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Sample records for abnormal glycoproteins identified

  1. Global analysis of glycoproteins identifies markers of endotoxin tolerant monocytes and GPR84 as a modulator of TNFα expression.

    Science.gov (United States)

    Müller, Mario M; Lehmann, Roland; Klassert, Tilman E; Reifenstein, Stella; Conrad, Theresia; Moore, Christoph; Kuhn, Anna; Behnert, Andrea; Guthke, Reinhard; Driesch, Dominik; Slevogt, Hortense

    2017-04-12

    Exposure of human monocytes to lipopolysaccharide (LPS) induces a temporary insensitivity to subsequent LPS challenges, a cellular state called endotoxin tolerance. In this study, we investigated the LPS-induced global glycoprotein expression changes of tolerant human monocytes and THP-1 cells to identify markers and glycoprotein targets capable to modulate the immunosuppressive state. Using hydrazide chemistry and LC-MS/MS analysis, we analyzed glycoprotein expression changes during a 48 h LPS time course. The cellular snapshots at different time points identified 1491 glycoproteins expressed by monocytes and THP-1 cells. Label-free quantitative analysis revealed transient or long-lasting LPS-induced expression changes of secreted or membrane-anchored glycoproteins derived from intracellular membrane coated organelles or from the plasma membrane. Monocytes and THP-1 cells demonstrated marked differences in glycoproteins differentially expressed in the tolerant state. Among the shared differentially expressed glycoproteins G protein-coupled receptor 84 (GPR84) was identified as being capable of modulating pro-inflammatory TNFα mRNA expression in the tolerant cell state when activated with its ligand Decanoic acid.

  2. Identifying the Viral Genes Encoding Envelope Glycoproteins for Differentiation of Cyprinid herpesvirus 3 Isolates

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    Se Chang Park

    2013-01-01

    Full Text Available Cyprinid herpes virus 3 (CyHV-3 diseases have been reported around the world and are associated with high mortalities of koi (Cyprinus carpio. Although little work has been conducted on the molecular analysis of this virus, glycoprotein genes identified in the present study seem to be valuable targets for genetic comparison of this virus. Three envelope glycoprotein genes (ORF25, 65 and 116 of the CyHV-3 isolates from the USA, Israel, Japan and Korea were compared, and interestingly, sequence insertions or deletions were observed in these target regions. In addition, polymorphisms were presented in microsatellite zones from two glycoprotein genes (ORF65 and 116. In phylogenetic tree analysis, the Korean isolate was remarkably distinguished from USA, Israel, Japan isolates. These findings may be suitable for many applications including isolates differentiation and phylogeny studies.

  3. Identifying the Viral Genes Encoding Envelope Glycoproteins for Differentiation of Cyprinid herpesvirus 3 Isolates

    Science.gov (United States)

    Han, Jee Eun; Kim, Ji Hyung; Renault, Tristan; Choresca, Casiano; Shin, Sang Phil; Jun, Jin Woo; Park, Se Chang

    2013-01-01

    Cyprinid herpes virus 3 (CyHV-3) diseases have been reported around the world and are associated with high mortalities of koi (Cyprinus carpio). Although little work has been conducted on the molecular analysis of this virus, glycoprotein genes identified in the present study seem to be valuable targets for genetic comparison of this virus. Three envelope glycoprotein genes (ORF25, 65 and 116) of the CyHV-3 isolates from the USA, Israel, Japan and Korea were compared, and interestingly, sequence insertions or deletions were observed in these target regions. In addition, polymorphisms were presented in microsatellite zones from two glycoprotein genes (ORF65 and 116). In phylogenetic tree analysis, the Korean isolate was remarkably distinguished from USA, Israel, Japan isolates. These findings may be suitable for many applications including isolates differentiation and phylogeny studies. PMID:23435236

  4. A novel PET imaging protocol identifies seizure-induced regional overactivity of P-glycoprotein at the blood-brain barrier

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    Bankstahl, Jens P.; Bankstahl, Marion; Kuntner, Claudia; Stanek, Johann; Wanek, Thomas; Meier, Martin; Ding, Xiao-Qi; Müller, Markus; Langer, Oliver; Löscher, Wolfgang

    2013-01-01

    About one third of epilepsy patients are pharmacoresistant. Overexpression of P-glycoprotein and other multidrug transporters at the blood-brain barrier is thought to play an important role in drug-refractory epilepsy. Thus, quantification of regionally different P-glycoprotein activity in the brain in vivo is essential to identify P-glycoprotein overactivity as the relevant mechanism for drug-resistance in an individual patient. Using the radiolabeled P-glycoprotein substrate (R)-[11C]verapamil and different doses of co-administered tariquidar, which is an inhibitor of P-glycoprotein, we evaluated whether small-animal positron emission tomography (PET) can quantify regional changes in transporter function in the rat brain at baseline and 48 h after a pilocarpine-induced status epilepticus. P-glycoprotein expression was additionally quantified by immunohistochemistry. To reveal putative seizure-induced changes in blood-brain barrier integrity, we performed gadolinium-enhanced magnetic resonance scans on a 7.0 Tesla small-animal scanner. Before P-glycoprotein modulation, brain uptake of (R)-[11C]verapamil was low in all regions investigated in control and post-status epilepticus rats. After administration of 3 mg/kg tariquidar, which inhibits P-glycoprotein only partially, we observed increased regional differentiation in brain activity uptake in post-status epilepticus versus control rats, which diminished after maximal P-glycoprotein inhibition. Regional increases in the efflux rate constant k2, but not in distribution volume VT or influx rate constant K1, correlated significantly with increases in P-glycoprotein expression measured by immunohistochemistry. This imaging protocol proves to be suitable to detect seizure-induced regional changes in P-glycoprotein activity and is readily applicable to humans, with the aim to detect relevant mechanisms of pharmacoresistance in epilepsy in vivo. PMID:21677164

  5. Development of glycoprotein capture-based label-free method for the high-throughput screening of differential glycoproteins in hepatocellular carcinoma.

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    Chen, Rui; Tan, Yexiong; Wang, Min; Wang, Fangjun; Yao, Zhenzhen; Dong, Liwei; Ye, Mingliang; Wang, Hongyang; Zou, Hanfa

    2011-07-01

    A robust, reproducible, and high throughput method was developed for the relative quantitative analysis of glycoprotein abundances in human serum. Instead of quantifying glycoproteins by glycopeptides in conventional quantitative glycoproteomics, glycoproteins were quantified by nonglycosylated peptides derived from the glycoprotein digest, which consists of the capture of glycoproteins in serum samples and the release of nonglycopeptides by trypsin digestion of captured glycoproteins followed by two-dimensional liquid chromatography-tandem MS analysis of released peptides. Protein quantification was achieved by comparing the spectrum counts of identified nonglycosylated peptides of glycoproteins between different samples. This method was demonstrated to have almost the same specificity and sensitivity in glycoproteins quantification as capture at glycopeptides level. The differential abundance of proteins present at as low as nanogram per milliliter levels was quantified with high confidence. The established method was applied to the analysis of human serum samples from healthy people and patients with hepatocellular carcinoma (HCC) to screen differential glycoproteins in HCC. Thirty eight glycoproteins were found with substantial concentration changes between normal and HCC serum samples, including α-fetoprotein, the only clinically used marker for HCC diagnosis. The abundance changes of three glycoproteins, i.e. galectin-3 binding protein, insulin-like growth factor binding protein 3, and thrombospondin 1, which were associated with the development of HCC, were further confirmed by enzyme-linked immunosorbent assay. In conclusion, the developed method was an effective approach to quantitatively analyze glycoproteins in human serum and could be further applied in the biomarker discovery for HCC and other cancers.

  6. Dystroglycan and muscular dystrophies related to the dystrophin-glycoprotein complex.

    Science.gov (United States)

    Sciandra, Francesca; Bozzi, Manuela; Bianchi, Marzia; Pavoni, Ernesto; Giardina, Bruno; Brancaccio, Andrea

    2003-01-01

    Dystroglycan (DG) is an adhesion molecule composed of two subunits, alpha and beta, that are produced by the post-translational cleavage of a single precursor molecule. DG is a pivotal component of the dystrophin-glycoprotein complex (DGC), which connects the extracellular matrix to the cytoskeleton in skeletal muscle and many other tissues. Some muscular dystrophies are caused by mutations of DGC components, such as dystrophin, sarcoglycan or laminin-2, or also of DGC-associated molecules, such as caveolin-3. DG-null mice died during early embriogenesis and no neuromuscular diseases directly associated to genetic abnormalities of DG were identified so far. However, DG plays a crucial role for muscle integrity since its targeting at the sarcolemma is often perturbed in DGC-related neuromuscular disorders.

  7. Ammonia transport in the kidney by Rhesus glycoproteins

    Science.gov (United States)

    Verlander, Jill W.

    2014-01-01

    Renal ammonia metabolism is a fundamental element of acid-base homeostasis, comprising a major component of both basal and physiologically altered renal net acid excretion. Over the past several years, a fundamental change in our understanding of the mechanisms of renal epithelial cell ammonia transport has occurred, replacing the previous model which was based upon diffusion equilibrium for NH3 and trapping of NH4+ with a new model in which specific and regulated transport of both NH3 and NH4+ across renal epithelial cell membranes via specific membrane proteins is required for normal ammonia metabolism. A major advance has been the recognition that members of a recently recognized transporter family, the Rhesus glycoprotein family, mediate critical roles in renal and extrarenal ammonia transport. The erythroid-specific Rhesus glycoprotein, Rh A Glycoprotein (Rhag), was the first Rhesus glycoprotein recognized as an ammonia-specific transporter. Subsequently, the nonerythroid Rh glycoproteins, Rh B Glycoprotein (Rhbg) and Rh C Glycoprotein (Rhcg), were cloned and identified as ammonia transporters. They are expressed in specific cell populations and membrane domains in distal renal epithelial cells, where they facilitate ammonia secretion. In this review, we discuss the distribution of Rhbg and Rhcg in the kidney, the regulation of their expression and activity in physiological disturbances, the effects of genetic deletion on renal ammonia metabolism, and the molecular mechanisms of Rh glycoprotein-mediated ammonia transport. PMID:24647713

  8. Analytical Pipeline for Discovery and Verification of Glycoproteins from Plasma-Derived Extracellular Vesicles as Breast Cancer Biomarkers.

    Science.gov (United States)

    Chen, I-Hsuan; Aguilar, Hillary Andaluz; Paez Paez, J Sebastian; Wu, Xiaofeng; Pan, Li; Wendt, Michael K; Iliuk, Anton B; Zhang, Ying; Tao, W Andy

    2018-05-15

    Glycoproteins comprise more than half of current FDA-approved protein cancer markers, but the development of new glycoproteins as disease biomarkers has been stagnant. Here we present a pipeline to develop glycoproteins from extracellular vesicles (EVs) through integrating quantitative glycoproteomics with a novel reverse phase glycoprotein array and then apply it to identify novel biomarkers for breast cancer. EV glycoproteomics show promise in circumventing the problems plaguing current serum/plasma glycoproteomics and allowed us to identify hundreds of glycoproteins that have not been identified in blood. We identified 1,453 unique glycopeptides representing 556 glycoproteins in EVs, among which 20 were verified significantly higher in individual breast cancer patients. We further applied a novel glyco-specific reverse phase protein array to quantify a subset of the candidates. Together, this study demonstrates the great potential of this integrated pipeline for biomarker discovery.

  9. Defining glycoprotein cancer biomarkers by MS in conjunction with glycoprotein enrichment.

    Science.gov (United States)

    Song, Ehwang; Mechref, Yehia

    2015-01-01

    Protein glycosylation is an important and common post-translational modification. More than 50% of human proteins are believed to be glycosylated to modulate the functionality of proteins. Aberrant glycosylation has been correlated to several diseases, such as inflammatory skin diseases, diabetes mellitus, cardiovascular disorders, rheumatoid arthritis, Alzheimer's and prion diseases, and cancer. Many approved cancer biomarkers are glycoproteins which are not highly abundant proteins. Therefore, effective qualitative and quantitative assessment of glycoproteins entails enrichment methods. This chapter summarizes glycoprotein enrichment methods, including lectin affinity, immunoaffinity, hydrazide chemistry, hydrophilic interaction liquid chromatography, and click chemistry. The use of these enrichment approaches in assessing the qualitative and quantitative changes of glycoproteins in different types of cancers are presented and discussed. This chapter highlights the importance of glycoprotein enrichment techniques for the identification and characterization of new reliable cancer biomarkers.

  10. Global identification of prokaryotic glycoproteins based on an Escherichia coli proteome microarray.

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    Zong-Xiu Wang

    Full Text Available Glycosylation is one of the most abundant protein posttranslational modifications. Protein glycosylation plays important roles not only in eukaryotes but also in prokaryotes. To further understand the roles of protein glycosylation in prokaryotes, we developed a lectin binding assay to screen glycoproteins on an Escherichia coli proteome microarray containing 4,256 affinity-purified E.coli proteins. Twenty-three E.coli proteins that bound Wheat-Germ Agglutinin (WGA were identified. PANTHER protein classification analysis showed that these glycoprotein candidates were highly enriched in metabolic process and catalytic activity classes. One sub-network centered on deoxyribonuclease I (sbcB was identified. Bioinformatics analysis suggests that prokaryotic protein glycosylation may play roles in nucleotide and nucleic acid metabolism. Fifteen of the 23 glycoprotein candidates were validated by lectin (WGA staining, thereby increasing the number of validated E. coli glycoproteins from 3 to 18. By cataloguing glycoproteins in E.coli, our study greatly extends our understanding of protein glycosylation in prokaryotes.

  11. Glycoprotein on cell surfaces

    International Nuclear Information System (INIS)

    Muramatsu, T.

    1975-01-01

    There are conjugated polysaccharides in cell membranes and outside of animal cells, and they play important role in the control of cell behavior. In this paper, the studies on the glycoprotein on cell surfaces are reported. It was found that the glycoprotein on cell surfaces have both N-glycoside type and O-glycoside type saccharic chains. Therefore it can be concluded that the basic structure of the saccharic chains in the glycoprotein on cell surfaces is similar to that of blood serum and body fluid. The main glycoprotein in the membranes of red blood corpuscles has been studied most in detail, and it also has both types of saccharic chains. The glycoprotein in liver cell membranes was found to have only the saccharic chains of acid type and to be in different pattern from that in endoplasmic reticula and nuclear membranes, which also has the saccharic chains of neutral type. The structure of the saccharic chains of H-2 antigen, i.e. the peculiar glycoprotein on the surfaces of lymph system cells, has been studied, and it is similar to the saccharic chains of glycoprotein in blood serum. The saccharic chain structures of H-2 antigen and TL antigen are different. TL, H-2 (D), Lna and H-2 (K) are the glycoprotein on cell surfaces, and are independent molecules. The analysis of the saccharic chain patterns on cell surfaces was carried out, and it was shown that the acid type saccharic chains were similar to those of ordinary glycoprotein, because the enzyme of pneumococci hydrolyzed most of the acid type saccharic chains. The change of the saccharic chain patterns of glycoprotein on cell surfaces owing to canceration and multiplication is complex matter. (Kako, I.)

  12. Low rate doses effects of gamma radiation on glycoproteins of transmembrane junctions in fibroblasts

    International Nuclear Information System (INIS)

    Bringas, J.E.; Caceres, J.L.

    1996-01-01

    Glycoproteins of trans-membrane junctions are molecules that help to bind cells with the extracellular matrix. Integrins are the most important trans-membrane molecules among others. The damage of gamma radiation on those proteins could be an important early event that causes membrane abnormalities which may lead to cell malfunction and cancer induced by radiation due to cell dissociation. Randomized blocks with 3 repetitions of mouse embryo fibroblast cultures, were irradiated with Cobalt-60 gamma rays, during 20 days. Biological damage to glycoproteins and integrins was evaluated by cellular growth and fibroblast proliferative capacity. Integrins damage was studied by isolation by column immunoaffinity chromatography migrated on SDS-Page under reducing and non reducing conditions, and inhibition of integrins extracellular matrix adhesion by monoclonal antibodies effect. The dose/rate (0.05 Gy/day-0.2 Gy/day) of gamma given to cells did not show damage evidence on glycoproteins and integrins. If damage happened, it was repaired by cells very soon, was delayed by continuous cellular division or by glycoproteins characteristic of being multiple extracellular ligatures. Bio effects became more evident with an irradiation time greater than 20 days or a high dose/rate. (authors). 6 refs

  13. Three-Dimensionally Functionalized Reverse Phase Glycoprotein Array for Cancer Biomarker Discovery and Validation.

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    Pan, Li; Aguilar, Hillary Andaluz; Wang, Linna; Iliuk, Anton; Tao, W Andy

    2016-11-30

    Glycoproteins have vast structural diversity that plays an important role in many biological processes and have great potential as disease biomarkers. Here, we report a novel functionalized reverse phase protein array (RPPA), termed polymer-based reverse phase glycoprotein array (polyGPA), to capture and profile glycoproteomes specifically, and validate glycoproteins. Nitrocellulose membrane functionalized with globular hydroxyaminodendrimers was used to covalently capture preoxidized glycans on glycoproteins from complex protein samples such as biofluids. The captured glycoproteins were subsequently detected using the same validated antibodies as in RPPA. We demonstrated the outstanding specificity, sensitivity, and quantitative capabilities of polyGPA by capturing and detecting purified as well as endogenous α-1-acid glycoprotein (AGP) in human plasma. We further applied quantitative N-glycoproteomics and the strategy to validate a panel of glycoproteins identified as potential biomarkers for bladder cancer by analyzing urine glycoproteins from bladder cancer patients or matched healthy individuals.

  14. Glycoproteins and protein glycations identified in barley grain and malt by 2D-HPLC

    Czech Academy of Sciences Publication Activity Database

    Žídková, Jitka; Petry-Podgorska, Inga; Laštovičková, Markéta; Bobálová, Janette

    2013-01-01

    Roč. 20, č. 1 (2013), s. 43 ISSN 1211-5894. [Discussion in Structural Molecular Biology /11./. 14.03.2013-16.03.2013, Nové Hrady] R&D Projects: GA ČR(CZ) GPP503/12/P395 Institutional support: RVO:68081715 Keywords : barley grain * glycoproteins * 2D-HPLC * MS/MS Subject RIV: CB - Analytical Chemistry, Separation

  15. Hidden chromosomal abnormalities in pleuropulmonary blastomas identified by multiplex FISH

    International Nuclear Information System (INIS)

    Quilichini, Benoit; Andre, Nicolas; Bouvier, Corinne; Chrestian, Marie-Anne; Rome, Angelique; Intagliata, Dominique; Coze, Carole; Lena, Gabriel; Zattara, Helene

    2006-01-01

    Pleuropulmonary blastoma (PPB) is a rare childhood dysontogenetic intrathoracic neoplasm associated with an unfavourable clinical behaviour. We report pathological and cytogenetic findings in two cases of PPB at initial diagnosis and recurrence. Both tumors were classified as type III pneumoblastoma and histological findings were similar at diagnosis and relapse. In both cases, conventional cytogenetic techniques revealed complex numerical and structural chromosomal abnormalities. Molecular cytogenetic analysis (interphase/metaphase FISH and multicolor FISH) identified accurately chromosomal aberrations. In one case, TP53 gene deletion was detected on metaphase FISH. To date, only few cytogenetic data have been published about PPB. The PPB genetic profile remains to be established and compared to others embryonal neoplasia. Our cytogenetic data are discussed reviewing cytogenetics PPBs published cases, illustrating the contribution of multicolor FISH in order to identify pathogenetically important recurrent aberrations in PPB

  16. Recent Progress in Electrochemical Biosensors for Glycoproteins

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    Uichi Akiba

    2016-12-01

    Full Text Available This review provides an overview of recent progress in the development of electrochemical biosensors for glycoproteins. Electrochemical glycoprotein sensors are constructed by combining metal and carbon electrodes with glycoprotein-selective binding elements including antibodies, lectin, phenylboronic acid and molecularly imprinted polymers. A recent trend in the preparation of glycoprotein sensors is the successful use of nanomaterials such as graphene, carbon nanotube, and metal nanoparticles. These nanomaterials are extremely useful for improving the sensitivity of glycoprotein sensors. This review focuses mainly on the protocols for the preparation of glycoprotein sensors and the materials used. Recent improvements in glycoprotein sensors are discussed by grouping the sensors into several categories based on the materials used as recognition elements.

  17. A comparison of visual and quantitative methods to identify interstitial lung abnormalities

    OpenAIRE

    Kliment, Corrine R.; Araki, Tetsuro; Doyle, Tracy J.; Gao, Wei; Dupuis, Jos?e; Latourelle, Jeanne C.; Zazueta, Oscar E.; Fernandez, Isis E.; Nishino, Mizuki; Okajima, Yuka; Ross, James C.; Est?par, Ra?l San Jos?; Diaz, Alejandro A.; Lederer, David J.; Schwartz, David A.

    2015-01-01

    Background: Evidence suggests that individuals with interstitial lung abnormalities (ILA) on a chest computed tomogram (CT) may have an increased risk to develop a clinically significant interstitial lung disease (ILD). Although methods used to identify individuals with ILA on chest CT have included both automated quantitative and qualitative visual inspection methods, there has been not direct comparison between these two methods. To investigate this relationship, we created lung density met...

  18. Upper airway alterations/abnormalities in a case series of obstructive sleep apnea patients identified with cone-beam CT

    International Nuclear Information System (INIS)

    Shigeta, Y.; Shintaku, W.H.; Clark, G.T.; Enciso, R.; Ogawa, T.

    2007-01-01

    There are many factors that influence the configuration of the upper airway and may contribute to the development of obstructive sleep apnea (OSA). This paper presents a series of 12 consecutive OSA cases where various upper airway alteration/abnormalities were identified using 3D anatomic reconstructions generated from cone-beam CT (CBCT) images. Some cases exhibited more than one type of abnormality and below we describe each of the six types identified with CBCT in this case series. (orig.)

  19. Upper airway alterations/abnormalities in a case series of obstructive sleep apnea patients identified with cone-beam CT

    Energy Technology Data Exchange (ETDEWEB)

    Shigeta, Y; Shintaku, W H; Clark, G T [Orofacial Pain/Oral Medicine Center, Div. of Diagnostic Sciences, School of Dentistry, Univ. of Southern California, Los Angeles, CA (United States); Enciso, R [Div. of Craniofacial Sciences and Therapeutics, School of Dentistry, Univ. of Southern California, Los Angeles, CA (United States); Ogawa, T [Dept. of Fixed Prosthodontic Dentistry, Tsurumi Univ., School of Dental Medicine, Tsurumi (Japan)

    2007-06-15

    There are many factors that influence the configuration of the upper airway and may contribute to the development of obstructive sleep apnea (OSA). This paper presents a series of 12 consecutive OSA cases where various upper airway alteration/abnormalities were identified using 3D anatomic reconstructions generated from cone-beam CT (CBCT) images. Some cases exhibited more than one type of abnormality and below we describe each of the six types identified with CBCT in this case series. (orig.)

  20. Cell wall O-glycoproteins and N-glycoproteins: biosynthesis and some functional aspects.

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    Eric eNguema-Ona

    2014-10-01

    Full Text Available Cell wall O-glycoproteins and N-glycoproteins are two types of glycomolecules whose glycans are structurally complex. They are both assembled and modified within the endomembrane system, i.e., the endoplasmic reticulum (ER and the Golgi apparatus, before their transport to their final locations within or outside the cell. In contrast to extensin, the O-glycan chains of arabinogalactan proteins are highly heterogeneous consisting mostly of (i a short oligo-arabinoside chain of three to four residues, and (ii a larger -1,3-linked galactan backbone with -1,6-linked side chains containing galactose, arabinose and, often, fucose, rhamnose or glucuronic acid. The fine structure of arabinogalactan chains varies between, and within plant species, and is important for the functional activities of the glycoproteins. With regards to N-glycans, ER-synthesizing events are highly conserved in all eukaryotes studied so far since they are essential for efficient protein folding. In contrast, evolutionary adaptation of N-glycan processing in the Golgi apparatus has given rise to a variety of organism-specific complex structures. Therefore, plant complex-type N-glycans contain specific glyco-epitopes such as core 1,2-xylose, core 1,3-fucose residues and Lewisa substitutions on the terminal position of the antenna. Like O-glycans, N-glycans of proteins are essential for their stability and function. Mutants affected in the glycan metabolic pathways have provided valuable information on the role of N-/O-glycoproteins in the control of growth, morphogenesis and adaptation to biotic and abiotic stresses. With regards to O-glycoproteins only extensin and arabinogalactan proteins are considered herein. The biosynthesis of these glycoproteins and functional aspects are presented and discussed in this review.

  1. A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and hemopexin: Implications for small molecule compound-mediated neuroprotection.

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    Takuya Kanno

    Full Text Available Therapeutic agents to the central nervous system (CNS need to be efficiently delivered to the target site of action at appropriate therapeutic levels. However, a limited number of effective drugs for the treatment of neurological diseases has been developed thus far. Further, the pharmacological mechanisms by which such therapeutic agents can protect neurons from cell death have not been fully understood. We have previously reported the novel small-molecule compound, 2-[mesityl(methylamino]-N-[4-(pyridin-2-yl-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316, as a unique neuroprotectant against oxidative injury and a highly promising remedy for the treatment of amyotrophic lateral sclerosis (ALS. One of the remarkable characteristics of WN1316 is that its efficacious doses in ALS mouse models are much less than those against oxidative injury in cultured human neuronal cells. It is also noted that the WN1316 cytoprotective activity observed in cultured cells is totally dependent upon the addition of fetal bovine serum in culture medium. These findings led us to postulate some serum factors being tightly linked to the WN1316 efficacy. In this study, we sieved through fetal bovine serum proteins and identified two N-linked glycoproteins, alpha-2-HS-glycoprotein (AHSG and hemopexin (HPX, requisites to exert the WN1316 cytoprotective activity against oxidative injury in neuronal cells in vitro. Notably, the removal of glycan chains from these molecules did not affect the WN1316 cytoprotective activity. Thus, two glycoproteins, AHSG and HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316, showing a concrete evidence for the novel glycan-independent function of serum glycoproteins in neuroprotective drug efficacy.

  2. Characterization of gel-separated glycoproteins using two-step proteolytic digestion combined with sequential microcolumns and mass spectrometry

    DEFF Research Database (Denmark)

    Larsen, Martin Røssel; Højrup, Peter; Roepstorff, Peter

    2005-01-01

    present a new technique that allows characterization of low amounts of glycoproteins separated by gel electrophoresis. The method takes advantage of sequential specific and nonspecific enzymatic treatment followed by selective purification and characterization of the glycopeptides using graphite powder......Protein glycosylation can be vital for changing the function or physiochemical properties of a protein. Abnormal glycosylation can lead to protein malfunction, resulting in severe diseases. Therefore, it is important to develop techniques for characterization of such modifications in proteins...... at a sensitivity level comparable with state-of-the-art proteomics. Whereas techniques exist for characterization of high abundance glycoproteins, no single method is presently capable of providing information on both site occupancy and glycan structure on a single band excised from an electrophoretic gel. We...

  3. Identification, isolation, and N-terminal sequencing of style glycoproteins associated with self-incompatibility in Nicotiana alata.

    Science.gov (United States)

    Jahnen, W; Batterham, M P; Clarke, A E; Moritz, R L; Simpson, R J

    1989-05-01

    S-Gene-associated glycoproteins (S-glycoproteins) from styles of Nicotiana alata, identified by non-equilibrium two-dimensional electrophoresis, were purified by cation exchange fast protein liquid chromatography with yields of 0.5 to 8 micrograms of protein per style, depending on the S-genotype of the plant. The method relies on the highly basic nature of the S-glycoproteins. The elution profiles of the different S-glycoproteins from the fast protein liquid chromatography column were characteristic of each S-glycoprotein, and could be used to establish the S-genotype of plants in outbreeding populations. In all cases, the S-genotype predicted from the style protein profile corresponded to that predicted from DNA gel blot analysis using S-allele-specific DNA probes and to that established by conventional breeding tests. Amino-terminal sequences of five purified S-glycoproteins showed a high degree of homology with the previously published sequences of N. alata and Lycopersicon esculentum S-glycoproteins.

  4. Use of λgt11 to isolate genes for two pseudorabies virus glycoproteins with homology to herpes simplex virus and varicella-zoster virus glycoproteins

    International Nuclear Information System (INIS)

    Petrovskis, E.A.; Timmins, J.G.; Post, L.E.

    1986-01-01

    A library of pseudorabies virus (PRV) DNA fragments was constructed in the expression cloning vector λgt11. The library was screened with antisera which reacted with mixtures of PRV proteins to isolate recombinant bacteriophages expressing PRV proteins. By the nature of the λgt11 vector, the cloned proteins were expressed in Escherichia coli as β-galactosidase fusion proteins. The fusion proteins from 35 of these phages were purified and injected into mice to raise antisera. The antisera were screened by several different assays, including immunoprecipitation of [ 14 C]glucosamine-labeled PRV proteins. This method identified phages expressing three different PRV glycoproteins: the secreted glycoprotein, gX; gI; and a glycoprotein that had not been previously identified, which we designate gp63. The gp63 and gI genes map adjacent to each other in the small unique region of the PRV genome. The DNA sequence was determined for the region of the genome encoding gp63 and gI. It was found that gp63 has a region of homology with a herpes simplex virus type 1 (HSV-1) protein, encoded by US7, and also with varicella-zoster virus (VZV) gpIV. The gI protein sequence has a region of homology with HSV-1 gE and VZV gpI. It is concluded that PRV, HSV, and VZV all have a cluster of homologous glycoprotein genes in the small unique components of their genomes and that the organization of these genes is conserved

  5. Dimers of beta 2-glycoprotein I mimic the in vitro effects of beta 2-glycoprotein I-anti-beta 2-glycoprotein I antibody complexes

    NARCIS (Netherlands)

    Lutters, B. C.; Meijers, J. C.; Derksen, R. H.; Arnout, J.; de Groot, P. G.

    2001-01-01

    Anti-beta(2)-glycoprotein I antibodies are thought to cause lupus anticoagulant activity by forming bivalent complexes with beta(2)-glycoprotein I (beta(2)GPI). To test this hypothesis, chimeric fusion proteins were constructed of the dimerization domain (apple 4) of factor XI and beta(2)GPI. Both a

  6. HLA-A*0201-restricted CD8+ cytotoxic T lymphocyte epitopes identified from herpes simplex virus glycoprotein D

    DEFF Research Database (Denmark)

    Chentoufi, Aziz Alami; Zhang, Xiuli; Lamberth, Kasper

    2008-01-01

    Evidence obtained from both animal models and humans suggests that T cells specific for HSV-1 and HSV-2 glycoprotein D (gD) contribute to protective immunity against herpes infection. However, knowledge of gD-specific human T cell responses is limited to CD4+ T cell epitopes, with no CD8+ T cell ...... following ocular or genital infection with either HSV-1 or HSV-2. The functional gD CD8+ T cell epitopes described herein are potentially important components of clinical immunotherapeutic and immunoprophylactic herpes vaccines.......Evidence obtained from both animal models and humans suggests that T cells specific for HSV-1 and HSV-2 glycoprotein D (gD) contribute to protective immunity against herpes infection. However, knowledge of gD-specific human T cell responses is limited to CD4+ T cell epitopes, with no CD8+ T cell...

  7. Glycoproteins and sialyl transferase of human B lymphoblastoid cell lines

    International Nuclear Information System (INIS)

    Lui, S.W.L.; Ng, M.H.

    1980-01-01

    We used two radiolabeling methods to study glycoproteins on the surface of lymphoblastoid cells. One of the methods affects tritiation of residues which are oxidized with galactose oxidase and the other causes tritiation of neuraminic acid residues. This approach was shown to allow a better resolution of cell surface glycoproteins than if either method were used alone. Glycoproteins of B 1 - 19 cells which harbor the Epstein-Barr virus genomes were compared with those of its parental cell line, BJAB, which does not harbor the viral genomes. These studies did not reveal a unique viral protein. A 28,000 mol. wt. glycoprotein was found to be the most prominent neuraminic acidlabeled product of B 1 - 19 cells and also of the two other cell lines, Raji and Ly38, which harbor the EBV genomes. A similar molecular weight species from BJAB cells identified by galactose oxidase labeling might be deficient in neuraminic acid residues as it was poorly labeled by the periodate oxidation method. The neuraminic acid content and level of sialyl transferase of BJAB cells were found to be lower than those of the other cell lines studied. (auth.)

  8. Comparative Profiling of Triple-Negative Breast Carcinomas Tissue Glycoproteome by Sequential Purification of Glycoproteins and Stable Isotope Labeling

    Directory of Open Access Journals (Sweden)

    Xiang Chen

    2016-01-01

    Full Text Available Background: Women with triple negative breast cancers (TNBCs have a poor prognosis due to lack of suitable targeted therapies. Changes in the protein glycosylation are increasingly being recognized as an important modification associated with cancer etiology. Methods: In an attempt to identify TNBC biomarkers with greater diagnostic and prognostic capabilities, hydrazide- based chemistry method combined with LC-MS/MS were used to purify and identify N-linked glycopeptides or glycoproteins of tissues from TNBC patients. Results: A total of 550 unique N-linked glycoproteins were identified, among these proteins, 72 unique N-linked glycoproteins were significantly regulated in tumor tissues, of which 56 proteins were upregulated and 16 proteins were downregulated. To assess the validity of the results, three selected proteins including Vascular endothelial growth factor receptor 1, Insulin receptor, Tissue factor pathway inhibitor were selected for western blot analysis, and these proteins were found as potential biomarkers of TNBC. The top three pathways of differentially expressed glycoproteins participated in were caveolar-mediated endocytosis signaling, agrin interactions at neuromuscular junction and LXR/RXR activation. Conclusion: This work provides potential glycoprotein markers to function as a novel tissue-based biomarker for TNBC.

  9. Colonic epithelium is diffusely abnormal in ulcerative colitis and colorectal cancer.

    OpenAIRE

    Gibson, P; Rosella, O; Nov, R; Young, G

    1995-01-01

    The hypothesis that the colonic epithelium is diffusely abnormal in ulcerative colitis was examined by comparing disease related responses in expression of markers of differentiation by colonic crypt cells to culture with and without butyrate. Cells were isolated from patients with normal colon (15), cancer (24), ulcerative colitis (19), or Crohn's disease (16). Alkaline phosphatase activities were measured in cell homogenates and the rate of glycoprotein synthesis assessed at the end of 24 h...

  10. Glycoprotein biosynthesis by human normal platelets

    International Nuclear Information System (INIS)

    Rodriguez, P.; Bello, O.; Apitz-Castro, R.

    1987-01-01

    Incorporation of radioactive Man, Gal, Fuc, Glc-N, and NANA into washed human normal platelets and endogenous glycoproteins has been found. Both parameters were time dependent. Analysis of hydrolyzed labeled glycoproteins by paper chromatography revealed that the radioactive monosaccharide incubated with the platelets had not been converted into other sugars. Acid hydrolysis demonstrates the presence of a glycosidic linkage. All the effort directed to the demonstration of the existence of a lipid-sugar intermediate in intact human platelets yielded negative results for Man and Glc-N used as precursors. The incorporation of these sugars into glycoproteins is insensitive to bacitracin, suggesting no involvement of lipid-linked saccharides in the synthesis of glycoproteins in human blood platelets. The absence of inhibition of the glycosylation process in the presence of cycloheximide suggests that the sugars are added to proteins present in the intact platelets. These results support the contention that glycoprotein biosynthesis in human blood platelets observed under our experimental conditions is effected through direct sugar nucleotide glycosylation

  11. The peanut lectin-binding glycoproteins of human epidermal keratinocytes

    International Nuclear Information System (INIS)

    Morrison, A.I.; Keeble, S.; Watt, F.M.

    1988-01-01

    The peanut lectin (PNA) is known to bind more strongly to keratinocytes that are undergoing terminal differentiation than to proliferating keratinocytes. In order to investigate the significance of this change in cell-surface carbohydrate authors have identified the PNA-binding glycoproteins of cultured human keratinocytes and antibodies against them. Two heavily glycosylated bands of 110 and 250 kDa were resolved by PAGE of [ 14 C]galactose- or [ 14 C]mannose- and [ 14 C]glucosamine-labeled cell extracts eluted with galactose from PNA affinity columns. The higher molecular weight band was also detected on PNA blots of unlabeled cell extracts transferred to nitrocellulose. Both bands were sensitive to pronase digestion, but only the 250-kDa band was digested with trypsin. A rabbit antiserum that we prepared (anti-PNA-gp) immunoprecipitated both bands from cell extracts. In contrast to PNA, anti-PNA-gp bound equally to proliferating and terminally differentiating cells, indicating that some epitope(s) of the PNA-binding glycoproteins is present on the cell surface prior to terminal differentiation. When keratinocytes grown as a monolayer in low-calcium medium were switched to medium containing 2 mM calcium ions in order to induce desmosome formation and stratification, there was a dramatic redistribution of the PNA-binding glycoproteins, which became concentrated at the boundaries between cells. This may suggest a role for the glycoproteins in cell-cell interactions during stratification

  12. Studies on pregnancy associated alpha2-glycoprotein (alpha2-PAG) in screening of malignant tumors

    International Nuclear Information System (INIS)

    Akiyama, Mitoshi; Hoshiga, Noriko; Kobuke, Kyoko; Kyoizume, Seishi; Hakoda, Masayuki

    1984-01-01

    The measurement of α 2 -glycoprotein (α 2 -PAG) by enzyme immunoassay (EIA) method was established and its clinical significance was studied. The normal value of serum α 2 -PAG was 2.7+-3.7 μg/ml in men and 8.7+-9.8 μg/ml in women. However, significant difference was observed according to the presence of pregnancy history. α 2 -PAG was significantly higher in male patients with lung cancer (a mean of 18.2+-18.6 μg/ml or other cancers (a mean of 12.4+-12.8 μg/ml) than in norm al male people. One of the tumor markers, such as α 2 -PAG, CEA, AFP and ferritin, or more showed an abnormal value in many of the patients with malignant tumors. One marker or more were also abnormal in 128 of 428 atomic bomb survivors (29.9%), of whom 23 (18%) had abnormal values in two or more markers. (Namekawa, K.)

  13. The haemagglutination activity of equine herpesvirus type 1 glycoprotein C.

    Science.gov (United States)

    Andoh, Kiyohiko; Hattori, Shiho; Mahmoud, Hassan Y A H; Takasugi, Maaya; Shimoda, Hiroshi; Bannai, Hiroshi; Tsujimura, Koji; Matsumura, Tomio; Kondo, Takashi; Kirisawa, Rikio; Mochizuki, Masami; Maeda, Ken

    2015-01-02

    Equine herpesvirus type 1 (EHV-1) has haemagglutination (HA) activity toward equine red blood cells (RBCs), but the identity of its haemagglutinin is unknown. To identify the haemagglutinin of EHV-1, the major glycoproteins of EHV-1 were expressed in 293T cells, and the cells or cell lysates were mixed with equine RBCs. The results showed that only EHV-1 glycoprotein C (gC)-producing cells adsorbed equine RBCs, and that the lysate of EHV-1 gC-expressing cells agglutinated equine RBCs. EHV-1 lacking gC did not show HA activity. HA activity was inhibited by monoclonal antibodies (MAbs) specific for gC, but not by antibodies directed against other glycoproteins. In addition, HA activity was not inhibited by the addition of heparin. These results indicate that EHV-1 gC can bind equine RBCs irrespective of heparin, in contrast to other herpesvirus gC proteins. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Cancer Biomarker Discovery: Lectin-Based Strategies Targeting Glycoproteins

    Directory of Open Access Journals (Sweden)

    David Clark

    2012-01-01

    Full Text Available Biomarker discovery can identify molecular markers in various cancers that can be used for detection, screening, diagnosis, and monitoring of disease progression. Lectin-affinity is a technique that can be used for the enrichment of glycoproteins from a complex sample, facilitating the discovery of novel cancer biomarkers associated with a disease state.

  15. Identifying decreased peristalsis of abnormal small bowel segments in Crohn's disease using cine MR enterography: the frozen bowel sign.

    Science.gov (United States)

    Guglielmo, Flavius F; Mitchell, Donald G; O'Kane, Patrick L; Deshmukh, Sandeep P; Roth, Christopher G; Burach, Ilene; Burns, Aaron; Dulka, Susan; Parker, Laurence

    2015-06-01

    The purpose of this study was to evaluate whether affected bowel in Crohn's disease patients can be identified by observing decreased peristalsis (frozen bowel sign) using cine balanced steady-state free precession (cine BSSFP) images. 5 radiologists independently reviewed cine BSSFP sequences from randomized MR Enterography (MRE) exams for 30 normal and 30 Crohn's disease patients, graded overall small bowel peristalsis from slowest to fastest, and graded peristalsis for the most abnormal small bowel segment. Sensitivity and specificity of the frozen bowel sign for diagnosing Crohn's disease were calculated. T tests of the peristalsis difference between abnormal segments and overall small bowel were conducted. For 5 readers, the sensitivity and specificity of cine BSSFP of the frozen bowel sign for diagnosing Crohn's disease ranged from 70% to 100% and 87% to 100%, respectively. There were significant differences in peristalsis between abnormal small bowel segments and the overall small bowel for Crohn's patients, but not in the overall small bowel between normal-MRE patients and Crohn's disease patients. Abnormal Crohn's small bowel segments have significantly decreased peristalsis compared to normal small bowel, which can be identified using cine BSSFP sequences as the frozen bowel sign.

  16. Solubilization of glycoproteins of envelope viruses by detergents

    International Nuclear Information System (INIS)

    Berezin, V.E.; Zaides, V.M.; Artamsnov, A.F.; Isaeva, E.S.; Zhdanov, V.M.

    1986-01-01

    The action of a number of known ionic and nonionic detergents, as well as the new nonionic detergent MESK, on envelope viruses was investigated. It was shown that the nonionic detergents MESK, Triton X-100, and octyl-β-D-glucopyranoside selectively solubilize the outer glycoproteins of the virus particles. The nonionic detergent MESK has the mildest action. Using MESK, purified glycoproteins of influenza, parainfluenza, Venezuelan equine encephalomyelitis, vesicular stomatitis, rabies, and herpes viruses were obtained. The procedure for obtaining glycoproteins includes incubation of the virus suspension with the detergent MESK, removal of subvirus structures by centrifuging, and purification of glycoproteins from detergents by dialysis. Isolated glycoproteins retain a native structure and biological activity and possess high immunogenicity. The detergent MESK is promising for laboratory tests and with respect to the production of subunit vaccines

  17. Isolation and characterization of broadly neutralizing human monoclonal antibodies to the e1 glycoprotein of hepatitis C virus

    DEFF Research Database (Denmark)

    Meunier, Jean-Christophe; Russell, Rodney S; Goossens, Vera

    2008-01-01

    monoclonal antibodies (MAbs) directed against HCV glycoprotein E1, which may have the potential to control HCV infection. We have identified two MAbs that can strongly neutralize HCV-pseudotyped particles (HCVpp) bearing the envelope glycoproteins of genotypes 1a, 1b, 4a, 5a, and 6a and less strongly...

  18. Nucleic acid-binding glycoproteins which solubilize nucleic acids in dilute acid: re-examination of the Ustilago maydis glycoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Unrau, P.; Champ, D.R.; Young, J.L.; Grant, C.E.

    1980-01-01

    Holloman reported the isolation from Ustilago maydis of a glycoprotein which prevented the precipitation of nucleic acids in cold 5% trichloroacetic acid. Two glycoprotein fractions from U. maydis with this nucleic acid-solubilizing activity were isolated in our laboratory using improved purification procedures. The activity was not due to nuclease contamination. The glycoproteins are distinguished by: their ability to bind to concanavalin A-Sepharose; their differential binding to double- and single-stranded deoxyribonucleic acid, and to ribonucleic acid; their molecular weights (46,000 and 69,000); and the relative amounts present in growing versus nongrowing cells. Both fractions required sulfhydryl-reducing conditions for optimal yields, specific activity, and stability. Nucleic acid binding was cooperative, the minimum number of glycoproteins required to make a native T7 DNA molecule soluble in dilute acid being estimated at 2 and 15, respectively.

  19. Profiling of Concanavalin A-Binding Glycoproteins in Human Hepatic Stellate Cells Activated with Transforming Growth Factor-β1

    Directory of Open Access Journals (Sweden)

    Yannan Qin

    2014-11-01

    Full Text Available Glycoproteins play important roles in maintaining normal cell functions depending on their glycosylations. Our previous study indicated that the abundance of glycoproteins recognized by concanavalin A (ConA was increased in human hepatic stellate cells (HSCs following activation by transforming growth factor-β1 (TGF-β1; however, little is known about the ConA-binding glycoproteins (CBGs of HSCs. In this study, we employed a targeted glycoproteomics approach using lectin-magnetic particle conjugate-based liquid chromatography-tandem mass spectrometry to compare CBG profiles between LX-2 HSCs with and without activation by TGF-β1, with the aim of discovering novel CBGs and determining their possible roles in activated HSCs. A total of 54 and 77 proteins were identified in the quiescent and activated LX-2 cells, respectively. Of the proteins identified, 14.3% were glycoproteins and 73.3% were novel potential glycoproteins. Molecules involved in protein processing in the endoplasmic reticulum (e.g., calreticulin and calcium signaling (e.g., 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase β-2 [PLCB2] were specifically identified in activated LX-2 cells. Additionally, PLCB2 expression was upregulated in the cytoplasm of the activated LX-2 cells, as well as in the hepatocytes and sinusoidal cells of liver cirrhosis tissues. In conclusion, the results of this study may aid future investigations to find new molecular mechanisms involved in HSC activation and antifibrotic therapeutic targets.

  20. eEF-2 Phosphorylation Down-Regulates P-Glycoprotein Over-Expression in Rat Brain Microvessel Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Xing Hua Tang

    Full Text Available We investigated whether glutamate, NMDA receptors, and eukaryote elongation factor-2 kinase (eEF-2K/eEF-2 regulate P-glycoprotein expression, and the effects of the eEF-2K inhibitor NH125 on the expression of P-glycoprotein in rat brain microvessel endothelial cells (RBMECs.Cortex was obtained from newborn Wistar rat brains. After surface vessels and meninges were removed, the pellet containing microvessels was resuspended and incubated at 37°C in culture medium. Cell viability was assessed by the MTT assay. RBMECs were identified by immunohistochemistry with anti-vWF. P-glycoprotein, phospho-eEF-2, and eEF-2 expression were determined by western blot analysis. Mdr1a gene expression was analyzed by RT-PCR.Mdr1a mRNA, P-glycoprotein and phospho-eEF-2 expression increased in L-glutamate stimulated RBMECs. P-glycoprotein and phospho-eEF-2 expression were down-regulated after NH125 treatment in L-glutamate stimulated RBMECs.eEF-2K/eEF-2 should have played an important role in the regulation of P-glycoprotein expression in RBMECs. eEF-2K inhibitor NH125 could serve as an efficacious anti-multidrug resistant agent.

  1. An improved radioimmunoassay for urinary Tamm-Horsfall glycoprotein

    International Nuclear Information System (INIS)

    Dawnay, A.B. St. J.; Thornley, C.; Cattell, W.R.

    1982-01-01

    A rapid specific radioimmunoassay has been used to measure Tamm-Horsfall glycoprotein (TH glycoprotein) in urine, and the method described. The apparent concentration increased with increasing dilution of urine in water, reaching a plateau at 1 in 20. This increase was greater the higher the osmolality and TH glycoprotein concentration and the lower the pH of the original sample. The apparent concentration of TH glycoprotein in neat or diluted urine was not affected by freezing or by storage at 4 0 C or room temperature for at least 2 days. A physiological range for the urinary excretion rate was established as 22-56 mg/24h, (considerably higher than the amount present in serum) based on samples from 29 individuals with normal renal function, as defined by their creatinine clearance. There was no significant correlation between serum concentrations of TH glycoprotein and its urinary excretion rate, nor between urinary excretion rate and creatinine clearance. (author)

  2. Orthobunyavirus ultrastructure and the curious tripodal glycoprotein spike.

    Directory of Open Access Journals (Sweden)

    Thomas A Bowden

    Full Text Available The genus Orthobunyavirus within the family Bunyaviridae constitutes an expanding group of emerging viruses, which threaten human and animal health. Despite the medical importance, little is known about orthobunyavirus structure, a prerequisite for understanding virus assembly and entry. Here, using electron cryo-tomography, we report the ultrastructure of Bunyamwera virus, the prototypic member of this genus. Whilst Bunyamwera virions are pleomorphic in shape, they display a locally ordered lattice of glycoprotein spikes. Each spike protrudes 18 nm from the viral membrane and becomes disordered upon introduction to an acidic environment. Using sub-tomogram averaging, we derived a three-dimensional model of the trimeric pre-fusion glycoprotein spike to 3-nm resolution. The glycoprotein spike consists mainly of the putative class-II fusion glycoprotein and exhibits a unique tripod-like arrangement. Protein-protein contacts between neighbouring spikes occur at membrane-proximal regions and intra-spike contacts at membrane-distal regions. This trimeric assembly deviates from previously observed fusion glycoprotein arrangements, suggesting a greater than anticipated repertoire of viral fusion glycoprotein oligomerization. Our study provides evidence of a pH-dependent conformational change that occurs during orthobunyaviral entry into host cells and a blueprint for the structure of this group of emerging pathogens.

  3. The glycoprotein of measles virus

    International Nuclear Information System (INIS)

    Anttonen, O.; Jokinen, M.; Salmi, A.; Vainionpaeae, R.; Gahmberg, C.G.

    1980-01-01

    Measles virus was propagated in VERO cells and purified from the culture supernatants by two successive tartrate-density-gradient centrifugations. Surface carbohydrates were labelled both in vitro and in vivo with 3 H after treatment with galactose oxidase/NaB 3 H 4 or with [ 3 H]glucosamine. The major labelled glycoprotein in measles virions had a mol.wt. of 79000. After labelling with periodate/NaB 3 H 4 , which would result in specific labelling of sialic acid residues, the 79000-mol.wt. glycoprotein was very weakly labelled. This suggested that there is no or a very low amount of sialic acid in the virions. Further analysis of the glycoprotein showed that galactose is the terminal carbohydrate unit in the oligosaccharide, and the molecular weight of the glycopeptide obtained after Pronase digestion is about 3000. The oligosaccharide is attached to the polypeptide through an alkali-stable bond, indicating a N-glycosidic asparagine linkage. (author)

  4. Metabolomic changes in patients with chronic obstructive pulmonary disease with abnormal Savda syndrome.

    Science.gov (United States)

    Xu, Wei-Fang; Upur, Halmurat; Wu, Yu-Hua; Mamtimin, Batur; Yang, Jian; Ga, Yong-Juan; You, Li

    2015-02-01

    The aim of this study was to determine the metabolic biomarkers for abnormal Savda syndrome in patients with chronic obstructive pulmonary disease (COPD). Based on Traditional Uyghur Medicine (TUM) theory, a total of 103 patients with COPD were classified into abnormal Savda and non-abnormal Savda syndrome groups and 52 healthy volunteers acted as the control group. Blood samples from the three groups were analyzed using nuclear magnetic resonance (NMR) spectroscopy combined with orthogonal projection to latent structure-discriminant analysis. NMR tests showed that the regional distributions of the patients with COPD with abnormal Savda syndrome, those with non-abnormal Savda syndrome and the control group were completely separate (P>0.05). The patients with COPD with abnormal Savda syndrome exhibited relatively low levels of amino acids, glycoproteins and unsaturated lipids (PAbnormal Savda syndrome was one of the main types of syndrome among the patients with COPD; increased age, a longer duration of illness and a higher disease severity were characteristic of this type of syndrome. In addition, the present study provided biochemical evidence for the TUM theory-based classification of patients with COPD; these biomarkers can be used in the clinic for the diagnosis of COPD with abnormal Savda syndrome. The study also demonstrated that the plasma metabolic disorder in patients with COPD with abnormal Savda syndrome was more serious than that in the control and COPD with non-abnormal Savda syndrome groups. The plasma metabolic disorder was also associated with a low immune function of the body and endocrine and energy metabolism disorders.

  5. Characterization of canine herpesvirus glycoprotein C expressed by a recombinant baculovirus in insect cells.

    Science.gov (United States)

    Xuan, X; Maeda, K; Mikami, T; Otsuka, H

    1996-12-01

    The gene encoding the canine herpesvirus (CHV) glycoprotein C (gC) homologue has been identified by sequence homology analyses with other well studied herpesviruses. Previously, we have identified three CHV glycoproteins, gp145/112, gp80 and gp47 using a panel of monoclonal antibodies (MAbs). To determine which CHV glycoprotein corresponds to gC, a recombinant baculovirus which contains the putative CHV gC structural gene under the baculovirus polyhedrin promoter was constructed. The recombinant baculovirus expressed gC-related polypeptides (44-62 kDa), which reacted only with MAbs against CHV gp80, indicating that the previously identified CHV gp80 is the translation product of the gC gene. The baculovirus expressed gC was glycosylated and transported to the surface of infected cells. At least seven neutralizing epitopes were conserved on the gC produced in insect cells. It was found that the recombinant baculovirus infected cells adsorbed murine erythrocytes as is the case for CHV-infected cells. The hemadsorption activity was inhibited by heparin, indicating that the CHV gC binds to heparan sulfate on the surface of murine erythrocytes. Mice immunized with the recombinant gC produced strong neutralizing antibodies. Our results suggest that CHV gC produced in insect cells may be useful as a subunit vaccine to control CHV infections.

  6. Development of oligoclonal nanobodies for targeting the tumor-associated glycoprotein 72 antigen

    DEFF Research Database (Denmark)

    Sharifzadeh, Zahra; Rahbarizadeh, Fatemeh; Shokrgozar, Mohammad Ali

    2013-01-01

    The tumor-associated glycoprotein 72 (TAG-72) is a membrane mucin whose over-expression is correlated with advanced tumor stage and increased invasion and metastasis. In this study, we identified a panel of four nanobodies, single variable domains of dromedary heavy-chain antibodies that specific...

  7. Enhancement of Ebola Virus Infection via Ficolin-1 Interaction with the Mucin Domain of GP Glycoprotein.

    Science.gov (United States)

    Favier, Anne-Laure; Gout, Evelyne; Reynard, Olivier; Ferraris, Olivier; Kleman, Jean-Philippe; Volchkov, Viktor; Peyrefitte, Christophe; Thielens, Nicole M

    2016-06-01

    Ebola virus infection requires the surface viral glycoprotein to initiate entry into the target cells. The trimeric glycoprotein is a highly glycosylated viral protein which has been shown to interact with host C-type lectin receptors and the soluble complement recognition protein mannose-binding lectin, thereby enhancing viral infection. Similarly to mannose-binding lectin, ficolins are soluble effectors of the innate immune system that recognize particular glycans at the pathogen surface. In this study, we demonstrate that ficolin-1 interacts with the Zaire Ebola virus (EBOV) glycoprotein, and we characterized this interaction by surface plasmon resonance spectroscopy. Ficolin-1 was shown to bind to the viral glycoprotein with a high affinity. This interaction was mediated by the fibrinogen-like recognition domain of ficolin-1 and the mucin-like domain of the viral glycoprotein. Using a ficolin-1 control mutant devoid of sialic acid-binding capacity, we identified sialylated moieties of the mucin domain to be potential ligands on the glycoprotein. In cell culture, using both pseudotyped viruses and EBOV, ficolin-1 was shown to enhance EBOV infection independently of the serum complement. We also observed that ficolin-1 enhanced EBOV infection on human monocyte-derived macrophages, described to be major viral target cells,. Competition experiments suggested that although ficolin-1 and mannose-binding lectin recognized different carbohydrate moieties on the EBOV glycoprotein, the observed enhancement of the infection likely depended on a common cellular receptor/partner. In conclusion, ficolin-1 could provide an alternative receptor-mediated mechanism for enhancing EBOV infection, thereby contributing to viral subversion of the host innate immune system. A specific interaction involving ficolin-1 (M-ficolin), a soluble effector of the innate immune response, and the glycoprotein (GP) of EBOV was identified. Ficolin-1 enhanced virus infection instead of tipping the

  8. The lipid accumulation product as a useful index for identifying abnormal glucose regulation in young Korean women.

    Science.gov (United States)

    Oh, J-Y; Sung, Y-A; Lee, H J

    2013-04-01

    The lipid accumulation product, a combination of waist circumference and triglycerides concentration, has been suggested as a better marker for abnormal glucose regulation than BMI. We aimed to compare the lipid accumulation product and BMI as useful markers for abnormal glucose regulation in young Korean women. The lipid accumulation product was calculated using the formula [waist circumference (cm) - 58] × triglycerides (mmol/l). Glucose tolerance status was determined using a 75-g oral glucose tolerance test in 2810 Korean women aged 18-39 years from the general population. The prevalence of abnormal glucose regulation was 6.8% (isolated impaired fasting glucose 1.8%, isolated impaired glucose tolerance 4.0%; impaired fasting glucose + impaired glucose tolerance 0.4% and diabetes mellitus 0.6%). According to the quintile distributions of the lipid accumulation product and BMI, women with a lipid accumulation product quintile greater than their BMI quintile exhibited significantly greater areas under the curve and higher levels of 2-h post-load glucose, insulin, homeostasis model analysis of insulin resistance and lipid profiles than did women with a BMI quintile greater than their lipid accumulation product quintile. Multiple logistic regression revealed that the lipid accumulation product exhibited a higher odds ratio for abnormal glucose regulation than did BMI after adjusting for age, systolic blood pressure, HDL cholesterol, previous history of gestational diabetes and family history of diabetes (odds ratios 3.5 and 2.6 of the highest vs. the lowest quintiles of lipid accumulation product and BMI, respectively). The lipid accumulation product could be useful for identifying the young Korean women with abnormal glucose regulation. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  9. The hydroxyapatite-binding regions of a rat salivary glycoprotein.

    Science.gov (United States)

    Embery, G; Green, D R

    1989-09-01

    The regions of a salivary sulphated glycoprotein which are involved in its attachment to hydroxyapatite (Biogel HTP) have been characterised. The sulphated glycoprotein, a 35S-labelled preparation from mixed palatal and buccal minor gland secretions of the rat was bound onto hydroxyapatite and the resultant glycoprotein-hydroxyapatite complex was sequentially digested with pronase E and alpha-L-fucosidase, a treatment which released 86.8% +/- 1.7% of the radioactivity of the initially bound glycoprotein. The fragments which remained attached to the hydroxyapatite after enzymic digestion were fractionated on Sephadex G-25 and analysed for carbohydrate and amino acid components. A range of amino acids were detected which could reflect both glycosylated and non-glycosylated-binding regions. Sialic acid, although considered to be involved in the attachment process was not detected in any of the fragments remaining after enzymic digestion, a finding which provides indirect evidence that the enzymically liberated products do not subsequently re-attach to the hydroxyapatite surface. The notable feature of the fractions with average Mr estimated at 1000 or less is the high proportion of N-acetylhexosamine and N-acetylgalactosamine. It is apparent that the hexosamine residues, which normally bear the ester sulphate moieties of sulphated glycoproteins, play an important role in the attachment of sulphated glycoproteins to hydroxyapatite.

  10. Isolation of allergenically active glycoprotein from Prosopis juliflora pollen.

    Science.gov (United States)

    Thakur, I S

    1989-03-01

    An allergenically active glycoprotein was homogeneously isolated from the aqueous extract of Prosopis juliflora pollen by ConA-Sepharose affinity chromatography. The molecular weight of this glycoprotein was 20,000 dalton, determined by gel filtration and SDS-PAGE. This fraction showed a total carbohydrate concentration of 25%. The purified glycoprotein revealed immunochemically most antigenic or allergenic and demonstrated homogeneous after reaction with P. juliflora pollen antiserum, characterized by gel diffusion, Immunoelectrophoresis and Radioallergosorbent test.

  11. Intracellular localization of hydroxyproline-rich glycoprotein biosynthesis

    International Nuclear Information System (INIS)

    Robinson, D.G.; Andreae, M.; Glas, A.R.; Sauer, A.

    1984-01-01

    The structural proteins of plant cell walls are glycoproteins characterized by O-glucosidic linkages to hydroxyproline or serine. Proline, not hydroxyproline, is the translatable amino acid in hydroxyproline-rich glycoproteins (HRGP). Hydroxylation and arabinosylation of proline are sequential, post-translational events. Because of this, there is no a priori reason for expecting HRGP synthesis to follow the well-established route for secretory and plasma membrane (PM) glycoproteins, i.e., from endoplasmic reticulum (ER) via the Golgi apparatus (GA) to the PM. In this paper, two plausible alternatives for HRGO secretion are examined. Because a feature of the majority of dicotyledons is overlapping GA and PM regions in sucrose density gradients, the authors have used two monocotyledonous systems to determine the distribution of HRGP and enzyme activity

  12. High-resolution Anorectal Manometry for Identifying Defecatory Disorders and Rectal Structural Abnormalities in Women.

    Science.gov (United States)

    Prichard, David O; Lee, Taehee; Parthasarathy, Gopanandan; Fletcher, Joel G; Zinsmeister, Alan R; Bharucha, Adil E

    2017-03-01

    Contrary to conventional wisdom, the rectoanal gradient during evacuation is negative in many healthy people, undermining the utility of anorectal high-resolution manometry (HRM) for diagnosing defecatory disorders. We aimed to compare HRM and magnetic resonance imaging (MRI) for assessing rectal evacuation and structural abnormalities. We performed a retrospective analysis of 118 patients (all female; 51 with constipation, 48 with fecal incontinence, and 19 with rectal prolapse; age, 53 ± 1 years) assessed by HRM, the rectal balloon expulsion test (BET), and MRI at Mayo Clinic, Rochester, Minnesota, from February 2011 through March 2013. Thirty healthy asymptomatic women (age, 37 ± 2 years) served as controls. We used principal components analysis of HRM variables to identify rectoanal pressure patterns associated with rectal prolapse and phenotypes of patients with prolapse. Compared with patients with normal findings from the rectal BET, patients with an abnormal BET had lower median rectal pressure (36 vs 22 mm Hg, P = .002), a more negative median rectoanal gradient (-6 vs -29 mm Hg, P = .006) during evacuation, and a lower proportion of evacuation on the basis of MRI analysis (median of 40% vs 80%, P < .0001). A score derived from rectal pressure and anorectal descent during evacuation and a patulous anal canal was associated (P = .005) with large rectoceles (3 cm or larger). A principal component (PC) logistic model discriminated between patients with and without prolapse with 96% accuracy. Among patients with prolapse, there were 2 phenotypes, which were characterized by high (PC1) or low (PC2) anal pressures at rest and squeeze along with higher rectal and anal pressures (PC1) or a higher rectoanal gradient during evacuation (PC2). In a retrospective analysis of patients assessed by HRM, measurements of rectal evacuation by anorectal HRM, BET, and MRI were correlated. HRM alone and together with anorectal descent during evacuation may identify

  13. Non-small-bowel abnormalities identified during small bowel capsule endoscopy

    NARCIS (Netherlands)

    Hoedemakers, Reinier; Westerhof, Jessie; Weersma, Rinse K.; Koornstra, Jan J.

    2014-01-01

    AIM: To investigate the incidence of non-small-bowel abnormalities in patients referred for small bowel capsule endoscopy, this single center study was performed. METHODS: Small bowel capsule endoscopy is an accepted technique to investigate obscure gastrointestinal bleeding. This is defined as

  14. Analysis of glycoprotein-derived oligosaccharides in glycoproteins detected on two-dimensional gel by capillary electrophoresis using on-line concentration method.

    Science.gov (United States)

    Kamoda, Satoru; Nakanishi, Yasuharu; Kinoshita, Mitsuhiro; Ishikawa, Rika; Kakehi, Kazuaki

    2006-02-17

    Capillary electrophoresis (CE) is an effective tool to analyze carbohydrate mixture derived from glycoproteins with high resolution. However, CE has a disadvantage that a few nanoliters of a sample solution are injected to a narrow capillary. Therefore, we have to prepare a sample solution of high concentration for CE analysis. In the present study, we applied head column field-amplified sample stacking method to the analysis of N-linked oligosaccharides derived from glycoprotein separated by two-dimensional gel electrophoresis. Model studies demonstrated that we achieved 60-360 times concentration effect on the analysis of carbohydrate chains labeled with 3-aminobenzoic acid (3-AA). The method was applied to the analysis of N-linked oligosaccharides from glycoproteins separated and detected on PAGE gel. Heterogeneity of alpha1-acid glycoprotein (AGP), i.e. glycoforms, was examined by 2D-PAGE and N-linked oligosaccharides were released by in-gel digestion with PNGase F. The released oligosaccharides were derivatized with 3-AA and analyzed by CE. The results showed that glycoforms having lower pI values contained a larger amount of tetra- and tri-antennary oligosaccharides. In contrast, glycoforms having higher pI values contained bi-antennary oligosaccharides abundantly. The result clearly indicated that the spot of a glycoprotein glycoform detected by Coomassie brilliant blue staining on 2D-PAGE gel is sufficient for quantitative profiling of oligosaccharides.

  15. Humanizing recombinant glycoproteins from Chinese hamster ovary cells

    DEFF Research Database (Denmark)

    Hansen, Anders Holmgaard; Amann, Thomas; Kol, Stefan

    With new tools for gene-editing like zinc-fingers, TALENS and CRISPR, it is now feasible totailor-make the N-Glycoforms for therapeutic glycoproteins that have previously been almost impossible. We here demonstrate a case of humanizing a recombinant human glycoprotein that in Wild type (WT) Chinese...

  16. Determination of P-Glycoprotein Expression by Flow Cytometry in Hematological Malignancies

    Directory of Open Access Journals (Sweden)

    Berkay Saraymen

    2016-03-01

    Full Text Available Objective: Determination the expression of P-glycoprotein is especially problematic for normal tissues because immuno­logical methods are limited in terms of sensitivity. We aimed to determine the expression of P-glycoprotein and CD34 by flow cytometry, and to evaluate the level of expression of P-glycoprotein and CD34 with unresponsive to treatment in pa­tients diagnosed with hematologic malignancy. Methods: Our study included fifty patients diagnosed with acute myeloblastic leukemia and acute lymphoblastic leuke­mia, and twenty healthy controls who were admitted to Erci­yes University Hematology-Oncology Hospital. The suspend­ed cells from bone marrow samples of patients and the pe­ripheral blood samples of healthy people were marked with P-glycoprotein phycoerythrin and CD34 FITC or PerCP Cy 5.5; and then surface expression was measured by means of flow cytometry. Results: In 6 of 30 acute myeloblastic leukemia patients P-glycoprotein and CD34 expression, in 6 of 20 acute lympho­blastic leukemia patients P-glycoprotein, in 5 of them CD34 expression were determined. A significant relation between P-glycoprotein and CD34 expressions in acute myeloblas­tic leukemia and acute lymphoblastic leukemia bone marrow samples was reported. Conclusion: Our data indicate that flow cytometry is more reliable, precise and faster than molecular methods for mea­suring P-glycoprotein expression and suggests the pos­sibility of a significant relationship between P-glycoprotein and CD34 expressions in acute myeloblastic leukemia and acute lymphoblastic leukemia bone marrow samples. The blast cells expressing CD34 on their surface along with P-glycoprotein simultaneously show that multi drug resistance 1 gene is mostly active in immature cells.

  17. Glycoproteins of mouse vaginal epithelium: differential expression related to estrous cyclicity

    DEFF Research Database (Denmark)

    Horvat, B; Multhaupt, H A; Damjanov, I

    1993-01-01

    We used lectin overlay blotting and SDS-PAGE to analyze the estrous cycle-specific expression of mouse vaginal epithelial glycoproteins. Seven lectins chosen for their differential carbohydrate-binding specificity revealed 15 glycoproteins that showed cycle-related expression. Each lectin had...... in proestrus, coincident with the transformation of two superficial layers of vaginal squamous epithelium into mucinous cuboidal cells. Electron microscopic lectin histochemistry revealed the glycoproteins in the mucinous granules of surface cuboidal cells and in the lumen of the vagina. Our results illustrate...... the complexity of glycoconjugate synthesis in mouse vagina and reveal the distinct cycle-specific patterns of individual glycoprotein expression. These cyclic glycoproteins could serve as vaginal biochemical markers for the specific phases of the estrous cycle....

  18. Herpesvirus glycoproteins undergo multiple antigenic changes before membrane fusion.

    Directory of Open Access Journals (Sweden)

    Daniel L Glauser

    Full Text Available Herpesvirus entry is a complicated process involving multiple virion glycoproteins and culminating in membrane fusion. Glycoprotein conformation changes are likely to play key roles. Studies of recombinant glycoproteins have revealed some structural features of the virion fusion machinery. However, how the virion glycoproteins change during infection remains unclear. Here using conformation-specific monoclonal antibodies we show in situ that each component of the Murid Herpesvirus-4 (MuHV-4 entry machinery--gB, gH/gL and gp150--changes in antigenicity before tegument protein release begins. Further changes then occurred upon actual membrane fusion. Thus virions revealed their final fusogenic form only in late endosomes. The substantial antigenic differences between this form and that of extracellular virions suggested that antibodies have only a limited opportunity to block virion membrane fusion.

  19. Structural magnetic resonance imaging can identify trigeminal system abnormalities in classical trigeminal neuralgia

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    Danielle DeSouza

    2016-10-01

    Full Text Available Classical trigeminal neuralgia (TN is a chronic pain disorder that has been described as one ofthe most severe pains one can suffer. The most prevalent theory of TN etiology is that the trigeminal nerve is compressed at the root entry zone (REZ by blood vessels. However, there is significant evidence showing a lack of neurovascular compression (NVC for many cases of classical TN. Furthermore, a considerable number of patients who are asymptomatic have MR evidence of NVC. Since there is no validated animal model that reproduces the clinical features of TN, our understanding of TN pathology mainly comes from biopsy studies that have limitations. Sophisticated structural MRI techniques including diffusion tensor imaging provide new opportunities to assess the trigeminal nerves and CNS to provide insight into TN etiology and pathogenesis. Specifically, studies have used high-resolution structural MRI methods to visualize patterns of trigeminal nerve-vessel relationships and to detect subtle pathological features at the trigeminal REZ. Structural MRI has also identified CNS abnormalities in cortical and subcortical gray matter and white matter and demonstrated that effective neurosurgical treatment for TN is associated with a reversal of specific nerve and brain abnormalities. In conclusion, this review highlights the advanced structural neuroimaging methods that are valuable tools to assess the trigeminal system in TN and may inform our current understanding of TN pathology. These methods may in the future have clinical utility for the development of neuroimaging-based biomarkers of TN.

  20. Glycoprotein Enrichment Analytical Techniques: Advantages and Disadvantages.

    Science.gov (United States)

    Zhu, R; Zacharias, L; Wooding, K M; Peng, W; Mechref, Y

    2017-01-01

    Protein glycosylation is one of the most important posttranslational modifications. Numerous biological functions are related to protein glycosylation. However, analytical challenges remain in the glycoprotein analysis. To overcome the challenges associated with glycoprotein analysis, many analytical techniques were developed in recent years. Enrichment methods were used to improve the sensitivity of detection, while HPLC and mass spectrometry methods were developed to facilitate the separation of glycopeptides/proteins and enhance detection, respectively. Fragmentation techniques applied in modern mass spectrometers allow the structural interpretation of glycopeptides/proteins, while automated software tools started replacing manual processing to improve the reliability and throughput of the analysis. In this chapter, the current methodologies of glycoprotein analysis were discussed. Multiple analytical techniques are compared, and advantages and disadvantages of each technique are highlighted. © 2017 Elsevier Inc. All rights reserved.

  1. Identification of active pocket and protein druggability within envelope glycoprotein GP2 from Ebola virus

    Directory of Open Access Journals (Sweden)

    Beuy Joob

    2014-12-01

    Full Text Available The drug searching for combating the present outbreak of Ebola virus infection is the urgent activity at present. Finding the new effective drug at present must base on the molecular analysis of the pathogenic virus. The in-depth analysis of the viral protein to find the binding site, active pocket is needed. Here, the authors analyzed the envelope glycoprotein GP2 from Ebola virus. Identification of active pocket and protein druggability within envelope glycoprotein GP2 from Ebola virus was done. According to this assessment, 7 active pockets with varied druggability could be identified.

  2. The promoter for a variant surface glycoprotein gene expression site in Trypanosoma brucei

    NARCIS (Netherlands)

    Zomerdijk, J. C.; Ouellette, M.; ten Asbroek, A. L.; Kieft, R.; Bommer, A. M.; Clayton, C. E.; Borst, P.

    1990-01-01

    The variant-specific surface glycoprotein (VSG) gene 221 of Trypanosoma brucei is transcribed as part of a 60 kb expression site (ES). We have identified the promoter controlling this multigene transcription unit by the use of 221 chromosome-enriched DNA libraries and VSG gene 221 expression site

  3. Developing baculovirus-insect cell expression systems for humanized recombinant glycoprotein production

    International Nuclear Information System (INIS)

    Jarvis, Donald L.

    2003-01-01

    The baculovirus-insect cell expression system is widely used to produce recombinant glycoproteins for many different biomedical applications. However, due to the fundamental nature of insect glycoprotein processing pathways, this system is typically unable to produce recombinant mammalian glycoproteins with authentic oligosaccharide side chains. This minireview summarizes our current understanding of insect protein glycosylation pathways and our recent efforts to address this problem. These efforts have yielded new insect cell lines and baculoviral vectors that can produce recombinant glycoproteins with humanized oligosaccharide side chains

  4. Identification of a mouse synaptic glycoprotein gene in cultured neurons.

    Science.gov (United States)

    Yu, Albert Cheung-Hoi; Sun, Chun Xiao; Li, Qiang; Liu, Hua Dong; Wang, Chen Ran; Zhao, Guo Ping; Jin, Meilei; Lau, Lok Ting; Fung, Yin-Wan Wendy; Liu, Shuang

    2005-10-01

    Neuronal differentiation and aging are known to involve many genes, which may also be differentially expressed during these developmental processes. From primary cultured cerebral cortical neurons, we have previously identified various differentially expressed gene transcripts from cultured cortical neurons using the technique of arbitrarily primed PCR (RAP-PCR). Among these transcripts, clone 0-2 was found to have high homology to rat and human synaptic glycoprotein. By in silico analysis using an EST database and the FACTURA software, the full-length sequence of 0-2 was assembled and the clone was named as mouse synaptic glycoprotein homolog 2 (mSC2). DNA sequencing revealed transcript size of mSC2 being smaller than the human and rat homologs. RT-PCR indicated that mSC2 was expressed differentially at various culture days. The mSC2 gene was located in various tissues with higher expression in brain, lung, and liver. Functions of mSC2 in neurons and other tissues remain elusive and will require more investigation.

  5. Regulation of glycoprotein synthesis in yeast by mating pheromones

    International Nuclear Information System (INIS)

    Tanner, W.

    1984-01-01

    In Saccharomyces cerevisiae, glycosylated proteins amount to less than 2% of the cell protein. Two intensively studied examples of yeast glycoproteins are the external cell wall - associated invertase and the vacuolar carboxypeptidase Y. Recently, it was shown that the mating pheromone, alpha factor, specifically and strongly inhibits the synthesis of N-glycosylated proteins in haploid a cells, whereas O-glycosylated proteins are not affected. In this paper, the pathways of glycoprotein biosynthesis are summarized briefly, and evidence is presented that mating pheomones have a regulatory function in glycoprotein synthesis

  6. Engineered CHO cells for production of diverse, homogeneous glycoproteins

    DEFF Research Database (Denmark)

    Yang, Zhang; Wang, Shengjun; Halim, Adnan

    2015-01-01

    Production of glycoprotein therapeutics in Chinese hamster ovary (CHO) cells is limited by the cells' generic capacity for N-glycosylation, and production of glycoproteins with desirable homogeneous glycoforms remains a challenge. We conducted a comprehensive knockout screen of glycosyltransferas...

  7. Bioinformatics Analysis of Envelope Glycoprotein E epitopes of ...

    African Journals Online (AJOL)

    The E glycoprotein of dengue virus is responsible for the viral binding to the receptor. The crystal structure of envelope glycoprotein has already been determined. However, where the well-defined Bcell and T-cell epitopes are located is still a question. Because of the large variations among the four dengue genotypes, it is ...

  8. The Purification of a Blood Group A Glycoprotein: An Affinity Chromatography Experiment.

    Science.gov (United States)

    Estelrich, J.; Pouplana, R.

    1988-01-01

    Describes a purification process through affinity chromatography necessary to obtain specific blood group glycoproteins from erythrocytic membranes. Discusses the preparation of erythrocytic membranes, extraction of glycoprotein from membranes, affinity chromatography purification, determination of glycoproteins, and results. (CW)

  9. MR imaging of abnormal synovial processes

    International Nuclear Information System (INIS)

    Quinn, S.F.; Sanchez, R.; Murray, W.T.; Silbiger, M.L.; Ogden, J.; Cochran, C.

    1987-01-01

    MR imaging can directly image abnormal synovium. The authors reviewed over 50 cases with abnormal synovial processes. The abnormalities include Baker cysts, semimembranous bursitis, chronic shoulder bursitis, peroneal tendon ganglion cyst, periarticular abscesses, thickened synovium from rheumatoid and septic arthritis, and synovial hypertrophy secondary to Legg-Calve-Perthes disease. MR imaging has proved invaluable in identifying abnormal synovium, defining the extent and, to a limited degree, characterizing its makeup

  10. Prediction and identification of mouse cytotoxic T lymphocyte epitopes in Ebola virus glycoproteins

    Directory of Open Access Journals (Sweden)

    Wu Shipo

    2012-06-01

    Full Text Available Abstract Background Ebola viruses (EBOVs cause severe hemorrhagic fever with a high mortality rate. At present, there are no licensed vaccines or efficient therapies to combat EBOV infection. Previous studies have shown that both humoral and cellular immune responses are crucial for controlling Ebola infection. CD8+ T cells play an important role in mediating vaccine-induced protective immunity. The objective of this study was to identify H-2d-specific T cell epitopes in EBOV glycoproteins (GPs. Results Computer-assisted algorithms were used to predict H-2d-specific T cell epitopes in two species of EBOV (Sudan and Zaire GP. The predicted peptides were synthesized and identified in BALB/c mice immunized with replication-deficient adenovirus vectors expressing the EBOV GP. Enzyme-linked immunospot assays and intracellular cytokine staining showed that the peptides RPHTPQFLF (Sudan EBOV, GPCAGDFAF and LYDRLASTV (Zaire EBOV could stimulate splenoctyes in immunized mice to produce large amounts of interferon-gamma. Conclusion Three peptides within the GPs of two EBOV strains were identified as T cell epitopes. The identification of these epitopes should facilitate the evaluation of vaccines based on the Ebola virus glycoprotein in a BALB/c mouse model.

  11. Isolation and characterization of two antigenic glycoproteins from the pollen of Prosopis juliflora.

    Science.gov (United States)

    Thakur, I S

    1991-03-01

    Two antigenically active glycoprotein fractions were isolated from crude extract of the pollen of Prosopis juliflora using DEAE-cellulose ion exchange chromatography. The glycoproteins gave single band on polyacrylamide gel electrophoresis. The molecular weight of these two glycoprotein was 20,000 and 10,000 as determined by gel filtration on Sephadex G-75. With the help of crossed immunoelectrophoresis and gel diffusion crude extract exhibited twelve and three precipitating antigens suggesting its heterogeneous nature; and the purified glycoprotein fractions however formed single precipitin band on gel diffusion test and immunoelectrophoresis. As tested by ELISA the polyclonal antisera raised in rabbit showed strong binding affinity with glycoprotein of MW 20,000. These result indicates that the two glycoprotein fractions are not antigenically identical.

  12. A Systematic Approach to Identify Sources of Abnormal Interior Noise for a High-Speed Train

    Directory of Open Access Journals (Sweden)

    Jie Zhang

    2018-01-01

    Full Text Available A systematic approach to identify sources of abnormal interior noise occurring in a high-speed train is presented and applied in this paper to resolve a particular noise issue. This approach is developed based on a number of previous dealings with similar noise problems. The particular noise issue occurs in a Chinese high-speed train. It is measured that there is a difference of 7 dB(A in overall Sound Pressure Level (SPL between two nominally identical VIP cabins at 250 km/h. The systematic approach is applied to identify the root cause of the 7 dB(A difference. Well planned measurements are performed in both the VIP cabins. Sound pressure contributions, either in terms of frequency band or in terms of facing area, are analyzed. Order analysis is also carried out. Based on these analyses, it is found that the problematic frequency is the sleeper passing frequency of the train, and an area on the roof contributes the most. In order to determine what causes that area to be the main contributor without disassembling the structure of the roof, measured noise and vibration data for different train speeds are further analyzed. It is then reasoned that roof is the main contributor caused by sound pressure behind the panel. Up to this point, panels of the roof are removed, revealing that a hole of 300 cm2 for running cables is presented behind the red area without proper sound insulation. This study can provide a basis for abnormal interior noise analysis and control of high-speed trains.

  13. Purification and characterization of the glycoprotein allergen from Prosopis juliflora pollen.

    Science.gov (United States)

    Thakur, I S

    1991-02-01

    Highly active glycoprotein allergens have been isolated from pollen of Prosopis juliflora by a combination of Sephadex G-100 gel filtration and Sodium dodecyl sulphate-Poly-acrylamide gel electrophoresis. The glycoprotein fraction was homogeneous, and had molecular weight 20,000. The purified glycoprotein allergen contained 20% carbohydrate, mainly arabinose and galactose. Enzymatic digestion of glycoprotein with protease released glycopeptides of molecular weight ranging from less than 1,000 to more than 5,000 on Sephadex G-25 gel filtration. Antigenicity or allergenicity testing of these glycopeptides by immunodiffusion, immunoelectrophoresis, and radioallergosorbent test indicated complete loss of allergenic activity after digestion with protease whereas incubation with beta-D-galactosidase and periodate oxidation had little affect on the allergenic activity of the glycoprotein fraction. But incubation with alpha-D-glucosidase did not affect the allergenic activity significantly. All these tests indicated that protein played significant role in allergenicity of P. juliflora pollen.

  14. Strategies to overcome or circumvent P-glycoprotein mediated multidrug resistance.

    Science.gov (United States)

    Yuan, Hongyu; Li, Xun; Wu, Jifeng; Li, Jinpei; Qu, Xianjun; Xu, Wenfang; Tang, Wei

    2008-01-01

    Cancer patients who receive chemotherapy often experience intrinsic or acquired resistance to a broad spectrum of chemotherapeutic agents. The phenomenon, termed multidrug resistance (MDR), is often associated with the over-expression of P-glycoprotein, a transmembrane protein pump, which can enhance efflux of a various chemicals structurally unrelated at the expense of ATP depletion, resulting in decrease of the intracellular cytotoxic drug accumulation. The MDR has been a big threaten to the human health and the war fight for it continues. Although several other mechanisms for MDR are elucidated in recent years, considerable efforts attempting to inverse MDR are involved in exploring P-glycoprotein modulators and suppressing P-glycoprotein expression. In this review, we will report on the recent advances in various strategies for overcoming or circumventing MDR mediated by P-glycoprotein.

  15. A Functional Henipavirus Envelope Glycoprotein Pseudotyped Lentivirus Assay System

    Directory of Open Access Journals (Sweden)

    Broder Christopher C

    2010-11-01

    Full Text Available Abstract Background Hendra virus (HeV and Nipah virus (NiV are newly emerged zoonotic paramyxoviruses discovered during outbreaks in Queensland, Australia in 1994 and peninsular Malaysia in 1998/9 respectively and classified within the new Henipavirus genus. Both viruses can infect a broad range of mammalian species causing severe and often-lethal disease in humans and animals, and repeated outbreaks continue to occur. Extensive laboratory studies on the host cell infection stage of HeV and NiV and the roles of their envelope glycoproteins have been hampered by their highly pathogenic nature and restriction to biosafety level-4 (BSL-4 containment. To circumvent this problem, we have developed a henipavirus envelope glycoprotein pseudotyped lentivirus assay system using either a luciferase gene or green fluorescent protein (GFP gene encoding human immunodeficiency virus type-1 (HIV-1 genome in conjunction with the HeV and NiV fusion (F and attachment (G glycoproteins. Results Functional retrovirus particles pseudotyped with henipavirus F and G glycoproteins displayed proper target cell tropism and entry and infection was dependent on the presence of the HeV and NiV receptors ephrinB2 or B3 on target cells. The functional specificity of the assay was confirmed by the lack of reporter-gene signals when particles bearing either only the F or only G glycoprotein were prepared and assayed. Virus entry could be specifically blocked when infection was carried out in the presence of a fusion inhibiting C-terminal heptad (HR-2 peptide, a well-characterized, cross-reactive, neutralizing human mAb specific for the henipavirus G glycoprotein, and soluble ephrinB2 and B3 receptors. In addition, the utility of the assay was also demonstrated by an examination of the influence of the cytoplasmic tail of F in its fusion activity and incorporation into pseudotyped virus particles by generating and testing a panel of truncation mutants of NiV and HeV F

  16. Labelled antibody techniques in glycoprotein estimation

    International Nuclear Information System (INIS)

    Hazra, D.K.; Ekins, R.P.; Edwards, R.; Williams, E.S.

    1977-01-01

    The problems in the radioimmunoassay of the glycoprotein hormones (pituitary LH, FSH and TSH and human chlorionic gonadotrophin HGG) are reviewed viz: limited specificity and sensitivity in the clinical context, interpretation of disparity between bioassay and radioimmunoassay, and interlaboratory variability. The advantages and limitations of the labelled antibody techniques - classical immonoradiometric methods and 2-site or 125 I-anti-IgG indirect labelling modifications are reviewed in general, and their theoretical potential in glycoprotein assays examined in the light of previous work. Preliminary experiments in the development of coated tube 2-site assay for glycoproteins using 125 I anti-IgG labelling are described, including conditions for maximizing solid phase extraction of the antigen, iodination of anti-IgG, and assay conditions such as effects of temperature of incubation with antigen 'hormonefree serum', heterologous serum and detergent washing. Experiments with extraction and antigen-specific antisera raised in the same or different species are described as exemplified by LH and TSH assay systems, the latter apparently promising greater sensitivity than radioimmunoassay. Proposed experimental and mathematical optimisation and validation of the method as an assay system is outlined, and the areas for further work delineated. (orig.) [de

  17. Identification of broadly reactive epitopes targeting major glycoproteins of Herpes simplex virus (HSV) 1 and 2 - An immunoinformatics analysis.

    Science.gov (United States)

    Chauhan, Varun; Goyal, Kapil; Singh, Mini P

    2018-07-01

    Infections due to both HSV-1 and HSV-2 constitute an enormous health burden worldwide. Development of vaccine against herpes infections is a WHO supported public health priority. The viral glycoproteins have always been the major hotspots for vaccine designing. The present study was aimed to identify the conserved T and B cell epitopes in the major glycoproteins of both HSV-1 and HSV-2 via rigorous computational approaches. Identification of promiscuous T cell epitopes is of utmost importance in vaccine designing as such epitopes are capable of binding to several allelic forms of HLA and could generate effective immune response in the host. The criteria designed for identification of T and B cell epitopes was that it should be conserved in both HSV-1 and 2, promiscuous, have high affinity towards HLA alleles, should be located on the surface of glycoproteins and not be present in the glycosylation sites. This study led to the identification of 17 HLA Class II and 26 HLA Class I T cell epitopes, 9 linear and some conformational B cell epitopes. The identified T cell epitopes were further subjected to molecular docking analysis to analyze their binding patterns. Altogether we have identified 4 most promising regions in glycoproteins (2-gB, 1-gD, 1-gH) of HSV-1 and 2 which are promiscuous to HLA Class II alleles and have overlapping HLA Class I and B cell epitopes, which could be very useful in generating both arms of immune response in the host i.e. adaptive as well as humoral immunity. Further the authors propose the cross-validation of the identified epitopes in experimental settings for confirming their immunogenicity to support the present findings. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Structures and Functions of Pestivirus Glycoproteins: Not Simply Surface Matters.

    Science.gov (United States)

    Wang, Fun-In; Deng, Ming-Chung; Huang, Yu-Liang; Chang, Chia-Yi

    2015-06-29

    Pestiviruses, which include economically important animal pathogens such as bovine viral diarrhea virus and classical swine fever virus, possess three envelope glycoproteins, namely Erns, E1, and E2. This article discusses the structures and functions of these glycoproteins and their effects on viral pathogenicity in cells in culture and in animal hosts. E2 is the most important structural protein as it interacts with cell surface receptors that determine cell tropism and induces neutralizing antibody and cytotoxic T-lymphocyte responses. All three glycoproteins are involved in virus attachment and entry into target cells. E1-E2 heterodimers are essential for viral entry and infectivity. Erns is unique because it possesses intrinsic ribonuclease (RNase) activity that can inhibit the production of type I interferons and assist in the development of persistent infections. These glycoproteins are localized to the virion surface; however, variations in amino acids and antigenic structures, disulfide bond formation, glycosylation, and RNase activity can ultimately affect the virulence of pestiviruses in animals. Along with mutations that are driven by selection pressure, antigenic differences in glycoproteins influence the efficacy of vaccines and determine the appropriateness of the vaccines that are currently being used in the field.

  19. Adipokine zinc-α2-glycoprotein regulated by growth hormone and linked to insulin sensitivity.

    Science.gov (United States)

    Balaz, Miroslav; Ukropcova, Barbara; Kurdiova, Timea; Gajdosechova, Lucia; Vlcek, Miroslav; Janakova, Zuzana; Fedeles, Jozef; Pura, Mikulas; Gasperikova, Daniela; Smith, Steven R; Tkacova, Ruzena; Klimes, Iwar; Payer, Juraj; Wolfrum, Christian; Ukropec, Jozef

    2015-02-01

    Hypertrophic obesity is associated with impaired insulin sensitivity and lipid-mobilizing activity of zinc-α2-glycoprotein. Adipose tissue (AT) of growth hormone (GH) -deficient patients is characterized by extreme adipocyte hypertrophy due to defects in AT lipid metabolism. It was hypothesized that zinc-α2-glycoprotein is regulated by GH and mediates some of its beneficial effects in AT. AT from patients with GH deficiency and individuals with obesity-related GH deficit was obtained before and after 5-year and 24-month GH supplementation therapy. GH action was tested in primary human adipocytes. Relationships of GH and zinc-α2-glycoprotein with adipocyte size and insulin sensitivity were evaluated in nondiabetic patients with noncancerous cachexia and hypertrophic obesity. AT in GH-deficient adults displayed a substantial reduction of zinc-α2-glycoprotein. GH therapy normalized AT zinc-α2-glycoprotein. Obesity-related relative GH deficit was associated with almost 80% reduction of zinc-α2-glycoprotein mRNA in AT. GH increased zinc-α2-glycoprotein mRNA in both AT of obese men and primary human adipocytes. Interdependence of GH and zinc-α2-glycoprotein in regulating AT morphology and metabolic phenotype was evident from their relationship with adipocyte size and AT-specific and whole-body insulin sensitivity. The results demonstrate that GH is involved in regulation of AT zinc-α2-glycoprotein; however, the molecular mechanism linking GH and zinc-α2-glycoprotein in AT is yet unknown. © 2014 The Obesity Society.

  20. Galectin-3 induces clustering of CD147 and integrin-β1 transmembrane glycoprotein receptors on the RPE cell surface.

    Directory of Open Access Journals (Sweden)

    Claudia S Priglinger

    Full Text Available Proliferative vitreoretinopathy (PVR is a blinding disease frequently occurring after retinal detachment surgery. Adhesion, migration and matrix remodeling of dedifferentiated retinal pigment epithelial (RPE cells characterize the onset of the disease. Treatment options are still restrained and identification of factors responsible for the abnormal behavior of the RPE cells will facilitate the development of novel therapeutics. Galectin-3, a carbohydrate-binding protein, was previously found to inhibit attachment and spreading of retinal pigment epithelial cells, and thus bares the potential to counteract PVR-associated cellular events. However, the identities of the corresponding cell surface glycoprotein receptor proteins on RPE cells are not known. Here we characterize RPE-specific Gal-3 containing glycoprotein complexes using a proteomic approach. Integrin-β1, integrin-α3 and CD147/EMMPRIN, a transmembrane glycoprotein implicated in regulating matrix metalloproteinase induction, were identified as potential Gal-3 interactors on RPE cell surfaces. In reciprocal immunoprecipitation experiments we confirmed that Gal-3 associated with CD147 and integrin-β1, but not with integrin-α3. Additionally, association of Gal-3 with CD147 and integrin-β1 was observed in co-localization analyses, while integrin-α3 only partially co-localized with Gal-3. Blocking of CD147 and integrin-β1 on RPE cell surfaces inhibited binding of Gal-3, whereas blocking of integrin-α3 failed to do so, suggesting that integrin-α3 is rather an indirect interactor. Importantly, Gal-3 binding promoted pronounced clustering and co-localization of CD147 and integrin-β1, with only partial association of integrin-α3. Finally, we show that RPE derived CD147 and integrin-β1, but not integrin-α3, carry predominantly β-1,6-N-actyl-D-glucosamine-branched glycans, which are high-affinity ligands for Gal-3. We conclude from these data that extracellular Gal-3 triggers

  1. Galectin-3 Induces Clustering of CD147 and Integrin-β1 Transmembrane Glycoprotein Receptors on the RPE Cell Surface

    Science.gov (United States)

    Priglinger, Claudia S.; Szober, Christoph M.; Priglinger, Siegfried G.; Merl, Juliane; Euler, Kerstin N.; Kernt, Marcus; Gondi, Gabor; Behler, Jennifer; Geerlof, Arie; Kampik, Anselm; Ueffing, Marius; Hauck, Stefanie M.

    2013-01-01

    Proliferative vitreoretinopathy (PVR) is a blinding disease frequently occurring after retinal detachment surgery. Adhesion, migration and matrix remodeling of dedifferentiated retinal pigment epithelial (RPE) cells characterize the onset of the disease. Treatment options are still restrained and identification of factors responsible for the abnormal behavior of the RPE cells will facilitate the development of novel therapeutics. Galectin-3, a carbohydrate-binding protein, was previously found to inhibit attachment and spreading of retinal pigment epithelial cells, and thus bares the potential to counteract PVR-associated cellular events. However, the identities of the corresponding cell surface glycoprotein receptor proteins on RPE cells are not known. Here we characterize RPE-specific Gal-3 containing glycoprotein complexes using a proteomic approach. Integrin-β1, integrin-α3 and CD147/EMMPRIN, a transmembrane glycoprotein implicated in regulating matrix metalloproteinase induction, were identified as potential Gal-3 interactors on RPE cell surfaces. In reciprocal immunoprecipitation experiments we confirmed that Gal-3 associated with CD147 and integrin-β1, but not with integrin-α3. Additionally, association of Gal-3 with CD147 and integrin-β1 was observed in co-localization analyses, while integrin-α3 only partially co-localized with Gal-3. Blocking of CD147 and integrin-β1 on RPE cell surfaces inhibited binding of Gal-3, whereas blocking of integrin-α3 failed to do so, suggesting that integrin-α3 is rather an indirect interactor. Importantly, Gal-3 binding promoted pronounced clustering and co-localization of CD147 and integrin-β1, with only partial association of integrin-α3. Finally, we show that RPE derived CD147 and integrin-β1, but not integrin-α3, carry predominantly β-1,6-N-actyl-D-glucosamine-branched glycans, which are high-affinity ligands for Gal-3. We conclude from these data that extracellular Gal-3 triggers clustering of CD147 and

  2. Glycoprotein expression by adenomatous polyps of the colon

    Science.gov (United States)

    Roney, Celeste A.; Xie, Jianwu; Xu, Biying; Jabour, Paul; Griffiths, Gary; Summers, Ronald M.

    2008-03-01

    Colon cancer is the second leading cause of cancer related deaths in the United States. Specificity in diagnostic imaging for detecting colorectal adenomas, which have a propensity towards malignancy, is desired. Adenomatous polyp specimens of the colon were obtained from the mouse model of colorectal cancer called adenomatous polyposis coli-multiple intestinal neoplasia (APC Min). Histological evaluation, by the legume protein Ulex europaeus agglutinin I (UEA-1), determined expression of the glycoprotein α-L-fucose. FITC-labelled UEA-1 confirmed overexpression of the glycoprotein by the polyps on fluorescence microscopy in 17/17 cases, of which 13/17 included paraffin-fixed mouse polyp specimens. In addition, FITC-UEA-1 ex vivo multispectral optical imaging of 4/17 colonic specimens displayed over-expression of the glycoprotein by the polyps, as compared to non-neoplastic mucosa. Here, we report the surface expression of α-L-fucosyl terminal residues by neoplastic mucosal cells of APC specimens of the mouse. Glycoprotein expression was validated by the carbohydrate binding protein UEA-1. Future applications of this method are the development of agents used to diagnose cancers by biomedical imaging modalities, including computed tomographic colonography (CTC). UEA-1 targeting to colonic adenomas may provide a new avenue for the diagnosis of colorectal carcinoma by CT imaging.

  3. Histochemical and structural analysis of mucous glycoprotein secreted by the gill of Mytilus edulis

    International Nuclear Information System (INIS)

    Ahn, Hae-Young.

    1988-01-01

    Studies were carried out to characterized various mucous cells in the gill filament, to ascertain structural characteristics of the secreted mucous glycoproteins, and to determine the ability of the gill epithelium to incorporate [ 14 C]glucosamine as a precursor in the biosynthesis and secretion of mucous glycoproteins. Using histochemical staining techniques, mucous cells containing neutral and acidic mucins were found in the lateral region, whereas mucous cells containing primarily neutral or sulfated mucins were found in the postlateral region. Serotonin, but not dopamine, stimulated the mucous secretion. In tissues pretreated with [ 14 C]glucosamine, the secreted glycoproteins contain incorporated radiolabel. Analysis by column chromatography using Bio-Gel P-2 and P-6 shows that the secretion contains two glycoprotein populations. Glycoprotein II has a molecular weight of 2.3 x 10 4 daltons. Upon alkaline reductive borohydride cleavage of the O-glycosidic linkages of glycoprotein I, about 70% of the radiolabel was removed from the protein. Gas chromatographic analysis of the carbohydrate composition shows that the glycoproteins contains N-acetylglucosamine (GluNAc), N-acetylgalactosamine (GalNAc), and galactose, fucose and mannose. Amino acid analysis shows that the glycoproteins are rich in serine, threonine and proline

  4. Monoclonal antibody to an external epitope of the human mdr1 P-glycoprotein

    NARCIS (Netherlands)

    Arceci, R. J.; Stieglitz, K.; Bras, J.; Schinkel, A.; Baas, F.; Croop, J.

    1993-01-01

    A membrane glycoprotein, termed P-glycoprotein, has been shown to be responsible for cross-resistance to a broad range of structurally and functionally distinct cytotoxic agents. P-glycoprotein, encoded in humans by the mdr1 gene, functions as an energy-dependent efflux pump to exclude these

  5. THE ROLE OF P-GLYCOPROTEIN IN RATIONAL PHARMACOTHERAPY IN CARDIOLOGY

    Directory of Open Access Journals (Sweden)

    A. V. Shulkin

    2015-09-01

    Full Text Available On the basis of the analysis of published data the role of P-glycoprotein, carrier protein, in rational pharmacotherapy in cardiology was shown on the example of its substrates – digoxin, antiplatelet agents and anticoagulants. Determination of C3435T polymorphism of multidrug resistance gene (MDR1, encoding P-glycoprotein, in pharmacotherapy with digoxin, antiplatelet drugs (clopidogrel tikagrelol, prasugrel and anticoagulants (dabigatran etexilate, rivaroxaban, edoxaban is not feasible in routine practice. Drug in- teractions have clinical implications for the efficacy and safety of pharmacotherapy in coadministration of these drugs with P-glycoprotein substrates, inducers and inhibitors.

  6. P-glycoprotein and multidrug resistance protein activities in relation to treatment outcome in acute myeloid leukemia

    NARCIS (Netherlands)

    de Vries, EGE; van Putten, WLJ; Verdonck, LF; Ossenkoppele, GJ; Verhoef, GEG; Vellenga, E

    Despite treatment with intensive chemotherapy, a considerable number of patients with acute myeloid leukemia (AML) die from their disease due to the occurrence of resistance. Overexpression of the transporter proteins P-glycoprotein (P-gp) and multidrug resistance protein (MRP) 1 has been identified

  7. Structures and Functions of Pestivirus Glycoproteins: Not Simply Surface Matters

    Directory of Open Access Journals (Sweden)

    Fun-In Wang

    2015-06-01

    Full Text Available Pestiviruses, which include economically important animal pathogens such as bovine viral diarrhea virus and classical swine fever virus, possess three envelope glycoproteins, namely Erns, E1, and E2. This article discusses the structures and functions of these glycoproteins and their effects on viral pathogenicity in cells in culture and in animal hosts. E2 is the most important structural protein as it interacts with cell surface receptors that determine cell tropism and induces neutralizing antibody and cytotoxic T-lymphocyte responses. All three glycoproteins are involved in virus attachment and entry into target cells. E1-E2 heterodimers are essential for viral entry and infectivity. Erns is unique because it possesses intrinsic ribonuclease (RNase activity that can inhibit the production of type I interferons and assist in the development of persistent infections. These glycoproteins are localized to the virion surface; however, variations in amino acids and antigenic structures, disulfide bond formation, glycosylation, and RNase activity can ultimately affect the virulence of pestiviruses in animals. Along with mutations that are driven by selection pressure, antigenic differences in glycoproteins influence the efficacy of vaccines and determine the appropriateness of the vaccines that are currently being used in the field.

  8. Importance of the short cytoplasmic domain of the feline immunodeficiency virus transmembrane glycoprotein for fusion activity and envelope glycoprotein incorporation into virions

    International Nuclear Information System (INIS)

    Celma, Cristina C.P.; Paladino, Monica G.; Gonzalez, Silvia A.; Affranchino, Jose L.

    2007-01-01

    The mature form of the envelope (Env) glycoprotein of lentiviruses is a heterodimer composed of the surface (SU) and transmembrane (TM) subunits. Feline immunodeficiency virus (FIV) possesses a TM glycoprotein with a cytoplasmic tail of approximately 53 amino acids which is unusually short compared with that of the other lentiviral glycoproteins (more than 100 residues). To investigate the relevance of the FIV TM cytoplasmic domain to Env-mediated viral functions, we characterized the biological properties of a series of Env glycoproteins progressively shortened from the carboxyl terminus. All the mutant Env proteins were efficiently expressed in feline cells and processed into the SU and TM subunits. Deletion of 5 or 11 amino acids from the TM C-terminus did not significantly affect Env surface expression, fusogenic activity or Env incorporation into virions, whereas removal of 17 or 23 residues impaired Env-mediated cell-to-cell fusion. Further truncation of the FIV TM by 29 residues resulted in an Env glycoprotein that was poorly expressed at the cell surface, exhibited only 20% of the wild-type Env fusogenic capacity and was inefficiently incorporated into virions. Remarkably, deletion of the TM C-terminal 35 or 41 amino acids restored or even enhanced Env biological functions. Indeed, these mutant Env glycoproteins bearing cytoplasmic domains of 18 or 12 amino acids were found to be significantly more fusogenic than the wild-type Env and were efficiently incorporated into virions. Interestingly, truncation of the TM cytoplasmic domain to only 6 amino acids did not affect Env incorporation into virions but abrogated Env fusogenicity. Finally, removal of the entire TM cytoplasmic tail or deletion of as many as 6 amino acids into the membrane-spanning domain led to a complete loss of Env functions. Our results demonstrate that despite its relatively short length, the FIV TM cytoplasmic domain plays an important role in modulating Env-mediated viral functions

  9. Quantitative mass spectrometric analysis of glycoproteins combined with enrichment methods.

    Science.gov (United States)

    Ahn, Yeong Hee; Kim, Jin Young; Yoo, Jong Shin

    2015-01-01

    Mass spectrometry (MS) has been a core technology for high sensitive and high-throughput analysis of the enriched glycoproteome in aspects of quantitative assays as well as qualitative profiling of glycoproteins. Because it has been widely recognized that aberrant glycosylation in a glycoprotein may involve in progression of a certain disease, the development of efficient analysis tool for the aberrant glycoproteins is very important for deep understanding about pathological function of the glycoprotein and new biomarker development. This review first describes the protein glycosylation-targeting enrichment technologies mainly employing solid-phase extraction methods such as hydrizide-capturing, lectin-specific capturing, and affinity separation techniques based on porous graphitized carbon, hydrophilic interaction chromatography, or immobilized boronic acid. Second, MS-based quantitative analysis strategies coupled with the protein glycosylation-targeting enrichment technologies, by using a label-free MS, stable isotope-labeling, or targeted multiple reaction monitoring (MRM) MS, are summarized with recent published studies. © 2014 The Authors. Mass Spectrometry Reviews Published by Wiley Periodicals, Inc.

  10. Somatosensory abnormalities in knee OA.

    Science.gov (United States)

    Wylde, Vikki; Palmer, Shea; Learmonth, Ian D; Dieppe, Paul

    2012-03-01

    The aim of this study was to use quantitative sensory testing (QST) to explore the range and prevalence of somatosensory abnormalities demonstrated by patients with advanced knee OA. One hundred and seven knee OA patients and 50 age- and sex-matched healthy participants attended a 1-h QST session. Testing was performed on the medial side of the knee and the pain-free forearm. Light-touch thresholds were assessed using von Frey filaments, pressure pain thresholds using a digital pressure algometer, and thermal sensation and pain thresholds using a Thermotest MSA. Significant differences in median threshold values from knee OA patients and healthy participants were identified using Mann-Whitney U-tests. The z-score transformations were used to determine the prevalence of the different somatosensory abnormalities in knee OA patients. Testing identified 70% of knee OA patients as having at least one somatosensory abnormality. Comparison of median threshold values between knee OA patients and healthy participants revealed that patients had localized thermal and tactile hypoaesthesia and pressure hyperalgesia at the osteoarthritic knee. Tactile hypoaesthesia and pressure hyperalgesia were also present at the pain-free forearm. The most prevalent somatosensory abnormalities were tactile hypoaesthesia and pressure hyperalgesia, evident in between 20 and 34% of patients. This study found that OA patients demonstrate an array of somatosensory abnormalities, of which the most prevalent were tactile hypoaesthesia and pressure hyperalgesia. Further research is now needed to establish the clinical implications of these somatosensory abnormalities.

  11. Isolation and characterization of broadly neutralizing human monoclonal antibodies to the e1 glycoprotein of hepatitis C virus

    DEFF Research Database (Denmark)

    Meunier, Jean-Christophe; Russell, Rodney S.; Goossens, Vera

    2008-01-01

    The relative importance of humoral and cellular immunity in the prevention or clearance of hepatitis C virus (HCV) infection is poorly understood. However, there is considerable evidence that neutralizing antibodies are involved in disease control. Here we describe the detailed analysis of human...... monoclonal antibodies (MAbs) directed against HCV glycoprotein E1, which may have the potential to control HCV infection. We have identified two MAbs that can strongly neutralize HCV-pseudotyped particles (HCVpp) bearing the envelope glycoproteins of genotypes 1a, 1b, 4a, 5a, and 6a and less strongly...... neutralize HCVpp bearing the envelope glycoproteins of genotype 2a. Genotype 3a was not neutralized. The epitopes for both MAbs were mapped to the region encompassing amino acids 313 to 327. In addition, robust neutralization was also observed against cell culture-adapted viruses of genotypes 1a and 2a...

  12. A Method for Determining the Content of Glycoproteins in Biological Samples

    Directory of Open Access Journals (Sweden)

    Yang Gao

    2016-11-01

    Full Text Available The glycoprotein purified from the mycelium extract of Tremella fuciformis was marked with iodine through the iodine substitution reaction. The content of iodine, which is indicative of the amount of the marked tremella glycoprotein (ITG, was detected with Inductively coupled plasma mass spectrometry (ICP-MS. The method was found to be stable, sensitive, and accurate at detecting the content of iodine-substituted glycoprotein, and was used in the quantitative analysis of biological samples, including blood and organs. Different biological samples were collected from rats after oral administration of ITG, and were tested for iodine content by ICP-MS to calculate the amount of ITG in the samples. The results suggested that ICP-MS is a sensitive, stable, and accurate method for detection of iodinated glycoproteins in blood and organs.

  13. Shedding of soluble glycoprotein 1 detected during acute Lassa virus infection in human subjects.

    Science.gov (United States)

    Branco, Luis M; Grove, Jessica N; Moses, Lina M; Goba, Augustine; Fullah, Mohammed; Momoh, Mambu; Schoepp, Randal J; Bausch, Daniel G; Garry, Robert F

    2010-11-09

    Lassa hemorrhagic fever (LHF) is a neglected tropical disease with significant impact on the health care system, society, and economy of Western and Central African nations where it is endemic. With a high rate of infection that may lead to morbidity and mortality, understanding how the virus interacts with the host's immune system is of great importance for generating vaccines and therapeutics. Previous work by our group identified a soluble isoform of the Lassa virus (LASV) GP1 (sGP1) in vitro resulting from the expression of the glycoprotein complex (GPC) gene [1, 2]. Though no work has directly been done to demonstrate the function of this soluble isoform in arenaviral infections, evidence points to immunomodulatory effects against the host's immune system mediated by a secreted glycoprotein component in filoviruses, another class of hemorrhagic fever-causing viruses. A significant fraction of shed glycoprotein isoforms during viral infection and biogenesis may attenuate the host's inflammatory response, thereby enhancing viral replication and tissue damage. Such shed glycoprotein mediated effects were previously reported for Ebola virus (EBOV), a filovirus that also causes hemorrhagic fever with nearly 90 percent fatality rates [3 - 5]. The identification of an analogous phenomenon in vivo could establish a new correlate of LHF infection leading to the development of sensitive diagnostics targeting the earliest molecular events of the disease. Additionally, the reversal of potentially untoward immunomodulatory functions mediated by sGP1 could potentiate the development of novel therapeutic intervention. To this end, we investigated the presence of sGP1 in the serum of suspected LASV patients admitted to the Kenema Government Hospital (KGH) Lassa Fever Ward (LFW), in Kenema, Sierra Leone that tested positive for viral antigen or displayed classical signs of Lassa fever. It is reasonable to expect that a narrow window exists for detection of sGP1 as the sole

  14. Glycoprotein of the wall of sycamore tissue-culture cells.

    Science.gov (United States)

    Heath, M F; Northcote, D H

    1971-12-01

    1. A glycoprotein containing a large amount of hydroxyproline is present in the cell walls of sycamore callus cells. This protein is insoluble and remained in the alpha-cellulose when a mild separation procedure was used to obtain the polysaccharide fractions of the wall. The glycoprotein contained a high proportion of arabinose and galactose. 2. Soluble glycopeptides were prepared from the alpha-cellulose fraction when peptide bonds were broken by hydrazinolysis. The soluble material was fractionated by gel filtration and one glycopeptide was further purified by electrophoresis; it had a composition of 10% hydroxyproline, 35% arabinose and 55% galactose, and each hydroxyproline residue carried a glycosyl radical so that the oligosaccharides on the glycopeptide had an average degree of polymerization of 9. 3. The extraction of the glycopeptides was achieved without cleavage of glycosyl bonds, so that the glycoprotein cannot act as a covalent cross-link between the major polysaccharides of the wall. 4. The wall protein approximates in conformation to polyhydroxyproline and therefore it probably has similar physicochemical properties to polyhydroxyproline. This is discussed in relation to the function of the glycoprotein and its effect on the physical and chemical nature of the wall.

  15. Thyroid hormone upregulates zinc-α2-glycoprotein production in the liver but not in adipose tissue.

    Directory of Open Access Journals (Sweden)

    Rafael Simó

    Full Text Available Overproduction of zinc-α2-glycoprotein by adipose tissue is crucial in accounting for the lipolysis occurring in cancer cachexia of certain malignant tumors. The main aim of this study was to explore whether thyroid hormone could enhance zinc-α2-glycoprotein production in adipose tissue. In addition, the regulation of zinc-α2-glycoprotein by thyroid hormone in the liver was investigated. We performed in vitro (HepG2 cells and primary human adipocytes and in vivo (C57BL6/mice experiments addressed to examine the effect of thyroid hormone on zinc-α2-glycoprotein production (mRNA and protein levels in liver and visceral adipose tissue. We also measured the zinc-α2-glycoprotein serum levels in a cohort of patients before and after controlling their hyperthyroidism. Our results showed that thyroid hormone up-regulates zinc-α2-glycoprotein production in HepG2 cells in a dose-dependent manner. In addition, the zinc-α2-glycoprotein proximal promoter contains functional thyroid hormone receptor binding sites that respond to thyroid hormone treatment in luciferase reporter gene assays in HepG2 cells. Furthermore, zinc-α2-glycoprotein induced lipolysis in HepG2 in a dose-dependent manner. Our in vivo experiments in mice confirmed the up-regulation of zinc-α2-glycoprotein induced by thyroid hormone in the liver, thus leading to a significant increase in zinc-α2-glycoprotein circulating levels. However, thyroid hormone did not regulate zinc-α2-glycoprotein production in either human or mouse adipocytes. Finally, in patients with hyperthyroidism a significant reduction of zinc-α2-glycoprotein serum levels was detected after treatment but was unrelated to body weight changes. We conclude that thyroid hormone up-regulates the production of zinc-α2-glycoprotein in the liver but not in the adipose tissue. The neutral effect of thyroid hormones on zinc-α2-glycoprotein expression in adipose tissue could be the reason why zinc-α2-glycoprotein is not

  16. Thyroid hormone upregulates zinc-α2-glycoprotein production in the liver but not in adipose tissue.

    Science.gov (United States)

    Simó, Rafael; Hernández, Cristina; Sáez-López, Cristina; Soldevila, Berta; Puig-Domingo, Manel; Selva, David M

    2014-01-01

    Overproduction of zinc-α2-glycoprotein by adipose tissue is crucial in accounting for the lipolysis occurring in cancer cachexia of certain malignant tumors. The main aim of this study was to explore whether thyroid hormone could enhance zinc-α2-glycoprotein production in adipose tissue. In addition, the regulation of zinc-α2-glycoprotein by thyroid hormone in the liver was investigated. We performed in vitro (HepG2 cells and primary human adipocytes) and in vivo (C57BL6/mice) experiments addressed to examine the effect of thyroid hormone on zinc-α2-glycoprotein production (mRNA and protein levels) in liver and visceral adipose tissue. We also measured the zinc-α2-glycoprotein serum levels in a cohort of patients before and after controlling their hyperthyroidism. Our results showed that thyroid hormone up-regulates zinc-α2-glycoprotein production in HepG2 cells in a dose-dependent manner. In addition, the zinc-α2-glycoprotein proximal promoter contains functional thyroid hormone receptor binding sites that respond to thyroid hormone treatment in luciferase reporter gene assays in HepG2 cells. Furthermore, zinc-α2-glycoprotein induced lipolysis in HepG2 in a dose-dependent manner. Our in vivo experiments in mice confirmed the up-regulation of zinc-α2-glycoprotein induced by thyroid hormone in the liver, thus leading to a significant increase in zinc-α2-glycoprotein circulating levels. However, thyroid hormone did not regulate zinc-α2-glycoprotein production in either human or mouse adipocytes. Finally, in patients with hyperthyroidism a significant reduction of zinc-α2-glycoprotein serum levels was detected after treatment but was unrelated to body weight changes. We conclude that thyroid hormone up-regulates the production of zinc-α2-glycoprotein in the liver but not in the adipose tissue. The neutral effect of thyroid hormones on zinc-α2-glycoprotein expression in adipose tissue could be the reason why zinc-α2-glycoprotein is not related to weight

  17. 3,3′,4,4′,5-Pentachlorobiphenyl Inhibits Drug Efflux Through P-Glycoprotein in KB-3 Cells Expressing Mutant Human P-Glycoprotein

    Directory of Open Access Journals (Sweden)

    Hiroshi Fujise

    2004-01-01

    Full Text Available The effects on the drug efflux of 3,3′,4,4′,5-pentachlorobiphenyl (PCB-126, the most toxic of all coplanar polychlorinated biphenyls (Co-PCBs, were examined in KB-3 cells expressing human wild-type and mutant P-glycoprotein in which the 61st amino acid was substituted for serine or phenylalanine (KB3-Phe61. In the cells expressing P-glycoproteins, accumulations of vinblastine and colchicine decreased form 85% to 92% and from 62% to 91%, respectively, and the drug tolerances for these chemicals were increased. In KB3-Phe61, the decreases in drug accumulation were inhibited by adding PCB-126 in a way similar to that with cyclosporine A: by adding 1 μM PCB-126, the accumulations of vinblastine and colchicine increased up to 3.3- and 2.3-fold, respectively. It is suggested that PCB-126 decreased the drug efflux by inhibiting the P-glycoprotein in KB3-Phe61. Since there were various P-glycoproteins and many congeners of Co-PCBs, this inhibition has to be considered a new cause of the toxic effects of Co-PCBs.

  18. Prediction of conserved sites and domains in glycoproteins B, C and D of herpes viruses.

    Science.gov (United States)

    Rasheed, Muhammad Asif; Ansari, Abdur Rahman; Ihsan, Awais; Navid, Muhammad Tariq; Ur-Rehman, Shahid; Raza, Sohail

    2018-03-01

    Glycoprotein B (gB), C (gC) and D (gD) of herpes simplex virus are implicated in virus adsorption and penetration. The gB, gC and gD are glycoproteins for different processes of virus binding and attachment to the host cells. Moreover, their expression is necessary and sufficient to induce cell fusion in the absence of other glycoproteins. Egress of herpes simplex virus (HSV) and other herpes viruses from cells involves extensive modification of cellular membranes and sequential envelopment, de-envelopment and re-envelopment steps. Viral glycoproteins are important in these processes, and frequently two or more glycoproteins can largely suffice in any step. Hence, we target the 3 important glycoproteins (B, C and D) of eight different herpes viruses of different species. These species include human (HSV1 and 2), bovine (BHV1), equine (EHV1 and 4), chicken (ILT1 and MDV2) and pig (PRV1). By applying different bioinformatics tools, we highlighted the conserved sites in these glycoproteins which might be most significant regarding attachment and infection of the viruses. Moreover the conserved domains in these glycoproteins are also highlighted. From this study, we will able to analyze the role of different viral glycoproteins of different species during herpes virus adsorption and penetration. Moreover, this study will help to construct the antivirals that target the glycoproteins of different herpes viruses. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Prevalence of knee abnormalities in patients with osteoarthritis and anterior cruciate ligament injury identified with peripheral magnetic resonance imaging: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Wu, H. [McMaster Univ., Dept. of Medical Sciences, Hamilton, Ontario (Canada)]. E-mail: wuh5@mcmaster.ca; Webber, C. [Hamilton Health Sciences, Dept. of Nuclear Medicine, Hamilton, Ontario (Canada); McMaster Univ., Dept. of Radiology, Hamilton, Ontario (Canada); Fuentes, C.O. [Hamilton Health Sciences, Dept. of Radiology, Hamilton, Ontario (Canada); Benson, R.; Beattie, K. [McMaster Univ., Dept. of Medical Sciences, Hamilton, Ontario (Canada); Adachi, J.D.; Xie, X. [McMaster Univ., Dept. of Medical Sciences, Hamilton, Ontario (Canada); Jabbari, F. [Hamilton Health Sciences, Hamilton, Ontario (Canada); Levy, D.R. [McMaster Univ., Sports Medicine, Dept. of Family Medicine and Dept. of Medicine, Hamilton, Ontario (Canada)

    2007-06-15

    To assess, with a peripheral magnetic resonance imaging system (pMRI), the prevalence of bony and soft tissue abnormalities in the knee joints of normal subjects, osteoarthritis (OA) patients, and individuals who have suffered an anterior cruciate ligament (ACL) rupture; and 2) to compare the prevalence among groups. Magnetic resonance (MR) images of 28 healthy, 32 OA, and 26 ACL damaged knees were acquired with a 1.0-T pMRI system. Two radiologists grade the presence and severity of 9 MR image features: cartilage degeneration, osteophytes, subchondral cyst, bone marrow edema, meniscal abnormality, ligament integrity, loose bodies, popliteal cysts, and joint effusion. Ten of 28 healthy (35.7%), 24 of 26 ACL (92.3%), and all OA knees (100%) showed prevalent cartilage defects; 5 healthy (17.9%), 20 ACL (76.9%), and all OA knees (100%) had osteophytes; and 9 normal (32.1%), 21 ACL (80.8%), and 29 OA knees (90.6%) had meniscal abnormalities. One-half of the knees in the OA group (16 of 32, 50%) had subchondral cysts, and almost one-half had bone marrow edema (15 of 32, 46.9%). These features were not common in the ACL group (7.7%, and 11.5%, respectively) and were not observed in healthy knees. The OA group had the most severe cartilage defects, osteophytes, bone marrow edema, subchondral cysts, and meniscal abnormalities; the ACL group showed more severe cartilage defects, osteophytes, and meniscal abnormalities than did normal subjects. The results suggest that knees that have sustained ACL damage have OA-like features, most subjects (19 of 26, 73.1%) could be identified as in the early stage of OA. The prominent abnormalities present in ACL-damaged knees are cartilage defects, osteophytes, and meniscal abnormalities. (author)

  20. Prevalence of knee abnormalities in patients with osteoarthritis and anterior cruciate ligament injury identified with peripheral magnetic resonance imaging: a pilot study

    International Nuclear Information System (INIS)

    Wu, H.; Webber, C.; Fuentes, C.O.; Benson, R.; Beattie, K.; Adachi, J.D.; Xie, X.; Jabbari, F.; Levy, D.R.

    2007-01-01

    To assess, with a peripheral magnetic resonance imaging system (pMRI), the prevalence of bony and soft tissue abnormalities in the knee joints of normal subjects, osteoarthritis (OA) patients, and individuals who have suffered an anterior cruciate ligament (ACL) rupture; and 2) to compare the prevalence among groups. Magnetic resonance (MR) images of 28 healthy, 32 OA, and 26 ACL damaged knees were acquired with a 1.0-T pMRI system. Two radiologists grade the presence and severity of 9 MR image features: cartilage degeneration, osteophytes, subchondral cyst, bone marrow edema, meniscal abnormality, ligament integrity, loose bodies, popliteal cysts, and joint effusion. Ten of 28 healthy (35.7%), 24 of 26 ACL (92.3%), and all OA knees (100%) showed prevalent cartilage defects; 5 healthy (17.9%), 20 ACL (76.9%), and all OA knees (100%) had osteophytes; and 9 normal (32.1%), 21 ACL (80.8%), and 29 OA knees (90.6%) had meniscal abnormalities. One-half of the knees in the OA group (16 of 32, 50%) had subchondral cysts, and almost one-half had bone marrow edema (15 of 32, 46.9%). These features were not common in the ACL group (7.7%, and 11.5%, respectively) and were not observed in healthy knees. The OA group had the most severe cartilage defects, osteophytes, bone marrow edema, subchondral cysts, and meniscal abnormalities; the ACL group showed more severe cartilage defects, osteophytes, and meniscal abnormalities than did normal subjects. The results suggest that knees that have sustained ACL damage have OA-like features, most subjects (19 of 26, 73.1%) could be identified as in the early stage of OA. The prominent abnormalities present in ACL-damaged knees are cartilage defects, osteophytes, and meniscal abnormalities. (author)

  1. ABNORMAL UTERINE BLEEDING- UTILITY OF DILATATION AND CURETTAGE IN IDENTIFYING ISOLATED ENDOMETRIAL PATHOLOGY

    Directory of Open Access Journals (Sweden)

    Radhika Gollapudi

    2016-12-01

    Full Text Available BACKGROUND Abnormal uterine bleeding is defined as any bleeding not conforming to the normal cyclical pattern as well as to the normal amount and frequency of menstrual cycle. Abnormal uterine bleeding can occur due to gynaecological as well as medical causes. Gynaecological causes include organic and nonorganic factors. It has various clinical presentations such as menorrhagia, polymenorrhagia, metrorrhagia and intermenstrual bleeding. Dilatation and Curettage (D and C is a safe and effective outpatient procedure performed in patients with AUB. It provides endometrial tissue for examination of histological variations of endometrium thus guiding in further management. MATERIALS AND METHODS This is a retrospective study of patients presenting with AUB over a period of one year (2015-2016 done in the Department of Obstetrics and Gynaecology at a tertiary care hospital. 89 patients with complaints of AUB attributable to isolated endometrial cause were included in the study. Patients with AUB due to vaginal, cervical causes, leiomyomas, adnexal pathology, medical causes and complications of pregnancy were excluded from the study. A structured proforma regarding the patient’s complaints, pattern of bleeding, medical, surgical history and a general systemic and pelvic examination was used to evaluate all patients. RESULTS Among all the patients who presented with AUB during the study period, 89 patients were identified to have isolated endometrial pathology as a cause of abnormal uterine bleeding. In our study, age of patients presenting with AUB ranged from 24 years to 70 years. AUB was most commonly seen in the age group of 41-50 years (42.6%. Menorrhagia in 32.5% was the most common presentation of AUB. The commonest histopathological finding was proliferative phase endometrium (25.84% followed by secretory phase endometrium (19.1%. Hyperplasia was observed in 19.1%, which included simple hyperplasia (6.74%, complex hyperplasia without atypia in

  2. Glycoprotein and proteoglycan techniques

    International Nuclear Information System (INIS)

    Beeley, J.G.

    1985-01-01

    The aim of this book is to describe techniques which can be used to answer some of the basic questions about glycosylated proteins. Methods are discussed for isolation, compositional analysis, and for determination of the primary structure of carbohydrate units and the nature of protein-carbohydrate linkages of glycoproteins and proteoglycans. High resolution NMR is considered, as well as radioactive labelling techniques. (Auth.)

  3. HIV-1 envelope glycoprotein

    Science.gov (United States)

    Caulfield, Michael; Cupo, Albert; Dean, Hansi; Hoffenberg, Simon; King, C. Richter; Klasse, P. J.; Marozsan, Andre; Moore, John P.; Sanders, Rogier W.; Ward, Andrew; Wilson, Ian; Julien, Jean-Philippe

    2017-08-22

    The present application relates to novel HIV-1 envelope glycoproteins, which may be utilized as HIV-1 vaccine immunogens, and antigens for crystallization, electron microscopy and other biophysical, biochemical and immunological studies for the identification of broad neutralizing antibodies. The present invention encompasses the preparation and purification of immunogenic compositions, which are formulated into the vaccines of the present invention.

  4. [Prevalence of congenital abnormalities identified in fetuses with 13, 18 and 21 chromosomal trisomy].

    Science.gov (United States)

    Emer, Caroline Soares Cristofari; Duque, Julio Alejandro Peña; Müller, Ana Lúcia Letti; Gus, Rejane; Sanseverino, Maria Teresa Vieira; da Silva, André Anjos; Magalhães, José Antonio de Azevedo

    2015-07-01

    To describe the prevalence of malformations found in fetuses with trisomy of chromosomes 13, 18 and 21 by identifying the most frequent within each condition. A retrospective cross-sectional study with the analysis of trisomy cases of chromosomes 13, 18 and 21 diagnosed through fetal karyotype obtained by amniocentesis/cordocentesis, between October 1994 and May 2014, at a Teaching Hospital in Brazil Southern Region. Malformations identified through morphological ultrasonography were described and, subsequently, confirmed in newborn examinations and/or fetal autopsy. The results were analyzed using Fisher's test and analysis of variance (ANOVA), with a 5% level of significance (p=0.05). Sixty-nine cases of trisomy were diagnosed among 840 exams; nine were excluded due to outcome outside Hospital de Clínicas de Porto Alegre or incomplete records, remaining 60 cases (nine cases of chromosome 13 trisomy, 26 of chromosome 18, and 25 of chromosome 21). In all three groups, heart disease occurred in most cases; the ventricular septal defect was more prevalent and occurred in 66.7% of the trisomy 13 group. Gastrointestinal abnormalities were more prevalent in the trisomy 18 group, especially omphalocele (38.5%; pmalformations significantly differed among the trisomy groups. Hand defects occurred in 50% of trisomy 18 cases, and in 44.4% of all trisomy 13 cases (pmalformations identified at ultrasound are suggestive of trisomy and represent an important tool for etiologic diagnosis and prenatal and pre-conception genetic counseling.

  5. 'Leukodystrophy-like' phenotype in children with myelin oligodendrocyte glycoprotein antibody-associated disease.

    Science.gov (United States)

    Hacohen, Yael; Rossor, Thomas; Mankad, Kshitij; Chong, Wk 'Kling'; Lux, Andrew; Wassmer, Evangeline; Lim, Ming; Barkhof, Frederik; Ciccarelli, Olga; Hemingway, Cheryl

    2018-04-01

    To review the demographics and clinical and paraclinical parameters of children with myelin oligodendrocyte glycoprotein (MOG) antibody-associated relapsing disease. In this UK-based, multicentre study, 31 children with MOG antibody-associated relapsing disease were studied retrospectively. Of the 31 children studied, 14 presented with acute disseminated encephalomyelitis (ADEM); they were younger (mean 4.1y) than the remainder (mean 8.5y) who presented with optic neuritis and/or transverse myelitis (p<0.001). Similarly, children who had an abnormal brain magnetic resonance imaging (MRI) at onset (n=20) were younger than patients with normal MRI at onset (p=0.001) or at follow-up (p<0.001). 'Leukodystrophy-like' MRI patterns of confluent largely symmetrical lesions was seen during the course of the disease in 7 out of 14 children with a diagnosis of ADEM, and was only seen in children younger than 7 years of age. Their disability after a 3-year follow-up was mild to moderate, and most patients continued to relapse, despite disease-modifying treatments. MOG antibody should be tested in children presenting with relapsing neurological disorders associated with confluent, bilateral white matter changes, and distinct enhancement pattern. Children with MOG antibody-associated disease present with age-related differences in phenotypes, with a severe leukoencephalopathy phenotype in the very young and normal intracranial MRI in the older children. This finding suggests a susceptibility of the very young and myelinating brain to MOG antibody-mediated mechanisms of damage. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination manifest with an age-related phenotype. Children with MOG antibody and 'leukodystrophy-like' imaging patterns tend to have poor response to second-line immunotherapy. © 2017 Mac Keith Press.

  6. Quantitative proteomic analysis for high-throughput screening of differential glycoproteins in hepatocellular carcinoma serum

    International Nuclear Information System (INIS)

    Gao, Hua-Jun; Chen, Ya-Jing; Zuo, Duo; Xiao, Ming-Ming; Li, Ying; Guo, Hua; Zhang, Ning; Chen, Rui-Bing

    2015-01-01

    Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths. Novel serum biomarkers are required to increase the sensitivity and specificity of serum screening for early HCC diagnosis. This study employed a quantitative proteomic strategy to analyze the differential expression of serum glycoproteins between HCC and normal control serum samples. Lectin affinity chromatography (LAC) was used to enrich glycoproteins from the serum samples. Quantitative mass spectrometric analysis combined with stable isotope dimethyl labeling and 2D liquid chromatography (LC) separations were performed to examine the differential levels of the detected proteins between HCC and control serum samples. Western blot was used to analyze the differential expression levels of the three serum proteins. A total of 2,280 protein groups were identified in the serum samples from HCC patients by using the 2D LC-MS/MS method. Up to 36 proteins were up-regulated in the HCC serum, whereas 19 proteins were down-regulated. Three differential glycoproteins, namely, fibrinogen gamma chain (FGG), FOS-like antigen 2 (FOSL2), and α-1,6-mannosylglycoprotein 6-β-N-acetylglucosaminyltransferase B (MGAT5B) were validated by Western blot. All these three proteins were up-regulated in the HCC serum samples. A quantitative glycoproteomic method was established and proven useful to determine potential novel biomarkers for HCC

  7. Crystallization and preliminary X-ray analysis of Chandipura virus glycoprotein G

    International Nuclear Information System (INIS)

    Baquero, Eduard; Buonocore, Linda; Rose, John K.; Bressanelli, Stéphane; Gaudin, Yves; Albertini, Aurélie A.

    2012-01-01

    Chandipura virus glycoprotein ectodomain (Gth) was purified and crystallized at pH 7.5. X-ray diffraction data set was collected to a resolution of 3.1 Å. Fusion in members of the Rhabdoviridae virus family is mediated by the G glycoprotein. At low pH, the G glycoprotein catalyzes fusion between viral and endosomal membranes by undergoing a major conformational change from a pre-fusion trimer to a post-fusion trimer. The structure of the G glycoprotein from vesicular stomatitis virus (VSV G), the prototype of Vesiculovirus, has recently been solved in its trimeric pre-fusion and post-fusion conformations; however, little is known about the structural details of the transition. In this work, a soluble form of the ectodomain of Chandipura virus G glycoprotein (CHAV G th ) was purified using limited proteolysis of purified virus; this soluble ectodomain was also crystallized. This protein shares 41% amino-acid identity with VSV G and thus its structure could provide further clues about the structural transition of rhabdoviral glycoproteins induced by low pH. Crystals of CHAV G th obtained at pH 7.5 diffracted X-rays to 3.1 Å resolution. These crystals belonged to the orthorhombic space group P2 1 2 1 2, with unit-cell parameters a = 150.3, b = 228.2, c = 78.8 Å. Preliminary analysis of the data based on the space group and the self-rotation function indicated that there was no trimeric association of the protomers. This unusual oligomeric status could result from the presence of fusion intermediates in the crystal

  8. Synthetic glycopeptides and glycoproteins with applications in biological research

    Directory of Open Access Journals (Sweden)

    Ulrika Westerlind

    2012-05-01

    Full Text Available Over the past few years, synthetic methods for the preparation of complex glycopeptides have been drastically improved. The need for homogenous glycopeptides and glycoproteins with defined chemical structures to study diverse biological phenomena further enhances the development of methodologies. Selected recent advances in synthesis and applications, in which glycopeptides or glycoproteins serve as tools for biological studies, are reviewed. The importance of specific antibodies directed to the glycan part, as well as the peptide backbone has been realized during the development of synthetic glycopeptide-based anti-tumor vaccines. The fine-tuning of native chemical ligation (NCL, expressed protein ligation (EPL, and chemoenzymatic glycosylation techniques have all together enabled the synthesis of functional glycoproteins. The synthesis of structurally defined, complex glycopeptides or glyco-clusters presented on natural peptide backbones, or mimics thereof, offer further possibilities to study protein-binding events.

  9. The glycoproteins of Marburg and Ebola virus and their potential roles in pathogenesis.

    Science.gov (United States)

    Feldmann, H; Volchkov, V E; Volchkova, V A; Klenk, H D

    1999-01-01

    Filoviruses cause systemic infections that can lead to severe hemorrhagic fever in human and non-human primates. The primary target of the virus appears to be the mononuclear phagocytic system. As the virus spreads through the organism, the spectrum of target cells increases to include endothelial cells, fibroblasts, hepatocytes, and many other cells. There is evidence that the filovirus glycoprotein plays an important role in cell tropism, spread of infection, and pathogenicity. Biosynthesis of the glycoprotein forming the spikes on the virion surface involves cleavage by the host cell protease furin into two disulfide linked subunits GP1 and GP2. GP1 is also shed in soluble form from infected cells. Different strains of Ebola virus show variations in the cleavability of the glycoprotein, that may account for differences in pathogenicity, as has been observed with influenza viruses and paramyxoviruses. Expression of the spike glycoprotein of Ebola virus, but not of Marburg virus, requires transcriptional editing. Unedited GP mRNA yields the nonstructural glycoprotein sGP, which is secreted extensively from infected cells. Whether the soluble glycoproteins GP1 and sGP interfere with the humoral immune response and other defense mechanisms remains to be determined.

  10. Three-dimensionally Functionalized Reverse Phase Glycoprotein Array for Cancer Biomarker Discovery and Validation

    OpenAIRE

    Pan, Li; Aguilar, Hillary Andaluz; Wang, Linna; Iliuk, Anton; Tao, W. Andy

    2016-01-01

    Glycoproteins have vast structural diversity which plays an important role in many biological processes and have great potential as disease biomarkers. Here we report a novel functionalized reverse phase protein array (RPPA), termed polymer-based reverse phase GlycoProtein Array (polyGPA), to specifically capture and profile glycoproteomes, and validate glycoproteins. Nitrocellulose membrane functionalized with globular hydroxyaminodendrimers was used to covalently capture pre-oxidized glycan...

  11. Filamentous fungi as production organisms for glycoproteins of bio-medical interest

    NARCIS (Netherlands)

    Maras, M.; Die, I. van; Contreras, R.; Hondel, C.A.M.J.J. van den

    1999-01-01

    Filamentous fungi are commonly used in the fermentation industry for large scale production of glycoproteins. Several of these proteins can be produced in concentrations up to 20-40 g per litre. The production of heterologous glycoproteins is at least one or two orders of magnitude lower but

  12. Shedding of soluble glycoprotein 1 detected during acute Lassa virus infection in human subjects

    Directory of Open Access Journals (Sweden)

    Momoh Mambu

    2010-11-01

    Full Text Available Abstract Background Lassa hemorrhagic fever (LHF is a neglected tropical disease with significant impact on the health care system, society, and economy of Western and Central African nations where it is endemic. With a high rate of infection that may lead to morbidity and mortality, understanding how the virus interacts with the host's immune system is of great importance for generating vaccines and therapeutics. Previous work by our group identified a soluble isoform of the Lassa virus (LASV GP1 (sGP1 in vitro resulting from the expression of the glycoprotein complex (GPC gene 12. Though no work has directly been done to demonstrate the function of this soluble isoform in arenaviral infections, evidence points to immunomodulatory effects against the host's immune system mediated by a secreted glycoprotein component in filoviruses, another class of hemorrhagic fever-causing viruses. A significant fraction of shed glycoprotein isoforms during viral infection and biogenesis may attenuate the host's inflammatory response, thereby enhancing viral replication and tissue damage. Such shed glycoprotein mediated effects were previously reported for Ebola virus (EBOV, a filovirus that also causes hemorrhagic fever with nearly 90% fatality rates 345. The identification of an analogous phenomenon in vivo could establish a new correlate of LHF infection leading to the development of sensitive diagnostics targeting the earliest molecular events of the disease. Additionally, the reversal of potentially untoward immunomodulatory functions mediated by sGP1 could potentiate the development of novel therapeutic intervention. To this end, we investigated the presence of sGP1 in the serum of suspected LASV patients admitted to the Kenema Government Hospital (KGH Lassa Fever Ward (LFW, in Kenema, Sierra Leone that tested positive for viral antigen or displayed classical signs of Lassa fever. Results It is reasonable to expect that a narrow window exists for

  13. Report to Congress on abnormal occurrences

    International Nuclear Information System (INIS)

    1993-06-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health and safety and requires a quarterly report of such events to be made to Congress. This report covers the period January through March 1993. There is one abnormal occurrence at a nuclear power plant disposed in this report that involved a steam generator tube rupture at Palo Verde Unit 2, and none for fuel cycle facilities. Three abnormal occurrences involving medical misadminstrations (two therapeutic and one diagnostic) at NRC-licensed facilities are also discussed in this report. No abnormal occurrences were reported by NRC's Agreement States. The report also contains information updating previously reported abnormal occurrences

  14. Co-treatment by docetaxel and vinblastine breaks down P-glycoprotein mediated chemo-resistance

    Directory of Open Access Journals (Sweden)

    Mahsa Mohseni

    2016-03-01

    Results: Combination treatment of the cells with docetaxel and vinblastine decreased the IC50 values for docetaxel from (30±3.1 to (15±2.6 nM and for vinblastine from (30±5.9 to (5±5.6 nM (P≤0.05.               P-glycoprotein mRNA expression level showed a significant up-regulation in the cells incubated with each drug alone (P≤0.001. Incubation of the cells with combined concentrations of both agents neutralized P-glycoprotein overexpression (P≤0.05. Adding verapamil, a P-glycoprotein inhibitor caused a further increase in the percentage of apoptotic cells when the cells were treated with both agents.  Conclusion:Our results suggest that combination therapy along with P-glycoprotein inhibition can be considered as a novel approach to improve the efficacy of chemotherapeutics in cancer patients with high P-glycoprotein expression.

  15. Role of Conserved Oligomeric Golgi Complex in the Abnormalities of Glycoprotein Processing in Breast Cancer Cells

    Science.gov (United States)

    2006-05-01

    of COG complex function we utilized RNA interference assay to knockdown COG3p subunit of COG complex in normal and breast cancer cells and other tumor...protein trafficking, but the role of the COG complex in the abnormal glycosylation and secretion of tumor markers in breast cancer cells remains... COG complex in breast cancer cells MCF7 had been elevated 2-4 times in comparison to HB2 cells (Figure 5 A). The expression of HeLa COG3 CD44 ab

  16. Effects of chronic ethanol administration on hepatic glycoprotein secretion in the rat

    International Nuclear Information System (INIS)

    Sorrell, M.F.; Nauss, J.M.; Donohue, T.M. Jr.; Tuma, D.J.

    1983-01-01

    The effects of chronic ethanol feeding on protein and glycoprotein synthesis and secretion were studied in rat liver slices. Liver slices from rats fed ethanol for 4-5 wk showed a decreased ability to incorporate [ 14 C]glucosamine into medium trichloracetic acid-precipitable proteins when compared to the pair-fed controls; however, the labeling of hepatocellular glycoproteins was unaffected by chronic ethanol treatment. Immunoprecipitation of radiolabeled secretory (serum) glycoproteins with antiserum against rat serum proteins showed a similar marked inhibition in the appearance of glucosamine-labeled proteins in the medium of slices from ethanol-fed rats. Minimal effects, however, were noted in the labeling of intracellular secretory glycoproteins. Protein synthesis, as determined by measuring [ 14 C]leucine incorporation into medium and liver proteins, was decreased in liver slices from ethanol-fed rats as compared to the pair-fed controls. This was the case for both total proteins as well as immunoprecipitable secretory proteins, although the labeling of secretory proteins retained in the liver slices was reduced to a lesser extent than total radiolabeled hepatic proteins. When the terminal sugar, [ 14 C]fucose, was employed as a precursor in order to more closely focus on the final steps of hepatic glycoprotein secretion, liver slices obtained from chronic ethanol-fed rats exhibited impaired secretion of fucose-labeled proteins into the medium. When ethanol (5 or 10 mM) was added to the incubation medium containing liver slices from the ethanol-fed rats, the alterations in protein and glycoprotein synthesis and secretion caused by the chronic ethanol treatment were further potentiated. The results of this study indicate that liver slices prepared from chronic ethanol-fed rats exhibit both impaired synthesis and secretion of proteins and glycoproteins, and these defects are further potentiated by acute ethanol administration

  17. P-glycoprotein in autoimmune rheumatic diseases.

    Science.gov (United States)

    García-Carrasco, M; Mendoza-Pinto, C; Macias Díaz, S; Vera-Recabarren, M; Vázquez de Lara, L; Méndez Martínez, S; Soto-Santillán, P; González-Ramírez, R; Ruiz-Arguelles, A

    2015-07-01

    P-glycoprotein (Pgp) is a transmembrane protein of 170 kD encoded by the multidrug resistance 1 (MDR-1) gene, localized on chromosome 7. More than 50 polymorphisms of the MDR-1 gene have been described; a subset of these has been shown to play a pathophysiological role in the development of inflammatory bowel disease, femoral head osteonecrosis induced by steroids, lung cancer and renal epithelial tumors. Polymorphisms that have a protective effect on the development of conditions such as Parkinson disease have also been identified. P-glycoprotein belongs to the adenosine triphosphate binding cassette transporter superfamily and its structure comprises a chain of approximately 1280 aminoacid residues with an N-C terminal structure, arranged as 2 homologous halves, each of which has 6 transmembrane segments, with a total of 12 segments with 2 cytoplasmic nucleotide binding domains. Many cytokines like interleukin 2 and tumor necrosis factor alpha increase Pgp expression and activity. Pgp functions as an efflux pump for a variety of toxins in order to protect particular organs and tissues as the central nervous system. Pgp transports a variety of substrates including glucocorticoids while other drugs such as tacrolimus and cyclosporine A act as modulators of this protein. The most widely used method to measure Pgp activity is flow cytometry using naturally fluorescent substrates such as anthracyclines or rhodamine 123. The study of drug resistance and its association to Pgp began with the study of resistance to chemotherapy in the treatment of cancer and antiretroviral therapy for human immunodeficiency virus; however, the role of Pgp in the treatment of systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis has been a focus of study lately and has emerged as an important mechanism by which treatment failure occurs. The present review analyzes the role of Pgp in these autoimmune diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. A Novel Method for Detection of Glycoproteins on Sodium Dodecyl Sulphate Polyacrylamide Gel Using Radio-Iodinated Tyrosine

    DEFF Research Database (Denmark)

    Nalla, Amarnadh; Draz, Hossam M.; Dole, Anita

    2009-01-01

    The aim of this study is to develop a novel method for detection of glycoproteins on polyacrylamide gel. In this method, radio-iodinated-tyrosine (125I-tyrosine) was conjugated to glycoprotein by schiff's base mechanism on the sodium dodecyl sulfate- polyacrylamide gel. Ovalbumin and Concanavalin...... of glycoproteins using 125I-tyrosine selectively detected ovalbumin. Present results showed that MPD enhanced glycoprotein detection method can be used as a sensitive tool for the detection of glycoproteins on polyacrylamide gel...

  19. Spatial Localization of the Ebola Virus Glycoprotein Mucin-Like Domain Determined by Cryo-Electron Tomography

    OpenAIRE

    Tran, Erin E. H.; Simmons, James A.; Bartesaghi, Alberto; Shoemaker, Charles J.; Nelson, Elizabeth; White, Judith M.; Subramaniam, Sriram

    2014-01-01

    The Ebola virus glycoprotein mucin-like domain (MLD) is implicated in Ebola virus cell entry and immune evasion. Using cryo-electron tomography of Ebola virus-like particles, we determined a three-dimensional structure for the full-length glycoprotein in a near-native state and compared it to that of a glycoprotein lacking the MLD. Our results, which show that the MLD is located at the apex and the sides of each glycoprotein monomer, provide a structural template for analysis of MLD function.

  20. P-glycoprotein targeted nanoscale drug carriers

    KAUST Repository

    Li, Wengang; Abu Samra, Dina Bashir Kamil; Merzaban, Jasmeen; Khashab, Niveen M.

    2013-01-01

    Multi-drug resistance (MDR) is a trend whereby tumor cells exposed to one cytotoxic agent develop cross-resistance to a range of structurally and functionally unrelated compounds. P -glycoprotein (P -gp) efflux pump is one of the mostly studied drug

  1. Identifying drug-induced repolarization abnormalities from distinct ECG patterns in congenital long QT syndrome: a study of sotalol effects on T-wave morphology

    DEFF Research Database (Denmark)

    Graff, Claus; Andersen, Mads P; Xue, Joel Q

    2009-01-01

    BACKGROUND: The electrocardiographic QT interval is used to identify drugs with potential harmful effects on cardiac repolarization in drug trials, but the variability of the measurement can mask drug-induced ECG changes. The use of complementary electrocardiographic indices of abnormal repolariz......BACKGROUND: The electrocardiographic QT interval is used to identify drugs with potential harmful effects on cardiac repolarization in drug trials, but the variability of the measurement can mask drug-induced ECG changes. The use of complementary electrocardiographic indices of abnormal...... are typical ECG patterns in LQT2. Blinded to labels, the new morphology measures were tested in a third group of 39 healthy subjects receiving sotalol. Over 3 days the sotalol group received 0, 160 and 320 mg doses, respectively, and a 12-lead Holter ECG was recorded for 22.5 hours each day. Drug...... with QTcF, p ECG patterns in LQT2 carriers effectively quantified repolarization changes induced by sotalol. Further studies are needed to validate whether this measure has...

  2. A new in vivo method to study P-glycoprotein transport in tumors and the blood-brain barrier

    NARCIS (Netherlands)

    Hendrikse, NH; de Vries, EGE; Eriks-Fluks, L; van der Graaf, WTA; Hospers, GAP; Willemsen, ATM; Vaalburg, W; Franssen, EJF

    1999-01-01

    Drug resistance is a major cause of chemotherapy failure in cancer treatment, One reason is the overexpression of the drug efflux pump P-glycoprotein (P-gp), involved in multidrug resistance (MDR), In vivo pharmacokinetic analysis of P-gp transport might identify the capacity of modulation by P-gp

  3. Exome analysis identified a novel mutation in the RBP4 gene in a consanguineous pedigree with retinal dystrophy and developmental abnormalities.

    Directory of Open Access Journals (Sweden)

    Catherine Cukras

    Full Text Available Retinitis Pigmentosa (RP is a common form of retinal degeneration characterized by photoreceptor degeneration and retinal pigment epithelium (RPE atrophy causing loss of visual field and acuities. Exome sequencing identified a novel homozygous splice site variant (c.111+1G>A in the gene encoding retinol binding protein 4 (RBP4. This change segregated with early onset, progressive, and severe autosomal recessive retinitis pigmentosa (arRP in an eight member consanguineous pedigree of European ancestry. Additionally, one patient exhibited developmental abnormalities including patent ductus arteriosus and chorioretinal and iris colobomas. The second patient developed acne from young age and extending into the 5(th decade. Both patients had undetectable levels of RBP4 in the serum suggesting that this mutation led to either mRNA or protein instability resulting in a null phenotype. In addition, the patients exhibited severe vitamin A deficiency, and diminished serum retinol levels. Circulating transthyretin levels were normal. This study identifies the RBP4 splice site change as the cause of RP in this pedigree. The presence of developmental abnormalities and severe acne in patients with retinal degeneration may indicate the involvement of genes that regulate vitamin A absorption, transport and metabolism.

  4. Exome analysis identified a novel mutation in the RBP4 gene in a consanguineous pedigree with retinal dystrophy and developmental abnormalities.

    Science.gov (United States)

    Cukras, Catherine; Gaasterland, Terry; Lee, Pauline; Gudiseva, Harini V; Chavali, Venkata R M; Pullakhandam, Raghu; Maranhao, Bruno; Edsall, Lee; Soares, Sandra; Reddy, G Bhanuprakash; Sieving, Paul A; Ayyagari, Radha

    2012-01-01

    Retinitis Pigmentosa (RP) is a common form of retinal degeneration characterized by photoreceptor degeneration and retinal pigment epithelium (RPE) atrophy causing loss of visual field and acuities. Exome sequencing identified a novel homozygous splice site variant (c.111+1G>A) in the gene encoding retinol binding protein 4 (RBP4). This change segregated with early onset, progressive, and severe autosomal recessive retinitis pigmentosa (arRP) in an eight member consanguineous pedigree of European ancestry. Additionally, one patient exhibited developmental abnormalities including patent ductus arteriosus and chorioretinal and iris colobomas. The second patient developed acne from young age and extending into the 5(th) decade. Both patients had undetectable levels of RBP4 in the serum suggesting that this mutation led to either mRNA or protein instability resulting in a null phenotype. In addition, the patients exhibited severe vitamin A deficiency, and diminished serum retinol levels. Circulating transthyretin levels were normal. This study identifies the RBP4 splice site change as the cause of RP in this pedigree. The presence of developmental abnormalities and severe acne in patients with retinal degeneration may indicate the involvement of genes that regulate vitamin A absorption, transport and metabolism.

  5. Multiple genes encode the major surface glycoprotein of Pneumocystis carinii

    DEFF Research Database (Denmark)

    Kovacs, J A; Powell, F; Edman, J C

    1993-01-01

    hydrophobic region at the carboxyl terminus. The presence of multiple related msg genes encoding the major surface glycoprotein of P. carinii suggests that antigenic variation is a possible mechanism for evading host defenses. Further characterization of this family of genes should allow the development......The major surface antigen of Pneumocystis carinii, a life-threatening opportunistic pathogen in human immunodeficiency virus-infected patients, is an abundant glycoprotein that functions in host-organism interactions. A monoclonal antibody to this antigen is protective in animals, and thus...... blot studies using chromosomal or restricted DNA, the major surface glycoproteins are the products of a multicopy family of genes. The predicted protein has an M(r) of approximately 123,000, is relatively rich in cysteine residues (5.5%) that are very strongly conserved, and contains a well conserved...

  6. Abnormal Bleeding during Menopause Hormone Therapy: Insights for Clinical Management

    Directory of Open Access Journals (Sweden)

    Sebastião Freitas De Medeiros

    2013-01-01

    Full Text Available Objective Our objective was to review the involved mechanisms and propose actions for controlling/treating abnormal uterine bleeding during climacteric hormone therapy. Methods A systemic search of the databases SciELO, MEDLINE, and Pubmed was performed for identifying relevant publications on normal endometrial bleeding, abnormal uterine bleeding, and hormone therapy bleeding. Results Before starting hormone therapy, it is essential to exclude any abnormal organic condition, identify women at higher risk for bleeding, and adapt the regimen to suit eachwoman's characteristics. Abnormal bleeding with progesterone/progestogen only, combined sequential, or combined continuous regimens may be corrected by changing the progestogen, adjusting the progestogen or estrogen/progestogen doses, or even switching the initial regimen to other formulation. Conclusion To diminish the occurrence of abnormal bleeding during hormone therapy (HT, it is important to tailor the regimen to the needs of individual women and identify those with higher risk of bleeding. The use of new agents as adjuvant therapies for decreasing abnormal bleeding in women on HT awaits future studies.

  7. A locus identified on chromosome18p11.31 is associated with hippocampal abnormalities in a family with mesial temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Claudia Vianna Maurer-Morelli

    2012-08-01

    Full Text Available We aimed to identify the region harboring a putative candidate gene associated with hippocampal abnormalities (HAb in a family with mesial temporal lobe epilepsy (MTLE. Genome-wide scan was performed in one large kindred with MTLE using a total of 332 microsatellite markers at ~12cM intervals. An additional 13 markers were genotyped in the candidate region. Phenotypic classes were defined according to the presence of hippocampal atrophy and/or hyperintense hippocampal T2 signal detected on magnetic resonance imaging. We identified a significant positive LOD score on chromosome 18p11.31 with a Zmax of 3.12 at D18S452. Multipoint LOD scores and haplotype analyses localized the candidate locus within a 6cM interval flanked by D18S976 and D18S967. We present here evidence that HAb, which were previously related mainly to environmental risk factors, may be influenced by genetic predisposition. This finding may have major impact in the study of the mechanisms underlying abnormalities in mesial temporal lobe structures and their relationship with MTLE.

  8. Mechanism of feline immunodeficiency virus envelope glycoprotein-mediated fusion

    International Nuclear Information System (INIS)

    Garg, Himanshu; Fuller, Frederick J.; Tompkins, Wayne A.F.

    2004-01-01

    Feline immunodeficiency virus (FIV) shares remarkable homology to primate lentiviruses, human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). The process of lentiviral env glycoprotein-mediated fusion of membranes is essential for viral entry and syncytia formation. A detailed understanding of this phenomenon has helped identify new targets for antiviral drug development. Using a model based on syncytia formation between FIV env-expressing cells and a feline CD4+ T cell line we have studied the mechanism of FIV env-mediated fusion. Using this model we show that FIV env-mediated fusion mechanism and kinetics are similar to HIV env. Syncytia formation could be blocked by CXCR4 antagonist AMD3100, establishing the importance of this receptor in FIV gp120 binding. Interestingly, CXCR4 alone was not sufficient to allow fusion by a primary isolate of FIV, as env glycoprotein from FIV-NCSU 1 failed to induce syncytia in several feline cell lines expressing CXCR4. Syncytia formation could be inhibited at a post-CXCR4 binding step by synthetic peptide T1971, which inhibits interaction of heptad repeat regions of gp41 and formation of the hairpin structure. Finally, using site-directed mutagenesis, we also show that a conserved tryptophan-rich region in the membrane proximal ectodomain of gp41 is critical for fusion, possibly at steps post hairpin structure formation

  9. Ergonomics for enhancing detection of machine abnormalities.

    Science.gov (United States)

    Illankoon, Prasanna; Abeysekera, John; Singh, Sarbjeet

    2016-10-17

    Detecting abnormal machine conditions is of great importance in an autonomous maintenance environment. Ergonomic aspects can be invaluable when detection of machine abnormalities using human senses is examined. This research outlines the ergonomic issues involved in detecting machine abnormalities and suggests how ergonomics would improve such detections. Cognitive Task Analysis was performed in a plant in Sri Lanka where Total Productive Maintenance is being implemented to identify sensory types that would be used to detect machine abnormalities and relevant Ergonomic characteristics. As the outcome of this research, a methodology comprising of an Ergonomic Gap Analysis Matrix for machine abnormality detection is presented.

  10. Identification of structural and secretory lectin-binding glycoproteins of normal and cancerous human prostate.

    Science.gov (United States)

    Lad, P M; Cooper, J F; Learn, D B; Olson, C V

    1984-12-07

    We have utilized the technique of lectin-loading of SDS gels with iodinated concanavalin A and wheat germ agglutinin to identify glycoproteins in prostatic and seminal fluids as well as in prostate tissue fractions. The following subunits which bound both lectins were detected: (a) 50, 43 and 38 kDa subunits common to prostatic and seminal fluids, and an additional 55 kDa subunit which predominates only in prostatic fluid; (b) 78, 55, 50 and 43 kDa subunits in prostatic tissue cytosol and (c) 195, 170, 135, 116 and 95 kDa subunits present in the particulate fractions of prostatic tissue. Immunoblotting using specific rabbit antibodies revealed the 50 kDa band to be prostatic acid phosphatase and the 38 kDa band to be prostate-specific antigen. Interestingly, antibodies directed toward prostatic acid phosphatase were found to cross-react with the 43 kDa band. Fractionation on sucrose gradients showed that several of these particulate glycoproteins were associated with a vesicle fraction enriched in adenylate cyclase activity, implying that they are plasma membrane glycoproteins. Comparison of soluble and particulate fractions of normal and cancerous tissue homogenates was made by densitometric scanning of autoradiograms of lectin-loaded gels. Similar relative intensities of lectin-binding were obtained for corresponding proteins in normal and cancerous tissue fractions. Also, immunoblotting showed no differences in prostatic acid phosphatase or prostate-specific antigen between normal and cancerous soluble homogenate fractions. Our results suggest that major lectin-binding proteins are conserved in the transition from normal to cancerous tissue. These results may be useful in developing a multiple-marker profile of metastatic prostate cancer and for the design of imaging agents, such as monoclonal antibodies, to prominent soluble and particulate prostate glycoproteins.

  11. Glycoproteins of axonal transport: affinity chromatography on fucose-specific lectins

    Energy Technology Data Exchange (ETDEWEB)

    Gustavsson, S.; Ohlson, C.; Karlsson, J.O.

    1982-03-01

    Rapidly transported fucose-labeled glycoproteins from axons of rabbit retinal ganglion cells were solubilized with nonionic detergents. The solubilized components were subjected to affinity chromatography on three different fucose-specific lectins. A recently characterized fucose-specific lectin from Aleuria aurantia bound reversibly approximately 60% of the applied protein-bound radioactivity. The lectins from Lotus tetragonolobus and Ulex europaeus bound are very small proportions of the labeled rapidly transported glycoproteins.

  12. Detection of bovine herpesvirus 4 glycoprotein B and thymidine kinase DNA by PCR assays in bovine milk

    NARCIS (Netherlands)

    Wellenberg, G.J.; Verstraten, E.; Belak, S.; Verschuren, S.B.E.; Rijsewijk, F.A.M.; Peshev, R.; Oirschot, van J.T.

    2001-01-01

    A polymerase chain reaction (PCR) assay was developed to detect bovine herpesvirus 4 (BHV4) glycoprotein B (gB) DNA, and a nested-PCR assay was modified for the detection of BHV4 thymidine kinase (TK) DNA in bovine milk samples. To identify false-negative PCR results, internal control templates were

  13. Development of a radioimmunoassay for 'Tamm-Horsfall-like' glycoprotein in serum and cerebrospinal fluid

    International Nuclear Information System (INIS)

    Hartmann, L.; Bringuier, A.-F.; Schuller, E.

    1983-01-01

    Affinity chromatography purification was combined with a radioimmunoassay for 'Tamm-Horsfall-like' glycoprotein. This enabled serum comcentrations to be established and to demonstrate its presence in cerebrospinal fluid for the first time. This assay method used in different circumstances suggests a multifocal synthesis. Nevertheless, urinary Tamm-Horsfall glycoprotein so far must be distinguished from the serum or cerebrospinal fluid Tamm-Horsfall-like glycoprotein. (Auth.)

  14. Spatial localization of the Ebola virus glycoprotein mucin-like domain determined by cryo-electron tomography.

    Science.gov (United States)

    Tran, Erin E H; Simmons, James A; Bartesaghi, Alberto; Shoemaker, Charles J; Nelson, Elizabeth; White, Judith M; Subramaniam, Sriram

    2014-09-01

    The Ebola virus glycoprotein mucin-like domain (MLD) is implicated in Ebola virus cell entry and immune evasion. Using cryo-electron tomography of Ebola virus-like particles, we determined a three-dimensional structure for the full-length glycoprotein in a near-native state and compared it to that of a glycoprotein lacking the MLD. Our results, which show that the MLD is located at the apex and the sides of each glycoprotein monomer, provide a structural template for analysis of MLD function. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  15. Glycoproteins functionalized natural and synthetic polymers for prospective biomedical applications: A review.

    Science.gov (United States)

    Tabasum, Shazia; Noreen, Aqdas; Kanwal, Arooj; Zuber, Mohammad; Anjum, Muhammad Naveed; Zia, Khalid Mahmood

    2017-05-01

    Glycoproteins have multidimensional properties such as biodegradability, biocompatibility, non-toxicity, antimicrobial and adsorption properties; therefore, they have wide range of applications. They are blended with different polymers such as chitosan, carboxymethyl cellulose (CMC), polyvinyl pyrrolidone (PVP), polycaprolactone (PCL), heparin, polystyrene fluorescent nanoparticles (PS-NPs) and carboxyl pullulan (PC) to improve their properties like thermal stability, mechanical properties, resistance to pH, chemical stability and toughness. Considering the versatile charateristics of glycoprotein based polymers, this review sheds light on synthesis and characterization of blends and composites of glycoproteins, with natural and synthetic polymers and their potential applications in biomedical field such as drug delivery system, insulin delivery, antimicrobial wound dressing uses, targeting of cancer cells, development of anticancer vaccines, development of new biopolymers, glycoproteome research, food product and detection of dengue glycoproteins. All the technical scientific issues have been addressed; highlighting the recent advancement. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Identification of abnormal movement state and avoidance strategy for mobile robots

    Institute of Scientific and Technical Information of China (English)

    CAI Zi-xing; DUAN Zhuo-hua; ZHANG Hui-tuan; YU Jin-xia

    2006-01-01

    Abnormal movement states for a mobile robot were identified by four multi-layer perceptron. In the presence of abnormality, avoidance strategies were designed to guarantee the safety of the robot. Firstly, the kinematics of the normal and abnormal movement states were exploited, 8 kinds of features were extracted. Secondly, 4 multi-layer perceptrons were employed to classify the features for four 4-driving wheels into 4 kinds of states, i.e. normal, blocked, deadly blocked, and slipping. Finally,avoidance strategies were designed based on this. Experiment results show that the methods can identify most abnormal movement states and avoid the abnormality correctly and timely.

  17. A Directed Molecular Evolution Approach to Improved Immunogenicity of the HIV-1 Envelope Glycoprotein

    Science.gov (United States)

    Du, Sean X.; Xu, Li; Zhang, Wenge; Tang, Susan; Boenig, Rebecca I.; Chen, Helen; Mariano, Ellaine B.; Zwick, Michael B.; Parren, Paul W. H. I.; Burton, Dennis R.; Wrin, Terri; Petropoulos, Christos J.; Ballantyne, John A.; Chambers, Michael; Whalen, Robert G.

    2011-01-01

    A prophylactic vaccine is needed to slow the spread of HIV-1 infection. Optimization of the wild-type envelope glycoproteins to create immunogens that can elicit effective neutralizing antibodies is a high priority. Starting with ten genes encoding subtype B HIV-1 gp120 envelope glycoproteins and using in vitro homologous DNA recombination, we created chimeric gp120 variants that were screened for their ability to bind neutralizing monoclonal antibodies. Hundreds of variants were identified with novel antigenic phenotypes that exhibit considerable sequence diversity. Immunization of rabbits with these gp120 variants demonstrated that the majority can induce neutralizing antibodies to HIV-1. One novel variant, called ST-008, induced significantly improved neutralizing antibody responses when assayed against a large panel of primary HIV-1 isolates. Further study of various deletion constructs of ST-008 showed that the enhanced immunogenicity results from a combination of effective DNA priming, an enhanced V3-based response, and an improved response to the constant backbone sequences. PMID:21738594

  18. Preparation of 131I-asialo-α1-acid glycoprotein

    International Nuclear Information System (INIS)

    Rijk, P.P. van

    1975-01-01

    α 1 -Acid glycoprotein (orosomucoid) was prepared from a byproduct of the ethanol plasma fractionation by means of ion-exchange procedures. Immunoelectrophoresis suggested a high degree of purity; the purified protein contained 13.5% sialic acid and 17.8% hexose. The α 1 -acid glycoprotein was modified by removal of sialic acid with neurominidase (E.C. 3.2.1.18) followed by iodination with 131 I. The purpose of the preparation, its potential use as a pharmacon for liver-function studies in nuclear medicine, is the subject of further study

  19. Nipah virus infection and glycoprotein targeting in endothelial cells

    Directory of Open Access Journals (Sweden)

    Maisner Andrea

    2010-11-01

    Full Text Available Abstract Background The highly pathogenic Nipah virus (NiV causes fatal respiratory and brain infections in animals and humans. The major hallmark of the infection is a systemic endothelial infection, predominantly in the CNS. Infection of brain endothelial cells allows the virus to overcome the blood-brain-barrier (BBB and to subsequently infect the brain parenchyma. However, the mechanisms of NiV replication in endothelial cells are poorly elucidated. We have shown recently that the bipolar or basolateral expression of the NiV surface glycoproteins F and G in polarized epithelial cell layers is involved in lateral virus spread via cell-to-cell fusion and that correct sorting depends on tyrosine-dependent targeting signals in the cytoplasmic tails of the glycoproteins. Since endothelial cells share many characteristics with epithelial cells in terms of polarization and protein sorting, we wanted to elucidate the role of the NiV glycoprotein targeting signals in endothelial cells. Results As observed in vivo, NiV infection of endothelial cells induced syncytia formation. The further finding that infection increased the transendothelial permeability supports the idea of spread of infection via cell-to-cell fusion and endothelial cell damage as a mechanism to overcome the BBB. We then revealed that both glycoproteins are expressed at lateral cell junctions (bipolar, not only in NiV-infected primary endothelial cells but also upon stable expression in immortalized endothelial cells. Interestingly, mutation of tyrosines 525 and 542/543 in the cytoplasmic tail of the F protein led to an apical redistribution of the protein in endothelial cells whereas tyrosine mutations in the G protein had no effect at all. This fully contrasts the previous results in epithelial cells where tyrosine 525 in the F, and tyrosines 28/29 in the G protein were required for correct targeting. Conclusion We conclude that the NiV glycoprotein distribution is responsible for

  20. Isolation of glycoproteins from brown algae

    DEFF Research Database (Denmark)

    2015-01-01

    The present invention relates to a novel process for the isolation of unique anti-oxidative glycoproteins from the pH precipitated fractions of enzymatic extracts of brown algae. Two brown seaweeds viz, Fucus serratus and Fucus vesiculosus were hydrolysed by using 3 enzymes viz, Alcalase, Viscozyme...

  1. Molecular cloning and expression of cDNA encoding a lumenal calcium binding glycoprotein from sarcoplasmic reticulum

    International Nuclear Information System (INIS)

    Leberer, E.; Charuk, J.H.M.; MacLennan, D.H.; Green, N.M.

    1989-01-01

    Antibody screening was used to isolate a cDNA encoding the 160-kDa glycoprotein of rabbit skeletal muscle sarcoplasmic reticulum. The cDNA is identical to that encoding the 53-kDa glycoprotein except that it contains an in-frame insertion of 1,308 nucleotides near its 5' end, apparently resulting from alternative splicing. The protein encoded by the cDNA would contain a 19-residue NH 2 -terminal signal sequence and a 453-residue COOH-terminal sequence identical to the 53-kDa glycoprotein. It would also contain a 436-amino acid insert between these sequences. This insert would be highly acidic, suggesting that it might bind Ca 2+ . The purified 160-kDa glycoprotein and the glycoprotein expressed in COS-1 cells transfected with cDNA encoding the 160-kDa glycoprotein were shown to bind 45 C 2+ in a gel overlay assay. The protein was shown to be located in the lumen of the sarcoplasmic reticulum and to be associated through Ca 2+ with the membrane. The authors propose that this lumenal Ca 2+ binding glycoprotein of the sarcoplasmic reticulum be designated sarcalumenin

  2. Computational identification of epitopes in the glycoproteins of novel bunyavirus (SFTS virus) recognized by a human monoclonal antibody (MAb 4-5)

    Science.gov (United States)

    Zhang, Wenshuai; Zeng, Xiaoyan; Zhang, Li; Peng, Haiyan; Jiao, Yongjun; Zeng, Jun; Treutlein, Herbert R.

    2013-06-01

    In this work, we have developed a new approach to predict the epitopes of antigens that are recognized by a specific antibody. Our method is based on the "multiple copy simultaneous search" (MCSS) approach which identifies optimal locations of small chemical functional groups on the surfaces of the antibody, and identifying sequence patterns of peptides that can bind to the surface of the antibody. The identified sequence patterns are then used to search the amino-acid sequence of the antigen protein. The approach was validated by reproducing the binding epitope of HIV gp120 envelop glycoprotein for the human neutralizing antibody as revealed in the available crystal structure. Our method was then applied to predict the epitopes of two glycoproteins of a newly discovered bunyavirus recognized by an antibody named MAb 4-5. These predicted epitopes can be verified by experimental methods. We also discuss the involvement of different amino acids in the antigen-antibody recognition based on the distributions of MCSS minima of different functional groups.

  3. Australine, a pyrrolizidine alkaloid that inhibits amyloglucosidase and glycoprotein processing

    International Nuclear Information System (INIS)

    Tropea, J.E.; Molyneux, R.J.; Kaushal, G.P.; Pan, Y.T.; Mitchell, M.; Elbein, A.D.

    1989-01-01

    Australine is a polyhydroxylated pyrrolizidine alkaloid that was isolated from the seeds of the Australian tree Castanospermum australe and characterized by NMR and X-ray diffraction analysis. Since swainsonine and catanospermine are polyhydroxylated indolizidine alkaloids that inhibit specific glycosidases, the authors tested australine against a variety of exoglycosidases to determine whether it would inhibit any of these enzymes. This alkaloid proved to be a good inhibitor of the α-glucosidase amyloglucosidase (50% inhibition at 5.8 μM), but it did not inhibit β-glucosidase, α- or β-mannosidase, or α- or β-galactosidase. The inhibition of amyloglucosidase was of a competitive nature. Australine also inhibited the glycoprotein processing enzyme glucosidase I, but had only slight activity toward glucosidase II. When incubated with cultured cells, this alkaloid inhibited glycoprotein processing at the glucosidase I step and caused the accumulation of glycoproteins with Glc 3 Man 7-9 (GlcNAc) 2 -oligosaccharides

  4. Statins Suppress Ebola Virus Infectivity by Interfering with Glycoprotein Processing.

    Science.gov (United States)

    Shrivastava-Ranjan, Punya; Flint, Mike; Bergeron, Éric; McElroy, Anita K; Chatterjee, Payel; Albariño, César G; Nichol, Stuart T; Spiropoulou, Christina F

    2018-05-01

    Ebola virus (EBOV) infection is a major public health concern due to high fatality rates and limited effective treatments. Statins, widely used cholesterol-lowering drugs, have pleiotropic mechanisms of action and were suggested as potential adjunct therapy for Ebola virus disease (EVD) during the 2013-2016 outbreak in West Africa. Here, we evaluated the antiviral effects of statin (lovastatin) on EBOV infection in vitro Statin treatment decreased infectious EBOV production in primary human monocyte-derived macrophages and in the hepatic cell line Huh7. Statin treatment did not interfere with viral entry, but the viral particles released from treated cells showed reduced infectivity due to inhibition of viral glycoprotein processing, as evidenced by decreased ratios of the mature glycoprotein form to precursor form. Statin-induced inhibition of infectious virus production and glycoprotein processing was reversed by exogenous mevalonate, the rate-limiting product of the cholesterol biosynthesis pathway, but not by low-density lipoprotein. Finally, statin-treated cells produced EBOV particles devoid of the surface glycoproteins required for virus infectivity. Our findings demonstrate that statin treatment inhibits EBOV infection and suggest that the efficacy of statin treatment should be evaluated in appropriate animal models of EVD. IMPORTANCE Treatments targeting Ebola virus disease (EVD) are experimental, expensive, and scarce. Statins are inexpensive generic drugs that have been used for many years for the treatment of hypercholesterolemia and have a favorable safety profile. Here, we show the antiviral effects of statins on infectious Ebola virus (EBOV) production. Our study reveals a novel molecular mechanism in which statin regulates EBOV particle infectivity by preventing glycoprotein processing and incorporation into virus particles. Additionally, statins have anti-inflammatory and immunomodulatory effects. Since inflammation and dysregulation of the immune

  5. A decision support system for identifying abnormal operating procedures in a nuclear power plant

    International Nuclear Information System (INIS)

    Hsieh, Min-Han; Hwang, Sheue-Ling; Liu, Kang-Hong; Liang, Sheau-Farn Max; Chuang, Chang-Fu

    2012-01-01

    Highlights: ► A decision support system has been constructed and verified. ► The operator's decision-making time was decreased by about 25%. ► The accuracy was increased by about 18%. ► The system prevents overlooking important information. ► Fewer erroneous solutions were implemented, and the mental workload was reduced. - Abstract: In order to prevent safety hazards that can result from inappropriate decisions made by the operators of a nuclear power plant (NPP), this study was undertaken to develop a decision support system to reduce the complexity of the decision-making process by aiding operators’ cognitive activities, integrating unusual symptoms, and identifying the most suitable abnormal operating procedure (AOP) for operators. The study was conducted from the perspective of human factors engineering in order to compare the process that operators originally used to select an AOP with a process that included a support system for AOP identification. The results of the study indicated that the existence of a support system reduces errors by quickly suggesting likely AOPs. With such a support system in place, there were clear improvements in human performance, i.e., decision-making time decreased by about 25%, and the accuracy of the operators’ decisions, judged by the successful resolution of specific problems, increased by about 18%. In addition, there were fewer erroneous solutions implemented, and the mental workload was reduced. Hence, the decision support system is proposed as a training tool in identifying AOPs in the main control room (MCR).

  6. Left globus pallidus abnormality in never-medicated patients with schizophrenia

    International Nuclear Information System (INIS)

    Early, T.S.; Reiman, E.M.; Raichle, M.E.; Spitznagel, E.L.

    1987-01-01

    Schizophrenia is a severe psychiatric disorder characterized by onset in young adulthood, the occurrence of hallucinations and delusions, and the development of enduring psychosocial disability. The pathophysiology of this disorder remains unknown. Studies of cerebral blood flow and metabolism designed to identify brain abnormalities in schizophrenia have been limited by inadequate methods of anatomical localization and the possibility of persistent medication effects. The authors have now used positron emission tomography and a validated method of anatomical localization in an attempt to identify abnormalities of regional cerebral blood flow in newly diagnosed never-medicated patients with schizophrenia. An exploratory study of 5 patients and 10 normal control subjects identified abnormally high blood flow in the left globus pallidus of patients with schizophrenia. A replication study of 5 additional patients and 10 additional control subjects confirmed this finding. No other abnormalities were found

  7. A glycoprotein with anti-inflammatory properties secreted by an Aspergillus nidulans modified strain

    Directory of Open Access Journals (Sweden)

    J. C. F. Queiroz

    2007-01-01

    Full Text Available Total RNA from lipopolysaccharide (LPS-stimulated rat macrophages used to treat protoplasts from an Aspergillus nidulans strain originated the RT2 regenerated strain, whose culture supernatant showed anti-inflammatory activity in Wistar rats. The protein fraction presenting such anti-inflammatory activity was purified and biochemically identified. The screening of the fraction responsible for such anti-inflammatory property was performed by evaluating the inhibition of carrageenan-induced paw edema in male Swiss mice. Biochemical analyses of the anti-inflammatory protein used chromatography, carbohydrates quantification of the protein sample, amino acids content analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE. Total sugar quantification revealed 32% glycosylation of the protein fraction. Amino acid analysis of such fraction showed a peculiar pattern presenting 29% valine. SDS-PAGE revealed that the protein sample is pure and its molecular weight is about 40kDa. Intravenous injection of the isolated substance into mice significantly inhibited carrageenan-induced paw edema. The isolated glycoprotein decreased carrageenan-induced paw edema in a prostaglandin-dependent phase, suggesting an inhibitory effect of the isolated glycoprotein on prostaglandin synthesis.

  8. The expression and serological reactivity of recombinant canine herpesvirus 1 glycoprotein D

    Directory of Open Access Journals (Sweden)

    MarkéŽta Vaňkov‡á

    2016-01-01

    Full Text Available The aim of this work was to express recombinant glycoprotein D of canine herpesvirus 1 in bacterial cells and to evaluate its diagnostic sensitivity and specificity when compared to traditional serological methods. The gene fragment coding glycoprotein D of canine herpesvirus 1 was amplified by polymerase chain reaction, cloned into plasmid vector and expressed in Escherichia coli cells. Recombinant protein was then purified and used as an antigen in immunoblot for a detection of canine herpesvirus 1 specific antibodies. Antibody testing was performed on the panel of 100 canine sera by immunoblot with recombinant glycoprotein D as antigen and compared with indirect immunofluorescence assay. Serum samples were collected from 83 dogs with no history of canine herpesvirus 1 or reproductive disorders, and from 17 dogs from breeding kennels with a history of canine herpesvirus 1 related reproductive disorders. Sensitivity of glycoprotein D based immunoblot was 89.2% and specificity was 93%. Kappa value was calculated to be 0.8 between immunoblot and indirect immunofluorescence assay. Antibodies against canine herpesvirus 1 infection were detected in 33% of samples by immunoblot assay. Our study confirms that recombinant glycoprotein D expressed in bacterial cells could be used as a suitable and sensitive antigen for immunological tests and that herpesvirus infection seems to be common among the canine population in the Czech Republic.

  9. Global site-specific analysis of glycoprotein N-glycan processing.

    Science.gov (United States)

    Cao, Liwei; Diedrich, Jolene K; Ma, Yuanhui; Wang, Nianshuang; Pauthner, Matthias; Park, Sung-Kyu Robin; Delahunty, Claire M; McLellan, Jason S; Burton, Dennis R; Yates, John R; Paulson, James C

    2018-06-01

    N-glycans contribute to the folding, stability and functions of the proteins they decorate. They are produced by transfer of the glycan precursor to the sequon Asn-X-Thr/Ser, followed by enzymatic trimming to a high-mannose-type core and sequential addition of monosaccharides to generate complex-type and hybrid glycans. This process, mediated by the concerted action of multiple enzymes, produces a mixture of related glycoforms at each glycosite, making analysis of glycosylation difficult. To address this analytical challenge, we developed a robust semiquantitative mass spectrometry (MS)-based method that determines the degree of glycan occupancy at each glycosite and the proportion of N-glycans processed from high-mannose type to complex type. It is applicable to virtually any glycoprotein, and a complete analysis can be conducted with 30 μg of protein. Here, we provide a detailed description of the method that includes procedures for (i) proteolytic digestion of glycoprotein(s) with specific and nonspecific proteases; (ii) denaturation of proteases by heating; (iii) sequential treatment of the glycopeptide mixture with two endoglycosidases, Endo H and PNGase F, to create unique mass signatures for the three glycosylation states; (iv) LC-MS/MS analysis; and (v) data analysis for identification and quantitation of peptides for the three glycosylation states. Full coverage of site-specific glycosylation of glycoproteins is achieved, with up to thousands of high-confidence spectra hits for each glycosite. The protocol can be performed by an experienced technician or student/postdoc with basic skills for proteomics experiments and takes ∼7 d to complete.

  10. Homologous and heterologous antibody responses of mice immunized with purified feline herpesvirus type 1 and canine herpesvirus glycoproteins.

    Science.gov (United States)

    Limcumpao, J A; Horimoto, T; Xuan, X N; Tohya, Y; Azetaka, M; Takahashi, E; Mikami, T

    1991-06-01

    The three glycoproteins each of feline herpesvirus type 1 (FHV-1) and canine herpesvirus (CHV) were purified by affinity chromatography using glycoprotein-specific monoclonal antibodies and used individually or in combination in immunizing mice to determine their relative immunogenicity. All the glycoproteins induced detectable virus neutralizing antibodies to the homologous virus but FHV-1 gp143/108 and its cross-reacting counterpart, CHV gp145/112, elicited the highest titers not only to the homologous virus but to the heterologous virus as well. The production of ELISA antibodies after glycoprotein immunization was variable, while hemagglutination-inhibiting antibodies were produced by only 1 out of 10 FHV-1 gp60-inoculated mice. In general, the antibody titers induced by CHV glycoproteins were lower than those by FHV-1 glycoproteins. These results indicate that these glycoproteins may be useful as subunit vaccines against FHV-1 and CHV infections.

  11. Curcumin as a Modulator of P-Glycoprotein in Cancer: Challenges and Perspectives

    Directory of Open Access Journals (Sweden)

    Vanessa Lopes-Rodrigues

    2016-11-01

    Full Text Available Multidrug resistance (MDR presents a serious challenge to the efficiency of cancer treatment, and may be associated with the overexpression of drug efflux pumps. P-glycoprotein (P-gp is a drug efflux pump often found overexpressed in cases of acquired MDR. Nevertheless, there are no P-gp inhibitors being used in the current clinical practice, due to toxicity problems, drug interactions, or pharmacokinetic issues. Therefore, it is important to identify novel inhibitors of P-gp activity or expression. Curcumin is a secondary metabolite isolated from the turmeric of Curcuma longa L. which has been associated with several biological activities, particularly P-gp modulatory activity (by inhibiting both P-gp function and expression. However, curcumin shows extensive metabolism and instability, which has justified the recent and intensive search for analogs of curcumin that maintain the P-gp modulatory activity but have enhanced stability. This review summarizes and compares the effects of curcumin and several curcumin analogs on P-glycoprotein function and expression, emphasizing the potential of these molecules for the possible development of safe and effective inhibitors of P-gp to overcome MDR in human cancer.

  12. Bioactivity of proteins isolated from Lactobacillus plantarum L67 treated with Zanthoxylum piperitum DC glycoprotein.

    Science.gov (United States)

    Song, S; Oh, S; Lim, K-T

    2015-06-01

    Lactobacilli in the human gastrointestinal tract have beneficial effects on the health of their host. To enhance these effects, the bioactivity of lactobacilli can be fortified through exogenous dietary or pharmacological agents, such as glycoproteins. To elucidate the inductive effect of Zanthoxylum piperitum DC (ZPDC) glycoprotein on Lactobacillus plantarum L67, we evaluated the radical-scavenging activity, anti-oxidative enzymes (SOD, GPx and CAT), growth rate, ATPase activity and β-galactosidase activity of this strain. When Lact. plantarum L67 was treated with ZPDC glycoprotein at different concentrations, the intensities of a few SDS-PAGE bands were slightly changed. The amount of a 23 kDa protein was increased upon treatment with increasing concentrations of ZPDC glycoprotein. The results of this study indicate that the radical-scavenging activity for O2(-) and OH¯, but not for the DPPH radical, increased in a concentration-dependent manner after treatment with ZPDC glycoprotein. The activation of anti-oxidative enzymes (SOD, GPx and CAT), growth rate and β-galactosidase activity also increased in a concentration-dependent manner in response to ZPDC glycoprotein treatment, whereas ATPase activity was decreased. In summary, ZPDC glycoprotein stimulated an increase in the bioactivity of Lact. plantarum L67. Significance and impact of the study: This study demonstrated that Lactobacillus plantarum L67 possesses anti-oxidative activity. This strain of lactic bacteria has been known to have various probiotic uses, such as yogurt starters and dietary additional supplements. We found, through this experiment, that the protein has a strong anti-oxidative character, and the activity can be enhanced by treatment with Zanthoxylum piperitum DC (ZPDC) glycoprotein. This study may be application of Lact. plantarum L67 treated by ZPDC glycoprotein in yogurt fermentation. It could be one of the avenues of minimizing yogurt postacidification during storage. In addition

  13. Report to Congress on abnormal occurrences

    International Nuclear Information System (INIS)

    1990-10-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from April 1 through June 30, 1990. The report discusses six abnormal occurrences, none involving a nuclear power plant. There were five abnormal occurrences at NRC licensees: (1) deficiencies in brachytherapy program; (2) a radiation overexposure of a radiographer; (3) a medical diagnostic misadministration; (4) administration of iodine-131 to a lactating female with subsequent uptake by her infant; and (5) a medical therapy misadministration. An Agreement State (Arizona) reported an abnormal occurrence involving a medical diagnostic misadministration. The report also contains information that updates a previously reported occurrence

  14. Australine, a pyrrolizidine alkaloid that inhibits amyloglucosidase and glycoprotein processing

    Energy Technology Data Exchange (ETDEWEB)

    Tropea, J.E.; Molyneux, R.J.; Kaushal, G.P.; Pan, Y.T.; Mitchell, M.; Elbein, A.D. (Univ. of Texas Health Science Center, San Antonio (USA))

    1989-03-07

    Australine is a polyhydroxylated pyrrolizidine alkaloid that was isolated from the seeds of the Australian tree Castanospermum australe and characterized by NMR and X-ray diffraction analysis. Since swainsonine and catanospermine are polyhydroxylated indolizidine alkaloids that inhibit specific glycosidases, the authors tested australine against a variety of exoglycosidases to determine whether it would inhibit any of these enzymes. This alkaloid proved to be a good inhibitor of the {alpha}-glucosidase amyloglucosidase (50% inhibition at 5.8 {mu}M), but it did not inhibit {beta}-glucosidase, {alpha}- or {beta}-mannosidase, or {alpha}- or {beta}-galactosidase. The inhibition of amyloglucosidase was of a competitive nature. Australine also inhibited the glycoprotein processing enzyme glucosidase I, but had only slight activity toward glucosidase II. When incubated with cultured cells, this alkaloid inhibited glycoprotein processing at the glucosidase I step and caused the accumulation of glycoproteins with Glc{sub 3}Man{sub 7-9}(GlcNAc){sub 2}-oligosaccharides.

  15. The effect of P-glycoprotein on methadone hydrochloride flux in equine intestinal mucosa.

    Science.gov (United States)

    Linardi, R L; Stokes, A M; Andrews, F M

    2013-02-01

    Methadone is an effective analgesic opioid that may have a place for the treatment of pain in horses. However, its absorption seems to be impaired by the presence of a transmembrane protein, P-glycoprotein, present in different tissues including the small intestine in other species. This study aims to determine the effect of the P-glycoprotein on methadone flux in the equine intestinal mucosa, as an indicator of in vivo drug absorption. Jejunum tissues from five horses were placed into the Ussing chambers and exposed to methadone solution in the presence or absence of Rhodamine 123 or verapamil. Electrical measurements demonstrated tissue viability for 120 min, and the flux of methadone across the jejunal membrane (mucosal to submucosal direction) was calculated based on the relative drug concentration measured by ELISA. The flux of methadone was significantly higher only in the presence of verapamil. P-glycoprotein was immunolocalized in the apical membrane of the jejunal epithelial cells (enterocytes), mainly located in the tip of the villi compared to cells of the crypts. P-glycoprotein is present in the equine jejunum and may possibly mediate the intestinal transport of methadone. This study suggests that P-glycoprotein may play a role in the poor intestinal absorption of methadone in vivo. © 2012 Blackwell Publishing Ltd.

  16. [Pregnancy-specific beta-glycoprotein in the serum of women with a complicated early pregnancy].

    Science.gov (United States)

    Radikov, N

    1989-01-01

    The author determined pregnancy specific beta 1-glycoprotein in 109 women with threatened early pregnancy as 32 of the women suffered from abortus imminens with several unsuccessful pregnancies in the past as well as 67 women with abortus incipiens with bleeding ex utero. The author established that 87% of women with abortus imminens and preserved pregnancies had values of beta 1-glycoprotein close to those of normal pregnancy for the respective gestational week. 93% of women with abortus incipiens preserved pregnancies till term, but the specific glycoprotein was with in normal ranges. Spontaneous abortion occurred in 7% of women with low values under the 10th percentile. The present study show that examination of pregnancy specific beta 1-glycoprotein in women with threatened early pregnancy is of prognostic significance for the outcome of pregnancy.

  17. Study on the extraction and purification of glycoprotein from the yellow seahorse, Hippocampus kuda Bleeker

    Science.gov (United States)

    Su, Yuting; Xu, Yongjian

    2015-01-01

    The optimum parameters of extraction for glycoprotein from seahorse were examined and determined by Box-Behnken combined with ultrasonic extraction technology. Column chromatography of glycoprotein was used for further purification. The optimal extraction conditions of seahorse glycoprotein were extracting time 4.3 h, salt concentration 0.08 mol/L, extracting temperature 73°C, raw material, and water ratio 1:6. At the optimal conditions, the yield of saccharide reached to 1.123%, and the yield of protein reached to 5.898%. For purifying the crude glycoprotein, the stage renounces of DEAE-52 column chromatography were done, respectively, with 0.05, 0.1, 0.5 mol/L NaHCO3 solution, and further purification was done with Sephadex G-100 column chromatography. Finally, two pieces of seahorse glycoprotein were obtained by the column chromatography, that is, HG-11 and HG-21. The saccharide content was 56.7975% and 39.479%, the protein content was 30.5475% and 51.747%, respectively. PMID:26288722

  18. Improved radioimmunoassay for urinary Tamm-Horsfall glycoprotein. Investigation and resolution of factors affecting its quantification

    Energy Technology Data Exchange (ETDEWEB)

    Dawney, A B.St.J.; Thornley, C; Cattell, W R [Saint Bartholomew' s Hospital, London (UK)

    1982-09-15

    A rapid specific radioimmunoassay has been used to measure Tamm-Horsfall glycoprotein (TH glycoprotein) in urine, and the method described. The apparent concentration increased with increasing dilution of urine in water, reaching a plateau at 1 in 20. This increase was greater the higher the osmolality and TH glycoprotein concentration and the lower the pH of the original sample. The apparent concentration of TH glycoprotein in neat or diluted urine was not affected by freezing or by storage at 4/sup 0/C or room temperature for at least 2 days. A physiological range for the urinary excretion rate was established as 22-56 mg/24h, (considerably higher than the amount present in serum) based on samples from 29 individuals with normal renal function, as defined by their creatinine clearance. There was no significant correlation between serum concentrations of TH glycoprotein and its urinary excretion rate, nor between urinary excretion rate and creatinine clearance.

  19. Next generation sequencing identifies abnormal Y chromosome and candidate causal variants in premature ovarian failure patients.

    Science.gov (United States)

    Lee, Yujung; Kim, Changshin; Park, YoungJoon; Pyun, Jung-A; Kwack, KyuBum

    2016-12-01

    Premature ovarian failure (POF) is characterized by heterogeneous genetic causes such as chromosomal abnormalities and variants in causal genes. Recently, development of techniques made next generation sequencing (NGS) possible to detect genome wide variants including chromosomal abnormalities. Among 37 Korean POF patients, XY karyotype with distal part deletions of Y chromosome, Yp11.32-31 and Yp12 end part, was observed in two patients through NGS. Six deleterious variants in POF genes were also detected which might explain the pathogenesis of POF with abnormalities in the sex chromosomes. Additionally, the two POF patients had no mutation in SRY but three non-synonymous variants were detected in genes regarding sex reversal. These findings suggest candidate causes of POF and sex reversal and show the propriety of NGS to approach the heterogeneous pathogenesis of POF. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Abnormal Spatial Asymmetry of Selective Attention in ADHD

    Science.gov (United States)

    Chan, Edgar; Mattingley, Jason B.; Huang-Pollock, Cynthia; English, Therese; Hester, Robert; Vance, Alasdair; Bellgrove, Mark A.

    2009-01-01

    Background: Evidence for a selective attention abnormality in children with attention deficit hyperactivity disorder (ADHD) has been hard to identify using conventional methods from cognitive science. This study tested whether the presence of selective attention abnormalities in ADHD may vary as a function of perceptual load and target…

  1. The macrophage CD163 surface glycoprotein is an erythroblast adhesion receptor

    DEFF Research Database (Denmark)

    Fabriek, Babs O; Polfliet, Machteld M J; Vloet, Rianka P M

    2007-01-01

    Erythropoiesis occurs in erythroblastic islands, where developing erythroblasts closely interact with macrophages. The adhesion molecules that govern macrophage-erythroblast contact have only been partially defined. Our previous work has implicated the rat ED2 antigen, which is highly expressed...... on the surface of macrophages in erythroblastic islands, in erythroblast binding. In particular, the monoclonal antibody ED2 was found to inhibit erythroblast binding to bone marrow macrophages. Here, we identify the ED2 antigen as the rat CD163 surface glycoprotein, a member of the group B scavenger receptor...... that it enhanced erythroid proliferation and/or survival, but did not affect differentiation. These findings identify CD163 on macrophages as an adhesion receptor for erythroblasts in erythroblastic islands, and suggest a regulatory role for CD163 during erythropoiesis....

  2. Fbs1 protects the malfolded glycoproteins from the attack of peptide:N-glycanase

    International Nuclear Information System (INIS)

    Yamaguchi, Yoshiki; Hirao, Takeshi; Sakata, Eri; Kamiya, Yukiko; Kurimoto, Eiji; Yoshida, Yukiko; Suzuki, Tadashi; Tanaka, Keiji; Kato, Koichi

    2007-01-01

    Fbs1 is a cytosolic lectin putatively operating as a chaperone as well as a substrate-recognition subunit of the SCF Fbs1 ubiquitin ligase complex. To provide structural and functional basis of preferential binding of Fbs1 to unfolded glycoproteins, we herein characterize the interaction of Fbs1 with a heptapeptide carrying Man 3 GlcNAc 2 by nuclear magnetic resonance (NMR) spectroscopy and other biochemical methods. Inspection of the NMR data obtained by use of the isotopically labeled glycopeptide indicated that Fbs1 interacts with sugar-peptide junctions, which are shielded in native glycoprotein, in many cases, but become accessible to Fbs1 in unfolded glycoproteins. Furthermore, Fbs1 was shown to inhibit deglycosylation of denatured ribonuclease B by a cytosolic peptide:N-glycanase (PNGase). On the basis of these data, we suggest that Fbs1 captures malfolded glycoproteins, protecting them from the attack of PNGase, during the chaperoning or ubiquitinating operation in the cytosol

  3. Purification and characterization of a soluble glycoprotein from garlic (Allium sativum) and its in vitro bioactivity.

    Science.gov (United States)

    Wang, Yan; Zou, Tingting; Xiang, Minghui; Jin, Chenzhong; Zhang, Xuejiao; Chen, Yong; Jiang, Qiuqing; Hu, Yihong

    2016-10-02

    A soluble glycoprotein was purified to homogeneity from ripe garlic (Allium sativum) bulbs using ammonium sulfate precipitation, Sephadex G-100 gel filtration, and diethylaminoethyl-52 cellulose anion-exchange chromatography. A native mass of 55.7 kDa estimated on gel permeation chromatography and a molecular weight of 13.2 kDa observed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis supported that the glycoprotein is a homotetramer. β-Elimination reaction result suggested that the glycoprotein is an N-linked type. Fourier-transform infrared spectroscopy proved that it contains sugar. Gas chromatography-mass spectrometer analysis showed that its sugar component was galactose. The glycoprotein has 1,1-diphenyl-2-picrylhydrazil free radical scavenging activity and the peroxidation inhibition ability to polyunsaturated fatty acid. These results indicated that the glycoprotein has potential for food additives, functional foods, and even biotechnological and medical applications.

  4. A Carbohydrate Moiety of Secreted Stage-Specific Glycoprotein 4 Participates in Host Cell Invasion by Trypanosoma cruzi Extracellular Amastigotes

    Science.gov (United States)

    Florentino, Pilar T. V.; Real, Fernando; Orikaza, Cristina M.; da Cunha, Julia P. C.; Vitorino, Francisca N. L.; Cordero, Esteban M.; Sobreira, Tiago J. P.; Mortara, Renato A.

    2018-01-01

    Trypanosoma cruzi is the etiologic agent of Chagas’ disease. It is known that amastigotes derived from trypomastigotes in the extracellular milieu are infective in vitro and in vivo. Extracellular amastigotes (EAs) have a stage-specific surface antigen called Ssp-4, a GPI-anchored glycoprotein that is secreted by the parasites. By immunoprecipitation with the Ssp-4-specific monoclonal antibodies (mAb) 2C2 and 1D9, we isolated the glycoprotein from EAs. By mass spectrometry, we identified the core protein of Ssp-4 and evaluated mRNA expression and the presence of Ssp-4 carbohydrate epitopes recognized by mAb1D9. We demonstrated that the carbohydrate epitope recognized by mAb1D9 could promote host cell invasion by EAs. Although infectious EAs express lower amounts of Ssp-4 compared with less-infectious EAs (at the mRNA and protein levels), it is the glycosylation of Ssp-4 (identified by mAb1D9 staining only in infectious strains and recognized by galectin-3 on host cells) that is the determinant of EA invasion of host cells. Furthermore, Ssp-4 is secreted by EAs, either free or associated with parasite vesicles, and can participate in host-cell interactions. The results presented here describe the possible role of a carbohydrate moiety of T. cruzi surface glycoproteins in host cell invasion by EA forms, highlighting the potential of these moieties as therapeutic and vaccine targets for the treatment of Chagas’ disease. PMID:29692765

  5. Factors associated with abnormal spirometry among HIV-infected individuals.

    Science.gov (United States)

    Drummond, M Bradley; Huang, Laurence; Diaz, Philip T; Kirk, Gregory D; Kleerup, Eric C; Morris, Alison; Rom, William; Weiden, Michael D; Zhao, Enxu; Thompson, Bruce; Crothers, Kristina

    2015-08-24

    HIV-infected individuals are susceptible to development of chronic lung diseases, but little is known regarding the prevalence and risk factors associated with different spirometric abnormalities in this population. We sought to determine the prevalence, risk factors and performance characteristics of risk factors for spirometric abnormalities among HIV-infected individuals. Cross-sectional cohort study. We analyzed cross-sectional US data from the NHLBI-funded Lung-HIV consortium - a multicenter observational study of heterogeneous groups of HIV-infected participants in diverse geographic sites. Logistic regression analysis was performed to determine factors statistically significantly associated with spirometry patterns. A total of 908 HIV-infected individuals were included. The median age of the cohort was 50 years, 78% were men and 68% current smokers. An abnormal spirometry pattern was present in 37% of the cohort: 27% had obstructed and 10% had restricted spirometry patterns. Overall, age, smoking status and intensity, history of Pneumocystis infection, asthma diagnosis and presence of respiratory symptoms were independently associated with an abnormal spirometry pattern. Regardless of the presence of respiratory symptoms, five HIV-infected participants would need to be screened with spirometry to diagnose two individuals with any abnormal spirometry pattern. Nearly 40% of a diverse US cohort of HIV-infected individuals had an abnormal spirometry pattern. Specific characteristics including age, smoking status, respiratory infection history and respiratory symptoms can identify those at risk for abnormal spirometry. The high prevalence of abnormal spirometry and the poor predictive capability of respiratory symptoms to identify abnormal spirometry should prompt clinicians to consider screening spirometry in HIV-infected populations.

  6. Annotating Human P-Glycoprotein Bioassay Data.

    Science.gov (United States)

    Zdrazil, Barbara; Pinto, Marta; Vasanthanathan, Poongavanam; Williams, Antony J; Balderud, Linda Zander; Engkvist, Ola; Chichester, Christine; Hersey, Anne; Overington, John P; Ecker, Gerhard F

    2012-08-01

    Huge amounts of small compound bioactivity data have been entering the public domain as a consequence of open innovation initiatives. It is now the time to carefully analyse existing bioassay data and give it a systematic structure. Our study aims to annotate prominent in vitro assays used for the determination of bioactivities of human P-glycoprotein inhibitors and substrates as they are represented in the ChEMBL and TP-search open source databases. Furthermore, the ability of data, determined in different assays, to be combined with each other is explored. As a result of this study, it is suggested that for inhibitors of human P-glycoprotein it is possible to combine data coming from the same assay type, if the cell lines used are also identical and the fluorescent or radiolabeled substrate have overlapping binding sites. In addition, it demonstrates that there is a need for larger chemical diverse datasets that have been measured in a panel of different assays. This would certainly alleviate the search for other inter-correlations between bioactivity data yielded by different assay setups.

  7. Report to Congress on abnormal occurrences, October--December 1992

    International Nuclear Information System (INIS)

    1993-03-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from October 1 through December 31, 1992. There are two abnormal occurrences at nuclear power plants and six abnormal occurrences involving medical misadministration (all therapeutic) at NRC-licensed facilities discussed in this report. No abnormal occurrences were reported by the NRC's Agreement States. The report also contains information updating three previously reported abnormal occurrences

  8. Report to congress on abnormal occurrences: January--March 1992

    International Nuclear Information System (INIS)

    1992-07-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as abnormal occurrence as an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to congress. This report covers the period from January 1 through March 31, 1992. The abnormal occurrences involving medical therapy misadministrations at NRC-licensed facilities are discussed in this report. There were no abnormal occurrences at a nuclear power plant, and none were reported by NRC's Agreement States. The report also contains information updating some previously reported abnormal occurrences

  9. Chemoenzymatic site-specific labeling of influenza glycoproteins as a tool to observe virus budding in real time.

    Directory of Open Access Journals (Sweden)

    Maximilian Wei-Lin Popp

    Full Text Available The influenza virus uses the hemagglutinin (HA and neuraminidase (NA glycoproteins to interact with and infect host cells. While biochemical and microscopic methods allow examination of the early steps in flu infection, the genesis of progeny virions has been more difficult to follow, mainly because of difficulties inherent in fluorescent labeling of flu proteins in a manner compatible with live cell imaging. We here apply sortagging as a chemoenzymatic approach to label genetically modified but infectious flu and track the flu glycoproteins during the course of infection. This method cleanly distinguishes influenza glycoproteins from host glycoproteins and so can be used to assess the behavior of HA or NA biochemically and to observe the flu glycoproteins directly by live cell imaging.

  10. Intestinal mucus and juice glycoproteins have a liquid crystalline structure

    International Nuclear Information System (INIS)

    Denisova, E.A.; Lazarev, P.I.; Vazina, A.A.; Zheleznaya, L.A.

    1985-01-01

    X-ray diffraction patterns have been obtained from the following components of canine gastrointestinal tract: (1) native small intestine mucus layer; (2) the precipitate of the flocks formed in the duodenal juice with decreasing pH; (3) concentrated solutions of glycoproteins isolated from the duodenal juice. The X-ray patterns consist of a large number of sharp reflections of spacings between about 100 and 4 A. Some reflections are common for all components studied. All the patterns are interpreted as arising from the glycoprotein molecules ordered into a liquid crystalline structure. (author)

  11. Immunohistochemical abnormalities of fibrillin in cardiovascular tissues in Marfan's syndrome.

    Science.gov (United States)

    Fleischer, K J; Nousari, H C; Anhalt, G J; Stone, C D; Laschinger, J C

    1997-04-01

    Molecular defects in the glycoprotein fibrillin are believed to be responsible for impaired structural integrity of cardiovascular, skeletal, and ocular tissues in Marfan's syndrome (MFS). Traditionally, excellent results have been achieved with the Bentall composite graft repair of aneurysms of the ascending aorta in MFS. However, because of the potential complications associated with prosthetic valves, there is growing interest in techniques that preserve the native aortic valve. Between May 1994 and February 1995, 15 patients with a history of concomitant or remote aortic root aneurysms or dissection underwent operation for valvular heart disease. Specimens of aortic valve, ascending aortic wall, and mitral valve were obtained specifically to observe differences in fibrillin content and architecture between patients with (n = 9) and without (n = 6) MFS. In addition, control specimens of aortic valve, aortic wall, and mitral valve were obtained from 4 patients with isolated valvular or coronary artery disease but no evidence of connective tissue disorders or other aortic pathologic conditions. Fibrillin immunostaining using indirect immunofluorescence was used. Specimens were coded and graded by a blinded observer to determine quantity, homogeneity, and fragmentation of fibrillin. Observed fibrillin abnormalities in MFS and control patients were limited to the midportion (elastin-associated microfibrils) of the aortic valve, aortic wall, and mitral valve tissues. Fibrillin abnormalities of aortic valve, aortic wall, and mitral valve tissues were seen in all patients with MFS and were most severe in those older than 20 years. Similar fibrillin abnormalities of aortic valve and aortic wall specimens were observed in control patients more than 60 years old. Even in the setting of a normal-appearing aortic valve, the current rationale for widespread use of valve-sparing repairs of aortic root aneurysms in patients with MFS and patients older than 60 years should be

  12. Platelet Glycoprotein Ib-IX and Malignancy

    Science.gov (United States)

    2010-09-01

    provide a unique microenvironment supporting the accumulation of more platelets and the elaboration of a fibrin - rich network produced by coagulation...process and can initiate the formation of a platelet - rich thrombus by tethering the platelet to a thrombogenic surface. Several ligands binding to GP Ib... Platelet Glycoprotein Ib-IX and Malignancy PRINCIPAL INVESTIGATOR: Jerry Ware, Ph.D

  13. The quality control of glycoprotein folding in the endoplasmic reticulum, a trip from trypanosomes to mammals

    Directory of Open Access Journals (Sweden)

    A.J. Parodi

    1998-05-01

    Full Text Available The present review deals with the stages of synthesis and processing of asparagine-linked oligosaccharides occurring in the lumen of the endoplasmic reticulum and their relationship to the acquisition by glycoproteins of their proper tertiary structures. Special emphasis is placed on reactions taking place in trypanosomatid protozoa since their study has allowed the detection of the transient glucosylation of glycoproteins catalyzed by UDP-Glc:glycoprotein glucosyltransferase and glucosidase II. The former enzyme has the unique property of covalently tagging improperly folded conformations by catalyzing the formation of protein-linked Glc1Man7GlcNAc2, Glc1Man8GlcNac2 and Glc1Man9GlcNAc2 from the unglucosylated proteins. Glucosyltransferase is a soluble protein of the endoplasmic reticulum that recognizes protein domains exposed in denatured but not in native conformations (probably hydrophobic amino acids and the innermost N-acetylglucosamine unit that is hidden from macromolecular probes in most native glycoproteins. In vivo, the glucose units are removed by glucosidase II. The influence of oligosaccharides in glycoprotein folding is reviewed as well as the participation of endoplasmic reticulum chaperones (calnexin and calreticulin that recognize monoglucosylated species in the same process. A model for the quality control of glycoprotein folding in the endoplasmic reticulum, i.e., the mechanism by which cells recognize the tertiary structure of glycoproteins and only allow transit to the Golgi apparatus of properly folded species, is discussed. The main elements of this control are calnexin and calreticulin as retaining components, the UDP-Glc:glycoprotein glucosyltransferase as a sensor of tertiary structures and glucosidase II as the releasing agent.

  14. Boronic Acid-Based Approach for Separation and Immobilization of Glycoproteins and Its Application in Sensing

    Directory of Open Access Journals (Sweden)

    Lin Liu

    2013-10-01

    Full Text Available Glycoproteins influence a broad spectrum of biological processes including cell-cell interaction, host-pathogen interaction, or protection of proteins against proteolytic degradation. The analysis of their glyco-structures and concentration levels are increasingly important in diagnosis and proteomics. Boronic acids can covalently react with cis-diols in the oligosaccharide chains of glycoproteins to form five- or six-membered cyclic esters. Based on this interaction, boronic acid-based ligands and materials have attracted much attention in both chemistry and biology as the recognition motif for enrichment and chemo/biosensing of glycoproteins in recent years. In this work, we reviewed the progress in the separation, immobilization and detection of glycoproteins with boronic acid-functionalized materials and addressed its application in sensing.

  15. T wave abnormalities, high body mass index, current smoking and high lipoprotein (a levels predict the development of major abnormal Q/QS patterns 20 years later. A population-based study

    Directory of Open Access Journals (Sweden)

    Sundstrom Johan

    2006-03-01

    Full Text Available Abstract Background Most studies on risk factors for development of coronary heart disease (CHD have been based on the clinical outcome of CHD. Our aim was to identify factors that could predict the development of ECG markers of CHD, such as abnormal Q/QS patterns, ST segment depression and T wave abnormalities, in 70-year-old men, irrespective of clinical outcome. Methods Predictors for development of different ECG abnormalities were identified in a population-based study using stepwise logistic regression. Anthropometrical and metabolic factors, ECG abnormalities and vital signs from a health survey of men at age 50 were related to ECG abnormalities identified in the same cohort 20 years later. Results At the age of 70, 9% had developed a major abnormal Q/QS pattern, but 63% of these subjects had not been previously hospitalized due to MI, while 57% with symptomatic MI between age 50 and 70 had no major Q/QS pattern at age 70. T wave abnormalities (Odds ratio 3.11, 95% CI 1.18–8.17, high lipoprotein (a levels, high body mass index (BMI and smoking were identified as significant independent predictors for the development of abnormal major Q/QS patterns. T wave abnormalities and high fasting glucose levels were significant independent predictors for the development of ST segment depression without abnormal Q/QS pattern. Conclusion T wave abnormalities on resting ECG should be given special attention and correlated with clinical information. Risk factors for major Q/QS patterns need not be the same as traditional risk factors for clinically recognized CHD. High lipoprotein (a levels may be a stronger risk factor for silent myocardial infarction (MI compared to clinically recognized MI.

  16. Cytogenetic abnormalities in Tunisian women with premature ovarian failure.

    Science.gov (United States)

    Ayed, Wiem; Amouri, Ahlem; Hammami, Wajih; Kilani, Olfa; Turki, Zinet; Harzallah, Fatma; Bouayed-Abdelmoula, Nouha; Chemkhi, Imen; Zhioua, Fethi; Slama, Claude Ben

    2014-12-01

    To identify the distribution of chromosome abnormalities among Tunisian women with premature ovarian failure (POF) referred to the department of Cytogenetic at the Pasteur Institute of Tunis (Tunisia), standard cytogenetic analysis was carried out in a total of 100 women younger than 40 affected with premature ovarian failure. We identified 18 chromosomal abnormalities, including seven X-numerical anomalies in mosaic and non-mosaic state (45,X; 47,XXX), four sex reversal, three X-structural abnormalities (terminal deletion and isochromosomes), one autosomal translocation and one supernumerary marker. The overall prevalence of chromosomal abnormalities was 18% in our cohort. X chromosome aneuploidy was the most frequent aberration. This finding confirms the essential role of X chromosome in ovarian function and underlies the importance of cytogenetic investigations in the routine management of POF. Copyright © 2014 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  17. Report on Congress on abnormal occurrences

    International Nuclear Information System (INIS)

    1991-06-01

    Section 208 of the energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from January 1 through March 31, 1991. The report discusses six abnormal occurrences, none of which involved a nuclear power plant. Five of the events occurred at NRC-licensed facilities: one involved a significant degradation of plant safety at a nuclear fuel cycle facility, one involved a medical diagnostic misadministration, and three involved medical therapy misadministrations. An Agreement State (Arizona) reported one abnormal occurrence that involved medical therapy misadministrations

  18. Mucus glycoprotein secretion by tracheal explants: effects of pollutants

    International Nuclear Information System (INIS)

    Last, J.A.; Kaizu, T.

    1980-01-01

    Tracheal slices incubated with radioactive precursors in tissue culture medium secrete labeled mucus glycoproteins into the culture medium. We have used an in vivtro approach, a combined method utilizing exposure to pneumotoxins in vivo coupled with quantitation of mucus secretion rates in vitro, to study the effects of inhaled pollutants on mucus biosynthesis by rat airways. In addition, we have purified the mucus glycoproteins secreted by rat tracheal explants in order to determine putative structural changes that might by the basis for the observed augmented secretion rates after exposure of rats to H2SO4 aerosols in combination with high ambient levels of ozone. After digestion with papain, mucus glycoproteins secreted by tracheal explants may be separated into five fractions by ion-exchange chromatography, with recovery in high yield, on columns of DEAE-cellulose. Each of these five fractions, one neutral and four acidic, migrates as a single unique spot upon cellulose acetate electrophoresis at pH values of 8.6 and 1.2. The neutral fraction, which is labeled with [3H] glucosamine, does not contain radioactivity when Na2 35SO4 is used as the precursor. Acidic fractions I to IV are all labeled with either 3H-glucosamine or Na2 35SO4 as precursor. Acidic fraction II contains sialic acid as the terminal sugar on its oligosaccharide side chains, based upon its chromatographic behavior on columns of wheat-germ agglutinin-Agarose. Treatment of this fraction with neuraminidase shifts its elution position in the gradient to a lower salt concentration, coincident with acidic fraction I. After removal of terminal sialic acid residues with either neuraminidase or low pH treatment, the resultant terminal sugar on the oligosaccharide side chains is fucose. These results are identical with those observed with mucus glycoproteins secreted by cultured human tracheal explants and purified by these same techniques

  19. Glycan structures contain information for the spatial arrangement of glycoproteins in the plasma membrane.

    Directory of Open Access Journals (Sweden)

    M Kristen Hall

    Full Text Available Glycoconjugates at the cell surface are crucial for cells to communicate with each other and the extracellular microenvironment. While it is generally accepted that glycans are vectorial biopolymers, their information content is unclear. This report provides evidence that distinct N-glycan structures influence the spatial arrangement of two integral membrane glycoproteins, Kv3.1 and E-cadherin, at the adherent membrane which in turn alter cellular properties. Distinct N-glycan structures were generated by heterologous expression of these glycoproteins in parental and glycosylation mutant Chinese hamster ovary cell lines. Unlike the N-linked glycans, the O-linked glycans of the mutant cell lines are similar to those of the parental cell line. Western and lectin blots of total membranes and GFP immunopurified samples, combined with glycosidase digestion reactions, were employed to verify the glycoproteins had predominantly complex, oligomannose, and bisecting type N-glycans from Pro(-5, Lec1, and Lec10B cell lines, respectively. Based on total internal reflection fluorescence and differential interference contrast microscopy techniques, and cellular assays of live parental and glycosylation mutant CHO cells, we propose that glycoproteins with complex, oligomannose or bisecting type N-glycans relay information for localization of glycoproteins to various regions of the plasma membrane in both a glycan-specific and protein-specific manner, and furthermore cell-cell interactions are required for deciphering much of this information. These distinct spatial arrangements also impact cell adhesion and migration. Our findings provide direct evidence that N-glycan structures of glycoproteins contribute significantly to the information content of cells.

  20. Report to Congress on abnormal occurrences, July--September 1992

    International Nuclear Information System (INIS)

    1992-12-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from July 1 through September 30, 1992. There were no abnormal occurrences at a nuclear power plant. Two abnormal occurrences involving medical misadministrations (both therapeutic) and one involving overexposure of a radiographer at NRC-licensed facilities were discussed in this report. In addition, another abnormal occurrence was reported by an NRC Agreement State. The report also contains information updating a previously reported abnormal occurrence

  1. Sequencing of a patient with balanced chromosome abnormalities and neurodevelopmental disease identifies disruption of multiple high risk loci by structural variation.

    Directory of Open Access Journals (Sweden)

    Jonathon Blake

    Full Text Available Balanced chromosome abnormalities (BCAs occur at a high frequency in healthy and diseased individuals, but cost-efficient strategies to identify BCAs and evaluate whether they contribute to a phenotype have not yet become widespread. Here we apply genome-wide mate-pair library sequencing to characterize structural variation in a patient with unclear neurodevelopmental disease (NDD and complex de novo BCAs at the karyotype level. Nucleotide-level characterization of the clinically described BCA breakpoints revealed disruption of at least three NDD candidate genes (LINC00299, NUP205, PSMD14 that gave rise to abnormal mRNAs and could be assumed as disease-causing. However, unbiased genome-wide analysis of the sequencing data for cryptic structural variation was key to reveal an additional submicroscopic inversion that truncates the schizophrenia- and bipolar disorder-associated brain transcription factor ZNF804A as an equally likely NDD-driving gene. Deep sequencing of fluorescent-sorted wild-type and derivative chromosomes confirmed the clinically undetected BCA. Moreover, deep sequencing further validated a high accuracy of mate-pair library sequencing to detect structural variants larger than 10 kB, proposing that this approach is powerful for clinical-grade genome-wide structural variant detection. Our study supports previous evidence for a role of ZNF804A in NDD and highlights the need for a more comprehensive assessment of structural variation in karyotypically abnormal individuals and patients with neurocognitive disease to avoid diagnostic deception.

  2. Sequencing of a Patient with Balanced Chromosome Abnormalities and Neurodevelopmental Disease Identifies Disruption of Multiple High Risk Loci by Structural Variation

    Science.gov (United States)

    Blake, Jonathon; Riddell, Andrew; Theiss, Susanne; Gonzalez, Alexis Perez; Haase, Bettina; Jauch, Anna; Janssen, Johannes W. G.; Ibberson, David; Pavlinic, Dinko; Moog, Ute; Benes, Vladimir; Runz, Heiko

    2014-01-01

    Balanced chromosome abnormalities (BCAs) occur at a high frequency in healthy and diseased individuals, but cost-efficient strategies to identify BCAs and evaluate whether they contribute to a phenotype have not yet become widespread. Here we apply genome-wide mate-pair library sequencing to characterize structural variation in a patient with unclear neurodevelopmental disease (NDD) and complex de novo BCAs at the karyotype level. Nucleotide-level characterization of the clinically described BCA breakpoints revealed disruption of at least three NDD candidate genes (LINC00299, NUP205, PSMD14) that gave rise to abnormal mRNAs and could be assumed as disease-causing. However, unbiased genome-wide analysis of the sequencing data for cryptic structural variation was key to reveal an additional submicroscopic inversion that truncates the schizophrenia- and bipolar disorder-associated brain transcription factor ZNF804A as an equally likely NDD-driving gene. Deep sequencing of fluorescent-sorted wild-type and derivative chromosomes confirmed the clinically undetected BCA. Moreover, deep sequencing further validated a high accuracy of mate-pair library sequencing to detect structural variants larger than 10 kB, proposing that this approach is powerful for clinical-grade genome-wide structural variant detection. Our study supports previous evidence for a role of ZNF804A in NDD and highlights the need for a more comprehensive assessment of structural variation in karyotypically abnormal individuals and patients with neurocognitive disease to avoid diagnostic deception. PMID:24625750

  3. Design and synthesis of an antigenic mimic of the Ebola glycoprotein

    OpenAIRE

    Rutledge, Ryan D.; Huffman, Brian J.; Cliffel, David E.; Wright, David W.

    2008-01-01

    An antigenic mimic of the Ebola glycoprotein was synthesized and tested for its ability to be recognized by an anti-Ebola glycoprotein antibody. Epitope-mapping procedures yielded a suitable epitope that, when presented on the surface of a nanoparticle, forms a structure that is recognized by an antibody specific for the native protein. This mimic-antibody interaction has been quantitated through ELISA and QCM-based methods and yielded an affinity (Kd = 12 × 10−6 M) within two orders of magni...

  4. A functional glycoproteomics approach identifies CD13 as a novel E-selectin ligand in breast cancer.

    Science.gov (United States)

    Carrascal, M A; Silva, M; Ferreira, J A; Azevedo, R; Ferreira, D; Silva, A M N; Ligeiro, D; Santos, L L; Sackstein, R; Videira, P A

    2018-05-17

    The glycan moieties sialyl-Lewis-X and/or -A (sLe X/A ) are the primary ligands for E-selectin, regulating subsequent tumor cell extravasation into distant organs. However, the nature of the glycoprotein scaffolds displaying these glycans in breast cancer remains unclear and constitutes the focus of the present investigation. We isolated glycoproteins that bind E-selectin from the CF1_T breast cancer cell line, derived from a patient with ductal carcinoma. Proteins were identified using bottom-up proteomics approach by nanoLC-orbitrap LTQ-MS/MS. Data were curated using bioinformatics tools to highlight clinically relevant glycoproteins, which were validated by flow cytometry, Western blot, immunohistochemistry and in-situ proximity ligation assays in clinical samples. We observed that the CF1_T cell line expressed sLe X , but not sLe A and the E-selectin reactivity was mainly on N-glycans. MS and bioinformatics analysis of the targeted glycoproteins, when narrowed down to the most clinically relevant species in breast cancer, identified CD44 glycoprotein (HCELL) and CD13 as key E-selectin ligands. Additionally, the co-expression of sLe X -CD44 and sLe X -CD13 was confirmed in clinical breast cancer tissue samples. Both CD44 and CD13 glycoforms display sLe X in breast cancer and bind E-selectin, suggesting a key role in metastasis development. Such observations provide a novel molecular rationale for developing targeted therapeutics. While HCELL expression in breast cancer has been previously reported, this is the first study indicating that CD13 functions as an E-selectin ligand in breast cancer. This observation supports previous associations of CD13 with metastasis and draws attention to this glycoprotein as an anti-cancer target. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Identification of Abnormal Stem Cells Using Raman Spectroscopy

    DEFF Research Database (Denmark)

    Harkness, Linda; Novikov, Sergey M; Beermann, Jonas

    2012-01-01

    The clinical use of stem cells in cell-based therapeutics for degenerative diseases requires development of criteria for defining normal stem cells to ensure safe transplantation. Currently, identification of abnormal from normal stem cells is based on extensive ex vivo and in vivo testing. Raman...... microscopy is a label-free method for rapid and sensitive detection of changes in cells' bio-molecular composition. Here, we report that by using Raman spectroscopy, we were able to map the distribution of different biomolecules within 2 types of stem cells: adult human bone marrow-derived stromal stem cells...... and human embryonic stem cells and to identify reproducible differences in Raman's spectral characteristics that distinguished genetically abnormal and transformed stem cells from their normal counterparts. Raman microscopy can be prospectively employed as a method for identifying abnormal stem cells in ex...

  6. Involvement of Leishmania donovani major surface glycoprotein ...

    Indian Academy of Sciences (India)

    The major surface glycoprotein gp63 of the kinetoplastid protozoal parasite Leishmania is implicated as a ligand mediating uptake of the parasite into, and survival within, the host macrophage. By expressing gp63 antisense RNA from an episomal vector in L. donovani promastigotes, gp63-deficient transfectants were ...

  7. Bioinformatics Analysis of Envelope Glycoprotein E epitopes of ...

    African Journals Online (AJOL)

    User

    2011-05-02

    May 2, 2011 ... 1National Centre of Excellence in Molecular Biology, University of the Punjab Lahore, Pakistan. 2Department of ..... E glycoprotein and its interaction with antibody with the method of molecular dynamics and molecular model ...

  8. Structure of a Pestivirus Envelope Glycoprotein E2 Clarifies Its Role in Cell Entry

    Directory of Open Access Journals (Sweden)

    Kamel El Omari

    2013-01-01

    Full Text Available Enveloped viruses have developed various adroit mechanisms to invade their host cells. This process requires one or more viral envelope glycoprotein to achieve cell attachment and membrane fusion. Members of the Flaviviridae such as flaviviruses possess only one envelope glycoprotein, E, whereas pestiviruses and hepacivirus encode two glycoproteins, E1 and E2. Although E2 is involved in cell attachment, it has been unclear which protein is responsible for membrane fusion. We report the crystal structures of the homodimeric glycoprotein E2 from the pestivirus bovine viral diarrhea virus 1 (BVDV1 at both neutral and low pH. Unexpectedly, BVDV1 E2 does not have a class II fusion protein fold, and at low pH the N-terminal domain is disordered, similarly to the intermediate postfusion state of E2 from sindbis virus, an alphavirus. Our results suggest that the pestivirus and possibly the hepacivirus fusion machinery are unlike any previously observed.

  9. Structure of a Pestivirus Envelope Glycoprotein E2 Clarifies Its Role in Cell Entry

    Science.gov (United States)

    El Omari, Kamel; Iourin, Oleg; Harlos, Karl; Grimes, Jonathan M.; Stuart, David I.

    2013-01-01

    Summary Enveloped viruses have developed various adroit mechanisms to invade their host cells. This process requires one or more viral envelope glycoprotein to achieve cell attachment and membrane fusion. Members of the Flaviviridae such as flaviviruses possess only one envelope glycoprotein, E, whereas pestiviruses and hepacivirus encode two glycoproteins, E1 and E2. Although E2 is involved in cell attachment, it has been unclear which protein is responsible for membrane fusion. We report the crystal structures of the homodimeric glycoprotein E2 from the pestivirus bovine viral diarrhea virus 1 (BVDV1) at both neutral and low pH. Unexpectedly, BVDV1 E2 does not have a class II fusion protein fold, and at low pH the N-terminal domain is disordered, similarly to the intermediate postfusion state of E2 from sindbis virus, an alphavirus. Our results suggest that the pestivirus and possibly the hepacivirus fusion machinery are unlike any previously observed. PMID:23273918

  10. Report to Congress on abnormal occurrences, July--September 1975

    International Nuclear Information System (INIS)

    1976-01-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health and safety, and a quarterly report on such events is to be made to Congress. The second such report to Congress on abnormal occurrences is presented. The first report identified abnormal occurrences at licensed nuclear power plants during the first six months of 1975. The current report includes the results of a review of events at nuclear power plants for the third quarter of 1975 and the results of a review for overexposure to radiation at all licensed facilities for a nine-month period. The NRC has determined that there were no abnormal occurrences at licensed nuclear power plants during the period and there were no abnormal occurrences involving overexposure to radiation at NRC-licensed facilities from January 1 to September 30, 1975. Therefore, the current report comprises an updating of information concerning events reported to the Congress in the first report dated October 1975. Status is reported as of November 25, 1975

  11. A Carbohydrate Moiety of Secreted Stage-Specific Glycoprotein 4 Participates in Host Cell Invasion by Trypanosoma cruzi Extracellular Amastigotes

    Directory of Open Access Journals (Sweden)

    Pilar T. V. Florentino

    2018-04-01

    Full Text Available Trypanosoma cruzi is the etiologic agent of Chagas’ disease. It is known that amastigotes derived from trypomastigotes in the extracellular milieu are infective in vitro and in vivo. Extracellular amastigotes (EAs have a stage-specific surface antigen called Ssp-4, a GPI-anchored glycoprotein that is secreted by the parasites. By immunoprecipitation with the Ssp-4-specific monoclonal antibodies (mAb 2C2 and 1D9, we isolated the glycoprotein from EAs. By mass spectrometry, we identified the core protein of Ssp-4 and evaluated mRNA expression and the presence of Ssp-4 carbohydrate epitopes recognized by mAb1D9. We demonstrated that the carbohydrate epitope recognized by mAb1D9 could promote host cell invasion by EAs. Although infectious EAs express lower amounts of Ssp-4 compared with less-infectious EAs (at the mRNA and protein levels, it is the glycosylation of Ssp-4 (identified by mAb1D9 staining only in infectious strains and recognized by galectin-3 on host cells that is the determinant of EA invasion of host cells. Furthermore, Ssp-4 is secreted by EAs, either free or associated with parasite vesicles, and can participate in host-cell interactions. The results presented here describe the possible role of a carbohydrate moiety of T. cruzi surface glycoproteins in host cell invasion by EA forms, highlighting the potential of these moieties as therapeutic and vaccine targets for the treatment of Chagas’ disease.

  12. Report to Congress on abnormal occurrences, July--September 1988

    International Nuclear Information System (INIS)

    1989-01-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from July 1 to September 30, 1988. For this reporting period, there were no abnormal occurrences at nuclear power plants licensed to operate. There were two abnormal occurrences under other NRC-issued licenses: multiple medical therapy misadministrations at a single hospital and a medical diagnostic misadministration. There was one abnormal occurrence reported by an Agreement State (Texas) involving a medical diagnostic misadministration. The report also contains information updating some previously reported abnormal occurrences

  13. Rhodocytin (aggretin) activates platelets lacking alpha(2)beta(1) integrin, glycoprotein VI, and the ligand-binding domain of glycoprotein Ibalpha

    DEFF Research Database (Denmark)

    Bergmeier, W; Bouvard, D; Eble, J A

    2001-01-01

    Although alpha(2)beta(1) integrin (glycoprotein Ia/IIa) has been established as a platelet collagen receptor, its role in collagen-induced platelet activation has been controversial. Recently, it has been demonstrated that rhodocytin (also termed aggretin), a snake venom toxin purified from the v...

  14. Comparison of glycoprotein expression between ovarian and colon adenocarcinomas

    DEFF Research Database (Denmark)

    Multhaupt, H A; Arenas-Elliott, C P; Warhol, M J

    1999-01-01

    , carcinoembryonic antigen, and cytokeratins 7 and 20 to detect tumor-associated glycoproteins and keratin proteins in ovarian and colonic carcinomas. RESULTS: CA125, carcinoembryonic antigen, and cytokeratins 7 and 20 can distinguish between colonic and serous or endometrioid adenocarcinomas of the ovary in both...... primary and metastatic lesions. Mucinous ovarian adenocarcinomas differed in that they express carcinoembryonic antigen and cytokeratins 7 and 20 and weakly express CA125. The other glycoprotein antigens were equally expressed by ovarian and colonic adenocarcinomas and therefore were of no use...... in distinguishing between these 2 entities. CONCLUSION: A panel of monoclonal antibodies against cytokeratins 7 and 20 antigens, CA125, and carcinoembryonic antigen is useful in differentiating serous and endometrioid adenocarcinomas of the ovary from colonic adenocarcinomas. Mucinous ovarian adenocarcinomas cannot...

  15. Extracellular Glycoproteins in Embryogenic Culture of Pumpkin (Cucurbita pepo L.

    Directory of Open Access Journals (Sweden)

    Hana Čipčić Paljetak

    2011-01-01

    Full Text Available The extracellular proteins in three distinctly induced embryogenic lines of pumpkin (Cucurbita pepo L. cultivated in four MS media modified regarding the nitrogen composition or auxin presence/absence have been analyzed. Extracellular glycoproteins containing α-D-mannose were specifically detected by the lectine concavalin A. During the cultivation of embryogenic tissue in the medium supplemented with reduced nitrogen, the embryos were mostly arrested at preglobular and globular developmental stages, which coincide with the absence of protein secretion. Secreted glycoproteins of 76, 68, 37 and 34 kDa were detected only if any of the three lines were cultivated in the medium that stimulates embryo development, irrespectively of the addition of 2,4-dichlorophenoxyacetic acid or tunicamycin. The glycoprotein of 64 kDa was detected in all lines cultivated in hormone-free MS medium with conventional nitrogen sources and it appears to be associated with embryo maturation. Tunicamycin treatment did not influence embryogenesis, although it specifically affected glycosylation of proteins in the investigated lines. Our results show that besides auxin, the source of nitrate is of great importance for proper protein glycosylation, excretion and developmental transition of pumpkin somatic embryos.

  16. Parenchymal abnormalities associated with developmental venous anomalies

    Energy Technology Data Exchange (ETDEWEB)

    San Millan Ruiz, Diego; Gailloud, Philippe [Johns Hopkins Hospital, Division of Interventional Neuroradiology, Baltimore, MD (United States); Delavelle, Jacqueline [Geneva University Hospital, Neuroradiology Section, Department of Radiology and Medical Informatics, Geneva (Switzerland); Yilmaz, Hasan; Ruefenacht, Daniel A. [Geneva University Hospital, Section of Interventional Neuroradiology, Department of Clinical Neurosciences, Geneva (Switzerland); Piovan, Enrico; Bertramello, Alberto; Pizzini, Francesca [Verona City Hospital, Service of Neuroradiology, Verona (Italy)

    2007-12-15

    To report a retrospective series of 84 cerebral developmental venous anomalies (DVAs), focusing on associated parenchymal abnormalities within the drainage territory of the DVA. DVAs were identified during routine diagnostic radiological work-up based on magnetic resonance imaging (MRI) (60 cases), computed tomography (CT) (62 cases) or both (36 cases). Regional parenchymal modifications within the drainage territory of the DVA, such as cortical or subcortical atrophy, white matter density or signal alterations, dystrophic calcifications, presence of haemorrhage or a cavernous-like vascular malformation (CVM), were noted. A stenosis of the collecting vein of the DVA was also sought for. Brain abnormalities within the drainage territory of a DVA were encountered in 65.4% of the cases. Locoregional brain atrophy occurred in 29.7% of the cases, followed by white matter lesions in 28.3% of MRI investigations and 19.3% of CT investigations, CVMs in 13.3% of MRI investigations and dystrophic calcification in 9.6% of CT investigations. An intracranial haemorrhage possibly related to a DVA occurred in 2.4% cases, and a stenosis on the collecting vein was documented in 13.1% of cases. Parenchymal abnormalities were identified for all DVA sizes. Brain parenchymal abnormalities were associated with DVAs in close to two thirds of the cases evaluated. These abnormalities are thought to occur secondarily, likely during post-natal life, as a result of chronic venous hypertension. Outflow obstruction, progressive thickening of the walls of the DVA and their morphological organization into a venous convergence zone are thought to contribute to the development of venous hypertension in DVA. (orig.)

  17. Report to Congress on abnormal occurrences, April--June 1989

    International Nuclear Information System (INIS)

    1989-10-01

    The Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. For this reporting period, there was one abnormal occurrence at nuclear power plants licensed to operate involving significant deficiencies in management controls at Slurry Nuclear Power Station. There was one abnormal occurrence under other NRC-issued licenses; the event involved a medical therapy misadministration. One other abnormal occurrence, involving industrial radiography overexposures, was reported by an Agreement State (Texas). 40 refs

  18. IgA antibodies against β2 glycoprotein I in hemodialysis patients are an independent risk factor for mortality.

    Science.gov (United States)

    Serrano, Antonio; García, Florencio; Serrano, Manuel; Ramírez, Elisa; Alfaro, F Javier; Lora, David; de la Cámara, Agustín Gómez; Paz-Artal, Estela; Praga, Manuel; Morales, Jose M

    2012-06-01

    Cardiovascular complications are the most important cause of death in patients on dialysis with end-stage renal disease. Antibodies reacting with β-glycoprotein I seem to play a pathogenic role in antiphospholipid syndrome and stroke and are involved in the origin of atherosclerosis. Here we evaluated the presence of anticardiolipin and anti-β-glycoprotein I antibodies together with other vascular risk factors and their relationship with mortality and cardiovascular morbidity in a cohort of 124 hemodialysis patients prospectively followed for 2 years. Of these, 41 patients were significantly positive for IgA anti-β-glycoprotein I, and the remaining had normal values. At 24 months, overall and cardiovascular mortality and thrombotic events were all significantly higher in patients with high anti-β-glycoprotein I antibodies. Multivariate analysis using Cox regression modeling found that age, hypoalbuminemia, use of dialysis catheters, and IgA β-glycoprotein I antibodies were independent risk factors for death. Thus, IgA antibodies to β-glycoprotein I are detrimental to the clinical outcome of hemodialysis patients.

  19. Radiologic evaluation of structural abnormalities of the foot

    International Nuclear Information System (INIS)

    Adler, Y.T.; Tolliver, R.A.; Stern, D.S.; Fruin, M.E.

    1987-01-01

    This exhibit concentrates on often overlooked, unfamiliar biomechanical or structural abnormalities of the foot. Pericalcaneal pathology and its correlation with the presence of heel spurs is illustrated. In the tarsal area, coalitions, prehallux, and their relationships to abnormalities of the longitudinal arch are discussed. Distally, medial, dorsal and tailor's bunions are demonstrated. Pain and disability often precede obvious deformity, and a radiologist familiar with the early findings on x-ray studies may be the first member of the medical team to identify structural abnormalities. Diagnosis allows prompt institution of appropriate therapy, reducing the period of patient discomfort and disability

  20. In silico-based vaccine design against Ebola virus glycoprotein

    Directory of Open Access Journals (Sweden)

    Dash R

    2017-03-01

    Full Text Available Raju Dash,1 Rasel Das,2 Md Junaid,3 Md Forhad Chowdhury Akash,4 Ashekul Islam,5 SM Zahid Hosen1 1Molecular Modeling and Drug Design Laboratory (MMDDL, Pharmacology Research Division, Bangladesh Council of Scientific and Industrial Research (BCSIR, Chittagong, Bangladesh; 2Nanotechnology and Catalysis Research Center, University of Malaya, Kuala Lumpur, Malaysia; 3Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh; 4Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, Bangladesh; 5Department of Biochemistry and Molecular Biology, University of Chittagong, Chittagong, Bangladesh Abstract: Ebola virus (EBOV is one of the lethal viruses, causing more than 24 epidemic outbreaks to date. Despite having available molecular knowledge of this virus, no definite vaccine or other remedial agents have been developed yet for the management and avoidance of EBOV infections in humans. Disclosing this, the present study described an epitope-based peptide vaccine against EBOV, using a combination of B-cell and T-cell epitope predictions, followed by molecular docking and molecular dynamics simulation approach. Here, protein sequences of all glycoproteins of EBOV were collected and examined via in silico methods to determine the most immunogenic protein. From the identified antigenic protein, the peptide region ranging from 186 to 220 and the sequence HKEGAFFLY from the positions of 154–162 were considered the most potential B-cell and T-cell epitopes, correspondingly. Moreover, this peptide (HKEGAFFLY interacted with HLA-A*32:15 with the highest binding energy and stability, and also a good conservancy of 83.85% with maximum population coverage. The results imply that the designed epitopes could manifest vigorous enduring defensive immunity against EBOV. Keywords: Ebola virus, epitope, glycoprotein, vaccine design

  1. Nonsense mutation in the glycoprotein Ibα coding sequence associated with Bernard-Soulier syndrome

    International Nuclear Information System (INIS)

    Ware, J.; Russell, S.R.; Vicente, V.; Scharf, R.E.; Tomer, A.; McMillian, R.; Ruggeri, Z.M.

    1990-01-01

    Three distinct gene products, the α and β chains of glycoprotein (GP) Ib and GP IX, constitute the platelet membrane GP Ib-IX complex, a receptor for von Willebrand factor and thrombin involved in platelet adhesion and aggregation. Defective function of the GP Ib-IX complex is the hallmark of a rare congenital bleeding disorder of still undefined pathogenesis, the Bernard-Soulier syndrome. The authors have analyzed the molecular basis of the disease in one patient in whom immunoblotting of solubilized platelets demonstrated absence of normal GP Ibα but presence of a smaller immunoreactive species. The truncated polypeptide was also present, along with normal protein, in platelets from the patient's mother and two of his four children. Genetic characterization identified a nucleotide transition changing the Trp-343 codon (TGG) to a nonsense codon (TGA). Such a mutation explains the origin of the smaller GP Ibα, which by lacking half of the sequence on the carboxyl-terminal side, including the transmembrane domain, cannot be properly inserted in the platelet membrane. Both normal and mutant codons were found in the patient, suggesting that he is a compound heterozygote with a still unidentified defect in the other GP Ibα allele. Nonsense mutation and truncated GP Ibα polypeptide were found to cosegregate in four individuals through three generations and were associated with either Bernard-Soulier syndrome or carrier state phenotype. The molecular abnormality demonstrated in this family provides evidence that defective synthesis of GP Ibα alters the membrane expression of the GP Ib-IX complex and may be responsible for Bernard-Soulier syndrome

  2. MicroRNA expression in rainbow trout (Oncorhynchus mykiss) vaccinated with a DNA vaccine encoding the glycoprotein gene of Viral hemorrhagic septicemia virus

    DEFF Research Database (Denmark)

    Bela-Ong, Dennis; Schyth, Brian Dall; Lorenzen, Niels

    particularly to sea-farmed rainbow trout and thus necessitates strategies to mitigate potential disease outbreaks. A DNA vaccine encoding the glycoprotein gene of VHSV has been developed and shown to elicit protective immune responses in laboratory trials. It is important to identify key factors as biomarkers...

  3. The immune system modulator a1-acid glycoprotein inhibits insulin and IGF1 induced protein synthesis in C2C12 myotubes

    Science.gov (United States)

    Alpha-1 acid glycoprotein (AGP) has previously been demonstrated by our laboratory to be negatively correlated with growth rate in newborn piglets. However, a mechanism of action for AGP in growth has not been identified. Previous research has demonstrated that AGP can modify adipose tissue metabo...

  4. Glycoprotein Ibalpha signalling in platelet apoptosis and clearance

    NARCIS (Netherlands)

    van der Wal, E.

    2010-01-01

    Storage of platelets at low temperature reduces bacterial growth and might better preserve the haemostatic function of platelets than current procedures. Incubation at 0C is known to expose ?-N-acetyl-D-glucosamine-residues on glycoprotein (GP)Ibalpha inducing receptor-clustering and platelet

  5. Heterotaxy syndromes and abnormal bowel rotation

    Energy Technology Data Exchange (ETDEWEB)

    Newman, Beverley [Stanford University, Lucile Packard Children' s Hospital, Department of Radiology, Stanford, CA (United States); Koppolu, Raji; Sylvester, Karl [Lucile Packard Children' s Hospital at Stanford, Department of Surgery, Stanford, CA (United States); Murphy, Daniel [Lucile Packard Children' s Hospital at Stanford, Department of Cardiology, Stanford, CA (United States)

    2014-05-15

    Bowel rotation abnormalities in heterotaxy are common. As more children survive cardiac surgery, the management of gastrointestinal abnormalities has become controversial. To evaluate imaging of malrotation in heterotaxy with surgical correlation and provide an algorithm for management. Imaging reports of heterotaxic children with upper gastrointestinal (UGI) and/or small bowel follow-through (SBFT) were reviewed. Subsequently, fluoroscopic images were re-reviewed in conjunction with CT/MR studies. The original reports and re-reviewed images were compared and correlated with surgical findings. Nineteen of 34 children with heterotaxy underwent UGI, 13/19 also had SBFT. In 15/19 reports, bowel rotation was called abnormal: 11 malrotation, 4 non-rotation, no cases of volvulus. Re-review, including CT (10/19) and MR (2/19), designated 17/19 (90%) as abnormal, 10 malrotation (abnormal bowel arrangement, narrow or uncertain length of mesentery) and 7 non-rotation (small bowel and colon on opposite sides plus low cecum with probable broad mesentery). The most useful CT/MR findings were absence of retroperitoneal duodenum in most abnormal cases and location of bowel, especially cecum. Abnormal orientation of mesenteric vessels suggested malrotation but was not universal. Nine children had elective bowel surgery; non-rotation was found in 4/9 and malrotation was found in 5/9, with discrepancies (non-rotation at surgery, malrotation on imaging) with 4 original interpretations and 1 re-review. We recommend routine, early UGI and SBFT studies once other, urgent clinical concerns have been stabilized, with elective laparoscopic surgery in abnormal or equivocal cases. Cross-sectional imaging, usually obtained for other reasons, can contribute diagnostically. Attempting to assess mesenteric width is important in differentiating non-rotation from malrotation and more accurately identifies appropriate surgical candidates. (orig.)

  6. Heterotaxy syndromes and abnormal bowel rotation

    International Nuclear Information System (INIS)

    Newman, Beverley; Koppolu, Raji; Sylvester, Karl; Murphy, Daniel

    2014-01-01

    Bowel rotation abnormalities in heterotaxy are common. As more children survive cardiac surgery, the management of gastrointestinal abnormalities has become controversial. To evaluate imaging of malrotation in heterotaxy with surgical correlation and provide an algorithm for management. Imaging reports of heterotaxic children with upper gastrointestinal (UGI) and/or small bowel follow-through (SBFT) were reviewed. Subsequently, fluoroscopic images were re-reviewed in conjunction with CT/MR studies. The original reports and re-reviewed images were compared and correlated with surgical findings. Nineteen of 34 children with heterotaxy underwent UGI, 13/19 also had SBFT. In 15/19 reports, bowel rotation was called abnormal: 11 malrotation, 4 non-rotation, no cases of volvulus. Re-review, including CT (10/19) and MR (2/19), designated 17/19 (90%) as abnormal, 10 malrotation (abnormal bowel arrangement, narrow or uncertain length of mesentery) and 7 non-rotation (small bowel and colon on opposite sides plus low cecum with probable broad mesentery). The most useful CT/MR findings were absence of retroperitoneal duodenum in most abnormal cases and location of bowel, especially cecum. Abnormal orientation of mesenteric vessels suggested malrotation but was not universal. Nine children had elective bowel surgery; non-rotation was found in 4/9 and malrotation was found in 5/9, with discrepancies (non-rotation at surgery, malrotation on imaging) with 4 original interpretations and 1 re-review. We recommend routine, early UGI and SBFT studies once other, urgent clinical concerns have been stabilized, with elective laparoscopic surgery in abnormal or equivocal cases. Cross-sectional imaging, usually obtained for other reasons, can contribute diagnostically. Attempting to assess mesenteric width is important in differentiating non-rotation from malrotation and more accurately identifies appropriate surgical candidates. (orig.)

  7. Report to Congress on abnormal occurrences, April--June 1988

    International Nuclear Information System (INIS)

    1988-12-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from April 1 to June 30, 1988. For this reporting period, there were no abnormal occurrences at nuclear power plants licensed to operate. There were two abnormal occurrences at other NRC licensees: a significant breakdown in management and procedural controls at a medical facility and a medical diagnostic misadministration. There was one abnormal occurrence reported by an Agreement State (Texas) involving radioactive material released during a transportation accident. The report also contains information updating some previously reported abnormal occurrences

  8. The Objective Identification and Quantification of Interstitial Lung Abnormalities in Smokers.

    Science.gov (United States)

    Ash, Samuel Y; Harmouche, Rola; Ross, James C; Diaz, Alejandro A; Hunninghake, Gary M; Putman, Rachel K; Onieva, Jorge; Martinez, Fernando J; Choi, Augustine M; Lynch, David A; Hatabu, Hiroto; Rosas, Ivan O; Estepar, Raul San Jose; Washko, George R

    2017-08-01

    Previous investigation suggests that visually detected interstitial changes in the lung parenchyma of smokers are highly clinically relevant and predict outcomes, including death. Visual subjective analysis to detect these changes is time-consuming, insensitive to subtle changes, and requires training to enhance reproducibility. Objective detection of such changes could provide a method of disease identification without these limitations. The goal of this study was to develop and test a fully automated image processing tool to objectively identify radiographic features associated with interstitial abnormalities in the computed tomography scans of a large cohort of smokers. An automated tool that uses local histogram analysis combined with distance from the pleural surface was used to detect radiographic features consistent with interstitial lung abnormalities in computed tomography scans from 2257 individuals from the Genetic Epidemiology of COPD study, a longitudinal observational study of smokers. The sensitivity and specificity of this tool was determined based on its ability to detect the visually identified presence of these abnormalities. The tool had a sensitivity of 87.8% and a specificity of 57.5% for the detection of interstitial lung abnormalities, with a c-statistic of 0.82, and was 100% sensitive and 56.7% specific for the detection of the visual subtype of interstitial abnormalities called fibrotic parenchymal abnormalities, with a c-statistic of 0.89. In smokers, a fully automated image processing tool is able to identify those individuals who have interstitial lung abnormalities with moderate sensitivity and specificity. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  9. Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism

    Directory of Open Access Journals (Sweden)

    Nathan H. Vande Burgt

    2015-10-01

    Full Text Available Tetherin is an interferon-induced, intrinsic cellular response factor that blocks release of numerous viruses, including Ebola virus, from infected cells. As with many viruses targeted by host factors, Ebola virus employs a tetherin antagonist, the viral glycoprotein (EboGP, to counteract restriction and promote virus release. Unlike other tetherin antagonists such as HIV-1 Vpu or KSHV K5, the features within EboGP needed to overcome tetherin are not well characterized. Here, we describe sequences within the EboGP ectodomain and membrane spanning domain (msd as necessary to relieve tetherin restriction of viral particle budding. Fusing the EboGP msd to a normally secreted form of the glycoprotein effectively promotes Ebola virus particle release. Cellular protein or lipid anchors could not substitute for the EboGP msd. The requirement for the EboGP msd was not specific for filovirus budding, as similar results were seen with HIV particles. Furthermore trafficking of chimeric proteins to budding sites did not correlate with an ability to counter tetherin. Additionally, we find that a glycoprotein construct, which mimics the cathepsin-activated species by proteolytic removal of the EboGP glycan cap and mucin domains, is unable to counteract tetherin. Combining these results suggests an important role for the EboGP glycan cap and msd in tetherin antagonism.

  10. The incidence of associated abnormalities in patients with sacrococcygeal teratoma

    NARCIS (Netherlands)

    Kremer, Marijke E. B.; Althof, Jessica F.; Derikx, Joep P. M.; van Baren, Robertine; Heij, Hugo A.; Wijnen, Marc H. W. A.; Wijnen, René M. H.; van der Zee, David C.; van Heurn, L. W. Ernest

    2018-01-01

    Gross genetic causes for SCT are unknown; however, it might be associated with other abnormalities. We assessed the incidence of associated abnormalities in a large national cohort of neonates with SCT and aimed to identify predictive risk factors. The medical records were reviewed of 235

  11. Serum-SP/sub 1/-pregnancy-specific-. beta. -glycoprotein in choriocarcinoma and other neoplastic disease

    Energy Technology Data Exchange (ETDEWEB)

    Searle, F; Leake, B A; Bagshawe, K D; Dent, J [Charing Cross Group of Hospitals, London (UK)

    1978-03-18

    A radioimmunoassay for a placental glycoprotein, ..beta../sub 1/SP/sub 1/, capable of detecting 2 ..mu..g/l of the glycoprotein in serum was used to measure concentrations of ..beta../sub 1/SP/sub 1/ in patients with choriocarcinoma, teratoma, colonic cancer, breast cancer, and ovarian cancer. Twelve out of 94 (13%) healthy men and healthy non-pregnant women had detectable serum-..beta../sub 1/SP/sub 1/ concentrations. Concentrations up to 50,000 ..mu..g/l were found in the sera of patients with hydatidiform mole, invasive mole, choriocarcinoma, and malignant teratoma. ..beta../sub 1/-glycoprotein concentrations were generally much lower than corresponding concentrations of chorionic gonadotrophin which is the most reliable marker for trophoblastic tumors. In a few cases, however, ..beta../sub 1/-glycoprotein measurements may be useful in the detection of minimal residual tumor. The slightly raised values found in some patients with carcinoma of the colon, breast, or ovary seem unlikely to be useful for diagnostic purposes or for monitoring the course of these cancers.

  12. Hepatitis C Virus E2 Envelope Glycoprotein Core Structure

    Energy Technology Data Exchange (ETDEWEB)

    Kong, Leopold; Giang, Erick; Nieusma, Travis; Kadam, Rameshwar U.; Cogburn, Kristin E.; Hua, Yuanzi; Dai, Xiaoping; Stanfield, Robyn L.; Burton, Dennis R.; Ward, Andrew B.; Wilson, Ian A.; Law, Mansun

    2014-08-26

    Hepatitis C virus (HCV), a Hepacivirus, is a major cause of viral hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV envelope glycoproteins E1 and E2 mediate fusion and entry into host cells and are the primary targets of the humoral immune response. The crystal structure of the E2 core bound to broadly neutralizing antibody AR3C at 2.65 angstroms reveals a compact architecture composed of a central immunoglobulin-fold β sandwich flanked by two additional protein layers. The CD81 receptor binding site was identified by electron microscopy and site-directed mutagenesis and overlaps with the AR3C epitope. The x-ray and electron microscopy E2 structures differ markedly from predictions of an extended, three-domain, class II fusion protein fold and therefore provide valuable information for HCV drug and vaccine design.

  13. Immunoglobulin-E reactivity to wine glycoproteins in heavy drinkers

    DEFF Research Database (Denmark)

    Gonzalez-Quintela, Arturo; Gomez-Rial, Jose; Valcarcel, Catalina

    2011-01-01

    and biological significance of IgE antibodies to N-glycans from wine glycoproteins in heavy drinkers. A structured questionnaire, skin prick tests, serum IgE levels, IgE-immunoblotting to wine extracts, and basophil activation tests were used to characterize 20 heavy drinkers and 10 control subjects. Eleven...... heavy drinkers (55%) showed IgE binding to proteins in wine extracts. The proteins were identified by mass spectrometry as grape-derived vacuolar invertase and thaumatin-like protein. Immunoblot reactivity was closely associated with the presence of IgE to CCDs and was inhibited by preincubation...... with a glycoconjugate containing bromelain-type N-glycans. The same conjugate, CCD-bearing allergens, and wine extracts activated basophils in patients with high-titer CCD-specific IgE but not in healthy controls. There was no relationship between immunoblot reactivity and consumption of any specific type of wine...

  14. Structure of a trimeric variant of the Epstein-Barr virus glycoprotein B

    Energy Technology Data Exchange (ETDEWEB)

    Backovic, Marija [Northwestern Univ., Evanston, IL (United States); Longnecker, Richard [Northwestern Univ., Chicago, IL (United States); Jardetzky, Theodore S [Northwestern Univ., Evanston, IL (United States)

    2009-03-16

    Epstein-Barr virus (EBV) is a herpesvirus that is associated with development of malignancies of lymphoid tissue. EBV infections are life-long and occur in >90% of the population. Herpesviruses enter host cells in a process that involves fusion of viral and cellular membranes. The fusion apparatus is comprised of envelope glycoprotein B (gB) and a heterodimeric complex made of glycoproteins H and L. Glycoprotein B is the most conserved envelope glycoprotein in human herpesviruses, and the structure of gB from Herpes simplex virus 1 (HSV-1) is available. Here, we report the crystal structure of the secreted EBV gB ectodomain, which forms 16-nm long spike-like trimers, structurally homologous to the postfusion trimers of the fusion protein G of vesicular stomatitis virus (VSV). Comparative structural analyses of EBV gB and VSV G, which has been solved in its pre and postfusion states, shed light on gB residues that may be involved in conformational changes and membrane fusion. Also, the EBV gB structure reveals that, despite the high sequence conservation of gB in herpesviruses, the relative orientations of individual domains, the surface charge distributions, and the structural details of EBV gB differ from the HSV-1 protein, indicating regions and residues that may have important roles in virus-specific entry.

  15. Developmental localization and the role of hydroxyproline rich glycoproteins during somatic embryogenesis of banana (Musa spp. AAA

    Directory of Open Access Journals (Sweden)

    Menzel Diedrik

    2011-02-01

    Full Text Available Abstract Background Hydroxyproline rich glycoproteins (HRGPs are implicated to have a role in many aspects of plant growth and development but there is limited knowledge about their localization and function during somatic embryogenesis of higher plants. In this study, the localization and function of hydroxyproline rich glycoproteins in embryogenic cells (ECs and somatic embryos of banana were investigated by using immunobloting and immunocytochemistry with monoclonal JIM11 and JIM20 antibodies as well as by treatment with 3,4-dehydro-L-proline (3,4-DHP, an inhibitor of extensin biosynthesis, and by immunomodulation with the JIM11 antibody. Results Immunofluorescence labelling of JIM11 and JIM20 hydroxyproline rich glycoprotein epitopes was relatively weak in non-embryogenic cells (NECs, mainly on the edge of small cell aggregates. On the other hand, hydroxyproline rich glycoprotein epitopes were found to be enriched in early embryogenic cells as well as in various developmental stages of somatic embryos. Embryogenic cells (ECs, proembryos and globular embryos showed strong labelling of hydroxyproline rich glycoprotein epitopes, especially in their cell walls and outer surface layer, so-called extracellular matrix (ECM. This hydroxyproline rich glycoprotein signal at embryo surfaces decreased and/or fully disappeared during later developmental stages (e.g. pear-shaped and cotyledonary stages of embryos. In these later developmental embryogenic stages, however, new prominent hydroxyproline rich glycoprotein labelling appeared in tri-cellular junctions among parenchymatic cells inside these embryos. Overall immunofluorescence labelling of late stage embryos with JIM20 antibody was weaker than that of JIM11. Western blot analysis supported the above immunolocalization data. The treatment with 3,4-DHP inhibited the development of embryogenic cells and decreased the rate of embryo germination. Embryo-like structures, which developed after 3,4-DHP

  16. Current controversies in prenatal diagnosis 2: Cell-free DNA prenatal screening should be used to identify all chromosome abnormalities.

    Science.gov (United States)

    Chitty, Lyn S; Hudgins, Louanne; Norton, Mary E

    2018-02-01

    Noninvasive prenatal testing (NIPT) using cell-free DNA (cfDNA) from maternal serum has been clinically available since 2011. This technology has revolutionized our ability to screen for the common aneuploidies trisomy 21 (Down syndrome), trisomy 18, and trisomy 13. More recently, clinical laboratories have offered screening for other chromosome abnormalities including sex chromosome abnormalities and copy number variants (CNV) without little published data on the sensitivity, specificity, and positive predictive value. In this debate, the pros and cons of performing prenatal screening via cfDNA for all chromosome abnormalities is discussed. At the time of the debate in 2017, the general consensus was that the literature does not yet support using this technology to screen for all chromosome abnormalities and that education is key for both providers and the patients so that the decision-making process is as informed as possible. © 2018 John Wiley & Sons, Ltd.

  17. Rat macrophages: membrane glycoproteins in differentiation and function

    NARCIS (Netherlands)

    van den Berg, T. K.; Döpp, E. A.; Dijkstra, C. D.

    2001-01-01

    Macrophages (mphi) play a crucial role in the immune system. The rat offers unique advantages for studying the biology of mphi. Firstly, monoclonal antibodies (mAb) against many rat mphi surface glycoproteins have become available. These have not only demonstrated a considerable heterogeneity among

  18. Mechanism of Binding to Ebola Virus Glycoprotein by the ZMapp, ZMAb, and MB-003 Cocktail Antibodies

    OpenAIRE

    Davidson, Edgar; Bryan, Christopher; Fong, Rachel H.; Barnes, Trevor; Pfaff, Jennifer M.; Mabila, Manu; Rucker, Joseph B.; Doranz, Benjamin J.

    2015-01-01

    Cocktails of monoclonal antibodies (MAbs) that target the surface glycoprotein (GP) of Ebola virus (EBOV) are effective in nonhuman primate models and have been used under emergency compassionate-treatment protocols in human patients. However, the amino acids that form the detailed binding epitopes for the MAbs in the ZMapp, ZMAb, and the related MB-003 cocktails have yet to be identified. Other binding properties that define how each MAb functionally interacts with GP—such as affinity, epito...

  19. Electrophoretic demonstration of glycoproteins, lipoproteins, and phosphoproteins in human and bovine enamel

    DEFF Research Database (Denmark)

    Kirkeby, S; Moe, D; Bøg-Hansen, T C

    1990-01-01

    Enamel proteins from fully mineralized human molars and from bovine tooth germs were separated by electrophoresis. The gels were stained for detection of glycoproteins, lipoproteins, and phosphoproteins. Glycoproteins were shown by periodic acid-Schiff staining and lectin blotting. In mature human...... enamel a number of high molecular weight proteins could be demonstrated after ethylenediaminetetra-acetic acid demineralization and subsequent Triton X-100 extraction. These proteins are suggested to be lipoproteins. Phosphoproteins could only be visualized in enamel matrix from the tooth germs....

  20. Report to Congress on abnormal occurrences, January--March 1978

    International Nuclear Information System (INIS)

    1978-01-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. The report, the twelfth in the series, covers the period from January 1 to March 31, 1978. The following incidents or events in that time period were determined by the Commission to be significant and reportable: (1) There was one abnormal occurrence at the 68 nuclear power plants licensed to operate. The event involved insulation failures in containment electrical penetrations. (2) There were no abnormal occurrences at fuel cycle facilities (other than nuclear power plants). (3) There were no abnormal occurrences at other license facilities. (4) There was one abnormal occurrence reported by an Agreement State Licensee. The event involved an overexposure of a radiographer. The report also contains information updating previously reported abnormal occurrences

  1. Report to Congress on abnormal occurrences, July--September 1991

    International Nuclear Information System (INIS)

    1991-12-01

    Section 108 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health and safety and requires a quarterly report of such events to be made to Congress. This report covers the period July through September 1991. The report discusses two abnormal occurrences at NRC-licensed facilities, neither involving a nuclear power plant. One involved radiation exposures to members of the public from a lost radioactive source and the other involved a medical diagnostic midadministration. The Agreement States reported no abnormal occurrences. The report also contains information that updates some previously reported abnormal occurrences

  2. Effect of expression of P-glycoprotein on technetium-99m methoxyisobutylisonitrile single photon emission computed tomography of brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Shibata, Yasushi; Matsumura, Akira; Nose, Tadao [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine

    2002-08-01

    The expression of P-glycoprotein was investigated imunohistochemically in 26 brain tumor tissues and compared with the findings of technetium-99m methoxyisobutylisonitrile single photon emission computed tomography ({sup 99m}Tc-MIBI SPECT) to clarify the effect of P-glycoprotein on the diagnostic accuracy. P-glycoprotein labeling index of both tumor cells and vascular endothelial cells showed no clear relationship with the findings of {sup 99m}Tc-MIBI SPECT imaging. Expression of P-glycoprotein has no effect on the diagnostic accuracy of {sup 99m}Tc-MIBI SPECT. (author)

  3. Changes in intestinal absorption of nutrients and brush border glycoproteins after total parenteral nutrition in rats.

    Science.gov (United States)

    Miura, S; Tanaka, S; Yoshioka, M; Serizawa, H; Tashiro, H; Shiozaki, H; Imaeda, H; Tsuchiya, M

    1992-01-01

    The effect of total parenteral nutrition on nutrients absorption and glycoprotein changes of brush border membrane was examined in rat small intestine. In total parenteral nutrition rats, a marked decrease in activity of brush border enzymes was observed mainly in the proximal and middle segments of the intestine. Galactose perfusion of jejunal segment showed that hexose absorption was significantly inhibited, while intestinal absorption of glycine or dipeptide, glycylglycine was not significantly affected by total parenteral nutrition treatment. When brush border membrane glycoprotein profile was examined by [3H]-glucosamine or [3H]-fucose incorporation into jejunal loops, significant changes were observed in the glycoprotein pattern of brush border membrane especially in the high molecular weight range over 120 kDa after total parenteral nutrition treatment, suggesting strong dependency of glycoprotein synthesis on luminal substances. Molecular weight of sucrase isomaltase in brush border membrane detected by specific antibody showed no significant difference, however, in total parenteral nutrition and control rats. Also, molecular weight of specific sodium glucose cotransporter of intestinal brush border membrane detected by selective photoaffinity labelling was not altered in total parenteral nutrition rats. It may be that prolonged absence of oral food intake may produce significant biochemical changes in brush border membrane glycoprotein and absorptive capacity of small intestine, but these changes were not observed in all brush border membrane glycoproteins. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:1582592

  4. Carcinoma-specific Ulex europaeus agglutinin-I binding glycoproteins of human colorectal carcinoma and its relation to carcinoembryonic antigen.

    Science.gov (United States)

    Matsushita, Y; Yonezawa, S; Nakamura, T; Shimizu, S; Ozawa, M; Muramatsu, T; Sato, E

    1985-08-01

    Glycoproteins binding to Ulex europaeus agglutinin-I (UEA-I) lectin, which recognizes the terminal alpha-L-fucose residue, were analyzed in 18 cases of human colorectal carcinoma by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by the Western blotting method. In the distal large bowel (descending and sigmoid colon and rectum), high-molecular-weight glycoproteins binding to UEA-I existed in carcinoma tissue but not in normal mucosa. In the proximal large bowel (ascending and transverse colon), high-molecular-weight glycoproteins binding to UEA-I were found both in normal mucosa and in carcinoma tissue, whereas those from the carcinoma tissue had an apparently lower molecular weight as compared to the weight of those from the normal mucosa. Thus there is a biochemical difference in UEA-I binding glycoproteins between the normal mucosa and the carcinoma tissue, although in our previous histochemical study no difference was observed in UEA-I binding glycoproteins of the proximal large bowel between the carcinoma tissue and the normal mucosa. Furthermore, carcinoembryonic antigen from the carcinoma tissue was found to have the same electrophoretical mobility as the UEA-I binding glycoproteins.

  5. Extra-oviductal expression of oviductal glycoprotein 1 in mouse ...

    Indian Academy of Sciences (India)

    2017-01-11

    Jan 11, 2017 ... oestrogen-dependent protein, oviduct-specific glycoprotein. 1 (Ovgp1) also ... the tissues collected were testis, epididymis, prostate gland and seminal vesicle. ... The antigenic sites were unmasked by incuba- tion of sections ...

  6. Celastraceae sesquiterpenes as a new class of modulators that bind specifically to human P-glycoprotein and reverse cellular multidrug resistance.

    Science.gov (United States)

    Muñoz-Martínez, Francisco; Lu, Peihua; Cortés-Selva, Fernando; Pérez-Victoria, José María; Jiménez, Ignacio A; Ravelo, Angel G; Sharom, Frances J; Gamarro, Francisco; Castanys, Santiago

    2004-10-01

    Overexpression of ABCB1 (MDR1) P-glycoprotein, a multidrug efflux pump, is one mechanism by which tumor cells may develop multidrug resistance (MDR), preventing the successful chemotherapeutic treatment of cancer. Sesquiterpenes from Celastraceae family are natural compounds shown previously to reverse MDR in several human cancer cell lines and Leishmania strains. However, their molecular mechanism of reversion has not been characterized. In the present work, we have studied the ability of 28 dihydro-beta-agarofuran sesquiterpenes to reverse the P-glycoprotein-dependent MDR phenotype and elucidated their molecular mechanism of action. Cytotoxicity assays using human MDR1-transfected NIH-3T3 cells allowed us to select the most potent sesquiterpenes reversing the in vitro resistance to daunomycin and vinblastine. Flow cytometry experiments showed that the above active compounds specifically inhibited drug transport activity of P-glycoprotein in a saturable, concentration-dependent manner (K(i) down to 0.24 +/- 0.01 micromol/L) but not that of ABCC1 (multidrug resistance protein 1; MRP1), ABCC2 (MRP2), and ABCG2 (breast cancer resistance protein; BCRP) transporters. Moreover, sesquiterpenes inhibited at submicromolar concentrations the P-glycoprotein-mediated transport of [(3)H]colchicine and tetramethylrosamine in plasma membrane from CH(R)B30 cells and P-glycoprotein-enriched proteoliposomes, supporting that P-glycoprotein is their molecular target. Photoaffinity labeling in plasma membrane and fluorescence spectroscopy experiments with purified protein suggested that sesquiterpenes interact with transmembrane domains of P-glycoprotein. Finally, sesquiterpenes modulated P-glycoprotein ATPase-activity in a biphasic, concentration-dependent manner: they stimulated at very low concentrations but inhibited ATPase activity as noncompetitive inhibitors at higher concentrations. Sesquiterpenes from Celastraceae are promising P-glycoprotein modulators with potential

  7. Glycoprotein H of herpes simplex virus type 1 requires glycoprotein L for transport to the surfaces of insect cells

    NARCIS (Netherlands)

    Westra, DF; Glazenburg, KL; Harmsen, MC; Tiran, A; Scheffer, AJ; Welling, GW; The, TH; WellingWester, S

    In mammalian cells, formation of heterooligomers consisting of the glycoproteins H and L (gH and gL) of herpes simplex virus type 1 is essential for the cell-to-cell spread of virions and for the penetration of virions into cells. We examined whether formation of gH1/gL1 heterooligomers and cell

  8. Report to Congress on abnormal occurrences, January--March 1977

    International Nuclear Information System (INIS)

    1977-01-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report, the eighth in the series, covers the period from January 1 to March 31, 1977. The NRC has determined that during this period: there were no abnormal occurrences at the 63 nuclear power plants licensed to operate; there were no abnormal occurrences at fuel cycle facilities (other than nuclear power plants); and there was one abnormal occurrence at other licensee facilities. The event involved an inadvertent radiation exposure to two painters while working in an area where industrial radiography was being performed. This report also contains information updating previously reported abnormal occurrences

  9. MDR1 P-glycoprotein transports endogenous opioid peptides

    NARCIS (Netherlands)

    Oude Elferink, R. P.; Zadina, J.

    2001-01-01

    MDR1 P-glycoprotein is generally regarded as an efflux pump for amphipathic toxic compounds. The question remains, however, whether certain endogenous compounds are also substrates for this transporter. Certain peptides have been shown to interact with MDR1 Pgp as well and we have therefore

  10. Abnormal Uterine Bleeding: American College of Nurse-Midwives.

    Science.gov (United States)

    2016-07-01

    Variations in uterine bleeding, termed abnormal uterine bleeding, occur commonly among women and often are physiologic in nature with no significant consequences. However, abnormal uterine bleeding can cause significant distress to women or may signify an underlying pathologic condition. Most women experience variations in menstrual and perimenstrual bleeding in their lifetimes; therefore, the ability of the midwife to differentiate between normal and abnormal bleeding is a key diagnostic skill. A comprehensive history and use of the PALM-COEIN classification system will provide clear guidelines for clinical management, evidence-based treatment, and an individualized plan of care. The purpose of this Clinical Bulletin is to define and describe classifications of abnormal uterine bleeding, review updated terminology, and identify methods of assessment and treatment using a woman-centered approach. © 2016 by the American College of Nurse-Midwives.

  11. Prediction of exposed domains of envelope glycoprotein in Indian HIV-1 isolates and experimental confirmation of their immunogenicity in humans

    Directory of Open Access Journals (Sweden)

    Mohabatkar H.

    2004-01-01

    Full Text Available We describe the impact of subtype differences on the seroreactivity of linear antigenic epitopes in envelope glycoprotein of HIV-1 isolates from different geographical locations. By computer analysis, we predicted potential antigenic sites of envelope glycoprotein (gp120 and gp4l of this virus. For this purpose, after fetching sequences of proteins of interest from data banks, values of hydrophilicity, flexibility, accessibility, inverted hydrophobicity, and secondary structure were considered. We identified several potential antigenic epitopes in a B subtype strain of envelope glycoprotein of HIV-1 (IIIB. Solid- phase peptide synthesis methods of Merrifield and Fmoc chemistry were used for synthesizing peptides. These synthetic peptides corresponded mainly to the C2, V3 and CD4 binding sites of gp120 and some parts of the ectodomain of gp41. The reactivity of these peptides was tested by ELISA against different HIV-1-positive sera from different locations in India. For two of these predicted epitopes, the corresponding Indian consensus sequences (LAIERYLKQQLLGWG and DIIGDIRQAHCNISEDKWNET (subtype C were also synthesized and their reactivity was tested by ELISA. These peptides also distinguished HIV-1-positive sera of Indians with C subtype infections from sera from HIV-negative subjects.

  12. Expression of variable viruses as herpes simplex glycoprotein D and varicella zoster gE glycoprotein using a novel plasmid based expression system in insect cell

    Directory of Open Access Journals (Sweden)

    A.M. Al-Sulaiman

    2017-11-01

    Full Text Available Several prokaryotic and eukaryotic expression systems have been used for in vitro production of viruses’ proteins. However eukaryotic expression system was always the first choice for production of proteins that undergo post-translational modification such as glycosylation. Recombinant baculoviruses have been widely used as safe vectors to express heterologous genes in the culture of insect cells, but the manipulation involved in creating, titrating, and amplifying viral stocks make it time consuming and laborious. Therefore, to facilitate rapid expression in insect cell, a plasmid based expression system was used to express herpes simplex type 1 glycoprotein D (HSV-1 gD and varicella zoster glycoprotein E (VZV gE. Recombinant plasmids were generated, transfected into insect cells (SF9, and both glycoproteins were expressed 48 h post-infection. A protein with approximately molecular weight of 64-kDa and 98-kDa for HSV-1 gD and VZV gE respectively was expressed and confirmed by SDS. Proteins were detected in insect cells cytoplasm and outer membrane by immunofluorescence. The antigenicity and immunoreactivity of each protein were confirmed by immunoblot and ELISA. Results suggest that this system can be an alternative to the traditional baculovirus expression for small scale expression system in insect cells.

  13. RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord.

    Directory of Open Access Journals (Sweden)

    David G Brohawn

    Full Text Available ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned >50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR for identification of differentially expressed genes (DEG's. Ingenuity Pathways Analysis (IPA and Weighted Gene Co-expression Network Analysis (WGCNA identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF found to be a major pathway regulator (IPA and TNFα-induced protein 2 (TNFAIP2 as a major network "hub" gene (WGCNA. Using the oPOSSUM algorithm, we analyzed transcription factors (TF controlling expression of the nine DEG/hub genes in the ALS samples and identified TF's involved in inflammation (NFkB, REL, NFkB1 and macrophage function (NR1H2::RXRA heterodimer. Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be

  14. Expression of bovine herpesvirus 1 glycoproteins gI and gIII in transfected murine cells

    International Nuclear Information System (INIS)

    Fitzpatrick, D.R.; Zamb, T.; Parker, M.D.; van Drunen Littel-van den Hurk, S.; Babiuk, L.A.; Lawman, M.J.P.

    1988-01-01

    Genes encoding two of the major glycoproteins of bovine herpesvirus 1 (BHV-1), gI and gIII, were cloned into the eucaryotic expression vectors pRSVcat and pSV2neo and transfected into murine LMTK - cells, and cloned cell lines were established. The relative amounts of gI or gIII expressed from the two vectors were similar. Expression of gI was cell associated and localized predominantly in the perinuclear region, but nuclear and plasma membrane staining was also observed. Expression of gI was additionally associated with cell fusion and the formation of polykaryons and giant cells. Expression of gIII was localized predominantly in the nuclear and plasma membranes. Radioimmunoprecipitation in the presence or absence of tunicamycin revealed that the recombinant glycoproteins were proteolytically processed and glycosylated and had molecular weights similar to those of the forms of gI and gIII expressed in BHV-1 infected bovine cells. However, both recombinant glycoproteins were glycosylated to a lesser extent than were the forms found in BHV-1 infected bovine cells. For gI, a deficiency in N-linked glycosylated of the amino-terminal half of the protein was identified; for gIII, a deficiency in O-linked glycosylation was implicated. The reactivity pattern of a panel of gI- and gIII-specific monoclonal antibodies, including six which recognize conformation-dependent epitopes, was found to be unaffected by the glycosylation differences and was identical for transfected of BHV-1-infected murine cells. Use of the transfected cells as targets in immune-mediated cytotoxicity assays demonstrated the functional recognition of recombinant gI and gIII by murine antibody and cytotoxic T lymphocytes

  15. Splenic abnormalities: a comparative review of ultrasound, microbubble-enhanced ultrasound and computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Peddu, P.; Shah, M.; Sidhu, P.S. E-mail: paul.sidhu@kingsch.nhs.uk

    2004-09-01

    The ultrasound appearances of abnormalities of the spleen are reviewed and images compared with computed tomography. Focal lesions, both benign and malignant, trauma, infarction and congenital abnormalities are presented. The use of microbubble ultrasound contrast media as an aid to identifying and characterizing abnormalities is discussed.

  16. Assessment of lectin and HILIC based enrichment protocols for characterization of serum glycoproteins by mass spectrometry

    DEFF Research Database (Denmark)

    Calvano, Cosima D; Zambonin, Carlo G; Jensen, Ole Nørregaard

    2008-01-01

    glycosylation profiles are associated with certain human ailments. Glycoprotein analysis by mass spectrometry of biological samples, such as blood serum, is hampered by sample complexity and the low concentration of the potentially informative glycopeptides and -proteins. We assessed the utility of lectin...... of 63 glycosylation sites in 38 proteins were identified by both methods, demonstrating distinct differences and complementarity. Serial application of custom-made microcolumns of mixed, immobilized lectins proved efficient for recovery and analysis of glycopeptides from serum samples of breast cancer...

  17. Report to Congress on abnormal occurrences, October--December 1991

    International Nuclear Information System (INIS)

    1992-03-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence of an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health and safety and requires a quarterly report of such events to be made to Congress. This report covers the period October through December 1991. Five abnormal occurrences at NRC-licensed facilities are discussed in this report. None of these occurrences involved a nuclear power plant. Four involved medical therapy misadministrations and one involved a medical diagnostic misadministration. The NRC's Agreement States reported three abnormal occurrences. Two involved exposures of non-radiation workers and one involved a medical therapy misadministration. The report also contains information that updates some previously reported abnormal occurrences

  18. Report to Congress on abnormal occurrences, April--June 1992

    International Nuclear Information System (INIS)

    1992-09-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event that the nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from April 1 through June 30, 1992. Five abnormal occurrences are discussed in this report. One involved an extended loss of high-head safety injection capability at the Shearon Harris Nuclear Power Plant. The other four involved medical misadministrations (three therapeutic and one diagnostic) at NRC-licensed facilities. No abnormal occurrences were reported by NRC's Agreement States. The report also contains information updating a previously reported abnormal occurrence

  19. Report to Congress on abnormal occurrences, October-December 1987

    International Nuclear Information System (INIS)

    1988-03-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from October 1 to December 31, 1987. The report states that for this reporting period, these was one abnormal occurrence at the NRC licensees; the item involved the suspension of license of an oil and gas well tracer company for noncompliance with NRC regulatory requirements. There were no abnormal occurrences report by the Agreement States. The report also contains information updating some previously reported abnormal occurrences

  20. A review on the relation between the brain-serum concentration ratio of drugs and the influence of P-glycoprotein

    DEFF Research Database (Denmark)

    Ejsing, Thomas Broeng; Morling, Niels; Linnet, Kristian

    2007-01-01

    This overview on the brain-serum relationship for drugs illustrates the importance of the drug transporter P-glycoprotein at the blood-brain barrier. Generally, an inverse relationship exists between the magnitude of the brain-serum ratio and the influence of P-glycoprotein. Concerning the pharma...... the pharmacogenomics of P-glycoprotein, no clear effect of single nucleotide polymorphisms (SNPs) has been demonstrated in humans....

  1. Secretion of hepatitis C virus envelope glycoproteins depends on assembly of apolipoprotein B positive lipoproteins.

    Directory of Open Access Journals (Sweden)

    Vinca Icard

    Full Text Available The density of circulating hepatitis C virus (HCV particles in the blood of chronically infected patients is very heterogeneous. The very low density of some particles has been attributed to an association of the virus with apolipoprotein B (apoB positive and triglyceride rich lipoproteins (TRL likely resulting in hybrid lipoproteins known as lipo-viro-particles (LVP containing the viral envelope glycoproteins E1 and E2, capsid and viral RNA. The specific infectivity of these particles has been shown to be higher than the infectivity of particles of higher density. The nature of the association of HCV particles with lipoproteins remains elusive and the role of apolipoproteins in the synthesis and assembly of the viral particles is unknown. The human intestinal Caco-2 cell line differentiates in vitro into polarized and apoB secreting cells during asymmetric culture on porous filters. By using this cell culture system, cells stably expressing E1 and E2 secreted the glycoproteins into the basal culture medium after one week of differentiation concomitantly with TRL secretion. Secreted glycoproteins were only detected in apoB containing density fractions. The E1-E2 and apoB containing particles were unique complexes bearing the envelope glycoproteins at their surface since apoB could be co-immunoprecipitated with E2-specific antibodies. Envelope protein secretion was reduced by inhibiting the lipidation of apoB with an inhibitor of the microsomal triglyceride transfer protein. HCV glycoproteins were similarly secreted in association with TRL from the human liver cell line HepG2 but not by Huh-7 and Huh-7.5 hepatoma cells that proved deficient for lipoprotein assembly. These data indicate that HCV envelope glycoproteins have the intrinsic capacity to utilize apoB synthesis and lipoprotein assembly machinery even in the absence of the other HCV proteins. A model for LVP assembly is proposed.

  2. False-negative type-specific glycoprotein G antibody responses in STI clinic patients with recurrent HSV-1 or HSV-2 DNA positive genital herpes, The Netherlands

    NARCIS (Netherlands)

    van Rooijen, Martijn S.; Roest, Wim; Hansen, Gino; Kwa, David; de Vries, Henry J. C.

    2016-01-01

    Herpes simplex virus (HSV) type-discriminating antibody tests (glycoprotein G (gG) directed) are used to identify naïve persons and differentiate acute infections from recurrences. We studied test characteristics of three commercially available antibody tests in patients with recurrent (established

  3. Abnormal biodistribution of radiogallium in persons treated with phenytoin

    International Nuclear Information System (INIS)

    Lentle, B.C.; Starreveld, Elout; Catz, Zolly; Penney, Heather; Turner, A.R.

    1983-01-01

    After incidentally observing a patient in whom abnormal uptake of gallium-67 citrate appeared to be explained by treatment with phenytoin, we have conducted a prospective study. Of sixteen persons with a seizure disorder treated with phenytoin, five (31 percent) had abnormal uptake of radiogallium either in the mediastinum, pulmonary hilum or both. Of nineteen historical control patients only one had such abnormal uptake. Phenytoin may thus cause the false-positive uptake of radiogallium in lymph nodes; this finding may also prove to have nosological importance in identifying patients at particular risk of the side-effects of this drug

  4. Report to Congress on abnormal occurrences, July--September 1989

    International Nuclear Information System (INIS)

    1990-01-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from July 1 to September 30, 1989. For this reporting period, there were five abnormal occurrences. One abnormal occurrence took place at a licensed nuclear power plant and involved significant deficiencies associated with the containment recirculation sump at the Trojan facility. The other four abnormal occurrences took place under other NRC-issued licenses: the first involved a medical diagnostic misadministration; the second involved a medical therapy misadministration; the third involved a radiation overexposure of a radiographer; and the fourth involved a significant breakdown and careless disregard of the radiation safety program at three of a licensee's manufacturing facilities. The Agreement States reported no abnormal occurrences during the reporting period. The report also contains information that updates some previously reported abnormal occurrences. 17 refs

  5. Report to Congress on abnormal occurrences, July-September 1986

    International Nuclear Information System (INIS)

    1987-04-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from July 1 to September 30, 1986. The report states that for this reporting period, there were four abnormal occurrences at the nuclear power plants licensed to operate. The events were (1) a differential pressure switch problem in safety systems at LaSalle facility, (2) abnormal cooldown and depressurization transient at Catawba Unit 2, (3) significant safeguards deficiencies at Wolf Creek and Fort St. Vrain, and (4) significant deficiencies in access controls at River Bend Station. There was one abnormal occurrence at the other NRC licensees; it involved a therapeutic medical misadministration. There was one abnormal occurrence reported by an Agreement State; it involved a therapeutic medical misadministration. The report also contains information updating some previously reported abnormal occurrences

  6. Report to Congress on abnormal occurrences, April--June 1978

    International Nuclear Information System (INIS)

    1978-01-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report, the thirteenth in the series, covers the period from April 1 to June 30, 1978. The following incidents or events in that period were determined by the Commission to be significant and reportable: (1) There were two abnormal occurrences at the 69 nuclear power plants licensed to operate. One involved a generic concern pertaining to fuel assembly control rod guide tube integrity. The second involved an overexposure of two radiation protection technicians. (2) There were no abnormal occurrences at fuel cycle facilities (other than nuclear power plants). (3) There were no abnormal occurrences at other licensee facilities. (4) There was one abnormal occurrence reported by an agreement state. The event involved willful violations of regulations and subsequent termination of a license. This report also contains information updating previously reported abnormal occurrences

  7. Identifying abnormal connectivity in patients using Dynamic Causal Modelling of fMRI responses.

    Directory of Open Access Journals (Sweden)

    Mohamed L Seghier

    2010-08-01

    Full Text Available Functional imaging studies of brain damaged patients offer a unique opportunity to understand how sensori-motor and cognitive tasks can be carried out when parts of the neural system that support normal performance are no longer available. In addition to knowing which regions a patient activates, we also need to know how these regions interact with one another, and how these inter-regional interactions deviate from normal. Dynamic Causal Modelling (DCM offers the opportunity to assess task-dependent interactions within a set of regions. Here we review its use in patients when the question of interest concerns the characterisation of abnormal connectivity for a given pathology. We describe the currently available implementations of DCM for fMRI responses, varying from the deterministic bilinear models with one-state equation to the stochastic nonlinear models with two-state equations. We also highlight the importance of the new Bayesian model selection and averaging tools that allow different plausible models to be compared at the single subject and group level. These procedures allow inferences to be made at different levels of model selection, from features (model families to connectivity parameters. Following a critical review of previous DCM studies that investigated abnormal connectivity we propose a systematic procedure that will ensure more flexibility and efficiency when using DCM in patients. Finally, some practical and methodological issues crucial for interpreting or generalising DCM findings in patients are discussed.

  8. A hybrid monolithic column based on boronate-functionalized graphene oxide nanosheets for online specific enrichment of glycoproteins.

    Science.gov (United States)

    Zhou, Chanyuan; Chen, Xiaoman; Du, Zhuo; Li, Gongke; Xiao, Xiaohua; Cai, Zongwei

    2017-05-19

    A hybrid monolithic column based on aminophenylboronic acid (APBA)-functionalized graphene oxide (GO) has been developed and used for selective enrichment of glycoproteins. The APBA/GO composites were homogeneously incorporated into a polymer monolithic column with the help of oligomer matrix and followed by in situ polymerization. The effect of dispersion of APBA/GO composites in the polymerization mixture on the performance of the monolithic column was explored in detail. The presence of graphene oxide not only enlarged the BET surface area from 6.3m 2 /g to 169.4m 2 /g, but also provided abundant boronic acid moieties for glycoprotein extraction, which improved the enrichment selectivity and efficiency for glycoproteins. The APBA/GO hybrid monolithic column was incorporated into a sequential injection system, which facilitated online extraction of proteins. Combining the superior properties of extraordinary surface area of GO and the affinity interaction of APBA to glycoproteins, the APBA/GO hybrid monolithic column showed higher enrichment factors for glycoproteins than other proteins without cis-diol-containing groups. Also, under comparable or even shorter processing time and without the addition of any organic solvent, it showed higher binding capacity toward glycoproteins compared with the conventional boronate affinity monolithic column. The practical applicability of this system was demonstrated by processing of egg white samples for extraction of ovalbumin and ovotransferrin, and satisfactory results were obtained by assay with SDS-PAGE. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Cytogenetic abnormalities and fragile-x syndrome in Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Reddy Kavita S

    2005-01-01

    Full Text Available Abstract Background Autism is a behavioral disorder with impaired social interaction, communication, and repetitive and stereotypic behaviors. About 5–10 % of individuals with autism have 'secondary' autism in which an environmental agent, chromosome abnormality, or single gene disorder can be identified. Ninety percent have idiopathic autism and a major gene has not yet been identified. We have assessed the incidence of chromosome abnormalities and Fragile X syndrome in a population of autistic patients referred to our laboratory. Methods Data was analyzed from 433 patients with autistic traits tested using chromosome analysis and/or fluorescence in situ hybridization (FISH and/or molecular testing for fragile X syndrome by Southern and PCR methods. Results The median age was 4 years. Sex ratio was 4.5 males to 1 female [354:79]. A chromosome (cs abnormality was found in 14/421 [3.33 %] cases. The aberrations were: 4/14 [28%] supernumerary markers; 4/14 [28%] deletions; 1/14 [7%] duplication; 3/14 [21%] inversions; 2/14 [14%] translocations. FISH was performed on 23 cases for reasons other than to characterize a previously identified cytogenetic abnormality. All 23 cases were negative. Fragile-X testing by Southern blots and PCR analysis found 7/316 [2.2 %] with an abnormal result. The mutations detected were: a full mutation (fM and abnormal methylation in 3 [43 %], mosaic mutations with partial methylation of variable clinical significance in 3 [43%] and a permutation carrier [14%]. The frequency of chromosome and fragile-X abnormalities appears to be within the range in reported surveys (cs 4.8-1.7%, FRAX 2–4%. Limitations of our retrospective study include paucity of behavioral diagnostic information, and a specific clinical criterion for testing. Conclusions Twenty-eight percent of chromosome abnormalities detected in our study were subtle; therefore a high resolution cytogenetic study with a scrutiny of 15q11.2q13, 2q37 and Xp23

  10. Feeling Abnormal: Simulation of Deviancy in Abnormal and Exceptionality Courses.

    Science.gov (United States)

    Fernald, Charles D.

    1980-01-01

    Describes activity in which student in abnormal psychology and psychology of exceptional children classes personally experience being judged abnormal. The experience allows the students to remember relevant research, become sensitized to the feelings of individuals classified as deviant, and use caution in classifying individuals as abnormal.…

  11. Thiolated polymers: evidence for the formation of disulphide bonds with mucus glycoproteins.

    Science.gov (United States)

    Leitner, Verena M; Walker, Greg F; Bernkop-Schnürch, Andreas

    2003-09-01

    Disulphide bonds between thiolated polymers (thiomers) and cysteine-rich subdomains of mucus glycoproteins are supposed to be responsible for the enhanced mucoadhesive properties of thiomers. This study set out to provide evidence for these covalent interactions using poly(acrylic acid)-cysteine conjugates of 2 and 450 kDa (PAA2-Cys, PAA450-Cys) displaying 402.5-776.0 micromol thiol groups per gram polymer. The effect of the disulphide bond breaker cysteine on thiomer-mucin disulphide bonds was monitored by (1) mucoadhesion studies and (2) rheological studies. Furthermore, (3) diffusion studies and (4) gel filtration studies were performed with thiomer-mucus mixtures. The addition of cysteine significantly (Ppolymer. Gel filtration studies showed that PAA2-Cys was able to form disulphide bonds with mucin glycoproteins resulting in an altered elution profile of the mucin/PAA2-Cys mixture in comparison to mucin alone or mucin/PAA2 mixture. According to these results, the study provides evidence for the formation of covalent bonds between thiomer and mucus glycoproteins.

  12. Cytoplasmic tail domain of glycoprotein B is essential for HHV-6 infection

    Energy Technology Data Exchange (ETDEWEB)

    Mahmoud, Nora F. [Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe (Japan); Faculty of Pharmacy, Suez Canal University, Ismailia (Egypt); Jasirwan, Chyntia [Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe (Japan); Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine, University of Indonesia (Indonesia); Kanemoto, Satoshi; Wakata, Aika; Wang, Bochao; Hata, Yuuki [Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe (Japan); Nagamata, Satoshi [Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe (Japan); Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe (Japan); Kawabata, Akiko [Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe (Japan); Tang, Huamin [Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe (Japan); Department of Immunology, Nanjing Medical University, Nanjing (China); Mori, Yasuko, E-mail: ymori@med.kobe-u.ac.jp [Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe (Japan)

    2016-03-15

    Human herpesvirus 6 (HHV-6) glycoprotein B (gB) is an abundantly expressed viral glycoprotein required for viral entry and cell fusion, and is highly conserved among herpesviruses. The present study examined the function of HHV-6 gB cytoplasmic tail domain (CTD). A gB CTD deletion mutant was constructed which, in contrast to its revertant, could not be reconstituted. Moreover, deletion of gB cytoplasmic tail impaired the intracellular transport of gB protein to the trans-Golgi network (TGN). Taken together, these results suggest that gB CTD is critical for HHV-6 propagation and important for intracellular transportation. - Highlights: • Glycoprotein B (gB) is highly conserved among herpesviruses. • HHV-6 gB is also abundantly expressed in virions. • In the present study, we showed the function of HHV-6 gB cytoplasmic tail domain (CTD). • We found that deletion of gB CTD impairs the intracellular transport of gB protein to the trans-Golgi network (TGN), and CTD of gB is critical for HHV-6 propagation.

  13. Cytoplasmic tail domain of glycoprotein B is essential for HHV-6 infection

    International Nuclear Information System (INIS)

    Mahmoud, Nora F.; Jasirwan, Chyntia; Kanemoto, Satoshi; Wakata, Aika; Wang, Bochao; Hata, Yuuki; Nagamata, Satoshi; Kawabata, Akiko; Tang, Huamin; Mori, Yasuko

    2016-01-01

    Human herpesvirus 6 (HHV-6) glycoprotein B (gB) is an abundantly expressed viral glycoprotein required for viral entry and cell fusion, and is highly conserved among herpesviruses. The present study examined the function of HHV-6 gB cytoplasmic tail domain (CTD). A gB CTD deletion mutant was constructed which, in contrast to its revertant, could not be reconstituted. Moreover, deletion of gB cytoplasmic tail impaired the intracellular transport of gB protein to the trans-Golgi network (TGN). Taken together, these results suggest that gB CTD is critical for HHV-6 propagation and important for intracellular transportation. - Highlights: • Glycoprotein B (gB) is highly conserved among herpesviruses. • HHV-6 gB is also abundantly expressed in virions. • In the present study, we showed the function of HHV-6 gB cytoplasmic tail domain (CTD). • We found that deletion of gB CTD impairs the intracellular transport of gB protein to the trans-Golgi network (TGN), and CTD of gB is critical for HHV-6 propagation.

  14. Neural glycoprotein M6a is released in extracellular vesicles and modulated by chronic stressors in blood

    OpenAIRE

    Monteleone, Melisa C.; Billi, Silvia C.; Brocco, Marcela A.; Frasch, Alberto C.

    2017-01-01

    Membrane neuronal glycoprotein M6a is highly expressed in the brain and contributes to neural plasticity promoting neurite growth and spine and synapse formation. We have previously showed that chronic stressors alter hippocampal M6a mRNA levels in rodents and tree shrews. We now show that M6a glycoprotein can be detected in mouse blood. M6a is a transmembrane glycoprotein and, as such, unlikely to be free in blood. Here we demonstrate that, in blood, M6a is transported in extracellular vesic...

  15. Glycoprotein fucosylation is increased in seminal plasma of subfertile men

    Directory of Open Access Journals (Sweden)

    Beata Olejnik

    2015-04-01

    Full Text Available Fucose, the monosaccharide frequent in N- and O-glycans, is a part of Lewis-type antigens that are known to mediate direct sperm binding to the zona pellucida. Such interaction was found to be inhibited in vitroby fucose-containing oligo- and polysaccharides, as well as neoglycoproteins. The objective of this study was to screen seminal plasma proteins of infertile/subfertile men for the content and density of fucosylated glycoepitopes, and compare them to samples of fertile normozoospermic subjects. Seminal proteins were separated in polyacrylamide gel electrophoresis and blotted onto nitrocellulose membrane and probed with fucose-specific Aleuria aurantia lectin (AAL. Twelve electrophoretic bands were selected for quantitative densitometric analysis. It was found that the content, and especially the density of fucosylated glycans, were higher in glycoproteins present in seminal plasma of subfertile men. No profound differences in fucosylation density were found among the groups of normozoospermic, oligozoospermic, asthenozoospermic, and oligoasthenozoospermic subfertile men. According to the antibody probing, AAL-reactive bands can be attributed to male reproductive tract glycoproteins, including prostate-specific antigen, prostatic acid phosphatase, glycodelin and chorionic gonadotropin. Fibronectin, α1 -acid glycoprotein, α1 -antitrypsin, immunoglobulin G and antithrombin III may also contribute to this high fucosylation. It is suggested that the abundant fucosylated glycans in the sperm environment could interfere with the sperm surface and disturb the normal course of the fertilization cascade.

  16. Feline immunodeficiency virus envelope glycoprotein mediates apoptosis in activated PBMC by a mechanism dependent on gp41 function

    International Nuclear Information System (INIS)

    Garg, Himanshu; Joshi, Anjali; Tompkins, Wayne A.

    2004-01-01

    Feline Immunodeficiency Virus (FIV) is a lentivirus that causes immunodeficiency in cats, which parallels HIV-1-induced immunodeficiency in humans. It has been established that HIV envelope (Env) glycoprotein mediates T cell loss via a mechanism that requires CXCR4 binding. The Env glycoprotein of FIV, similar to HIV, requires CXCR4 binding for viral entry, as well as inducing membrane fusion leading to syncytia formation. However, the role of FIV Env in T cell loss and the molecular mechanisms governing this process have not been elucidated. We studied the role of Env glycoprotein in FIV-mediated T cell apoptosis in an in vitro model. Our studies demonstrate that membrane-expressed FIV Env induces apoptosis in activated feline peripheral blood mononuclear cells (PBMC) by a mechanism that requires CXCR4 binding, as the process was inhibited by CXCR4 antagonist AMD3100 in a dose-dependent manner. Interestingly, studies regarding the role of CD134, the recently identified primary receptor of FIV, suggest that binding to CD134 may not be important for induction of apoptosis in PBMC. However, inhibiting Env-mediated fusion post CXCR4 binding by FIV gp41-specific fusion inhibitor also inhibited apoptosis. Under similar conditions, a fusion-defective gp41 mutant was unable to induce apoptosis in activated PBMC. Our findings are the first report suggesting the potential of FIV Env to mediate apoptosis in bystander cells by a process that is dependent on gp41 function

  17. MRI appearance of surgically proven abnormal accessory anterior-inferior tibiofibular ligament (Bassett's ligament)

    International Nuclear Information System (INIS)

    Subhas, Naveen; Vinson, Emily N.; Cothran, R.L.; Helms, Clyde A.; Santangelo, James R.; Nunley, James A.

    2008-01-01

    A thickened accessory anterior-inferior tibiofibular ligament (Bassett's ligament) of the ankle can be a cause of ankle impingement. Its imaging appearance is not well described. The purpose of this study was to determine if the ligament could be identified on magnetic resonance imaging (MRI), to determine associated abnormalities, and to determine if MRI could be used to differentiate normal from abnormal. Eighteen patients with a preoperative ankle MRI and an abnormal Bassett's ligament reported at surgery were found retrospectively. A separate cohort of 18 patients was selected as a control population. The presence of Bassett's ligament and its thickness were noted. The integrity and appearance of the lateral ankle ligaments, talar dome cartilage, and anterolateral gutter were also noted. In 34 of the 36 cases (94%), Bassett's ligament was identified on MRI. The ligament was seen in all three imaging planes and most frequently in the axial plane. The mean thickness of the ligament in the surgically abnormal cases was 2.37 mm, compared with 1.87 mm in the control with a p value = 0.015 (t test). Nine of the 18 abnormal cases (50%) had talar dome cartilage lesions as a result of contact with the ligament at surgery, with only 3 cases of high-grade defects seen on MRI. Fourteen of the 18 abnormal cases (78%) had of synovitis or scarring in the lateral gutter at surgery, with only 5 cases with scarring seen on MRI. The anterior-inferior tibiofibular ligament was abnormal or torn in 8 of the 18 abnormal cases (44%) by MRI and confirmed in only 3 cases at surgery. Bassett's ligament can be routinely identified on MRI and was significantly thicker in patients who had it resected at surgery. An abnormal Bassett's ligament is often present in the setting of a normal anterior-inferior tibiofibular ligament. The cartilage abnormalities and synovitis associated with an abnormal Bassett's ligament are poorly detected by conventional MRI. (orig.)

  18. Separation and identification of carp pituitary proteins and glycoproteins

    Czech Academy of Sciences Publication Activity Database

    Ryšlavá, H.; Janatová, M.; Čalounová, G.; Selicharová, Irena; Barthová, J.; Barth, Tomislav

    2005-01-01

    Roč. 50, č. 9 (2005), 430-437 ISSN 1212-1819 R&D Projects: GA MZe(CZ) QF3028 Institutional research plan: CEZ:AV0Z4055905 Keywords : carp hormones * glycoproteins * oligosaccharide chains Subject RIV: CE - Biochemistry Impact factor: 0.254, year: 2005

  19. Report to Congress on abnormal occurrences, April--June 1977

    International Nuclear Information System (INIS)

    1977-01-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report, the ninth in the series, covers the period from April 1 to June 30, 1977. The NRC has determined that during this period: there were two abnormal occurrences at the 64 nuclear power plants licensed to operate, one involved a breach of a plant's physical security system and the other involved degraded fuel rods; there were no abnormal occurrences at fuel cycle facilities (other than nuclear power plants); and there were two abnormal occurrences at other licensee facilities, one involved improper radioactive source handling procedures and the other involved overexposure of two radiographers. Information updating previously reported abnormal occurrences is also included

  20. Report to Congress on abnormal occurrences, January--March 1989

    International Nuclear Information System (INIS)

    1989-08-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health and safety and requires a Quarterly report of such events to be made to Congress. This report covers the period January 1 to March 31, 1989. For this reporting period, there were two abnormal occurrences at nuclear power plants licensed to operate. The first had generic implications and involved a plug failure resulting in a steam generator tube leak at North Anna Unit 1. The second involved a steam generator tube rupture at McGuire Unit 1. There were three abnormal occurrences under other NRC-issued licenses. Two involved medical therapy misadministrations and one involved a medical diagnostic misadministration. There were no abnormal occurrences reported by the Agreement States. The report also contains information updating some previously reported abnormal occurrences

  1. Purification and partial characterization of low molecular weight vicilin-like glycoprotein from the seeds of Citrullus lanatus.

    Science.gov (United States)

    Yadav, Sushila; Tomar, Anil Kumar; Jithesh, O; Khan, Meraj Alam; Yadav, R N; Srinivasan, A; Singh, Tej P; Yadav, Savita

    2011-12-01

    The watermelon (Citrullus lanatus) seeds are highly nutritive and contain large amount of proteins and many beneficial minerals such as magnesium, calcium, potassium, iron, phosphorous, zinc etc. In various parts of the world, C. lanatus seed extracts are used to cure cancer, cardiovascular diseases, hypertension, and blood pressure. C. lanatus seed extracts are also used as home remedy for edema and urinary tract problems. In this study, we isolated protein fraction of C. lanatus seeds using various protein separation methods. We successfully purified a low molecular weight vicilin-like glycoprotein using chromatographic methods followed by SDS-PAGE and MALDI-TOF/MS identification. This is the first report of purification of a vicilin like polypeptide from C. lanatus seeds. In next step, we extracted mRNA from immature seeds and reverse transcribed it using suitable forward and reverse primers for purified glycoprotein. The PCR product was analysed on 1% agarose gel and was subsequently sequenced by Dideoxy DNA sequencing method. An amino acid translation of the gene is in agreement with amino acid sequences of the identified peptides.

  2. Human platelet glycoprotein IX: An adhesive prototype of leucine-rich glycoproteins with flank-center-flank structures

    International Nuclear Information System (INIS)

    Hickey, M.J.; Williams, S.A.; Roth, G.J.

    1989-01-01

    The glycoprotein (GP) Ib-IX complex on the surface of human platelets functions as the von Willebrand factor receptor and mediates von Willebrand factor-dependent platelet adhesion to blood vessels. GPIX is a relatively small (M r , 17,000) protein that may provide for membrane insertion and orientation of the larger component of the complex. GPIb (M r , 165,000). Using antibody screening, the authors cloned a cDNA encoding GPIX from a human erythroleukemia cell cDNA library constructed in phage λgt11. Lacking a 5' untranslated region and start codon, the cDNA sequence includes 604 nucleotides, beginning with 495 bases at the 5' end coding for 165 amino acids, followed by a stop codon and 106 noncoding bases at the 3' end. By Northern blot analysis, the GPIX cDNA hybridizes with a single 1.0-kilobase species of platelet poly(A) + RNA. Translation of the cDNA sequence gives a predicted protein sequence beginning with a truncated putative signal sequence of 5 amino acids followed by a sequence of 17 amino acids matching that determined directly by Edman degradation of intact GPIX. GPIX contains a leucine-rich glycoprotein (LRG) sequence of 24 amino acids similar to conserved LRG sequences in GPIb and other proteins from humans, Drosophila, and yeast. The role of the flank-LRG center-flank structure in the evolution and function of the LRG proteins remains to be defined

  3. Encoding asymmetry of the N-glycosylation motif facilitates glycoprotein evolution.

    Directory of Open Access Journals (Sweden)

    Ryan Williams

    Full Text Available Protein N-glycosylation is found in all domains of life and has a conserved role in glycoprotein folding and stability. In animals, glycoproteins transit through the Golgi where the N-glycans are trimmed and rebuilt with sequences that bind lectins, an innovation that greatly increases structural diversity and redundancy of glycoprotein-lectin interaction at the cell surface. Here we ask whether the natural tension between increasing diversity (glycan-protein interactions and site multiplicity (backup and status quo might be revealed by a phylogenic examination of glycoproteins and NXS/T(X ≠ P N-glycosylation sites. Site loss is more likely by mutation at Asn encoded by two adenosine (A-rich codons, while site gain is more probable by generating Ser or Thr downstream of an existing Asn. Thus mutations produce sites at novel positions more frequently than the reversal of recently lost sites, and therefore more paths though sequence space are made available to natural selection. An intra-species comparison of secretory and cytosolic proteins revealed a departure from equilibrium in sequences one-mutation-away from NXS/T and in (A content, indicating strong selective pressures and exploration of N-glycosylation positions during vertebrate evolution. Furthermore, secretory proteins have evolved at rates proportional to N-glycosylation site number, indicating adaptive interactions between the N-glycans and underlying protein. Given the topology of the genetic code, mutation of (A is more often nonsynonomous, and Lys, another target of many PTMs, is also encoded by two (A-rich codons. An examination of acetyl-Lys sites in proteins indicated similar evolutionary dynamics, consistent with asymmetry of the target and recognition portions of modified sites. Our results suggest that encoding asymmetry is an ancient mechanism of evolvability that increases diversity and experimentation with PTM site positions. Strong selective pressures on PTMs may have

  4. Inguinal Abnormalities in Male Patients with Acetabular Fractures Treated Using an Ilioinguinal Exposure

    Directory of Open Access Journals (Sweden)

    Reza Firoozabadi

    2015-09-01

    Full Text Available Purpose: Surgeons performing an ilioinguinal exposure for acetabular fracture surgery need to be aware of aberrant findings such as inguinal hernias and spermatic cord lesions. The purpose of this study is to report these occurrences in a clinical series of adult males undergoing acetabular fracture fixation and a series of adult male cadavers. The secondary aim is to characterize these abnormalities to aid surgeons in detecting these abnormalities preoperatively and coordinating a surgical plan with a general surgeon.Methods: Clinical study- Retrospective review of treated acetabular fractures through an ilioinguinal approach. Incidence of inguinal canal and spermatic cord abnormalities requiring general surgery consultation were identified. Corresponding CT scans were reviewed and radiographic characteristics of the spermatic cord abnormalities and/or hernias were noted.Cadaveric study- 18 male cadavers dissected bilaterally using an ilioinguinal exposure. The inguinal canal and the contents of the spermatic cord were identified and characterized.Results: Clinical Study- 5.7% (5/87 of patients had spermatic cord lesion and/or inguinal hernia requiring general surgical intervention. Preoperative pelvic CT scan review identified abnormalities noted intraoperatively in four of the five patients. Cord lipomas visualized as enlargements of the spermatic cord with homogeneous density. Hernias visualized as enlarged spermatic cords with heterogeneous density. Cadaver Study- 31% (11/36 of cadavers studied had spermatic cord and/or inguinal canal abnormalities. Average cord diameter in those with abnormalities was 24.9 mm (15-28 compared to 16 mm (11-22 in normal cords, which was statistically significant.Conclusion: The clinical and cadaveric findings emphasize the importance of understanding inguinal abnormalities and the value of detecting them preoperatively. The preoperative pelvic CT scans were highly sensitive in detecting inguinal abnormalities.

  5. Partial Tmem106b reduction does not correct abnormalities due to progranulin haploinsufficiency.

    Science.gov (United States)

    Arrant, Andrew E; Nicholson, Alexandra M; Zhou, Xiaolai; Rademakers, Rosa; Roberson, Erik D

    2018-06-22

    Loss of function mutations in progranulin (GRN) are a major cause of frontotemporal dementia (FTD). Progranulin is a secreted glycoprotein that localizes to lysosomes and is critical for proper lysosomal function. Heterozygous GRN mutation carriers develop FTD with TDP-43 pathology and exhibit signs of lysosomal dysfunction in the brain, with increased levels of lysosomal proteins and lipofuscin accumulation. Homozygous GRN mutation carriers develop neuronal ceroid lipofuscinosis (NCL), an earlier-onset lysosomal storage disorder caused by severe lysosomal dysfunction. Multiple genome-wide association studies have shown that risk of FTD in GRN mutation carriers is modified by polymorphisms in TMEM106B, which encodes a lysosomal membrane protein. Risk alleles of TMEM106B may increase TMEM106B levels through a variety of mechanisms. Brains from FTD patients with GRN mutations exhibit increased TMEM106B expression, and protective TMEM106B polymorphisms are associated with decreased TMEM106B expression. Together, these data raise the possibility that reduction of TMEM106B levels may protect against the pathogenic effects of progranulin haploinsufficiency. We crossed Tmem106b +/- mice with Grn +/- mice, which model the progranulin haploinsufficiency of GRN mutation carriers and develop age-dependent social deficits and lysosomal abnormalities in the brain. We tested whether partial Tmem106b reduction could normalize the social deficits and lysosomal abnormalities of Grn +/- mice. Partial reduction of Tmem106b levels did not correct the social deficits of Grn +/- mice. Tmem106b reduction also failed to normalize most lysosomal abnormalities of Grn +/- mice, except for β-glucuronidase activity, which was suppressed by Tmem106b reduction and increased by progranulin insufficiency. These data do not support the hypothesis that Tmem106b reduction protects against the pathogenic effects of progranulin haploinsufficiency, but do show that Tmem106b reduction normalizes some

  6. The Lyssavirus glycoprotein: A key to cross-immunity.

    Science.gov (United States)

    Buthelezi, Sindisiwe G; Dirr, Heini W; Chakauya, Ereck; Chikwamba, Rachel; Martens, Lennart; Tsekoa, Tsepo L; Stoychev, Stoyan H; Vandermarliere, Elien

    2016-11-01

    Rabies is an acute viral encephalomyelitis in warm-blooded vertebrates, caused by viruses belonging to Rhabdovirus family and genus Lyssavirus. Although rabies is categorised as a neglected disease, the rabies virus (RABV) is the most studied amongst Lyssaviruses which show nearly identical infection patterns. In efforts to improving post-exposure prophylaxis, several anti-rabies monoclonal antibodies (mAbs) targeting the glycoprotein (G protein) sites I, II, III and G5 have been characterized. To explore cross-neutralization capacity of available mAbs and discover new possible B-cell epitopes, we have analyzed all available glycoprotein sequences from Lyssaviruses with a focus on sequence variation and conservation. This information was mapped on the structure of a representative G protein. We proposed several possible cross-neutralizing B-cell epitopes (GUVTTTF, WLRTV, REECLD and EHLVVEEL) in complement to the already well-characterized antigenic sites. The research could facilitate development of novel cross-reactive mAbs against RABV and even more broad, against possibly all Lyssavirus members. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Glycoprotein Ibα clustering in platelet storage and function

    NARCIS (Netherlands)

    Gitz, E.

    2013-01-01

    Platelets are anucleated, discoid-shaped cells that play an essential role in the formation of a hemostatic plug to prevent blood loss from injured vessels. Initial platelet arrest at the damaged arterial vessel wall is mediated through the interaction between the platelet receptor glycoprotein (GP)

  8. The Correlation between Electroencephalography Amplitude and Interictal Abnormalities: Audit study

    Directory of Open Access Journals (Sweden)

    Sami F. Al-Rawas

    2014-10-01

    Full Text Available Objectives: The aim of this study was to establish the relationship between background amplitude and interictal abnormalities in routine electroencephalography (EEG. Methods: This retrospective audit was conducted between July 2006 and December 2009 at the Department of Clinical Physiology at Sultan Qaboos University Hospital (SQUH in Muscat, Oman. A total of 1,718 electroencephalograms (EEGs were reviewed. All EEGs were from patients who had been referred due to epilepsy, syncope or headaches. EEGs were divided into four groups based on their amplitude: group one ≤20 μV; group two 21–35 μV; group three 36–50 μV, and group four >50 μV. Interictal abnormalities were defined as epileptiform discharges with or without associated slow waves. Abnormalities were identified during periods of resting, hyperventilation and photic stimulation in each group. Results: The mean age ± standard deviation of the patients was 27 ± 12.5 years. Of the 1,718 EEGs, 542 (31.5% were abnormal. Interictal abnormalities increased with amplitude in all four categories and demonstrated a significant association (P <0.05. A total of 56 EEGs (3.3% had amplitudes that were ≤20 μV and none of these showed interictal epileptiform abnormalities. Conclusion: EEG amplitude is an important factor in determining the presence of interictal epileptiform abnormalities in routine EEGs. This should be taken into account when investigating patients for epilepsy. A strong argument is made for considering long-term EEG monitoring in order to identify unexplained seizures which may be secondary to epilepsy. It is recommended that all tertiary institutions provide EEG telemetry services.

  9. Glucocorticoid-regulated and constitutive trafficking of proteolytically processed cell surface-associated glycoproteins in wild type and variant rat hepatoma cells

    International Nuclear Information System (INIS)

    Amacher, S.L.; Goodman, L.J.; Bravo, D.A.; Wong, K.Y.; Goldfine, I.D.; Hawley, D.M.; Firestone, G.L.

    1989-01-01

    Glucocorticoids regulate the trafficking of mouse mammary tumor virus (MMTV) glycoproteins to the cell surface in the rat hepatoma cell line M1.54, but not in the immunoselected sorting variant CR4. To compare the localization of MMTV glycoproteins to another proteolytically processed glycoprotein, both wild type M1.54 cells and variant CR4 cells were transfected with a human insulin receptor (hIR) expression vector, pRSVhIR. The production of cell surface hIR was monitored in dexamethasone-treated and -untreated wild type M1.54 and variant CR4 cells by indirect immunofluorescence, direct plasma membrane immunoprecipitation, and by [125I] insulin binding. In both wild type and variant rat hepatoma cells, hIR were localized at the cell surface in the presence or in the absence of 1 microM dexamethasone. In contrast, the glucocorticoid-regulated trafficking of cell surface MMTV glycoproteins occurred only in wild type M1.54 cells. We conclude that the hIR, which undergoes posttranslational processing reactions similar to MMTV glycoproteins, does not require glucocorticoids to be transported to the plasma membrane and is representative of a subset of cell surface glycoproteins whose trafficking is constitutive in rat hepatoma cells. Thus, MMTV glycoproteins and hIR provide specific cell surface markers to characterize the glucocorticoid-regulated and constitutive sorting pathways

  10. Replacement of the cytoplasmic domain alters sorting of a viral glycoprotein in polarized cells.

    OpenAIRE

    Puddington, L; Woodgett, C; Rose, J K

    1987-01-01

    The envelope glycoprotein (G protein) of vesicular stomatitis virus (VSV) is transported to the basolateral plasma membrane of polarized epithelial cells, whereas the hemagglutinin glycoprotein (HA protein) of influenza virus is transported to the apical plasma membrane. To determine if the cytoplasmic domain of VSV G protein might be important in directing G protein to the basolateral membrane, we derived polarized Madin-Darby canine kidney cell lines expressing G protein or G protein with i...

  11. Efficacy of soluble glycoprotein fraction from Allium sativum purified by size exclusion chromatography on murine Schistosomiasis mansoni.

    Science.gov (United States)

    Aly, Ibrahim; Taher, Eman E; El-Sayed, Hoda; Mohammed, Faten A; ELnain, Gehan; Hamad, Rabab S; Bayoumy, Elsayed M

    2017-06-01

    In this work, the efficiency of crude MeOH extracts and soluble glycoprotein fraction of Allium sativum purified by size-exclusion chromatography (SEC) on parasitological, histopathological and some biochemical parameters in Schistosoma mansoni infected mice were investigated. Animals were infected by tail immersion with 100 cercariae/each mouse and divided into five groups in addition to the normal control. The results revealed a significant decrease in mean worm burden in all treated mice especially in the group treated with soluble glycoprotein fraction of A. sativum as compared to infected non-treated control with the disappearance of female worms. Administration of the studied extracts revealed remarkable amelioration in the levels of all the measured parameters in S. mansoni infected mice. In addition, treatment of mice with crude A. sativum MeOH extract and soluble glycoprotein fraction of A. sativum decreased significantly the activities of studied enzymes as compared to the infected untreated group. The highest degrees of enhancement in pathological changes was observed in the treated one with soluble glycoprotein fraction of A. sativum compared to the infected group represented by small sized, late fibro-cellular granuloma, the decrease in cellular constituents and degenerative changes in eggs. In conclusion, A. sativum treatment had effective schistosomicidal activities, through reduction of worm burden and tissue eggs, especially when it was given in purified glycoprotein fraction. Moreover, the soluble glycoprotein fraction of A. sativum largely modulates both the size and the number of granulomas. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Mutations in the Schmallenberg Virus Gc Glycoprotein Facilitate Cellular Protein Synthesis Shutoff and Restore Pathogenicity of NSs Deletion Mutants in Mice.

    Science.gov (United States)

    Varela, Mariana; Pinto, Rute Maria; Caporale, Marco; Piras, Ilaria M; Taggart, Aislynn; Seehusen, Frauke; Hahn, Kerstin; Janowicz, Anna; de Souza, William Marciel; Baumgärtner, Wolfgang; Shi, Xiaohong; Palmarini, Massimo

    2016-06-01

    Serial passage of viruses in cell culture has been traditionally used to attenuate virulence and identify determinants of viral pathogenesis. In a previous study, we found that a strain of Schmallenberg virus (SBV) serially passaged in tissue culture (termed SBVp32) unexpectedly displayed increased pathogenicity in suckling mice compared to wild-type SBV. In this study, we mapped the determinants of SBVp32 virulence to the viral genome M segment. SBVp32 virulence is associated with the capacity of this virus to reach high titers in the brains of experimentally infected suckling mice. We also found that the Gc glycoprotein, encoded by the M segment of SBVp32, facilitates host cell protein shutoff in vitro Interestingly, while the M segment of SBVp32 is a virulence factor, we found that the S segment of the same virus confers by itself an attenuated phenotype to wild-type SBV, as it has lost the ability to block the innate immune system of the host. Single mutations present in the Gc glycoprotein of SBVp32 are sufficient to compensate for both the attenuated phenotype of the SBVp32 S segment and the attenuated phenotype of NSs deletion mutants. Our data also indicate that the SBVp32 M segment does not act as an interferon (IFN) antagonist. Therefore, SBV mutants can retain pathogenicity even when they are unable to fully control the production of IFN by infected cells. Overall, this study suggests that the viral glycoprotein of orthobunyaviruses can compensate, at least in part, for the function of NSs. In addition, we also provide evidence that the induction of total cellular protein shutoff by SBV is determined by multiple viral proteins, while the ability to control the production of IFN maps to the NSs protein. The identification of viral determinants of pathogenesis is key to the development of prophylactic and intervention measures. In this study, we found that the bunyavirus Gc glycoprotein is a virulence factor. Importantly, we show that mutations in the Gc

  13. Recombinant pestivirus E2 glycoproteins prevent viral attachment to permissive and non permissive cells with different efficiency.

    Science.gov (United States)

    Asfor, A S; Wakeley, P R; Drew, T W; Paton, D J

    2014-08-30

    Bovine viral diarrhoea virus (BVDV) is an economically important animal pathogen, which like other pestiviruses has similar molecular biological features to hepaciviruses, including human Hepatitis C virus. The pestivirus E2 glycoproteins are the major target for virus-neutralising antibodies, as well as playing a role in receptor binding and host range restriction. In this study, recombinant E2 glycoproteins (rE2) derived from three different pestivirus species were examined for their inhibitory effects on pestivirus infectivity in cell culture. Histidine-tagged rE2 glycoproteins of BVDV type 2 strain 178003, BVDV type 1 strain Oregon C24V and CSFV strain Alfort 187 were produced in Spodoptera frugiperda insect cells and purified under native conditions. The ability of rE2 glycoprotein to inhibit the infection of permissive cells by both homologous and heterologous virus was compared, revealing that the inhibitory effects of rE2 glycoproteins correlated with the predicted similarity of the E2 structures in the recombinant protein and the test virus. This result suggests that the sequence and structure of E2 are likely to be involved in the host specificity of pestiviruses at their point of uptake into cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Prevalence of Metabolic Abnormalities and Association with Obesity among Saudi College Students

    OpenAIRE

    Abolfotouh, Mostafa A.; Al-Alwan, Ibrahim A.; Al-Rowaily, Mohammed A.

    2012-01-01

    Aim. (i) To estimate the prevalence of the metabolic abnormalities among Saudi college students in Riyadh, Saudi Arabia, and (ii) to investigate the association between different indicators of body composition and these abnormalities. Methods. A total of 501 college students participated in a cross-sectional study. Anthropometric assessments, BP measurements, and biochemical assessment were done. Metabolic abnormalities were identified. Results. Applying BMI, 21.9 % and 20.6% of students were...

  15. Membrane glycoproteins of differentiating skeletal muscle cells

    International Nuclear Information System (INIS)

    Miller, K.R.; Remy, C.N.; Smith, P.B.

    1987-01-01

    The composition of N-linked glycoprotein oligosaccharides was studied in myoblasts and myotubes of the C2 muscle cell line. Oligosaccharides were radioactively labelled for 15 hr with [ 3 H] mannose and plasma membranes isolated. Ten glycopeptides were detected by SDS-PAGE and fluorography. The extent of labelling was 4-6 fold greater in myoblasts vs myotubes. A glycopeptide of Mr > 100,000 was found exclusively in myoblast membranes. Lectin chromatography revealed that the proportion of tri-, tetranntenary, biantennary and high mannose chains was similar throughout differentiation. The high mannose chain fraction was devoid of hybrid chains. The major high mannose chain contained nine mannose residues. The higher level of glycopeptide labelling in myoblasts vs myotubes corresponded to a 5-fold greater rate of protein synthesis. Pulse-chase experiments were used to follow the synthesis of the Dol-oligosaccharides. Myoblasts and myotubes labelled equivalently the glucosylated tetradecasaccharide but myoblasts labelled the smaller intermediates 3-4 greater than myotubes. Myoblasts also exhibited a 2-3 fold higher Dol-P dependent glycosyl transferase activity for chain elongation and Dol-sugar synthesis. Together these results show that the degree of protein synthesis and level of Dol-P are contributing factors in the higher capacity of myoblasts to produce N-glycoproteins compared to myotubes

  16. Highly variable penetrance of abnormal phenotypes in embryonic lethal knockout mice

    Science.gov (United States)

    Wilson, Robert; Geyer, Stefan H.; Reissig, Lukas; Rose, Julia; Szumska, Dorota; Hardman, Emily; Prin, Fabrice; McGuire, Christina; Ramirez-Solis, Ramiro; White, Jacqui; Galli, Antonella; Tudor, Catherine; Tuck, Elizabeth; Mazzeo, Cecilia Icoresi; Smith, James C.; Robertson, Elizabeth; Adams, David J.; Mohun, Timothy; Weninger, Wolfgang J.

    2017-01-01

    Background: Identifying genes that are essential for mouse embryonic development and survival through term is a powerful and unbiased way to discover possible genetic determinants of human developmental disorders. Characterising the changes in mouse embryos that result from ablation of lethal genes is a necessary first step towards uncovering their role in normal embryonic development and establishing any correlates amongst human congenital abnormalities. Methods: Here we present results gathered to date in the Deciphering the Mechanisms of Developmental Disorders (DMDD) programme, cataloguing the morphological defects identified from comprehensive imaging of 220 homozygous mutant and 114 wild type embryos from 42 lethal and subviable lines, analysed at E14.5. Results: Virtually all mutant embryos show multiple abnormal phenotypes and amongst the 42 lines these affect most organ systems. Within each mutant line, the phenotypes of individual embryos form distinct but overlapping sets. Subcutaneous edema, malformations of the heart or great vessels, abnormalities in forebrain morphology and the musculature of the eyes are all prevalent phenotypes, as is loss or abnormal size of the hypoglossal nerve. Conclusions: Overall, the most striking finding is that no matter how profound the malformation, each phenotype shows highly variable penetrance within a mutant line. These findings have challenging implications for efforts to identify human disease correlates. PMID:27996060

  17. Effect of an aqueous extract of Scoparia dulcis on plasma and tissue glycoproteins in streptozotocin induced diabetic rats.

    Science.gov (United States)

    Latha, M; Pari, L

    2005-02-01

    The influence of Scoparia dulcis, a traditionally used plant for the treatment of diabetes mellitus, was examined in streptozotocin diabetic rats on dearrangement in glycoprotein levels. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin. An aqueous extract of Scoparia dulcis plant was administered orally for 6 weeks. The effect of the Scoparia dulcis extract on blood glucose, plasma insulin, plasma and tissue glycoproteins studied was in comparison to glibenclamide. The levels of blood glucose and plasma glycoproteins were increased significantly whereas the level of plasma insulin was significantly decreased in diabetic rats. There was a significant decrease in the level of sialic acid and elevated levels of hexose, hexosamine and fucose in the liver and kidney of streptozotocin diabetic rats. Oral administration of Scoparia dulcis plant extract (SPEt) to diabetic rats led to decreased levels of blood glucose and plasma glycoproteins. The levels of plasma insulin and tissue sialic acid were increased whereas the levels of tissue hexose, hexosamine and fucose were near normal. The present study indicates that Scoparia dulcis possesses a significant beneficial effect on glycoproteins in addition to its antidiabetic effect.

  18. Association between abnormal serum myelin-specific protein levels and white matter integrity in first-episode and drug-naïve patients with major depressive disorder.

    Science.gov (United States)

    Jiang, Linling; Cheng, Yuqi; Jiang, Hongyan; Xu, Jian; Lu, Jin; Shen, Zonglin; Lu, Yi; Liu, Fang; Li, Luqiong; Xu, Xiufeng

    2018-05-01

    Although the structural abnormalities of white matter (WM) have been described in patients with major depressive disorder (MDD), the neuropathological changes remain unclear. The current study aimed to investigate the myelin oligodendrocyte glycoprotein (MOG) and myelin-associated glycoprotein (MAG) levels and their correlations with WM integrity in first-episode, drug-naïve MDD patients. We obtained diffusion tensor images of 102 first-episode, drug-naïve MDD patients and 81 age- and sex-matched controls. Serum MOG and MAG levels of all participants were measured and compared between the two groups. The correlations between WM integrity and MOG and MAG levels were examined. MOG and MAG serum levels were significantly higher in MDD patients than in controls. Patients with MDD also showed decreased fractional anisotropy (FA) and axial diffusivity in the WM of the bilateral thalamus, right hippocampus, right temporal lobe, and left pulvinar. At the whole-brain level, no regions showed any correlations of diffusivity parameters with MOG or MAG levels in healthy subjects. However, we observed two-way correlations between the MOG and MAG levels and the FA and mean diffusivity values in the WM of the left middle frontal lobe, right inferior parietal lobe, and right supplementary motor area in MDD patients. Further investigation with a larger sample size and longitudinal studies are required to better understand the neuropathology of WM integrity in MDD. Our findings represent the first evidence of a relationship between abnormal serum myelin-specific protein levels and impaired WM integrity, which may help to better understand the neurobiological mechanisms of MDD. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Cereal n-glycoproteins enrichment by lectin affinity monolithic chromatography

    Czech Academy of Sciences Publication Activity Database

    Flodrová, Dana; Bobálová, Janette; Laštovičková, Markéta

    2016-01-01

    Roč. 44, č. 2 (2016), s. 286-297 ISSN 0133-3720 R&D Projects: GA ČR(CZ) GPP503/12/P395 Institutional support: RVO:68081715 Keywords : barley * wheat * glycoprotein * mass spectrometry * lectin chromatography Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 0.496, year: 2016

  20. Motor Control Abnormalities in Parkinson’s Disease

    Science.gov (United States)

    Mazzoni, Pietro; Shabbott, Britne; Cortés, Juan Camilo

    2012-01-01

    The primary manifestations of Parkinson’s disease are abnormalities of movement, including movement slowness, difficulties with gait and balance, and tremor. We know a considerable amount about the abnormalities of neuronal and muscle activity that correlate with these symptoms. Motor symptoms can also be described in terms of motor control, a level of description that explains how movement variables, such as a limb’s position and speed, are controlled and coordinated. Understanding motor symptoms as motor control abnormalities means to identify how the disease disrupts normal control processes. In the case of Parkinson’s disease, movement slowness, for example, would be explained by a disruption of the control processes that determine normal movement speed. Two long-term benefits of understanding the motor control basis of motor symptoms include the future design of neural prostheses to replace the function of damaged basal ganglia circuits, and the rational design of rehabilitation strategies. This type of understanding, however, remains limited, partly because of limitations in our knowledge of normal motor control. In this article, we review the concept of motor control and describe a few motor symptoms that illustrate the challenges in understanding such symptoms as motor control abnormalities. PMID:22675667

  1. TROPHOBLASTIC β1 – GLYCOPROTEIN SYNTHESIS IN SEROPOSITIVE PREGNANT WOMEN

    Directory of Open Access Journals (Sweden)

    R. N. Bogdanovich

    2005-01-01

    Full Text Available Abstract. The level of trophoblastic β1 – glycoprotein (SP–1 was determined in the blood sera of 200 healthy pregnant women and 184 women with threatened abortions in term till 20 weeks of pregnancy. In group of women experiencing recurrent abortions in 38 % cases antibodies to chorionic gonadotropin, in 39,5 % cases antibodies to phospholipids, in 25,5 % – antibodies to tireoglobulin were revealed in significant amounts. In 20,65 % lupus anticoagulant was found. The majority of women in this group had changes in homeostasis. The presence of autoantibodies during pregnancy is the unfavourable factor in the development of placental insufficiency. This is proved by the decreased secretion of trophoblastic β1 – glycoprotein – a marker of the fetal part of placenta. (Med. Immunol., 2005, vol.7, № 1, pp. 85588

  2. Quantitative Secretome Analysis of Activated Jurkat Cells Using Click Chemistry-Based Enrichment of Secreted Glycoproteins.

    Science.gov (United States)

    Witzke, Kathrin E; Rosowski, Kristin; Müller, Christian; Ahrens, Maike; Eisenacher, Martin; Megger, Dominik A; Knobloch, Jürgen; Koch, Andrea; Bracht, Thilo; Sitek, Barbara

    2017-01-06

    Quantitative secretome analyses are a high-performance tool for the discovery of physiological and pathophysiological changes in cellular processes. However, serum supplements in cell culture media limit secretome analyses, but serum depletion often leads to cell starvation and consequently biased results. To overcome these limiting factors, we investigated a model of T cell activation (Jurkat cells) and performed an approach for the selective enrichment of secreted proteins from conditioned medium utilizing metabolic marking of newly synthesized glycoproteins. Marked glycoproteins were labeled via bioorthogonal click chemistry and isolated by affinity purification. We assessed two labeling compounds conjugated with either biotin or desthiobiotin and the respective secretome fractions. 356 proteins were quantified using the biotin probe and 463 using desthiobiotin. 59 proteins were found differentially abundant (adjusted p-value ≤0.05, absolute fold change ≥1.5) between inactive and activated T cells using the biotin method and 86 using the desthiobiotin approach, with 31 mutual proteins cross-verified by independent experiments. Moreover, we analyzed the cellular proteome of the same model to demonstrate the benefit of secretome analyses and provide comprehensive data sets of both. 336 proteins (61.3%) were quantified exclusively in the secretome. Data are available via ProteomeXchange with identifier PXD004280.

  3. Glycoprotein component of plant cell walls

    International Nuclear Information System (INIS)

    Cooper, J.B.; Chen, J.A.; Varner, J.E.

    1984-01-01

    The primary wall surrounding most dicotyledonous plant cells contains a hydroxyproline-rich glycoprotein (HRGP) component named extensin. A small group of glycopeptides solubilized from isolated cell walls by proteolysis contained a repeated pentapeptide glycosylated by tri- and tetraarabinosides linked to hydroxyproline and, by galactose, linked to serine. Recently, two complementary approaches to this problem have provided results which greatly increase the understanding of wall extensin. In this paper the authors describe what is known about the structure of soluble extensin secreted into the walls of the carrot root cells

  4. Report to Congress on abnormal occurrences, January--March 1990

    International Nuclear Information System (INIS)

    1990-07-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from January 1 through March 31, 1990. for this reporting period, there were 10 abnormal occurrences. One involved the loss of vital ac power with a subsequent reactor coolant system heat-up at the Vogtle Unit 1 nuclear power plant during shutdown. The event was investigated by an NRC Incident Investigation Team (IIT). The other nine abnormal occurrences involved nuclear material licensees and are described in detail under other NRC-issued licenses: eight of these involved medical therapy misadministrations; the other involved the receipt of an unshielded radioactive source at Amersham Corporation in Burlington, Massachusetts. The latter event was also investigated by an NRC IIT. No abnormal occurrences were reported by the Agreement States. The report also contains information that updates a previously reported abnormal occurrence

  5. Report to Congress on abnormal occurrences, April-June 1986

    International Nuclear Information System (INIS)

    1987-01-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from April 1 to June 30, 1986. The report states that for this reporting period, there were two abnormal occurrences at the nuclear power plants licensed to operate. One involved an out of sequence control rod withdrawal and the other involved a boiling water reactor emergency core cooling system design deficiency. There were five abnormal occurrences at the other NRC licensees. Two involved willful failure to report diagnostic medical misadministrations to the NRC; one involved a therapeutic medical misadministration; and two involved diagnostic medical misadministrations. There were two abnormal occurrences reported by the Agreement States. One involved an uncontrolled release of krypton-85 to an unrestricted area; the other involved a contaminated radiopharmaceutical used in diagnostic administrations. The report also contains information updating some previously reported abnormal occurrences

  6. Glycan shield and fusion activation of a deltacoronavirus spike glycoprotein fine-tuned for enteric infections.

    Science.gov (United States)

    Xiong, Xiaoli; Tortorici, M Alejandra; Snijder, Joost; Yoshioka, Craig; Walls, Alexandra C; Li, Wentao; McGuire, Andrew T; Rey, Félix A; Bosch, Berend-Jan; Veesler, David

    2017-11-01

    Coronaviruses recently emerged as major human pathogens causing outbreaks of severe acute respiratory syndrome and Middle-East respiratory syndrome. They utilize the spike (S) glycoprotein anchored in the viral envelope to mediate host attachment and fusion of the viral and cellular membranes to initiate infection. The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response. We report here the 3.5 Å resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified delta genus. Structural and glycoproteomics data indicate that the glycans of PDCoV S are topologically conserved when compared with the human respiratory coronavirus HCoV-NL63 S, resulting in similar surface areas being shielded from neutralizing antibodies and implying that both viruses are under comparable immune pressure in their respective hosts. The structure further reveals a shortened S 2 ' activation loop, containing a reduced number of basic amino acids, which participates to rendering the spike largely protease-resistant. This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity. IMPORTANCE Coronaviruses use transmembrane spike (S) glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes. We determined a near-atomic resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic porcine deltacoronavirus (PDCoV), which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide. Structural and glycoproteomics data reveal that PDCoV S is

  7. Appearance and cellular distribution of lectin-like receptors for alpha 1-acid glycoprotein in the developing rat testis

    DEFF Research Database (Denmark)

    Andersen, U O; Bøg-Hansen, T C; Kirkeby, S

    1996-01-01

    A histochemical avidin-biotin technique with three different alpha 1-acid glycoprotein glycoforms showed pronounced alterations in the cellular localization of two alpha 1-acid glycoprotein lectin-like receptors during cell differentiation in the developing rat testis. The binding of alpha 1-acid...

  8. The UL24 protein of herpes simplex virus 1 affects the sub-cellular distribution of viral glycoproteins involved in fusion

    Energy Technology Data Exchange (ETDEWEB)

    Ben Abdeljelil, Nawel; Rochette, Pierre-Alexandre; Pearson, Angela, E-mail: angela.pearson@iaf.inrs.ca

    2013-09-15

    Mutations in UL24 of herpes simplex virus type 1 can lead to a syncytial phenotype. We hypothesized that UL24 affects the sub-cellular distribution of viral glycoproteins involved in fusion. In non-immortalized human foreskin fibroblasts (HFFs) we detected viral glycoproteins B (gB), gD, gH and gL present in extended blotches throughout the cytoplasm with limited nuclear membrane staining; however, in HFFs infected with a UL24-deficient virus (UL24X), staining for the viral glycoproteins appeared as long, thin streaks running across the cell. Interestingly, there was a decrease in co-localized staining of gB and gD with F-actin at late times in UL24X-infected HFFs. Treatment with chemical agents that perturbed the actin cytoskeleton hindered the formation of UL24X-induced syncytia in these cells. These data support a model whereby the UL24 syncytial phenotype results from a mislocalization of viral glycoproteins late in infection. - Highlights: • UL24 affects the sub-cellular distribution of viral glycoproteins required for fusion. • Sub-cellular distribution of viral glycoproteins varies in cell-type dependent manner. • Drugs targeting actin microfilaments affect formation of UL24-related syncytia in HFFs.

  9. Increased platelet expression of glycoprotein IIIa following aspirin treatment in aspirin-resistant but not aspirin-sensitive subjects

    Science.gov (United States)

    Floyd, Christopher N; Goodman, Timothy; Becker, Silke; Chen, Nan; Mustafa, Agnesa; Schofield, Emma; Campbell, James; Ward, Malcolm; Sharma, Pankaj; Ferro, Albert

    2014-01-01

    Aims Aspirin is widely used as an anti-platelet agent for cardiovascular prophylaxis. Despite aspirin treatment, many patients experience recurrent thrombotic events, and aspirin resistance may contribute to this. We examined the prevalence of aspirin resistance in a healthy population, and investigated whether the platelet proteome differed in aspirin-resistant subjects. Methods Ninety-three healthy subjects received aspirin 300 mg daily for 28 days. Before and at the end of treatment, urine was taken to determine 11-dehydrothromboxane B2, and blood was taken to measure arachidonic acid (AA)-induced aggregation of platelet-rich plasma and to interrogate the platelet proteome by mass spectrometric analysis with further confirmation of findings using Western blotting. Results In two of the 93 subjects, neither AA-induced aggregation nor urinary 11-dehydrothromboxane B2 was effectively suppressed by aspirin, despite measurable plasma salicylate concentrations, suggesting the presence of true aspirin resistance. Despite no detectable differences in the platelet proteome at baseline, following aspirin a marked increase was seen in platelet glycoprotein IIIa expression in the aspirin-resistant but not aspirin-sensitive subjects. An increase in platelet glycoprotein IIIa expression with aspirin resistance was confirmed in a separate cohort of 17 patients with stable coronary artery disease on long term aspirin treatment, four of whom exhibited aspirin resistance. Conclusions In a healthy population, true aspirin resistance is uncommon but exists. Resistance is associated with an increase in platelet glycoprotein IIIa expression in response to aspirin. These data shed new light on the mechanism of aspirin resistance, and provide the potential to identify aspirin-resistant subjects using a novel biomarker. PMID:25099258

  10. Formation of high-order oligomers is required for functional bioactivity of an African bat henipavirus surface glycoprotein.

    Science.gov (United States)

    Behner, Laura; Zimmermann, Louisa; Ringel, Marc; Weis, Michael; Maisner, Andrea

    2018-05-01

    Hendra virus (HeV) and Nipah virus (NiV) are highly pathogenic henipaviruses originating from fruit bats in Australia and Asia that can cause severe infections in livestock and humans. In recent years, also African bat henipaviruses were identified at the nucleic acid level. To assess their potential to replicate in non-bat species, several studies were performed to characterize the two surface glycoproteins required for virus entry and spread by cell-cell fusion. It has been shown that surface expression and fusion-helper function of the receptor-binding G protein of Kumasi virus (KV), the prototypic Ghanaian bat henipavirus, is reduced compared to other non-African henipavirus G proteins. Immunostainings and pulse-chase analysis revealed a delayed export of KV G from the ER. As defects in oligomerization of viral glycoproteins can be responsible for limited surface transport thereby restricting the bioactivity, we analyzed the oligomerization pattern of KV G. In contrast to HeV and NiV whose G proteins are known to be expressed at a dimer-tetramer ratio of 1:1, KV G almost exclusively formed stable tetramers or higher oligomers. KV G also showed less stringent requirements for defined stalk cysteines to form dimers and tetramers. Interestingly, any changes in the oligomeric forms negatively affected the fusion-helper activity although surface expression and receptor binding was unchanged. This clearly indicates that the formation of mostly higher oligomeric KV G forms is not a deficiency responsible for ER retention, but is rather a basic structural feature essential for the bioactivity of this African bat henipavirus glycoprotein. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Radiographic Abnormalities in the Feet of Diabetic Patients with Neuropathy and Foot Ulceration.

    Science.gov (United States)

    Viswanathan, Vijay; Kumpatla, Satyavani; Rao, V Narayan

    2014-11-01

    People with diabetic neuropathy are frequently prone to several bone and joint abnormalities. Simple radiographic findings have been proven to be quite useful in the detection of such abnormalities, which might be helpful not only for early diagnosis but also in following the course of diabetes through stages of reconstruction of the ulcerated foot.The present study was designed to identify the common foot abnormalities in south Indian diabetic subjects with and without neuropathy using radiographic imaging. About 150 (M:F 94:56) subjects with type 2 diabetes were categorised into three groups: Group I (50 diabetic patients), Group II (50 patients with neuropathy), and Group III (50 diabetic patients with both neuropathy and foot ulceration). Demographic details, duration of diabetes and HbA1c values were recorded. Vibration perception threshold was measured for assessment of neuropathy. Bone and joint abnormalities in the feet and legs of the study subjects were identified using standardised dorsi-plantar and lateral weight-bearing radiographs. Radiographic findings of the study subjects revealed that those with both neuropathy and foot ulceration and a longer duration of diabetes had more number of bone and joint abnormalities. Subjects with neuropathy alone also showed presence of several abnormalities, including periosteal reaction, osteopenia, and Charcot changes. The present findings highlight the impact of neuropathy and duration of diabetes on the development of foot abnormalities in subjects with diabetes. Using radiographic imaging can help in early identification of abnormalities and better management of the diabetic foot.

  12. Multiple genes encode the major surface glycoprotein of Pneumocystis carinii

    DEFF Research Database (Denmark)

    Kovacs, J A; Powell, F; Edman, J C

    1993-01-01

    The major surface antigen of Pneumocystis carinii, a life-threatening opportunistic pathogen in human immunodeficiency virus-infected patients, is an abundant glycoprotein that functions in host-organism interactions. A monoclonal antibody to this antigen is protective in animals, and thus this a...

  13. The Plasmin-Sensitive Protein Pls in Methicillin-Resistant Staphylococcus aureus (MRSA Is a Glycoprotein.

    Directory of Open Access Journals (Sweden)

    Isabelle Bleiziffer

    2017-01-01

    Full Text Available Most bacterial glycoproteins identified to date are virulence factors of pathogenic bacteria, i.e. adhesins and invasins. However, the impact of protein glycosylation on the major human pathogen Staphylococcus aureus remains incompletely understood. To study protein glycosylation in staphylococci, we analyzed lysostaphin lysates of methicillin-resistant Staphylococcus aureus (MRSA strains by SDS-PAGE and subsequent periodic acid-Schiff's staining. We detected four (>300, ∼250, ∼165, and ∼120 kDa and two (>300 and ∼175 kDa glycosylated surface proteins with strain COL and strain 1061, respectively. The ∼250, ∼165, and ∼175 kDa proteins were identified as plasmin-sensitive protein (Pls by mass spectrometry. Previously, Pls has been demonstrated to be a virulence factor in a mouse septic arthritis model. The pls gene is encoded by the staphylococcal cassette chromosome (SCCmec type I in MRSA that also encodes the methicillin resistance-conferring mecA and further genes. In a search for glycosyltransferases, we identified two open reading frames encoded downstream of pls on the SCCmec element, which we termed gtfC and gtfD. Expression and deletion analysis revealed that both gtfC and gtfD mediate glycosylation of Pls. Additionally, the recently reported glycosyltransferases SdgA and SdgB are involved in Pls glycosylation. Glycosylation occurs at serine residues in the Pls SD-repeat region and modifying carbohydrates are N-acetylhexosaminyl residues. Functional characterization revealed that Pls can confer increased biofilm formation, which seems to involve two distinct mechanisms. The first mechanism depends on glycosylation of the SD-repeat region by GtfC/GtfD and probably also involves eDNA, while the second seems to be independent of glycosylation as well as eDNA and may involve the centrally located G5 domains. Other previously known Pls properties are not related to the sugar modifications. In conclusion, Pls is a glycoprotein and

  14. Comparative Studies of Vertebrate Platelet Glycoprotein 4 (CD36

    Directory of Open Access Journals (Sweden)

    Roger S. Holmes

    2012-09-01

    Full Text Available Platelet glycoprotein 4 (CD36 (or fatty acyl translocase [FAT], or scavenger receptor class B, member 3 [SCARB3] is an essential cell surface and skeletal muscle outer mitochondrial membrane glycoprotein involved in multiple functions in the body. CD36 serves as a ligand receptor of thrombospondin, long chain fatty acids, oxidized low density lipoproteins (LDLs and malaria-infected erythrocytes. CD36 also influences various diseases, including angiogenesis, thrombosis, atherosclerosis, malaria, diabetes, steatosis, dementia and obesity. Genetic deficiency of this protein results in significant changes in fatty acid and oxidized lipid uptake. Comparative CD36 amino acid sequences and structures and CD36 gene locations were examined using data from several vertebrate genome projects. Vertebrate CD36 sequences shared 53–100% identity as compared with 29–32% sequence identities with other CD36-like superfamily members, SCARB1 and SCARB2. At least eight vertebrate CD36 N-glycosylation sites were conserved which are required for membrane integration. Sequence alignments, key amino acid residues and predicted secondary structures were also studied. Three CD36 domains were identified including cytoplasmic, transmembrane and exoplasmic sequences. Conserved sequences included N- and C-terminal transmembrane glycines; and exoplasmic cysteine disulphide residues; TSP-1 and PE binding sites, Thr92 and His242, respectively; 17 conserved proline and 14 glycine residues, which may participate in forming CD36 ‘short loops’; and basic amino acid residues, and may contribute to fatty acid and thrombospondin binding. Vertebrate CD36 genes usually contained 12 coding exons. The human CD36 gene contained transcription factor binding sites (including PPARG and PPARA contributing to a high gene expression level (6.6 times average. Phylogenetic analyses examined the relationships and potential evolutionary origins of the vertebrate CD36 gene with vertebrate

  15. Report to Congress on abnormal occurrences, January-March 1983

    International Nuclear Information System (INIS)

    1983-09-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from January 1 to March 31, 1983. The report states that for this report period, there were three abnormal occurrences at the nuclear power plants licensed by the NRC to operate. The first involved a main feedwater line break due to water hammer. The second involved management and procedural control deficiencies. The third involved failure of the automatic reactor trip system. There were no abnormal occurrences for the other NRC licensees. There were six abnormal occurrences at Agreement State licensees. One involved an individual who ingested and was contaminated by radioactive material. Four involved lost or stolen radioactive sources. One involved radioactive contamination of a metals production facility

  16. Molecular organization in bacterial cell membranes. Specific labelling and topological distribution of glycoproteins and proteins in Streptomyces albus membranes

    Energy Technology Data Exchange (ETDEWEB)

    Larraga, V; Munoz, E [Consejo Superior de Investigaciones Cientificas, Madrid (Spain). Instituto de Biologia Celular

    1975-05-01

    The paper reports about an investigation into the question of the specific labelling and topological distribution of glycoproteins and proteins in Streptomyces albus membranes. The method of sample preparation is described: Tritium labelling of glycoproteins in protoplasts and membranes, iodination of proteins, trypsin treatment and polyacrylamide gel electrophoresis. The findings suggest an asymmetrical distribution of the glycoproteins in membranes and a weak accessibility to iodine label. A structural model of the plasma membranes of Streptomyces albus is proposed similar to the general 'fluid mosaic' model of Singer and Nicholson.

  17. Magnetization transfer imaging identifies basal ganglia abnormalities in adult ADHD that are invisible to conventional T1 weighted voxel-based morphometry

    Directory of Open Access Journals (Sweden)

    Arjun Sethi

    2017-01-01

    Full Text Available In childhood, Attention Deficit Hyperactivity Disorder (ADHD is reliably associated with reduced volume of the striatum. In contrast, striatal abnormalities are infrequently detected in voxel-based morphometry (VBM neuroimaging studies of adults with ADHD. This discrepancy has been suggested to reflect normalisation of striatal morphology with age and prolonged treatment of symptoms. If so, this would indicate that while striatal abnormalities are linked to symptom expression in childhood, they cannot explain the persistence of these symptoms in adulthood. However, this may not be case. Instead, we hypothesized that the lack of evidence for striatal abnormalities in adult ADHD may reflect poor sensitivity of typical (T1-weighted neuroimaging to detect subcortical differences. To address this, we acquired both magnetisation transfer (MT saturation maps optimised for subcortical contrast, and conventional T1-weighted images in 30 adults with ADHD and 30 age, IQ, gender and handedness-matched controls. Using VBM of both datasets, we demonstrate volumetric reductions within the left ventral striatum on MT that are not observed on identically pre-processed T1-weighted images from the same participants. Nevertheless, both techniques reported similar sensitivity to cortical abnormalities in the right inferior parietal lobe. Additionally, we show that differences in striatal iron may potentially explain this reduced sensitivity of T1-weighted images in adults. Together, these findings indicate that prior VBM studies reporting no abnormalities in striatal volume in adult ADHD might have been compromised by the methodological insensitivity of T1-weighted VBM to subcortical differences, and that structural abnormalities of the striatum in ADHD do indeed persist into adulthood.

  18. Generating Isoform-Specific Antibodies : Lessons from Nucleocytoplasmic Glycoprotein Skp1

    NARCIS (Netherlands)

    West, Christopher M.; Van Der Wel, Hanke; Chinoy, Zoiesha; Boons, Geert Jan; Gauthier, Ted J.; Taylor, Carol M.; Xu, Yuechi

    2015-01-01

    Antibodies that discriminate protein isoforms differing by modifications at specific amino acids have revolutionized studies of their functions. Skp1 is a novel nucleocytoplasmic glycoprotein that is hydroxylated at proline-143 and then O-glycosylated by a pentasaccharide attached via a GlcNAcα1,

  19. Direct chemical modification and voltammetric detection of glycans in glycoproteins

    Czech Academy of Sciences Publication Activity Database

    Trefulka, Mojmír; Paleček, Emil

    2014-01-01

    Roč. 48, NOV2014 (2014), s. 52-55 ISSN 1388-2481 R&D Projects: GA ČR(CZ) GAP301/11/2055 Institutional support: RVO:68081707 Keywords : Glycoproteins * Chemical modification * Os(VI)L complexes Subject RIV: BO - Biophysics Impact factor: 4.847, year: 2014

  20. Irradiation of rat brain reduces P-glycoprotein expression and function

    NARCIS (Netherlands)

    Bart, J.; Nagengast, W. B.; Coppes, R. P.; Wegman, T. D.; van der Graaf, W. T. A.; Groen, H. J. M.; Vaalburg, W.; de Vries, E. G. E.; Hendrikse, N. H.

    2007-01-01

    The blood - brain barrier ( BBB) hampers delivery of several drugs including chemotherapeutics to the brain. The drug efflux pump P- glycoprotein ( P- gp), expressed on brain capillary endothelial cells, is part of the BBB. P- gp expression on capillary endothelium decreases 5 days after brain

  1. An unusual dependence of human herpesvirus-8 glycoproteins-induced cell-to-cell fusion on heparan sulfate

    International Nuclear Information System (INIS)

    Tiwari, Vaibhav; Darmani, Nissar A.; Thrush, Gerald R.; Shukla, Deepak

    2009-01-01

    Human herpesvirus-8 (HHV-8) is known to interact with cell surface heparan sulfate (HS) for entry into a target cell. Here we investigated the role of HS during HHV-8 glycoproteins-induced cell fusion. Interestingly, the observed fusion demonstrated an unusual dependence on HS as evident from following lines of evidence: (1) a significant reduction in cell-to-cell fusion occurred when target cells were treated with heparinase; (2) in a competition assay, when the effector cells expressing HHV-8 glycoproteins were challenged with soluble HS, cell-to-cell fusion was reduced; and, (3) co-expression of HHV-8 glycoproteins gH-gL on target cells resulted in inhibition of cell surface HS expression. Taken together, our results indicate that cell surface HS can play an additional role during HHV-8 pathogenesis.

  2. An unusual dependence of human herpesvirus-8 glycoproteins-induced cell-to-cell fusion on heparan sulfate

    Energy Technology Data Exchange (ETDEWEB)

    Tiwari, Vaibhav [Department of Ophthalmology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific and College of Optometry, Western University of Health Sciences, Pomona, CA 91766 (United States); Darmani, Nissar A.; Thrush, Gerald R. [Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific and College of Optometry, Western University of Health Sciences, Pomona, CA 91766 (United States); Shukla, Deepak, E-mail: dshukla@uic.edu [Department of Ophthalmology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612 (United States)

    2009-12-18

    Human herpesvirus-8 (HHV-8) is known to interact with cell surface heparan sulfate (HS) for entry into a target cell. Here we investigated the role of HS during HHV-8 glycoproteins-induced cell fusion. Interestingly, the observed fusion demonstrated an unusual dependence on HS as evident from following lines of evidence: (1) a significant reduction in cell-to-cell fusion occurred when target cells were treated with heparinase; (2) in a competition assay, when the effector cells expressing HHV-8 glycoproteins were challenged with soluble HS, cell-to-cell fusion was reduced; and, (3) co-expression of HHV-8 glycoproteins gH-gL on target cells resulted in inhibition of cell surface HS expression. Taken together, our results indicate that cell surface HS can play an additional role during HHV-8 pathogenesis.

  3. The diversity of abnormal hormone receptors in adrenal Cushing's syndrome allows novel pharmacological therapies

    Directory of Open Access Journals (Sweden)

    Lacroix A.

    2000-01-01

    Full Text Available Recent studies from several groups have indicated that abnormal or ectopic expression and function of adrenal receptors for various hormones may regulate cortisol production in ACTH-independent hypercortisolism. Gastric inhibitory polypeptide (GIP-dependent Cushing's syndrome has been described in patients with either unilateral adenoma or bilateral macronodular adrenal hyperplasia; this syndrome results from the large adrenal overexpression of the GIP receptor without any activating mutation. We have conducted a systematic in vivo evaluation of patients with adrenal Cushing's syndrome in order to identify the presence of abnormal hormone receptors. In macronodular adrenal hyperplasia, we have identified, in addition to GIP-dependent Cushing's syndrome, other patients in whom cortisol production was regulated abnormally by vasopressin, ß-adrenergic receptor agonists, hCG/LH, or serotonin 5HT-4 receptor agonists. In patients with unilateral adrenal adenoma, the abnormal expression or function of GIP or vasopressin receptor has been found, but the presence of ectopic or abnormal hormone receptors appears to be less prevalent than in macronodular adrenal hyperplasia. The identification of the presence of an abnormal adrenal receptor offers the possibility of a new pharmacological approach to control hypercortisolism by suppressing the endogenous ligands or by using specific antagonists for the abnormal receptors.

  4. Contribution of the attachment G glycoprotein to pathogenicity and immunogenicity of avian metapneumovirus subgroup C.

    Science.gov (United States)

    Govindarajan, Dhanasekaran; Kim, Shin-Hee; Samal, Siba K

    2010-03-01

    Avian metapneumovirus (AMPV) causes an upper respiratory tract infection in turkeys leading to serious economic losses to the turkey industry. The G glycoprotein of AMPV is known to be associated with viral attachment and pathogenesis. In this study, we determined the role of the G glycoprotein in the pathogenicity and immunogenicity of AMPV strain Colorado (AMPV/CO). Recombinant AMPV/CO lacking the G protein (rAMPV/CO-deltaG) was generated using a reverse-genetics system. The recovered rAMPV/CO-deltaG replicated slightly better than did wild-type AMPV in Vero cells. However, deletion of the G gene in AMPV resulted in attenuation of the virus in turkeys. The mutant virus induced less-severe clinical signs and a weaker immune response in turkeys than did the wild-type AMPV. Our results suggest that the G glycoprotein is an important determinant for the pathogenicity and immunogenicity of AMPV.

  5. Podoplanin - a small glycoprotein with many faces

    OpenAIRE

    Ugorski, Maciej; Dziegiel, Piotr; Suchanski, Jaroslaw

    2016-01-01

    Podoplanin is a small membrane glycoprotein with a large number of O-glycoside chains and therefore it belongs to mucin-type proteins. It can be found on the surface of many types of normal cells originating from various germ layers. It is present primarily on the endothelium of lymphatic vessels, type I pneumocytes and glomerular podocytes. Increased levels of podoplanin or its neo-expression have been found in numerous types of human carcinomas, but it is especially common in squamous cell ...

  6. [Research progress on ebola virus glycoprotein].

    Science.gov (United States)

    Ding, Guo-Yong; Wang, Zhi-Yu; Gao, Lu; Jiang, Bao-Fa

    2013-03-01

    Ebola virus (EBOV) causes outbreaks of a highly lethal hemorrhagic fever in humans and there are no effective therapeutic or prophylactic treatments available. The glycoprotein (GP) of EBOV is a transmembrane envelope protein known to play multiple functions including virus attachment and entry, cell rounding and cytotoxicity, down-regulation of host surface proteins, and enhancement of virus assembly and budding. GP is the primary target of protective immunity and the key target for developing neutralizing antibodies. In this paper, the research progress on genetic structure, pathogenesis and immunogenicity of EBOV GP in the last 5 years is reviewed.

  7. Chromosomal abnormalities in a psychiatric population

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, K.E.; Lubetsky, M.J.; Wenger, S.L.; Steele, M.W. [Univ. of Pittsburgh Medical Center, PA (United States)

    1995-02-27

    Over a 3.5 year period of time, 345 patients hospitalized for psychiatric problems were evaluated cytogenetically. The patient population included 76% males and 94% children with a mean age of 12 years. The criteria for testing was an undiagnosed etiology for mental retardation and/or autism. Cytogenetic studies identified 11, or 3%, with abnormal karyotypes, including 4 fragile X positive individuals (2 males, 2 females), and 8 with chromosomal aneuploidy, rearrangements, or deletions. While individuals with chromosomal abnormalities do not demonstrate specific behavioral, psychiatric, or developmental problems relative to other psychiatric patients, our results demonstrate the need for an increased awareness to order chromosomal analysis and fragile X testing in those individuals who have combinations of behavioral/psychiatric, learning, communication, or cognitive disturbance. 5 refs., 1 fig., 2 tabs.

  8. Report to Congress on abnormal occurrences, July--September 1977. Quarterly report

    International Nuclear Information System (INIS)

    1977-11-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report, the tenth in the series, covers the period July 1 to September 30, 1977. The NRC has determined that during this period there were no abnormal occurrences at the 65 nuclear power plants licensed to operate nor at fuel cycle facilities. There was one abnormal occurrence at other licensee facilities, which involved the loss and recovery of a radioactive source and probable overexposure. This report also contains information updating previously reported abnormal occurrences

  9. Report to Congress on abnormal occurrences, July-September 1987

    International Nuclear Information System (INIS)

    1988-03-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from July 1 to September 30, 1987. The report states that for this reporting period, there were two abnormal occurrences at the nuclear power plants licensed to operate. The first involved a significant degradation of plant safety at Oyster Creek; and the second involved a steam generator tube rupture at North Anna Unit 1. There were four abnormal occurrences at the other NRC licensees. The first involved a therapeutic medical misadministration; the second involved a failure to report diagnostic medical misadministrations; the third involved the suspension of a well logging company's license; and the fourth involved the suspension of an industrial radiography company's license. There were two abnormal occurrences reported by an Agreement State (New York). The first involved a hospital contamination incident and the second involved therapeutic medical misadministrations. The report also contains information updating some previously reported abnormal occurrences

  10. Phosphorylation of varicella-zoster virus glycoprotein gpI by mammalian casein kinase II and casein kinase I

    International Nuclear Information System (INIS)

    Grose, C.; Jackson, W.; Traugh, J.A.

    1989-01-01

    Varicella-zoster virus (VZV) glycoprotein gpI is the predominant viral glycoprotein within the plasma membranes of infected cells. This viral glycoprotein is phosphorylated on its polypeptide backbone during biosynthesis. In this report, the authors investigated the protein kinases which participate in the phosphorylation events. Under in vivo conditions, VZV gpI was phosphorylated on its serine and threonine residues by protein kinases present within lysates of either VZV-infected or uninfected cells. Because this activity was diminished by heparin, a known inhibitor of casein kinase II, isolated gpI was incubated with purified casein kinase II and shown to be phosphorylated in an in vitro assay containing [γ- 32 P]ATP. The same glycoprotein was phosphorylated when [ 32 P]GTP was substituted for [ 32 P]ATP in the protein kinase assay. They also tested whether VZV gpI was phosphorylated by two other ubiquitous mammalian protein kinases--casein kinase I and cyclic AMP-dependent kinase--and found that only casein kinase I modified gpI. When the predicted 623-amino-acid sequence of gpI was examined, two phosphorylation sites known to be optimal for casein kinase II were observed. In summary, this study showed that VZV gpI was phosphorylated by each of two mammalian protein kinases (casein kinase I and casein kinase II) and that potential serine-threonine phosphorylation sites for each of these two kinases were present in the viral glycoprotein

  11. Urinary excretion of beta 2-glycoprotein-1 (apolipoprotein H) and other markers of tubular malfunction in "non-tubular" renal disease.

    Science.gov (United States)

    Flynn, F V; Lapsley, M; Sansom, P A; Cohen, S L

    1992-07-01

    To determine whether urinary beta 2-glycoprotein-1 assays can provide improved discrimination between chronic renal diseases which are primarily of tubular or glomerular origin. Urinary beta 2-glycoprotein-1, retinol-binding protein, alpha 1-microglobulin, beta 2-microglobulin, N-acetyl-beta-D-glucosa-minidase and albumin were measured in 51 patients with primary glomerular disease, 23 with obstructive nephropathy, and 15 with polycystic kidney disease, and expressed per mmol of creatinine. Plasma beta 2-glycoprotein-1 was assayed in 52 patients and plasma creatinine in all 89. The findings were compared between the diagnostic groups and with previously published data relating to primary tubular disorders. All 31 patients with plasma creatinine greater than 200 mumol/l excreted increased amounts of beta 2-glycoprotein-1, retinol-binding protein, and alpha 1-microglobulin, and 29 had increased N-acetyl-beta-D-glucosaminidase; the quantities were generally similar to those found in comparable patients with primary tubular pathology. Among 58 with plasma creatinine concentrations under 200 mumol/l, increases in beta 2-glycoprotein-1, retinol-binding protein, and alpha 1-microglobulin excretion were less common and much smaller, especially in those with obstructive nephropathy and polycystic disease. The ratios of the excretion of albumin to the other proteins provided the clearest discrimination between the patients with glomerular or tubular malfunction, but an area of overlap was present which embraced those with obstructive nephropathy and polycystic disease. Increased excretion of beta 2-glycoprotein-1 due to a raised plasma concentration or diminution of tubular reabsorption, or both, is common in all the forms of renal disease investigated, and both plasma creatinine and urinary albumin must be taken into account when interpreting results. Ratios of urinary albumin: beta 2-glycoprotein-1 greater than 1000 are highly suggestive of primary glomerular disease and

  12. A sheep hydatid cyst glycoprotein as receptors for three toxic lectins, as well as Abrus precatorius and Ricinus communis agglutinins.

    Science.gov (United States)

    Wu, A M; Song, S C; Wu, J H; Pfüller, U; Chow, L P; Lin, J Y

    1995-01-18

    The binding properties of a glycoprotein with blood group P1 specificity isolated from sheep hydatid cyst fluid with Gal and GalNAc specific lectins was investigated by quantitative precipitin and precipitin inhibition assays. The glycoprotein completely precipitated Ricinus communis agglutinin (RCA1), Abrus precatorius agglutinin (APA) and Mistletoe toxic lectin-I (ML-I). Only 1.0 microgram of P1 glycoprotein was required to precipitate 50% of 5.1 micrograms ML-I nitrogen. It also reacted well with abrin-a and ricin, precipitating over 73% of the lectin nitrogen added, but poorly or weakly with Dolichos biflorus (DBL), Vicia villosa (VVL, a mixture of A4, A2B2 and B4), VVL-B4, Arachis hypogaea (PNA), Maclura pomifera (MPL), Bauchinia purpurea alba (BPL) and Wistaria floribunda (WFL) lectins. When an inhibition assay in the range of 5.1 micrograms N to 5.9 micrograms N of lectins (ML-I, abrin-a; ricin, RCA1, and APA, and 10 micrograms P1 active glycoprotein interaction was performed; from 76 to 100% of the precipitations were inhibited by 0.44 and 0.52 mumol of Gal alpha 1-->4Gal and Gal beta 1-->4GlcNAc, respectively, but not or insignificantly with 1.72 mumol of GlcNAc. The Gal alpha 1-->4Gal disaccharide found in this P1 active glycoprotein is a frequently occurring sequence of many glycosphingolipids located at the surface of mammalian cell membranes, especially human erythrocytes and intestinal cells for ligand binding and microbial toxin attachment. The present finding suggests that the Gal alpha 1-->4Gal beta 1-->4GlcNAc sequence in this P1 active glycoprotein is one of the best glycoprotein receptors for three toxic lectins (ricin, abrin-a, and ML-I) as well as for APA, and RCA1, and the result of inhibition assay implies that these lectins are recognizing part or all of the Gal alpha 1-->4Gal beta 1-->4GlcNAc sequence in the P1 active glycoprotein.

  13. The Neutralizing Linear Epitope of Human Herpesvirus 6A Glycoprotein B Does Not Affect Virus Infectivity.

    Science.gov (United States)

    Wakata, Aika; Kanemoto, Satoshi; Tang, Huamin; Kawabata, Akiko; Nishimura, Mitsuhiro; Jasirwan, Chyntia; Mahmoud, Nora Fahmy; Mori, Yasuko

    2018-03-01

    Human herpesvirus 6A (HHV-6A) glycoprotein B (gB) is a glycoprotein consisting of 830 amino acids and is essential for the growth of the virus. Previously, we reported that a neutralizing monoclonal antibody (MAb) called 87-y-13 specifically reacts with HHV-6A gB, and we identified its epitope residue at asparagine (Asn) 347 on gB. In this study, we examined whether the epitope recognized by the neutralizing MAb is essential for HHV-6A infection. We constructed HHV-6A bacterial artificial chromosome (BAC) genomes harboring substitutions at Asn347, namely, HHV-6A BACgB(N347K) and HHV-6A BACgB(N347A). These mutant viruses could be reconstituted and propagated in the same manner as the wild type and their revertants, and MAb 87-y-13 could not inhibit infection by either mutant. In a cell-cell fusion assay, Asn at position 347 on gB was found to be nonessential for cell-cell fusion. In addition, in building an HHV-6A gB homology model, we found that the epitope of the neutralizing MAb is located on domain II of gB and is accessible to solvents. These results indicate that Asn at position 347, the linear epitope of the neutralizing MAb, does not affect HHV-6A infectivity. IMPORTANCE Glycoprotein B (gB) is one of the most conserved glycoproteins among all herpesviruses and is a key factor for virus entry. Therefore, antibodies targeted to gB may neutralize virus entry. Human herpesvirus 6A (HHV-6A) encodes gB, which is translated to a protein of about 830 amino acids (aa). Using a monoclonal antibody (MAb) for HHV-6A gB, which has a neutralizing linear epitope, we analyzed the role of its epitope residue, N347, in HHV-6A infectivity. Interestingly, this gB linear epitope residue, N347, was not essential for HHV-6A growth. By constructing a homology model of HHV-6A gB, we found that N347 was located in the region corresponding to domain II. Therefore, with regard to its neutralizing activity against HHV-6A infection, the epitope on gB might be exposed to solvents

  14. Determinants of foamy virus envelope glycoprotein mediated resistance to superinfection

    International Nuclear Information System (INIS)

    Berg, Angelika; Pietschmann, Thomas; Rethwilm, Axel; Lindemann, Dirk

    2003-01-01

    Little is known about the nature of foamy virus (FV) receptor molecules on target cells and their interaction with the viral glycoproteins. Similar to other viruses, cellular expression of the FV Env protein is sufficient to induce resistance to exogenous FV, a phenomenon called superinfection resistance (SIR). In this study we define determinants of the FV Env protein essential for mediating SIR. FV Env requires the extracellular domains of the SU and the TM subunits as well as membrane anchorage, efficient cell surface transport, and most probably correct subunit processing. This is in contrast to murine leukemia virus where secreted proteins comprising the receptor-binding domain in SU are sufficient to induce SIR. Furthermore, we demonstrate that cellular expression of the prototype FV envelope proteins induces SIR against pseudotypes with glycoproteins of other FV species, including of simian, feline, bovine, and equine origin. This implies that all of them use the same receptor molecules for viral entry

  15. Dynamic upper respiratory abnormalities in Thoroughbred racehorses in South Africa

    Directory of Open Access Journals (Sweden)

    Javier E. Mirazo

    2014-11-01

    Full Text Available Upper airway endoscopy at rest has been the diagnostic method of choice for equine upper respiratory tract (URT conditions. Development of high-speed treadmill endoscopy improved the sensitivity of URT endoscopy by allowing observation of the horse’s nasopharynx and larynx during exercise. However, treadmill exercise may not always accurately represent the horse’s normal exercise as track surface, rider, tack and environmental variables are altered. Recently, the development of dynamic overground endoscopy (DOE has addressed some of these shortcomings. A retrospective study was undertaken to describe the URT abnormalities detected during DOE in racehorses presenting with poor performance and/or abnormal respiratory noise. Patient records of Thoroughbred racehorses undergoing DOE from November 2011 to August 2012 were reviewed. Data collected included signalment, primary complaint, distance exercised, maximum speed and dynamic airway abnormalities detected. Fifty-two horses underwent DOE for investigation of poor performance and/or abnormal respiratory noise. The main abnormalities detected included axial deviation of the aryepiglottic folds (40%, vocal cord collapse (35%, abnormal arytenoid function (33% and dorsal displacement of the soft palate (25%. A total of 40 horses were diagnosed with one or more abnormalities of the URT (77%. Fifteen horses (29% had a single abnormality and 25 horses (48% had multiple abnormalities. This study showed that DOE is a useful technique for investigating dynamic disorders of the URT in racehorses in South Africa. The total number and type of dynamic pathological conditions were comparable with those identified in similar populations in other geographical locations.

  16. Intercellular transfer of P-glycoprotein from the drug resistant human bladder cancer cell line BIU-87 does not require cell-to-cell contact.

    Science.gov (United States)

    Zhou, Hui-liang; Zheng, Yong-jun; Cheng, Xiao-zhi; Lv, Yi-song; Gao, Rui; Mao, Hou-ping; Chen, Qin

    2013-09-01

    The efflux activity of transmembrane P-glycoprotein prevents various therapeutic drugs from reaching lethal concentrations in cancer cells, resulting in multidrug resistance. We investigated whether drug resistant bladder cancer cells could transfer functional P-glycoprotein to sensitive parental cells. Drug sensitive BIU-87 bladder cancer cells were co-cultured for 48 hours with BIU-87/ADM, a doxorubicin resistant derivative of the same cell line, in a Transwell® system that prevented cell-to-cell contact. The presence of P-glycoprotein in recipient cell membranes was established using fluorescein isothiocyanate, laser scanning confocal microscopy and Western blot. P-glycoprotein mRNA levels were compared between cell types. Rhodamine 123 efflux assay was done to confirm that P-glycoprotein was biologically active. The amount of P-glycoprotein protein in BIU-87 cells co-cultured with BIU-87/ADM was significantly higher than in BIU-87 cells (0.44 vs 0.25) and BIU-87/H33342 cells (0.44 vs 0.26, each p transfer. P-glycoprotein mRNA expression was significantly higher in BIU-87/ADM cells than in co-cultured BIU-87 cells (1.28 vs 0.30), BIU-87/H33342 (0.28) and BIU-87 cells (0.25, each p <0.001), ruling out a genetic mechanism. After 30 minutes of efflux, rhodamine 123 fluorescence intensity was significantly lower in BIU-87/ADM cells (5.55 vs 51.45, p = 0.004) and co-cultured BIU-87 cells than in BIU-87 cells (14.22 vs 51.45, p <0.001), indicating that P-glycoprotein was functional. Bladder cancer cells can acquire functional P-glycoprotein through a nongenetic mechanism that does not require direct cell contact. This mechanism is consistent with a microparticle mediated process. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  17. Report to Congress on abnormal occurrences: [Quarterly report], January-March 1987

    International Nuclear Information System (INIS)

    1987-10-01

    The Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from January 1 to March 31, 1987. The report states that for this reporting period, there was one abnormal occurrence at the nuclear power plants licensed to operate. The item involved the NRC suspension of power operations of the Peach Bottom Facility due to inattentiveness of the control room staff. There were seven abnormal occurrences at the other NRC licensees. Four involved diagnostic medical misadministrations; the other three involved breakdowns in management controls at three separate industrial radiography licensees. There were two abnormal occurrences reported by the Agreement States. Both involved breakdowns in management controls at industrial radiography licensees. The report also contains information updating some previously reported abnormal occurrences. Appendix A contains the criteria used to define an abnormal occurrence. 13 refs

  18. Abnormal uterine bleeding

    Science.gov (United States)

    Anovulatory bleeding; Abnormal uterine bleeding - hormonal; Polymenorrhea - dysfunctional uterine bleeding ... ACOG committee opinion no. 557: Management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women. Reaffirmed 2015. www. ...

  19. An unusual dependence of human herpesvirus-8 Glycoproteins-induced cell-to-cell fusion on heparan sulfate

    Science.gov (United States)

    Tiwari, Vaibhav; Darmani, Nissar A.; Thrush, Gerald R.; Shukla, Deepak

    2009-01-01

    Human herpes virus 8 (HHV-8) is known to interact with cell surface heparan sulfate (HS) for entry into a target cell. Here we investigated the role of HS during HHV-8 glycoproteins induced cell fusion. Interestingly, the observed fusion demonstrated an unusual dependence on HS as evident from following lines of evidence: 1) a significant reduction in cell-to-cell fusion occurred when target cells were treated with heparinase; 2) in a competition assay, when the effector cells expressing HHV-8 glycoproteins were challenged with soluble HS, cell-to-cell fusion was reduced; and, 3) coexpression of HHV-8 glycoproteins gH-gL on target cells resulted in inhibition of cell surface HS expression. Taken together, our results indicate that cell surface HS can play an additional role during HHV-8 pathogenesis. PMID:19747451

  20. Comparative Analysis of Whey N-Glycoproteins in Human Colostrum and Mature Milk Using Quantitative Glycoproteomics.

    Science.gov (United States)

    Cao, Xueyan; Song, Dahe; Yang, Mei; Yang, Ning; Ye, Qing; Tao, Dongbing; Liu, Biao; Wu, Rina; Yue, Xiqing

    2017-11-29

    Glycosylation is a ubiquitous post-translational protein modification that plays a substantial role in various processes. However, whey glycoproteins in human milk have not been completely profiled. Herein, we used quantitative glycoproteomics to quantify whey N-glycosylation sites and their alteration in human milk during lactation; 110 N-glycosylation sites on 63 proteins and 91 N-glycosylation sites on 53 proteins were quantified in colostrum and mature milk whey, respectively. Among these, 68 glycosylation sites on 38 proteins were differentially expressed in human colostrum and mature milk whey. These differentially expressed N-glycoproteins were highly enriched in "localization", "extracellular region part", and "modified amino acid binding" according to gene ontology annotation and mainly involved in complement and coagulation cascades pathway. These results shed light on the glycosylation sites, composition and biological functions of whey N-glycoproteins in human colostrum and mature milk, and provide substantial insight into the role of protein glycosylation during infant development.

  1. Report to Congress on abnormal occurrences, April--June 1993

    International Nuclear Information System (INIS)

    1993-09-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health and safety and requires a quarterly report of such events to be made to Congress. This report covers the period April through June 1993, and discusses four abnormal occurrences at NRC-licensed facilities, three involving medical brachytherapy misadministrations and one involving a research reactor that operated without a safety system. One pool irradiation facility contamination event, two medical misadministrations (one ''sodium iodide'' and one brachytherapy), and one industrial radiographer overexposure event that were reported by NRC Agreement States are also discussed. The report also contains information updating one previously reported abnormal occurrence and information on three other events of interest

  2. Molecular cloning of S1 glycoprotein gene of infectious bronchitis ...

    African Journals Online (AJOL)

    In vitro protein expression is an important method of obtaining large amounts of viral proteins to investigate their biological properties. The S1 glycoprotein of infectious bronchitis virus, due to its effective immune-dominant role is an appropriate candidate for production of recombinant vaccine against infectious bronchitis ...

  3. The Lyssavirus glycoprotein: A key to cross-immunity

    International Nuclear Information System (INIS)

    Buthelezi, Sindisiwe G.; Dirr, Heini W.; Chakauya, Ereck; Chikwamba, Rachel; Martens, Lennart; Tsekoa, Tsepo L.; Stoychev, Stoyan H.; Vandermarliere, Elien

    2016-01-01

    Rabies is an acute viral encephalomyelitis in warm-blooded vertebrates, caused by viruses belonging to Rhabdovirus family and genus Lyssavirus. Although rabies is categorised as a neglected disease, the rabies virus (RABV) is the most studied amongst Lyssaviruses which show nearly identical infection patterns. In efforts to improving post-exposure prophylaxis, several anti-rabies monoclonal antibodies (mAbs) targeting the glycoprotein (G protein) sites I, II, III and G5 have been characterized. To explore cross-neutralization capacity of available mAbs and discover new possible B-cell epitopes, we have analyzed all available glycoprotein sequences from Lyssaviruses with a focus on sequence variation and conservation. This information was mapped on the structure of a representative G protein. We proposed several possible cross-neutralizing B-cell epitopes (GUVTTTF, WLRTV, REECLD and EHLVVEEL) in complement to the already well-characterized antigenic sites. The research could facilitate development of novel cross-reactive mAbs against RABV and even more broad, against possibly all Lyssavirus members. -- Highlights: •The current PEP has raised safety and availability concerns. •Cocktails of mAbs have been proposed as alternative treatment. •Amino acid conservation amongst Lyssavirus G proteins was studied. •Possible cross-neutralizing B-cell epitopes were proposed.

  4. The Lyssavirus glycoprotein: A key to cross-immunity

    Energy Technology Data Exchange (ETDEWEB)

    Buthelezi, Sindisiwe G. [Council for Scientific and Industrial Research, Biosciences Unit, Pretoria (South Africa); Protein Structure-Function Research Unit, School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg (South Africa); Dirr, Heini W. [Protein Structure-Function Research Unit, School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg (South Africa); Chakauya, Ereck; Chikwamba, Rachel [Council for Scientific and Industrial Research, Biosciences Unit, Pretoria (South Africa); Martens, Lennart [Unit for Computational Omics and Systems Biology, Medical Biotechnology Center, VIB, Ghent (Belgium); Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, Ghent (Belgium); Tsekoa, Tsepo L. [Council for Scientific and Industrial Research, Biosciences Unit, Pretoria (South Africa); Stoychev, Stoyan H., E-mail: Sstoychev@csir.co.za [Council for Scientific and Industrial Research, Biosciences Unit, Pretoria (South Africa); Vandermarliere, Elien [Unit for Computational Omics and Systems Biology, Medical Biotechnology Center, VIB, Ghent (Belgium); Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, Ghent (Belgium); Bioinformatics Institute Gent, Ghent University, Ghent (Belgium)

    2016-11-15

    Rabies is an acute viral encephalomyelitis in warm-blooded vertebrates, caused by viruses belonging to Rhabdovirus family and genus Lyssavirus. Although rabies is categorised as a neglected disease, the rabies virus (RABV) is the most studied amongst Lyssaviruses which show nearly identical infection patterns. In efforts to improving post-exposure prophylaxis, several anti-rabies monoclonal antibodies (mAbs) targeting the glycoprotein (G protein) sites I, II, III and G5 have been characterized. To explore cross-neutralization capacity of available mAbs and discover new possible B-cell epitopes, we have analyzed all available glycoprotein sequences from Lyssaviruses with a focus on sequence variation and conservation. This information was mapped on the structure of a representative G protein. We proposed several possible cross-neutralizing B-cell epitopes (GUVTTTF, WLRTV, REECLD and EHLVVEEL) in complement to the already well-characterized antigenic sites. The research could facilitate development of novel cross-reactive mAbs against RABV and even more broad, against possibly all Lyssavirus members. -- Highlights: •The current PEP has raised safety and availability concerns. •Cocktails of mAbs have been proposed as alternative treatment. •Amino acid conservation amongst Lyssavirus G proteins was studied. •Possible cross-neutralizing B-cell epitopes were proposed.

  5. The albumin of the brown trout (Salmo trutta) is a glycoprotein.

    Science.gov (United States)

    Metcalf, V J; Brennan, S O; Chambers, G K; George, P M

    1998-07-28

    The albumin from an Atlantic salmonid, the brown trout (Salmo trutta), is 1730 Da higher in molecular mass than the albumin from a Pacific salmonid, the chinook salmon (Oncorhynchus tshawytscha), at 65230 Da. Digestion with neuraminidase revealed that purified brown trout albumin contained sialic acid while chinook salmon albumin did not. Concanavalin A-sepharose affinity chromatography was used to purify a glycopeptide from a total tryptic digest of brown trout albumin. The mass of this glycopeptide (3815 Da) was determined by mass spectrometry, and the sequence largely confirmed by N-terminal sequencing. The identified sequence of IAHCCNQSYSM-, contains an Asn-Gln-Ser glycosylation site and is identical to residues 475-485 derived from the cDNA of the albumin from the Atlantic salmon, the closest relative of the brown trout. Glycosylation of albumin is very unusual, and has not been identified in either reptilian or mammalian albumins. The finding of a glycoalbumin in salmonids, ancient members of the teleost fish subclass, coupled with evidence of albumin glycosylation in the oldest vertebrates, agnathans, as well as amphibians, suggests that albumin was originally a glycoprotein, but lost this modification sometime between the divergence of amphibians and reptiles.

  6. Copy Number Variations Found in Patients with a Corpus Callosum Abnormality and Intellectual Disability.

    Science.gov (United States)

    Heide, Solveig; Keren, Boris; Billette de Villemeur, Thierry; Chantot-Bastaraud, Sandra; Depienne, Christel; Nava, Caroline; Mignot, Cyril; Jacquette, Aurélia; Fonteneau, Eric; Lejeune, Elodie; Mach, Corinne; Marey, Isabelle; Whalen, Sandra; Lacombe, Didier; Naudion, Sophie; Rooryck, Caroline; Toutain, Annick; Caignec, Cédric Le; Haye, Damien; Olivier-Faivre, Laurence; Masurel-Paulet, Alice; Thauvin-Robinet, Christel; Lesne, Fabien; Faudet, Anne; Ville, Dorothée; des Portes, Vincent; Sanlaville, Damien; Siffroi, Jean-Pierre; Moutard, Marie-Laure; Héron, Delphine

    2017-06-01

    To evaluate the role that chromosomal micro-rearrangements play in patients with both corpus callosum abnormality and intellectual disability, we analyzed copy number variations (CNVs) in patients with corpus callosum abnormality/intellectual disability STUDY DESIGN: We screened 149 patients with corpus callosum abnormality/intellectual disability using Illumina SNP arrays. In 20 patients (13%), we have identified at least 1 CNV that likely contributes to corpus callosum abnormality/intellectual disability phenotype. We confirmed that the most common rearrangement in corpus callosum abnormality/intellectual disability is inverted duplication with terminal deletion of the 8p chromosome (3.2%). In addition to the identification of known recurrent CNVs, such as deletions 6qter, 18q21 (including TCF4), 1q43q44, 17p13.3, 14q12, 3q13, 3p26, and 3q26 (including SOX2), our analysis allowed us to refine the 2 known critical regions associated with 8q21.1 deletion and 19p13.1 duplication relevant for corpus callosum abnormality; report a novel 10p12 deletion including ZEB1 recently implicated in corpus callosum abnormality with corneal dystrophy; and) report a novel pathogenic 7q36 duplication encompassing SHH. In addition, 66 variants of unknown significance were identified in 57 patients encompassed candidate genes. Our results confirm the relevance of using microarray analysis as first line test in patients with corpus callosum abnormality/intellectual disability. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Role of scintigraphy in focally abnormal sonograms of fatty livers

    International Nuclear Information System (INIS)

    Lisbona, R.; Mishkin, S.; Derbekyan, V.; Novales-Diaz, J.A.; Roy, A.; Sanders, L.

    1988-01-01

    Fatty infiltration of the liver may cause a range of focal abnormalities on hepatic sonography which may simulate hepatic nodular lesions. Discrete deposits of fat or islands of normal tissue which are uninvolved by fatty infiltration may stand out as potential space-occupying lesions on the sonograms. Twelve patients with such focally abnormal ultrasound images were referred for liver scintigraphy with 133 Xe and /sup 99m/Tc colloidal SPECT studies to clarify the issue. These examinations helped identify, in nine of 12 patients, the innocent nature of the sonographic abnormalities which were simply related to the fat deposition process. Further, [/sup 99m/Tc]RBC scans defined the additional pathologic process in three patients in whom actual space-occupying lesions were indeed present in the liver. Scintigraphy has an important role to play in the understanding of focal hepatic ultrasound abnormalities particularly in unsuspected hepatic steatosis

  8. Role of scintigraphy in focally abnormal sonograms of fatty livers

    Energy Technology Data Exchange (ETDEWEB)

    Lisbona, R.; Mishkin, S.; Derbekyan, V.; Novales-Diaz, J.A.; Roy, A.; Sanders, L.

    1988-06-01

    Fatty infiltration of the liver may cause a range of focal abnormalities on hepatic sonography which may simulate hepatic nodular lesions. Discrete deposits of fat or islands of normal tissue which are uninvolved by fatty infiltration may stand out as potential space-occupying lesions on the sonograms. Twelve patients with such focally abnormal ultrasound images were referred for liver scintigraphy with /sup 133/Xe and /sup 99m/Tc colloidal SPECT studies to clarify the issue. These examinations helped identify, in nine of 12 patients, the innocent nature of the sonographic abnormalities which were simply related to the fat deposition process. Further, (/sup 99m/Tc)RBC scans defined the additional pathologic process in three patients in whom actual space-occupying lesions were indeed present in the liver. Scintigraphy has an important role to play in the understanding of focal hepatic ultrasound abnormalities particularly in unsuspected hepatic steatosis.

  9. Urine - abnormal color

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003139.htm Urine - abnormal color To use the sharing features on this page, please enable JavaScript. The usual color of urine is straw-yellow. Abnormally colored urine ...

  10. Tooth - abnormal colors

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003065.htm Tooth - abnormal colors To use the sharing features on this page, please enable JavaScript. Abnormal tooth color is any color other than white to yellowish- ...

  11. Glycoprotein profiles of macrophages at different stages of activation as revealed by lectin binding after electrophoretic separation.

    Science.gov (United States)

    Irimura, T; North, S M; Nicolson, G L

    1987-01-01

    Glycoprotein profiles of rat macrophages (M phi) at different stages of activation were studied by examining the reactivity of various lectins to the glycoproteins separated by polyacrylamide gel electrophoresis. Ricinus communis agglutinin 1 (RCA1) revealed several components including glycoproteins of Mr 160 kDa and 65 kDa prominent in resident M phi. A pokeweed mitogen (PWM) isolectin, Pa-4, recognizes branched poly(N-acetyllactosamine)-type carbohydrate chains, and revealed a significant increase in glycoproteins of Mr ranging from 70 kDa to 150 kDa on thioglycolate-elicited M phi. Increased reactivity of PWM to thioglycolate-elicited M phi was observed by direct binding of 125I-labeled Pa-4 to intact or glutaraldehyde-fixed M phi. Histochemical staining of formaldehyde-fixed M phi in vitro with biotinylated Pa-4 was consistent with the gel analysis, that is, resident M phi had no reactivity while thioglycolate-elicited M phi showed slight reactivity. Alveolar and intratumoral M phi bound more Pa-4 than resident or thioglycolate-elicited M phi. The PWM isolectin may therefore serve as a marker for an early stage of M phi activation.

  12. Prevalence of Metabolic Abnormalities and Association with Obesity among Saudi College Students

    Directory of Open Access Journals (Sweden)

    Mostafa A. Abolfotouh

    2012-01-01

    Full Text Available Aim. (i To estimate the prevalence of the metabolic abnormalities among Saudi college students in Riyadh, Saudi Arabia, and (ii to investigate the association between different indicators of body composition and these abnormalities. Methods. A total of 501 college students participated in a cross-sectional study. Anthropometric assessments, BP measurements, and biochemical assessment were done. Metabolic abnormalities were identified. Results. Applying BMI, 21.9 % and 20.6% of students were classified as overweight and obese, respectively. Central obesity was prevalent in 26.9% and 42.2% of students based on WC and WHtR, respectively. Other metabolic abnormalities were hypertension (23.6% and abnormal FPG level (22.6%. Three or more abnormalities were prevalent in 7.8% of students and increased significantly to 26.4%, 20%, and 17.6 in obese subjects based on BMI, WC, and WHtR, respectively. With the exception of abnormal FPG, prevalence of individual metabolic abnormalities as well as the number of these abnormalities significantly increased with increasing BMI, WC, and WHtR (P<0.001 each. Conclusion. Our findings provide evidence for the presence of MS in Saudi college students. Central adiposity contributes to the high incidence of individual MS components. College health programs that promote healthful lifestyle and avoidance of adult weight gain are recommended.

  13. N-terminal sequence of human leukocyte glycoprotein Mo1: conservation across species and homology to platelet IIb/IIIa.

    Science.gov (United States)

    Pierce, M W; Remold-O'Donnell, E; Todd, R F; Arnaout, M A

    1986-12-12

    Mo1 and gp160-gp93 are two surface membrane glycoprotein heterodimers present on granulocytes and monocytes derived from humans and guinea pigs, respectively. We purified both antigens and found that their alpha subunits had identical N-termini which were significantly homologous to the alpha subunit of the human adhesion platelet glycoprotein IIb/IIIa.

  14. Insights into the Evolution of Hydroxyproline-Rich Glycoproteins from 1000 Plant Transcriptomes.

    Science.gov (United States)

    Johnson, Kim L; Cassin, Andrew M; Lonsdale, Andrew; Wong, Gane Ka-Shu; Soltis, Douglas E; Miles, Nicholas W; Melkonian, Michael; Melkonian, Barbara; Deyholos, Michael K; Leebens-Mack, James; Rothfels, Carl J; Stevenson, Dennis W; Graham, Sean W; Wang, Xumin; Wu, Shuangxiu; Pires, J Chris; Edger, Patrick P; Carpenter, Eric J; Bacic, Antony; Doblin, Monika S; Schultz, Carolyn J

    2017-06-01

    The carbohydrate-rich cell walls of land plants and algae have been the focus of much interest given the value of cell wall-based products to our current and future economies. Hydroxyproline-rich glycoproteins (HRGPs), a major group of wall glycoproteins, play important roles in plant growth and development, yet little is known about how they have evolved in parallel with the polysaccharide components of walls. We investigate the origins and evolution of the HRGP superfamily, which is commonly divided into three major multigene families: the arabinogalactan proteins (AGPs), extensins (EXTs), and proline-rich proteins. Using motif and amino acid bias, a newly developed bioinformatics pipeline, we identified HRGPs in sequences from the 1000 Plants transcriptome project (www.onekp.com). Our analyses provide new insights into the evolution of HRGPs across major evolutionary milestones, including the transition to land and the early radiation of angiosperms. Significantly, data mining reveals the origin of glycosylphosphatidylinositol (GPI)-anchored AGPs in green algae and a 3- to 4-fold increase in GPI-AGPs in liverworts and mosses. The first detection of cross-linking (CL)-EXTs is observed in bryophytes, which suggests that CL-EXTs arose though the juxtaposition of preexisting SP n EXT glycomotifs with refined Y-based motifs. We also detected the loss of CL-EXT in a few lineages, including the grass family (Poaceae), that have a cell wall composition distinct from other monocots and eudicots. A key challenge in HRGP research is tracking individual HRGPs throughout evolution. Using the 1000 Plants output, we were able to find putative orthologs of Arabidopsis pollen-specific GPI-AGPs in basal eudicots. © 2017 American Society of Plant Biologists. All Rights Reserved.

  15. Evaluating the Effects of Cytomegalovirus Glycoprotein B on the Maturation and Function of Monocyte-derived dendritic cells

    Directory of Open Access Journals (Sweden)

    Afsson shariat

    2015-11-01

    Full Text Available Background & Objectives: Interaction of cytomegalovirus glycoprotein B with toll-like receptors of dendritic cells leads to early signaling and innate immune responses. The aim of this study is to evaluate the effects of cytomegalovirus glycoprotein B on the maturation and function of monocyte-derived dendritic cells in treated groups in comparison with control groups. Materials & Methods: Blood samples were taken from 5 healthy volunteers. Following the generation of monocyte-derived dendritic cells on the fifth day of cell culture, half of the immature dendritic cells were treated with cytomegalovirus glycoprotein B, and the rest of them were induced to mature dendritic untreated cells and were used as the control group. The maturation and function of dendritic cells were evaluated in these two groups. Results: The gene expression level of toll-like receptor-4 significantly increased in the group treated with glycoprotein B (p < 0.05, whereas there were no significant differences in the expression rates of CD83, CD86, CD1a, and HLA-DR and the secretion of IL-23 from monocyte-derived dendritic cells between the treated groups and the controls. Conclusion: The increase in the gene expression of toll-like receptor-4 in monocyte-derived dendritic cells treated with cytomegalovirus glycoprotein B showed that cell contact is required to elicit cellular antiviral response and toll-like receptor activation. Thus, it is critical to recognize the viral and cellular determinants of the immune system in order to develop new therapeutic strategies against cytomegalovirus.

  16. The hypobranchial mucin of the whelk Buccinum undatum L. Properties of the mucin and of the glycoprotein component.

    Science.gov (United States)

    Hunt, S; Jevons, F R

    1965-12-01

    1. The composition of the hypobranchial mucin from Buccinum undatum is reported. 2. The amino acid composition was determined; aspartic acid and glutamic acid contribute almost 24% of the total amino acids in the mucin. 3. Serine, threonine and alanine, in the proportions 2:1:1 respectively, were detected as N-terminal residues, implying the presence of at least four protein chains. 4. A glycoprotein component was isolated by phenol precipitation. 5. The glycoprotein contained 8% of neutral sugars comprising glucose, galactose, mannose and fucose, and 4.5% of hexosamine, comprising glucosamine and galactosamine in equal proportions. 6. A method is described for the preparation of glycopeptides from the glycoprotein. 7. The comparative biochemistry of the mucin is discussed.

  17. Lysosomal abnormalities in hereditary spastic paraplegia types SPG15 and SPG11

    Science.gov (United States)

    Renvoisé, Benoît; Chang, Jaerak; Singh, Rajat; Yonekawa, Sayuri; FitzGibbon, Edmond J; Mankodi, Ami; Vanderver, Adeline; Schindler, Alice B; Toro, Camilo; Gahl, William A; Mahuran, Don J; Blackstone, Craig; Pierson, Tyler Mark

    2014-01-01

    Objective Hereditary spastic paraplegias (HSPs) are among the most genetically diverse inherited neurological disorders, with over 70 disease loci identified (SPG1-71) to date. SPG15 and SPG11 are clinically similar, autosomal recessive disorders characterized by progressive spastic paraplegia along with thin corpus callosum, white matter abnormalities, cognitive impairment, and ophthalmologic abnormalities. Furthermore, both have been linked to early-onset parkinsonism. Methods We describe two new cases of SPG15 and investigate cellular changes in SPG15 and SPG11 patient-derived fibroblasts, seeking to identify shared pathogenic themes. Cells were evaluated for any abnormalities in cell division, DNA repair, endoplasmic reticulum, endosomes, and lysosomes. Results Fibroblasts prepared from patients with SPG15 have selective enlargement of LAMP1-positive structures, and they consistently exhibited abnormal lysosomal storage by electron microscopy. A similar enlargement of LAMP1-positive structures was also observed in cells from multiple SPG11 patients, though prominent abnormal lysosomal storage was not evident. The stabilities of the SPG15 protein spastizin/ZFYVE26 and the SPG11 protein spatacsin were interdependent. Interpretation Emerging studies implicating these two proteins in interactions with the late endosomal/lysosomal adaptor protein complex AP-5 are consistent with shared abnormalities in lysosomes, supporting a converging mechanism for these two disorders. Recent work with Zfyve26−/− mice revealed a similar phenotype to human SPG15, and cells in these mice had endolysosomal abnormalities. SPG15 and SPG11 are particularly notable among HSPs because they can also present with juvenile parkinsonism, and this lysosomal trafficking or storage defect may be relevant for other forms of parkinsonism associated with lysosomal dysfunction. PMID:24999486

  18. Co-assembly of viral envelope glycoproteins regulates their polarized sorting in neurons.

    Directory of Open Access Journals (Sweden)

    Rafael Mattera

    2014-05-01

    Full Text Available Newly synthesized envelope glycoproteins of neuroinvasive viruses can be sorted in a polarized manner to the somatodendritic and/or axonal domains of neurons. Although critical for transneuronal spread of viruses, the molecular determinants and interregulation of this process are largely unknown. We studied the polarized sorting of the attachment (NiV-G and fusion (NiV-F glycoproteins of Nipah virus (NiV, a paramyxovirus that causes fatal human encephalitis, in rat hippocampal neurons. When expressed individually, NiV-G exhibited a non-polarized distribution, whereas NiV-F was specifically sorted to the somatodendritic domain. Polarized sorting of NiV-F was dependent on interaction of tyrosine-based signals in its cytosolic tail with the clathrin adaptor complex AP-1. Co-expression of NiV-G with NiV-F abolished somatodendritic sorting of NiV-F due to incorporation of NiV-G•NiV-F complexes into axonal transport carriers. We propose that faster biosynthetic transport of unassembled NiV-F allows for its proteolytic activation in the somatodendritic domain prior to association with NiV-G and axonal delivery of NiV-G•NiV-F complexes. Our study reveals how interactions of viral glycoproteins with the host's transport machinery and between themselves regulate their polarized sorting in neurons.

  19. Use of a fragment of glycoprotein G-2 produced in the baculovirus expression system for detecting herpes simplex virus type 2-specific antibodies

    NARCIS (Netherlands)

    Ikoma, M; Liljeqvist, JA; Glazenburg, KL; The, TH; Welling-Wester, S; Groen, J.

    Fragments of glycoprotein G (gG-2(281-594His)), comprising residues 281 to 594 of herpes simplex virus type 2 (HSV-2), glycoprotein G of HSV-1 (gG-1(t26-189His)), and glycoprotein D of HSV-1 (gD-1(1-313)), were expressed in the baculovirus expression system to develop an assay for the detection of

  20. Mechanical circulatory support is associated with loss of platelet receptors glycoprotein Ibα and glycoprotein VI.

    Science.gov (United States)

    Lukito, P; Wong, A; Jing, J; Arthur, J F; Marasco, S F; Murphy, D A; Bergin, P J; Shaw, J A; Collecutt, M; Andrews, R K; Gardiner, E E; Davis, A K

    2016-11-01

    Essentials Relationship of acquired von Willebrand disease (VWD) and platelet dysfunction is explored. Patients with ventricular assist devices and on extracorporeal membrane oxygenation are investigated. Acquired VWD and platelet receptor shedding is demonstrated in the majority of patients. Loss of platelet adhesion receptors glycoprotein (GP) Ibα and GPVI may increase bleeding risk. Background Ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) are associated with bleeding that is not fully explained by anticoagulant or antiplatelet use. Exposure of platelets to elevated shear in vitro leads to increased shedding. Objectives To investigate whether loss of platelet receptors occurs in vivo, and the relationship with acquired von Willebrand syndrome (AVWS). Methods Platelet counts, coagulation tests and von Willebrand factor (VWF) analyses were performed on samples from 21 continuous flow VAD (CF-VAD), 20 ECMO, 12 heart failure and seven aortic stenosis patients. Levels of platelet receptors were measured by flow cytometry or ELISA. Results The loss of high molecular weight VWF multimers was observed in 18 of 19 CF-VAD and 14 of 20 ECMO patients, consistent with AVWS. Platelet receptor shedding was demonstrated by elevated soluble glycoprotein (GP) VI levels in plasma and significantly reduced surface GPIbα and GPVI levels in CF-VAD and ECMO patients as compared with healthy donors. Platelet receptor levels were also significantly reduced in heart failure patients. Conclusions These data link AVWS and increased platelet receptor shedding in patients with CF-VADs or ECMO for the first time. Loss of the platelet surface receptors GPIbα and GPVI in heart failure, CF-VAD and ECMO patients may contribute to ablated platelet adhesion/activation, and limit thrombus formation under high/pathologic shear conditions. © 2016 International Society on Thrombosis and Haemostasis.

  1. Plant abnormality inspection device

    International Nuclear Information System (INIS)

    Takenaka, Toshio.

    1990-01-01

    The present invention concerns a plant abnormality inspection device for conducting remote or automatic patrolling inspection in a plant and, more particularly, relates to such a device as capable of detecting abnormal odors. That is, the device comprises a moving device for moving to a predetermined position in the plant, a plurality of gas sensors for different kind of gases to be inspected mounted thereon, a comparator for comparing the concentration of a gas detected by the gas sensor with the normal gas concentration at the predetermined position and a judging means for judging the absence or presence of abnormality depending on the combination of the result of the comparison and deliverying a signal if the state is abnormal. As a result, a slight amount of gas responsible to odors released upon abnormality of the plant can be detected by a plurality of gas sensors for different kinds gases to rapidly and easily find abnormal portions in the plant. (I.S.)

  2. Report to Congress on abnormal occurrences, January--March 1988

    International Nuclear Information System (INIS)

    1988-07-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from January 1 to March 31, 1988. For this reporting period, there were three abnormal occurrences at nuclear power plants licensed to operate: a potential for common mode failure of safety-related components due to a degraded instrument air system at Fort Calhoun; common mode failures of main steam isolation valves at Perry Unit 1; and a cracked pipe weld in a safety injection system at Farley Unit 2. There were six abnormal occurrences at other NRC licensees: a diagnostic medical misadministration; a breakdown in management controls at the Georgia Institute of Technology reactor facility; release of polonium-210 from static elimination devices manufactured by the 3M Company; two therapeutic medical misadministrationS; and a significant widespread breakdown in the radiation safety program at Case Western Reserve University research laboratories. There was one abnormal occurrence reported by an Agreement State (Texas) involving radiation injury to two radiographers. The report also contains information updating some previously reported abnormal occurrences. 43 refs

  3. Synthesis of Structures Related to Antifreeze Glycoproteins

    OpenAIRE

    Fyrner, Timmy

    2005-01-01

    In this thesis, synthesis of structures related to antifreeze glycoproteins (AFGPs) are presented. Synthetic routes to a protected carbohydrate derivative, 2,3,4,6-tetra-O-benzyl-β-galactopyranosyl-(1→3)-2-deoxy-2-azido-4,6-di-O-benzyl-β-D-thio-1-galactopyranoside, and a tBu-Ala-Thr-Ala-Fmoc tripeptide, are described. These compounds are meant to be used in the assembly of AFGPs and analogues thereof. A Gal-GlcN disaccharide was synthesized via glycosylation between the donor, bromo-2-O-benzo...

  4. Virion Glycoprotein-Mediated Immune Evasion by Human Cytomegalovirus: a Sticky Virus Makes a Slick Getaway

    Science.gov (United States)

    Gardner, Thomas J.

    2016-01-01

    SUMMARY The prototypic herpesvirus human cytomegalovirus (CMV) exhibits the extraordinary ability to establish latency and maintain a chronic infection throughout the life of its human host. This is even more remarkable considering the robust adaptive immune response elicited by infection and reactivation from latency. In addition to the ability of CMV to exist in a quiescent latent state, its persistence is enabled by a large repertoire of viral proteins that subvert immune defense mechanisms, such as NK cell activation and major histocompatibility complex antigen presentation, within the cell. However, dissemination outside the cell presents a unique existential challenge to the CMV virion, which is studded with antigenic glycoprotein complexes targeted by a potent neutralizing antibody response. The CMV virion envelope proteins, which are critical mediators of cell attachment and entry, possess various characteristics that can mitigate the humoral immune response and prevent viral clearance. Here we review the CMV glycoprotein complexes crucial for cell attachment and entry and propose inherent properties of these proteins involved in evading the CMV humoral immune response. These include viral glycoprotein polymorphism, epitope competition, Fc receptor-mediated endocytosis, glycan shielding, and cell-to-cell spread. The consequences of CMV virion glycoprotein-mediated immune evasion have a major impact on persistence of the virus in the population, and a comprehensive understanding of these evasion strategies will assist in designing effective CMV biologics and vaccines to limit CMV-associated disease. PMID:27307580

  5. Complement inhibition enables tumor delivery of LCMV glycoprotein pseudotyped viruses in the presence of antiviral antibodies

    Directory of Open Access Journals (Sweden)

    Laura Evgin

    2016-01-01

    Full Text Available The systemic delivery of therapeutic viruses, such as oncolytic viruses or vaccines, is limited by the generation of neutralizing antibodies. While pseudotyping of rhabdoviruses with the lymphocytic choriomeningitis virus glycoprotein has previously allowed for multiple rounds of delivery in mice, this strategy has not translated to other animal models. For the first time, we provide experimental evidence that antibodies generated against the lymphocytic choriomeningitis virus glycoprotein mediate robust complement-dependent viral neutralization via activation of the classical pathway. We show that this phenotype can be capitalized upon to deliver maraba virus pseudotyped with the lymphocytic choriomeningitis virus glycoprotein in a Fischer rat model in the face of neutralizing antibody through the use of complement modulators. This finding changes the understanding of the humoral immune response to arenaviruses, and also describes methodology to deliver viral vectors to their therapeutic sites of action without the interference of neutralizing antibody.

  6. Structural and functional analysis of bovine herpesvirus 1 minor glycoproteins

    NARCIS (Netherlands)

    Baranowski, E.; Keil, G.; Lyaku, J.; Rijsewijk, F.A.M.; Oirschot, van J.T.; Pastoret, P.P.; Thiry, E.

    1996-01-01

    This paper focuses on the structure and functions of bovine herpesvirus 1 minor glycoproteins gH, gE, gG and gp42. It reviews the progress which has been made in their identification and characterization, in the study of their temporal expression and processing in infected cells, and finally in the

  7. Raman optical activity of proteins and glycoproteins

    International Nuclear Information System (INIS)

    Smyth, E.

    2000-03-01

    Raman optical activity (ROA), measured in this project as a small difference in the intensity of Raman scattering from chiral molecules in right- and left-circularly polarised incident laser light, offers the potential to provide more information about the structure of biological molecules in aqueous solution than conventional spectroscopic techniques. Chapter one contains a general discussion of the relative merits of different spectroscopic techniques for structure determination of biomolecules, as well as a brief introduction to ROA. In Chapter two a theoretical analysis of ROA is developed, which extends the discussion in chapter one. The spectrometer setup and sample preparation is then discussed in chapter three. Instrument and sample conditions are monitored to ensure that the best results are obtained. As with any experimental project problems occur, which may result in a degradation of the spectra obtained. The cause of these problems was explored and remedied whenever possible. Chapter four introduces a brief account of protein, glycoprotein and carbohydrate structure and function, with a particular emphasis on the structure of proteins. In the remaining chapters experimental ROA results on proteins and glycoproteins, with some carbohydrate samples, from a wide range of sources are examined. For example, in chapter five some β-sheet proteins are examined. Structural features in these proteins are examined in the extended amide III region of their ROA spectra, revealing that ROA is sensitive to the rigidity or flexibility inherent in proteins. Chapter six concentrates on a group of proteins (usually glycoproteins) known as the serine proteinase inhibitors (serpins). Medically, the serpins are one of the most important groups of proteins of current interest, with wide-ranging implications in conditions such as Down's syndrome, Alzheimer's disease, and emphysema with associated cirrhosis of the liver. With favourable samples and conditions ROA may offer the

  8. The glycoprotein genes and gene junctions of the fish rhabdoviruses spring viremia of carp virus and hirame rhabdovirus: Analysis of relationships with other rhabdoviruses

    Science.gov (United States)

    Bjorklund, H.V.; Higman, K.H.; Kurath, G.

    1996-01-01

    The nucleotide sequences of the glycoprotein genes and all of the internal gene junctions of the fish pathogenic rhabdoviruses spring viremia of carp virus (SVCV) and hirame rhabdovirus (HIRRV) have been determined from cDNA clones generated from viral genomic RNA. The SVCV glycoprotein gene sequence is 1588 nucleotides (nt) long and encodes a 509 amino acid (aa) protein. The HIRRV glycoprotein gene sequence comprises 1612 nt, coding for a 508 aa protein. In sequence comparisons of 15 rhabdovirus glycoproteins, the SVCV glycoprotein gene showed the highest amino acid sequence identity (31.2–33.2%) with vesicular stomatitis New Jersey virus (VSNJV), Chandipura virus (CHPV) and vesicular stomatitis Indiana virus (VSIV). The HIRRV glycoprotein gene showed a very high amino acid sequence identity (74.3%) with the glycoprotein gene of another fish pathogenic rhabdovirus, infectious hematopoietic necrosis virus (IHNV), but no significant similarity with glycoproteins of VSIV or rabies virus (RABV). In phylogenetic analyses SVCV was grouped consistently with VSIV, VSNJV and CHPV in the Vesiculovirus genus of Rhabdoviridae. The fish rhabdoviruses HIRRV, IHNV and viral hemorrhagic septicemia virus (VHSV) showed close relationships with each other, but only very distant relationships with mammalian rhabdoviruses. The gene junctions are highly conserved between SVCV and VSIV, well conserved between IHNV and HIRRV, but not conserved between HIRRV/IHNV and RABV. Based on the combined results we suggest that the fish lyssa-type rhabdoviruses HIRRV, IHNV and VHSV may be grouped in their own genus within the family Rhabdoviridae. Aquarhabdovirus has been proposed for the name of this new genus.

  9. Abnormal ovarian cancer screening test result: women's informational, psychological and practical needs.

    Science.gov (United States)

    Ryan, Patricia Y; Graves, Kristi D; Pavlik, Edward J; Andrykowski, Michael A

    2007-01-01

    Considerable effort has been devoted to the identification of cost-effective approaches to screening for ovarian cancer (OC). Transvaginal ultrasound (TVS) is one such screening approach. Approximately 5-7% of routine TVS screening tests yield abnormal results. Some women experience significant distress after receipt of an abnormal TVS screening test. Four focus groups provided in-depth, qualitative data regarding the informational, psychological, and practical needs of women after the receipt of an abnormal TVS result. Through question and content analytic procedures, we identified four themes: anticipation, emotional response, role of the screening technician, and impact of prior cancer experiences. Results provide initial guidance toward development of interventions to promote adaptive responses after receipt of an abnormal cancer screening test result.

  10. Abnormal pressures as hydrodynamic phenomena

    Science.gov (United States)

    Neuzil, C.E.

    1995-01-01

    So-called abnormal pressures, subsurface fluid pressures significantly higher or lower than hydrostatic, have excited speculation about their origin since subsurface exploration first encountered them. Two distinct conceptual models for abnormal pressures have gained currency among earth scientists. The static model sees abnormal pressures generally as relict features preserved by a virtual absence of fluid flow over geologic time. The hydrodynamic model instead envisions abnormal pressures as phenomena in which flow usually plays an important role. This paper develops the theoretical framework for abnormal pressures as hydrodynamic phenomena, shows that it explains the manifold occurrences of abnormal pressures, and examines the implications of this approach. -from Author

  11. P-glycoprotein interaction with risperidone and 9-OH-risperidone studied in vitro, in knock-out mice and in drug-drug interaction experiments

    DEFF Research Database (Denmark)

    Ejsing, Thomas B.; Pedersen, Anne D.; Linnet, Kristian

    2005-01-01

    P-glycoprotein, risperidone, nortriptyline, cyclosporine A, drug-drug interaction, blood-brain barrier, knock-out mice......P-glycoprotein, risperidone, nortriptyline, cyclosporine A, drug-drug interaction, blood-brain barrier, knock-out mice...

  12. Tumor specific glycoproteins and method for detecting tumorigenic cancers

    International Nuclear Information System (INIS)

    Davidson, E.A.; Bolmer, S.D.

    1981-01-01

    The detection of tumour specific glycoproteins (TSGP) in human sera often indicates the presence of a malignant tumour in a patient. The distinguishing characteristics of TSGP isolated from the blood sera of cancer patients are described in detail together with methods of TSGP isolation and purification. Details are also given of radioimmunoassay techniques capable of detecting very low levels of serum TSGP with high specificity. (U.K.)

  13. The incidence of associated abnormalities in patients with sacrococcygeal teratoma.

    Science.gov (United States)

    Kremer, Marijke E B; Althof, Jessica F; Derikx, Joep P M; van Baren, Robertine; Heij, Hugo A; Wijnen, Marc H W A; Wijnen, René M H; van der Zee, David C; van Heurn, L W Ernest

    2018-01-31

    Gross genetic causes for SCT are unknown; however, it might be associated with other abnormalities. We assessed the incidence of associated abnormalities in a large national cohort of neonates with SCT and aimed to identify predictive risk factors. The medical records were reviewed of 235 consecutive neonates with SCT treated at the six pediatric surgical centers in the Netherlands from 1970 to 2010. Potential risk factors for associated abnormalities analyzed included sex, gestational age, tumor-volume/histology and Altman-classification. In 76 patients (32.3%) at least one associated abnormality was diagnosed, with hydronephrosis as the most common (16.2%) and hip dysplasia in 4.3%. Multiple abnormalities were documented for 21 (9.0%). Prematurity and Altman type IV SCT were associated with an increased risk of any associated abnormality. No association between increased tumor-volume and hydronephrosis or hip dysplasia was found. Patients with type IV Altman SCT had a fourfold risk of suffering from hydronephrosis compared to Altman type I SCT. SCT was associated with other abnormalities in one-third of children. Some were tumor-related while others were related to prematurity or occurred sporadically. In contrast to clinically obvious anomalies, hip dysplasia or hydronephrosis might be latently present with more subtle clinical presentation. We therefore suggest renal- and hip-ultrasound in all patients, certainly those with Altman type IV SCT. Level II (retrospective study). Copyright © 2018. Published by Elsevier Inc.

  14. Validation of an improved abnormality insertion method for medical image perception investigations

    Science.gov (United States)

    Madsen, Mark T.; Durst, Gregory R.; Caldwell, Robert T.; Schartz, Kevin M.; Thompson, Brad H.; Berbaum, Kevin S.

    2009-02-01

    The ability to insert abnormalities in clinical tomographic images makes image perception studies with medical images practical. We describe a new insertion technique and its experimental validation that uses complementary image masks to select an abnormality from a library and place it at a desired location. The method was validated using a 4-alternative forced-choice experiment. For each case, four quadrants were simultaneously displayed consisting of 5 consecutive frames of a chest CT with a pulmonary nodule. One quadrant was unaltered, while the other 3 had the nodule from the unaltered quadrant artificially inserted. 26 different sets were generated and repeated with order scrambling for a total of 52 cases. The cases were viewed by radiology staff and residents who ranked each quadrant by realistic appearance. On average, the observers were able to correctly identify the unaltered quadrant in 42% of cases, and identify the unaltered quadrant both times it appeared in 25% of cases. Consensus, defined by a majority of readers, correctly identified the unaltered quadrant in only 29% of 52 cases. For repeats, the consensus observer successfully identified the unaltered quadrant only once. We conclude that the insertion method can be used to reliably place abnormalities in perception experiments.

  15. Protein and Site Specificity of Fucosylation in Liver-Secreted Glycoproteins

    Czech Academy of Sciences Publication Activity Database

    Pompach, Petr; Ashline, David J.; Brnáková, Z.; Benicky, J.; Sanda, M.; Goldman, R.

    2014-01-01

    Roč. 13, č. 12 (2014), s. 5561-5569 ISSN 1535-3893 R&D Projects: GA MŠk LH13051; GA ČR GAP206/12/0503 Grant - others:Charles Univ.(CZ) UNCE_204025/2012 Institutional support: RVO:61388971 Keywords : fucose * glycoproteins * liver * site specificity Subject RIV: CE - Biochemistry Impact factor: 4.245, year: 2014

  16. Internalization and Axonal Transport of the HIV Glycoprotein gp120

    Science.gov (United States)

    Berth, Sarah; Caicedo, Hector Hugo; Sarma, Tulika; Morfini, Gerardo

    2015-01-01

    The HIV glycoprotein gp120, a neurotoxic HIV glycoprotein that is overproduced and shed by HIV-infected macrophages, is associated with neurological complications of HIV such as distal sensory polyneuropathy, but interactions of gp120 in the peripheral nervous system remain to be characterized. Here, we demonstrate internalization of extracellular gp120 in a manner partially independent of binding to its coreceptor CXCR4 by F11 neuroblastoma cells and cultured dorsal root ganglion neurons. Immunocytochemical and pharmacological experiments indicate that gp120 does not undergo trafficking through the endolysosomal pathway. Instead, gp120 is mainly internalized through lipid rafts in a cholesterol-dependent manner, with a minor fraction being internalized by fluid phase pinocytosis. Experiments using compartmentalized microfluidic chambers further indicate that, after internalization, endocytosed gp120 selectively undergoes retrograde but not anterograde axonal transport from axons to neuronal cell bodies. Collectively, these studies illuminate mechanisms of gp120 internalization and axonal transport in peripheral nervous system neurons, providing a novel framework for mechanisms for gp120 neurotoxicity. PMID:25636314

  17. Characterization of a novel brain barrier ex vivo insect-based P-glycoprotein screening model

    DEFF Research Database (Denmark)

    Andersson, O.; Badisco, L.; Hansen, A. H.

    2014-01-01

    In earlier studies insects were proposed as suitable models for vertebrate blood–brain barrier (BBB) permeability prediction and useful in early drug discovery. Here we provide transcriptome and functional data demonstrating the presence of a P-glycoprotein (Pgp) efflux transporter in the brain b...... has the potential to act as a robust and convenient model for assessing BBB permeability in early drug discovery.......In earlier studies insects were proposed as suitable models for vertebrate blood–brain barrier (BBB) permeability prediction and useful in early drug discovery. Here we provide transcriptome and functional data demonstrating the presence of a P-glycoprotein (Pgp) efflux transporter in the brain...

  18. Stable isotope labeling of glycoprotein expressed in silkworms using immunoglobulin G as a test molecule

    Energy Technology Data Exchange (ETDEWEB)

    Yagi, Hirokazu [Nagoya City University, Faculty and Graduate School of Pharmaceutical Sciences (Japan); Nakamura, Masatoshi [National Institute of Agrobiological Sciences, Genetic Resources Conservation Research Unit, Genetic Resources Center (Japan); Yokoyama, Jun [Taiyo Nippon Sanso Corporation, Tsukuba Laboratories (Japan); Zhang, Ying; Yamaguchi, Takumi [National Institutes of Natural Sciences, Institute for Molecular Science and Okazaki Institute for Integrative Bioscience (Japan); Kondo, Sachiko [Nagoya City University, Faculty and Graduate School of Pharmaceutical Sciences (Japan); Kobayashi, Jun [Yamaguchi University, Department of Biological and Environmental Sciences, Faculty of Agriculture (Japan); Kato, Tatsuya; Park, Enoch Y. [Shizuoka University, Laboratory of Biotechnology, Research Institute of Green Science and Technology (Japan); Nakazawa, Shiori [Nagoya University, Sugashima Marine Biological Laboratory, Graduate School of Science (Japan); Hashii, Noritaka; Kawasaki, Nana [National Institute of Health Sciences, Division of Biological Chemistry and Biologicals (Japan); Kato, Koichi, E-mail: kkato@phar.nagoya-cu.ac.jp [Nagoya City University, Faculty and Graduate School of Pharmaceutical Sciences (Japan)

    2015-06-15

    Silkworms serve as promising bioreactors for the production of recombinant proteins, including glycoproteins and membrane proteins, for structural and functional protein analyses. However, lack of methodology for stable isotope labeling has been a major deterrent to using this expression system for nuclear magnetic resonance (NMR) structural biology. Here we developed a metabolic isotope labeling technique using commercially available silkworm larvae. The fifth instar larvae were infected with baculoviruses for co-expression of recombinant human immunoglobulin G (IgG) as a test molecule, with calnexin as a chaperone. They were subsequently reared on an artificial diet containing {sup 15}N-labeled yeast crude protein extract. We harvested 0.1 mg of IgG from larva with a {sup 15}N-enrichment ratio of approximately 80 %. This allowed us to compare NMR spectral data of the Fc fragment cleaved from the silkworm-produced IgG with those of an authentic Fc glycoprotein derived from mammalian cells. Therefore, we successfully demonstrated that our method enables production of isotopically labeled glycoproteins for NMR studies.

  19. Human intestinal P-glycoprotein activity estimated by the model substrate digoxin

    DEFF Research Database (Denmark)

    Larsen, U L; Hyldahl Olesen, L; Nyvold, Charlotte Guldborg

    2007-01-01

    P-glycoprotein (Pgp) plays a part in the intestinal uptake of xenobiotics and has been associated with susceptibility to ulcerative colitis. The aim of this study was to examine Pgp activity in relation to age, gender, medical treatment (rifampicin or ketoconazole) and the multidrug resistance (MDR...

  20. Identification and partial characterization of Taastrup virus: a newly identified member species of the Mononegavirales

    International Nuclear Information System (INIS)

    Bock, J.O.; Lundsgaard, T.; Pedersen, P.A.; Christensen, L.S.

    2004-01-01

    We present a 8904-nt sequence of the central part of the RNA genome of a novel virus with a filovirus-like, nonidentical morphology named Taastrup virus (TV) detected in the leafhopper Psammotettix alienus. Sequence analysis identified five potential open reading frames (ORFs) and a complex pattern of homologies to various members of the Mononegavirales suggests a genome organization with the following order of genes: 3'-N-P-M-G-L-5'. Sequence analyses reveal an unusually large glycoprotein (G) containing both potential O-linked (14) and N-linked (9) glycosylation sites--a feature shared with the glycoproteins of Filoviridae and Pneumovirinae, and a nucleoprotein (N) with homology to the nucleoprotein of viral hemorrhagic septicemia virus (VHSV), a member of the Rhabdoviridae. Highly conserved domains were identified in the RNA-dependent RNA polymerase (L) between TV and other viruses within the order of Mononegavirales, and homology was found in particular with members of the Rhabdoviridae. The sequence similarities and the unique filovirus-like but nonidentical morphology unambiguously refer this newly identified virus to the order of Mononegavirales but to no family more than any, to other within the order

  1. Chicken galectin-1B inhibits Newcastle disease virus adsorption and replication through binding to hemagglutinin-neuraminidase (HN) glycoprotein.

    Science.gov (United States)

    Sun, Junfeng; Han, Zongxi; Qi, Tianming; Zhao, Ran; Liu, Shengwang

    2017-12-08

    Galectin-1 is an important immunoregulatory factor and can mediate the host-pathogen interaction via binding glycans on the surface of various viruses. We previously reported that avian respiratory viruses, including lentogenic Newcastle disease virus (NDV), can induce up-regulation of chicken galectin (CG)-1B in the primary target organ. In this study, we investigated whether CG-1B participated in the infectious process of NDV in chickens. We demonstrated that velogenic NDV induced up-regulation of CG-1B in target organs. We also found that CG-1B directly bound to NDV virions and inhibited their hemagglutination activity in vitro We confirmed that CG-1B interacted with NDV hemagglutinin-neuraminidase (HN) glycoprotein, in which the specific G4 N -glycans significantly contributed to the interaction between CG-1B and HN glycoprotein. The presence of extracellular CG-1B, rather than the internalization process, inhibited adsorption of NDV. The interaction between intracellular CG-1B and NDV HN glycoproteins inhibited cell-surface expression of HN glycoprotein and reduced the titer of progeny virus in NDV-infected DF-1 cells. Significantly, the replication of parental and HN glycosylation mutant viruses in CG-1B knockdown and overexpression cells demonstrated that the replication of NDV was correlated with the expression of CG-1B in a specific glycan-dependent manner. Collectively, our results indicate that CG-1B has anti-NDV activity by binding to N -glycans on HN glycoprotein. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Glycoprotein folding and quality-control mechanisms in protein-folding diseases

    Directory of Open Access Journals (Sweden)

    Sean P. Ferris

    2014-03-01

    Full Text Available Biosynthesis of proteins – from translation to folding to export – encompasses a complex set of events that are exquisitely regulated and scrutinized to ensure the functional quality of the end products. Cells have evolved to capitalize on multiple post-translational modifications in addition to primary structure to indicate the folding status of nascent polypeptides to the chaperones and other proteins that assist in their folding and export. These modifications can also, in the case of irreversibly misfolded candidates, signal the need for dislocation and degradation. The current Review focuses on the glycoprotein quality-control (GQC system that utilizes protein N-glycosylation and N-glycan trimming to direct nascent glycopolypeptides through the folding, export and dislocation pathways in the endoplasmic reticulum (ER. A diverse set of pathological conditions rooted in defective as well as over-vigilant ER quality-control systems have been identified, underlining its importance in human health and disease. We describe the GQC pathways and highlight disease and animal models that have been instrumental in clarifying our current understanding of these processes.

  3. Abnormal sound detection device

    International Nuclear Information System (INIS)

    Yamada, Izumi; Matsui, Yuji.

    1995-01-01

    Only components synchronized with rotation of pumps are sampled from detected acoustic sounds, to judge the presence or absence of abnormality based on the magnitude of the synchronized components. A synchronized component sampling means can remove resonance sounds and other acoustic sounds generated at a synchronously with the rotation based on the knowledge that generated acoustic components in a normal state are a sort of resonance sounds and are not precisely synchronized with the number of rotation. On the other hand, abnormal sounds of a rotating body are often caused by compulsory force accompanying the rotation as a generation source, and the abnormal sounds can be detected by extracting only the rotation-synchronized components. Since components of normal acoustic sounds generated at present are discriminated from the detected sounds, reduction of the abnormal sounds due to a signal processing can be avoided and, as a result, abnormal sound detection sensitivity can be improved. Further, since it is adapted to discriminate the occurrence of the abnormal sound from the actually detected sounds, the other frequency components which are forecast but not generated actually are not removed, so that it is further effective for the improvement of detection sensitivity. (N.H.)

  4. Report to Congress on abnormal occurrences, October-December 1986

    International Nuclear Information System (INIS)

    1987-07-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from October 1 to December 31, 1986. The report states that for this reporting period, there were three abnormal occurrences at the nuclear power plants licensed to operate. The events were (1) loss of low pressure service water systems at Oconee, (2) degraded safety systems due to incorrect torque switch settings on Rotors motor operators at Catawba and McGuire Nuclear Stations, and (3) a secondary system pipe break resulting in the death of four persons at Surry Unit 2. There were six abnormal occurrences at the other NRC licensees. One involved release of americium-241 inside a waste storage building at Wright-Patterson Air Force Base; three involved medical misadministrations, one therapeutic and two diagnostic; one involved a suspension of license for servicing teletherapy and radiography units; and one involved an immediately effective order modifying license and order to show cause issued to an industrial radiography company. There were no abnormal occurrences reported by the Agreement States. The report also contains information updating some previously reported abnormal occurrences

  5. The handicap of abnormal colour vision.

    Science.gov (United States)

    Cole, Barry L

    2004-07-01

    All people with abnormal colour vision, except for a few mildly affected deuteranomals, report that they experience problems with colour in everyday life and at work. Contemporary society presents them with increasing problems because colour is now so widely used in printed materials and in computer displays. Equal opportunity law gives them protection against unfair discrimination in employment, so a decision to exclude a person from employment on the grounds of abnormal colour vision must now be well supported by good evidence and sound argument. This paper reviews the investigations that have contributed to understanding the nature and consequences of the problems they have. All those with abnormal colour vision are at a disadvantage with comparative colour tasks that involve precise matching of colours or discrimination of fine colour differences either because of their loss of colour discrimination or anomalous perception of metamers. The majority have problems when colour is used to code information, in man-made colour codes and in naturally occurring colour codes that signal ripeness of fruit, freshness of meat or illness. They can be denied the benefit of colour to mark out objects and organise complex visual displays. They may be unreliable when a colour name is used as an identifier. They are slower and less successful in search when colour is an attribute of the target object or is used to organise the visual display. Because those with the more severe forms of abnormal colour vision perceive a very limited gamut of colours, they are at a disadvantage in the pursuit and appreciation of those forms of art that use colour.

  6. Predictors of abnormal heart rate response to dipyridamole in patients undergoing myocardial perfusion SPECT

    International Nuclear Information System (INIS)

    De Souza Leao Lima, R.; Machado, L.; Azevedo, A.B.; De Lorenzo, A.

    2011-01-01

    The objective of this study was to identify predictors of abnormal HR response to dipyridamole (DIP) in patients undergoing myocardial perfusion SPECT (MPS). Patients with a reduced heart rate (HR) response to DIP have higher cardiac mortality, but the mechanism is unknown. We studied 432 patients who underwent dual-isotope gated MPS. DIP (0.56 mg/kg) was infused over 4 min, and Tc-99m tetrofosmin was injected 3 min after the end of the infusion. MPS was semiquantitatively interpreted. Left ventricular ejection fraction (LVEF) and volumes were automatically calculated. The population was categorized into quartiles according to HR ratio, and characteristics in each quartile were compared. Logistic regression analysis was performed to identify predictors of abnormal HR response, using the lowest quartile as the independent variable. Patients with abnormal HR response were more frequently without chest pain, with a history of chronic renal failure and taking digoxin. Baseline HR was higher and had fewer symptoms during stress. The stress and rest perfusion defects were greater, but reversibility was not; in addition, LVEF was lower. Multivariable logistic regression analysis demonstrated that the independent predictors of abnormal HR response were baseline HR and low LVEF. LV dysfunction is an independent predictor of abnormal HR response to DIP, and the association between low LVEF and low HR ratio may explain the link between abnormal HR ratio and increased mortality. (author)

  7. Substantial excretion of digoxin via the intestinal mucosa and prevention of long-term digoxin accumulation in the brain by the mdr1a P-glycoprotein

    NARCIS (Netherlands)

    Mayer, U; Wagenaar, E; Beijnen, J.H; Smit, J.W; Meijer, D.K F; van Asperen, J.; Borst, P; Schinkel, A.H

    1 We have used mice with a disrupted mdrla P-glycoprotein gene (mdrIa (-/-) mice) to study the role of P-glycoprotein in the pharmacokinetics of digoxin, a model P-glycoprotein substrate. 2 [K-3]-digoxin at a dose of 0.2 mg kg(-1) was administered as a single i.v. or oral bolus injection. We

  8. Chromosomal abnormalities in 163 Tunisian couples with recurrent ...

    African Journals Online (AJOL)

    The aim of the present study was to identify the distribution of chromosome abnormalities among Tunisian couples with RM referred to the Department of Cytogenetic at the Pasteur Institute of Tunis (Tunisia) during the last five years. Standard cytogenetic analysis was carried out in a total of 163 couples presenting with two ...

  9. Conglutinin binds the HIV-1 envelope glycoprotein gp 160 and inhibits its interaction with cell membrane CD4

    DEFF Research Database (Denmark)

    Andersen, Ove; Sørensen, A M; Svehag, S E

    1991-01-01

    The highly glycosylated envelope glycoprotein (gp 160) of human immunodeficiency virus (HIV) interacts with the CD4 molecule present on the membrane of CD4+ cells and is involved in the pathobiology of HIV infection. Lectins bind glycoproteins through non-covalent interactions with specific hexose...... residues. The mammalian C-type lectin bovine conglutinin was examined for its ability to interact with recombinant gp160 (rgp160) produced in vaccinia virus-infected BHK21 cells. Specific binding of conglutinin to rgp160 was demonstrated by ELISA. The interaction of bovine conglutinin with rgp160...... of the binding of rgp160 to the CD4 receptor on CEM 13 cells, as demonstrated by FACS analyses. These results indicate that conglutinin may inhibit the infection with HIV-1 through its interaction with the viral envelope glycoprotein....

  10. Characterization of Vesicular Stomatitis Virus Recombinants That Express and Incorporate High Levels of Hepatitis C Virus Glycoproteins

    OpenAIRE

    Buonocore, Linda; Blight, Keril J.; Rice, Charles M.; Rose, John K.

    2002-01-01

    We generated recombinant vesicular stomatitis viruses (VSV) expressing genes encoding hybrid proteins consisting of the extracellular domains of hepatitis C virus (HCV) glycoproteins fused at different positions to the transmembrane and cytoplasmic domains of the VSV G glycoprotein (E1G and E2G). We show that these chimeric proteins are transported to the cell surface and incorporated into VSV virions efficiently. We also generated VSV recombinants in which the gene encoding the VSV G protein...

  11. Secondary Abnormalities of Neurotransmitters in Infants with Neurological Disorders

    Science.gov (United States)

    Garcia-Cazorla, A.; Serrano, M.; Perez-Duenas, B.; Gonzalez, V.; Ormazabal, A.; Pineda, M.; Fernandez-Alvarez, E.; Campistol, J. M. D.; Artuch, R. M. D.

    2007-01-01

    Neurotransmitters are essential in young children for differentiation and neuronal growth of the developing nervous system. We aimed to identify possible factors related to secondary neurotransmitter abnormalities in pediatric patients with neurological disorders. We analyzed cerebrospinal fluid (CSF) and biogenic amine metabolites in 56 infants…

  12. Protein and Glycoprotein Patterns Related to Morphogenesis in Mammillaria gracillis Pfeiff. Tissue Culture

    Directory of Open Access Journals (Sweden)

    Biljana Balen

    2002-01-01

    Full Text Available As plants with Crassulacean Acid Metabolism (CAM, cacti are highly affected by artificial environmental conditions in tissue culture. Plants of Mammillaria gracillis Pfeiff. (Cactaceae propagated in vitro produced callus spontaneously. This habituated callus regenerated normal and hyperhydric shoots without the addition of growth regulators. In order to compare habituated callus with the tumorous one, cactus cells were transformed with two strains of Agrobacterium tumefaciens: the wild strain B6S3 (tumour line TW and the rooty mutant GV3101 (tumour line TR. Gene expression in cactus plants, habituated callus, regenerated shoots and two tumour lines was analysed at the level of cellular and extracellular protein and glycoprotein profiles. Proteins were separated by SDS-polyacrylamide gel electrophoresis and 2-D PAGE electrophoresis and silver stained. Concavalin A-peroxidase staining detected glycoproteins with D-manose in their glycan component on protein blots. Developmentally specific protein patterns of Mammillaria gracillis tissue lines were detected. The 2-D PAGE electrophoresis revealed some tissue specific protein groups. The cellular glycoprotein of 42 kDa detected by ConA was highly expressed in undifferentiated tissues (habituated callus, TW and TR tumours and in hyperhydric regenerants. Tumours produced extracellular proteins of 33, 23 and 22 kDa. The N glycosylation of cellular and extracellular proteins was related to specific developmental stage of cactus tissue.

  13. Feline tetherin is characterized by a short N-terminal region and is counteracted by the feline immunodeficiency virus envelope glycoprotein.

    Science.gov (United States)

    Celestino, Michele; Calistri, Arianna; Del Vecchio, Claudia; Salata, Cristiano; Chiuppesi, Flavia; Pistello, Mauro; Borsetti, Alessandra; Palù, Giorgio; Parolin, Cristina

    2012-06-01

    Tetherin (BST2) is the host cell factor that blocks the particle release of some enveloped viruses. Two putative feline tetherin proteins differing at the level of the N-terminal coding region have recently been described and tested for their antiviral activity. By cloning and comparing the two reported feline tetherins (called here cBST2(504) and cBST2*) and generating specific derivative mutants, this study provides evidence that feline tetherin has a shorter intracytoplasmic domain than those of other known homologues. The minimal tetherin promoter was identified and assayed for its ability to drive tetherin expression in an alpha interferon-inducible manner. We also demonstrated that cBST2(504) is able to dimerize, is localized at the cellular membrane, and impairs human immunodeficiency virus type 1 (HIV-1) particle release, regardless of the presence of the Vpu antagonist accessory protein. While cBST2(504) failed to restrict wild-type feline immunodeficiency virus (FIV) egress, FIV mutants, bearing a frameshift at the level of the envelope-encoding region, were potently blocked. The transient expression of the FIV envelope glycoprotein was able to rescue mutant particle release from feline tetherin-positive cells but did not antagonize human BST2 activity. Moreover, cBST2(504) was capable of specifically immunoprecipitating the FIV envelope glycoprotein. Finally, cBST2(504) also exerted its function on HIV-2 ROD10 and on the simian immunodeficiency virus SIVmac239. Taken together, these results show that feline tetherin does indeed have a short N-terminal region and that the FIV envelope glycoprotein is the predominant factor counteracting tetherin restriction.

  14. Gamma-radiolysis of some glycoproteins in dilute aqueous solutions

    Energy Technology Data Exchange (ETDEWEB)

    Nagrani, S

    1981-01-01

    A study has been made of the radiation-induced damage of some glycoproteins in dilute aqueous solutions. By use of specific radical scavengers, the roles of the individual free radicals, formed by ..gamma..-radiolysis, in causing damage has been assessed. The most effective radical in causing damage to human and porcine glycopolypeptide is the OH radical. The structure of the different blood group glycopolypeptides determines the sensitivity towards the free radical attack. The glycopolypeptide shows depolymerization and a characteristic absorption at approximately 270 nm due to the formation of additional products on irradiation. Chemical changes of the irradiated glycopolypeptide solutions revealed significant damage to the oligosaccharide chain and the polypeptide core of the glycopolypeptide. The radiation-induced inactivation of another glycoprotein, external yeast invertase, due to different radical species at pH 7.0 decreases in the following order: ea-barq > OH radical > (SCN) radical/sub 2//sup -/ > Br radical/sub 2//sup -/. The structure of this enzyme, accounts for the mechanism of enzyme inactivation and the relative damage of carbohydrate and amino acid residues. The irradiated enzyme solutions show significant changes in their electrophoretic behaviour on cellogel electrophoresis due to the formation of radiolysis products, which also show characteristic absorption maxima at approximately 275 nm. (author).

  15. New insights into the Hendra virus attachment and entry process from structures of the virus G glycoprotein and its complex with Ephrin-B2.

    Directory of Open Access Journals (Sweden)

    Kai Xu

    Full Text Available Hendra virus and Nipah virus, comprising the genus Henipavirus, are recently emerged, highly pathogenic and often lethal zoonotic agents against which there are no approved therapeutics. Two surface glycoproteins, the attachment (G and fusion (F, mediate host cell entry. The crystal structures of the Hendra G glycoprotein alone and in complex with the ephrin-B2 receptor reveal that henipavirus uses Tryptophan 122 on ephrin-B2/B3 as a "latch" to facilitate the G-receptor association. Structural-based mutagenesis of residues in the Hendra G glycoprotein at the receptor binding interface document their importance for viral attachments and entry, and suggest that the stability of the Hendra-G-ephrin attachment complex does not strongly correlate with the efficiency of viral entry. In addition, our data indicates that conformational rearrangements of the G glycoprotein head domain upon receptor binding may be the trigger leading to the activation of the viral F fusion glycoprotein during virus infection.

  16. An alternative conformation of the gp41 heptad repeat 1 region coiled coil exists in the human immunodeficiency virus (HIV-1) envelope glycoprotein precursor

    International Nuclear Information System (INIS)

    Mische, Claudia C.; Yuan Wen; Strack, Bettina; Craig, Stewart; Farzan, Michael; Sodroski, Joseph

    2005-01-01

    The human immunodeficiency virus (HIV-1) transmembrane envelope glycoprotein, gp41, which mediates virus-cell fusion, exists in at least three different conformations within the trimeric envelope glycoprotein complex. The structures of the prefusogenic and intermediate states are unknown; structures representing the postfusion state have been solved. In the postfusion conformation, three helical heptad repeat 2 (HR2) regions pack in an antiparallel fashion into the hydrophobic grooves on the surface of a triple-helical coiled coil formed by the heptad repeat 1 (HR1) regions. We studied the prefusogenic conformation of gp41 by mutagenic alteration of membrane-anchored and soluble forms of the HIV-1 envelope glycoproteins. Our results indicate that, in the HIV-1 envelope glycoprotein precursor, the gp41 HR1 region is in a conformation distinct from that of a trimeric coiled coil. Thus, the central gp41 coiled coil is formed during the transition of the HIV-1 envelope glycoproteins from the precursor state to the receptor-bound intermediate

  17. Mapping of linear antibody epitopes of the glycoprotein of VHSV, a salmonid rhabdovirus

    DEFF Research Database (Denmark)

    Fernandez-Alonso, M.; Lorenzo, G.; Perez, L.

    1998-01-01

    antibodies (MAbs), only 2 non-neutralizing MAbs, I10 (aa 139-153) and IP1H3 (aa 399-413), could be mapped to specific peptides in the pepscan of the gpG. Mapping of these MAbs was confirmed by immunoblotting with recombinant proteins and/or other synthetic peptides covering those sequences. None......Antibody Linear epitopes of the glycoprotein G (gpG) of the viral haemorrhagic septicaemia virus (VHSV), a rhabdovirus of salmonids, were mapped by pepscan using overlapping 15-mer peptides covering the entire gpG sequence and ELISA with polyclonal and monoclonal murine and polyclonal trout...... antibodies. Among the regions recognized in the pepscan by the polyclonal antibodies (PAbs) were the previously identified phosphatidylserine binding heptad-repeats (Estepa & Coll 1996; Virology 216:60-70) and leucocyte stimulating peptides (Lorenzo et al. 1995; Virology 212:348-355). Among 17 monoclonal...

  18. Human platelet glycoprotein Ia. One component is only expressed on the surface of activated platelets and may be a granule constituent

    International Nuclear Information System (INIS)

    Bienz, D.; Clemetson, K.J.

    1989-01-01

    Glycoprotein Ia (GP Ia) is a relatively minor component of human blood platelets thought to be a receptor involved in collagen-induced platelet activation. However, some difficulties exist with the definition of this glycoprotein. The expression of GP Ia on resting (prostacyclin analogue-treated) and thrombin-activated platelets was compared by surface labeling with 125 I-lactoperoxidase. Intact platelets or platelets solubilized in sodium dodecyl sulfate were labeled with periodate/[ 3 H]NaBH 4 . Analysis on two-dimensional isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels showed that GP Ia is very poorly labeled in resting platelets. After activation a new spot (GP Ia*) appears with the same relative molecular mass as GP Ia under reducing conditions. GP Ia and Ia* can be clearly separated by two-dimensional nonreduced/reduced gel electrophoresis. Therefore, two glycoproteins which have been termed GP Ia exist in platelets with similar molecular weight and pI under reducing conditions. One of these (GP Ia*) is only surface-labeled when platelets are activated, indicating that it is only exposed on the surface of activated platelets. Supernatant from activated platelets contains this glycoprotein as well as other granule components. This glycoprotein is missing in platelets from two patients with collagen-response defects

  19. What is the value of ultrasound soft tissue measurements in the prediction of abnormal fetal growth?

    LENUS (Irish Health Repository)

    Farah, N

    2012-02-01

    Abnormal fetal growth increases the complications of pregnancy not only for the baby but also for the mother. Growth abnormalities also have lifelong consequences. These babies are at increased risk of insulin resistance, diabetes and hypertension later in life. It is important to identify these babies antenatally to optimise their clinical care. Although used extensively antenatally to monitor fetal growth, ultrasound has its limitations. Despite the use of more than 50 different formulae to estimate fetal weight, their performance has been poor at the extremes of fetal weight. Over the past 20 years there has been emerging interest in studying fetal soft tissue measurements to improve detection of growth abnormalities. This review paper outlines the value of soft tissue measurements in identifying fetal growth abnormalities, in estimating fetal weight and in managing diabetes mellitus in pregnancy.

  20. High-performance liquid chromatography of human glycoprotein hormones.

    Science.gov (United States)

    Chlenov, M A; Kandyba, E I; Nagornaya, L V; Orlova, I L; Volgin, Y V

    1993-02-12

    The chromatographic behavior of the glycoprotein hormones from human pituitary glands and of placental origin [thyroid-stimulating hormone, luteinizing hormone and chorionic gonadotropin (CG)] was studied. It was shown that hydrophobic interaction chromatography on a microparticulate packing and anion-exchange HPLC can be applied for the purification of these hormones. Reversed-phase HPLC on wide-pore C4-bonded silica at neutral pH can be applied for the determination of the above hormones and for the isolation of pure CG and its subunits.

  1. Electrocardiographic abnormalities in opiate addicts.

    Science.gov (United States)

    Wallner, Christina; Stöllberger, Claudia; Hlavin, Anton; Finsterer, Josef; Hager, Isabella; Hermann, Peter

    2008-12-01

    To determine in a cross-sectional study the prevalence of electrocardiographic (ECG) abnormalities in opiate addicts who were therapy-seeking and its association with demographic, clinical and drug-specific parameters. In consecutive therapy-seeking opiate addicts, a 12-lead ECG was registered within 24 hours after admission and evaluated according to a pre-set protocol between October 2004 and August 2006. Additionally, demographic, clinical and drug-specific parameters were recorded. Included were 511 opiate-addicts, 25% female, with a mean age of 29 years (range 17-59 years). One or more ECG abnormalities were found in 314 patients (61%). In the 511 patients we found most commonly ST abnormalities (19%), QTc prolongation (13%), tall R- and/or S-waves (11%) and missing R progression (10%). ECG abnormalities were more common in males than in females (64 versus 54%, P seizures less often (16 versus 27%, P opiate addicts. The most frequent ECG abnormalities are ST abnormalities, QTc prolongation and tall R- and/or S-waves. ST abnormalities are associated with cannabis, and QTc prolongation with methadone and benzodiazepines.

  2. Clinical outcomes and a high prevalence of abnormalities on comprehensive arterial and venous thrombophilia screening in TIA or ischaemic stroke patients with a patent foramen ovale, an inter-atrial septal aneurysm or both.

    Science.gov (United States)

    Lim, Soon Tjin; Murphy, Stephen J X; Smith, Deirdre R; Williams, Jennifer; Navarro, Silvia Gil; McCabe, John; Moore, David P; McHugh, Johnny; McCabe, Dominick J H

    2017-06-15

    Data are limited on the optimal management of cryptogenic TIA/stroke patients with a patent foramen ovale (PFO)±inter-atrial septal aneurysm (IASA), especially with an inherited thrombophilia. Prospectively-collected data on TIA/ischaemic stroke patients with PFO, IASA or both who received 'goal-directed secondary-prevention medical treatment' were analysed. All patients had trans-oesophageal echocardiography, anti-nuclear, anti-cardiolipin, anti-beta 2 glycoprotein I antibodies, rheumatoid factor, lupus anticoagulant, protein C&S, anti-thrombin, factor VIII activity, activated protein C resistance, Factor V Leiden, prothrombin gene and MTHFR-c.677C>T mutation screening. ENA and homocysteine were assessed in the latter study period. Eighty-three patients were recruited. Mean follow-up: 48.1months. Forty-seven patients (56.6%) had an isolated PFO, 32 (38.6%) a PFO and an IASA, and 4 (4.8%) an IASA alone. Eighteen (21.7%) had ≥1 abnormality on thrombophilia screening. The most important abnormalities which lead to treatment changes in 11 patients (13.3%) were primary anti-phospholipid syndrome (N=3; 3.6%), protein S deficiency (N=2; 2.4%) hyper-homocysteinaemia (N=6/72 screened, 8.3%). Four patients (4.8%) opted for PFO closure: two with protein S deficiency, and two with no identified thrombophilia. Seven (8.4%) had recurrent TIA/ischaemic stroke during follow-up (overall annualised incidence: 2.1%), of whom five had a PFO alone and two a PFO and IASA. Comprehensive arterial and venous thrombophilia screening is warranted in TIA/ischaemic stroke patients with a PFO±IASA, is conclusively abnormal in over a fifth, and informed important decision-making regarding individualised therapy in 13.3% of patients. The incidence of recurrent vascular events in this population is low on optimal, personalised secondary-prevention treatment, even with an underlying thrombophilia. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Magnetic enzyme reactors for isolation and study of heterogeneous glycoproteins

    International Nuclear Information System (INIS)

    Korecka, Lucie; Jezova, Jana; Bilkova, Zuzana; Benes, Milan; Horak, Daniel; Hradcova, Olga; Slovakova, Marcela; Viovy, Jean-Louis

    2005-01-01

    The newly developed magnetic micro- and nanoparticles with defined hydrophobicity and porosity were used for the preparation of magnetic enzyme reactors. Magnetic particles with immobilized proteolytic enzymes trypsin, chymotrypsin and papain and with enzyme neuraminidase were used to study the structure of heterogeneous glycoproteins. Factors such as the type of carrier, immobilization procedure, operational and storage stability, and experimental conditions were optimized

  4. Roentgenologic abnormalities in Down's syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Higuchi, Takehiko; Russell, W J; Komatsuda, Michio; Neriishi, Shotaro

    1968-07-25

    Roentgenograms of 28 patients with Down's syndrome were reviewed with emphasis on all previously reported abnormalities and any possible additional ones. Most of the abnormalities occurred with the same frequency as previously reported, but some less frequently reported findings were also seen. One abnormal vertebral measurement found in this series may be an additional stigma of Down's syndrome. All of the 27 cases studied cytogenetically had chromosomal abnormalities consistent with this disease. This study emphasizes the need for roentgenologic norms for the Japanese, and the desirability of combining chromosome studies with roentgenological abnormalities and clinical observations in diagnosing Down's syndrome. 19 references, 2 figures, 5 tables.

  5. N-terminal substitutions in HIV-1 gp41 reduce the expression of non-trimeric envelope glycoproteins on the virus

    International Nuclear Information System (INIS)

    Dey, Antu K.; David, Kathryn B.; Ray, Neelanjana; Ketas, Thomas J.; Klasse, Per J.; Doms, Robert W.; Moore, John P.

    2008-01-01

    The native, functional HIV-1 envelope glycoprotein (Env) complex is a trimer of two non-covalently associated subunits: the gp120 surface glycoprotein and the gp41 transmembrane glycoprotein. However, various non-functional forms of Env are present on virus particles and HIV-1-infected cells, some of which probably arise as the native complex decays. The aberrant forms include gp120-gp41 monomers and oligomers, as well as gp41 subunits from which gp120 has dissociated. The presence of non-functional Env creates binding sites for antibodies that do not recognize native Env complexes and that are, therefore, non-neutralizing. Non-native Env forms (monomers, dimers, tetramers and aggregates) can also arise when soluble gp140 proteins, lacking the cytoplasmic and transmembrane domains of gp41, are expressed for vaccine studies. We recently identified five amino acids in the gp41 N-terminal region (I535, Q543, S553, K567 and R588) that promote gp140 trimerization. We have now studied their influence on the function and antigenic properties of JR-FL Env expressed on the surfaces of pseudoviruses and Env-transfected cells. The 5 substitutions in gp41 reduce the expression of non-trimeric gp160s, without affecting trimer levels. Pseudovirions bearing the mutant Env are fully infectious with similar kinetics of Env-mediated fusion. Various non-neutralizing antibodies bind less strongly to the Env mutant, but neutralizing antibody binding is unaffected. Hence the gp41 substitutions do not adversely affect Env structure, supporting their use for making new Env-based vaccines. The mutant Env might also help in studies intended to correlate antibody binding to virus neutralization. Of note is that the 5 residues are much more frequent, individually or collectively, in viruses from subtypes other than B

  6. A Simplified Model of Glycoprotein Production within Cell Culture

    OpenAIRE

    Lambert, A. B.; Smith, F. T.; Velayudhan, A.

    2017-01-01

    Complex biological products, such as those used to treat various forms of cancer, are typically produced by mammalian cells in bioreactors. The most important class of such biological medicines is proteins. These typically bind to sugars (glycans) in a process known as glycosylation, creating glycoproteins, which are more stable and effective medicines. The glycans are large polymers that are formed by a long sequence of enzyme catalysed reactions. This sequence is not always completed, thus ...

  7. Report to Congress on abnormal occurrences, April-June 1985. Volume 8, No. 2

    International Nuclear Information System (INIS)

    1985-11-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. For this reporting period, there were three abnormal occurrences at the nuclear power plants licensed to operate: (1) inoperable safety injection pumps, (2) significant deficiencies in reactor operator training and material false statements, and (3) loss of main and auxiliary feedwater systems. There were four abnormal occurrences at the other NRC licensees. Three events involved diagnostic or therapeutic medical misadministrations; the other involved a breakdown in management controls. There was one abnormal occurrence reported by an Agreement State; the event involved overexposures of a radiographer and an assistant radiographer. The report also contains information updating some previously reported abnormal occurrences

  8. Ca 125 and Ca 19-9: two cancer-associated sialylsaccharide antigens on a mucus glycoprotein from human milk.

    Science.gov (United States)

    Hanisch, F G; Uhlenbruck, G; Dienst, C; Stottrop, M; Hippauf, E

    1985-06-03

    The cancer-associated antigens Ca 125 and Ca 19-9 were demonstrated by radioimmunoassay to form structural units of a mucus glycoprotein in human milk taken from healthy women four days after parturition. The glycoprotein precipitated with the casein fraction at pH 4.6 and was completely absent in the whey as judged from Ca 19-9 assay. It could be effectively enriched by phenol-saline extraction from soluble milk proteins and further purified by gel filtration on Sephacryl S300 and Sephacryl S400. The active component with a bouyant density of 1.41 g/ml in isopycnic density gradient centrifugation (CsCl) shared common physico-chemical and chemical characteristics of mucus glycoproteins. Carbohydrates representing about 68% by weight were conjugated to protein by alkali-labile linkages, exclusively and were essentially free of D-mannose. Activities of Ca 125 and Ca 19-9 were both destroyed by treatment with periodate, mild alkali or neuraminidase suggesting the antigens are sialylated saccharides bound to protein by alkali-labile linkages. The fraction of monosialylated saccharide alditols isolated after reductive beta-elimination from the mucus glycoprotein was shown to inhibit monoclonal antibodies anti-(Ca 125) and anti-(Ca 19-9) in radioimmunoassay.

  9. Genetic analysis of the SARS-coronavirus spike glycoprotein functional domains involved in cell-surface expression and cell-to-cell fusion

    International Nuclear Information System (INIS)

    Petit, Chad M.; Melancon, Jeffrey M.; Chouljenko, Vladimir N.; Colgrove, Robin; Farzan, Michael; Knipe, David M.; Kousoulas, K.G.

    2005-01-01

    The SARS-coronavirus (SARS-CoV) is the etiological agent of severe acute respiratory syndrome (SARS). The SARS-CoV spike (S) glycoprotein mediates membrane fusion events during virus entry and virus-induced cell-to-cell fusion. To delineate functional domains of the SARS-CoV S glycoprotein, single point mutations, cluster-to-lysine and cluster-to-alanine mutations, as well as carboxyl-terminal truncations were investigated in transient expression experiments. Mutagenesis of either the coiled-coil domain of the S glycoprotein amino terminal heptad repeat, the predicted fusion peptide, or an adjacent but distinct region, severely compromised S-mediated cell-to-cell fusion, while intracellular transport and cell-surface expression were not adversely affected. Surprisingly, a carboxyl-terminal truncation of 17 amino acids substantially increased S glycoprotein-mediated cell-to-cell fusion suggesting that the terminal 17 amino acids regulated the S fusogenic properties. In contrast, truncation of 26 or 39 amino acids eliminating either one or both of the two endodomain cysteine-rich motifs, respectively, inhibited cell fusion in comparison to the wild-type S. The 17 and 26 amino-acid deletions did not adversely affect S cell-surface expression, while the 39 amino-acid truncation inhibited S cell-surface expression suggesting that the membrane proximal cysteine-rich motif plays an essential role in S cell-surface expression. Mutagenesis of the acidic amino-acid cluster in the carboxyl terminus of the S glycoprotein as well as modification of a predicted phosphorylation site within the acidic cluster revealed that this amino-acid motif may play a functional role in the retention of S at cell surfaces. This genetic analysis reveals that the SARS-CoV S glycoprotein contains extracellular domains that regulate cell fusion as well as distinct endodomains that function in intracellular transport, cell-surface expression, and cell fusion

  10. Mining the O-mannose glycoproteome reveals cadherins as major O-mannosylated glycoproteins

    DEFF Research Database (Denmark)

    Vester-Christensen, Malene B; Halim, Adnan; Joshi, Hiren Jitendra

    2013-01-01

    The metazoan O-mannose (O-Man) glycoproteome is largely unknown. It has been shown that up to 30% of brain O-glycans are of the O-Man type, but essentially only alpha-dystroglycan (α-DG) of the dystrophin-glycoprotein complex is well characterized as an O-Man glycoprotein. Defects in O-Man...... glycosylation underlie congenital muscular dystrophies and considerable efforts have been devoted to explore this O-glycoproteome without much success. Here, we used our SimpleCell strategy using nuclease-mediated gene editing of a human cell line (MDA-MB-231) to reduce the structural heterogeneity of O-Man...... glycans and to probe the O-Man glycoproteome. In this breast cancer cell line we found that O-Man glycosylation is primarily found on cadherins and plexins on β-strands in extracellular cadherin and Ig-like, plexin and transcription factor domains. The positions and evolutionary conservation of O-Man...

  11. Chromosomal aneuploidies and copy number variations in posterior fossa abnormalities diagnosed by prenatal ultrasonography.

    Science.gov (United States)

    Lei, Ting; Feng, Jie-Ling; Xie, Ying-Jun; Xie, Hong-Ning; Zheng, Ju; Lin, Mei-Fang

    2017-11-01

    To explore the genetic aetiology of fetal posterior fossa abnormalities (PFAs). This study involved cases of PFAs that were identified by prenatal ultrasonographic screening and confirmed postnatally between January 2012 and January 2016. Conventional cytogenetic analyses and chromosomal microarray analysis were performed, and chromosomal aneuploidies and copy number variations (CNVs) were identified. Among 74 cases included in this study, 8 were of Blake's pouch cyst; 7, Dandy-Walker malformation; 11, vermian hypoplasia; 32, enlarged cisterna magna; and 16, cerebellar hypoplasia. The rates of nonbenign chromosomal aberrations (including chromosomal aneuploidies, pathogenic CNVs, and variants of unknown significance) were 2/8 (25.0%), 2/7 (28.5%), 8/11 (72.7%), 7/32 (21.9%), and 6/16 (37.5%), respectively. Cases were also classified as isolated PFAs (30/74), PFAs with other central nervous system (CNS) abnormalities (13/74), or PFAs with extra-CNS structural abnormalities (31/74). No fetuses with isolated PFAs or PFAs accompanied by other CNS abnormalities exhibited chromosomal aneuploidies or pathogenic CNVs. The rate of pathogenic chromosomal aberrations in the remaining fetuses was 17/31 (22.9%). The combined use of chromosomal microarray analysis and karyotype analysis might assist the prenatal diagnosis and management of PFAs, with extra-CNS structural abnormalities being detected by ultrasonography. © 2017 John Wiley & Sons, Ltd.

  12. Human CRISP-3 binds serum alpha(1)B-glycoprotein across species

    DEFF Research Database (Denmark)

    Udby, Lene; Johnsen, Anders H; Borregaard, Niels

    2010-01-01

    CRISP-3 was previously shown to be bound to alpha(1)B-glycoprotein (A1BG) in human serum/plasma. All mammalian sera are supposed to contain A1BG, although its presence in rodent sera is not well-documented. Since animal sera are often used to supplement buffers in experiments, in particular...

  13. Abnormality diagnosis device for nuclear reactor

    Energy Technology Data Exchange (ETDEWEB)

    Utsunomiya, Kazuhiro; Oyama, Shinmi; Sakaba, Hideo

    1989-02-21

    According to the present invention, abnormality such as abnormal increase of temperature in a nuclear reactor is detected to send a signal to control rod drives, etc. thereby stopping the operation of the nuclear reactor. Receiving/transmission device transmits a signal for conducting normal operation of an abnormality information section, as well as receives an echo signal from the abnormality information section to transmit an abnormal signal to a reactor protection system. The abnormality information section is disposed to fuel assemblies, receives a signal from the receiving/transmission device for conducting the normal operation to transmit a normal echo signal, as well as changes the echo signal when detecting the nuclear reactor abnormality. By the foregoing method, since the abnormality information section is disposed to the fuel assemblies, various effects can be attained such as: (1) there is no response delay from the occurrence of abnormality to emergency counter measure after detection, (2) high burnup degree for fuels can thus be possible to improve the economical property, (3) the abnormality information section can be taken out from the reactor container together with fuel assemablies by an existent take-out mechanism and (4) since wireless transmission and reception are established between the receiving/transmission device and the abnormality information section, cables are not required in the container. (K.M.).

  14. Up-regulation of P-glycoprotein expression by catalase via JNK activation in HepG2 cells.

    Science.gov (United States)

    Li, Lin; Xu, Jianfeng; Min, Taishan; Huang, Weida

    2006-01-01

    Overexpression of the MDR1 gene is one of the reasons for multidrug resistance (MDR). Some studies suggested that antioxidants could down-regulate MDR1 expression as a possible cancer treatment. In this report, we try to determine the effects of antioxidants (catalase or N-acetylcysteine [NAC]) on the regulation of intrinsic MDR1 overexpression in HepG2 cells. Adding catalase or N-acetylcysteine to the HepG2 culture led to a significant increase of MDR1 mRNA and P-glycoprotein drug transporter activity. After catalase or NAC treatment, a reduced intracellular reactive oxygen species (ROS) was observed. The JNK inhibitor SP600125 abolished the positive effects of catalase on drug transporter activity in a dose-dependent manner. Furthermore, the up-regulation of P-glycoprotein functions by catalase was only observed in HepG2 cells but not in other cell lines tested (MCF-7, A549, A431). These data suggested that catalase can up-regulate P-glycoprotein expression in HepG2 cells via reducing intracellular ROS, and JNK may mediate this process.

  15. A Single Center Experience on the Management of Placental Invasion Abnormalities

    Directory of Open Access Journals (Sweden)

    Alper Biler

    2016-03-01

    Full Text Available Objective: The aim of this study is to investigate our management of placental invasion abnormalities. Methods: A retrospective study was conducted on pa­tients admitted to a tertiary referral center with a diagno­sis of placental invasion abnormalities between 2011 and 2015. Risk factors and perinatal outcomes associated with placental invasion abnormalities were identified. Results: The overall incidence of placental invasion ab­normalities during the 5-year period was 8.3/10000 de­liveries, which showed an increasing trend. Ultrasonog­raphy and magnetic resonance imaging correctly identi­fied placental invasion abnormality in 36.7% and 68.7% cases, respectively. Majority of patients (55.1% with ad­herent placenta were diagnosed at the time of delivery. Of these patients, 22.4% underwent hysterectomy, 83.8% required at least one of the additional surgical procedures and 55% were transfused at least four units of packed red blood cell. Conclusion: Since placental invasion abnormalities are associated with significant morbidity, delivery should be scheduled in a tertiary center with appropriate expertise and facilities. J Clin Exp Invest 2016; 7 (1: 14-18

  16. Abnormal Event Detection in Wireless Sensor Networks Based on Multiattribute Correlation

    Directory of Open Access Journals (Sweden)

    Mengdi Wang

    2017-01-01

    Full Text Available Abnormal event detection is one of the vital tasks in wireless sensor networks. However, the faults of nodes and the poor deployment environment have brought great challenges to abnormal event detection. In a typical event detection technique, spatiotemporal correlations are collected to detect an event, which is susceptible to noises and errors. To improve the quality of detection results, we propose a novel approach for abnormal event detection in wireless sensor networks. This approach considers not only spatiotemporal correlations but also the correlations among observed attributes. A dependency model of observed attributes is constructed based on Bayesian network. In this model, the dependency structure of observed attributes is obtained by structure learning, and the conditional probability table of each node is calculated by parameter learning. We propose a new concept named attribute correlation confidence to evaluate the fitting degree between the sensor reading and the abnormal event pattern. On the basis of time correlation detection and space correlation detection, the abnormal events are identified. Experimental results show that the proposed algorithm can reduce the impact of interference factors and the rate of the false alarm effectively; it can also improve the accuracy of event detection.

  17. Palmitoylation of the cysteine-rich endodomain of the SARS-coronavirus spike glycoprotein is important for spike-mediated cell fusion

    International Nuclear Information System (INIS)

    Petit, Chad M.; Chouljenko, Vladimir N.; Iyer, Arun; Colgrove, Robin; Farzan, Michael; Knipe, David M.; Kousoulas, K.G.

    2007-01-01

    The SARS-coronavirus (SARS-CoV) is the etiological agent of the severe acute respiratory syndrome (SARS). The SARS-CoV spike (S) glycoprotein mediates membrane fusion events during virus entry and virus-induced cell-to-cell fusion. The cytoplasmic portion of the S glycoprotein contains four cysteine-rich amino acid clusters. Individual cysteine clusters were altered via cysteine-to-alanine amino acid replacement and the modified S glycoproteins were tested for their transport to cell-surfaces and ability to cause cell fusion in transient transfection assays. Mutagenesis of the cysteine cluster I, located immediately proximal to the predicted transmembrane, domain did not appreciably reduce cell-surface expression, although S-mediated cell fusion was reduced by more than 50% in comparison to the wild-type S. Similarly, mutagenesis of the cysteine cluster II located adjacent to cluster I reduced S-mediated cell fusion by more than 60% compared to the wild-type S, while cell-surface expression was reduced by less than 20%. Mutagenesis of cysteine clusters III and IV did not appreciably affect S cell-surface expression or S-mediated cell fusion. The wild-type S was palmitoylated as evidenced by the efficient incorporation of 3 H-palmitic acid in wild-type S molecules. S glycoprotein palmitoylation was significantly reduced for mutant glycoproteins having cluster I and II cysteine changes, but was largely unaffected for cysteine cluster III and IV mutants. These results show that the S cytoplasmic domain is palmitoylated and that palmitoylation of the membrane proximal cysteine clusters I and II may be important for S-mediated cell fusion

  18. Prevalence and predictors of an abnormal stress myocardial perfusion study in asymptomatic patients with type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    Scholte, Arthur J.H.A.; Schuijf, Joanne D.; Wall, Ernst E. van der; Bax, Jeroen J.; Kharagjitsingh, Antje V.; Dibbets-Schneider, Petra; Stokkel, Marcel P.

    2009-01-01

    The purpose of this study was to evaluate the prevalence of an abnormal stress myocardial perfusion study in a cohort of truly asymptomatic patients with type 2 diabetes mellitus using myocardial perfusion imaging by means of single photon emission computed tomography (SPECT). Secondly, we determined which clinical characteristics may predict an abnormal stress myocardial perfusion study in this population. A total of 120 asymptomatic patients (mean age 53±10 years) with type 2 diabetes mellitus and one or more risk factors for coronary artery disease were prospectively recruited from an outpatient diabetes clinic. All patients underwent myocardial perfusion imaging by means of adenosine 99m Tc sestamibi SPECT. Images were evaluated for the presence of perfusion abnormalities as well as other nonperfusion abnormalities that may indicate extensive ischaemia, including left ventricular dysfunction (defined as a left ventricular ejection fraction <45%), transient ischaemic dilatation and adenosine-induced ST segment depression. Multivariable analysis was performed using a backward selection strategy to identify potential predictors for an abnormal stress myocardial perfusion study. Finally, all patients were followed up for 12 months to determine the occurrence of cardiovascular events: (1) cardiac death, (2) nonfatal myocardial infarction, (3) unstable angina requiring hospitalization, (4) revascularization, or (5) stroke. Of the 120 patients, 40 (33%) had an abnormal stress study, including myocardial perfusion abnormalities in 30 patients (25%). In 10 patients (8%), indicators of extensive (possibly balanced ischaemia) were observed in the absence of abnormal perfusion. The multivariable analysis identified current smoking, duration of diabetes and the cholesterol/high-density lipoprotein (HDL) ratio as independent predictors of an abnormal stress study. During a follow-up period of 12 months six patients (5%) had a cardiovascular event. The current study revealed

  19. Prevalence and predictors of an abnormal stress myocardial perfusion study in asymptomatic patients with type 2 diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Scholte, Arthur J.H.A.; Schuijf, Joanne D.; Wall, Ernst E. van der; Bax, Jeroen J. [Leiden University Medical Center, Department of Cardiology, Albinusdreef 2, PO Box 9600, Leiden (Netherlands); Kharagjitsingh, Antje V. [Medisch Centrum Haaglanden, Department of Internal Medicine, The Hague (Netherlands); Dibbets-Schneider, Petra; Stokkel, Marcel P. [Leiden University Medical Center, Department of Nuclear Medicine, Leiden (Netherlands)

    2009-04-15

    The purpose of this study was to evaluate the prevalence of an abnormal stress myocardial perfusion study in a cohort of truly asymptomatic patients with type 2 diabetes mellitus using myocardial perfusion imaging by means of single photon emission computed tomography (SPECT). Secondly, we determined which clinical characteristics may predict an abnormal stress myocardial perfusion study in this population. A total of 120 asymptomatic patients (mean age 53{+-}10 years) with type 2 diabetes mellitus and one or more risk factors for coronary artery disease were prospectively recruited from an outpatient diabetes clinic. All patients underwent myocardial perfusion imaging by means of adenosine {sup 99m}Tc sestamibi SPECT. Images were evaluated for the presence of perfusion abnormalities as well as other nonperfusion abnormalities that may indicate extensive ischaemia, including left ventricular dysfunction (defined as a left ventricular ejection fraction <45%), transient ischaemic dilatation and adenosine-induced ST segment depression. Multivariable analysis was performed using a backward selection strategy to identify potential predictors for an abnormal stress myocardial perfusion study. Finally, all patients were followed up for 12 months to determine the occurrence of cardiovascular events: (1) cardiac death, (2) nonfatal myocardial infarction, (3) unstable angina requiring hospitalization, (4) revascularization, or (5) stroke. Of the 120 patients, 40 (33%) had an abnormal stress study, including myocardial perfusion abnormalities in 30 patients (25%). In 10 patients (8%), indicators of extensive (possibly balanced ischaemia) were observed in the absence of abnormal perfusion. The multivariable analysis identified current smoking, duration of diabetes and the cholesterol/high-density lipoprotein (HDL) ratio as independent predictors of an abnormal stress study. During a follow-up period of 12 months six patients (5%) had a cardiovascular event. The current study

  20. Molecular insight into conformational transmission of human P-glycoprotein

    International Nuclear Information System (INIS)

    Chang, Shan-Yan; Liu, Fu-Feng; Dong, Xiao-Yan; Sun, Yan

    2013-01-01

    P-glycoprotein (P-gp), a kind of ATP-binding cassette transporter, can export candidates through a channel at the two transmembrane domains (TMDs) across the cell membranes using the energy released from ATP hydrolysis at the two nucleotide-binding domains (NBDs). Considerable evidence has indicated that human P-gp undergoes large-scale conformational changes to export a wide variety of anti-cancer drugs out of the cancer cells. However, molecular mechanism of the conformational transmission of human P-gp from the NBDs to the TMDs is still unclear. Herein, targeted molecular dynamics simulations were performed to explore the atomic detail of the conformational transmission of human P-gp. It is confirmed that the conformational transition from the inward- to outward-facing is initiated by the movement of the NBDs. It is found that the two NBDs move both on the two directions (x and y). The movement on the x direction leads to the closure of the NBDs, while the movement on the y direction adjusts the conformations of the NBDs to form the correct ATP binding pockets. Six key segments (KSs) protruding from the TMDs to interact with the NBDs are identified. The relative movement of the KSs along the y axis driven by the NBDs can be transmitted through α-helices to the rest of the TMDs, rendering the TMDs to open towards periplasm in the outward-facing conformation. Twenty eight key residue pairs are identified to participate in the interaction network that contributes to the conformational transmission from the NBDs to the TMDs of human P-gp. In addition, 9 key residues in each NBD are also identified. The studies have thus provided clear insight into the conformational transmission from the NBDs to the TMDs in human P-gp

  1. Antigiardial activity of glycoproteins and glycopeptides from Ziziphus honey.

    Science.gov (United States)

    Mohammed, Seif Eldin A; Kabashi, Ahmed S; Koko, Waleed S; Azim, M Kamran

    2015-01-01

    Natural honey contains an array of glycoproteins, proteoglycans and glycopeptides. Size-exclusion chromatography fractionated Ziziphus honey proteins into five peaks with molecular masses in the range from 10 to >200 kDa. The fractionated proteins exhibited in vitro activities against Giardia lamblia with IC50 values ≤ 25 μg/mL. Results indicated that honey proteins were more active as antiprotozoal agents than metronidazole. This study indicated the potential of honey proteins and peptides as novel antigiardial agents.

  2. Occurrence of maxillary sinus abnormalities detected by cone beam CT in asymptomatic patients

    Directory of Open Access Journals (Sweden)

    Rege Inara Carneiro

    2012-08-01

    Full Text Available Abstract Background Although cone beam computed tomography (CBCT images of the maxillofacial region allow the inspection of the entire volume of the maxillary sinus (MS, identifying anatomic variations and abnormalities in the image volume, this is frequently neglected by oral radiologists when interpreting images of areas at a distance from the dentoalveolar region, such as the full anatomical aspect of the MS. The aim of this study was to investigate maxillary sinus abnormalities in asymptomatic patients by using CBCT. Methods 1113 CBCT were evaluated by two examiners and identification of abnormalities, the presence of periapical lesions and proximity to the lower sinus wall were recorded. Data were analyzed using descriptive statistics, chi-square tests and Kappa statistics. Results Abnormalities were diagnosed in 68.2% of cases (kappa = 0.83. There was a significant difference between genders (p Conclusions Abnormalities in maxillary sinus emphasizes how important it is for the dentomaxillofacial radiologist to undertake an interpretation of the whole volume of CBCT images.

  3. Report to Congress on abnormal occurrences, January-March 1985. Volume 8, No. 1

    International Nuclear Information System (INIS)

    1985-08-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from January 1 to March 31, 1985. The report states that for this reporting period, there was one abnormal occurrence at the nuclear power plants licensed to operate; the event involved a premature criticality during reactor startup. There were three abnormal occurrences at the other NRC licensees. Two events involved diagnostic medical misadministrations and the other event involved unlawful possession of radioactive material. There were four abnormal occurrences reported by an Agreement State (Texas). Three events involved radiation overexposures; the other event involved a well logging source which was apparently stolen, but later was recovered. The report also contains information updating some previously reported abnormal occurrences

  4. Glycan Reader: Automated Sugar Identification and Simulation Preparation for Carbohydrates and Glycoproteins

    Science.gov (United States)

    Jo, Sunhwan; Song, Kevin C.; Desaire, Heather; MacKerell, Alexander D.; Im, Wonpil

    2011-01-01

    Understanding how glycosylation affects protein structure, dynamics, and function is an emerging and challenging problem in biology. As a first step toward glycan modeling in the context of structural glycobiology, we have developed Glycan Reader and integrated it into the CHARMM-GUI, http://www.charmm-gui.org/input/glycan. Glycan Reader greatly simplifies the reading of PDB structure files containing glycans through (i) detection of carbohydrate molecules, (ii) automatic annotation of carbohydrates based on their three-dimensional structures, (iii) recognition of glycosidic linkages between carbohydrates as well as N-/O-glycosidic linkages to proteins, and (iv) generation of inputs for the biomolecular simulation program CHARMM with the proper glycosidic linkage setup. In addition, Glycan Reader is linked to other functional modules in CHARMM-GUI, allowing users to easily generate carbohydrate or glycoprotein molecular simulation systems in solution or membrane environments and visualize the electrostatic potential on glycoprotein surfaces. These tools are useful for studying the impact of glycosylation on protein structure and dynamics. PMID:21815173

  5. Carbohydrate-dependent binding of langerin to SodC, a cell wall glycoprotein of Mycobacterium leprae.

    Science.gov (United States)

    Kim, Hee Jin; Brennan, Patrick J; Heaslip, Darragh; Udey, Mark C; Modlin, Robert L; Belisle, John T

    2015-02-01

    Langerhans cells participate in the immune response in leprosy by their ability to activate T cells that recognize the pathogen, Mycobacterium leprae, in a langerin-dependent manner. We hypothesized that langerin, the distinguishing C-type lectin of Langerhans cells, would recognize the highly mannosylated structures in pathogenic Mycobacterium spp. The coding region for the extracellular and neck domain of human langerin was cloned and expressed to produce a recombinant active trimeric form of human langerin (r-langerin). Binding assays performed in microtiter plates, by two-dimensional (2D) Western blotting, and by surface plasmon resonance demonstrated that r-langerin possessed carbohydrate-dependent affinity to glycoproteins in the cell wall of M. leprae. This lectin, however, yielded less binding to mannose-capped lipoarabinomannan (ManLAM) and even lower levels of binding to phosphatidylinositol mannosides. However, the superoxide dismutase C (SodC) protein of the M. leprae cell wall was identified as a langerin-reactive ligand. Tandem mass spectrometry verified the glycosylation of a recombinant form of M. leprae SodC (rSodC) produced in Mycobacterium smegmatis. Analysis of r-langerin affinity by surface plasmon resonance revealed a carbohydrate-dependent affinity of rSodC (equilibrium dissociation constant [KD] = 0.862 μM) that was 20-fold greater than for M. leprae ManLAM (KD = 18.69 μM). These data strongly suggest that a subset of the presumptively mannosylated M. leprae glycoproteins act as ligands for langerin and may facilitate the interaction of M. leprae with Langerhans cells. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  6. Galactosemia, a single gene disorder with epigenetic consequences.

    LENUS (Irish Health Repository)

    Coman, David J

    2010-03-01

    Long-term outcomes of classic galactosemia (GAL) remain disappointing. It is unclear if the complications result mainly from prenatal-neonatal toxicity or persistent glycoprotein and glycolipid synthesis abnormalities. We performed gene expression profiling (T transcriptome) to characterize key-altered genes and gene clusters of four patients with GAL with variable outcomes maintained on a galactose-restricted diet, compared with controls. Significant perturbations of multiple cell signaling pathways were observed including mitogen-activated protein kinase (MAPK) signaling, regulation of the actin cytoskeleton, focal adhesion, and ubiquitin mediated proteolysis. A number of genes significantly altered were further investigated in the GAL cohort including SPARC (osteonectin) and S100A8 (S100 calcium-binding protein). The whole serum N-glycan profile and IgG glycosylation status of 10 treated patients with GAL were compared with healthy control serum and IgG using a quantitative high-throughput analytical HPLC platform. Increased levels of agalactosylated and monogalactosylated structures and decreases in certain digalactosylated structures were identified in the patients. The persistent abnormal glycosylation of serum glycoproteins seen with the microarray data indicates persisting metabolic dyshomeostasis and gene dysregulation in "treated" GAL. Strict restriction of dietary galactose is clearly life saving in the neonatal period; long-term severe galactose restriction may contribute to ongoing systemic abnormalities.

  7. Insights into the Evolution of Hydroxyproline-Rich Glycoproteins from 1000 Plant Transcriptomes1[OPEN

    Science.gov (United States)

    Cassin, Andrew M.; Soltis, Douglas E.; Miles, Nicholas W.; Melkonian, Michael; Melkonian, Barbara; Wu, Shuangxiu; Edger, Patrick P.; Carpenter, Eric J.

    2017-01-01

    The carbohydrate-rich cell walls of land plants and algae have been the focus of much interest given the value of cell wall-based products to our current and future economies. Hydroxyproline-rich glycoproteins (HRGPs), a major group of wall glycoproteins, play important roles in plant growth and development, yet little is known about how they have evolved in parallel with the polysaccharide components of walls. We investigate the origins and evolution of the HRGP superfamily, which is commonly divided into three major multigene families: the arabinogalactan proteins (AGPs), extensins (EXTs), and proline-rich proteins. Using motif and amino acid bias, a newly developed bioinformatics pipeline, we identified HRGPs in sequences from the 1000 Plants transcriptome project (www.onekp.com). Our analyses provide new insights into the evolution of HRGPs across major evolutionary milestones, including the transition to land and the early radiation of angiosperms. Significantly, data mining reveals the origin of glycosylphosphatidylinositol (GPI)-anchored AGPs in green algae and a 3- to 4-fold increase in GPI-AGPs in liverworts and mosses. The first detection of cross-linking (CL)-EXTs is observed in bryophytes, which suggests that CL-EXTs arose though the juxtaposition of preexisting SPn EXT glycomotifs with refined Y-based motifs. We also detected the loss of CL-EXT in a few lineages, including the grass family (Poaceae), that have a cell wall composition distinct from other monocots and eudicots. A key challenge in HRGP research is tracking individual HRGPs throughout evolution. Using the 1000 Plants output, we were able to find putative orthologs of Arabidopsis pollen-specific GPI-AGPs in basal eudicots. PMID:28446636

  8. International Team Identifies Biomarker for Scleroderma

    Science.gov (United States)

    ... Spotlight on Research International Team Identifies Biomarker for Scleroderma By Kirstie Saltsman, Ph.D. | May 5, 2014 ... molecule correlates with a more severe form of scleroderma, a chronic autoimmune disorder that involves the abnormal ...

  9. Fibrillin abnormalities and prognosis in Marfan syndrome and related disorders

    Energy Technology Data Exchange (ETDEWEB)

    Aoyama, T.; Furthmayr, H.; Francke, U.; Gasner, C. [Stanford Univ. Medical Center, CA (United States)

    1995-08-28

    Marfan syndrome (MFS), a multisystem autosomal-dominant disorder, is characterized by mutations of the fibrillin-1 (FBN1) gene and by abnormal patterns of synthesis, secretion, and matrix deposition of the fibrillin protein. To determine the sensitivity and specificity of fibrillin protein abnormalities in the diagnosis of MFS, we studied dermal fibroblasts from 57 patients with classical MFS, 15 with equivocal MFS, 8 with single-organ manifestations, and 16 with other connective tissue disorders including homocystinuria and Ehlers-Danlos syndrome. Abnormal fibrillin metabolism was identified in 70 samples that were classified into four different groups based on quantitation of fibrillin synthesis and matrix deposition. Significant correlations were found for phenotypic features including arachnodactyly, striae distensae, cardiovascular manifestations, and fibrillin groups II and IV, which included 70% of the MFS patients. In addition, these two groups were associated with shortened {open_quotes}event-free{close_quotes} survival and more severe cardiovascular complications than groups I and III. The latter included most of the equivocal MFS/single manifestation patients with fibrillin abnormalities. Our results indicate that fibrillin defects at the protein level per se are not specific for MFS, but that the drastically reduced fibrillin deposition, caused by a dominant-negative effect of abnormal fibrillin molecules in individuals defined as groups II and IV, is of prognostic and possibly diagnostic significance. 25 refs., 3 figs., 6 tabs.

  10. Multi-modality imaging review of congenital abnormalities of kidney and upper urinary tract.

    Science.gov (United States)

    Ramanathan, Subramaniyan; Kumar, Devendra; Khanna, Maneesh; Al Heidous, Mahmoud; Sheikh, Adnan; Virmani, Vivek; Palaniappan, Yegu

    2016-02-28

    Congenital abnormalities of the kidney and urinary tract (CAKUT) include a wide range of abnormalities ranging from asymptomatic ectopic kidneys to life threatening renal agenesis (bilateral). Many of them are detected in the antenatal or immediate postnatal with a significant proportion identified in the adult population with varying degree of severity. CAKUT can be classified on embryological basis in to abnormalities in the renal parenchymal development, aberrant embryonic migration and abnormalities of the collecting system. Renal parenchymal abnormalities include multi cystic dysplastic kidneys, renal hypoplasia, number (agenesis or supernumerary), shape and cystic renal diseases. Aberrant embryonic migration encompasses abnormal location and fusion anomalies. Collecting system abnormalities include duplex kidneys and Pelvi ureteric junction obstruction. Ultrasonography (US) is typically the first imaging performed as it is easily available, non-invasive and radiation free used both antenatally and postnatally. Computed tomography (CT) and magnetic resonance imaging (MRI) are useful to confirm the ultrasound detected abnormality, detection of complex malformations, demonstration of collecting system and vascular anatomy and more importantly for early detection of complications like renal calculi, infection and malignancies. As CAKUT are one of the leading causes of end stage renal disease, it is important for the radiologists to be familiar with the varying imaging appearances of CAKUT on US, CT and MRI, thereby helping in prompt diagnosis and optimal management.

  11. Computer-aided detection system for chest radiography: reducing report turnaround times of examinations with abnormalities.

    Science.gov (United States)

    Kao, E-Fong; Liu, Gin-Chung; Lee, Lo-Yeh; Tsai, Huei-Yi; Jaw, Twei-Shiun

    2015-06-01

    The ability to give high priority to examinations with pathological findings could be very useful to radiologists with large work lists who wish to first evaluate the most critical studies. A computer-aided detection (CAD) system for identifying chest examinations with abnormalities has therefore been developed. To evaluate the effectiveness of a CAD system on report turnaround times of chest examinations with abnormalities. The CAD system was designed to automatically mark chest examinations with possible abnormalities in the work list of radiologists interpreting chest examinations. The system evaluation was performed in two phases: two radiologists interpreted the chest examinations without CAD in phase 1 and with CAD in phase 2. The time information recorded by the radiology information system was then used to calculate the turnaround times. All chest examinations were reviewed by two other radiologists and were divided into normal and abnormal groups. The turnaround times for the examinations with pathological findings with and without the CAD system assistance were compared. The sensitivity and specificity of the CAD for chest abnormalities were 0.790 and 0.697, respectively, and use of the CAD system decreased the turnaround time for chest examinations with abnormalities by 44%. The turnaround times required for radiologists to identify chest examinations with abnormalities could be reduced by using the CAD system. This system could be useful for radiologists with large work lists who wish to first evaluate the most critical studies. © The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  12. Characterization of monomeric intermediates during VSV glycoprotein structural transition.

    Directory of Open Access Journals (Sweden)

    Aurélie A Albertini

    2012-02-01

    Full Text Available Entry of enveloped viruses requires fusion of viral and cellular membranes, driven by conformational changes of viral glycoproteins. Crystal structures provide static pictures of pre- and post-fusion conformations of these proteins but the transition pathway remains elusive. Here, using several biophysical techniques, including analytical ultracentrifugation, circular dichroïsm, electron microscopy and small angle X-ray scattering, we have characterized the low-pH-induced fusogenic structural transition of a soluble form of vesicular stomatitis virus (VSV glycoprotein G ectodomain (G(th, aa residues 1-422, the fragment that was previously crystallized. While the post-fusion trimer is the major species detected at low pH, the pre-fusion trimer is not detected in solution. Rather, at high pH, G(th is a flexible monomer that explores a large conformational space. The monomeric population exhibits a marked pH-dependence and adopts more elongated conformations when pH decreases. Furthermore, large relative movements of domains are detected in absence of significant secondary structure modification. Solution studies are complemented by electron micrographs of negatively stained viral particles in which monomeric ectodomains of G are observed at the viral surface at both pH 7.5 and pH 6.7. We propose that the monomers are intermediates during the conformational change and thus that VSV G trimers dissociate at the viral surface during the structural transition.

  13. Zonal variation in the distribution of an alpha 1-acid glycoprotein glycoform receptor in human adrenal cortex

    DEFF Research Database (Denmark)

    Andersen, U O; Bøg-Hansen, T C; Kirkeby, S

    1999-01-01

    receptor was located in the cytoplasm of glomerulosa and outer fasciculata cells. The intensity of the reaction product decreased in the fasciculata, and no staining was seen in inner fasciculata and reticularis. Inhibition with the simple sugars, mannose and GlcNAc confirmed a lectin-like reaction...... specific receptor. The binding of alpha 1-acid glycoprotein glycoform B and alpha 1-acid glycoprotein glycoform C to the glycoform specific receptor is inhibited by the steroid hormones cortisone, aldosterone, estradiol and progesterone but not by testosterone. The pronounced changes in the distribution...

  14. DNA vaccine expressing herpes simplex virus 1 glycoprotein C and D protects mice against herpes simplex keratitis

    OpenAIRE

    Li-Li Dong; Ru Tang; Yu-Jia Zhai; Tejsu Malla; Kai Hu

    2017-01-01

    AIM: To investigate whether DNA vaccine encoding herpes simplex virus 1 (HSV-1) glycoprotein C (gC) and glycoprotein D (gD) will achieve better protective effect against herpes simplex keratitis (HSK) than DNA vaccine encoding gD alone. METHODS: DNA vaccine expressing gD or gC combined gD (gD.gC) were constructed and carried by chitosan nanoparticle. The expression of fusion protein gD and gC were detected in DNA/nanoparticle transfected 293T cells by Western-blot. For immunization, mice w...

  15. Inhibition of Lassa virus glycoprotein cleavage and multicycle replication by site 1 protease-adapted alpha(1-antitrypsin variants.

    Directory of Open Access Journals (Sweden)

    Anna Maisa

    2009-06-01

    Full Text Available Proteolytic processing of the Lassa virus envelope glycoprotein precursor GP-C by the host proprotein convertase site 1 protease (S1P is a prerequisite for the incorporation of the subunits GP-1 and GP-2 into viral particles and, hence, essential for infectivity and virus spread. Therefore, we tested in this study the concept of using S1P as a target to block efficient virus replication.We demonstrate that stable cell lines inducibly expressing S1P-adapted alpha(1-antitrypsin variants inhibit the proteolytic maturation of GP-C. Introduction of the S1P recognition motifs RRIL and RRLL into the reactive center loop of alpha(1-antitrypsin resulted in abrogation of GP-C processing by endogenous S1P to a similar level observed in S1P-deficient cells. Moreover, S1P-specific alpha(1-antitrypsins significantly inhibited replication and spread of a replication-competent recombinant vesicular stomatitis virus expressing the Lassa virus glycoprotein GP as well as authentic Lassa virus. Inhibition of viral replication correlated with the ability of the different alpha(1-antitrypsin variants to inhibit the processing of the Lassa virus glycoprotein precursor.Our data suggest that glycoprotein cleavage by S1P is a promising target for the development of novel anti-arenaviral strategies.

  16. Termination of pregnancy for fetal abnormality: a meta-ethnography of women's experiences.

    Science.gov (United States)

    Lafarge, Caroline; Mitchell, Kathryn; Fox, Pauline

    2014-11-01

    Due to technological advances in antenatal diagnosis of fetal abnormalities, more women face the prospect of terminating pregnancies on these grounds. Much existing research focuses on women's psychological adaptation to this event. However, there is a lack of holistic understanding of women's experiences. This article reports a systematic review of qualitative studies into women's experiences of pregnancy termination for fetal abnormality. Eight databases were searched up to April 2014 for peer-reviewed studies, written in English, that reported primary or secondary data, used identifiable and interpretative qualitative methods, and offered a valuable contribution to the synthesis. Altogether, 4,281 records were screened; 14 met the inclusion criteria. The data were synthesised using meta-ethnography. Four themes were identified: a shattered world, losing and regaining control, the role of health professionals and the power of cultures. Pregnancy termination for fetal abnormality can be considered as a traumatic event that women experience as individuals, in their contact with the health professional community, and in the context of their politico-socio-legal environment. The range of emotions and experiences that pregnancy termination for fetal abnormality generates goes beyond the abortion paradigm and encompasses a bereavement model. Coordinated care pathways are needed that enable women to make their own decisions and receive supportive care. Copyright © 2014 Reproductive Health Matters. Published by Elsevier Ltd. All rights reserved.

  17. Adhesive activity of Lu glycoproteins is regulated by interaction with spectrin

    Energy Technology Data Exchange (ETDEWEB)

    An, Xiuli; Gauthier, Emilie; Zhang, Xihui; Guo, Xinhua; Anstee, David; Mohandas, Narla; Anne Chasis, Joel

    2008-03-18

    The Lutheran (Lu) and Lu(v13) blood group glycoproteins function as receptors for extracellular matrix laminins. Lu and Lu(v13) are linked to the erythrocyte cytoskeleton through a direct interaction with spectrin. However, neither the molecular basis of the interaction nor its functional consequences have previously been delineated. In the present study, we defined the binding motifs of Lu and Lu(v13) on spectrin and identified a functional role for this interaction. We found that the cytoplasmic domains of both Lu and Lu(v13) bound to repeat 4 of the spectrin chain. The interaction of full-length spectrin dimer to Lu and Lu(v13) was inhibited by repeat 4 of {alpha}-spectrin. Further, resealing of this repeat peptide into erythrocytes led to weakened Lu-cytoskeleton interaction as demonstrated by increased detergent extractability of Lu. Importantly, disruption of the Lu-spectrin linkage was accompanied by enhanced cell adhesion to laminin. We conclude that the interaction of the Lu cytoplasmic tail with the cytoskeleton regulates its adhesive receptor function.

  18. Clearance and binding of radiolabeled glycoproteins by cells of the murine mononuclear phagocyte system

    International Nuclear Information System (INIS)

    Imber, M.J.

    1982-01-01

    The clearance and binding of radiolabeled lactoferrin and fast α 2 -macroglobulin were studied. Both glycoproteins cleared rapidly following intravenous injection in mice, and both bound specifically to discrete receptors on murine peritoneal macrophages. The simultaneous presence of excess, unlabeled ligands specific for receptors recognizing terminal fucose, mannose, N-acetylglucosamine or galactose residues did not inhibit the clearance or binding of either lactoferrin or fast-α 2 M. The clearance and binding of enzymatically defucosylated lactoferrin was indistinguishable from native lactoferrin, indicating that terminal α(1-3)-linked fucose on lactoferrin is not necessary for receptor recognition. The clearance and binding of two fast -α 2 M forms, α 2 M-trypsin and α 2 M-MeNH 2 cross compete with each other. Saturation binding studies indicated that the total binding of mannosyl -BSA, fusocyl-BSA, and N-acetylglucosaminyl-BSA to macrophages activated by BCG was approximately 15% of the levels observed with inflammatory macrophages elicited by thioglycollate broth. Cross-competition binding studies demonstrated a common surface receptor mediated binding of all three neoglycoprotein ligands and was identical to the receptor on mononuclear phagocytes that binds mannosyl- and N-acetylglucosaminyl-terminated glycoproteins. These results suggest that difference between discrete states of macrophage function may be correlated with selective changes in levels of the surface receptor for mannose-containing glycoproteins

  19. Variations in Spike Glycoprotein Gene of MERS-CoV, South Korea, 2015.

    Science.gov (United States)

    Kim, Dae-Won; Kim, You-Jin; Park, Sung Han; Yun, Mi-Ran; Yang, Jeong-Sun; Kang, Hae Ji; Han, Young Woo; Lee, Han Saem; Kim, Heui Man; Kim, Hak; Kim, A-Reum; Heo, Deok Rim; Kim, Su Jin; Jeon, Jun Ho; Park, Deokbum; Kim, Joo Ae; Cheong, Hyang-Min; Nam, Jeong-Gu; Kim, Kisoon; Kim, Sung Soon

    2016-01-01

    An outbreak of nosocomial infections with Middle East respiratory syndrome coronavirus occurred in South Korea in May 2015. Spike glycoprotein genes of virus strains from South Korea were closely related to those of strains from Riyadh, Saudi Arabia. However, virus strains from South Korea showed strain-specific variations.

  20. Two lectin-like receptors for alpha 1-acid glycoprotein in mouse testis

    DEFF Research Database (Denmark)

    Andersen, U O; Kirkeby, S; Bøg-Hansen, T C

    1997-01-01

    Three glycoforms of alpha 1-acid glycoprotein (AGP) were biotinylated to examine their binding in mouse testis by light microscopy. The transition from one stage to another in the spermatogenic cycle is marked with an appearance of a receptor for the Concanavalin A (Con A) non-reactive glycoform...

  1. Modification-specific proteomic analysis of glycoproteins in human body fluids by mass spectrometry

    DEFF Research Database (Denmark)

    Bunkenborg, Jakob; Hägglund, Per; Jensen, Ole Nørregaard

    2007-01-01

    -glycosylated proteins in body fluids and other complex samples. An approach for identification of N-glycosylated proteins and mapping of their glycosylation sites is described. In this approach, glycoproteins are initially selectively purified by lectin chromatography. Following tryptic digestion, glycopeptides...

  2. Effect of dietary fat on hepatic liver X receptor expression in P-glycoprotein deficient mice: implications for cholesterol metabolism

    Directory of Open Access Journals (Sweden)

    Lee Stephen D

    2008-06-01

    Full Text Available Abstract Pgp (P-glycoprotein, MDR1, ABCB1 is an energy-dependent drug efflux pump that is a member of the ATP-binding cassette (ABC family of proteins. Preliminary studies have reported that nonspecific inhibitors of Pgp affect synthesis and esterification of cholesterol, putatively by blocking trafficking of cholesterol from the plasma membrane to the endoplasmic reticulum, and that relative increases in Pgp within a given cell type are associated with increased accumulation of cholesterol. Several key efflux proteins involved in the cholesterol metabolic pathway are transcriptionally regulated by the nuclear hormone liver X receptor (LXR. Therefore, to examine the interplay between P-glycoprotein and the cholesterol metabolic pathway, we utilized a high fat, normal cholesterol diet to upregulate LXRα without affecting dietary cholesterol. Our research has demonstrated that mice lacking in P-glycoprotein do not exhibit alterations in hepatic total cholesterol storage, circulating plasma total cholesterol levels, or total cholesterol concentration in the bile when compared to control animals on either a normal (25% calories from dietary fat or high fat (45% calories from dietary fat diet. However, p-glycoprotein deficient mice (Mdr1a-/-/1b-/- exhibit increased hepatic LXRα protein expression and an elevation in fecal cholesterol concentration when compared to controls.

  3. Normal and abnormal growth plate

    International Nuclear Information System (INIS)

    Kumar, R.; Madewell, J.E.; Swischuk, L.E.

    1987-01-01

    Skeletal growth is a dynamic process. A knowledge of the structure and function of the normal growth plate is essential in order to understand the pathophysiology of abnormal skeletal growth in various diseases. In this well-illustrated article, the authors provide a radiographic classification of abnormal growth plates and discuss mechanisms that lead to growth plate abnormalities

  4. Interaction of a novel Tn (GalNAc alpha 1-->Ser/Thr) glycoprotein with Gal, GalNAc and GlcNAc specific lectins.

    Science.gov (United States)

    Wu, A M; Wu, J H; Shen, F

    1994-01-14

    A naturally occurring Tn glycoprotein (Native ASG-Tn) with GalNAc alpha 1-->Ser/Thr as the only carbohydrate side chains, has been prepared from armadillo submandibular glands. In a quantitative precipitin assay, this glycoprotein completely precipitated Maclura pomifera (MPA), Vicia villosa B4 (VVL-B4) and Artocarpus integrifolia (Jacalin, AIL). It also reacted well with Helix pomatia (HPL) and Wistaria floribunda (WFL) and precipitated over 75% of the lectin nitrogen added, but poorly with Ricinus communis agglutinin (RCA1), ricin, peanut (Arachis hypogaea, PNA), Abrus precatorius agglutinin (APA) and Triticum vulgaris (WGA). This finding suggests that this novel Tn-glycoprotein may serve as a useful reagent for differentiating Tn and T specific monoclonal antibodies and lectins.

  5. Predictors of abnormal chest CT after blunt trauma: a critical appraisal of the literature

    International Nuclear Information System (INIS)

    Brink, M.; Kool, D.R.; Dekker, H.M.; Deunk, J.; Jager, G.J.; Kuijk, C. van; Edwards, M.J.R.; Blickman, J.G.

    2009-01-01

    Aim: To identify and to evaluate predictors that determine whether chest computed tomography (CT) is likely to reveal relevant injuries in adult blunt trauma patients. Methods: After a comprehensive literature search for original studies on blunt chest injury diagnosis, two independent observers included studies on the accuracy of parameters derived from history, physical examination, or diagnostic imaging that might predict injuries at (multidetector row) CT in adults and that allowed construction of 2 x 2 contingency tables. For each article, methodological quality was scored and relevant predictors for injuries at CT were extracted. For each predictor, sensitivity, specificity, positive and negative likelihood ratio and diagnostic odds ratio (DOR) including 95% confidence intervals were calculated. Results: Of 147 articles initially identified, the observers included 10 original studies in consensus. Abnormalities at physical examination (abnormal respiratory effort, need for assisted ventilation, reduced airentry, coma, chest wall tenderness) and pelvic fractures were significant predictors (DOR: 2.1-6.7). The presence of any injuries at conventional radiography of the chest (eight articles) was a more powerful significant predictor (DOR: 2.2-37). Abnormal chest ultrasonography (four articles) was the most accurate predictor for chest injury at CT (DOR: 491-infinite). Conclusion: The current literature indicates that in blunt trauma patients with abnormal physical examination, abnormal conventional radiography, or abnormal ultrasonography of the chest, CT was likely to reveal relevant chest injuries. However, there was no strong evidence to suggest that CT could be omitted in patients without these criteria, or whether these findings are beneficial for patients

  6. Abnormal antenatal sonogram: an indicator of disease severity in children with posterior urethral valves

    International Nuclear Information System (INIS)

    Harvie, S.; McLeod, L.; Acott, P.; Walsh, E.; Abdolell, M.; Macken, M.B.

    2009-01-01

    To review the association of an abnormal prenatal sonogram with most recent serum creatinine in patients with proven posterior urethral valves (PUV). Since 1992, all live-born patients between 1992-2004 with clinically proven PUV, with postnatally proven PUV, from 2 pediatric tertiary care centers, were reviewed for age at diagnosis, most recent serum creatinine, presence of chronic renal failure (CRF) (serum creatinine >2 standard deviations above normal for age), or end stage renal disease (dialysis or transplant). Available antenatal reports from the 2 centres and surrounding community hospitals were reviewed for gestational age (GA) at the time of ultrasound, volume of amniotic fluid, and urinary-tract abnormality. Thirty-four patients with proven PUV and prenatal sonograms were identified (1992-2004). Eighteen patients had abnormalities on their prenatal sonogram, with poor outcome in 5 (mean follow-up, 8 years [1-13 y]). No specific features were identified on prenatal sonogram. Sixteen patients had normal prenatal sonograms, with poor outcomes in 2 (mean follow-up, 8 years [3-13 y]). There is an increased risk of an abnormal serum creatinine among those patients with an abnormal prenatal study, odds ratio (OR) 2.6 (95% confidence interval, 0.35-32). PUV represents a spectrum of disease severity. A normal prenatal ultrasound does not preclude PUV. The majority of patients with a normal prenatal examination have good outcomes. The OR suggests that there may be increased risk for poor outcome in those with an abnormal prenatal examination. A multicenter study is necessary to obtain a larger sample size and more precise ORs. (author)

  7. Abnormal antenatal sonogram: an indicator of disease severity in children with posterior urethral valves

    Energy Technology Data Exchange (ETDEWEB)

    Harvie, S. [Peterborough Health Centre, Dept. of Radiology, Peterborough, Ontario (Canada); McLeod, L. [IWK Health Centre, Dept. of Obstetrics and Gynaecology, Halifax, Nova Scotia (Canada); Acott, P. [IWK Health Centre, Dept. of Nephrology, Halifax, Nova Scotia (Canada); Walsh, E. [Dr. Charles A. Janeway Children' s Health Centre, Dept. of Radiology, St. John' s, Newfoundland (Canada); Abdolell, M. [QE II Health Sciences Centre, Dept. of Radiology, Halifax, Nova Scotia (Canada); Macken, M.B., E-mail: mmacken@dal.ca [IWK Health Centre, Dept. of Diagnostic Imaging, Halifax, Nova Scotia (Canada)

    2009-10-15

    To review the association of an abnormal prenatal sonogram with most recent serum creatinine in patients with proven posterior urethral valves (PUV). Since 1992, all live-born patients between 1992-2004 with clinically proven PUV, with postnatally proven PUV, from 2 pediatric tertiary care centers, were reviewed for age at diagnosis, most recent serum creatinine, presence of chronic renal failure (CRF) (serum creatinine >2 standard deviations above normal for age), or end stage renal disease (dialysis or transplant). Available antenatal reports from the 2 centres and surrounding community hospitals were reviewed for gestational age (GA) at the time of ultrasound, volume of amniotic fluid, and urinary-tract abnormality. Thirty-four patients with proven PUV and prenatal sonograms were identified (1992-2004). Eighteen patients had abnormalities on their prenatal sonogram, with poor outcome in 5 (mean follow-up, 8 years [1-13 y]). No specific features were identified on prenatal sonogram. Sixteen patients had normal prenatal sonograms, with poor outcomes in 2 (mean follow-up, 8 years [3-13 y]). There is an increased risk of an abnormal serum creatinine among those patients with an abnormal prenatal study, odds ratio (OR) 2.6 (95% confidence interval, 0.35-32). PUV represents a spectrum of disease severity. A normal prenatal ultrasound does not preclude PUV. The majority of patients with a normal prenatal examination have good outcomes. The OR suggests that there may be increased risk for poor outcome in those with an abnormal prenatal examination. A multicenter study is necessary to obtain a larger sample size and more precise ORs. (author)

  8. Carbohydrates of influenza virus. I. Glycopeptides derived from viral glycoproteins after labeling with radioactive sugars

    International Nuclear Information System (INIS)

    Schwarz, R.T.; Schmidt, M.F.G.; Anwer, U.; Klenk, H.D.

    1977-01-01

    The carbohydrate moiety of the influenza glycoproteins NA, HA 1 , and HA 2 were analyzed by labeling with radioactive sugars. Analysis of glycopeptides obtained after digestion with Pronase indicated that there are at least two different types of carbohydrate side chains. The side chain of type I is composed of glucosamine, mannose, galactose, and fucose. It is found on NA, HA 1 , and HA 2 . The side chain of type II contains a high amount of mannose and is found only on NA and HA 2 . The molecular weights of the corresponding glycopeptides obtained from virus grown in chicken ambryo cells are 2,600 for type I and 2,000 for type II. The glycoproteins of virus grown in MDBK cells have a higher molecular weight than those of virus grown in chicken embryo cells, and there is a corresponding difference in the molecular weights of the glycopeptides. Under conditions of partial inhibition of glycosylation, virus particles were isolated that contained hemagglutinin with reduced carbohydrate content. Glycopeptide analysis indicated that this reduction is due to the lack of whole carbohydrate side chains and not to the incorporation of incomplete ones. This observation suggests that glycosylation of the viral glycoproteins involves en bloc transfer of the core sugars to the polypeptide chains

  9. Laryngopharyngeal abnormalities in hospitalized patients with dysphagia.

    Science.gov (United States)

    Postma, Gregory N; McGuirt, W Frederick; Butler, Susan G; Rees, Catherine J; Crandall, Heather L; Tansavatdi, Kristina

    2007-10-01

    To determine the prevalence of laryngopharyngeal (LP) abnormalities in hospitalized patients with dysphagia referred for flexible endoscopic evaluation of swallowing (FEES). Retrospective, blinded review by two otolaryngologists of 100 consecutive FEES studies performed and video-recorded by a speech-language pathologist (SLP). Two otolaryngologists reviewed videos of 100 consecutive FEES studies on hospitalized patients with dysphagia for the presence of abnormal LP findings. Sixty-one male and 38 female patients comprised the hospital dysphagia cohort. The mean age was 62. One subject could not be evaluated because of the severity of the retained secretions, leaving 99 subjects in the cohort. Seventy-six percent had been previously intubated, with a mean intubation duration of 13 days. The overall prevalence of abnormal LP findings was 79%. Forty-five percent of the patients presented with two or more findings, which included arytenoid edema (33%), granuloma (31%), vocal fold paresis (24%), mucosal lesions (17%), vocal fold bowing (14%), diffuse edema (11%), airway stenosis (3%), and ulcer (6%). There was a significant difference in LP findings between those individuals who had or had not been intubated. Hospitalized patients with dysphagia are at high risk for LP abnormalities, particularly if they have been intubated, and may benefit from either 1) an initial joint examination by the SLP and otolaryngologist or 2) an otolaryngologist's review of the recorded examination conducted by the SLP. Such otolaryngology involvement could identify airway stenosis patients at an earlier stage, initiate granuloma treatment sooner, enable earlier biopsy of unexpected lesions, and allow follow-up of mucosal and neuromuscular findings that do not respond to medical management.

  10. Incidence of abnormal offspring from cloning and other assisted reproductive technologies.

    Science.gov (United States)

    Hill, Jonathan R

    2014-02-01

    In animals produced by assisted reproductive technologies, two abnormal phenotypes have been characterized. Large offspring syndrome (LOS) occurs in offspring derived from in vitro cultured embryos, and the abnormal clone phenotype includes placental and fetal changes. LOS is readily apparent in ruminants, where a large calf or lamb derived from in vitro embryo production or cloning may weigh up to twice the expected body weight. The incidence of LOS varies widely between species. When similar embryo culture conditions are applied to nonruminant species, LOS either is not as dramatic or may even be unapparent. Coculture with serum and somatic cells was identified in the 1990s as a risk factor for abnormal development of ruminant pregnancies. Animals cloned from somatic cells may display a combination of fetal and placental abnormalities that are manifested at different stages of pregnancy and postnatally. In highly interventional technologies, such as nuclear transfer (cloning), the incidence of abnormal offspring continues to be a limiting factor to broader application of the technique. This review details the breadth of phenotypes found in nonviable pregnancies, together with the phenotypes of animals that survive the transition to extrauterine life. The focus is on animals produced using in vitro embryo culture and nuclear transfer in comparison to naturally occurring phenotypes.

  11. Glycosylation of dengue virus glycoproteins and their interactions with carbohydrate receptors: possible targets for antiviral therapy.

    Science.gov (United States)

    Idris, Fakhriedzwan; Muharram, Siti Hanna; Diah, Suwarni

    2016-07-01

    Dengue virus, an RNA virus belonging to the genus Flavivirus, affects 50 million individuals annually, and approximately 500,000-1,000,000 of these infections lead to dengue hemorrhagic fever or dengue shock syndrome. With no licensed vaccine or specific antiviral treatments available to prevent dengue infection, dengue is considered a major public health problem in subtropical and tropical regions. The virus, like other enveloped viruses, uses the host's cellular enzymes to synthesize its structural (C, E, and prM/M) and nonstructural proteins (NS1-5) and, subsequently, to glycosylate these proteins to produce complete and functional glycoproteins. The structural glycoproteins, specifically the E protein, are known to interact with the host's carbohydrate receptors through the viral proteins' N-glycosylation sites and thus mediate the viral invasion of cells. This review focuses on the involvement of dengue glycoproteins in the course of infection and the virus' exploitation of the host's glycans, especially the interactions between host receptors and carbohydrate moieties. We also discuss the recent developments in antiviral therapies that target these processes and interactions, focusing specifically on the use of carbohydrate-binding agents derived from plants, commonly known as lectins, to inhibit the progression of infection.

  12. Screening of extraction methods for glycoproteins from jellyfish ( Rhopilema esculentum) oral-arms by high performance liquid chromatography

    Science.gov (United States)

    Ren, Guoyan; Li, Bafang; Zhao, Xue; Zhuang, Yongliang; Yan, Mingyan; Hou, Hu; Zhang, Xiukun; Chen, Li

    2009-03-01

    In order to select an optimum extraction method for the target glycoprotein (TGP) from jellyfish ( Rhopilema esculentum) oral-arms, a high performance liquid chromatography (HPLC)-assay for the determination of the TGP was developed. Purified target glycoprotein was taken as a standard glycoprotein. The results showed that the calibration curves for peak area plotted against concentration for TGP were linear ( r = 0.9984, y = 4.5895 x+47.601) over concentrations ranging from 50 to 400 mgL-1. The mean extraction recovery was 97.84% (CV2.60%). The fractions containing TGP were isolated from jellyfish ( R. esculentum) oral-arms by four extraction methods: 1) water extraction (WE), 2) phosphate buffer solution (PBS) extraction (PE), 3) ultrasound-assisted water extraction (UA-WE), 4) ultrasound-assisted PBS extraction (UA-PE). The lyophilized extract was dissolved in Milli-Q water and analyzed directly on a short TSK-GEL G4000PWXL (7.8 mm×300 mm) column. Our results indicated that the UA-PE method was the optimum extraction method selected by HPLC.

  13. Aircraft Abnormal Conditions Detection, Identification, and Evaluation Using Innate and Adaptive Immune Systems Interaction

    Science.gov (United States)

    Al Azzawi, Dia

    Abnormal flight conditions play a major role in aircraft accidents frequently causing loss of control. To ensure aircraft operation safety in all situations, intelligent system monitoring and adaptation must rely on accurately detecting the presence of abnormal conditions as soon as they take place, identifying their root cause(s), estimating their nature and severity, and predicting their impact on the flight envelope. Due to the complexity and multidimensionality of the aircraft system under abnormal conditions, these requirements are extremely difficult to satisfy using existing analytical and/or statistical approaches. Moreover, current methodologies have addressed only isolated classes of abnormal conditions and a reduced number of aircraft dynamic parameters within a limited region of the flight envelope. This research effort aims at developing an integrated and comprehensive framework for the aircraft abnormal conditions detection, identification, and evaluation based on the artificial immune systems paradigm, which has the capability to address the complexity and multidimensionality issues related to aircraft systems. Within the proposed framework, a novel algorithm was developed for the abnormal conditions detection problem and extended to the abnormal conditions identification and evaluation. The algorithm and its extensions were inspired from the functionality of the biological dendritic cells (an important part of the innate immune system) and their interaction with the different components of the adaptive immune system. Immunity-based methodologies for re-assessing the flight envelope at post-failure and predicting the impact of the abnormal conditions on the performance and handling qualities are also proposed and investigated in this study. The generality of the approach makes it applicable to any system. Data for artificial immune system development were collected from flight tests of a supersonic research aircraft within a motion-based flight

  14. Surface (glyco-)proteins: primary structure and crystallization under microgravity conditions

    Science.gov (United States)

    Claus, H.; Akca, E.; Schultz, N.; Karbach, G.; Schlott, B.; Debaerdemaeker, T.; De Clercq, J.-P.; König, H.

    2001-08-01

    The Archaea comprise microorganisms that live under environmental extremes, like high temperature, low pH value or high salt concentration. Their cells are often covered by a single layer of (glyco)protein subunits (S-layer) in hexagonal arrangement. In order to get further hints about the molecular mechanisms of protein stabilization we compared the primary and secondary structures of archaeal S-layer (glyco)proteins. We found an increase of charged amino acids in the S-layer proteins of the extreme thermophilic species compared to their mesophilic counterparts. Our data and those of other authors suggest that ionic interactions, e.g., salt bridges seem to be played a major role in protein stabilization at high temperatures. Despite the differences in the growth optima and the predominance of some amino acids the primary structures of S-layers revealed also a significant degree of identity between phylogenetically related archaea. These obervations indicate that protein sequences of S-layers have been conserved during the evolution from extremely thermophilic to mesophilic life. To support these findings the three-dimensional structure of the S-layer proteins has to be elucidated. Recently, we described the first successful crystallization of an extreme thermophilic surface(glyco)protein under microgravity conditions.

  15. Epileptiform abnormalities predict delayed cerebral ischemia in subarachnoid hemorrhage.

    Science.gov (United States)

    Kim, J A; Rosenthal, E S; Biswal, S; Zafar, S; Shenoy, A V; O'Connor, K L; Bechek, S C; Valdery Moura, J; Shafi, M M; Patel, A B; Cash, S S; Westover, M B

    2017-06-01

    To identify whether abnormal neural activity, in the form of epileptiform discharges and rhythmic or periodic activity, which we term here ictal-interictal continuum abnormalities (IICAs), are associated with delayed cerebral ischemia (DCI). Retrospective analysis of continuous electroencephalography (cEEG) reports and medical records from 124 patients with moderate to severe grade subarachnoid hemorrhage (SAH). We identified daily occurrence of seizures and IICAs. Using survival analysis methods, we estimated the cumulative probability of IICA onset time for patients with and without delayed cerebral ischemia (DCI). Our data suggest the presence of IICAs indeed increases the risk of developing DCI, especially when they begin several days after the onset of SAH. We found that all IICA types except generalized rhythmic delta activity occur more commonly in patients who develop DCI. In particular, IICAs that begin later in hospitalization correlate with increased risk of DCI. IICAs represent a new marker for identifying early patients at increased risk for DCI. Moreover, IICAs might contribute mechanistically to DCI and therefore represent a new potential target for intervention to prevent secondary cerebral injury following SAH. These findings imply that IICAs may be a novel marker for predicting those at higher risk for DCI development. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  16. Abnormal Grief: Should We Consider a More Patient-Centered Approach?

    Science.gov (United States)

    Moayedoddin, Babak; Markowitz, John C

    2015-01-01

    Grief, the psychological reaction to the loss of a significant other, varies complexly in its cause, experience, evolution, and prognosis. Although most bereaved individuals experience a normal grieving process, some develop complicated grief (CG) or major depressive disorder (MDD). The DSM-5, which controversially altered the nosology, recognizes grief-related major depression (GRMD) as a diagnostic subtype if a patient meets MDD criteria two weeks post bereavement. The (DSM-5) tries to distinguish between grief and MDD, but remains a symptom-based, centered approach to grief that is not patient centered. This article reviews grief in its normal and abnormal dimensions. Using an illustrative clinical case in which interpersonal psychotherapy (IPT) was employed, we discuss the need for a more patient-centered approach to treating abnormal grief, considering the patient's personal history, perceptions, experiences of bereavement, and interpersonal environment. Clinical studies need to better identify subgroups of individuals susceptible to abnormal grief and to evaluate their response to early interventions.

  17. Prevalence of lung abnormalities in 55 patients with esophageal cancer

    International Nuclear Information System (INIS)

    Zan, Tiago Alves de Brito; Cordeiro, Jose Antonio; Franca, Fabricio Correa de; Muniz, Marcos Pontes; Borim, Aldenis Albenese; Cury, Patricia Maluf

    2001-01-01

    The objective was to identify lung abnormalities in patients with esophageal cancer, to compare the obtained data and to demonstrate its relationship with smoking. This was a series of cases type of cross-sectional study. We studied 55 patients with esophageal carcinoma diagnosed between 1998 and 2001 at Hospital de Base de Sao Jose do Rio Preto, SP, Brazil. Chest plain films and computed tomography scans were analyzed. The frequency of the tumors and other lung abnormalities in two groups of patients were compared: smokers and non-smokers. The results showed that forty-six (83%) patients had spinous cell carcinoma, seven (13%) adenocarcinomas, one (2%) carcinoma of small cells and one (2%) non-Hodgkin lymphoma. Forty-eight (87%) patients were smokers and seven (13%) were non-smokers. In the smokers group, 89% had spinous cell carcinoma, 9% adenocarcinoma and 2% small cells carcinoma. In the non-smokers group, 57% had adenocarcinoma, 28% spinous cell carcinoma and 15% non-Hodgkin lymphoma. Metastases were identified in four smokers and in two non-smokers. The prevalence of the lung abnormalities (interstitial infiltration, emphysema and pneumonia) was higher in the smokers group (73%) than in the non-smokers group (27%) (p = 0.03). We concluded that this fact reinforces the importance of evaluation of the lungs in patients with esophageal neoplasms. (author)

  18. Synthetic profiles of polypeptides of human oocytes and normal and abnormal preimplantation embryos.

    Science.gov (United States)

    Capmany, G; Bolton, V N

    1999-09-01

    There is considerable variation in the rate of development in vitro of individual preimplantation human embryos. The relationship between the rate of development and patterns of polypeptide synthesis in individual embryos was examined using SDS-PAGE and autoradiography. After incubation in [35S]methionine, 19 polypeptide bands were identified that change between fertilization and the morula stage. Although changes in two of the bands occurred in embryos that were developing normally and in ageing oocytes, and are thus independent of fertilization, the changes identified in the remaining 17 bands occurred only after fertilization. In embryos that were developing abnormally, as assessed by delayed cleavage, cleavage arrest or extensive fragmentation, the alteration in polypeptide synthetic profiles increased with increasing abnormality.

  19. The O-Linked Glycome and Blood Group Antigens ABO on Mucin-Type Glycoproteins in Mucinous and Serous Epithelial Ovarian Tumors.

    Directory of Open Access Journals (Sweden)

    Varvara Vitiazeva

    Full Text Available Mucins are heavily O-glycosylated proteins where the glycosylation has been shown to play an important role in cancer. Normal epithelial ovarian cells do not express secreted mucins, but their abnormal expression has previously been described in epithelial ovarian cancer and may relate to tumor formation and progression. The cyst fluids were shown to be a rich source for acidic glycoproteins. The study of these proteins can potentially lead to the identification of more effective biomarkers for ovarian cancer.In this study, we analyzed the expression of the MUC5AC and the O-glycosylation of acidic glycoproteins secreted into ovarian cyst fluids. The samples were obtained from patients with serous and mucinous ovarian tumors of different stages (benign, borderline, malignant and grades. The O-linked oligosaccharides were released and analyzed by negative-ion graphitized carbon Liquid Chromatography (LC coupled to Electrospray Ionization tandem Mass Spectrometry (ESI-MSn. The LC-ESI-MSn of the oligosaccharides from ovarian cyst fluids displayed differences in expression of fucose containing structures such as blood group ABO antigens and Lewis-type epitopes.The obtained data showed that serous and mucinous benign adenomas, mucinous low malignant potential carcinomas (LMPs, borderline and mucinous low-grade carcinomas have a high level of blood groups and Lewis type epitopes. In contrast, this type of fucosylated structures were low abundant in the high-grade mucinous carcinomas or in serous carcinomas. In addition, the ovarian tumors that showed a high level of expression of blood group antigens also revealed a strong reactivity towards the MUC5AC antibody. To visualize the differences between serous and mucinous ovarian tumors based on the O-glycosylation, a hierarchical cluster analysis was performed using mass spectrometry average compositions (MSAC.Mucinous benign and LMPs along with mucinous low-grade carcinomas appear to be different from

  20. Defining Abnormally Low Tenders

    DEFF Research Database (Denmark)

    Ølykke, Grith Skovgaard; Nyström, Johan

    2017-01-01

    The concept of an abnormally low tender is not defined in EU public procurement law. This article takes an interdisciplinary law and economics approach to examine a dataset consisting of Swedish and Danish judgments and verdicts concerning the concept of an abnormally low tender. The purpose...

  1. Simultaneous Pathoproteomic Evaluation of the Dystrophin-Glycoprotein Complex and Secondary Changes in the mdx-4cv Mouse Model of Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Sandra Murphy

    2015-06-01

    Full Text Available In skeletal muscle, the dystrophin-glycoprotein complex forms a membrane-associated assembly of relatively low abundance, making its detailed proteomic characterization in normal versus dystrophic tissues technically challenging. To overcome this analytical problem, we have enriched the muscle membrane fraction by a minimal differential centrifugation step followed by the comprehensive label-free mass spectrometric analysis of microsomal membrane preparations. This organelle proteomic approach successfully identified dystrophin and its binding partners in normal versus dystrophic hind limb muscles. The introduction of a simple pre-fractionation step enabled the simultaneous proteomic comparison of the reduction in the dystrophin-glycoprotein complex and secondary changes in the mdx-4cv mouse model of dystrophinopathy in a single analytical run. The proteomic screening of the microsomal fraction from dystrophic hind limb muscle identified the full-length dystrophin isoform Dp427 as the most drastically reduced protein in dystrophinopathy, demonstrating the remarkable analytical power of comparative muscle proteomics. Secondary pathoproteomic expression patterns were established for 281 proteins, including dystrophin-associated proteins and components involved in metabolism, signalling, contraction, ion-regulation, protein folding, the extracellular matrix and the cytoskeleton. Key findings were verified by immunoblotting. Increased levels of the sarcolemmal Na+/K+-ATPase in dystrophic leg muscles were also confirmed by immunofluorescence microscopy. Thus, the reduction of sample complexity in organelle-focused proteomics can be advantageous for the profiling of supramolecular protein complexes in highly intricate systems, such as skeletal muscle tissue.

  2. Development of Classification Models for Identifying “True” P-glycoprotein (P-gp Inhibitors Through Inhibition, ATPase Activation and Monolayer Efflux Assays

    Directory of Open Access Journals (Sweden)

    Anna Maria Bianucci

    2012-06-01

    Full Text Available P-glycoprotein (P-gp is an efflux pump involved in the protection of tissues of several organs by influencing xenobiotic disposition. P-gp plays a key role in multidrug resistance and in the progression of many neurodegenerative diseases. The development of new and more effective therapeutics targeting P-gp thus represents an intriguing challenge in drug discovery. P-gp inhibition may be considered as a valid approach to improve drug bioavailability as well as to overcome drug resistance to many kinds of tumours characterized by the over-expression of this protein. This study aims to develop classification models from a unique dataset of 59 compounds for which there were homogeneous experimental data on P-gp inhibition, ATPase activation and monolayer efflux. For each experiment, the dataset was split into a training and a test set comprising 39 and 20 molecules, respectively. Rational splitting was accomplished using a sphere-exclusion type algorithm. After a two-step (internal/external validation, the best-performing classification models were used in a consensus predicting task for the identification of compounds named as “true” P-gp inhibitors, i.e., molecules able to inhibit P-gp without being effluxed by P-gp itself and simultaneously unable to activate the ATPase function.

  3. Report to Congress on abnormal occurrences, October--December 1976

    International Nuclear Information System (INIS)

    1977-01-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report, the seventh in the series, covers the period from October 1 to December 31, 1976. The NRC has determined that during this period: (1) There were two abnormal occurrences at the 63 nuclear power plants licensed to operate. One event involved improper control rod withdrawals resulting in an unplanned reactor criticality. The second is a generic event pertaining to feedwater nozzle cracking in Boiling Water Reactors. The incidents had no actual impact on public health or safety. (2) There were five abnormal occurrences at other licensee facilities. The occurrences involved overexposures to radiography personnel; one event also involved high radiation levels in unrestricted areas. This report also contains information updating previously reported abnormal occurrences. This report does not contain information on activities in those states which have entered into agreements with the NRC for the assumption of certain regulatory authority pursuant to Section 274 of the Atomic Energy Act, as amended. Future reports will include Agreement State licensee activities as soon as procedures can be implemented

  4. Simple and Robust N-Glycan Analysis Based on Improved 2-Aminobenzoic Acid Labeling for Recombinant Therapeutic Glycoproteins.

    Science.gov (United States)

    Jeong, Yeong Ran; Kim, Sun Young; Park, Young Sam; Lee, Gyun Min

    2018-03-21

    N-glycans of therapeutic glycoproteins are critical quality attributes that should be monitored throughout all stages of biopharmaceutical development. To reduce both the time for sample preparation and the variations in analytical results, we have developed an N-glycan analysis method that includes improved 2-aminobenzoic acid (2-AA) labeling to easily remove deglycosylated proteins. Using this analytical method, 15 major 2-AA-labeled N-glycans of Enbrel ® were separated into single peaks in hydrophilic interaction chromatography mode and therefore could be quantitated. 2-AA-labeled N-glycans were also highly compatible with in-line quadrupole time-of-flight mass spectrometry (MS) for structural identification. The structures of 15 major and 18 minor N-glycans were identified from their mass values determined by quadrupole time-of-flight MS. Furthermore, the structures of 14 major N-glycans were confirmed by interpreting the MS/MS data of each N-glycan. This analytical method was also successfully applied to neutral N-glycans of Humira ® and highly sialylated N-glycans of NESP ® . Furthermore, the analysis data of Enbrel ® that were accumulated for 2.5 years demonstrated the high-level consistency of this analytical method. Taken together, the results show that a wide repertoire of N-glycans of therapeutic glycoproteins can be analyzed with high efficiency and consistency using the improved 2-AA labeling-based N-glycan analysis method. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  5. Evolutionary conservation of the lipopolysaccharide binding site of β₂-glycoprotein I

    NARCIS (Netherlands)

    Ağar, Çetin; de Groot, Philip G.; Marquart, J. Arnoud; Meijers, Joost C. M.

    2011-01-01

    β₂-Glycoprotein I (β₂GPI) is a highly abundant plasma protein and the major antigen for autoantibodies in the antiphospholipid syndrome. Recently, we have described a novel function of β₂GPI as scavenger of lipopolysaccharide (LPS). With this in mind we investigated the conservation of β₂GPI in

  6. Do asparagine-linked carbohydrate chains in glycoproteins have a preference for beta-bends?

    NARCIS (Netherlands)

    Beintema, Jaap J.

    X-ray structures of the conformation of carbohydrate moieties and connected regions of glycoproteins are summarized. Evidence is presented that there is some preference for carbohydrate attachment at β-bends. Evolution may have favored glycosylation to occur at bends to ensure free mobility of the

  7. Enhancement of feline immunodeficiency virus infection after immunization with envelope glycoprotein subunit vaccines.

    NARCIS (Netherlands)

    C.H.J. Siebelink (Kees); E.J. Tijhaar (Edwin); R.C. Huisman (Robin); W. Huisman (Willem); A. de Ronde; I.H. Darby; M.J. Francis; G.F. Rimmelzwaan (Guus); A.D.M.E. Osterhaus (Albert)

    1995-01-01

    textabstractCats were immunized three times with different recombinant feline immunodeficiency virus (FIV) candidate vaccines. Recombinant vaccinia virus (rVV)-expressed envelope glycoprotein with (vGR657) or without (vGR657 x 15) the cleavage site and an FIV envelope bacterial fusion protein

  8. The morphological classification of normal and abnormal red blood cell using Self Organizing Map

    Science.gov (United States)

    Rahmat, R. F.; Wulandari, F. S.; Faza, S.; Muchtar, M. A.; Siregar, I.

    2018-02-01

    Blood is an essential component of living creatures in the vascular space. For possible disease identification, it can be tested through a blood test, one of which can be seen from the form of red blood cells. The normal and abnormal morphology of the red blood cells of a patient is very helpful to doctors in detecting a disease. With the advancement of digital image processing technology can be used to identify normal and abnormal blood cells of a patient. This research used self-organizing map method to classify the normal and abnormal form of red blood cells in the digital image. The use of self-organizing map neural network method can be implemented to classify the normal and abnormal form of red blood cells in the input image with 93,78% accuracy testing.

  9. An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein Ligand-1 Collectively Control the Migration of Activated Human T-Cells

    KAUST Repository

    Ali, Amal J.

    2017-05-03

    Selectins guide the traffic of activated T-cells through the blood stream by mediating their tethering and rolling onto inflamed endothelium, in this way acting as beacons to help navigate them to sites of inflammation. Here, we present a comprehensive analysis of E-selectin ligands expressed on activated human T-cells. We identified several novel glycoproteins that function as E-selectin ligands. Specifically, we compared the role of P-selectin glycoprotein ligand-1 (PSGL-1) and CD43, known E-selectin ligands, to CD44, a ligand that has not previously been characterized as an E-selectin ligand on activated human T-cells. We showed that CD44 acts as a functional E-selectin ligand when expressed on both CD4+ and CD8+ T-cells. Moreover, the CD44 protein carries a binding epitope identifying it as hematopoietic cell E- and/or L-selectin ligand (HCELL). Furthermore, by knocking down these ligands individually or together in primary activated human T-cells, we demonstrated that CD44/HCELL, and not CD43, cooperates with PSGL-1 as a major E-selectin ligand. Additionally, we demonstrated the relevance of our findings to chronic autoimmune disease, by showing that CD44/HCELL and PSGL-1, but not CD43, from T-cells isolated from psoriasis patients, bind E-selectin.

  10. Fraction A of armadillo submandibular glycoprotein and its desialylated product as sialyl-Tn and Tn receptors for lectins.

    Science.gov (United States)

    Wu, A M; Shen, F; Herp, A; Song, S C; Wu, J H

    1995-02-27

    Fraction A of the armadillo submandibular glycoprotein (ASG-A) is one of the simplest glycoproteins among mammalian salivary mucins. The carbohydrate side chains of this mucous glycoprotein have one-third of the NeuAc alpha 2-->6GalNAc (sialyl-Tn) sequence and two thirds of Tn (GalNAc alpha-->Ser/Thr) residues. Those of the desialylated product (ASG-Tn) are almost exclusively unsubstituted GalNAc residues (Tn determinant). When the binding properties of these glycoproteins were tested by a precipitin assay with Gal, GalNAc and GlcNAc specific lectins, it was found that ASG-Tn reacted strongly with all of the Tn-active lectins and completely precipitated Vicia villosa (VVL both B4 and mixture of A and B), Maclura pomifera (MPA), and Artocarpus integrifolia (jacalin) lectins. However, it precipitated poorly or negligibly with Ricinus communis (RCA1); Dolichos biflorus (DBA); Viscum album, ML-I; Arachis hypogaea (PNA), and Triticum vulgaris (WGA). The reactivity of ASG-A (sialyl-Tn) was as active as that of ASG-Tn with MPA and less or slightly less active than that of ASG-Tn with VVL-A+B, VVL-B4, HPA, WFA, and jacalin, as one-third of its Tn was sialylated. These findings indicate that ASG-A and its desialylated product (ASG-Tn) are highly useful reagents for the differentiation of Tn, T (Gal beta 1-->3GalNAc), A (GalNAc alpha 1-->3Gal) or Gal specific lectins and monoclonal antibodies against such epitopes.

  11. Basigin (CD147), a multifunctional transmembrane glycoprotein with various binding partners.

    Science.gov (United States)

    Muramatsu, Takashi

    2016-05-01

    Basigin, also called CD147 or EMMPRIN, is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. Basigin has isoforms; the common form (basigin or basigin-2) has two immunoglobulin domains, and the extended form (basigin-1) has three. Basigin is the receptor for cyclophilins, S100A9 and platelet glycoprotein VI, whereas basigin-1 serves as the receptor for the rod-derived cone viability factor. Basigin tightly associates with monocarboxylate transporters and is essential for their cell surface translocation and activities. In the same membrane plane, basigin also associates with other proteins including GLUT1, CD44 and CD98. The carbohydrate portion of basigin is recognized by lectins, such as galectin-3 and E-selectin. These molecular recognitions form the basis for the role of basigin in the transport of nutrients, migration of inflammatory leukocytes and induction of matrix metalloproteinases. Basigin is important in vision, spermatogenesis and other physiological phenomena, and plays significant roles in the pathogenesis of numerous diseases, including cancer. Basigin is also the receptor for an invasive protein RH5, which is present in malaria parasites. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society.

  12. Characterisation of the carbohydrate components of Taenia solium metacestode glycoprotein antigens.

    Science.gov (United States)

    Restrepo, B I; Obregón-Henao, A; Mesa, M; Gil, D L; Ortiz, B L; Mejía, J S; Villota, G E; Sanzón, F; Teale, J M

    2000-05-01

    Human neurocysticercosis is caused by Taenia solium metacestodes. It usually affects the central nervous system of humans and can be confused with other brain pathologies. The Lens culinaris-binding glycoproteins from this parasite have been shown to be ideal targets for the development of a highly specific immunoassay for the diagnosis of neurocysticercosis. In the present study we characterised the carbohydrates associated with five antigenic glycoproteins of T. solium metacestodes in the range of 12-28 kilodaltons. Lectin-affinities and enzymatic deglycosylations suggested that each of the five antigens contain various glycoforms of asparagine-linked carbohydrates of the hybrid, complex and probably high mannose type. These carbohydrates accounted for at least 30-66% of the apparent molecular mass of the glycoconjugates. In contrast, there was no evidence for the presence of O-linked carbohydrates. Lectin affinity patterns suggested that the sugars are short and truncated in their biosynthetic route, and that some contain terminal galactose moieties. Elucidating the precise structure of the carbohydrates and establishing their role in antigenicity will be essential to design strategies to produce them in large and reproducible amounts for the development of improved immunoassays.

  13. Structural and functional analysis of glycoprotein butyrylcholinesterase using atomistic molecular dynamics

    Science.gov (United States)

    Bernardi, Austen; Faller, Roland

    Atomistic molecular dynamics (MD) has proven to be a powerful tool for studying the structure and dynamics of biological systems on nanosecond to microsecond time scales and nanometer length scales. In this work we study the effects of modifying the glycan distribution on the structure and function of full length monomeric butyrylcholinesterase (BChE). BChE exists as a monomer, dimer, or tetramer, and is a therapeutic glycoprotein with nine asparagine glycosylation sites per monomer. Each monomer acts as a stoichiometric scavenger for organophosphorus (OP) nerve agents (e.g. sarin, soman). Glycan distributions are highly heterogeneous and have been shown experimentally to affect certain glycoproteins' stability and reactivity. We performed structural analysis of various biologically relevant glycoforms of BChE using classical atomistic MD. Functional analysis was performed through binding energy simulations using umbrella sampling with BChE and OP cofactors. Additionally, we assess the quality of the glycans' conformational sampling. We found that the glycan distribution has a significant effect on the structure and function of BChE on timescales available to atomistic MD. This project is funded by the DTRA Grant HDTRA1-15-1-0054.

  14. Regional increase in P-glycoprotein function in the blood-brain barrier of patients with chronic schizophrenia : A PET study with [C-11]verapamil as a probe for P-glycoprotein function

    NARCIS (Netherlands)

    de Klerk, Onno L.; Willemsen, Antoon T. M.; Bosker, Fokko J.; Bartels, Anna L.; Hendrikse, N. Harry; den Boer, Johan A.; Dierckx, Rudy A.

    2010-01-01

    P-glycoprotein (P-gp), a major efflux pump in the blood-brain barrier (BBB) has a profound effect on entry of drugs, peptides and other substances into the central nervous system (CNS). The brain's permeability can be negatively influenced by modulation of the transport function of P-gp.

  15. Comparison of brain volume abnormalities between ADHD and conduct disorder in adolescence

    Science.gov (United States)

    Stevens, Michael C.; Haney-Caron, Emily

    2012-01-01

    Background Previous studies of brain structure abnormalities in conduct disorder and attention-deficit/hyperactivity disorder (ADHD) samples have been limited owing to cross-comorbidity, preventing clear understanding of which structural brain abnormalities might be specific to or shared by each disorder. To our knowledge, this study was the first direct comparison of grey and white matter volumes in diagnostically “pure” (i.e., no comorbidities) conduct disorder and ADHD samples. Methods Groups of adolescents with noncormobid conduct disorder and with noncomorbid, combined-subtype ADHD were compared with age- and sex-matched controls using DARTEL voxel-based analysis of T1-weighted brain structure images. Analysis of variance with post hoc analyses compared whole brain grey and white matter volumes among the groups. Results We included 24 adolescents in each study group. There was an overall 13% reduction in grey matter volume in adolescents with conduct disorder, reflecting numerous frontal, temporal, parietal and subcortical deficits. The same grey matter regions typically were not abnormal in those with ADHD. Deficits in frontal lobe regions previously identified in studies of patients with ADHD either were not detected, or group differences from controls were not as strong as those between the conduct disorder and control groups. White matter volume measurements did not differentiate conduct disorder and ADHD. Limitations Our modest sample sizes prevented meaningful examination of individual features of ADHD or conduct disorder, such as aggression, callousness, or hyperactive versus inattentive symptom subtypes. Conclusion The evidence supports theories of frontotemporal abnormalities in adolescents with conduct disorder, but raises questions about the prominence of frontal lobe and striatal structural abnormalities in those with noncomorbid, combined-subtype ADHD. The latter point is clinically important, given the widely held belief that ADHD is

  16. Analysis on effect of separation and purification of glycoprotein extracted from Camellia seeds and its functional activity as basis for the economic development of Camellia oleifera industry

    Directory of Open Access Journals (Sweden)

    Feng Aiguo

    2016-06-01

    Full Text Available Taking Camellia oleifera seeds as raw materials, this study explored extraction and purification of glycoprotein separated from Camellia seeds as well as its antitumor activity, aiming to provide a theoretical basis for the economic development of Camellia oleifera industry. Key impact factors of Camellia seed glycoprotein were extracted using buffer solution method and water extraction method and a regression model was set up. Methyl thiazolyl tetrazolium was used to evaluate the in vitro antitumor activity of glycoprotein extracted from Camellia seeds and Differential Scanning Calorimetry (DSC was used to measure its denaturation enthalpy value. Results indicated that protein and sugar yields were 8.96% and 17.05% respectively under optimal conditions when water extraction method was used. Crude glycoprotein extracted from Camellia oleifera had a certain inhibitory effect on human hepatoma cell HepG2, gastric cancer cell MGC-803 and breast cancer cell MCF-7 and crude glycoprotein extracted from Camellia oleifera by water-extraction and alcohol-precipitation method had a strong antitumor effect. Crude glycoprotein obtained in the two different ways was capable of scavenging DPPH, •OH and O2g- free radicals and also showed good reducing capacity. DSC measurement results revealed that specific rotation of COGP2a[α]n20${\\rm{COGP}}2{\\rm{a}}\\left[ \\alpha \\right]_n^{20} $ was - 32.5. Antitumor experiment in vitro showed that glycoprotein extracted from Camellia seeds in the two different ways had a certain inhibitory effect on HepG2, MGC-803 and MCF-7, which has important theoretical and realistic significances to promoting utilization value of camellia resources, strengthening Camellia oleifera’s comprehensive development and utilization of high added value as well as enriching types and functions of active glycoprotein.

  17. Characterization of glycoprotein C of HSZP strain of herpes simplex virus 1

    NARCIS (Netherlands)

    Oravcova, [No Value; Kudelova, M; Mlcuchova, J; Matis, J; Bystricka, M; Westra, DF; Welling-Wester, S; Rajcani, J

    Sequences of UL44 genes of strains HSZP, KOS and 17 of herpes simplex virus 1 (HSV-1) were determined and the amino acid sequences of corresponding glycoproteins (gC) were deduced. In comparison with the 17 strain, the HSZP strain showed specific changes in 3 nucleotides and in 2 amino acids (aa 139

  18. Use of radioactive glucosamine in the perfused rat liver to prepare α1-acid glycoprotein (orosomucoid) with 3H- or 14C-labelled sialic acid and N-acetylglucosamine residues

    International Nuclear Information System (INIS)

    Aronson, N.N. Jr.

    1982-01-01

    A method was developed whereby [1- 14 C]glucosamine was used in a perfused rat liver system to prepare over 2 mg of α 1 -acid glycoprotein with highly radioactive sialic acid and glucosamine residues. The liver secreted radioactive α 1 -acid glycoprotein over a 4-6 h period, and this glycoprotein was purified from the perfusate by chromatography on DEAE-cellulose at pH3.6. The sialic acid on the isolated glycoprotein had a specific radioactivity of 3.1 Ci/mol, whereas the glucosamine-specific radioactivity was 4.3 Ci/mole. The latter amino-sugar residues on the isolated protein were only 13-fold less radioactive than the initially added [1- 14 C]glucosamine. Orosomucoid with a specific radioactivity of 31.3 μCi/mg of protein was obtainable by using [6- 3 H]glucosamine. Many other radioactive glycoproteins were found to be secreted into the perfusate by the liver. Thus this experimental system should prove useful for obtaining other serum glycoproteins with highly radioactive sugar moieties. (author)

  19. Exome sequencing for prenatal diagnosis of fetuses with sonographic abnormalities.

    Science.gov (United States)

    Drury, Suzanne; Williams, Hywel; Trump, Natalie; Boustred, Christopher; Lench, Nicholas; Scott, Richard H; Chitty, Lyn S

    2015-10-01

    In the absence of aneuploidy or other pathogenic cytogenetic abnormality, fetuses with increased nuchal translucency (NT ≥ 3.5 mm) and/or other sonographic abnormalities have a greater incidence of genetic syndromes, but defining the underlying pathology can be challenging. Here, we investigate the value of whole exome sequencing in fetuses with sonographic abnormalities but normal microarray analysis. Whole exome sequencing was performed on DNA extracted from chorionic villi or amniocytes in 24 fetuses with unexplained ultrasound findings. In the first 14 cases sequencing was initially performed on fetal DNA only. For the remaining 10, the trio of fetus, mother and father was sequenced simultaneously. In 21% (5/24) cases, exome sequencing provided definitive diagnoses (Milroy disease, hypophosphatasia, achondrogenesis type 2, Freeman-Sheldon syndrome and Baraitser-Winter Syndrome). In a further case, a plausible diagnosis of orofaciodigital syndrome type 6 was made. In two others, a single mutation in an autosomal recessive gene was identified, but incomplete sequencing coverage precluded exclusion of the presence of a second mutation. Whole exome sequencing improves prenatal diagnosis in euploid fetuses with abnormal ultrasound scans. In order to expedite interpretation of results, trio sequencing should be employed, but interpretation can still be compromised by incomplete coverage of relevant genes. © 2015 John Wiley & Sons, Ltd.

  20. Highly efficient retrograde gene transfer into motor neurons by a lentiviral vector pseudotyped with fusion glycoprotein.

    Directory of Open Access Journals (Sweden)

    Miyabi Hirano

    Full Text Available The development of gene therapy techniques to introduce transgenes that promote neuronal survival and protection provides effective therapeutic approaches for neurological and neurodegenerative diseases. Intramuscular injection of adenoviral and adeno-associated viral vectors, as well as lentiviral vectors pseudotyped with rabies virus glycoprotein (RV-G, permits gene delivery into motor neurons in animal models for motor neuron diseases. Recently, we developed a vector with highly efficient retrograde gene transfer (HiRet by pseudotyping a human immunodeficiency virus type 1 (HIV-1-based vector with fusion glycoprotein B type (FuG-B or a variant of FuG-B (FuG-B2, in which the cytoplasmic domain of RV-G was replaced by the corresponding part of vesicular stomatitis virus glycoprotein (VSV-G. We have also developed another vector showing neuron-specific retrograde gene transfer (NeuRet with fusion glycoprotein C type, in which the short C-terminal segment of the extracellular domain and transmembrane/cytoplasmic domains of RV-G was substituted with the corresponding regions of VSV-G. These two vectors afford the high efficiency of retrograde gene transfer into different neuronal populations in the brain. Here we investigated the efficiency of the HiRet (with FuG-B2 and NeuRet vectors for retrograde gene transfer into motor neurons in the spinal cord and hindbrain in mice after intramuscular injection and compared it with the efficiency of the RV-G pseudotype of the HIV-1-based vector. The main highlight of our results is that the HiRet vector shows the most efficient retrograde gene transfer into both spinal cord and hindbrain motor neurons, offering its promising use as a gene therapeutic approach for the treatment of motor neuron diseases.

  1. Characterisation of the epitope for a herpes simplex virus glycoprotein B-specific monoclonal antibody with high protective capacity.

    Science.gov (United States)

    Däumer, Martin P; Schneider, Beate; Giesen, Doris M; Aziz, Sheriff; Kaiser, Rolf; Kupfer, Bernd; Schneweis, Karl E; Schneider-Mergener, Jens; Reineke, Ulrich; Matz, Bertfried; Eis-Hübinger, Anna M

    2011-05-01

    Monoclonal antibody (MAb) 2c, specific for glycoprotein B of herpes simplex virus (HSV), had been shown to mediate clearance of infection from the mucous membranes of mice, thereby completely inhibiting mucocutaneous inflammation and lethality, even in mice depleted of both CD4(+) and CD8(+) cells. Additionally, ganglionic infection was highly restricted. In vitro, MAb 2c exhibits a potent complement-independent neutralising activity against HSV type 1 and 2, completely inhibits the viral cell-to-cell spread as well as the syncytium formation induced by syncytial HSV strains (Eis-Hübinger et al. in Intervirology 32:351-360, 1991; Eis-Hübinger et al. in J Gen Virol 74:379-385, 1993). Here, we describe the mapping of the epitope for MAb 2c. The antibody was found to recognise a discontinuous epitope comprised of the HSV type 1 glycoprotein B residues 299 to 305 and one or more additional discontinuous regions that can be mimicked by the sequence FEDF. Identification of the epitope was confirmed by loss of antibody binding to mutated glycoprotein B with replacement of the epitopic key residues, expressed in COS-1 cells. Similarly, MAb 2c was not able to neutralise HSV mutants with altered key residues, and MAb 2c was ineffective in mice inoculated with such mutants. Interestingly, identification and fine-mapping of the discontinuous epitope was not achieved by binding studies with truncated glycoprotein B variants expressed in COS cells but by peptide scanning with synthetic overlapping peptides and peptide key motif analysis. Reactivity of MAb 2c was immensely increased towards a peptide composed of the glycoprotein B residues 299 to 305, a glycine linker, and a C-terminal FEDF motif. If it could be demonstrated that antibodies of the specificity and bioactivity of MAb 2c can be induced by the epitope or a peptide mimicking the epitope, strategies for active immunisation might be conceivable.

  2. Similar diagnostic performance for neurocysticercosis of three glycoprotein preparations from Taenia solium metacestodes.

    Science.gov (United States)

    Villota, Guido E; Gomez, Diana I; Volcy, Michel; Franco, Andrés F; Cardona, Edgar A; Isaza, Rodrigo; Sanzón, Fernando; Teale, Judy M; Restrepo, Blanca I

    2003-03-01

    The detection of antibodies to Taenia solium metacestodes is very important in the differential diagnosis of neurocysticercosis (NCC). In this study, an electroimmunotransfer blot (EITB) assay that uses an elaborate protocol with metacestode glycoproteins as antigens was compared with two other Western blots that use glycoproteins obtained using simpler methods, including an eluate from a lectin column, or the vesicular fluid (VF) of the parasite. The concordance between the three assays was 91% in patients with active NCC and 100% in patients with suspected NCC and previous documentation of negative serology. The specificities for the Western blots and the EITB assay were 98% and 100%, respectively (98% concordance). These data suggest that the simplest of these immunoassays, the one that uses the VF of T. solium metacestodes in a Western blot format, can be reliably used for the serologic diagnosis of NCC in developing countries where access to the EITB assay is difficult.

  3. A Potato cDNA Encoding a Homologue of Mammalian Multidrug Resistant P-Glycoprotein

    Science.gov (United States)

    Wang, W.; Takezawa, D.; Poovaiah, B. W.

    1996-01-01

    A homologue of the multidrug resistance (MDR) gene was obtained while screening a potato stolon tip cDNA expression library with S-15-labeled calmodulin. The mammalian MDR gene codes for a membrane-bound P-glycoprotein (170-180 kDa) which imparts multidrug resistance to cancerous cells. The potato cDNA (PMDR1) codes for a polypeptide of 1313 amino acid residues (ca. 144 kDa) and its structural features are very similar to the MDR P-glycoprotein. The N-terminal half of the PMDR1-encoded protein shares striking homology with its C-terminal half, and each half contains a conserved ATP-binding site and six putative transmembrane domains. Southern blot analysis indicated that potato has one or two MDR-like genes. PMDR1 mRNA is constitutively expressed in all organs studied with higher expression in the stem and stolon tip. The PMDR1 expression was highest during tuber initiation and decreased during tuber development.

  4. Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus

    DEFF Research Database (Denmark)

    Giang, Erick; Dorner, Marcus; Prentoe, Jannick C

    2012-01-01

    , and an effective vaccine should target conserved T- and B-cell epitopes of the virus. Conserved B-cell epitopes overlapping the CD81 receptor-binding site (CD81bs) on the E2 viral envelope glycoprotein have been reported previously and provide promising vaccine targets. In this study, we isolated 73 human m......Abs recognizing five distinct antigenic regions on the virus envelope glycoprotein complex E1E2 from an HCV-immune phage-display antibody library by using an exhaustive-panning strategy. Many of these mAbs were broadly neutralizing. In particular, the mAb AR4A, recognizing a discontinuous epitope outside the CD81......bs on the E1E2 complex, has an exceptionally broad neutralizing activity toward diverse HCV genotypes and protects against heterologous HCV challenge in a small animal model. The mAb panel will be useful for the design and development of vaccine candidates to elicit broadly neutralizing antibodies...

  5. Special report on abnormal climate in 2010

    International Nuclear Information System (INIS)

    2010-12-01

    This reports on abnormal climate in 2010 with impact on the each field. It is comprised of four chapters, which deal with Introduction with purpose of publish and background, current situation and cause of abnormal climate in 2010 on abnormal climate around the world and Korea, Action and impact against abnormal climate in 2010 to agriculture, industry and energy, prevention of disasters, forest, fishery products, environment and health, Evaluation and policy proposal. It also has an appendix about occurrence and damage on abnormal climate of the world in 2010 and media reports on abnormal climate in Korea in 2010.

  6. Herpes simplex virus (HSV)-specific proliferative and cytotoxic T-cell responses in humans immunized with an HSF type 2 glycoprotein subunit vaccine

    Energy Technology Data Exchange (ETDEWEB)

    Zarling, J.M.; Moran, P.A.; Brewer, L.; Ashley, R.; Corey, L.

    1988-12-01

    Studies were undertaken to determine whether immunization of humans with a herpes simplex virus type 2 (HSV-2) glycoprotein-subunit vaccine would result in the priming of both HSV-specific proliferating cells and cytotoxic T cells. Peripheral blood lymphocytes (PBL) from all eight vaccinees studied responded by proliferating after stimulation with HSV-2, HSV-1, and glycoprotein gB-1. The PBL of five of these eight vaccinees proliferated following stimulation with gD-2, whereas stimulation with Gd-1 resulted in relatively low or no proliferative responses. T-cell clones were generated from HSV-2-stimulated PBL of three vaccinees who demonstrated strong proliferative responses to HSV-1 and HSV-2. Of 12 clones studied in lymphoproliferative assays, 9 were found to be cross-reactive for HSV-1 and HSV-2. Of the approximately 90 T-cell clones isolated, 14 demonstrated HSV-specific cytotoxic activity. Radioimmunoprecipitation-polyacrylamide gel electrophoresis analyses confirmed that the vaccinees had antibodies only to HSV glycoproteins, not to proteins which are absent in the subunit vaccine, indicating that these vaccinees had not become infected with HSV. Immunization of humans with an HSV-2 glycoprotein-subunit vaccine thus results in the priming of T cells that proliferate in response to stimulation with HSV and its glycoproteins and T cells that have cytotoxic activity against HSV-infected cells. Such HSV-specific memory T cells were detected as late as 2 years following the last boost with the subunit vaccine.

  7. Identification and partial characterization of Taastrup virus: a newly identified member species of the Mononegavirales

    DEFF Research Database (Denmark)

    Bock, J.O.; Lundsgaard, T.; Pedersen, P.A.

    2004-01-01

    with the glycoproteins of Filoviridae and Pneumovirinae, and a nucleoprotein (N) with homology to the nucleoprotein of viral hemorrhagic septicemia virus (VHSV), a member of the Rhabdoviridae. Highly conserved domains were identified in the RNA-dependent RNA polymerase (L) between TV and other viruses within the order...... of Mononegavirales, and homology was found in particular with members of the Rhabdoviridae. The sequence similarities and the unique filovirus-like but nonidentical morphology unambiguously refer this newly identified virus to the order of Mononegavirales but to no family more than any to other within the order....

  8. Studies on the subunits of human glycoprotein hormones in relation to reproduction

    International Nuclear Information System (INIS)

    Hagen, C.

    1977-01-01

    In this review summarising present knowledge of the biological and immunological activity of the subunits of human glycoprotein hormones, the specificity of the α-subunit and β-subunit radioimmunoassays are discussed. The crossreaction studies performed with the α-subunit radioimmunoassays are aummarised in one table while those with the β-subunit radioimmunoassays are presented in a second table. (JIW)

  9. Dysfunction of bovine endogenous retrovirus K2 envelope glycoprotein is related to unsuccessful intracellular trafficking.

    Science.gov (United States)

    Nakaya, Yuki; Miyazawa, Takayuki

    2014-06-01

    Endogenous retroviruses (ERVs) are the remnants of retroviral infection of ancestral germ cells. Mutations introduced into ERVs halt the production of infectious agents, but their effects on the function of retroviral proteins are not fully understood. Retroviral envelope glycoproteins (Envs) are utilized in membrane fusion during viral entry, and we recently identified intact coding sequences for bovine endogenous retrovirus K1 (BERV-K1) and BERV-K2 Envs. Amino acid sequences of BERV-K1 Env (also called Fematrin-1) and BERV-K2 Env are similar, and both viruses are classified in the genus Betaretrovirus. While Fematrin-1 plays an important role in cell-to-cell fusion in bovine placenta, the BERV-K2 envelope gene is marginally expressed in vivo, and its recombinant Env protein is defective in membrane fusion due to inefficient cleavage of surface (SU) and transmembrane subunits. Here, we conducted chimeric analyses of Fematrin-1 and BERV-K2 Envs and revealed that defective maturation of BERV-K2 Env contributed to failed intracellular trafficking. Fluorescence microscopy and flow cytometric analysis suggested that in contrast to Fematrin-1 Env, BERV-K2 Env could not be transported from the endoplasmic reticulum to the trans-Golgi network, where cellular proteases required for processing retroviral Envs are localized. We also identified that one of the responsive regions of this phenomenon resided within a 65-amino-acid region of BERV-K2 SU. This is the first report to identify that retroviral Env SU is involved in the regulation of intracellular trafficking, and it may help to elucidate the maturation process of Fematrin-1 and other related Envs. Retroviruses utilize envelope glycoproteins (Envs) to enter host target cells. Mature retroviral Env is a heterodimer, which consists of surface (SU) and transmembrane (TM) subunits that are generated by the cleavage of an Env precursor protein in the trans-Golgi network. SU and TM mediate the recognition of the entry

  10. Report to Congress on abnormal occurrences. Volume 2, Number 4. Quarterly report, October-December 1979

    International Nuclear Information System (INIS)

    1980-04-01

    Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report, the nineteenth in the series, covers the period October 1 to December 31, 1979. During the period, there was one abnormal occurrence. The event occurred at an Agreement State licensee and involved overexposure of a hot cell operator. This report also contains information updating previously reported abnormal occurrences

  11. A Novel Fiber Optic Surface Plasmon Resonance Biosensors with Special Boronic Acid Derivative to Detect Glycoprotein

    Directory of Open Access Journals (Sweden)

    Yang Zhang

    2017-10-01

    Full Text Available We proposed and demonstrated a novel tilted fiber Bragg grating (TFBG-based surface plasmon resonance (SPR label-free biosensor via a special boronic acid derivative to detect glycoprotein with high sensitivity and selectivity. TFBG, as an effective sensing element for optical sensing in near-infrared wavelengths, possess the unique capability of easily exciting the SPR effect on fiber surface which coated with a nano-scale metal layer. SPR properties can be accurately detected by measuring the variation of transmitted spectra at optical communication wavelengths. In our experiment, a 10° TFBG coated with a 50 nm gold film was manufactured to stimulate SPR on a sensor surface. To detect glycoprotein selectively, the sensor was immobilized using designed phenylboronic acid as the recognition molecule, which can covalently bond with 1,2- or 1,3-diols to form five- or six-membered cyclic complexes for attaching diol-containing biomolecules and proteins. The phenylboronic acid was synthetized with long alkyl groups offering more flexible space, which was able to improve the capability of binding glycoprotein. The proposed TFBG-SPR sensors exhibit good selectivity and repeatability with a protein concentration sensitivity up to 2.867 dB/ (mg/mL and a limit of detection (LOD of 15.56 nM.

  12. Cellular and biophysical evidence for interactions between adenosine triphosphate and P-glycoprotein substrates

    DEFF Research Database (Denmark)

    Abraham, E H; Shrivastav, B; Salikhova, A Y

    2001-01-01

    P-glycoprotein is involved with the removal of drugs, most of them cations, from the plasma membrane and cytoplasm. Pgp is also associated with movement of ATP, an anion, from the cytoplasm to the extracellular space. The central question of this study is whether drug and ATP transport associated...

  13. Inactivated Recombinant Rabies Viruses Displaying Canine Distemper Virus Glycoproteins Induce Protective Immunity against Both Pathogens.

    Science.gov (United States)

    da Fontoura Budaszewski, Renata; Hudacek, Andrew; Sawatsky, Bevan; Krämer, Beate; Yin, Xiangping; Schnell, Matthias J; von Messling, Veronika

    2017-04-15

    The development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. Both canine distemper virus (CDV) and rabies virus (RABV) cause lethal disease in wild and domestic carnivores. While RABV vaccines are inactivated, the live-attenuated CDV vaccines retain residual virulence for highly susceptible wildlife species. In this study, we developed recombinant bivalent vaccine candidates based on recombinant vaccine strain rabies virus particles, which concurrently display the protective CDV and RABV glycoprotein antigens. The recombinant viruses replicated to near-wild-type titers, and the heterologous glycoproteins were efficiently expressed and incorporated in the viral particles. Immunization of ferrets with beta-propiolactone-inactivated recombinant virus particles elicited protective RABV antibody titers, and animals immunized with a combination of CDV attachment protein- and fusion protein-expressing recombinant viruses were protected from lethal CDV challenge. However, animals that were immunized with only a RABV expressing the attachment protein of CDV vaccine strain Onderstepoort succumbed to infection with a more recent wild-type strain, indicating that immune responses to the more conserved fusion protein contribute to protection against heterologous CDV strains. IMPORTANCE Rabies virus and canine distemper virus (CDV) cause high mortality rates and death in many carnivores. While rabies vaccines are inactivated and thus have an excellent safety profile and high stability, live-attenuated CDV vaccines can retain residual virulence in highly susceptible species. Here we generated recombinant inactivated rabies viruses that carry one of the CDV glycoproteins on their surface. Ferrets immunized twice with a mix of recombinant rabies viruses carrying the CDV fusion and attachment glycoproteins were protected from lethal CDV challenge, whereas all animals that received

  14. Ebola Viral Glycoprotein Bound to Its Endosomal Receptor Niemann-Pick C1.

    Science.gov (United States)

    Wang, Han; Shi, Yi; Song, Jian; Qi, Jianxun; Lu, Guangwen; Yan, Jinghua; Gao, George F

    2016-01-14

    Filoviruses, including Ebola and Marburg, cause fatal hemorrhagic fever in humans and primates. Understanding how these viruses enter host cells could help to develop effective therapeutics. An endosomal protein, Niemann-Pick C1 (NPC1), has been identified as a necessary entry receptor for this process, and priming of the viral glycoprotein (GP) to a fusion-competent state is a prerequisite for NPC1 binding. Here, we have determined the crystal structure of the primed GP (GPcl) of Ebola virus bound to domain C of NPC1 (NPC1-C) at a resolution of 2.3 Å. NPC1-C utilizes two protruding loops to engage a hydrophobic cavity on head of GPcl. Upon enzymatic cleavage and NPC1-C binding, conformational change in the GPcl further affects the state of the internal fusion loop, triggering membrane fusion. Our data therefore provide structural insights into filovirus entry in the late endosome and the molecular basis for design of therapeutic inhibitors of viral entry. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Pattern check of TLD disc readings - an important tool to identify abnormal conditions in workplace

    International Nuclear Information System (INIS)

    Pradhan, S.M.; Sneha, C.; Bhattacharya, M.; Sahai, M.K.; Pradeep, Ratna; Datta, D.; Bhatnagar, Amit

    2016-01-01

    Personnel monitoring for external radiation using CaSO 4 :Dy based TLD badge is well established in Indian radiation protection program. TLD badge enables evaluation of occupational dose based on the pattern and values of the three disc readings. Different patterns of disc readings are obtained depending on the type and energy of radiation in the workplace. Pattern not conforming to the radiation in the workplace also called as improper pattern can be a useful tool for investigation of any deviation / abnormality in workplace or monitoring practices. The paper presents different examples of improper pattern observed in monitoring that has helped to find out the deviations in the workplace or monitoring practices. Results of the experiments conducted to simulate some of the observed pattern are also presented in the paper

  16. Radioautographic study of the synthesis and migration of glycoproteins in the cells of the rat adrenal medulla

    International Nuclear Information System (INIS)

    Benchimol, Sarita; Cantin, Marc

    1978-01-01

    Rats were injected intravenously with ( 3 H) fucose to study the synthesis and migration of glycoproteins into adrenaline-storing and noradrenaline-storing cells of the adrenal medulla and to evaluate the fate of this radioactive sugar in both serum and adrenal-medulla at various time intervals. Radioactivity was decreased in serum by 50% between 5 and 20 min after the injection and by a hundred fold with 1 h. There was a sharp decrease in the radioactivity of the adrenal-medulla between 5 and 20 min after the injection and a slight, continuous decrease thereafter. The adrenal-medullae were fixed 5 min, 20 min, 1 h and 4 h after intravenous injection of [ 3 H] fucose, and radiautographs were analysed quantitatively after development in Microdol X. Kinetic analysis showed that, in both cell types, glycoprotein synthesis is completed in the Golgi complex and glycoproteins migrate subsequently to the secretory granules and to the cell coat. This analysis also revealed that [ 3 H] fucose moves much more rapidly in the Golgi complex of noradrenaline-storing cells than in that of adrenaline-storing cells and appears much earlier in the secretory granules of the former cell type [fr

  17. Viral load in children with congenital cytomegalovirus infection identified on newborn hearing screening.

    Science.gov (United States)

    Kawada, Jun-ichi; Torii, Yuka; Kawano, Yoshihiko; Suzuki, Michio; Kamiya, Yasuko; Kotani, Tomomi; Kikkawa, Fumitaka; Kimura, Hiroshi; Ito, Yoshinori

    2015-04-01

    Congenital cytomegalovirus (CMV) infection is the most common non-genetic cause of sensorineural hearing loss (SNHL) in children. However, congenital SNHL without other clinical abnormalities is rarely diagnosed as CMV-related in early infancy. The aim of this study was to identify and treat patients with congenital CMV-related SNHL or CMV-related clinical abnormalities other than SNHL. The association between CMV load and SNHL was also evaluated. Newborns who had abnormal hearing screening results or other clinical abnormalities were screened for congenital CMV infection by PCR of saliva or urine specimens, and identified infected patients were treated with valganciclovir (VGCV) for 6 weeks. The CMV load of patients with or without SNHL was compared at regular intervals during as well as after VGCV treatment. Of 127 infants with abnormal hearing screening results, and 31 infants with other clinical abnormalities, CMV infection was identified in 6 and 3 infants, respectively. After VGCV treatment, 1 case had improved hearing but the other 5 SNHL cases had little or no improvement. Among these 9 patients with or without SNHL at 1 year of age, there was no significant difference in CMV blood or urine load at diagnosis, but both were significantly higher in patients with SNHL during VGCV treatment. Selective CMV screening of newborns having an abnormal hearing screening result would be a reasonable strategy for identification of symptomatic congenital CMV infection. Prolonged detection of CMV in blood could be a risk factor for SNHL. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Chromosomal abnormalities in amenorrhea: a retrospective study and review of 637 patients in South India.

    Science.gov (United States)

    Dutta, Usha R; Ponnala, Rajitha; Pidugu, Vijaya Kumar; Dalal, Ashwin B

    2013-05-01

    The aim of the present study was to investigate the chromosomal abnormalities and to identify the most prevalent or frequent type of chromosomal abnormalities in cases of amenorrhea from the southern region of India. A total of 637 cases with amenorrhea were analyzed using G- banding, C-banding, Silver staining, and fluorescence in situ hybridization was done wherever necessary. Out of the 637 cases involved in our study, 132 abnormalities were detected. The incidence of chromosomal abnormalities in cases with primary and secondary amenorrhea was around 20.7 %. In addition to the numerical anomalies, various structural aberrations of the X chromosome like deletions, isochromosomes, duplications, ring chromosome, and also male karyotype were detected. Review of the literature and overall incidence of chromosomal abnormalities in patients with amenorrhea suggests the need for cytogenetic analysis to be performed in all the cases referred for amenorrhea with or without short stature. Precise identification of chromosomal abnormalities helps in confirming the provisional diagnosis; it helps the secondary amenorrhea patients in assisted reproduction and to understand the clinical heterogeneity involved and in efficient genetic counseling.

  19. Regional homogeneity of resting-state brain abnormalities in bipolar and unipolar depression.

    Science.gov (United States)

    Liu, Chun-Hong; Ma, Xin; Wu, Xia; Zhang, Yu; Zhou, Fu-Chun; Li, Feng; Tie, Chang-Le; Dong, Jie; Wang, Yong-Jun; Yang, Zhi; Wang, Chuan-Yue

    2013-03-05

    Bipolar disorder patients experiencing a depressive episode (BD-dep) without an observed history of mania are often misdiagnosed and are consequently treated as having unipolar depression (UD), leading to inadequate treatment and poor outcomes. An essential solution to this problem is to identify objective biological markers that distinguish BD-dep and UD patients at an early stage. However, studies directly comparing the brain dysfunctions associated with BD-dep and UD are rare. More importantly, the specificity of the differences in brain activity between these mental disorders has not been examined. With whole-brain regional homogeneity analysis and region-of-interest (ROI) based receiver operating characteristic (ROC) analysis, we aimed to compare the resting-state brain activity of BD-dep and UD patients. Furthermore, we examined the specific differences and whether these differences were attributed to the brain abnormality caused by BD-dep, UD, or both. Twenty-one bipolar and 21 unipolar depressed patients, as well as 26 healthy subjects matched for gender, age, and educational levels, participated in the study. We compared the differences in the regional homogeneity (ReHo) of the BD-dep and UD groups and further identified their pathophysiological abnormality. In the brain regions showing a difference between the BD-dep and UD groups, we further conducted receptive operation characteristic (ROC) analyses to confirm the effectiveness of the identified difference in classifying the patients. We observed ReHo differences between the BD-dep and UD groups in the right ventrolateral middle frontal gyrus, right dorsal anterior insular, right ventral anterior insular, right cerebellum posterior gyrus, right posterior cingulate cortex, right parahippocampal gyrus, and left cerebellum anterior gyrus. Further ROI comparisons and ROC analysis on these ROIs showed that the right parahippocampal gyrus reflected abnormality specific to the BD-dep group, while the right

  20. Incidence of upper tract abnormalities in patients with neurovesical dysfunction secondary to multiple sclerosis: analysis of risk factors at initial urologic evaluation.

    Science.gov (United States)

    Lemack, Gary E; Hawker, Kathleen; Frohman, Elliot

    2005-05-01

    To determine the incidence of upper tract abnormalities on renal ultrasonography in patients with multiple sclerosis (MS) referred for urologic evaluation, as well as to identify any risk factors present on the basis of the historical information and urodynamic findings. Data were derived from all patients with MS referred to the neurourology clinic during a 4-year period. The database was specifically queried for patients found to have upper tract abnormalities on screening renal ultrasonography. Demographic parameters, as well as laboratory values (creatinine) and urodynamic results, were evaluated for risk factors associated with abnormal upper tract findings. Of the 113 patients referred and evaluated, 66 completed both urodynamic testing and renal ultrasonography. Eleven (16.7%) had abnormal ultrasound findings, with focal caliectasis the most common finding. No demographic parameter (age, sex, time since MS diagnosis, MS pattern) was associated with a greater likelihood of abnormal renal ultrasonography on univariate analysis. Neither serum creatinine nor any urodynamic finding (including the presence of dyssynergia or the threshold and amplitude of detrusor overactivity) was associated with abnormal renal ultrasound findings. No patients in our series had any indication of obstructive uropathy more severe than mild hydronephrosis. Of the 16.7% of patients with any abnormal findings, most were noted to have minor caliectasis, likely to be of little clinical significance. Although no factors identifying patients at risk of renal abnormalities at presentation were found, ongoing evaluation of patients with baseline findings will serve to identify those at risk of progression.

  1. Understanding the Process of Envelope Glycoprotein Incorporation into Virions in Simian and Feline Immunodeficiency Viruses

    Directory of Open Access Journals (Sweden)

    José L. Affranchino

    2014-01-01

    Full Text Available The lentiviral envelope glycoproteins (Env mediate virus entry by interacting with specific receptors present at the cell surface, thereby determining viral tropism and pathogenesis. Therefore, Env incorporation into the virions formed by assembly of the viral Gag polyprotein at the plasma membrane of the infected cells is a key step in the replication cycle of lentiviruses. Besides being useful models of human immunodeficiency virus (HIV infections in humans and valuable tools for developing AIDS therapies and vaccines, simian and feline immunodeficiency viruses (SIV and FIV, respectively are relevant animal retroviruses; the study of which provides important information on how lentiviral replication strategies have evolved. In this review, we discuss the molecular mechanisms underlying the incorporation of the SIV and FIV Env glycoproteins into viral particles.

  2. Identification of three novel OA1 gene mutations identified in three families misdiagnosed with congenital nystagmus and carrier status determination by real-time quantitative PCR assay

    Directory of Open Access Journals (Sweden)

    Hamel Christian

    2003-01-01

    Full Text Available Abstract Background X-linked ocular albinism type 1 (OA1 is caused by mutations in OA1 gene, which encodes a membrane glycoprotein localised to melanosomes. OA1 mainly affects pigment production in the eye, resulting in optic changes associated with albinism including hypopigmentation of the retina, nystagmus, strabismus, foveal hypoplasia, abnormal crossing of the optic fibers and reduced visual acuity. Affected Caucasian males usually appear to have normal skin and hair pigment. Results We identified three previously undescribed mutations consisting of two intragenic deletions (one encompassing exon 6, the other encompassing exons 7–8, and a point mutation (310delG in exon 2. We report the development of a new method for diagnosis of heterozygous deletions in OA1 gene based on measurement of gene copy number using real-time quantitative PCR from genomic DNA. Conclusion The identification of OA1 mutations in families earlier reported as families with hereditary nystagmus indicate that ocular albinism type 1 is probably underdiagnosed. Our method of real-time quantitative PCR of OA1 exons with DMD exon as external standard performed on the LightCycler™ allows quick and accurate carrier-status assessment for at-risk females.

  3. Receptor-Targeted Nipah Virus Glycoproteins Improve Cell-Type Selective Gene Delivery and Reveal a Preference for Membrane-Proximal Cell Attachment.

    Directory of Open Access Journals (Sweden)

    Ruben R Bender

    2016-06-01

    Full Text Available Receptor-targeted lentiviral vectors (LVs can be an effective tool for selective transfer of genes into distinct cell types of choice. Moreover, they can be used to determine the molecular properties that cell surface proteins must fulfill to act as receptors for viral glycoproteins. Here we show that LVs pseudotyped with receptor-targeted Nipah virus (NiV glycoproteins effectively enter into cells when they use cell surface proteins as receptors that bring them closely enough to the cell membrane (less than 100 Å distance. Then, they were flexible in receptor usage as demonstrated by successful targeting of EpCAM, CD20, and CD8, and as selective as LVs pseudotyped with receptor-targeted measles virus (MV glycoproteins, the current standard for cell-type specific gene delivery. Remarkably, NiV-LVs could be produced at up to two orders of magnitude higher titers compared to their MV-based counterparts and were at least 10,000-fold less effectively neutralized than MV glycoprotein pseudotyped LVs by pooled human intravenous immunoglobulin. An important finding for NiV-LVs targeted to Her2/neu was an about 100-fold higher gene transfer activity when particles were targeted to membrane-proximal regions as compared to particles binding to a more membrane-distal epitope. Likewise, the low gene transfer activity mediated by NiV-LV particles bound to the membrane distal domains of CD117 or the glutamate receptor subunit 4 (GluA4 was substantially enhanced by reducing receptor size to below 100 Å. Overall, the data suggest that the NiV glycoproteins are optimally suited for cell-type specific gene delivery with LVs and, in addition, for the first time define which parts of a cell surface protein should be targeted to achieve optimal gene transfer rates with receptor-targeted LVs.

  4. Pumping of drugs by P-glycoprotein

    DEFF Research Database (Denmark)

    Litman, Thomas; Skovsgaard, Torben; Stein, Wilfred D

    2003-01-01

    The apparent inhibition constant, Kapp, for the blockade of P-glycoprotein (P-gp) by four drugs, verapamil, cyclosporin A, XR9576 (tariquidar), and vinblastine, was measured by studying their ability to inhibit daunorubicin and calcein-AM efflux from four strains of Ehrlich cells with different...... levels of drug resistance and P-gp content. For daunorubicin as a transport substrate, Kapp was independent of [P-gp] for verapamil but increased strictly linearly with [P-gp] for vinblastine, cyclosporin A, and XR9576. A theoretical analysis of the kinetics of drug pumping and its reversal shows...... but rather, in serial, i.e., a drug that is pumped from the cytoplasmic phase has to pass the preemptive route upon leaving the cell. Our results are consistent with the Sauna-Ambudkar two-step model for pumping by P-gp. We suggest that the vinblastine/cyclosporin A/XR9576-binding site accepts daunorubicin...

  5. Report on abnormal climate in 2011

    International Nuclear Information System (INIS)

    2011-12-01

    This paper reports of impact on abnormal climate in 2011. It has Introduction with purpose and background of publish and summary of this report. The cause and current state on abnormal climate of the world and Korea in 2011, Measurement and impact against abnormal climate in 2011 to agriculture, land and maritime, industry and energy, prevention of disasters, environment and health, assessment and advice on the policy. It lists the appendix about occurrence and damage on abnormal climate of the world and Korea in 2011 and media report data.

  6. Pregnancy Complications: Umbilical Cord Abnormalities

    Science.gov (United States)

    ... Umbilical cord abnormalities Umbilical cord abnormalities Now playing: E-mail to a friend Please fill in all fields. ... blood supply) to the baby. The two arteries transport waste from the baby to the placenta (where ...

  7. Abnormal anal cytology risk in women with known genital squamous intraepithelial lesion

    Directory of Open Access Journals (Sweden)

    Maria do Socorro Nobre

    2016-05-01

    Full Text Available The purpose of this study was to assess the risk of abnormal anal cytology in women with known genital squamous intraepithelial lesion. This study evaluated 200 women with and without genital squamous intraepithelial lesion who were recruited for anal Pap smears. Women who had abnormal results on equally or over atypical squamous cells of undetermined significance were classified as having abnormal anal cytology. A multiple logistic regression analysis (stepwise was performed to identify the risk for developing abnormal anal cytology. Data were analyzed using the SPSS 20.0 program. The average age was 41.09 (±12.64. Of the total participants, 75.5% did not practice anal sex, 91% did not have HPV-infected partners, 92% did not have any anal pathology, and 68.5% did not have anal bleeding. More than half (57.5% had genital SIL and a significant number developed abnormal anal cytology: 13% in the total sample and 17.4% in women with genital SIL. A significant association was observed between genital squamous intraepithelial lesion and anal squamous intraepithelial lesion (PR = 2.46; p = 0.03. In the logistic regression model, women having genital intraepithelial lesion were more likely to have abnormal anal Pap smear (aPR = 2.81; p = 0.02. This report shows that women with genital squamous intraepithelial lesion must be more closely screened for anal cancer.

  8. Esophagogastric junction outflow obstruction is often associated with coexistent abnormal esophageal body motility and abnormal bolus transit.

    Science.gov (United States)

    Zheng, E; Gideon, R M; Sloan, J; Katz, P O

    2017-10-01

    Currently, the diagnosis of esophageal motility disorders is in part based upon a hierarchical algorithm in which abnormalities of the esophagogastric junction (EGJ) is prioritized. An important metric in evaluating the EGJ is the integrated relaxation pressure (IRP). Patients who do not have achalasia but are found to have an elevated IRP are diagnosed with EGJ outflow obstruction. It has been our observation that a subset of these patients also has a second named motility disorder and may also have abnormal bolus transit. The aim of this study is to determine the frequency of abnormal body motility and or abnormal bolus movement in patients with EGJ outflow obstruction. Further, in an effort to evaluate the potential clinical value in measuring bolus transit as a complement to esophageal manometry, specifically in patients with EGJ outflow obstruction, we analyzed the presenting symptoms of these patients. A total of 807 patients with a mean age of 53 years completed esophageal function testing with impedance monitoring and high-resolution manometry between January 2012 and October 2016. There were 74 patients with achalasia who were excluded from the study. Of the remaining 733 patients, 138 (19%) had an elevated IRP and were given a diagnosis of EGJ outflow obstruction. Among these patients, 56 (40%) were diagnosed with an abnormal motility pattern to liquids (ineffective esophageal motility = 28, distal esophageal spasm = 19, Jackhammer = 6), of which 44 (76%) had abnormal bolus transit to liquids, viscous, or both. In contrast, there were 82 patients with EGJ outflow obstruction and normal esophageal motility, of which 33 (40%) had abnormal bolus transit. Patients with preserved esophageal motility and EGJ outflow obstruction were then evaluated. Of the 733 patients, 299 (40%) had intact esophageal motility. Of the 299 patients with normal esophageal motility, 56 patients had an elevated IRP, of which 16 (28%) had abnormal bolus transit. There were 243 (33

  9. Comparative radiochemical and radio-immunometrical study on trophoblast-dependent serum parameters under parturition, and radio-immunological detection of pregnancy-specific β1-glycoprotein [SP1] in early pregnancy

    International Nuclear Information System (INIS)

    Weber, K.A.E.

    1982-01-01

    77 deliveries were studied clinically and chemically bench-scale using data acquisition sheets applicable for computer operation. According to a catalog 30 normal, 32 abnormal and 15 births featuring EPH gestosis were clearly defined and classified. Radiochemical or radio-immunometrical methods were used to simultaneously analyse and evaluate statistically the following 'trophoblast-dependent serum parameters' in subpartem and postpartem maternal blood, and in aterialized or pooled venous-arterialized umbilicalchord blood in the case groups mentioned above: - 17 β-hydroxysteroid; NAD(P)-oxydoreductase (17 β-HSD; - free oestriol (fE 3 ); -β-subunit of Human Chorionic Gonadotropin (β-hCG); - Human Chorionic Somatomammatropin (hCS=hPL); - and pregnancy-specific β 1 -glycoprotein (SP 1 ). A systematic study was made for the statistical correlations between trophoblast - dependent serum parameters and plancental and neonatal findings as well as for possible correlations between the serum parameters in both the maternal and fetal blood distribution spaces. (orig./MG) [de

  10. Exercises to Improve Gait Abnormalities

    Science.gov (United States)

    ... Articles Directories Videos Resources Contact Exercises to Improve Gait Abnormalities Home » Article Categories » Exercise and Fitness Font Size: A A A A Exercises to Improve Gait Abnormalities Next Page The manner of how a ...

  11. The influence of brain abnormalities on psychosocial development, criminal history and paraphilias in sexual murderers.

    Science.gov (United States)

    Briken, Peer; Habermann, Niels; Berner, Wolfgang; Hill, Andreas

    2005-09-01

    The aim of this study was to investigate the number and type of brain abnormalities and their influence on psychosocial development, criminal history and paraphilias in sexual murderers. We analyzed psychiatric court reports of 166 sexual murderers and compared a group with notable signs of brain abnormalities (N = 50) with those without any signs (N = 116). Sexual murderers with brain abnormalities suffered more from early behavior problems. They were less likely to cohabitate with the victim at the time of the homicide and had more victims at the age of six years or younger. Psychiatric diagnoses revealed a higher total number of paraphilias: Transvestic fetishism and paraphilias not otherwise specified were more frequent in offenders with brain abnormalities. A binary logistic regression identified five predictors that accounted for 46.8% of the variance explaining the presence of brain abnormalities. Our results suggest the importance of a comprehensive neurological and psychological examination of this special offender group.

  12. Sequencing Chromosomal Abnormalities Reveals Neurodevelopmental Loci that Confer Risk across Diagnostic Boundaries

    DEFF Research Database (Denmark)

    Talkowski, Michael E.; Rosenfeld, Jill A.; Blumenthal, Ian

    2012-01-01

    Sequencing of balanced chromosomal abnormalities, combined with convergent genomic studies of gene expression, copy-number variation, and genome-wide association, identifies 22 new loci that contribute to autism and related neurodevelopmental disorders. These data support a polygenic risk model...

  13. Fetal heart rate abnormalities during and after external cephalic version: Which fetuses are at risk and how are they delivered?

    Science.gov (United States)

    Kuppens, Simone M; Smailbegovic, Ida; Houterman, Saskia; de Leeuw, Ingrid; Hasaart, Tom H

    2017-10-17

    Fetal heart rate abnormalities (FHR) during and after external cephalic version (ECV) are relatively frequent. They may raise concern about fetal wellbeing. Only occasionally they may lead to an emergency cesarean section. Prospective cohort study in 980 women (> 34 weeks gestation) with a singleton fetus in breech presentation. During and after external cephalic version (ECV) FHR abnormalities were recorded. Obstetric variables and delivery outcome were evaluated. Primary outcome was to identify which fetuses are at risk for FHR abnormalities. Secondary outcome was to identify a possible relationship between FHR abnormalities during and after ECV and mode of delivery and fetal distress during subsequent labor. The overall success rate of ECV was 60% and in 9% of the attempts there was an abnormal FHR pattern. In two cases FHR abnormalities after ECV led to an emergency CS. Estimated fetal weight per 100 g (OR 0.90, CI: 0.87-0.94) and longer duration of the ECV-procedure (OR 1.13, CI: 1.05-1.21) were factors significantly associated with the occurrence of FHR abnormalities. FHR abnormalities were not associated with the mode of delivery or the occurrence of fetal distress during subsequent labor. FHR abnormalities during and after ECV are more frequent with lower estimated fetal weight and longer duration of the procedure. FHR abnormalities during and after ECV have no consequences for subsequent mode of delivery. They do not predict whether fetal distress will occur during labor. The Eindhoven Breech Intervention Study, NCT00516555 . Date of registration: August 13, 2007.

  14. Profile of hematological abnormalities of Indian HIV infected individuals

    Directory of Open Access Journals (Sweden)

    Sharma Aman

    2009-08-01

    Full Text Available Abstract Background Hematological abnormalities are a common complication of HIV infection. These abnormalities increase as the disease advances. Bone marrow abnormalities occur in all stages of HIV infection. Methods Two hundred HIV infected individual were screened for hematological abnormalities from March 2007–March 2008. Absolute CD4 cell count analysis was carried out by flowcytometry. Depending on the results of the primary screening further investigations were performed, like iron studies, hemolytic work up, PNH work up and bone marrow evaluation. Other investigations included coagulation profile, urine analysis, blood culture (bacterial, fungal, mycobacterial, serology for Epstein Barr virus (EBV, Cytomegalovirus (CMV, Hepatitis B and C, and Parvo B19 infection. Results The most common hematological abnormality was anemia, seen in 65.5% (131/200 patients. Iron deficiency anemia was seen in 49.2% (/200 cases while anemia of chronic disease occurred in 50.7% (/200 cases. Bone marrow evaluation was carried out in 14 patients out of which staging marrow was performed in 2 cases of non-Hodgkin's lymphoma (NHL and did not show any bone marrow infiltration. In remaining12 cases bone marrow was done for evaluation of pancytopenia. Among patients with pancytopenia 50% (6/12 showed granulomas (4 were positive for AFB, 2 were positive for fungal cryptococci, 25% (3/12 showed hemophagocytosis. There was a strong negative correlation between anemia and CD4 counts in this study. Thrombocytopenia was seen in 7% (14/200 cases and had no significant correlation with CD4 counts. No patient had absolute neutrophil count (ANC Conclusion Anemia in HIV patients can be a good clinical indicator to predict and access the underlying immune status. Patients should be investigated for hematological manifestations and appropriate steps should be taken to identify and treat the reversible factors.

  15. Latent and Abnormal Functional Connectivity Circuits in Autism Spectrum Disorder.

    Science.gov (United States)

    Chen, Shuo; Xing, Yishi; Kang, Jian

    2017-01-01

    Autism spectrum disorder (ASD) is associated with disrupted brain networks. Neuroimaging techniques provide noninvasive methods of investigating abnormal connectivity patterns in ASD. In the present study, we compare functional connectivity networks in people with ASD with those in typical controls, using neuroimaging data from the Autism Brain Imaging Data Exchange (ABIDE) project. Specifically, we focus on the characteristics of intrinsic functional connectivity based on data collected by resting-state functional magnetic resonance imaging (rs-fMRI). Our aim was to identify disrupted brain connectivity patterns across all networks, instead of in individual edges, by using advanced statistical methods. Unlike many brain connectome studies, in which networks are prespecified before the edge connectivity in each network is compared between clinical groups, we detected the latent differentially expressed networks automatically. Our network-level analysis identified abnormal connectome networks that (i) included a high proportion of edges that were differentially expressed between people with ASD and typical controls; and (ii) showed highly-organized graph topology. These findings provide new insight into the study of the underlying neuropsychiatric mechanism of ASD.

  16. Memetics clarification of abnormal behavior

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: Biological medicine is hard to fully and scientifically explain the etiological factor and pathogenesis of abnormal behaviors; while, researches on philosophy and psychology (including memetics) are beneficial to better understand and explain etiological factor and pathogenesis of abnormal behaviors. At present, the theory of philosophy and psychology is to investigate the entity of abnormal behavior based on the views of memetics.METHODS: Abnormal behavior was researched in this study based on three aspects, including instinctive behavior disorder, poorly social-adapted behavior disorder and mental or body disease associated behavior disorder. Most main viewpoints of memetics were derived from "The Meme Machine", which was written by Susan Blackmore. When questions about abnormal behaviors induced by mental and psychological diseases and conduct disorder of teenagers were discussed, some researching achievements which were summarized by authors previously were added in this study, such as aggressive behaviors, pathologically aggressive behaviors, etc.RESULTS: The abnormal behaviors mainly referred to a part of people's substandard behaviors which were not according with the realistic social environment, culture background and the pathologic behaviors resulted from people's various psychological diseases. According to the theory of "meme", it demonstrated that the relevant behavioral obstacles of various psychological diseases, for example, the unusual behavior of schizophrenia, were caused, because the old meme was destroyed thoroughly but the new meme was unable to establish; psychoneurosis and personality disorder were resulted in hard establishment of meme; the behavioral obstacles which were ill-adapted to society, for example, various additional and homosexual behaviors, were because of the selfish replications and imitations of "additional meme" and "homosexual meme"; various instinct behavioral and congenital intelligent obstacles were not significance

  17. Neurologic abnormalities in murderers.

    Science.gov (United States)

    Blake, P Y; Pincus, J H; Buckner, C

    1995-09-01

    Thirty-one individuals awaiting trial or sentencing for murder or undergoing an appeal process requested a neurologic examination through legal counsel. We attempted in each instance to obtain EEG, MRI or CT, and neuropsychological testing. Neurologic examination revealed evidence of "frontal" dysfunction in 20 (64.5%). There were symptoms or some other evidence of temporal lobe abnormality in nine (29%). We made a specific neurologic diagnosis in 20 individuals (64.5%), including borderline or full mental retardation (9) and cerebral palsy (2), among others. Neuropsychological testing revealed abnormalities in all subjects tested. There were EEG abnormalities in eight of the 20 subjects tested, consisting mainly of bilateral sharp waves with slowing. There were MRI or CT abnormalities in nine of the 19 subjects tested, consisting primarily of atrophy and white matter changes. Psychiatric diagnoses included paranoid schizophrenia (8), dissociative disorder (4), and depression (9). Virtually all subjects had paranoid ideas and misunderstood social situations. There was a documented history of profound, protracted physical abuse in 26 (83.8%) and of sexual abuse in 10 (32.3%). It is likely that prolonged, severe physical abuse, paranoia, and neurologic brain dysfunction interact to form the matrix of violent behavior.

  18. Pattern of semen fluid abnormalities in male partners of infertile couples in southeastern, Nigeria.

    Science.gov (United States)

    Ugboaja, J O; Monago, E N; Obiechina, N J A

    2010-01-01

    The incidence of male infertility is increasing in our environment. There is a need to evaluate the pattern of abnormality with a view to recommending appropriate interventions. We aimed to to analyze the seminal fluid parameters of the male partners of the infertile couples managed in the hospital over a 12 month period and to identify the pattern of abnormalities. A retrospective study of all the semen samples of male partners of infertile couples submitted for analysis to the microbiology laboratory of Nnamdi Azikiwe University Teaching Hospital, Nnewi Nigeria between 1st January 2006 and 31st December 2006 The reports of the semen fluid analysis were retrieved from the records department and supplemented with the laboratory register. Out of the 348 semen sample reports evaluated, 237 (68.0%) had semen fluid abnormalities. 104 (30.0%) had single factor abnormalities while 133 (38.0%) had combined factor anomalies. Asthenozoospermia 58 (16.7%) was the main single abnormality, while Astheno-oligozoospermia 51 (14.7%) and Astheno-oligoteratozoospermia (13.2%) were the major combined factor abnormalities detected. Very few 5 (1.4%) of the patients had azospermia. The study showed a high rate of semen fluid abnormalities among the male partners of infertile women in our environment. The high preponderance of poor motility emphasizes the need to include men in programmes aimed at reducing sexually transmitted infections in Nigeria.

  19. Identifying specific prefrontal neurons that contribute to autism-associated abnormalities in physiology and social behavior

    DEFF Research Database (Denmark)

    Brumback, A C; Ellwood, I T; Kjaerby, C

    2017-01-01

    Functional imaging and gene expression studies both implicate the medial prefrontal cortex (mPFC), particularly deep-layer projection neurons, as a potential locus for autism pathology. Here, we explored how specific deep-layer prefrontal neurons contribute to abnormal physiology and behavior...... in mouse models of autism. First, we find that across three etiologically distinct models-in utero valproic acid (VPA) exposure, CNTNAP2 knockout and FMR1 knockout-layer 5 subcortically projecting (SC) neurons consistently exhibit reduced input resistance and action potential firing. To explore how altered...... SC neuron physiology might impact behavior, we took advantage of the fact that in deep layers of the mPFC, dopamine D2 receptors (D2Rs) are mainly expressed by SC neurons, and used D2-Cre mice to label D2R+ neurons for calcium imaging or optogenetics. We found that social exploration preferentially...

  20. Activation of the classical pathway of complement by tobacco glycoprotein (TGP).

    Science.gov (United States)

    Koethe, S M; Nelson, K E; Becker, C G

    1995-07-15

    Tobacco glycoprotein (TGP), a polyphenol-rich glycoprotein isolated from tobacco leaves, activates the classical complement pathway through a mechanism that appears to involve direct interaction with C1q. A binding site on C1q for TGP can be localized by competitive inhibition with DNA to a region located in the junction between the collagen-like and globular regions of the molecule. A protein with activity similar to TGP has also been isolated from cigarette smoke condensate (TGP-S); it shares a binding site on C1q with TGP and has similar functional activity, with the exception that complement activation does not proceed to formation of a C3 cleaving enzyme. The ability of TGP and TGP-S to activate complement can be partially duplicated using polyphenols associated with tobacco leaf and smoke, i.e., chlorogenic acid and rutin. These polyphenols also compete with TGP for a binding site on immobilized C1q, suggesting that the polyphenol portion of TGP is critical for activation of complement. These results provide an additional mechanism for complement activation by cigarette products that, in vivo, could result in a localized complement depletion, generation of biologically active complement cleavage products, and initiation of an inflammatory response.