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Sample records for abnormal glycoproteins identified

  1. Relationship of abnormal Tamm-Horsfall glycoprotein localization to renal morphology and function.

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    Chambers, R; Groufsky, A; Hunt, J S; Lynn, K L; McGiven, A R

    1986-07-01

    Tamm-Horsfall glycoprotein (TH) distribution was studied using a biotin-avidin immunoperoxidase technique in renal biopsies from 166 consecutive patients and 8 normal kidneys. Tubulointerstitial damage was independently assessed and graded. In 109 patients TH antibodies were measured by ELISA and in 30 of these urinary TH and beta 2-microglobulin excretions were measured by radioimmunoassay. In 124 biopsies only distal tubular epithelium and casts were stained. Glomerular space (8) or interstitial (34) deposits were seen in 42 biopsies; 16/68 with glomerulonephritis, 4/14 with systemic vasculitis, 12/33 with chronic interstitial nephritis, 1/8 with acute interstitial nephritis, 9/43 with other nephropathies. There was no correlation between TH distribution and the degree of tubulointerstitial damage (p greater than 0.5), urinary TH excretion (p greater than 0.05), urinary beta 2-microglobulin excretion (p greater than 0.05), glomerular filtration rate, urinary concentrating ability, or the incidence of pyuria. TH antibodies did not correlate with TH distribution (p greater than 0.5) or the degree of tubulointerstitial damage. Abnormal TH distribution showed no statistical relationship to the degree of tubulointerstitial damage, changes in renal function or levels of TH antibodies.

  2. Protein and glycoprotein abnormalities in platelets from human Chediak-Higashi syndrome: polyacrylamide gel electrophoretic study of platelets from five patients.

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    Ledezma, E; Apitz-Castro, R

    1985-10-01

    Polyacrylamide electrophoretic analysis of proteins and Tritium-labelled glycoproteins of the platelets from five patients with Chediak-Higashi Syndrome shows the existence of marked quantitative differences when compared to normal platelets. While the glycoprotein abnormalities are solely related to the plasma membrane, some of the abnormalities detected in the Coomasie blue pattern are probably representative of defects related to the dense bodies and the alpha-granules. Some of the abnormalities found may, in part, explain the variability of aggregatory responses described in these patients, as well as the marked tendency towards desaggregation exhibited by platelets from humans with the Chediak-Higashi Syndrome.

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

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    Coze Carole

    2006-01-01

    Full Text Available Abstract Background Pleuropulmonary blastoma (PPB is a rare childhood dysontogenetic intrathoracic neoplasm associated with an unfavourable clinical behaviour. Cases presentation 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. Conclusion 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.

  4. Hereditary increase of plasma histidine-rich glycoprotein associated with abnormal heparin binding (HRG Eindhoven).

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    Hoffmann, J J; Hennis, B C; Kluft, C; Vijgen, M

    1993-12-20

    Plasma histidine-rich glycoprotein (HRG) was found to be persistently increased in a patient with a history of recurrent arterial thromboembolic events. The mean concentration was 270% of normal pooled plasma. Increased HRG was found in eight of the 17 relatives studied, but none of them has experienced thrombo-embolism yet. Apparently, increased HRG was hereditary with autosomal dominant inheritance. A significant correlation was found between the increased plasma concentration of the protein and the age of the subjects (P Eindhoven.

  5. Leptin Reference Values and Cutoffs for Identifying Cardiometabolic Abnormalities in the Spanish Population.

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    Gijón-Conde, Teresa; Graciani, Auxiliadora; Guallar-Castillón, Pilar; Aguilera, M Teresa; Rodríguez-Artalejo, Fernando; Banegas, José R

    2015-08-01

    Estimate leptin reference values and calculate leptinemia cutoff values for identifying cardiometabolic abnormalities in Spain. Cross-sectional study carried out between 2008 and 2010 in 11 540 individuals representing the Spanish population aged ≥ 18 years. Data were obtained by standardized physical examination and analyses were performed at a central laboratory. Leptinemia was measured using ELISA. Cardiometabolic abnormality was defined as the presence of at least two of the following: high blood pressure, high triglycerides, reduced high density lipoprotein cholesterol, high insulin resistance values, and elevated C-reactive protein and glucose. Leptin values were higher in women than men (geometric mean, 21.9 and 6.6 ng/mL; P<.001). The median [interquartile range] was 24.5 [14.1-37.0] ng/mL in women, and 7.2 [3.3-14.3] ng/mL in men. In the multivariate analysis, leptin was significantly associated with anthropometric measures, insulin, and C-reactive protein, and inversely associated with age, smoking, and physical activity in women (r(2)=0.53; P<.001) and in men (r(2)=0.61; P<.001). The leptin values that identified cardiometabolic abnormality were 23.75 ng/mL in women (area under the curve, 0.722; sensitivity, 72.3%; specificity, 58.7%) and 6.45 ng/mL in men (area under the curve, 0.716; sensitivity, 71.4%; specificity, 60.2%). These results facilitate the interpretation of leptin values in clinical and population studies. Leptin has moderate sensitivity and specificity for identifying cardiometabolic abnormalities. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  6. Multimodal analyses identify linked functional and white matter abnormalities within the working memory network in schizophrenia.

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    Sugranyes, Gisela; Kyriakopoulos, Marinos; Dima, Danai; O'Muircheartaigh, Jonathan; Corrigall, Richard; Pendelbury, Gabrielle; Hayes, Daniel; Calhoun, Vince D; Frangou, Sophia

    2012-07-01

    Dysconnectivity between brain regions is thought to underlie the cognitive abnormalities that characterise schizophrenia (SZ). Consistent with this notion functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) studies in SZ have reliably provided evidence of abnormalities in functional integration and in white matter connectivity. Yet little is known about how alterations at the functional level related to abnormalities in anatomical connectivity. We obtained fMRI data during the 2-back working memory task from 25 patients with SZ and 19 healthy controls matched for age, sex and IQ. DTI data were also acquired in the same session. In addition to conventional unimodal analyses we extracted "features" [contrast maps for fMRI and fractional anisotropy (FA) for DTI] that were subjected to joint independent component analysis (JICA) in order to examine interactions between fMRI and DTI data sources. Conventional unimodal analyses revealed both functional and structural deficits in patients with SZ. The JICA identified regions of joint, multimodal brain sources that differed in patients and controls. The fMRI source implicated regions within the anterior cingulate and ventrolateral prefrontal cortex and in the cuneus where patients showed relative hypoactivation and within the frontopolar cortex where patients showed relative hyperactivation. The DTI source localised reduced FA in patients in the splenium and posterior cingulum. This study promotes our understanding of structure-function relationships in SZ by characterising linked functional and white matter changes that contribute to working memory dysfunction in this disorder. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. 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.

  8. Structural Magnetic Resonance Imaging Can Identify Trigeminal System Abnormalities in Classical Trigeminal Neuralgia

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    DeSouza, Danielle D.; Hodaie, Mojgan; Davis, Karen D.

    2016-01-01

    Classical trigeminal neuralgia (TN) is a chronic pain disorder that has been described as one of the 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. PMID:27807409

  9. Magnetic resonance imaging of the placenta identifies placental vascular abnormalities independently of Doppler ultrasound.

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    Messerschmidt, A; Baschat, A; Linduska, N; Kasprian, G; Brugger, P C; Bauer, A; Weber, M; Prayer, D

    2011-06-01

    To evaluate the relationship between placental vascular pathology detected by prenatal magnetic resonance imaging (MRI) and perinatal outcome. This was a retrospective, hospital-based, cross-sectional study in which all fetal MRI examinations of singleton pregnancies with vascular placental pathology (i.e. infarction with/without hemorrhage, subchorionic thrombi/hemorrhages, intervillous thrombi/hemorrhages, or retroplacental hematoma) in the period 2002-2007 were included. The extent of the pathology was expressed as a percentage of the total placental volume. Abnormalities of umbilical artery Doppler ultrasound examinations within 7 days between MRI and ultrasound examination were noted. Death in utero or postnatally was the primary outcome. Gestational age at MRI and at birth and the occurrence of intrauterine growth restriction (IUGR) were noted. Logistic regression analysis was performed to assess the impact of gestational age at MRI, extent of the vascular lesion and presence of pathological Doppler ultrasound measurements on the prediction of mortality. Fifty-nine structurally normal singleton pregnancies with placental vascular abnormalities were included in the analysis. Mortality rate was 36%; among the survivors, 87% were born before 37 + 0 gestational weeks and 50% suffered from IUGR. In 55% of the pregnancies pathological umbilical artery Doppler findings were identified, of which 27% were non-survivors. Mortality was predicted by earlier gestational age at fetal MRI for placental pathology (P < 0.05) and increasing extent of the vascular lesion (P < 0.05), but not by the presence of pathological Doppler ultrasound data. Accuracy of the prediction was 82%, sensitivity was 67% and specificity 89%. MRI-detected vascular placental pathologies may help to identify pregnancies at risk for adverse outcome and fetal death independently of umbilical artery Doppler status. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

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

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    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.)

  11. Vertebral venous system abnormalities identified with magnetic resonance imaging in sighthounds.

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    Vernon, John C; Durand, Alexane; Guevar, Julien; José-López, Roberto; Hammond, Gawain; Stalin, Catherine; Gutierrez-Quintana, Rodrigo

    2017-07-01

    In humans, abnormalities of the vertebral venous system are considered rare but significant causes of radiculopathy and myelopathy. Published information on abnormalities of the canine vertebral venous system is currently lacking. Aims of this retrospective descriptive study were to characterize magnetic resonance imaging (MRI) abnormalities of the vertebral venous system in a population of sighthounds, report prevalence of vertebral venous system abnormalities within that population and explore possible clinical significance. Our hospital database was searched over the period of 2002-2013 for sighthounds with MRI studies of the vertebral column. Medical records and MRI studies for included dogs were retrieved and findings were recorded by a single observer. A total of 92 sighthounds were sampled. Eleven cases (prevalence 12%) showed abnormal enlargement of the internal vertebral venous plexus (10/11 unilaterally, 1/11 bilaterally), external vertebral venous plexus (7/11 cases unilaterally), and/or intervertebral veins (8/11 unilaterally, 2/11 bilaterally, and 1/11 unilaterally and bilaterally at different sites). The majority of the abnormalities were right sided and the most common location for abnormalities was C6/7. Of the 11 cases, nine did not have a definitive diagnosis. Seven of those nine cases had an abnormality in a neuroanatomical localization that could wholly or partly explain the clinical signs. Findings indicated that, while the prevalence of vertebral venous system abnormalities was low in this sample of sighthounds, the majority of dogs with these abnormalities had clinical signs that matched the location of the abnormalities. Further prospective research is needed to investigate potential underlying aetiologies for vertebral venous system abnormalities in dogs and clarify their clinical significance. © 2017 American College of Veterinary Radiology.

  12. Kinematic analysis quantifies gait abnormalities associated with lameness in broiler chickens and identifies evolutionary gait differences.

    Science.gov (United States)

    Caplen, Gina; Hothersall, Becky; Murrell, Joanna C; Nicol, Christine J; Waterman-Pearson, Avril E; Weeks, Claire A; Colborne, G Robert

    2012-01-01

    This is the first time that gait characteristics of broiler (meat) chickens have been compared with their progenitor, jungle fowl, and the first kinematic study to report a link between broiler gait parameters and defined lameness scores. A commercial motion-capturing system recorded three-dimensional temporospatial information during walking. The hypothesis was that the gait characteristics of non-lame broilers (n = 10) would be intermediate to those of lame broilers (n = 12) and jungle fowl (n = 10, tested at two ages: immature and adult). Data analysed using multi-level models, to define an extensive range of baseline gait parameters, revealed inter-group similarities and differences. Natural selection is likely to have made jungle fowl walking gait highly efficient. Modern broiler chickens possess an unbalanced body conformation due to intense genetic selection for additional breast muscle (pectoral hypertrophy) and whole body mass. Together with rapid growth, this promotes compensatory gait adaptations to minimise energy expenditure and triggers high lameness prevalence within commercial flocks; lameness creating further disruption to the gait cycle and being an important welfare issue. Clear differences were observed between the two lines (short stance phase, little double-support, low leg lift, and little back displacement in adult jungle fowl; much double-support, high leg lift, and substantial vertical back movement in sound broilers) presumably related to mass and body conformation. Similarities included stride length and duration. Additional modifications were also identified in lame broilers (short stride length and duration, substantial lateral back movement, reduced velocity) presumably linked to musculo-skeletal abnormalities. Reduced walking velocity suggests an attempt to minimise skeletal stress and/or discomfort, while a shorter stride length and time, together with longer stance and double-support phases, are associated with

  13. Kinematic analysis quantifies gait abnormalities associated with lameness in broiler chickens and identifies evolutionary gait differences.

    Directory of Open Access Journals (Sweden)

    Gina Caplen

    Full Text Available This is the first time that gait characteristics of broiler (meat chickens have been compared with their progenitor, jungle fowl, and the first kinematic study to report a link between broiler gait parameters and defined lameness scores. A commercial motion-capturing system recorded three-dimensional temporospatial information during walking. The hypothesis was that the gait characteristics of non-lame broilers (n = 10 would be intermediate to those of lame broilers (n = 12 and jungle fowl (n = 10, tested at two ages: immature and adult. Data analysed using multi-level models, to define an extensive range of baseline gait parameters, revealed inter-group similarities and differences. Natural selection is likely to have made jungle fowl walking gait highly efficient. Modern broiler chickens possess an unbalanced body conformation due to intense genetic selection for additional breast muscle (pectoral hypertrophy and whole body mass. Together with rapid growth, this promotes compensatory gait adaptations to minimise energy expenditure and triggers high lameness prevalence within commercial flocks; lameness creating further disruption to the gait cycle and being an important welfare issue. Clear differences were observed between the two lines (short stance phase, little double-support, low leg lift, and little back displacement in adult jungle fowl; much double-support, high leg lift, and substantial vertical back movement in sound broilers presumably related to mass and body conformation. Similarities included stride length and duration. Additional modifications were also identified in lame broilers (short stride length and duration, substantial lateral back movement, reduced velocity presumably linked to musculo-skeletal abnormalities. Reduced walking velocity suggests an attempt to minimise skeletal stress and/or discomfort, while a shorter stride length and time, together with longer stance and double-support phases, are associated

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

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    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....

  15. Identifying the differences in mechanisms of mycophenolic acid controlling fucose content of glycoproteins expressed in different CHO cell lines.

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    Zhang, An; Tsang, Valerie Liu; Markely, Lam R; Kurt, Lutfiye; Huang, Yao-Ming; Prajapati, Shashi; Kshirsagar, Rashmi

    2016-11-01

    In the biopharmaceutical industry, glycosylation is a critical quality attribute that can modulate the efficacy of a therapeutic glycoprotein. Obtaining a consistent glycoform profile is desired because molecular function can be defined by its carbohydrate structures. Specifically, the fucose content of oligosaccharides in glycoproteins is one of the most important attributes that can significantly affect antibody-dependent cellular cytotoxicity (ADCC) activity. It is therefore important to understand the fucosylation pathway and be able to control fucosylation at the desired level to match predecessor materials in late stage and biosimilar programs. Several strategies were explored in this study and mycophenolic acid (MPA) was able to finely modulate the fucose content with the least undesired side effects. However, the response was significantly different between CHO cell lines of different lineages. Further experiments were then performed for a deeper understanding of the mechanism of fucosylation in different CHO cell lines. Results indicated that changes in the intracellular nucleotide involved in fucosylation pathway after MPA treatment are the main cause of the differences in fucosylation level response in different CHO cell lines. Differences in MPA metabolism in the various CHO cell lines directly resulted in different levels of afucosylation measured in antibodies produced by the CHO cell lines. Biotechnol. Bioeng. 2016;113: 2367-2376. © 2016 Wiley Periodicals, Inc.

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

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    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.

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

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    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.

  18. A systems biology approach identifies molecular networks defining skeletal muscle abnormalities in chronic obstructive pulmonary disease.

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    Nil Turan

    2011-09-01

    Full Text Available Chronic Obstructive Pulmonary Disease (COPD is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients.

  19. Identifying children with autism spectrum disorder based on their face processing abnormality: A machine learning framework.

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    Liu, Wenbo; Li, Ming; Yi, Li

    2016-08-01

    The atypical face scanning patterns in individuals with Autism Spectrum Disorder (ASD) has been repeatedly discovered by previous research. The present study examined whether their face scanning patterns could be potentially useful to identify children with ASD by adopting the machine learning algorithm for the classification purpose. Particularly, we applied the machine learning method to analyze an eye movement dataset from a face recognition task [Yi et al., 2016], to classify children with and without ASD. We evaluated the performance of our model in terms of its accuracy, sensitivity, and specificity of classifying ASD. Results indicated promising evidence for applying the machine learning algorithm based on the face scanning patterns to identify children with ASD, with a maximum classification accuracy of 88.51%. Nevertheless, our study is still preliminary with some constraints that may apply in the clinical practice. Future research should shed light on further valuation of our method and contribute to the development of a multitask and multimodel approach to aid the process of early detection and diagnosis of ASD. Autism Res 2016, 9: 888-898. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

  20. Glycoprotein synthesis

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    Schultz, Peter G. (La Jolla, CA); Wang, Lei (San Diego, CA); Zhang, Zhiwen (San Diego, CA)

    2010-11-16

    Methods for making glycoproteins, both in vitro and in vivo, are provided. One method involves incorporating an unnatural amino acid into a protein and attaching one or more saccharide moieties to the unnatural amino acid. Another method involves incorporating an unnatural amino acid that includes a saccharide moiety into a protein. Proteins made by both methods can be further modified with additional sugars.

  1. Glycoprotein synthesis

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    Schultz, Peter G. (La Jolla, CA); Wang, Lei (San Diego, CA); Zhang, Zhiwen (San Diego, CA)

    2010-11-02

    Methods for making glycoproteins, both in vitro and in vivo, are provided. One method involves incorporating an unnatural amino acid into a protein and attaching one or more saccharide moieties to the unnatural amino acid. Another method involves incorporating an unnatural amino acid that includes a saccharide moiety into a protein. Proteins made by both methods can be further modified with additional sugars.

  2. Glycoprotein synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Methods for making glycoproteins, both in vitro and in vivo, are provided. One method involves incorporating an unnatural amino acid into a protein and attaching one or more saccharide moieties to the unnatural amino acid. Another method involves incorporating an unnatural amino acid that includes a saccharide moiety into a protein. Proteins made by both methods can be further modified with additional sugars.

    2009-07-14

    Methods for making glycoproteins, both in vitro and in vivo, are provided. One method involves incorporating an unnatural amino acid into a protein and attaching one or more saccharide moieties to the unnatural amino acid. Another method involves incorporating an unnatural amino acid that includes a saccharide moiety into a protein. Proteins made by both methods can be further modified with additional sugars.

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

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    Brohawn, David G; O'Brien, Laura C; Bennett, James P

    2016-01-01

    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 helpful

  4. A cytogenetic abnormality and rare coding variants identify ABCA13 as a candidate gene in schizophrenia, bipolar disorder, and depression.

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    Knight, Helen M; Pickard, Benjamin S; Maclean, Alan; Malloy, Mary P; Soares, Dinesh C; McRae, Allan F; Condie, Alison; White, Angela; Hawkins, William; McGhee, Kevin; van Beck, Margaret; MacIntyre, Donald J; Starr, John M; Deary, Ian J; Visscher, Peter M; Porteous, David J; Cannon, Ronald E; St Clair, David; Muir, Walter J; Blackwood, Douglas H R

    2009-12-01

    Schizophrenia and bipolar disorder are leading causes of morbidity across all populations, with heritability estimates of approximately 80% indicating a substantial genetic component. Population genetics and genome-wide association studies suggest an overlap of genetic risk factors between these illnesses but it is unclear how this genetic component is divided between common gene polymorphisms, rare genomic copy number variants, and rare gene sequence mutations. We report evidence that the lipid transporter gene ABCA13 is a susceptibility factor for both schizophrenia and bipolar disorder. After the initial discovery of its disruption by a chromosome abnormality in a person with schizophrenia, we resequenced ABCA13 exons in 100 cases with schizophrenia and 100 controls. Multiple rare coding variants were identified including one nonsense and nine missense mutations and compound heterozygosity/homozygosity in six cases. Variants were genotyped in additional schizophrenia, bipolar, depression (n > 1600), and control (n > 950) cohorts and the frequency of all rare variants combined was greater than controls in schizophrenia (OR = 1.93, p = 0.0057) and bipolar disorder (OR = 2.71, p = 0.00007). The population attributable risk of these mutations was 2.2% for schizophrenia and 4.0% for bipolar disorder. In a study of 21 families of mutation carriers, we genotyped affected and unaffected relatives and found significant linkage (LOD = 4.3) of rare variants with a phenotype including schizophrenia, bipolar disorder, and major depression. These data identify a candidate gene, highlight the genetic overlap between schizophrenia, bipolar disorder, and depression, and suggest that rare coding variants may contribute significantly to risk of these disorders.

  5. OC01.03: Atypical karyotypic abnormalities not identified through NIPT: the value of identifying fetal anomalies at the first or second trimester scan?

    DEFF Research Database (Denmark)

    Petersen, Olav Bjørn; Ekelund, Charlotte; Hyett, Jon;

    2015-01-01

    Objectives: Using a population based database including >200,000 Danish pregnancies, we have previously shown that 23% of all phenotypically important chromosomal abnormalities would not be diagnosed using currently available NIPT techniques. The aim of the current study was to assess how many...

  6. The abilities of new anthropometric indices in identifying cardiometabolic abnormalities, and influence of residence area and lifestyle on these anthropometric indices in a Chinese community-dwelling population

    Directory of Open Access Journals (Sweden)

    Fu S

    2014-01-01

    Full Text Available Shihui Fu,1 Leiming Luo,1 Ping Ye,1 Yuan Liu,1 Bing Zhu,1 Yongyi Bai,1 Jie Bai2 1Department of Geriatric Cardiology, 2Department of Clinical Biochemistry, Chinese People's Liberation Army General Hospital, Beijing, People's Republic of China Objective: The study aimed to investigate the prevalence of overweight, obesity, and cardiometabolic abnormalities, the influence of residence area, occupation, and lifestyle on new anthropometric indices, and the relationship between anthropometric indices and cardiometabolic abnormalities in a Chinese community-dwelling population. Methods: The study included 4,868 residents through a large health check-up program in Beijing. Results: Overall obesity existed in 22.2% of men and 28.1% of women. 67.1% of men and 65.2% of women were overweight. 65.99% of men and 65.97% of women had central obesity. Residents of rural areas, manual workers, and smokers had significantly higher anthropometric indices. The power of each anthropometric index varied for identifying different cardiometabolic abnormalities, and the ability of the waist-to-height ratio to identify participants with greater than one or two cardiometabolic abnormalities was optimal. The appropriate cut-off values of all anthropometric indices for cardiometabolic abnormalities were obtained. Conclusion: Overweight is common for both sexes in the People's Republic of China, as are general and central obesity. Residents of rural areas, manual workers, and smokers have significantly higher anthropometric indices. Waist-to-height ratio has the ability to reflect the compound risk of different cardiometabolic abnormalities and the greatest potential to be widely applied in clinical practice. Keywords: anthropometric indices, residence area, lifestyle, cardiometabolic abnormalities, Chinese community-dwelling population

  7. 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)

  8. Proteomic dataset for altered glycoprotein expression upon GALNT3 knockdown in ovarian cancer cells.

    Science.gov (United States)

    Sheta, Razan; Roux-Dalvai, Florence; Woo, Christina M; Fournier, Frédéric; Bourassa, Sylvie; Bertozzi, Carolyn R; Droit, Arnaud; Bachvarov, Dimcho

    2016-09-01

    This article contains raw and processed data related to research published in "Role of the polypeptide N-acetylgalactosaminyltransferase 3 in ovarian cancer progression: possible implications in abnormal mucin O-glycosylation" [1]. The data presented here was obtained with the application of a bioorthogonal chemical reporter strategy analyzing differential glycoprotein expression following the knock-down (KD) of the GALNT3 gene in the epithelial ovarian cancer (EOC) cell line A2780s. LC-MS/MS mass spectrometry analysis was then performed and the processed data related to the identified glycoproteins show that several hundred proteins are differentially expressed between control and GALNT3 KD A2780s cells. The obtained data also uncover numerous novel glycoproteins; some of which could represent new potential EOC biomarkers and/or therapeutic targets.

  9. Diagnostic Value of Endometrial Sampling with Pipelle Suction Curettage for Identifying Endometrial Lesions in Patients with Abnormal Uterine Bleeding

    Directory of Open Access Journals (Sweden)

    F Behnamfar

    2004-06-01

    Full Text Available Background: While determining the cause of abnormal uterine bleeding, sampling from the endometrium is necessary. Considering that pipelle suction curettage can be performed on an out patient basis and does not require hospitalization, using anesthesia and cervical dilatation, we performed this study. The aim of this study was to compare the diagnostic value of dilatation and curettage (D&C with pipelle suction curettage. Methods: This study was quasiexperimental on 200 pre and postmenopausal patients with abnormal uterine bleeding who refered to Shabihkhani hospital in Kashan, Iran. Endometrial sampling was performed in all patients with two methods namely pipelle and D&C. A pathologist examined the samples each having a predetermined code. Results: The mean age of subjects was 46.2 ±6.2 years, minimum age was 35 years and the maximum was 70 years. The various pathological lab findings were proliferative endometrium, secretory endometrium, athrophic, decidua, cystic and adenomatous hyperplasia. The reports were the same in two methods except for 2 cases where they were different: secretory endometrium with D&C but cystic hyperplasia in pipelle method. Conclusions: The result of our study shows the comparability of obtaining endometrial sample by pipelle with D&C. Due to comfort and convenience of patients in pipelle methode especially in the office setting which does not need anesthesia, pipelle method can easily be employed instead of D&C. Keywords: Pipelle Suction Curette, Dilatation and Curettage, Premenopause, Postmenopause.

  10. Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1

    Energy Technology Data Exchange (ETDEWEB)

    Verhaak, Roel GW; Hoadley, Katherine A; Purdom, Elizabeth; Wang, Victoria; Qi, Yuan; Wilkerson, Matthew D; Miller, C Ryan; Ding, Li; Golub, Todd; Mesirov, Jill P; Alexe, Gabriele; Lawrence, Michael; O' Kelly, Michael; Tamayo, Pablo; Weir, Barbara A; Gabriel, Stacey; Winckler, Wendy; Gupta, Supriya; Jakkula, Lakshmi; Feiler, Heidi S; Hodgson, J Graeme; James, C David; Sarkaria, Jann N; Brennan, Cameron; Kahn, Ari; Spellman, Paul T; Wilson, Richard K; Speed, Terence P; Gray, Joe W; Meyerson, Matthew; Getz, Gad; Perou, Charles M; Hayes, D Neil; Network, The Cancer Genome Atlas Research

    2009-09-03

    The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM). We describe a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes and integrate multidimensional genomic data to establish patterns of somatic mutations and DNA copy number. Aberrations and gene expression of EGFR, NF1, and PDGFRA/IDH1 each define the Classical, Mesenchymal, and Proneural subtypes, respectively. Gene signatures of normal brain cell types show a strong relationship between subtypes and different neural lineages. Additionally, response to aggressive therapy differs by subtype, with the greatest benefit in the Classical subtype and no benefit in the Proneural subtype. We provide a framework that unifies transcriptomic and genomic dimensions for GBM molecular stratification with important implications for future studies.

  11. Blood metabolomics analysis identifies abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism in bipolar disorder.

    Science.gov (United States)

    Yoshimi, Noriko; Futamura, Takashi; Kakumoto, Keiji; Salehi, Alireza M; Sellgren, Carl M; Holmén-Larsson, Jessica; Jakobsson, Joel; Pålsson, Erik; Landén, Mikael; Hashimoto, Kenji

    2016-06-01

    Bipolar disorder (BD) is a severe and debilitating psychiatric disorder. However, the precise biological basis remains unknown, hampering the search for novel biomarkers. We performed a metabolomics analysis to discover novel peripheral biomarkers for BD. We quantified serum levels of 116 metabolites in mood-stabilized male BD patients (n = 54) and age-matched male healthy controls (n = 39). After multivariate logistic regression, serum levels of pyruvate, N-acetylglutamic acid, α-ketoglutarate, and arginine were significantly higher in BD patients than in healthy controls. Conversely, serum levels of β-alanine, and serine were significantly lower in BD patients than in healthy controls. Chronic (4-weeks) administration of lithium or valproic acid to adult male rats did not alter serum levels of pyruvate, N-acetylglutamic acid, β-alanine, serine, or arginine, but lithium administration significantly increased serum levels of α-ketoglutarate. The metabolomics analysis demonstrated altered serum levels of pyruvate, N-acetylglutamic acid, β-alanine, serine, and arginine in BD patients. The present findings suggest that abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism play a role in the pathogenesis of BD.

  12. Development of Classification Models for Identifying “True” P-glycoprotein (P-gp Inhibitors Through Inhibition, ATPase Activation and Monolayer Efflux Assays

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    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.

  13. Sequence variation of the glycoprotein gene identifies three distinct lineages within field isolates of viral hemorrhagic septicemia virus, a fish rhabdovirus

    Science.gov (United States)

    Benmansour, A.; Bascuro, B.; Monnier, A.F.; Vende, P.; Winton, J.R.; de Kinkelin, P.

    1997-01-01

    To evaluate the genetic diversity of viral haemorrhagic septicaemia virus (VHSV), the sequence of the glycoprotein genes (G) of 11 North American and European isolates were determined. Comparison with the G protein of representative members of the family Rhabdoviridae suggested that VHSV was a different virus species from infectious haemorrhagic necrosis virus (IHNV) and Hirame rhabdovirus (HIRRV). At a higher taxonomic level, VHSV, IHNV and HIRRV formed a group which was genetically closest to the genus Lyssavirus. Compared with each other, the G genes of VHSV displayed a dissimilar overall genetic diversity which correlated with differences in geographical origin. The multiple sequence alignment of the complete G protein, showed that the divergent positions were not uniformly distributed along the sequence. A central region (amino acid position 245-300) accumulated substitutions and appeared to be highly variable. The genetic heterogeneity within a single isolate was high, with an apparent internal mutation frequency of 1.2 x 10(-3) per nucleotide site, attesting the quasispecies nature of the viral population. The phylogeny separated VHSV strains according to the major geographical area of isolation: genotype I for continental Europe, genotype II for the British Isles, and genotype III for North America. Isolates from continental Europe exhibited the highest genetic variability, with sub-groups correlated partially with the serological classification. Neither neutralizing polyclonal sera, nor monoclonal antibodies, were able to discriminate between the genotypes. The overall structure of the phylogenetic tree suggests that VHSV genetic diversity and evolution fit within the model of random change and positive selection operating on quasispecies.

  14. Persistent expression and function of P-glycoprotein on peripheral blood lymphocytes identifies corticosteroid resistance in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Kansal, Amit; Tripathi, Deepak; Rai, Mohit K; Agarwal, Vikas

    2016-02-01

    Corticosteroids (CS) are the mainstay of treatment in systemic lupus erythematosus (SLE) patients. However, some patients have poor response to CS treatment. Among the multiple mechanisms of CS resistance, overexpression of P-glycoprotein (P-gp) on peripheral blood lymphocytes (PBL) may be one of them as this result in efflux of CS from lymphocytes. Thus, we evaluated the role of P-gp protein on PBLs in patients with SLE in its response to CS therapy. SLE patients (n = 42) (fulfilling ACR revised criteria) who were naïve to CS and immunosuppressive drugs were enrolled. Disease activity was assessed using SLE disease activity index (SLEDAI) and expression, and function of P-gp was evaluated by flow cytometry at baseline and after 3 months of therapy with CS. At 3 months, patients with SLEDAI >4 and SLEDAI ≤4 were grouped as nonresponders and responders, respectively. P-gp expression was significantly increased on PBLs of SLE patients as compared to healthy controls (p < 0.001). P-gp expression and function correlated with SLEDAI (r = 0.49, p = 0.005; and r = 0.49, p = 0.001, respectively). P-gp expression and function were not different in responders and nonresponders at baseline. However, at 3 months of CS therapy, P-gp expression and function decreased in responders (p < 0.001 and p < 0.005, respectively), whereas in nonresponders, it remained unchanged. Persistent overexpression and activity of P-gp are associated with poor response to CS in CS naïve patients of SLE.

  15. 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.

  16. SERIAL NECK ULTRASOUND IS MORE LIKELY TO IDENTIFY FALSE-POSITIVE ABNORMALITIES THAN CLINICALLY SIGNIFICANT DISEASE IN LOW-RISK PAPILLARY THYROID CANCER PATIENTS.

    Science.gov (United States)

    Yang, Samantha Peiling; Bach, Ariadne M; Tuttle, R Michael; Fish, Stephanie A

    2015-12-01

    American Thyroid Association (ATA) low-risk papillary thyroid cancer (PTC) patients without structural evidence of disease on initial posttreatment evaluation have a low risk of recurrence. Despite this, most patients undergo frequent surveillance neck ultrasound (US). The objective of the study was to evaluate the clinical utility of routine neck US in ATA low-risk PTC patients with no structural evidence of disease after their initial thyroid surgery. We performed a retrospective review of 171 ATA low-risk PTC patients after total thyroidectomy, with or without radioactive iodine (RAI) ablation, who had a neck US without suspicious findings after therapy. The main outcome measure was a comparison of the frequency of finding false-positive US abnormalities and the frequency of identifying structural disease recurrence. Over a median follow-up of 8 years, 171 patients underwent a median of 5 neck US (range 2-17). Structural recurrence with low-volume disease (≤1 cm) was identified in 1.2% (2/171) of patients at a median of 2.8 years (range 1.6-4.1 years) after their initial diagnosis. Recurrence was associated with rising serum thyroglobulin (Tg) level in 1 of the 2 patients and was detected without signs of biochemical recurrence in the other patient. Conversely, false-positive US abnormalities were identified in 67% (114/171) of patients after therapy, leading to additional testing without identifying clinically significant disease. In ATA low-risk patients without structural evidence of disease on initial surveillance evaluation, routine screening US is substantially more likely to identify false-positive results than clinically significant structural disease recurrence.

  17. 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.

  18. 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...

  19. Novel DDR2 mutation identified by whole exome sequencing in a Moroccan patient with spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type.

    Science.gov (United States)

    Mansouri, Maria; Kayserili, Hülya; Elalaoui, Siham Chafai; Nishimura, Gen; Iida, Aritoshi; Lyahyai, Jaber; Miyake, Noriko; Matsumoto, Naomichi; Sefiani, Abdelaziz; Ikegawa, Shiro

    2016-02-01

    Spondylo-meta-epiphyseal dysplasia (SMED), short limb-abnormal calcification type (SMED, SL-AC), is a very rare autosomal recessive disorder with various skeletal changes characterized by premature calcification leading to severe disproportionate short stature. Twenty-two patients have been reported until now, but only five mutations (four missense and one splice-site) in the conserved sequence encoding the tyrosine kinase domain of the DDR2 gene has been identified. We report here a novel DDR2 missense mutation, c.370C > T (p.Arg124Trp) in a Moroccan girl with SMED, SL-AC, identified by whole exome sequencing. Our study has expanded the mutational spectrum of this rare disease and it has shown that exome sequencing is a powerful and cost-effective tool for the diagnosis of clinically heterogeneous disorders such as SMED.

  20. Abnormal heart-rate response during cardiopulmonary exercise testing identifies cardiac dysfunction in symptomatic patients with non-obstructive coronary artery disease.

    Science.gov (United States)

    Chaudhry, Sundeep; Kumar, Naresh; Behbahani, Hushyar; Bagai, Akshay; Singh, Binoy K; Menasco, Nick; Lewis, Gregory D; Sperling, Laurence; Myers, Jonathan

    2017-02-01

    Symptomatic non-obstructive coronary artery disease is a growing clinical dilemma for which contemporary testing is proving to be of limited clinical utility. New methods are needed to identify cardiac dysfunction. This is a prospective observational cohort study conducted from December 2013 to August 2015 in two outpatient cardiology clinics (symptomatic cohort) and 24 outpatient practices throughout the US (healthy cohort) with centralized methodology and monitoring to compare heart-rate responses during cardiopulmonary exercise testing (CPET). Participants were 208 consecutive patients (median age, 61; range, 32-86years) with exercise intolerance and without prior heart or lung disease in whom coronary anatomy was defined and 116 healthy subjects (median age, 45; range, 26-66years). Compared to stress ECG, the novel change in heart-rate as a function of work-rate parameter (ΔHR-WR Slope) demonstrated significantly higher sensitivity to detect under-treated atherosclerosis with similar specificity. In men, area under the ROC curve increased from 60% to 94% for non-obstructive CAD and from 64% to 80% for obstructive CAD. In women, AUC increased from 64% to 85% for non-obstructive CAD and from 66% to 90% for obstructive CAD. ΔHR-WR Slope correctly reclassified abnormal studies in the non-obstructive CAD group from 22% to 81%; in the obstructive CAD group from 18% to 84% and in the revascularization group from 35% to 78%. Abnormal heart-rate response during CPET is more effective than stress ECG for identifying under-treated atherosclerosis and may be of utility to identify cardiac dysfunction in symptomatic patients with normal routine cardiac testing. Copyright © 2016 Swiss Tropical and Public Health Institute. Published by Elsevier Ireland Ltd.. All rights reserved.

  1. Glycoproteins: Occurrence and Significance

    Science.gov (United States)

    Wittmann, Valentin

    Protein glycosylation is regarded as the most complex form of post-translational modification leading to a heterogeneous expression of glycoproteins as mixtures of glycoforms. This chapter describes the structure and occurrence of glycoproteins with respect to their glycan chains. Discussed are different carbohydrate-peptide linkages including GPI anchors, common structures of N- and O-glycans, and the structure of glycosaminoglycans contained in proteoglycans. Also covered are the bacterial cell wall polymer peptidoglycan and the glycopeptide antibiotics of the vancomycin group. Properties and functions of the glycans contained in glycoproteins are dealt with in the next chapter of this book.

  2. The Accuracy of the VISA-P Questionnaire, Single-Leg Decline Squat, and Tendon Pain History to Identify Patellar Tendon Abnormalities in Adult Athletes.

    Science.gov (United States)

    Mendonça, Luciana de Michelis; Ocarino, Juliana Melo; Bittencourt, Natália Franco Netto; Fernandes, Ludmila Maria Oliveira; Verhagen, Evert; Fonseca, Sérgio Teixeira

    2016-08-01

    Study Design Cross-sectional clinical assessment. Background Patellar tendinopathy is not always accompanied by patellar tendon abnormalities (PTAs). Thus, clinical screening tools to help identify patients with patellar tendon pain who have PTAs could enhance clinical decision making and patient prognosis. Objectives To test the diagnostic accuracy of the Victorian Institute of Sport Assessment-Patella (VISA-P) questionnaire, a single-leg decline squat (SLDS), tendon pain history, age, and years of sports participation to identify athletes with symptomatic patellar tendons who have PTAs confirmed on imaging. Methods Data provided by ultrasound examination, the VISA-P questionnaire, the SLDS, tendon pain history, age, and years of sport participation were collected in 43 athletes. A classification and regression tree (CART) model was developed to verify variables associated with PTA occurrence. Likelihood ratios (LRs) were computed for positive and negative tests. Results The SLDS, VISA-P questionnaire, and tendon pain history were associated with PTA occurrence. Athletes with negative results on all 3 tests (CART model) had a lower likelihood of having PTAs (negative LR = 0.3; 95% confidence interval [CI]: 0.2, 0.5). The isolated use of the SLDS or tendon pain history (positive LR = 4.2; 95% CI: 2.3, 7.14 and 4.5; 95% CI: 1.8, 11.1, respectively) had similar influence on probability of PTA presence compared to the CART model (positive LR = 4.1; 95% CI: 2.5, 6.3). Conclusion Although the objective was to investigate a clinical test to identify PTAs, the combined use of the tests had greater accuracy to identify individuals without PTAs. Level of Evidence Diagnosis, level 3b. J Orthop Sports Phys Ther 2016;46(8):673-680. Epub 3 Jul 2016. doi:10.2519/jospt.2016.6192.

  3. Assessment of the ability of myocardial contrast echocardiography with harmonic power Doppler imaging to identify perfusion abnormalities in patients with Kawasaki disease at rest and during dipyridamole stress.

    Science.gov (United States)

    Ishii, M; Himeno, W; Sawa, M; Iemura, M; Furui, J; Muta, H; Sugahara, Y; Egami, K; Akagi, T; Ishibashi, M; Kato, H

    2002-01-01

    The aim of our study was to assess the ability of myocardial contrast echocardiography (MCE) with harmonic power Doppler imaging (HPDI) to identify perfusion abnormalities in patients with Kawasaki disease at rest and during pharmacological stress imaging with dipyridamole. Results were compared with those of 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) imaging as the clinical reference standard. MCE with HPDI was performed on 20 patients with a history of Kawasaki disease. Images were obtained at baseline and during dipyridamole infusion (0.56 mg x kg(-1)) in the apical two- and four-chamber views. Myocardial opacification suitable for the analysis was obtained in all patients. Nine patients with stenotic lesions had a reversible defect after dipyridamole infusion detected by both MCE with HPDI and SPECT, and 3 patients with a history of myocardial infarction had a partially or completely irreversible defect detected by both methods. Three patients with coronary aneurysm without stenotic lesion, 4 patients with regressed coronary aneurysm, and 2 patients with normal coronary artery in acute phase also had normal perfusion at rest and after pharmacological stress by both methods. A 96% concordance (kappa = 0.87) was obtained when comparing the respective segmental perfusion scores using the two methods at baseline, and an 86% concordance (kappa = 0.81) was obtained at postdipyridamole infusion. After combining baseline and postdipyridamole images, each segment was labeled as having normal perfusion, irreversible defects, or reversible defects. Using these classifications, concordance for the two methods was 92% (kappa = 0.87). MCE with HPDI is a safe and feasible method by which to detect asymptomatic ischemia due to severe stenotic lesion, and it may be an important addition to the modalities used to identify patients at risk for myocardial infarction as a complication of Kawasaki disease.

  4. Screen for abnormal mitochondrial phenotypes in mouse embryonic stem cells identifies a model for succinyl-CoA ligase deficiency and mtDNA depletion

    Directory of Open Access Journals (Sweden)

    Taraka R. Donti

    2014-02-01

    Full Text Available Mutations in subunits of succinyl-CoA synthetase/ligase (SCS, a component of the citric acid cycle, are associated with mitochondrial encephalomyopathy, elevation of methylmalonic acid (MMA, and mitochondrial DNA (mtDNA depletion. A FACS-based retroviral-mediated gene trap mutagenesis screen in mouse embryonic stem (ES cells for abnormal mitochondrial phenotypes identified a gene trap allele of Sucla2 (Sucla2SAβgeo, which was used to generate transgenic mice. Sucla2 encodes the ADP-specific β-subunit isoform of SCS. Sucla2SAβgeo homozygotes exhibited recessive lethality, with most mutants dying late in gestation (e18.5. Mutant placenta and embryonic (e17.5 brain, heart and muscle showed varying degrees of mtDNA depletion (20–60%. However, there was no mtDNA depletion in mutant liver, where the gene is not normally expressed. Elevated levels of MMA were observed in embryonic brain. SCS-deficient mouse embryonic fibroblasts (MEFs demonstrated a 50% reduction in mtDNA content compared with wild-type MEFs. The mtDNA depletion resulted in reduced steady state levels of mtDNA encoded proteins and multiple respiratory chain deficiencies. mtDNA content could be restored by reintroduction of Sucla2. This mouse model of SCS deficiency and mtDNA depletion promises to provide insights into the pathogenesis of mitochondrial diseases with mtDNA depletion and into the biology of mtDNA maintenance. In addition, this report demonstrates the power of a genetic screen that combines gene trap mutagenesis and FACS analysis in mouse ES cells to identify mitochondrial phenotypes and to develop animal models of mitochondrial dysfunction.

  5. Glycoprotein biosynthesis in calf kidney. Glycoprotein sialyltransferase activities towards serum glycoproteins and calf Tamm-Horsfall glycoprotein.

    Science.gov (United States)

    van Dijk, W; Lasthuis, A M; van den Eijnden, D H

    1979-04-18

    CMP-AcNeu:glycoprotein sialyltransltransltransltransltransferase of calf kidney cortex was characterized using serum glycoproteins and Tamm-Horsfall glycoprotein, obtained from calf urine, as acceptors. Native calf Tamm-Horsfall glycoprotein showed the best acceptor properties, followed by desialylated calf fetuin and desialylated human alpha 1-acid glycoprotein exhibiting V values of, respectively, 114, 63 and 41 nmol/h per g wet wt. of kidney cortex and Km values of 0.12, 0.16 and 0.26 mM glycoprotein acceptor. Desialylated ovine submaxillary mucine appeared to be a very poor acceptor. Tamm-Horsfall glycoprotein sialyltransferase could be distinguished from serum glycoprotein sialyltransferase by competition studies. In addition the two glycoprotein sialyltransferase activities showed different distributions over the three regions of the calf kidney: the ratios of the Tamm-Horsfall to serum glycoprotein sialyltransferase activities decreased from 3.3 in the cortex to 0.8 and 0.4 in the medulla and the papilla, respectively. It was concluded that in calf kidney at least two different sialyltransferases exist. The high cortical Tamm-Horsfall glycoprotein sialyltransferases activity corresponds markedly to the origin of the urinary Tamm-Horsfall glycoprotein, namely the distal part of the kidney tubule. Inactivation of glycoprotein sialyltransferase activity by preincubation at various temperatures and during storage at 0 degree C, could be reduced by the addition of CMP-AcNeu. The possible relevance towards the in vivo sialylation of this finding is discussed.

  6. Terminal Mannose Residues in Seminal Plasma Glycoproteins of Infertile Men Compared to Fertile Donors

    Directory of Open Access Journals (Sweden)

    Beata Olejnik

    2015-07-01

    Full Text Available The impact of seminal plasma components on the fertilization outcomes in humans is still under question. The increasing number of couples facing problems with conception raises the need for predictive biomarkers. Detailed understanding of the molecular mechanisms accompanying fertilization remains another challenge. Carbohydrate–protein recognition may be of key importance in this complex field. In this study, we analyzed the unique glycosylation pattern of seminal plasma proteins, the display of high-mannose and hybrid-type oligosaccharides, by means of their reactivity with mannose-specific Galanthus nivalis lectin. Normozoospermic infertile subjects presented decreased amounts of lectin-reactive glycoepitopes compared to fertile donors and infertile patients with abnormal semen parameters. Glycoproteins containing unveiled mannose were isolated in affinity chromatography, and 17 glycoproteins were identified in liquid chromatography-tandem mass spectrometry with electrospray ionization. The N-glycome of the isolated glycoproteins was examined in matrix-assisted laser desorption ionization mass spectrometry. Eleven out of 27 identified oligosaccharides expressed terminal mannose residues, responsible for lectin binding. We suggest that lowered content of high-mannose and hybrid type glycans in normozoospermic infertile patients may be associated with impaired sperm protection from preterm capacitation and should be considered in the search for new infertility markers.

  7. Terminal Mannose Residues in Seminal Plasma Glycoproteins of Infertile Men Compared to Fertile Donors

    Science.gov (United States)

    Olejnik, Beata; Jarząb, Anna; Kratz, Ewa M.; Zimmer, Mariusz; Gamian, Andrzej; Ferens-Sieczkowska, Mirosława

    2015-01-01

    The impact of seminal plasma components on the fertilization outcomes in humans is still under question. The increasing number of couples facing problems with conception raises the need for predictive biomarkers. Detailed understanding of the molecular mechanisms accompanying fertilization remains another challenge. Carbohydrate–protein recognition may be of key importance in this complex field. In this study, we analyzed the unique glycosylation pattern of seminal plasma proteins, the display of high-mannose and hybrid-type oligosaccharides, by means of their reactivity with mannose-specific Galanthus nivalis lectin. Normozoospermic infertile subjects presented decreased amounts of lectin-reactive glycoepitopes compared to fertile donors and infertile patients with abnormal semen parameters. Glycoproteins containing unveiled mannose were isolated in affinity chromatography, and 17 glycoproteins were identified in liquid chromatography-tandem mass spectrometry with electrospray ionization. The N-glycome of the isolated glycoproteins was examined in matrix-assisted laser desorption ionization mass spectrometry. Eleven out of 27 identified oligosaccharides expressed terminal mannose residues, responsible for lectin binding. We suggest that lowered content of high-mannose and hybrid type glycans in normozoospermic infertile patients may be associated with impaired sperm protection from preterm capacitation and should be considered in the search for new infertility markers. PMID:26147424

  8. 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.

  9. HIV-1 envelope glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. Meiotic abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-12-31

    Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

  11. Deletion(20q) as the sole abnormality in plasma cell myeloma is not associated with plasma cells as identified by cIg FISH.

    Science.gov (United States)

    White, Joanne S; Zordan, Adrian; Batzios, Crisoula; Campbell, Lynda J

    2012-12-01

    Deletion of 20q is a common finding in myeloid disorders but it is also observed in plasma cell myeloma (PCM). As a del(20q) in a patient receiving treatment for myeloma may indicate therapy-related myelodysplastic syndrome (t-MDS), it is important to differentiate chromosome abnormalities associated with myeloma from those reflecting t-MDS. We performed fluorescence in situ hybridization (FISH) using a 20q12 probe (D20S108) in conjunction with cytoplasmic immunoglobulin (cIg) staining in 20 PCM cases with a del(20q) in order to confirm the cell type involved. Of the nine cases studied with a clone showing a del(20q) as the sole abnormality, 8 of 9 demonstrated loss of the D20S108 signals in non-plasma cells only and 5 of 9 had either a confirmed myeloid malignancy in addition to PCM or showed evidence of dysplastic changes in the marrow; however, of the 11 patients with a del(20q) within a complex PCM karyotype, 4 of 11 showed loss of the D20S108 signals in plasma cells only and 7 of 11 showed no significant loss in either plasma cells or non-plasma cells. Therefore, our results indicate that a del(20q) as the sole abnormality in PCM is present in non-plasma cells and, therefore, suggests the presence of an associated myeloid malignancy. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Molecular karyotyping of single sperm with nuclear vacuoles identifies more chromosomal abnormalities in patients with testiculopathy than fertile controls: implications for ICSI.

    Science.gov (United States)

    Garolla, Andrea; Sartini, Barbara; Cosci, Ilaria; Pizzol, Damiano; Ghezzi, Marco; Bertoldo, Alessandro; Menegazzo, Massimo; Speltra, Elena; Ferlin, Alberto; Foresta, Carlo

    2015-11-01

    Is there a difference between molecular karyotype of single sperm selected by high-magnification microscopy from infertile patients with testicular damage and from proven fertile controls? The molecular karyotype of single sperm from patients with testiculopathy had a significantly higher percentage of chromosomal alterations than fertile controls. Infertile patients with testicular impairment have many sperm with aneuploidies and/or increased structural chromosome alterations. In these patients, sperm use by ICSI has poor outcome and raises concerns about the possible impact on pregnancy loss and transmission of genes abnormalities in offspring. High-magnification microscopy has been recently introduced to select morphologically better sperm aimed at improving ICSI outcome. However, there are no studies evaluating the molecular karyotype of sperm selected by this method. Three consecutive infertile patients with oligozoospermia due to testicular damage and three age-matched proven fertile men attending a tertiary care center, were enrolled in the study from September to November 2014. Inclusion criteria of patients were age ≥30 ≤35 years, at least 2 years of infertility, oligozoospermia (sperm count below 10 million), reduced testicular volumes high FSH plasma levels and absence of altered karyotype, Y chromosome microdeletions, cystic fibrosis transmembrane conductance regulator gene mutations, sperm infections, cigarette smoking, varicocele, obesity. Participants were evaluated for sperm parameters, sex hormones and testicular color-doppler ultrasound. From each semen sample, 20 sperm with large vacuoles (LVs), 20 with small vacuoles (SVs) and 20 with no vacuoles (NVs) were retrieved individually by a micromanipulator system. Each cell was further analyzed by whole genome amplification and array comparative genomic hybridization (aCGH). The aCGH allowed us to detect chromosomal aneuploidies, unbalanced translocations and complex abnormalities. Sperm selected

  13. Leukocyte abnormalities.

    Science.gov (United States)

    Gabig, T G

    1980-07-01

    Certain qualitative abnormalities in neutrophils and blood monocytes are associated with frequent, severe, and recurrent bacterial infections leading to fatal sepsis, while other qualitative defects demonstrated in vitro may have few or no clinical sequelae. These qualitative defects are discussed in terms of the specific functions of locomotion, phagocytosis, degranulation, and bacterial killing.

  14. Frequent screening with serial neck ultrasound is more likely to identify false-positive abnormalities than clinically significant disease in the surveillance of intermediate risk papillary thyroid cancer patients without suspicious findings on follow-up ultrasound evaluation.

    Science.gov (United States)

    Peiling Yang, Samantha; Bach, Ariadne M; Tuttle, R Michael; Fish, Stephanie A

    2015-04-01

    American Thyroid Association (ATA) intermediate-risk thyroid cancer patients who achieve an excellent treatment response demonstrate a low risk of structural disease recurrence. Despite this fact, most patients undergo frequent surveillance neck ultrasound (US) during follow-up. The objective of the study was to evaluate the clinical utility of routine screening neck US in ATA intermediate-risk patients documented to have a nonstimulated thyroglobulin less than 1.0 ng/mL and a neck US without suspicious findings after therapy. Retrospective review of 90 ATA intermediate-risk papillary thyroid carcinoma patients treated with total thyroidectomy and radioactive iodine ablation in a tertiary referral center. A comparison between the frequency of finding false-positive US abnormalities and the frequency of identifying structural disease recurrence in the study cohort was measured. Over a median of 10 years, 90 patients had a median of six US (range 2-16). Structural disease recurrence was identified in 10% (9 of 90) at a median of 6.3 years. Recurrence was associated with other clinical indicators of disease in 5 of the 90 patients (5.6%, 5 of 90) and was detected without other signs of recurrence in four patients (4.8%, 4 of 84). False-positive US abnormalities were identified in 57% (51 of 90), leading to additional testing, which failed to identify clinically significant disease. In ATA intermediate-risk patients who have a nonstimulated thyroglobulin less than 1.0 ng/mL and a neck US without suspicious findings after therapy, frequent US screening during follow-up is more likely to identify false-positive abnormalities than clinically significant structural disease recurrence.

  15. Protective effect of Cardiospermum halicacabum leaf extract on glycoprotein components on STZ-induced hyperglycemic rats

    Institute of Scientific and Technical Information of China (English)

    Chinnadurai Veeramani; Khalid S Al-Numair; Mohammed A Alsaif; Govindasamy Chandramohan; Nouf S Al-Numair; Kodukkur Viswanathan Pugalendi

    2012-01-01

    Objective: To investigate the protective role of Cardiospermum halicacabum (C. halicacabum) leaf extract on glycoprotein metabolism in streptozotocin (STZ)-induced diabetic rats. Methods:Diabetes was induced in male albino Wistar rats by intraperitonial administration of STZ. TheC. halicacabum leaf extract (CHE) was administered orally to normal and STZ-diabetic rats for 45 days. The effects of C. halicacabum leaf extract (CHE) on plasma and tissue glycoproteins (hexose, hexosamine, fucose and sialic acid) were determined. Results: The levels of plasma and tissues glycoproteins containing hexose, hexosamine and fucose were significantly increased in STZ-induced diabetic rats. In addition, the level of sialic acid significantly increased in plasma and liver while decreased in kidney of STZ-induced diabetic rats. After administration of CHE to diabetic rats, the metabolic alteration of glycoprotein reverted towards normal levels.Conclusions:The present study indicates that the CHE possesses a protective effect on abnormal glycoprotein metabolism in addition to its antihyperglycemic activity.

  16. Improved Monosynaptic Neural Circuit Tracing Using Engineered Rabies Virus Glycoproteins

    Directory of Open Access Journals (Sweden)

    Euiseok J. Kim

    2016-04-01

    Full Text Available Monosynaptic rabies virus tracing is a unique and powerful tool used to identify neurons making direct presynaptic connections onto neurons of interest across the entire nervous system. Current methods utilize complementation of glycoprotein gene-deleted rabies of the SAD B19 strain with its glycoprotein, B19G, to mediate retrograde transsynaptic spread across a single synaptic step. In most conditions, this method labels only a fraction of input neurons and would thus benefit from improved efficiency of transsynaptic spread. Here, we report newly engineered glycoprotein variants to improve transsynaptic efficiency. Among them, oG (optimized glycoprotein is a codon-optimized version of a chimeric glycoprotein consisting of the transmembrane/cytoplasmic domain of B19G and the extracellular domain of rabies Pasteur virus strain glycoprotein. We demonstrate that oG increases the tracing efficiency for long-distance input neurons up to 20-fold compared to B19G. oG-mediated rabies tracing will therefore allow identification and study of more complete monosynaptic input neural networks.

  17. Envelope glycoprotein of arenaviruses.

    Science.gov (United States)

    Burri, Dominique J; da Palma, Joel Ramos; Kunz, Stefan; Pasquato, Antonella

    2012-10-17

    Arenaviruses include lethal human pathogens which pose serious public health threats. So far, no FDA approved vaccines are available against arenavirus infections, and therapeutic options are limited, making the identification of novel drug targets for the development of efficacious therapeutics an urgent need. Arenaviruses are comprised of two RNA genome segments and four proteins, the polymerase L, the envelope glycoprotein GP, the matrix protein Z, and the nucleoprotein NP. A crucial step in the arenavirus life-cycle is the biosynthesis and maturation of the GP precursor (GPC) by cellular signal peptidases and the cellular enzyme Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P) yielding a tripartite mature GP complex formed by GP1/GP2 and a stable signal peptide (SSP). GPC cleavage by SKI-1/S1P is crucial for fusion competence and incorporation of mature GP into nascent budding virion particles. In a first part of our review, we cover basic aspects and newer developments in the biosynthesis of arenavirus GP and its molecular interaction with SKI-1/S1P. A second part will then highlight the potential of SKI-1/S1P-mediated processing of arenavirus GPC as a novel target for therapeutic intervention to combat human pathogenic arenaviruses.

  18. Envelope Glycoprotein of Arenaviruses

    Directory of Open Access Journals (Sweden)

    Antonella Pasquato

    2012-10-01

    Full Text Available Arenaviruses include lethal human pathogens which pose serious public health threats. So far, no FDA approved vaccines are available against arenavirus infections, and therapeutic options are limited, making the identification of novel drug targets for the development of efficacious therapeutics an urgent need. Arenaviruses are comprised of two RNA genome segments and four proteins, the polymerase L, the envelope glycoprotein GP, the matrix protein Z, and the nucleoprotein NP. A crucial step in the arenavirus life-cycle is the biosynthesis and maturation of the GP precursor (GPC by cellular signal peptidases and the cellular enzyme Subtilisin Kexin Isozyme-1 (SKI-1/Site-1 Protease (S1P yielding a tripartite mature GP complex formed by GP1/GP2 and a stable signal peptide (SSP. GPC cleavage by SKI-1/S1P is crucial for fusion competence and incorporation of mature GP into nascent budding virion particles. In a first part of our review, we cover basic aspects and newer developments in the biosynthesis of arenavirus GP and its molecular interaction with SKI-1/S1P. A second part will then highlight the potential of SKI-1/S1P-mediated processing of arenavirus GPC as a novel target for therapeutic intervention to combat human pathogenic arenaviruses.

  19. Identification and antigenicity of the major envelope glycoprotein of lymphadenopathy-associated virus

    Energy Technology Data Exchange (ETDEWEB)

    Montagnier, L.; Clavel, F.; Krust, B.; Chamaret, S.; Rey, F.; Barre-Sinoussi, F.; Chermann, J.C.

    1985-07-15

    The major envelope glycoprotein of the causative agent of Acquired Immune Deficiency Syndrome (AIDS) lymphadenopathy-associated virus (LAV) has been identified and characterized. The glycoprotein has an apparent molecular weight of 110,000-120,000 under denaturing conditions in polyacrylamide gel electrophoresis. Upon deglycosylation by a specific endoglycosydase, its size is reduced to 80,000. Cellular precursors of this glycoprotein have been detected with apparent molecular weight of 150,000 and 135,000. Nearly all AIDS and pre-AIDS patients have detectable antibodies against this viral glycoprotein.

  20. Analysis of lectin-bound glycoproteins in snake venom from the Elapidae and Viperidae families.

    Science.gov (United States)

    Nawarak, Jiraporn; Phutrakul, Suree; Chen, Shui-Tein

    2004-01-01

    This paper describes an efficient method of studying the glycoproteins found in snake venom. The glycosylation profiles of the Elapidae and Viperidae snake families were analyzed using FITC-labeled lectin glycoconjugates. The Con A-agarose affinity enrichment technique was used to fractionate glycoproteins from the N. naja kaouthia venom. The results revealed a large number of Con A binding glycoproteins, most of which have moderate to high molecular weights. To identify the proteins, the isolated glycoprotein fractions were subjected to two-dimensional electrophoresis and MALDI-TOF MS. Protein sequences were compared with published protein databases to determine for their biological functions.

  1. Lectin-based glycoproteomics to explore and analyze hepatocellular carcinoma-related glycoprotein markers.

    Science.gov (United States)

    Dai, Zhi; Zhou, Jian; Qiu, Shuang-Jian; Liu, Yin-Kun; Fan, Jia

    2009-09-01

    More and more new diagnostic biomarkers of hepatocellular carcinoma (HCC) have been found in association with advances in the standardization of 2-DE coupled with MS analysis. However, the diagnosis of HCC is still detected in the late stages of the disease, when treatment options are limited and prognosis is poor. The glycosylation of proteins is known to change in tumor cells during the development of HCC as the result of alterations in the levels of glycosyltransferases, such as increased fucosylation of Golgi Protein 73 and alpha-fetoprotein. These structural changes can influence the function or physiochemical properties of a protein, resulting in abnormal cancer cell behavior. Therefore, identification of HCC-related glycoprotein markers and analysis of glycan structural alterations might assist in the early detection of HCC. Here, we summarize lectin-based glycoproteomic strategies for the discovery of relevant biomarkers of HCC. The carbohydrate-binding specificities of different lectins offer a biological affinity approach that complements existing MS capabilities. These strategies involve the enrichment of glycoproteins or glycopeptides by lectins, followed by releasing carbohydrates with peptide-N-glycosidase F or reductive beta-elimination. The obtained glycopeptides are then identified by automated MS/MS and structural analysis of glycans is performed through modern methods such as quadrupole IT-TOF, MALDI-TOF/TOF and lectin microarray. These strategies will lead to faster and more clinically adaptable tests with greater sensitivity and specificity.

  2. Mutagenesis of Varicella-Zoster Virus Glycoprotein I (gI) Identifies a Cysteine Residue Critical for gE/gI Heterodimer Formation, gI Structure, and Virulence in Skin Cells▿

    Science.gov (United States)

    Oliver, Stefan L.; Sommer, Marvin H.; Reichelt, Mike; Rajamani, Jaya; Vlaycheva-Beisheim, Leonssia; Stamatis, Shaye; Cheng, Jason; Jones, Carol; Zehnder, James; Arvin, Ann M.

    2011-01-01

    Varicella-zoster virus (VZV) is the alphaherpesvirus that causes chicken pox (varicella) and shingles (zoster). The two VZV glycoproteins gE and gI form a heterodimer that mediates efficient cell-to-cell spread. Deletion of gI yields a small-plaque-phenotype virus, ΔgI virus, which is avirulent in human skin using the xenograft model of VZV pathogenesis. In the present study, 10 mutant viruses were generated to determine which residues were required for the typical function of gI. Three phosphorylation sites in the cytoplasmic domain of gI were not required for VZV virulence in vivo. Two deletion mutants mapped a gE binding region in gI to residues 105 to 125. A glycosylation site, N116, in this region did not affect virulence. Substitution of four cysteine residues highly conserved in the Alphaherpesvirinae established that C95 is required for gE/gI heterodimer formation. The C95A and Δ105–125 (with residues 105 to 125 deleted) viruses had small-plaque phenotypes with reduced replication kinetics in vitro similar to those of the ΔgI virus. The Δ105–125 virus was avirulent for human skin in vivo. In contrast, the C95A mutant replicated in vivo but with significantly reduced kinetics compared to those of the wild-type virus. In addition to abolished gE/gI heterodimer formation, gI from the C95A or the Δ105–125 mutant was not recognized by monoclonal antibodies that detect the canonical conformation of gI, demonstrating structural disruption of gI in these viruses. This alteration prevented gI incorporation into virus particles. Thus, residues C95 and 105 to 125 are critical for gI structure required for gE/gI heterodimer formation, virion incorporation, and ultimately, effective viral spread in human skin. PMID:21345964

  3. Metabotropic Glutamate Receptor Type 5 (mGluR5) Cortical Abnormalities in Focal Cortical Dysplasia Identified In Vivo With [11C]ABP688 Positron-Emission Tomography (PET) Imaging

    Science.gov (United States)

    DuBois, Jonathan M.; Rousset, Olivier G.; Guiot, Marie-Christine; Hall, Jeffery A.; Reader, Andrew J.; Soucy, Jean-Paul; Rosa-Neto, Pedro; Kobayashi, Eliane

    2016-01-01

    Metabotropic glutamate receptor type 5 (mGluR5) abnormalities have been described in tissue resected from epilepsy patients with focal cortical dysplasia (FCD). To determine if these abnormalities could be identified in vivo, we investigated mGluR5 availability in 10 patients with focal epilepsy and an MRI diagnosis of FCD using positron-emission tomography (PET) and the radioligand [11C]ABP688. Partial volume corrected [11C]ABP688 binding potentials (BPND) were computed using the cerebellum as a reference region. Each patient was compared to homotopic cortical regions in 33 healthy controls using region-of-interest (ROI) and vertex-wise analyses. Reduced [11C]ABP688 BPND in the FCD was seen in 7/10 patients with combined ROI and vertex-wise analyses. Reduced FCD BPND was found in 4/5 operated patients (mean follow-up: 63 months; Engel I), of whom surgical specimens revealed FCD type IIb or IIa, with most balloon cells showing negative or weak mGluR5 immunoreactivity as compared to their respective neuropil and normal neurons at the border of resections. [11C]ABP688 PET shows for the first time in vivo evidence of reduced mGluR5 availability in FCD, indicating focal glutamatergic alterations in malformations of cortical development, which cannot be otherwise clearly demonstrated through resected tissue analyses. PMID:27578494

  4. Surface Glycoproteins of Exosomes Shed by Myeloid-Derived Suppressor Cells Contribute to Function.

    Science.gov (United States)

    Chauhan, Sitara; Danielson, Steven; Clements, Virginia; Edwards, Nathan; Ostrand-Rosenberg, Suzanne; Fenselau, Catherine

    2017-01-06

    In this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs. We report successful modification of a surface chemistry method for use with exosomes and identify 21 surface N-glycoproteins on exosomes released by mouse mammary carcinoma-induced MDSCs. These glycoprotein identities and functionalities are compared with 93 N-linked glycoproteins identified on the surface of the parental cells. As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets. The "don't eat me" molecule CD47 and its binding partners thrombospondin-1 (TSP1) and signal regulatory protein α (SIRPα) were among the surface N-glycoproteins detected. Functional bioassays using antibodies to these three molecules demonstrated that CD47, TSP1, and to a lesser extent SIRPα facilitate exosome-mediated MDSC chemotaxis and migration.

  5. 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.

  6. Recent Progress in Electrochemical Biosensors for Glycoproteins.

    Science.gov (United States)

    Akiba, Uichi; Anzai, Jun-Ichi

    2016-12-01

    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.

  7. Recent Progress in Electrochemical Biosensors for Glycoproteins

    Directory of Open Access Journals (Sweden)

    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.

  8. Demethoxycurcumin modulates human P-glycoprotein function via uncompetitive inhibition of ATPase hydrolysis activity.

    Science.gov (United States)

    Teng, Yu-Ning; Hsieh, Yow-Wen; Hung, Chin-Chuan; Lin, Hui-Yi

    2015-01-28

    Curcuminoids are major components of Curcuma longa L., which is widely used as spice in food. This study aimed at identifying whether curcumin, demethoxycurcumin, and bisdemethoxycurcumin could modulate efflux function of human P-glycoprotein and be used as chemosensitizers in cancer treatments. Without altering P-glycoprotein expression levels and conformation, the purified curcuminoids significantly inhibited P-glycoprotein efflux function. In rhodamine 123 efflux and calcein-AM accumulation assays, demethoxycurcumin demonstrated the highest inhibition potency (inhibitory IC50 = 1.56 ± 0.13 μM) among the purified curcuminoids, as well as in the fold of reversal assays. Demethoxycurcumin inhibited P-glycoprotein-mediated ATP hydrolysis under concentrations of P-glycoprotein. These results suggested that demethoxycurcumin may be a potential additive natural product in combination with chemotherapeutic agents in drug-resistant cancers.

  9. Abnormal Uterine Bleeding FAQ

    Science.gov (United States)

    ... FREQUENTLY ASKED QUESTIONS FAQ095 GYNECOLOGIC PROBLEMS Abnormal Uterine Bleeding • What is a normal menstrual cycle? • When is bleeding abnormal? • At what ages is abnormal bleeding more ...

  10. Surface plasmon resonance for real-time study of lectin-carbohydrate interactions for the differentiation and identification of glycoproteins.

    Science.gov (United States)

    Safina, Gulnara; Duran, Iu Benet; Alasel, Mohammed; Danielsson, Bengt

    2011-06-15

    A study of specific interactions between lectins and glycoproteins has been carried out using surface plasmon resonance (SPR) in a flow-injection mode. Lectins were covalently immobilised on the surfaces of the microfluidic sensor chip via amine coupling and serum glycoproteins were injected into the flow channels. Specific lectin-glycoprotein interactions caused the shift of refractive index proportional to the mass concentration accumulated on the channel surface. Lectins showed different affinity to the tested glycoproteins and each glycoprotein displayed its own lectin-binding pattern. It is possible to distinguish and identify even glycoproteins with similar sugar structures by simple and quick screening. The working conditions of the assay were optimised. The lectin-based SPR made it possible to carry out the label-free detection of glycoproteins within a broad concentration range with a good linearity. Regeneration conditions for the surface of the sensor chip were found and optimised. Combination of 10mM HCl and 10mM glycine-HCl (pH 2.5) removes the bound glycoproteins from the lectin surface without damaging it. The kinetic and affinity parameters of lectin-glycoprotein binding were evaluated. The proposed method was tested on human glycosylated serum. Combination of the lectin panel with SPR is suitable both for specific screening and for sensitive assay of serum glycoproteins.

  11. Feasibility of body roundness index for identifying a clustering of cardiometabolic abnormalities compared to BMI, waist circumference and other anthropometric indices: the China Health and Nutrition Survey, 2008 to 2009.

    Science.gov (United States)

    Tian, Simiao; Zhang, Xiuzhi; Xu, Yang; Dong, Huimin

    2016-08-01

    The body mass index (BMI) and waist circumference (WC) are commonly used anthropometric measures for predicting cardiovascular diseases risk factors, but it is uncertain which specific measure might be the most appropriate predictor of a cluster of cardiometabolic abnormalities (CMA) in Chinese adults. A body shape index (ABSI) and body roundness index (BRI) have been recently developed as alternative anthropometric indices that may better reflect health status. The main aims of this study were to investigate the predictive capacity of ABSI and BRI in identifying various CMA compared to BMI, WC, waist-to-hip ratio (WHpR), and waist-to-height ratio (WHtR), and to determine whether there exists a best single predictor of all CMA.We used data from the 2009 wave of the China Health and Nutrition Survey, and the final analysis included 8126 adults aged 18 to 85 years with available fasting blood samples and anthropometric measurements. Receiver-operating characteristic (ROC) analyses were conducted to assess the best anthropometric indices to predict the risk of hypertension, diabetes, dyslipidemia, hyperuricemia, and metabolic syndrome (MetS). Logistic regression models were fit to evaluate the OR of each CMA according to anthropometric indices.In women, the ROC analysis showed that BRI and WHtR had the best predictive capability in identifying all of CMA (area under the curves [AUCs] ranged from 0.658 to 0.721). In men, BRI and WHtR were better predictor of hypertension, diabetes, and at least 1 CMA (AUC: 0.668, 0.708, and 0.698, respectively), whereas BMI and WC were more sensitive predictor of dyslipidemia, hyperuricemia, and MetS. Furthermore, the ABSI showed the lowest AUCs for each CMA. According to the multivariate logistic regression analysis, BRI and WHtR were superior in discriminating hyperuricemia and at least 1 CMA while BMI performed better in predicting hypertension, diabetes, and MetS in women. In men, WC and BRI were the 2 best predictor of all CMA

  12. Targeting prostaglandin E2 EP1 receptors prevents seizure-associated P-glycoprotein up-regulation

    NARCIS (Netherlands)

    Pekcec, A.; Unkrüer, B.; Schlichtiger, J.; Soerensen, J.; Hartz, A.M.S.; Bauer, B.; van Vliet, E.A.; Gorter, J.A.; Potschka, H.

    2009-01-01

    Up-regulation of the blood-brain barrier efflux transporter P-glycoprotein in central nervous system disorders results in restricted brain access and limited efficacy of therapeutic drugs. In epilepsies, seizure activity strongly triggers expression of P-glycoprotein. Here, we identified the prostag

  13. N-glycoprotein analysis discovers new up-regulated glycoproteins in colorectal cancer tissue.

    Science.gov (United States)

    Nicastri, Annalisa; Gaspari, Marco; Sacco, Rosario; Elia, Laura; Gabriele, Caterina; Romano, Roberto; Rizzuto, Antonia; Cuda, Giovanni

    2014-11-07

    Colorectal cancer is one of the leading causes of death due to cancer worldwide. Therefore, the identification of high-specificity and -sensitivity biomarkers for the early detection of colorectal cancer is urgently needed. Post-translational modifications, such as glycosylation, are known to play an important role in cancer progression. In the present work, we used a quantitative proteomic technique based on (18)O stable isotope labeling to identify differentially expressed N-linked glycoproteins in colorectal cancer tissue samples compared with healthy colorectal tissue from 19 patients undergoing colorectal cancer surgery. We identified 54 up-regulated glycoproteins in colorectal cancer samples, therefore potentially involved in the biological processes of tumorigenesis. In particular, nine of these (PLOD2, DPEP1, SE1L1, CD82, PAR1, PLOD3, S12A2, LAMP3, OLFM4) were found to be up-regulated in the great majority of the cohort, and, interestingly, the association with colorectal cancer of four (PLOD2, S12A2, PLOD3, CD82) has not been hitherto described.

  14. Enrichment and identification of glycoproteins in human saliva using lectin magnetic bead arrays.

    Science.gov (United States)

    Caragata, Michael; Shah, Alok K; Schulz, Benjamin L; Hill, Michelle M; Punyadeera, Chamindie

    2016-03-15

    Aberrant glycosylation of proteins is a hallmark of tumorigenesis and could provide diagnostic value in cancer detection. Human saliva is an ideal source of glycoproteins due to the relatively high proportion of glycosylated proteins in the salivary proteome. Moreover, saliva collection is noninvasive and technically straightforward, and the sample collection and storage is relatively easy. Although differential glycosylation of proteins can be indicative of disease states, identification of differential glycosylation from clinical samples is not trivial. To facilitate salivary glycoprotein biomarker discovery, we optimized a method for differential glycoprotein enrichment from human saliva based on lectin magnetic bead arrays (saLeMBA). Selected lectins from distinct reactivity groups were used in the saLeMBA platform to enrich salivary glycoproteins from healthy volunteer saliva. The technical reproducibility of saLeMBA was analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify the glycosylated proteins enriched by each lectin. Our saLeMBA platform enabled robust glycoprotein enrichment in a glycoprotein- and lectin-specific manner consistent with known protein-specific glycan profiles. We demonstrated that saLeMBA is a reliable method to enrich and detect glycoproteins present in human saliva.

  15. Glycoproteins of the carcinoembryonic antigen (CEA) family are expressed in sweat and sebaceous glands of human fetal and adult skin.

    Science.gov (United States)

    Metze, D; Bhardwaj, R; Amann, U; Eades-Perner, A M; Neumaier, M; Wagener, C; Jantscheff, P; Grunert, F; Luger, T A

    1996-01-01

    The carcinoembryonic antigen (CEA) family comprises a group of glycoproteins including the classical CEA, nonspecific cross-reacting antigens (NCA), and biliary glycoprotein (BGP). CEA glycoproteins have been identified in many glandular and mucosal tissues. In view of their putative role in cell adhesion, protein sorting, and signal transduction, CEA glycoproteins are thought to be involved in embryogenesis, architectual integrity, and secretory mechanisms of glandular epithelia. Since there are few data available on the expression of CEA-like proteins in human skin, the aim of this study was to immunohistochemically specify and localize the CEA glycoproteins in cutaneous adult and fetal glands using a panel of well-characterized antibodies. The secretory parts of eccrine sweat glands expressed CEA, NCA-90, and BGP, whereas apocrine glands remained unreactive for CEA glycoproteins. The ductal epithelia of both eccrine and apocrine glands contained CEA and NCA-90. Sebaceous glands were stained for BGP only. Electron microscopy of sweat glands showed CEA glycoprotein expression in cytoplasmic organelles and on microvilli lining the ductal surface. In sebaceous glands, BGP were demonstrated in small vesicles and along the cell membranes of differentiating sebocytes. Fetal development of cutaneous glands was associated with early expression of CEA glycoproteins. Additionally, mice transgenic for human CEA were shown to express CEA in sweat glands. The overall distribution of CEA glycoproteins in cutaneous glands was consistent with that in epithelia of other glandular tissues.

  16. Isolation of a surface glycoprotein from Myxococcus xanthus.

    OpenAIRE

    Maeba, P Y

    1986-01-01

    The isolation of a glycoprotein from vegetative cells of Myxococcus xanthus is reported. The protein, abbreviated VGP, was first identified during a survey of surface proteins as a major protein that could be radioiodinated in vegetative, but not developing, cells (P.Y. Maeba, J. Bacteriol. 155:1033-1041, 1983). The protein was extracted from membranes with Triton X-100 and subsequently purified by DEAE-cellulose chromatography, chromatofocusing, and gel filtration. The protein has an Mr of a...

  17. Abnormal Uterine Bleeding

    Science.gov (United States)

    ... first few months of a normal pregnancy. Some birth control pills or the intrauterine device (IUD) can also cause ... this type can significantly reduce abnormal bleeding. Like birth control pills, sometimes IUDs can actually cause abnormal bleeding. Tell ...

  18. 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 ...

  19. The simple detection of neuraminic acid-containing urinary oligosaccharides in patients with glycoprotein storage diseases.

    Science.gov (United States)

    Sewell, A C

    1983-01-01

    Urine samples from patients with different types of glycoprotein storage disease were chromatographed by gel filtration and the fractions analysed for sialic acid. Patients with mucolipidoses I and II excreted the largest amounts of bound sialic acid. One patient with GM1 gangliosidosis showed an abnormal level of sialyloligosaccharide excretion. Other patients showed normal results. With the present method mucolipidoses I and II, together with GM1 gangliosidosis, are readily distinguished from other possible oligosaccharidurias.

  20. The B-cell lymphoma 2 (BCL2)-inhibitors, ABT-737 and ABT-263, are substrates for P-glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Vogler, Meike, E-mail: mv62@le.ac.uk [MRC Toxicology Unit, University of Leicester, LE1 9HN Leicester (United Kingdom); Dickens, David, E-mail: David.Dickens@liverpool.ac.uk [Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, L69 3GL Liverpool (United Kingdom); Dyer, Martin J.S., E-mail: mjsd1@le.ac.uk [MRC Toxicology Unit, University of Leicester, LE1 9HN Leicester (United Kingdom); Owen, Andrew, E-mail: aowen@liverpool.ac.uk [Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, L69 3GL Liverpool (United Kingdom); Pirmohamed, Munir, E-mail: munirp@liv.ac.uk [Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, L69 3GL Liverpool (United Kingdom); Cohen, Gerald M., E-mail: gmc2@le.ac.uk [MRC Toxicology Unit, University of Leicester, LE1 9HN Leicester (United Kingdom)

    2011-05-06

    Highlights: {yields} The BCL2-inhibitor ABT-263 is a substrate for P-glycoprotein. {yields} Apoptosis is inhibited by P-glycoprotein expression. {yields} Overexpression of P-glycoprotein may contribute to resistance to ABT-263 or ABT-737. -- Abstract: Inhibition of BCL2 proteins is one of the most promising new approaches to targeted cancer therapy resulting in the induction of apoptosis. Amongst the most specific BCL2-inhibitors identified are ABT-737 and ABT-263. However, targeted therapy is often only effective for a limited amount of time because of the occurrence of drug resistance. In this study, the interaction of BCL2-inhibitors with the drug efflux transporter P-glycoprotein was investigated. Using {sup 3}H labelled ABT-263, we found that cells with high P-glycoprotein activity accumulated less drug. In addition, cells with increased P-glycoprotein expression were more resistant to apoptosis induced by either ABT-737 or ABT-263. Addition of tariquidar or verapamil sensitized the cells to BCL2-inhibitor treatment, resulting in higher apoptosis. Our data suggest that the BCL2-inhibitors ABT-737 and ABT-263 are substrates for P-glycoprotein. Over-expression of P-glycoprotein may be, at least partly, responsible for resistance to these BCL2-inhibitors.

  1. Ovine Herpesvirus 2 Glycoproteins B, H, and L Are Sufficient for, and Viral Glycoprotein Ov8 Can Enhance, Cell-Cell Membrane Fusion.

    Science.gov (United States)

    AlHajri, Salim M; Cunha, Cristina W; Nicola, Anthony V; Aguilar, Hector C; Li, Hong; Taus, Naomi S

    2017-03-15

    Ovine herpesvirus 2 (OvHV-2) is a gammaherpesvirus in the genus Macavirus that is carried asymptomatically by sheep. Infection of poorly adapted animals with OvHV-2 results in sheep-associated malignant catarrhal fever, a fatal disease characterized by lymphoproliferation and vasculitis. There is no treatment or vaccine for the disease and no cell culture system to propagate the virus. The lack of cell culture has hindered studies of OvHV-2 biology, including its entry mechanism. As an alternative method to study OvHV-2 glycoproteins responsible for membrane fusion as a part of the entry mechanism, we developed a virus-free cell-to-cell membrane fusion assay to identify the minimum required OvHV-2 glycoproteins to induce membrane fusion. OvHV-2 glycoproteins B, H, and L (gB, gH, and gL) were able to induce membrane fusion together but not when expressed individually. Additionally, open reading frame Ov8, unique to OvHV-2, was found to encode a transmembrane glycoprotein that can significantly enhance membrane fusion. Thus, OvHV-2 gB, gH, and gL are sufficient to induce membrane fusion, while glycoprotein Ov8 plays an enhancing role by an unknown mechanism.IMPORTANCE Herpesviruses enter cells via attachment of the virion to the cellular surface and fusion of the viral envelope with cellular membranes. Virus-cell membrane fusion is an important step for a successful viral infection. Elucidating the roles of viral glycoproteins responsible for membrane fusion is critical toward understanding viral entry. Entry of ovine herpesvirus 2 (OvHV-2), the causative agent of sheep associated-malignant catarrhal fever, which is one of the leading causes of death in bison and other ungulates, has not been well studied due to the lack of a cell culture system to propagate the virus. The identification of OvHV-2 glycoproteins that mediate membrane fusion may help identify viral and/or cellular factors involved in OvHV-2 cell tropism and will advance investigation of cellular

  2. CHROMOSOME ABNORMALITIES IN INFERTILITY

    Directory of Open Access Journals (Sweden)

    Mateja Smogavec

    2009-08-01

    Conclusions Chromosomal analysis is an important method in diagnostic procedures of infertility, because chromosomal abnormalities could play the important role in etiology of infertility and are more frequently detected in this group of patients compared to general population. In the infertile couples balanced chromosomal abnormalities are the main cause of spontaneous abortions. Sex chromosome aneuploidies are highly correlated to infertility of females and males.

  3. Hereditary urea cycle abnormality

    Science.gov (United States)

    ... vitro so the specific genetic cause is known. Teamwork between parents, the affected child, and doctors can help prevent severe illness. Alternative Names Abnormality of the urea cycle - hereditary; Urea cycle - hereditary abnormality Images Male urinary system Urea cycle References Lichter-Konecki ...

  4. 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......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...

  5. Correction of defective protein kinesis of human P-glycoprotein mutants by substrates and modulators.

    Science.gov (United States)

    Loo, T W; Clarke, D M

    1997-01-10

    There is growing evidence that abnormal protein folding or trafficking (protein kinesis) leads to diseases. We have used P-glycoprotein as a model protein to develop strategies to overcome defects in protein kinesis. Misprocessed mutants of the human P-glycoprotein are retained in the endoplasmic reticulum as core-glycosylated biosynthetic intermediates and rapidly degraded. Synthesis of the mutant proteins in the presence of drug substrates or modulators such as capsaicin, cyclosporin, vinblastine, or verapamil, however, resulted in the appearance of a fully glycosylated and functional protein at the cell surface. These effects were dose-dependent and occurred within a few hours after the addition of substrate. The ability to facilitate processing of the misfolded mutants appeared to be independent of the cell lines used and location of the mutation. P-glycoproteins with mutations in transmembrane segments, extracellular or cytoplasmic loops, the nucleotide-binding domains, or the linker region were processed to the fully mature form in the presence of these substrates. These drug substrates or modulators acted as specific chemical chaperones for P-glycoprotein because they were ineffective on the deltaF508 mutant of cystic fibrosis transmembrane conductance regulator. Therefore, one possible strategy to prevent protein misfolding is to carry out synthesis in the presence of specific substrates or modulators of the protein.

  6. Stabilization of lysosomal membrane and cell membrane glycoprotein profile by Semecarpus anacardium linn. nut milk extract in experimental hepatocellular carcinoma.

    Science.gov (United States)

    Premalatha, B; Sachdanandam, P

    2000-08-01

    Semecarpus anacardium Linn. nut milk extract administered orally at a dose of 200 mg/kg/day for 14 days exerted an in vivo stabilizing effect on lysosomal membrane and glycoprotein content in rat hepatocellular carcinoma. This was demonstrated in normal rats and in animals whose biomembranes were rendered fragile by induction of hepatocellular carcinoma with aflatoxin B(1) and subsequent treatment with Semecarpus anacardium nut extract. In this condition, the discharge of lysosomal enzymes increased significantly with a subsequent increase in glycoprotein components. The nut extract administration reversed these adverse changes to near normal in treated animals. The possible reason for this reversal is discussed. Such stabilization of biomembranes by Semecarpus anacardium nut extract may have a beneficial effect in the treatment of hepatocellular carcinoma and other cancers involving abnormal fragility of lysosomes and glycoprotein content providing the extract demonstrates safety in a full toxicity study. Copyright 2000 John Wiley & Sons, Ltd.

  7. Abnormal menstrual periods (image)

    Science.gov (United States)

    ... may have a variety of causes, such as endometrial hyperplasia, endometrial polyps, uterine fibroids, and abnormal thyroid or ... the endometrium becomes unusually thick it is called endometrial ... Hyperplasia may cause profuse or extended menstrual bleeding.

  8. "Jeopardy" in Abnormal Psychology.

    Science.gov (United States)

    Keutzer, Carolin S.

    1993-01-01

    Describes the use of the board game, Jeopardy, in a college level abnormal psychology course. Finds increased student interaction and improved application of information. Reports generally favorable student evaluation of the technique. (CFR)

  9. Chromosomal Abnormalities in ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-07-01

    Full Text Available The prevalence of fragile X syndrome, velocardiofacial syndrome (VCFS, and other cytogenetic abnormalities among 100 children (64 boys with combined type ADHD and normal intelligence was assessed at the NIMH and Georgetown University Medical Center.

  10. Chromosomal abnormalities and autism

    Directory of Open Access Journals (Sweden)

    Farida El-Baz

    2016-01-01

    Conclusion: Chromosomal abnormalities were not detected in the studied autistic children, and so the relation between the genetics and autism still needs further work up with different study methods and techniques.

  11. Abnormal protein aggregationand neurodegenerativediseases

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Abnormal protein aggregation or amyloid is the major cause ofmany neurodegenerative disorders. The present review focuses on the correlation between sequence and structure features of proteins related to the diseases and abnormal protein aggregation. Recent progress has improved our knowledge on understand-ing the mechanism of amyloid formation. We suggest a nucleation model for ordered protein aggregation, which can also explain pathogenesis mechanisms of these neurodegenerative diseases in vivo.

  12. Altered fetal growth, placental abnormalities, and stillbirth.

    Science.gov (United States)

    Bukowski, Radek; Hansen, Nellie I; Pinar, Halit; Willinger, Marian; Reddy, Uma M; Parker, Corette B; Silver, Robert M; Dudley, Donald J; Stoll, Barbara J; Saade, George R; Koch, Matthew A; Hogue, Carol; Varner, Michael W; Conway, Deborah L; Coustan, Donald; Goldenberg, Robert L

    2017-01-01

    Worldwide, stillbirth is one of the leading causes of death. Altered fetal growth and placental abnormalities are the strongest and most prevalent known risk factors for stillbirth. The aim of this study was to identify patterns of association between placental abnormalities, fetal growth, and stillbirth. Population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in 5 geographic areas in the U.S. Fetal growth abnormalities were categorized as small (90th percentile) for gestational age at death (stillbirth) or delivery (live birth) using a published algorithm. Placental examination by perinatal pathologists was performed using a standardized protocol. Data were weighted to account for the sampling design. Among 319 singleton stillbirths and 1119 singleton live births at ≥24 weeks at death or delivery respectively, 25 placental findings were investigated. Fifteen findings were significantly associated with stillbirth. Ten of the 15 were also associated with fetal growth abnormalities (single umbilical artery; velamentous insertion; terminal villous immaturity; retroplacental hematoma; parenchymal infarction; intraparenchymal thrombus; avascular villi; placental edema; placental weight; ratio birth weight/placental weight) while 5 of the 15 associated with stillbirth were not associated with fetal growth abnormalities (acute chorioamnionitis of placental membranes; acute chorioamionitis of chorionic plate; chorionic plate vascular degenerative changes; perivillous, intervillous fibrin, fibrinoid deposition; fetal vascular thrombi in the chorionic plate). Five patterns were observed: placental findings associated with (1) stillbirth but not fetal growth abnormalities; (2) fetal growth abnormalities in stillbirths only; (3) fetal growth abnormalities in live births only; (4) fetal growth abnormalities in stillbirths and live births in a similar manner; (5) a different pattern of fetal growth abnormalities in

  13. 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

  14. Archaeal S-layer glycoproteins: Post-translational modification in the face of extremes

    Directory of Open Access Journals (Sweden)

    Jerry eEichler

    2014-11-01

    Full Text Available Corresponding to the sole or basic component of the surface (S-layer surrounding the archaeal cell in most known cases, S-layer glycoproteins are in direct contact with the harsh environments that characterize niches where Archaea can thrive. Accordingly, early work examining archaeal S-layer glycoproteins focused on identifying those properties that allow members of this group of proteins to maintain their structural integrity in the face of extremes of temperature, pH and salinity, as well as other physical challenges. However, with expansion of the list of archaeal strains serving as model systems, as well as growth in the number of molecular tools available for the manipulation of these strains, studies on archaeal S-layer glycoproteins are currently more likely to consider the various post-translational modifications these polypeptides undergo. For instance, archaeal S-layer glycoproteins can undergo proteolytic cleavage, both N- and O-glycosylation, lipid-modification and oligomerization. In this mini-review, recent findings related to the post-translational modification of archaeal S-layer glycoproteins are considered.

  15. Ammonia secretion from fish gill depends on a set of Rh glycoproteins.

    Science.gov (United States)

    Nakada, Tsutomu; Westhoff, Connie M; Kato, Akira; Hirose, Shigehisa

    2007-04-01

    Ammonia excretion from the gill in teleost fish is essential for nitrogen elimination. Although numerous physiological studies have measured ammonia excretion, the mechanism of ammonia movement through the membranes of gill epithelial cells is still unknown. Mammalian Rh glycoproteins are members of a family of proteins that mediate ammonia transport in bacteria, yeast, and plants. We identified the Rh glycoprotein homologs, fRhag, fRhbg, fRhcg1, and fRhcg2, of the pufferfish, Takifugu rubripes. Northern blot, in situ hybridization, and immunohistochemistry revealed that the pufferfish erythroid Rh glycoprotein homologue fRhag was present in red blood cells and the hematological organs (spleen and kidney) in fish. All four pufferfish Rh glycoproteins are specifically localized in the gill and line the pillar cells, pavement cells, and the mitochondrion-rich cells. Heterologous expression in Xenopus oocytes showed that they mediate methylammonium (an analog of ammonium) transport. These results suggest that pufferfish Rh glycoproteins are involved in ammonia excretion from the gill. These findings challenge the classic view that ammonia excretion in the fish gill occurs by passive diffusion.

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

    Institute of Scientific and Technical Information of China (English)

    Beuy Joob; Viroj Wiwanitkit

    2014-01-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

    Beuy; Joob; Viroj; Wiwanitkit

    2014-01-01

    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 draggability within envelope glycoprotein GP2 from Ebola virus was done.According to this assessment,7 active pockets with varied draggability could be identified.

  18. Boronic acid functionalized peptidyl synthetic lectins: Combinatorial library design, peptide sequencing, and selective glycoprotein recognition

    Science.gov (United States)

    Bicker, Kevin L.; Sun, Jing; Lavigne, John J.; Thompson, Paul R.

    2011-01-01

    Aberrant glycosylation of cell membrane and secreted glycoproteins is a hallmark of various disease states, including cancer. The natural lectins currently used in the recognition of these glycoproteins are costly, difficult to produce, and unstable towards rigorous use. Herein we describe the design and synthesis of several boronic acid functionalized peptide-based synthetic lectin (SL) libraries, as well as the optimized methodology for obtaining peptide sequences of these SLs. SL libraries were subsequently used to identify SLs with as high as 5-fold selectivity for various glycoproteins. SLs will inevitably find a role in cancer diagnositics, given that they do not suffer from the drawbacks of natural lectins and that the combinatorial nature of these libraries allows for the identification of an SL for nearly any glycosylated biomolecule. PMID:21405093

  19. 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...

  20. [Hair shaft abnormalities].

    Science.gov (United States)

    Itin, P H; Düggelin, M

    2002-05-01

    Hair shaft disorders may lead to brittleness and uncombable hair. In general the hair feels dry and lusterless. Hair shaft abnormalities may occur as localized or generalized disorders. Genetic predisposition or exogenous factors are able to produce and maintain hair shaft abnormalities. In addition to an extensive history and physical examination the most important diagnostic examination to analyze a hair shaft problem is light microscopy. Therapy of hair shaft disorders should focus to the cause. In addition, minimizing traumatic influences to hair shafts, such as dry hair with an electric dryer, permanent waves and dyes is important. A short hair style is more suitable for such patients with hair shaft disorders.

  1. 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

    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...... 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...

  2. Suppressive effect of CORM-2 on LPS-induced platelet activation by glycoprotein mediated HS1 phosphorylation interference.

    Directory of Open Access Journals (Sweden)

    Dadong Liu

    Full Text Available In recent years, it has been discovered that septic patients display coagulation abnormalities. Platelets play a major role in the coagulation system. Studies have confirmed that carbon monoxide (CO has important cytoprotective and anti-inflammatory function. However, whether CO could alter abnormal activation of platelets and coagulation and thereby reduce the incidence of mortality during sepsis has not been defined. In this report, we have used CO-releasing molecules (CORM-2 to determine whether CO inhibits LPS-induced abnormal activation of platelets and have explored the potential mechanisms. LPS was used to induce activation of platelets in vitro, which were purified from the peripheral venous blood of healthy adult donors. CORM-2 was applied as a potential therapeutic agent. CORM-2 preconditioning and delayed treatment were also studied. We found that in the LPS groups, the function of platelets such as spreading, aggregation, and release were enhanced abnormally. By contrast, the platelets in the CORM-2 group were gently activated. Further studies showed that the expression of platelet membrane glycoproteins increased in the LPS group. Coincidently, both hematopoietic lineage cell-specific protein 1 and its phosphorylated form also increased dramatically. These phenomena were less dramatically seen in the CORM-2 groups. Taken together, we conclude that during LPS stimulation, platelets were abnormally activated, and this functional state may be associated with the signal that is transmitted between membrane glycoproteins and HS1. CORM-released CO suppresses the abnormal activation of platelets by interfering with glycoprotein-mediated HS1 phosphorylation.

  3. Chromosomal abnormalities and autism

    African Journals Online (AJOL)

    Farida El-Baz

    2015-06-19

    Jun 19, 2015 ... Received 19 April 2015; accepted 11 May 2015 ... Methods: This cross sectional study was conducted at the Child Psychiatry Clinic, ... Males are affected more than females, only one case had ... communication, repetitive behavior, abnormal movement ... course, age, sex and consanguinity of the patients.

  4. Cortical Abnormalities in ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-12-01

    Full Text Available Grey-matter abnormalities at the cortical surface and regional brain size were mapped by high-resolution MRI and surface-based, computational image analytical techniques in a group of 27 children and adolescents with attention deficit hyperactivity disorder (ADHD and 46 controls, matched by age and sex, at the University of California at Los Angeles.

  5. Neurological abnormalities predict disability

    DEFF Research Database (Denmark)

    Poggesi, Anna; Gouw, Alida; van der Flier, Wiesje

    2014-01-01

    To investigate the role of neurological abnormalities and magnetic resonance imaging (MRI) lesions in predicting global functional decline in a cohort of initially independent-living elderly subjects. The Leukoaraiosis And DISability (LADIS) Study, involving 11 European centres, was primarily aimed...

  6. Lacrimal system abnormalities.

    Science.gov (United States)

    Moore, B D

    1994-03-01

    This report outlines several of the more important abnormalities of the lacrimal system in infants and young children. Although rare, alacrima can be a very difficult clinical problem to treat. The most common cause of alacrima is the Riley-Day syndrome. Nasolacrimal duct obstruction is a very common anomaly in children. The clinical appearance and treatment of this disorder are discussed.

  7. Abnormalities of gonadal differentiation.

    Science.gov (United States)

    Berkovitz, G D; Seeherunvong, T

    1998-04-01

    Gonadal differentiation involves a complex interplay of developmental pathways. The sex determining region Y (SRY) gene plays a key role in testis determination, but its interaction with other genes is less well understood. Abnormalities of gonadal differentiation result in a range of clinical problems. 46,XY complete gonadal dysgenesis is defined by an absence of testis determination. Subjects have female external genitalia and come to clinical attention because of delayed puberty. Individuals with 46,XY partial gonadal dysgenesis usually present in the newborn period for the valuation of ambiguous genitalia. Gonadal histology always shows an abnormality of seminiferous tubule formation. A diagnosis of 46,XY true hermaphroditism is made if the gonads contain well-formed testicular and ovarian elements. Despite the pivotal role of the SRY gene in testis development, mutations of SRY are unusual in subjects with a 46,XY karyotype and abnormal gonadal development. 46,XX maleness is defined by testis determination in an individual with a 46,XX karyotype. Most affected individuals have a phenotype similar to that of Klinefelter syndrome. In contrast, subjects with 46,XX true hermaphroditism usually present with ambiguous genitalia. The majority of subjects with 46,XX maleness have Y sequences including SRY in genomic DNA. However, only rare subjects with 46,XX true hermaphroditism have translocated sequences encoding SRY. Mosaicism and chimaerism involving the Y chromosome can also be associated with abnormal gonadal development. However, the vast majority of subjects with 45,X/46,XY mosaicism have normal testes and normal male external genitalia.

  8. 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.

  9. Studies on the immuno-modulating and antitumor activities of Ganoderma lucidum (Reishi) polysaccharides: functional and proteomic analyses of a fucose-containing glycoprotein fraction responsible for the activities.

    Science.gov (United States)

    Wang, Yuan-Yuan; Khoo, Kay-Hooi; Chen, Shui-Tein; Lin, Chun-Cheng; Wong, Chi-Huey; Lin, Chun-Hung

    2002-04-01

    A fucose-containing glycoprotein fraction which stimulates spleen cell proliferation and cytokine expression has been identified from the water-soluble extract of Ganoderma lucidum. Proteomic analysis of mouse spleen cells treated with this glycoprotein fraction showed approximately 50% change of the proteome. Further studies on the activities of this glycoprotein fraction through selective proteolysis and glycosidic cleavage indicate that a fucose containing polysaccharide fraction is responsible for stimulating the expression of cytokines, especially IL-1, IL-2 and INF-gamma.

  10. Chromosomal abnormalities in patients with sperm disorders

    Directory of Open Access Journals (Sweden)

    L. Y. Pylyp

    2013-02-01

    Full Text Available Chromosomal abnormalities are among the most common genetic causes of spermatogenic disruptions. Carriers of chromosomal abnormalities are at increased risk of infertility, miscarriage or birth of a child with unbalanced karyotype due to the production of unbalanced gametes. The natural selection against chromosomally abnormal sperm usually prevents fertilization with sperm barring in cases of serious chromosomal abnormalities. However, assisted reproductive technologies in general and intracytoplasmic sperm injection in particular, enable the transmission of chromosomal abnormalities to the progeny. Therefore, cytogenetic studies are important in patients with male factor infertility before assisted reproduction treatment. The purpose of the current study was to investigate the types and frequencies of chromosomal abnormalities in 724 patients with infertility and to estimate the risk of chromosomal abnormalities detection in subgroups of patients depending on the severity of spermatogenic disruption, aiming at identifying groups of patients in need of cytogenetic studies. Karyotype analysis was performed in 724 blood samples of men attending infertility clinic. Chromosomal preparation was performed by standard techniques. At least 20 GTG-banded metaphase plates with the resolution from 450 to 750 bands per haploid set were analysed in each case. When chromosomal mosaicism was suspected, this number was increased to 50. Abnormal karyotypes were observed in 48 (6.6% patients, including 67% of autosomal abnormalities and 33% of gonosomal abnormalities. Autosomal abnormalities were represented by structural rearrangements. Reciprocal translocations were the most common type of structural chromosomal abnormalities in the studied group, detected with the frequency of 2.6% (n = 19, followed by Robertsonian translocation, observed with the frequency of 1.2% (n = 9. The frequency of inversions was 0.6% (n = 4. Gonosomal abnormalities included 14 cases

  11. Abnormal Bleeding During Menopause Hormone Therapy: Insights for Clinical Management

    OpenAIRE

    2013-01-01

    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 a...

  12. 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.

  13. 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.

  14. Liver abnormalities in pregnancy.

    Science.gov (United States)

    Than, Nwe Ni; Neuberger, James

    2013-08-01

    Abnormalities of liver function (notably rise in alkaline phosphatase and fall in serum albumin) are common in normal pregnancy, whereas rise in serum bilirubin and aminotransferase suggest either exacerbation of underlying pre-existing liver disease, liver disease related to pregnancy or liver disease unrelated to pregnancy. Pregnant women appear to have a worse outcome when infected with Hepatitis E virus. Liver diseases associated with pregnancy include abnormalities associated hyperemesis gravidarum, acute fatty liver disease, pre-eclampsia, cholestasis of pregnancy and HELLP syndrome. Prompt investigation and diagnosis is important in ensuring a successful maternal and foetal outcome. In general, prompt delivery is the treatment of choice for acute fatty liver, pre-eclampsia and HELLP syndrome and ursodeoxycholic acid is used for cholestasis of pregnancy although it is not licenced for this indication. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Nitrofurantoin and congenital abnormalities

    DEFF Research Database (Denmark)

    Czeizel, A.E.; Rockenbauer, M.; Sørensen, Henrik Toft;

    2001-01-01

    Objective: To study human teratogenic potential of oral nitrofurantoin treatment during pregnancy. Materials and Methods: Pair analysis of cases with congenital abnormalities and matched population controls in the population-based dataset of the Hungarian Case-Control Surveillance of Congenital...... or fetuses with Down’s syndrome (patient controls), 23 (2.8%) pregnant women were treated with nitrofurantoin. The above differences between population controls and cases may be connected with recall bias, because the case-control pair analysis did not indicate a teratogenic potential of nitrofurantoin use...... during the second and the third months of gestation, i.e. in the critical period for major congenital abnormalities. Conclusion: Treatment with nitrofurantoin during pregnancy does not present detectable teratogenic risk to the fetus....

  16. An automated data-driven DSP development approach for glycoproteins from yeast.

    Science.gov (United States)

    Rajamanickam, Vignesh; Krippl, Maximillian; Herwig, Christoph; Spadiut, Oliver

    2017-08-04

    Downstream process development for recombinant glycoproteins from yeast is cumbersome due to hyperglycosylation of target proteins. In a previous study, we purified three recombinant glycoproteins from Pichia pastoris using a simple two-step flowthrough mode approach using monolithic columns. In this study, we investigated a novel automated data science approach for identifying purification conditions for such glycoproteins using monolithic columns. We performed three sets of design of experiments in analytical scale to determine the separation efficiency of monolithic columns for three different recombinant horseradish peroxidase (HRP) isoenzymes. For ease of calculation, we introduced an arbitrary term, the relative impurity removal (IR), which is representative of the amount of impurities cleared. Both, the experimental part and the data analysis were automated and took less than 40 min for each HRP isoenzyme. We tested the identified purification conditions in laboratory scale and performed respective offline analyses to verify results from analytical scale. We found a clear correlation between the IR estimated online through our novel data-driven approach and the IR determined offline. Summarizing, we present a novel methodology, applying analytical scale advantages which can be used for fast and efficient DSP development for recombinant glycoproteins from yeast without offline analyses. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Platelet Glycoprotein lb-1X and Malignancy

    Science.gov (United States)

    2011-09-01

    patient with systemic lupus erythematosus . Am J Hematol 2001; 67:262-67. 20. Arthur JF, Dunkley S and Andrews RK. Platelet glycoprotein VI-related...Moroi M. Antibody against platelet membrane glyco- protein VI in a patient with systemic lupus erythematosus . Am J Hematol 2001; 67: 262–7. 9 Arthur JF...Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the

  18. P-Glycoprotein and Drug Resistance in Systemic Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Andrea Picchianti-Diamanti

    2014-03-01

    Full Text Available Autoimmune diseases such as systemic lupus erythematosus (SLE, rheumatoid arthritis (RA and psoriatic arthritis (PsA are chronic inflammatory disorders of unknown etiology characterized by a wide range of abnormalities of the immune system that may compromise the function of several organs, such as kidney, heart, joints, brain and skin. Corticosteroids (CCS, synthetic and biologic immunosuppressive agents have demonstrated the capacity to improve the course of autoimmune diseases. However, a significant number of patients do not respond or develop resistance to these therapies over time. P-glycoprotein (P-gp is a transmembrane protein that pumps several drugs out of the cell, including CCS and immunosuppressants; thus, its over-expression or hyper-function has been proposed as a possible mechanism of drug resistance in patients with autoimmune disorders. Recently, different authors have demonstrated that P-gp inhibitors, such as cyclosporine A (CsA and its analogue Tacrolimus, are able to reduce P-gp expression and or function in SLE, RA and PsA patients. These observations suggest that P-gp antagonists could be adopted to revert drug resistance and improve disease outcome. The complex inter-relationship among drug resistance, P-gp expression and autoimmunity still remains elusive.

  19. 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

  20. [Molecular abnormalities in lymphomas].

    Science.gov (United States)

    Delsol, G

    2010-11-01

    Numerous molecular abnormalities have been described in lymphomas. They are of diagnostic and prognostic value and are taken into account for the WHO classification of these tumors. They also shed some light on the underlying molecular mechanisms involved in lymphomas. Overall, four types of molecular abnormalities are involved: mutations, translocations, amplifications and deletions of tumor suppressor genes. Several techniques are available to detect these molecular anomalies: conventional cytogenetic analysis, multicolor FISH, CGH array or gene expression profiling using DNA microarrays. In some lymphomas, genetic abnormalities are responsible for the expression of an abnormal protein (e.g. tyrosine-kinase, transcription factor) detectable by immunohistochemistry. In the present review, molecular abnormalities observed in the most frequent B, T or NK cell lymphomas are discussed. In the broad spectrum of diffuse large B-cell lymphomas microarray analysis shows mostly two subgroups of tumors, one with gene expression signature corresponding to germinal center B-cell-like (GCB: CD10+, BCL6 [B-Cell Lymphoma 6]+, centerine+, MUM1-) and a subgroup expressing an activated B-cell-like signature (ABC: CD10-, BCL6-, centerine-, MUM1+). Among other B-cell lymphomas with well characterized molecular abnormalies are follicular lymphoma (BCL2 deregulation), MALT lymphoma (Mucosa Associated Lymphoid Tissue) [API2-MALT1 (mucosa-associated-lymphoid-tissue-lymphoma-translocation-gene1) fusion protein or deregulation BCL10, MALT1, FOXP1. MALT1 transcription factors], mantle cell lymphoma (cycline D1 [CCND1] overexpression) and Burkitt lymphoma (c-Myc expression). Except for ALK (anaplastic lymphoma kinase)-positive anaplastic large cell lymphoma, well characterized molecular anomalies are rare in lymphomas developed from T or NK cells. Peripheral T cell lymphomas not otherwise specified are a heterogeneous group of tumors with frequent but not recurrent molecular abnormalities

  1. Interaction of mouse hepatitis virus (MHV) spike glycoprotein with receptor glycoprotein MHVR is required for infection with an MHV strain that expresses the hemagglutinin-esterase glycoprotein

    NARCIS (Netherlands)

    Gagneten, S; Gout, O; Dubois-Dalcq, M; Rottier, P; Rossen, J; Holmes, K V

    1995-01-01

    In addition to the spike (S) glycoprotein that binds to carcinoembryonic antigen-related receptors on the host cell membrane, some strains of mouse coronavirus (mouse hepatitis virus [MHV]) express a hemagglutinin esterase (HE) glycoprotein with hemagglutinating and acetylesterase activity. Virions

  2. 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.…

  3. The inhibitory and combinative mechanism of HZ08 with P-glycoprotein expressed on the membrane of Caco-2 cell line

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yanyan; Hu, Yahui; Feng, Yidong; Kodithuwakku, Nandani Darshika; Fang, Weirong [State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009 (China); Li, Yunman, E-mail: yunmanlicpu@hotmail.com [State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009 (China); Huang, Wenlong [Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009 (China)

    2014-01-15

    Recently, the research and development of agents to reverse the phenomenon of multidrug resistance has been an attractive goal as well as a key approach to elevating the clinical survival of cancer patients. Although three generations of P-glycoprotein modulators have been identified, poor clearance and metabolism render these agents too toxic to be used in clinical application. HZ08, which has been under investigation for several years, shows a dramatic reversal effect with low cytotoxicity. For the first time, we aimed to describe the interaction between HZ08 and P-glycoprotein in Caco-2 cell line in which P-glycoprotein is overexpressed naturally. Cytotoxicity and multidrug resistance reversal assays, together with flow cytometry, fluorescence microscopy and siRNA interference as well as Caco-2 monolayer transport model were employed in this study to evaluate the interaction between HZ08 and P-glycoprotein. This study revealed that HZ08 was capable of reversing adriamycin resistance mediated by P-glycoprotein as a result of intracellular enhancement of adriamycin accumulation, which was found to be superior to verapamil. In addition, we confirmed that HZ08 suppressed the transport of Rhodamine123 in the Caco-2 monolayer model but had little effect on P-glycoprotein expression. The transport of HZ08 was diminished by P-glycoprotein inhibitors (verapamil and LY335979) and its accumulation was increased via siRNA targeting MDR1 in Caco-2 cells. Furthermore, considering the binding site of P-glycoprotein, verapamil performed as a competitive inhibitor with HZ08. In conclusion, as a P-glycoprotein substrate, HZ08 inhibited P-glycoprotein activity and may share the same binding site of verapamil to P-glycoprotein. - Highlights: • The cytotoxicity and reversing effect of HZ08 was measured in Caco-2 cell line. • HZ08 inhibited the transport of Rhodamine123 across Caco-2 cell monolayer. • The efflux ratio of HZ08 was dropped when combined with P-glycoprotein

  4. 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.

  5. Common glycoproteins expressing polylactosamine-type glycans on matched patient primary and metastatic melanoma cells show different glycan profiles.

    Science.gov (United States)

    Kinoshita, Mitsuhiro; Mitsui, Yosuke; Kakoi, Naotaka; Yamada, Keita; Hayakawa, Takao; Kakehi, Kazuaki

    2014-02-07

    Recently, we reported comparative analysis of glycoproteins which express cancer-specific N-glycans on various cancer cells and identified 24 glycoproteins having polylactosamine (polyLacNAc)-type N-glycans that are abundantly present in malignant cells [ Mitsui et al., J. Pharm. Biomed. Anal. 2012 , 70 , 718 - 726 ]. In the present study, we applied the technique to comparative studies on common glycoproteins present in the matched patient primary and metastatic melanoma cell lines. Metastatic melanoma cells (WM266-4) contained a large amount of polyLacNAc-type N-glycans in comparison with primary melanoma cells (WM115). To identify the glycoproteins expressing these N-glycans, glycopeptides having polyLacNAc-type N-glycans were captured by a Datura stramonium agglutinin (DSA)-immobilized agarose column. The captured glycopeptides were analyzed by LC/MS after removing N-glycans, and some glycoproteins such as basigin, lysosome-associated membrane protein-1 (LAMP-1), and chondroitin sulfate proteoglycan 4 (CSPG4) were identified in both WM115 and WM266-4 cells. The expression level of polyLacNAc of CSPG4 in WM266-4 cells was significantly higher than that in WM115 cells. In addition, sulfation patterns of chondroitin sulfate (CS) chains in CSPG4 showed dramatic changes between these cell lines. These data show that characteristic glycans attached to common proteins observed in different stages of cancer cells will be useful markers for determining degree of malignancies of tumor cells.

  6. 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.

  7. 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.)

  8. Analgesic effects of glycoproteins from Panax ginseng root in mice.

    Science.gov (United States)

    Wang, Ying; Chen, Yinghong; Xu, Hong; Luo, Haoming; Jiang, Ruizhi

    2013-07-30

    The root of Panax ginseng C.A. Mey has various beneficial pharmacological effects. The present study aimed to evaluate the analgesic activities of glycoproteins from the root of Panax ginseng C.A. Mey in mice. Glycoproteins were isolated and purified from the root of Panax ginseng C.A. Mey. Physicochemical properties and molecular mass were determined by chemical assay and HPLC. Acetic acid-induced writhing and hot-plate tests were employed to study the analgesic effect of glycoproteins and compared with that of aspirin or morphine. The locomotor activity was tested in mice by using actophometer. Four glycoproteins were obtained. The glycoproteins which protein content was the highest (73.04%) displayed dose-dependent analgesic effect. In writhing test, the glycoproteins significantly inhibited writhes (PPanax ginseng C.A. Mey exhibited significant analgesic activities and the proteins were the active site, providing evidence for its pharmacal use. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Method of detecting genetic translocations identified with chromosomal abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Gray, Joe W. (Livermore, CA); Pinkel, Daniel (Walnut Creek, CA); Tkachuk, Douglas (Livermore, CA)

    2001-01-01

    Methods and compositions for staining based upon nucleic acid sequence that employ nucleic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyses. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods and reagents are provided for the detection of genetic rearrangements. Probes and test kits are provided for use in detecting genetic rearrangements, particularly for use in tumor cytogenetics, in the detection of disease related loci, specifically cancer, such as chronic myelogenous leukemia (CML) and for biological dosimetry. Methods and reagents are described for cytogenetic research, for the differentiation of cytogenetically similar but genetically different diseases, and for many prognostic and diagnostic applications.

  10. Method of detecting genetic deletions identified with chromosomal abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Gray, Joe W; Pinkel, Daniel; Tkachuk, Douglas

    2013-11-26

    Methods and compositions for staining based upon nucleic acid sequence that employ nucleic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyzes. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acids probes are typically of a complexity greater tha 50 kb, the complexity depending upon the cytogenetic application. Methods and reagents are provided for the detection of genetic rearrangements. Probes and test kits are provided for use in detecting genetic rearrangements, particlularly for use in tumor cytogenetics, in the detection of disease related loci, specifically cancer, such as chronic myelogenous leukemia (CML) and for biological dosimetry. Methods and reagents are described for cytogenetic research, for the differentiation of cytogenetically similar ut genetically different diseases, and for many prognostic and diagnostic applications.

  11. Method of detecting genetic deletions identified with chromosomal abnormalities

    Science.gov (United States)

    Gray, Joe W; Pinkel, Daniel; Tkachuk, Douglas

    2013-11-26

    Methods and compositions for staining based upon nucleic acid sequence that employ nucleic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyzes. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acids probes are typically of a complexity greater tha 50 kb, the complexity depending upon the cytogenetic application. Methods and reagents are provided for the detection of genetic rearrangements. Probes and test kits are provided for use in detecting genetic rearrangements, particlularly for use in tumor cytogenetics, in the detection of disease related loci, specifically cancer, such as chronic myelogenous leukemia (CML) and for biological dosimetry. Methods and reagents are described for cytogenetic research, for the differentiation of cytogenetically similar ut genetically different diseases, and for many prognostic and diagnostic applications.

  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. Russia: An Abnormal Country

    Directory of Open Access Journals (Sweden)

    Steven Rosefielde

    2005-06-01

    Full Text Available Andrei Shleifer and Daniel Treisman recently rendered a summary verdict on the post Soviet Russian transition experience finding that the Federation had become a normal country with the west's assistance, and predicting that it would liberalize and develop further like other successful nations of its type. This essay demonstrates that they are mistaken on the first count, and are likely to be wrong on the second too. It shows factually, and on the norms elaborated by Pareto, Arrow and Bergson that Russia is an abnormal political economy unlikely to democratize, westernize or embrace free enterprise any time soon

  15. Abnormal ionization in sonoluminescence

    Science.gov (United States)

    Zhang, Wen-Juan; An, Yu

    2015-04-01

    Sonoluminescence is a complex phenomenon, the mechanism of which remains unclear. The present study reveals that an abnormal ionization process is likely to be present in the sonoluminescing bubble. To fit the experimental data of previous studies, we assume that the ionization energies of the molecules and atoms in the bubble decrease as the gas density increases and that the decrease of the ionization energy reaches about 60%-70% as the bubble flashes, which is difficult to explain by using previous models. Project supported by the Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20120002110031) and the National Natural Science Foundation of China (Grant No. 11334005).

  16. Engineering molecular crystals with abnormally weak cohesion.

    Science.gov (United States)

    Maly, Kenneth E; Gagnon, Eric; Wuest, James D

    2011-05-14

    Adding astutely placed methyl groups to hexaphenylbenzene increases molecular weight but simultaneously weakens key C-H···π interactions, thereby leading to decreased enthalpies of sublimation and showing that materials with abnormally weak cohesion can be made by identifying and then obstructing interactions that help control association.

  17. Syringic acid, a novel natural phenolic acid, normalizes hyperglycemia with special reference to glycoprotein components in experimental diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Jayachandran Muthukumaran; Subramani Srinivasan; Vinayagam Ramachandran; Udaiyar Muruganathan

    2013-01-01

    Objective:To evaluate the antidiabetic effect of syringic acid, a natural phenolic compound on the levels of glycoprotein components in plasma and tissues of alloxan induced diabetic rats. Methods:Diabetes was induced in maleWistar rats by a single intraperitoneal injection of alloxan(150 mg/kg b.w).Syringic acid(50 mg/kg b.w) was administered orally for30 d.The effects of syringic acid on plasma glucose, insulin,C-peptide, plasma and tissue glycoproteins were studied.Results:Oral administration of syringic acid(50 mg/kg b.w) for30 d positively modulates the glycemic status in alloxan induced diabetic rats.The levels of plasma glucose were decreased with significant increase of plasma insulin andC-peptide level.The altered levels of plasma and tissue glycoprotein components were restored to near normal.No significant changes were noticed in normal rats treated with syringic acid.Conclusions:The present findings suggest that syringic acid can potentially ameliorate glycoprotein components abnormalities in addition to its antidiabetic effect in experimental diabetes, further clinical studies are required to evaluate the use of syringic acid as an effective therapeutic agent for the treatment of diabetes mellitus.

  18. Most neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunits

    Science.gov (United States)

    Robinson, James E.; Hastie, Kathryn M.; Cross, Robert W.; Yenni, Rachael E.; Elliott, Deborah H.; Rouelle, Julie A.; Kannadka, Chandrika B.; Smira, Ashley A.; Garry, Courtney E.; Bradley, Benjamin T.; Yu, Haini; Shaffer, Jeffrey G.; Boisen, Matt L.; Hartnett, Jessica N.; Zandonatti, Michelle A.; Rowland, Megan M.; Heinrich, Megan L.; Martínez-Sobrido, Luis; Cheng, Benson; de la Torre, Juan C.; Andersen, Kristian G.; Goba, Augustine; Momoh, Mambu; Fullah, Mohamed; Gbakie, Michael; Kanneh, Lansana; Koroma, Veronica J.; Fonnie, Richard; Jalloh, Simbirie C.; Kargbo, Brima; Vandi, Mohamed A.; Gbetuwa, Momoh; Ikponmwosa, Odia; Asogun, Danny A.; Okokhere, Peter O.; Follarin, Onikepe A.; Schieffelin, John S.; Pitts, Kelly R.; Geisbert, Joan B.; Kulakoski, Peter C.; Wilson, Russell B.; Happi, Christian T.; Sabeti, Pardis C.; Gevao, Sahr M.; Khan, S. Humarr; Grant, Donald S.; Geisbert, Thomas W.; Saphire, Erica Ollmann; Branco, Luis M.; Garry, Robert F.

    2016-01-01

    Lassa fever is a severe multisystem disease that often has haemorrhagic manifestations. The epitopes of the Lassa virus (LASV) surface glycoproteins recognized by naturally infected human hosts have not been identified or characterized. Here we have cloned 113 human monoclonal antibodies (mAbs) specific for LASV glycoproteins from memory B cells of Lassa fever survivors from West Africa. One-half bind the GP2 fusion subunit, one-fourth recognize the GP1 receptor-binding subunit and the remaining fourth are specific for the assembled glycoprotein complex, requiring both GP1 and GP2 subunits for recognition. Notably, of the 16 mAbs that neutralize LASV, 13 require the assembled glycoprotein complex for binding, while the remaining 3 require GP1 only. Compared with non-neutralizing mAbs, neutralizing mAbs have higher binding affinities and greater divergence from germline progenitors. Some mAbs potently neutralize all four LASV lineages. These insights from LASV human mAb characterization will guide strategies for immunotherapeutic development and vaccine design. PMID:27161536

  19. The DNA sequence of the equine herpesvirus 4 gene encoding glycoprotein gp17/18, the homologue of herpes simplex virus glycoprotein gD.

    Science.gov (United States)

    Cullinane, A A; Neilan, J; Wilson, L; Davison, A J; Allen, G

    1993-09-01

    The nucleotide sequence of the gene to the left of the gI gene of equine herpesvirus 4 (EHV-4) was determined. The gene encodes a peptide of 402 amino acids with an unprocessed M(r) of 45,323. The predicted polypeptide has several features of a glycoprotein including a hydrophobic signal sequence, a membrane spanning domain and four potential N-linked glycosylation sites within the proposed external domain. The predicted amino acid sequence of EHV-4 gD shows 83% identity with that of equine herpesvirus 1 gD. Conservation of the tertiary structure is suggested by the alignment of six cysteine residues with those of the gD of six other alphaherpesviruses. Screening a lambda gt11/EHV-4 expression library with monoclonal antibodies against several of the most abundant EHV-4 glycoproteins unequivocally identified the protein encoded by the EHV-4 gD gene as gp17/18.

  20. Abnormal grain growth in undoped strontium and barium titanate

    Energy Technology Data Exchange (ETDEWEB)

    Baeurer, M., E-mail: m.baeurer@ikm.uka.de [Institut fuer Keramik im Maschinenbau, Universitaet Karlsruhe, Karlsruhe (Germany); Shih, S.-J.; Bishop, C. [Department of Materials, University of Oxford, Oxford (United Kingdom); Harmer, M.P. [Center for Advanced Materials and Nanotechnology, Lehigh University, Bethlehem, PA (United States); Cockayne, D. [Department of Materials, University of Oxford, Oxford (United Kingdom); Hoffmann, M.J. [Institut fuer Keramik im Maschinenbau, Universitaet Karlsruhe, Karlsruhe (Germany)

    2010-01-15

    Abnormal grain growth is a commonly observed phenomenon in perovskite materials. In order to study this phenomenon, grain growth experiments were conducted over a temperature range from 1425 to 1600 deg. C for the model system SrTiO{sub 3} to analyse the nucleation of abnormal grains and to identify the growth mechanism involved for normal and abnormal grains. Grain boundaries of normal and abnormal grains were investigated in quenched samples by high-resolution transmission electron microscopy and by energy-dispersive spectroscopy in a scanning transmission electron microscope. No amorphous film was observed at the grain boundaries for either normal or abnormal grains. Non-stoichiometry at the grain boundaries was identified as a possible reason for the differences in growth speed. The results are compared to the nucleation and growth of abnormal grains in BaTiO{sub 3}.

  1. Use of lambdagt11 to isolate genes for two pseudorabies virus glycoproteins with homology to herpes simplex virus and varicella-zoster virus glycoproteins

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-10-01

    A library of pseudorabies virus (PRV) DNA fragments was constructed in the expression cloning vector lambdagt11. 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 lambdagt11 vector, the cloned proteins were expressed in Escherichia coli as ..beta..-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 (/sup 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.

  2. The prevalence of chromosomal abnormalities in subgroups of infertile men.

    Science.gov (United States)

    Dul, E C; Groen, H; van Ravenswaaij-Arts, C M A; Dijkhuizen, T; van Echten-Arends, J; Land, J A

    2012-01-01

    The prevalence of chromosomal abnormalities is assumed to be higher in infertile men and inversely correlated with sperm concentration. Although guidelines advise karyotyping infertile men, karyotyping is costly, therefore it would be of benefit to identify men with the highest risk of chromosomal abnormalities, possibly by using parameters other than sperm concentration. The aim of this study was to evaluate several clinical parameters in azoospermic and non-azoospermic men, in order to assess the prevalence of chromosomal abnormalities in different subgroups of infertile men. In a retrospective cohort of 1223 azoospermic men and men eligible for ICSI treatment, we studied sperm parameters, hormone levels and medical history for an association with chromosomal abnormalities. The prevalence of chromosomal abnormalities in the cohort was 3.1%. No association was found between chromosomal abnormalities and sperm volume, concentration, progressive motility or total motile sperm count. Azoospermia was significantly associated with the presence of a chromosomal abnormality [15.2%, odds ratio (OR) 7.70, P chromosomal abnormalities (OR 2.96, P = 0.013). Azoospermic men with a positive andrologic history had a lower prevalence of chromosomal abnormalities than azoospermic men with an uneventful history (OR 0.28, P = 0.047). In non-azoospermic men, we found that none of the studied variables were associated with the prevalence of chromosomal abnormalities. We show that the highest prevalence of chromosomal abnormalities is found in hypergonadotrophic azoospermic men with an uneventful andrologic history.

  3. Detection of Receptor-Induced Glycoprotein Conformational Changes on Enveloped Virions by Using Confocal Micro-Raman Spectroscopy

    Science.gov (United States)

    Lu, Xiaonan; Liu, Qian; Benavides-Montano, Javier A.; Nicola, Anthony V.; Aston, D. Eric; Rasco, Barbara A.

    2013-01-01

    Conformational changes in the glycoproteins of enveloped viruses are critical for membrane fusion, which enables viral entry into cells and the pathological cell-cell fusion (syncytia) associated with some viral infections. However, technological capabilities for identifying viral glycoproteins and their conformational changes on actual enveloped virus surfaces are generally scarce, challenging, and time-consuming. Our model, Nipah virus (NiV), is a syncytium-forming biosafety level 4 pathogen with a high mortality rate (40 to 75%) in humans. Once the NiV attachment glycoprotein (G) (NiV-G) binds the cell receptor ephrinB2 or -B3, G triggers conformational changes in the fusion glycoprotein (F) that result in membrane fusion and viral entry. We demonstrate that confocal micro-Raman spectroscopy can, within minutes, simultaneously identify specific G and F glycoprotein signals and receptor-induced conformational changes in NiV-F on NiV virus-like particles (VLPs). First, we identified reproducible G- and F-specific Raman spectral features on NiV VLPs containing M (assembly matrix protein), G, and/or F or on NiV/vesicular stomatitis virus (VSV) pseudotyped virions via second-derivative transformations and principal component analysis (PCA). Statistical analyses validated our PCA models. Dynamic temperature-induced conformational changes in F and G or receptor-induced target membrane-dependent conformational changes in F were monitored in NiV pseudovirions in situ in real time by confocal micro-Raman spectroscopy. Advantageously, Raman spectroscopy can identify specific protein signals in relatively impure samples. Thus, this proof-of-principle technological development has implications for the rapid identification and biostability characterization of viruses in medical, veterinary, and food samples and for the analysis of virion glycoprotein conformational changes in situ during viral entry. PMID:23283947

  4. Fetal calcifications are associated with chromosomal abnormalities.

    Directory of Open Access Journals (Sweden)

    Ellika Sahlin

    Full Text Available The biological importance of calcifications occasionally noted in fetal tissues (mainly liver at autopsy or ultrasound is largely unexplored. Previous reports hint at an association to infection, circulatory compromise, malformations or chromosomal abnormalities. To identify factors associated with calcifications, we have performed a case-control study on the largest cohort of fetuses with calcifications described thus far.One-hundred and fifty-one fetuses with calcifications and 302 matched controls were selected from the archives of the Department of Pathology, Karolinska University Hospital. Chromosome analysis by karyotyping or quantitative fluorescence-polymerase chain reaction was performed. Autopsy and placenta reports were scrutinized for presence of malformations and signs of infection.Calcifications were mainly located in the liver, but also in heart, bowel, and other tissues. Fetuses with calcifications showed a significantly higher proportion of chromosomal abnormalities than controls; 50% vs. 20% (p<0.001. The most frequent aberrations among cases included trisomy 21 (33%, trisomy 18 (22%, and monosomy X (18%. A similar distribution was seen among controls. When comparing cases and controls with chromosomal abnormalities, the cases had a significantly higher prevalence of malformations (95% vs. 77%, p=0.004. Analyzed the other way around, cases with malformations had a significantly higher proportion of chromosomal abnormalities compared with controls, (66% vs. 31%, p<0.001.The presence of fetal calcifications is associated with high risk of chromosomal abnormality in combination with malformations. Identification of a calcification together with a malformation at autopsy more than doubles the probability of detecting a chromosomal abnormality, compared with identification of a malformation only. We propose that identification of a fetal tissue calcification at autopsy, and potentially also at ultrasound examination, should infer

  5. A Rare Stapes Abnormality

    Directory of Open Access Journals (Sweden)

    Hala Kanona

    2015-01-01

    Full Text Available The aim of this study is to increase awareness of rare presentations, diagnostic difficulties alongside management of conductive hearing loss and ossicular abnormalities. We report the case of a 13-year-old female reporting progressive left-sided hearing loss and high resolution computed tomography was initially reported as normal. Exploratory tympanotomy revealed an absent stapedius tendon and lack of connection between the stapes superstructure and footplate. The footplate was fixed. Stapedotomy and stapes prosthesis insertion resulted in closure of the air-bone gap by 50 dB. A review of world literature was performed using MedLine. Middle ear ossicular discontinuity can result in significant conductive hearing loss. This can be managed effectively with surgery to help restore hearing. However, some patients may not be suitable or decline surgical intervention and can be managed safely conservatively.

  6. Abnormal fetal head shape: aetiology and management

    DEFF Research Database (Denmark)

    Petersen, Olav Bjørn; David, Anna; Thomasson, Louise

    2007-01-01

    Background: Abnormal head shape is an uncommon finding on prenatal ultrasound, often associated with breech presentation, spinabifida, aneuploidy or secondary to oligohydramnios or fetal position. Other aetiologies are rarer and may be more difficult to define. Objective: To determine the aetiolo...... incidence of genetic syndromes, in the absence of a clear diagnosis, referral to a tertiary centre and genetic input is advised as detection of subtle sonographic features may aid diagnosis, allowing for targeted molecular analysis. An algorithm for management will be proposed....... and define management pathways for fetuses with an abnormal skull shape. Methods: Our FMU databases were searched to ascertain all fetuses with an abnormal skull shape. Sonographic findings, diagnosis and outcome were reviewed. Results: Of the 370 cases identified, 31.6% were associated with spinabifida...

  7. Partial Characterization of a Vicilin-Like Glycoprotein from Seeds of Flowering Tobacco (Nicotiana sylvestris

    Directory of Open Access Journals (Sweden)

    Jared Q. Gerlach

    2009-01-01

    Full Text Available A vicilin-like glycoprotein from the seeds of Nicotiana sylvestris, flowering tobacco, has been identified using nanoLC/ESI-MS/MS. Sequences from a fragment of protein demonstrated homology with vicilins from other members of the Solanaceae family, notably potato (Solanum demissum. Reducing and nonreducing SDS-PAGE analyses of the identified protein indicated that fragments resulting from in situ proteolytic processing are joined by intrachain disulphide bonds. Staining with Con A lectin was specifically inhibited by mannose suggested the presence of -linked glycosylation which was confirmed by carbohydrate compositional analysis of PVDF-bound protein subunits. HPAEC-PAD analysis of the monosaccharides released from the glycoprotein by acid hydrolysis revealed glucosamine and mannose. -acetylglucosamine termination of attached oligosaccharides was further verified by inhibitable WGA lectin staining. Immunostaining of PVDF-bound N. sylvestris proteins with antibodies against G. max total protein demonstrated cross-staining at masses corresponding to fragments from the proteolytically processed protein subunits.

  8. P-glycoprotein regulating biphasic insulin secretion in rat pancreatic beta cells

    Institute of Scientific and Technical Information of China (English)

    TANG Yun-zhao; LI Dai-qing; SUN Fu-jun; LI Li; YU De-min

    2009-01-01

    Background A 65-kD mdr1(multi-drug resistance protein 1,P-glycoprotein)-like protein has been suggested to be the regulatory protein to the chloride channel protein 3(CIC-3)mediating insulin granules acidification and release in mouse pancreatic beta cells.But the protein has not been deeply investigated.In this study,we identified existence of the 65-kda protein in rat islets and preliminarily explored its biological functions.Methods Total RNAs of rat kidneys served as positive controls,and pancreas,islets and INS-1 cells were extracted for reverse-transcript PCR(RT-PCR),respectively.The cDNAs were run with specific primers selected from the mRNA of abcblb encoding P-glycoprotein.All PCR products were visualized in agarose gel electrophoresis and sequenced.Homogenates of rat islets and INS-1 cells were applied to SDS-PAGE.P-glycoprotein was detected by a specific monoclonal antibody,C219.Biphasic insulin release was measured in static incubations of rat islets with radioimmunology assay.Results Compared with positive control,expression of the P-glycoprotein mRNA segments were detected in the islets,INS-1 cells and pancreas.Sequence analysis confirmed that the PCR products were matched with mRNA of P-glycoprotein.A 65-kda protein was recognized by the antibody in the islets homogenate but not in that of INS-1 cells in Western-blotting.Instead,the homogenate of INS-1 cells contained a 160-kda protein recognized by the antibody.Insulin secretion of rat islets were stimulated by high glucose(16.7mmol/L),and showed biphasic curve during 60-minute incubation.After co-incubation with cyclosporine A(CsA),specific inhibitor to P-glycoprotein,the second phase of insulin secretion was reduced significantly while the first phase was not influenced.Conclusions The 65-kda protein expressed in rat islets is most likely a mini-P-glycoprotein.It may play a key role regulating biphasic insulin release.

  9. Biodiversity of multiple Pregnancy-Associated Glycoprotein (PAG) family: gene cloning and chorionic protein purification in domestic and wild eutherians (Placentalia) - a review

    OpenAIRE

    Szafranska, Bozena; Panasiewicz, Grzegorz; Majewska, Marta

    2006-01-01

    International audience; This review presents a broad overview of chorionic glycoproteins encoded by the Pregnancy-Associated Glycoprotein (PAG) gene family and also serves to illustrate how the recent discovery of the PAG family has contributed to our general knowledge of genome evolution, placental transcription and placental protein expression. The complex and large PAG family is restricted to the Artiodactyla order, although single PAG-like genes have also been identified in species outsid...

  10. 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

  11. Inflammatory glycoproteins in cardiometabolic disorders, autoimmune diseases and cancer

    NARCIS (Netherlands)

    Connelly, Margery A.; Gruppen, Eke G.; Otvos, James D.; Dullaart, Robin P. F.

    2016-01-01

    The physiological function initially attributed to the oligosaccharide moieties or glycans on inflammatory glycoproteins was to improve protein stability. However, it is now clear that glycans play a prominent role in glycoprotein structure and function and in some cases contribute to disease

  12. Isolation and partial characterization of rat gastric mucous glycoprotein

    NARCIS (Netherlands)

    Spee-Brand, R.; Strous, G.J.A.M.; Kramer, M.F.

    1980-01-01

    Mucus glycoproteins from the rat stomach were characterized after their isolation from homogenates of the superficial gastric mucosa by equilibrium centrifugation in CsCl density gradients. Water-soluble as well as water-insoluble glycoproteins were studied. The latter were solubilized by 2-mercapto

  13. Congenital nasal piriform aperture stenosis with vestibular abnormality

    Energy Technology Data Exchange (ETDEWEB)

    Rajaram, Smitha; Raghavan, Ashok [Sheffield Children' s Hospital, Department of Paediatric Radiology, Sheffield (United Kingdom); Bateman, Neil [Sheffield Children' s Hospital, ENT Department, Sheffield (United Kingdom)

    2008-10-15

    We present a neonate with congenital nasal piriform aperture stenosis associated with an abnormal vestibular aperture. Radiological evaluation with CT is essential to confirm the diagnosis and delineate the anatomy for surgical planning. Extension of the scan field of view to include the petrous temporal bone is essential to identify associated abnormalities of the vestibule. (orig.)

  14. 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…

  15. Solubilization of glycoproteins of envelope viruses by detergents

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-11-20

    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-..beta..-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.

  16. Autoshaping of abnormal children.

    Science.gov (United States)

    Deckner, C W; Wilcox, L M; Maisto, S A; Blanton, R L

    1980-09-01

    Three experimentally naive abnormal children were exposed to a terminal operant contingency, i.e., reinforcement was delivered only if the children pressed a panel during intervals when it was lighted. Despite the absence of both successive approximation and manual shaping, it was found that each child began to respond discriminatively within a small number of trials. These data replicated previous animal studies concerned with the phenomena of autoshaping and signal-controlled responding. It was also found, however, that one type of autoshaping, the classical conditioning procedure, had a powerful suppressive effect on the discriminative responding. An experimental analysis that consisted procedure, had a powerful suppressive effect on discriminative responding. An experimental analysis that consisted of intrasubject reversal an multiple baseline designs established the internal validity of the findings. The finding of rapid acquisition of signal-controlled responding obtained with the initial procedure is suggessted to have practical significance. The disruptive effects of the classical form of autoshaping are discussed in terms of negative behavioral contrast.

  17. Communication and abnormal behaviour.

    Science.gov (United States)

    Crown, S

    1979-01-01

    In this paper the similarities between normal and abnormal behaviour are emphasized and selected aspects of communication, normal and aberrant, between persons are explored. Communication in a social system may be verbal or non-verbal: one person's actions cause a response in another person. This response may be cognitive, behavioural or physiological. Communication may be approached through the individual, the social situation or social interaction. Psychoanalysis approaches the individual in terms of the coded communications of psychoneurotic symptoms or psychotic behaviour; the humanist-existential approach is concerned more with emotional expression. Both approaches emphasize the development of individual identity. The interaction between persons and their social background is stressed. Relevant are sociological concepts such as illness behaviour, stigma, labelling, institutionalization and compliance. Two approaches to social interactions are considered: the gamesplaying metaphor, e.g. back pain as a psychosocial manipulation--the 'pain game'; and the 'spiral of reciprocal perspectives' which emphasizes the interactional complexities of social perceptions. Communicatory aspects of psychological treatments are noted: learning a particular metaphor such as 'resolution' of the problem (psychotherapy), learning more 'rewarding' behaviour (learning theory) or learning authenticity or self-actualization (humanist-existential).

  18. Abnormally dark or light skin

    Science.gov (United States)

    Hyperpigmentation; Hypopigmentation; Skin - abnormally light or dark ... Normal skin contains cells called melanocytes. These cells produce melanin , the substance that gives skin its color. Skin with ...

  19. 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...

  20. New monoclonal antibodies to the Ebola virus glycoprotein: Identification and analysis of the amino acid sequence of the variable domains.

    Science.gov (United States)

    Panina, A A; Aliev, T K; Shemchukova, O B; Dement'yeva, I G; Varlamov, N E; Pozdnyakova, L P; Bokov, M N; Dolgikh, D A; Sveshnikov, P G; Kirpichnikov, M P

    2016-03-01

    We determined the nucleotide and amino acid sequences of variable domains of three new monoclonal antibodies to the glycoprotein of Ebola virus capsid. The framework and hypervariable regions of immunoglobulin heavy and light chains were identified. The primary structures were confirmed using massspectrometry analysis. Immunoglobulin database search showed the uniqueness of the sequences obtained.

  1. 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

  2. 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

  3. Application of whole genome exon sequencing technology in identifying clone of hereditary fibrinogen abnormality family pathogenic gene%全基因组外显子测序技术在遗传性纤维蛋白原异常家系致病基因的克隆鉴定中的应用

    Institute of Scientific and Technical Information of China (English)

    刘晓娣; 张新友; 宋通微; 洪澄英

    2016-01-01

    目的:研究采用全基因组外显子测序技术在遗传性纤维蛋白原异常家系致病基因鉴定中的应用价值。方法采集12例遗传性纤维蛋白原异常患者及其核心家庭成员外周血检测凝血指标,并提取其基因组DNA进行全基因组外显子测序,分析测序结果,探讨遗传性纤维蛋白原异常的分子机制。结果全基因组外显子测序结果显示:先证者A1、A4以及B2均为FGA基因g.1233G>A突变,A1的妹妹、A4的父亲以及B2的母亲均携带有相同的突变;A2、A7、B4和B5均为FGG基因g.10819G>A突变,家系成员中A2的母亲和外婆、A7的姐姐和女儿、B4的母亲和B5的母亲均携带有相同的突变;A3、A5、A6、B1和B3及其相关亲属共10例携带有FGB基因g.9692A>G突变。先证者及家系主要成员中发生Fg基因突变的成员APTT、PT和TT均明显延长,但Fg活性显著降低。结论遗传性纤维蛋白原异常可由多种Fg基因外显子突变导致,FGB和FGG外显子突变较为常见。%Objective To research the applicative value of whole genome exon sequencing technology in identifying clone of hereditary fibrinogen abnormality family pathogenic gene. Methods Peripheral blood of 12 patients with hereditary fibrinogen abnormality and core family members was collected to detect coagulation index. And genomic DNA was received whole genome exon sequencing. Test results were analyzed to explore molecular mechanism of hereditary fibrinogen abnormality. Results Results of whole genome exon sequencing technology showed probandA1, A4, and B2 all had FGA gene g. 1233G>A mutation. A1’s sister, A4’s father, and B2’s mother carried the same mutation. A2, A7, B4 and B5 all had FGA gene, g.10819G>A mutation. A2’s mother and grandmother, A7’s sister and daughter, B4’s mother and B5’s mother carried the same mutation. A3, A5, A6, B1 and B3 and 10 people in their related family had FGA gene g.9692A>G mutation. In proband and

  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. Salivary agglutinin/glycoprotein-340/DMBT1

    DEFF Research Database (Denmark)

    Ligtenberg, Antoon J M; Veerman, Enno C I; Nieuw Amerongen, Arie V

    2007-01-01

    Salivary agglutinin (SAG), lung glycoprotein-340 (gp-340) and Deleted in Malignant Brain Tumours 1 (DMBT1) are three names for identical proteins encoded by the dmbt1 gene. DMBT1/SAG/gp-340 belongs to the scavenger receptor cysteine-rich (SRCR) superfamily of proteins, a superfamily of secreted...... or membrane-bound proteins with SRCR domains that are highly conserved down to sponges, the most ancient metazoa. On the one hand, DMBT1 may represent an innate defence factor acting as a pattern recognition molecule. It interacts with a broad range of pathogens, including cariogenic streptococci...... and Helicobacter pylori, influenza viruses and HIV, but also with mucosal defence proteins, such as IgA, surfactant proteins and MUC5B. Stimulation of alveolar macrophage migration, suppression of neutrophil oxidative burst and activation of the complement cascade point further to an important role...

  6. Immunological aspects of pregnancy-associated glycoproteins.

    Science.gov (United States)

    Dosogne, H; Massart-Leën, A M; Burvenich, C

    2000-01-01

    The incidence of severe cases of acute E. coli mastitis in dairy cows is highest during early lactation. This phenomenon has been associated with a decreased function and decreased numbers of circulating polymorphonuclear neutrophil leukocytes (PMN). The cause of this impaired function and decreased number is poorly understood. Stress, hormonal and metabolic alterations around parturition and the onset of lactation may play a role in this phenomenon. Several molecules, such as cortisol and beta-hydroxybutyrate have been found to alter the oxidative burst activity of circulating PMN around parturition. Pregnancy-Associated Glycoprotein (bPAG) could also be involved. The theory of immunosuppression by bPAG was investigated because analogous glycoproteins produced by the placenta of other species exert local immunosuppression in order to maintain the histoincompatible feto-maternal unit. The production and subsequent release into the maternal circulation of bPAG is ensured by the binucleate cells from the trophoblast and starts already at implantation. However, peak levels are only reached 1 week before parturition. Due to the long half-life time of this molecule, high levels are found in plasma until 2 weeks after calving. The co-occurrence of the impairment of PMN oxidative burst activity in the early postpartum period and a peak in plasma bPAG concentrations might support the hypothesis of an immunosuppressive effect of PAG. Moreover, an inhibitory effect of bPAG on the proliferation of bovine bone marrow progenitor cells has been found recently in our laboratory. bPAG occurs in colostrum, but its effect on milk cells has not been clarified. It is concluded that interaction between the physiology of reproduction and lactation on the one side and immune function on the other side in dairy cattle requires further research.

  7. Factors predictive of abnormal semen parameters in male partners ...

    African Journals Online (AJOL)

    of couples attending the infertility clinic of a tertiary hospital in south-western ... treatment targeted at the identified aetiological factors. .... that prognosis is inversely proportional to the number of abnormal .... Semen parameters and hormone.

  8. Abnormal pressure in hydrocarbon environments

    Science.gov (United States)

    Law, B.E.; Spencer, C.W.

    1998-01-01

    Abnormal pressures, pressures above or below hydrostatic pressures, occur on all continents in a wide range of geological conditions. According to a survey of published literature on abnormal pressures, compaction disequilibrium and hydrocarbon generation are the two most commonly cited causes of abnormally high pressure in petroleum provinces. In young (Tertiary) deltaic sequences, compaction disequilibrium is the dominant cause of abnormal pressure. In older (pre-Tertiary) lithified rocks, hydrocarbon generation, aquathermal expansion, and tectonics are most often cited as the causes of abnormal pressure. The association of abnormal pressures with hydrocarbon accumulations is statistically significant. Within abnormally pressured reservoirs, empirical evidence indicates that the bulk of economically recoverable oil and gas occurs in reservoirs with pressure gradients less than 0.75 psi/ft (17.4 kPa/m) and there is very little production potential from reservoirs that exceed 0.85 psi/ft (19.6 kPa/m). Abnormally pressured rocks are also commonly associated with unconventional gas accumulations where the pressuring phase is gas of either a thermal or microbial origin. In underpressured, thermally mature rocks, the affected reservoirs have most often experienced a significant cooling history and probably evolved from an originally overpressured system.

  9. Systemic abnormalities in liver disease

    Institute of Scientific and Technical Information of China (English)

    Masami Minemura; Kazuto Tajiri; Yukihiro Shimizu

    2009-01-01

    Systemic abnormalities often occur in patients with liver disease. In particular, cardiopulmonary or renal diseases accompanied by advanced liver disease can be serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to such abnormalities in the management of patients with liver diseases.

  10. Tick-borne encephalitis virus NS1 glycoprotein during acute and persistent infection of cells.

    Science.gov (United States)

    Bugrysheva, J V; Matveeva, V A; Dobrikova, E Y; Bykovskaya, N V; Korobova, S A; Bakhvalova, V N; Morozova, O V

    2001-08-01

    Tick-borne encephalitis virus (TBEV) was propagated in porcine embryo kidney (PS) cells until 48 h whereas human kidney (RH) cells maintained the virus persistence during at least 2 months. One of possible reasons of flavivirus chronic infection might be abnormal NS1 gene expression. Immunoblotting with monoclonal antibodies (MAbs) revealed the similarity of the intracellular and secreted NS1 nonstructural glycoprotein size and linear antigenic determinants in both the infected cell lines. However, according to the competitive binding of MAbs with the TBEV NS1 extracellular glycoprotein, its contiguous epitopes differed for acute or persistent infection. To map the TBEV NS1 glycoprotein antigenic determinants its recombinant analogues were used. All the studied MAbs could bind with the full-length NS1 recombinant protein. Deletion of the TBEV NS1 gene internal region resulted in defective NS1d1 protein without the region between 269 and 333 a.a. Lack of NS1d1 binding with 20B4 MAb and diminished binding with 22H8 and 17C3 MAbs permitted to map their antigenic determinants within or nearby deleted region, respectively. Interaction of other MAbs with the NS1 and NS1d1 recombinant proteins did not differ, suggesting that their epitopes were located in the region of N-terminal 268 a.a. or C-terminal 19 a.a. of the TBEV NS1 protein. The second NS1d2 truncated protein contained the first N-terminal 33 a.a. of the TBEV NS1 protein and was able to bind with 29G9 MAb. Taken together the data stand for the differences in the N-terminal structure of the TBEV NS1 multimers secreted from the acute and persistent infected cells whereas the intracellular and secreted monomer processing was the same. The modified NS1 protein oligomers in the RH cellular line might slow virus replication and could result in the TBEV persistence.

  11. Characterization of an equine herpesvirus type 1 gene encoding a glycoprotein (gp13) with homology to herpes simplex virus glycoprotein C.

    Science.gov (United States)

    Allen, G P; Coogle, L D

    1988-08-01

    The molecular structure of the equine herpesvirus type 1 (EHV-1) gene encoding glycoprotein 13 (gp13) was analyzed. The gene is contained within a 1.8-kilobase AccI-EcoRI restriction fragment mapping at map coordinates 0.136 to 0.148 in the UL region of the EHV-1 genome and is transcribed from right to left. Determination of the nucleotide sequence of the DNA fragment revealed a complete transcriptional unit composed of typical regulatory promoter elements upstream to a long open reading frame (1,404 base pairs) that encoded a 468-amino-acid primary translation product of 51 kilodaltons. The predicted protein has the characteristic features of a membrane-spanning protein: an N-terminal signal sequence, a hydrophobic membrane anchor region, a charged C-terminal cytoplasmic tail, and an exterior domain with nine potential N-glycosylation sites. The EHV-1 DNA sequences expressed in lambda gt11 as gp13 epitopes were present in the open reading frame. Amino acid sequences composing a major antigenic site, recognized by 35% of a panel of 42 anti-gp13 monoclonal antibodies, were identified in the N-terminal surface domain of the deduced gp13 molecule. Comparison of the EHV-1 gp13 DNA sequence with that encoding glycoproteins of other alphaherpesviruses revealed no detectable homology. However, a search for homology at the amino acid level showed regions of significant sequence similarity between the amino acids of the carboxy half of EHV-1 gp13 and those of the same region of gC-like glycoproteins of herpes simplex virus (gC-1 and gC-2), pseudorabies herpesvirus (gIII), and varicella-zoster virus (gp66). The sequences of the N-terminal portion of gp13, by contrast, were much less conserved. The results of these studies indicate that EHV-1 gp13 is the structural homolog of herpes simplex virus glycoprotein C and further suggest that the epitope-containing N-terminal amino acid sequences of the herpesvirus gC-like glycoproteins have undergone more extensive evolutionary

  12. [Glycoprotein hexoses in feces of infants with lactose intolerance].

    Science.gov (United States)

    Filippvskiĭ, G K; Klimov, L Ia

    1995-01-01

    A modified method for estimation of total glycoprotein hexoses in feces, based on their measurements in the blood serum, is presented. Sixty-six nursing children with lactose intolerance, breastfed or formula fed, were examined; formula fed babies were kept on mixtures with high and low lactose content. Glycoprotein hexose parameters were as follows (X +/- m): 13.51 +/- 1.93, 12.05 +/- 2.20, and 3.69 +/- 0.47 g/l feces. In control children without lactose intolerance (n = 33) this value was 3.6 +/- 0.79 g/l. Increased glycoprotein excretion is connected with glycocalix and small intestinal enterocyte alteration.

  13. Metabolic labeling of Caenorhabditis elegans primary embryonic cells with azido-sugars as a tool for glycoprotein discovery.

    Directory of Open Access Journals (Sweden)

    Amanda R Burnham-Marusich

    Full Text Available Glycobiology research with Caenorhabditis elegans (C. elegans has benefitted from the numerous genetic and cell biology tools available in this system. However, the lack of a cell line and the relative inaccessibility of C. elegans somatic cells in vivo have limited the biochemical approaches available in this model. Here we report that C. elegans primary embryonic cells in culture incorporate azido-sugar analogs of N-acetylgalactosamine (GalNAc and N-acetylglucosamine (GlcNAc, and that the labeled glycoproteins can be analyzed by mass spectrometry. By using this metabolic labeling approach, we have identified a set of novel C. elegans glycoprotein candidates, which include several mitochondrially-annotated proteins. This observation was unexpected given that mitochondrial glycoproteins have only rarely been reported, and it suggests that glycosylation of mitochondrially-annotated proteins might occur more frequently than previously thought. Using independent experimental strategies, we validated a subset of our glycoprotein candidates. These include a mitochondrial, atypical glycoprotein (ATP synthase α-subunit, a predicted glycoprotein (aspartyl protease, ASP-4, and a protein family with established glycosylation in other species (actin. Additionally, we observed a glycosylated isoform of ATP synthase α-subunit in bovine heart tissue and a primate cell line (COS-7. Overall, our finding that C. elegans primary embryonic cells are amenable to metabolic labeling demonstrates that biochemical studies in C. elegans are feasible, which opens the door to labeling C. elegans cells with other radioactive or azido-substrates and should enable the identification of additional post-translationally modified targets and analysis of the genes required for their modification using C. elegans mutant libraries.

  14. Elevation of glycoprotein nonmetastatic melanoma protein B in type 1 Gaucher disease patients and mouse models.

    Science.gov (United States)

    Kramer, Gertjan; Wegdam, Wouter; Donker-Koopman, Wilma; Ottenhoff, Roelof; Gaspar, Paulo; Verhoek, Marri; Nelson, Jessica; Gabriel, Tanit; Kallemeijn, Wouter; Boot, Rolf G; Laman, Jon D; Vissers, Johannes P C; Cox, Timothy; Pavlova, Elena; Moran, Mary Teresa; Aerts, Johannes M; van Eijk, Marco

    2016-09-01

    Gaucher disease is caused by inherited deficiency of lysosomal glucocerebrosidase. Proteome analysis of laser-dissected splenic Gaucher cells revealed increased amounts of glycoprotein nonmetastatic melanoma protein B (gpNMB). Plasma gpNMB was also elevated, correlating with chitotriosidase and CCL18, which are established markers for human Gaucher cells. In Gaucher mice, gpNMB is also produced by Gaucher cells. Correction of glucocerebrosidase deficiency in mice by gene transfer or pharmacological substrate reduction reverses gpNMB abnormalities. In conclusion, gpNMB acts as a marker for glucosylceramide-laden macrophages in man and mouse and gpNMB should be considered as candidate biomarker for Gaucher disease in treatment monitoring.

  15. Imaging findings of sternal abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Franquet, T. [Dept. of Radiology, Hospital de Sant Pau, Universidad Autonoma de Barcelona (Spain); Gimenez, A. [Dept. of Radiology, Hospital de Sant Pau, Universidad Autonoma de Barcelona (Spain); Alegret, X. [Dept. of Radiology, Hospital de Sant Pau, Universidad Autonoma de Barcelona (Spain); Sanchis, E. [Dept. of Radiology, Hospital de Sant Pau, Universidad Autonoma de Barcelona (Spain); Rivas, A. [Dept. of Radiology, Hospital Vall d`Hebron, Universidad Autonoma de Barcelona (Spain)

    1997-05-01

    Radiographic findings in the sternal abnormalities are often nonspecific, showing appearances from a localized benign lesion to an aggressive lesion as seen with infections and malignant neoplasms. A specific diagnosis of sternal abnormalities can be suggested on the basis of CT and MR characteristics. Familiarity with the presentation and variable appearance of sternal abnormalities may aid the radiologist is suggesting a specific diagnosis. We present among others characteristic radiographic findings of hemangioma, chondrosarcoma, hydatid disease, and SAPHO syndrome. In those cases in which findings are not specific, cross-sectional imaging modalities may help the clinician in their management. (orig.)

  16. Detection of glycoproteins in the Acanthamoeba plasma membrane

    Energy Technology Data Exchange (ETDEWEB)

    Paatero, G.I.L. (Abo Akademi (Finland)); Gahmberg, C.G. (Univ. of Helsinki (Finland))

    1988-11-01

    In the present study the authors have shown that glycoproteins are present in the plasma membrane of Acanthamoeba castellanii by utilizing different radioactive labeling techniques. Plasma membrane proteins in the amoeba were iodinated by {sup 125}I-lactoperoxidase labeling and the solubilized radiolabeled glycoproteins were separated by lectin-Sepharose affinity chromatography followed by polyacrylamide gel electrophoresis. The periodate/NaB{sup 3}H{sub 4} and galactose oxidase/NaB{sup 3}H{sub 4} labeling techniques were used for labeling of surface carbohydrates in the amoeba. Several surface-labeled glycoproteins were observed in addition to a diffusely labeled region with M{sub r} of 55,000-75,000 seen on electrophoresis, which could represent glycolipids. The presence of glycoproteins in the plasma membrane of Acanthamoeba castellanii was confirmed by metabolic labeling with ({sup 35}S)methionine followed by lectin-Sepharose affinity chromatography and polyacrylamide gel electrophoresis.

  17. 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.

  18. KDN-containing glycoprotein from loach skin mucus.

    Science.gov (United States)

    Nakagawa, H; Hama, Y; Sumi, T; Li, S C; Li, Y T

    2001-01-01

    It has been widely recognized that the mucus coat of fish plays a variety of important physical, chemical, and physiological functions. One of the major constituents of the mucus coat is mucus glycoprotein. We found that sialic acids in the skin mucus of the loach, Misgurnus anguillicaudatus, consisted predominantly of KDN. Subsequently, we isolated KDN-containing glycoprotein from loach skin mucus and characterized its chemical nature and structure. Loach mucus glycoprotein was purified from the Tris-HCl buffer extract of loach skin mucus by DEAE-cellulose chromatography, Nuclease P1 treatment, and Sepharose CL-6B gel filtration. The purified mucus glycoprotein was found to contain 38.5 KDN, 0.5% NeuAc, 25.0% GalNAc, 3.5% Gal, 0.5% GlcNAc and 28% amino acids. Exhaustive Actinase digestion of the glycoprotein yielded a glycopeptide with a higher sugar content and higher Thr and Ser contents. The molecular size of this glycopeptide was approximately 1/12 of the intact glycoprotein. These results suggest that approximately 11 highly glycosylated polypeptide units are linked in tandem through nonglycosylated peptides to form the glycoporotein molecule. The oligosaccharide alditols liberated from the loach mucus glycoprotein by alkaline borohydride treatment were separated by Sephadex G-25 gel filtration and HPLC. The purified sugar chains were analyzed b --> 6GalNAc-ol, KDNalpha2 --> 3(GalNAcbeta1 --> 14)GalNAc-ol, KDNalpha2 --> 6(GalNAcalpha1 --> 3)GalNAc-ol, KDNalpha2 --> 6(Gal3alpha1--> 3)GalNAc-ol, and NeuAcalpha2 --> 6Gal NAc-ol. It is estimated that one loach mucus glycoprotein molecule contains more than 500 KDN-containing sugar chains that are linked to Thr and Ser residues of the protein core through GalNAc.

  19. Retinal glycoprotein enrichment by concanavalin a enabled identification of novel membrane autoantigen synaptotagmin-1 in equine recurrent uveitis.

    Science.gov (United States)

    Swadzba, Margarete E; Hauck, Stefanie M; Naim, Hassan Y; Amann, Barbara; Deeg, Cornelia A

    2012-01-01

    Complete knowledge of autoantigen spectra is crucial for understanding pathomechanisms of autoimmune diseases like equine recurrent uveitis (ERU), a spontaneous model for human autoimmune uveitis. While several ERU autoantigens were identified previously, no membrane protein was found so far. As there is a great overlap between glycoproteins and membrane proteins, the aim of this study was to test whether pre-enrichment of retinal glycoproteins by ConA affinity is an effective tool to detect autoantigen candidates among membrane proteins. In 1D Western blots, the glycoprotein preparation allowed detection of IgG reactions to low abundant proteins in sera of ERU patients. Synaptotagmin-1, a Ca2+-sensing protein in synaptic vesicles, was identified as autoantigen candidate from the pre-enriched glycoprotein fraction by mass spectrometry and was validated as a highly prevalent autoantigen by enzyme-linked immunosorbent assay. Analysis of Syt1 expression in retinas of ERU cases showed a downregulation in the majority of ERU affected retinas to 24%. Results pointed to a dysregulation of retinal neurotransmitter release in ERU. Identification of synaptotagmin-1, the first cell membrane associated autoantigen in this spontaneous autoimmune disease, demonstrated that examination of tissue fractions can lead to the discovery of previously undetected novel autoantigens. Further experiments will address its role in ERU pathology.

  20. P‑glycoprotein inhibition increases the transport of dauricine across the blood‑brain barrier.

    Science.gov (United States)

    Dong, Pei-Liang; Han, Hua; Zhang, Tian-Yu; Yang, Bingyou; Wang, Qiu-Hong; Eerdun, Gao-Wa

    2014-03-01

    Dauricine is the major bioactive component isolated from the roots of Menispermum dauricum D.C. The aim of the present study was to investigate the role of P‑glycoprotein in the transport of dauricine across the blood‑brain barrier by pre‑treatment with the P‑glycoprotein inhibitor verapamil. Sprague Dawley rats were divided into a verapamil group (pretreated with verapamil at a dose of 20 mg/kg) and a control group (pretreated with the same volume of normal saline). After 90 min, the animals were injected intravenously with dauricine (10 mg/kg). At 15, 30 and 60 min after dauricine administration, the levels of dauricine in the blood and brain were detected by high‑performance liquid chromatography. Compared with the control group, the dauricine concentration in the brains of the rats in the verapamil group was significantly increased. Furthermore, the brain‑plasma ratio of dauricine in the rats pretreated with verapamil was significantly higher than that of the animals in the control group. However, there was no difference identified between dauricine levels in the plasma of the verapamil and the control groups. The results indicated that dauricine is able to pass the blood‑brain barrier, and that P‑glycoprotein has an important role in the transportation of dauricine across the blood‑brain barrier.

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

    Science.gov (United States)

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

    2015-01-01

    Objective 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. Methods 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. Results 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. Conclusion A quantitative glycoproteomic method was established and proven useful to determine potential novel biomarkers for HCC. PMID:26487969

  2. Pregnancy Complications: Umbilical Cord Abnormalities

    Science.gov (United States)

    ... defects. These tests may include a detailed ultrasound, amniocentesis (to check for chromosomal abnormalities) and in some ... the provider may recommend additional tests, such as amniocentesis and a detailed ultrasound, to diagnose or rule ...

  3. 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

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

    Science.gov (United States)

    Dash, Raju; Das, Rasel; Junaid, Md; Akash, Md Forhad Chowdhury; Islam, Ashekul; Hosen, SM Zahid

    2017-01-01

    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. PMID:28356762

  5. 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.

  6. P-glycoprotein targeted nanoscale drug carriers

    KAUST Repository

    Li, Wengang

    2013-02-01

    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 carrying processes that shuttle the drugs out of tumor cells. Thus, P -gp inhibitors have attracted a lot of attention as they can stop cancer drugs from being pumped out of target cells with the consumption of ATP. Using quantitive structure activity relationship (QSAR), we have successfully synthesized a series of novel P -gp inhibitors. The obtained dihydropyrroloquinoxalines series were fully characterized and then tested against bacterial and tumor assays with over-expressed P -gps. All compounds were bioactive especially compound 1c that had enhanced antibacterial activity. Furthermore, these compounds were utilized as targeting vectors to direct drug delivery vehicles such as silica nanoparticles (SNPs) to cancerous Hela cells with over expressed P -gps. Cell uptake studies showed a successful accumulation of these decorated SNPs in tumor cells compared to undecorated SNPs. The results obtained show that dihydropyrroloquinoxalines constitute a promising drug candidate for targeting cancers with MDR. Copyright © 2013 American Scientific Publishers All rights reserved.

  7. Abnormal lung development in congenital diaphragmatic hernia.

    Science.gov (United States)

    Ameis, Dustin; Khoshgoo, Naghmeh; Keijzer, Richard

    2017-06-01

    The outcomes of patients diagnosed with congenital diaphragmatic hernia (CDH) have recently improved. However, mortality and morbidity remain high, and this is primarily caused by the abnormal lung development resulting in pulmonary hypoplasia and persistent pulmonary hypertension. The pathogenesis of CDH is poorly understood, despite the identification of certain candidate genes disrupting normal diaphragm and lung morphogenesis in animal models of CDH. Defects within the lung mesenchyme and interstitium contribute to disturbed distal lung development. Frequently, a disturbance in the development of the pleuroperitoneal folds (PPFs) leads to the incomplete formation of the diaphragm and subsequent herniation. Most candidate genes identified in animal models have so far revealed relatively few strong associations in human CDH cases. CDH is likely a highly polygenic disease, and future studies will need to reconcile how disturbances in the expression of multiple genes cause the disease. Herein, we summarize the available literature on abnormal lung development associated with CDH. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Women's initial experience of abnormal papanicolaou smear.

    Science.gov (United States)

    Mitchell, Susan; Hall, Vincent P

    2009-06-01

    To discover the early subjective experience of women affected by abnormal Papanicolaou smear, a qualitative study was undertaken with 8 North Carolina women, 4 to 12 months postnotification of their first abnormal result. Data were analyzed via grounded theory methodology to identify a core theory that could guide interventions to improve follow-up for cancer prevention. This theoretical process is described as a labyrinth journey-an imperative healing process undertaken by all participants, who undertook the following tasks: evaluating peril, seeking refuge, obtaining information, and reframing their self-image. Women who also learned they were infected with the human papillomavirus faced a prolonged sense of threat to their sense of sexual well-being. Their additional tasks related to reevaluating their sexual self-image, and they continued to work on these reframing tasks throughout their 1st year's journey. Progress through the labyrinth depended upon emotional or spiritual support, nonjudgmental acceptance and access to accurate information.

  9. Mitochondrial abnormalities in the myofibrillar myopathies.

    Science.gov (United States)

    Jackson, S; Schaefer, J; Meinhardt, M; Reichmann, H

    2015-11-01

    Myofibrillar myopathies are a genetically diverse group of skeletal muscle disorders, with distinctive muscle histopathology. Causative mutations have been identified in the genes MYOT, LDB3, DES, CRYAB, FLNC, BAG3, DNAJB6, FHL1, PLEC and TTN, which encode proteins which either reside in the Z-disc or associate with the Z-disc. Mitochondrial abnormalities have been described in muscle from patients with a myofibrillar myopathy. We reviewed the literature to determine the extent of mitochondrial dysfunction in each of the myofibrillar myopathy subtypes. Abnormal mitochondrial distribution is a frequent finding in each of the subtypes, but a high frequency of COX-negative or ragged red fibres, a characteristic finding in some of the conventional mitochondrial myopathies, is a rare finding. Few in vitro studies of mitochondrial function have been performed in affected patients.

  10. 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.

  11. Molecular insight into conformational transmission of human P-glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Shan-Yan [Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Liu, Fu-Feng, E-mail: fufengliu@tju.edu.cn, E-mail: ysun@tju.edu.cn; Dong, Xiao-Yan; Sun, Yan, E-mail: fufengliu@tju.edu.cn, E-mail: ysun@tju.edu.cn [Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072 (China)

    2013-12-14

    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.

  12. Molecular insight into conformational transmission of human P-glycoprotein

    Science.gov (United States)

    Chang, Shan-Yan; Liu, Fu-Feng; Dong, Xiao-Yan; Sun, Yan

    2013-12-01

    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.

  13. The development of an integrated platform to identify breast cancer glycoproteome changes in human serum.

    Science.gov (United States)

    Zeng, Zhi; Hincapie, Marina; Haab, Brian B; Hanash, Samir; Pitteri, Sharon J; Kluck, Steven; Hogan, Jason M; Kennedy, Jacob; Hancock, William S

    2010-05-07

    Protein glycosylation represents one of the major post-translational modifications and can have significant effects on protein function. Moreover, changes in the carbohydrate structure are increasingly being recognized as an important modification associated with cancer etiology. In this report, we describe the development of a proteomics approach to identify breast cancer related changes in either concentration and/or the carbohydrate structures of glycoprotein(s) present in blood samples. Diseased and healthy serum samples were processed by an optimized sample preparation protocol using multiple lectin affinity chromatography (M-LAC) that partitions serum proteins based on glycan characteristics. Subsequently, three separate procedures, 1D SDS-PAGE, isoelectric focusing and an antibody microarray, were applied to identify potential candidate markers for future study. The combination of these three platforms is illustrated in this report with the analysis of control and cancer glycoproteomic fractions. Firstly, a molecular weight based separation of glycoproteins by 1D SDS-PAGE was performed, followed by protein, glycoprotein staining, lectin blotting and LC-MS analysis. To refine or confirm the list of interesting glycoproteins, isoelectric focusing (targeting sialic acid changes) and an antibody microarray (used to detect neutral glycan shifts) were selected as the orthogonal methods. As a result, several glycoproteins including alpha-1B-glycoprotein, complement C3, alpha-1-antitrypsin and transferrin were identified as potential candidates for further study.

  14. Fetal akinesia and associated abnormalities on prenatal MRI.

    Science.gov (United States)

    Nemec, Stefan F; Höftberger, Romana; Nemec, Ursula; Bettelheim, Dieter; Brugger, Peter C; Kasprian, Gregor; Amann, Gabriele; Rotmensch, Siegfried; Graham, John M; Rimoin, David L; Prayer, Daniela

    2011-05-01

    In view of the increasing role of magnetic resonance imaging (MRI) as an adjunct to prenatal ultrasonography (US), this study sought to demonstrate the visualization of fetal akinesia and associated abnormalities on MRI. This retrospective study included six fetuses with akinesia and associated abnormalities, depicted on fetal MRI after suspicious prenatal US. The whole fetus was assessed for musculoskeletal abnormalities and associated pathological conditions elsewhere. Fetal outcome data were compared with prenatal imaging. US and MRI findings were also compared. Akinesia resulting in arthrogryposis was seen in 6/6 fetuses, with abnormal musculature in 5/6 fetuses. Associated brain abnormalities were found in 2/6 fetuses; facial abnormalities in 3/6; lung hypoplasia in 3/6; and polyhydramnios in 2/6. There were 5/6 pregnancies that were terminated and one individual died neonatally. MRI and brain autopsy were concordant in 4/6 cases. MRI and body autopsy were concordant in 1/6 cases and in 5/6 cases, autopsy revealed additional abnormalities. In addition to US, MRI correctly identified central nervous system findings in four cases and lung hypoplasia in three cases. Our MRI results demonstrate fetal akinesia and associated abnormalities, which may have an impact on perinatal management, as an adjunct to prenatal US. Copyright © 2011 John Wiley & Sons, Ltd.

  15. Identification of Potential Glycoprotein Biomarkers in Estrogen Receptor Positive (ER+ and Negative (ER- Human Breast Cancer Tissues by LC-LTQ/FT-ICR Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Suzan M. Semaan, Xu Wang, Alan G. Marshall, Qing-Xiang Amy Sang

    2012-01-01

    Full Text Available Breast cancer is the second most fatal cancer in American women. To increase the life expectancy of patients with breast cancer new diagnostic and prognostic biomarkers and drug targets must be identified. A change in the glycosylation on a glycoprotein often causes a change in the function of that glycoprotein; such a phenomenon is correlated with cancerous transformation. Thus, glycoproteins in human breast cancer estrogen receptor positive (ER+ tissues and those in the more advanced stage of breast cancer, estrogen receptor negative (ER- tissues, were compared. Glycoproteins showing differences in glycosylation were examined by 2-dimensional gel electrophoresis with double staining (glyco- and total protein staining and identified by reversed-phase nano-liquid chromatography coupled with a hybrid linear quadrupole ion trap/ Fourier transform ion cyclotron resonance mass spectrometer. Among the identified glycosylated proteins are alpha 1 acid glycoprotein, alpha-1-antitrypsin, calmodulin, and superoxide dismutase mitochondrial precursor that were further verified by Western blotting for both ER+ and ER- human breast tissues. Results show the presence of a possible glycosylation difference in alpha-1-antitrypsin, a potential tumor-derived biomarker for breast cancer progression, which was expressed highest in the ER- samples.

  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. [Diagnosticum of abnormalities of plant meiotic division].

    Science.gov (United States)

    Shamina, N V

    2006-01-01

    Abnormalities of plant meiotic division leading to abnormal meiotic products are summarized schematically in the paper. Causes of formation of monads, abnormal diads, triads, pentads, polyads, etc. have been observed in meiosis with both successive and simultaneous cytokinesis.

  18. Thyroid abnormality in perimenopausal women with abnormal uterine bleeding

    Directory of Open Access Journals (Sweden)

    Prasanna Byna

    2015-11-01

    Full Text Available Background: AUB is a common but complicated clinical presentation and occurs in 15-20% of women between menarche to menopause and significantly affects the women's health. Women with thyroid dysfunction often have menstrual irregularities, infertility and increased morbidity during pregnancy. The objective of present study is to find the correlation between thyroid disorders and AUB in perimenopausal women attending gynecology OPD. Methods: In the present study, fifty five patients with AUB were included and were evaluated for the cause including thyroid abnormality. Thyroid function tests were done in all patients. Results: Among 55 patients, 12 patients were diagnosed as hypothyroidism and 7 as hyperthyroidism, women with AUB 36 (65.4% were euthyroid. Among 19 women with thyroid abnormality, heavy menstrual bleeding was seen in 8 (42% women, 6 (31.57% had polymenorrhagia, 5 (26.31% had oligomenorrhoea. The frequent menstrual abnormality in women with hypothyroidism (12 women was heavy menstrual bleeding in 5 (41.6% women, 3 (25% had oligomennorhoea, 4 (33.3% had polymenorrhagia. Out of 7 women with hyperthyroidism, 2 (28.57% had oligomenorrhoea, 3 (42.8% had heavy menstrual bleeding, 2 (28.57% had polymenorrhagia. In a total of 55 patients with AUB, 11 (20% had structural abnormalities in uterus and ovaries. 5 (9% had adenomyosis, 3 (5.4% had ovarian cysts, 3 (5.4% had fibroids. Conclusions: It is important to screen all women for thyroid abnormality who are presenting with AUB especially with non-structural causes of AUB. Correction of thyroid abnormalities also relieves AUB. This will avoid unnecessary hormonal treatment and surgery. [Int J Res Med Sci 2015; 3(11.000: 3250-3253

  19. Role of zona pellucida glycoproteins during fertilization in humans.

    Science.gov (United States)

    Gupta, Satish Kumar

    2015-04-01

    In the last decade, scientific investigations pertaining to the role of zona pellucida (ZP) glycoproteins during fertilization in humans have led to new insights. This has been achieved using purified native/recombinant human zona proteins and transgenic mice expressing human ZP glycoproteins. The proposed model in mice of ZP glycoprotein-3 (ZP3) acting as primary sperm receptor and ZP glycoprotein-2 (ZP2) as secondary sperm receptor has been modified for sperm-egg binding in humans. ZP glycoprotein-1 (ZP1), ZP3, and ZP glycoprotein-4 (ZP4) have been shown to bind to the capacitated human sperm. ZP2 binds to the acrosome-reacted human spermatozoa. Further, the eggs obtained from transgenic mice expressing human ZP2 alone or in conjunction with other human instead of mouse zona proteins showed binding of human sperm, suggesting that ZP2 might also play a role in sperm-egg binding. This function has been mapped to a domain corresponding to amino acid residues 51-144 of ZP2. In contrast to mice, where ZP3 is the primary agonist for inducing the acrosome reaction, in humans, the acrosome reaction can be mediated by ZP1, ZP3, and ZP4. The effect of mutations in the genes encoding zona proteins on the ZP morphology and infertility has not been established. Further, the role of autoantibodies against ZP in women with 'unexplained infertility' leading to poor outcome of in vitro fertilization is currently controversial and needs further investigations. Understanding the role of ZP glycoproteins during human fertilization facilitates the development of new contraceptives and strategies to overcome the problem of infertility.

  20. Acrosome reaction: relevance of zona pellucida glycoproteins

    Institute of Scientific and Technical Information of China (English)

    Satish K Gupta; Beena Bhandari

    2011-01-01

    During mammalian fertilisation,the zona pellucida(ZP)matrix surrounding the oocyte is responsible for the binding of the spermatozoa to the oocyte and induction of the acrosome reaction(AR)in the ZP-bound spermatozoon.The AR is crucial for the penetration of the ZP matrix by spermatozoa.The ZP matrix in mice is composed of three glycoproteins designated ZP1,ZP2 and ZP3,whereas in humans,it is composed of four(ZP1,ZP2,ZP3 and ZP4).ZP3 acts as the putative primary sperm receptor and is responsible for AR induction in mice,whereas in humans(in addition to ZP3),ZP1 and ZP4 also induce the AR.The ability of ZP3 to induce the AR resides in its C-terminal fragment.O-linked glycans are critical for the murine ZP3-mediated AR.However,N-linked glycans of human ZP1,ZP3 and ZP4 have important roles in the induction of the AR.Studies with pharmacological inhibitors showed that the ZP3-induced AR involves the activation of the G1-coupled receptor pathway,whereas ZP1-and ZP4-mediated ARs are independent of this pathway.The ZP3-induced AR involves the activation of T-type voltage-operated calcium channels(VOCCs),whereas ZP1-and ZP4-induced ARs involve both T-and L-type VOCCs.To conclude,in mice,ZP3 is primarily responsible for the binding of capacitated spermatozoa to the ZP matrix and induction of the AR,whereas in humans(in addition to ZP3),ZP1 and ZP4 also participate in these stages of fertilisation.

  1. Kidney transplantation in abnormal bladder

    Directory of Open Access Journals (Sweden)

    Shashi K Mishra

    2007-01-01

    Full Text Available Structural urologic abnormalities resulting in dysfunctional lower urinary tract leading to end stage renal disease may constitute 15% patients in the adult population and up to 20-30% in the pediatric population. A patient with an abnormal bladder, who is approaching end stage renal disease, needs careful evaluation of the lower urinary tract to plan the most satisfactory technical approach to the transplant procedure. Past experience of different authors can give an insight into the management and outcome of these patients. This review revisits the current literature available on transplantation in abnormal bladder and summarizes the clinical approach towards handling this group of difficult transplant patients. We add on our experience as we discuss the various issues. The outcome of renal transplant in abnormal bladder is not adversely affected when done in a reconstructed bladder. Correct preoperative evaluation, certain technical modification during transplant and postoperative care is mandatory to avoid complications. Knowledge of the abnormal bladder should allow successful transplantation with good outcome.

  2. Identification of the S-layer glycoproteins and their covalently linked glycans in the halophilic archaeon Haloarcula hispanica.

    Science.gov (United States)

    Lu, Hua; Lü, Yang; Ren, Jinwei; Wang, Zhongfu; Wang, Qian; Luo, Yuanming; Han, Jing; Xiang, Hua; Du, Yuguo; Jin, Cheng

    2015-11-01

    Haloarcula hispanica is one of members of the Halobacteriaceae, which displays particularly low restriction activity and is therefore important as one of the most tractable haloarchaea for archaeal genetic research. Although the Har. hispanica S-layer protein has been reported glycosylated, the S-layer glycoprotein and its glycosylation have not been investigated yet. In this study, the S-layer proteins of Har. hispanica were extracted and characterized. The S-layer was found containing two different glycoproteins which shared highly similar amino acid sequences. The genes coding for these two S-layer glycoproteins were found next to each other in the genome. Moreover, the N- and O-linked glycans were released from these two S-layer glycoproteins for structural determination. Based on the mass spectrometry and nuclear magnetic resonance, the N-glycan was determined as a branched trisaccharide containing a 225 Da residue corresponded to a 2-amino-6-sulfo-2, 6-dideoxy-quinovose, which was the first time that a naturally occurring form of sulfoquinovosamine was identified. Besides, the O-glycan was characterized as a Glcα-1,4-Gal disaccharide by mass spectrometry combined with monosaccharide composition analysis and glycosidase treatment. The determination of the N- and O-glycan structure will be helpful for studying the diverse protein glycosylation pathways in archaea utilizing H. hispanica as a new model.

  3. Laurus nobilis L. Seed Extract Reveals Collateral Sensitivity in Multidrug-Resistant P-Glycoprotein-Expressing Tumor Cells.

    Science.gov (United States)

    Saab, Antoine M; Guerrini, Alessandra; Zeino, Maen; Wiench, Benjamin; Rossi, Damiano; Gambari, Roberto; Sacchetti, Gianni; Greten, Henry Johannes; Efferth, Thomas

    2015-01-01

    The frequent failure of standard cancer chemotherapy requires the development of novel drugs capable of killing otherwise drug-resistant tumors. Here, we have investigated a chloroform extract of Laurus nobilis seeds. Fatty acids and 23 constituents of the volatile fraction were identified by gas chromotography/flame ionization detection (GC/FID) and gas chromatography/mass spectrometry (GC/MS), in good agreement with (1)H NMR (nuclear magnetic resonance) spectrum. Multidrug-resistant P-glycoprotein-expressing CEM/ADR5000 leukemia cells were hypersensitive (collaterally sensitive) toward this extract compared to drug-sensitive CCRF-CEM cells, whereas CEM/ADR5000 cells were 2586-fold resistant to doxorubicin as control drug. Collateral sensitivity was verified by measurement of apoptotic cells by flow cytometry. The log10IC50 values of 3 compounds in the extract (limonene, eucalyptol, oleic acid) did not correlate with mRNA expression of the P-glycoprotein-coding ABCB1/MDR1 gene and accumulation of the P-glycoprotein substrate rhodamine in the NCI panel of tumor cell lines. A microarray-based profile of 20 genes predicted resistance to doxorubicin and 7 other anticancer drugs involved in the multidrug resistance phenotype but not to limonene, eucalyptol and oleic acid. In conclusion, our results show that Laurus nobilis seed extract is suitable to kill multidrug-resistant P-glycoprotein expressing tumor cells.

  4. Dissection of Genetic Mechanism of Abnormal Heading in Hybrid Rice

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hong-jun; QU Li-jun; XIANG Chao; WANG Hui; XIA Jia-fa; LI Ze-fu; GAO Yong-ming; SHI Ying-yao

    2014-01-01

    Abnormal heading in hybrid rice production has caused great economic loss in recent years, but the genetic basis of this phenomenon remains elusive. In this study, we developed four testcross populations using 38 introgression lines (ILs) from Shuhui 527 (SH527)/Fuhui 838 (FH838)//SH527 population as male parents and four male sterile lines (MSLs; namely II-32A, Xieqingzao A, Gang 46A and Jin 23A) as female parents. Progeny testing allowed us to identify 55 abnormal heading combinations in Hefei, but had late heading date in Hangzhou and Guangzhou of China. By one-and two-way analysis of variance, a total of 21 QTLs and 31 pairs of epistatic QTLs associated with photosensitivity were identified in the four populations, respectively. Genotypic analysis showed that the IL parent of most abnormal heading combinations showed some introgressions at markers RM331 and RM3395 on chromosome 8 (strongly associated with the known genes OsHAP3H/DTH8/Ghd8/LHD1) of donor FH838 alleles, and these two markers were also identified as affecting photosensitivity. The observation that the recipient parent (SH527), donor parent (FH838), their testcross combinations with four MSLs, and the IL parents of abnormal heading combinations had normal heading date in Hefei suggested that OsHAP3H/DTH8/Ghd8/LHD1 showed no independent regulation on abnormal heading in the abnormal heading combinations. It is noteworthy that complex epistasis among RM331 or RM3395 with other loci, including dominant × additive, additive × dominant, and dominant × dominant epistases, were identified only in the four testcross populations of the current study, but not in the SH527/FH838//SH527 population, suggesting the cause of abnormal heading in abnormal heading combinations in Hefei and delayed heading in Hangzhou and Guangzhou.

  5. Abnormal insulin levels and vertigo.

    Science.gov (United States)

    Proctor, C A

    1981-10-01

    Fifty patients with unexplained vertigo (36) or lightheadedness (14) are evaluated, all of whom had abnormal ENGs and normal audiograms. Five hour insulin glucose tolerance tests were performance on all patients, with insulin levels being obtained fasting and at one-half, one, two, and three hours. The results of this investigation were remarkable. Borderline or abnormal insulin levels were discovered in 82% of patients; 90% were found to have either an abnormal glucose tolerance test or at least borderline insulin levels. The response to treatment in these dizzy patients was also startling, with appropriate low carbohydrate diets improving the patient's symptoms in 90% of cases. It is, therefore, apparent that the earliest identification of carbohydrate imbalance with an insulin glucose tolerance test is extremely important in the work-up of the dizzy patients.

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

    Science.gov (United States)

    de Medeiros, Sebastião Freitas; Yamamoto, Márcia Marly Winck; Barbosa, Jacklyne Silva

    2013-01-01

    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. PMID:24665210

  7. Expression and Characterization of HIV-1 Envelope Glycoprotein in Pichia Pastoris

    Institute of Scientific and Technical Information of China (English)

    ZHAO Li-hui; YU Xiang-hui; JIANG Chun-lai; WU Yong-ge; SHEN Jia-cong; KONG Wei

    2008-01-01

    To obtain a sufficient amount of glycoprotein for further studying the structure and function of HIV-1 envelope glycoprotein, amplified and modified HIV-1 envelope glycoprotein gene which recombined subtypes(850amino acids) from Guangxi in China was inserted into Pichiapastoris expression vector pPICZaB; then the recombinant plasmid was transported into the yeast cells to induce the expression of Env protein with methanol. The results of SDS-PAGE and Western blot indicate that the envelope glycoprotein could be expressed in Pichia pastoris with productions of a 120000 glycoprotein and a 41000 glycoprotein, which showed satisfactory immunogenicity by indirect ELISA.

  8. Proteolysis of specific porcine zona pellucida glycoproteins by boar acrosin.

    Science.gov (United States)

    Dunbar, B S; Dudkiewicz, A B; Bundman, D S

    1985-04-01

    The morphologic and biochemical effects on the structure and constituent glycoproteins of the zona pellucida (ZP) by a specific sperm enzyme, acrosin, and a nonsperm enzyme, trypsin, have been evaluated. Intact porcine ZP matricies, exposed to either acrosin or trypsin, were analyzed microscopically. Changes in specific glycoproteins were monitored by high-resolution two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and the silver-based color stain, GELCODE. Although these enzymes did not alter the macroscopic properties of the ZP matrix, the 2D-PAGE ZP protein patterns were markedly altered. The high molecular weight glycoprotein families (II and III) were sensitive to proteolytic digestion, whereas the major glycoprotein family (I) of the porcine zona was only partially proteolyzed by acrosin and trypsin. Furthermore, it was demonstrated that acrosin had unique substrate specificity compared to that of trypsin, since the ZP peptide patterns were found to be different. These studies are the first to demonstrate which integral glycoproteins of the native porcine ZP matrix are specifically proteolyzed by acrosin from the homologous species and that this proteolysis occurs without the dissolution of the native porcine matrix.

  9. Glycoprotein labeling with click chemistry (GLCC) and carbohydrate detection.

    Science.gov (United States)

    Wu, Zhengliang L; Huang, Xinyi; Burton, Andrew J; Swift, Karl A D

    2015-08-14

    Molecular labeling and detection techniques are essential to research in life science. Here, a method for glycoprotein labeling/carbohydrate detection through glycan replacement, termed glycoprotein labeling with click chemistry (GLCC), is described. In this method, a glycoprotein is first treated with specific glycosidases to remove certain sugar residues, a procedure that creates acceptor sites for a specific glycosyltransferase. A 'clickable' monosaccharide is then installed onto these sites by the glycosyltransferase. This modified glycoprotein is then conjugated to a reporter molecule using a click chemistry reaction. For glycoproteins that already contain vacant glycosylation sites, deglycosylation is not needed before the labeling step. As a demonstration, labeling on fetal bovine fetuin, mouse immunoglobulin IgG and bacterial expressed human TNFα and TNFβ are shown. Compared to traditional ways of protein labeling, labeling at glycosylation sites with GLCC is considerably more specific and less likely to have adverse effects, and, when utilized as a method for carbohydrate detection, this method is also highly specific and sensitive.

  10. 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.

  11. Pregnancy-specific beta-1-glycoprotein (SP1) in cultured amniotic fluid cells.

    Science.gov (United States)

    Heikinheimo, M; Wahlström, T; Aula, P; Virtanen, I; Seppälä, M

    1980-12-01

    The synthesis of pregnancy-specific beta-1-glycoprotein (SP1) was studied in amniotic fluid cell cultures using RIA, immunoperoxidase, and immunofluorescence techniques. SP1 was found by RIA in all 11 sonicates and in 21 of 26 culture media. The SP1-immunoreactive material was immunologically similar to maternal serum SP1. Immunoperoxidase and indirect immunofluorescence staining were positive in large cells identified as epithelial amniotic cells by labeling with antikeratin antibodies. Fibroblast-like cells were occasionally found in cultures, but they did not contain demonstrable amounts of SP1. The physiological significance of the findings presented remains unclear.

  12. HIV envelope glycoprotein imaged at high resolution | Center for Cancer Research

    Science.gov (United States)

    The outer surface of the human immunodeficiency virus (HIV) is surrounded by an envelope studded with spike-shaped glycoproteins called Env that help the deadly virus identify, bind, and infect cells. When unbound, Env exists in a “closed” conformational state. Upon binding with target cells, such as CD4+ T cells, the protein transitions to an “open” configuration. Given that Env is the only viral protein expressed on HIV’s surface, knowing its detailed structure—especially in the unbound state—may be critical for designing antibodies and vaccines against HIV.

  13. 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...

  14. The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth

    Science.gov (United States)

    Rhee, David K.; Marcelino, Jose; Baker, MacArthur; Gong, Yaoqin; Smits, Patrick; Lefebvre, Véronique; Jay, Gregory D.; Stewart, Matthew; Wang, Hongwei; Warman, Matthew L.; Carpten, John D.

    2005-01-01

    The long-term integrity of an articulating joint is dependent upon the nourishment of its cartilage component and the protection of the cartilage surface from friction-induced wear. Loss-of-function mutations in lubricin (a secreted glycoprotein encoded by the gene PRG4) cause the human autosomal recessive disorder camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP). A major feature of CACP is precocious joint failure. In order to delineate the mechanism by which lubricin protects joints, we studied the expression of Prg4 mRNA during mouse joint development, and we created lubricin-mutant mice. Prg4 began to be expressed in surface chondrocytes and synoviocytes after joint cavitation had occurred and remained strongly expressed by these cells postnatally. Mice lacking lubricin were viable and fertile. In the newborn period, their joints appeared normal. As the mice aged, we observed abnormal protein deposits on the cartilage surface and disappearance of underlying superficial zone chondrocytes. In addition to cartilage surface changes and subsequent cartilage deterioration, intimal cells in the synovium surrounding the joint space became hyperplastic, which further contributed to joint failure. Purified or recombinant lubricin inhibited the growth of these synoviocytes in vitro. Tendon and tendon sheath involvement was present in the ankle joints, where morphologic changes and abnormal calcification of these structures were observed. We conclude that lubricin has multiple functions in articulating joints and tendons that include the protection of surfaces and the control of synovial cell growth. PMID:15719068

  15. Retroviral Env Glycoprotein Trafficking and Incorporation into Virions

    Directory of Open Access Journals (Sweden)

    Tsutomu Murakami

    2012-01-01

    Full Text Available Together with the Gag protein, the Env glycoprotein is a major retroviral structural protein and is essential for forming infectious virus particles. Env is synthesized, processed, and transported to certain microdomains at the plasma membrane and takes advantage of the same host machinery for its trafficking as that used by cellular glycoproteins. Incorporation of Env into progeny virions is probably mediated by the interaction between Env and Gag, in some cases with the additional involvement of certain host factors. Although several general models have been proposed to explain the incorporation of retroviral Env glycoproteins into virions, the actual mechanism for this process is still unclear, partly because structural data on the Env protein cytoplasmic tail is lacking. This paper presents the current understanding of the synthesis, trafficking, and virion incorporation of retroviral Env proteins.

  16. Processing of virus-specific glycoproteins of varicella zoster virus

    Energy Technology Data Exchange (ETDEWEB)

    Namazue, J.; Campo-Vera, H.; Kitamura, K.; Okuno, T.; Yamanishi, K.

    1985-05-01

    Monoclonal antibodies to varicella zoster virus (VZV) glycoproteins were used to study the processing of three glycoproteins with molecular weights of 83K-94K (gp 2), 64K (gp 3), and 55K (gp 5). Immunoprecipitation experiments performed with VZV-infected cells, pulse labeled with (/sup 3/H)glucosamine in the presence of tunicamycin, suggest that O-linked oligosaccharide is present on the glycoprotein of gp 2. Use of the enzyme endo-beta-N-acetylglucosaminidase H revealed that the fully processed form of gp 3 had high-mannose type and that of gp 5 had only complex type of N-linked oligosaccharides. Experiments with monensin suggest that the precursor form (116K) of gp 3 is cleaved during the processing from Golgi apparatus to cell surface membrane. The extension of O-linked oligosaccharide chain and the complex type of N-linked oligosaccharide chains also occurs during this processing.

  17. A Retrospective Study of Congenital Cardiac Abnormality Associated with Scoliosis

    Science.gov (United States)

    Ucpunar, Hanifi; Sevencan, Ahmet; Balioglu, Mehmet Bulent; Albayrak, Akif; Polat, Veli

    2016-01-01

    Study Design Retrospective study. Purpose To identify the incidence of congenital cardiac abnormalities in patients who had scoliosis and underwent surgical treatment for scoliosis. Overview of Literature Congenital and idiopathic scoliosis (IS) are associated with cardiac abnormalities. We sought to establish and compare the incidence of congenital cardiac abnormalities in patients with idiopathic and congenital scoliosis (CS) who underwent surgical treatment for scoliosis. Methods Ninety consecutive scoliosis patients, who underwent surgical correction of scoliosis, were classified as CS (55 patients, 28 female [51%]) and IS (35 patients, 21 female [60%]). The complete data of the patients, including medical records, plain radiograph and transthoracic echocardiography were retrospectively assessed. Results We found that mitral valve prolapse was the most common cardiac abnormality in both patients with IS (nine patients, 26%) and CS (13 patients, 24%). Other congenital cardiac abnormalities were atrial septal aneurysm (23% of IS patients, 18% of CS patients), pulmonary insufficiency (20% of IS patients, 4% of CS patients), aortic insufficiency (17% of IS patients), atrial septal defect (11% of IS patients, 13% of CS patients), patent foramen ovale (15% of CS patients), dextrocardia (4% of CS patients), bicuspid aortic valve (3% of IS patients), aortic stenosis (2% of CS patients), ventricular septal defect (2% of CS patients), and cardiomyopathy (2% of CS patients). Conclusions We determined the increased incidence of congenital cardiac abnormalities among patients with congenital and IS. Mitral valve prolapse appeared to be the most prevalent congenital cardiac abnormality in both groups. PMID:27114761

  18. Cardiac abnormalities after subarachnoid hemorrhage

    NARCIS (Netherlands)

    Bilt, I.A.C. van der

    2016-01-01

    Aneurysmal subarachnoid hemorrhage(aSAH) is a devastating neurological disease. During the course of the aSAH several neurological and medical complications may occur. Cardiac abnormalities after aSAH are observed often and resemble stress cardiomyopathy or Tako-tsubo cardiomyopathy(Broken Heart Syn

  19. Congenital abnormalities in methylmercury poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Gilani, S.H.

    1975-04-01

    This study was undertaken to determine the teratogenic potential of methylmercury on chick embryogenesis. Methylmercuric chloride was dissolved in sodium bicarbonate (0.2%) and administered to the chick embryos at doses ranging from 0.0009 to 0.010 mg per egg. The injections were made at days 2 and 3 on incubation (Groups A and B). All the embryos including controls were examined on the 7th day of incubation. Methylmercury poisoning was observed to be both embryolethal and teratogenic. Within the two groups, embryolethality was higher in Group A. The following congenital abnormalities were observed: exencephaly, shortened and twisted limbs, microphthalmia, shortened and twisted neck, beak abnormalities, everted viscera, reduced body size and hemorrhage all over the body. Exencephaly and limb abnormalities were very common. No differences in the incidence and types of gross abnormalities within both the groups (A and B) were noted. The incidence of malformations among the controls was low. The results of present investigation show that methylmercury poisoning is both embryolethal and teratogenic to early chick embryogenesis. (auth)

  20. 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.

  1. Square-wave voltammetry assays for glycoproteins on nanoporous gold

    Science.gov (United States)

    Pandey, Binod; Bhattarai, Jay K.; Pornsuriyasak, Papapida; Fujikawa, Kohki; Catania, Rosa; Demchenko, Alexei V.; Stine, Keith J.

    2014-01-01

    Electrochemical enzyme-linked lectinsorbent assays (ELLA) were developed using nanoporous gold (NPG) as a solid support for protein immobilization and as an electrode for the electrochemical determination of the product of the reaction between alkaline phosphatase (ALP) and p-aminophenyl phosphate (p-APP), which is p-aminophenol (p-AP). Glycoproteins or concanavalin A (Con A) and ALP conjugates were covalently immobilized onto lipoic acid self-assembled monolayers on NPG. The binding of Con A – ALP (or soybean agglutinin – ALP) conjugate to glycoproteins covalently immobilized on NPG and subsequent incubation with p-APP substrate was found to result in square-wave voltammograms whose peak difference current varied with the identity of the glycoprotein. NPG presenting covalently bound glycoproteins was used as the basis for a competitive electrochemical assay for glycoproteins in solution (transferrin and IgG). A kinetic ELLA based on steric hindrance of the enzyme-substrate reaction and hence reduced enzymatic reaction rate after glycoprotein binding is demonstrated using immobilized Con A–ALP conjugates. Using the immobilized Con A-ALP conjugate, the binding affinity of immunoglobulin G (IgG) was found to be 105 nM, and that for transferrin was found to be 650 nM. Minimal interference was observed in the presence of 5 mg mL−1 BSA as a model serum protein in both the kinetic and competitive ELLA. Inhibition studies were performed with methyl D-mannoside for the binding of TSF and IgG to Con A-ALP; IC50 values were found to be 90 μM and 286 μM, respectively. Surface coverages of proteins were estimated using solution depletion and the BCA protein concentration assay. PMID:24611035

  2. Monoclonal antibody mapping of the envelope glycoprotein of the dengue 2 virus, Jamaica.

    Science.gov (United States)

    Roehrig, J T; Bolin, R A; Kelly, R G

    1998-07-05

    Although dengue (DEN) virus is the etiologic agent of dengue fever, the most prevalent vector-borne viral disease in the world, precise information on the antigenic structure of the dengue virion is limited. We have prepared a set of murine monoclonal antibodies (MAbs) specific for the envelope (E) glycoprotein of DEN 2 virus and used these antibodies in a comprehensive biological and biochemical analysis to identify 16 epitopes. Following domain nomenclature developed for the related flavivirus, tick-borne encephalitis, three functional domains were identified. Five epitopes associated with domain A were arranged in three spatially independent regions. These A-domain epitopes were destroyed by reduction, and antibodies reactive with these epitopes were able to block virus hemagglutination, neutralize virus infectivity, and block virus-mediated cell membrane fusion. Domain-A epitopes were present on the full-length E glycoprotein, a 45-kDa tryptic peptide representing its first 400 amino acids (aa) and a 22-kDa tryptic peptide representing at least aa 1-120. Four epitopes mapped into domain B, as determined by their partial resistance to reduction and the localization of these epitopes on a 9-kDa tryptic or chymotryptic peptide fragment (aa 300-400). One domain-B-reactive MAb was also capable of binding to a DEN 2 synthetic peptide corresponding to aa 333-351 of the E glycoprotein, confirming the location of this domain. Domain-B epitopes elicited MAbs that were potent neutralizers of virus infectivity and blocked hemagglutination, but they did not block virus-mediated cell-membrane fusion. Domains A and B were spatially associated. As with tick-borne encephalitis virus, determination of domain C was more problematic; however, at least four epitopes had biochemical characteristics consistent with C-domain epitopes.

  3. Core Structure of S2 from the Human Coronavirus NL63 Spike Glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Zheng,Q.; Deng, Y.; Liu, J.; van der Hoek, L.; Berkhout, B.; Lu, M.

    2006-01-01

    Human coronavirus NL63 (HCoV-NL63) has recently been identified as a causative agent of acute respiratory tract illnesses in infants and young children. The HCoV-NL63 spike (S) protein mediates virion attachment to cells and subsequent fusion of the viral and cellular membranes. This viral entry process is a primary target for vaccine and drug development. HCoV-NL63 S is expressed as a single-chain glycoprotein and consists of an N-terminal receptor-binding domain (S1) and a C-terminal transmembrane fusion domain (S2). The latter contains two highly conserved heptad-repeat (HR) sequences that are each extended by 14 amino acids relative to those of the SARS coronavirus or the prototypic murine coronavirus, mouse hepatitis virus. Limited proteolysis studies of the HCoV-NL63 S2 fusion core identify an {alpha}-helical domain composed of a trimer of the HR segments N57 and C42. The crystal structure of this complex reveals three C42 helices entwined in an oblique and antiparallel manner around a central triple-stranded coiled coil formed by three N57 helices. The overall geometry comprises distinctive high-affinity conformations of interacting cross-sectional layers of the six helices. As a result, this structure is unusually stable, with an apparent melting temperature of 78 {sup o}C in the presence of the denaturant guanidine hydrochloride at 5 M concentration. The extended HR regions may therefore be required to prime the group 1 S glycoproteins for their fusion-activating conformational changes during viral entry. Our results provide an initial basis for understanding an intriguing interplay between the presence or absence of proteolytic maturation among the coronavirus groups and the membrane fusion activity of their S glycoproteins. This study also suggests a potential strategy for the development of improved HCoV-NL63 fusion inhibitors.

  4. Alternative promoter usage of the membrane glycoprotein CD36

    Directory of Open Access Journals (Sweden)

    Whatling Carl

    2006-03-01

    Full Text Available Abstract Background CD36 is a membrane glycoprotein involved in a variety of cellular processes such as lipid transport, immune regulation, hemostasis, adhesion, angiogenesis and atherosclerosis. It is expressed in many tissues and cell types, with a tissue specific expression pattern that is a result of a complex regulation for which the molecular mechanisms are not yet fully understood. There are several alternative mRNA isoforms described for the gene. We have investigated the expression patterns of five alternative first exons of the CD36 gene in several human tissues and cell types, to better understand the molecular details behind its regulation. Results We have identified one novel alternative first exon of the CD36 gene, and confirmed the expression of four previously known alternative first exons of the gene. The alternative transcripts are all expressed in more than one human tissue and their expression patterns vary highly in skeletal muscle, heart, liver, adipose tissue, placenta, spinal cord, cerebrum and monocytes. All alternative first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins. The alternative promoters lack TATA-boxes and CpG islands. The upstream region of exon 1b contains several features common for house keeping gene and monocyte specific gene promoters. Conclusion Tissue-specific expression patterns of the alternative first exons of CD36 suggest that the alternative first exons of the gene are regulated individually and tissue specifically. At the same time, the fact that all first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins may suggest that the alternative first exons are coregulated in this cell type and environmental condition. The molecular mechanisms regulating CD36 thus appear to be unusually complex, which might reflect the multifunctional role of the gene in different tissues and cellular conditions.

  5. 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

  6. 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

    this antigen is a good candidate for development as a vaccine to prevent or control P. carinii infection. We have cloned and sequenced seven related but unique genes encoding the major surface glycoprotein of rat P. carinii. Partial amino acid sequencing confirmed the identity of these genes. Based on Southern...... 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...

  7. Lack of homozygotes for the most frequent disease allele in carbohydrate-deficient glycoprotein syndrome type 1A.

    OpenAIRE

    MATTHIJS, G; Schollen, E.; van Schaftingen, E; Cassiman, J. J.; Jaeken, J.

    1998-01-01

    Carbohydrate-deficient-glycoprotein syndrome type 1 (CDG1; also known as "Jaeken syndrome") is an autosomal recessive disorder characterized by defective glycosylation. Most patients show a deficiency of phosphomannomutase (PMM), the enzyme that converts mannose 6-phosphate to mannose 1-phosphate in the synthesis of GDP-mannose. The disease is linked to chromosome 16p13, and mutations have recently been identified in the PMM2 gene in CDG1 patients with a PMM deficiency (CDG1A). The availabili...

  8. 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

  9. 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.

  10. Craniofacial abnormalities in Hutchinson-Gilford progeria syndrome.

    Science.gov (United States)

    Ullrich, N J; Silvera, V M; Campbell, S E; Gordon, L B

    2012-09-01

    HGPS is a rare syndrome of segmental premature aging. Our goal was to expand the scope of structural bone and soft-tissue craniofacial abnormalities in HGPS through CT or MR imaging. Using The Progeria Research Foundation Medical and Research Database, 98 imaging studies on 25 patients, birth to 14.1 years of age, were comprehensively reviewed. Eight newly identified abnormalities involving the calvaria, skull base, and soft tissues of the face and orbits were present with prevalences between 43% and 100%. These included J-shaped sellas, a mottled appearance and increased vascular markings of the calvaria, abnormally configured mandibular condyles, hypoplastic articular eminences, small zygomatic arches, prominent parotid glands, and optic nerve kinking. This expanded craniofacial characterization helps link disease features and improves our ability to evaluate how underlying genetic and cellular abnormalities culminate in a disease phenotype.

  11. Cytogenetic analysis of chromosomal abnormalities in Sri Lankan children

    Institute of Scientific and Technical Information of China (English)

    Colombo; Sri Lanka

    2015-01-01

    Background: Cytogenetic analysis is a valuable investigation in the diagnostic work up of children with suspected chromosomal disorders. The objective of this study was to describe the prevalence of various types of chromosomal abnormalities in Sri Lankan children undergoing cytogenetic analysis. Methods: Cytogenetic reports of 1554 consecutive children with suspected chromosomal disorders who underwent karyotyping in two genetic centers in Sri Lanka from January 2006 to December 2011 were reviewed retrospectively. Results: A total of 1548 children were successfully karyotyped. Abnormal karyotypes were found in 783 (50.6%) children. Numerical and structural abnormalities accounted for 90.8% and 9.2%, respectively. Down syndrome was the commonest aneuploidy identifi ed. Other various autosomal and sex chromosomal aneuploidies as well as micro-deletion syndromes were also detected. Conclusions: The prevalence of chromosomal abnormalities in Sri Lankan children undergoing cytogenetic analysis for suspected chromosomal disorders was relatively higher than that in Caucasian and other Asian populations.

  12. Mammalian Otolin: a multimeric glycoprotein specific to the inner ear that interacts with otoconial matrix protein Otoconin-90 and Cerebellin-1.

    Directory of Open Access Journals (Sweden)

    Michael R Deans

    Full Text Available The mammalian otoconial membrane is a dense extracellular matrix containing bio-mineralized otoconia. This structure provides the mechanical stimulus necessary for hair cells of the vestibular maculae to respond to linear accelerations and gravity. In teleosts, Otolin is required for the proper anchoring of otolith crystals to the sensory maculae. Otoconia detachment and subsequent entrapment in the semicircular canals can result in benign paroxysmal positional vertigo (BPPV, a common form of vertigo for which the molecular basis is unknown. Several cDNAs encoding protein components of the mammalian otoconia and otoconial membrane have recently been identified, and mutations in these genes result in abnormal otoconia formation and balance deficits.Here we describe the cloning and characterization of mammalian Otolin, a protein constituent of otoconia and the otoconial membrane. Otolin is a secreted glycoprotein of ∼70 kDa, with a C-terminal globular domain that is homologous to the immune complement C1q, and contains extensive posttranslational modifications including hydroxylated prolines and glycosylated lysines. Like all C1q/TNF family members, Otolin multimerizes into higher order oligomeric complexes. The expression of otolin mRNA is restricted to the inner ear, and immunohistochemical analysis identified Otolin protein in support cells of the vestibular maculae and semi-circular canal cristae. Additionally, Otolin forms protein complexes with Cerebellin-1 and Otoconin-90, two protein constituents of the otoconia, when expressed in vitro. Otolin was also found in subsets of support cells and non-sensory cells of the cochlea, suggesting that Otolin is also a component of the tectorial membrane.Given the importance of Otolin in lower organisms, the molecular cloning and biochemical characterization of the mammalian Otolin protein may lead to a better understanding of otoconial development and vestibular dysfunction.

  13. Allergenic Characterization of 27-kDa Glycoprotein, a Novel Heat Stable Allergen, from the Pupa of Silkworm, Bombyx mori.

    Science.gov (United States)

    Jeong, Kyoung Yong; Son, Mina; Lee, June Yong; Park, Kyung Hee; Lee, Jae-Hyun; Park, Jung-Won

    2016-01-01

    Boiled silkworm pupa is a traditional food in Asia, and patients with silkworm pupa food allergy are common in these regions. Still now only one allergen from silkworm, arginine kinase, has been identified. The purpose of this study was to identify novel food allergens in silkworm pupa by analyzing a protein extract after heat treatment. Heat treated extracts were examined by proteomic analysis. A 27-kDa glycoprotein was identified, expressed in Escherichia coli, and purified. IgE reactivity of the recombinant protein was investigated by ELISA. High molecular weight proteins (above 100 kDa) elicited increased IgE binding after heat treatment compared to that before heat treatment. The molecular identities of these proteins, however, could not be determined. IgE reactivity toward a 27-kDa glycoprotein was also increased after heating the protein extract. The recombinant protein was recognized by IgE antibodies from allergic subjects (33.3%). Glycation or aggregation of protein by heating may create new IgE binding epitopes. Heat stable allergens are shown to be important in silkworm allergy. Sensitization to the 27-kDa glycoprotein from silkworm may contribute to elevation of IgE to silkworm.

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

    OpenAIRE

    2009-01-01

    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 str...

  15. Emergence of porcine reproductive and respiratory syndrome virus deletion mutants: Correlation with the porcine antibody response to a hypervariable site in the ORF 3 structural glycoprotein

    DEFF Research Database (Denmark)

    Oleksiewicz, M.B.; Bøtner, Anette; Toft, P.;

    2000-01-01

    By using porcine immune sera to select a library of phage-displayed random peptides. we identified an antigenic sequence (RKASLSTS) in the C-terminus of the ORF 3 structural glycoprotein of European-type porcine reproductive and respiratory syndrome virus (PRRSV). Through the use of overlapping....... These distinctions suggested that deletion mutants were a hitherto unrecognized subtype of European-type PRRSV. Currently, deletion mutants appear to be outcompeting nondeleted viruses in the field, highlighting the importance of the porcine antibody response against the minor structural glycoproteins of European...

  16. Structural and quantitative comparison of cerebrospinal fluid glycoproteins in Alzheimer's disease patients and healthy individuals.

    NARCIS (Netherlands)

    Sihlbom, C.; Davidsson, P.; Sjogren, M.; Wahlund, L.O.; Nilsson, C.L.

    2008-01-01

    Glycoproteins in cerebrospinal fluid (CSF) are altered in Alzheimer's Disease (AD) patients compared to control individuals. We have utilized albumin depletion prior to 2D gel electrophoresis to enhance glycoprotein concentration for image analysis as well as structural glycoprotein determination wi

  17. Nail abnormalities in rheumatoid arthritis.

    Science.gov (United States)

    Michel, C; Cribier, B; Sibilia, J; Kuntz, J L; Grosshans, E

    1997-12-01

    Many nail abnormalities have traditionally been described in association with rheumatoid arthritis (RA), but their specificity has never been assessed in a controlled study. Our purpose was to evaluate the frequency and the specificity of nail changes associated with RA in a case-controlled study including 50 patients suffering from RA and 50 controls. For each patient, a general skin examination was performed and the 20 nails were examined. The nail features were noted and classified. A chi 2 test or a Fisher test was used to compare the two groups. The only nail abnormalities significantly associated with RA were longitudinal ridging on nine or 10 finger nails (29 patients in the RA group vs. three in the controls, chi 2: P nail (24 patients vs. 10, chi 2: P nail changes were noticed but were not frequent enough to be significant. The presence of longitudinal ridging on the finger nails was significantly associated with RA.

  18. Neuroendocrine abnormalities in Parkinson's disease.

    Science.gov (United States)

    De Pablo-Fernández, Eduardo; Breen, David P; Bouloux, Pierre M; Barker, Roger A; Foltynie, Thomas; Warner, Thomas T

    2017-02-01

    Neuroendocrine abnormalities are common in Parkinson's disease (PD) and include disruption of melatonin secretion, disturbances of glucose, insulin resistance and bone metabolism, and body weight changes. They have been associated with multiple non-motor symptoms in PD and have important clinical consequences, including therapeutics. Some of the underlying mechanisms have been implicated in the pathogenesis of PD and represent promising targets for the development of disease biomarkers and neuroprotective therapies. In this systems-based review, we describe clinically relevant neuroendocrine abnormalities in Parkinson's disease to highlight their role in overall phenotype. We discuss pathophysiological mechanisms, clinical implications, and pharmacological and non-pharmacological interventions based on the current evidence. We also review recent advances in the field, focusing on the potential targets for development of neuroprotective drugs in Parkinson's disease and suggest future areas for research.

  19. Mastoid abnormalities in Down syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Glass, R.B.J.; Yousefzadeh, D.K.; Roizen, N.J.

    1989-06-01

    Hearing loss and otitis media are commonly associated with Down syndrome. Hypoplasia of the mastoids is seen in many affected children and sclerosis of mastoid bones is not uncommon in Down syndrome. Awareness and early recognition of mastoid abnormality may lead to appropriate and timely therapy, thereby preserving the child's hearing or compensating for hearing loss; factors which are important for learning and maximum development.

  20. Computed tomography of thymic abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Schnyder, P.; Candardjis, G.

    1987-05-01

    Computed tomographic examinations of 38 patients with surgically and histologically proven diagnosis were reviewed. Twenty subjects (52%) had an invasive thymoma and 16% an hyperplastic thymus. Myasthenia gravis was present in 6 cases (16%) of thymic abnormalities, four (10,5%) with invasive thymoma and two (5%) with thymic hyperplasia. Graves' disease was also present in one case of thymic hyperplasia. We emphasize the contribution of CT to the diagnosis and the prognosis.

  1. Characterization of Site-Specific N-Glycopeptide Isoforms of α-1-Acid Glycoprotein from an Interlaboratory Study Using LC-MS/MS.

    Science.gov (United States)

    Lee, Ju Yeon; Lee, Hyun Kyoung; Park, Gun Wook; Hwang, Heeyoun; Jeong, Hoi Keun; Yun, Ki Na; Ji, Eun Sun; Kim, Kwang Hoe; Kim, Jun Seok; Kim, Jong Won; Yun, Sung Ho; Choi, Chi-Won; Kim, Seung Il; Lim, Jong-Sun; Jeong, Seul-Ki; Paik, Young-Ki; Lee, Soo-Youn; Park, Jisook; Kim, Su Yeon; Choi, Young-Jin; Kim, Yong-In; Seo, Jawon; Cho, Je-Yoel; Oh, Myoung Jin; Seo, Nari; An, Hyun Joo; Kim, Jin Young; Yoo, Jong Shin

    2016-12-02

    Glycoprotein conformations are complex and heterogeneous. Currently, site-specific characterization of glycopeptides is a challenge. We sought to establish an efficient method of N-glycoprotein characterization using mass spectrometry (MS). Using alpha-1-acid glycoprotein (AGP) as a model N-glycoprotein, we identified its tryptic N-glycopeptides and examined the data reproducibility in seven laboratories running different LC-MS/MS platforms. We used three test samples and one blind sample to evaluate instrument performance with entire sample preparation workflow. 165 site-specific N-glycopeptides representative of all N-glycosylation sites were identified from AGP 1 and AGP 2 isoforms. The glycopeptide fragmentations by collision-induced dissociation or higher-energy collisional dissociation (HCD) varied based on the MS analyzer. Orbitrap Elite identified the greatest number of AGP N-glycopeptides, followed by Triple TOF and Q-Exactive Plus. Reproducible generation of oxonium ions, glycan-cleaved glycopeptide fragment ions, and peptide backbone fragment ions was essential for successful identification. Laboratory proficiency affected the number of identified N-glycopeptides. The relative quantities of the 10 major N-glycopeptide isoforms of AGP detected in four laboratories were compared to assess reproducibility. Quantitative analysis showed that the coefficient of variation was N-glycopeptide isoforms of AGP from control and disease plasma sample.

  2. 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...

  3. Meiotic abnormalities in infertile males.

    Science.gov (United States)

    Egozcue, J; Sarrate, Z; Codina-Pascual, M; Egozcue, S; Oliver-Bonet, M; Blanco, J; Navarro, J; Benet, J; Vidal, F

    2005-01-01

    Meiotic anomalies, as reviewed here, are synaptic chromosome abnormalities, limited to germ cells that cannot be detected through the study of the karyotype. Although the importance of synaptic errors has been underestimated for many years, their presence is related to many cases of human male infertility. Synaptic anomalies can be studied by immunostaining of synaptonemal complexes (SCs), but in this case their frequency is probably underestimated due to the phenomenon of synaptic adjustment. They can also be studied in classic meiotic preparations, which, from a clinical point of view, is still the best approach, especially if multiplex fluorescence in situ hybridization is at hand to solve difficult cases. Sperm chromosome FISH studies also provide indirect evidence of their presence. Synaptic anomalies can affect the rate of recombination of all bivalents, produce achiasmate small univalents, partially achiasmate medium-sized or large bivalents, or affect all bivalents in the cell. The frequency is variable, interindividually and intraindividually. The baseline incidence of synaptic anomalies is 6-8%, which may be increased to 17.6% in males with a severe oligozoospermia, and to 27% in normozoospermic males with one or more previous IVF failures. The clinical consequences are the production of abnormal spermatozoa that will produce a higher number of chromosomally abnormal embryos. The indications for a meiotic study in testicular biopsy are provided.

  4. [Lacrimal and salivatory glycoproteins in ophthalmic herpes].

    Science.gov (United States)

    Reuk, S E; Terekhina, N A

    2016-01-01

    to compare tear, saliva, and plasma levels of acute phase proteins (APPs) of inflammation in patients with herpes keratitis and to use the RESULTS in treatment evaluation. APPs were measured in tears, oral fluid, and blood plasma from 22 adults and 34 children with ophthalmic herpes as well as 68 healthy controls using immunoturbidimetric and spectrophotometric methods of detection. High levels of C-reactive protein and orosomucoid, low levels of ceruloplasmin, α1-antitrypsin, and transferrin in tears from patients with herpes keratitis as well as abnormal tear, saliva, and plasma APPs levels at discharge are poor prognostic signs. They all indicate that corneal inflammation is still intense and that the treatment should not be ceased yet. Severity of APPs concentration changes in tear from patients with herpes keratitis correlates with the depth of corneal lesions, recurrence rate, and disease dynamics. Quantitative determination of acute phase proteins in tear and oral fluid is an early and sensitive inflammation test and may be also used for non-invasive monitoring and antiviral treatment evaluation. Oral fluid allows to extend the capabilities of non-invasive diagnostics of ophthalmic herpes.

  5. Folding of viral envelope glycoproteins in the endoplasmic reticulum

    NARCIS (Netherlands)

    Braakman, L.J.; Anken, E. van

    2000-01-01

    Viral glycoproteins fold and oligomerize in the endoplasmic reticulum of the host cell. They employ the cellular machinery and receive assistance from cellular folding factors. During the folding process, they are retained in the compartment and their structural quality is checked by the quality con

  6. Spinosad is a potent inhibitor of canine P-glycoprotein

    NARCIS (Netherlands)

    Schrickx, Johannes A

    2014-01-01

    Inhibition of the drug transporter P-glycoprotein (P-gp) by the oral flea preventative spinosad has been suggested as the underlying cause of the drug-drug interaction with ivermectin. In this study, an in vitro model consisting of canine cells was validated to describe the inhibitory effect of drug

  7. beta(2)-Glycoprotein I : evolution, structure and function

    NARCIS (Netherlands)

    de Groot, P. G.; Meijers, J. C. M.

    2011-01-01

    beta(2)-Glycoprotein I (beta(2)-GPI) is a protein that circulates in blood at high concentrations. The function of beta(2)-GPI has long been an enigma. More than 20 years ago, it was discovered that beta(2)-GPI is the major antigen for the circulating antibodies in the antiphospholipid syndrome. How

  8. 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.

  9. 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 destru

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

    DEFF Research Database (Denmark)

    Yang, Zhang; Wang, Shengjun; Halim, Adnan;

    2015-01-01

    genes controlling N-glycosylation in CHO cells and constructed a design matrix that facilitates the generation of desired glycosylation, such as human-like alpha 2,6-linked sialic acid capping. This engineering approach will aid the production of glycoproteins with improved properties and therapeutic...

  11. 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)

  12. Magnetic enzyme reactors for isolation and study of heterogeneous glycoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Korecka, Lucie [Department of Analytical Chemistry, University of Pardubice, Namesti Cs. Legii 565, 532 10 Pardubice (Czech Republic)]. E-mail: lucie.korecka@upce.cz; Jezova, Jana [Department of Analytical Chemistry, University of Pardubice, Namesti Cs. Legii 565, 532 10 Pardubice (Czech Republic); Bilkova, Zuzana [Department of Biological and Biochemical Sciences, University of Pardubice, Namesti Cs. Legii 565, 532 10 Pardubice (Czech Republic); Benes, Milan [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovskeho Namesti 2, 162 06 Prague (Czech Republic); Horak, Daniel [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovskeho Namesti 2, 162 06 Prague (Czech Republic); Hradcova, Olga [Department of Biological and Biochemical Sciences, University of Pardubice, Namesti Cs. Legii 565, 532 10 Pardubice (Czech Republic); Slovakova, Marcela [Department of Biological and Biochemical Sciences, University of Pardubice, Namesti Cs. Legii 565, 532 10 Pardubice (Czech Republic); Laboratoire Physicochimie Curie, UMR 168 CNRS/Institute Curie, Paris Cedex 05 (France); Viovy, Jean-Louis [Laboratoire Physicochimie Curie, UMR 168 CNRS/Institute Curie, Paris Cedex 05 (France)

    2005-05-15

    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.

  13. 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)

  14. [Obtaining monoclonal antibodies against outer membrane glycoproteins of Entamoeba histolytica].

    Science.gov (United States)

    Agundis, C; Isibasi, A; Ortíz, V; Reyes, J L; Paniagua, J; Ramírez, A; Kumate, J

    1990-01-01

    The goal of this paper was the production of monoclonal antibodies capable of detecting relevant antigens from the surface of Entamoeba histolytica trophozoites, with the purpose of using them as a diagnostic test. The cellular fusion for obtaining the monoclonal antibodies (mAb) was done with spleen cells from BALB/c mice, previously immunized with glycoproteins from the membrane, as well as Sp2/0 cells. The hybridoma supernatants were tested with ELISA, using glycoproteins and lipopeptide phosphoglycans (LPPG) as antigens. Seven hybridomas producing mAb against the glycoproteins were found. Among these, three recognize LPPG. The ability of reacting with the mAb against two molecules disappeared for all the LPPG positive ones when were treated with meta-periodate, and only three reacted against the glycoproteins. All of the mAb were of the Ig M isotypes. They were characterized by Dot blot and Western blot assays. From the results, one may deduce that some mAb recognize as epitopes the polysaccharide portion, and thus infer that they are directed of against the surface and therefore, in the future, could be used with a diagnostic purpose.

  15. The HIV-1 envelope glycoproteins: folding, function and vaccin design

    NARCIS (Netherlands)

    Sanders, Rogier W.

    2003-01-01

    The need for a vaccine against HIV is obvious, but the development of an effective vaccine has met with frustrations. The HIV envelope glycoproteins, residing in the viral membrane, are the sole viral proteins exposed on the outside of virus particles and are therefore major targets for vaccine

  16. Fasciola hepatica Surface Tegument: Glycoproteins at the Interface of Parasite and Host*

    Science.gov (United States)

    Ravidà, Alessandra; Cwiklinski, Krystyna; Aldridge, Allison M.; Clarke, Paul; Thompson, Roisin; Gerlach, Jared Q.; Kilcoyne, Michelle; Hokke, Cornelis H.; Dalton, John P.; O'Neill, Sandra M.

    2016-01-01

    Fasciola hepatica, commonly known as liver fluke, is a trematode that causes Fasciolosis in ruminants and humans. The outer tegumental coat of F. hepatica (FhTeg) is a complex metabolically active biological matrix that is continually exposed to the host immune system and therefore makes a good vaccine target. F. hepatica tegumental coat is highly glycosylated and helminth-derived immunogenic oligosaccharide motifs and glycoproteins are currently being investigated as novel vaccine candidates. This report presents the first systematic characterization of FhTeg glycosylation using lectin microarrays to characterize carbohydrates motifs present, and lectin histochemistry to localize these on the F. hepatica tegument. We discovered that FhTeg glycoproteins are predominantly oligomannose oligosaccharides that are expressed on the spines, suckers and tegumental coat of F. hepatica and lectin blot analysis confirmed the abundance of N- glycosylated proteins. Although some oligosaccharides are widely distributed on the fluke surface other subsets are restricted to distinct anatomical regions. We selectively enriched for FhTeg mannosylated glycoprotein subsets using lectin affinity chromatography and identified 369 proteins by mass spectrometric analysis. Among these proteins are a number of potential vaccine candidates with known immune modulatory properties including proteases, protease inhibitors, paramyosin, Venom Allergen-like II, Enolase and two proteins, nardilysin and TRIL, that have not been previously associated with F. hepatica. Furthermore, we provide a comprehensive insight regarding the putative glycosylation of FhTeg components that could highlight the importance of further studies examining glycoconjugates in host-parasite interactions in the context of F. hepatica infection and the development of an effective vaccine. PMID:27466253

  17. Fasciola hepatica Surface Tegument: Glycoproteins at the Interface of Parasite and Host.

    Science.gov (United States)

    Ravidà, Alessandra; Cwiklinski, Krystyna; Aldridge, Allison M; Clarke, Paul; Thompson, Roisin; Gerlach, Jared Q; Kilcoyne, Michelle; Hokke, Cornelis H; Dalton, John P; O'Neill, Sandra M

    2016-10-01

    Fasciola hepatica, commonly known as liver fluke, is a trematode that causes Fasciolosis in ruminants and humans. The outer tegumental coat of F. hepatica (FhTeg) is a complex metabolically active biological matrix that is continually exposed to the host immune system and therefore makes a good vaccine target. F. hepatica tegumental coat is highly glycosylated and helminth-derived immunogenic oligosaccharide motifs and glycoproteins are currently being investigated as novel vaccine candidates. This report presents the first systematic characterization of FhTeg glycosylation using lectin microarrays to characterize carbohydrates motifs present, and lectin histochemistry to localize these on the F. hepatica tegument. We discovered that FhTeg glycoproteins are predominantly oligomannose oligosaccharides that are expressed on the spines, suckers and tegumental coat of F. hepatica and lectin blot analysis confirmed the abundance of N- glycosylated proteins. Although some oligosaccharides are widely distributed on the fluke surface other subsets are restricted to distinct anatomical regions. We selectively enriched for FhTeg mannosylated glycoprotein subsets using lectin affinity chromatography and identified 369 proteins by mass spectrometric analysis. Among these proteins are a number of potential vaccine candidates with known immune modulatory properties including proteases, protease inhibitors, paramyosin, Venom Allergen-like II, Enolase and two proteins, nardilysin and TRIL, that have not been previously associated with F. hepatica Furthermore, we provide a comprehensive insight regarding the putative glycosylation of FhTeg components that could highlight the importance of further studies examining glycoconjugates in host-parasite interactions in the context of F. hepatica infection and the development of an effective vaccine. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. 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...

  19. Protein N-glycosylation in Archaea: defining Haloferax volcanii genes involved in S-layer glycoprotein glycosylation.

    Science.gov (United States)

    Abu-Qarn, Mehtap; Eichler, Jerry

    2006-07-01

    In this study, characterization of the N-glycosylation process in the haloarchaea Haloferax volcanii was undertaken. Initially, putative Hfx. volcanii homologues of genes involved in eukaryal or bacterial N-glycosylation were identified by bioinformatics. Reverse transcription polymerase chain reaction (RT-PCR) confirmed that the proposed N-glycosylation genes are transcribed, indicative of true proteins being encoded. Where families of related gene sequences were detected, differential transcription of family members under a variety of physiological and environmental conditions was shown. Gene deletions point to certain genes, like alg11, as being essential yet revealed that others, such as the two versions of alg5, are not. Deletion of alg5-A did, however, lead to slower growth and interfered with surface (S)-layer glycoprotein glycosylation, as detected by modified migration on SDS-PAGE and glycostaining approaches. As deletion of stt3, the only component of the oligosaccharide transferase complex detected in Archaea, did not affect cell viability, it appears that N-glycosylation is not essential in Hfx. volcanii. Deletion of stt3 did, nonetheless, hinder both cell growth and S-layer glycoprotein glycosylation. Thus, with genes putatively involved in Hfx. volcanii protein glycosylation identified and the ability to address the roles played by the encoded polypeptides in modifying a reporter glycoprotein, the steps of the archaeal N-glycosylation pathway can be defined.

  20. BAD-lectins: boronic acid-decorated lectins with enhanced binding affinity for the selective enrichment of glycoproteins.

    Science.gov (United States)

    Lu, Ying-Wei; Chien, Chih-Wei; Lin, Po-Chiao; Huang, Li-De; Chen, Chang-Yang; Wu, Sz-Wei; Han, Chia-Li; Khoo, Kay-Hooi; Lin, Chun-Cheng; Chen, Yu-Ju

    2013-09-03

    The weak and variable binding affinities exhibited by lectin-carbohydrate interactions have often compromised the practical utility of lectin in capturing glycoproteins for glycoproteomic applications. We report here the development and applications of a new type of hybrid biomaterial, namely a boronic acid-decorated lectin (BAD-lectin), for efficient bifunctional glycoprotein labeling and enrichment. Our binding studies showed an enhanced affinity by BAD-lectin, likely to be mediated via the formation of boronate ester linkages between the lectin and glycan subsequent to the initial recognition process and thus preserving its glycan-specificity. Moreover, when attached to magnetic nanoparticles (BAD-lectin@MNPs), 2 to 60-fold improvement on detection sensitivity and enrichment efficiency for specific glycoproteins was observed over the independent use of either lectin or BA. Tested at the level of whole cell lysates for glycoproteomic applications, three different types of BAD-lectin@MNPs exhibited excellent specificities with only 6% overlapping among the 295 N-linked glycopeptides identified. As many as 236 N-linked glycopeptides (80%) were uniquely identified by one of the BAD-lectin@MNPs. These results indicated that the enhanced glycan-selective recognition and binding affinity of BAD-lectin@MNPs will facilitate a complementary identification of the under-explored glycoproteome.

  1. Platelet receptor expression and shedding: glycoprotein Ib-IX-V and glycoprotein VI.

    Science.gov (United States)

    Gardiner, Elizabeth E; Andrews, Robert K

    2014-04-01

    Quantity, quality, and lifespan are 3 important factors in the physiology, pathology, and transfusion of human blood platelets. The aim of this review is to discuss the proteolytic regulation of key platelet-specific receptors, glycoprotein(GP)Ib and GPVI, involved in the function of platelets in hemostasis and thrombosis, and nonimmune or immune thrombocytopenia. The scope of the review encompasses the basic science of platelet receptor shedding, practical aspects related to laboratory analysis of platelet receptor expression/shedding, and clinical implications of using the proteolytic fragments as platelet-specific biomarkers in vivo in terms of platelet function and clearance. These topics can be relevant to platelet transfusion regarding both changes in platelet receptor expression occurring ex vivo during platelet storage and/or clinical use of platelets for transfusion. In this regard, quantitative analysis of platelet receptor profiles on blood samples from individuals could ultimately enable stratification of bleeding risk, discrimination between causes of thrombocytopenia due to impaired production vs enhanced clearance, and monitoring of response to treatment prior to change in platelet count.

  2. The psychosocial impact of an abnormal cervical smear result.

    Science.gov (United States)

    Drolet, Mélanie; Brisson, Marc; Maunsell, Elizabeth; Franco, Eduardo L; Coutlée, François; Ferenczy, Alex; Fisher, William; Mansi, James A

    2012-10-01

    Data on the impact of abnormal cervical smear results on health-related quality of life (HrQoL) are scarce. We aimed to (i) prospectively assess the HrQoL of women who were informed of an abnormal smear result; (ii) identify predictors of greater negative psychosocial impact of an abnormal result; and (iii) prospectively estimate the quality-adjusted life-years (QALYs) lost following an abnormal result. Between 08/2006 and 08/2008, 492 women with an abnormal result and 460 women with a normal result, frequency matched for age and clinic, were recruited across Canada. HrQoL was measured at recruitment and 4 and 12 weeks later with the EuroQol, Short Form-12, short Spielberg State-Trait Anxiety Inventory (STAI) and HPV Impact Profile. Three blocks of potential predictors of higher psychosocial impact were tested by hierarchical modeling: (i) socio-demographics; (ii) sexual activity; and (iii) smear result severity, communication, and understanding. Receiving an abnormal result significantly increased anxiety (STAI mean difference between both groups = 8.3). Initial anxiety decreased over time for the majority of women. However, 35% of women had clinically meaningful anxiety at 12 weeks (i.e. STAI scores ≥0.5 standard deviation of the controls). These women reported a lower socio-economic level, did not completely understand the information about their result and perceived themselves at higher risk of cancer. QALY lost following an abnormal result were between 0.007 and 0.009. Receiving an abnormal smear has a statistically significant and clinically meaningful negative impact on mental health. However, this negative impact subsides after 12 weeks for the majority of women. Copyright © 2011 John Wiley & Sons, Ltd.

  3. Functional neuroimaging abnormalities in idiopathic generalized epilepsy

    Directory of Open Access Journals (Sweden)

    Megan L. McGill

    2014-01-01

    Full Text Available Magnetic resonance imaging (MRI techniques have been used to quantitatively assess focal and network abnormalities. Idiopathic generalized epilepsy (IGE is characterized by bilateral synchronous spike–wave discharges on electroencephalography (EEG but normal clinical MRI. Dysfunctions involving the neocortex, particularly the prefrontal cortex, and thalamus likely contribute to seizure activity. To identify possible morphometric and functional differences in the brains of IGE patients and normal controls, we employed measures of thalamic volumes, cortical thickness, gray–white blurring, fractional anisotropy (FA measures from diffusion tensor imaging (DTI and fractional amplitude of low frequency fluctuations (fALFF in thalamic subregions from resting state functional MRI. Data from 27 patients with IGE and 27 age- and sex-matched controls showed similar thalamic volumes, cortical thickness and gray–white contrast. There were no differences in FA values on DTI in tracts connecting the thalamus and prefrontal cortex. Functional analysis revealed decreased fALFF in the prefrontal cortex (PFC subregion of the thalamus in patients with IGE. We provide minimum detectable effect sizes for each measure used in the study. Our analysis indicates that fMRI-based methods are more sensitive than quantitative structural techniques for characterizing brain abnormalities in IGE.

  4. Brain Abnormalities in Neuromyelitis Optica Spectrum Disorder

    Science.gov (United States)

    Kim, Woojun; Kim, Su-Hyun; Huh, So-Young; Kim, Ho Jin

    2012-01-01

    Neuromyelitis optica (NMO) is an idiopathic inflammatory syndrome of the central nervous system that is characterized by severe attacks of optic neuritis (ON) and myelitis. Until recently, NMO was considered a disease without brain involvement. However, since the discovery of NMO-IgG/antiaqaporin-4 antibody, the concept of NMO was broadened to NMO spectrum disorder (NMOSD), and brain lesions are commonly recognized. Furthermore, some patients present with brain symptoms as their first manifestation and develop recurrent brain symptoms without ON or myelitis. Brain lesions with characteristic locations and configurations can be helpful in the diagnosis of NMOSD. Due to the growing recognition of brain abnormalities in NMOSD, these have been included in the NMO and NMOSD diagnostic criteria or guidelines. Recent technical developments such as diffusion tensor imaging, MR spectroscopy, and voxel-based morphometry reveal new findings related to brain abnormalities in NMOSD that were not identified using conventional MRI. This paper focuses on the incidence and characteristics of the brain lesions found in NMOSD and the symptoms that they cause. Recent studies using advanced imaging techniques are also introduced. PMID:23259063

  5. Brain Abnormalities in Neuromyelitis Optica Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Woojun Kim

    2012-01-01

    Full Text Available Neuromyelitis optica (NMO is an idiopathic inflammatory syndrome of the central nervous system that is characterized by severe attacks of optic neuritis (ON and myelitis. Until recently, NMO was considered a disease without brain involvement. However, since the discovery of NMO-IgG/antiaqaporin-4 antibody, the concept of NMO was broadened to NMO spectrum disorder (NMOSD, and brain lesions are commonly recognized. Furthermore, some patients present with brain symptoms as their first manifestation and develop recurrent brain symptoms without ON or myelitis. Brain lesions with characteristic locations and configurations can be helpful in the diagnosis of NMOSD. Due to the growing recognition of brain abnormalities in NMOSD, these have been included in the NMO and NMOSD diagnostic criteria or guidelines. Recent technical developments such as diffusion tensor imaging, MR spectroscopy, and voxel-based morphometry reveal new findings related to brain abnormalities in NMOSD that were not identified using conventional MRI. This paper focuses on the incidence and characteristics of the brain lesions found in NMOSD and the symptoms that they cause. Recent studies using advanced imaging techniques are also introduced.

  6. Mapping paratope on antithrombotic antibody 6B4 to epitope on platelet glycoprotein Ibalpha via molecular dynamic simulations.

    Directory of Open Access Journals (Sweden)

    Xiang Fang

    Full Text Available Binding of platelet receptor glycoprotein Ibα (GPIbα to the A1 domain of von Willebrand factor (vWF is a critical step in both physiologic hemostasis and pathologic thrombosis, for initiating platelet adhesion to subendothelium of blood vessels at sites of vascular injury. Gain-of-function mutations in GPIbα contribute to an abnormally high-affinity binding of platelets to vWF and can lead to thrombosis, an accurate complication causing heart attack and stroke. Of various antithrombotic monoclonal antibodies (mAbs targeting human GPIbα, 6B4 is a potent one to inhibit the interaction between GPIbα and vWF-A1 under static and flow conditions. Mapping paratope to epitope with mutagenesis experiments, a traditional route in researches of these antithrombotic mAbs, is usually expensive and time-consuming. Here, we suggested a novel computational procedure, which combines with homology modeling, rigid body docking, free and steered molecular dynamics (MD simulations, to identify key paratope residues on 6B4 and their partners on GPIbα, with hypothesis that the stable hydrogen bonds and salt bridges are the important linkers between paratope and epitope residues. Based on a best constructed model of 6B4 bound with GPIbα, the survival ratios and rupture times of all detected hydrogen bonds and salt bridges in binding site were examined via free and steered MD simulations and regarded as indices of thermal and mechanical stabilizations of the bonds, respectively. Five principal paratope residues with their partners were predicted with their high survival ratios and/or long rupture times of involved hydrogen bonds, or with their hydrogen bond stabilization indices ranked in top 5. Exciting, the present results were in good agreement with previous mutagenesis experiment data, meaning a wide application prospect of our novel computational procedure on researches of molecular of basis of ligand-receptor interactions, various antithrombotic mAbs and

  7. 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.

  8. Low-set ears and pinna abnormalities

    Science.gov (United States)

    Low-set ears; Microtia; "Lop" ear; Pinna abnormalities; Genetic defect-pinna; Congenital defect-pinna ... conditions: Abnormal folds or location of the pinna Low-set ears No opening to the ear canal ...

  9. Relationship among sera lipoprotein abnormalities in healthy ...

    African Journals Online (AJOL)

    Relationship among sera lipoprotein abnormalities in healthy individuals with background of diabetic sibling. ... As the prevalence of lipoprotein abnormalities in adolescents is increasing dramatically, the identification of ... Article Metrics.

  10. Abnormal Cervical Cancer Screening Test Results

    Science.gov (United States)

    ... FREQUENTLY ASKED QUESTIONS FAQ187 GYNECOLOGIC PROBLEMS Abnormal Cervical Cancer Screening Test Results • What is cervical cancer screening? • What causes abnormal cervical cancer screening test results? • ...

  11. [Phenomenology of abnormal body perceptions].

    Science.gov (United States)

    Schäfer, M L

    1983-01-01

    The present paper deals with the problematic nature of the phenomenological grasping of the consciousness of the body and its pathological modifications. The reasoning is oriented by the doctrine of Husserl of the so-called sentiments as the fundamentals of the experience of the own body. This basic approach does not only seem to be basically for a psychology of the consciousness of the body, but also to give the theoretical-conceptual structure for a great number of psychopathological modifications. Subsequent to a criticism of the conventional use of the term 'hallucination of the body' we attempt to chart elements of a scheme of the abnormal consciousness of the body.

  12. Foot abnormalities of wild birds

    Science.gov (United States)

    Herman, C.M.; Locke, L.N.; Clark, G.M.

    1962-01-01

    The various foot abnormalities that occur in birds, including pox, scaly-leg, bumble-foot, ergotism and freezing are reviewed. In addition, our findings at the Patuxent Wildlife Research Center include pox from dove, mockingbird, cowbird, grackle and several species of sparrows. Scaly-leg has been particularly prevalent on icterids. Bumble foot has been observed in a whistling swan and in a group of captive woodcock. Ergotism is reported from a series of captive Canada geese from North Dakota. Several drug treatments recommended by others are presented.

  13. Identifying Activity

    CERN Document Server

    Lewis, Adrian S

    2009-01-01

    Identification of active constraints in constrained optimization is of interest from both practical and theoretical viewpoints, as it holds the promise of reducing an inequality-constrained problem to an equality-constrained problem, in a neighborhood of a solution. We study this issue in the more general setting of composite nonsmooth minimization, in which the objective is a composition of a smooth vector function c with a lower semicontinuous function h, typically nonsmooth but structured. In this setting, the graph of the generalized gradient of h can often be decomposed into a union (nondisjoint) of simpler subsets. "Identification" amounts to deciding which subsets of the graph are "active" in the criticality conditions at a given solution. We give conditions under which any convergent sequence of approximate critical points finitely identifies the activity. Prominent among these properties is a condition akin to the Mangasarian-Fromovitz constraint qualification, which ensures boundedness of the set of...

  14. The heterodimeric glycoprotein hormone, GPA2/GPB5, regulates ion transport across the hindgut of the adult mosquito, Aedes aegypti.

    Directory of Open Access Journals (Sweden)

    Jean-Paul Paluzzi

    Full Text Available A family of evolutionarily old hormones is the glycoprotein cysteine knot-forming heterodimers consisting of alpha- (GPA and beta-subunits (GPB, which assemble by noncovalent bonds. In mammals, a common glycoprotein hormone alpha-subunit (GPA1 pairs with unique beta-subunits that establish receptor specificity, forming thyroid stimulating hormone (GPA1/TSHβ and the gonadotropins luteinizing hormone (GPA1/LHβ, follicle stimulating hormone (GPA1/FSHβ, choriogonadotropin (GPA1/CGβ. A novel glycoprotein heterodimer was identified in vertebrates by genome analysis, called thyrostimulin, composed of two novel subunits, GPA2 and GPB5, and homologs occur in arthropods, nematodes and cnidarians, implying that this neurohormone system existed prior to the emergence of bilateral metazoans. In order to discern possible physiological roles of this hormonal signaling system in mosquitoes, we have isolated the glycoprotein hormone genes producing the alpha- and beta-subunits (AedaeGPA2 and AedaeGPB5 and assessed their temporal expression profiles in the yellow and dengue-fever vector, Aedes aegypti. We have also isolated a putative receptor for this novel mosquito hormone, AedaeLGR1, which contains features conserved with other glycoprotein leucine-rich repeating containing G protein-coupled receptors. AedaeLGR1 is expressed in tissues of the alimentary canal such as the midgut, Malpighian tubules and hindgut, suggesting that this novel mosquito glycoprotein hormone may regulate ionic and osmotic balance. Focusing on the hindgut in adult stage A. aegypti, where AedaeLGR1 was highly enriched, we utilized the Scanning Ion-selective Electrode Technique (SIET to determine if AedaeGPA2/GPB5 modulated cation transport across this epithelial tissue. Our results suggest that AedaeGPA2/GPB5 does indeed participate in ionic and osmotic balance, since it appears to inhibit natriuresis and promote kaliuresis. Taken together, our findings imply this hormone may play an

  15. The prevalence of chromosomal abnormalities in subgroups of infertile men

    NARCIS (Netherlands)

    Dul, E. C.; Groen, H.; van Ravenswaaij-Arts, C. M. A.; Dijkhuizen, T.; van Echten-Arends, J.; Land, J. A.

    2012-01-01

    BACKGROUND: The prevalence of chromosomal abnormalities is assumed to be higher in infertile men and inversely correlated with sperm concentration. Although guidelines advise karyotyping infertile men, karyotyping is costly, therefore it would be of benefit to identify men with the highest risk of c

  16. 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…

  17. On Regularity of Abnormal Subriemannian Geodesics

    CERN Document Server

    Tan, Kanghai

    2012-01-01

    We prove the smoothness of abnormal minimizers of subriemannian manifolds of step 3 with a nilpotent basis. We prove that rank 2 Carnot groups of step 4 admit no strictly abnormal minimizers. For any subriemannian manifolds of step less than 7, we show all abnormal minimizers have no corner type singularities, which partly generalize the main result of Leonardi-Monti.

  18. Trophoblast glycoprotein promotes pancreatic ductal adenocarcinoma cell metastasis through Wnt/planar cell polarity signaling.

    Science.gov (United States)

    He, Ping; Jiang, Shuheng; Ma, Mingze; Wang, Yang; Li, Rongkun; Fang, Fang; Tian, Guangang; Zhang, Zhigang

    2015-07-01

    Trophoblast glycoprotein (TPBG), a 72 kDa glycoprotein was identified using a monoclonal antibody, which specifically binds human trophoblast. The expression of TPBG in normal tissues is limited; however, it is upregulated in numerous types of cancer. When TPBG is expressed at a high level, this usually indicates a poor clinical outcome. In the present study, it was demonstrated that TPBG was more commonly observed in human pancreatic ductal adenocarcinoma (PDAC) compared with normal pancreatic tissue. Immunohistochemical analysis of PDAC tissue microarrays indicated that the expression of TPBG in PDAC tissues was closely correlated with the tumor-node-metastasis stage of the tumor. Silencing of TPBG in PDAC cell lines resulted in a decreased ability of cancer cell migration and invasion. Further investigation demonstrated that the Wnt/planar cell polarity signaling pathway was suppressed, as the expression of Wnt5a and the activation of c-Jun N-terminal kinase was inhibited following TPBG knockdown. In conclusion, the present study provided evidence that TPBG is involved in PDAC metastasis, and that TPBG and its associated signaling pathways may be a suitable target for PDAC therapy.

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

    Science.gov (United States)

    Lopes-Rodrigues, Vanessa; Sousa, Emília; Vasconcelos, M. Helena

    2016-01-01

    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. PMID:27834897

  20. Silencing of P-glycoprotein increases mortality in temephos-treated Aedes aegypti larvae.

    Science.gov (United States)

    Figueira-Mansur, J; Ferreira-Pereira, A; Mansur, J F; Franco, T A; Alvarenga, E S L; Sorgine, M H F; Neves, B C; Melo, A C A; Leal, W S; Masuda, H; Moreira, M F

    2013-12-01

    Re-emergence of vector-borne diseases such as dengue and yellow fever, which are both transmitted by the Aedes aegypti mosquito, has been correlated with insecticide resistance. P-glycoproteins (P-gps) are ATP-dependent efflux pumps that are involved in the transport of substrates across membranes. Some of these proteins have been implicated in multidrug resistance (MDR). In this study, we identified a putative P-glycoprotein in the Ae. aegypti database based on its significantly high identity with Anopheles gambiae, Culex quinquefasciatus, Drosophila melanogaster and human P-gps. The basal ATPase activity of ATP-binding cassette transporters in larvae was significantly increased in the presence of MDR modulators (verapamil and quinidine). An eightfold increase in Ae. aegypti P-gp (AaegP-gp) gene expression was detected in temephos-treated larvae as determined by quantitative PCR. To analyse the potential role of AaegP-gp in insecticide efflux, a temephos larvicide assay was performed in the presence of verapamil. The results showed an increase of 24% in temephos toxicity, which is in agreement with the efflux reversing effect. RNA interference (RNAi)-mediated silencing of the AaegP-gp gene caused a significant increase in temephos toxicity (57%). In conclusion, we have demonstrated for the first time in insects that insecticide-induced P-gp expression can be involved in the modulation of insecticide efflux.

  1. Clinical Significance of an Alloantibody against the Kell Blood Group Glycoprotein

    Science.gov (United States)

    Mattaloni, Stella Maris; Arnoni, Carine; Céspedes, Rosario; Nonaka, Claudia; Trucco Boggione, Carolina; Luján Brajovich, Melina Eliana; Trejo, Andrea; Zani, Néstor; Biondi, Claudia Silvia; Castilho, Lilian; Cotorruelo, Carlos Miquel

    2017-01-01

    Background Kell null (K0) individuals can produce anti-Ku, an antibody against many epitopes in the Kell glycoprotein, after transfusion and/or pregnancy. Since sensitized K0 patients are rare, little is known about anti-Ku clinical relevance and in particular about its association to hemolytic disease of the fetus and newborn. Case Report This work describes a case of neonatal hyperbilirubinemia due to immune-mediated erythrocyte destruction by an alloantibody directed against the Kell glycoprotein. Serologic and molecular approaches identified an anti-Ku alloantibody in maternal serum. A homozygous IVS3 + 1g>a point mutation (KEL*02N.06 allele) was found to be responsible for the lack of Kell antigen expression in the mother's red blood cell and subsequent alloimmunization after a previous pregnancy. Even though in most cases Kell antibodies are clinically severe and may cause suppression of erythropoiesis, in our case the newborn had a moderate anemia and hyperbilirubinemia that was successfully treated with phototherapy without requiring exchange transfusion. Serological and molecular studies performed in the proband's family members allowed us to provide them with proper counseling regarding alloimmunization after transfusion and/or pregnancy. Conclusions This case enlarges the understanding of the clinical significance of alloantibodies against Kell blood group antigens.

  2. 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.

  3. A directed molecular evolution approach to improved immunogenicity of the HIV-1 envelope glycoprotein.

    Directory of Open Access Journals (Sweden)

    Sean X Du

    Full Text Available 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.

  4. 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.

  5. Abnormal visuomotor processing in schizophrenia

    Directory of Open Access Journals (Sweden)

    Siân E. Robson

    2016-01-01

    Full Text Available Subtle disturbances of visual and motor function are known features of schizophrenia and can greatly impact quality of life; however, few studies investigate these abnormalities using simple visuomotor stimuli. In healthy people, electrophysiological data show that beta band oscillations in sensorimotor cortex decrease during movement execution (event-related beta desynchronisation (ERBD, then increase above baseline for a short time after the movement (post-movement beta rebound (PMBR; whilst in visual cortex, gamma oscillations are increased throughout stimulus presentation. In this study, we used a self-paced visuomotor paradigm and magnetoencephalography (MEG to contrast these responses in patients with schizophrenia and control volunteers. We found significant reductions in the peak-to-peak change in amplitude from ERBD to PMBR in schizophrenia compared with controls. This effect was strongest in patients who made fewer movements, whereas beta was not modulated by movement in controls. There was no significant difference in the amplitude of visual gamma between patients and controls. These data demonstrate that clear abnormalities in basic sensorimotor processing in schizophrenia can be observed using a very simple MEG paradigm.

  6. Chromosomal phenotypes and submicroscopic abnormalities

    Directory of Open Access Journals (Sweden)

    Devriendt Koen

    2004-01-01

    Full Text Available Abstract The finding, during the last decade, that several common, clinically delineated syndromes are caused by submicroscopic deletions or, more rarely, by duplications, has provided a powerful tool in the annotation of the human genome. Since most microdeletion/microduplication syndromes are defined by a common deleted/duplicated region, abnormal dosage of genes located within these regions can explain the phenotypic similarities among individuals with a specific syndrome. As such, they provide a unique resource towards the genetic dissection of complex phenotypes such as congenital heart defects, mental and growth retardation and abnormal behaviour. In addition, the study of phenotypic differences in individuals with the same microdeletion syndrome may also become a treasury for the identification of modifying factors for complex phenotypes. The molecular analysis of these chromosomal anomalies has led to a growing understanding of their mechanisms of origin. Novel tools to uncover additional submicroscopic chromosomal anomalies at a higher resolution and higher speed, as well as the novel tools at hand for deciphering the modifying factors and epistatic interactors, are 'on the doorstep' and will, besides their obvious diagnostic role, play a pivotal role in the genetic dissection of complex phenotypes.

  7. A rhomboid protease gene deletion affects a novel oligosaccharide N-linked to the S-layer glycoprotein of Haloferax volcanii.

    Science.gov (United States)

    Parente, Juliana; Casabuono, Adriana; Ferrari, María Celeste; Paggi, Roberto Alejandro; De Castro, Rosana Esther; Couto, Alicia Susana; Giménez, María Inés

    2014-04-18

    Rhomboid proteases occur in all domains of life; however, their physiological role is not completely understood, and nothing is known of the biology of these enzymes in Archaea. One of the two rhomboid homologs of Haloferax volcanii (RhoII) is fused to a zinc finger domain. Chromosomal deletion of rhoII was successful, indicating that this gene is not essential for this organism; however, the mutant strain (MIG1) showed reduced motility and increased sensitivity to novobiocin. Membrane preparations of MIG1 were enriched in two glycoproteins, identified as the S-layer glycoprotein and an ABC transporter component. The H. volcanii S-layer glycoprotein has been extensively used as a model to study haloarchaeal protein N-glycosylation. HPLC analysis of oligosaccharides released from the S-layer glycoprotein after PNGase treatment revealed that MIG1 was enriched in species with lower retention times than those derived from the parent strain. Mass spectrometry analysis showed that the wild type glycoprotein released a novel oligosaccharide species corresponding to GlcNAc-GlcNAc(Hex)2-(SQ-Hex)6 in contrast to the mutant protein, which contained the shorter form GlcNAc2(Hex)2-SQ-Hex-SQ. A glycoproteomics approach of the wild type glycopeptide fraction revealed Asn-732 peptide fragments linked to the sulfoquinovose-containing oligosaccharide. This work describes a novel N-linked oligosaccharide containing a repeating SQ-Hex unit bound to Asn-732 of the H. volcanii S-layer glycoprotein, a position that had not been reported as glycosylated. Furthermore, this study provides the first insight on the biological role of rhomboid proteases in Archaea, suggesting a link between protein glycosylation and this protease family.

  8. Tailor-Made Boronic Acid Functionalized Magnetic Nanoparticles with a Tunable Polymer Shell-Assisted for the Selective Enrichment of Glycoproteins/Glycopeptides.

    Science.gov (United States)

    Zhang, Xihao; Wang, Jiewen; He, Xiwen; Chen, Langxing; Zhang, Yukui

    2015-11-11

    Biomedical sciences, and in particular biomarker research, demand efficient glycoproteins enrichment platforms. In this work, we present a facile and time-saving method to synthesize phenylboronic acid and copolymer multifunctionalized magnetic nanoparticles (NPs) using a distillation-precipitation polymerization (DPP) technique. The polymer shell is obtained through copolymerization of two monomers-affinity ligand 3-acrylaminophenylboronic acid (AAPBA) and a hydrophilic functional monomer. The resulting hydrophilic Fe3O4@P(AAPBA-co-monomer) NPs exhibit an enhanced binding capacity toward glycoproteins by an additional functional monomer complementary to the surface presentation of the target protein. The effects of monomer ratio of AAPBA to hydrophilic comonomers on the binding of glycoproteins are systematically investigated. The morphology, structure, and composition of all the synthesized microspheres are characterized by transmission electron microscopy (TEM), X-ray powder diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), and vibrating sample magnetometer (VSM). The hydrophilic Fe3O4@P(AAPBA-co-monomer) microspheres show an excellent performance in the separation of glycoproteins with high binding capacity; And strong magnetic response allows them to be easily separated from solution in the presence of an external magnetic field. Moreover, both synthetic Fe3O4@P(AAPBA) and copolymeric NPs show good adsorption to glycoproteins in physiological conditions (pH 7.4). The Fe3O4@P(AAPBA-co-monomer) NPs are successfully utilized to selectively capture and identify the low-abundance glycopeptides from the tryptic digest of horseradish peroxidase (HRP). In addition, the selective isolation and enrichment of glycoproteins from the egg white samples at physiological condition is obtained by Fe3O4@P(AAPBA-co-monomer) NPs as adsorbents.

  9. Spiral CT of acute pulmonary thromboembolism: evaluation of pleuroparenchymal abnormalities.

    Science.gov (United States)

    Johnson, P T; Wechsler, R J; Salazar, A M; Fisher, A M; Nazarian, L N; Steiner, R M

    1999-01-01

    The goal of this work was to identify and categorize the spectrum of pulmonary parenchymal and pleural abnormalities identified by CT in patients with acute pulmonary thromboembolism (PE). A review of interpretations from 4,715 consecutive contrast-enhanced thoracic CT studies identified 41 examinations in which the diagnosis of PE was reported. Thirty-four studies were available for review, and two radiologists confirmed intraluminal defects in 31 patients. The number of emboli were counted and localized using bronchopulmonary nomenclature. Associated parenchymal and pleural abnormalities were tabulated. Of the 31 patients, 13 underwent confirmatory or correlative studies including angiography, radionuclide study, or autopsy. In addition, deep venous thrombosis was confirmed by ultrasound or MRI in 13 patients. An average of 7.5 emboli per patient was detected. Pleuroparenchymal findings were as follows: Nine patients (29%) had no acute pulmonary parenchymal or pleural abnormality. In the remaining 22 patients, pleural effusion was the most common abnormality, found in 14 of 31 (45%). Ten patients (32%) had peripheral wedge-shaped parenchymal opacities suggestive of pulmonary infarction. Normally enhancing lobar atelectasis was seen in nine patients (29%). Six patients (19%) demonstrated heterogeneous parenchymal enhancement within nonaerated lung, two of whom had pathologically proven pulmonary infarct. Thirteen of 31 patients underwent high resolution CT; a typical mosaic perfusion pattern was seen in only 1 patient. Twenty-nine percent of patients with acute PE had no acute lung parenchymal abnormality on CT; thus, the absence of parenchymal abnormality on CT does not exclude PE. High resolution CT mosaic perfusion was not a common feature of acute pulmonary embolism. Regions of decreased enhancement within nonaerated lung, seen in 19%, may prove to be an indicator of pulmonary infarction; however, this is a nonspecific finding.

  10. Computer simulation modeling of abnormal behavior: a program approach.

    Science.gov (United States)

    Reilly, K D; Freese, M R; Rowe, P B

    1984-07-01

    A need for modeling abnormal behavior on a comprehensive, systematic basis exists. Computer modeling and simulation tools offer especially good opportunities to establish such a program of studies. Issues concern deciding which modeling tools to use, how to relate models to behavioral data, what level of modeling to employ, and how to articulate theory to facilitate such modeling. Four levels or types of modeling, two qualitative and two quantitative, are identified. Their properties are examined and interrelated to include illustrative applications to the study of abnormal behavior, with an emphasis on schizophrenia.

  11. 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

  12. Incorporation of Spike and Membrane Glycoproteins into Coronavirus Virions

    Directory of Open Access Journals (Sweden)

    Makoto Ujike

    2015-04-01

    Full Text Available The envelopes of coronaviruses (CoVs contain primarily three proteins; the two major glycoproteins spike (S and membrane (M, and envelope (E, a non-glycosylated protein. Unlike other enveloped viruses, CoVs bud and assemble at the endoplasmic reticulum (ER-Golgi intermediate compartment (ERGIC. For efficient virion assembly, these proteins must be targeted to the budding site and to interact with each other or the ribonucleoprotein. Thus, the efficient incorporation of viral envelope proteins into CoV virions depends on protein trafficking and protein–protein interactions near the ERGIC. The goal of this review is to summarize recent findings on the mechanism of incorporation of the M and S glycoproteins into the CoV virion, focusing on protein trafficking and protein–protein interactions.

  13. 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

    OBJECTIVE: Tumor-associated antigens may be expressed as surface glycoproteins. These molecules undergo qualitative and quantitative modifications during cell differentiation and malignant transformation. During malignant transformation, incomplete glycosylation is common, and certain glycosylation...... pathways are preferred. These antigens might help distinguish between ovarian and colonic adenocarcinomas in the primary and metastatic lesions. Different cytokeratins have been proposed as relatively organ-specific antigens. DESIGN: We used monoclonal antibodies against T1, Tn, sialosyl-Tn, B72.3, CA125......, 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...

  14. Rheologic studies on middle ear effusions and their mucus glycoproteins.

    Science.gov (United States)

    FitzGerald, J E; Green, G G; Birchall, J P; Pearson, J P

    1989-04-01

    The properties of pooled thick and thin middle ear effusions, from children with otitis media with effusion, were studied by viscometry. Mucus glycoproteins were responsible for effusion viscosity. Their percentage by weight in thick and thin effusions was 25% and 8.2%, respectively. N-acetylcysteine and 0.2 mol/L of mercaptoethanol caused a 39% viscosity drop in a 5-mg/mL glycoprotein solution, whereas S-carboxymethylcysteine had no effect. Treatment of thick effusions with 0.2 mol/L of mercaptoethanol initially caused a viscosity decrease followed by a gradual increase. Higher reducing agent concentrations (0.5 mol/L) caused a more rapid decrease followed by a rapid increase, presumably by causing nonspecific aggregation of reduced protein molecules. These results suggest that the concentration of and the time that a mucolytic is in the middle ear would be of prime importance in achieving the desired decrease in viscosity.

  15. Mice deficient for the extracellular matrix glycoprotein tenascin-r show physiological and structural hallmarks of increased hippocampal excitability, but no increased susceptibility to seizures in the pilocarpine model of epilepsy.

    Science.gov (United States)

    Brenneke, F; Bukalo, O; Dityatev, A; Lie, A A

    2004-01-01

    Recognition molecules provide important cues for neuronal survival, axonal fasciculation, axonal pathfinding, synaptogenesis, synaptic plasticity, and regeneration. Our previous studies revealed a link between perisomatic inhibition and the extracellular matrix glycoprotein tenascin-R (TN-R). Therefore, we here studied neuronal excitability and epileptic susceptibility in mice constitutively deficient in TN-R. In vitro analysis of populational spikes in hippocampal slices of TN-R-deficient mice revealed a significant increase in multiple spikes in the CA1 region, as compared with wild-type mice. This difference between genotypes was only partially reduced after blockade of GABA(A) receptors with picrotoxin, indicating a deficit in GABAergic inhibition and an increase in intrinsic excitability of CA1 pyramidal cells in TN-R-deficient mice. Using a battery of immunohistochemical markers and histological stainings, we were able to identify two abnormalities in the hippocampus of TN-R-deficient mice possibly related to increased excitability: the high number of glial fibrillary acidic protein-positive astrocytes and low number of calretinin-positive interneurons in the CA1 and CA3 regions. In order to test whether the revealed abnormalities give rise to increased susceptibility to seizures in TN-R-deficient mice, we used the pilocarpine model of epilepsy. No genotype-specific differences were found with regard to the time-course of pilocarpine-induced and spontaneous seizures, neuronal cell loss, aberrant sprouting and distribution of synaptic and inhibitory interneuron markers. However, pilocarpine-induced astrogliosis and reduction in calretinin-positive interneurons were less pronounced in TN-R mutants, thereby resulting in an occlusion of effects induced by TN-R deficiency and pilocarpine. Thus, TN-R-deficient mutants show several electrophysiological and morphological hallmarks of increased neuronal excitability, which, however, do not give rise to more

  16. Surface-exposed glycoproteins of hyperthermophilic Sulfolobus solfataricus P2 show a common N-glycosylation profile.

    Science.gov (United States)

    Palmieri, Gianna; Balestrieri, Marco; Peter-Katalinić, Jasna; Pohlentz, Gottfried; Rossi, Mosè; Fiume, Immacolata; Pocsfalvi, Gabriella

    2013-06-07

    Cell surface proteins of hyperthermophilic Archaea actively participate in intercellular communication, cellular uptake, and energy conversion to sustain survival strategies in extreme habitats. Surface (S)-layer glycoproteins, the major component of the S-layers in many archaeal species and the best-characterized prokaryotic glycoproteins, were shown to have a large structural diversity in their glycan compositions. In spite of this, knowledge on glycosylation of proteins other than S-layer proteins in Archaea is quite limited. Here, the N-glycosylation pattern of cell-surface-exposed proteins of Sulfolobus solfataricus P2 were analyzed by lectin affinity purification, HPAEC-PAD, and multiple mass spectrometry-based techniques. Detailed analysis of SSO1273, one of the most abundant ABC transporters present in the cell surface fraction of S. solfataricus, revealed a novel glycan structure composed of a branched sulfated heptasaccharide, Hex4(GlcNAc)2 plus sulfoquinovose where Hex is d-mannose and d-glucose. Having one monosaccharide unit more than the glycan of the S-layer glycoprotein of S. acidocaldarius, this is the most complex archaeal glycan structure known today. SSO1273 protein is heavily glycosylated and all 20 theoretical N-X-S/T (where X is any amino acid except proline) consensus sequence sites were confirmed. Remarkably, we show that several other proteins in the surface fraction of S. solfataricus are N-glycosylated by the same sulfated oligosaccharide and we identified 56 N-glycosylation sites in this subproteome.

  17. 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.

  18. The cholesterol-binding motif of the HIV-1 glycoprotein gp41 regulates lateral sorting and oligomerization.

    Science.gov (United States)

    Schwarzer, Roland; Levental, Ilya; Gramatica, Andrea; Scolari, Silvia; Buschmann, Volker; Veit, Michael; Herrmann, Andreas

    2014-10-01

    Enveloped viruses often use membrane lipid rafts to assemble and bud, augment infection and spread efficiently. However, the molecular bases and functional consequences of the partitioning of viral glycoproteins into microdomains remain intriguing questions in virus biology. Here, we measured Foerster resonance energy transfer by fluorescence lifetime imaging microscopy (FLIM-FRET) to study the role of distinct membrane proximal regions of the human immunodeficiency virus glycoprotein gp41 for lipid raft partitioning in living Chinese hamster ovary cells (CHO-K1). Gp41 was labelled with a fluorescent protein at the exoplasmic face of the membrane, preventing any interference of the fluorophore with the proposed role of the transmembrane and cytoplasmic domains in lateral organization of gp41. Raft localization was deduced from interaction with an established raft marker, a fluorescently tagged glycophosphatidylinositol anchor and the cholesterol recognition amino acid consensus (CRAC) was identified as the crucial lateral sorting determinant in CHO-K1 cells. Interestingly, the raft association of gp41 indicates a substantial cell-to-cell heterogeneity of the plasma membrane microdomains. In complementary fluorescence polarization microscopy, a distinct CRAC requirement was found for the oligomerization of the gp41 variants. Our data provide further insight into the molecular basis and biological implications of the cholesterol dependent lateral sorting of viral glycoproteins for virus assembly at cellular membranes. © 2014 John Wiley & Sons Ltd.

  19. An analysis of amino acid sequences surrounding archaeal glycoprotein sequons

    OpenAIRE

    Mehtap Abu-Qarn; Jerry Eichler

    2006-01-01

    Despite having provided the first example of a prokaryal glycoprotein, little is known of the rules governing the N-glycosylation process in Archaea. As in Eukarya and Bacteria, archaeal N-glycosylation takes place at the Asn residues of Asn-X-Ser/Thr sequons. Since not all sequons are utilized, it is clear that other factors, including the context in which a sequon exists, affect glycosylation efficiency. As yet, t...

  20. Method for analysing glycoprotein isoforms by capillary electrophoresis

    OpenAIRE

    Frutos, Mercedes de; Díez-Masa, José Carlos; Morales-Cid, Gabriel

    2011-01-01

    [EN] The present invention relates to a new method for the purification, concentration, separation and determination of the isoforms of alpha-1-acid glycoprotein (AGP) in human blood serum samples using capillary electrophoresis. The new method is based on the immunocapture and preconcentration of the sample within the separation capillary by using an immunoadsorbent phase magnetically immobilized within the electrophoresis capillary and the subsequent desorption and separation of the glycopr...

  1. Pneumocystis carinii glycoprotein A binds macrophage mannose receptors.

    OpenAIRE

    O'Riordan, D.M.; Standing, J E; Limper, A H

    1995-01-01

    Pneumocystis carinii causes life-threatening pneumonia in patients with impaired immunity. Recent studies suggest that alveolar macrophages interact with P. carinii through macrophage mannose receptors. However, the ligand(s) on P. carinii that is recognized by these receptors has not been fully defined. P. carinii contains a major mannose-rich surface antigen complex termed glycoprotein A (gpA). It was therefore hypothesized that gpA binds directly to macrophage mannose receptors and mediate...

  2. Reelin glycoprotein: structure, biology and roles in health and disease.

    Science.gov (United States)

    Fatemi, S H

    2005-03-01

    Reelin glycoprotein is a secretory serine protease with dual roles in mammalian brain: embryologically, it guides neurons and radial glial cells to their corrected positions in the developing brain; in adult brain, Reelin is involved in a signaling pathway which underlies neurotransmission, memory formation and synaptic plasticity. Disruption of Reelin signaling pathway by mutations and selective hypermethylation of the Reln gene promoter or following various pre- or postnatal insults may lead to cognitive deficits present in neuropsychiatric disorders like autism or schizophrenia.

  3. Antibody Derived Peptides for Detection of Ebola Virus Glycoprotein

    OpenAIRE

    Luis Mario Rodríguez-Martínez; Alan Roberto Marquez-Ipiña; Felipe López-Pacheco; Roberto Pérez-Chavarría; Juan Carlos González-Vázquez; Everardo González-González; Grissel Trujillo-de Santiago; César Alejandro Ponce-Ponce de León; Yu Shrike Zhang; Mehmet Remzi Dokmeci; Ali Khademhosseini; Mario Moisés Alvarez

    2015-01-01

    Background: Current Ebola virus (EBOV) detection methods are costly and impractical for epidemic scenarios. Different immune-based assays have been reported for the detection and quantification of Ebola virus (EBOV) proteins. In particular, several monoclonal antibodies (mAbs) have been described that bind the capsid glycoprotein (GP) of EBOV GP. However, the currently available platforms for the design and production of full-length mAbs are cumbersome and costly. The use of antibody fragment...

  4. CHROMOSOMAL ABNORMALITIES IN PATIENTS WITH RECURRENT MISCARRIAGE

    Directory of Open Access Journals (Sweden)

    Daniela Mierla

    2012-06-01

    Full Text Available Chromosomal abnormalities are involved in the etiology of recurrent spontaneous pregnancy loss and sub-fertility. The purpose of this study was to determine the frequency and contribution of chromosomal abnormalities in recurrent miscarriages. The results obtained and literature review are helpful in understanding the importance of cytogenetics analysis of female infertility. To investigate the distribution of chromosomal abnormalities in the Romanian population with recurrent miscarriage, karyotype analysis by G-banding was performed from peripheral blood in 967 women infertility. Results: Chromosomal abnormalities were found to 79 women (8,17%. The percentage of chromosomal abnormalities in the studied population correlates with the data in the literature. Chromosomal abnormalities could play the important role in etiology of infertility and are more frequently detected in this group of patients compared to general population. In the infertile couples balanced chromosomal abnormalities are the main cause of spontaneous abortions.

  5. Mouse oviduct-specific glycoprotein is an egg-associated ZP3-independent sperm-adhesion ligand.

    Science.gov (United States)

    Lyng, Robert; Shur, Barry D

    2009-11-01

    Mouse sperm-egg binding requires a multiplicity of receptor-ligand interactions, including an oviduct-derived, high molecular weight, wheat germ agglutinin (WGA)-binding glycoprotein that associates with the egg coat at ovulation. Herein, we report the purification and identification of this sperm-binding ligand. WGA-binding, high molecular weight glycoproteins isolated from hormonally primed mouse oviduct lysates competitively inhibit sperm-egg binding in vitro. Within this heterogeneous glycoprotein preparation, a distinct 220 kDa protein selectively binds to sperm surfaces, and was identified by sequence analysis as oviduct-specific glycoprotein (OGP). The sperm-binding activity of OGP was confirmed by the loss of sperm-binding following immunodepletion of OGP from oviduct lysates, and by the ability of both immunoprecipitated OGP and natively purified OGP to competitively inhibit sperm-egg binding. As expected, OGP is expressed by the secretory cells of the fimbriae and infundibulum; however, in contrast to previous reports, OGP is also associated with both the zona pellucida and the perivitelline space of mouse oocytes. Western blot analysis and lectin affinity chromatography demonstrate that whereas the bulk of OGP remains soluble in the ampullar fluid, distinct glycoforms associate with the cumulus matrix, zona pellucida and perivitelline space. The sperm-binding activity of OGP is carbohydrate-dependent and restricted to a relatively minor peanut agglutinin (PNA)-binding glycoform that preferentially associates with the sperm surface, zona pellucida and perivitelline space, relative to other more abundant glycoforms. Finally, pretreatment of two-cell embryos, which do not normally bind sperm, with PNA-binding OGP stimulates sperm binding.

  6. A double responsive smart upconversion fluorescence sensing material for glycoprotein.

    Science.gov (United States)

    Guo, Ting; Deng, Qiliang; Fang, Guozhen; Yun, Yaguang; Hu, Yongjin; Wang, Shuo

    2016-11-15

    A novel strategy was developed to prepare double responsive smart upconversion fluorescence material for highly specific enrichment and sensing of glycoprotein. The novel double responsive smart sensing material was synthesized by choosing Horse radish peroxidase (HRP) as modal protein, the grapheme oxide (GO) as support material, upconversion nanoparticles (UCNPs) as fluorescence signal reporter, N-isopropyl acrylamide (NIPAAM) and 4-vinylphenylboronic acid (VPBA) as functional monomers. The structure and component of smart sensing material was investigated by transmission electron microscopy (TEM), Scanning electron microscopy (SEM), X-ray photoelectron spectroscopic (XPS) and Fourier transform infrared (FTIR), respectively. These results illustrated the smart sensing material was prepared successfully. The recognition characterizations of smart sensing material were evaluated, and results showed that the fluorescence intensity of smart sensing material was reduced gradually, as the concentration of protein increased, and the smart sensing material showed selective recognition for HRP among other proteins. Furthermore, the recognition ability of the smart sensing material for glycoprotein was regulated by controlling the pH value and temperature. Therefore, this strategy opens up new way to construct smart material for detection of glycoprotein.

  7. Characterization of an estrogen-induced oviduct membrane glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Poola, I.; Lucas, J.J.

    1986-05-01

    During estrogen-induced chick oviduct differentiation a number of N-linked membrane glycoproteins are induced as judged by GDP-(/sup 14/C)Man labeling of endogenous acceptors, /sup 125/I-con A labeling as well as coomassie blue and PAS staining of SDS polyacrylamide gels. The authors have begun to characterize one of these glycoproteins having an M/sub r/ of 91 KDa. The protein has been purified via preparative SDS-PAGE and electroelution. The purified protein migrates as a single band on analytical SDS-PAGE and comigrates with an endogenous membrane glycoprotein labeled with GDP-(/sup 14/C)Man. Amino acid analysis indicates a high proportion of GLU and ASP residues (110 and 66 moles respectively). N-terminal sequence analysis by gas phase instrumentation yielded the following: X-X-VAL-ASP-VAL-ASP-ALA-THR-VAL-GLU-GLU-ASP-GLU. The protein contains about 2% neutral sugar including 6 mol Man, 2 mol Gal, 1 mol Fuc, 4 mol GlcNAc, 1 mol GalNAc and 1 mol sialic acid per mole of protein. The presence of the GalNAc residue suggests the protein contains an O-linked oligosaccharide moiety in addition to the N-linked chain(s). The detailed structure of the carbohydrate moieties is currently under investigation.

  8. 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.

  9. 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.

  10. Platelet membrane glycoproteins and their function: an overview.

    Science.gov (United States)

    Kunicki, T J

    1989-07-01

    The membrane glycoproteins (GP) of human platelets act as receptors that mediate two important functions, adhesion to the subendothelial matrix and platelet-platelet cohesion, or aggregation. Many of these glycoprotein receptors exist as noncovalently linked heterodimers, including those that belong to the supergene family of adhesion receptors called the integrins. Human platelets contain at least five members of this integrin family, including a collagen receptor (GP Ia-IIa; alpha 2, beta 1), a fibronectin receptor (GP Ic-IIa; alpha 5, beta 1), a laminin receptor (GP Ic'-IIa; alpha 6, beta 1), a vitronectin receptor (VnR; alpha v, beta 3), and a promiscuous, activation-dependent receptor that is thought to be the receptor most responsible for fibrinogen-dependent, platelet-platelet cohesion (GP IIb-IIIa; alpha IIb, beta 3). Some, but not all, of the integrins bind to a tripeptide sequence, arginine-glycine-aspartic acid (RGD), on the adhesive proteins. In addition to the integrins, platelets contain other membrane glyco-proteins: GP Ib-IX, a receptor for von Willebrand factor, which is thought to be the receptor most responsible for platelet adhesion to the subendothelial matrix in a flowing system; GP V, which may be associated with GP Ib-IX and whose function remains unknown; and GP IV (GP IIIb), which functions as a receptor for thrombospondin and collagen.

  11. Role of sialidase in glycoprotein utilization by Tannerella forsythia.

    Science.gov (United States)

    Roy, Sumita; Honma, Kiyonobu; Douglas, C W Ian; Sharma, Ashu; Stafford, Graham P

    2011-11-01

    The major bacterial pathogens associated with periodontitis include Tannerella forsythia. We previously discovered that sialic acid stimulates biofilm growth of T. forsythia, and that sialidase activity is key to utilization of sialoconjugate sugars and is involved in host-pathogen interactions in vitro. The aim of this work was to assess the influence of the NanH sialidase on initial biofilm adhesion and growth in experiments where the only source of sialic acid was sialoglycoproteins or human oral secretions. After showing that T. forsythia can utilize sialoglycoproteins for biofilm growth, we showed that growth and initial adhesion with sialylated mucin and fetuin were inhibited two- to threefold by the sialidase inhibitor oseltamivir. A similar reduction (three- to fourfold) was observed with a nanH mutant compared with the wild-type. Importantly, these data were replicated using clinically relevant serum and saliva samples as substrates. In addition, the ability of the nanH mutant to form biofilms on glycoprotein-coated surfaces could be restored by the addition of purified NanH, which we show is able to cleave sialic acid from the model glycoprotein fetuin and, much less efficiently, 9-O-acetylated bovine submaxillary mucin. These data show for the first time that glycoprotein-associated sialic acid is likely to be a key in vivo nutrient source for T. forsythia when growing in a biofilm, and suggest that sialidase inhibitors might be useful adjuncts in periodontal therapy.

  12. Abnormalities of the upper extremities on fetal magnetic resonance imaging.

    Science.gov (United States)

    Nemec, S F; Kasprian, G; Brugger, P C; Bettelheim, D; Amann, G; Nemec, U; Rotmensch, S; Graham, J M; Rimoin, D L; Lachman, R S; Prayer, D

    2011-11-01

    In view of the increasing use of fetal magnetic resonance imaging (MRI) as an adjunct to prenatal ultrasonography, we sought to demonstrate the visualization of upper extremity abnormalities and associated defects on MRI, with regard to fetal outcomes and compared with ultrasound imaging. This retrospective study included 29 fetuses with upper extremity abnormalities visualized with fetal MRI following suspicious ultrasound findings and confirmed by postnatal assessment or autopsy. On a 1.5-Tesla unit, dedicated sequences were applied to image the extremities. Central nervous system (CNS) and extra-CNS anomalies were assessed to define extremity abnormalities as isolated or as complex, with associated defects. Fetal outcome was identified from medical records. MRI and ultrasound findings, when available, were compared. Isolated upper extremity abnormalities were found in three (10.3%) fetuses. In 26 (89.7%) fetuses complex abnormalities, including postural extremity disorders (21/26) and structural extremity abnormalities (15/26), were demonstrated. Associated defects involved: face (15/26); musculoskeletal system (14/26); thorax and cardio/pulmonary system (12/26); lower extremities (12/26); brain and skull (10/26); and abdomen (8/26). Of the 29 cases, 18 (62.1%) pregnancies were delivered and 11 (37.9%) were terminated. MRI and US findings were compared in 27/29 cases: the diagnosis was concordant in 14 (51.9%) of these cases, and additional findings were made on MRI in 13/27 (48.1%) cases. Visualization of upper extremity abnormalities on fetal MRI enables differentiation between isolated defects and complex ones, which may be related to poor fetal prognosis. MRI generally confirms the ultrasound diagnosis, and may provide additional findings in certain cases. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

  13. Abnormal Returns and Contrarian Strategies

    Directory of Open Access Journals (Sweden)

    Ivana Dall'Agnol

    2003-12-01

    Full Text Available We test the hypothesis that strategies which are long on portfolios of looser stocks and short on portfolios of winner stocks generate abnormal returns in Brazil. This type of evidence for the US stock market was interpreted by The Bondt and Thaler (1985 as reflecting systematic evaluation mistakes caused by investors overreaction to news related to the firm performance. We found evidence of contrarian strategies profitability for horizons from 3 months to 3 years in a sample of stock returns from BOVESPA and SOMA from 1986 to 2000. The strategies are more profitable for shorter horizons. Therefore, there was no trace of the momentum effect found by Jagadeesh and Titman (1993 for the same horizons with US data. There are remaing unexplained positive returns for contrarian strategies after accounting for risk, size, and liquidity. We also found that the strategy profitability is reduced after the Real Plan, which suggests that the Brazilian stock market became more efficient after inflation stabilization.

  14. [Cytogenetic abnormalities and gene mutations in myeloid leukemia].

    Science.gov (United States)

    Kato, Naoko; Kitamura, Toshio

    2009-10-01

    Myeloid leukemia is a clinically and genetically heterogeneous disease. Cytogenetic studies have revealed specific chromosomal abnormalities, such as translocations, and inversions. Fusion proteins derived from these abnormalities were identified in various subtypes of leukemia. Because most of these fusion proteins were not sufficient to induce leukemia by themselves in mouse models, additional oncogenic events have been thought to be necessary for leukemogenesis. Recently, a hypothesis called "two-hit model" for leukemia has been proposed. Two broad classes of mutations that proliferative or survival advantage of hematopoietic progenitors and impaired differentiation are required for inducing leukemia. In this article, we summarize some typical chromosomal abnormalities or gene mutations associated with myeloid leukemia on the basis of this hypothesis.

  15. Screening for chromosomal abnormalities in 2650 infertile couples undergoing ICSI.

    Science.gov (United States)

    Kayed, Hesham F; Mansour, Ragaa T; Aboulghar, Mohamed A; Serour, Gamal I; Amer, Alaa E; Abdrazik, Ashraf

    2006-03-01

    Chromosomal abnormalities are the major contributor to the genetic risks of infertility treatment associated with intracytoplasmic sperm injection (ICSI). The study objective was to assess prospectively the frequency of chromosomal aberrations in couples undergoing ICSI. A total of 2650 infertile couples (5300 patients) underwent chromosome analysis before undergoing ICSI in the Egyptian IVF-ET Centre. Heparinized blood samples were cultured, harvested and banded according to standard methods. Overall, 96.94% of the patients studied (5138/5300) had a normal karyotype, while the remaining 162 patients (3.06%) had an abnormal karyotype. Male patients constituted the majority of abnormalities; 138 males (85.19%) and 24 females (14.81%). These chromosomal aberrations included 117 cases (2.2%) of sex chromosome abnormalities; 113 males and four females. Forty-five patients (0.85%) had autosomal aberrations; 25 of them were males and 20 were females. The current data show that chromosomal abnormalities affect 3.06% of infertile patients, and occur in both sexes, but more predominantly in males undergoing ICSI for male factor infertility. It is recommended that chromosomal analysis be performed before undergoing ICSI, to identify patients who can be offered preimplantation genetic diagnosis.

  16. 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.

  17. EVALUATION OF STRIDOR AND ABNORMAL CRY IN INFANTS

    Directory of Open Access Journals (Sweden)

    Sridhar Reddy

    2016-05-01

    Full Text Available INTRODUCTION Turbulent flow due to partial obstruction of the airway gives rise to abnormal or unwanted noise. Noise originating in the larynx or trachea is typically high-pitched and termed ‘stridor’. Laryngomalacia is the most common congenital cause of stridor in infants. In this study, we have analysed the cases of stridor and abnormal cry in infants that have presented to our institute over a span of one year. AIM To identify the causes of stridor and abnormal cry in infants presenting to our institute. MATERIALS AND METHODS This is a retrospective study of 50 cases of stridor and abnormal cry in infants that presented at a Tertiary Care ENT Hospital in South India from Jan 2015 to Dec 2015. Children below the age of 12 months that presented to our department with stridor and abnormal cry were included in our study. RESULTS The cases were evaluated in terms of Age, Sex ratio, Aetiology and Presenting features and statistically analysed. CONCLUSION The sheer volume of paediatric cases presenting with airway problems and other disease entities necessitates the need for establishment of a dedicated Paediatric ENT wing in every Tertiary Care Hospital.

  18. Sensitivity of P-glycoprotein tryptophan residues to benzodiazepines and ATP interaction.

    Science.gov (United States)

    Lima, Sofia A C; Cordeiro-da-Silva, Anabela; de Castro, Baltazar; Gameiro, Paula

    2007-01-01

    Plasma membrane P-glycoprotein is a member of the ATP-binding cassette family of membrane transporters. In the present study tryptophan intrinsic fluorescence was used to understand the P-glycoprotein response to three benzodiazepines (bromazepam, chlordiazepoxide and flurazepam) in the presence and absence of ATP. Fluorescence emission spectra showed a red shift on the maximal emission wavelength upon interaction of P-glycoprotein with all benzodiazepines. Benzodiazepine association with nucleotide-bound P-glycoprotein also showed this trend and the quenching profile was attributed to a sphere-of-action model, for static fluorescence. Furthermore, quenching data of benzodiazepine-bound P-glycoprotein with ATP were concentration dependent and saturable, indicating that nucleotide binds to P-glycoprotein whether drug is present or not. These results seems in agreement with the proposal of the ATP-switch model by Higgins and Linton, where substrate binding to the transporters initiates the transport cycle by increasing the ATP binding affinity.

  19. Alpha1-acid glycoprotein post-translational modifications: a comparative two dimensional electrophoresis based analysis

    Directory of Open Access Journals (Sweden)

    P. Roncada

    2010-04-01

    Full Text Available Alpha1-acid glycoprotein (AGP is an immunomodulatory protein expressed by hepatocytes in response to the systemic reaction that follows tissue damage caused by inflammation, infection or trauma. A proteomic approach based on two dimensional electrophoresis, immunoblotting and staining of 2DE gels with dyes specific for post-translational modifications (PTMs such as glycosylation and phosphorylation has been used to evaluate the differential interspecific protein expression of AGP purified from human, bovine and ovine sera. By means of these techniques, several isoforms have been identified in the investigated species: they have been found to change both with regard to the number of isoforms expressed under physiological condition and with regard to the quality of PTMs (i.e. different oligosaccharidic chains, presence/absence of phosphorilations. In particular, it is suggested that bovine serum AGP may have one of the most complex pattern of PTMs among serum proteins of mammals studied so far.

  20. 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

    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...... 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...

  1. Expression of the glycoprotein gene from a fish rhabdovirus by using baculovirus vectors

    Energy Technology Data Exchange (ETDEWEB)

    Koener, J.F.; Leong, J.A.C. (Oregon State Univ., Corvallis (United States))

    1990-01-01

    A cDNA fragment containing the gene encoding the glycoprotein of infectious hematopoietic necrosis virus was inserted into Autographa californica baculovirus vectors under the control of the polyhedrin promoter. A 66-kilodalton protein, identical in size to the glycosylated glycoprotein of infectious hematopoietic necrosis virus, was expressed at high levels in Spodoptera frugiperda cells infected with the recombinant viruses. The expressed protein reacted with antiserum to the glycoprotein on Western blots.

  2. Monensin and FCCP inhibit the intracellular transport of alphavirus membrane glycoproteins

    OpenAIRE

    Kaariainen, L; Hashimoto, K.; Saraste, J; Virtanen, I; Penttinen, K

    1980-01-01

    Temperature-sensitive mutants of semliki forest virus (SFV) and sindbis virus (SIN) were used to study the intracellular transport of virus membrane glycoproteins in infected chicken embryo fibroblasts. When antisera against purified glycoproteins and (125)I- labeled protein A from staphylococcus aureus were used only small amounts of virus glycoproteins were detected at the surface of SFV ts-1 and SIN Ts-10 infected cells incubated at the restrictive temperature (39 degrees C). When the muta...

  3. Biochemical abnormalities in Pearson syndrome.

    Science.gov (United States)

    Crippa, Beatrice Letizia; Leon, Eyby; Calhoun, Amy; Lowichik, Amy; Pasquali, Marzia; Longo, Nicola

    2015-03-01

    Pearson marrow-pancreas syndrome is a multisystem mitochondrial disorder characterized by bone marrow failure and pancreatic insufficiency. Children who survive the severe bone marrow dysfunction in childhood develop Kearns-Sayre syndrome later in life. Here we report on four new cases with this condition and define their biochemical abnormalities. Three out of four patients presented with failure to thrive, with most of them having normal development and head size. All patients had evidence of bone marrow involvement that spontaneously improved in three out of four patients. Unique findings in our patients were acute pancreatitis (one out of four), renal Fanconi syndrome (present in all patients, but symptomatic only in one), and an unusual organic aciduria with 3-hydroxyisobutyric aciduria in one patient. Biochemical analysis indicated low levels of plasma citrulline and arginine, despite low-normal ammonia levels. Regression analysis indicated a significant correlation between each intermediate of the urea cycle and the next, except between ornithine and citrulline. This suggested that the reaction catalyzed by ornithine transcarbamylase (that converts ornithine to citrulline) might not be very efficient in patients with Pearson syndrome. In view of low-normal ammonia levels, we hypothesize that ammonia and carbamylphosphate could be diverted from the urea cycle to the synthesis of nucleotides in patients with Pearson syndrome and possibly other mitochondrial disorders.

  4. Semen abnormalities with SSRI antidepressants.

    Science.gov (United States)

    2015-01-01

    Despite decades of widespread use, the adverse effect profile of "selective" serotonin reuptake inhibitor (SSRI) antidepressants has still not been fully elucidated. Studies in male animals have shown delayed sexual development and reduced fertility. Three prospective cohort studies conducted in over one hundred patients exposed to an SSRI for periods ranging from 5 weeks to 24 months found altered semen param-eters after as little as 3 months of exposure: reduced sperm concentration, reduced sperm motility, a higher percentage of abnormal spermatozoa, and increased levels of sperm DNA fragmentation. One clinical trial showed growth retardation in children considered depressed who were exposed to SSRls. SSRls may have endocrine disrupting properties. Dapoxetine is a short-acting serotonin reuptake inhibitor that is chemically related to fluoxetine and marketed in the European Union for men complaining of premature ejaculation. But the corresponding European summary of product characteristics does not mention any effects on fertility. In practice, based on the data available as of mid-2014, the effects of SSRI exposure on male fertility are unclear. However, it is a risk that should be taken into account and pointed out to male patients who would like to father a child or who are experiencing fertility problems.

  5. Hemostatic abnormalities in liver cirrhosis

    Directory of Open Access Journals (Sweden)

    Kendal YALÇIN

    2009-06-01

    Full Text Available In this study, 44 patients with liver cirrhosis were investigated for hemostatic parameters. Patients with spontaneous bacterial peritonitis, hepatocellular carcinoma, hepatorenal syndrome and cholestatic liver diseases were excluded. Patients were classified by Child-Pugh criterion and according to this 4 patients were in Class A, 20 in Class B and 20 in C. Regarding to these results, it was aimed to investigate the haematological disturbances in liver cirrhotic patients.In the result there was a correlation between activated partial thromboplastin time, serum iron, ferritin, transferrin, haptoglobin and Child-Pugh classification. Besides there was no correlation between prothrombin time, factor 8 and 9, protein C and S, anti-thrombin 3, fibrinogen, fibrin degradation products, serum iron binding capacity, hemoglobin, leukocyte, mean corpuscular volume and Child-Pugh classification.There were significant difference, in terms of AST, ferritin, haptoglobulin, sex and presence of ascites between groups (p0.05. In the summary, we have found correlation between hemostatic abnormalities and disease activity and clinical prognosis in patients with liver cirrhosis which is important in the management of these patients. This is also important for identification of liver transplant candidiates earlier.

  6. Identifying potential virulence determinants in viral haemorrhagic septicaemia virus (VHSV) for rainbow trout

    DEFF Research Database (Denmark)

    Campbell, Scott; Collet, Bertrand; Einer-Jensen, Katja

    2009-01-01

    We identified viral haemorrhagic septicaemia virus (VHSV) isolates classified within Genotype Ib which are genetically similar (>99.4% glycoprotein amino acid identity) yet, based on their isolation history, were suspected to differ in virulence in juvenile rainbow trout. The virulence of an isol......We identified viral haemorrhagic septicaemia virus (VHSV) isolates classified within Genotype Ib which are genetically similar (>99.4% glycoprotein amino acid identity) yet, based on their isolation history, were suspected to differ in virulence in juvenile rainbow trout. The virulence...... the same experimental infection routes (...

  7. [Renal abnormalities in ankylosing spondylitis].

    Science.gov (United States)

    Samia, Barbouch; Hazgui, Faiçal; Abdelghani, Khaoula Ben; Hamida, Fethi Ben; Goucha, Rym; Hedri, Hafedh; Taarit, Chokri Ben; Maiz, Hedi Ben; Kheder, Adel

    2012-07-01

    We will study the epidemiologic, clinical, biological, therapeutic, prognostic characteristics and predictive factors of development of nephropathy in ankylosing spondylitis patients. We retrospectively reviewed the medical record of 32 cases with renal involvement among 212 cases of ankylosing spondylitis followed in our service during the period spread out between 1978 and 2006. The renal involvement occurred in all patients a mean of 12 years after the clinical onset of the rheumatic disease. Thirty-two patients presented one or more signs of renal involvement: microscopic hematuria in 22 patients, proteinuria in 23 patients, nephrotic syndrome in 11 patients and decreased renal function in 24 patients (75%). Secondary renal amyloidosis (13 patients), which corresponds to a prevalence of 6,1% and tubulointerstitial nephropathy (7 patients) were the most common cause of renal involvement in ankylosing spondylitis followed by IgA nephropathy (4 patients). Seventeen patients evolved to the end stage renal disease after an average time of 29.8 ± 46 months. The average follow-up of the patients was 4,4 years. By comparing the 32 patients presenting a SPA and renal disease to 88 with SPA and without nephropathy, we detected the predictive factors of occurred of nephropathy: tobacco, intense inflammatory syndrome, sacroileite stage 3 or 4 and presence of column bamboo. The finding of 75% of the patients presented a renal failure at the time of the diagnosis of renal involvement suggests that evidence of renal abnormality involvement should be actively sought in this disease. Copyright © 2011 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  8. Platelet enzyme abnormalities in leukemias

    Directory of Open Access Journals (Sweden)

    S Sharma

    2011-01-01

    Full Text Available Aim of the Study: The aim of this study was to evaluate platelet enzyme activity in cases of leukemia. Materials and Methods: Platelet enzymes glucose-6-phosphate dehydrogenase (G6PD, pyruvate kinase (PK and hexokinase (HK were studied in 47 patients of acute and chronic leukemia patients, 16 patients with acute myeloid leukemia (AML(13 relapse, three in remission, 12 patients with acute lymphocytic leukemia (ALL (five in relapse, seven in remission, 19 patients with chronic myeloid leukemia (CML. Results: The platelet G6PD activity was significantly low in cases of AML, ALL and also in CML. G6PD activity was normalized during AML remission. G6PD activity, although persistently low during ALL remission, increased significantly to near-normal during remission (P < 0.05 as compared with relapse (P < 0.01. Platelet PK activity was high during AML relapse (P < 0.05, which was normalized during remission. Platelet HK however was found to be decreased during all remission (P < 0.05. There was a significant positive correlation between G6PD and PK in cases of AML (P < 0.001 but not in ALL and CML. G6PD activity did not correlate with HK activity in any of the leukemic groups. A significant positive correlation was however seen between PK and HK activity in cases of ALL remission (P < 0.01 and CML (P < 0.05. Conclusions: Both red cell and platelet enzymes were studied in 36 leukemic patients and there was no statistically significant correlation between red cell and platelet enzymes. Platelet enzyme defect in leukemias suggests the inherent abnormality in megakaryopoiesis and would explain the functional platelet defects in leukemias.

  9. Genes and brain malformations associated with abnormal neuron positioning.

    Science.gov (United States)

    Moffat, Jeffrey J; Ka, Minhan; Jung, Eui-Man; Kim, Woo-Yang

    2015-11-05

    Neuronal positioning is a fundamental process during brain development. Abnormalities in this process cause several types of brain malformations and are linked to neurodevelopmental disorders such as autism, intellectual disability, epilepsy, and schizophrenia. Little is known about the pathogenesis of developmental brain malformations associated with abnormal neuron positioning, which has hindered research into potential treatments. However, recent advances in neurogenetics provide clues to the pathogenesis of aberrant neuronal positioning by identifying causative genes. This may help us form a foundation upon which therapeutic tools can be developed. In this review, we first provide a brief overview of neural development and migration, as they relate to defects in neuronal positioning. We then discuss recent progress in identifying genes and brain malformations associated with aberrant neuronal positioning during human brain development.

  10. Monensin and FCCP inhibit the intracellular transport of alphavirus membrane glycoproteins.

    Science.gov (United States)

    Kääriäinen, L; Hashimoto, K; Saraste, J; Virtanen, I; Penttinen, K

    1980-12-01

    Temperature-sensitive mutants of semliki forest virus (SFV) and sindbis virus (SIN) were used to study the intracellular transport of virus membrane glycoproteins in infected chicken embryo fibroblasts. When antisera against purified glycoproteins and (125)I- labeled protein A from staphylococcus aureus were used only small amounts of virus glycoproteins were detected at the surface of SFV ts-1 and SIN Ts-10 infected cells incubated at the restrictive temperature (39 degrees C). When the mutant-infected cells were shifted to the permissive temperature (28 degrees C), in the presence of cycloheximide, increasing amounts of virus glycoproteins appeared at the cell surface from 20 to 80 min after the shift. Both monensin (10muM) and carbonylcyanide-p- trifluoromethoxyphenylhydrazone (FCCP; 10-20 muM) inhibited the appearance of virus membrane glycoproteins at the cell surface. Vinblastine sulfate (10 mug/ml) inhibited the transport by approximately 50 percent, whereas cytochalasin B (1 mug/ml) had only a marginal effect. Intracellular distribution of virus glycoproteins in the mutant-infected cells was visualized in double-fluorescence studies using lectins as markers for endoplasmic reticulum and Golgi apparatus. At 39 degrees C, the virus membrane glycoproteins were located at the endoplasmic reticulum, whereas after shift to 28 degrees C, a bright juxtanuclear reticular fluorescence was seen in the location of the Golgi apparatus. In the presence of monensin, the virus glycoproteins could migrate to the Golgi apparatus, although transport to the cell surface did not take place. When the shift was carried out in the presence of FCCP, negligible fluorescence was seen in the Golgi apparatus and the glycoproteins apparently remained in the rough endoplasmic reticulum. A rapid inhibition in the accumulation of virus glycoproteins at the cell surface was obtained when FCCP was added during the active transport period, whereas with monensin there was a delay of

  11. Abnormal Raman spectral phenomenon of silicon nanowires

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The Raman spectra of two one-dimensional silicon nanowire samples with different excitation wavelengths were measured and an abnormal phenomenon was discovered that the Raman spectral features change with the wavelengths of excitation. Closer analysis of the crystalline structure of samples and the changes in Raman spectral features showed that the abnormal behavior is the result of resonance Raman scattering selection effect.

  12. An Abnormal Vibrational Mode of Torsion Pendulum

    Institute of Scientific and Technical Information of China (English)

    赵亮; 涂英; 顾邦明; 胡忠坤; 罗俊

    2003-01-01

    In the experiment for the determination of the gravitational constant G, we found an abnormal vibrational mode of the torsion pendulum. The abnormal mode disappeared as a magnetic damper was introduced to the torsion pendulum system. Our experimental results also show that the magnetic damper can be used to suppress the high frequency vibrational noises to torsion pendulums effectively.

  13. Nail abnormalities in patients with vitiligo*

    Science.gov (United States)

    Topal, Ilteris Oguz; Gungor, Sule; Kocaturk, Ozgur Emek; Duman, Hatice; Durmuscan, Mustafa

    2016-01-01

    Background Vitiligo is an acquired pigmentary skin disorder affecting 0.1-4% of the general population. The nails may be affected in patients with an autoimmune disease such as psoriasis, and in those with alopecia areata. It has been suggested that nail abnormalities should be apparent in vitiligo patients. Objective We sought to document the frequency and clinical presentation of nail abnormalities in vitiligo patients compared to healthy volunteers. We also examined the correlations between nail abnormalities and various clinical parameters. Methods This study included 100 vitiligo patients and 100 healthy subjects. Full medical histories were collected from the subjects, who underwent thorough general and nail examinations. All nail changes were noted. In the event of clinical suspicion of a fungal infection, additional mycological investigations were performed. Results Nail abnormalities were more prevalent in the patients (78%) than in the controls (55%) (p=0.001). Longitudinal ridging was the most common finding (42%), followed by (in descending order): leukonychia, an absent lunula, onycholysis, nail bed pallor, onychomycosis, splinter hemorrhage and nail plate thinning. The frequency of longitudinal ridging was significantly higher in patients than in controls (p<0.001). Conclusions Nail abnormalities were more prevalent in vitiligo patients than in controls. Systematic examination of the nails in such patients is useful because nail abnormalities are frequent. However, the causes of such abnormalities require further study. Longitudinal ridging and leukonychia were the most common abnormalities observed in this study. PMID:27579738

  14. An Abnormal Psychology Community Based Interview Assignment

    Science.gov (United States)

    White, Geoffry D.

    1977-01-01

    A course option in abnormal psychology involves students in interviewing and observing the activities of individuals in the off-campus community who are concerned with some aspect of abnormal psychology. The technique generates student interest in the field when they interview people about topics such as drug abuse, transsexualism, and abuse of…

  15. [CHROMOSOMAL ABNORMALITIES IN PATIENTS WITH INFERTILITY].

    Science.gov (United States)

    Pylyp, L Y; Spinenko, L O; Verhoglyad, N V; Kashevarova, O O; Zukin, V D

    2015-01-01

    To assess the frequency and structure of chromosomal abnormalities in patients with infertility, a retrospective analysis of cytogenetic studies of 3414 patients (1741 females and 1673 males), referred to the Clinic of reproductive medicine "Nadiya" from 2007 to 2012, was performed. Chromosomal abnormalities were detected in 2.37% patients: 2.79% in males and 1.95% in females. Balanced structural chromosomal abnormalities prevailed over numerical abnormalities and corresponded to 80.2% of all chromosomal abnormalities detected in the studied group. Sex chromosome abnormalities made up 23.5% of chromosomal pathology (19/81) and included gonosomal aneuploidies in 84% of cases (16/19) and structural abnormalities of chromosome Y in 16% of cases (3/19). The low level sex chromosome mosaicism was detected with the frequency of 0.55%. Our results highlight the importance of cytogenetic studies in patients seeking infertility treatment by assisted reproductive technologies, since an abnormal finding not only provide a firm diagnosis to couples with infertility, but also influences significantly the approach to infertility treatment in such patients.

  16. Expression of CD1d protein in human testis showing normal and abnormal spermatogenesis.

    Science.gov (United States)

    Adly, Mohamed A; Abdelwahed Hussein, Mahmoud-Rezk

    2011-05-01

    CD1d is a member of CD1 family of transmembrane glycoproteins, which represent antigen-presenting molecules. Immunofluorescent staining methods were utilized to examine expression pattern of CD1d in human testicular specimens. In testis showing normal spermatogenesis, a strong CD1d cytoplasmic expression was seen the Sertoli cells, spermatogonia, and Leydig cells. A moderate expression was observed in the spermatocytes. In testes showing maturation arrest, CD1d expression was strong in the Sertoli cells and weak in spermatogonia and spermatocytes compared to testis with normal spermatogenesis. In Sertoli cell only syndrome, CD1d expression was strong in the Sertoli and Leydig cells. This preliminary study displayed testicular infertility-related changes in CD1d expression. The ultrastructural changes associated with with normal and abnormal spermatogenesis are open for further investigations.

  17. Postoperative cardiac arrest in children with congenital heart abnormalities

    OpenAIRE

    2013-01-01

    BACKGROUND The exact survival rates and markers of survival after postoperative cardiac arrest in children with congenital heart abnormalities are unknown. METHODS In this one-year study, we identified children younger than seven years of age with postoperative cardiac arrest in our pediatric cardiac intensive care unit database. Parameters from perioperative, pre-arrest, and resuscitation periods were analyzed for these patients. Comparisons were made between survivors and non-survivors afte...

  18. Endocrine abnormalities in dilated cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Ankit Jain

    2015-01-01

    Full Text Available Background: Progress has been made in the understanding of cellular and molecular mechanisms of hormone action and its effects on the cardiac tissue. There is evidence from observational studies that patients with postpartum cardiomyopathy improve after inhibition of release of prolactin from the pituitary by bromocriptine. This has renewed interest in the role of hormones in the pathogenesis of cardiomyopathy, especially in women. We intended to assess the hormonal changes in female patients with dilated cardiomyopathy (DCM. Methods: Twenty female patients aged 20-40 years old (mean age 29 ΁ 5.6 years with a diagnosis of idiopathic DCMP with left ventricular ejection fraction [EF] <35% and a stable clinical course in the last 3 months were included in the study. All the patients were in New York Heart Association (NYHA Class II or III. All the patients underwent clinical evaluation followed by blood sampling for hormonal analysis. Blood was taken after overnight fasting and analyzed for thyroid stimulating hormone (TSH, T3, T4, insulin-like growth factor I (IGF-I, prolactin, insulin, parathyroid hormone (PTH, and 25 (OH Vitamin D. The results were compared with twenty age and sex matched controls. Results: The mean EF of the twenty patients was 24.4 ΁ 5.3% and duration of symptoms was 29.1 ΁ 24 months. Insulin growth factor 1 levels were significantly lower than normal. Fifty percent of the patients had levels lower than normal, but there was no correlation of IGF-I with NYHA class and EF. Testing of the thyroid hormones revealed that TSH levels were similar between patient and controls though 40% of the patients had elevated TSH levels. Of these patients, 5% (1 had hypothyroid. In addition to this, 10% (2 had isolated low T3, suggestive of the low T3 syndrome. None of the thyroid abnormalities showed a correlation with NYHA class or EF. All other hormone concentrations were comparable in both groups. Conclusion: In this cohort of female

  19. Liver abnormalities and endocrine diseases.

    Science.gov (United States)

    Burra, Patrizia

    2013-08-01

    The liver and its pleotropic functions play a fundamental role in regulating metabolism, and is also an inevitable target of multiple metabolic disorders. The numerous and constant relationships and feedback mechanisms between the liver and all endocrine organs is reflected by the fact that an alteration of one oftentimes results in the malfunction of the other. Hypo- and hyperthyroidism are frequently associated with hepatic alterations, and thyroid diseases must be excluded in transaminase elevation of unknown cause. Drugs such as propylthiouracil, used in the treatment of hyperthyroidism, may induce liver damage, and other drugs such as amiodarone, carbamazepine, and several chemotherapeutic agents can lead to both thyroid and liver abnormalities. Liver diseases such as hepatitis, hepatocellular carcinoma, and cirrhosis may cause altered levels of thyroid hormones, and alcoholic liver disease, both due to the noxious substance ethanol as well as to the hepatic damage it causes, may be responsible for altered thyroid function. Both excess and insufficiency of adrenal function may result in altered liver function, and adrenocortical dysfunction may be present in patients with cirrhosis, especially during episodes of decompensation. Again an important player which affects both the endocrine system and the liver, alcohol may be associated with pseudo-Cushing syndrome. Sex hormones, both intrinsic as well as extrinsically administered, have an important impact on liver function. While oestrogens are related to cholestatic liver damage, androgens are the culprit of adenomas and hepatocellular carcinoma, among others. Chronic liver disease, on the other hand, has profound repercussions on sex hormone metabolism, inducing feminization in men and infertility and amenorrhoea in women. Lastly, metabolic syndrome, the pandemia of the present and future centuries, links the spectrum of liver damage ranging from steatosis to cirrhosis, to the array of endocrine alterations

  20. Imaging findings in fetal diaphragmatic abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Alamo, Leonor; Gudinchet, Francois [University Hospital Center of Lausanne, Unit of Radiopediatrics, Department of Radiology, Lausanne (Switzerland); Meuli, Reto [University Hospital Center of Lausanne, Department of Radiology, Lausanne (Switzerland)

    2015-12-15

    Imaging plays a key role in the detection of a diaphragmatic pathology in utero. US is the screening method, but MRI is increasingly performed. Congenital diaphragmatic hernia is by far the most often diagnosed diaphragmatic pathology, but unilateral or bilateral eventration or paralysis can also be identified. Extralobar pulmonary sequestration can be located in the diaphragm and, exceptionally, diaphragmatic tumors or secondary infiltration of the diaphragm from tumors originating from an adjacent organ have been observed in utero. Congenital abnormalities of the diaphragm impair normal lung development. Prenatal imaging provides a detailed anatomical evaluation of the fetus and allows volumetric lung measurements. The comparison of these data with those from normal fetuses at the same gestational age provides information about the severity of pulmonary hypoplasia and improves predictions about the fetus's outcome. This information can help doctors and families to make decisions about management during pregnancy and after birth. We describe a wide spectrum of congenital pathologies of the diaphragm and analyze their embryological basis. Moreover, we describe their prenatal imaging findings with emphasis on MR studies, discuss their differential diagnosis and evaluate the limits of imaging methods in predicting postnatal outcome. (orig.)

  1. The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation

    Directory of Open Access Journals (Sweden)

    Reichardt Holger M

    2008-05-01

    Full Text Available Abstract Background Pregnancy represents an exclusive situation in which the immune and the endocrine system cooperate to prevent rejection of the embryo by the maternal immune system. While immature dendritic cells (iDC in the early pregnancy decidua presumably contribute to the establishment of peripheral tolerance, glycoprotein-hormones of the transforming growth factor beta (TGF-beta family including activin A (ActA and inhibin A (InA are candidates that could direct the differentiation of DCs into a tolerance-inducing phenotype. Methods To test this hypothesis we generated iDCs from peripheral-blood-monocytes and exposed them to TGF-beta1, ActA, as well as InA and Dexamethasone (Dex as controls. Results Both glycoprotein-hormones prevented up-regulation of HLA-DR during cytokine-induced DC maturation similar to Dex but did not influence the expression of CD 40, CD 83 and CD 86. Visualization of the F-actin cytoskeleton confirmed that the DCs retained a partially immature phenotype under these conditions. The T-cell stimulatory capacity of DCs was reduced after ActA and InA exposure while the secretion of cytokines and chemokines was unaffected. Conclusion These findings suggest that ActA and InA interfere with selected aspects of DC maturation and may thereby help preventing activation of allogenic T-cells by the embryo. Thus, we have identified two novel members of the TGF-beta superfamily that could promote the generation of tolerance-inducing DCs.

  2. Structural characteristics and antiviral activity of multiple peptides derived from MDV glycoproteins B and H

    Directory of Open Access Journals (Sweden)

    Wang Ming

    2011-04-01

    Full Text Available Abstract Background Marek's disease virus (MDV, which is widely considered to be a natural model of virus-induced lymphoma, has the potential to cause tremendous losses in the poultry industry. To investigate the structural basis of MDV membrane fusion and to identify new viral targets for inhibition, we examined the domains of the MDV glycoproteins gH and gB. Results Four peptides derived from the MDV glycoprotein gH (gHH1, gHH2, gHH3, and gHH5 and one peptide derived from gB (gBH1 could efficiently inhibit plaque formation in primary chicken embryo fibroblast cells (CEFs with 50% inhibitory concentrations (IC50 of below 12 μM. These peptides were also significantly able to reduce lesion formation on chorioallantoic membranes (CAMs of infected chicken embryos at a concentration of 0.5 mM in 60 μl of solution. The HR2 peptide from Newcastle disease virus (NDVHR2 exerted effects on MDV specifically at the stage of virus entry (i.e., in a cell pre-treatment assay and an embryo co-treatment assay, suggesting cross-inhibitory effects of NDV HR2 on MDV infection. None of the peptides exhibited cytotoxic effects at the concentrations tested. Structural characteristics of the five peptides were examined further. Conclusions The five MDV-derived peptides demonstrated potent antiviral activity, not only in plaque formation assays in vitro, but also in lesion formation assays in vivo. The present study examining the antiviral activity of these MDV peptides, which are useful as small-molecule antiviral inhibitors, provides information about the MDV entry mechanism.

  3. Characterization of a surface glycoprotein from Echinococcus multilocularis and its mucosal vaccine potential in dogs.

    Directory of Open Access Journals (Sweden)

    Hirokazu Kouguchi

    Full Text Available Alveolar echinococcosis is a refractory disease caused by the metacestode stage of Echinococcus multilocularis. The life cycle of this parasite is maintained primarily between foxes and many species of rodents; thus, dogs are thought to be a minor definitive host except in some endemic areas. However, dogs are highly susceptible to E. multilocularis infection. Because of the close contact between dogs and humans, infection of dogs with this parasite can be an important risk to human health. Therefore, new measures and tools to control and prevent parasite transmission required. Using 2-dimensional electrophoresis followed by western blot (2D-WB analysis, a large glycoprotein component of protoscoleces was identified based on reactivity to intestinal IgA in dogs experimentally infected with E. multilocularis. This component, designated SRf1, was purified by gel filtration using a Superose 6 column. Glycosylation analysis and immunostaining revealed that SRf1 could be distinguished from Em2, a major mucin-type antigen of E. multilocularis. Dogs (n=6 were immunized intranasally with 500 µg of SRf1 with cholera toxin subunit B by using a spray syringe, and a booster was given orally using an enteric capsule containing 15 mg of the same antigen. As a result, dogs immunized with this antigen showed an 87.6% reduction in worm numbers compared to control dogs (n=5 who received only PBS administration. A weak serum antibody response was observed in SRf1-immunized dogs, but there was no correlation between antibody response and worm number. We demonstrated for the first time that mucosal immunization using SRf1, a glycoprotein component newly isolated from E. multilocularis protoscoleces, induced a protection response to E. multilocularis infection in dogs. Thus, our data indicated that mucosal immunization using surface antigens will be an important tool to facilitate the development of practical vaccines for definitive hosts.

  4. Conservative management of placenta previa complicated by abnormal placentation.

    Science.gov (United States)

    Bręborowicz, Grzegorz H; Markwitz, Wiesław; Gaca, Michał; Koziołek, Agnieszka; Ropacka-Lesiak, Mariola; Dera, Anna; Brych, Mariusz; Szymankiewicz-Bręborowicz, Marta; Kruszyński, Grzegorz; Gruca-Stryjak, Karolina; Madejczyk, Mateusz; Szpera-Goździewicz, Agata; Krzyścin, Mariola

    2013-07-01

    Abnormal implantation of placenta previa is life-threatening condition. The purpose of this study was to evaluate the impact of the conservative management of pregnancies with such complication on maternal morbidity rate and the chance for uterine preservation (fertility). Eleven patients with abnormal implantation of placenta previa were analyzed prospectively. This complication was diagnosed antenatally by two-dimensional ultrasound and color flow Doppler. The following outcomes were analyzed: need for blood transfusion, admission and duration of stay in intensive care unit, infections, coagulopathies, time between cesarean section and delivery of placenta, hysterectomy and preservation of uterus. Among the 20 085 women who had a singleton gestation, 11 (0.054%) were identified with placenta previa with abnormal placentation. In five patients (group A), hysterectomy was performed because of hemorrhage or placenta ablation. In six patients (group B), conservative management succeeded and placenta were preserved. In group A, placenta were delivered earlier (2 d-8 weeks) in comparison with group B (6-15 weeks). Estimated blood loss during the delayed delivery of placenta was higher in the group with hysterectomy (respectively, 450-1600 and 300-500 ml). Conservative management of placenta previa with abnormal implantation decreases the risk of severe hemorrhage at the time of delivery and can preserve fertility.

  5. Synthesis and translocation of gangliosides and glycoproteins during urethane anesthesia

    Energy Technology Data Exchange (ETDEWEB)

    Domowicz, M.S.; Kivatinitz, S.C.; Caputto, B.L.; Caputto, R.

    1988-05-01

    In this work, we have studied (a) the contents of gangliosides, glycoproteins, and phospholipids of the vesicle and plasma membrane fractions from brains of anesthetized and control rats and chickens and (b) the labeling of gangliosides and glycoproteins in the retina ganglion cell layer and optic tectum of urethane-anesthetized and control chickens after intraocular injection of a labeled N-acetylneuraminic acid precursor and the distribution of the label after subcellular fractionation. We found an increase in the content of gangliosides relative to protein in the vesicle fraction of both anesthetized rats and chickens relative to their controls. Other values were not affected by anesthesia. These results do not reflect a faster synthesis of gangliosides stimulated by urethane, because their rate of labeling was diminished in anesthetized animals. During the 4-h period after the animals were injected intraocularly with the radioactive precursor, the highest values of ganglioside-specific radioactivity were found in the vesicle fraction of control and anesthetized animals; at longer intervals, the specific radioactivity of the vesicle and plasma membrane fractions became rather similar. These data are in accordance with previous studies from this laboratory suggesting that the synthesis of the carbohydrate chain of gangliosides is regulated by the physiological demands made by the neurotransmitting system.

  6. Interaction of native and asialo rat sublingual glycoproteins with lectins.

    Science.gov (United States)

    Wu, A M; Herp, A; Song, S C; Wu, J H; Chang, K S

    1995-01-01

    The binding properties of the rat sublingual glycoprotein (RSL) and its asialo product with lectins were characterized by quantitative precipitin(QPA) and precipitin inhibition(QPIA) assays. Among twenty lectins tested for QPA, native RSL reacted well only with Artocarpus integrifolia (jacalin), but weakly or not at all with the other lectins. However, its asialo product (asialo-RSL) reacted strongly with many Gal and GalNAc specific lectins-it bound best to three of the GalNAc alpha 1-->Ser/Thr (Tn) and/or Gal beta 1-->4GlcNAc (II) active lectins [jacalin, Wistaria floribunda and Ricinus communis agglutinins] and completely precipitated each of these three lectins. Asialo-RSL also reacted well with Abrus precatorius, Glycine max, Bauhinia purpurea alba, and Maclura pomifera agglutinins, and abrin-a, but not with Arachis hypogeae and Dolichos biflorus agglutinins. The interaction between asialo-RSL and lectins were inhibited by either Gal beta 1-->4GlcNAc, p-NO2-phenyl alpha-GalNAc or both. The mapping of the precipitation and inhibition profiles leads to the conclusion that the asialo rat sublingual glycoprotein provides important ligands for II (Gal beta 1-->4GlcNAc beta 1-->) and Tn (GalNAc alpha 1-->Ser/Thr) active lectins.

  7. 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.

  8. Abnormalities in centrosome number in human embryos and embryonic stem cells.

    Science.gov (United States)

    Gu, Yi-Fan; OuYang, Qi; Dai, Can; Lu, Chang-Fu; Lin, Ge; Gong, Fei; Lu, Guang-Xiu

    2016-05-01

    Chromosomal abnormalities are common in human embryos. Previous studies have suggested links between centrosome number and chromosome abnormalities, but information regarding abnormalities in centrosome number in human embryos is limited. We analyzed abnormalities in centrosome number in human embryos and embryonic stem cells (hESCs). Following normal fertilization, supernumerary centrosomes were present at rates of 7.3% in two-pronucleus (2PN)-stage zygotes and 6.5% in first-cleavage zygotes. Supernumerary centrosomes were also detected in 24.4% of blastomeres from 60% of embryos derived from 2PN zygotes. Conversely, in mono- (1PN) and tri-pronucleus (3PN) zygotes, the frequency of abnormal centrosome number increased substantially at first cleavage. Rates in blastomeres of Day-3 embryos, however, were about the same between embryos derived from 1PN and 2PN zygotes, whereas abnormalities in centrosome number were higher in those from 3PN zygotes. By comparison, the rate of abnormal centrosome numbers in hESCs was 1.5-11.2%. Thus, abnormalities in centrosome number existed in human zygotes and cleaved embryos-especially those resulting from aberrant fertilization-but the frequency of such abnormalities was lower in hESCs derived from these embryos. These findings identify a source of the chromosomal instability in human embryos and hESCs, and highlight new safety issues for human assisted reproductive technology. Mol. Reprod. Dev. 83: 392-404, 2016. © 2016 Wiley Periodicals, Inc.

  9. The Newest Hypothesis about Vitiligo: Most of the Suggested Pathogeneses of Vitiligo Can Be Attributed to Lack of One Factor, Zinc-α2-Glycoprotein

    OpenAIRE

    Bagherani, Nooshin

    2012-01-01

    Zinc- α 2-glycoprotein (ZAG) is a recently identified adipokine, assigned to the chromosome 7q22.1. It is a multidisciplinary protein, which is secreted in various body fluids. The ZAG plays roles in lipolysis, regulation of metabolism, cell proliferation and differentiation, regulation of melanin synthesis, cell adhesion, immunoregulation, and so forth. Vitiligo is the most common depigmenting skin disorder, characterized by acquired, progressive, and circumscribed amelanosis of the skin and...

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

    Energy Technology Data Exchange (ETDEWEB)

    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 ({sup 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 ({sup 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 {times} 10{sup 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.

  11. Characterization of Lassa virus glycoprotein oligomerization and influence of cholesterol on virus replication.

    Science.gov (United States)

    Schlie, Katrin; Maisa, Anna; Lennartz, Frank; Ströher, Ute; Garten, Wolfgang; Strecker, Thomas

    2010-01-01

    Mature glycoprotein spikes are inserted in the Lassa virus envelope and consist of the distal subunit GP-1, the transmembrane-spanning subunit GP-2, and the signal peptide, which originate from the precursor glycoprotein pre-GP-C by proteolytic processing. In this study, we analyzed the oligomeric structure of the viral surface glycoprotein. Chemical cross-linking studies of mature glycoprotein spikes from purified virus revealed the formation of trimers. Interestingly, sucrose density gradient analysis of cellularly expressed glycoprotein showed that in contrast to trimeric mature glycoprotein complexes, the noncleaved glycoprotein forms monomers and oligomers spanning a wide size range, indicating that maturation cleavage of GP by the cellular subtilase SKI-1/S1P is critical for formation of the correct oligomeric state. To shed light on a potential relation between cholesterol and GP trimer stability, we performed cholesterol depletion experiments. Although depletion of cholesterol had no effect on trimerization of the glycoprotein spike complex, our studies revealed that the cholesterol content of the viral envelope is important for the infectivity of Lassa virus. Analyses of the distribution of viral proteins in cholesterol-rich detergent-resistant membrane areas showed that Lassa virus buds from membrane areas other than those responsible for impaired infectivity due to cholesterol depletion of lipid rafts. Thus, derivation of the viral envelope from cholesterol-rich membrane areas is not a prerequisite for the impact of cholesterol on virus infectivity.

  12. Structural analysis of N- and O-glycans released from glycoproteins

    DEFF Research Database (Denmark)

    Jensen, Pia Hønnerup; Karlsson, Niclas G; Kolarich, Daniel;

    2012-01-01

    This protocol shows how to obtain a detailed glycan compositional and structural profile from purified glycoproteins or protein mixtures, and it can be used to distinguish different isobaric glycan isomers. Glycoproteins are immobilized on PVDF membranes before the N-glycans are enzymatically...

  13. 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 researc

  14. Investigating the biomarker potential of glycoproteins using comparative glycoprofiling - application to tissue inhibitor of metalloproteinases-1

    DEFF Research Database (Denmark)

    Thøgersen, Ida; Lademann, Ulrik Axel; Offenberg, Hanne Kjær;

    2008-01-01

    Cancer-induced alterations of protein glycosylations are well-known phenomena. Hence, the glycoprofile of certain glycoproteins can potentially be used as biomarkers for early diagnosis. However, there are a substantial number of candidates and the techniques for measuring their biomarker potential...... tool for biomarker investigation of low-abundant glycoproteins....

  15. 21 CFR 866.5420 - Alpha-1-glycoproteins immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-1-glycoproteins immunological test system. 866.5420 Section 866.5420 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5420 Alpha-1-glycoproteins immunological...

  16. 21 CFR 866.5425 - Alpha-2-glycoproteins immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-2-glycoproteins immunological test system. 866.5425 Section 866.5425 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5425 Alpha-2-glycoproteins immunological...

  17. 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

  18. Glycoproteins from sugarcane plants regulate cell polarity of Ustilago scitaminea teliospores.

    Science.gov (United States)

    Millanes, Ana-María; Fontaniella, Blanca; Legaz, María-Estrella; Vicente, Carlos

    2005-03-01

    Saccharum officinarum, cv. Mayarí, is a variety of sugarcane resistant to smut disease caused by Ustilago scitaminea. Sugarcane naturally produces glycoproteins that accumulate in the parenchymatous cells of stalks. These glycoproteins contain a heterofructan as polysaccharide moiety. The concentration of these glycoproteins clearly increases after inoculation of sugarcane plants with smut teliospores, although major symptoms of disease are not observed. These glycoproteins induce homotypic adhesion and inhibit teliospore germination. When glycoproteins from healthy, non-inoculated plants are fractionated, they inhibit actin capping, which occurs before teliospore germination. However, inoculation of smut teliospores induce glycoprotein fractions that promote teliospore polarity and are different from those obtained from healthy plants. These fractions exhibit arginase activity, which is strongly enhanced in inoculated plants. Arginase from healthy plants binds to cell wall teliospores and it is completely desorpted by sucrose, but only 50% of arginase activity from inoculated plants is desorpted by the disaccharide. The data presented herein are consistent with a model of excess arginase entry into teliospores. Arginase synthesized by sugarcane plants as a response to the experimental infection would increase the synthesis of putrescine, which impedes polarization at concentration values higher than 0.05 mM. However, smut teliospores seem to be able to change the pattern of glycoprotein production by sugarcane, thereby promoting the synthesis of different glycoproteins that activate polarization after binding to their cell wall ligand.

  19. Novel thermo-responsive fucose binding ligands for glycoprotein purification by affinity precipitation.

    Science.gov (United States)

    Arnold, Lindsay; Chen, Rachel

    2014-02-01

    Novel thermo-responsive affinity sugar binders were developed by fusing a bacterial fucose lectin with a thermo-responsive polypeptide. These designer affinity ligand fusions were produced using an Escherichia coli system capable of extracellular secretion of recombinant proteins and were isolated with a high recovery yield (95%) directly from growth medium by Inverse Temperature Cycling (ITC). With horse radish peroxidase (HRP) as a model protein, we demonstrate here that the designer thermo-responsive ligands are capable of interacting with glycans on a glycoprotein, a property that was used to develop a novel affinity precipitation method for glycoprotein purification. The method, requiring only simple process steps, affords full recovery of a target glycoprotein, and is effective at a target glycoprotein concentration as low as 1.4 pM in the presence of large amounts of contaminants. By developing other sugar binders in the similar fashion, the method should be highly useful for glycoprotein purification and detection.

  20. Loop-acting diuretics do not bind to Tamm-Horsfall urinary glycoprotein.

    Science.gov (United States)

    Brunisholz, M C; Lynn, K L; Hunt, J S

    1987-09-01

    1. Binding between the radiolabelled loop-acting diuretics ([14C]frusemide, [14C]ethacrynic acid and [3H]bumetanide) and human Tamm-Horsfall glycoprotein or human serum albumin in vitro was evaluated by equilibrium dialysis. 2. The diuretic action and binding to urinary Tamm-Horsfall glycoprotein of the radiolabelled diuretics in vivo, after intravenous administration, were examined in rabbits. 3. In vitro, all three radiolabelled diuretics bound strongly to human serum albumin, but not to Tamm-Horsfall glycoprotein. 4. Radiolabelled frusemide and bumetanide, but not ethacrynic acid, caused a diuresis in rabbits, but no binding between the drugs and Tamm-Horsfall glycoprotein was seen in vivo. 5. Binding to Tamm-Horsfall glycoprotein does not appear to be an important mechanism in the action of loop diuretics.

  1. 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...... a unique binding pattern different from the patterns revealed by other lectins. However, several estrous cycle phase-specific glycoproteins reacted with more than one lectin. The most prominent of these glycoproteins (M(r) 92-95 KD) was weakly expressed in late diestrus and fully expressed only...... 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...

  2. Developmental and mutational changes of glycoproteins in the mouse neuronal retina: studies with bovine galactosyltransferase.

    Science.gov (United States)

    Wallenfels, B

    1979-07-01

    Bovine galactosyltransferase (lactose synthase; EC 2.4.1.22) which catalyzes the transfer of galactose from UDPgalactose to glycoproteins with N-acetylglucosamine as the terminal residue of their oligosaccharide side chains was used to label glycoproteins of mouse retina with [14C]galactose. The glycoproteins were separated by isoelectric focusing in the first dimension and by sodium dodecyl sulfate gel electrophoresis in the second dimension. Their position on the gel was determined by autofluorography. With this method, quantitative as well as qualitative changes in the glycoprotein composition of the neuronal mouse retina during postnatal development were observed. Furthermore, it was found that the photoreceptor loss in mice with retinal degeneration was paralleled by the disappearance of certain glycoprotein bands.

  3. Production of Highly Sialylated Recombinant Glycoproteins Using Ricinus communis Agglutinin-I-Resistant CHO Glycosylation Mutants.

    Science.gov (United States)

    Goh, John S Y; Chan, Kah Fai; Song, Zhiwei

    2015-01-01

    The degree of sialylation of therapeutic glycoproteins affects its circulatory half-life and efficacy because incompletely sialylated glycoproteins are cleared from circulation by asialoglycoprotein receptors present in the liver cells. Mammalian expression systems, often employed in the production of these glycoprotein drugs, produce heterogeneously sialylated products. Here, we describe how to produce highly sialylated glycoproteins using a Chinese hamster ovary (CHO) cell glycosylation mutant called CHO-gmt4 with human erythropoietin (EPO) as a model glycoprotein. The protocol describes how to isolate and characterize the CHO glycosylation mutants and how to assess the sialylation of the recombinant protein using isoelectric focusing (IEF). It further describes how to inactivate the dihydrofolate reductase (DHFR) gene in these cells using zinc finger nuclease (ZFN) technology to enable gene amplification and the generation of stable cell lines producing highly sialylated EPO.

  4. Binding of soluble glycoproteins from sugarcane juice to cells of Acetobacter diazotrophicus.

    Science.gov (United States)

    Legaz, M E; de Armas, R; Barriguete, E; Vicente, C

    2000-09-01

    Sugarcane produces two different pools of glycoproteins containing a heterofructan as glycidic moiety, tentatively defined as high-molecular mass (HMMG) and mid-molecular mass (MMMG) glycoproteins. Both kinds of glycoproteins can be recovered in sugarcane juice. Fluorescein-labelled glycoproteins are able to bind to Acetobacter diazotrophicus cells, a natural endophyte of sugarcane. This property implies the aggregation of bacterial cells in liquid culture after addition of HMMG or MMMG. Anionic glycoproteins seem to be responsible for the binding activity whereas cationic fraction is not retained on the surface ofA. diazotrophicus. Bound HMMG is competitively desorbed by sucrose whereas MMMG is desorbed by glucosamine or fructose. On this basis, a hypothesis about the discriminatory ability of sugarcane to choose the compatible endophyte from several possible ones is proposed.

  5. Effect of reduced renal mass on renal ammonia transporter family, Rh C glycoprotein and Rh B glycoprotein, expression.

    Science.gov (United States)

    Kim, Hye-Young; Baylis, Chris; Verlander, Jill W; Han, Ki-Hwan; Reungjui, Sirirat; Handlogten, Mary E; Weiner, I David

    2007-10-01

    Kidneys can maintain acid-base homeostasis, despite reduced renal mass, through adaptive changes in net acid excretion, of which ammonia excretion is the predominant component. The present study examines whether these adaptations are associated with changes in the ammonia transporter family members, Rh B glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg). We used normal Sprague-Dawley rats and a 5/6 ablation-infarction model of reduced renal mass; control rats underwent sham operation. After 1 wk, glomerular filtration rate, assessed as creatinine clearance, was decreased, serum bicarbonate was slightly increased, and Na(+) and K(+) were unchanged. Total urinary ammonia excretion was unchanged, but urinary ammonia adjusted for creatinine clearance, an index of per nephron ammonia metabolism, increased significantly. Although reduced renal mass did not alter total Rhcg protein expression, both light microscopy and immunohistochemistry with quantitative morphometric analysis demonstrated hypertrophy of both intercalated cells and principal cells in the cortical and outer medullary collecting duct that was associated with increased apical and basolateral Rhcg polarization. Rhbg expression, analyzed using immunoblot analysis, immunohistochemistry, and measurement of cell-specific expression, was unchanged. We conclude that altered subcellular localization of Rhcg contributes to adaptive changes in single-nephron ammonia metabolism and maintenance of acid-base homeostasis in response to reduced renal mass.

  6. Abnormal Event Detection Using Local Sparse Representation

    DEFF Research Database (Denmark)

    Ren, Huamin; Moeslund, Thomas B.

    2014-01-01

    We propose to detect abnormal events via a sparse subspace clustering algorithm. Unlike most existing approaches, which search for optimized normal bases and detect abnormality based on least square error or reconstruction error from the learned normal patterns, we propose an abnormality measurem...... is found that satisfies: the distance between its local space and the normal space is large. We evaluate our method on two public benchmark datasets: UCSD and Subway Entrance datasets. The comparison to the state-of-the-art methods validate our method's effectiveness....

  7. Numerically abnormal chromosome constitutions in humans

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-12-31

    Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.

  8. P-glycoprotein levels predict poor outcome in patients with osteosarcoma.

    Science.gov (United States)

    Hornicek, F J; Gebhardt, M C; Wolfe, M W; Kharrazi, F D; Takeshita, H; Parekh, S G; Zurakowski, D; Mankin, H J

    2000-04-01

    To evaluate the relationship between the expression of P-glycoprotein by osteosarcomas and the rate of metastasis and death, a retrospective review of 172 patients who were diagnosed with osteosarcoma between 1987 and 1992 was performed. Forty patients had P-glycoprotein levels available. The majority of the osteosarcomas were Stage II-B (33 patients), with the remaining seven being Stage III. Tumor sites included 25 femurs, seven humeri, five tibias, and one each of pelvis, radius, and fibula. The patients with Stage III disease at presentation were treated differently from the time of diagnosis and therefore, these seven patients with Stage III osteosarcoma were excluded from additional analyses. The expression of P-glycoprotein by cultured tumor cells from biopsy specimens was determined using immunofluorescent microscopy. In the 33 patients with Stage IIB osteosarcoma with detectable P-glycoprotein, 67% (10 of 15) had metastases develop as compared with 28% (five of 18) of patients with undetectable P-glycoprotein. Similarly, 53% (eight of 15) of patients with tumors expressing P-glycoprotein died of disease compared with 11% (two of 18) with no detectable P-glycoprotein. Expression of P-glycoprotein by tumor cells seems to be associated with an estimated ninefold increase in the odds of death and a fivefold increase in the odds of metastases in patients with Stage IIB osteosarcoma. Kaplan-Meier survivorship analysis revealed that patients with detectable P-glycoprotein fared worse in terms of survival time and metastasis-free survival. Adjusting for covariates in the Cox proportional hazards model, expression of P-glycoprotein and its level were significantly predictive of time to death in patients with Stage IIB osteosarcoma.

  9. The Mechanism of Henipavirus Fusion: Examining the Relationships between the Attachment and Fusion Glycoproteins

    Institute of Scientific and Technical Information of China (English)

    Andrew C. Hickey; Christopher C. Broder

    2009-01-01

    The henipaviruses, represented by Nipah virus and Hendra virus, are emerging zoonotic viral pathogens responsible for repeated outbreaks associated with high morbidity and mortality in Australia, Southeast Asia, India and Bangladesh. These viruses enter host cells via a class I viral fusion mechanism mediated by their attachment and fusion envelope glycoproteins; efficient membrane fusion requires both these glycoproteins in conjunction with specific virus receptors present on susceptible host cells. The henipavirus attachment glycoprotein interacts with a cellular B class ephrin protein receptor triggering conformational alterations leading to the activation of the viral fusion (F) glycoprotein. The analysis of monoclonal antibody (mAb) reactivity with G has revealed measurable alterations in the antigenic structure of the glycoprotein following its binding interaction with receptor. These observations only appear to occur with full-length native G glycoprotein, which is a tetrameric oligomer, and not with soluble forms of G (sG), which are disulfide-linked dimers. Single amino acid mutations in a heptad repeat-like structure within the stalk domain of G can disrupt its association with F and subsequent membrane fusion promotion activity. Notably, these mutants of G also appear to confer a postreceptor bound conformation implicating the stalk domain as an important element in the G glycoprotein's structure and functional relationship with F. Together, these observations suggest fusion is dependent on a specific interaction between the F and G glycoproteins of the henipaviruses. Further, receptor binding induces measurable changes in the G glycoprotein that appear to be greatest in respect to the interactions between the pairs of dimers comprising its native tetrameric structure. These receptor-induced conformational changes may be associated with the G glycoprotein's promotion of the fusion activity of F.

  10. 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

    glycoprotein glycoforms to their receptors is inhibited by steroids. Testosterone, oestradiol and progesterone inhibited the binding of alpha 1-acid glycoprotein glycoform A to its receptor. Cortisone, aldosterone, oestradiol and progesterone inhibited the binding of alpha 1-acid glycoprotein glycoforms B...

  11. Magnetic resonance imaging and histological studies of corpus callosal and hippocampal abnormalities linked to doublecortin deficiency.

    Science.gov (United States)

    Kappeler, Caroline; Dhenain, Marc; Phan Dinh Tuy, Françoise; Saillour, Yoann; Marty, Serge; Fallet-Bianco, Catherine; Souville, Isabelle; Souil, Evelyne; Pinard, Jean-Marc; Meyer, Gundela; Encha-Razavi, Ferechté; Volk, Andreas; Beldjord, Cherif; Chelly, Jamel; Francis, Fiona

    2007-01-10

    Mutated doublecortin (DCX) gives rise to severe abnormalities in human cortical development. Adult Dcx knockout mice show no major neocortical defects but do have a disorganized hippocampus. We report here the developmental basis of these hippocampal abnormalities. A heterotopic band of neurons was identified starting at E17.5 in the CA3 region and progressing throughout the CA1 region by E18.5. At neonatal stages, the CA1 heterotopic band was reduced, but the CA3 band remained unchanged, continuing into adulthood. Thus, in mouse, migration of CA3 neurons is arrested during development, whereas CA1 cell migration is retarded. On the Sv129Pas background, magnetic resonance imaging (MRI) also suggested abnormal dorsal hippocampal morphology, displaced laterally and sometimes rostrally and associated with medial brain structure abnormalities. MRI and cryosectioning showed agenesis of the corpus callosum in Dcx knockout mice on this background and an intermediate, partial agenesis in heterozygote mice. Wild-type littermates showed no callosal abnormalities. Hippocampal and corpus callosal abnormalities were also characterized in DCX-mutated human patients. Severe hippocampal hypoplasia was identified along with variable corpus callosal defects ranging from total agenesis to an abnormally thick or thin callosum. Our data in the mouse, identifying roles for Dcx in hippocampal and corpus callosal development, might suggest intrinsic roles for human DCX in the development of these structures.

  12. A study of cluster behavioral abnormalities in down syndrome

    Directory of Open Access Journals (Sweden)

    Bhattacharyya Ranjan

    2009-02-01

    Full Text Available Background :The behavioral phenotype in Down syndrome follows a characteristic pattern. Aims: To find the incidence of behavioral abnormalities in Down syndrome, to compare these findings with other causes of intellectual disability and normal population and to cluster these abnormalities. Settings :One hundred forty mentally challenged people attending at tertiary care set up and from various non-governmental organizations were included in the study. Patients from both rural and urban set up participated in the study. The age-matched group from normal population was also studied for comparison. Design :The study design is a cross-sectional survey done independently by four observers. Materials and Methods :A semi-structured proforma for demographic profile has been used. The behavioral abnormalities are assessed by using DASH II (Diagnostic Assessment for the Severely Handicapped second modified version scale. Statistical Analysis :Demographic comparison has been done by analysis of variance. Correlation matrix has been run to identify correlation between individual items. Principal component analysis has been used for grouping the behavioral pattern. Results :Behavioral abnormalities as expected are more common in people having intellectual disability than the normal population. The Down syndrome group unlike other causes of intellectual disability shows higher scores in Stereotypy. Impulse control and Mania subscales. Factor analysis yields five characteristic factor structures, namely, hyperactive-impulsive, biological functions, affective, neurotic and organic-pervasive developmental disorder clusters. Conclusions :Contrary to the conventional belief of docile-fun and music loving prototype, individuals diagnosed with Down syndrome show clusters of behavioral abnormalities and management can vary depending on these target symptoms.

  13. SERUM CHEMISTRY ABNORMALITIES IN CHILDREN WITH UNPROVOKED SEIZURES

    Directory of Open Access Journals (Sweden)

    J. Akhondian MD

    2009-01-01

    Full Text Available ObjectiveMost children brought to the emergency department (ED for evaluation of seizures undergo an extensive laboratory workup. Since results are usually negative, the value of such routine laboratory workups has been questioned. A group of children with unprovoked seizures was prospectively studied to determine the diagnostic values of routine serum chemistries and to identify risk factors predictive of abnormal findings.Materials & MethodsAll patients evaluated at the ED of the Ghaem hospital during a consecutive 12 months period between Jan 2004 through Jan 2005 were studied. We collected data for patient's demographics, details of the history of present illness (including vomiting, diarrhea, apnea, medication use, past history of seizures, family history of seizures, metabolic disorders or other chronic medical illnesses, neonatal history and neurological examination as well as nutritional status, type and time of seizure. The role of abnormal serum chemistries as a seizure trigger factor was assessed in patients with a history of seizure.ResultsA total of 210 patients (mean age 19.2 months with unprovoked seizures were evaluated. Twenty- three serum abnormalities were noted in the patients (12 cases of hyponatremia, 7 of hypoglycemia, 4 of hypokalemia, 4 of uremia. The incidence of abnormal serum biochemical values was higher in patients with a first seizure, younger patients, and those with gastrointestinal symptoms.ConclusionAccording to the present study, one can conclude that in children younger than 2 years and having no structural CNS abnormality, electrolyte and glucose screening is recommended only for a first unprovoked seizure, when gastrointestinal symptoms or symptoms suggesting electrolyte disturbances are present.Keywords:Unprovoked, Seizure, Biochemistry, Children

  14. SERUM CHEMISTRY ABNORMALITIES IN CHILDREN WITH UNPROVOKED SEIZURES

    Directory of Open Access Journals (Sweden)

    J. Akhondian MD,

    2007-02-01

    Full Text Available ObjectiveMost children brought to the emergency department (ED for evaluation of seizures undergo an extensive laboratory workup. Since results are usually negative, the value of such routine laboratory workups has been questioned. A group of children with unprovoked seizures was prospectively studied to determine the diagnostic values of routine serum chemistries and to identify risk factors predictive of abnormal findings.Materials & MethodsAll patients evaluated at the ED of the Ghaem hospital during a consecutive 12 months period between Jan 2004 through Jan 2005 were studied. We collected data for patient's demographics, details of the history of present illness (including vomiting, diarrhea, apnea, medication use, past history of seizures, family history of seizures, metabolic disorders or other chronic medical illnesses, neonatal history and neurological examination as well as nutritional status, type and time of seizure. The role of abnormal serum chemistries as a seizure trigger factor was assessed in patients with a history of seizure.ResultsA total of 210 patients (mean age 19.2 months with unprovoked seizures were evaluated. Twenty- three serum abnormalities were noted in the patients (12 cases of hyponatremia, 7 of hypoglycemia, 4 of hypokalemia, 4 of uremia. The incidence of abnormal serum biochemical values was higher in patients with a first seizure, younger patients, and those with gastrointestinal symptoms.ConclusionAccording to the present study, one can conclude that in children younger than 2 years and having no structural CNS abnormality, electrolyte and glucose screening is recommended only for a first unprovoked seizure, when gastrointestinal symptoms or symptoms suggesting electrolyte disturbances are present.

  15. 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.

  16. Multiple resting state network functional connectivity abnormalities in mild traumatic brain injury.

    Science.gov (United States)

    Stevens, Michael C; Lovejoy, David; Kim, Jinsuh; Oakes, Howard; Kureshi, Inam; Witt, Suzanne T

    2012-06-01

    Several reports show that traumatic brain injury (TBI) results in abnormalities in the coordinated activation among brain regions. Because most previous studies examined moderate/severe TBI, the extensiveness of functional connectivity abnormalities and their relationship to postconcussive complaints or white matter microstructural damage are unclear in mild TBI. This study characterized widespread injury effects on multiple integrated neural networks typically observed during a task-unconstrained "resting state" in mild TBI patients. Whole brain functional connectivity for twelve separate networks was identified using independent component analysis (ICA) of fMRI data collected from thirty mild TBI patients mostly free of macroscopic intracerebral injury and thirty demographically-matched healthy control participants. Voxelwise group comparisons found abnormal mild TBI functional connectivity in every brain network identified by ICA, including visual processing, motor, limbic, and numerous circuits believed to underlie executive cognition. Abnormalities not only included functional connectivity deficits, but also enhancements possibly reflecting compensatory neural processes. Postconcussive symptom severity was linked to abnormal regional connectivity within nearly every brain network identified, particularly anterior cingulate. A recently developed multivariate technique that identifies links between whole brain profiles of functional and anatomical connectivity identified several novel mild TBI abnormalities, and represents a potentially important new tool in the study of the complex neurobiological sequelae of TBI.

  17. Effect of an antiretroviral regimen containing ritonavir boosted lopinavir on intestinal and hepatic CYP3A, CYP2D6 and P-glycoprotein in HIV-infected patients.

    NARCIS (Netherlands)

    Wyen, C.; Fuhr, U.; Frank, D.; Aarnoutse, R.E.; Klaassen, T.; Lazar, A.; Seeringer, A.; Doroshyenko, O.; Kirchheiner, J.C.; Abdulrazik, F.; Schmeisser, N.; Lehmann, C.; Hein, W.; Schomig, E.; Burger, D.M.; Fatkenheuer, G.; Jetter, A.

    2008-01-01

    This study aimed to quantify the inhibition of cytochrome P450 (CYP3A), CYP2D6, and P-glycoprotein in human immunodeficiency virus (HIV)-infected patients receiving an antiretroviral therapy (ART) containing ritonavir boosted lopinavir, and to identify factors influencing ritonavir and lopinavir pha

  18. Characterization of intramolecular disulfide bonds and secondary modifications of the glycoprotein from viral hemorrhagic septicemia virus, a fish rhabdovirus

    DEFF Research Database (Denmark)

    Einer-Jensen, Katja; Nielsen, Thomas Krogh; Roepstorff, Peter

    1998-01-01

    Viral hemorrhagic septicemia virus (VHSV) infections cause high losses in cultured rainbow trout in Europe. Attempts to produce a recombinant vaccine based on the transmembrane glycoprotein (G protein) have indicated that proper folding is important for the antigenicity and immunogenicity...... of the protein, The present study was initiated to identify the disulfide bonds and other structural aspects relevant to vaccine design. The N-terminal amino acid residue was identified as being a pyroglutamic acid, corresponding to Gln21 of the primary transcript, Peptides from endoproteinase-degraded G protein...... structure of the G protein. Three of four predicted N-linked oligosaccharides were found to be predominantly biantennary complex-type structures, Furthermore, an O-linked glycan near the N terminus was identified. Alignment of the VHSV G protein,vith five other rhabdovirus G proteins indicates that eight...

  19. Neuronal migration abnormalities and its possible implications for schizophrenia

    Directory of Open Access Journals (Sweden)

    Kenji eTanigaki

    2015-03-01

    Full Text Available Schizophrenia is a complex mental disorder that displays behavioral deficits such as decreased sensory gating, reduced social interaction and working memory deficits. The neurodevelopmental model is one of the widely accepted hypotheses of the etiology of schizophrenia. Subtle developmental abnormalities of the brain which stated long before the onset of clinical symptoms are thought to lead to the emergence of illness. Schizophrenia has strong genetic components but its underlying molecular pathogenesis is still poorly understood. Genetic linkage and association studies have identified several genes involved in neuronal migrations as candidate susceptibility genes for schizophrenia, although their effect size is small. Recent progress in copy number variation studies also has identified much higher risk loci such as 22q11. Based on these genetic findings, we are now able to utilize genetically-defined animal models. Here we summarize the results of neurodevelopmental and behavioral analysis of genetically-defined animal models. Furthermore, animal model experiments have demonstrated that embryonic and perinatal neurodevelopmental insults in neurogenesis and neuronal migrations cause neuronal functional and behavioral deficits in affected adult animals, which are similar to those of schizophrenic patients. However, these findings do not establish causative relationship. Genetically-defined animal models are a critical approach to explore the relationship between neuronal migration abnormalities and behavioral abnormalities relevant to Schizophrenia.

  20. Amphibian abnormalities on National Wildlife Refuges

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This fact sheet outlines a study done to 1) find the percentage of abnormal frogs and toads on the nation’s National Wildlife Refuges and 2) determine how the...

  1. On two abnormal sharks from Gujarat

    Digital Repository Service at National Institute of Oceanography (India)

    Gopalan, U.K.

    The description of the two abnormal sharks, Carchariaswalbeehmi and Eulamia dussumieri collected from Gujarat, India, is given Of these C walbeehmi was double-headed The other shark E dussumieri had thumb snouted albino...

  2. immunological arthritis Prevalence of biochemical and abnormalities ...

    African Journals Online (AJOL)

    1991-02-02

    Feb 2, 1991 ... immunological abnormalities noted were a positive rheumatoid factor (78,9%), positive ... Rheumatoid arthritis (RA) is a systemic disease characterised by the occurrence of articular and ..... treatment. Br Med] 1982; 285: ...

  3. The glycometabolism abnormality among schizophrenia patients

    Institute of Scientific and Technical Information of China (English)

    吴小立

    2013-01-01

    Objective To explore the potential glycometabolism abnormality and the related factors of schizophrenia patients in China. Methods This cross-sectional study included 44 healthy controls(group 1) and 178 inpatient

  4. Structural characterization of the glycoprotein GP2 core domain from the CAS virus, a novel arenavirus-like species.

    Science.gov (United States)

    Koellhoffer, Jayne F; Dai, Zhou; Malashkevich, Vladimir N; Stenglein, Mark D; Liu, Yanyun; Toro, Rafael; S Harrison, Joseph; Chandran, Kartik; DeRisi, Joseph L; Almo, Steven C; Lai, Jonathan R

    2014-04-03

    Fusion of the viral and host cell membranes is a necessary first step for infection by enveloped viruses and is mediated by the envelope glycoprotein. The transmembrane subunits from the structurally defined "class I" glycoproteins adopt an α-helical "trimer-of-hairpins" conformation during the fusion pathway. Here, we present our studies on the envelope glycoprotein transmembrane subunit, GP2, of the CAS virus (CASV). CASV was recently identified from annulated tree boas (Corallus annulatus) with inclusion body disease and is implicated in the disease etiology. We have generated and characterized two protein constructs consisting of the predicted CASV GP2 core domain. The crystal structure of the CASV GP2 post-fusion conformation indicates a trimeric α-helical bundle that is highly similar to those of Ebola virus and Marburg virus GP2 despite CASV genome homology to arenaviruses. Denaturation studies demonstrate that the stability of CASV GP2 is pH dependent with higher stability at lower pH; we propose that this behavior is due to a network of interactions among acidic residues that would destabilize the α-helical bundle under conditions where the side chains are deprotonated. The pH-dependent stability of the post-fusion structure has been observed in Ebola virus and Marburg virus GP2, as well as other viruses that enter via the endosome. Infection experiments with CASV and the related Golden Gate virus support a mechanism of entry that requires endosomal acidification. Our results suggest that, despite being primarily arenavirus like, the transmembrane subunit of CASV is extremely similar to the filoviruses.

  5. Basilar artery migraine and reversible imaging abnormalities.

    Science.gov (United States)

    Maytal, J; Libman, R B; Lustrin, E S

    1998-01-01

    We report a case of a basilar artery migraine in a 17-year-old boy with transient CT and MR abnormalities after each of two migraine episodes. A repeat MR study 6 months after the last event showed complete resolution of the lesion. Transient abnormalities on brain images similar to those shown in our case have been reported in patients with migraine and other neurologic conditions and are most likely related to cerebral vasogenic edema.

  6. Abnormal Chromosome Segregation May Trigger Tumors

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ Cancer is a primary threat to human health as it kills millions of people each year.Scientists have shown that 75% of human cancers have an abnormal number of chromosomes in cells,and the proportion of the cells with an abnormal chromosome number is tightly and positively related to malignance progression and metastasis of cancers. But the pathological mechanism behind the anomaly still remains unknown.

  7. Abnormal Asymmetry of Brain Connectivity in Schizophrenia

    OpenAIRE

    Ribolsi, Michele; Zafiris J Daskalakis; Siracusano, Alberto; Koch, Giacomo

    2014-01-01

    Recently, a growing body of data has revealed that beyond a dysfunction of connectivity among different brain areas in schizophrenia patients (SCZ), there is also an abnormal asymmetry of functional connectivity compared with healthy subjects. The loss of the cerebral torque and the abnormalities of gyrification, with an increased or more complex cortical folding in the right hemisphere may provide an anatomical basis for such aberrant connectivity in SCZ. Furthermore, diffusion tensor imagin...

  8. Prevalence of asymptomatic urinary abnormalities among adolescents

    Directory of Open Access Journals (Sweden)

    Mohamed Fouad

    2016-01-01

    Full Text Available To determine the prevalence of asymptomatic urinary abnormalities in adolescents, first morning clean mid-stream urine specimens were obtained from 2500 individuals and examined by dipstick and light microscopy. Adolescents with abnormal screening results were reexamined after two weeks and those who had abnormal results twice were subjected to systemic clinical examination and further clinical and laboratory investigations. Eight hundred and three (32.1% individuals had urinary abnormalities at the first screening, which significantly decreased to 345 (13.8% at the second screening, (P <0.001. Hematuria was the most common urinary abnormalities detected in 245 (9.8% adolescents who had persistent urine abnormalities; 228 (9.1% individuals had non glomerular hematuria. The hematuria was isolated in 150 (6% individuals, combined with leukocyturia in 83 (3.3% individuals, and combined with proteinuria in 12 (0.5% individuals. Leukocyturia was detected in 150 (6% of all studied adolescents; it was isolated in 39 (1.6% individuals and combined with proteinuria in 28 (1.1% of them. Asymp- tomatic bacteriuria was detected in 23 (0.9% of all studied adolescents; all the cases were females. Proteinuria was detected in 65 (2.6% of all the studied adolescents; 45 (1.8% indivi- duals had <0.5 g/day and twenty (0.8% individuals had 0.5-3 g/day. Asymptomatic urinary abnormalities were more common in males than females and adolescents from rural than urban areas (P <0.01 and (P <0.001, respectively. The present study found a high prevalence of asymptomatic urinary abnormalities among adolescents in our population.

  9. Nail abnormalities in patients with vitiligo

    OpenAIRE

    Topal, Ilteris Oguz; Gungor, Sule; Kocaturk, Ozgur Emek; Duman, Hatice; Durmuscan, Mustafa

    2016-01-01

    Abstract: Background: Vitiligo is an acquired pigmentary skin disorder affecting 0.1-4% of the general population. The nails may be affected in patients with an autoimmune disease such as psoriasis, and in those with alopecia areata. It has been suggested that nail abnormalities should be apparent in vitiligo patients. Objective: We sought to document the frequency and clinical presentation of nail abnormalities in vitiligo patients compared to healthy volunteers. We also examined the corre...

  10. Cerebral abnormalities in adults with ataxia-telangiectasia.

    Science.gov (United States)

    Lin, D D M; Barker, P B; Lederman, H M; Crawford, T O

    2014-01-01

    Ataxia-telangiectasia, an autosomal recessive disorder caused by defect of the ataxia-telangiectasia mutated gene, is characterized by progressive neurologic impairment with cerebellar atrophy, ocular and cutaneous telangiectasia, immunodeficiency, heightened sensitivity to ionizing radiation and susceptibility to developing lymphoreticular malignancy. Supratentorial brain abnormalities have been reported only rarely. In this study, brain MRI was performed in 10 adults with ataxia-telangiectasia having stable neurologic impairment. Intracerebral telangiectasia with multiple punctate hemosiderin deposits were identified in 60% of subjects. These lesions were apparently asymptomatic. They are similar in appearance to radiation-induced telangiectasia and to cryptogenic vascular malformations. Also noted, in the 2 oldest subjects, was extensive white matter T2 hyperintensity, and in 1 of these a space-occupying fluid collection consistent with transudative capillary leak and edema as evidenced by reduced levels of metabolites on MR spectroscopic imaging. Asymptomatic supratentorial vascular abnormalities appear to be common in adults with ataxia-telangiectasia.

  11. Saliency-based abnormal event detection in crowded scenes

    Science.gov (United States)

    Shi, Yanjiao; Liu, Yunxiang; Zhang, Qing; Yi, Yugen; Li, Wenju

    2016-11-01

    Abnormal event detection plays a critical role for intelligent video surveillance, and detection in crowded scenes is a challenging but more practical task. We present an abnormal event detection method for crowded video. Region-wise modeling is proposed to address the inconsistent detected motion of the same object due to different depths of field. Comparing to traditional block-wise modeling, the region-wise method not only can reduce heavily the number of models to be built but also can enrich the samples for training the normal events model. In order to reduce the computational burden and make the region-based anomaly detection feasible, a saliency detection technique is adopted in this paper. By identifying the salient parts of the image sequences, the irrelevant blocks are ignored, which removes the disturbance and improves the detection performance further. Experiments on the benchmark dataset and comparisons with the state-of-the-art algorithms validate the advantages of the proposed method.

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

    Science.gov (United States)

    Pohlentz, Gottfried; Xia, Guoqing; Hussain, Muzaffar; Foster, Simon; Peters, Georg

    2017-01-01

    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 (SCC)mec 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 Pls glycosyl

  13. An analysis of amino acid sequences surrounding archaeal glycoprotein sequons.

    Science.gov (United States)

    Abu-Qarn, Mehtap; Eichler, Jerry

    2007-05-01

    Despite having provided the first example of a prokaryal glycoprotein, little is known of the rules governing the N-glycosylation process in Archaea. As in Eukarya and Bacteria, archaeal N-glycosylation takes place at the Asn residues of Asn-X-Ser/Thr sequons. Since not all sequons are utilized, it is clear that other factors, including the context in which a sequon exists, affect glycosylation efficiency. As yet, the contribution to N-glycosylation made by sequon-bordering residues and other related factors in Archaea remains unaddressed. In the following, the surroundings of Asn residues confirmed by experiment as modified were analyzed in an attempt to define sequence rules and requirements for archaeal N-glycosylation.

  14. An analysis of amino acid sequences surrounding archaeal glycoprotein sequons

    Directory of Open Access Journals (Sweden)

    Mehtap Abu-Qarn

    2006-01-01

    Full Text Available Despite having provided the first example of a prokaryal glycoprotein, little is known of the rules governing the N-glycosylation process in Archaea. As in Eukarya and Bacteria, archaeal N-glycosylation takes place at the Asn residues of Asn-X-Ser/Thr sequons. Since not all sequons are utilized, it is clear that other factors, including the context in which a sequon exists, affect glycosylation efficiency. As yet, the contribution to N-glycosylation made by sequon-bordering residues and other related factors in Archaea remains unaddressed. In the following, the surroundings of Asn residues confirmed by experiment as modified were analyzed in an attempt to define sequence rules and requirements for archaeal N-glycosylation.

  15. Myelin-associated glycoprotein and its axonal receptors.

    Science.gov (United States)

    Schnaar, Ronald L; Lopez, Pablo H H

    2009-11-15

    Myelin-associated glycoprotein (MAG) is expressed on the innermost myelin membrane wrap, directly apposed to the axon surface. Although it is not required for myelination, MAG enhances long-term axon-myelin stability, helps to structure nodes of Ranvier, and regulates the axon cytoskeleton. In addition to its role in axon-myelin stabilization, MAG inhibits axon regeneration after injury; MAG and a discrete set of other molecules on residual myelin membranes at injury sites actively signal axons to halt elongation. Both the stabilizing and the axon outgrowth inhibitory effects of MAG are mediated by complementary MAG receptors on the axon surface. Two MAG receptor families have been described, sialoglycans (specifically gangliosides GD1a and GT1b) and Nogo receptors (NgRs). Controversies remain about which receptor(s) mediates which of MAG's biological effects. Here we review the findings and challenges in associating MAG's biological effects with specific receptors.

  16. Small-angle scattering study of Aspergillus awamori glycoprotein glucoamylase

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, A. E., E-mail: schmidt@omrb.pnpi.spb.ru; Shvetsov, A. V. [National Research Center “Kurchatov Institute”, Konstantinov Petersburg Nuclear Physics Institute (Russian Federation); Kuklin, A. I. [Joint Institute for Nuclear Research (Russian Federation); Lebedev, D. V.; Surzhik, M. A.; Sergeev, V. R.; Isaev-Ivanov, V. V. [National Research Center “Kurchatov Institute”, Konstantinov Petersburg Nuclear Physics Institute (Russian Federation)

    2016-01-15

    Glucoamylase from fungus Aspergillus awamori is glycoside hydrolase that catalyzes the hydrolysis of α-1,4- and α-1,6-glucosidic bonds in glucose polymers and oligomers. This glycoprotein consists of a catalytic domain and a starch-binding domain connected by an O-glycosylated polypeptide chain. The conformation of the linker, the relative arrangement of the domains, and the structure of the full-length enzyme are unknown. The structure of the recombinant glucoamylase GA1 was studied by molecular modelling and small-angle neutron scattering (SANS) methods. The experimental SANS data provide evidence that glucoamylase exists as a monomer in solution and contains a glycoside component, which makes a substantial contribution to the scattering. The model of full-length glucoamylase, which was calculated without taking into account the effect of glycosylation, is consistent with the experimental data and has a radius of gyration of 33.4 ± 0.6 Å.

  17. INTERFERON SELECTIVELY INHIBITS THE SYNTHESIS OF MAYARO VIRUS GLYCOPROTEINS

    Directory of Open Access Journals (Sweden)

    Davis F. Ferreira

    1998-09-01

    Full Text Available We have previously observed that interferon (recIFNa2b blocks the process of morphogenesis of Mayaro virus in TC7 cells (monkey kidney. In this work we show that IFNa inhibits preferentially virus glycoproteins and their precursors, and this effect is probably correlated to the alterations in the morphogenesis process previously observed.Observamos anteriormente que o Interferon (IFN recombinante a2b bloqueia o processo de morfogênese do vírus Mayaro em células TC7 (rim de macaco. Neste trabalho demonstramos que o IFNa inibe preferencialmente as glicoproteínas virais e seus precursores e que este efeito está, provavelmente, correlacionado com as alterações no processo de morfogênese previamente observadas.

  18. Stereoselective Modulation of P-Glycoprotein by Chiral Small Molecules.

    Science.gov (United States)

    Carocci, Alessia; Catalano, Alessia; Turi, Francesco; Lovece, Angelo; Cavalluzzi, Maria M; Bruno, Claudio; Colabufo, Nicola A; Contino, Marialessandra; Perrone, Maria G; Franchini, Carlo; Lentini, Giovanni

    2016-01-01

    Inhibition of drug efflux pumps such as P-glycoprotein (P-gp) is an approach toward combating multidrug resistance, which is a significant hurdle in current cancer treatments. To address this, N-substituted aryloxymethyl pyrrolidines were designed and synthesized in their homochiral forms in order to investigate the stereochemical requirements for the binding site of P-gp. Our study provides evidence that the chiral property of molecules could be a strategy for improving the capacity for interacting with P-gp, as the most active compounds of the series stereoselectively modulated this efflux pump. The naphthalene-1-yl analogue (R)-2-[(2,3-dichlorophenoxy)methyl]-1-(naphthalen-1-ylmethyl)pyrrolidine) [(R)-7 a] emerged foremost for its potency and stereoselectivity toward P-gp, with the S enantiomer being nearly inactive. The modulation of P-gp by (R)-7 a involved consumption of ATP, thus demonstrating that the compound behaves as a P-gp substrate.

  19. Small-angle scattering study of Aspergillus awamori glycoprotein glucoamylase

    Science.gov (United States)

    Schmidt, A. E.; Shvetsov, A. V.; Kuklin, A. I.; Lebedev, D. V.; Surzhik, M. A.; Sergeev, V. R.; Isaev-Ivanov, V. V.

    2016-01-01

    Glucoamylase from fungus Aspergillus awamori is glycoside hydrolase that catalyzes the hydrolysis of α-1,4- and α-1,6-glucosidic bonds in glucose polymers and oligomers. This glycoprotein consists of a catalytic domain and a starch-binding domain connected by an O-glycosylated polypeptide chain. The conformation of the linker, the relative arrangement of the domains, and the structure of the full-length enzyme are unknown. The structure of the recombinant glucoamylase GA1 was studied by molecular modelling and small-angle neutron scattering (SANS) methods. The experimental SANS data provide evidence that glucoamylase exists as a monomer in solution and contains a glycoside component, which makes a substantial contribution to the scattering. The model of full-length glucoamylase, which was calculated without taking into account the effect of glycosylation, is consistent with the experimental data and has a radius of gyration of 33.4 ± 0.6 Å.

  20. Structure of the Epstein-Barr virus major envelope glycoprotein.

    Science.gov (United States)

    Szakonyi, Gerda; Klein, Michael G; Hannan, Jonathan P; Young, Kendra A; Ma, Runlin Z; Asokan, Rengasamy; Holers, V Michael; Chen, Xiaojiang S

    2006-11-01

    Epstein-Barr virus (EBV) infection of B cells is associated with lymphoma and other human cancers. EBV infection is initiated by the binding of the viral envelope glycoprotein (gp350) to the cell surface receptor CR2. We determined the X-ray structure of the highly glycosylated gp350 and defined the CR2 binding site on gp350. Polyglycans shield all but one surface of the gp350 polypeptide, and we demonstrate that this glycan-free surface is the receptor-binding site. Deglycosylated gp350 bound CR2 similarly to the glycosylated form, suggesting that glycosylation is not important for receptor binding. Structure-guided mutagenesis of the glycan-free surface disrupted receptor binding as well as binding by a gp350 monoclonal antibody, a known inhibitor of virus-receptor interactions. These results provide structural information for developing drugs and vaccines to prevent infection by EBV and related viruses.

  1. Variation in the Major Surface Glycoprotein Genes in Pneumocystis jirovecii

    Science.gov (United States)

    Kutty, Geetha; Maldarelli, Frank; Achaz, Guillaume; Kovacs, Joseph A.

    2008-01-01

    The genome of Pneumocystis, which causes life-threatening pneumonia in immunosuppressed patients, contains a multi-copy gene family that encodes the major surface glycoprotein (Msg). Pneumocystis can vary the expressed Msg, presumably as a mechanism to avoid host immune responses. Analysis of 24 msg gene sequences obtained from a single human Pneumocystis isolate demonstrated that the sequences segregate into two branches. Based on a number of analyses, recombination among msg genes appears to be an important mechanism for generating msg diversity. Intra-branch recombination occurred more frequently than inter-branch recombination. Restriction fragment length polymorphism analysis demonstrated substantial variation in the repertoire of the msg gene family among isolates of human Pneumocystis, which was not observed in laboratory isolates of rat or mouse Pneumocystis; this may be the result of examining outbred vs. captive populations. Increased diversity in the Msg repertoire, generated in part by recombination, increases the potential for antigenic variation in this abundant surface protein. PMID:18627244

  2. Bioskin as an affinity matrix for the separation of glycoproteins.

    Science.gov (United States)

    Vicente, C; Sebastián, B; Fontaniella, B; Márquez, A; Xavier Filho, L; Legaz, M E

    2001-05-11

    Bioskin is a natural product produced by a mixed culture of Acetobacter xylinum, Saccharomyces cerevisiae and S. pombe cultured on media containing sucrose. It is of fibrillar nature able to retain some proteins, such as cytochrome c, by adsorption, and mainly composed of glucosamine and N-acetyl-D-glucosamine. This makes it possible that, at an adequate pH value, proteins charged as polyanionic molecules, such as catalase, can be retained by ionic adsorption using the positively charged amino groups of the matrix. In addition, bioskin can also be used as an affinity matrix to retain glycoproteins able to perform specific affinity reactions with the amino sugars of the matrix, such as invertase, fetuin or ovalbumin. Its possible use as a chromatographic support is discussed.

  3. Crystal Structure of the Human Cytomegalovirus Glycoprotein B.

    Directory of Open Access Journals (Sweden)

    Heidi G Burke

    2015-10-01

    Full Text Available Human cytomegalovirus (HCMV, a dsDNA, enveloped virus, is a ubiquitous pathogen that establishes lifelong latent infections and caused disease in persons with compromised immune systems, e.g., organ transplant recipients or AIDS patients. HCMV is also a leading cause of congenital viral infections in newborns. Entry of HCMV into cells requires the conserved glycoprotein B (gB, thought to function as a fusogen and reported to bind signaling receptors. gB also elicits a strong immune response in humans and induces the production of neutralizing antibodies although most anti-gB Abs are non-neutralizing. Here, we report the crystal structure of the HCMV gB ectodomain determined to 3.6-Å resolution, which is the first atomic-level structure of any betaherpesvirus glycoprotein. The structure of HCMV gB resembles the postfusion structures of HSV-1 and EBV homologs, establishing it as a new member of the class III viral fusogens. Despite structural similarities, each gB has a unique domain arrangement, demonstrating structural plasticity of gB that may accommodate virus-specific functional requirements. The structure illustrates how extensive glycosylation of the gB ectodomain influences antibody recognition. Antigenic sites that elicit neutralizing antibodies are more heavily glycosylated than those that elicit non-neutralizing antibodies, which suggest that HCMV gB uses glycans to shield neutralizing epitopes while exposing non-neutralizing epitopes. This glycosylation pattern may have evolved to direct the immune response towards generation of non-neutralizing antibodies thus helping HCMV to avoid clearance. HCMV gB structure provides a starting point for elucidation of its antigenic and immunogenic properties and aid in the design of recombinant vaccines and monoclonal antibody therapies.

  4. Karyotype versus microarray testing for genetic abnormalities after stillbirth.

    Science.gov (United States)

    Reddy, Uma M; Page, Grier P; Saade, George R; Silver, Robert M; Thorsten, Vanessa R; Parker, Corette B; Pinar, Halit; Willinger, Marian; Stoll, Barbara J; Heim-Hall, Josefine; Varner, Michael W; Goldenberg, Robert L; Bukowski, Radek; Wapner, Ronald J; Drews-Botsch, Carolyn D; O'Brien, Barbara M; Dudley, Donald J; Levy, Brynn

    2012-12-06

    Genetic abnormalities have been associated with 6 to 13% of stillbirths, but the true prevalence may be higher. Unlike karyotype analysis, microarray analysis does not require live cells, and it detects small deletions and duplications called copy-number variants. The Stillbirth Collaborative Research Network conducted a population-based study of stillbirth in five geographic catchment areas. Standardized postmortem examinations and karyotype analyses were performed. A single-nucleotide polymorphism array was used to detect copy-number variants of at least 500 kb in placental or fetal tissue. Variants that were not identified in any of three databases of apparently unaffected persons were then classified into three groups: probably benign, clinical significance unknown, or pathogenic. We compared the results of karyotype and microarray analyses of samples obtained after delivery. In our analysis of samples from 532 stillbirths, microarray analysis yielded results more often than did karyotype analysis (87.4% vs. 70.5%, P<0.001) and provided better detection of genetic abnormalities (aneuploidy or pathogenic copy-number variants, 8.3% vs. 5.8%; P=0.007). Microarray analysis also identified more genetic abnormalities among 443 antepartum stillbirths (8.8% vs. 6.5%, P=0.02) and 67 stillbirths with congenital anomalies (29.9% vs. 19.4%, P=0.008). As compared with karyotype analysis, microarray analysis provided a relative increase in the diagnosis of genetic abnormalities of 41.9% in all stillbirths, 34.5% in antepartum stillbirths, and 53.8% in stillbirths with anomalies. Microarray analysis is more likely than karyotype analysis to provide a genetic diagnosis, primarily because of its success with nonviable tissue, and is especially valuable in analyses of stillbirths with congenital anomalies or in cases in which karyotype results cannot be obtained. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.).

  5. Genetic abnormalities in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Zamboni Giuseppe

    2003-01-01

    Full Text Available Abstract The incidence and mortality of pancreatic adenocarcinoma are nearly coincident having a five-year survival of less than 5%. Enormous advances have been made in our knowledge of the molecular alterations commonly present in ductal cancer and other pancreatic malignancies. One significant outcome of these studies is the recognition that common ductal cancers have a distinct molecular fingerprint compared to other nonductal or endocrine tumors. Ductal carcinomas typically show alteration of K-ras, p53, p16INK4, DPC4 and FHIT, while other pancreatic tumor types show different aberrations. Among those tumors arising from the exocrine pancreas, only ampullary cancers have a molecular fingerprint that may involve some of the same genes most frequently altered in common ductal cancers. Significant molecular heterogeneity also exists among pancreatic endocrine tumors. Nonfunctioning pancreatic endocrine tumors have frequent mutations in MEN-1 and may be further subdivided into two clinically relevant subgroups based on the amount of chromosomal alterations. The present review will provide a brief overview of the genetic alterations that have been identified in the various subgroups of pancreatic tumors. These results have important implications for the development of genetic screening tests, early diagnosis, and prognostic genetic markers.

  6. Preparation of Concanavalin A-Chelating Magnetic Nanoparticles for Selective Enrichment of Glycoproteins.

    Science.gov (United States)

    Dong, Liping; Feng, Shun; Li, Shanshan; Song, Peipei; Wang, Jide

    2015-07-07

    In this work, a soft and nondestructive approach was developed to prepare concanavalin A-chelating magnetic nanoparticles (Con A-MNPs) for selective enrichment of glycoproteins. Ethylenediamine tetraacetic acid-modified-MNPs (EDTA-MNPs) were prepared by a one-pot chemical coprecipitation method first, and then, Cu(II) cations were used as bridge groups to immobilize Con A on EDTA-MNPs. The as-prepared absorbents with a mean diameter of 15 nm showed a strong magnetic response to an externally applied magnetic field. The results of thermogravimetric analysis showed the content of immobilized Con A was up to 28 wt %. For glycoprotein ovalbumin, the maximum capacity and equilibrium constant were 72.41 mg/g and 0.6035 L/mg, respectively. The as-prepared nanocomposites exhibited a remarkable selectivity for glycoproteins and can enrich glycoproteins specifically from a mixture of glycoprotein and nonglycoprotein even at a molar ratio of 1:600. It was also successfully applied for the enrichment of glycoproteins from real egg white samples. We expect that our finding will serve as a helpful template for others to design new adsorbents for enriching glycoproteins.

  7. Protective Role of α2HS-Glycoprotein in HBV-Associated Liver Failure

    Directory of Open Access Journals (Sweden)

    Xue-Gong Fan

    2011-06-01

    Full Text Available n this study, levels of plasma α2-Heremans-Schmid glycoprotein, serum tumor necrosis factor-α, serum liver function parameters and short-term mortality were measured in 100 hepatitis B patients. Release of interleukin-6 and tumor necrosis factor-α from the lipopolysaccharide-stimulated peripheral blood mononuclear cells in the presence/absence of spermine and α2-Heremans-Schmid glycoprotein were analyzed by enzyme-linked immunosorbent assay to determine the significance and potential mechanism of α2-Heremans-Schmid glycoprotein in hepatitis B virus-associated liver damage. Results showed that serum α2-Heremans-Schmid glycoprotein levels in acute-on-chronic liver failure patients were significantly lower than that in chronic hepatitis B patients or healthy controls (p < 0.05. A negative dependence between serum human α2-Heremans-Schmid glycoprotein and tumor necrosis factor-α levels was observed. Interleukin-6 and tumor necrosis factor-α levels in the lipopolysaccharide-induced peripheral blood mononuclear cell supernates were significantly reduced by spermine and/or α2-Heremans-Schmid glycoprotein. The latter two proteins jointly inhibited cytokine release. These observations suggest that plasma α2-Heremans-Schmid glycoprotein is an independent marker of liver damage and a prognostic indicator of hepatitis B virus chronicity. It may reduce liver inflammation by partially inhibiting release of inflammatory factors from activated peripheral blood mononuclear cells.

  8. The contribution of chromosomal abnormalities to congenital heart defects: a population-based study.

    Science.gov (United States)

    Hartman, Robert J; Rasmussen, Sonja A; Botto, Lorenzo D; Riehle-Colarusso, Tiffany; Martin, Christa L; Cragan, Janet D; Shin, Mikyong; Correa, Adolfo

    2011-12-01

    We aimed to assess the frequency of chromosomal abnormalities among infants with congenital heart defects (CHDs) in an analysis of population-based surveillance data. We reviewed data from the Metropolitan Atlanta Congenital Defects Program, a population-based birth-defects surveillance system, to assess the frequency of chromosomal abnormalities among live-born infants and fetal deaths with CHDs delivered from January 1, 1994, to December 31, 2005. Among 4430 infants with CHDs, 547 (12.3%) had a chromosomal abnormality. CHDs most likely to be associated with a chromosomal abnormality were interrupted aortic arch (type B and not otherwise specified; 69.2%), atrioventricular septal defect (67.2%), and double-outlet right ventricle (33.3%). The most common chromosomal abnormalities observed were trisomy 21 (52.8%), trisomy 18 (12.8%), 22q11.2 deletion (12.2%), and trisomy 13 (5.7%). In conclusion, in our study, approximately 1 in 8 infants with a CHD had a chromosomal abnormality. Clinicians should have a low threshold at which to obtain testing for chromosomal abnormalities in infants with CHDs, especially those with certain types of CHDs. Use of new technologies that have become recently available (e.g., chromosomal microarray) may increase the identified contribution of chromosomal abnormalities even further.

  9. Multi-modality imaging review of congenital abnormalities of kidney and upper urinary tract

    Institute of Scientific and Technical Information of China (English)

    Subramaniyan Ramanathan; Devendra Kumar; Maneesh Khanna; Mahmoud Al Heidous; Adnan Sheikh; Vivek Virmani; Yegu Palaniappan

    2016-01-01

    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, noninvasive 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.

  10. Adenotonsillar hypertrophy as a risk factor of dentofacial abnormality in Korean children.

    Science.gov (United States)

    Kim, Dong-Kyu; Rhee, Chae Seo; Yun, Pil-Young; Kim, Jeong-Whun

    2015-11-01

    No studies for the role of adenotonsillar hypertrophy in development of dentofacial abnormalities have been performed in Asian pediatric population. Thus, we aimed to investigate the relationship between adenotonsillar hypertrophy and dentofacial abnormalities in Korean children. The present study included consecutive children who visited a pediatric clinic for sleep-disordered breathing due to habitual mouth breathing, snoring or sleep apnea. Their palatine tonsils and adenoids were graded by oropharyngeal endoscopy and lateral cephalometry. Anterior open bite, posterior crossbite, and Angle's class malocclusions were evaluated for dentofacial abnormality. The receiver-operating characteristic curve analysis was used to identify age cutoffs to predict dentofacial abnormality. A total of 1,083 children were included. The presence of adenotonsillar hypertrophy was significantly correlated with the prevalence of dentofacial abnormality [adjusted odds ratio = 4.587, 95% CI (2.747-7.658)] after adjusting age, sex, body mass index, allergy, and Korean version of obstructive sleep apnea-18 score. The cutoff age associated with dentofacial abnormality was 5.5 years (sensitivity = 75.5%, specificity = 67%) in the children with adenotonsillar hypertrophy and 6.5 years (sensitivity = 70.6%, specificity = 57%) in those without adenotonsillar hypertrophy. In conclusion, adenotonsillar hypertrophy may be a risk factor for dentofacial abnormalities in Korean children and early surgical intervention could be considered with regards to dentofacial abnormality.

  11. 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.

  12. Effects of pronase and neuraminidase treatment on a myelin-associated glycoprotein in developing brain.

    Science.gov (United States)

    Quarles, R H

    1976-04-15

    Rats (14 days old) were injected with [14c]fucose and young adult rats with [3H]fucose in order to label the myelin-associated glycoproteins. As previously reported, the major [14C]fucose-labelled glycoprotein in the immature myelin had a higher apparent molecular weight on sodium dodecyl sulphate/polyacrylamide gels that the [3H]fucose-labelled glycoprotein in mature myelin. This predominant doubly labelled glycoprotein component was partially purified by preparative gel electrophoresis and converted to glycopeptides by extensive Pronase digestion. Gel filtration on Sephadex G-50 separated the glycopeptides into several clases, which were designted A,B, C AND D, from high to low molecular weight. The 14C-labelled glycopeptides from immature myeline were enriched in the highest-molecular-weight class A relative to the 3H-labelled glycopeptides from mature myelin. Neuraminidase treatment of the glycoprotein before Pronase digestion greatly decreased the proportion of glycopeptides fractionating in the higher-molecular-weight classes and largely eliminated the developmental differences that were apparent by gel filtration. However, neuraminidase treatment did not decrease the magnitude of the developmental difference revealed by electrophoresing the intact glycoprotein on sodium dodecyl sulphate gels, although it did decrease the apparent molecular weight of the glycoprotein from both the 15-day-old and adult rats by an amount comparable in magnitude to that developmental difference. The results from gel filtration of glycopeptides indicate that there is a higher content of large molecular weight, sialic acid-rich oligosaccharide units in the glycoprotein of immature myelin. However, the higher apparent molecular weight for the glycoprotein from 15-day-old rats on sodium dodcyl sulphate gels is not due primarily to its higher sialic acid content.

  13. 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

  14. The effect of associated structural malformations in the prediction of chromosomal abnormality risk of fetuses with echogenic bowel.

    Science.gov (United States)

    Ekin, Atalay; Gezer, Cenk; Taner, Cuneyt Eftal; Ozeren, Mehmet

    2016-01-01

    Our aim is to determine the frequency of chromosomal abnormalities and also to identify the role of structural malformations on the chromosomal abnormality risk among fetuses with echogenic bowel. Over a 6-year period fetuses with echogenic bowel (FEB) were retrospectively evaluated. The pregnancies with intra-amniotic bleeding history, congenital infection, cystic fibrosis and intrauterine growth retardation were excluded from the study. Types and frequency of sonographically detected fetal malformations were identified. Chromosomal abnormality incidences according to association with soft markers and major fetal abnormalities were compared. Of the 281 fetuses with echogenic bowel, 105 (37.37%) were isolated, 78 (27.76%) were associated with soft markers and 98 (34.87%) were associated with major abnormalities. There were 30 (10.7%) fetuses with abnormal karyotypes. The chromosomal abnormality rate of the groups of isolated FEB, FEB + soft markers and FEB + major abnormalities were 6.7%, 7.7% and 17.4%, respectively. Chromosomal abnormality risk in fetuses with echogenic bowel should be evaluated according to additional sonographic findings. Association of structural malformations increases the chromosomal abnormality risk, although this risk is not significant with the presence of soft markers alone.

  15. Discovery and Characterization of Phage Display-Derived Human Monoclonal Antibodies against RSV F Glycoprotein.

    Directory of Open Access Journals (Sweden)

    Zhifeng Chen

    Full Text Available Respiratory syncytial virus (RSV is a leading cause of lower respiratory tract infection in infants, the elderly and in immunosuppressed populations. The vast majority of neutralizing antibodies isolated from human subjects target the RSV fusion (F glycoprotein, making it an attractive target for the development of vaccines and therapeutic antibodies. Currently, Synagis® (palivizumab is the only FDA approved antibody drug for the prevention of RSV infection, and there is a great need for more effective vaccines and therapeutics. Phage display is a powerful tool in antibody discovery with the advantage that it does not require samples from immunized subjects. In this study, Morphosys HuCAL GOLD® phage libraries were used for panning against RSV prefusion and postfusion F proteins. Panels of human monoclonal antibodies (mAbs against RSV F protein were discovered following phage library panning and characterized. Antibodies binding specifically to prefusion or postfusion F proteins and those binding both conformations were identified. 3B1 is a prototypic postfusion F specific antibody while 2E1 is a prototypic prefusion F specific antibody. 2E1 is a potent broadly neutralizing antibody against both RSV A and B strains. Epitope mapping experiments identified a conformational epitope spanning across three discontinuous sections of the RSV F protein, as well as critical residues for antibody interaction.

  16. 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.

  17. Electrocardiographic abnormalities and serum magnesium in patients with subarachnoid hemorrhage

    NARCIS (Netherlands)

    van den Bergh, Walter M; Algra, Ale; Rinkel, Gabriël J E

    2004-01-01

    BACKGROUND AND PURPOSE: ECG abnormalities and hypomagnesemia frequently occur after aneurysmal subarachnoid hemorrhage (SAH). Because hypomagnesemia is associated with several ECG abnormalities, we studied whether hypomagnesemia mediates ECG abnormalities after SAH. METHODS: We prospectively studied

  18. Varicella-zoster virus glycoprotein I is essential for growth of virus in Vero cells.

    OpenAIRE

    Cohen, J I; Nguyen, H.

    1997-01-01

    Varicella-zoster virus (VZV) encodes at least six glycoproteins. Glycoprotein I (gI), the product of open reading frame 67, is a 58- to 62-kDa glycoprotein found in VZV-infected cells. We constructed two VZV gI deletion mutants. Immunoprecipitation of VZV gE from infected cells indicated that cells infected with VZV deleted for gI expressed a gE that was larger (100 kDa) than that expressed in cells infected with the parental virus (98 kDa). Cell-associated or cell-free VZV deleted for gI gre...

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    A. V. Shulkin

    2013-01-01

    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.

  1. Identification of the milk fat globule membrane proteins. I. Isolation and partial characterization of glycoprotein B.

    Science.gov (United States)

    Basch, J J; Farrell, H M; Greenberg, R

    1976-11-02

    The salt soluble proteins from the fat globule membrane of cow's milk were resolved into three fractions by Sephadex column chromatography in sodium dodecyl sulfate. One of the fractions, termed glycoprotein B, was purified by rechromatography to essentially one band on sodium dodecyl sulfate gel electrophoresis. It was found to contain 14% carbohydrate including sialic acid, mannose, galactose, glucose, glucosamine and galactosamine. The amino acid composition of glycoprotein B was determined; it has amino terminal serine and carboxyl terminal leucine. The molecular weight of this glycoprotein as estimated by sodium dodecyl sulfate gel electrophoresis is 49 500.

  2. Crystal structure of the Epstein-Barr virus (EBV) glycoprotein H/glycoprotein L (gH/gL) complex.

    Science.gov (United States)

    Matsuura, Hisae; Kirschner, Austin N; Longnecker, Richard; Jardetzky, Theodore S

    2010-12-28

    The Epstein-Barr virus (EBV) is a γ-herpesvirus that infects B cells and epithelial cells and that has been linked to malignancies in both cell types in vivo. EBV, like other herpesviruses, has three glycoproteins, glycoprotein B (gB), gH, and gL, that form the core membrane fusion machinery mediating viral penetration into the cell. The gH and gL proteins associate to form a heterodimeric complex, which is necessary for efficient membrane fusion and also implicated in direct binding to epithelial cell receptors required for viral entry. To gain insight into the mechanistic role of gH/gL, we determined the crystal structure of the EBV gH/gL complex. The structure is comprised of four domains organized along the longest axis of the molecule. Comparisons with homologous HSV-2 gH/gL and partial pseudorabies virus gH structures support the domain boundaries determined for the EBV gH/gL structure and illustrate significant differences in interdomain packing angles. The gL subunit and N-terminal residues of gH form a globular domain at one end of the structure, implicated in interactions with gB and activation of membrane fusion. The C-terminal domain of gH, proximal to the viral membrane, is also implicated in membrane fusion. The gH/gL structure locates an integrin binding motif, implicated in epithelial cell entry, on a prominent loop in the central region of the structure. Multiple regions of gH/gL, including its two extreme ends, are functionally important, consistent with the multiple roles of gH/gL in EBV entry.

  3. 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.

  4. Serum Glycoprotein Biomarker Discovery and Qualification Pipeline Reveals Novel Diagnostic Biomarker Candidates for Esophageal Adenocarcinoma.

    Science.gov (United States)

    Shah, Alok K; Cao, Kim-Anh Lê; Choi, Eunju; Chen, David; Gautier, Benoît; Nancarrow, Derek; Whiteman, David C; Saunders, Nicholas A; Barbour, Andrew P; Joshi, Virendra; Hill, Michelle M

    2015-11-01

    We report an integrated pipeline for efficient serum glycoprotein biomarker candidate discovery and qualification that may be used to facilitate cancer diagnosis and management. The discovery phase used semi-automated lectin magnetic bead array (LeMBA)-coupled tandem mass spectrometry with a dedicated data-housing and analysis pipeline; GlycoSelector (http://glycoselector.di.uq.edu.au). The qualification phase used lectin magnetic bead array-multiple reaction monitoring-mass spectrometry incorporating an interactive web-interface, Shiny mixOmics (http://mixomics-projects.di.uq.edu.au/Shiny), for univariate and multivariate statistical analysis. Relative quantitation was performed by referencing to a spiked-in glycoprotein, chicken ovalbumin. We applied this workflow to identify diagnostic biomarkers for esophageal adenocarcinoma (EAC), a life threatening malignancy with poor prognosis in the advanced setting. EAC develops from metaplastic condition Barrett's esophagus (BE). Currently diagnosis and monitoring of at-risk patients is through endoscopy and biopsy, which is expensive and requires hospital admission. Hence there is a clinical need for a noninvasive diagnostic biomarker of EAC. In total 89 patient samples from healthy controls, and patients with BE or EAC were screened in discovery and qualification stages. Of the 246 glycoforms measured in the qualification stage, 40 glycoforms (as measured by lectin affinity) qualified as candidate serum markers. The top candidate for distinguishing healthy from BE patients' group was Narcissus pseudonarcissus lectin (NPL)-reactive Apolipoprotein B-100 (p value = 0.0231; AUROC = 0.71); BE versus EAC, Aleuria aurantia lectin (AAL)-reactive complement component C9 (p value = 0.0001; AUROC = 0.85); healthy versus EAC, Erythroagglutinin Phaseolus vulgaris (EPHA)-reactive gelsolin (p value = 0.0014; AUROC = 0.80). A panel of 8 glycoforms showed an improved AUROC of 0.94 to discriminate EAC from BE. Two biomarker candidates

  5. Blood-Brain Barrier Abnormalities Caused by HIV-1 gp120: Mechanistic and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Louboutin

    2012-01-01

    Full Text Available The blood-brain barrier (BBB is compromised in many systemic and CNS diseases, including HIV-1 infection of the brain. We studied BBB disruption caused by HIV-1 envelope glycoprotein 120 (gp120 as a model. Exposure to gp120, whether acute [by direct intra-caudate-putamen (CP injection] or chronic [using SV(gp120, an experimental model of ongoing production of gp120] disrupted the BBB, and led to leakage of vascular contents. Gp120 was directly toxic to brain endothelial cells. Abnormalities of the BBB reflect the activity of matrix metalloproteinases (MMPs. These target laminin and attack the tight junctions between endothelial cells and BBB basal laminae. MMP-2 and MMP-9 were upregulated following gp120-injection. Gp120 reduced laminin and tight junction proteins. Reactive oxygen species (ROS activate MMPs. Injecting gp120 induced lipid peroxidation. Gene transfer of antioxidant enzymes protected against gp120-induced BBB abnormalities. NMDA upregulates the proform of MMP-9. Using the NMDA receptor (NMDAR-1 inhibitor, memantine, we observed partial protection from gp120-induced BBB injury. Thus, (1 HIV-envelope gp120 disrupts the BBB; (2 this occurs via lesions in brain microvessels, MMP activation and degradation of vascular basement membrane and vascular tight junctions; (3 NMDAR-1 activation plays a role in this BBB injury; and (4 antioxidant gene delivery as well as NMDAR-1 antagonists may protect the BBB.

  6. Dopaminergic system abnormalities Etiopathogenesis of dystonia

    Institute of Scientific and Technical Information of China (English)

    Shuhui Wu; Huifang Shang; Xiaoyi Zou

    2008-01-01

    BACKGROUND: Much research has focused on the close relationship between etiopathogenesis of dystonia and abnormalities of the dopaminergic system. Nevertheless, details of the mechanism are still not clear.OBJECTIVE: To review studies from the past few years about pathogenesis and molecular interactions involved in the relationship between dystonia and abnormalities of the dopaminergic system.RETRIEVAL STRATEGY: Using the key words "dystonia" and "dopamine", PubMed database and SCI databases were searched from January 1990 to December 2005 for relevant English publications. A total of 73 articles were searched and, initially, all articles were selected. Inclusive criteria: studies based on pathogenesis and molecular interactions involved in the relationship between dystonia and abnormalities of the dopaminergic system. Exclusive criteria: duplicated studies. A total of 19 articles were extracted after preliminary screening.LITERATURE EVALUATION: The data sources were the PubMed and SCI databases. The types of articles chosen were reviews and original articles.DATA SYNTHESIS: Metabolism and function of dopamine in the central nervous system: the chemical constitution of dopamine is a single benzene ring. The encephalic regions of dopamine synthesis and their fiber projections comprise four nervous system pathways. One of these pathways is the substantia nigra-striatum dopamine pathway, which is a side-loop of the basal ganglia circuitry that participates in movement control and plays a main role in the adjustment of extracorticospinal tract movement. Dopamine can lead to the facilitation of movement. Dystonia and abnormalities of the dopaminergic system: different modes of dopamine abnormality exist in various forms of dystonia. Abnormalities of the dopaminergic system in several primary dystonias: at present, fifteen gene loci of primary dystonia have been reported (DYT1-DYT15). The relationship between abnormalities of the dopaminergic system and the

  7. MRI of fetal GI tract abnormalities.

    Science.gov (United States)

    Veyrac, C; Couture, A; Saguintaah, M; Baud, C

    2004-01-01

    We describe the magnetic resonance (MR) patterns of a variety of fetal gastrointestinal (GI) abnormalities. Thirty-two fetuses between 23 and 38 weeks' gestation with abnormal appearance of the GI tract by ultrasound underwent MR imaging with T1- and T2-weighted sequences. The MR aspect of intestinal atresia (duodenal atresia, one case; small bowel atresia, nine cases) included dilatation of the bowel loops, accurate assessment of the normal bowel distal to the atresia (except in the patient with multiple atresia and apple-peel syndrome), and micro-rectum with decreased T1 signal (except in the patient with duodenal atresia). Megacystis-microcolon-intestinal hypoperistalsis syndrome (one case) was indicated by an abnormal signal of the entire bowel and an abnormal pattern for the urinary tract. Meconium pseudocysts (two cases) were easily differentiated from enteric cysts (two cases). High anorectal malformations with (two cases) or without (one case) urinary fistula and cloacal malformation (one case) are described and MR findings are discussed. The capability of MR imaging to demonstrate the normal bowel with intraperitoneal anomalies (e.g., congenital diaphragmatic hernia, and sacrococcygeal teratoma) is emphasized. MR imaging is informative in the diagnosis of GI tract abnormalities, especially the severe malformations, with much more accuracy than sonography.

  8. OPHTHALMOLOGIC ABNORMALITIES IN CHILDREN WITH IMPAIRED HEARING

    Directory of Open Access Journals (Sweden)

    Inderjit

    2014-02-01

    Full Text Available AIM: To determine the nature of ophthalmologic abnormalities in severe and profound grades of hearing impaired children and to treat visual impairment if any at the earliest . MATERIAL AND METHODS: Study was conducted on100 children in the age group of 5 - 14 years with severe and profound hearing loss visiting outpatient department of Ram Lal Eye and ENT hospital Govt. Medical College Amritsar and subjected to detailed ophthalmological examination. RESULTS: 100 children in the age group 5 - 14 years with hearing impairment were enrolled for t he study , 68 had profound and 32 had severe hearing loss . Visual disorders were found to be as high as 71%. Highest percentage was seen in children aged 7 years. Majority of them (50% had refractive error. Out of these 50 children , 28(56% had myopia , 10 (20% hypermetropia and 12(24% had astigmatism . The other ophthalmic abnormalities in our study were conjunctivitis 14(19.71% , fundus abnormalities and squint 11(15.49% , blepharitis 5 (7.04% , vitamin A deficiency 6 (8.04% , amblyopia 8 (11.26% , pupil disorder 3 (4.22% , cataract 3 (4.22% and heterochromia iridis 7 (9.85%. CONCLUSION : The high prevalence of ophthalmic abnormalities in deaf children mandate screening them for possible ophthalmic abnormalities. Early diagnosis and correction of visual d isturbances would go a long way in social and professional performance of these children.

  9. Prevalence of asymptomatic urinary abnormalities among adolescents.

    Science.gov (United States)

    Fouad, Mohamed; Boraie, Maher

    2016-05-01

    To determine the prevalence of asymptomatic urinary abnormalities in adolescents, first morning clean mid-stream urine specimens were obtained from 2500 individuals and examined by dipstick and light microscopy. Adolescents with abnormal screening results were reexamined after two weeks and those who had abnormal results twice were subjected to systemic clinical examination and further clinical and laboratory investigations. Eight hundred and three (32.1%) individuals had urinary abnormalities at the first screening, which significantly decreased to 345 (13.8%) at the second screening, (P adolescents who had persistent urine abnormalities; 228 (9.1%) individuals had non glomerular hematuria. The hematuria was isolated in 150 (6%) individuals, combined with leukocyturia in 83 (3.3%) individuals, and combined with proteinuria in 12 (0.5%) individuals. Leukocyturia was detected in 150 (6%) of all studied adolescents; it was isolated in 39 (1.6%) individuals and combined with proteinuria in 28 (1.1%) of them. Asymptomatic bacteriuria was detected in 23 (0.9%) of all studied adolescents; all the cases were females. Proteinuria was detected in 65 (2.6%) of all the studied adolescents; 45 (1.8%) individuals had adolescents from rural than urban areas (P adolescents in our population.

  10. Characteristics of patients with sensory neuropathy diagnosed with abnormal small nerve fibres on skin biopsy

    OpenAIRE

    De Sousa, E A; Hays, A P; Chin, R L; Sander, H W; Brannagan, T H

    2006-01-01

    Clinical, laboratory and electrodiagnostic (EDX) characteristics of 62 patients with sensory neuropathy with abnormal skin biopsies were reviewed. Reduced epidermal nerve fibre density (ENFD) was seen in 71% and morphological changes with normal ENFD were seen in 29% of the patients. Patients with small fibre sensory neuropathy may have associated large fibre loss undetected by routine EDX. Identified associations included abnormal glucose metabolism, Lyme vaccination, monoclonal gammopathy, ...

  11. Renal Abnormalities in Patients with Sickle Cell Disease: A Single Center Report from Saudi Arabia

    OpenAIRE

    Aleem Aamer

    2008-01-01

    Patients with sickle cell disease (SCD) are at increased risk of serious morbidity and mortality. Renal abnormalities in SCD are well known but renal involvement in Saudi patients with SCD has not been studied. We sought to identify renal abnormalities in adolescent and adult Saudi patients with SCD. We prospectively studied 73 patients with SCD followed up at King Khalid University Hospital, Riyadh, Saudi Arabia from July 2005 to November 2006,. All patients underwent evaluation of kidney fu...

  12. Preparation of a high-performance multi-lectin affinity chromatography (HP-M-LAC) adsorbent for the analysis of human plasma glycoproteins.

    Science.gov (United States)

    Kullolli, Majlinda; Hancock, William S; Hincapie, Marina

    2008-08-01

    We report on the preparation of an improved multi-lectin affinity support for HPLC separations. We combined the selectivity of three different lectins: concanavalin A (ConA), wheat germ agglutinin (WGA), and jacalin (JAC). Each lectin was first covalently immobilized onto a polymeric matrix and then the three lectin media were combined in equal ratios. The beads were packed into a column to produce a mixed-bed multi-lectin HPLC column (high-performance multi-lectin affinity chromatography (HP-M-LAC)) for fast chromatographic affinity separations. The support was characterized with respect to kinetics of immobilization, ligand density, and binding capacity for human plasma glycoproteins. A high lectin density (15 mg/mL of beads) was found to be optimal for the binding of glycoproteins from human plasma. A single clinical sample can be fractionated in less than 10 min per run, making this a useful sample preparation tool for proteomics/glycoproteomics studies associated with disease abnormalities.

  13. The GCTM-5 Epitope Associated with the Mucin-Like Glycoprotein FCGBP Marks Progenitor Cells in Tissues of Endodermal Origin

    Science.gov (United States)

    Stamp, Lincon A.; Braxton, David R.; Wu, Jun; Akopian, Veronika; Hasegawa, Kouichi; Chandrasoma, Parakrama T.; hawes, Susan M.; Mclean, Catriona; Petrovic, Lydia m.; WANG, KASPER; Pera, Martin F.

    2013-01-01

    Monoclonal antibodies against cell surface markers are powerful tools in the study of tissue regeneration, repair, and neoplasia, but there is a paucity of specific reagents to identify stem and progenitor cells in tissues of endodermal origin. The epitope defined by the GCTM-5 monoclonal antibody is a putative marker of hepatic progenitors. We sought to analyze further the distribution of the GCTM-5 antigen in normal tissues and disease states and to characterize the antigen biochemically. The GCTM-5 epitope was specifically expressed on tissues derived from the definitive endoderm, in particular the fetal gut, liver, and pancreas. Antibody reactivity was detected in subpopulations of normal adult biliary and pancreatic duct cells, and GCTM-5-positive cells isolated from the nonparenchymal fraction of adult liver expressed markers of progenitor cells. The GCTM-5-positive cell populations in liver and pancreas expanded greatly in numbers in disease states such as biliary atresia, cirrhosis, and pancreatitis. Neoplasms arising in these tissues also expressed the GCTM-5 antigen, with pancreatic adenocarcinoma in particular showing strong and consistent reactivity. The GCTM-5 epitope was also strongly displayed on cells undergoing intestinal metaplasia in Barrett’s esophagus, a precursor to esophageal carcinoma. Biochemical, mass spectrometry, and immunochemical studies revealed that the GCTM-5 epitope is associated with the mucin-like glycoprotein FCGBP. The GCTM-5 epitope on the mucin-like glycoprotein FCGBP is a cell surface marker for the study of normal differentiation lineages, regeneration, and disease progression in tissues of endodermal origin. PMID:22761039

  14. 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.

  15. Antiplatelet activity of L-sulforaphane by regulation of platelet activation factors, glycoprotein IIb/IIIa and thromboxane A2.

    Science.gov (United States)

    Oh, Chung-Hun; Shin, Jang-In; Mo, Sang Joon; Yun, Sung-Jo; Kim, Sung-Hoon; Rhee, Yun-Hee

    2013-07-01

    L-sulforaphane was identified as an anticarcinogen that could produce quinine reductase and a phase II detoxification enzyme. In recent decades, multi-effects of L-sulforaphane may have been investigated, but, to the authors' knowledge, the antiplatelet activation of L-sulforaphane has not been studied yet.In this study, 2 μg/ml of collagen, 50 μg/ml of ADP and 5 μg/ml of thrombin were used for platelet aggregations with or without L-sulforaphane. L-sulforaphane inhibited the platelet aggregation dose-dependently. Among these platelet activators, collagen was most inhibited by L-sulforaphane, which markedly decreased collagen-induced glycoprotein IIb/IIIa activation and thromboxane A2 (TxA2) formation in vitro. L-sulforaphane also reduced the collagen and epinephrine-induced pulmonary embolism, but did not affect prothrombin time (PT) in vivo. This finding demonstrated that L-sulforaphane inhibited the platelet activation through an intrinsic pathway.L-sulforaphane had a beneficial effect on various pathophysiological pathways of the collagen-induced platelet aggregation and thrombus formation as a selective inhibition of cyclooxygenase and glycoprotein IIb/IIIa antagonist. Thus, we recommend L-sulforaphane as a potential antithrombotic drug.

  16. Applying the functional abnormality ontology pattern to anatomical functions

    Directory of Open Access Journals (Sweden)

    Hoehndorf Robert

    2010-03-01

    Full Text Available Abstract Background Several biomedical ontologies cover the domain of biological functions, including molecular and cellular functions. However, there is currently no publicly available ontology of anatomical functions. Consequently, no explicit relation between anatomical structures and their functions is expressed in the anatomy ontologies that are available for various species. Such an explicit relation between anatomical structures and their functions would be useful both for defining the classes of the anatomy and the phenotype ontologies accurately. Results We provide an ontological analysis of functions and functional abnormalities. From this analysis, we derive an approach to the automatic extraction of anatomical functions from existing ontologies which uses a combination of natural language processing, graph-based analysis of the ontologies and formal inferences. Additionally, we introduce a new relation to link material objects to processes that realize the function of these objects. This relation is introduced to avoid a needless duplication of processes already covered by the Gene Ontology in a new ontology of anatomical functions. Conclusions Ontological considerations on the nature of functional abnormalities and their representation in current phenotype ontologies show that we can extract a skeleton for an ontology of anatomical functions by using a combination of process, phenotype and anatomy ontologies automatically. We identify several limitations of the current ontologies that still need to be addressed to ensure a consistent and complete representation of anatomical functions and their abnormalities. Availability The source code and results of our analysis are available at http://bioonto.de.

  17. Abnormal retinal development associated with FRMD7 mutations.

    Science.gov (United States)

    Thomas, Mervyn G; Crosier, Moira; Lindsay, Susan; Kumar, Anil; Araki, Masasuke; Leroy, Bart P; McLean, Rebecca J; Sheth, Viral; Maconachie, Gail; Thomas, Shery; Moore, Anthony T; Gottlob, Irene

    2014-08-01

    Idiopathic infantile nystagmus (IIN) is a genetically heterogeneous disorder, often associated with FRMD7 mutations. As the appearance of the retina is reported to be normal based on conventional fundus photography, IIN is postulated to arise from abnormal cortical development. To determine whether the afferent visual system is involved in FRMD7 mutations, we performed in situ hybridization studies in human embryonic and fetal stages (35 days post-ovulation to 9 weeks post-conception). We show a dynamic retinal expression pattern of FRMD7 during development. We observe expression within the outer neuroblastic layer, then in the inner neuroblastic layer and at 9 weeks post-conception a bilaminar expression pattern. Expression was also noted within the developing optic stalk and optic disk. We identified a large cohort of IIN patients (n = 100), and performed sequence analysis which revealed 45 patients with FRMD7 mutations. Patients with FRMD7 mutations underwent detailed retinal imaging studies using ultrahigh-resolution optical coherence tomography. The tomograms were compared with a control cohort (n = 60). The foveal pit was significantly shallower in FRMD7 patients (P < 0.0001). The optic nerve head morphology was abnormal with significantly decreased optic disk area, retinal nerve fiber layer thickness, cup area and cup depth in FRMD7 patients (P < 0.0001). This study shows for the first time that abnormal afferent system development is associated with FRMD7 mutations and could be an important etiological factor in the development of nystagmus.

  18. Advances in understanding paternally transmitted Chromosomal Abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, F; Sloter, E; Wyrobek, A J

    2001-03-01

    Multicolor FISH has been adapted for detecting the major types of chromosomal abnormalities in human sperm including aneuploidies for clinically-relevant chromosomes, chromosomal aberrations including breaks and rearrangements, and other numerical abnormalities. The various sperm FISH assays have been used to evaluate healthy men, men of advanced age, and men who have received mutagenic cancer therapy. The mouse has also been used as a model to investigate the mechanism of paternally transmitted genetic damage. Sperm FISH for the mouse has been used to detect chromosomally abnormal mouse sperm, while the PAINT/DAPI analysis of mouse zygotes has been used to evaluate the types of chromosomal defects that can be paternally transmitted to the embryo and their effects on embryonic development.

  19. Abnormal Grain Growth Suppression in Aluminum Alloys

    Science.gov (United States)

    Hales, Stephen J. (Inventor); Claytor, Harold Dale (Inventor); Alexa, Joel A. (Inventor)

    2015-01-01

    The present invention provides a process for suppressing abnormal grain growth in friction stir welded aluminum alloys by inserting an intermediate annealing treatment ("IAT") after the welding step on the article. The IAT may be followed by a solution heat treatment (SHT) on the article under effectively high solution heat treatment conditions. In at least some embodiments, a deformation step is conducted on the article under effective spin-forming deformation conditions or under effective superplastic deformation conditions. The invention further provides a welded article having suppressed abnormal grain growth, prepared by the process above. Preferably the article is characterized with greater than about 90% reduction in area fraction abnormal grain growth in any friction-stir-welded nugget.

  20. Enhanced monitoring of abnormal emergency department demands

    KAUST Repository

    Harrou, Fouzi

    2016-06-13

    This paper presents a statistical technique for detecting signs of abnormal situation generated by the influx of patients at emergency department (ED). The monitoring strategy developed was able to provide early alert mechanisms in the event of abnormal situations caused by abnormal patient arrivals to the ED. More specifically, This work proposed the application of autoregressive moving average (ARMA) models combined with the generalized likelihood ratio (GLR) test for anomaly-detection. ARMA was used as the modelling framework of the ARMA-based GLR anomaly-detection methodology. The GLR test was applied to the uncorrelated residuals obtained from the ARMA model to detect anomalies when the data did not fit the reference ARMA model. The ARMA-based GLR hypothesis testing scheme was successfully applied to the practical data collected from the database of the pediatric emergency department (PED) at Lille regional hospital center, France. © 2015 IEEE.

  1. XYY chromosome abnormality in sexual homicide perpetrators.

    Science.gov (United States)

    Briken, Peer; Habermann, Niels; Berner, Wolfgang; Hill, Andreas

    2006-03-05

    In a retrospective investigation of the court reports about sexual homicide perpetrators chromosome analysis had been carried out in 13 of 166 (7.8%) men. Three men (1.8%) with XYY chromosome abnormality were found. This rate is much higher than that found in unselected samples of prisoners (0.7-0.9%) or in the general population (0.01%). The three men had shown prepubescent abnormalities, school problems, and had suffered from physical abuse. The chromosome analysis in all cases had been carried out in connection with the forensic psychiatric court report due to the sexual homicide. However, two men had earlier psychiatric referrals. All were diagnosed as sexual sadistic, showed a psychopathic syndrome or psychopathy according to the Psychopathy Checklist-Revised [Hare RD, 1991, The Hare Psychopathy Checklist-Revised, Toronto, Ontario, Canada: Multi-Health Systems]. Two were multiple murderers. Especially forensic psychiatrists should be vigilant of the possibility of XYY chromosome abnormalities in sexual offenders.

  2. Parsing abnormal grain growth in specialty aluminas

    Science.gov (United States)

    Lawrence, Abigail Kremer

    Grain growth in alumina is strongly affected by the impurities present in the material. Certain impurity elements are known to have characteristic effects on abnormal grain growth in alumina. Specialty alumina powders contain multiple impurity species including MgO, CaO, SiO2, and Na 2O. In this work, sintered samples made from alumina powders containing various amounts of the impurities in question were characterized by their grain size and aspect ratio distributions. Multiple quantitative methods were used to characterize and classify samples with varying microstructures. The grain size distributions were used to partition the grain size population into subpopulations depending on the observed deviation from normal behavior. Using both grain size and aspect ratio a new visual representation for a microstructure was introduced called a morphology frequency map that gives a fingerprint for the material. The number of subpopulations within a sample and the shape of the distribution on the morphology map provided the basis for a classification scheme for different types of microstructures. Also using the two parameters a series of five metrics were calculated that describe the character of the abnormal grains in the sample, these were called abnormal character values. The abnormal character values describe the fraction of grains that are considered abnormal, the average magnitude of abnormality (including both grain size and aspect ratio), the average size, and variance in size. The final metric is the correlation between grain size and aspect ratio for the entire population of grains. The abnormal character values give a sense of how different from "normal" the sample is, given the assumption that a normal sample has a lognormal distribution of grain size and a Gaussian distribution of aspect ratios. In the second part of the work the quantified measures of abnormality were correlated with processing parameters such as composition and heat treatment conditions. A

  3. Neurological abnormalities associated with CDMA exposure.

    Science.gov (United States)

    Hocking, B; Westerman, R

    2001-09-01

    Dysaesthesiae of the scalp and neurological abnormality after mobile phone use have been reported previously, but the roles of the phone per se or the radiations in causing these findings have been questioned. We report finding a neurological abnormality in a patient after accidental exposure of the left side of the face to mobile phone radiation [code division multiple access (CDMA)] from a down-powered mobile phone base station antenna. He had headaches, unilateral left blurred vision and pupil constriction, unilateral altered sensation on the forehead, and abnormalities of current perception thresholds on testing the left trigeminal ophthalmic nerve. His nerve function recovered during 6 months follow-up. His exposure was 0.015-0.06 mW/cm(2) over 1-2 h. The implications regarding health effects of radiofrequency radiation are discussed.

  4. Persistent Pain and Sensory Abnormalities after Abdominoplasty

    DEFF Research Database (Denmark)

    Presman, Benjamin; Finnerup, Kenneth; Andresen, Sven Robert

    2015-01-01

    University Hospital, Denmark. The questionnaire included questions about pain and sensory abnormalities located to the abdominal skin, and physical and psychological function; patient satisfaction with surgery was rated on a 4-point scale. RESULTS: One hundred seventy patients answered the questionnaire......%) patients. The majority of patients reported improvement on all physical and psychological factors. Patients with pain were more often disappointed with the surgery and unwilling to recommend the surgery. CONCLUSIONS: Overall, patients were satisfied with the procedure, although abnormal abdominal skin....... Fourteen patients (8.2%) reported pain within the past 7 days related to the abdominoplasty. Abnormal abdominal skin sensation was common and reported by 138 patients (81%). Sensory hypersensitivity was associated with the presence of persistent pain. Satisfaction with the procedure was reported by 149 (88...

  5. Abnormal Head Position in Infantile Nystagmus Syndrome

    Science.gov (United States)

    Noval, Susana; González-Manrique, Mar; Rodríguez-Del Valle, José María; Rodríguez-Sánchez, José María

    2011-01-01

    Infantile nystagmus is an involuntary, bilateral, conjugate, and rhythmic oscillation of the eyes which is present at birth or develops within the first 6 months of life. It may be pendular or jerk-like and, its intensity usually increases in lateral gaze, decreasing with convergence. Up to 64% of all patients with nystagmus also present strabismus, and even more patients have an abnormal head position. The abnormal head positions are more often horizontal, but they may also be vertical or take the form of a tilt, even though the nystagmus itself is horizontal. The aim of this article is to review available information about the origin and treatment of the abnormal head position associated to nystagmus, and to describe our treatment strategies. PMID:24533187

  6. A mechanistic understanding of allosteric immune escape pathways in the HIV-1 envelope glycoprotein.

    Directory of Open Access Journals (Sweden)

    Anurag Sethi

    Full Text Available The HIV-1 envelope (Env spike, which consists of a compact, heterodimeric trimer of the glycoproteins gp120 and gp41, is the target of neutralizing antibodies. However, the high mutation rate of HIV-1 and plasticity of Env facilitates viral evasion from neutralizing antibodies through various mechanisms. Mutations that are distant from the antibody binding site can lead to escape, probably by changing the conformation or dynamics of Env; however, these changes are difficult to identify and define mechanistically. Here we describe a network analysis-based approach to identify potential allosteric immune evasion mechanisms using three known HIV-1 Env gp120 protein structures from two different clades, B and C. First, correlation and principal component analyses of molecular dynamics (MD simulations identified a high degree of long-distance coupled motions that exist between functionally distant regions within the intrinsic dynamics of the gp120 core, supporting the presence of long-distance communication in the protein. Then, by integrating MD simulations with network theory, we identified the optimal and suboptimal communication pathways and modules within the gp120 core. The results unveil both strain-dependent and -independent characteristics of the communication pathways in gp120. We show that within the context of three structurally homologous gp120 cores, the optimal pathway for communication is sequence sensitive, i.e. a suboptimal pathway in one strain becomes the optimal pathway in another strain. Yet the identification of conserved elements within these communication pathways, termed inter-modular hotspots, could present a new opportunity for immunogen design, as this could be an additional mechanism that HIV-1 uses to shield vulnerable antibody targets in Env that induce neutralizing antibody breadth.

  7. Neurologic Correlates of Gait Abnormalities in Cerebral Palsy: Implications for Treatment

    Science.gov (United States)

    Zhou, Joanne; Butler, Erin E.; Rose, Jessica

    2017-01-01

    Cerebral palsy (CP) is the most common movement disorder in children. A diagnosis of CP is often made based on abnormal muscle tone or posture, a delay in reaching motor milestones, or the presence of gait abnormalities in young children. Neuroimaging of high-risk neonates and of children diagnosed with CP have identified patterns of neurologic injury associated with CP, however, the neural underpinnings of common gait abnormalities remain largely uncharacterized. Here, we review the nature of the brain injury in CP, as well as the neuromuscular deficits and subsequent gait abnormalities common among children with CP. We first discuss brain injury in terms of mechanism, pattern, and time of injury during the prenatal, perinatal, or postnatal period in preterm and term-born children. Second, we outline neuromuscular deficits of CP with a focus on spastic CP, characterized by muscle weakness, shortened muscle-tendon unit, spasticity, and impaired selective motor control, on both a microscopic and functional level. Third, we examine the influence of neuromuscular deficits on gait abnormalities in CP, while considering emerging information on neural correlates of gait abnormalities and the implications for strategic treatment. This review of the neural basis of gait abnormalities in CP discusses what is known about links between the location and extent of brain injury and the type and severity of CP, in relation to the associated neuromuscular deficits, and subsequent gait abnormalities. Targeted treatment opportunities are identified that may improve functional outcomes for children with CP. By providing this context on the neural basis of gait abnormalities in CP, we hope to highlight areas of further research that can reduce the long-term, debilitating effects of CP. PMID:28367118

  8. Nuchal translucency: an ultrasound marker for fetal chromosomal abnormalities

    Directory of Open Access Journals (Sweden)

    Gregório Lorenzo Acácio

    2001-01-01

    Full Text Available CONTEXT: The literature shows an association between several ultrasound markers and chromosome abnormality. Among these, measurement of nuchal translucency has been indicated as a screening method for aneuploidy. The trisomy of chromosome 21 has been most evaluated. OBJECTIVE: To define the best fixed cutoff point for nuchal translucency, with the assistance of the ROC curve, and its accuracy in screening all fetal aneuploidy and trisomy 21 in a South American population. TYPE OF STUDY: Validation of a diagnostic test. SETTING: This study was carried out at the State University of Campinas, Campinas, Brazil. PARTICIPANTS: 230 patients examined by ultrasound at two tertiary-level private centers, at 10 to 14 weeks of gestation. DIAGNOSTIC TEST: The participants consisted of all those patients who had undergone ultrasound imaging at 10 to 14 weeks of gestation to measure nuchal translucency and who had had the fetal or neonatal karyotype identified. MAIN MEASUREMENTS: Maternal age, gestational age, nuchal translucency measurement, fetal or neonatal karyotype. RESULTS: Prevalence of chromosomal defects -- 10%; mean age -- 35.8 years; mean gestational age -- 12 weeks and 2 days; nuchal translucency (NT thickness -- 2.18 mm. The best balance between sensitivity and specificity were values that were equal to or higher than 2.5 mm for overall chromosomal abnormalities as well as for the isolated trisomy 21. The sensitivity for overall chromosomal abnormalities and trisomy 21 were 69.5% and 75%, respectively, and the positive likelihood ratios were 5.5 and 5.0, respectively. CONCLUSION: The measurement of nuchal translucency was found to be fairly accurate as an ultrasound marker for fetal abnormalities and measurements equal to or higher than 2.5 mm were the best fixed cutoff points.

  9. Baculovirus expression of the glycoprotein gene of Lassa virus and characterization of the recombinant protein.

    Science.gov (United States)

    Hummel, K B; Martin, M L; Auperin, D D

    1992-09-01

    A recombinant baculovirus was constructed that expresses the glycoprotein gene of Lassa virus (Josiah strain) under the transcriptional control of the polyhedrin promoter. The expressed protein (B-LSGPC) comigrated with the authentic viral glycoprotein as observed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), was reactive with monoclonal antibodies (MAbs) in Western blots, and was glycosylated. Although the recombinant protein was not processed into the mature glycoproteins, G1 and G2, it demonstrated reactivity with all known epitopes as measured by indirect immunofluorescence (IFA), and it was immunogenic, eliciting antisera in rabbits that recognized whole virus in IFAs. Regarding future applications to diagnostic assays, the recombinant glycoprotein proved to be an effective substitute for Lassa virus-infected mammalian cells in IFAs and it was able to distinguish sera from several human cases of Lassa fever, against a panel of known negative sera of African origin, in an enzyme immunoassay (EIA).

  10. Generation and Characterization of an scFv Directed against Site II of Rabies Glycoprotein

    Directory of Open Access Journals (Sweden)

    Shukra M. Aavula

    2011-01-01

    Full Text Available Recombinant antibody phage display technology is a vital tool that facilitates identification of specific binding molecules to a target enabling the rapid generation and selection of high affinity, fully human, or mouse antibody product candidates essentially directed towards disease target appropriate for antibody therapy. In this study, a recombinant single-chain Fv antibody fragment (scFv A11 was isolated from immune spleen cells obtained from mice immunized with inactivated rabies virus (Pasteur strain using standard methodology and was characterized for its specificity towards the rabies virus glycoprotein. Epitope mapping using peptide libraries and truncated glycoprotein polypeptides suggested that A11 bound to the antigenic site II of rabies glycoprotein against which a majority of rabies virus neutralizing antibodies are directed. The use of the above technology could, therefore, allow development of scFvs with different specificities against the rabies glycoprotein as an alternative to the more cumbersome protocols used for the development of monoclonal antibodies.

  11. Serum sialic acid and glycoprotein levels in some Libyan cancer patients.

    Science.gov (United States)

    Balo, N N; Ishaq, M

    1991-01-01

    Sialic acid is a common conjugate of some serum glycoproteins and glycolipids. Elevated levels of serum sialic acid and alterations in serum glycoproteins have been observed in certain types of cancer. In this study sialic acid concentration in the sera of patients with various types of cancer was determined. In addition to this, serum glycoproteins were also analysed by electrophoretic method. Our results indicate that serum sialic acid levels are generally raised in all types of cancer studied. This increase was more pronounced in case of lung, bronchogenic, intestinal and breast cancer. Some alterations in the serum glycoprotein profiles were also observed, particularly in bronchogenic and gall bladder cancer where an additional band in the low molecular weight region was present and in lung, breast and lymphoma where a band in the middle molecular weight region was found missing when compared with normals.

  12. Purification of the envelope glycoproteins of western equine encephalitis virus by glass wool column chromatography.

    OpenAIRE

    Yamamoto, K.; Simizu, B

    1980-01-01

    Glass wool column chromatography was used for separation of the two glycoproteins of western equine encephalitis virus. Cross-contamination of each protein separated was confirmed to be negligible by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

  13. Evaluation of the expression of P-glycoprotein in propoxur-resistant Caco-2 cells.

    Directory of Open Access Journals (Sweden)

    Shabnam Yazdian

    2014-10-01

    Full Text Available There is a great concern about the effect of propoxur, as one of the more common N-methyl carbamate pesticides, on human health due to its extensive use in agricultural and non-agricultural applications. Caco-2 cells became resistant to propoxur, and the resistance was confirmed through MTT assay. Then the cell membrane integrity and P-glycoprotein expression were measured by LDH assay and western blot analysis, respectively and compared to the parent cells.  Contrary to what was expected, the expression of P-glycoprotein in propoxur resistant cells was lower than parent cells.This study indicates that the resistance to propoxur may not be related to P-glycoprotein expression directly, since P-glycoprotein expression has decreased in these cells.

  14. 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.

  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. Antibody to the E3 Glycoprotein Protects Mice against Lethal Venezuelan Equine Encephalitis Virus Infection▿

    Science.gov (United States)

    Parker, Michael D.; Buckley, Marilyn J.; Melanson, Vanessa R.; Glass, Pamela J.; Norwood, David; Hart, Mary Kate

    2010-01-01

    Six monoclonal antibodies were isolated that exhibited specificity for a furin cleavage site deletion mutant (V3526) of Venezuelan equine encephalitis virus (VEEV). These antibodies comprise a single competition group and bound the E3 glycoprotein of VEEV subtype I viruses but failed to bind the E3 glycoprotein of other alphaviruses. These antibodies neutralized V3526 virus infectivity but did not neutralize the parental strain of Trinidad donkey (TrD) VEEV. However, the E3-specific antibodies did inhibit the production of virus from VEEV TrD-infected cells. In addition, passive immunization of mice demonstrated that antibody to the E3 glycoprotein provided protection against lethal VEEV TrD challenge. This is the first recognition of a protective epitope in the E3 glycoprotein. Furthermore, these results indicate that E3 plays a critical role late in the morphogenesis of progeny virus after E3 appears on the surfaces of infected cells. PMID:20926570

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

    Science.gov (United States)

    Wang, Xiaojin; Xia, Ning; Liu, Lin

    2013-01-01

    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. PMID:24141187

  18. 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.

  19. Distribution of surface glycoproteins on influenza A virus determined by electron cryotomography.

    Science.gov (United States)

    Wasilewski, Sebastian; Calder, Lesley J; Grant, Tim; Rosenthal, Peter B

    2012-12-07

    We use electron cryotomography to reconstruct virions of two influenza A H3N2 virus strains. The maps reveal the structure of the viral envelope containing hemagglutinin (HA) and neuraminidase (NA) glycoproteins and the virus interior containing a matrix layer and an assembly of ribonucleoprotein particles (RNPs) that package the genome. We build a structural model for the viral surface by locating copies of the X-ray structure of the HA ectodomain into density peaks on the virus surface. We calculate inter-glycoprotein distances and the fractional volume occupied by glycoproteins. The models suggest that for typical HA densities on virus, Fabs can bind to epitopes on the HA stem domain. The models also show how membrane curvature may influence the number of glycoproteins that can simultaneously interact with a target surface of receptors.

  20. Spectrum of lithium induced thyroid abnormalities: a current perspective

    Directory of Open Access Journals (Sweden)

    Kibirige Davis

    2013-02-01

    Full Text Available Abstract Background Lithium is an integral drug used in the management of acute mania, unipolar and bipolar depression and prophylaxis of bipolar disorders. Thyroid abnormalities associated with treatment with lithium have been widely reported in medical literature to date. These include goitre, hypothyroidism, hyperthyroidism and autoimmune thyroiditis. This current review explores the varied thyroid abnormalities frequently encountered among patients on lithium therapy and their management, since lithium is still a fundamental and widely drug used in psychiatry and Internal Medicine. Methods PubMed database and Google scholar were used to search for relevant English language articles relating to lithium therapy and thyroid abnormalities up to December 2012. The search terms used were lithium treatment, thyroid abnormalities, thyroid dysfunction, goitre, hypothyroidism, hyperthyroidism, thyrotoxicosis, autoimmune thyroiditis, lithium toxicity, treatment of affective disorders and depression and side effects of antipsychotic drugs. Reference lists of the identified articles were further used to identify other studies. Results Lithium affects normal thyroid functioning through multiple mechanisms. At the cellular level, it decreases thyroid hormone synthesis and release. It also decreases peripheral deiodination of tetraiodothyronine (T4 or thyroxine by decreasing the activity of type I 5’ de-iodinase enzyme. Hypothyroidism and goitre (clinically and/ultrasonographically detected are the most prevalent thyroid abnormalities among patients on long term lithium therapy. Lithium induced hyperthyroidism is very infrequent. Lithium increases the propensity to thyroid autoimmunity in susceptible individuals due to its effect of augmenting the activity of B lymphocytes and reducing the ratio of circulating suppressor to cytotoxic T cells. Conclusions Thyroid function tests (serum thyroid stimulating hormone, free thyroid hormones-T4 and

  1. Temporal abnormalities in children with developmental dyscalculia.

    Science.gov (United States)

    Vicario, Carmelo Mario; Rappo, Gaetano; Pepi, Annamaria; Pavan, Andrea; Martino, Davide

    2012-01-01

    Recent imaging studies have associated Developmental dyscalculia (DD) to structural and functional alterations corresponding Parietal and the Prefrontal cortex (PFC). Since these areas were shown also to be involved in timing abilities, we hypothesized that time processing is abnormal in DD. We compared time processing abilities between 10 children with pure DD (8 years old) and 11 age-matched healthy children. Results show that the DD group underestimated duration of a sub-second scale when asked to perform a time comparison task. The timing abnormality observed in our DD participants is consistent with evidence of a shared fronto-parietal neural network for representing time and quantity.

  2. Occult intraspinal abnormalities and congenital scoliosis

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Erfani

    2007-06-01

    Full Text Available

    BACKGROUND: Congenital scoliosis occurs because of either the failure of formation or the failure of segmentation or both. Evaluation of the incidence and the types of occult intraspinal abnormalities in congenital scoliosis is the subject of this study.

    METHODS: During a period of 29 years, 103 patients with congenital scoliosis were studied. MRI was used in 46 patients, myelography or CT myelography was used in 64 patients and both MRI and myelography or CT myelography were used in 7 patients for intraspinal abnormalities.

    RESULTS: In the MRI group, among the 46 patients, 19 patients (41.3% had intraspinal abnormalities consisting syringomyelia in 9 (19.5% diastematomyelia in 8 (17.4%, tethered cord syndrome in 6 (13%, low conus in 5 (10.8% and diplomyelia in 3 (6.5% of the patients. In the myelography group, among the 64 patients, 17 (26.5% had intraspinal abnormalities and diastematomyelia was the most common one found in 14 (21.8% patients.

    CONCLUSIONS: Intraspinal abnormalities are frequent in congenital scoliosis. Syringomyelia may be associated with congenital scoliosis. In congenital scoliosis, rib fusion may be an indicator of intraspinal abnormalities in MRI. A significant difference between clinical findings and intraspinal anomalies (P<0.05 was noted. Moreover, we believe that total spinal MRI with coronal, sagittal and axial views is a valuable tool in determining the intraspinal abnormalities in congenital scoliosis. This method is highly

  3. Hemorheological abnormalities in human arterial hypertension

    Science.gov (United States)

    Lo Presti, Rosalia; Hopps, Eugenia; Caimi, Gregorio

    2014-05-01

    Blood rheology is impaired in hypertensive patients. The alteration involves blood and plasma viscosity, and the erythrocyte behaviour is often abnormal. The hemorheological pattern appears to be related to some pathophysiological mechanisms of hypertension and to organ damage, in particular left ventricular hypertrophy and myocardial ischemia. Abnormalities have been observed in erythrocyte membrane fluidity, explored by fluorescence spectroscopy and electron spin resonance. This may be relevant for red cell flow in microvessels and oxygen delivery to tissues. Although blood viscosity is not a direct target of antihypertensive therapy, the rheological properties of blood play a role in the pathophysiology of arterial hypertension and its vascular complications.

  4. Electrocardiographic abnormalities in patients with subarachnoid hemorrhage.

    Science.gov (United States)

    Sommargren, Claire E

    2002-01-01

    Subarachnoid hemorrhage is a serious neurological disorder that is often complicated by the occurrence of electrocardiographic abnormalities unexplained by preexisting cardiac conditions. These morphological waveform changes and arrhythmias often are unrecognized or misinterpreted, potentially placing patients at risk for inappropriate management. Many previous investigations were retrospective and relied on data collected in an unsystematic manner. More recent studies that included use of serial electrocardiograms and Holter recordings have provided new insight into the high prevalence of electrocardiographic changes in subarachnoid hemorrhage. Research on the prevalence, duration, and clinical significance of these electrocardiographic abnormalities and on associated factors and etiological theories is reviewed.

  5. Nonpathologizing trauma interventions in abnormal psychology courses.

    Science.gov (United States)

    Hoover, Stephanie M; Luchner, Andrew F; Pickett, Rachel F

    2016-01-01

    Because abnormal psychology courses presuppose a focus on pathological human functioning, nonpathologizing interventions within these classes are particularly powerful and can reach survivors, bystanders, and perpetrators. Interventions are needed to improve the social response to trauma on college campuses. By applying psychodynamic and feminist multicultural theory, instructors can deliver nonpathologizing interventions about trauma and trauma response within these classes. We recommend class-based interventions with the following aims: (a) intentionally using nonpathologizing language, (b) normalizing trauma responses, (c) subjectively defining trauma, (d) challenging secondary victimization, and (e) questioning the delineation of abnormal and normal. The recommendations promote implications for instructor self-reflection, therapy interventions, and future research.

  6. Anaesthesia in operations of congenital craniofacial abnormalities

    Directory of Open Access Journals (Sweden)

    Jahangirie B

    1996-07-01

    Full Text Available Some syndromes that are characterized by abnormalities of the skull, facial bones, and mandibule, most of these patients are from the pediatric population. For the anaesthetic management of patients with various craniofacial dysostosis are as follows: 1 The necessary for careful evaluation of the airway by simply observing the patient. 2 Evaluation of the patient for abnormalities of the heart and lungs. 3 Patients may also have increased intracranial pressure. 4 Anaesthetic drugs and techniques: no particular drugs is recommended. Techniques controlled ventilation. 5 All patients should be cared in the intensive care unit after operation between 24-48 hours

  7. Optimization of irinotecan chronotherapy with P-glycoprotein inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Filipski, Elisabeth; Berland, Elodie [INSERM, U776 “Rythmes biologiques et cancers”, CAMPUS CNRS, 7 rue Guy Môquet, F-94801 Villejuif (France); Univ Paris-Sud, UMR-S0776, Orsay F-91405 (France); Ozturk, Narin [INSERM, U776 “Rythmes biologiques et cancers”, CAMPUS CNRS, 7 rue Guy Môquet, F-94801 Villejuif (France); Univ Paris-Sud, UMR-S0776, Orsay F-91405 (France); Istanbul University Faculty of Pharmacy, Department of Pharmacology, Beyazit TR-34116, Istanbul (Turkey); Guettier, Catherine [Assistance Publique-Hôpitaux de Paris, Unité de Chronothérapie, Département de Cancérologie, Hôpital Paul Brousse, Villejuif F-94807 (France); Horst, Gijsbertus T.J. van der [Department of Genetics, Erasmus University Medical Center, 3000 CA Rotterdam (Netherlands); Lévi, Francis [INSERM, U776 “Rythmes biologiques et cancers”, CAMPUS CNRS, 7 rue Guy Môquet, F-94801 Villejuif (France); Univ Paris-Sud, UMR-S0776, Orsay F-91405 (France); Assistance Publique-Hôpitaux de Paris, Unité de Chronothérapie, Département de Cancérologie, Hôpital Paul Brousse, Villejuif F-94807 (France); and others

    2014-02-01

    The relevance of P-glycoprotein (P-gp) for irinotecan chronopharmacology was investigated in female B6D2F{sub 1} mice. A three-fold 24 h change in the mRNA expression of Abcb1b was demonstrated in ileum mucosa, with a maximum at Zeitgeber Time (ZT) 15 (p < 0.001). No rhythm was found for abcb1a in ileum mucosa, or for Abcb1a/b in Glasgow osteosarcoma (GOS), a mouse tumor cell line moderately sensitive to irinotecan. Non-tumor-bearing mice received irinotecan (50 mg/kg/day i.v. × 4 days) as a single agent or combined with P-gp inhibitor PSC833 (6.25 mg/kg/day i.p. × 4 days) at ZT3 or ZT15, respectively corresponding to the worst or the best irinotecan tolerability. Endpoints involved survival, body weight change and hematologic toxicity. Antitumor efficacy was studied in GOS-bearing mice receiving irinotecan (25, 30 or 40 mg/kg/day × 4 days) and +/− PSC833 at ZT3 or ZT15, with survival, body weight change, and tumor growth inhibition as endpoints. Non-tumor bearing mice lost an average of 17% or 9% of their body weight according to irinotecan administration at ZT3 or ZT15 respectively (p < 0.001). Dosing at ZT15 rather than ZT3 reduced mean leucopenia (9% vs 53%; p < 0.001). PSC833 aggravated irinotecan lethal toxicity from 4 to ∼ 60%. In tumor-bearing mice, body weight loss was ∼ halved in the mice on irinotecan or irinotecan–PSC833 combination at ZT15 as compared to ZT3 (p < 0.001). PSC833–irinotecan at ZT15 increased tumor inhibition by ∼ 40% as compared to irinotecan only at ZT15. In conclusion, P-gp was an important determinant of the circadian balance between toxicity and efficacy of irinotecan. - Highlights: • Irinotecan chronotolerance and chronoefficacy change as drug was applied with PSC833. • P-glycoprotein is an important player of the toxicity and efficacy of irinotecan. • Timing should be considered if chemotherapy is performed with a MDR1 inhibitor.

  8. CT and MR imaging of odontoid abnormalities: A pictorial review

    Directory of Open Access Journals (Sweden)

    Nishchint Jain

    2016-01-01

    Full Text Available Odontoid process is the central pillar of the craniovertebral junction. Imaging of this small structure continues to be a challenge for the radiologists due to complex bony and ligamentous anatomy. A wide range of developmental and acquired abnormalities of odontoid have been identified. Their accurate radiologic evaluation is important as different lesions have markedly different clinical course, patient management, and prognosis. This article seeks to provide knowledge for interpreting appearances of odontoid on computed tomography (CT and magnetic resonance imaging (MRI with respect to various disease processes, along with providing a quick review of the embryology and relevant anatomy.

  9. Bronchial Sparganosis mansoni accompanied by abnormal hyperplasia diagnosed by bronchoscopy

    Institute of Scientific and Technical Information of China (English)

    BAI Jing; HE Zhi-yi; LIU Guang-nan; ZHANG Jian-quan; DENG Jing-min; LI Mei-hua; ZHONG Xiao-ning

    2012-01-01

    Pulmonary sparganosis mansoni is rare in humans and bronchial sparganosis mansoni has not been reported.We reported a patient with a soft-tissue mass in the right hilum area on a chest computed tomography (CT) scan that was suspected of being lung cancer.Bronchoscopy identified sparganum larvae.Bronchial sparganosis mansoni accompanied by abnormal hyperplasia was diagnosed by histopathology.We introduced our experience and reviewed the clinical characteristics of three pulmonary sparganosis mansoni cases and three pleural cavity sparganosis mansoni cases that have been reoorted.

  10. Machupo Virus Glycoprotein Determinants for Human Transferrin Receptor 1 Binding and Cell Entry

    Science.gov (United States)

    2011-07-01

    and form enveloped virions [1]. Seven arenaviruses cause viral hemorrhagic fever in humans: the Old World arenaviruses Lassa and ‘Lujo,’ and the New...hemorrhagic fever in humans. MACV, as well as other pathogenic New World arenaviruses, enter cells after their GP1 attachment glycoprotein binds to... fever in humans. MACV, as well as other pathogenic New World arenaviruses, enter cells after their GP1 attachment glycoprotein binds to their cellular

  11. 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.

  12. Spatial distribution of Reissner's fiber glycoproteins in the filum terminale of the rat and rabbit.

    Science.gov (United States)

    Molina, B; Rodríguez, E M; Peruzzo, B; Caprile, T; Nualart, F

    2001-03-01

    The subcommissural organ secretes into the third ventricle glycoproteins that condense to form the Reissner's fiber (RF). At the distal end of the central canal of the spinal cord, the RF-glycoproteins accumulate in the form of an irregular mass known as massa caudalis. Antibodies against RF-glycoproteins and a set of lectins were used at the light and electron microscopic level to investigate the spatial distribution of the massa caudalis material in the rat and rabbit filum terminale. In the sacral region of the rat, the central canal presents gaps between the ependymal cells through which RF-glycoproteins spread out. The bulk of massa caudalis material, however, escapes through openings in the dorsal wall of the terminal ventricle. In the rabbit, the massa caudalis is formed within the ependymal canal, at the level of the second coccygeal vertebra, it accumulates within preterminal and terminal dilatations of the central canal, and it escapes out through gaps in the dorsal ependymal wall of the terminal ventricle. The existence of wide intercellular spaces and a large orifice (neuroporous) in the dorsal ependymal wall of the terminal ventricle, and the passage of RF-material through them, appear to be conserved evolutionary features. After leaving the terminal ventricle of the rat and rabbit, RF-glycoproteins establish a close spatial association with the numerous blood vessels irrigating the filum terminale, suggesting that in these species the blood vessels are the site of destination of the RF-glycoproteins escaping from the central canal, thus resembling the situation found in lower vertebrates. When passing from the RF stage to the massa caudalis stage, the rabbit RF-glycoproteins lose their sialic acid residues, exposing galactose as the terminal residue. Since this sialic acid-galactose modification of RF-glycoproteins had also been described in lamprey larvae, it may be regarded as a conserved evolutionary feature associated with the formation of the

  13. Isolation of coronavirus envelope glycoproteins and interaction with the viral nucleocapsid.

    OpenAIRE

    Sturman, L S; Holmes, K V; Behnke, J.

    1980-01-01

    The two envelope glycoproteins and the viral nucleocapsid of the coronavirus A59 were isolated by solubilization of the viral membrane with Nonidet P-40 at 4 degrees C followed by sucrose density gradient sedimentation. Isolated E2 consisted of rosettes of peplomers, whereas E1, the membrane glycoprotein, was irregular and amorphous. Under certain conditions significant interactions occurred between components of Nonidet P-40-disrupted virions. Incubation of the Nonidet P-40-disrupted virus a...

  14. Distinct glycan-charged phosphodolichol carriers are required for the assembly of the pentasaccharide N-linked to the Haloferax volcanii S-layer glycoprotein.

    Science.gov (United States)

    Guan, Ziqiang; Naparstek, Shai; Kaminski, Lina; Konrad, Zvia; Eichler, Jerry

    2010-12-01

    In Archaea, dolichol phosphates have been implicated as glycan carriers in the N-glycosylation pathway, much like their eukaryal counterparts. To clarify this relation, highly sensitive liquid chromatography/mass spectrometry was employed to detect and characterize glycan-charged phosphodolichols in the haloarchaeon Haloferax volcanii. It is reported that Hfx. volcanii contains a series of C(55) and C(60) dolichol phosphates presenting saturated isoprene subunits at the α and ω positions and sequentially modified with the first, second, third and methylated fourth sugar subunits comprising the first four subunits of the pentasaccharide N-linked to the S-layer glycoprotein, a reporter of N-glycosylation. Moreover, when this glycan-charged phosphodolichol pool was examined in cells deleted of agl genes encoding glycosyltransferases participating in N-glycosylation and previously assigned roles in adding pentasaccharide residues one to four, the composition of the lipid-linked glycans was perturbed in the identical manner as was S-layer glycoprotein N-glycosylation in these mutants. In contrast, the fifth sugar of the pentasaccharide, identified as mannose in this study, is added to a distinct dolichol phosphate carrier. This represents the first evidence that in Archaea, as in Eukarya, the oligosaccharides N-linked to glycoproteins are sequentially assembled from glycans originating from distinct phosphodolichol carriers.

  15. Prominent 85-kDa oligomannosidic glycoproteins of rat brain are signal regulatory proteins and include the SHP substrate-1 for tyrosine phosphatases.

    Science.gov (United States)

    Bartoszewicz, Z P; Jaffe, H; Sasaki, M; Möller, J R; Stebbins, J W; Gebrekristos, H; Quarles, R H

    1999-04-01

    The glycoprotein component in rat brain reacting most strongly with Galanthus nivalis agglutinin (GNA) on western blots migrates as an 85-kDa band. GNA identifies mannose-rich oligosaccharides because it is highly specific for terminal alpha-mannose residues. After purification of this 85-kDa glycoprotein band by chromatography on GNA-agarose and preparative gel electrophoresis, binding of other lectins demonstrated the presence of fucose and a trace of galactose, but no sialic acid. Treatment with N-Glycanase or endoglycosidase H produced a 65-kDa band, indicating that it consisted of about one-fourth N-linked oligomannosidic carbohydrate moieties. High-performance anion-exchange chromatography and fluorescence-assisted carbohydrate electrophoresis indicated that the major carbohydrate moiety is a heptasaccharide with the structure Manalpha1-6(Manalpha1-3)Manalpha1-6(Manalpha1-3) Manbeta1-4Glc-NAcbeta1-4GlcNAc (Man5GlcNAc2). Determination of amino acid sequences of peptides produced by endoproteinase digestion demonstrated that this 85-kDa mannose-rich glycoprotein component contained the SHP substrate-1 for phosphotyrosine phosphatases and at least one other member of the signal-regulatory protein (SIRP) family. The unusually high content of oligomannosidic carbohydrate moieties on these receptor-like members of the immunoglobulin superfamily in neural tissue could be of functional significance for intercellular adhesion or signaling.

  16. AglJ adds the first sugar of the N-linked pentasaccharide decorating the Haloferax volcanii S-layer glycoprotein.

    Science.gov (United States)

    Kaminski, Lina; Abu-Qarn, Mehtap; Guan, Ziqiang; Naparstek, Shai; Ventura, Valeria V; Raetz, Christian R H; Hitchen, Paul G; Dell, Anne; Eichler, Jerry

    2010-11-01

    Like the Eukarya and Bacteria, the Archaea also perform N glycosylation. Using the haloarchaeon Haloferax volcanii as a model system, a series of Agl proteins involved in the archaeal version of this posttranslational modification has been identified. In the present study, the participation of HVO_1517 in N glycosylation was considered, given its homology to a known component of the eukaryal N-glycosylation pathway and because of the genomic proximity of HVO_1517 to agl genes encoding known elements of the H. volcanii N-glycosylation process. By combining the deletion of HVO_1517 with mass spectrometric analysis of both dolichol phosphate monosaccharide-charged carriers and the S-layer glycoprotein, evidence was obtained showing the participation of HVO_1517, renamed AglJ, in adding the first hexose of the N-linked pentasaccharide decorating this reporter glycoprotein. The deletion of aglJ, however, did not fully prevent the attachment of a hexose residue to the S-layer glycoprotein. Moreover, in the absence of AglJ, the level of only one of the three monosaccharide-charged dolichol phosphate carriers detected in the cell was reduced. Nonetheless, in cells lacking AglJ, no further sugar subunits were added to the remaining monosaccharide-charged dolichol phosphate carriers or to the monosaccharide-modified S-layer glycoprotein, pointing to the importance of the sugar added through the actions of AglJ for proper N glycosylation. Finally, while aglJ can be deleted, H. volcanii surface layer integrity is compromised in the absence of the encoded protein.

  17. MAGIC: an automated N-linked glycoprotein identification tool using a Y1-ion pattern matching algorithm and in silico MS² approach.

    Science.gov (United States)

    Lynn, Ke-Shiuan; Chen, Chen-Chun; Lih, T Mamie; Cheng, Cheng-Wei; Su, Wan-Chih; Chang, Chun-Hao; Cheng, Chia-Ying; Hsu, Wen-Lian; Chen, Yu-Ju; Sung, Ting-Yi

    2015-02-17

    Glycosylation is a highly complex modification influencing the functions and activities of proteins. Interpretation of intact glycopeptide spectra is crucial but challenging. In this paper, we present a mass spectrometry-based automated glycopeptide identification platform (MAGIC) to identify peptide sequences and glycan compositions directly from intact N-linked glycopeptide collision-induced-dissociation spectra. The identification of the Y1 (peptideY0 + GlcNAc) ion is critical for the correct analysis of unknown glycoproteins, especially without prior knowledge of the proteins and glycans present in the sample. To ensure accurate Y1-ion assignment, we propose a novel algorithm called Trident that detects a triplet pattern corresponding to [Y0, Y1, Y2] or [Y0-NH3, Y0, Y1] from the fragmentation of the common trimannosyl core of N-linked glycopeptides. To facilitate the subsequent peptide sequence identification by common database search engines, MAGIC generates in silico spectra by overwriting the original precursor with the naked peptide m/z and removing all of the glycan-related ions. Finally, MAGIC computes the glycan compositions and ranks them. For the model glycoprotein horseradish peroxidase (HRP) and a 5-glycoprotein mixture, a 2- to 31-fold increase in the relative intensities of the peptide fragments was achieved, which led to the identification of 7 tryptic glycopeptides from HRP and 16 glycopeptides from the mixture via Mascot. In the HeLa cell proteome data set, MAGIC processed over a thousand MS(2) spectra in 3 min on a PC and reported 36 glycopeptides from 26 glycoproteins. Finally, a remarkable false discovery rate of 0 was achieved on the N-glycosylation-free Escherichia coli data set. MAGIC is available at http://ms.iis.sinica.edu.tw/COmics/Software_MAGIC.html .

  18. Identification of OmpA-Like Protein of Tannerella forsythia as an O-Linked Glycoprotein and Its Binding Capability to Lectins

    Science.gov (United States)

    Horie, Toshi; Inomata, Megumi; Into, Takeshi; Hasegawa, Yoshiaki; Kitai, Noriyuki; Yoshimura, Fuminobu; Murakami, Yukitaka

    2016-01-01

    Bacterial glycoproteins are associated with physiological and pathogenic functions of bacteria. It remains unclear whether bacterial glycoproteins can bind to specific classes of lectins expressed on host cells. Tannerella forsythia is a gram-negative oral anaerobe that contributes to the development of periodontitis. In this study, we aimed to find lectin-binding glycoproteins in T. forsythia. We performed affinity chromatography of wheat germ agglutinin, which binds to N-acetylglucosamine (GlcNAc) and sialic acid (Sia), and identified OmpA-like protein as the glycoprotein that has the highest affinity. Mass spectrometry revealed that OmpA-like protein contains O-type N-acetylhexosamine and hexose. Fluorometry quantitatively showed that OmpA-like protein contains Sia. OmpA-like protein was found to bind to lectins including E-selectin, P-selectin, L-selectin, Siglec-5, Siglec-9, Siglec-10, and DC-SIGN. The binding of OmpA-like protein to these lectins, except for the Siglecs, depends on the presence of calcium. N-acetylneuraminic acid (NeuAc), which is the most abundant Sia, inhibited the binding of OmpA-like protein to all of these lectins, whereas GlcNAc and mannose only inhibited the binding to DC-SIGN. We further found that T. forsythia adhered to human oral epithelial cells, which express E-selectin and P-selectin, and that this adhesion was inhibited by addition of NeuAc. Moreover, adhesion of an OmpA-like protein-deficient T. forsythia strain to the cells was reduced compared to that of the wild-type strain. Our findings indicate that OmpA-like protein of T. forsythia contains O-linked sugar chains that can mediate interactions with specific lectins. This interaction is suggested to facilitate adhesion of T. forsythia to the surface of host cells. PMID:27711121

  19. Identification of OmpA-Like Protein of Tannerella forsythia as an O-Linked Glycoprotein and Its Binding Capability to Lectins.

    Science.gov (United States)

    Horie, Toshi; Inomata, Megumi; Into, Takeshi; Hasegawa, Yoshiaki; Kitai, Noriyuki; Yoshimura, Fuminobu; Murakami, Yukitaka

    2016-01-01

    Bacterial glycoproteins are associated with physiological and pathogenic functions of bacteria. It remains unclear whether bacterial glycoproteins can bind to specific classes of lectins expressed on host cells. Tannerella forsythia is a gram-negative oral anaerobe that contributes to the development of periodontitis. In this study, we aimed to find lectin-binding glycoproteins in T. forsythia. We performed affinity chromatography of wheat germ agglutinin, which binds to N-acetylglucosamine (GlcNAc) and sialic acid (Sia), and identified OmpA-like protein as the glycoprotein that has the highest affinity. Mass spectrometry revealed that OmpA-like protein contains O-type N-acetylhexosamine and hexose. Fluorometry quantitatively showed that OmpA-like protein contains Sia. OmpA-like protein was found to bind to lectins including E-selectin, P-selectin, L-selectin, Siglec-5, Siglec-9, Siglec-10, and DC-SIGN. The binding of OmpA-like protein to these lectins, except for the Siglecs, depends on the presence of calcium. N-acetylneuraminic acid (NeuAc), which is the most abundant Sia, inhibited the binding of OmpA-like protein to all of these lectins, whereas GlcNAc and mannose only inhibited the binding to DC-SIGN. We further found that T. forsythia adhered to human oral epithelial cells, which express E-selectin and P-selectin, and that this adhesion was inhibited by addition of NeuAc. Moreover, adhesion of an OmpA-like protein-deficient T. forsythia strain to the cells was reduced compared to that of the wild-type strain. Our findings indicate that OmpA-like protein of T. forsythia contains O-linked sugar chains that can mediate interactions with specific lectins. This interaction is suggested to facilitate adhesion of T. forsythia to the surface of host cells.

  20. Lipid modification gives rise to two distinct Haloferax volcanii S-layer glycoprotein populations.

    Science.gov (United States)

    Kandiba, Lina; Guan, Ziqiang; Eichler, Jerry

    2013-03-01

    The S-layer glycoprotein is the sole component of the protein shell surrounding Haloferax volcanii cells. The deduced amino acid sequence of the S-layer glycoprotein predicts the presence of a C-terminal membrane-spanning domain. However, several earlier observations, including the ability of EDTA to selectively solubilize the protein, are inconsistent with the presence of a trans-membrane sequence. In the present report, sequential solubilization of the S-layer glycoprotein by EDTA and then with detergent revealed the existence of two distinct populations of the S-layer glycoprotein. Whereas both S-layer glycoprotein populations underwent signal peptide cleavage and N-glycosylation, base hydrolysis followed by mass spectrometry revealed that a lipid, likely archaetidic acid, modified only the EDTA-solubilized version of the protein. These observations are consistent with the S-layer glycoprotein being initially synthesized as an integral membrane protein and subsequently undergoing a processing event in which the extracellular portion of the protein is separated from the membrane-spanning domain and transferred to a waiting lipid moiety.

  1. The importance of drug-transporting P-glycoproteins in toxicology.

    Science.gov (United States)

    van Tellingen, O

    2001-03-31

    The importance of specific transport in toxicology is becoming increasingly clear and the work on P-glycoprotein has certainly been a major contribution to these growing insights. P-Glycoproteins were discovered by their ability to confer multidrug resistance in mammalian tumour cells. They are localised in the cell membrane where they actively extrude a wide range of compounds including many anti-cancer drugs from the cell. Besides in tumour cells, drug-transporting P-glycoproteins are also expressed in a polarised fashion in normal tissues that perform an excretory or barrier function, such as the liver, kidneys, intestines, brain endothelial cells. Based on this expression profile, it has been proposed that P-glycoproteins are important in protecting the host by reducing exposure to xenobiotics. Further studies with P-glycoprotein knockout mice have clearly established this protective function. In general, the clearance of substrate drugs is lower in knockout mice due to a diminished hepatobiliary excretion, direct intestinal excretion and/or increased enterohepatic cycling. Moreover, their uptake in sanctuary sites, such as the brain or the foetus, was profoundly higher in P-glycoprotein knockout mice, as was the uptake of drugs from the gastro-intestinal tract into the systemic circulation following oral ingestion. These results clearly highlight the impact that transport proteins can play in toxicology.

  2. Bile canalicular cationic dye secretion as a model for P-glycoprotein mediated transport.

    Science.gov (United States)

    Thalhammer, T; Stapf, V; Gajdzik, L; Graf, J

    1994-04-01

    This study explores properties of P-glycoprotein dependent membrane transport in rat liver with the use of acridine orange as the substrate. We studied the biliary secretion of the dye, its binding to canalicular membrane P-glycoprotein, and effects of the inhibitor cyclosporin A: acridine orange is excreted into bile together with less hydrophobic and glucuronidated metabolites. Cyclosporin A inhibited both the secretion of acridine orange and of its metabolites. In TR- animals, a rat strain that is deficient of the canalicular multi-specific organic anion transport system, non-metabolized acridine orange is the predominant species in bile and its secretion is also inhibited by cyclosporin A. Binding of acridine orange to liver P-glycoprotein was analyzed by photoaffinity labeling with azidopine, a substrate of P-glycoprotein dependent transport in multi-drug resistant tumor cells. Labeling of the immunoprecipitated P-glycoprotein was inhibited by acridine orange, verapamil, and by cyclosporin A. The results show that biliary secretion of acridine orange is highly analogous to P-glycoprotein mediated membrane drug transport in tumor cells that exhibit multi-drug resistance.

  3. Bypassing P-Glycoprotein Drug Efflux Mechanisms: Possible Applications in Pharmacoresistant Schizophrenia Therapy

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    Famida G. Hoosain

    2015-01-01

    Full Text Available The efficient noninvasive treatment of neurodegenerative disorders is often constrained by reduced permeation of therapeutic agents into the central nervous system (CNS. A vast majority of bioactive agents do not readily permeate into the brain tissue due to the existence of the blood-brain barrier (BBB and the associated P-glycoprotein efflux transporter. The overexpression of the MDR1 P-glycoprotein has been related to the occurrence of multidrug resistance in CNS diseases. Various research outputs have focused on overcoming the P-glycoprotein drug efflux transporter, which mainly involve its inhibition or bypassing mechanisms. Studies into neurodegenerative disorders have shown that the P-glycoprotein efflux transporter plays a vital role in the progression of schizophrenia, with a noted increase in P-glycoprotein function among schizophrenic patients, thereby reducing therapeutic outcomes. In this review, we address the hypothesis that methods employed in overcoming P-glycoprotein in cancer and other disease states at the level of the BBB and intestine may be applied to schizophrenia drug delivery system design to improve clinical efficiency of drug therapies. In addition, the current review explores polymers and drug delivery systems capable of P-gp inhibition and modulation.

  4. Molecular docking studies with rabies virus glycoprotein to design viral therapeutics

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    Tomar N

    2010-01-01

    Full Text Available The genome of rabies virus encodes five proteins; the nucleoprotein, the phosphoprotein, the matrix protein, the glycoprotein, and the RNA-dependent RNA polymerase. Among these, the glycoprotein is the most important as it is the major contributor to pathogenicity and virus neutralizing antibody response. Keeping in mind that glycoprotein is the only protein exposed on the surface of virus and is thought to be responsible for the interaction with the cell membrane, it was attempted to target glycoprotein by a ligand polyethylene glycol 4000, which blocks its active site, as seen by molecular operating environment software, so that it may be possible to prevent the spread of virus into the host. The ligand polyethylene glycol 4000 was retrieved from Research Collaboratory for Structural Bioinformatics protein data bank by providing the glycoprotein sequence to the databank. In this study it was observed that the ligand was successfully docked on a major portion of antigenic site II of glycoprotein by mimicking the virus neutralizing antibodies. This knowledge may be important for the development of novel therapies for the treatment of rabies and other viral diseases in the future.

  5. Use of Machine Learning to Identify Children with Autism and Their Motor Abnormalities

    Science.gov (United States)

    Crippa, Alessandro; Salvatore, Christian; Perego, Paolo; Forti, Sara; Nobile, Maria; Molteni, Massimo; Castiglioni, Isabella

    2015-01-01

    In the present work, we have undertaken a proof-of-concept study to determine whether a simple upper-limb movement could be useful to accurately classify low-functioning children with autism spectrum disorder (ASD) aged 2-4. To answer this question, we developed a supervised machine-learning method to correctly discriminate 15 preschool children…

  6. A proposed multidisciplinary approach for identifying feeding abnormalities in children with cerebral palsy.

    Science.gov (United States)

    Santoro, Amelia; Lang, Maria Bianca Dasso; Moretti, Elena; Sellari-Franceschini, Stefano; Orazini, Laura; Cipriani, Paola; Cioni, Giovanni; Battini, Roberta

    2012-06-01

    Children with neurodevelopmental disabilities, such as cerebral palsy, frequently have associated oral motor dysfunction, which leads to feeding difficulties, risk of aspiration, prolonged feeding times, and malnutrition with its attendant physical compromise. The authors propose a comprehensive multidisciplinary assessment, including neurological and dysphagia examination and ear, nose, and throat examination, to evaluate clinical indicators and severity of feeding impairment in children affected by neurodevelopmental disorders. A representative sample of 40 children with cerebral palsy (spastic, dyskinetic, or mixed), intellectual disability, and feeding problems was included in the study. A specific multidisciplinary evaluation and standardized mealtime observation in patients with cerebral palsy appear feasible and appropriate to recognize proactive indicators of dysphagia and to establish personalized programs of gastric and rehabilitative interventions.

  7. Use of Machine Learning to Identify Children with Autism and Their Motor Abnormalities

    Science.gov (United States)

    Crippa, Alessandro; Salvatore, Christian; Perego, Paolo; Forti, Sara; Nobile, Maria; Molteni, Massimo; Castiglioni, Isabella

    2015-01-01

    In the present work, we have undertaken a proof-of-concept study to determine whether a simple upper-limb movement could be useful to accurately classify low-functioning children with autism spectrum disorder (ASD) aged 2-4. To answer this question, we developed a supervised machine-learning method to correctly discriminate 15 preschool children…

  8. The use of diagnostic imaging for identifying abnormal gas accumulations in cetaceans and pinnipeds.

    Directory of Open Access Journals (Sweden)

    Sophie eDennison

    2012-06-01

    Full Text Available Recent dogma suggested that marine mammals are not at risk of decompression sickness (DCS due to a number of evolutionary adaptations. Several proposed adaptations exist. Lung compression and alveolar collapse that terminate gas exchange before a depth is reached where supersaturation is significant and bradycardia with peripheral vasoconstriction affecting the distribution, and dynamics of blood and tissue nitrogen levels. Published accounts of gas and fat emboli and dysbaric osteonecrosis in marine mammals and theoretical modeling have challenged this view-point, suggesting that decompression-like symptoms may occur under certain circumstances, contrary to common belief. Diagnostic imaging modalities are invaluable tools for the non-invasive examination of animals for evidence of gas and have been used to demonstrate the presence of incidental decompression-related renal gas accumulations in some stranded cetaceans. Diagnostic imaging has also contributed to the recognition of clinically significant gas accumulations in live and dead cetaceans and pinnipeds. Understanding the appropriate application and limitations of the available imaging modalities is important for accurate interpretation of results. The presence of gas may be incidental and must be interpreted cautiously alongside all other available data including clinical examination, clinical laboratory testing, gas analysis, necropsy examination and histology results.

  9. Bloch spin waves and emergent structure in protein folding with HIV envelope glycoprotein as an example

    Science.gov (United States)

    Dai, Jin; Niemi, Antti J.; He, Jianfeng; Sieradzan, Adam; Ilieva, Nevena

    2016-03-01

    We inquire how structure emerges during the process of protein folding. For this we scrutinize collective many-atom motions during all-atom molecular dynamics simulations. We introduce, develop, and employ various topological techniques, in combination with analytic tools that we deduce from the concept of integrable models and structure of discrete nonlinear Schrödinger equation. The example we consider is an α -helical subunit of the HIV envelope glycoprotein gp41. The helical structure is stable when the subunit is part of the biological oligomer. But in isolation, the helix becomes unstable, and the monomer starts deforming. We follow the process computationally. We interpret the evolving structure both in terms of a backbone based Heisenberg spin chain and in terms of a side chain based XY spin chain. We find that in both cases the formation of protein supersecondary structure is akin the formation of a topological Bloch domain wall along a spin chain. During the process we identify three individual Bloch walls and we show that each of them can be modelled with a precision of tenths to several angstroms in terms of a soliton solution to a discrete nonlinear Schrödinger equation.

  10. Characterization of the Receptor-binding Domain of Ebola Glycoprotein in Viral Entry

    Institute of Scientific and Technical Information of China (English)

    Jizhen Wang; Balaji Manicassamy; Michael Caffrey; Lijun Rong

    2011-01-01

    Ebola virus infection causes severe hemorrhagic fever in human and non-human primates with high mortality.Viral entry/infection is initiated by binding of glycoprotein GP protein on Ebola virion to host cells,followed by fusion of virus-cell membrane also mediated by GP.Using an human immunodeficiency virus (HIV)-based pseudotyping system,the roles of 41 Ebola GP1 residues in the receptor-binding domain in viral entry were studied by alanine scanning substitutions.We identified that four residues appear to be involved in protein folding/structure and four residues are important for viral entry.An improved entry interference assay was developed and used to study the role of these residues that are important for viral entry.It was found that R64 and K95 are involved in receptor binding.In contrast,some residues such as I170 are important for viral entry,but do not play a major role in receptor binding as indicated by entry interference assay and/or protein binding data,suggesting that these residues are involved in post-binding steps of viral entry.Furthermore,our results also suggested that Ebola and Marburg viruses share a common cellular molecule for entry.

  11. 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.

  12. A Method for Comprehensive Glycosite-Mapping and Direct Quantitation of Serum Glycoproteins.

    Science.gov (United States)

    Hong, Qiuting; Ruhaak, L Renee; Stroble, Carol; Parker, Evan; Huang, Jincui; Maverakis, Emanual; Lebrilla, Carlito B

    2015-12-04

    A comprehensive glycan map was constructed for the top eight abundant glycoproteins in plasma using both specific and nonspecific enzyme digestions followed by nano liquid chromatography (LC)-chip/quadrupole time-of-flight mass spectrometry (MS) analysis. Glycopeptides were identified using an in-house software tool, GPFinder. A sensitive and reproducible multiple reaction monitoring (MRM) technique on a triple quadrupole MS was developed and applied to quantify immunoglobulins G, A, M, and their site-specific glycans simultaneously and directly from human serum/plasma without protein enrichments. A total of 64 glycopeptides and 15 peptides were monitored for IgG, IgA, and IgM in a 20 min ultra high performance (UP)LC gradient. The absolute protein contents were quantified using peptide calibration curves. The glycopeptide ion abundances were normalized to the respective protein abundances to separate protein glycosylation from protein expression. This technique yields higher method reproducibility and less sample loss when compared with the quantitation method that involves protein enrichments. The absolute protein quantitation has a wide linear range (3-4 orders of magnitude) and low limit of quantitation (femtomole level). This rapid and robust quantitation technique, which provides quantitative information for both proteins and glycosylation, will further facilitate disease biomarker discoveries.

  13. Temozolomide competes for P-glycoprotein and contributes to chemoresistance in glioblastoma cells.

    Science.gov (United States)

    Munoz, Jessian L; Walker, Nykia D; Scotto, Kathleen W; Rameshwar, Pranela

    2015-10-10

    Chemotherapeutic resistance can occur by P-glycoprotein (P-gp), a 12-transmembrane ATP-dependent drug efflux pump. Glioblastoma (GBM) has poor survival rate and uniformly acquired chemoresistance to its frontline agent, Temozolomide (TMZ). Despite much effort, overcoming TMZ resistance remains a challenge. We reported on autonomous induction of TMZ resistance by increased transcription MDR1, the gene for P-gp. This study investigated how P-gp and TMZ interact to gain resistance. Using an experimental model of Adriamycin-resistant DC3F cells (DC3F/Adx), we showed that increased P-gp caused TMZ resistance. Increasing concentrations of TMZ competed with Calcein for P-gp, resulting in reduced efflux in the DC3F/Adx cells. Three different inhibitors of P-gp reversed the resistance to TMZ in two different GBM cell lines, by increasing active Caspase 3. Molecular modeling predicted the binding sites to be the intracellular region of P-gp and also identified specific amino acids and kinetics of energy for the efflux of TMZ. Taken together, we confirmed P-gp targeting of TMZ, a crucial regulator of TMZ resistance in GBM. This study provides insights on the effectiveness by which TMZ competes with other P-gp substrates, thereby opening the door for combined targeted therapies.

  14. Structural Basis for Platelet Collagen Responses by the Immune-type Receptor Glycoprotein VI

    Energy Technology Data Exchange (ETDEWEB)

    Horii,K.; Kahn, M.; Herr, A.

    2006-01-01

    Activation of circulating platelets by exposed vessel wall collagen is a primary step in the pathogenesis of heart attack and stroke, and drugs to block platelet activation have successfully reduced cardiovascular morbidity and mortality. In humans and mice, collagen activation of platelets is mediated by glycoprotein VI (GPVI), a receptor that is homologous to immune receptors but bears little sequence similarity to known matrix protein adhesion receptors. Here we present the crystal structure of the collagen-binding domain of human GPVI and characterize its interaction with a collagen-related peptide. Like related immune receptors, GPVI contains 2 immunoglobulin-like domains arranged in a perpendicular orientation. Significantly, GPVI forms a back-to-back dimer in the crystal, an arrangement that could explain data previously obtained from cell-surface GPVI inhibition studies. Docking algorithms identify 2 parallel grooves on the GPVI dimer surface as collagen-binding sites, and the orientation and spacing of these grooves precisely match the dimensions of an intact collagen fiber. These findings provide a structural basis for the ability of an immunetype receptor to generate signaling responses to collagen and for the development of GPVI inhibitors as new therapies for human cardiovascular disease.

  15. Structure of the Membrane Anchor of Pestivirus Glycoprotein Erns, a Long Tilted Amphipathic Helix

    Science.gov (United States)

    Aberle, Daniel; Muhle-Goll, Claudia; Bürck, Jochen; Wolf, Moritz; Reißer, Sabine; Luy, Burkhard; Wenzel, Wolfgang; Ulrich, Anne S.; Meyers, Gregor

    2014-01-01

    Erns is an essential virion glycoprotein with RNase activity that suppresses host cellular innate immune responses upon being partially secreted from the infected cells. Its unusual C-terminus plays multiple roles, as the amphiphilic helix acts as a membrane anchor, as a signal peptidase cleavage site, and as a retention/secretion signal. We analyzed the structure and membrane binding properties of this sequence to gain a better understanding of the underlying mechanisms. CD spectroscopy in different setups, as well as Monte Carlo and molecular dynamics simulations confirmed the helical folding and showed that the helix is accommodated in the amphiphilic region of the lipid bilayer with a slight tilt rather than lying parallel to the surface. This model was confirmed by NMR analyses that also identified a central stretch of 15 residues within the helix that is fully shielded from the aqueous layer, which is C-terminally followed by a putative hairpin structure. These findings explain the strong membrane binding of the protein and provide clues to establishing the Erns membrane contact, processing and secretion. PMID:24586172

  16. Positive evolution of the glycoprotein (GP) gene is related to transmission of the Ebola virus.

    Science.gov (United States)

    Jing, Y X; Wang, L N; Wu, X M; Song, C X

    2016-03-28

    Ebola hemorrhagic fever is a fatal disease caused by the negative-strand RNA of the Ebola virus. A high-intensity outbreak of this fever was reported in West Africa last year; however, there is currently no definitive treatment strategy available for this disease. In this study, we analyzed the molecular evolutionary history and attempted to determine the positive selection sites in the Ebola genes using multiple-genomic sequences of the various Ebola virus subtypes, in order to gain greater clarity into the evolution of the virus and its various subtypes. Only the glycoprotein (GP) gene was positively selected among the 8 Ebola genes, with the other genes remaining in the purification stage. The positive selection sites in the GP gene were identified by a random-site model; these sites were found to be located in the mucin-like region, which is associated with transmembrane protein binding. Additionally, different branches of the phylogenetic tree displayed different positive sites, which in turn was responsible for differences in the cell adhesion ability of the virus. In conclusion, the pattern of positive sites in the GP gene is associated with the epidemiology and prevalence of Ebola in different areas.

  17. Global rescue of defects in HIV-1 envelope glycoprotein incorporation: implications for matrix structure.

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    Philip R Tedbury

    Full Text Available The matrix (MA domain of HIV-1 Gag plays key roles in membrane targeting of Gag, and envelope (Env glycoprotein incorporation into virions. Although a trimeric MA structure has been available since 1996, evidence for functional MA trimers has been elusive. The mechanism of HIV-1 Env recruitment into virions likewise remains unclear. Here, we identify a point mutation in MA that rescues the Env incorporation defects imposed by an extensive panel of MA and Env mutations. Mapping the mutations onto the putative MA trimer reveals that the incorporation-defective mutations cluster at the tips of the trimer, around the perimeter of a putative gap in the MA lattice into which the cytoplasmic tail of gp41 could insert. By contrast, the rescue mutation is located at the trimer interface, suggesting that it may confer rescue of Env incorporation via modification of MA trimer interactions, a hypothesis consistent with additional mutational analysis. These data strongly support the existence of MA trimers in the immature Gag lattice and demonstrate that rescue of Env incorporation defects is mediated by modified interactions at the MA trimer interface. The data support the hypothesis that mutations in MA that block Env incorporation do so by imposing a steric clash with the gp41 cytoplasmic tail, rather than by disrupting a specific MA-gp41 interaction. The importance of the trimer interface in rescuing Env incorporation suggests that the trimeric arrangement of MA may be a critical factor in permitting incorporation of Env into the Gag lattice.

  18. 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.

  19. Histidine-rich glycoprotein protects from systemic Candida infection.

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    Victoria Rydengård

    2008-08-01

    Full Text Available Fungi, such as Candida spp., are commonly found on the skin and at mucosal surfaces. Yet, they rarely cause invasive infections in immunocompetent individuals, an observation reflecting the ability of our innate immune system to control potentially invasive microbes found at biological boundaries. Antimicrobial proteins and peptides are becoming increasingly recognized as important effectors of innate immunity. This is illustrated further by the present investigation, demonstrating a novel antifungal role of histidine-rich glycoprotein (HRG, an abundant and multimodular plasma protein. HRG bound to Candida cells, and induced breaks in the cell walls of the organisms. Correspondingly, HRG preferentially lysed ergosterol-containing liposomes but not cholesterol-containing ones, indicating a specificity for fungal versus other types of eukaryotic membranes. Both antifungal and membrane-rupturing activities of HRG were enhanced at low pH, and mapped to the histidine-rich region of the protein. Ex vivo, HRG-containing plasma as well as fibrin clots exerted antifungal effects. In vivo, Hrg(-/- mice were susceptible to infection by C. albicans, in contrast to wild-type mice, which were highly resistant to infection. The results demonstrate a key and previously unknown antifungal role of HRG in innate immunity.

  20. HIV-1 envelope glycoprotein immunogens to induce broadly neutralizing antibodies.

    Science.gov (United States)

    Sliepen, Kwinten; Sanders, Rogier W

    2016-01-01

    The long pursuit for a vaccine against human immunodeficiency virus 1 (HIV-1) has recently been boosted by a number of exciting developments. An HIV-1 subunit vaccine ideally should elicit potent broadly neutralizing antibodies (bNAbs), but raising bNAbs by vaccination has proved extremely difficult because of the characteristics of the HIV-1 envelope glycoprotein complex (Env). However, the isolation of bNAbs from HIV-1-infected patients demonstrates that the human humoral immune system is capable of making such antibodies. Therefore, a focus of HIV-1 vaccinology is the elicitation of bNAbs by engineered immunogens and by using vaccination strategies aimed at mimicking the bNAb maturation pathways in HIV-infected patients. Important clues can also be taken from the successful subunit vaccines against hepatitis B virus and human papillomavirus. Here, we review the different types of HIV-1 immunogens and vaccination strategies that are being explored in the search for an HIV-1 vaccine that induces bNAbs.