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Choi, Sangdun,Chang, Mi Sook,Stuecker, Tara,Chung, Christine,Newcombe, David A.,Venkateswaran, Kasthuri Korea Genome Organization 2012 Genomics & informatics Vol.10 No.4
In this study, fosmid cloning strategies were used to assess the microbial populations in water from the International Space Station (ISS) drinking water system (henceforth referred to as Prebiocide and Tank A water samples). The goals of this study were: to compare the sensitivity of the fosmid cloning strategy with that of traditional culture-based and 16S rRNA-based approaches and to detect the widest possible spectrum of microbial populations during the water purification process. Initially, microbes could not be cultivated, and conventional PCR failed to amplify 16S rDNA fragments from these low biomass samples. Therefore, randomly primed rolling-circle amplification was used to amplify any DNA that might be present in the samples, followed by size selection by using pulsed-field gel electrophoresis. The amplified high-molecular- weight DNA from both samples was cloned into fosmid vectors. Several hundred clones were randomly selected for sequencing, followed by Blastn/Blastx searches. Sequences encoding specific genes from Burkholderia, a species abundant in the soil and groundwater, were found in both samples. Bradyrhizobium and Mesorhizobium, which belong to rhizobia, a large community of nitrogen fixers often found in association with plant roots, were present in the Prebiocide samples. Ralstonia, which is prevalent in soils with a high heavy metal content, was detected in the Tank A samples. The detection of many unidentified sequences suggests the presence of potentially novel microbial fingerprints. The bacterial diversity detected in this pilot study using a fosmid vector approach was higher than that detected by conventional 16S rRNA gene sequencing.
Toll-like receptors: promising therapeutic targets for inflammatory diseases
Asma Achek,Dhanusha Yesudhas,Sangdun Choi 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.8
The health of living organisms is constantlychallenged by bacterial and viral threats. The recognitionof pathogenic microorganisms by diverse receptors triggersa variety of host defense mechanisms, leading to theireradication. Toll-like receptors (TLRs), which are type Itransmembrane proteins, recognize specific signatures ofthe invading microbes and activate a cascade of downstreamsignals inducing the secretion of inflammatorycytokines, chemokines, and type I interferons. The TLRresponse not only counteracts the pathogens but also initiatesand shapes the adaptive immune response. Undernormal conditions, inflammation is downregulated after theremoval of the pathogen and cellular debris. However, adysfunctional TLR-mediated response maintains a chronicinflammatory state and leads to local and systemic deleteriouseffects in host cells and tissues. Such inappropriateTLR response has been attributed to the development andprogression of multiple diseases such as cancer, autoimmune,and inflammatory diseases. In this review, we discussthe emerging role of TLRs in the pathogenesis ofinflammatory diseases and how targeting of TLRs offers apromising therapeutic strategy for the prevention andtreatment of various inflammatory diseases. Additionally,we highlight a number of TLR-targeting agents that are inthe developmental stage or in clinical trials.
Nanoinformatics: Emerging Databases and Available Tools
Panneerselvam, Suresh,Choi, Sangdun Molecular Diversity Preservation International (MD 2014 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.15 No.5
<P>Nanotechnology has arisen as a key player in the field of nanomedicine. Although the use of engineered nanoparticles is rapidly increasing, safety assessment is also important for the beneficial use of new nanomaterials. Considering that the experimental assessment of new nanomaterials is costly and laborious, <I>in silico</I> approaches hold promise. Several major challenges in nanotechnology indicate a need for nanoinformatics. New database initiatives such as ISA-TAB-Nano, caNanoLab, and Nanomaterial Registry will help in data sharing and developing data standards, and, as the amount of nanomaterials data grows, will provide a way to develop methods and tools specific to the nanolevel. In this review, we describe emerging databases and tools that should aid in the progress of nanotechnology research.</P>
Durai, Prasannavenkatesh,Batool, Maria,Shah, Masaud,Choi, Sangdun Nature Publishing Group 2015 Experimental and molecular medicine Vol.47 No.8
<P>Middle East respiratory syndrome coronavirus (MERS-CoV) causes high fever, cough, acute respiratory tract infection and multiorgan dysfunction that may eventually lead to the death of the infected individuals. MERS-CoV is thought to be transmitted to humans through dromedary camels. The occurrence of the virus was first reported in the Middle East and it subsequently spread to several parts of the world. Since 2012, about 1368 infections, including ~487 deaths, have been reported worldwide. Notably, the recent human-to-human ‘superspreading' of MERS-CoV in hospitals in South Korea has raised a major global health concern. The fatality rate in MERS-CoV infection is four times higher compared with that of the closely related severe acute respiratory syndrome coronavirus infection. Currently, no drug has been clinically approved to control MERS-CoV infection. In this study, we highlight the potential drug targets that can be used to develop anti-MERS-CoV therapeutics.</P>
The triumph of chemically enhanced cellular reprogramming: a patent review
Anwar, Muhammad Ayaz,Kim, Songmee,Choi, Sangdun Informa UK (Ashley Publications) 2016 Expert opinion on therapeutic patents Vol.26 No.2
<P>Introduction: The revolutionary discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka has exposed science to new horizons. However, genetic modifications render reprogrammed cells unstable; for that reason, non-genetic modification approaches are actively under investigation. Among these, the use of small molecules is safe, and these molecules minimally affect the genome. Although iPSCs are ready for clinical trials there are many caveats hindering successful therapy, and small molecules are the best alternative to overcome those caveats. Areas covered: Small molecules are playing an active role in generating and improving the quality of iPSCs. In this review, we will highlight the imperative role of small molecules in accelerating the successful translation of basic research into clinical use. Particularly, those ligands that replace the need for reprogramming factors will be discussed. Expert opinion: Stem cell research is promising for harvesting medical benefits in near future. The invention of new techniques, mechanisms elucidation, and identification of novel compounds for stem cell creation has certainly established a solid foundation for regenerative medicine. This is the beginning of a new era for the cure of most disabling diseases, and small molecules will have a definite role in successful therapeutic use of iPSCs.</P>
Durai, Prasannavenkatesh,Govindaraj, Rajiv Gandhi,Choi, Sangdun Published by Blackwell Pub. on behalf of the Feder 2013 The FEBS journal Vol.280 No.23
<P>Proinflammatory responses by Toll‐like receptors (TLRs) to malaria infection are considered to be a significant factor in suppressing pathogen growth and in disease control. The key protozoan parasite <I>Plasmodium falciparum</I> causes malaria through glycosylphosphatidylinositols (GPIs), which induce the host immune response mainly via TLR2 signalling. Experimental studies have suggested that malarial GPIs from <I>P. falciparum</I> are recognized by the TLR2 subfamily. However, the interaction site and their involvement in the activation mechanism are still unknown. A better understanding of the detailed structure of the TLR–GPI interaction is important for the design of more effective anti‐malarial therapeutics. We used a molecular docking method to predict the binding regions of malarial GPIs with the TLR2 subfamily members. We also employed molecular dynamics simulations and principal component analysis to understand ligand‐induced conformational changes of the TLR2 subfamily. We observed the expected structural changes upon ligand binding, and significant movements were found in loop regions located in the ligand‐binding site of the TLR2 subfamily. We further propose that the binding modes of malarial GPIs are similar to lipopeptides, and that the lipid portions of the ligands could play an essential role in selective dimerization of the TLR2 subfamily.</P>
Hwang, Dong-Youn,Hong, Sunghoi,Jeong, Joo-Won,Choi, Sangdun,Kim, Hansoo,Kim, Jangwoo,Kim, Kwang-Soo Blackwell Publishing Ltd 2009 Journal of Neurochemistry Vol.111 No.5
<P>Abstract</P><P>Midbrain dopamine (mDA) neurons play critical roles in the regulation of voluntary movement and their dysfunction is associated with Parkinson’s disease. Pitx3 has been implicated in the proper development of mDA neurons in the substantia nigra pars compacta, which are selectively lost in Parkinson’s disease. However, the basic mechanisms underlying its role in mDA neuron development and/or survival are poorly understood. Toward this goal, we sought to identify downstream target genes of Pitx3 by comparing gene expression profiles in mDA neurons of wild-type and Pitx3-deficient aphakia mice. This global gene expression analysis revealed many potential target genes of Pitx3; in particular, the expression of vesicular monoamine transporter 2 and dopamine transporter, responsible for dopamine storage and reuptake, respectively, is greatly reduced in mDA neurons by Pitx3 ablation. In addition, gain-of-function analyses and chromatin immunoprecipitation strongly indicate that Pitx3 may directly activate transcription of vesicular monoamine transporter 2 and dopamine transporter genes, critically contributing to neurotransmission and/or survival of mDA neurons. As the two genes have been known to be regulated by Nurr1, another key dopaminergic transcription factor, we propose that Pitx3 and Nurr1 may coordinately regulate mDA specification and survival, at least in part, through a merging and overlapping downstream pathway.</P>