Epigenetic regulation of kallikrein-related peptidases: there is a whole new world out there

2012 ◽  
Vol 393 (5) ◽  
pp. 319-330 ◽  
Author(s):  
Maria D. Pasic ◽  
Ekaterina Olkhov ◽  
Bharati Bapat ◽  
George M. Yousef
Keyword(s):  
Epigenetic Regulation ◽  
Small Rnas ◽  
Experimental Validation ◽  
Target Prediction ◽  
Transcriptional Level ◽  
Potential Contribution ◽  
Epigenetic Changes ◽  
Disease Biomarkers ◽  
Essential Step ◽  
Wide Range

AbstractThe human kallikreins are a cluster of 15 kallikreins and kallikrein-related peptidases (KLKs). Evidence shows the involvement of KLKs in a wide range of pathophysiological processes, and underscores their potential contribution to cancer, skin and neurodegenerative disorders. The control ofKLKexpression is not fully elucidated. Understanding the mechanisms controllingKLKexpression is an essential step towards exploring the pathogenesis of several diseases and the use of KLKs as disease biomarkers and/or therapeutic targets. Recently, epigenetic changes (including methylation, histone modification and microRNAs [miRNAs]) have drawn attention as a new dimension for controllingKLKexpression. Reports showed the effect of methylation on the expression ofKLKgenes. This was also shown to have potential utility as a prognostic marker in cancer. miRNAs are small RNAs that control the expression of their targets at the post-transcriptional level. Target prediction showed that KLKs are potential targets of miRNAs that are dysregulated in tumors, including prostate, kidney and ovarian cancers, with downstream effect on tumor proliferation. Experimental validation remains an essential step to confirm the KLK-miRNA interaction. Epigenetic regulation of KLKs holds promise for an array of therapeutic applications in many diseases including cancer.

scholarly journals cis-Encoded Small RNAs, a Conserved Mechanism for Repression of Polysaccharide Utilization in Bacteroides

2016 ◽  
Vol 198 (18) ◽  
pp. 2410-2418 ◽  
Author(s):  
Yanlu Cao ◽  
Konrad U. Förstner ◽  
Jörg Vogel ◽  
C. Jeffrey Smith
Keyword(s):  
Small Rnas ◽  
Nutritive Value ◽  
Hierarchical Control ◽  
Gene Clusters ◽  
Regulatory Control ◽  
Energy Sources ◽  
Transcriptional Level ◽  
Human Gut ◽  
Content Type ◽  
Wide Range

ABSTRACTBacteroidesis a major component of the human gut microbiota which has a broad impact on the development and physiology of its host and a potential role in a wide range of disease syndromes. The predominance of this genus is due in large part to expansion of paralogous gene clusters, termedpolysaccharideutilizationloci (PULs), dedicated to the uptake and catabolism of host-derived and dietary polysaccharides. The nutritive value and availability of polysaccharides in the gut vary greatly; thus, their utilization is hierarchical and strictly controlled. A typical PUL includes regulatory genes that induce PUL expression in response to the presence of specific glycan substrates. However, the existence of additional regulatory mechanisms has been predicted to explain phenomena such as hierarchical control and catabolite repression. In this report, a previously unknown layer of regulatory control was discovered inBacteroides fragilis. Exploratory transcriptome sequencing (RNA-seq) analysis revealed the presence ofcis-encoded antisense small RNAs (sRNAs) associated with 15 (30%) of theB. fragilisPULs. A model system using the Don (degradation of N-glycans) PUL showed that thedonSsRNA negatively regulated Don expression at the transcriptional level, resulting in a decrease in N-glycan utilization. Additional studies performed with otherBacteroidesspecies indicated that this regulatory mechanism is highly conserved and, interestingly, that the regulated PULs appear to be closely linked to the utilization of host-derived glycans rather than dietary plant polysaccharides. The findings described here demonstrate a global control mechanism underlying known PUL regulatory circuits and provide insight into regulation ofBacteroidesphysiology.IMPORTANCEThe human gut is colonized by a dense microbiota which is essential to the health and normal development of the host. A key to gut homeostasis is the preservation of a stable, diverse microbiota.Bacteroidesis a dominant genus in the gut, and the ability ofBacteroidesspecies to efficiently compete for a wide range of glycan energy sources is a crucial advantage for colonization. Glycan utilization is mediated by a large number ofpolysaccharideutilizationloci (PULs) which are regulated by substrate induction. In this report, a novel family of antisense sRNAs is described whose members repress gene expression in a distinct subset of PULs. This repression downregulates PUL expression in the presence of energy sources that are more readily utilized such as glucose, thereby allowing efficient glycan utilization.

scholarly journals Role of Physical Exercise and Nutraceuticals in Modulating Molecular Pathways of Osteoarthritis

2021 ◽  
Vol 22 (11) ◽  
pp. 5722
Author(s):  
Alessandro de Sire ◽  
Nicola Marotta ◽  
Cinzia Marinaro ◽  
Claudio Curci ◽  
Marco Invernizzi ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Synergistic Effects ◽  
Molecular Pathways ◽  
Epigenetic Changes ◽  
Pathological Features ◽  
Oxidative Signaling ◽  
Cartilage Extracellular Matrix ◽  
Wide Range ◽  
Comprehensive Picture

Osteoarthritis (OA) is a painful and disabling disease that affects millions of patients. Its etiology is largely unknown, but it is most likely multifactorial. OA pathogenesis involves the catabolism of the cartilage extracellular matrix and is supported by inflammatory and oxidative signaling pathways and marked epigenetic changes. To delay OA progression, a wide range of exercise programs and naturally derived compounds have been suggested. This literature review aims to analyze the main signaling pathways and the evidence about the synergistic effects of these two interventions to counter OA. The converging nutrigenomic and physiogenomic intervention could slow down and reduce the complex pathological features of OA. This review provides a comprehensive picture of a possible signaling approach for targeting OA molecular pathways, initiation, and progression.

Design Optimization of RML Glove for Improved Grasp Performance

2018 ◽  
Author(s):  
Teja Vanteddu ◽  
Bijo Sebastian ◽  
Pinhas Ben-Tzvi
Keyword(s):  
Design Optimization ◽  
Daily Living ◽  
Experimental Validation ◽  
Large Diameter ◽  
Future Research ◽  
Linkage Mechanism ◽  
Design Variables ◽  
Wide Range ◽  
Optimal Values ◽  
Optimal Set

This paper describes the design optimization of the RML Glove in order to improve its grasp performance. The existing design is limited to grasping objects of large diameter (> 110mm) due to its inability in attaining high bending angles. For an exoskeleton glove to be effective in its use as an assistive and rehabilitation device for Activities of Daily Living (ADL), it should be able to interact with objects over a wide range of sizes. Motivated by these limitations, the kinematics of the existing linkage mechanism was analyzed in detail and the design variables were identified. Two different cost functions were formulated and compared in their ability to yield optimal values for the design variables. The optimal set of design variables was chosen based on the grasp angles achieved and the resulting mechanism was simulated in CAD for feasibility testing. An exoskeleton mechanism corresponding to the index finger was manufactured with the chosen design variables and detailed experimental validation was performed to illustrate the improvement in grasp performance over the existing design. The paper ends with a summary of the experimental results and directions for future research.

scholarly journals Epigenomics of Plant’s Responses to Environmental Stress

2017 ◽  
Author(s):  
Suresh Kumar
Keyword(s):  
Gene Expression ◽  
Nuclear Dna ◽  
Environmental Stresses ◽  
Transcriptional Level ◽  
Epigenetic Changes ◽  
Post Translational Modifications ◽  
Genome Wide ◽  
A Cell ◽  
Non Coding Rnas ◽  
Function Activity

Genome-wide epigenetic changes in plants are being reported during the development and environmental stresses, which are often correlated with gene expression at the transcriptional level. Sum total of the biochemical changes in nuclear DNA, post-translational modifications in histone proteins and variations in the biogenesis of non-coding RNAs in a cell is known as epigenome. These changes are often responsible for variation in expression of the gene without any change in the underlying nucleotide sequence. The changes might also cause variation in chromatin structure resulting into the changes in function/activity of the genome. The epigenomic changes are dynamic with respect to the endogenous and/or environmental stimuli which affect phenotypic plasticity of the organism. Both, the epigenetic changes and variation in gene expression might return to the pre-stress state soon after withdrawal of the stress. However, a part of the epigenetic changes may be retained which is reported to play role in acclimatization, adaptation as well as in the evolutionary processes. Understanding epigenome-engineering for improved stress tolerance in plants has become essential for better utilization of the genetic factors. This review delineates the importance of epigenomics towards possible improvement of plant’s responses to environmental stresses for climate resilient agriculture.

scholarly journals Comprehensive Overview and Assessment of microRNA Target Prediction Tools in Homo sapiens and Drosophila melanogaster

2019 ◽  
Vol 14 (5) ◽  
pp. 432-445 ◽  
Author(s):  
Muniba Faiza ◽  
Khushnuma Tanveer ◽  
Saman Fatihi ◽  
Yonghua Wang ◽  
Khalid Raza
Keyword(s):  
Drosophila Melanogaster ◽  
Mirna Target ◽  
Homo Sapiens ◽  
Target Prediction ◽  
Computational Prediction ◽  
Transcriptional Level ◽  
Mirna Target Prediction ◽  
Microrna Target ◽  
Prediction Tools ◽  
Mirna Targets

Background: MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression at the post-transcriptional level through complementary base pairing with the target mRNA, leading to mRNA degradation and blocking translation process. Many dysfunctions of these small regulatory molecules have been linked to the development and progression of several diseases. Therefore, it is necessary to reliably predict potential miRNA targets. Objective: A large number of computational prediction tools have been developed which provide a faster way to find putative miRNA targets, but at the same time, their results are often inconsistent. Hence, finding a reliable, functional miRNA target is still a challenging task. Also, each tool is equipped with different algorithms, and it is difficult for the biologists to know which tool is the best choice for their study. Methods: We analyzed eleven miRNA target predictors on Drosophila melanogaster and Homo sapiens by applying significant empirical methods to evaluate and assess their accuracy and performance using experimentally validated high confident mature miRNAs and their targets. In addition, this paper also describes miRNA target prediction algorithms, and discusses common features of frequently used target prediction tools. Results: The results show that MicroT, microRNA and CoMir are the best performing tool on Drosopihla melanogaster; while TargetScan and miRmap perform well for Homo sapiens. The predicted results of each tool were combined in order to improve the performance in both the datasets, but any significant improvement is not observed in terms of true positives. Conclusion: The currently available miRNA target prediction tools greatly suffer from a large number of false positives. Therefore, computational prediction of significant targets with high statistical confidence is still an open challenge.

scholarly journals sRNA Target Prediction Organizing Tool (SPOT) Integrates Computational and Experimental Data To Facilitate Functional Characterization of Bacterial Small RNAs

mSphere ◽  
2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Alisa M. King ◽  
Carin K. Vanderpool ◽  
Patrick H. Degnan
Keyword(s):  
Experimental Data ◽  
Stress Responses ◽  
Small Rnas ◽  
Metabolic Regulation ◽  
Functional Characterization ◽  
Target Prediction ◽  
Structure Stability ◽  
Accurate Identification ◽  
Mrna Targets

Small RNAs (sRNAs) regulate gene expression in diverse bacteria by interacting with mRNAs to change their structure, stability, or translation. Hundreds of sRNAs have been identified in bacteria, but characterization of their regulatory functions is limited by difficulty with sensitive and accurate identification of mRNA targets. Thus, new robust methods of bacterial sRNA target identification are in demand. Here, we describe our small RNA target prediction organizing tool (SPOT), which streamlines the process of sRNA target prediction by providing a single pipeline that combines available computational prediction tools with customizable results filtering based on experimental data. SPOT allows the user to rapidly produce a prioritized list of predicted sRNA-target mRNA interactions that serves as a basis for further experimental characterization. This tool will facilitate elucidation of sRNA regulons in bacteria, allowing new discoveries regarding the roles of sRNAs in bacterial stress responses and metabolic regulation.

scholarly journals Policies for promoting diaspora investment in countries of origin

2020 ◽  
Vol 10 (1) ◽  
pp. 104-116
Author(s):  
Sanja Franc ◽  
Marina Perić Kasel ◽  
Ivona Škreblin Kirbiš
Keyword(s):  
Developing Countries ◽  
Job Creation ◽  
National Development ◽  
Business Development ◽  
Financial Capital ◽  
Potential Contribution ◽  
Wide Range ◽  
Policy Measures ◽  
Transnational Entrepreneurship ◽  
Diaspora Engagement

Investments from the diaspora and transnational entrepreneurship represent significant areas for potential contribution to national development. Due to the fact that diaspora members have the ability to connect with a wide range of potential partners and supporters in both their countries of origin and countries of residence, and thus create opportunities for investment, trade and outsourcing, developing countries which seek human and financial capital should put more focus on facilitation and promotion measures for collaboration with the diaspora. The main aim of this paper is to define and discuss most commonly used policy measures for promoting diaspora investments and transnational entrepreneurship in developing countries and giving recommendations for diaspora engagement. The analysis indicates that policy measures and the degree to which countries have begun to engage their diaspora vary, while most of them still miss an adequate institutional framework for promoting transnational networks which can be an important channel for fostering business development, job creation and innovation.

scholarly journals Plugging Small RNAs into the Network

mSystems ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Lars Barquist
Keyword(s):  
Small Rnas ◽  
Posttranscriptional Regulation ◽  
Network Inference ◽  
Functional Characterization ◽  
The State ◽  
Diverse Range ◽  
Regulatory Interactions ◽  
Link Type ◽  
Wide Range

ABSTRACT Small RNAs (sRNAs) have been discovered in every bacterium examined and have been shown to play important roles in the regulation of a diverse range of behaviors, from metabolism to infection. However, despite a wide range of available techniques for discovering and validating sRNA regulatory interactions, only a minority of these molecules have been well characterized. In part, this is due to the nature of posttranscriptional regulation: the activity of an sRNA depends on the state of the transcriptome as a whole, so characterization is best carried out under the conditions in which it is naturally active. In this issue of mSystems, Arrieta-Ortiz and colleagues (M. L. Arrieta-Ortiz, C. Hafemeister, B. Shuster, N. S. Baliga, et al., mSystems 5:e00057-20, 2020, https://doi.org/10.1128/mSystems.00057-20) present a network inference approach based on estimating sRNA activity across transcriptomic compendia. This shows promise not only for identifying new sRNA regulatory interactions but also for pinpointing the conditions in which these interactions occur, providing a new avenue toward functional characterization of sRNAs.

scholarly journals Posttranscriptional mechanisms involving microRNA-27a and b contribute to fast-specific and glucocorticoid-mediated myostatin expression in skeletal muscle

2011 ◽  
Vol 300 (1) ◽  
pp. C124-C137 ◽  
Author(s):  
David L. Allen ◽  
Amanda S. Loh
Keyword(s):  
Receptor Expression ◽  
Luciferase Reporter ◽  
Potential Contribution ◽  
Recognition Sequence ◽  
Luciferase Reporter Construct ◽  
Glucocorticoid Treatment ◽  
Wide Range ◽  
Expression Construct

Expression of the antigrowth factor myostatin (MSTN) differs between fast and slow skeletal muscles and is increased in nearly every form of muscle atrophy, but the contribution of transcriptional vs. posttranscriptional mechanisms to its differing expression in these states has not been defined. We show here that levels of mature MSTN mRNA were sixfold greater in fast vs. slow muscle and were increased twofold in fast muscle in response to dexamethasone (Dex) injection in vivo and in C2C12 myotubes following Dex treatment in vitro, but that levels of MSTN pre-mRNA, a readout of transcription, only minimally and nonsignificantly differed in these states. Moreover, Dex treatment with or without cotransfection with a glucocorticoid receptor expression construct had only modest effects on mouse MSTN promoter activity in C2C12 myotubes. We therefore explored the potential contribution of posttranscriptional mechanisms, and the role of the microRNAs miR-27a and b in particular, on MSTN expression. The MSTN 3′-untranslated region (UTR) contains a putative recognition sequence for miR-27a and b that is conserved across a wide range of vertebrate species. Cotransfection of a MSTN 3′-UTR-luciferase construct with a miR-27b expression construct significantly attenuated by approximately half while mutation of the miR-27 recognition sequence significantly increased by approximately twofold the activity of a MSTN 3′-UTR construct and decreased mRNA degradation of a luciferase reporter construct in C2C12 myotubes. Expression of miR-27a and b was almost sixfold greater in slow-twitch than in fast-twitch muscle in vivo, and miR-27a expression was significantly decreased by nearly half by glucocorticoid treatment in vitro. Finally, the miR-27a and b promoters were activated by cotransfection with the slow-specific signaling molecules calcineurin and peroxisome proliferator-activated receptor-γ coactivator-1α. The present data represent the first demonstration that posttranscriptional mechanisms involving miR-27a and b may contribute to fast-specific and glucocorticoid-dependent myostatin expression in muscle.

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