scholarly journals Molecular Bases and Phenotypic Determinants of Aromatase Excess Syndrome

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Maki Fukami ◽  
Makio Shozu ◽  
Tsutomu Ogata
Keyword(s):  
Molecular Mechanisms ◽  
Genetic Disorders ◽  
Start Codon ◽  
Neighboring Gene ◽  
Autosomal Dominant Disorder ◽  
Chimeric Genes ◽  
Noncoding Exon ◽  
Translation Start ◽  
Phenotype Analysis ◽  
Molecular Bases

Aromatase excess syndrome (AEXS) is a rare autosomal dominant disorder characterized by gynecomastia. This condition is caused by overexpression ofCYP19A1encoding aromatase, and three types of cryptic genomic rearrangement aroundCYP19A1, that is, duplications, deletions, and inversions, have been identified in AEXS. Duplications appear to have causedCYP19A1overexpression because of an increased number of physiological promoters, whereas deletions and inversions would have induced wideCYP19A1expression due to the formation of chimeric genes consisting of a noncoding exon(s) of a neighboring gene andCYP19A1coding exons. Genotype-phenotype analysis implies that phenotypic severity of AEXS is primarily determined by the expression pattern ofCYP19A1and the chimeric genes and by the structural property of the fused exons with a promoter function (i.e., the presence or the absence of a natural translation start codon). These results provide novel information about molecular mechanisms of human genetic disorders and biological function of estrogens.

scholarly journals Advances in hepatic transport: Molecular mechanisms, genetic disorders, and treatment. A summary of the 1998 AASLD single topic conference

Hepatology ◽  
1998 ◽  
Vol 28 (6) ◽  
pp. 1713-1719 ◽  
Author(s):  
Allan W. Wolkoff ◽  
Frederick J. Suchy ◽  
Richard H. Moseley ◽  
Peter J. Meier ◽  
John L. Gollan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Genetic Disorders ◽  
Hepatic Transport

scholarly journals Genome-wide promoter analysis, homology modeling and protein interaction network of Dehydration Responsive Element Binding (DREB) gene family in Solanum tuberosum

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261215
Author(s):  
Qurat-ul ain-Ali ◽  
Nida Mushtaq ◽  
Rabia Amir ◽  
Alvina Gul ◽  
Muhammad Tahir ◽  
...  
Keyword(s):  
Abiotic Stress ◽  
Gene Family ◽  
Stress Responses ◽  
Promoter Analysis ◽  
Molecular Mechanisms ◽  
Regulatory Elements ◽  
Start Codon ◽  
Gene Promoters ◽  
Responsive Element ◽  
Dreb Gene

Dehydration Responsive Element Binding (DREB) regulates the expression of numerous stress-responsive genes, and hence plays a pivotal role in abiotic stress responses and tolerance in plants. The study aimed to develop a complete overview of the cis-acting regulatory elements (CAREs) present in S. tuberosum DREB gene promoters. A total of one hundred and four (104) cis-regulatory elements (CREs) were identified from 2.5kbp upstream of the start codon (ATG). The in-silico promoter analysis revealed variable sets of cis-elements and functional diversity with the predominance of light-responsive (30%), development-related (20%), abiotic stress-responsive (14%), and hormone-responsive (12%) elements in StDREBs. Among them, two light-responsive elements (Box-4 and G-box) were predicted in 64 and 61 StDREB genes, respectively. Two development-related motifs (AAGAA-motif and as-1) were abundant in StDREB gene promoters. Most of the DREB genes contained one or more Myeloblastosis (MYB) and Myelocytometosis (MYC) elements associated with abiotic stress responses. Hormone-responsive element i.e. ABRE was found in 59 out of 66 StDREB genes, which implied their role in dehydration and salinity stress. Moreover, six proteins were chosen corresponding to A1-A6 StDREB subgroups for secondary structure analysis and three-dimensional protein modeling followed by model validation through PROCHECK server by Ramachandran Plot. The predicted models demonstrated >90% of the residues in the favorable region, which further ensured their reliability. The present study also anticipated pocket binding sites and disordered regions (DRs) to gain insights into the structural flexibility and functional annotation of StDREB proteins. The protein association network determined the interaction of six selected StDREB proteins with potato proteins encoded by other gene families such as MYB and NAC, suggesting their similar functional roles in biological and molecular pathways. Overall, our results provide fundamental information for future functional analysis to understand the precise molecular mechanisms of the DREB gene family in S. tuberosum.

scholarly journals Molecular Inverse Comorbidity between Alzheimer’s disease and Lung Cancer: new insights from Matrix Factorization

2019 ◽  
Author(s):  
Alessandro Greco ◽  
Jon Sanchez Valle ◽  
Vera Pancaldi ◽  
Anaïs Baudot ◽  
Emmanuel Barillot ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Matrix Factorization ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Biological Data ◽  
Biological Data Analysis ◽  
Specific Factors ◽  
Molecular Bases

AbstractMatrix Factorization (MF) is an established paradigm for large-scale biological data analysis with tremendous potential in computational biology.We here challenge MF in depicting the molecular bases of epidemiologically described Disease-Disease (DD) relationships. As use case, we focus on the inverse comorbidity association between Alzheimer’s disease (AD) and lung cancer (LC), described as a lower than expected probability of developing LC in AD patients. To the day, the molecular mechanisms underlying DD relationships remain poorly explained and their better characterization might offer unprecedented clinical opportunities.To this goal, we extend our previously designed MF-based framework for the molecular characterization of DD relationships. Considering AD-LC inverse comorbidity as a case study, we highlight multiple molecular mechanisms, among which the previously identified immune system and mitochondrial metabolism. We then discriminate mechanisms specific to LC from those shared with other cancers through a pancancer analysis. Additionally, new candidate molecular players, such as Estrogen Receptor (ER), CDH1 and HDAC, are pinpointed as factors that might underlie the inverse relationship, opening the way to new investigations. Finally, some lung cancer subtype-specific factors are also detected, suggesting the existence of heterogeneity across patients also in the context of inverse comorbidity.

scholarly journals Molecular mechanisms and clinical manifestations of rare genetic disorders associated with type I collagen

2019 ◽  
Vol 8 (2) ◽  
pp. 98-107 ◽  
Author(s):  
Yanqin Lu ◽  
Shie Zhang ◽  
Yanzhou Wang ◽  
Xiuzhi Ren ◽  
Jinxiang Han
Keyword(s):  
Molecular Mechanisms ◽  
Type I Collagen ◽  
Genetic Disorders ◽  
Clinical Manifestations ◽  
Type I

scholarly journals Activation of the complement system by pathogenic fungi.

1996 ◽  
Vol 9 (1) ◽  
pp. 34-46 ◽  
Author(s):  
T R Kozel
Keyword(s):  
Complement System ◽  
Host Resistance ◽  
Molecular Mechanisms ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Complement Cascade ◽  
Experimental Animals ◽  
Molecular Bases ◽  
The Complement System

Fungi have been studied as prototype activators of the complement cascade since the early 1900s. More recently, attention has focused on the role of the complement system in the pathogenesis of fungal infections. The interactions of Cryptococcus neoformans and Candida albicans with the complement system are the most widely characterized; however, all pathogenic fungi examined to date have the ability to initiate the complement cascade. The molecular mechanisms for initiation and regulation of the complement cascade differ from one fungus to another, most likely reflecting differences in the structure of the outer layers of the cell wall. The molecular bases for such differences remain to be identified. Studies of mycoses in experimental animals with induced or congenital deficiencies in the complement system demonstrate that complement is an important innate system for control of fungal infection. Contributions to host resistance include opsonization and generation of inflammatory mediators. Inflammation induced by chemotactic products of the complement system may contribute to the pathogenesis of some fungal infections.

scholarly journals Blues in the Brain and Beyond: Molecular Bases of Major Depressive Disorder and Relative Pharmacological and Non-Pharmacological Treatments

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1089 ◽  
Author(s):  
Elisabetta Maffioletti ◽  
Alessandra Minelli ◽  
Daniela Tardito ◽  
Massimo Gennarelli
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Molecular Mechanisms ◽  
Pharmacological Treatments ◽  
Major Depressive ◽  
Reciprocal Interactions ◽  
Evidence Based Treatments ◽  
Molecular Effects ◽  
Molecular Bases ◽  
The Brain

Despite the extensive research conducted in recent decades, the molecular mechanisms underlying major depressive disorder (MDD) and relative evidence-based treatments remain unclear. Various hypotheses have been successively proposed, involving different biological systems. This narrative review aims to critically illustrate the main pathogenic hypotheses of MDD, ranging from the historical ones based on the monoaminergic and neurotrophic theories, through the subsequent neurodevelopmental, glutamatergic, GABAergic, inflammatory/immune and endocrine explanations, until the most recent evidence postulating a role for fatty acids and the gut microbiota. Moreover, the molecular effects of established both pharmacological and non-pharmacological approaches for MDD are also reviewed. Overall, the existing literature indicates that the molecular mechanisms described in the context of these different hypotheses, rather than representing alternative ones to each other, are likely to contribute together, often with reciprocal interactions, to the development of MDD and to the effectiveness of treatments, and points at the need for further research efforts in this field.

The metabolite repair enzyme Nit1 is a dual-targeted amidase that disposes of damaged glutathione in Arabidopsis

2019 ◽  
Vol 476 (4) ◽  
pp. 683-697 ◽  
Author(s):  
Thomas D. Niehaus ◽  
Jenelle A. Patterson ◽  
Danny C. Alexander ◽  
Jakob S. Folz ◽  
Michal Pyc ◽  
...  
Keyword(s):  
In Vitro Transcription ◽  
Start Codon ◽  
Repair System ◽  
Leaf Extracts ◽  
Physiological Processes ◽  
Translation Start ◽  
Targeting Peptide ◽  
Cellular Compartments ◽  
Metabolite Repair

Abstract The tripeptide glutathione (GSH) is implicated in various crucial physiological processes including redox buffering and protection against heavy metal toxicity. GSH is abundant in plants, with reported intracellular concentrations typically in the 1–10 mM range. Various aminotransferases can inadvertently transaminate the amino group of the γ-glutamyl moiety of GSH to produce deaminated glutathione (dGSH), a metabolite damage product. It was recently reported that an amidase known as Nit1 participates in dGSH breakdown in mammals and yeast. Plants have a hitherto uncharacterized homolog of the Nit1 amidase. We show that recombinant Arabidopsis Nit1 (At4g08790) has high and specific amidase activity towards dGSH. Ablating the Arabidopsis Nit1 gene causes a massive accumulation of dGSH and other marked changes to the metabolome. All plant Nit1 sequences examined had predicted plastidial targeting peptides with a potential second start codon whose use would eliminate the targeting peptide. In vitro transcription/translation assays show that both potential translation start codons in Arabidopsis Nit1 were used and confocal microscopy of Nit1–GFP fusions in plant cells confirmed both cytoplasmic and plastidial localization. Furthermore, we show that Arabidopsis enzymes present in leaf extracts convert GSH to dGSH at a rate of 2.8 pmol min−1 mg−1 in the presence of glyoxalate as an amino acceptor. Our data demonstrate that plants have a dGSH repair system that is directed to at least two cellular compartments via the use of alternative translation start sites.

scholarly journals Clinical and Genetic Overview of Paroxysmal Movement Disorders and Episodic Ataxias

2020 ◽  
Vol 21 (10) ◽  
pp. 3603 ◽  
Author(s):  
Giacomo Garone ◽  
Alessandro Capuano ◽  
Lorena Travaglini ◽  
Federica Graziola ◽  
Fabrizia Stregapede ◽  
...  
Keyword(s):  
Movement Disorders ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Single Gene ◽  
Point Of View ◽  
Whole Exome ◽  
Genetic Features ◽  
Neurogenetic Disorders ◽  
Next Generation Sequencing Ngs ◽  
Molecular Bases

Paroxysmal movement disorders (PMDs) are rare neurological diseases typically manifesting with intermittent attacks of abnormal involuntary movements. Two main categories of PMDs are recognized based on the phenomenology: Paroxysmal dyskinesias (PxDs) are characterized by transient episodes hyperkinetic movement disorders, while attacks of cerebellar dysfunction are the hallmark of episodic ataxias (EAs). From an etiological point of view, both primary (genetic) and secondary (acquired) causes of PMDs are known. Recognition and diagnosis of PMDs is based on personal and familial medical history, physical examination, detailed reconstruction of ictal phenomenology, neuroimaging, and genetic analysis. Neurophysiological or laboratory tests are reserved for selected cases. Genetic knowledge of PMDs has been largely incremented by the advent of next generation sequencing (NGS) methodologies. The wide number of genes involved in the pathogenesis of PMDs reflects a high complexity of molecular bases of neurotransmission in cerebellar and basal ganglia circuits. In consideration of the broad genetic and phenotypic heterogeneity, a NGS approach by targeted panel for movement disorders, clinical or whole exome sequencing should be preferred, whenever possible, to a single gene approach, in order to increase diagnostic rate. This review is focused on clinical and genetic features of PMDs with the aim to (1) help clinicians to recognize, diagnose and treat patients with PMDs as well as to (2) provide an overview of genes and molecular mechanisms underlying these intriguing neurogenetic disorders.

scholarly journals Inducible molecular switches for the study of long-term potentiation

2003 ◽  
Vol 358 (1432) ◽  
pp. 797-804 ◽  
Author(s):  
Gaël Hédou ◽  
Isabelle M. Mansuy
Keyword(s):  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Knock Out ◽  
Technical Developments ◽  
Term Potentiation ◽  
Dependent Protein ◽  
Strength And Plasticity ◽  
Regulated Gene Expression ◽  
Molecular Bases

This article reviews technical and conceptual advances in unravelling the molecular bases of long-term potentiation (LTP), learning and memory using genetic approaches. We focus on studies aimed at testing a model suggesting that protein kinases and protein phosphatases balance each other to control synaptic strength and plasticity. We describe how gene ‘knock-out’ technology was initially exploited to disrupt the Ca 2+ /calmodulin-dependent protein kinase II α (CaMKII α ) gene and how refined knock-in techniques later allowed an analysis of the role of distinct phosphorylation sites in CaMKII. Further to gene recombination, regulated gene expression using the tetracycline-controlled transactivator and reverse tetracycline-controlled transactivator systems, a powerful new means for modulating the activity of specific molecules, has been applied to CaMKII α and the opposing protein phosphatase calcineurin. Together with electro-physiological and behavioural evaluation of the engineered mutant animals, these genetic methodologies have helped gain insight into the molecular mechanisms of plasticity and memory. Further technical developments are, however, awaited for an even higher level of finesse.

scholarly journals Identification of promoter elements responsible for the regulation of MDR1 from Candida albicans, a major facilitator transporter involved in azole resistance

Microbiology ◽  
2006 ◽  
Vol 152 (12) ◽  
pp. 3701-3722 ◽  
Author(s):  
Bénédicte Rognon ◽  
Zuzana Kozovska ◽  
Alix T. Coste ◽  
Giacomo Pardini ◽  
Dominique Sanglard
Keyword(s):  
Candida Albicans ◽  
Molecular Mechanisms ◽  
Specific Binding ◽  
Perfect Match ◽  
Regulatory Elements ◽  
High Expression ◽  
Start Codon ◽  
Bzip Transcription Factor ◽  
Reporter System ◽  
Transcriptional Responses

Upregulation of the MDR1 (multidrug resistance 1) gene is involved in the development of resistance to antifungal agents in clinical isolates of the pathogen Candida albicans. To better understand the molecular mechanisms underlying the phenomenon, the cis-acting regulatory elements present in the MDR1 promoter were characterized using a β-galactosidase reporter system. In an azole-susceptible strain, transcription of this reporter is transiently upregulated in response to either benomyl or H2O2, whereas its expression is constitutively high in an azole-resistant strain (FR2). Two cis-acting regulatory elements within the MDR1 promoter were identified that are necessary and sufficient to confer the same transcriptional responses on a heterologous promoter (CDR2). One, a benomyl response element (BRE), is situated at position −296 to −260 with respect to the ATG start codon. It is required for benomyl-dependent MDR1 upregulation and is also necessary for constitutive high expression of MDR1. A second element, termed H 2O2 response element (HRE), is situated at position −561 to −520. The HRE is required for H2O2-dependent MDR1 upregulation, but dispensable for constitutive high expression. Two potential binding sites (TTAG/CTAA) for the bZip transcription factor Cap1p (Candida AP-1 protein) lie within the HRE. Moreover, inactivation of CAP1 abolished the transient response to H2O2. Cap1p, which has been previously implicated in cellular responses to oxidative stress, may thus play a trans-acting and positive regulatory role in the H2O2-dependent transcription of MDR1. A minimal BRE (−290 to −273) that is sufficient to detect in vitro sequence-specific binding of protein complexes in crude extracts prepared from C. albicans was also defined. Interestingly, the sequence includes a perfect match to the consensus binding sequence of Mcm1p, raising the possibility that MDR1 may be a direct target of this MADS box transcriptional activator. In conclusion, while the identity of the trans-acting factors that bind to the BRE and HRE remains to be confirmed, the tools developed during this characterization of the cis-acting elements of the MDR1 promoter should now serve to elucidate the nature of the components that modulate its activity.

Sign in / Sign up

Export Citation Format

Share Document