• Title/Summary/Keyword: Biological design

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치료저항성 우울증의 연구에서 패러다임의 전환 (Paradigm Shift in the Study of Treatment Resistant Depression)

  • 김용구
    • 생물정신의학
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    • 제23권2호
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    • pp.37-40
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    • 2016
  • Treatment-resistant depression (TRD) is a major public health problem. It is estimated that about 30% of patients with major depressive disorder do not show substantial clinical improvement to somatic or psychosocial treatment. Most of studies for TRD have focused on the subjects already known as TRD. Patients with unipolar depressive episodes that do not respond satisfactorily to numerous sequential treatment regimens were included in the TRD studies. Such post hoc experimental design can be regarded only as consequences of having TRD, rather than as causal risk factors for it. Although informative, data derived from such studies often do not allow a distinction to be made between cause and effect. So, we should shift paradigm toward examining the risk for developing TRD in untreated depressed patients. To deal with this problem, untreated depressed patients should be enrolled in the study to identify biological markers for treatment resistance. The peripheral or central biological markers should be explored before starting treatment. Subsequent systematic administration of treatments with appropriate monitoring in the subjects can determine the risk for developing treatment resistance in untreated individuals. Such information could give a cue to improve the initial diagnosis and provide more effective treatment for TRD.

광 조사에 따른 온도분포를 이용한 생체조직 내 비정상조직 탐지에 대한 연구 (A Study on the Detection of Abnormal Tissues in Biological Tissue Using Temperature Distribution According to Light Irradiation)

  • 고동국;임익태
    • 대한기계학회논문집B
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    • 제41권5호
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    • pp.303-309
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    • 2017
  • 본 연구에서는 비정상조직(파라핀)을 가진 생체조직에 광을 조사하고 그에 따른 조직의 표면온도와 비정상조직 주위에서의 온도분포를 실험과 해석적 방법을 통해 분석하였다. 파라핀을 이용하여 비정상 조직을 모사한 후 조사하는 광의 파장과 시간을 변화시키면서 조직 주위에서의 온도를 K형 열전대를 사용하여 측정하였다. 또한 전산열전달 기법을 이용하여 해석적으로 조직에 대한 온도분포를 예측하였다. 정상조직과 비정상조직의 주위에서의 온도는 차이가 있었으며, 비정상조직이 있는 경우 표면과 조직 주위의 온도가 높게 나타났다.

Structure-Based Virtual Screening of Protein Tyrosine Phosphatase Inhibitors: Significance, Challenges, and Solutions

  • Reddy, Rallabandi Harikrishna;Kim, Hackyoung;Cha, Seungbin;Lee, Bongsoo;Kim, Young Jun
    • Journal of Microbiology and Biotechnology
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    • 제27권5호
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    • pp.878-895
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    • 2017
  • Phosphorylation, a critical mechanism in biological systems, is estimated to be indispensable for about 30% of key biological activities, such as cell cycle progression, migration, and division. It is synergistically balanced by kinases and phosphatases, and any deviation from this balance leads to disease conditions. Pathway or biological activity-based abnormalities in phosphorylation and the type of involved phosphatase influence the outcome, and cause diverse diseases ranging from diabetes, rheumatoid arthritis, and numerous cancers. Protein tyrosine phosphatases (PTPs) are of prime importance in the process of dephosphorylation and catalyze several biological functions. Abnormal PTP activities are reported to result in several human diseases. Consequently, there is an increased demand for potential PTP inhibitory small molecules. Several strategies in structure-based drug designing techniques for potential inhibitory small molecules of PTPs have been explored along with traditional drug designing methods in order to overcome the hurdles in PTP inhibitor discovery. In this review, we discuss druggable PTPs and structure-based virtual screening efforts for successful PTP inhibitor design.

Cell-Based Assay Design for High-Content Screening of Drug Candidates

  • Nierode, Gregory;Kwon, Paul S.;Dordick, Jonathan S.;Kwon, Seok-Joon
    • Journal of Microbiology and Biotechnology
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    • 제26권2호
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    • pp.213-225
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    • 2016
  • To reduce attrition in drug development, it is crucial to consider the development and implementation of translational phenotypic assays as well as decipher diverse molecular mechanisms of action for new molecular entities. High-throughput fluorescence and confocal microscopes with advanced analysis software have simplified the simultaneous identification and quantification of various cellular processes through what is now referred to as high-content screening (HCS). HCS permits automated identification of modifiers of accessible and biologically relevant targets and can thus be used to detect gene interactions or identify toxic pathways of drug candidates to improve drug discovery and development processes. In this review, we summarize several HCS-compatible, biochemical, and molecular biology-driven assays, including immunohistochemistry, RNAi, reporter gene assay, CRISPR-Cas9 system, and protein-protein interactions to assess a variety of cellular processes, including proliferation, morphological changes, protein expression, localization, post-translational modifications, and protein-protein interactions. These cell-based assay methods can be applied to not only 2D cell culture but also 3D cell culture systems in a high-throughput manner.

Investigation on the Effects of Three X${\rightarrow}$Histidine Replacements on Thermostability of ${\alpha}$-Amylase from Bacillus amyloliquefaciens

  • Haghani, Karimeh;Khajeh, Khosro;Naderi-Manesh, Hossein;Ranjbar, Bijan
    • Journal of Microbiology and Biotechnology
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    • 제22권5호
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    • pp.592-599
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    • 2012
  • Bacillus licheniformis ${\alpha}$-amylase (BLA), a thermophilic counterpart of Bacillus amyloliquefaciens ${\alpha}$-amylase (BAA), is an appropriate model for the design of stabilizing mutations in BAA. BLA has 10 more histidines than BAA. Considering this prominent difference, in the present study, three out of these positions (I34, Q67, and P407; located in the thermostability determinant 1 region and Ca-III binding site of BAA) were replaced with histidine in BAA, using the site-directed mutagenesis technique. The results showed that the thermostability of P407H and Q67H mutants had increased, but no significant changes were observed in their kinetic parameters compared to that of the wild type. I34H replacement resulted in complete loss of enzyme activity. Moreover, fluorescence and circular dichroism data indicated a more rigid structure for the P407H variant compared with that of the wild-type BAA. However, the flexibility of Q67H and I34H mutants increased in comparison with that of wild-type enzyme.

생체지표를 활용한 웹기반의 실험동물 군(郡) 분리 프로그램 (Web Program for Laboratory Animal Group Separation Based on Biological Characteristics)

  • 김창환;이대상
    • KSBB Journal
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    • 제27권1호
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    • pp.40-44
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    • 2012
  • The laboratory animal group separation is dividing animal population into subgroups, which have similar average and standard deviation values among the subgroups, based on the biological characteristics such as body weight, glucose level in blood, etc. Although group separation is very important and initial step in experimental design, it needs a labor intensive process for researchers because of making similar average and standard deviation values among the subgroups using the raw biological characteristics. To reduce the labor cost and increase the efficiency of animal grouping, we developed a web program named as laboratory animal group separation (LAGS) program. This LAGS uses biological characteristics of population, number of group, and the number of elements per each subgroup as input data. The LAGS automatically separates the population into each subgroup that has similar statistical data such as average and standard deviation values among subgroups. It also provides researchers with the extraordinary data generated in the process of grouping and the final grouping results by graphical display. Through our LAGS, researchers can validate and confirm results of laboratory animal group separation by just a few mouse clicks.

Shikimate Metabolic Pathway Engineering in Corynebacterium glutamicum

  • Park, Eunhwi;Kim, Hye-Jin;Seo, Seung-Yeul;Lee, Han-Na;Choi, Si-Sun;Lee, Sang Joung;Kim, Eung-Soo
    • Journal of Microbiology and Biotechnology
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    • 제31권9호
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    • pp.1305-1310
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    • 2021
  • Shikimate is a key high-demand metabolite for synthesizing valuable antiviral drugs, such as the anti-influenza drug, oseltamivir (Tamiflu). Microbial-based strategies for shikimate production have been developed to overcome the unstable and expensive supply of shikimate derived from traditional plant extraction processes. In this study, a microbial cell factory using Corynebacterium glutamicum was designed to overproduce shikimate in a fed-batch culture system. First, the shikimate kinase gene (aroK) responsible for converting shikimate to the next step was disrupted to facilitate the accumulation of shikimate. Several genes encoding the shikimate bypass route, such as dehydroshikimate dehydratase (QsuB), pyruvate kinase (Pyk1), and quinate/shikimate dehydrogenase (QsuD), were disrupted sequentially. An artificial operon containing several shikimate pathway genes, including aroE, aroB, aroF, and aroG were overexpressed to maximize the glucose uptake and intermediate flux. The rationally designed shikimate-overproducing C. glutamicum strain grown in an optimized medium produced approximately 37.3 g/l of shikimate in 7-L fed-batch fermentation. Overall, rational cell factory design and culture process optimization for the microbial-based production of shikimate will play a key role in complementing traditional plant-derived shikimate production processes.

경도인지장애와 알츠하이머병 치매의 생물학적 표지자로서 뇌파와 사건유발전위의 임상적 의미 (Clinical Implications of EEG and ERP as Biological Markers for Alzheimer's Disease and Mild Cognitive Impairment)

  • 김창규;김현택;이승환
    • 생물정신의학
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    • 제20권4호
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    • pp.119-128
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    • 2013
  • Objectives Memory impairment is a very important mental health issue for elderly and adults. Mild cognitive impairment (MCI) is a prodromal stage of Alzheimer's disease (AD). Early detection of the prodromal stage of patients with AD is an important topic of interest for both mental health clinicians and policy makers. Methods Electroencephalograpgy (EEG) has been used as a possible biological marker for patients with MCI, and AD. In this review, we will summarize the clinical implications of EEG and ERP as a biological marker for AD and MCI. Results EEG power density, functional coupling, spectral coherence, synchronization, and connectivity were analyzed and proved their clinical efficacy in patients with the prodromal stage of AD. Serial studies on late event-related potentials (ERPs) were also conducted in MCI patients as well as healthy elders. Even though these EEG and ERP studies have some limitations for their design and method, their clinical implications are increasing rapidly. Conclusion EEG and ERP can be used as biological markers of AD and MCI. Also they can be used as useful tools for early detection of AD and MCI patients. They are useful and sensitive research tools for AD and MCI patients. However, some problems remain to be solved until they can be practical measures in clinical setting.

Design of Quorum Quenching Microbial Vessel to Enhance Cell Viability for Biofouling Control in Membrane Bioreactor

  • Cheong, Won-Suk;Kim, Sang-Ryoung;Oh, Hyun-Suk;Lee, Sang H.;Yeon, Kyung-Min;Lee, Chung-Hak;Lee, Jung-Kee
    • Journal of Microbiology and Biotechnology
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    • 제24권1호
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    • pp.97-105
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    • 2014
  • Quorum quenching (QQ) with a microbial vessel has recently been reported as an economically feasible biofouling control platform in a membrane bioreactor (MBR) for wastewater treatment. In this study, a quorum quenching MBR with a ceramic microbial vessel (CMV) was designed to overcome the extremely low F/M ratio inside a microbial vessel. The CMV was prepared with a monolithic ceramic microporous membrane and AHL-degrading QQ bacteria, Pseudomonas sp. 1A1. The "inner flow feeding mode" was introduced, under which fresh feed was supplied to the MBR only through the center lumen in the CMV. The inner flow feeding mode facilitated nutrient transport to QQ bacteria in the CMV and thus enabled relatively long-term maintenance of cell viability. The quorum quenching effect of the CMV on controlling membrane biofouling in the MBR was more pronounced with the inner flow feeding mode, which was identified by the slower increase in the transmembrane pressure as well as by the visual observation of a biocake that formed on the used membrane surface. In the QQ MBR with the CMV, the concentrations of extracellular polymeric substances were substantially decreased in the biocake on the membrane surface compared with those in the conventional MBR. The CMV also showed its potential with effective biofouling control over long-term operation of the QQ MBR.

From genome sequencing to the discovery of potential biomarkers in liver disease

  • Oh, Sumin;Jo, Yeeun;Jung, Sungju;Yoon, Sumin;Yoo, Kyung Hyun
    • BMB Reports
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    • 제53권6호
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    • pp.299-310
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    • 2020
  • Chronic liver disease progresses through several stages, fatty liver, steatohepatitis, cirrhosis, and eventually, it leads to hepatocellular carcinoma (HCC) over a long period of time. Since a large proportion of patients with HCC are accompanied by cirrhosis, it is considered to be an important factor in the diagnosis of liver cancer. This is because cirrhosis leads to an irreversible harmful effect, but the early stages of chronic liver disease could be reversed to a healthy state. Therefore, the discovery of biomarkers that could identify the early stages of chronic liver disease is important to prevent serious liver damage. Biomarker discovery at liver cancer and cirrhosis has enhanced the development of sequencing technology. Next generation sequencing (NGS) is one of the representative technical innovations in the biological field in the recent decades and it is the most important thing to design for research on what type of sequencing methods are suitable and how to handle the analysis steps for data integration. In this review, we comprehensively summarized NGS techniques for identifying genome, transcriptome, DNA methylome and 3D/4D chromatin structure, and introduced framework of processing data set and integrating multi-omics data for uncovering biomarkers.