• Title/Summary/Keyword: structural alterations

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The Homeobox and Genetic Disease: Structure and Dynamics of Wild Type and Mutant Homeodomain Proteins

  • Ferretti, James A.
    • BMB Reports
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    • v.34 no.1
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    • pp.1-7
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    • 2001
  • Structural and physical properties of type wild type and various selected mutants of the vnd/NK-2 homeodomain, the protein product of the homeobox, and the implication in genetic disease are reviewed. The structure, dynamics and thermodynamics have been Investigated by NMR and by calorimetry. The interactions responsible for the nucleotide sequence-specific binding of the homeodomain to its consensus DNA binding site have been identified. There is a strong correlation between significant structural alterations within the homeodomain or its DNA complex and the appearance of genetic disease. Mutations in positions known to be important in genetic disease have been examined carefully For example, mutation of position 52 of vnd/NK-2 results in a significant structural modification and mutation of position 54 alters the DNA binding specificity and amity The $^{15}N$ relaxation behavior and heteronuclear Overhauser effect data was used to characterize and describe the protein backbone dynamics. These studies were carried out on the wild type and the double mutant proteins both in the free and in the DNA bound states. Finally, the thermodynamic properties associated with DNA binding are described for the vnd/NK-2 homeodomain. These thermodynamic measurements reinforce the hypothesis that water structure around a protein and around DNA significantly contribute to the protein-DNA binding behavior. The results, taken together, demonstrate that structure and dynamic studies of proteins combined with thermodynamic measurements provide a significantly more complete picture of the solution behavior than the individual studies.

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Electrophoretic Tissue Clearing and Labeling Methods for Volume Imaging of Whole Organs

  • Kim, Dai Hyun;Ahn, Hyo Hyun;Sun, Woong;Rhyu, Im Joo
    • Applied Microscopy
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    • v.46 no.3
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    • pp.134-139
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    • 2016
  • Detailed structural and molecular imaging of intact organs has incurred academic interest because the associated technique is expected to provide innovative information for biological investigation and pathological diagnosis. The conventional methods for volume imaging include reconstruction of images obtained from serially sectioned tissues. This approach requires intense manual work which involves inevitable uncertainty and much time to assemble the whole image of a target organ. Recently, effective tissue clearing techniques including CLARITY and ACT-PRESTO have been reported that enables visualization of molecularly labeled structures within intact organs in three dimensions. The central principle of the methods is transformation of intact tissue into an optically transpicuous and macromolecule permeable state without loss of intrinsic structural integrity. The rapidly evolving protocols enable morphological analysis and molecular labeling of normal and pathological characteristics in large assembled biological systems with single-cell resolution. The deep tissue volume imaging will provide fundamental information about mutual interaction among adjacent structures such as connectivity of neural circuits; meso-connectome and clinically significant structural alterations according to pathologic mechanisms or treatment procedures.

Crystal structure of unphosphorylated Spo0F from Paenisporosarcina sp. TG-14, a psychrophilic bacterium isolated from an Antarctic glacier

  • Lee, Chang Woo;Park, Sun-Ha;Jeong, Chang Sook;Lee, Chang Sup;Hong, Jong Wook;Park, Hyun Ho;Park, Hyun;Park, HaJeung;Lee, Jun Hyuck
    • Biodesign
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    • v.6 no.4
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    • pp.84-91
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    • 2018
  • Spo0F is a response regulator that modulates sporulation, undergoes phosphorylation for phosphorelay signal transduction, and interacts with various regulatory proteins; however, the mechanisms through which phosphorylation induces structural changes and regulates interactions with binding partners remain unclear. Here, we determined the unphosphorylated crystal structure of Spo0F from the psychrophilic bacterium Paenisporosarcina sp. TG-14 (PaSpo0F) and established a phosphorylation-state structural model. We found that PaSpo0F underwent structural changes (Lys54 and Lys102) by phosphorylation and generated new interactions (Lys102/Gln10 and Lys54/Glu84) to stabilize the ${\beta}4/{\alpha}4$ and ${\beta}1/{\alpha}1$ loop structures, which are important target-protein binding sites. Analysis of Bacillus subtilis Spo0 variants revealed movement by BsSpo0F Thr82 and Tyr84 residues following interaction with BsSpo0B, providing insight into the movement of corresponding residues in PaSpo0F (Thr80 and Tyr82), with further analysis of BsSpo0F/BsRapH interaction revealing alterations in the ${\beta}4/{\alpha}4$ loop region. These results suggest that phosphorylation-induced structural rearrangement might be essential for PaSpo0F activation and expand the understanding of Spo0F-specific activation mechanisms during sporulation.

A Simulation Study on the Structural Optimization of a 800 V 4H-SiC Power DMOSFET (800 V급 4H-SiC DMOSFET 전력 소자 구조 최적화 시뮬레이션)

  • Choi, Chang-Yong;Kang, Min-Seok;Bahng, Wook;Kim, Sang-Cheol;Kim, Nam-Kyun;Koo, Sang-Mo
    • Journal of the Korean Institute of Electrical and Electronic Material Engineers
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    • v.22 no.8
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    • pp.637-640
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    • 2009
  • In this work, we demonstrate 800 V 4H-SiC power DMOSFETs with several structural alterations to obtain a low threshold voltage ($V_{TH}$) and a high figure of merit ($V_B\;^2/R_{SP,ON}$), To optimize the device performance, we consider four design parameters; (a) the doping concentration ($N_{CSL}$) of current spreading layer (CSL) beneath the p-base region, (b) the thickness of p-base ($t_{BASE}$), (c) the doping concentration ($N_J$) and width ($W_J$) of a JFET region, (d) the doping concentration ($N_{EPI}$) and thickness ($t_{EPI}$) of epi-layer. These parameters are optimized using 2D numerical simulation and the 4H-SiC DMOSFET structure results in a threshold voltage ($V_{TH}$) below $^{\sim}$3.8 V, and high figure of merit ($V_B\;^2/R_{SP,ON}$>$^{\sim}$200 $MW/cm^2$) for a power MOSFET in $V_B\;^{\sim}$800 V range.

Two cases of chronic pancreatitis associated with anomalous pancreaticobiliary ductal union and SPINK1 mutation

  • Rho, Eun Sam;Kim, Earl;Koh, Hong;Yoo, Han-Wook;Lee, Beom Hee;Kim, Gu-Hwan
    • Clinical and Experimental Pediatrics
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    • v.56 no.5
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    • pp.227-230
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    • 2013
  • Chronic pancreatitis is a progressive inflammatory disease resulting from repeated episodes of acute pancreatitis that impair exocrine function and eventually produce endocrine insufficiency. Some causes of chronic pancreatitis appear to be associated with alterations in the serine-protease inhibitor, Kazal type 1 (SPINK1), cationic trypsinogen (PRSS1), and cystic fibrosis-transmembrane conductance regulator (CFTR ) genes, or with structural disorders in the pancreaticobiliary ductal system, such as pancreatic divisum or anomalous pancreaticobiliary ductal union (APBDU). However, it is unusual to observe both genetic alteration and structural anomaly. Here, we report 2 cases with both APBDU and a mutation in the SPINK1 genes, and we discuss the implications of these findings in clinical practice.

A system of multiple controllers for attenuating the dynamic response of multimode floor structures to human walking

  • Battista, Ronaldo C.;Varela, Wendell D.
    • Smart Structures and Systems
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    • v.23 no.5
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    • pp.467-478
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    • 2019
  • Composite floor structures formed by continuous slab panels may be susceptible to excessive vibrations, even when properly designed in terms of ultimate limit state criteria. This is due to the inherent vibration characteristics of continuous floor slabs composed by precast orthotropic reinforced concrete panels supported by steel beams. These floor structures display close spaced multimode vibration frequencies and this dynamic characteristic results in a non-trivial vibration problem. Structural stiffening and/or insertion of struts between floors are the usual tentative solution applied to existing vibrating floor structures. Such structural alterations are in general expensive and unsuitable. In this paper, this vibration problem is analyzed on the basis of results obtained from experimental measurements in typical composite floors and their theoretical counterpart obtained with computational modeling simulations. A passive control system composed by multiple synchronized dynamic attenuators (MSDA) was designed and installed in these floor structures and its efficiency was evaluated both experimentally and through numerical simulations. The results obtained from experimental tests of the continuous slab panels under human walking dynamic action proved the effectiveness of this control system in reducing vibrations amplitudes.

Live Load Distribution in Prestressed Concrete I-Girder Bridges (I형 프리스트레스트 콘크리트 거더교의 활하중 분배)

  • Kim, Kwang-Yang;Kang, Dae-Hui;Lee, Hwan-Woo
    • Proceedings of the Computational Structural Engineering Institute Conference
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    • 2008.04a
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    • pp.288-293
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    • 2008
  • The standard prestressed concrete I-girder bridge (PSC I-girder bridge) is one of the most prevalent types for small and medium bridges in Korea. When determining the member forces in a section to assess the safety of girder in this type of bridge, the general practice is to use the simplified practical equations or the live load distribution factors proposed in design standards rather than the precise analysis through the finite element method or so. Meanwhile, the live load distribution factors currently used in Korean design practice are just a reflection of overseas research results or design standards without alterations. Therefore, it is necessary to develop an equation of the live load distribution factors fit for the design conditions of Korea, considering the standardized section of standard PSC I-girder bridges and the design strength of concrete. In this study, to develop an equation of the live load distribution factors, a parametric analysis and sensitivity analysis were carried out on the parameters such as width of bridge, span length, girder spacing, width of traffic lane, etc. Then, an equation of live load distribution factors was developed through the multiple linear regression analysis on the results of parametric analysis. When the actual practice engineers design a bridge with the equation of live load distribution factors developed here, they will determine the design of member forces ensuring the appropriate safety rate more easily. Moreover, in the preliminary design, this model is expected to save much time for the repetitive design to improve the structural efficiency of PSC I-girder bridges.

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Alterations of Cortical Folding Patterns in Patients with Bipolar I Disorder : Analysis of Local Gyrification Index (제1형 양극성장애 환자에서 대뇌피질 주름 패턴의 변형 : Local Gyrification Index 분석)

  • Lee, Junyong;Han, Kyu-Man;Won, Eunsoo;Lee, Min-Soo;Ham, Byung-Joo
    • Korean Journal of Biological Psychiatry
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    • v.24 no.4
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    • pp.225-234
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    • 2017
  • Objectives Local gyrification reflects the early neural development of cortical connectivity, and is regarded as a potential neural endophenotype in psychiatric disorders. Several studies have suggested altered local gyrification in patients with bipolar I disorder (BD-I). The purpose of the present study was to investigate the alterations in the cortical gyrification of whole brain cortices in patients with BD-I. Methods Twenty-two patients with BD-I and age and sex-matched 22 healthy controls (HC) were included in this study. All participants underwent T1-weighted structural magnetic resonance imaging (MRI). The local gyrification index (LGI) of 66 cortical regions were analyzed using the FreeSurfer (Athinoula A. Martinos Center for Biomedical Imaging). One-way analysis of covariance (ANCOVA) was used to analyze the difference of LGI values between two groups adjusting for age and sex as covariates. Results The patients with BD-I showed significant hypogyria in the left pars opercularis (uncorrected-p = 0.049), the left rostral anterior cingulate gyrus (uncorrected-p = 0.012), the left caudal anterior cingulate gyrus (uncorrected-p = 0.033). However, these findings were not significant after applying the multiple comparison correction. Severity or duration of illness were not significantly correlated with LGI in the patients with BD-I. Conclusions Our results of lower LGI in the anterior cingulate cortex and the ventrolateral prefrontal cortex in the BD-I group implicate that altered cortical gyrification in neural circuits involved in emotion-processing may contribute to pathophysiology of BD-I.

Profiling of Gene Expression According to Cancer Stage in Clear Cell Type of Renal Cell Carcinoma

  • Won, Nam-Hee;Ryu, Yeon-Mi;Kim, Ki-Nam;Kim, Meyoung-Kon
    • Molecular & Cellular Toxicology
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    • v.1 no.1
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    • pp.62-71
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    • 2005
  • For toxicity model in the kidney, renal cell carcinoma (RCC) is one of the most important model to assess the structural and functional alterations. Most RCCs are sporadic, and environmental agents are suspected to play a role in the etiology of the disease. In this study, we discovered novel evidence for previously unknown gene expression patterns related to progression according to cancer stage in RCC. Four clear cell RCC tissue samples along with five corresponding patient-matched normal kidney tissue samples were obtained from patients undergoing partial or radical nephrectomy. To examine the difference of gene expression profile in clear cell RCC, radioactive cDNA microarrays were used to evaluate changes in the expression of 1,152 genes in a total. Using $^{33}P-labeled$ probes, this method provided highly sensitive gene expression profiles including drug metabolism, and cellular signaling. 29 genes were identified with expression levels that differed by more than 2.0 value of z-ratio, compared with that in control. Whereas expression of 38 genes were decreased by less than-2.0 value of z-ratio. In conclusion, this study has identified 67 gene expression alterations in clear-cell type of RCC. Most notably, genes involved in cell growth were up-regulated in stage I more than stage III whereas genes involved in signal transduction were down-regulated in which both stage I and stage III. The identified alteraions of gene expression will likely give in sight in to clear cell RCC and tumor progression.

Purification, Structural Characterization, and Biological Activity of Polysaccharides from Lentinus velutinus

  • Udchumpisai, Wascharin;Bangyeekhun, Eakaphun
    • Mycobiology
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    • v.48 no.1
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    • pp.51-57
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    • 2020
  • A polysaccharide (LVP) was purified from fruiting body of Lentinus velutinus by ethanol precipitation fractionation and DEAE and Sephadex G-100 column chromatography. The yield of purified polysaccharide was 0.025%. Molecular characteristics of LVP were determined by gel permeation chromatography, FT-IR spectroscopy, and thin-layer chromatography. Our results revealed that LVP is a polysaccharide composed of only glucose units, and has a molecular weight of 336 kDa. Biological activity assays indicated that LVP exhibits both cytotoxic and antioxidant activity. LVP showed specific cytotoxicity against cancer cells (HeLa and HepG2 cells), and alterations in cancer cell morphology were found after LVP treatment.