• Title/Summary/Keyword: gene discovery

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The Pleiotropic Face of CREB Family Transcription Factors

  • Md. Arifur Rahman Chowdhury;Jungeun An;Sangyun Jeong
    • Molecules and Cells
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    • v.46 no.7
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    • pp.399-413
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    • 2023
  • cAMP responsive element-binding protein (CREB) is one of the most intensively studied phosphorylation-dependent transcription factors that provide evolutionarily conserved mechanisms of differential gene expression in vertebrates and invertebrates. Many cellular protein kinases that function downstream of distinct cell surface receptors are responsible for the activation of CREB. Upon functional dimerization of the activated CREB to cis-acting cAMP responsive elements within the promoters of target genes, it facilitates signal-dependent gene expression. From the discovery of CREB, which is ubiquitously expressed, it has been proven to be involved in a variety of cellular processes that include cell proliferation, adaptation, survival, differentiation, and physiology, through the control of target gene expression. In this review, we highlight the essential roles of CREB proteins in the nervous system, the immune system, cancer development, hepatic physiology, and cardiovascular function and further discuss a wide range of CREB-associated diseases and molecular mechanisms underlying the pathogenesis of these diseases.

Monitoring antimalarial drug-resistance markers in Somalia

  • Abdifatah Abdullahi Jalei;Kesara Na-Bangchang;Phunuch Muhamad;Wanna Chaijaroenkul
    • Parasites, Hosts and Diseases
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    • v.61 no.1
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    • pp.78-83
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    • 2023
  • The use of an effective antimalarial drug is the cornerstone of malaria control. However, the development and spread of resistant Plasmodium falciparum strains have placed the global eradication of malaria in serious jeopardy. Molecular marker analysis constitutes the hallmark of the monitoring of Plasmodium drug-resistance. This study included 96 P. falciparum PCR-positive samples from southern Somalia. The P. falciparum chloroquine resistance transporter gene had high frequencies of K76T, A220S, Q271E, N326S, and R371I point mutations. The N86Y and Y184F mutant alleles of the P. falciparum multidrug resistance 1 gene were present in 84.7 and 62.4% of the isolates, respectively. No mutation was found in the P. falciparum Kelch-13 gene. This study revealed that chloroquine resistance markers are present at high frequencies, while the parasite remains sensitive to artemisinin (ART). The continuous monitoring of ART-resistant markers and in vitro susceptibility testing are strongly recommended to track resistant strains in real time.

Animal Models for the IGF-1 Signal System in Longevity (장수와 관련된 IGF-1 신호 시스템을 연구하기 위한 동물 모델)

  • Kwak, Inseok
    • Journal of Life Science
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    • v.22 no.10
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    • pp.1428-1433
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    • 2012
  • Longevity is an exciting but difficult subject to study because it is determined by complex processes that require the coordinated action of several genetic factors as well as physiological and environmental influences. Genetic approaches have been applied to animal models to identify the molecular mechanism responsible for longevity. Several experimental model organisms obtained over the last decades suggest that the complete deletion of a single gene by gene targeting has proven to be an invaluable tool for the discovery of the mechanisms underlying longevity. The first discovery of long-lived mutants came from Caenorhabditis elegans research, which identified the insulin/IGF-1 pathway as responsible for longevity in this worm. IGF-1 is a multifunctional polypeptide that has sequence similarity to insulin and is involved in normal growth and development of cells. Several factors in the IGF-1 system have since been studied by gene targeting in the control of longevity in lower species, including nematode and fruit fly. In addition, significant progress has been made using mice models to extend the lifespan by targeted mutations that interfere with growth hormone/IGF-1 and IGF-1 signaling cascades. A recent finding that IGF-1 is involved in aging in mice was achieved by using liver-specific knockout mutant mice, and this clearly demonstrated that the IGF-1 signal pathway can extend the lifespan in both invertebrates and vertebrate models. Although the underlying molecular mechanisms for the control of longevity are not fully understood, it is widely accepted that reduced IGF-1 signaling plays an important role in the control of aging and longevity. Several genes involved in the IGF-1 signaling system are reviewed in relation to longevity in genetically modified mice models.

Dendritic Cell-Mediated Mechanisms Triggered by LT-IIa-B5, a Mucosal Adjuvant Derived from a Type II Heat-Labile Enterotoxin of Escherichia coli

  • Lee, Chang Hoon;Hajishengallis, George;Connell, Terry D.
    • Journal of Microbiology and Biotechnology
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    • v.27 no.4
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    • pp.709-717
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    • 2017
  • Mucosal tissues are the initial site through which most pathogens invade. As such, vaccines and adjuvants that modulate mucosal immune functions have emerged as important agents for disease prevention. Herein, we investigated the immunomodulatory mechanisms of the B subunit of Escherichia coli heat-labile enterotoxin type IIa ($LT-IIa-B_5$), a potent non-toxic mucosal adjuvant. Alternations in gene expression in response to $LT-IIa-B_5$ were identified using a genome-wide transcriptional microarray that focused on dendritic cells (DC), a type of cell that broadly orchestrates adaptive and innate immune responses. We found that $LT-IIa-B_5$ enhanced the homing capacity of DC into the lymph nodes and selectively regulated transcription of pro-inflammatory cytokines, chemokines, and cytokine receptors. These data are consistent with a model in which directional activation and differentiation of immune cells by $LT-IIa-B_5$ serve as a critical mechanism whereby this potent adjuvant amplifies mucosal immunity to co-administered antigens.

Rule Discovery for Cancer Classification using Genetic Programming based on Arithmetic Operators (산술 연산자 기반 유전자 프로그래밍을 이용한 암 분류 규칙 발견)

  • 홍진혁;조성배
    • Journal of KIISE:Software and Applications
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    • v.31 no.8
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    • pp.999-1009
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    • 2004
  • As a new approach to the diagnosis of cancers, bioinformatics attracts great interest these days. Machine teaming techniques have produced valuable results, but the field of medicine requires not only highly accurate classifiers but also the effective analysis and interpretation of them. Since gene expression data in bioinformatics consist of tens of thousands of features, it is nearly impossible to represent their relations directly. In this paper, we propose a method composed of a feature selection method and genetic programming. Rank-based feature selection is adopted to select useful features and genetic programming based arithmetic operators is used to generate classification rules with features selected. Experimental results on Lymphoma cancer dataset, in which the proposed method obtained 96.6% test accuracy as well as useful classification rules, have shown the validity of the proposed method.

Molecular Diagnosis for Personalized Target Therapy in Gastric Cancer

  • Cho, Jae Yong
    • Journal of Gastric Cancer
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    • v.13 no.3
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    • pp.129-135
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    • 2013
  • Gastric cancer is the second leading cause of cancer-related deaths worldwide. In advanced and metastatic gastric cancer, the conventional chemotherapy with limited efficacy shows an overall survival period of about 10 months. Patient specific and effective treatments known as personalized cancer therapy is of significant importance. Advances in high-throughput technologies such as microarray and next generation sequencing for genes, protein expression profiles and oncogenic signaling pathways have reinforced the discovery of treatment targets and personalized treatments. However, there are numerous challenges from cancer target discoveries to practical clinical benefits. Although there is a flood of biomarkers and target agents, only a minority of patients are tested and treated accordingly. Numerous molecular target agents have been under investigation for gastric cancer. Currently, targets for gastric cancer include the epidermal growth factor receptor family, mesenchymal-epithelial transition factor axis, and the phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathways. Deeper insights of molecular characteristics for gastric cancer has enabled the molecular classification of gastric cancer, the diagnosis of gastric cancer, the prediction of prognosis, the recognition of gastric cancer driver genes, and the discovery of potential therapeutic targets. Not only have we deeper insights for the molecular diversity of gastric cancer, but we have also prospected both affirmative potentials and hurdles to molecular diagnostics. New paradigm of transdisciplinary team science, which is composed of innovative explorations and clinical investigations of oncologists, geneticists, pathologists, biologists, and bio-informaticians, is mandatory to recognize personalized target therapy.

Deep-sea Hydrothermal Vents: Ecology and Evolution

  • Won, Yong-Jin
    • Journal of Ecology and Environment
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    • v.29 no.2
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    • pp.175-183
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    • 2006
  • The discovery of deep-sea hydrothermal vents and their ecosystems is a monumental landmark in the history of Ocean Sciences. Deep-sea hydrothermal vents are scattered along the global mid-ocean ridges and back-arc basins. Under sea volcanic phenomena related to underlying magma activities along mid-ocean ridges generate extreme habitats for highly specialized communities of animals. Multidisciplinary research efforts during past three decades since the first discovery of hydrothermal vents along the Galapagos Rift in 1977 revealed fundamental components of physiology, ecology, and evolution of specialized vent communities of micro and macro fauna. Heterogeneous regional geological settings and tectonic plate history have been considered as important geophysical and evolutionary factors for current patterns of taxonomic composition and distribution of vent faunas among venting sites in the World Ocean basins. It was found that these communities are based on primary production of chemosynthetic bacteria which directly utilize reduced compounds, mostly $H_2S$ and $CH_4$, mixed in vent fluids. Symbioses between these bacteria and their hosts, vent invertebrates, are foundation of the vent ecosystem. Gene flow and population genetic studies in parallel with larval biology began to unveil hidden dispersal barrier under deep sea as well as various dispersal characteristics cross taxa. Comparative molecular phylogenetics of vent animals revealed that vent faunas are closely related to those of cold-water seeps in general. In perspective additional interesting discoveries are anticipated particularly with further refined and expanded studies aided by new instrumental technologies.

Q-omics: Smart Software for Assisting Oncology and Cancer Research

  • Lee, Jieun;Kim, Youngju;Jin, Seonghee;Yoo, Heeseung;Jeong, Sumin;Jeong, Euna;Yoon, Sukjoon
    • Molecules and Cells
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    • v.44 no.11
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    • pp.843-850
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    • 2021
  • The rapid increase in collateral omics and phenotypic data has enabled data-driven studies for the fast discovery of cancer targets and biomarkers. Thus, it is necessary to develop convenient tools for general oncologists and cancer scientists to carry out customized data mining without computational expertise. For this purpose, we developed innovative software that enables user-driven analyses assisted by knowledge-based smart systems. Publicly available data on mutations, gene expression, patient survival, immune score, drug screening and RNAi screening were integrated from the TCGA, GDSC, CCLE, NCI, and DepMap databases. The optimal selection of samples and other filtering options were guided by the smart function of the software for data mining and visualization on Kaplan-Meier plots, box plots and scatter plots of publication quality. We implemented unique algorithms for both data mining and visualization, thus simplifying and accelerating user-driven discovery activities on large multiomics datasets. The present Q-omics software program (v0.95) is available at http://qomics.sookmyung.ac.kr.

LitCovid-AGAC: cellular and molecular level annotation data set based on COVID-19

  • Ouyang, Sizhuo;Wang, Yuxing;Zhou, Kaiyin;Xia, Jingbo
    • Genomics & Informatics
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    • v.19 no.3
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    • pp.23.1-23.7
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    • 2021
  • Currently, coronavirus disease 2019 (COVID-19) literature has been increasing dramatically, and the increased text amount make it possible to perform large scale text mining and knowledge discovery. Therefore, curation of these texts becomes a crucial issue for Bio-medical Natural Language Processing (BioNLP) community, so as to retrieve the important information about the mechanism of COVID-19. PubAnnotation is an aligned annotation system which provides an efficient platform for biological curators to upload their annotations or merge other external annotations. Inspired by the integration among multiple useful COVID-19 annotations, we merged three annotations resources to LitCovid data set, and constructed a cross-annotated corpus, LitCovid-AGAC. This corpus consists of 12 labels including Mutation, Species, Gene, Disease from PubTator, GO, CHEBI from OGER, Var, MPA, CPA, NegReg, PosReg, Reg from AGAC, upon 50,018 COVID-19 abstracts in LitCovid. Contain sufficient abundant information being possible to unveil the hidden knowledge in the pathological mechanism of COVID-19.

Identification of a novel circularized transcript of the AML1 gene

  • Xu, Ai-Ning;Chen, Xiu-Hua;Tan, Yan-Hong;Qi, Xi-Ling;Xu, Zhi-Fang;Zhang, Lin-Lin;Ren, Fang-Gang;Bian, Si-Cheng;Chen, Yi;Wang, Hong-Wei
    • BMB Reports
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    • v.46 no.3
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    • pp.163-168
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    • 2013
  • The AML1 gene is an essential transcription factor regulating the differentiation of hematopoietic stem cells into mature blood cells. Though at least 12 different alternatively spliced AML1 mRNAs are generated, three splice variants (AML1a, AML1b and AML1c) have been characterized. Here, using the reverse transcription-polymerase chain reaction with outward-facing primers, we identified a novel non-polyadenylated transcript from the AML1 gene, with exons 5 and 6 scrambled. The novel transcript resisted RNase R digestion, indicating it is a circular RNA structure that may originate from products of mRNA alternative splicing. The expression of the novel transcript in different cells or cell lines of human and a number of other species matched those of the canonical transcripts. The discovery provides additional evidence that circular RNA could stably exist in vivo in human, and may also help to understand the mechanism of the regulation of the AML1 gene transcription.