scholarly journals Increased α-2,8-sialyltransferase 8B (ST8SIA2) expression in schizophrenia superior temporal gyrus

2018 ◽  
Author(s):  
Toni M. Mueller ◽  
Stefani D. Yates ◽  
James H. Meador-Woodruff
Keyword(s):  
Sialic Acid ◽  
Protein Expression ◽  
Superior Temporal Gyrus ◽  
Compensatory Mechanism ◽  
Nucleotide Polymorphisms ◽  
Gene Encoding ◽  
Protein Levels ◽  
Neural Cell Adhesion ◽  
The Face ◽  
The Relationship

AbstractReduced polysialylation of neural cell adhesion molecule (NCAM) in schizophrenia has been suggested to contribute to abnormal neuroplasticity and neurodevelopmental features of this illness. The posttranslational addition of sialic acid is mediated by sialyltransferases, and polysialylation (the addition of ≥ 8 α -2,8-linked sialic acid residues) is catalyzed by three enzymes: ST8SIA2 (also called STX), ST8SIA4 (also called PST), and/or ST8SIA3. ST8SIA2 and ST8SIA4 are the primary mediators of NCAM polysialylation. The gene encoding ST8SIA2 maps to schizophrenia risk locus 15q26, and single nucleotide polymorphisms (SNPs) and SNP haplotypes of the ST8SIA2 gene have been associated with schizophrenia in multiple populations. The current study in elderly schizophrenia (N = 16) and comparison (N = 14) subjects measured the protein expression of NCAM, polysialylated-NCAM (PSANCAM), and three poly-α-2,8-sialyltransferases (ST8SIA2, ST8SIA3, and ST8SIA4) in postmortem superior temporal gyrus. Although expression of NCAM, PSA-NCAM, ST8SIA3, and ST8SIA4 were not different in schizophrenia, increased protein levels of ST8SIA2 were identified. It has been reported that ST8SIA2 mutations associated with increased schizophrenia risk impair PSA-NCAM synthesis, suggesting that increased protein expression of ST8SIA2 may represent a compensatory mechanism in the face of impaired enzyme function. This interpretation is further supported by our finding that the relationship between ST8SIA2 enzyme expression and PSA-NCAM levels are different between schizophrenia and comparison subjects. Together these findings suggest a possible neurodevelopmentally-regulated mechanism which could contribute to abnormal synaptic plasticity evident in schizophrenia.

scholarly journals Variation of genes encoding KAT1, AADAT and IDO1 as a potential risk of depression development

2018 ◽  
Vol 52 ◽  
pp. 95-103 ◽  
Author(s):  
Paulina Wigner ◽  
Piotr Czarny ◽  
Ewelina Synowiec ◽  
Michał Bijak ◽  
Monika Talarowska ◽  
...  
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Nucleotide Polymorphisms ◽  
Male Population ◽  
Gene Encoding ◽  
Single Nucleotide ◽  
Genes Encoding ◽  
Numerous Data ◽  
Tryptophan Catabolites ◽  
Hydroxyanthranilic Acid ◽  
The Relationship

AbstractBackground:Numerous data suggests that the disorders of tryptophan catabolites (TRYCATs) pathway, including a decreased level of tryptophan or evaluated concentration of harmful TRYCATs −kynurenine, quinolinic acid, 3-hydroxyanthranilic acid, 3-hydroxytryptophan − may cause the occurrence of DD symptoms. In this work, we assessed the relationship between single-nucleotide polymorphisms (SNPs) of KAT1, KAT2 and IDO1 gene encoding, and the risk of depression development. Our study was performed on the DNA isolated from peripheral blood of 281 depressed patients and 236 controls. We genotyped, by using TaqMan probes, four polymorphisms: c.*456G > A of KAT1 (rs10988134), c.975-7T > C of AADAT (rs1480544), c.-1849C > A (rs3824259) and c.-1493G > C(rs10089084)of IDO1. We found that only the A/A genotype of c.*456G > A − KAT1 (rs10988134) increased the risk of depression occurrence. Interestingly, when we stratified the study group according to gender, this relationship was present only in male population. However, a gene–gene analysis revealed a link between the T/T-C/C genotype of c.975-7T > C − AADAT (rs1480544)or c.-1493G > C − IDO1 (rs10089084) and C/C-C/A genotype of c.975-7T > C − AADAT (rs1480544)and c. −1849C > A − IDO1 (rs3824259) and the disease. Moreover, we found, that the c.975-7T > C − AADAT and c. *456G > A KAT1 (rs10988134) polymorphisms may modulate the effectiveness of selective serotonin reuptake inhibitors therapy. Concluding, our results confirm the hypothesis formulated in our recently published article that the SNPs of genes involved in TRYCATs pathway may modulate the risk of depression. This provides some further evidence that the pathway plays the crucial role in development of the disease.

Relationship of ERCC1 genotype variant with mRNA expression and ERCC1 protein levels in advanced urothelial carcinoma (UC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 260-260
Author(s):  
Elizabeth A. Guancial ◽  
Lillian Werner ◽  
Joaquim Bellmunt ◽  
Nikitas Nikitas ◽  
Edward C. Stack ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Excision Repair ◽  
Predictive Biomarker ◽  
Mrna Levels ◽  
Nuclear Staining ◽  
Protein Levels ◽  
Tissue Arrays ◽  
Platinum Based Chemotherapy ◽  
The Relationship

260 Background: DNA repair factors may be predictive for response to chemotherapies that produce DNA damage. While low ERCC1 protein and mRNA levels have been reported as associated with improved outcomes in metastatic UC patients treated with platinum-based chemotherapy, the relationship between genotype, mRNA expression, and protein level is unknown. The ERCC1 germline 19007C>T single-nucleotide polymorphism (SNP) is functionally associated with reduced translation of ERCC1 mRNA. We investigated the relationship between ERCC1 germline SNP, ERCC1 tumor mRNA and protein expression, in a cohort of patients with advanced UC who received first-line, platinum-based chemotherapy. Methods: A cohort of clinically annotated, uniformly-treated advanced UC patients with FFPE primary tumor tissue available was identified through the Hellenic cooperative Oncology Group (HECOG) (N=93). Genomic DNA extraction, nested PCR, and restriction fragment length polymorphism techniques for the 19007C>T SNP were performed to identify C/C, C/T and T/T genotypes. ERCC1 mRNA expression was interrogated using Nanostring nCounter profiling. IHC analysis was performed on tissue arrays using an ERCC1 antibody. Percent of positive nuclear staining was categorized as quartiles using previously identified cut-points. Results: ERCC1 C/T genotype was identified in 30/61 samples (49%) and T/T in 14/61 samples (23%). In 54 patients with both SNP and mRNA data available, T/T genotype was associated with the highest level of mRNA expression, followed by the C/T genotype (p=0.04). Neither ERCC1 genotype (N=44) nor ERCC1 mRNA expression (N=54) was associated with ERCC1 protein expression as measured by IHC (p=0.52 and p=0.13, respectively). Conclusions: ERCC1 19007C>T is associated with increased ERCC1 mRNA expression. However, neither genotype nor mRNA are surrogates for ERCC1 protein detected by IHC in advanced UC tumors. This suggests that while genotype influences mRNA expression of ERCC1, the use of the nucleotide excision repair pathway as a predictive biomarker of platinum-sensitivity may be more complex than previously appreciated and require the integrative use of proteomics, genomics and epigenomics.

Abstract 16546: microRNA(miR)-451 Regulates Cardiac Growth and Myocardial Reactive Oxidative Species (ROS) Level via Nrf2 and AMPK Pathways

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Young-Eun Cho ◽  
Chongxu Zhang ◽  
Ravi Ranjan ◽  
John W Christman ◽  
Lei Xiao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Hypertrophy ◽  
Protein Expression ◽  
Ventricular Myocytes ◽  
Ischemia Reperfusion ◽  
Fold Increase ◽  
Protective Role ◽  
Compensatory Mechanism ◽  
The Relationship ◽  
Nrf2 Expression

The role of miR-451 in certain cardiac diseases was recently reported including ischemia/reperfusion and hypertrophic cardiomyopathy. Oxidative stress is known to involve in the above diseases. Currently the relationship between miR-451 and cardiac oxidative stress is unknown. We thus hypothesize that miR-451 act as a key mediator for cardiac hypertrophy via regulating myocardial ROS level and antioxidant pathways. We first compared the heart/body weight (HW/BW) ratio between age- & gender-matched miR-451 knockout (KO) and wild-type (WT) mice. Increase of HW/BW was found in KO mice (6.1±0.1 vs 4.8±0.1 mg/g in WT, p<0.01). Expression of fetal genes ANF (2.9-fold↑) and β-MHC (4.0-fold↑) was also significantly increased in KO hearts, as well as the ROS level (2.3-fold↑, p<0.05) in KO hearts. Consistently, both the protein expression and activation levels of the oxidation-regulating gene Nrf2 decreased the same extent (~33%↓, p<0.05) in KO hearts. In contrast, the protein expression of the direct antioxidants HO-1 and SOD3 were found significantly increased in KO hearts, suggesting a compensatory mechanism to quench the increased cardiac ROS. Since we previously showed that phosphorylation (p) of AMPKα was inhibited in cardiac hypertrophy, thus the p-AMPKα level was tested and found significantly (76%↓, p<0.05) decreased in KO heart, consistent with the hypertrophy in KO heart. In order to further explore the relationship between Nrf2 and AMPKα, cultured adult rat ventricular myocytes (ARVM) was treated with an Nrf2 activator sulforaphane, which induced 1.4-fold increase in p-AMPKα (p<0.01); whereas the AMPK activator AICAR didn’t affect Nrf2 expression in ARVM, suggesting Nrf2 is upstream from AMPK. When miR-451 mimics were overexpressed in cultured cardiac myocytes, Nrf2 was significantly increased (2.3-fold↑, p<0.05) with overexpression of miR-451 mimics vs control, suggesting miR-451 regulates Nrf2 expression. Taken together, our data show that miR-451 activates cardiac Nrf2 and its downstream AMPK signaling pathway; whereas antioxidants HO-1 and SOD3 act as compensatory mechanism for increased cardiac ROS when miR-451 is defect. miR-451 plays a novel protective role against cardiac oxidative stress, and also mediates cardiac hypertrophy.

The Relationship between Seeker and Spiritual Guide as portrayed in contemporary Western Sufi Autobiographies

2011 ◽  
Vol 5 (2) ◽  
pp. 297-332
Author(s):  
Kate Zebiri
Keyword(s):  
Life Writing ◽  
New Age ◽  
The Self ◽  
Individual Autonomy ◽  
Religious Authority ◽  
The Face ◽  
The Relationship ◽  
Insight Into ◽  
Continuity And Discontinuity

This article aims to explore the Shaykh-mur?d (disciple) or teacher-pupil relationship as portrayed in Western Sufi life writing in recent decades, observing elements of continuity and discontinuity with classical Sufism. Additionally, it traces the influence on the texts of certain developments in religiosity in contemporary Western societies, especially New Age understandings of religious authority. Studying these works will provide an insight into the diversity of expressions of contemporary Sufism, while shedding light on a phenomenon which seems to fly in the face of contemporary social and religious trends which deemphasize external authority and promote the authority of the self or individual autonomy.

Mimetic Monsters

2010 ◽  
Vol 4 (1) ◽  
pp. 85-93
Author(s):  
Timothy Beal
Keyword(s):  
The Other ◽  
Jewish Tradition ◽  
Book Of Job ◽  
Edge Of Chaos ◽  
The Face ◽  
The Relationship

This article reads between two recent explorations of the relationship between religion, chaos, and the monstrous: Catherine Keller’s Face of the Deep and Author's Religion and Its Monsters. Both are oriented toward the edge of chaos and order; both see the primordial and chaotic as generative; both pursue monstrous mythological figures as divine personifications of primordial chaos; both find a deep theological ambivalences in Christian and Jewish tradition with regard to the monstrous, chaotic divine; both are critical of theological and cultural tendencies to demonize chaos and the monstrous; and finally, both read the divine speech from the whirlwind in the book of Job as a revelation of divine chaos. But whereas one sees it as a call for laughter, a chaotic life-affirming laughter with Leviathan in the face of the deep, the other sees it as an incarnation of theological horror, leaving Job and the reader overwhelmed and out-monstered by God. Must it be one way or the other? Can laughter and horror coincide in the face of the deep?

INTERCONNECTION OF SUSTAINABLE DEVELOPMENT COMPONENTS FOR THE INDIGENOUS PEOPLES OF THE NORTH

2020 ◽  
Vol 2 (8) ◽  
pp. 101-110
Author(s):  
N. N. ILYSHEVA ◽  
◽  
E. V. KARANINA ◽  
G. P. LEDKOV ◽  
E. V. BALDESKU ◽  
...  
Keyword(s):  
Climate Change ◽  
Sustainable Development ◽  
Economic Development ◽  
Indigenous Peoples ◽  
Ecological Footprint ◽  
Positive Relationship ◽  
The North ◽  
Strong Positive Relationship ◽  
The Face ◽  
The Relationship

The article deals with the problem of achieving sustainable development. The purpose of this study is to reveal the relationship between the components of sustainable development, taking into account the involvement of indigenous peoples in nature conservation. Climate change makes achieving sustainable development more difficult. Indigenous peoples are the first to feel the effects of climate change and play an important role in the environmental monitoring of their places of residence. The natural environment is the basis of life for indigenous peoples, and biological resources are the main source of food security. In the future, the importance of bioresources will increase, which is why economic development cannot be considered independently. It is assumed that the components of resilience are interrelated and influence each other. To identify this relationship, a model for the correlation of sustainable development components was developed. The model is based on the methods of correlation analysis and allows to determine the tightness of the relationship between economic development and its ecological footprint in the face of climate change. The correlation model was tested on the statistical materials of state reports on the environmental situation in the Khanty-Mansiysk Autonomous Okrug – Yugra. The approbation revealed a strong positive relationship between two components of sustainable development of the region: economy and ecology.

MiR-493 Induces Cytotoxic Autophagy in Prostate Cancer Cells through Regulation on PHLPP2

2020 ◽  
Vol 21 (14) ◽  
pp. 1451-1456 ◽  
Author(s):  
Jun Deng ◽  
Ming Ma ◽  
Wei Jiang ◽  
Liangliang Zheng ◽  
Suping Cui
Keyword(s):  
Prostate Cancer ◽  
Protein Expression ◽  
Cell Function ◽  
Mrna Levels ◽  
Prostate Cancer Cells ◽  
Potent Inducer ◽  
Qrt Pcr ◽  
Autophagy Gene ◽  
The Relationship ◽  
Cancer Inhibition

Background: MiR-493 promotes the proliferation of prostate cancer (PC) cells by targeting PHLPP2. We aimed to explore the relationship between miR-493 and autophagy in PC. Methods: qRT-PCR and western blotting were used to determine the mRNA levels and protein expression of miR-493, PHLPP2, autophagy gene BECN1 and ATG7 in PC cells. The autophagy gene expression was determined after PC cells transfected with miR-493 precursor or PHLPP2 precursor. Corresponding changes of autophagy phenotype and PC cell function were also studied. Results: The mRNA levels and protein expression of miR-493, PHLPP2, BECN1 and ATG7 in PC cells were significantly decreased in PC cells. Overexpression of miR-493 or PHLPP2 markedly upregulated the expression levels of BECN1 and ATG7 in PC cells. Overexpression of miR-493 and PHLPP2 markedly promoted autophagy, and inhibited the invasion and cloning formation of PC cells. Conclusion: MiR-493 is a potent inducer of cytotoxic autophagy that leads to prostate cancer inhibition by regulating on PHLPP2.

MiR-335-5p Inhibits β-Amyloid (Aβ) Accumulation to Attenuate Cognitive Deficits Through Targeting c-jun-N-terminal Kinase 3 in Alzheimer’s Disease

2020 ◽  
Vol 17 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Dan Wang ◽  
Zhifu Fei ◽  
Song Luo ◽  
Hai Wang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Western Blot ◽  
Mrna Expression ◽  
Cognitive Deficits ◽  
Protein Levels ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
The Relationship

Objectives: Alzheimer's disease (AD), also known as senile dementia, is a common neurodegenerative disease characterized by progressive cognitive impairment and personality changes. Numerous evidences have suggested that microRNAs (miRNAs) are involved in the pathogenesis and development of AD. However, the exact role of miR-335-5p in the progression of AD is still not clearly clarified. Methods: The protein and mRNA levels were measured by western blot and RNA extraction and quantitative real-time PCR (qRT-PCR), respectively. The relationship between miR-335-5p and c-jun-N-terminal kinase 3 (JNK3) was confirmed by dual-luciferase reporter assay. SH-SY5Y cells were transfected with APP mutant gene to establish the in vitro AD cell model. Flow cytometry and western blot were performed to evaluate cell apoptosis. The APP/PS1 transgenic mice were used as an in vivo AD model. Morris water maze test was performed to assess the effect of miR- 335-5p on the cognitive deficits in APP/PS1 transgenic mice. Results: The JNK3 mRNA expression and protein levels of JNK3 and β-Amyloid (Aβ) were significantly up-regulated, and the mRNA expression of miR-335-5p was down-regulated in the brain tissues of AD patients. The expression levels of miR-335-5p and JNK3 were significantly inversely correlated. Further, the dual Luciferase assay verified the relationship between miR-335- 5p and JNK3. Overexpression of miR-335-5p significantly decreased the protein levels of JNK3 and Aβ and inhibited apoptosis in SH-SY5Y/APPswe cells, whereas the inhibition of miR-335-5p obtained the opposite results. Moreover, the overexpression of miR-335-5p remarkably improved the cognitive abilities of APP/PS1 mice. Conclusion: The results revealed that the increased JNK3 expression, negatively regulated by miR-335-5p, may be a potential mechanism that contributes to Aβ accumulation and AD progression, indicating a novel approach for AD treatment.

Plebiscitary Politics and the Threats to Legality

2019 ◽  
pp. 275-289
Author(s):  
Claudius Härpfer
Keyword(s):  
The State ◽  
Short Term ◽  
Political Processes ◽  
The Face ◽  
State Of Affairs ◽  
The Relationship

In recent times we find many plebiscitary acts that seek to democratically legitimize political processes in any direction. They have in common that they interrupt the normal routine of representative democracies to a certain degree and create an extra-daily state of affairs, which entails not only direct but also indirect consequences. The text attempts to systematize some of these mechanisms from a Weberian perspective using Brexit as an example. After a brief overview of Weber’s short-term politically inspired statements on plebiscitary democracy, the text systematizes Weber’s understanding of the state as a bureaucratic apparatus that requires any kind of leader to be controlled. Subsequently, the text discusses the relationship between domination, legality, and rationality in order to finally point out the danger of erosion of truth and legality through the emergence of competing consensus communities in the face of competing conceptions of order.

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