• Title/Summary/Keyword: Human structure and function

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Distinct Repressive Properties of the Mammalian and Fish Orphan Nuclear Receptors SHP and DAX-1

  • Park, Yun-Yong;Teyssier, Catherine;Vanacker, Jean-Marc;Choi, Hueng-Sik
    • Molecules and Cells
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    • v.23 no.3
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    • pp.331-339
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    • 2007
  • It has been suggested that the structure and function of nuclear receptors are evolutionally conserved. Here, we compare the molecular functions of the nile tilapia (Oreochromis niloticus) small heterodimer partner (nSHP/NR0B2) and the Dosage-sensitive sex reversal AHC critical region on X chromosome gene 1 (nDAX-1/NR0B1) with those of human SHP and DAX-1 (hSHP and hDAX-1, respectively). We found that, upon transient cotransfection of human cells, nDAX-1 repressed the activity of tilapia SF-1 (nSF-1) but not that of human SF-1, although the physical interaction with human SF-1 was retained. Similarly, nSHP repressed the activity of nSF-1, whereas hSHP did not, pointing to divergent evolution of SHP/SF-1 in fish and human. We thus propose that the repressive functions of SHP and DAX-1 have been conserved in fish and mammals although with different transcriptional targets and mechanisms. These differences provide new insights into the physiological diversification of atypical orphan nuclear receptors during vertebrate evolution.

Functional Molecular Structure of Band 4.5 Protein of Human Erythrocyte Membrane (인체 적혈구막 Band 4.5 단백질의 기능적인 분자구조)

  • Hah, Jong-Sik
    • The Korean Journal of Physiology
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    • v.20 no.2
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    • pp.209-217
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    • 1986
  • The functional molecular weight of band 4.5 polypeptide was measured by applying the classical target theory to radiation inactivation data of the cytochalasin B binding. Band 4.5 polypeptides purified from human erythrocyte membranes were irradiated at -45 to $-50^{\circ}C$ with an increasing dose of 1.5 MeV electron beam, and after thawing, cytochalasin B binding activities were assayed. Each activity measured was reduced as a simple exponential function of radiation dose. $D_{37}$, dose appeared to be 6.7 mega rads, from which the target size (radiation sensitive mass) of band 4.5 polypeptide was calculated to be 95,500 daltons. This result with other informations available in literature suggests that band 4.5 polypeptide may exist as a dimer in human erythrocytes.

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Histomorphological changes in the common carotid artery of the male rat in induced hypogonadism

  • Cheruiyot, Isaac;Olabu, Beda;Kamau, Martin;Ongeti, Kevin;Mandela, Pamela
    • Anatomy and Cell Biology
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    • v.51 no.4
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    • pp.284-291
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    • 2018
  • The role of androgens in the development of cardiovascular diseases remains controversial. The current study therefore sought to determine the changes in the histomorphology of the common carotid artery of the male rat in orchidectomy-induced hypogonadism. Twenty-two Rattus norvegicus male rats aged 2 months were used. The rats were randomly assigned into baseline (n=4), experimental (n=9), and control (n=9) groups. Hypogonadism was surgically induced in the experimental group by bilateral orchiectomy under local anesthesia. At experiment weeks 3, 6, and 9, three rats from each group (experimental and control) were euthanized, their common carotid artery harvested, and routine processing was done for paraffin embedding, sectioning, and staining. The photomicrographs were taken using a digital photomicroscope for morphometric analysis. Orchidectomy resulted in the development of vascular fibrosis, with a significant increase in collagen fiber density and decrease in smooth muscle and elastic fiber density. Moreover, there was development of intimal hyperplasia, with fragmentation of medial elastic lamellae in the common carotid artery of the castrated rats. Orchidectomy induces adverse changes in structure of the common carotid artery of the male rat. These changes may impair vascular function, therefore constituting a possible structural basis for the higher incidences of cardiovascular diseases observed in hypogonadism.

Functional Assessments of Spodpotera Cell-expressed Human Erythrocyte-type Glucose Transport Protein with a Site-directed Mutagenesis

  • Lee, Chong-Kee
    • Biomedical Science Letters
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    • v.14 no.2
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    • pp.119-122
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    • 2008
  • The baculovirus/insect cell expression system is of great value in the study of structure-function relationships in mammalian glucose-transport proteins by site-directed mutagenesis and for the large-scale production of these proteins for mechanistic and biochemical studies. In order to exploit this, the effects of substitution at the highly conserved residue glutamine 282 of the human erythrocyte-type glucose transporter have been examined by in vitro site-directed mutagenesis. The modified human transport protein has been expressed in Spodoptera frugiperda 21 cells by using the recombinant baculovirus AcNPV-GTL. To assess the functional integrity of the expressed transporter, measurements of the transport inhibitor cytochalasin B binding were performed, involving the membranes prepared from 4 days post infection with no virus, with wild-type virus or AcNPV-GTL virus. Data obtained showed that there was little or no D-glucose-inhibitable binding in cells infected with the wild type or no virus. Only the recombinant virus infected cells exhibited specific binding, which is inhibitable by D- but not by L-glucose. However, there was a notable reduction in the affinity for the potent inhibitor cytochalasin B when binding measurements of AcNPV-GTL were compared with those of AcNPV-GT, which has no substitution. It is thus suggested that although the modified and unmodified human transporters differed slightly in their affinity for cytochalasin B, the glutamine substitution did not interfere the heterologous expression of the human transporter in the insect cells.

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Binding modes of artemisinin to malarial TCTP demonstrated by computer modeling

  • Chai, Jin-Sun;Kim, Choon-Mi
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.315.2-315.2
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    • 2002
  • The translationally controlled tumor-associated proteins (TCTPs) are a highly conserved and abundantly expressed family of eukaryotic proteins that are implicated in both cell growth and human acute allergic response but whose intracellular biochemical function has remained elusive. There are reports that antimalarial drug, artemisinin. binds to Plasmodium falciparum TCTP. however, its 3D structure has not been known. (omitted)

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A MULTI-OBJECTIVE OPTIMIZATION FOR CAPITAL STRUCTURE IN PRIVATELY-FINANCED INFRASTRUCTURE PROJECTS

  • S.M. Yun;S.H. Han;H. Kim
    • International conference on construction engineering and project management
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    • 2007.03a
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    • pp.509-519
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    • 2007
  • Private financing is playing an increasing role in public infrastructure construction projects worldwide. However, private investors/operators are exposed to the financial risk of low profitability due to the inaccurate estimation of facility demand, operation income, maintenance costs, etc. From the operator's perspective, a sound and thorough financial feasibility study is required to establish the appropriate capital structure of a project. Operators tend to reduce the equity amount to minimize the level of risk exposure, while creditors persist to raise it, in an attempt to secure a sufficient level of financial involvement from the operators. Therefore, it is important for creditors and operators to reach an agreement for a balanced capital structure that synthetically considers both profitability and repayment capacity. This paper presents an optimal capital structure model for successful private infrastructure investment. This model finds the optimized point where the profitability is balanced with the repayment capacity, with the use of the concept of utility function and multi-objective GA (Generic Algorithm)-based optimization. A case study is presented to show the validity of the model and its verification. The research conclusions provide a proper capital structure for privately-financed infrastructure projects through a proposed multi-objective model.

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Effects of Material Properties and Fabric Structure Characteristics of Graduated Compression Stockings (GCS) on the Skin Pressure Distributions

  • Liu Rong;Kwok Yi-Lin;Li Yi;Lao Terence-T;Zhang Xin
    • Fibers and Polymers
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    • v.6 no.4
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    • pp.322-331
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    • 2005
  • Graduated compression stockings (GCS) have been widely used for the prophylaxis and treatment of venous diseases. Their gradient pressure function largely related to their fabric structure and material properties. By combing fabric physical testing and wear trials, this study investigated the GCSs fabric structure and material properties at different locations along the stocking hoses, and quantitatively analyzed the effects of fabrics on skin pressure longitudinal and transverse distributions. We concluded that, Structural characteristics and material properties of stocking fabrics were not uniform along the hoses, but a gradual variation from ankle to thigh regions, which significantly influenced the corresponding skin pressure gradient distributions; Tensile (WT, EM) and shearing properties (G) generated most significant differences among ankle, knee and thigh regions along the stocking hose, which significantly influenced the skin pressure lognitudinal gradient distribution. More material indices generating significant gradual changes occurred in the fabric wale direction along stocking hose, meaning that materials properties in wale direction would exert more important impact on the skin pressure gradient performances. And, the greater tensibility and smoother surface of fabric in wale direction would contribute to put stocking on and off, and facilitate wearers' leg extension-flexion movements. The indices of WT and EM of stocking fabrics in series A have strong linear correlations with skin pressure lognitudinal distribution, which largely related to their better performances in gradual changes of material properties. Skin pressure applied by fabric with same material properties produced pronounced differences among four different directions around certain cross-sections of human leg, especially at the ankle region; and, the skin pressure magnitudes at ankle region were more easily influenced by the materials properties, which were considered to be largely related to the anatomic structure of human leg.

Simple and Efficient Methods for the Response Estimation of Building Structure Subjected to Human Induced Loads (무리하중을 받는 구조물의 간편하고 효율적인 응답추정)

  • Kim, Tae-Ho;Lee, Dong-Guen;Min, Kyung-Won
    • Journal of the Earthquake Engineering Society of Korea
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    • v.9 no.4 s.44
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    • pp.19-28
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    • 2005
  • Long span structures with low natural frequencies such as shopping malls, large offices, and assembly rooms may experience signification dynamic responses due to human activities. In many cases, the group activities are common thing in comparison with the single activity. The purpose of this study is to evaluate the responses of building structure subjected to group human loads using mode shapes. For this purpose, equations to estimate the magnitudes ol responses ol structure subjected to group walking loads are derived. And the correlation of loads is verified for identifying the relation of each human load composing of group human loads using two load cells. The method is proposed for evaluating the responses of structure subjected to group loads using mode shapes and correlation function related to each human loads. The effectiveness ol the proposed method is verified analytically using a simple beam and floor and experimentally on a footbridge measuring the structural response induced by group pedestrians for the case of synchronization or not. Results indicate that the amplitudes of group walking loads can be easily estimated if the mode shapes are available, and that the corresponding structural responses can be estimated easily by the simple response measurement using the proposed method.

Ig G fusion 단백질을 사용한 리간드-수용체의 상호작용

  • 천혜경
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.11a
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    • pp.143-145
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    • 1994
  • Chimeric fusion proteins involving IgG have proven valuable in studying protein-protein interactions and may possess therapeutic applications as well. For example, three receptor subtypes for the natriuretic peptides, when fused to the Fc portion of human IgG ${\gamma}$ chain, were quantitatively and qualitatively indistinguishable from the native receptor, thus allowing detailed structure-function studies of the receptor. In an attempt to block human immunodeficiency virus infectivity with soluble derivatives of CD4, a CD4/IgG Fc chimeric molecule was shown to increase the plasma half life of soluble CD4 and possessed the added advantage of IgG Fc-mediated placental transfer. In the case of the KGFR, this approach provided a framework for dissection of its ligand binding domains and made it possible to demonstrate that high affinity binding sites for two ligands, aFGF and KGF, reside within different receptor Ig-like domains. Chimeric molecules fused to immunoglobulins would have the advantages of secretion from transfected cells as well as detection and purification from medium utilizing Staphylococcus aureus Protein A. In addition, where highly related receptors make their discrimination very hard due to the difficulties in generating specific immunochemical probes, IgG fusion protein with tailor-made specificities confers particular advantages to elucidate patterns of receptor distribution and expression. The approach described here may have general applications in defining ligand-receptor interactions as well as searching for specific agonists and antagonists of receptor function.

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Activating and inactivating mutations of the human, rat, equine and eel luteinizing hormone/chorionic gonadotropin receptors (LH/CGRs)

  • Min, Kwan-Sik;Byambaragchaa, Munkhzaya;Choi, Seung-Hee;Joo, Hyo-Eun;Kim, Sang-Gwon;Kim, Yean-Ji;Park, Gyeong-Eun
    • Journal of Animal Reproduction and Biotechnology
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    • v.36 no.4
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    • pp.169-174
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    • 2021
  • Mutations in the luteinizing hormone/chorionic gonadotropin receptors (LH/CGRs), representatives of the G protein-coupled receptor family, have been rapidly identified over the last 20 years. This review aims to compare and analyze the data reported the activating and inactivating mutations of the LH/CGRs between human, rat, equine and fish, specifically (Japanese eel Anguilla japonica). Insights obtained through detailed study of these naturally-occurring mutations provide a further update of structure-function relationship of these receptors. Specifically, we present a variety of data on eel LH/CGR. These results provide important information about LH/CGR function in fish and the regulation of mutations of the highly conserved amino acids in glycoprotein hormone receptors.