0
selected
-
1.
Roles for α-Synuclein in Gene Expression.
Somayaji, M, Lanseur, Z, Choi, SJ, Sulzer, D, Mosharov, EV
Genes. 2021;(8)
Abstract
α-Synuclein (α-Syn) is a small cytosolic protein associated with a range of cellular compartments, including synaptic vesicles, the nucleus, mitochondria, endoplasmic reticulum, Golgi apparatus, and lysosomes. In addition to its physiological role in regulating presynaptic function, the protein plays a central role in both sporadic and familial Parkinson's disease (PD) via a gain-of-function mechanism. Because of this, several recent strategies propose to decrease α-Syn levels in PD patients. While these therapies may offer breakthroughs in PD management, the normal functions of α-Syn and potential side effects of its depletion require careful evaluation. Here, we review recent evidence on physiological and pathological roles of α-Syn in regulating activity-dependent signal transduction and gene expression pathways that play fundamental role in synaptic plasticity.
-
2.
Role of Phytonutrients in Nutrigenetics and Nutrigenomics Perspective in Curing Breast Cancer.
Bhattacharya, T, Dutta, S, Akter, R, Rahman, MH, Karthika, C, Nagaswarupa, HP, Murthy, HCA, Fratila, O, Brata, R, Bungau, S
Biomolecules. 2021;(8)
Abstract
Breast cancer (BC) is one of the most common type of cancer and an important contributor to female mortality. Several genes and epigenetic modifications are involved in the development and progression of BC. Research in phytochemistry, nutrigenomics, and nutrigenetics has provided strong evidence that certain phytonutrients are able to modulate gene expression at transcriptional and post-transcriptional levels. Such phytonutrients may also be beneficial to prevent and treat BC. In this review, we will focus on the nutrigenomic effects of various phytochemicals including polyphenols, phytosterols, terpenoids, alkaloids, and other compounds from different sources. Overall, these phytonutrients are found to inhibit BC cell proliferation, differentiation, invasion, metastasis, angiogenesis, and induce apoptotic cell death by targeting various molecular pathways. They also alter epigenetic mechanisms and enhance the chemosensitivity and radiosensitivity of cancer cells. Such phytochemicals may be used for the effective management of BC patients in the clinical setting in the future. The present article aims to summarize the specific molecular pathways involved in the genetic effects of phytochemicals in BC.
-
3.
The Diagnostic Performance of Afirma Gene Expression Classifier for the Indeterminate Thyroid Nodules: A Meta-Analysis.
Liu, Y, Pan, B, Xu, L, Fang, D, Ma, X, Lu, H
BioMed research international. 2019;:7150527
Abstract
BACKGROUND Approximately 15 to 30% of thyroid nodules evaluated by fine-needle aspiration (FNA) were classified as indeterminate; the accurate diagnostic molecular tests of these nodules remain a challenge. We aimed to evaluate the diagnostic performance of Afirma gene expression classifier (GEC) for the indeterminate thyroid nodules (ITNs). METHODS Studies published from January 2005 to December 2018 were systematically reviewed. The gold reference standard relied on the histopathologic results diagnosis from thyroidectomy surgical specimens. MetaDisc software was used to investigate the pooled sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curves. RESULTS A total of 18 studies involving 5290 patients with 3290 cases of ITNs were included. Collected data revealed that the pooled sensitivity of GEC was 95.5% (95% CI 93.3%-97.0%, p < 0.001), the specificity was 22.1% (95% CI 19.4%-24.9%, p < 0.001), the NPV was 88.2% (95% CI 0.833-0.921, p < 0.001), the PPV was 44.3% (95% CI 0.416-0.471, p < 0.001), and the DOR was 5.25 (95% CI 3.42-8.04, p= 0.855). CONCLUSION The GEC has quite high sensitivity of 95.5% but low specificity of 22.1%. The high sensitivity makes it probable to rule out malignant nodules. Thus, over half of nodules with GEC-suspicious results still require further validation like molecular markers, diagnostic surgery, or long follow-up, which limits its use in future clinical practice.
-
4.
UTR-Dependent Control of Gene Expression in Plants.
Srivastava, AK, Lu, Y, Zinta, G, Lang, Z, Zhu, JK
Trends in plant science. 2018;(3):248-259
-
-
Free full text
-
Abstract
Throughout their lives, plants sense many developmental and environmental stimuli, and activation of optimal responses against these stimuli requires extensive transcriptional reprogramming. To facilitate this activation, plant mRNA contains untranslated regions (UTRs) that significantly increase the coding capacity of the genome by producing multiple mRNA variants from the same gene. In this review we compare UTRs of arabidopsis (Arabidopsis thaliana) and rice (Oryza sativum) at the genome scale to highlight their complexity in crop plants. We discuss different modes of UTR-based regulation with emphasis on genes that regulate multiple plant processes, including flowering, stress responses, and nutrient homeostasis. We demonstrate functional specificity in genes with variable UTR length and propose future research directions.
-
5.
Endocrine disruptors in 2015: Epigenetic transgenerational inheritance.
Skinner, MK
Nature reviews. Endocrinology. 2016;(2):68-70
-
-
Free full text
-
Abstract
Endocrine disruptors are critical environmental exposures that influence health and can promote epigenetic transgenerational inheritance of disease and abnormal physiology. Advances in 2015 included analyses of the effects of endocrine disruptors on human disease, further examples of endocrine disruptors promoting transgenerational behavioural effects, insights into effects of endocrine disruptors on epigenetic programming of primordial germ cells and the finding that endocrine disruptors can transgenerationally promote genetic mutations.
-
6.
The genetic signatures of pediatric high-grade glioma: no longer a one-act play.
Diaz, AK, Baker, SJ
Seminars in radiation oncology. 2014;(4):240-7
-
-
Free full text
-
Abstract
Advances in understanding pediatric high-grade glioma (pHGG) genetics have revealed key differences between pHGG and adult HGG and have uncovered unique molecular drivers among subgroups within pHGG. The 3 core adult HGG pathways, the receptor tyrosine kinase-Ras-phosphatidylinositide 3-kinase, p53, and retinoblastoma networks, are also disrupted in pHGG, but they exhibit a different spectrum of effectors targeted by mutation. There are also similarities and differences in the genomic landscape of diffuse intrinsic pontine glioma (DIPG) and pediatric nonbrainstem (pNBS)-HGG. In 2012, histone H3 mutations were identified in nearly 80% of DIPGs and ~35% of pNBS-HGG. These were the first reports of histone mutations in human cancer, implicating novel biology in pediatric gliomagenesis. Additionally, DIPG and midline pNBS-HGG vary in the frequency and specific histone H3 amino acid substitution compared with pNBS-HGGs arising in the cerebral hemispheres, demonstrating a molecular difference among pHGG subgroups. The gene expression signatures as well as DNA methylation signatures of these tumors are also distinctive, reflecting a combination of the driving mutations and the developmental context from which they arise. These data collectively highlight unique selective pressures within the developing brainstem and solidify DIPG as a specific molecular and biological entity among pHGGs. Emerging studies continue to identify novel mutations that distinguish subgroups of pHGG. The molecular heterogeneity among pHGGs will undoubtedly have clinical implications moving forward. The discovery of unique oncogenic drivers is a critical first step in providing patients with appropriate, targeted therapies. Despite these insights, our vantage point has been largely limited to an in-depth analysis of protein coding sequences. Given the clear importance of histone mutations in pHGG, it will be interesting to see how aberrant epigenetic regulation contributes to tumorigenesis in the pediatric context. New mechanistic insights may allow for the identification of distinct vulnerabilities in this devastating spectrum of childhood tumors.
-
7.
The effect of green tea extract on fat oxidation at rest and during exercise: evidence of efficacy and proposed mechanisms.
Hodgson, AB, Randell, RK, Jeukendrup, AE
Advances in nutrition (Bethesda, Md.). 2013;(2):129-40
Abstract
Green tea is made from the leaves of the Camellia sinensis L plant, which is rich in polyphenol catechins and caffeine. There is increasing interest in the potential role of green tea extract (GTE) in fat metabolism and its influence on health and exercise performance. A number of studies have observed positive effects of GTE on fat metabolism at rest and during exercise, following both shorter and longer term intake. However, overall, the literature is inconclusive. The fact that not all studies observed effects may be related to differences in study designs, GTE bioavailability, and variation of the measurement (fat oxidation). In addition, the precise mechanisms of GTE in the human body that increase fat oxidation are unclear. The often-cited in vitro catechol-O-methyltransferase mechanism is used to explain the changes in substrate metabolism with little in vivo evidence to support it. Also, changes in expression of fat metabolism genes with longer term GTE intake have been implicated at rest and with exercise training, including the upregulation of fat metabolism enzyme gene expression in the skeletal muscle and downregulation of adipogenic genes in the liver. The exact molecular signaling that activates changes to fat metabolism gene expression is unclear but may be driven by PPAR-γ coactivator 1-α and PPARs. However, to date, evidence from human studies to support these adaptations is lacking. Clearly, more studies have to be performed to elucidate the effects of GTE on fat metabolism as well as improve our understanding of the underlying mechanisms.
-
8.
Gene expression profiling in acute myeloid leukaemia.
de Jonge, HJ, Huls, G, de Bont, ES
The Netherlands journal of medicine. 2011;(4):167-76
Abstract
Acute myeloid leukaemia (AML) is a heterogeneous disease characterised by clonal malignant haematopoiesis with a differentiation arrest and excessive proliferation of leukaemic blasts. Over the past decades, the heterogeneity of AML has been illustrated by evolving classifications based on morphology (French-American-British classification (FAB classification), cytogenetic abnormalities (e.g. t(8;21), monosomies etc.), phenotype and÷or molecular abnormalities (e.g. Fms-like tyrosine kinase 3 gene internal tandem duplication (FLT3-ITD), mutations in nucleophosmin 1 (NPM1) and the transcription factor CCAAT ÷enhancer binding protein a (CEBPA), etc.). The current World Health Organisation (WHO) 2008 classification has integrated these classification modalities. Clinically, dissection of AML into various subtypes allows better survival prediction, but has still limited impact on treatment strategies, with the exception of all-trans retinoic acid treatment for AML-M3 and no allogeneic haematopoietic cell transplantation in complete remission (CR1) for patients with normal karyotype bearing an NPM1 mutation without FLT3-ITD. However, enhanced understanding of the molecular biology of AML will likely result in more 'tailor-made' therapies, for example by adding specific tyrosine kinase inhibitors to standard chemotherapy. In this review, we summarise the variables currently used to classify AML. Specifically, the contribution of microarrays in classification, prognosis and understanding of pathobiology of AML is discussed.
-
9.
[Effect of environmental chemicals on the genes and the gene expression].
Ueda, K
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan. 2009;(12):1501-6
-
-
Free full text
-
Abstract
Chemicals act on biological molecules and affect their functions. DNA is one of the most important targets, damaging of which could lead to diverse diseases including cancer. The mode of action of chemicals to DNA contains chemical reaction and protein factor-mediated modulation of the function. In this review, these actions are described in view of effects of chemicals on DNA. First, oxidative damage of DNA is described in several cases of chemicals focusing on its mechanisms involving metals such as copper. We have demonstrated: DNA binding of copper ions prior to reduction-oxidation reaction is crucial for the damaging, probably due to the proximal attack of reactive oxygen species; reduction of the bound copper induces a conformational change of DNA strand through rearrangement of copper-coordination geometry; RNA, another nucleic acid, is more liable to oxidative damage than DNA. Impact of RNA damage on oxidative stress-related diseases is discussed. Second, a group of chemicals called endocrine disruptors is described. Phthalate esters are ubiquitous endocrine disruptors of which mechanisms are still elusive. Here, we present our research performed for elucidation of the active metabolite and molecular target. Novel candidates of active metabolite are suggested. Finally, toxicological activity dynamics are described, showing several chemicals exert toxic potential by structural alteration in the environment, metabolism, or both. These imply gene-environment interactions that would underlie various diseases induced by environmental chemicals.
-
10.
Dynamic and combinatorial control of gene expression by nuclear retinoic acid receptors (RARs).
Rochette-Egly, C, Germain, P
Nuclear receptor signaling. 2009;:e005
Abstract
Nuclear retinoic acid receptors (RARs) are transcriptional regulators controlling the expression of specific subsets of genes in a ligand-dependent manner. The basic mechanism for switching on transcription of cognate target genes involves RAR binding at specific response elements and a network of interactions with coregulatory protein complexes, the assembly of which is directed by the C-terminal ligand-binding domain of RARs. In addition to this scenario, new roles for the N-terminal domain and the ubiquitin-proteasome system recently emerged. Moreover, the functions of RARs are not limited to the regulation of cognate target genes, as they can transrepress other gene pathways. Finally, RARs are also involved in nongenomic biological activities such as the activation of translation and of kinase cascades. Here we will review these mechanisms, focusing on how kinase signaling and the proteasome pathway cooperate to influence the dynamics of RAR transcriptional activity.