Shaping the nebulous enhancer in the era of high-throughput assays and genome editing

2019 ◽  
Vol 21 (3) ◽  
pp. 836-850
Author(s):  
Edwin Yu-Kiu Ho ◽  
Qin Cao ◽  
Mengting Gu ◽  
Ricky Wai-Lun Chan ◽  
Qiong Wu ◽  
...  
Keyword(s):  
Genome Editing ◽  
High Throughput ◽  
Wide Spectrum ◽  
Data Interpretation ◽  
Future Studies ◽  
Transcriptional Enhancers ◽  
The Past ◽  
Genome Wide ◽  
Gray Areas ◽  
Practical Implications

Abstract Since the 1st discovery of transcriptional enhancers in 1981, their textbook definition has remained largely unchanged in the past 37 years. With the emergence of high-throughput assays and genome editing, which are switching the paradigm from bottom-up discovery and testing of individual enhancers to top-down profiling of enhancer activities genome-wide, it has become increasingly evidenced that this classical definition has left substantial gray areas in different aspects. Here we survey a representative set of recent research articles and report the definitions of enhancers they have adopted. The results reveal that a wide spectrum of definitions is used usually without the definition stated explicitly, which could lead to difficulties in data interpretation and downstream analyses. Based on these findings, we discuss the practical implications and suggestions for future studies.

scholarly journals DrosophilaModels of Tauopathies: What Have We Learned?

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Marc Gistelinck ◽  
Jean-Charles Lambert ◽  
Patrick Callaerts ◽  
Bart Dermaut ◽  
Pierre Dourlen
Keyword(s):  
Frontotemporal Dementia ◽  
High Throughput ◽  
Neurodegenerative Disorders ◽  
Genetic Model ◽  
Model Organism ◽  
Molecular Pathways ◽  
Protein Tau ◽  
Microtubule Associated Protein Tau ◽  
The Past ◽  
Genome Wide

Aggregates of the microtubule-associated protein Tau are neuropathological hallmark lesions in Alzheimer's disease (AD) and related primary tauopathies. In addition, Tau is genetically implicated in a number of human neurodegenerative disorders including frontotemporal dementia (FTD) and Parkinson's disease (PD). The exact mechanism by which Tau exerts its neurotoxicity is incompletely understood. Here, we give an overview of how studies using the genetic model organismDrosophilaover the past decade have contributed to the molecular understanding of Tau neurotoxicity. We compare the different available readouts for Tau neurotoxicity in flies and review the molecular pathways in which Tau has been implicated. Finally, we emphasize that the integration of genome-wide approaches in human or mice with high-throughput genetic validation inDrosophilais a fruitful approach.

The evolution of the customer delight construct

2018 ◽  
Vol 30 (1) ◽  
pp. 57-75 ◽  
Author(s):  
Edwin N. Torres ◽  
Giulio Ronzoni
Keyword(s):  
Past Research ◽  
Service Industries ◽  
Future Research ◽  
Content Type ◽  
Future Studies ◽  
Human Needs ◽  
The Past ◽  
New Instrument ◽  
Customer Delight ◽  
Practical Implications

Purpose The present research aims to summarize the literature on customer delight, identify trends and debates, create an instrument to measure delight and propose directions for future research. Design/methodology/approach A comprehensive review of the literature has been undertaken. Flowing from a variety of conceptual, qualitative and quantitative articles, operational measures have been identified, and an instrument to measure customer delight has been proposed. Findings Past research on customer delight identified various emotions that trigger delight, as well as human needs, traits and behaviors associated with delightful experiences, and features of the service experience commonly related to delight. On the basis of these findings, the researchers have developed an instrument to measure customer delight. Practical implications The proposed instrument enables managers to measure customer delight in various service settings. Measuring and attaining higher levels of customer delight can help generate greater loyalty as compared to customer satisfaction. Originality/value The authors unify the conceptualization and measurement of customer delight and create a new instrument to measure the construct. Similarities and debates in the past research are identified, and directions for the future of customer delight are presented. Future studies can further test and validate the presented instrument in various service industries.

scholarly journals Hepatitis-C (HCV)-Related Social Stigma; Development of a Scale

2016 ◽  
Vol 04 (01) ◽  
pp. 01-08
Author(s):  
Ayesha Noor ◽  
Keyword(s):  
Hepatitis C ◽  
Social Stigma ◽  
Hiv Stigma ◽  
Factor Solution ◽  
Future Studies ◽  
The Past ◽  
Related Stigma ◽  
Stigma Development ◽  
Practical Implications ◽  
Item Scale

In the past two decades, there has been a substantial research on disease related stigma especially the HIV stigma. However, only a few studies address the issue of HCV related social stigma. Through this study a scale was developed to measure HCV related social stigma. The scale was developed using literature review and interview with 26 individuals divided in five different groups. The nineteen item scale developed after this activity was distributed among 221 respondents. Results indicate that the scale shows robust psychometric properties with good alpha value having a four factor solution. The results are discussed with theoretical and practical implications that how this scale will facilitate measurement of HCV related social stigma in future studies.

scholarly journals The Comprehensive “Omics” Approach from Metabolomics to Advanced Omics for Development of Immune Checkpoint Inhibitors: Potential Strategies for Next Generation of Cancer Immunotherapy

2021 ◽  
Vol 22 (13) ◽  
pp. 6932
Author(s):  
Sang Jun Yoon ◽  
Chae Bin Lee ◽  
Soon Uk Chae ◽  
Seong Jun Jo ◽  
Soo Kyung Bae
Keyword(s):  
High Throughput ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Drug Response ◽  
Checkpoint Inhibitors ◽  
Mechanisms Of Action ◽  
Future Studies ◽  
The Past ◽  
Novel Approaches ◽  
Cancer Immunotherapies

In the past decade, immunotherapies have been emerging as an effective way to treat cancer. Among several categories of immunotherapies, immune checkpoint inhibitors (ICIs) are the most well-known and widely used options for cancer treatment. Although several studies continue, this treatment option has yet to be developed into a precise application in the clinical setting. Recently, omics as a high-throughput technique for understanding the genome, transcriptome, proteome, and metabolome has revolutionized medical research and led to integrative interpretation to advance our understanding of biological systems. Advanced omics techniques, such as multi-omics, single-cell omics, and typical omics approaches, have been adopted to investigate various cancer immunotherapies. In this review, we highlight metabolomic studies regarding the development of ICIs involved in the discovery of targets or mechanisms of action and assessment of clinical outcomes, including drug response and resistance and propose biomarkers. Furthermore, we also discuss the genomics, proteomics, and advanced omics studies providing insights and comprehensive or novel approaches for ICI development. The overview of ICI studies suggests potential strategies for the development of other cancer immunotherapies using omics techniques in future studies.

Impact of microRNAs on molecular epidemiology

2011 ◽  
Vol 152 (16) ◽  
pp. 633-641 ◽  
Author(s):  
Katalin Gőcze ◽  
Katalin Gombos ◽  
Gábor Pajkos ◽  
Ingrid Magda ◽  
Ágoston Ember ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Cancer Research ◽  
Molecular Epidemiology ◽  
Wide Spectrum ◽  
Translation Regulation ◽  
Rna Sequences ◽  
Serum Mirna ◽  
The Past ◽  
Non Coding Rna ◽  
Free Serum

Cancer research concerning short non-coding RNA sequences and functionally linked to RNA interference (RNAi) have reached explosive breakthrough in the past decade. Molecular technology applies microRNA in extremely wide spectrum from molecular tumor prediction, diagnostics, progression monitoring and prevention. Functional analysis of tissue miRNA and cell-free serum miRNA in posttranscription and translation regulation innovated and restructured the knowledge on the field. This review focuses on molecular epidemiology and primary prevention aspects of the small non-coding RNA sequences. Orv. Hetil., 2011, 152, 633–641.

The Medicinal Chemistry of Therapeutic Peptides: Recent Developments in Synthesis and Design Optimizations

2019 ◽  
Vol 26 (13) ◽  
pp. 2330-2355 ◽  
Author(s):  
Anutthaman Parthasarathy ◽  
Sasikala K. Anandamma ◽  
Karunakaran A. Kalesh
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Therapeutic Potential ◽  
The Past ◽  
Recombinant Production ◽  
Tremendous Progress ◽  
Recent Developments ◽  
Therapeutic Peptides ◽  
Development Processes ◽  
Delivery Strategies

Peptide therapeutics has made tremendous progress in the past decade. Many of the inherent weaknesses of peptides which hampered their development as therapeutics are now more or less effectively tackled with recent scientific and technological advancements in integrated drug discovery settings. These include recent developments in synthetic organic chemistry, high-throughput recombinant production strategies, highresolution analytical methods, high-throughput screening options, ingenious drug delivery strategies and novel formulation preparations. Here, we will briefly describe the key methodologies and strategies used in the therapeutic peptide development processes with selected examples of the most recent developments in the field. The aim of this review is to highlight the viable options a medicinal chemist may consider in order to improve a specific pharmacological property of interest in a peptide lead entity and thereby rationally assess the therapeutic potential this class of molecules possesses while they are traditionally (and incorrectly) considered ‘undruggable’.

Recent Advances in Therapeutic Applications of Bisbenzimidazoles

2020 ◽  
Vol 16 (4) ◽  
pp. 454-486 ◽  
Author(s):  
Smita Verma ◽  
Vishnuvardh Ravichandiran ◽  
Nihar Ranjan ◽  
Swaran J.S. Flora
Keyword(s):  
Heterocyclic Compounds ◽  
Wide Spectrum ◽  
Dna Recognition ◽  
Present Review ◽  
Pharmacological Activities ◽  
Structural Motifs ◽  
Therapeutic Applications ◽  
The Past ◽  
Recent Advances

Nitrogen-containing heterocycles are one of the most common structural motifs in approximately 80% of the marketed drugs. Of these, benzimidazoles analogues are known to elicit a wide spectrum of pharmaceutical activities such as anticancer, antibacterial, antiparasitic, antiviral, antifungal as well as chemosensor effect. Based on the benzimidazole core fused heterocyclic compounds, crescent-shaped bisbenzimidazoles were developed which provided an early breakthrough in the sequence-specific DNA recognition. Over the years, a number of functional variations in the bisbenzimidazole core have led to the emergence of their unique properties and established them as versatile ligands against several classes of pathogens. The present review provides an overview of diverse pharmacological activities of the bisbenzimidazole analogues in the past decade with a brief account of its development through the years.

Cucurbitacins as Anticancer Agents: A Patent Review

2019 ◽  
Vol 14 (2) ◽  
pp. 133-143 ◽  
Author(s):  
Hidayat Hussain ◽  
Ivan R. Green ◽  
Muhammad Saleem ◽  
Khanzadi F. Khattak ◽  
Muhammad Irshad ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Wide Spectrum ◽  
Biological Effects ◽  
Therapeutic Effects ◽  
Cytotoxic Effects ◽  
Natural Sources ◽  
Oh Groups ◽  
Drug Candidates ◽  
The Past ◽  
Wide Range

Background: Cucurbitacins belong to a group of tetracyclic triterpenoids that display a wide range of biological effects. In the past, numerous cucurbitacins have been isolated from natural sources and many active compounds have been synthesized using the privileged scaffold in order to enhance its cytotoxic effects. Objective: his review covers patents on the therapeutic effects of natural cucurbitacins and their synthetic analogs published during the past decade. By far, the majority of patents published are related to cancer and Structure-Activity Relationships (SAR) of these compounds are included to lend gravitas to this important class of natural products. Methods: The date about the published patents was downloaded via online open access patent databases. Results: Cucurbitacins display significant cytotoxic properties, in particular cucurbitacins B and D which possess very potent effects towards a number of cancer cells. Numerous cucurbitacins isolated from natural sources have been derivatized through chemical modification at the C(2)-OH and C(25)- OH groups. Most importantly, an acyl ester of the C(25)-OH and, iso-propyl, n-propyl and ethyl ether groups of the C(2)-OH demonstrated the most increased cytotoxic activity. Conclusion: The significant cytotoxic effects of natural and semi-synthetic cucurbitacins make them attractive as new drug candidates. Moreover, cucurbitacins have the capability to form conjugates with other anticancer drugs which will synergistically enhance their anticancer effects. The authors believe that in order to get lead compounds, there should be a greater focus on the synthesis of homodimers, heterodimers, and halo derivatives of cucurbitacins. In the opinion of the authors the analysis of the published patents on the cucurbitacins indicates that these compounds can be developed into a regimen to treat a wide spectrum of cancers.

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