider the early origins of these problems in childhood. We estimated the influence of biological and adoptive mothers’ depression and antisocial behavior on growth in child externalizing and internalizing behaviors across early childhood using data from a prospective adoption study. Participants were 346 matched triads of physically healthy children (196 boys; 150 girls), biological mothers (BM), and adoptive mothers (AM). Latent growth curve models were estimated using AM reports of child internalizing and externalizing behaviors at ages 18, 27, and 54 months. Predictors of intercept (18 months) but not slope were identified. BM lifetime histories of major depressive disorder predicted child externalizing behaviors and BM antisocial behavior predicted child internalizing behavior. AM depressive symptoms and antisocial behavior were associated with both child outcomes. AM paths, but not BM paths were partially replicated using adopted fathers’ reports of child outcomes. BM obstetric complications, prenatal depressive symptoms, and postnatal adoptive family contact with BM did not account for BM paths. This adoption study distinguished risks conferred by biological mothers’ depression and antisocial behavior to children’s behaviors from those associated with adoptive mothers’ related symptoms. Future studies should examine gene-environment interplay to explain the emergence of serious problem trajectories in later childhood. PMID:23408036

  9. Influences of biological and adoptive mothers' depression and antisocial behavior on adoptees' early behavior trajectories.

    Kerr, David C R; Leve, Leslie D; Harold, Gordon T; Natsuaki, Misaki N; Neiderhiser, Jenae M; Shaw, Daniel S; Reiss, David

    2013-07-01

    Research clearly demonstrates that parents pass risk for depression and antisocial behavior on to their children. However, most research confounds genetic and environmental mechanisms by studying genetically related individuals. Furthermore, most studies focus on either depression or antisocial behavior in parents or children, despite evidence of co-occurrence and shared etiology, and few consider the early origins of these problems in childhood. We estimated the influence of biological and adoptive mothers' depression and antisocial behavior on growth in child externalizing and internalizing behaviors across early childhood using data from a prospective adoption study. Participants were 346 matched triads of physically healthy children (196 boys; 150 girls), biological mothers (BM), and adoptive mothers (AM). Latent growth curve models were estimated using AM reports of child internalizing and externalizing behaviors at ages 18, 27, and 54 months. Predictors of intercept (18 months) but not slope were identified. BM lifetime histories of major depressive disorder predicted child externalizing behaviors and BM antisocial behavior predicted child internalizing behavior. AM depressive symptoms and antisocial behavior were associated with both child outcomes. AM paths, but not BM paths were partially replicated using adopted fathers' reports of child outcomes. BM obstetric complications, prenatal depressive symptoms, and postnatal adoptive family contact with BM did not account for BM paths. This adoption study distinguished risks conferred by biological mothers' depression and antisocial behavior to children's behaviors from those associated with adoptive mothers' related symptoms. Future studies should examine gene-environment interplay to explain the emergence of serious problem trajectories in later childhood.

  10. Competencia digital y literacidad: nuevos formatos narrativos en el videojuego «Dragon Age: Orígenes» Digital Competence and Literacy: Developing New Narrative Formats. The «Dragon Age: Origins» Videogame

    Amando López Valero

    2011-03-01

    Full Text Available Este artículo tiene como ejes conceptuales la competencia digital, la literacidad y los nuevos formatos narrativos. El aprendizaje permanente incluye las mismas como claves de la formación de la persona y sobre todo, como elemento que va a contribuir a su inserción en una sociedad dinámica y cambiante. Tras analizar dichas dimensiones, las mismas serán reflejadas en el videojuego denominado «Dragon Age: Orígenes», galardonado con el premio juego de rol del año en el año 2009. El desarrollo de la competencia digital conlleva una nueva alfabetización y en la misma es preciso hallar recursos motivadores para que dicha adquisición sea a la vez una cuestión lúdica y formativa. Otro aspecto relevante que será tratado en el texto tiene que ver con la multimodalidad textual (Kress & Van Leeuwen, 2001, sobre todo con los nuevos formatos narrativos. Este hecho supone un importante avance social ya que las formas de lectura varían apareciendo formas distintas más motivadoras para el usuario pero no por ello poseen menor calidad. Éste es el caso de «Dragon Age: Orígenes», un juego de rol basado en la fantasía heroica ubicado en un mundo novedoso. Dicho juego se convierte en una excelente historia para ser leída y experimentada.The approach of this article is centered on the concepts of digital competence and new narrative formats. We aim to apply these dimensions to the videogame «Dragon Age Origins», winner of the 2009 videogame of the year award. Its features - plot, characters and interactivity – make it ideal reading material in other formats and are highly motivational for young people. The development of digital competence signifies new literacy, and it is necessary to find new stimulating resources that combine the fun and formative dimensions. Equally relevant are multimodal texts (Kress & Van Leeuwen, 2001, especially new narrative formats that imply social progress, as the ways of reading are different. The texts have

  11. Postpartum Depression - Multiple Languages

    ... Русский (Russian) Bilingual PDF Health Information Translations Postpartum Depression - English PDF Postpartum Depression - Русский (Russian) PDF Postpartum Depression - English MP3 ...

  12. Major Depression Among Adults

    ... Depressive Episode Among Adolescents Data Sources Share Major Depression Definitions Major depression is one of the most ... Bethesda, MD 20892-9663 Follow Us Facebook Twitter YouTube Google Plus NIMH Newsletter NIMH RSS Feed NIMH ...

  13. Recognizing teen depression

    ... medlineplus.gov/ency/patientinstructions/000648.htm Recognizing teen depression To use the sharing features on this page, ... life. Be Aware of the Risk for Teen Depression Your teen is more at risk for depression ...

  14. Sadness and Depression

    ... Videos for Educators Search English Español Sadness and Depression KidsHealth / For Kids / Sadness and Depression Print en ... big difference in your life. When Sadness Is Depression When you're in a sad mood, it ...

  15. Postpartum Depression Facts

    ... Where can I find more information? Share Postpartum Depression Facts Download PDF Download ePub Download Mobi Order ... for herself or her family. What is postpartum depression? Postpartum depression is a mood disorder that can ...

  16. Depression and College Students

    ... depression and other mental health issues? Reference Share Depression and College Students Download PDF Download ePub Order ... Answers to college students’ frequently asked questions about depression Feeling moody, sad, or grouchy? Who doesn’t ...

  17. Differential co-expression and regulation analyses reveal different mechanisms underlying major depressive disorder and subsyndromal symptomatic depression.

    Xu, Fan; Yang, Jing; Chen, Jin; Wu, Qingyuan; Gong, Wei; Zhang, Jianguo; Shao, Weihua; Mu, Jun; Yang, Deyu; Yang, Yongtao; Li, Zhiwei; Xie, Peng

    2015-04-03

    Recent depression research has revealed a growing awareness of how to best classify depression into depressive subtypes. Appropriately subtyping depression can lead to identification of subtypes that are more responsive to current pharmacological treatment and aid in separating out depressed patients in which current antidepressants are not particularly effective. Differential co-expression analysis (DCEA) and differential regulation analysis (DRA) were applied to compare the transcriptomic profiles of peripheral blood lymphocytes from patients with two depressive subtypes: major depressive disorder (MDD) and subsyndromal symptomatic depression (SSD). Six differentially regulated genes (DRGs) (FOSL1, SRF, JUN, TFAP4, SOX9, and HLF) and 16 transcription factor-to-target differentially co-expressed gene links or pairs (TF2target DCLs) appear to be the key differential factors in MDD; in contrast, one DRG (PATZ1) and eight TF2target DCLs appear to be the key differential factors in SSD. There was no overlap between the MDD target genes and SSD target genes. Venlafaxine (Efexor™, Effexor™) appears to have a significant effect on the gene expression profile of MDD patients but no significant effect on the gene expression profile of SSD patients. DCEA and DRA revealed no apparent similarities between the differential regulatory processes underlying MDD and SSD. This bioinformatic analysis may provide novel insights that can support future antidepressant R&D efforts.

  18. Update of sleep alterations in depression

    Andrés Barrera Medina

    2014-09-01

    Full Text Available Sleep disturbances in depression are up to 70%. Patients frequently have difficulty in falling asleep, frequent awakenings during the night and non-restorative sleep. Sleep abnormalities in depression are mainly characterized by increased rapid eye movement (REM sleep and reduced slow wave sleep. Among the mechanisms of sleep disturbances in depression are hyperactivation of the hypothalamic-pituitary-adrenal axis, CLOCK gene polymorphism and primary sleep disorders. The habenula is a structure regulating the activities of monoaminergic neurons in the brain. The hyperactivation of the habenula has also been implicated, together with sleep disturbances, in depression. The presence of depression in primary sleep disorders is common. Sleep disturbances treatment include pharmacotherapy or Cognitive Behavioral Therapy.

  19. Update of sleep alterations in depression

    Medina, Andrés Barrera; Lechuga, DeboraYoaly Arana; Escandón, Oscar Sánchez; Moctezuma, Javier Velázquez

    2014-01-01

    Sleep disturbances in depression are up to 70%. Patients frequently have difficulty in falling asleep, frequent awakenings during the night and non-restorative sleep. Sleep abnormalities in depression are mainly characterized by increased rapid eye movement (REM) sleep and reduced slow wave sleep. Among the mechanisms of sleep disturbances in depression are hyperactivation of the hypothalamic-pituitary-adrenal axis, CLOCK gene polymorphism and primary sleep disorders. The habenula is a structure regulating the activities of monoaminergic neurons in the brain. The hyperactivation of the habenula has also been implicated, together with sleep disturbances, in depression. The presence of depression in primary sleep disorders is common. Sleep disturbances treatment include pharmacotherapy or Cognitive Behavioral Therapy. PMID:26483922

  20. Testing the Effect of Internal Genes Derived from a Wild-Bird-Origin H9N2 Influenza A Virus on the Pathogenicity of an A/H7N9 Virus

    Wen Su

    2015-09-01

    Full Text Available Since 2013, avian influenza A(H7N9 viruses have diversified into multiple lineages by dynamically reassorting with other viruses, especially H9N2, in Chinese poultry. Despite concerns about the pandemic threat posed by H7N9 viruses, little is known about the biological properties of H7N9 viruses that may recruit internal genes from genetically distinct H9N2 viruses circulating among wild birds. Here, we generated 63 H7N9 reassortants derived from an avian H7N9 and a wild-bird-origin H9N2 virus. Compared with the wild-type parent, 25/63 reassortants had increased pathogenicity in mice. A reassortant containing PB1 of the H9N2 virus was highly lethal to mice and chickens but was not transmissible to guinea pigs by airborne routes; however, three substitutions associated with adaptation to mammals conferred airborne transmission to the virus. The emergence of the H7N9-pandemic reassortant virus highlights that continuous monitoring of H7N9 viruses is needed, especially at the domestic poultry/wild bird interface.

  1. Epigenetics and depression: return of the repressed.

    Dalton, Victoria S; Kolshus, Erik; McLoughlin, Declan M

    2014-02-01

    Epigenetics has recently emerged as a potential mechanism by which adverse environmental stimuli can result in persistent changes in gene expression. Epigenetic mechanisms function alongside the DNA sequence to modulate gene expression and ultimately influence protein production. The current review provides an introduction and overview of epigenetics with a particular focus on preclinical and clinical studies relevant to major depressive disorder (MDD). PubMed and Web of Science databases were interrogated from January 1995 up to December 2012 using combinations of search terms, including "epigenetic", "microRNA" and "DNA methylation" cross referenced with "depression", "early life stress" and "antidepressant". There is an association between adverse environmental stimuli, such as early life stress, and epigenetic modification of gene expression. Epigenetic changes have been reported in humans with MDD and may serve as biomarkers to improve diagnosis. Antidepressant treatments appear to reverse or initiate compensatory epigenetic alterations that may be relevant to their mechanism of action. As a narrative review, the current report was interpretive and qualitative in nature. Epigenetic modification of gene expression provides a mechanism for understanding the link between long-term effects of adverse life events and the changes in gene expression that are associated with depression. Although still a developing field, in the future, epigenetic modifications of gene expre