scholarly journals The role of gene regulatory sites in development predisposition to preeclampsia

2020 ◽  
pp. 35-38
Author(s):  
В.Н. Сереброва ◽  
Е.А. Трифонова ◽  
А.Ю. Ворожищева ◽  
В.А. Степанов
Keyword(s):  
Ethnic Groups ◽  
Genetic Architecture ◽  
Placental Tissue ◽  
Regulatory Mechanisms ◽  
Expression Variability ◽  
Polymorphic Variants ◽  
Gene Regulatory ◽  
First Time ◽  
Regulatory Sites

Преэклампсия (ПЭ) - одно из наиболее тяжелых гипертензивных расстройств беременности, этиология и патогенез которого оста- ются на сегодняшний день плохо изученными. Поскольку ключевая роль в этиопатогенезе ПЭ отводится плацентарной ткани, изу- чение вариабельности уровня экспрессии генов в плаценте и механизмов регуляции данных изменений являются перспективными направлениями. Цель исследования - охарактеризовать генетическую архитектуру ПЭ по системе регуляторных однонуклеотидных полиморфизмов (rSNP) нового гена-кандидата SYDE1 , выявленного впервые по результатам анализа транскриптома плацентарной ткани. В работе было изучено два наиболее значимых rSNP гена SYDE1 (rs56153523, rs8109071). Исследование проводилось в трех этнических группах: буряты, русские, якуты. Результаты проведенного исследования демонстрируют ассоциацию rSNP гена SYDE1 с развитием ПЭ в выборках бурятов (rs56153523) и русских (rs56153523, rs8109071). Preeclampsia (PE) is one of the most serious hypertensive pregnancy disorders, which etiology and pathogenesis is remained poorly under- stood. Since a key role in the etiopathogenesis of PE is given to the placental tissue, the study of the gene expression variability in the pla- cental tissue and of the regulatory mechanisms of these changes is a promising approach. The purpose of this research was to characterize of the genetic architecture of PE on the basis of regulatory polymorphic variants (rSNPs) of the new SYDE1 candidate gene, identified for the first time by the results of the transcriptome analysis in placental tissue. In this work, we analyzed the two most significant rSNPs of the SYDE1 gene (rs56153523, rs8109071). The study was conducted in three ethnic groups: Buryats, Russians, Yakuts. We have detected associations of the rSNPs of SYDE1 gene with the development of preeclampsia in ethnic groups Buryat (rs56153523) and Russian (rs56153523, rs8109071).

Analysis of the genetic architecture of preeclampsia in the context of evolutionary medicine

2020 ◽  
pp. 69-70
Author(s):  
В.Н. Сереброва ◽  
Е.А. Трифонова ◽  
В.А. Степанов
Keyword(s):  
Differentially Expressed Genes ◽  
Significant Role ◽  
Genetic Architecture ◽  
Placental Tissue ◽  
Evolutionary Medicine ◽  
Differentially Expressed ◽  
Hereditary Predisposition ◽  
Adaptive Changes ◽  
Polymorphic Variants

В настоящем исследовании впервые применен эволюционный подход к изучению генетической архитектуры преэклампсии (ПЭ) по системе регуляторных однонуклеотидных полиморфных вариантов (rSNP) дифференциально экспрессирующихся генов (ДЭГ), выявленных благодаря анализу транскриптома плаценты. Полученные результаты демонстрируют значимую роль 10 rSNP 8 ДЭГ и их адаптивных изменений на макроэволюционном и/или микроэволюционном уровне в формировании наследственной подверженности к ПЭ у русских и якутов. In this research first applied evolutionary approach to study of the PE genetics architecture via the regulatory polymorphic variants (rSNPs) of differentially expressed genes (DEG), identified by analysis of the transcriptome in placental tissue. The results demonstrate а significant role of 10 rSNP 8 DEG and their adaptive changes at the macroevolutionary and/or microevolutionary level in the formation of hereditary predisposition to PE in Russians and Yakuts.

Transcriptional coregulator RIP140: an essential regulator of physiology

2017 ◽  
Vol 58 (3) ◽  
pp. R147-R158 ◽  
Author(s):  
Jaya Nautiyal
Keyword(s):  
Nuclear Receptors ◽  
Physiological Processes ◽  
Reproductive Axis ◽  
Transcriptional Coregulators ◽  
Transcriptional Coregulator ◽  
Gene Regulatory ◽  
Drive Gene ◽  
Regulatory Decisions ◽  
Regulatory Sites

Transcriptional coregulators drive gene regulatory decisions in the transcriptional space. Although transcription factors including all nuclear receptors provide a docking platform for coregulators to bind, these proteins bring enzymatic capabilities to the gene regulatory sites. RIP140 is a transcriptional coregulator essential for several physiological processes, and aberrations in its function may lead to diseased states. Unlike several other coregulators that are known either for their coactivating or corepressing roles, in gene regulation, RIP140 is capable of acting both as a coactivator and a corepressor. The role of RIP140 in female reproductive axis and recent findings of its role in carcinogenesis and adipose biology have been summarised.

scholarly journals Design of Conditionally Active STATs: Insights into STAT Activation and Gene Regulatory Function

1999 ◽  
Vol 19 (4) ◽  
pp. 2913-2920 ◽  
Author(s):  
Lawrence H. Milocco ◽  
Jennifer A. Haslam ◽  
Jonathan Rosen ◽  
H. Martin Seidel
Keyword(s):  
Tyrosine Phosphorylation ◽  
Nuclear Translocation ◽  
Regulatory Function ◽  
Nuclear Localization Sequence ◽  
Wild Type ◽  
Localization Sequence ◽  
Gene Regulatory ◽  
First Time ◽  
Insight Into

ABSTRACT The STAT (signal transducer and activator of transcription) signaling pathway is activated by a large number of cytokines and growth factors. We sought to design a conditionally active STAT that could not only provide insight into basic questions about STAT function but also serve as a powerful tool to determine the precise biological role of STATs. To this end, we have developed a conditionally active STAT by fusing STATs with the ligand-binding domain of the estrogen receptor (ER). We have demonstrated that the resulting STAT-ER chimeras are estrogen-inducible transcription factors that retain the functional and biochemical characteristics of the cognate wild-type STATs. In addition, these tools have allowed us to evaluate separately the contribution of tyrosine phosphorylation and dimerization to STAT function. We have for the first time provided experimental data supporting the model that the only apparent role of STAT tyrosine phosphorylation is to drive dimerization, as dimerization alone is sufficient to unmask a latent STAT nuclear localization sequence and induce nuclear translocation, sequence-specific DNA binding, and transcriptional activity.

Associative studies of polymorphic variants of adrenergic receptor genes and tardive dyskinesia in schizophrenia

2021 ◽  
pp. 36-40
Author(s):  
И.В. Пожидаев ◽  
Д.З. Падерина ◽  
О.Ю. Федоренко ◽  
А.С. Бойко ◽  
Е.Г. Корнетова ◽  
...  
Keyword(s):  
Tardive Dyskinesia ◽  
Adrenergic Receptor ◽  
Polymorphic Variant ◽  
Adrenergic System ◽  
Antipsychotic Therapy ◽  
Schizophrenic Patients ◽  
Basic Functions ◽  
Polymorphic Variants ◽  
First Time

Адренергическая система, наряду с дофаминергической, серотонинергической и глутаматергической системами, играет важную роль в патофизиологии шизофрении и ответе на применяемую фармакотерапию. Тардивная или поздняя дискинезия (ТД) относится к серьезным побочным эффектам и может развиваться у больных шизофренией на фоне длительного использования антипсихотиков. Важная роль в патогенезе ТД принадлежит генетическим факторам. Целью настоящего исследования явился поиск возможных ассоциаций полиморфных вариантов генов ADRβ1 и ADRA1A с развитием ТД у больных шизофренией, получающих антипсихотическую терапию. Выборка составила 449 пациентов из русской популяции Сибирского региона с верифицированным диагнозом шизофрения, из которых 121 пациент соответствовал критериям ТД. Генотипирование полиморфных вариантов rs1801253, rs2036108, rs472865 генов ADRβ1 и ADRA1A проведено методом ПЦР в реальном времени амплификатором QuantStudio 5 с использованием наборов TaqMan. Ассоциативный анализ частот генотипов и аллелей оценивался с помощью критерия χ2 в программе R 3.6.2 с использованием базовых функций и дополнительного пакета SNPassoc. Распределение частот генотипов и аллелей для полиморфного варианта rs2036108 гена ADRA1A значимо отличается в группах пациентов с ТД и без побочного эффекта (для генотипов р = 0,028; для аллелей р = 0,040). Впервые была выявлена ассоциация полиморфного варианта rs2036108 гена ADRA1A с ТД у больных шизофренией. Необходимы дальнейшие исследования роли генов адренергических рецепторов в развитии ТД для разработки фармакогенетических подходов к персонализации терапии. The adrenergic system, along with the dopaminergic, serotonergic and glutamatergic systems, plays an important role in the pathophysiology of schizophrenia and response to the applied pharmacotherapy. Tardive or late dyskinesia (TD) is a serious side effect and can develop in schizophrenic patients with prolonged use of antipsychotics. An important role in the pathogenesis of TD belongs to genetic factors. The aim of this study was to search for possible associations of polymorphic variants of the ADRβ1 and ADRA1A genes with the development of tardive dyskinesia in schizophrenic patients receiving antipsychotic therapy. We examined 449 patients from Russian population of Siberian region with verified diagnosis of schizophrenia. 121 patients from whole group met the criteria for tardive dyskinesia. Genotyping of the polymorphic variants rs1801253, rs2036108, rs472865 of the ADRβ1 and ADRA1A genes was performed by real-time PCR using a QuantStudio 5 amplifier using TaqMan kits. The associative analysis of the frequencies of genotypes and alleles was assessed using the χ2 test in the R 3.6.2 program using basic functions and an additional SNPassoc package. The distribution of genotype and allele frequencies for the rs2036108 polymorphic variant of the ADRA1A gene significantly differs in the groups of patients with tardive dyskinesia and without side effects (for genotypes p = 0.028; for alleles p = 0.040). For the first time, the association of the rs2036108 polymorphic variant of the ADRA1A gene with tardive dyskinesia in schizophrenic patients was revealed. Further studies of the role of adrenergic receptor genes in the development of tardive dyskinesia are required to develop pharmacogenetic approaches to personalizing therapy.

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe
Keyword(s):  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Epigenetic Inheritance ◽  
Nematode Caenorhabditis Elegans ◽  
Histone Methyltransferases ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Recent Developments ◽  
Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

Psychological Resilience Provides No Independent Protection From Suicidal Risk

Crisis ◽  
2016 ◽  
Vol 37 (2) ◽  
pp. 130-139 ◽  
Author(s):  
Danica W. Y. Liu ◽  
A. Kate Fairweather-Schmidt ◽  
Richard Burns ◽  
Rachel M. Roberts ◽  
Kaarin J. Anstey
Keyword(s):  
Risk Factors ◽  
Well Being ◽  
Current Status ◽  
Psychological Resilience ◽  
Cross Sectional ◽  
Life Project ◽  
Resilience Factors ◽  
First Time

Abstract. Background: Little is known about the role of resilience in the likelihood of suicidal ideation (SI) over time. Aims: We examined the association between resilience and SI in a young-adult cohort over 4 years. Our objectives were to determine whether resilience was associated with SI at follow-up or, conversely, whether SI was associated with lowered resilience at follow-up. Method: Participants were selected from the Personality and Total Health (PATH) Through Life Project from Canberra and Queanbeyan, Australia, aged 28–32 years at the first time point and 32–36 at the second. Multinomial, linear, and binary regression analyses explored the association between resilience and SI over two time points. Models were adjusted for suicidality risk factors. Results: While unadjusted analyses identified associations between resilience and SI, these effects were fully explained by the inclusion of other suicidality risk factors. Conclusion: Despite strong cross-sectional associations, resilience and SI appear to be unrelated in a longitudinal context, once risk/resilience factors are controlled for. As independent indicators of psychological well-being, suicidality and resilience are essential if current status is to be captured. However, the addition of other factors (e.g., support, mastery) makes this association tenuous. Consequently, resilience per se may not be protective of SI.

Synergetic Theory of Document in Evolution of Document Science

2018 ◽  
pp. 1060-1068
Author(s):  
Galina A. Dvoenosova ◽  
Keyword(s):  
Social Role ◽  
Scientific Study ◽  
Self Organization ◽  
Universal Theory ◽  
Social Self ◽  
Social Goal ◽  
The Social ◽  
Synergetic Theory ◽  
First Time

The article assesses synergetic theory of document as a new development in document science. In information society the social role of document grows, as information involves all members of society in the process of documentation. The transformation of document under the influence of modern information technologies increases its interest to representatives of different sciences. Interdisciplinary nature of document as an object of research leads to an ambiguous interpretation of its nature and social role. The article expresses and contends the author's views on this issue. In her opinion, social role of document is incidental to its being a main social tool regulating the life of civilized society. Thus, the study aims to create a scientific theory of document, explaining its nature and social role as a tool of social (goal-oriented) action and social self-organization. Substantiation of this idea is based on application of synergetics (i.e., universal theory of self-organization) to scientific study of document. In the synergetic paradigm, social and historical development is seen as the change of phases of chaos and order, and document is considered a main tool that regulates social relations. Unlike other theories of document, synergetic theory studies document not as a carrier and means of information transfer, but as a unique social phenomenon and universal social tool. For the first time, the study of document steps out of traditional frameworks of office, archive, and library. The document is placed on the scales with society as a global social system with its functional subsystems of politics, economy, culture, and personality. For the first time, the methods of social sciences and modern sociological theories are applied to scientific study of document. This methodology provided a basis for theoretical vindication of nature and social role of document as a tool of social (goal-oriented) action and social self-organization. The study frames a synergetic theory of document with methodological foundations and basic concepts, synergetic model of document, laws of development and effectiveness of document in the social continuum. At the present stage of development of science, it can be considered the highest form of theoretical knowledge of document and its scientific explanatory theory.

Association of genetic polymorphism of cytokines and antioxidant enzymes with the development of asbestosis

2020 ◽  
Vol 60 (12) ◽  
pp. 898-903
Author(s):  
Lyudmila P. Kuzmina ◽  
Anastasiya G. Khotuleva ◽  
Evgeniy V. Kovalevsky ◽  
Nikolay N. Anokhin ◽  
Iraklij M. Tskhomariya
Keyword(s):  
Antioxidant Enzymes ◽  
Genetic Polymorphism ◽  
Genetic Predisposition ◽  
Risk Groups ◽  
Dust Exposure ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Gstp1 Gene ◽  
Polymorphic Variants

Introduction. Various industries widely use chrysotile asbestos, which determines the relevance of research aimed at the prevention of asbestos-related diseases. It is promising to assess the role of specific genes, which products are potentially involved in the development and regulation of certain links in the pathogenesis of asbestosis, forming a genetic predisposition to the disease. The study aims to analyze the presence of associations of genetic polymorphism of cytokines and antioxidant enzymes with asbestosis development. Materials and methods. Groups were formed for examination among employees of OJSC "Uralasbest" with an established diagnosis of asbestosis and without lung diseases. For each person included in the study, dust exposure doses were calculated considering the percentage of time spent at the workplace during the shift for the entire work time. Genotyping of single nucleotide polymorphisms of cytokines IL1b (rs16944), IL4 (rs2243250), IL6 (rs1800795), TNFα (rs1800629) and antioxidant enzymes SOD2 (rs4880), GSTP1 (rs1610011), CAT (rs1001179) was carried out. Results. The authors revealed the associations of polymorphic variants A511G IL1b gene (OR=2.457, 95% CI=1.232-4.899) and C47T SOD2 gene (OR=1.705, 95% CI=1.055-2.756) with the development of asbestosis. There was an increase in the T allele IL4 gene (C589T) frequency in persons with asbestosis at lower values of dust exposure doses (OR=2.185, 95% CI=1.057-4.514). The study showed the associations of polymorphism C589T IL4 gene and C174G IL6 gene with more severe asbestosis, polymorphism A313G GSTP1 gene with pleural lesions in asbestosis. Conclusion. Polymorphic variants of the genes of cytokines and antioxidant enzymes, the protein products directly involved in the pathogenetic mechanisms of the formation of asbestosis, contribute to forming a genetic predisposition to the development and severe course of asbestosis. Using the identified genetic markers to identify risk groups for the development and intense period of asbestos-related pathology will optimize treatment and preventive measures, considering the organism's characteristics.

Physical Warmth Attenuates Ethnocentric Bias under Mortality Salience: An Embodied Terror Management Perspective

2020 ◽  
Author(s):  
Armand Chatard ◽  
Margaux Renoux ◽  
Jean Monéger ◽  
Leila Selimbegovic
Keyword(s):  
Mortality Salience ◽  
Terror Management ◽  
Negative Consequences ◽  
Defensive Reaction ◽  
Worldview Defense ◽  
Management Perspective ◽  
Physical Warmth ◽  
Alternative Means ◽  
First Time

Research indicates that individuals often deal with mortality salience by affirming beliefs in national or cultural superiority (worldview defense). Because worldview defense may be associated with negative consequences (discrimination), it is important to identify alternative means to deal with death-related thoughts. In line with an embodied terror management perspective, we evaluate for the first time the role of physical warmth in reducing defensive reaction to mortality salience. We predicted that, like social affiliation (social warmth), physical warmth could reduce worldview defense when mortality is salient. In this exploratory (preregistered) study, 202 French participants were primed with death-related thoughts, or an aversive control topic, in a heated room or a non-heated room. The main outcome was worldview defense (ethnocentric bias). We found no main effect of mortality salience on worldview defense. However, physical warmth reduced worldview defense when mortality was salient. Implications for an embodied terror management perspective are discussed.

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