scholarly journals Introduction: Metals in Biology: α-Ketoglutarate/Iron-Dependent Dioxygenases

2015 ◽  
Vol 290 (34) ◽  
pp. 20700-20701 ◽  
Author(s):  
F. Peter Guengerich
Keyword(s):  
Protein Modification ◽  
Genomic Analysis ◽  
Current Understanding ◽  
Epigenetic Mechanisms ◽  
Oxidation Reactions ◽  
General Introduction ◽  
Dna And Rna ◽  
Damaged Dna

Four minireviews deal with aspects of the α-ketoglutarate/iron-dependent dioxygenases in this eighth Thematic Series on Metals in Biology. The minireviews cover a general introduction and synopsis of the current understanding of mechanisms of catalysis, the roles of these dioxygenases in post-translational protein modification and de-modification, the roles of the ten-eleven translocation (Tet) dioxygenases in the modification of methylated bases (5mC, T) in DNA relevant to epigenetic mechanisms, and the roles of the AlkB-related dioxygenases in the repair of damaged DNA and RNA. The use of α-ketoglutarate (alternatively termed 2-oxoglutarate) as a co-substrate in so many oxidation reactions throughout much of nature is notable and has surprisingly emerged from biochemical and genomic analysis. About 60 of these enzymes are now recognized in humans, and a number have been identified as having critical functions.

scholarly journals The Placenta as a Target of Epigenetic Alterations in Women with Gestational Diabetes Mellitus and Potential Implications for the Offspring

Epigenomes ◽  
2021 ◽  
Vol 5 (2) ◽  
pp. 13
Author(s):  
Dennise Lizárraga ◽  
Alejandra García-Gasca
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Adult Life ◽  
International Diabetes Federation ◽  
Main Function ◽  
Epigenetic Mechanisms ◽  
Molecular Alterations ◽  
Dna And Rna ◽  
In Pregnancy

Gestational diabetes mellitus (GDM) is a pregnancy complication first detected in the second or third trimester in women that did not show evident glucose intolerance or diabetes before gestation. In 2019, the International Diabetes Federation reported that 15.8% of live births were affected by hyperglycemia during pregnancy, of which 83.6% were due to gestational diabetes mellitus, 8.5% were due to diabetes first detected in pregnancy, and 7.9% were due to diabetes detected before pregnancy. GDM increases the susceptibility to developing chronic diseases for both the mother and the baby later in life. Under GDM conditions, the intrauterine environment becomes hyperglycemic, while also showing high concentrations of fatty acids and proinflammatory cytokines, producing morphological, structural, and molecular modifications in the placenta, affecting its function; these alterations may predispose the baby to disease in adult life. Molecular alterations include epigenetic mechanisms such as DNA and RNA methylation, chromatin remodeling, histone modifications, and expression of noncoding RNAs (ncRNAs). The placenta is a unique organ that originates only in pregnancy, and its main function is communication between the mother and the fetus, ensuring healthy development. Thus, this review provides up-to-date information regarding two of the best-documented (epigenetic) mechanisms (DNA methylation and miRNA expression) altered in the human placenta under GDM conditions, as well as potential implications for the offspring.

scholarly journals Integrative Genomics with Mediation Analysis in a Survival Context

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Szilárd Nemes ◽  
Toshima Z. Parris ◽  
Anna Danielsson ◽  
Zakaria Einbeigi ◽  
Gunnar Steineck ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Genomic Analysis ◽  
Mrna Levels ◽  
Integrative Genomics ◽  
Asymptotic Results ◽  
Data Set ◽  
Cancer Data ◽  
Dna And Rna ◽  
Altered Gene

DNA copy number aberrations (DCNA) and subsequent altered gene expression profiles may have a major impact on tumor initiation, on development, and eventually on recurrence and cancer-specific mortality. However, most methods employed in integrative genomic analysis of the two biological levels, DNA and RNA, do not consider survival time. In the present note, we propose the adoption of a survival analysis-based framework for the integrative analysis of DCNA and mRNA levels to reveal their implication on patient clinical outcome with the prerequisite that the effect of DCNA on survival is mediated by mRNA levels. The specific aim of the paper is to offer a feasible framework to test the DCNA-mRNA-survival pathway. We provide statistical inference algorithms for mediation based on asymptotic results. Furthermore, we illustrate the applicability of the method in an integrative genomic analysis setting by using a breast cancer data set consisting of 141 invasive breast tumors. In addition, we provide implementation in R.

Cu(III)-Mediated Aerobic Oxidations

Synthesis ◽  
2018 ◽  
Vol 51 (02) ◽  
pp. 334-358 ◽  
Author(s):  
Jean-Philip Lumb ◽  
Kenneth Esguerra
Keyword(s):  
Cross Coupling ◽  
Coupling Reactions ◽  
Oxidation Reactions ◽  
General Introduction ◽  
Model Complexes ◽  
Bond Forming ◽  
Cross Coupling Reactions ◽  
Carbon Carbon Bond ◽  
Bond Forming Reactions ◽  
Type 3

CuIII species have been invoked in many copper-catalyzed transformations including cross-coupling reactions and oxidation reactions. In this review, we will discuss seminal discoveries that have advanced our understanding of the CuI/CuIII redox cycle in the context of C–C and C–heteroatom aerobic cross-coupling reactions, as well as C–H oxidation reactions mediated by CuIII–dioxygen adducts.1 General Introduction2 Early Examples of CuIII Complexes3 Aerobic CuIII-Mediated Carbon–Heteroatom Bond-Forming Reactions4 Aerobic CuIII-Mediated Carbon–Carbon Bond-Forming Reactions5 Bioinorganic Studies of CuIII Complexes from CuI and O2 5.1 O2 Activation5.2 Biomimetic CuIII Complexes from CuI and Dioxygen5.2.1 Type-3 Copper Enzymes and Dinuclear Cu Model Complexes5.2.2 Particulate Methane Monooxygenase and Di- and Trinuclear Cu Model Complexes5.2.3 Dopamine–β-Monooxygenase and Mononuclear Cu Model Complexes6 Conclusion

scholarly journals Novel RNA Markers in Prostate Cancer: Functional Considerations and Clinical Translation

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Julia M. A. Pickl ◽  
Doreen Heckmann ◽  
Leonie Ratz ◽  
Sabine M. Klauck ◽  
Holger Sültmann
Keyword(s):  
Prostate Cancer ◽  
Noncoding Rna ◽  
Tumor Development ◽  
Genomic Analysis ◽  
Diagnosis And Therapy ◽  
Sequencing Technologies ◽  
Dna And Rna ◽  
Functional Genomic Analysis ◽  
Novel Transcripts

The availability of ultra-high throughput DNA and RNA sequencing technologies in recent years has led to the identification of numerous novel transcripts, whose functions are unknown as yet. Evidence is accumulating that many of these molecules are deregulated in diseases, including prostate cancer, and potentially represent novel targets for diagnosis and therapy. In particular, functional genomic analysis of microRNA (miRNA) and long noncoding RNA (lncRNA) in cancer is likely to contribute insights into tumor development. Here, we compile recent efforts to catalog differential expression of miRNA and lncRNA in prostate cancer and to understand RNA function in tumor progression. We further highlight technologies for molecular characterization of noncoding RNAs and provide an overview of current activities to exploit them for the diagnosis and therapy of this complex tumor.

scholarly journals Mutual Correlation between Non-Coding RNA and S-Adenosylmethionine in Human Cancer: Roles and Therapeutic Opportunities

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3264
Author(s):  
Laura Mosca ◽  
Francesca Vitiello ◽  
Luigi Borzacchiello ◽  
Alessandra Coppola ◽  
Roberta Veglia Tranchese ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Human Cancer ◽  
Transcriptional Level ◽  
Epigenetic Mechanisms ◽  
Therapeutic Approaches ◽  
Mutual Correlation ◽  
Dna And Rna ◽  
Non Coding Rna ◽  
Epigenetic Methylation ◽  
Non Coding Rnas

Epigenetics includes modifications in DNA methylation, histone and chromatin structure, and expression of non-coding RNAs (ncRNAs), especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Knowledge of the relationships between S-adenosylmethionine (AdoMet or SAM), the universal methyl donor for all epigenetic methylation reactions and miRNAs or lncRNAs in human cancer may provide helpful insights for the development of new end more effective anticancer therapeutic approaches. In recent literature, a complex network of mutual interconnections between AdoMet and miRNAs or lncRNAs has been reported and discussed. Indeed, ncRNAs expression may be regulated by epigenetic mechanisms such as DNA and RNA methylation and histone modifications. On the other hand, miRNAs or lncRNAs may influence the epigenetic apparatus by modulating the expression of its enzymatic components at the post-transcriptional level. Understanding epigenetic mechanisms, such as dysregulation of miRNAs/lncRNAs and DNA methylation, has become of central importance in modern research. This review summarizes the recent findings on the mechanisms by which AdoMet and miRNA/lncRNA exert their bioactivity, providing new insights to develop innovative and more efficient anticancer strategies based on the interactions between these epigenetic modulators.

scholarly journals EPEN-25. EXCEPTIONAL CLINICAL AND IMAGING RESPONSE TO TRK-INHIBITION IN A PATIENT WITH SUPRATENTORIAL EPENDYMOMA HARBORING NTRK2 GENE FUSION

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii312-iii313
Author(s):  
Ross Mangum ◽  
Jacquelyn Reuther ◽  
Adekunle Adesina ◽  
Marcia Kukreja ◽  
Daniel Curry ◽  
...  
Keyword(s):  
Tumor Recurrence ◽  
Gene Fusion ◽  
Genomic Analysis ◽  
Leptomeningeal Carcinomatosis ◽  
Kinase Domain ◽  
Dna And Rna ◽  
Pediatric Ependymoma ◽  
Ffpe Tumor ◽  
Poor Outcomes ◽  
Supratentorial Ependymoma

Abstract BACKGROUND Patients with metastatic pediatric ependymoma have limited therapeutic options and poor outcomes. Approximately ¾ of supratentorial ependymomas are driven by C11ORF95-RELA fusions, and the remaining by a heterogeneous group of fusion events. We present a six year-old male diagnosed with supratentorial ependymoma with leptomeningeal carcinomatosis harboring an NTRK2-fusion. Local and distant multifocal, intracranial and intraspinal tumor recurrence occurred seven months following gross total resection of the primary lesion and proton beam craniospinal irradiation. METHODS DNA and RNA from FFPE tumor were used for targeted sequencing using an 81-gene fusion panel and 124-gene mutation panel. Separately, capture transcriptome sequencing, exome sequencing, and copy number array were performed as part of the Texas KidsCanSeq study, an NHGRI/NCI-funded Clinical Sequencing Evidence-Generating Research (CSER) consortium project. All sequencing was carried out in CLIA-certified laboratories. RESULTS An in-frame fusion between 5’ exons 1–3 of KANK1 and 3’ exons 16–21 of NTRK2, predicted to retain the kinase domain, was identified. At tumor recurrence, therapy was initiated with Larotrectinib, an FDA-approved pan-TRK inhibitor. Clinical improvement in cognitive speed, motor strength, and coordination was observed at two weeks with significant tumor response on MRI at two and four months. CONCLUSION TRK gene fusions have not previously been reported in ependymoma. Further tumor characterization by methylation profiling is underway and will be of diagnostic interest given the apparent discordance between tumor histology and molecular findings. This case highlights the potential impact of clinical genomic analysis for children with CNS tumors.

scholarly journals Real-Time Polymerase Chain Reaction: Applications in Diagnostic Microbiology

2013 ◽  
Vol 1 (1) ◽  
pp. 28-36 ◽  
Author(s):  
Kordo B.A. Saeed ◽  
Nusreen S. Ahmad
Keyword(s):  
Polymerase Chain Reaction ◽  
Infectious Diseases ◽  
Real Time ◽  
Standard Test ◽  
Rt Pcr ◽  
General Introduction ◽  
Chain Reaction ◽  
Dna And Rna ◽  
Polymerase Chain ◽  
Diagnostic Microbiology

The polymerase chain reaction (PCR) has revolutionized the detection of DNA and RNA. Real-Time PCR (RT-PCR) is becoming the gold standard test for accurate, sensitive and fast diagnosis for a large range of infectious agents. Benefits of this procedure over conventional methods for measuring RNA include its sensitivity, high throughout and quantification. RT-PCR assays have advanced the diagnostic abilities of clinical laboratories particularly microbiology and infectious diseases. In this review we would like to briefly discuss RT-PCR in diagnostic microbiology laboratory, beginning with a general introduction to RT-PCR and its principles, setting up an RT-PCR, including multiplex systems and the avoidance and remediation of contamination issues. A segment of the review would be devoted to the application of RT-PCR in clinical practice concentrating on its role in the diagnosis and treatment of infectious diseases.

scholarly journals Epigenetic Landscape of Liquid Biopsy in Colorectal Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Aitor Rodriguez-Casanova ◽  
Nicolás Costa-Fraga ◽  
Aida Bao-Caamano ◽  
Rafael López-López ◽  
Laura Muinelo-Romay ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Liquid Biopsy ◽  
Current Knowledge ◽  
Monitoring And Evaluation ◽  
Precision Oncology ◽  
Epigenetic Mechanisms ◽  
Epigenetic Alterations ◽  
Liquid Biopsies ◽  
Dna And Rna

Colorectal cancer (CRC) is one of the most common malignancies and is a major cause of cancer-related deaths worldwide. Thus, there is a clinical need to improve early detection of CRC and personalize therapy for patients with this disease. In the era of precision oncology, liquid biopsy has emerged as a major approach to characterize the circulating tumor elements present in body fluids, including cell-free DNA and RNA, circulating tumor cells, and extracellular vesicles. This non-invasive tool has allowed the identification of relevant molecular alterations in CRC patients, including some indicating the disruption of epigenetic mechanisms. Epigenetic alterations found in solid and liquid biopsies have shown great utility as biomarkers for early detection, prognosis, monitoring, and evaluation of therapeutic response in CRC patients. Here, we summarize current knowledge of the most relevant epigenetic mechanisms associated with cancer development and progression, and the implications of their deregulation in cancer cells and liquid biopsy of CRC patients. In particular, we describe the methodologies used to analyze these epigenetic alterations in circulating tumor material, and we focus on the clinical utility of epigenetic marks in liquid biopsy as tumor biomarkers for CRC patients. We also discuss the great challenges and emerging opportunities of this field for the diagnosis and personalized management of CRC patients.

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