Sighting optics including an optical element having a first focal length and a second focal length and methods for sighting

Science.gov (United States)

Crandall, David Lynn

2011-08-16

Sighting optics include a front sight and a rear sight positioned in a spaced-apart relation. The rear sight includes an optical element having a first focal length and a second focal length. The first focal length is selected so that it is about equal to a distance separating the optical element and the front sight and the second focal length is selected so that it is about equal to a target distance. The optical element thus brings into simultaneous focus for a user images of the front sight and the target.

In vivo imaging and specific targeting of P-glycoprotein expression in multidrug resistant nude mice xenografts with [125I]MRK-16 monoclonal antibody

International Nuclear Information System (INIS)

Scott, Andrew M.; Rosa, Eddie; Mehta, Bippin M.; Divgi, Chaitanya R.; Finn, Ronald D.; Biedler, June L.; Tsuruo, Takashi; Kalaigian, Hovannes; Larson, Steven M.

1995-01-01

Multidrug resistance (MDR) in tumors is associated with P-glycoprotein (Pgp) expression. In vivo quantitation of Pgp may allow MDR to be evaluated noninvasively prior to treatment planning. The purpose of this study was to radiolabel MRK-16, a monoclonal antibody that targets an external epitope of P-glycoprotein, and perform in vivo quantitation of P-glycoprotein in a MDR xenograft nude mouse model. MRK-16 was labeled with 125 I by the iodogen method, with subsequent purification by size exclusion chromatography. Groups of 10 Balb/c mice were each xenografted with colchicine-resistant or -sensitive neuroblastoma cell lines, respectively. Whole body clearance and tumor uptake over time was quantitated by gamma camera imaging, and biodistribution studies were performed with [ 125 ]MRK-16 and an isotype matched control antibody, A33. Quantitative autoradiography and immunohistochemistry analysis of tumors was also evaluated to confirm specific targeting of [ 125 I]MRK-16. Peak tumor uptake was at 2-3 days post-injection, and was significantly greater in resistance compared to sensitive tumors (mean % injected dose/g ± SD) (18.76 ± 2.94 vs 10.93 ± 0.96; p 125 I]MRK-16 was confirmed by comparison to [ 131 I]A33 in biodistribution studies, and localized to cellular components of tissue stroma by comparison of histologic and autoradiographic sections of sensitive and resistant tumors. Immunoblot analysis demonstrated a 4.5-fold difference in P-glycoprotein expression between sensitive and resistant cell lines without colchicine selective pressure. We conclude that in vivo quantitation of P-glycoprotein in MDR tumors can be performed with [ 125 I]MRK-16. These findings suggest a potential clinical application for radiolabeled MRK-16 in the in vivo evaluation of multidrug resistance in tumors

Focal Targeting of the Bacterial Envelope by Antimicrobial Peptides

Directory of Open Access Journals (Sweden)

Rafi eRashid

2016-06-01

Full Text Available Antimicrobial peptides (AMPs are utilized by both eukaryotic and prokaryotic organisms. AMPs such as the human beta defensins, human neutrophil peptides, human cathelicidin, and many bacterial bacteriocins are cationic and capable of binding to anionic regions of the bacterial surface. Cationic AMPs (CAMPs target anionic lipids (e.g. phosphatidylglycerol (PG and cardiolipins (CL in the cell membrane and anionic components (e.g. lipopolysaccharide (LPS and lipoteichoic acid (LTA of the cell envelope. Bacteria have evolved mechanisms to modify these same targets in order to resist CAMP killing, e.g. lysinylation of PG to yield cationic lysyl-PG and alanylation of LTA. Since CAMPs offer a promising therapeutic alternative to conventional antibiotics, which are becoming less effective due to rapidly emerging antibiotic resistance, there is a strong need to improve our understanding about the AMP mechanism of action. Recent literature suggests that AMPs often interact with the bacterial cell envelope at discrete foci. Here we review recent AMP literature, with an emphasis on focal interactions with bacteria, including (1 CAMP disruption mechanisms, (2 delocalization of membrane proteins and lipids by CAMPs, and (3 CAMP sensing systems and resistance mechanisms. We conclude with new approaches for studying the bacterial membrane, e.g., lipidomics, high resolution imaging and non-detergent-based membrane domain extraction.

Targeted Molecular Dynamics to determine Focal Adhesion Targeting Domain Folding Intermediates

Directory of Open Access Journals (Sweden)

Pallavi Mohanty

2017-10-01

Full Text Available The Focal adhesion kinase (FAT domain of Focal Adhesion Kinase is a four helical bundle known for conformational plasticity. FAT adopts two distinctly different conformations i.e., close (cFAT and arm-exchanged (aeFAT states under native conditions [1]. The slow transition from cFAT to aeFAT is likely to proceed through an open intermediate state that allows YENV motif to attain β-turn conformation and phosphorylation of Y925 by Src kinases [2]. The two end states of FAT are known to interact with Paxillin and are responsible for maintaining steady state in Heart while intermediate conformation interacts with Grb2-SH2 leading to Pathological Cardiac Hypertrophy (PAH [2]. 10ns Targeted Molecular Dynamics (TMD was done between c- and aeFAT in order to explore the conformational transition and to capture pathologically relevant oFAT. Cluster and dynamic cross correlation analysis (DCCA of TMD generated trajectory was done and the selected FAT intermediate was docked with Grb2-SH2 using HADDOCK v2.2 docking followed by molecular dynamics. Conservation analysis of FAT-Grb2 binding site was done using CONSURF [3]. A Pharmacophore FAT-Grb2 complex was generated using SPARKv1.2 and submitted for Virtual screening using BLAZE v4. Drug likeliness and ADMET properties were calculated using MOLINSPIRATION tool. TMD reveals six clusters and DCCA showed positively and negatively correlated region along the transition pathway. Intermediates with competence for Grb2 interaction were docked with Grb2 and best binding complex was further refined. MMPBSA binding energy calculations revealed the best binding pose where the phosphorylated YENV motif of Human FAT interacted with a charged and hydrophobic pocket of Grb2. The conservation analysis showed that the charged pocket was more conserved in comparison with the hydrophobic pocket, hence providing useful insights on binding and specificity determining residues in Grb2. Virtual screening using the pharmacophore

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

Science.gov (United States)

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

1999-01-01

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

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

Science.gov (United States)

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

2018-03-01

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

Conformational Dynamics of the Focal Adhesion Targeting Domain Control Specific Functions of Focal Adhesion Kinase in Cells

KAUST Repository

Kadaré, Gress

2015-01-02

Focal adhesion (FA) kinase (FAK) regulates cell survival and motility by transducing signals from membrane receptors. The C-terminal FA targeting (FAT) domain of FAK fulfils multiple functions, including recruitment to FAs through paxillin binding. Phosphorylation of FAT on Tyr925 facilitates FA disassembly and connects to the MAPK pathway through Grb2 association, but requires dissociation of the first helix (H1) of the four-helix bundle of FAT. We investigated the importance of H1 opening in cells by comparing the properties of FAK molecules containing wild-type or mutated FAT with impaired or facilitated H1 openings. These mutations did not alter the activation of FAK, but selectively affected its cellular functions, including self-association, Tyr925 phosphorylation, paxillin binding, and FA targeting and turnover. Phosphorylation of Tyr861, located between the kinase and FAT domains, was also enhanced by the mutation that opened the FAT bundle. Similarly phosphorylation of Ser910 by ERK in response to bombesin was increased by FAT opening. Although FAK molecules with the mutation favoring FAT opening were poorly recruited at FAs, they efficiently restored FA turnover and cell shape in FAK-deficient cells. In contrast, the mutation preventing H1 opening markedly impaired FAK function. Our data support the biological importance of conformational dynamics of the FAT domain and its functional interactions with other parts of the molecule.

Implementation of focal zooming on the Nike KrF laser

Energy Technology Data Exchange (ETDEWEB)

Kehne, D. M.; Karasik, M.; Weaver, J. L.; Chan, Y.; Obenschain, S. P. [Plasma Physics Division, Naval Research Laboratory, Washington, DC 20375 (United States); Aglitsky, Y. [Science Applications International, McLean, Virginia 22150 (United States); Smyth, Z.; Lehmberg, R. H. [Research Support Instruments, Inc., Lanham, Maryland 20706 (United States); Terrell, S. [Commonwealth Technologies, Inc., Alexandria, Virginia 22315 (United States)

2013-01-15

In direct drive inertial confinement laser fusion, a pellet containing D-T fuel is imploded by ablation arising from absorption of laser energy at its outer surface. For optimal coupling, the focal spot of the laser would continuously decrease to match the reduction in the pellet's diameter, thereby minimizing wasted energy. A krypton-fluoride laser ({lambda}= 248 nm) that incorporates beam smoothing by induced spatial incoherence has the ability to produce a high quality focal profile whose diameter varies with time, a property known as focal zooming. A two-stage focal zoom has been demonstrated on the Nike laser at the Naval Research Laboratory. In the experiment, a 4.4 ns laser pulse was created in which the on-target focal spot diameter was 1.3 mm (full width at half maximum) for the first 2.4 ns and 0.28 mm for the final 2 ns. These two diameters appear in time-integrated focal plane equivalent images taken at several locations in the amplification chain. Eight of the zoomed output beams were overlapped on a 60 {mu}m thick planar polystyrene target. Time resolved images of self-emission from the rear of the target show the separate shocks launched by the two corresponding laser focal diameters.

Implementation of focal zooming on the Nike KrF laser

International Nuclear Information System (INIS)

Kehne, D. M.; Karasik, M.; Weaver, J. L.; Chan, Y.; Obenschain, S. P.; Aglitsky, Y.; Smyth, Z.; Lehmberg, R. H.; Terrell, S.

2013-01-01

In direct drive inertial confinement laser fusion, a pellet containing D-T fuel is imploded by ablation arising from absorption of laser energy at its outer surface. For optimal coupling, the focal spot of the laser would continuously decrease to match the reduction in the pellet's diameter, thereby minimizing wasted energy. A krypton-fluoride laser (λ= 248 nm) that incorporates beam smoothing by induced spatial incoherence has the ability to produce a high quality focal profile whose diameter varies with time, a property known as focal zooming. A two-stage focal zoom has been demonstrated on the Nike laser at the Naval Research Laboratory. In the experiment, a 4.4 ns laser pulse was created in which the on-target focal spot diameter was 1.3 mm (full width at half maximum) for the first 2.4 ns and 0.28 mm for the final 2 ns. These two diameters appear in time-integrated focal plane equivalent images taken at several locations in the amplification chain. Eight of the zoomed output beams were overlapped on a 60 μm thick planar polystyrene target. Time resolved images of self-emission from the rear of the target show the separate shocks launched by the two corresponding laser focal diameters.

Implementation of focal zooming on the Nike KrF laser

Science.gov (United States)

Kehne, D. M.; Karasik, M.; Aglitsky, Y.; Smyth, Z.; Terrell, S.; Weaver, J. L.; Chan, Y.; Lehmberg, R. H.; Obenschain, S. P.

2013-01-01

In direct drive inertial confinement laser fusion, a pellet containing D-T fuel is imploded by ablation arising from absorption of laser energy at its outer surface. For optimal coupling, the focal spot of the laser would continuously decrease to match the reduction in the pellet's diameter, thereby minimizing wasted energy. A krypton-fluoride laser (λ = 248 nm) that incorporates beam smoothing by induced spatial incoherence has the ability to produce a high quality focal profile whose diameter varies with time, a property known as focal zooming. A two-stage focal zoom has been demonstrated on the Nike laser at the Naval Research Laboratory. In the experiment, a 4.4 ns laser pulse was created in which the on-target focal spot diameter was 1.3 mm (full width at half maximum) for the first 2.4 ns and 0.28 mm for the final 2 ns. These two diameters appear in time-integrated focal plane equivalent images taken at several locations in the amplification chain. Eight of the zoomed output beams were overlapped on a 60 μm thick planar polystyrene target. Time resolved images of self-emission from the rear of the target show the separate shocks launched by the two corresponding laser focal diameters.

Dosimetry Modeling for Focal Low-Dose-Rate Prostate Brachytherapy

Energy Technology Data Exchange (ETDEWEB)

Al-Qaisieh, Bashar [Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Mason, Josh, E-mail: joshua.mason@nhs.net [Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Bownes, Peter; Henry, Ann [Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Dickinson, Louise [Division of Surgery and Interventional Science, University College London, London (United Kingdom); Department of Radiology, Northwick Park Hospital, London North West NHS Trust, London (United Kingdom); Ahmed, Hashim U. [Division of Surgery and Interventional Science, University College London, London (United Kingdom); University College London Hospital, London (United Kingdom); Emberton, Mark [University College London Hospital, London (United Kingdom); Langley, Stephen [St Luke' s Cancer Centre, Guildford (United Kingdom)

2015-07-15

Purpose: Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA). Methods and Materials: Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focal (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations. Results: WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm{sup 3} was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types. Conclusions: Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a notable

Detection is unaffected by the deployment of focal attention

Directory of Open Access Journals (Sweden)

Jeff eMoher

2013-05-01

Full Text Available There has been much debate regarding how much information humans can extract from their environment without the use of limited attentional resources. In a recent study, Theeuwes, Van der Burg, and Belopolsky (2008 argued that even detection of simple feature targets is not possible without selection by focal attention. Supporting this claim, they found response time benefits in a simple feature (color detection task when a target letter’s identity was repeated on consecutive trials, suggesting that the letter was selected by focal attention and identified prior to detection. This intertrial repetition benefit remained even when observers were required to simultaneously identify a central digit. However, we found that intertrial repetition benefits disappeared when a simple color target was presented among a heterogeneously (rather than homogeneously colored set of distractors, thus reducing its bottom-up salience. Still, detection performance remained high. Thus, detection performance was unaffected by whether a letter was focally attended and identified prior to detection or not. Intertrial identity repetition benefits also disappeared when observers were required to perform a simultaneous, attention-demanding central task (Experiment 2, or when unfamiliar Chinese characters were used (Experiment 3. Together, these results suggest that while shifts of focal attention can be affected by target salience, by the availability of excess cognitive resources, and by target familiarity, detection performance itself is unaffected by these manipulations and is thus unaffected by the deployment of focal attention.

A Functional Henipavirus Envelope Glycoprotein Pseudotyped Lentivirus Assay System

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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

Experimental Focal Cerebral Ischemia

DEFF Research Database (Denmark)

Christensen, Thomas

2007-01-01

Focal cerebral ischemia due to occlusion of a major cerebral artery is the cause of ischemic stroke which is a major reason of mortality, morbidity and disability in the populations of the developed countries. In the seven studies summarized in the thesis focal ischemia in rats induced by occlusion...... in the penumbra is recruited in the infarction process leading to a progressive growth of the infarct. The penumbra hence constitutes an important target for pharmacological treatment because of the existence of a therapeutic time window during which treatment with neuroprotective compounds may prevent...

Structural and Antigenic Definition of Hepatitis C Virus E2 Glycoprotein Epitopes Targeted by Monoclonal Antibodies

Directory of Open Access Journals (Sweden)

Giuseppe Sautto

2013-01-01

Full Text Available Hepatitis C virus (HCV is the major cause of chronic liver disease as well as the major indication for liver transplantation worldwide. Current standard of care is not completely effective, not administrable in grafted patients, and burdened by several side effects. This incomplete effectiveness is mainly due to the high propensity of the virus to continually mutate under the selective pressure exerted by the host immune response as well as currently administered antiviral drugs. The E2 envelope surface glycoprotein of HCV (HCV/E2 is the main target of the host humoral immune response and for this reason one of the major variable viral proteins. However, broadly cross-neutralizing monoclonal antibodies (mAbs directed against HCV/E2 represent a promising tool for the study of virus-host interplay as well as for the development of effective prophylactic and therapeutic approaches. In the last few years many anti-HCV/E2 mAbs have been evaluated in preclinical and clinical trials as possible candidate antivirals, particularly for administration in pre- and post-transplant settings. In this review we summarize the antigenic and structural characteristics of HCV/E2 determined through the use of anti-HCV/E2 mAbs, which, given the absence of a crystal structure of this glycoprotein, represent currently the best tool available.

Selection of focal earthworm species as non-target soil organisms for environmental risk assessment of genetically modified plants.

Science.gov (United States)

van Capelle, Christine; Schrader, Stefan; Arpaia, Salvatore

2016-04-01

By means of a literature survey, earthworm species of significant relevance for soil functions in different biogeographical regions of Europe (Atlantic, Boreal, Mediterranean) were identified. These focal earthworm species, defined here according to the EFSA Guidance Document on the environmental risk assessment (ERA) of genetically modified plants, are typical for arable soils under crop rotations with maize and/or potatoes within the three regions represented by Ireland, Sweden and Spain, respectively. Focal earthworm species were selected following a matrix of four steps: Identification of functional groups, categorization of non-target species, ranking species on ecological criteria, and final selection of focal species. They are recommended as appropriate non-target organisms to assess environmental risks of genetically modified (GM) crops; in this case maize and potatoes. In total, 44 literature sources on earthworms in arable cropping systems including maize or potato from Ireland, Sweden and Spain were collected, which present information on species diversity, individual density and specific relevance for soil functions. By means of condensed literature data, those species were identified which (i) play an important functional role in respective soil systems, (ii) are well adapted to the biogeographical regions, (iii) are expected to occur in high abundances under cultivation of maize or potato and (iv) fulfill the requirements for an ERA test system based on life-history traits. First, primary and secondary decomposers were identified as functional groups being exposed to the GM crops. In a second step, anecic and endogeic species were categorized as potential species. In step three, eight anecic and endogeic earthworm species belonging to the family Lumbricidae were ranked as relevant species: Aporrectodea caliginosa, Aporrectodea rosea, Aporrectodea longa, Allolobophora chlorotica, Lumbricus terrestris, Lumbricus friendi, Octodrilus complanatus and

Context cue focality influences strategic prospective memory monitoring.

Science.gov (United States)

Hunter Ball, B; Bugg, Julie M

2018-02-12

Monitoring the environment for the occurrence of prospective memory (PM) targets is a resource-demanding process that produces cost (e.g., slower responding) to ongoing activities. However, research suggests that individuals are able to monitor strategically by using contextual cues to reduce monitoring in contexts in which PM targets are not expected to occur. In the current study, we investigated the processes supporting context identification (i.e., determining whether or not the context is appropriate for monitoring) by testing the context cue focality hypothesis. This hypothesis predicts that the ability to monitor strategically depends on whether the ongoing task orients attention to the contextual cues that are available to guide monitoring. In Experiment 1, participants performed an ongoing lexical decision task and were told that PM targets (TOR syllable) would only occur in word trials (focal context cue condition) or in items starting with consonants (nonfocal context cue condition). In Experiment 2, participants performed an ongoing first letter judgment (consonant/vowel) task and were told that PM targets would only occur in items starting with consonants (focal context cue condition) or in word trials (nonfocal context cue condition). Consistent with the context cue focality hypothesis, strategic monitoring was only observed during focal context cue conditions in which the type of ongoing task processing automatically oriented attention to the relevant features of the contextual cue. These findings suggest that strategic monitoring is dependent on limited-capacity processing resources and may be relatively limited when the attentional demands of context identification are sufficiently high.

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

Science.gov (United States)

Song, Ehwang; Mechref, Yehia

2015-01-01

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

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

International Nuclear Information System (INIS)

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

2009-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2009-12-18

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

Simulation of the Focal Spot of the Accelerator Bremsstrahlung Radiation

Science.gov (United States)

Sorokin, V.; Bespalov, V.

2016-06-01

Testing of thick-walled objects by bremsstrahlung radiation (BR) is primarily performed via high-energy quanta. The testing parameters are specified by the focal spot size of the high-energy bremsstrahlung radiation. In determining the focal spot size, the high- energy BR portion cannot be experimentally separated from the low-energy BR to use high- energy quanta only. The patterns of BR focal spot formation have been investigated via statistical modeling of the radiation transfer in the target material. The distributions of BR quanta emitted by the target for different energies and emission angles under normal distribution of the accelerated electrons bombarding the target have been obtained, and the ratio of the distribution parameters has been determined.

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

Science.gov (United States)

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

2015-06-29

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

Treatment planning for prostate focal laser ablation in the face of needle placement uncertainty

Energy Technology Data Exchange (ETDEWEB)

Cepek, Jeremy, E-mail: jcepek@robarts.ca; Fenster, Aaron [Robarts Research Institute, London, Ontario N6A 5K8, Canada and Biomedical Engineering, The University of Western Ontario, London, Ontario N6A 5B9 (Canada); Lindner, Uri; Trachtenberg, John [Department of Surgical Oncology, Division of Urology, University Health Network, Toronto, Ontario M5G 2C4 (Canada); Davidson, Sean R. H. [Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2M9 (Canada); Haider, Masoom A. [Department of Medical Imaging, Sunnybrook Health Sciences Center, Toronto, Ontario M4N 3M5, Canada and Department of Medical Imaging, University of Toronto, Toronto, Ontario M5S 2J7 (Canada); Ghai, Sangeet [Department of Medical Imaging, University Health Network, Toronto, Ontario M5G 2M9 (Canada)

2014-01-15

Purpose: To study the effect of needle placement uncertainty on the expected probability of achieving complete focal target destruction in focal laser ablation (FLA) of prostate cancer. Methods: Using a simplified model of prostate cancer focal target, and focal laser ablation region shapes, Monte Carlo simulations of needle placement error were performed to estimate the probability of completely ablating a region of target tissue. Results: Graphs of the probability of complete focal target ablation are presented over clinically relevant ranges of focal target sizes and shapes, ablation region sizes, and levels of needle placement uncertainty. In addition, a table is provided for estimating the maximum target size that is treatable. The results predict that targets whose length is at least 5 mm smaller than the diameter of each ablation region can be confidently ablated using, at most, four laser fibers if the standard deviation in each component of needle placement error is less than 3 mm. However, targets larger than this (i.e., near to or exceeding the diameter of each ablation region) require more careful planning. This process is facilitated by using the table provided. Conclusions: The probability of completely ablating a focal target using FLA is sensitive to the level of needle placement uncertainty, especially as the target length approaches and becomes greater than the diameter of ablated tissue that each individual laser fiber can achieve. The results of this work can be used to help determine individual patient eligibility for prostate FLA, to guide the planning of prostate FLA, and to quantify the clinical benefit of using advanced systems for accurate needle delivery for this treatment modality.

Glycoprotein on cell surfaces

International Nuclear Information System (INIS)

Muramatsu, T.

1975-01-01

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

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...

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

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

2009-01-01

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

Evaluation of Hemodynamics in Focal Steatosis and Focal Spared Lesion of the Liver Using Contrast-Enhanced Ultrasonography with Sonazoid

International Nuclear Information System (INIS)

Shiozawa, K.; Watanabe, M.; Ikehara, T.; Kogame, M.; Shinohara, M.; Shinohara, M.; Ishii, K.; Igarashi, Y.; Sumino, Y.; Shiozawa, K.; Makino, H.

2014-01-01

We aim to investigate the hemodynamics in focal steatosis and focal spared lesion of the liver using contrast-enhanced ultrasonography (CEUS) with Sonazoid. The subjects were 47 patients with focal steatosis and focal spared lesion. We evaluated enhancement patterns (hyper enhancement, iso enhancement, and hypo enhancement) in the vascular phase and the presence or absence of a hypoechoic area in the post vascular phase for these lesions using CEUS. Of the 24 patients with focal steatosis, the enhancement pattern was iso enhancement in 19 and hypo enhancement in 5. Hypoechoic areas were noted in the post vascular phase in 3 patients. Of the 23 patients with focal spared lesions, the enhancement pattern was iso enhancement in 18 and hyper enhancement in 5. No hypoechoic areas were noted in the post vascular phase in any patient. The hemodynamics in focal steatosis and focal spared lesions in non diffuse fatty liver can be observed using low-invasive procedures in real-time by CEUS. It was suggested that differences in the dynamics of enhancement in the vascular phase of CEUS were influenced by the fat deposits in the target lesion, the surrounding liver parenchyma, and the third inflow.

Glycoprotein expression by adenomatous polyps of the colon

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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.

Structures and Functions of Pestivirus Glycoproteins: Not Simply Surface Matters

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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.

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

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Se Chang Park

2013-01-01

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

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

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

2013-01-01

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

In silico screening for inhibitors of p-glycoprotein that target the nucleotide binding domains.

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Brewer, Frances K; Follit, Courtney A; Vogel, Pia D; Wise, John G

2014-12-01

Multidrug resistances and the failure of chemotherapies are often caused by the expression or overexpression of ATP-binding cassette transporter proteins such as the multidrug resistance protein, P-glycoprotein (P-gp). P-gp is expressed in the plasma membrane of many cell types and protects cells from accumulation of toxins. P-gp uses ATP hydrolysis to catalyze the transport of a broad range of mostly hydrophobic compounds across the plasma membrane and out of the cell. During cancer chemotherapy, the administration of therapeutics often selects for cells which overexpress P-gp, thereby creating populations of cancer cells resistant to a variety of chemically unrelated chemotherapeutics. The present study describes extremely high-throughput, massively parallel in silico ligand docking studies aimed at identifying reversible inhibitors of ATP hydrolysis that target the nucleotide-binding domains of P-gp. We used a structural model of human P-gp that we obtained from molecular dynamics experiments as the protein target for ligand docking. We employed a novel approach of subtractive docking experiments that identified ligands that bound predominantly to the nucleotide-binding domains but not the drug-binding domains of P-gp. Four compounds were found that inhibit ATP hydrolysis by P-gp. Using electron spin resonance spectroscopy, we showed that at least three of these compounds affected nucleotide binding to the transporter. These studies represent a successful proof of principle demonstrating the potential of targeted approaches for identifying specific inhibitors of P-gp. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

[Research progress on ebola virus glycoprotein].

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

2013-03-01

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

P-glycoprotein trafficking as a therapeutic target to optimize CNS drug delivery.

Science.gov (United States)

Davis, Thomas P; Sanchez-Covarubias, Lucy; Tome, Margaret E

2014-01-01

The primary function of the blood-brain barrier (BBB)/neurovascular unit is to protect the central nervous system (CNS) from potentially harmful xenobiotic substances and maintain CNS homeostasis. Restricted access to the CNS is maintained via a combination of tight junction proteins as well as a variety of efflux and influx transporters that limits the transcellular and paracellular movement of solutes. Of the transporters identified at the BBB, P-glycoprotein (P-gp) has emerged as the transporter that is the greatest obstacle to effective CNS drug delivery. In this chapter, we provide data to support intracellular protein trafficking of P-gp within cerebral capillary microvessels as a potential target for improved drug delivery. We show that pain-induced changes in P-gp trafficking are associated with changes in P-gp's association with caveolin-1, a key scaffolding/trafficking protein that colocalizes with P-gp at the luminal membrane of brain microvessels. Changes in colocalization with the phosphorylated and nonphosphorylated forms of caveolin-1, by pain, are accompanied by dynamic changes in the distribution, relocalization, and activation of P-gp "pools" between microvascular endothelial cell subcellular compartments. Since redox-sensitive processes may be involved in signaling disassembly of higher-order structures of P-gp, we feel that manipulating redox signaling, via specific protein targeting at the BBB, may protect disulfide bond integrity of P-gp reservoirs and control trafficking to the membrane surface, providing improved CNS drug delivery. The advantage of therapeutic drug "relocalization" of a protein is that the physiological impact can be modified, temporarily or long term, despite pathology-induced changes in gene transcription. © 2014 Elsevier Inc. All rights reserved.

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

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Takuya Kanno

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

Impact of region contouring variability on image-based focal therapy evaluation

Science.gov (United States)

Gibson, Eli; Donaldson, Ian A.; Shah, Taimur T.; Hu, Yipeng; Ahmed, Hashim U.; Barratt, Dean C.

2016-03-01

Motivation: Focal therapy is an emerging low-morbidity treatment option for low-intermediate risk prostate cancer; however, challenges remain in accurately delivering treatment to specified targets and determining treatment success. Registered multi-parametric magnetic resonance imaging (MPMRI) acquired before and after treatment can support focal therapy evaluation and optimization; however, contouring variability, when defining the prostate, the clinical target volume (CTV) and the ablation region in images, reduces the precision of quantitative image-based focal therapy evaluation metrics. To inform the interpretation and clarify the limitations of such metrics, we investigated inter-observer contouring variability and its impact on four metrics. Methods: Pre-therapy and 2-week-post-therapy standard-of-care MPMRI were acquired from 5 focal cryotherapy patients. Two clinicians independently contoured, on each slice, the prostate (pre- and post-treatment) and the dominant index lesion CTV (pre-treatment) in the T2-weighted MRI, and the ablated region (post-treatment) in the dynamic-contrast- enhanced MRI. For each combination of clinician contours, post-treatment images were registered to pre-treatment images using a 3D biomechanical-model-based registration of prostate surfaces, and four metrics were computed: the proportion of the target tissue region that was ablated and the target:ablated region volume ratio for each of two targets (the CTV and an expanded planning target volume). Variance components analysis was used to measure the contribution of each type of contour to the variance in the therapy evaluation metrics. Conclusions: 14-23% of evaluation metric variance was attributable to contouring variability (including 6-12% from ablation region contouring); reducing this variability could improve the precision of focal therapy evaluation metrics.

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.

Focal adhesion kinase-dependent focal adhesion recruitment of SH2 domains directs SRC into focal adhesions to regulate cell adhesion and migration.

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Wu, Jui-Chung; Chen, Yu-Chen; Kuo, Chih-Ting; Wenshin Yu, Helen; Chen, Yin-Quan; Chiou, Arthur; Kuo, Jean-Cheng

2015-12-18

Directed cell migration requires dynamical control of the protein complex within focal adhesions (FAs) and this control is regulated by signaling events involving tyrosine phosphorylation. We screened the SH2 domains present in tyrosine-specific kinases and phosphatases found within FAs, including SRC, SHP1 and SHP2, and examined whether these enzymes transiently target FAs via their SH2 domains. We found that the SRC_SH2 domain and the SHP2_N-SH2 domain are associated with FAs, but only the SRC_SH2 domain is able to be regulated by focal adhesion kinase (FAK). The FAK-dependent association of the SRC_SH2 domain is necessary and sufficient for SRC FA targeting. When the targeting of SRC into FAs is inhibited, there is significant suppression of SRC-mediated phosphorylation of paxillin and FAK; this results in an inhibition of FA formation and maturation and a reduction in cell migration. This study reveals an association between FAs and the SRC_SH2 domain as well as between FAs and the SHP2_N-SH2 domains. This supports the hypothesis that the FAK-regulated SRC_SH2 domain plays an important role in directing SRC into FAs and that this SRC-mediated FA signaling drives cell migration.

Inhibition of human immunodeficiency virus (HIV) infection in vitro by anticarbohydrate monoclonal antibodies: peripheral glycosylation of HIV envelope glycoprotein gp120 may be a target for virus neutralization

DEFF Research Database (Denmark)

Hansen, J E; Clausen, H; Nielsen, C

1990-01-01

), and the cell type used as the infection target (MT4, PMC, or selected T4 lymphocytes). Inhibition was observed when viruses were preincubated with MAbs but not when cells were preincubated with MAbs before inoculation, and the MAbs were shown to precipitate 125I-labeled gp120. The MAbs therefore define...... carbohydrate structures expressed by the viral envelope glycoprotein gp120, indicating that glycans of the viral envelope are possible targets for immunotherapy or vaccine development or both....

Recent Progress in Electrochemical Biosensors for Glycoproteins

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Uichi Akiba

2016-12-01

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

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

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

2016-06-01

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

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

Science.gov (United States)

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

2011-07-01

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

Dual targeting of EGFR and focal adhesion kinase in 3D grown HNSCC cell cultures

International Nuclear Information System (INIS)

Eke, Iris; Cordes, Nils

2011-01-01

Purpose: Epidermal growth factor receptor (EGFR) and focal adhesion kinase (FAK) show frequent overexpression and hyperactivity in various human malignancies including head and neck squamous cell carcinomas (HNSCC). To examine effects of dual EGFR/FAK inhibition on cellular radiosensitivity of HNSCC cells in a more physiological environment, we employed a previously established laminin-rich extracellular matrix (lrECM) based three-dimensional (3D) cell culture model. Materials and methods: UTSCC15 and SAS HNSCC cell lines stably transfected with EGFR-CFP or CFP were used. Single or combined EGFR (Cetuximab, siRNA) and FAK (TAE226, siRNA) inhibition were accomplished prior to measuring clonogenic survival and protein expression and phosphorylation. Immunofluorescence enabled visualization of EGFR-CFP and FAK. Results: Cetuximab resulted in higher radiosensitization in EGFR-CFP overexpressing cell lines than CFP controls. Single EGFR or FAK inhibition mediated radiosensitization, while dual EGFR/FAK targeting further augmented this effect. Despite signaling alterations upon Cetuximab and siRNA knockdown, analysis of protein expression and phosphorylation indicates EGFR and FAK signaling coexistence without obvious overlap. Conclusions: Combined EGFR/FAK targeting yielded stronger radiosensitization than either approach alone, which might be based on non-overlapping downstream signaling. Whether dual targeting of EGFR and FAK can reasonably be combined with radiotherapy and chemotherapy needs clarification.

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

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Eric eNguema-Ona

2014-10-01

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

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

Science.gov (United States)

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

2017-04-12

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

Henipavirus Mediated Membrane Fusion, Virus Entry and Targeted Therapeutics

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Dimitar B. Nikolov

2012-02-01

Full Text Available The Paramyxoviridae genus Henipavirus is presently represented by the type species Hendra and Nipah viruses which are both recently emerged zoonotic viral pathogens responsible for repeated outbreaks associated with high morbidity and mortality in Australia, Southeast Asia, India and Bangladesh. These enveloped viruses bind and enter host target cells through the coordinated activities of their attachment (G and class I fusion (F envelope glycoproteins. The henipavirus G glycoprotein interacts with host cellular B class ephrins, triggering conformational alterations in G that lead to the activation of the F glycoprotein, which facilitates the membrane fusion process. Using the recently published structures of HeV-G and NiV-G and other paramyxovirus glycoproteins, we review the features of the henipavirus envelope glycoproteins that appear essential for mediating the viral fusion process, including receptor binding, G-F interaction, F activation, with an emphasis on G and the mutations that disrupt viral infectivity. Finally, recent candidate therapeutics for henipavirus-mediated disease are summarized in light of their ability to inhibit HeV and NiV entry by targeting their G and F glycoproteins.

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

NARCIS (Netherlands)

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

2001-01-01

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

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

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Ryan Williams

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

TRIM15 is a focal adhesion protein that regulates focal adhesion disassembly

Science.gov (United States)

Uchil, Pradeep D.; Pawliczek, Tobias; Reynolds, Tracy D.; Ding, Siyuan; Hinz, Angelika; Munro, James B.; Huang, Fang; Floyd, Robert W.; Yang, Haitao; Hamilton, William L.; Bewersdorf, Joerg; Xiong, Yong; Calderwood, David A.; Mothes, Walther

2014-01-01

ABSTRACT Focal adhesions are macromolecular complexes that connect the actin cytoskeleton to the extracellular matrix. Dynamic turnover of focal adhesions is crucial for cell migration. Paxillin is a multi-adaptor protein that plays an important role in regulating focal adhesion dynamics. Here, we identify TRIM15, a member of the tripartite motif protein family, as a paxillin-interacting factor and a component of focal adhesions. TRIM15 localizes to focal contacts in a myosin-II-independent manner by an interaction between its coiled-coil domain and the LD2 motif of paxillin. Unlike other focal adhesion proteins, TRIM15 is a stable focal adhesion component with restricted mobility due to its ability to form oligomers. TRIM15-depleted cells display impaired cell migration and reduced focal adhesion disassembly rates, in addition to enlarged focal adhesions. Thus, our studies demonstrate a cellular function for TRIM15 as a regulatory component of focal adhesion turnover and cell migration. PMID:25015296

Glycoprotein biosynthesis by human normal platelets

International Nuclear Information System (INIS)

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

1987-01-01

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

Statins Suppress Ebola Virus Infectivity by Interfering with Glycoprotein Processing.

Science.gov (United States)

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

2018-05-01

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

Targeting P-selectin glycoprotein ligand-1/P-selectin interactions as a novel therapy for metabolic syndrome.

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Patel, Madhukar S; Miranda-Nieves, David; Chen, Jiaxuan; Haller, Carolyn A; Chaikof, Elliot L

2017-05-01

Obesity-induced insulin resistance and metabolic syndrome continue to pose an important public health challenge worldwide as they significantly increase the risk of type 2 diabetes and atherosclerotic cardiovascular disease. Advances in the pathophysiologic understanding of this process has identified that chronic inflammation plays a pivotal role. In this regard, given that both animal models and human studies have demonstrated that the interaction of P-selectin glycoprotein ligand-1 (PSGL-1) with P-selectin is not only critical for normal immune response but also is upregulated in the setting of metabolic syndrome, PSGL-1/P-selectin interactions provide a novel target for preventing and treating resultant disease. Current approaches of interfering with PSGL-1/P-selectin interactions include targeted antibodies, recombinant immunoglobulins that competitively bind P-selectin, and synthetic molecular therapies. Experimental models as well as clinical trials assessing the role of these modalities in a variety of diseases have continued to contribute to the understanding of PSGL-1/P-selectin interactions and have demonstrated the difficulty in creating clinically relevant therapeutics. Most recently, however, computational simulations have further enhanced our understanding of the structural features of PSGL-1 and related glycomimetics, which are responsible for high-affinity selectin interactions. Leveraging these insights for the design of next generation agents has thus led to development of a promising synthetic method for generating PSGL-1 glycosulfopeptide mimetics for the treatment of metabolic syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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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.

Antigenic properties of the human immunodeficiency virus envelope glycoprotein gp120 on virions bound to target cells.

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Meron Mengistu

2015-03-01

Full Text Available The HIV-1 envelope glycoprotein, gp120, undergoes multiple molecular interactions and structural rearrangements during the course of host cell attachment and viral entry, which are being increasingly defined at the atomic level using isolated proteins. In comparison, antigenic markers of these dynamic changes are essentially unknown for single HIV-1 particles bound to target cells. Such markers should indicate how neutralizing and/or non-neutralizing antibodies might interdict infection by either blocking infection or sensitizing host cells for elimination by Fc-mediated effector function. Here we address this deficit by imaging fluorescently labeled CCR5-tropic HIV-1 pseudoviruses using confocal and superresolution microscopy to track the exposure of neutralizing and non-neutralizing epitopes as they appear on single HIV-1 particles bound to target cells. Epitope exposure was followed under conditions permissive or non-permissive for viral entry to delimit changes associated with virion binding from those associated with post-attachment events. We find that a previously unexpected array of gp120 epitopes is exposed rapidly upon target cell binding. This array comprises both neutralizing and non-neutralizing epitopes, the latter being hidden on free virions yet capable of serving as potent targets for Fc-mediated effector function. Under non-permissive conditions for viral entry, both neutralizing and non-neutralizing epitope exposures were relatively static over time for the majority of bound virions. Under entry-permissive conditions, epitope exposure patterns changed over time on subsets of virions that exhibited concurrent variations in virion contents. These studies reveal that bound virions are distinguished by a broad array of both neutralizing and non-neutralizing gp120 epitopes that potentially sensitize a freshly engaged target cell for destruction by Fc-mediated effector function and/or for direct neutralization at a post-binding step

The Mycobacterium tuberculosis cell-surface glycoprotein apa as a potential adhesin to colonize target cells via the innate immune system pulmonary C-type lectin surfactant protein A.

Science.gov (United States)

Ragas, Aude; Roussel, Lucie; Puzo, Germain; Rivière, Michel

2007-02-23

Tuberculosis is still a major health problem, and understanding the mechanism by which Mycobacterium tuberculosis (Mtb) invades and colonizes its host target cells remains an important issue for the control of infection. The innate immune system C-type lectins (C-TLs), including the human pulmonary surfactant protein A (PSP-A), have been recently identified as determinant players in the early recognition of the invading pathogen and in mounting the host defense response. Although the antigenic lipoglycan mannosylated lipoarabinomannan is currently considered to be the major C-TL target on the mycobacterial surface, the recognition by some C-TLs of the only mycobacterial species composing the "Mtb complex" indicates that mannosylated lipoarabinomannan cannot account alone for this specificity. Thus, we searched for the mycobacterial molecules targeted by human PSP-A, focusing our attention on the Mtb surface glycoproteins. We developed an original functional proteomic approach based on a lectin blot assay using crude human bronchoalveolar lavage fluid as a source of physiological PSP-A. Combined with selective cell-surface protein extraction and mass spectrometry peptide mapping, this strategy allowed us to identify the Apa (alanine- and proline-rich antigenic) glycoprotein as new potential target for PSP-A. This result was supported by direct binding of PSP-A to purified Apa. Moreover, EDTA addition or deglycosylation of purified Apa samples completely abolished the interaction, demonstrating that the interaction is calcium- and mannose-dependent, as expected. Finally, we provide convincing evidence that Apa, formerly considered as mainly secreted, is associated with the cell wall for a sufficiently long time to aid in the attachment of PSP-A. Because, to date, Apa seems to be restricted to the Mtb complex strains, we propose that it may account for the selective recognition of those strains by PSP-A and other immune system C-TLs containing homologous functional

Screening of extraction methods for glycoproteins from jellyfish ( Rhopilema esculentum) oral-arms by high performance liquid chromatography

Science.gov (United States)

Ren, Guoyan; Li, Bafang; Zhao, Xue; Zhuang, Yongliang; Yan, Mingyan; Hou, Hu; Zhang, Xiukun; Chen, Li

2009-03-01

In order to select an optimum extraction method for the target glycoprotein (TGP) from jellyfish ( Rhopilema esculentum) oral-arms, a high performance liquid chromatography (HPLC)-assay for the determination of the TGP was developed. Purified target glycoprotein was taken as a standard glycoprotein. The results showed that the calibration curves for peak area plotted against concentration for TGP were linear ( r = 0.9984, y = 4.5895 x+47.601) over concentrations ranging from 50 to 400 mgL-1. The mean extraction recovery was 97.84% (CV2.60%). The fractions containing TGP were isolated from jellyfish ( R. esculentum) oral-arms by four extraction methods: 1) water extraction (WE), 2) phosphate buffer solution (PBS) extraction (PE), 3) ultrasound-assisted water extraction (UA-WE), 4) ultrasound-assisted PBS extraction (UA-PE). The lyophilized extract was dissolved in Milli-Q water and analyzed directly on a short TSK-GEL G4000PWXL (7.8 mm×300 mm) column. Our results indicated that the UA-PE method was the optimum extraction method selected by HPLC.

Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus

DEFF Research Database (Denmark)

Giang, Erick; Dorner, Marcus; Prentoe, Jannick C

2012-01-01

, and an effective vaccine should target conserved T- and B-cell epitopes of the virus. Conserved B-cell epitopes overlapping the CD81 receptor-binding site (CD81bs) on the E2 viral envelope glycoprotein have been reported previously and provide promising vaccine targets. In this study, we isolated 73 human m......Abs recognizing five distinct antigenic regions on the virus envelope glycoprotein complex E1E2 from an HCV-immune phage-display antibody library by using an exhaustive-panning strategy. Many of these mAbs were broadly neutralizing. In particular, the mAb AR4A, recognizing a discontinuous epitope outside the CD81......bs on the E1E2 complex, has an exceptionally broad neutralizing activity toward diverse HCV genotypes and protects against heterologous HCV challenge in a small animal model. The mAb panel will be useful for the design and development of vaccine candidates to elicit broadly neutralizing antibodies...

Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism

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Nathan H. Vande Burgt

2015-10-01

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

Focal myositis

International Nuclear Information System (INIS)

Kransdorf, M.J.; Temple, H.T.; Sweet, D.E.

1998-01-01

Focal myositis is a pseudotumor of soft tissue that typically occurs in the deep soft tissue of the extremities, and is a relatively rare lesion. There is a wide clinical spectrum, with approximately one-third of patients with focal myositis subsequently developing polymyositis, and clinical symptoms of generalized weakness, fever, myalgia, and weight loss, with elevation of creatine phosphokinase. We report the case of a patient with focal myositis who subsequently developed myositis ossificans-like features. (orig.)

The Lyssavirus glycoprotein: A key to cross-immunity.

Science.gov (United States)

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

2016-11-01

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

Chicken galectin-1B inhibits Newcastle disease virus adsorption and replication through binding to hemagglutinin-neuraminidase (HN) glycoprotein.

Science.gov (United States)

Sun, Junfeng; Han, Zongxi; Qi, Tianming; Zhao, Ran; Liu, Shengwang

2017-12-08

Galectin-1 is an important immunoregulatory factor and can mediate the host-pathogen interaction via binding glycans on the surface of various viruses. We previously reported that avian respiratory viruses, including lentogenic Newcastle disease virus (NDV), can induce up-regulation of chicken galectin (CG)-1B in the primary target organ. In this study, we investigated whether CG-1B participated in the infectious process of NDV in chickens. We demonstrated that velogenic NDV induced up-regulation of CG-1B in target organs. We also found that CG-1B directly bound to NDV virions and inhibited their hemagglutination activity in vitro We confirmed that CG-1B interacted with NDV hemagglutinin-neuraminidase (HN) glycoprotein, in which the specific G4 N -glycans significantly contributed to the interaction between CG-1B and HN glycoprotein. The presence of extracellular CG-1B, rather than the internalization process, inhibited adsorption of NDV. The interaction between intracellular CG-1B and NDV HN glycoproteins inhibited cell-surface expression of HN glycoprotein and reduced the titer of progeny virus in NDV-infected DF-1 cells. Significantly, the replication of parental and HN glycosylation mutant viruses in CG-1B knockdown and overexpression cells demonstrated that the replication of NDV was correlated with the expression of CG-1B in a specific glycan-dependent manner. Collectively, our results indicate that CG-1B has anti-NDV activity by binding to N -glycans on HN glycoprotein. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Ammonia transport in the kidney by Rhesus glycoproteins

Science.gov (United States)

Verlander, Jill W.

2014-01-01

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

Focal myositis

Energy Technology Data Exchange (ETDEWEB)

Kransdorf, M.J. [Saint Mary`s Hospital, Richmond, VA (United States). Dept. of Radiol.]|[Department of Radiologic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States); Temple, H.T. [Department of Orthopedic Surgery, University of Virginia Health Sciences Center, Charlottesville, Virginia (United States)]|[Department of Orthopedic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States); Sweet, D.E. [Department of Orthopedic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States)

1998-05-01

Focal myositis is a pseudotumor of soft tissue that typically occurs in the deep soft tissue of the extremities, and is a relatively rare lesion. There is a wide clinical spectrum, with approximately one-third of patients with focal myositis subsequently developing polymyositis, and clinical symptoms of generalized weakness, fever, myalgia, and weight loss, with elevation of creatine phosphokinase. We report the case of a patient with focal myositis who subsequently developed myositis ossificans-like features. (orig.) With 3 figs., 25 refs.

Infrared MUSIC from Z technology focal planes

International Nuclear Information System (INIS)

Waters, C.R.; Sommese, A.; Johnston, D.; Landau, H.

1989-01-01

Presented is the Multiple Signal Classification (MUSIC) algorithm which uses the high frequency differences in sensed time signals to discriminate, count, and accurately locate closely spaced targets. Z technology focal planes allow the implementation of this algorithm and the trade-off between finer spatial resolution systems and systems with coarser resolution but higher sampling rates

Inhibition of Lassa virus glycoprotein cleavage and multicycle replication by site 1 protease-adapted alpha(1-antitrypsin variants.

Directory of Open Access Journals (Sweden)

Anna Maisa

2009-06-01

Full Text Available Proteolytic processing of the Lassa virus envelope glycoprotein precursor GP-C by the host proprotein convertase site 1 protease (S1P is a prerequisite for the incorporation of the subunits GP-1 and GP-2 into viral particles and, hence, essential for infectivity and virus spread. Therefore, we tested in this study the concept of using S1P as a target to block efficient virus replication.We demonstrate that stable cell lines inducibly expressing S1P-adapted alpha(1-antitrypsin variants inhibit the proteolytic maturation of GP-C. Introduction of the S1P recognition motifs RRIL and RRLL into the reactive center loop of alpha(1-antitrypsin resulted in abrogation of GP-C processing by endogenous S1P to a similar level observed in S1P-deficient cells. Moreover, S1P-specific alpha(1-antitrypsins significantly inhibited replication and spread of a replication-competent recombinant vesicular stomatitis virus expressing the Lassa virus glycoprotein GP as well as authentic Lassa virus. Inhibition of viral replication correlated with the ability of the different alpha(1-antitrypsin variants to inhibit the processing of the Lassa virus glycoprotein precursor.Our data suggest that glycoprotein cleavage by S1P is a promising target for the development of novel anti-arenaviral strategies.

Solubilization of glycoproteins of envelope viruses by detergents

International Nuclear Information System (INIS)

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

1986-01-01

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

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

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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.

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.

Determinants of foamy virus envelope glycoprotein mediated resistance to superinfection

International Nuclear Information System (INIS)

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

2003-01-01

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

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

Science.gov (United States)

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

2014-08-30

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

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

Science.gov (United States)

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

2018-07-01

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

Vesicular stomatitis virus expressing a chimeric Sindbis glycoprotein containing an Fc antibody binding domain targets to Her2/neu overexpressing breast cancer cells

International Nuclear Information System (INIS)

Bergman, Ira; Whitaker-Dowling, Patricia; Gao Yanhua; Griffin, Judith A.; Watkins, Simon C.

2003-01-01

Vesicular stomatitis virus (VSV) is a candidate for development for cancer therapy. It is an oncolytic virus that is safe in humans. Recombinant virus can be made directly from plasmid components. We attempted to create a virus that targeted specifically to breast cancer cells. Nonreplicating and replicating pseudotype VSV were created whose only surface glycoprotein (gp) was a Sindbis gp, called Sindbis-ZZ, modified to severely reduce its native binding function and to contain the Fc-binding domain of Staphylococcus aureus protein A. When titered on Her2/neu overexpressing SKBR3 human breast cancer cells, pseudotype VSV coated with Sindbis-ZZ had 5 /ml. This work demonstrates the ability to easily create, directly from plasmid components, an oncolytic replicating VSV with a restricted host cell range

Focal retinal phlebitis.

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Hoang, Quan V; Freund, K Bailey; Klancnik, James M; Sorenson, John A; Cunningham, Emmett T; Yannuzzi, Lawrence A

2012-01-01

To report three cases of solitary, focal retinal phlebitis. An observational case series. Three eyes in three patients were noted to have unilateral decreased vision, macular edema, and a focal retinal phlebitis, which was not at an arteriovenous crossing. All three patients developed a branch retinal vein occlusion at the site of inflammation. These patients had no other evidence of intraocular inflammation, including vitritis, retinitis, retinal vasculitis, or choroiditis, nor was there any systemic disorder associated with inflammation, infection, or coagulation identified. Focal retinal phlebitis appears to be an uncommon and unique entity that produces macular edema and ultimately branch retinal vein occlusion. In our patients, the focal phlebitis and venous occlusion did not occur at an arteriovenous crossing, which is the typical site for branch retinal venous occlusive disease. This suggests that our cases represent a distinct clinical entity, which starts with a focal abnormality in the wall of a retinal venule, resulting in surrounding exudation and, ultimately, ends with branch retinal vein occlusion.

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

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

2004-10-01

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

The pestivirus Erns glycoprotein interacts with E2 in both infected cells and mature virions

International Nuclear Information System (INIS)

Lazar, Catalin; Zitzmann, Nicole; Dwek, Raymond A.; Branza-Nichita, Norica

2003-01-01

E rns is a pestivirus envelope glycoprotein indispensable for virus attachment and infection of target cells. Unlike the other two envelope proteins E1 and E2, E rns lacks a transmembrane domain and a vast quantity is secreted into the medium of infected cells. The protein is also present in fractions of pure pestivirus virions, raising the important and intriguing question regarding the mechanism of its attachment to the pestivirus envelope. In this study a direct interaction between E rns and E2 glycoproteins was demonstrated in both pestivirus-infected cells and mature virions. By co- and sequential immunoprecipitation we showed that an E rns -E2 heterodimer is assembled very early after translation of the viral polyprotein and before its processing is completed. Our results suggest that E rns is attached to the pestivirus envelope via a direct interaction with E2 and explain the role of E rns in the initial virus-target cell interaction

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

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

2013-09-15

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

Suppression of β3-integrin in mice triggers a neuropilin-1-dependent change in focal adhesion remodelling that can be targeted to block pathological angiogenesis

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Tim S. Ellison

2015-09-01

Full Text Available Anti-angiogenic treatments against αvβ3-integrin fail to block tumour growth in the long term, which suggests that the tumour vasculature escapes from angiogenesis inhibition through αvβ3-integrin-independent mechanisms. Here, we show that suppression of β3-integrin in mice leads to the activation of a neuropilin-1 (NRP1-dependent cell migration pathway in endothelial cells via a mechanism that depends on NRP1's mobilisation away from mature focal adhesions following VEGF-stimulation. The simultaneous genetic targeting of both molecules significantly impairs paxillin-1 activation and focal adhesion remodelling in endothelial cells, and therefore inhibits tumour angiogenesis and the growth of already established tumours. These findings provide a firm foundation for testing drugs against these molecules in combination to treat patients with advanced cancers.

An improved radioimmunoassay for urinary Tamm-Horsfall glycoprotein

International Nuclear Information System (INIS)

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

1982-01-01

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

Focal Suppression of Distractor Sounds by Selective Attention in Auditory Cortex.

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Schwartz, Zachary P; David, Stephen V

2018-01-01

Auditory selective attention is required for parsing crowded acoustic environments, but cortical systems mediating the influence of behavioral state on auditory perception are not well characterized. Previous neurophysiological studies suggest that attention produces a general enhancement of neural responses to important target sounds versus irrelevant distractors. However, behavioral studies suggest that in the presence of masking noise, attention provides a focal suppression of distractors that compete with targets. Here, we compared effects of attention on cortical responses to masking versus non-masking distractors, controlling for effects of listening effort and general task engagement. We recorded single-unit activity from primary auditory cortex (A1) of ferrets during behavior and found that selective attention decreased responses to distractors masking targets in the same spectral band, compared with spectrally distinct distractors. This suppression enhanced neural target detection thresholds, suggesting that limited attention resources serve to focally suppress responses to distractors that interfere with target detection. Changing effort by manipulating target salience consistently modulated spontaneous but not evoked activity. Task engagement and changing effort tended to affect the same neurons, while attention affected an independent population, suggesting that distinct feedback circuits mediate effects of attention and effort in A1. © The Author 2017. Published by Oxford University Press.

Focal Adhesion Kinase as a Potential Target in AML and MDS.

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Carter, Bing Z; Mak, Po Yee; Wang, Xiangmeng; Yang, Hui; Garcia-Manero, Guillermo; Mak, Duncan H; Mu, Hong; Ruvolo, Vivian R; Qiu, Yihua; Coombes, Kevin; Zhang, Nianxiang; Ragon, Brittany; Weaver, David T; Pachter, Jonathan A; Kornblau, Steven; Andreeff, Michael

2017-06-01

Although overexpression/activation of focal adhesion kinase (FAK) is widely known in solid tumors to control cell growth, survival, invasion, metastasis, gene expression, and stem cell self-renewal, its expression and function in myeloid leukemia are not well investigated. Using reverse-phase protein arrays in large cohorts of newly diagnosed acute myeloid leukemia (AML) and myeloid dysplastic syndrome (MDS) samples, we found that high FAK expression was associated with unfavorable cytogenetics ( P = 2 × 10 -4 ) and relapse ( P = 0.02) in AML. FAK expression was significantly lower in patients with FLT3 -ITD ( P = 0.0024) or RAS ( P = 0.05) mutations and strongly correlated with p-SRC and integrinβ3 levels. FAK protein levels were significantly higher in CD34 + ( P = 5.42 × 10 -20 ) and CD34 + CD38 - MDS ( P = 7.62 × 10 -9 ) cells compared with normal CD34 + cells. MDS patients with higher FAK in CD34 + cells tended to have better overall survival ( P = 0.05). FAK expression was significantly higher in MDS patients who later transformed to compared with those who did not transform to AML and in AML patients who transformed from MDS compared with those with de novo AML. Coculture with mesenchymal stromal cells (MSC) increased FAK expression in AML cells. Inhibition of FAK decreased MSC-mediated adhesion/migration and viability of AML cells and prolonged survival in an AML xenograft murine model. Our results suggest that FAK regulates leukemia-stromal interactions and supports leukemia cell survival; hence, FAK is a potential therapeutic target in myeloid leukemia. Mol Cancer Ther; 16(6); 1133-44. ©2017 AACR . ©2017 American Association for Cancer Research.

Orthobunyavirus ultrastructure and the curious tripodal glycoprotein spike.

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Thomas A Bowden

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

Focal myositis

International Nuclear Information System (INIS)

Galloway, H.R.; Dahlstrom, J.E.; Bennett, G.M.

2001-01-01

Focal myositis is a rare, benign focal inflammation of muscle. The lesion often presents as a mass that may be mistaken for a soft tissue sarcoma. This report describes the MRI and histopathological features of a case and illustrates how the diagnosis may be suspected on the basis of the MR findings. Copyright (2001) Blackwell Science Pty Ltd

Treatment strategy based on targeting P-glycoprotein on peripheral lymphocytes in patients with systemic autoimmune disease.

Science.gov (United States)

Tsujimura, Shizuyo; Tanaka, Yoshiya

2012-02-01

Although corticosteroids, immunosuppressants and disease-modifying antirheumatic drugs (DMARDs) are widely used in the treatment of various systemic autoimmune diseases such as systemic lupus erythematosus (SLE), we often experience patients with systemic autoimmune diseases who are resistant to these treatments. P-glycoprotein (P-gp) of membrane transporters, a product of the multiple drug resistance (MDR)-1 gene, is known to play a pivotal role in the acquisition of drug resistance to chemotherapy in malignancy. However, the relevance of MDR-1 and P-gp to resting and activated lymphocytes, which are the major target in the treatment of systemic autoimmune diseases, remains unclear. Studies from our laboratories found surface expression of P-gp on peripheral lymphocytes in patients with SLE and a significant correlation between the expression level and disease activity. Such expression is induced not only by genotoxic stresses but also by various stimuli including cytokines, resulting in active efflux of drugs from the cytoplasm of lymphocytes, resulting in drug-resistance and high disease activity. However, the use of both P-gp antagonists (e.g., cyclosporine) and inhibition of P-gp synthesis with intensive immunosuppressive therapy successfully reduces the efflux of corticosteroids from lymphocytes in vitro, suggesting that P-gp antagonists and P-gp synthesis inhibitors could be used to overcome drug-resistance in vivo and improve outcome. In conclusion, lymphocytes activated by various stimuli in patients with highly active disease apparently acquire MDR-1-mediated multidrug resistance against corticosteroids and probably some DMARDs, which are substrates of P-gp. Inhibition/reduction of P-gp could overcome such drug resistance. The expression of P-gp on lymphocytes is a promising marker of drug resistance and a suitable target to combat drug resistance in patients with active systemic autoimmune diseases.

Focal Therapy: Patients, Interventions, and Outcomes—A Report from a Consensus Meeting

Science.gov (United States)

Donaldson, Ian A.; Alonzi, Roberto; Barratt, Dean; Barret, Eric; Berge, Viktor; Bott, Simon; Bottomley, David; Eggener, Scott; Ehdaie, Behfar; Emberton, Mark; Hindley, Richard; Leslie, Tom; Miners, Alec; McCartan, Neil; Moore, Caroline M.; Pinto, Peter; Polascik, Thomas J.; Simmons, Lucy; van der Meulen, Jan; Villers, Arnauld; Willis, Sarah; Ahmed, Hashim U.

2015-01-01

Background Focal therapy as a treatment option for localized prostate cancer (PCa) is an increasingly popular and rapidly evolving field. Objective To gather expert opinion on patient selection, interventions, and meaningful outcome measures for focal therapy in clinical practice and trial design. Design, setting, and participants Fifteen experts in focal therapy followed a modified two-stage RAND/University of California, Los Angeles (UCLA) Appropriateness Methodology process. All participants independently scored 246 statements prior to rescoring at a face-to-face meeting. The meeting occurred in June 2013 at the Royal Society of Medicine, London, supported by the Wellcome Trust and the UK Department of Health. Outcome measurements and statistical analysis Agreement, disagreement, or uncertainty were calculated as the median panel score. Consensus was derived from the interpercentile range adjusted for symmetry level. Results and limitations Of 246 statements, 154 (63%) reached consensus. Items of agreement included the following: patients with intermediate risk and patients with unifocal and multifocal PCa are eligible for focal treatment; magnetic resonance imaging–targeted or template-mapping biopsy should be used to plan treatment; planned treatment margins should be 5 mm from the known tumor; prostate volume or age should not be a primary determinant of eligibility; foci of indolent cancer can be left untreated when treating the dominant index lesion; histologic outcomes should be defined by targeted biopsy at 1 yr; residual disease in the treated area of ≤3 mm of Gleason 3 + 3 did not need further treatment; and focal retreatment rates of ≤20% should be considered clinically acceptable but subsequent whole-gland therapy deemed a failure of focal therapy. All statements are expert opinion and therefore constitute level 5 evidence and may not reflect wider clinical consensus. Conclusions The landscape of PCa treatment is rapidly evolving with new

Focal pancreatic enlargement: differentiation between pancreatic adenocarcinoma and focal pancreatitis on CT and ERCP

International Nuclear Information System (INIS)

Kim, Eun Kyung; Kim, Ki Whang; Lee, Jong Tae; Kim, Hee Soo; Yoo, Hyung Sik; Yu, Jeong Sik; Yoon, Sang Wook

1995-01-01

To differentiate the pancreatic adenocarcinoma from focal pancreatitis on CT and ERCP in cases of focal pancreatic enlargement. We analysed CT findings of 66 patients of pancreatic adenocarcinoma (n = 45) or focal pancreatitis (n = 21) with respect to size, density, calcification, pancreatic or biliary duct dilatation, fat plane obliteration around the vessels, direction of retroperitoneal extension, lymphadenopathy, pseudocyst formation and atrophy of pancreas. ERCP available in 48 patients were analysed in respect to morphologic appearance of CBD and pancreatic duct, and distance between the two ducts. The patients in focal pancreatitis were younger with more common history of alcohol drinking. There was no statistical difference in calcifications of the mass (18% in the adenocarcinoma, 33% in the focal pancreatitis), but a tendency of denser, larger number of calcifications was noted in focal pancreatitis. The finding of fat plane obliteration around the vessels were more common in pancreatic adenocarcinoma, and fascial thickenings were more prominent in focal pancreatitis, although not statistically significant. On ERCP, there were no differential points of CBD, pancreatic duct morphology, but distance between the two ducts at the lesion center was more wider in focal pancreatitis. Differentiating focal pancreatitis from pancreatic adenocarcinoma is difficult. However, we should consider the possibility of focal pancreatitis in cases of patients with young age, having alcoholic history in association with CT findings of large numbers of and dense calcifications, and ERCP findings of prominent separation of two duct at the lesion center

The glycoprotein of measles virus

International Nuclear Information System (INIS)

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

1980-01-01

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

Cell Surface Glycoprotein of Reactive Stromal Fibroblasts as a Potential Antibody Target in Human Epithelial Cancers

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Garin-Chesa, Pilar; Old, Lloyd J.; Rettig, Wolfgang J.

1990-09-01

The F19 antigen is a cell surface glycoprotein (M_r, 95,000) of human sarcomas and proliferating, cultured fibroblasts that is absent from resting fibroblasts in normal adult tissues. Normal and malignant epithelial cells are also F19^-. The present immunohistochemical study describes induction of F19 in the reactive mesenchyme of epithelial tumors. F19^+ fibroblasts were found in primary and metastatic carcinomas, including colorectal (18 of 18 cases studied), breast (14/14), ovarian (21/21), bladder (9/10), and lung carcinomas (13/13). In contrast, the stroma of benign colorectal adenomas, fibrocystic disease and fibroadenomas of breast, benign prostate hyperplasia, in situ bladder carcinomas, and benign ovarian tumors showed no or only moderate numbers of F19^+ fibroblasts. Analysis of dermal incision wounds revealed that F19 is strongly induced during scar formation. Comparison of F19 with the extracellular matrix protein tenascin, a putative marker of tumor mesenchyme, showed a cellular staining pattern for F19 vs. the extracellular matrix pattern for tenascin and widespread expression of tenascin in F19^- normal tissues and benign tumors. Our results suggest that the F19^+ phenotype correlates with specialized fibroblast functions in wound healing and malignant tumor growth. Because of its abundance in tumor mesenchyme, F19 may serve as a target for antibodies labeled with radioisotopes or toxic agents, or inflammatogenic antibodies, in carcinoma patients.

Transparent meta-analysis: does aging spare prospective memory with focal vs. non-focal cues?

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Bob Uttl

Full Text Available BACKGROUND: Prospective memory (ProM is the ability to become aware of a previously-formed plan at the right time and place. For over twenty years, researchers have been debating whether prospective memory declines with aging or whether it is spared by aging and, most recently, whether aging spares prospective memory with focal vs. non-focal cues. Two recent meta-analyses examining these claims did not include all relevant studies and ignored prevalent ceiling effects, age confounds, and did not distinguish between prospective memory subdomains (e.g., ProM proper, vigilance, habitual ProM (see Uttl, 2008, PLoS ONE. The present meta-analysis focuses on the following questions: Does prospective memory decline with aging? Does prospective memory with focal vs. non-focal cues decline with aging? Does the size of age-related declines with focal vs. non-focal cues vary across ProM subdomains? And are age-related declines in ProM smaller than age-related declines in retrospective memory? METHODS AND FINDINGS: A meta-analysis of event-cued ProM using data visualization and modeling, robust count methods, and conventional meta-analysis techniques revealed that first, the size of age-related declines in ProM with both focal and non-focal cues are large. Second, age-related declines in ProM with focal cues are larger in ProM proper and smaller in vigilance. Third, age-related declines in ProM proper with focal cues are as large as age-related declines in recall measures of retrospective memory. CONCLUSIONS: The results are consistent with Craik's (1983 proposal that age-related declines on ProM tasks are generally large, support the distinction between ProM proper vs. vigilance, and directly contradict widespread claims that ProM, with or without focal cues, is spared by aging.

The Lyssavirus glycoprotein: A key to cross-immunity

International Nuclear Information System (INIS)

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

2016-01-01

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

The Lyssavirus glycoprotein: A key to cross-immunity

Energy Technology Data Exchange (ETDEWEB)

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

2016-11-15

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

“Focal thyroid inferno” on color Doppler ultrasonography: A specific feature of focal Hashimoto's thyroiditis

International Nuclear Information System (INIS)

Fu, Xianshui; Guo, Limei; Zhang, Huabin; Ran, Weiqiang; Fu, Peng; Li, Zhiqiang; Chen, Wen; Jiang, Ling; Wang, Jinrui; Jia, Jianwen

2012-01-01

Purpose: To evaluate color-Doppler features predictive of focal Hashimoto's thyroiditis. Materials and methods: A total of 521 patients with 561 thyroid nodules that underwent surgeries or gun biopsies were included in this study. These nodules were divided into three groups: focal Hashimoto's thyroiditis (104 nodules in 101 patients), benignity other than focal Hashimoto's thyroiditis (73 nodules in 70 patients), and malignancy (358 nodules in 350 patients). On color Doppler sonography, four vascularity types were determined as: hypovascularity, marked internal flow, marked peripheral flow and focal thyroid inferno. The χ 2 test was performed to seek the potential vascularity type with the predictive ability of certain thyroid pathology. Furthermore, the gray-scale features of each nodule were also studied. Results: The vascularity type I (hypovascularity) was more often seen in focal Hashimoto's thyroiditis than other benignity and malignancy (46% vs. 20.5% and 19%). While the type II (marked internal flow) showed the opposite tendency (26.9% [focal Hashimoto's thyroiditis] vs. 45.2% [other benignity] and 52.8% [malignancy]). However, type III (marked peripheral flow) was unable to predict any thyroid pathology. Importantly, type IV (focal thyroid inferno) was exclusive to focal Hashimoto's thyroiditis. All 8 type IV nodules appeared to be solid, hypoechoic, and well-defined. Using “focal thyroid inferno” as an indicator of FHT, the diagnostic sensitivity and specificity were 7.7% and 100% respectively. Conclusions: The vascularity type of “focal thyroid inferno” is specific for focal Hashimoto thyroiditis. Recognition of this particular feature may avoid unnecessary interventional procedures for some solid hypoechoic thyroid nodules suspicious of malignancy.

Chimeric HIV-1 envelope glycoproteins with potent intrinsic granulocyte-macrophage colony-stimulating factor (GM-CSF) activity

NARCIS (Netherlands)

Isik, Gözde; van Montfort, Thijs; Boot, Maikel; Cobos Jiménez, Viviana; Kootstra, Neeltje A.; Sanders, Rogier W.

2013-01-01

HIV-1 acquisition can be prevented by broadly neutralizing antibodies (BrNAbs) that target the envelope glycoprotein complex (Env). An ideal vaccine should therefore be able to induce BrNAbs that can provide immunity over a prolonged period of time, but the low intrinsic immunogenicity of HIV-1 Env

HIGH PERFORMANCE PIAA CORONAGRAPHY WITH COMPLEX AMPLITUDE FOCAL PLANE MASKS

International Nuclear Information System (INIS)

Guyon, Olivier; Martinache, Frantz; Belikov, Ruslan; Soummer, Remi

2010-01-01

We describe a coronagraph approach where the performance of a Phase-Induced Amplitude Apodization (PIAA) coronagraph is improved by using a partially transmissive phase-shifting focal plane mask and a Lyot stop. This approach combines the low inner working angle offered by phase mask coronagraphy, the full throughput and uncompromized angular resolution of the PIAA approach, and the design flexibility of Apodized Pupil Lyot Coronagraph. A PIAA complex mask coronagraph (PIAACMC) is fully described by the focal plane mask size, or, equivalently, its complex transmission which ranges from 0 (opaque) to -1 (phase shifting). For all values of the transmission, the PIAACMC theoretically offers full on-axis extinction and 100% throughput at large angular separations. With a pure phase focal plane mask (complex transmission = -1), the PIAACMC offers 50% throughput at 0.64 λ/D while providing total extinction of an on-axis point source. This performance is very close to the 'fundamental performance limit' of coronagraphy derived from first principles. For very high contrast level, imaging performance with PIAACMC is in practice limited by the angular size of the on-axis target (usually a star). We show that this fundamental limitation must be taken into account when choosing the optimal value of the focal plane mask size in the PIAACMC design. We show that the PIAACMC enables visible imaging of Jupiter-like planets at ∼1.2 λ/D from the host star, and can therefore offer almost three times more targets than a PIAA coronagraph optimized for this type of observation. We find that for visible imaging of Earth-like planets, the PIAACMC gain over a PIAA is probably much smaller, as coronagraphic performance is then strongly constrained by stellar angular size. For observations at 'low' contrast (below ∼ 10 8 ), the PIAACMC offers significant performance enhancement over PIAA. This is especially relevant for ground-based high contrast imaging systems in the near-IR, where

Epitope Dampening Monotypic Measles Virus Hemagglutinin Glycoprotein Results in Resistance to Cocktail of Monoclonal Antibodies

Science.gov (United States)

Lech, Patrycja J.; Tobin, Gregory J.; Bushnell, Ruth; Gutschenritter, Emily; Pham, Linh D.; Nace, Rebecca; Verhoeyen, Els; Cosset, François-Loïc; Muller, Claude P.; Russell, Stephen J.; Nara, Peter L.

2013-01-01

The measles virus (MV) is serologically monotypic. Life-long immunity is conferred by a single attack of measles or following vaccination with the MV vaccine. This is contrary to viruses such as influenza, which readily develop resistance to the immune system and recur. A better understanding of factors that restrain MV to one serotype may allow us to predict if MV will remain monotypic in the future and influence the design of novel MV vaccines and therapeutics. MV hemagglutinin (H) glycoprotein, binds to cellular receptors and subsequently triggers the fusion (F) glycoprotein to fuse the virus into the cell. H is also the major target for neutralizing antibodies. To explore if MV remains monotypic due to a lack of plasticity of the H glycoprotein, we used the technology of Immune Dampening to generate viruses with rationally designed N-linked glycosylation sites and mutations in different epitopes and screened for viruses that escaped monoclonal antibodies (mAbs). We then combined rationally designed mutations with naturally selected mutations to generate a virus resistant to a cocktail of neutralizing mAbs targeting four different epitopes simultaneously. Two epitopes were protected by engineered N-linked glycosylations and two epitopes acquired escape mutations via two consecutive rounds of artificial selection in the presence of mAbs. Three of these epitopes were targeted by mAbs known to interfere with receptor binding. Results demonstrate that, within the epitopes analyzed, H can tolerate mutations in different residues and additional N-linked glycosylations to escape mAbs. Understanding the degree of change that H can tolerate is important as we follow its evolution in a host whose immunity is vaccine induced by genotype A strains instead of multiple genetically distinct wild-type MVs. PMID:23300970

Dual-layer electrode-driven liquid crystal lens with electrically tunable focal length and focal plane

Science.gov (United States)

Zhang, Y. A.; Lin, C. F.; Lin, J. P.; Zeng, X. Y.; Yan, Q.; Zhou, X. T.; Guo, T. L.

2018-04-01

Electric-field-driven liquid crystal (ELC) lens with tunable focal length and their depth of field has been extensively applied in 3D display and imaging systems. In this work, a dual-layer electrode-driven liquid crystal (DELC) lens with electrically tunable focal length and controllable focal plane is demonstrated. ITO-SiO2-AZO electrodes with the dual-layer staggered structure on the top substrate are used as driven electrodes within a LC cell, which permits the establishment of an alternative controllability. The focal length of the DELC lens can be adjusted from 1.41 cm to 0.29 cm when the operating voltage changes from 15 V to 40 V. Furthermore, the focal plane of the DELC lens can selectively move by changing the driving method of the applied voltage to the next driven electrodes. This work demonstrates that the DELC lens has potential applications in imaging systems because of electrically tunable focal length and controllable focal plane.

The hydroxyapatite-binding regions of a rat salivary glycoprotein.

Science.gov (United States)

Embery, G; Green, D R

1989-09-01

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

Isolation of allergenically active glycoprotein from Prosopis juliflora pollen.

Science.gov (United States)

Thakur, I S

1989-03-01

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

Intracellular localization of hydroxyproline-rich glycoprotein biosynthesis

International Nuclear Information System (INIS)

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

1984-01-01

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

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

Science.gov (United States)

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

2006-02-17

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

Humanizing recombinant glycoproteins from Chinese hamster ovary cells

DEFF Research Database (Denmark)

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

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

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

Directory of Open Access Journals (Sweden)

Berkay Saraymen

2016-03-01

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

Focal spot motion of linear accelerators and its effect on portal image analysis

International Nuclear Information System (INIS)

Sonke, Jan-Jakob; Brand, Bob; Herk, Marcel van

2003-01-01

The focal spot of a linear accelerator is often considered to have a fully stable position. In practice, however, the beam control loop of a linear accelerator needs to stabilize after the beam is turned on. As a result, some motion of the focal spot might occur during the start-up phase of irradiation. When acquiring portal images, this motion will affect the projected position of anatomy and field edges, especially when low exposures are used. In this paper, the motion of the focal spot and the effect of this motion on portal image analysis are quantified. A slightly tilted narrow slit phantom was placed at the isocenter of several linear accelerators and images were acquired (3.5 frames per second) by means of an amorphous silicon flat panel imager positioned ∼0.7 m below the isocenter. The motion of the focal spot was determined by converting the tilted slit images to subpixel accurate line spread functions. The error in portal image analysis due to focal spot motion was estimated by a subtraction of the relative displacement of the projected slit from the relative displacement of the field edges. It was found that the motion of the focal spot depends on the control system and design of the accelerator. The shift of the focal spot at the start of irradiation ranges between 0.05-0.7 mm in the gun-target (GT) direction. In the left-right (AB) direction the shift is generally smaller. The resulting error in portal image analysis due to focal spot motion ranges between 0.05-1.1 mm for a dose corresponding to two monitor units (MUs). For 20 MUs, the effect of the focal spot motion reduces to 0.01-0.3 mm. The error in portal image analysis due to focal spot motion can be reduced by reducing the applied dose rate

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

DEFF Research Database (Denmark)

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

1993-01-01

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

Virion Glycoprotein-Mediated Immune Evasion by Human Cytomegalovirus: a Sticky Virus Makes a Slick Getaway

Science.gov (United States)

Gardner, Thomas J.

2016-01-01

SUMMARY The prototypic herpesvirus human cytomegalovirus (CMV) exhibits the extraordinary ability to establish latency and maintain a chronic infection throughout the life of its human host. This is even more remarkable considering the robust adaptive immune response elicited by infection and reactivation from latency. In addition to the ability of CMV to exist in a quiescent latent state, its persistence is enabled by a large repertoire of viral proteins that subvert immune defense mechanisms, such as NK cell activation and major histocompatibility complex antigen presentation, within the cell. However, dissemination outside the cell presents a unique existential challenge to the CMV virion, which is studded with antigenic glycoprotein complexes targeted by a potent neutralizing antibody response. The CMV virion envelope proteins, which are critical mediators of cell attachment and entry, possess various characteristics that can mitigate the humoral immune response and prevent viral clearance. Here we review the CMV glycoprotein complexes crucial for cell attachment and entry and propose inherent properties of these proteins involved in evading the CMV humoral immune response. These include viral glycoprotein polymorphism, epitope competition, Fc receptor-mediated endocytosis, glycan shielding, and cell-to-cell spread. The consequences of CMV virion glycoprotein-mediated immune evasion have a major impact on persistence of the virus in the population, and a comprehensive understanding of these evasion strategies will assist in designing effective CMV biologics and vaccines to limit CMV-associated disease. PMID:27307580

Glycoprotein-Specific Antibodies Produced by DNA Vaccination Protect Guinea Pigs from Lethal Argentine and Venezuelan Hemorrhagic Fever

Science.gov (United States)

Golden, Joseph W.; Maes, Piet; Kwilas, Steven A.; Ballantyne, John

2016-01-01

ABSTRACT Several members of the Arenaviridae can cause acute febrile diseases in humans, often resulting in lethality. The use of convalescent-phase human plasma is an effective treatment in humans infected with arenaviruses, particularly species found in South America. Despite this, little work has focused on developing potent and defined immunotherapeutics against arenaviruses. In the present study, we produced arenavirus neutralizing antibodies by DNA vaccination of rabbits with plasmids encoding the full-length glycoprotein precursors of Junín virus (JUNV), Machupo virus (MACV), and Guanarito virus (GTOV). Geometric mean neutralizing antibody titers, as measured by the 50% plaque reduction neutralization test (PRNT50), exceeded 5,000 against homologous viruses. Antisera against each targeted virus exhibited limited cross-species binding and, to a lesser extent, cross-neutralization. Anti-JUNV glycoprotein rabbit antiserum protected Hartley guinea pigs from lethal intraperitoneal infection with JUNV strain Romero when the antiserum was administered 2 days after challenge and provided some protection (∼30%) when administered 4 days after challenge. Treatment starting on day 6 did not protect animals. We further formulated an IgG antibody cocktail by combining anti-JUNV, -MACV, and -GTOV antibodies produced in DNA-vaccinated rabbits. This cocktail protected 100% of guinea pigs against JUNV and GTOV lethal disease. We then expanded on this cocktail approach by simultaneously vaccinating rabbits with a combination of plasmids encoding glycoproteins from JUNV, MACV, GTOV, and Sabia virus (SABV). Sera collected from rabbits vaccinated with the combination vaccine neutralized all four targets. These findings support the concept of using a DNA vaccine approach to generate a potent pan-arenavirus immunotherapeutic. IMPORTANCE Arenaviruses are an important family of emerging viruses. In infected humans, convalescent-phase plasma containing neutralizing antibodies can

Herpesvirus glycoproteins undergo multiple antigenic changes before membrane fusion.

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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.

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

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

2016-11-30

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

Glycoprotein Enrichment Analytical Techniques: Advantages and Disadvantages.

Science.gov (United States)

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

2017-01-01

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

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

International Nuclear Information System (INIS)

Jarvis, Donald L.

2003-01-01

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

Characterization of LIL laser UV focal spot

International Nuclear Information System (INIS)

Mangeant, M.; Dubois, J.L.; Behar, G.; Arroyo, P.; Durand, V.; Lahonde, C.

2006-01-01

One way to get the fusion of hydrogen in laboratory consists in heating and compressing a DT fuel capsule by using a laser. To reach this aim requires a new generation of high power laser facility. Cea (French board for atomic energy) is developing for this purpose a new 240 laser line facility, the LMJ facility. The LIL which is the prototype of four LMJ laser lines is operational now. In order to confirm the technical choices, a systematic characterization of LIL was carried out. A particular effort has been provided to measure the 3ω high energy focal spot (1.5 kJ/700 ps and 5 ns for one beam) and the synchronization of laser beams onto the target, which are key issues for the plasma production. An experimental device, SAT-3ω (a 3ω laser focal spot analysis) has been designed to perform these measures. That diagnostic which is located at the end of the laser lines delivered its first results during the 2004 quadruplet qualification campaigns. The near field imaging showed no diaphony and vignetting. Low power spots allowed us to control we had no ghost. The energy measurement quality showed the photometric transfer function was perfectly known. Our caustic image are given with an average dynamic range of 800, a spatial resolution of 10 μm and diameter accuracy about 1% for 50% and 3% for 90% of encircled energy. The high energy focal spot diameters are in agreement with low and very low energy diameters. The phase plate and 14 GHz effects are similar to what we had expected. For a laser shot completed with a continuous phase plate at 14 GHz, and for an energy level of 1.5 kJ per beam at 351 nm, the focal beam diameter at 3% of the peak level is (875 ± 45) μm

Regulation of glycoprotein synthesis in yeast by mating pheromones

International Nuclear Information System (INIS)

Tanner, W.

1984-01-01

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

Engineered CHO cells for production of diverse, homogeneous glycoproteins

DEFF Research Database (Denmark)

Yang, Zhang; Wang, Shengjun; Halim, Adnan

2015-01-01

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

How to diagnose and treat focal therapy failure and recurrence?

Science.gov (United States)

Barret, Eric; Harvey-Bryan, Kadi-Ann; Sanchez-Salas, Rafael; Rozet, Francois; Galiano, Marc; Cathelineau, Xavier

2014-05-01

Focal therapy presents an alternative option for disease-targeted therapy while preserving erectile and urinary function without compromising oncological outcome. Such treatment, which preserves normal prostate parenchyma, presents a clinical challenge to the urologist, as typical disease surveillance parameters are not as reliable in post-ablation follow-up. We propose an integrated approach to post-ablation surveillance to identify treatment failure as well as recurrence. Post-ablation prostate-specific antigen kinetics, imaging based on multiparametric MRI and control biopsies are the tools currently used to follow patients after focal therapy. Good treatment response is indicated by a negative control biopsy, absence of persistent lesion on post-treatment imaging and a reduction in prostate-specific antigen of at least 50%. When histological evidence of therapeutic failure or recurrence is present, different options of management may be proposed to the patient including active surveillance, focal salvage therapy or radical salvage treatment, depending on the characteristics of the lesion found. A recommended post-ablation surveillance protocol is presented as well as a discussion of management strategies based on the data currently available.

Bioinformatics Analysis of Envelope Glycoprotein E epitopes of ...

African Journals Online (AJOL)

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

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

Science.gov (United States)

Estelrich, J.; Pouplana, R.

1988-01-01

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

Systems considerations in mosaic focal planes

Science.gov (United States)

White, K. P., III

1983-08-01

Two key reasons for pursuing the development of mosaic focal planes are reviewed and it is shown that rapid frame repetition rate is the only requirement that can be solved no other way than through mosaic focal planes. With the view that spaceborne mosaic focal plane sensors are necessarily 'smart sensors' requiring a lot of onboard processing just to function, it is pointed out that various artificial intelligence techniques may be the most appropriate to incorporate in the data processing. Finally, a novel mosaic focal plane design is proposed, termed a virtual mosaic focal plane, in response to other system constraints.

Classification of Focal and Non Focal Epileptic Seizures Using Multi-Features and SVM Classifier.

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Sriraam, N; Raghu, S

2017-09-02

Identifying epileptogenic zones prior to surgery is an essential and crucial step in treating patients having pharmacoresistant focal epilepsy. Electroencephalogram (EEG) is a significant measurement benchmark to assess patients suffering from epilepsy. This paper investigates the application of multi-features derived from different domains to recognize the focal and non focal epileptic seizures obtained from pharmacoresistant focal epilepsy patients from Bern Barcelona database. From the dataset, five different classification tasks were formed. Total 26 features were extracted from focal and non focal EEG. Significant features were selected using Wilcoxon rank sum test by setting p-value (p z > 1.96) at 95% significance interval. Hypothesis was made that the effect of removing outliers improves the classification accuracy. Turkey's range test was adopted for pruning outliers from feature set. Finally, 21 features were classified using optimized support vector machine (SVM) classifier with 10-fold cross validation. Bayesian optimization technique was adopted to minimize the cross-validation loss. From the simulation results, it was inferred that the highest sensitivity, specificity, and classification accuracy of 94.56%, 89.74%, and 92.15% achieved respectively and found to be better than the state-of-the-art approaches. Further, it was observed that the classification accuracy improved from 80.2% with outliers to 92.15% without outliers. The classifier performance metrics ensures the suitability of the proposed multi-features with optimized SVM classifier. It can be concluded that the proposed approach can be applied for recognition of focal EEG signals to localize epileptogenic zones.

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

Science.gov (United States)

Thakur, I S

1991-03-01

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

Comparison of different approaches to the numerical calculation of the LMJ focal

Directory of Open Access Journals (Sweden)

Bourgeade A.

2013-11-01

Full Text Available The beam smoothing in the focal plane of high power lasers is of particular importance to laser-plasma interaction studies in order to minimize plasma parametric and hydrodynamic instabilities on the target. Here we investigate the focal spot structure in different geometrical configurations where standard paraxial hypotheses are no longer verified. We present numerical studies in the cases of single flat top square beam, LMJ quadruplet and complete ring of quads with large azimuth angle. Different calculations are made with Fresnel diffraction propagation model in the paraxial approximation and full vector Maxwell's equations. The first model is based on Fourier transform from near to far field method. The second model uses first spherical wave decomposition in plane waves with Fourier transform and propagates them to the focal spot. These two different approaches are compared with Miró [1] modeling results using paraxial or Feit and Fleck options. The methods presented here are generic for focal spot calculations. They can be used for other complex geometric configurations and various smoothing techniques. The results will be used as boundary conditions in plasma interaction computations.

Comparison of Long-Term Clinical Outcomes of Lesions Exhibiting Focal and Segmental Peri-Stent Contrast Staining.

Science.gov (United States)

Tokuda, Takahiro; Yamawaki, Masahiro; Takahara, Mitsuyohi; Mori, Shinsuke; Makino, Kenji; Honda, Yosuke; Takafuji, Hiroya; Takama, Takuro; Tsutsumi, Masakazu; Sakamoto, Yasunari; Takimura, Hideyuki; Kobayashi, Norihiro; Araki, Motoharu; Hirano, Keisuke; Ito, Yoshiaki

2016-03-18

Peri-stent contrast staining (PSS) after metallic drug-eluting stent deployment is associated with target lesion revascularization and very late stent thrombosis. However, the type of PSS that influences the clinical outcomes is unknown. Therefore, we aimed to reveal which PSS type was influencing clinical outcomes. This study included 5580 de novo lesions of 4405 patients who were implanted with a first- or second-generation drug-eluting stent and who were evaluated using follow-up angiography within 12 months after stent implantation. We compared the clinical outcomes of patients divided into focal PSS and segmental PSS groups for 6 years after stent implantation. Total PSS was observed in 97 lesions (2.2%), of which 42 and 55 lesions were focal and segmental PSS, respectively. Baseline characteristics were similar between groups, except for intraoperative chronic total occlusion (segmental PSS=47.3% versus focal PSS=11.9%, P=0.0001). The incidence of segmental PSS tended to be higher in patients with a first-generation drug-eluting stent (83.6% versus 16.4%, P=0.05). The cumulative incidence of stent thrombosis in the 6 years of segmental PSS group was significantly higher than that of the focal PSS group (13.9% versus 0%, P=0.04). The cumulative incidence of overall target lesion revascularization for restenosis, excluding target lesion revascularization procedures for stent thrombosis, was significantly higher in the segmental PSS group (38.0% versus 0%, P=0.01). The incidence of segmental PSS tended to be higher in patients with a first-generation drug-eluting stent and appeared to be significantly associated with target lesion revascularization and stent thrombosis. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Characterisation of the carbohydrate components of Taenia solium metacestode glycoprotein antigens.

Science.gov (United States)

Restrepo, B I; Obregón-Henao, A; Mesa, M; Gil, D L; Ortiz, B L; Mejía, J S; Villota, G E; Sanzón, F; Teale, J M

2000-05-01

Human neurocysticercosis is caused by Taenia solium metacestodes. It usually affects the central nervous system of humans and can be confused with other brain pathologies. The Lens culinaris-binding glycoproteins from this parasite have been shown to be ideal targets for the development of a highly specific immunoassay for the diagnosis of neurocysticercosis. In the present study we characterised the carbohydrates associated with five antigenic glycoproteins of T. solium metacestodes in the range of 12-28 kilodaltons. Lectin-affinities and enzymatic deglycosylations suggested that each of the five antigens contain various glycoforms of asparagine-linked carbohydrates of the hybrid, complex and probably high mannose type. These carbohydrates accounted for at least 30-66% of the apparent molecular mass of the glycoconjugates. In contrast, there was no evidence for the presence of O-linked carbohydrates. Lectin affinity patterns suggested that the sugars are short and truncated in their biosynthetic route, and that some contain terminal galactose moieties. Elucidating the precise structure of the carbohydrates and establishing their role in antigenicity will be essential to design strategies to produce them in large and reproducible amounts for the development of improved immunoassays.

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

Science.gov (United States)

Thakur, I S

1991-02-01

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

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

Science.gov (United States)

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

2008-01-01

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

Glycoprotein-Specific Antibodies Produced by DNA Vaccination Protect Guinea Pigs from Lethal Argentine and Venezuelan Hemorrhagic Fever.

Science.gov (United States)

Golden, Joseph W; Maes, Piet; Kwilas, Steven A; Ballantyne, John; Hooper, Jay W

2016-01-20

Several members of the Arenaviridae can cause acute febrile diseases in humans, often resulting in lethality. The use of convalescent-phase human plasma is an effective treatment in humans infected with arenaviruses, particularly species found in South America. Despite this, little work has focused on developing potent and defined immunotherapeutics against arenaviruses. In the present study, we produced arenavirus neutralizing antibodies by DNA vaccination of rabbits with plasmids encoding the full-length glycoprotein precursors of Junín virus (JUNV), Machupo virus (MACV), and Guanarito virus (GTOV). Geometric mean neutralizing antibody titers, as measured by the 50% plaque reduction neutralization test (PRNT(50)), exceeded 5,000 against homologous viruses. Antisera against each targeted virus exhibited limited cross-species binding and, to a lesser extent, cross-neutralization. Anti-JUNV glycoprotein rabbit antiserum protected Hartley guinea pigs from lethal intraperitoneal infection with JUNV strain Romero when the antiserum was administered 2 days after challenge and provided some protection (∼30%) when administered 4 days after challenge. Treatment starting on day 6 did not protect animals. We further formulated an IgG antibody cocktail by combining anti-JUNV, -MACV, and -GTOV antibodies produced in DNA-vaccinated rabbits. This cocktail protected 100% of guinea pigs against JUNV and GTOV lethal disease. We then expanded on this cocktail approach by simultaneously vaccinating rabbits with a combination of plasmids encoding glycoproteins from JUNV, MACV, GTOV, and Sabia virus (SABV). Sera collected from rabbits vaccinated with the combination vaccine neutralized all four targets. These findings support the concept of using a DNA vaccine approach to generate a potent pan-arenavirus immunotherapeutic. Arenaviruses are an important family of emerging viruses. In infected humans, convalescent-phase plasma containing neutralizing antibodies can mitigate the

Mechanism of feline immunodeficiency virus envelope glycoprotein-mediated fusion

International Nuclear Information System (INIS)

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

2004-01-01

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

'Focal thyroid inferno' on color Doppler ultrasonography: A specific feature of focal Hashimoto's thyroiditis

Energy Technology Data Exchange (ETDEWEB)

Fu, Xianshui, E-mail: fuxs1968@163.com [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Guo, Limei, E-mail: guolimei@bjmu.edu.cn [Department of Pathology, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Zhang, Huabin, E-mail: huabinzhang@bjmu.edu.cn [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Ran, Weiqiang, E-mail: ranwq-sina@vip.sina.com [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Fu, Peng, E-mail: fupeng01@gmail.com [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Li, Zhiqiang, E-mail: lizhq126@126.com [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Chen, Wen, E-mail: wendy7989@sina.com [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Jiang, Ling, E-mail: papayaling@yahoo.com.cn [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Wang, Jinrui, E-mail: jinrui_wang@sina.com [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China); Jia, Jianwen, E-mail: drjia88@sohu.com [Department of Ultrasound, Peking University Third Hospital, 49 Huayuanbeilu Road, Beijing 100191 (China)

2012-11-15

Purpose: To evaluate color-Doppler features predictive of focal Hashimoto's thyroiditis. Materials and methods: A total of 521 patients with 561 thyroid nodules that underwent surgeries or gun biopsies were included in this study. These nodules were divided into three groups: focal Hashimoto's thyroiditis (104 nodules in 101 patients), benignity other than focal Hashimoto's thyroiditis (73 nodules in 70 patients), and malignancy (358 nodules in 350 patients). On color Doppler sonography, four vascularity types were determined as: hypovascularity, marked internal flow, marked peripheral flow and focal thyroid inferno. The {chi}{sup 2} test was performed to seek the potential vascularity type with the predictive ability of certain thyroid pathology. Furthermore, the gray-scale features of each nodule were also studied. Results: The vascularity type I (hypovascularity) was more often seen in focal Hashimoto's thyroiditis than other benignity and malignancy (46% vs. 20.5% and 19%). While the type II (marked internal flow) showed the opposite tendency (26.9% [focal Hashimoto's thyroiditis] vs. 45.2% [other benignity] and 52.8% [malignancy]). However, type III (marked peripheral flow) was unable to predict any thyroid pathology. Importantly, type IV (focal thyroid inferno) was exclusive to focal Hashimoto's thyroiditis. All 8 type IV nodules appeared to be solid, hypoechoic, and well-defined. Using 'focal thyroid inferno' as an indicator of FHT, the diagnostic sensitivity and specificity were 7.7% and 100% respectively. Conclusions: The vascularity type of 'focal thyroid inferno' is specific for focal Hashimoto thyroiditis. Recognition of this particular feature may avoid unnecessary interventional procedures for some solid hypoechoic thyroid nodules suspicious of malignancy.

Focal dermal hypoplasia without focal dermal hypoplasia

NARCIS (Netherlands)

Contreras-Capetillo, Silvina N.; Lombardi, Maria Paola; Pinto-Escalante, Doris; Hennekam, Raoul C.

2014-01-01

Focal dermal hypoplasia (FDH; Goltz-Gorlin syndrome) is an X-linked dominant disorder affecting mainly tissues of ectodermal and mesodermal origin. The phenotype is characterized by hypoplastic linear skin lesions, eye malformations, hair and teeth anomalies, and multiple limbs malformations. The

Product Seeding: Word-of-Mouth Effects For and Beyond the Focal Product

Directory of Open Access Journals (Sweden)

Bart Yakov

2017-11-01

Full Text Available In a classic seeded WOM marketing campaign, a company sends product samples to a selected group of influencers, and encourages them share the product information and their own opinions with other consumers. Positive effects include more WOM for the focal product in the target segment, but also in additional segments. But there are additional spillover effects on the brand and the product category level and they are negative. More conversations about the focal product reduced the “off-topic” conversations about other brands in the same category as well as other products of the same brand. These negative brand and category spillover effects are stronger when the focal product is of a more functional nature. Marketers tend to consider only positive spillovers to be beneficial for a company, but negative spillovers should not be immediately classified as “bad news.” There are upsides to this effect that managers can use in their favor.

Labelled antibody techniques in glycoprotein estimation

International Nuclear Information System (INIS)

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

1977-01-01

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

Enhanced Gene Transfer with Fusogenic Liposomes Containing Vesicular Stomatitis Virus G Glycoprotein

Science.gov (United States)

Abe, Akihiro; Miyanohara, Atsushi; Friedmann, Theodore

1998-01-01

Exposure of Lipofectin-DNA complexes to the partially purified G glycoprotein of the vesicular stomatitis virus envelope (VSV-G) results in loss of serum-mediated inhibition and in enhanced efficiency of gene transfer. Sucrose density gradient sedimentation analysis indicated that the VSV-G associates physically with the DNA-lipid complex to produce a VSV-G liposome. The ability to incorporate surrogate viral or cellular envelope components such as VSV-G into liposomes may allow more-efficient and possibly targeted gene delivery by lipofection, both in vitro and in vivo. PMID:9621082

Dual focal-spot imaging for phase extraction in phase-contrast radiography

International Nuclear Information System (INIS)

Donnelly, Edwin F.; Price, Ronald R.; Pickens, David R.

2003-01-01

The purpose of this study was to evaluate dual focal spot imaging as a method for extracting the phase component from a phase-contrast radiography image. All measurements were performed using a microfocus tungsten-target x-ray tube with an adjustable focal-spot size (0.01 mm to 0.045 mm). For each object, high-resolution digital radiographs were obtained with two different focal spot sizes to produce matched image pairs in which all other geometric variables as well as total exposure and tube kVp were held constant. For each image pair, a phase extraction was performed using pixel-wise division. The phase-extracted image resulted in an image similar to the standard image processing tool commonly referred to as 'unsharp masking' but with the additional edge-enhancement produced by phase-contrast effects. The phase-extracted image illustrates the differences between the two images whose imaging parameters differ only in focal spot size. The resulting image shows effects from both phase contrast as well as geometric unsharpness. In weakly attenuating materials the phase-contrast effect predominates, while in strongly attenuating materials the phase effects are so small that they are not detectable. The phase-extracted image in the strongly attenuating object reflects differences in geometric unsharpness. The degree of phase extraction depends strongly on the size of the smallest focal spot used. This technique of dual-focal spot phase-contrast radiography provides a simple technique for phase-component (edge) extraction in phase-contrast radiography. In strongly attenuating materials the phase-component is overwhelmed by differences in geometric unsharpness. In these cases the technique provides a form of unsharp masking which also accentuates the edges. Thus, the two effects are complimentary and may be useful in the detection of small objects

MRI-guided prostate focal laser ablation therapy using a mechatronic needle guidance system

Science.gov (United States)

Cepek, Jeremy; Lindner, Uri; Ghai, Sangeet; Davidson, Sean R. H.; Trachtenberg, John; Fenster, Aaron

2014-03-01

Focal therapy of localized prostate cancer is receiving increased attention due to its potential for providing effective cancer control in select patients with minimal treatment-related side effects. Magnetic resonance imaging (MRI)-guided focal laser ablation (FLA) therapy is an attractive modality for such an approach. In FLA therapy, accurate placement of laser fibers is critical to ensuring that the full target volume is ablated. In practice, error in needle placement is invariably present due to pre- to intra-procedure image registration error, needle deflection, prostate motion, and variability in interventionalist skill. In addition, some of these sources of error are difficult to control, since the available workspace and patient positions are restricted within a clinical MRI bore. In an attempt to take full advantage of the utility of intraprocedure MRI, while minimizing error in needle placement, we developed an MRI-compatible mechatronic system for guiding needles to the prostate for FLA therapy. The system has been used to place interstitial catheters for MRI-guided FLA therapy in eight subjects in an ongoing Phase I/II clinical trial. Data from these cases has provided quantification of the level of uncertainty in needle placement error. To relate needle placement error to clinical outcome, we developed a model for predicting the probability of achieving complete focal target ablation for a family of parameterized treatment plans. Results from this work have enabled the specification of evidence-based selection criteria for the maximum target size that can be confidently ablated using this technique, and quantify the benefit that may be gained with improvements in needle placement accuracy.

Influence of the focal point position on the properties of a laser-produced plasma

International Nuclear Information System (INIS)

Kasperczuk, A.; Pisarczyk, T.; Badziak, J.; Miklaszewski, R.; Parys, P.; Rosinski, M.; Wolowski, J.; Stenz, CH.; Ullschmied, J.; Krousky, E.; Masek, K.; Pfeifer, M.; Rohlena, K.; Skala, J.; Pisarczyk, P.

2007-01-01

This paper deals with investigations of the influence of the focusing lens focal point position on the properties of a plasma produced by a defocused laser beam. The experiment was carried out at the Prague Asterix Laser System iodine laser [K. Jungwirth, A. Cejnarova, L. Juha, B. Kralikova, J. Krasa, E. Krousky, P. Krupickova, L. Laska, K. Masek, T. Mocek, M. Pfeifer, A. Prag, O. Renner, K. Rohlena, B. Rus, J. Skala, P. Straka, and J. Ullschmied, Phys. Plasmas 8, 2495 (2001)] by using the third harmonic of laser radiation (λ=0.438 μm), laser energy of 70 J, pulse duration of 250 ps (full width at half-maximum), and beam spot radii of 250 and 400 μm. Cu and Ta were chosen as target materials. The experimental data were obtained by means of a three-frame interferometric system, ion collectors, and crater replica techniques. The reported results allow formulating an important hypothesis that the laser-produced plasma modifies strongly the laser intensity distribution. It is shown how such a modification depends on the relative position and distance of the focal point to the target surface. Of particular importance is whether the focal point is located inside or in front of the target. The irradiation geometry is crucial for the possibility of generating plasma jets by laser radiation. Well-formed jet-like plasma structures can be created if an initially homogeneous laser intensity distribution is transformed in the plasma to an annular one

FAK dimerization controls its kinase-dependent functions at focal adhesions

KAUST Repository

Brami-Cherrier, Karen; Gervasi, Nicolas; Arsenieva, Diana A.; Walkiewicz, Katarzyna; Boutterin, Marie Claude; Ortega, Á lvaro Darí o; Leonard, Paul G.; Seantier, Bastien; Gasmi, Laï la; Bouceba, Tahar; Kadaré , Gress; Girault -, Jean Antoine; Arold, Stefan T.

2014-01-01

Focal adhesion kinase (FAK) controls adhesion-dependent cell motility, survival, and proliferation. FAK has kinase-dependent and kinase-independent functions, both of which play major roles in embryogenesis and tumor invasiveness. The precise mechanisms of FAK activation are not known. Using x-ray crystallography, small angle x-ray scattering, and biochemical and functional analyses, we show that the key step for activation of FAK's kinase-dependent functions-autophosphorylation of tyrosine-397-requires site-specific dimerization of FAK. The dimers form via the association of the N-terminal FERM domain of FAK and are stabilized by an interaction between FERM and the C-terminal FAT domain. FAT binds to a basic motif on FERM that regulates co-activation and nuclear localization. FAK dimerization requires local enrichment, which occurs specifically at focal adhesions. Paxillin plays a dual role, by recruiting FAK to focal adhesions and by reinforcing the FAT:FERM interaction. Our results provide a structural and mechanistic framework to explain how FAK combines multiple stimuli into a site-specific function. The dimer interfaces we describe are promising targets for blocking FAK activation. © 2014 The Authors.

FAK dimerization controls its kinase-dependent functions at focal adhesions

KAUST Repository

Brami-Cherrier, Karen

2014-01-30

Focal adhesion kinase (FAK) controls adhesion-dependent cell motility, survival, and proliferation. FAK has kinase-dependent and kinase-independent functions, both of which play major roles in embryogenesis and tumor invasiveness. The precise mechanisms of FAK activation are not known. Using x-ray crystallography, small angle x-ray scattering, and biochemical and functional analyses, we show that the key step for activation of FAK\\'s kinase-dependent functions-autophosphorylation of tyrosine-397-requires site-specific dimerization of FAK. The dimers form via the association of the N-terminal FERM domain of FAK and are stabilized by an interaction between FERM and the C-terminal FAT domain. FAT binds to a basic motif on FERM that regulates co-activation and nuclear localization. FAK dimerization requires local enrichment, which occurs specifically at focal adhesions. Paxillin plays a dual role, by recruiting FAK to focal adhesions and by reinforcing the FAT:FERM interaction. Our results provide a structural and mechanistic framework to explain how FAK combines multiple stimuli into a site-specific function. The dimer interfaces we describe are promising targets for blocking FAK activation. © 2014 The Authors.

WE-E-BRE-04: Dual Focal Spot Dose Painting for Precision Preclinical Radiobiological Investigations

Energy Technology Data Exchange (ETDEWEB)

Stewart, J; Lindsay, P [Princess Margaret Cancer Centre, Toronto (Canada); University of Toronto, Toronto (Canada); Jaffray, D [Princess Margaret Cancer Centre, Toronto (Canada); The Techna Institute for the Advancement of Technology for Health, Toronto (Canada)

2014-06-15

Purpose: Recent progress in small animal radiotherapy systems has provided the foundation for delivering the heterogeneous, millimeter scale dose distributions demanded by preclinical radiobiology investigations. Despite advances in preclinical dose planning, delivery of highly heterogeneous dose distributions is constrained by the fixed collimation systems and large x-ray focal spot common in small animal radiotherapy systems. This work proposes a dual focal spot dose optimization and delivery method with a large x-ray focal spot used to deliver homogeneous dose regions and a small focal spot to paint spatially heterogeneous dose regions. Methods: Two-dimensional dose kernels were measured for a 1 mm circular collimator with radiochromic film at 10 mm depth in a solid water phantom for the small and large x-ray focal spots on a recently developed small animal microirradiator. These kernels were used in an optimization framework which segmented a desired dose distribution into low- and high-spatial frequency regions for delivery by the large and small focal spot, respectively. For each region, the method determined an optimal set of stage positions and beam-on times. The method was demonstrated by optimizing a bullseye pattern consisting of 0.75 mm radius circular target and 0.5 and 1.0 mm wide rings alternating between 0 and 2 Gy. Results: Compared to a large focal spot technique, the dual focal spot technique improved the optimized dose distribution: 69.2% of the optimized dose was within 0.5 Gy of the intended dose for the large focal spot, compared to 80.6% for the dual focal spot method. The dual focal spot design required 14.0 minutes of optimization, and will require 178.3 minutes for automated delivery. Conclusion: The dual focal spot optimization and delivery framework is a novel option for delivering conformal and heterogeneous dose distributions at the preclinical level and provides a new experimental option for unique radiobiological investigations

WE-E-BRE-04: Dual Focal Spot Dose Painting for Precision Preclinical Radiobiological Investigations

International Nuclear Information System (INIS)

Stewart, J; Lindsay, P; Jaffray, D

2014-01-01

Purpose: Recent progress in small animal radiotherapy systems has provided the foundation for delivering the heterogeneous, millimeter scale dose distributions demanded by preclinical radiobiology investigations. Despite advances in preclinical dose planning, delivery of highly heterogeneous dose distributions is constrained by the fixed collimation systems and large x-ray focal spot common in small animal radiotherapy systems. This work proposes a dual focal spot dose optimization and delivery method with a large x-ray focal spot used to deliver homogeneous dose regions and a small focal spot to paint spatially heterogeneous dose regions. Methods: Two-dimensional dose kernels were measured for a 1 mm circular collimator with radiochromic film at 10 mm depth in a solid water phantom for the small and large x-ray focal spots on a recently developed small animal microirradiator. These kernels were used in an optimization framework which segmented a desired dose distribution into low- and high-spatial frequency regions for delivery by the large and small focal spot, respectively. For each region, the method determined an optimal set of stage positions and beam-on times. The method was demonstrated by optimizing a bullseye pattern consisting of 0.75 mm radius circular target and 0.5 and 1.0 mm wide rings alternating between 0 and 2 Gy. Results: Compared to a large focal spot technique, the dual focal spot technique improved the optimized dose distribution: 69.2% of the optimized dose was within 0.5 Gy of the intended dose for the large focal spot, compared to 80.6% for the dual focal spot method. The dual focal spot design required 14.0 minutes of optimization, and will require 178.3 minutes for automated delivery. Conclusion: The dual focal spot optimization and delivery framework is a novel option for delivering conformal and heterogeneous dose distributions at the preclinical level and provides a new experimental option for unique radiobiological investigations

Neuraminidase treatment of respiratory syncytial virus-infected cells or virions, but not target cells, enhances cell-cell fusion and infection

International Nuclear Information System (INIS)

Barretto, Naina; Hallak, Louay K.; Peeples, Mark E.

2003-01-01

Respiratory syncytial virus (RSV) infection of HeLa cells induces fusion, but transient expression of the three viral glycoproteins induces fusion poorly, if at all. We found that neuraminidase treatment of RSV-infected cells to remove sialic acid (SA) increases fusion dramatically and that the same treatment of transiently transfected cells expressing the three viral glycoproteins, or even cells expressing the fusion (F) protein alone, results in easily detectable fusion. Neuraminidase treatment of the effector cells, expressing the viral glycoproteins, enhanced fusion while treatment of the target cells did not. Likewise, infectivity was increased by treating virions with neuraminidase, but not by treating target cells. Reduction of charge repulsion by removal of the negatively charged SA is unlikely to explain this effect, since removal of negative charges from either membrane would reduce charge repulsion. Infection with neuraminidase-treated virus remained heparan-sulfate-dependent, indicating that a novel attachment mechanism is not revealed by SA removal. Interestingly, neuraminidase enhancement of RSV infectivity was less pronounced in a virus expressing both the G and the F glycoproteins, compared to virus expressing only the F glycoprotein, possibly suggesting that the G protein sterically hinders access of the neuraminidase to its fusion-enhancing target

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

Science.gov (United States)

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

2015-02-01

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

Next generation sub-millimeter wave focal plane array coupling concepts: an ESA TRP project to develop multichroic focal plane pixels for future CMB polarization experiments

Science.gov (United States)

Trappe, N.; Bucher, M.; De Bernardis, P.; Delabrouille, J.; Deo, P.; DePetris, M.; Doherty, S.; Ghribi, A.; Gradziel, M.; Kuzmin, L.; Maffei, B.; Mahashabde, S.; Masi, S.; Murphy, J. A.; Noviello, F.; O'Sullivan, C.; Pagano, L.; Piacentini, F.; Piat, M.; Pisano, G.; Robinson, M.; Stompor, R.; Tartari, A.; van der Vorst, M.; Verhoeve, P.

2016-07-01

The main objective of this activity is to develop new focal plane coupling array concepts and technologies that optimise the coupling from reflector optics to the large number of detectors for next generation sub millimetre wave telescopes particularly targeting measurement of the polarization of the cosmic microwave background (CMB). In this 18 month TRP programme the consortium are tasked with developing, manufacturing and experimentally verifying a prototype multichroic pixel which would be suitable for the large focal plane arrays which will be demanded to reach the required sensitivity of future CMB polarization missions. One major development was to have multichroic operation to potentially reduce the required focal plane size of a CMB mission. After research in the optimum telescope design and definition of requirements based on a stringent science case review, a number of compact focal plane architecture concepts were investigated before a pixel demonstrator consisting of a planar mesh lens feeding a backend Resonant Cold Electron Bolometer RCEB for filtering and detection of the dual frequency signal was planned for manufacture and test. In this demonstrator the frequencies of the channels was chosen to be 75 and 105 GHz in the w band close to the peak CMB signal. In the next year the prototype breadboards will be developed to test the beams produced by the manufactured flat lenses fed by a variety of antenna configurations and the spectral response of the RCEBs will also be verified.

Focal adhesion kinase a potential therapeutic target for pancreatic cancer and malignant pleural mesothelioma.

Science.gov (United States)

Kanteti, Rajani; Mirzapoiazova, Tamara; Riehm, Jacob J; Dhanasingh, Immanuel; Mambetsariev, Bolot; Wang, Jiale; Kulkarni, Prakash; Kaushik, Garima; Seshacharyulu, Parthasarathy; Ponnusamy, Moorthy P; Kindler, Hedy L; Nasser, Mohd W; Batra, Surinder K; Salgia, Ravi

2018-04-03

The non-receptor cytoplasmic tyrosine kinase, Focal Adhesion Kinase (FAK) is known to play a key role in a variety of normal and cancer cellular functions such as survival, proliferation, migration and invasion. It is highly active and overexpressed in various cancers including Pancreatic Ductal Adenocarcinoma (PDAC) and Malignant Pleural Mesothelioma (MPM). Here, initially, we demonstrate that FAK is overexpressed in both PDAC and MPM cell lines. Then we analyze effects of two small molecule inhibitors PF-573228, and PF-431396, which are dual specificity inhibitors of FAK and proline rich tyrosine kinase 2 (PYK2), as well as VS-6063, another small molecule inhibitor that specifically inhibits FAK but not PYK2 for cell growth, motility and invasion of PDAC and MPM cell lines. Treatment with PF-573228, PF-431396 and VS-6063 cells resulted in a dose-dependent inhibition of growth and anchorage-independent colony formation in both cancer cell lines. Furthermore, these compounds suppressed the phosphorylation of FAK at its active site, Y397, and functionally induced significant apoptosis and cell cycle arrest in both cell lines. Using the ECIS (Electric cell-substrate impedance sensing) system, we found that treatment of both PF compounds suppressed adherence and migration of PDAC cells on fibronectin. Interestingly, 3D-tumor organoids derived from autochthonous KC (Kras;PdxCre) mice treated with PF-573228 revealed a significant decrease in tumor organoid size and increase in organoid cell death. Taken together, our results show that FAK is an important target for mesothelioma and pancreatic cancer therapy that merit further translational studies.

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

International Nuclear Information System (INIS)

Ahn, Hae-Young.

1988-01-01

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

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

NARCIS (Netherlands)

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

1993-01-01

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

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.

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

International Nuclear Information System (INIS)

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

2007-01-01

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

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.

N-glycan maturation mutants in Lotus japonicus for basic and applied glycoprotein research

DEFF Research Database (Denmark)

Pedersen, Carina T.; Loke, Ian; Lorentzen, Andrea

2017-01-01

Studies of protein N-glycosylation are important for answering fundamental questions on the diverse functions of glycoproteins in plant growth and development. Here we generated and characterised a comprehensive collection of Lotus japonicusLORE1 insertion mutants, each lacking the activity of one...... in the target glyco-genes. For example, both mass spectrometry and immunoblotting experiments suggest that proteins derived from the α1,3-fucosyltransferase (Lj3fuct) mutant completely lacked α1,3-core fucosylation. Mass spectrometry also suggested that the Lotus japonicus convicilin 2 was one of the main...

Glycoprotein of the wall of sycamore tissue-culture cells.

Science.gov (United States)

Heath, M F; Northcote, D H

1971-12-01

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

Focal midbrain tumors in children

NARCIS (Netherlands)

Vandertop, W. P.; Hoffman, H. J.; Drake, J. M.; Humphreys, R. P.; Rutka, J. T.; Amstrong, D. C.; Becker, L. E.

1992-01-01

The clinical and neuroradiological features of focal midbrain tumors in 12 children are described, and the results of their surgical management are presented. Patients with a focal midbrain tumor usually exhibit either symptoms and signs of raised intracranial pressure caused by an obstructive

Diagnostic imaging in focal epilepsy

International Nuclear Information System (INIS)

Zlatareva, D.

2013-01-01

Focal epilepsies account for 60% of all seizure disorders worldwide. In this review the classic and new classification system of epileptic seizures and syndromes as well as genetic forms are discussed. Magnetic resonance (MR) is the technique of choice for diagnostic imaging in focal epilepsy because of its sensitivity and high tissue contrast. The review is focused on the lack of consensus of imaging protocols and reported findings in refractory epilepsy. The most frequently encountered MRI findings in epilepsy are reported and their imaging characteristics are depicted. Diagnosis of hippocampal sclerosis and malformations of cortical development as two major causes of refractory focal epilepsy is described in details. Some promising new techniques as positron emission tomography computed tomography (PET/CT) and MR and PET/CT fusion are briefly discussed. Also the relevance of adequate imaging in focal epilepsy, some practical points in imaging interpretation and differential diagnosis are highlighted. (author)

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

Directory of Open Access Journals (Sweden)

Zong-Xiu Wang

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

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

Directory of Open Access Journals (Sweden)

Rafael Simó

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

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

Science.gov (United States)

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

2014-01-01

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

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

Directory of Open Access Journals (Sweden)

Hiroshi Fujise

2004-01-01

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

Third-generation intelligent IR focal plane arrays

Science.gov (United States)

Caulfield, H. John; Jack, Michael D.; Pettijohn, Kevin L.; Schlesselmann, John D.; Norworth, Joe

1998-03-01

SBRC is at the forefront of industry in developing IR focal plane arrays including multi-spectral technology and '3rd generation' functions that mimic the human eye. 3rd generation devices conduct advanced processing on or near the FPA that serve to reduce bandwidth while performing needed functions such as automatic target recognition, uniformity correction and dynamic range enhancement. These devices represent a solution for processing the exorbitantly high bandwidth coming off large area FPAs without sacrificing systems sensitivity. SBRC's two-color approach leverages the company's HgCdTe technology to provide simultaneous multiband coverage, from short through long wave IR, with near theoretical performance. IR systems that are sensitive to different spectral bands achieve enhanced capabilities for target identification and advanced discrimination. This paper will provide a summary of the issues, the technology and the benefits of SBRC's third generation smart and two-color FPAs.

RTG diagnostics of dental focal infection

International Nuclear Information System (INIS)

Petrasova, A.; Ondrasovicova, J.; Cecctkova, A.

2008-01-01

The theory of focal infection has always been and still is a controversial issue for many dentists and scientists. Even though the focal infection does not occupy the first place in modern medicine, its understanding is imperative. The authors summarized the knowledge about dental focal infection and its relationship to systemic the diseases of the whole body in their publication and they also focused on the radiodiagnostics of this disease. (authors)

On the relationships between electron spot size, focal spot size, and virtual source position in Monte Carlo simulations

International Nuclear Information System (INIS)

Sterpin, E.; Chen, Y.; Lu, W.; Mackie, T. R.; Olivera, G. H.; Vynckier, S.

2011-01-01

Purpose: Every year, new radiotherapy techniques including stereotactic radiosurgery using linear accelerators give rise to new applications of Monte Carlo (MC) modeling. Accurate modeling requires knowing the size of the electron spot, one of the few parameters to tune in MC models. The resolution of integrated megavoltage imaging systems, such as the tomotherapy system, strongly depends on the photon spot size which is closely related to the electron spot. The aim of this article is to clarify the relationship between the electron spot size and the photon spot size (i.e., the focal spot size) for typical incident electron beam energies and target thicknesses. Methods: Three electron energies (3, 5.5, and 18 MeV), four electron spot sizes (FWHM=0, 0.5, 1, and 1.5 mm), and two tungsten target thicknesses (0.15 and 1 cm) were considered. The formation of the photon beam within the target was analyzed through electron energy deposition with depth, as well as photon production at several phase-space planes placed perpendicular to the beam axis, where only photons recorded for the first time were accounted for. Photon production was considered for ''newborn'' photons intersecting a 45x45 cm 2 plane at the isocenter (85 cm from source). Finally, virtual source position and ''effective'' focal spot size were computed by backprojecting all the photons from the bottom of the target intersecting a 45x45 cm 2 plane. The virtual source position and focal spot size were estimated at the plane position where the latter is minimal. Results: In the relevant case of considering only photons intersecting the 45x45 cm 2 plane, the results unambiguously showed that the effective photon spot is created within the first 0.25 mm of the target and that electron and focal spots may be assumed to be equal within 3-4%. Conclusions: In a good approximation photon spot size equals electron spot size for high energy X-ray treatments delivered by linear accelerators.

Evaluation of focused ultrasound algorithms: Issues for reducing pre-focal heating and treatment time.

Science.gov (United States)

Yiannakou, Marinos; Trimikliniotis, Michael; Yiallouras, Christos; Damianou, Christakis

2016-02-01

Due to the heating in the pre-focal field the delay between successive movements in high intensity focused ultrasound (HIFU) are sometimes as long as 60s, resulting to treatment time in the order of 2-3h. Because there is generally a requirement to reduce treatment time, we were motivated to explore alternative transducer motion algorithms in order to reduce pre-focal heating and treatment time. A 1 MHz single element transducer with 4 cm diameter and 10 cm focal length was used. A simulation model was developed that estimates the temperature, thermal dose and lesion development in the pre-focal field. The simulated temperature history that was combined with the motion algorithms produced thermal maps in the pre-focal region. Polyacrylimde gel phantom was used to evaluate the induced pre-focal heating for each motion algorithm used, and also was used to assess the accuracy of the simulation model. Three out of the six algorithms having successive steps close to each other, exhibited severe heating in the pre-focal field. Minimal heating was produced with the algorithms having successive steps apart from each other (square, square spiral and random). The last three algorithms were improved further (with small cost in time), thus eliminating completely the pre-focal heating and reducing substantially the treatment time as compared to traditional algorithms. Out of the six algorithms, 3 were successful in eliminating the pre-focal heating completely. Because these 3 algorithms required no delay between successive movements (except in the last part of the motion), the treatment time was reduced by 93%. Therefore, it will be possible in the future, to achieve treatment time of focused ultrasound therapies shorter than 30 min. The rate of ablated volume achieved with one of the proposed algorithms was 71 cm(3)/h. The intention of this pilot study was to demonstrate that the navigation algorithms play the most important role in reducing pre-focal heating. By evaluating in

Design of an ignition target for the laser megajoule, mitigating parametric instabilities

Science.gov (United States)

Laffite, S.; Loiseau, P.

2010-10-01

Laser plasma interaction (LPI) is a critical issue in ignition target design. Based on both scaling laws and two-dimensional calculations, this article describes how we can constrain a laser megajoule (LMJ) [J. Ebrardt and J. M. Chaput, J. Phys.: Conf. Ser. 112, 032005 (2008)] target design by mitigating LPI. An ignition indirect drive target has been designed for the 2/3 LMJ step. It requires 0.9 MJ and 260 TW of laser energy and power, to achieve a temperature of 300 eV in a rugby-shaped Hohlraum and give a yield of about 20 MJ. The study focuses on the analysis of linear gain for stimulated Raman and Brillouin scatterings. Enlarging the focal spot is an obvious way to reduce linear gains. We show that this reduction is nonlinear with the focal spot size. For relatively small focal spot area, linear gains are significantly reduced by enlarging the focal spot. However, there is no benefit in too large focal spots because of necessary larger laser entrance holes, which require more laser energy. Furthermore, this leads to the existence, for a given design, of a minimum value for linear gains for which we cannot go below.

Design of an ignition target for the laser megajoule, mitigating parametric instabilities

International Nuclear Information System (INIS)

Laffite, S.; Loiseau, P.

2010-01-01

Laser plasma interaction (LPI) is a critical issue in ignition target design. Based on both scaling laws and two-dimensional calculations, this article describes how we can constrain a laser megajoule (LMJ) [J. Ebrardt and J. M. Chaput, J. Phys.: Conf. Ser. 112, 032005 (2008)] target design by mitigating LPI. An ignition indirect drive target has been designed for the 2/3 LMJ step. It requires 0.9 MJ and 260 TW of laser energy and power, to achieve a temperature of 300 eV in a rugby-shaped Hohlraum and give a yield of about 20 MJ. The study focuses on the analysis of linear gain for stimulated Raman and Brillouin scatterings. Enlarging the focal spot is an obvious way to reduce linear gains. We show that this reduction is nonlinear with the focal spot size. For relatively small focal spot area, linear gains are significantly reduced by enlarging the focal spot. However, there is no benefit in too large focal spots because of necessary larger laser entrance holes, which require more laser energy. Furthermore, this leads to the existence, for a given design, of a minimum value for linear gains for which we cannot go below.

Glycoprotein and proteoglycan techniques

International Nuclear Information System (INIS)

Beeley, J.G.

1985-01-01

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

HIV-1 envelope glycoprotein

Science.gov (United States)

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

2017-08-22

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

Materials, devices, techniques, and applications for Z-plane focal plane array technology; Proceedings of the Meeting, Orlando, FL, Mar. 29, 30, 1989

Science.gov (United States)

Carson, John C.

1989-09-01

The papers contained in this volume focus on the implementation and application of Z-plane focal array technology. Topics discussed include civil and military applications of Z-plane technology, electronic design and technology for on-scale plane signal processing, detector development and fabrication technology, and Z-plane module development and producibility. Papers are presented on future capabilities of Z-plane technology, comparison of planar and Z-plane focal plane technologies for dim target detection, Z-plane modules as target extraction engines, and high complexity tape automated bonding application for space hardware.

The Role of the MHV Receptor and Related Glycoproteins in Murine Hepatitis Virus Infection of Murine Cell Lines

Science.gov (United States)

1995-04-13

vaccinia virus-T7 RNA polymerase s y stem for e xpression of target genes . Mol . Cell . BioI . 7 : 2538-2544 . Gagneten , S ., Gout , 0 ., Dubois-Dalcq...glycoprotein. These results showed f or the first time that two murine CEA- related genes can be co-expressed in some cell lines from inbred mice...49 Southern Hybridization ................ . ............ 50 Subcloning of PCR Products and Gene Cloning ........ 51 Growth

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Synthetic glycopeptides and glycoproteins with applications in biological research

Directory of Open Access Journals (Sweden)

Ulrika Westerlind

2012-05-01

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

Targeting caspase-3 as dual therapeutic benefits by RNAi facilitating brain-targeted nanoparticles in a rat model of Parkinson's disease.

Science.gov (United States)

Liu, Yang; Guo, Yubo; An, Sai; Kuang, Yuyang; He, Xi; Ma, Haojun; Li, Jianfeng; Lu, Jing; Lv, Jing; Zhang, Ning; Jiang, Chen

2013-01-01

The activation of caspase-3 is an important hallmark in Parkinson's disease. It could induce neuron death by apoptosis and microglia activation by inflammation. As a result, inhibition the activation of caspase-3 would exert synergistic dual effect in brain in order to prevent the progress of Parkinson's disease. Silencing caspase-3 genes by RNA interference could inhibit the activation of caspase-3. We developed a brain-targeted gene delivery system based on non-viral gene vector, dendrigraft poly-L-lysines. A rabies virus glycoprotein peptide with 29 amino-acid linked to dendrigraft poly-L-lysines could render gene vectors the ability to get across the blood brain barrier by specific receptor mediated transcytosis. The resultant brain-targeted vector was complexed with caspase-3 short hairpin RNA coding plasmid DNA, yielding nanoparticles. In vivo imaging analysis indicated the targeted nanoparticles could accumulate in brain more efficiently than non-targeted ones. A multiple dosing regimen by weekly intravenous administration of the nanoparticles could reduce activated casapse-3 levels, significantly improve locomotor activity and rescue dopaminergic neuronal loss and in Parkinson's disease rats' brain. These results indicated the rabies virus glycoprotein peptide modified brain-targeted nanoparticles were promising gene delivery system for RNA interference to achieve anti-apoptotic and anti-inflammation synergistic therapeutic effects by down-regulation the expression and activation of caspase-3.

Targeting caspase-3 as dual therapeutic benefits by RNAi facilitating brain-targeted nanoparticles in a rat model of Parkinson's disease.

Directory of Open Access Journals (Sweden)

Yang Liu

Full Text Available The activation of caspase-3 is an important hallmark in Parkinson's disease. It could induce neuron death by apoptosis and microglia activation by inflammation. As a result, inhibition the activation of caspase-3 would exert synergistic dual effect in brain in order to prevent the progress of Parkinson's disease. Silencing caspase-3 genes by RNA interference could inhibit the activation of caspase-3. We developed a brain-targeted gene delivery system based on non-viral gene vector, dendrigraft poly-L-lysines. A rabies virus glycoprotein peptide with 29 amino-acid linked to dendrigraft poly-L-lysines could render gene vectors the ability to get across the blood brain barrier by specific receptor mediated transcytosis. The resultant brain-targeted vector was complexed with caspase-3 short hairpin RNA coding plasmid DNA, yielding nanoparticles. In vivo imaging analysis indicated the targeted nanoparticles could accumulate in brain more efficiently than non-targeted ones. A multiple dosing regimen by weekly intravenous administration of the nanoparticles could reduce activated casapse-3 levels, significantly improve locomotor activity and rescue dopaminergic neuronal loss and in Parkinson's disease rats' brain. These results indicated the rabies virus glycoprotein peptide modified brain-targeted nanoparticles were promising gene delivery system for RNA interference to achieve anti-apoptotic and anti-inflammation synergistic therapeutic effects by down-regulation the expression and activation of caspase-3.

The dispersion-focalization theory of sound systems

Science.gov (United States)

Schwartz, Jean-Luc; Abry, Christian; Boë, Louis-Jean; Vallée, Nathalie; Ménard, Lucie

2005-04-01

The Dispersion-Focalization Theory states that sound systems in human languages are shaped by two major perceptual constraints: dispersion driving auditory contrast towards maximal or sufficient values [B. Lindblom, J. Phonetics 18, 135-152 (1990)] and focalization driving auditory spectra towards patterns with close neighboring formants. Dispersion is computed from the sum of the inverse squared inter-spectra distances in the (F1, F2, F3, F4) space, using a non-linear process based on the 3.5 Bark critical distance to estimate F2'. Focalization is based on the idea that close neighboring formants produce vowel spectra with marked peaks, easier to process and memorize in the auditory system. Evidence for increased stability of focal vowels in short-term memory was provided in a discrimination experiment on adult French subjects [J. L. Schwartz and P. Escudier, Speech Comm. 8, 235-259 (1989)]. A reanalysis of infant discrimination data shows that focalization could well be the responsible for recurrent discrimination asymmetries [J. L. Schwartz et al., Speech Comm. (in press)]. Recent data about children vowel production indicate that focalization seems to be part of the perceptual templates driving speech development. The Dispersion-Focalization Theory produces valid predictions for both vowel and consonant systems, in relation with available databases of human languages inventories.

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

OpenAIRE

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

2016-01-01

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

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

Science.gov (United States)

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

2003-01-01

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

Seven tesla MRI improves detection of focal cortical dysplasia in patients with refractory focal epilepsy

NARCIS (Netherlands)

Veersema, Tim J; Ferrier, Cyrille H; van Eijsden, Pieter; Gosselaar, Peter H; Aronica, Eleonora; Visser, Fredy; Zwanenburg, Jaco M; de Kort, Gerard A P; Hendrikse, Jeroen; Luijten, Peter R; Braun, Kees P J

Objective: The aim of this study is to determine whether the use of 7 tesla (T) MRI in clinical practice leads to higher detection rates of focal cortical dysplasias in possible candidates for epilepsy surgery. Methods: In our center patients are referred for 7 T MRI if lesional focal epilepsy is

Novel target configurations for selective ionization state studies in molybdenum

International Nuclear Information System (INIS)

Ilcisin, K.J.; Feldman, U.; Schwob, J.L.; Wouters, A.; Suckewer, S.; Princeton Univ., NJ

1990-03-01

Details of experiments aimed at achieving low ionization state selectivity in molybdenum are presented. Targets are excited with a 10 J CO 2 laser and the resultant VUV spectrum (300--700 Angstrom) has been studied. Combinations of focal spot size, target depth, and target geometries are compared. Simple attenuation of energy is shown not to vary ionization stage composition significantly. Experiments conducted with grazing incidence targets result only in a hot plasma. Modular targets with cooling cylinders of various radii demonstrated good selectivity of the ionization states, but with low absolute signals. Finally, results from combinations of focal spot adjustment and radiative cooling illustrate increased control over desired plasma temperature and density for spectroscopic studies of molybdenum. 7 refs., 14 figs

Periodontitis in patients with focal tuberculosis

Directory of Open Access Journals (Sweden)

Alexandrova Е.А.

2010-12-01

Full Text Available The research goal is to investigate the mechanisms of formation and peculiarities of periodontitis in patients with focal tuberculosis. Patients with periodontitis and focal tuberculosis are proved to develop local inflammatory reaction with increased infection and activation of proinflammatory cytokines in parodontal pockets fluid. The main risk factor of frequent and durable recurrence of parodontal pathology in case of focal tuberculosis was the development of pathologic process as a cause of disbalance of lipid peroxidation and antioxidant system, endotoxicosis syndrome

Expansive focal cemento-osseous dysplasia.

Science.gov (United States)

Bulut, Emel Uzun; Acikgoz, Aydan; Ozan, Bora; Zengin, Ayse Zeynep; Gunhan, Omer

2012-01-01

To present a case of expansive focal cemento-osseous dysplasia and emphasize the importance of differential diagnosis. Cemento-osseous dysplasia is categorized into three subtypes on the basis of the clinical and radiographic features: Periapical, focal and florid. The focal type exhibits a single site of involvement in any tooth-bearing or edentulous area of the jaws. These lesions are usually asymptomatic; therefore, they are frequently diagnosed incidentally during routine radiographic examinations. Lesions are usually benign, show limited growth, and do not require further surgical intervention, but periodic follow-up is recommended because occasionally, this type of dysplasia progresses into florid osseous dysplasia and simple bone cysts are formed. A 24-year-old female patient was referred to our clinic for swelling in the left edentulous mandibular premolarmolar region and felt discomfort when she wore her prosthetics. She had no pain, tenderness or paresthesia. Clinical examination showed that the swelling in the posterior mandible that was firm, nonfluctuant and covered by normal mucosa. On panoramic radiography and computed tomography, a well defined lesion of approximately 1.5 cm in diameter of mixed density was observed. The swelling increased slightly in size over 2 years making it difficult to use prosthetics and, therefore, the lesion was totally excised under local anesthesia, and surgical specimens were submitted for histopathological examination. The histopathological diagnosis was focal cemento-osseous dysplasia. In the present case, because of the increasing size of the swelling making it difficult to use prosthetics, young age of the patient and localization of the lesion, in the initial examination, cemento-ossifying fibroma was suspected, and the lesion was excised surgically; the histopathological diagnosis confirmed it as focal cemento-osseous dysplasia. We present a case of expansive focal cemento-osseous dysplasia. Differential diagnosis

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

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

OpenAIRE

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

2015-01-01

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

Genetic analysis of heptad-repeat regions in the G2 fusion subunit of the Junin arenavirus envelope glycoprotein

International Nuclear Information System (INIS)

York, Joanne; Agnihothram, Sudhakar S.; Romanowski, Victor; Nunberg, Jack H.

2005-01-01

The G2 fusion subunit of the Junin virus envelope glycoprotein GP-C contains two hydrophobic heptad-repeat regions that are postulated to form a six-helix bundle structure required for the membrane fusion activity of Class I viral fusion proteins. We have investigated the role of these heptad-repeat regions and, specifically, the importance of the putative interhelical a and d position sidechains by using alanine-scanning mutagenesis. All the mutant glycoproteins were expressed and transported to the cell surface. Proteolytic maturation at the subtilisin kexin isozyme-1/site-1-protease (SKI-1/S1P) cleavage site was observed in all but two of the mutants. Among the adequately cleaved mutant glycoproteins, four positions in the N-terminal region (I333, L336, L347 and L350) and two positions in the C-terminal region (R392 and W395) were shown to be important determinants of cell-cell fusion. Taken together, our results indicate that α-helical coiled-coil structures are likely critical in promoting arenavirus membrane fusion. These findings support the inclusion of the arenavirus GP-C among the Class I viral fusion proteins and suggest pharmacologic and immunologic strategies for targeting arenavirus infection and hemorrhagic fever

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

Directory of Open Access Journals (Sweden)

Mahsa Mohseni

2016-03-01

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

Characterization of glycoprotein biopharmaceutical products by Caliper LC90 CE-SDS gel technology.

Science.gov (United States)

Chen, Grace; Ha, Sha; Rustandi, Richard R

2013-01-01

Over the last decade, science has greatly improved in the area of protein sizing and characterization. Efficient high-throughput methods are now available to substitute for the traditional labor-intensive SDS-PAGE methods, which alternatively take days to analyze a very limited number of samples. Currently, PerkinElmer(®) (Caliper) has designed an automated chip-based fluorescence detection method capable of analyzing proteins in minutes with sensitivity similar to standard SDS-PAGE. Here, we describe the use and implementation of this technology to characterize and screen a large number of formulations of target glycoproteins in the 14-200 kDa molecular weight range.

Added Value of Contrast-Enhanced Ultrasound on Biopsies of Focal Hepatic Lesions Invisible on Fusion Imaging Guidance.

Science.gov (United States)

Kang, Tae Wook; Lee, Min Woo; Song, Kyoung Doo; Kim, Mimi; Kim, Seung Soo; Kim, Seong Hyun; Ha, Sang Yun

2017-01-01

To assess whether contrast-enhanced ultrasonography (CEUS) with Sonazoid can improve the lesion conspicuity and feasibility of percutaneous biopsies for focal hepatic lesions invisible on fusion imaging of real-time ultrasonography (US) with computed tomography/magnetic resonance images, and evaluate its impact on clinical decision making. The Institutional Review Board approved this retrospective study. Between June 2013 and January 2015, 711 US-guided percutaneous biopsies were performed for focal hepatic lesions. Biopsies were performed using CEUS for guidance if lesions were invisible on fusion imaging. We retrospectively evaluated the number of target lesions initially invisible on fusion imaging that became visible after applying CEUS, using a 4-point scale. Technical success rates of biopsies were evaluated based on histopathological results. In addition, the occurrence of changes in clinical decision making was assessed. Among 711 patients, 16 patients (2.3%) were included in the study. The median size of target lesions was 1.1 cm (range, 0.5-1.9 cm) in pre-procedural imaging. After CEUS, 15 of 16 (93.8%) focal hepatic lesions were visualized. The conspicuity score was significantly increased after adding CEUS, as compared to that on fusion imaging (p making for 11 of 16 patients (68.8%). The addition of CEUS could improve the conspicuity of focal hepatic lesions invisible on fusion imaging. This dual guidance using CEUS and fusion imaging may affect patient management via changes in clinical decision-making.

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

Science.gov (United States)

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

2018-03-01

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

Glycoproteins and sialyl transferase of human B lymphoblastoid cell lines

International Nuclear Information System (INIS)

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

1980-01-01

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

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

International Nuclear Information System (INIS)

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

1983-01-01

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

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

Science.gov (United States)

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

1989-05-01

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

The peanut lectin-binding glycoproteins of human epidermal keratinocytes

International Nuclear Information System (INIS)

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

1988-01-01

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

An empirical assessment of the focal species hypothesis.

Science.gov (United States)

Lindenmayer, D B; Lane, P W; Westgate, M J; Crane, M; Michael, D; Okada, S; Barton, P S

2014-12-01

Biodiversity surrogates and indicators are commonly used in conservation management. The focal species approach (FSA) is one method for identifying biodiversity surrogates, and it is underpinned by the hypothesis that management aimed at a particular focal species will confer protection on co-occurring species. This concept has been the subject of much debate, in part because the validity of the FSA has not been subject to detailed empirical assessment of the extent to which a given focal species actually co-occurs with other species in an assemblage. To address this knowledge gap, we used large-scale, long-term data sets of temperate woodland birds to select focal species associated with threatening processes such as habitat isolation and loss of key vegetation attributes. We quantified co-occurrence patterns among focal species, species in the wider bird assemblage, and species of conservation concern. Some, but not all, focal species were associated with high levels of species richness. One of our selected focal species was negatively associated with the occurrence of other species (i.e., it was an antisurrogate)-a previously undescribed property of nominated focal species. Furthermore, combinations of focal species were not associated with substantially elevated levels of bird species richness, relative to levels associated with individual species. Our results suggest that although there is some merit to the underpinning concept of the FSA, there is also a need to ensure that actions are sufficiently flexible because management tightly focused on a given focal species may not benefit some other species, including species of conservation concern, such of which might not occur in species-rich assemblages. © 2014 Society for Conservation Biology.

Molecular Targets for Targeted Radionuclide Therapy

International Nuclear Information System (INIS)

Mather, S.J.

2009-01-01

radiolabelled regulatory peptides and their metabolically stabilised analogues. Antigen epitopes: Antibodies, as unlabelled biological drugs, are becoming of increasing interest. They exert an antibody-dependent cellular cytotoxicity which leads to lysis of tumour cells. Radiolabelled versions of these (and other) antibodies are being developed worldwide. The disadvantage of the long circulating time of antibodies can be solved by engineering fragments such as diabodies, bivalent single chain variable fragments (scFv), minibodies or by pretargeting approaches. Transmembrane transporters: Other interesting targets are transporters for radiolabelled amino acids and nutrients. Cancer cells require an increased supply of many such nutrients and obtain these by increased expression of some types of amino-acid transporter. A more detailed analysis of the relationship between amino-acid uptake and transporter expression in normal and malignant cells would be very valuable in identifying the clinical therapeutic potential of this class of tracer. Tumour blood supply: Tumours require an efficient blood supply to grow and metastatise and active angiogenesis of new blood vessels is a feature of many tumours. Specific receptors expressed during this process represent a novel class of targets for TRT. Extra-cellular matrix: Recently, another relevant class of target antigens has raised interest. Lectins, or carbohydrate binding proteins, recognize specific oligosaccharide structures on glycoproteins and glycolipids. It is well known that protein and lipid glycosylation are consistently altered in cancer cells for the aberrant activity of specific glycosyltransferase and glycosydases. Experimental evidence demonstrated that tumor growth and progression may depend, at least in part, on the presence of altered glycoproteins on the cell surface, which can mediate aberrant receptor-ligand interactions. (author)

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

DEFF Research Database (Denmark)

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

2009-01-01

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

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

OpenAIRE

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

2014-01-01

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

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.

Second-hit mosaic mutation in mTORC1 repressor DEPDC5 causes focal cortical dysplasia-associated epilepsy.

Science.gov (United States)

Ribierre, Théo; Deleuze, Charlotte; Bacq, Alexandre; Baldassari, Sara; Marsan, Elise; Chipaux, Mathilde; Muraca, Giuseppe; Roussel, Delphine; Navarro, Vincent; Leguern, Eric; Miles, Richard; Baulac, Stéphanie

2018-04-30

DEP domain-containing 5 protein (DEPDC5) is a repressor of the recently recognized amino acid-sensing branch of the mTORC1 pathway. So far, its function in the brain remains largely unknown. Germline loss-of-function mutations in DEPDC5 have emerged as a major cause of familial refractory focal epilepsies, with case reports of sudden unexpected death in epilepsy (SUDEP). Remarkably, a fraction of patients also develop focal cortical dysplasia (FCD), a neurodevelopmental cortical malformation. We therefore hypothesized that a somatic second-hit mutation arising during brain development may support the focal nature of the dysplasia. Here, using postoperative human tissue, we provide the proof of concept that a biallelic 2-hit - brain somatic and germline - mutational mechanism in DEPDC5 causes focal epilepsy with FCD. We discovered a mutation gradient with a higher rate of mosaicism in the seizure-onset zone than in the surrounding epileptogenic zone. Furthermore, we demonstrate the causality of a Depdc5 brain mosaic inactivation using CRISPR-Cas9 editing and in utero electroporation in a mouse model recapitulating focal epilepsy with FCD and SUDEP-like events. We further unveil a key role of Depdc5 in shaping dendrite and spine morphology of excitatory neurons. This study reveals promising therapeutic avenues for treating drug-resistant focal epilepsies with mTORC1-targeting molecules.

Multiple genes encode the major surface glycoprotein of Pneumocystis carinii

DEFF Research Database (Denmark)

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

1993-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1982-03-01

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

Do focal colors look particularly "colorful"?

Science.gov (United States)

Witzel, Christoph; Franklin, Anna

2014-04-01

If the most typical red, yellow, green, and blue were particularly colorful (i.e., saturated), they would "jump out to the eye." This would explain why even fundamentally different languages have distinct color terms for these focal colors, and why unique hues play a prominent role in subjective color appearance. In this study, the subjective saturation of 10 colors around each of these focal colors was measured through a pairwise matching task. Results show that subjective saturation changes systematically across hues in a way that is strongly correlated to the visual gamut, and exponentially related to sensitivity but not to focal colors.

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

International Nuclear Information System (INIS)

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

1983-01-01

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

Genetic Diversity Underlying the Envelope Glycoproteins of Hepatitis C Virus: Structural and Functional Consequences and the Implications for Vaccine Design

Directory of Open Access Journals (Sweden)

Alexander W. Tarr

2015-07-01

Full Text Available In the 26 years since the discovery of Hepatitis C virus (HCV a major global research effort has illuminated many aspects of the viral life cycle, facilitating the development of targeted antivirals. Recently, effective direct-acting antiviral (DAA regimens with >90% cure rates have become available for treatment of chronic HCV infection in developed nations, representing a significant advance towards global eradication. However, the high cost of these treatments results in highly restricted access in developing nations, where the disease burden is greatest. Additionally, the largely asymptomatic nature of infection facilitates continued transmission in at risk groups and resource constrained settings due to limited surveillance. Consequently a prophylactic vaccine is much needed. The HCV envelope glycoproteins E1 and E2 are located on the surface of viral lipid envelope, facilitate viral entry and are the targets for host immunity, in addition to other functions. Unfortunately, the extreme global genetic and antigenic diversity exhibited by the HCV glycoproteins represents a significant obstacle to vaccine development. Here we review current knowledge of HCV envelope protein structure, integrating knowledge of genetic, antigenic and functional diversity to inform rational immunogen design.

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

Science.gov (United States)

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

2014-09-01

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

Inverse-designed stretchable metalens with tunable focal distance

Science.gov (United States)

Callewaert, Francois; Velev, Vesselin; Jiang, Shizhou; Sahakian, Alan Varteres; Kumar, Prem; Aydin, Koray

2018-02-01

In this paper, we present an inverse-designed 3D-printed all-dielectric stretchable millimeter wave metalens with a tunable focal distance. A computational inverse-design method is used to design a flat metalens made of disconnected polymer building blocks with complex shapes, as opposed to conventional monolithic lenses. The proposed metalens provides better performance than a conventional Fresnel lens, using lesser amount of material and enabling larger focal distance tunability. The metalens is fabricated using a commercial 3D-printer and attached to a stretchable platform. Measurements and simulations show that the focal distance can be tuned by a factor of 4 with a stretching factor of only 75%, a nearly diffraction-limited focal spot, and with a 70% relative focusing efficiency, defined as the ratio between power focused in the focal spot and power going through the focal plane. The proposed platform can be extended for design and fabrication of multiple electromagnetic devices working from visible to microwave radiation depending on scaling of the devices.

Ignition target and laser-plasma instabilities

International Nuclear Information System (INIS)

Laffite, S.; Loiseau, P.

2010-01-01

For the first time indirect drive ignition targets have been designed with the constraint of limiting laser-plasma instabilities. The amplification of these instabilities is directly proportional to the luminous flux density, it means to the sizes of the focal spots too. This study shows that increasing the sizes of the focal spots does not reduce linear amplification gains in a proportional way because the global optimization of the target implies changes in hydrodynamical conditions that in turn have an impact on the value of the amplification gain. The design of the target is a 2-step approach: the first step aims at assuring a uniform irradiation and compression of the target. The first step requires information concerning the laser focusing spots, the dimensions of the hohlraum, the inert gas contained in it, the materials of the wall. The second step is an optimization approach whose aim is to reduce the risk of laser-plasmas instabilities. This optimization is made through simulations of the amplification gains of stimulated Raman and Brillouin backscattering. This method has allowed us to design an optimized target for a rugby-shaped hohlraum. (A.C.)

Glycoengineering of Human Cell Lines Using Zinc Finger Nuclease Gene Targeting

DEFF Research Database (Denmark)

Steentoft, Catharina; Bennett, Eric Paul; Clausen, Henrik

2013-01-01

Lectin affinity chromatography is a powerful technique for isolation of glycoproteins carrying a specific glycan structure of interest. However, the enormous diversity of glycans present on the cell surface, as well as on individual proteins, makes it difficult to isolate an entire glycoproteome...... with one or even a series of lectins. Here we present a technique to generate cell lines with homogenous truncated O-glycans using zinc finger nuclease gene targeting. Because of their simplified O-glycoproteome, the cells have been named SimpleCells. Glycoproteins from SimpleCells can be isolated...... in a single purification step by lectin chromatography performed on a long lectin column. This protocol describes Zinc finger nuclease gene targeting of human cells to simplify the glycoproteome, as well as lectin chromatography and isolation of glycopeptides from total cell lysates of SimpleCells....

Added value of contrast-enhanced ultrasound on biopsies of focal hepatic lesions invisible on fusion imaging guidance

Energy Technology Data Exchange (ETDEWEB)

Kang, Tae Wook; Lee, Min Woo; Song, Kyoung Doo; Kim, Mimi; Kim, Seung Soo; Kim, Seong Hyun; Ha, Sang Yun [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2017-01-15

To assess whether contrast-enhanced ultrasonography (CEUS) with Sonazoid can improve the lesion conspicuity and feasibility of percutaneous biopsies for focal hepatic lesions invisible on fusion imaging of real-time ultrasonography (US) with computed tomography/magnetic resonance images, and evaluate its impact on clinical decision making. The Institutional Review Board approved this retrospective study. Between June 2013 and January 2015, 711 US-guided percutaneous biopsies were performed for focal hepatic lesions. Biopsies were performed using CEUS for guidance if lesions were invisible on fusion imaging. We retrospectively evaluated the number of target lesions initially invisible on fusion imaging that became visible after applying CEUS, using a 4-point scale. Technical success rates of biopsies were evaluated based on histopathological results. In addition, the occurrence of changes in clinical decision making was assessed. Among 711 patients, 16 patients (2.3%) were included in the study. The median size of target lesions was 1.1 cm (range, 0.5–1.9 cm) in pre-procedural imaging. After CEUS, 15 of 16 (93.8%) focal hepatic lesions were visualized. The conspicuity score was significantly increased after adding CEUS, as compared to that on fusion imaging (p < 0.001). The technical success rate of biopsy was 87.6% (14/16). After biopsy, there were changes in clinical decision making for 11 of 16 patients (68.8%). The addition of CEUS could improve the conspicuity of focal hepatic lesions invisible on fusion imaging. This dual guidance using CEUS and fusion imaging may affect patient management via changes in clinical decision-making.

Added value of contrast-enhanced ultrasound on biopsies of focal hepatic lesions invisible on fusion imaging guidance

International Nuclear Information System (INIS)

Kang, Tae Wook; Lee, Min Woo; Song, Kyoung Doo; Kim, Mimi; Kim, Seung Soo; Kim, Seong Hyun; Ha, Sang Yun

2017-01-01

To assess whether contrast-enhanced ultrasonography (CEUS) with Sonazoid can improve the lesion conspicuity and feasibility of percutaneous biopsies for focal hepatic lesions invisible on fusion imaging of real-time ultrasonography (US) with computed tomography/magnetic resonance images, and evaluate its impact on clinical decision making. The Institutional Review Board approved this retrospective study. Between June 2013 and January 2015, 711 US-guided percutaneous biopsies were performed for focal hepatic lesions. Biopsies were performed using CEUS for guidance if lesions were invisible on fusion imaging. We retrospectively evaluated the number of target lesions initially invisible on fusion imaging that became visible after applying CEUS, using a 4-point scale. Technical success rates of biopsies were evaluated based on histopathological results. In addition, the occurrence of changes in clinical decision making was assessed. Among 711 patients, 16 patients (2.3%) were included in the study. The median size of target lesions was 1.1 cm (range, 0.5–1.9 cm) in pre-procedural imaging. After CEUS, 15 of 16 (93.8%) focal hepatic lesions were visualized. The conspicuity score was significantly increased after adding CEUS, as compared to that on fusion imaging (p < 0.001). The technical success rate of biopsy was 87.6% (14/16). After biopsy, there were changes in clinical decision making for 11 of 16 patients (68.8%). The addition of CEUS could improve the conspicuity of focal hepatic lesions invisible on fusion imaging. This dual guidance using CEUS and fusion imaging may affect patient management via changes in clinical decision-making

Stretch activates human myometrium via ERK, caldesmon and focal adhesion signaling.

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Yunping Li

2009-10-01

Full Text Available An incomplete understanding of the molecular mechanisms responsible for myometrial activation from the quiescent pregnant state to the active contractile state during labor has hindered the development of effective therapies for preterm labor. Myometrial stretch has been implicated clinically in the initiation of labor and the etiology of preterm labor, but the molecular mechanisms involved in the human have not been determined. We investigated the mechanisms by which gestation-dependent stretch contributes to myometrial activation, by using human uterine samples from gynecologic hysterectomies and Cesarean sections. Here we demonstrate that the Ca requirement for activation of the contractile filaments in human myometrium increases with caldesmon protein content during gestation and that an increase in caldesmon phosphorylation can reverse this inhibitory effect during labor. By using phosphotyrosine screening and mass spectrometry of stretched human myometrial samples, we identify 3 stretch-activated focal adhesion proteins, FAK, p130Cas, and alpha actinin. FAK-Y397, which signals integrin engagement, is constitutively phosphorylated in term human myometrium whereas FAK-Y925, which signals downstream ERK activation, is phosphorylated during stretch. We have recently identified smooth muscle Archvillin (SmAV as an ERK regulator. A newly produced SmAV-specific antibody demonstrates gestation-specific increases in SmAV protein levels and stretch-specific increases in SmAV association with focal adhesion proteins. Thus, whereas increases in caldesmon levels suppress human myometrium contractility during pregnancy, stretch-dependent focal adhesion signaling, facilitated by the ERK activator SmAV, can contribute to myometrial activation. These results suggest that focal adhesion proteins may present new targets for drug discovery programs aimed at regulation of uterine contractility.

Herpes simplex virus type 2 glycoprotein H interacts with integrin αvβ3 to facilitate viral entry and calcium signaling in human genital tract epithelial cells.

Science.gov (United States)

Cheshenko, Natalia; Trepanier, Janie B; González, Pablo A; Eugenin, Eliseo A; Jacobs, William R; Herold, Betsy C

2014-09-01

Herpes simplex virus (HSV) entry requires multiple interactions at the cell surface and activation of a complex calcium signaling cascade. Previous studies demonstrated that integrins participate in this process, but their precise role has not been determined. These studies were designed to test the hypothesis that integrin αvβ3 signaling promotes the release of intracellular calcium (Ca2+) stores and contributes to viral entry and cell-to-cell spread. Transfection of cells with small interfering RNA (siRNA) targeting integrin αvβ3, but not other integrin subunits, or treatment with cilengitide, an Arg-Gly-Asp (RGD) mimetic, impaired HSV-induced Ca2+ release, viral entry, plaque formation, and cell-to-cell spread of HSV-1 and HSV-2 in human cervical and primary genital tract epithelial cells. Coimmunoprecipitation studies and proximity ligation assays indicated that integrin αvβ3 interacts with glycoprotein H (gH). An HSV-2 gH-null virus was engineered to further assess the role of gH in the virus-induced signaling cascade. The gH-2-null virus bound to cells and activated Akt to induce a small Ca2+ response at the plasma membrane, but it failed to trigger the release of cytoplasmic Ca2+ stores and was impaired for entry and cell-to-cell spread. Silencing of integrin αvβ3 and deletion of gH prevented phosphorylation of focal adhesion kinase (FAK) and the transport of viral capsids to the nuclear pore. Together, these findings demonstrate that integrin signaling is activated downstream of virus-induced Akt signaling and facilitates viral entry through interactions with gH by activating the release of intracellular Ca2+ and FAK phosphorylation. These findings suggest a new target for HSV treatment and suppression. Herpes simplex viruses are the leading cause of genital disease worldwide, the most common infection associated with neonatal encephalitis, and a major cofactor for HIV acquisition and transmission. There is no effective vaccine. These

Strategies for induction of catalytic antibodies toward HIV-1 glycoprotein gp120 in autoimmune prone mice.

Science.gov (United States)

Durova, Oxana M; Vorobiev, Ivan I; Smirnov, Ivan V; Reshetnyak, Andrew V; Telegin, Georgy B; Shamborant, Olga G; Orlova, Nadezda A; Genkin, Dmitry D; Bacon, Andrew; Ponomarenko, Natalia A; Friboulet, Alain; Gabibov, Alexander G

2009-11-01

Tremendous efforts to produce an efficient vaccine for HIV infection have been unsuccessful. The ability of HIV to utilize sophisticated mechanisms to escape killing by host immune system rises dramatic problems in the development of antiviral therapeutics. The HIV infection proceeds by interaction of coat viral glycoprotein gp120 trimer with CD4(+) receptor of the lymphocyte. Thus this surface antigen may be regarded as a favorable target for immunotherapy. In the present study, we have developed three different strategies to produce gp120-specific response in autoimmune prone mice (SJL strain) as potential tools for production "catalytic vaccine". Therefore (i) reactive immunization by peptidylphosphonate, structural part of the coat glycoprotein, (ii) immunization by engineered fused epitopes of gp120 and encephalogenic peptide, a part of myelin basic protein, and (iii) combined vaccination by DNA and corresponding gp120 fragments incorporated into liposomes were investigated. In the first two cases monoclonal antibodies and their recombinant fragments with amidolytic and gp120-specific proteolytic activities were characterized. In the last case, catalytic antibodies with virus neutralizing activity proved in cell line models were harvested.

Preparation of 131I-asialo-α1-acid glycoprotein

International Nuclear Information System (INIS)

Rijk, P.P. van

1975-01-01

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

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...

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

International Nuclear Information System (INIS)

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

1989-01-01

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

Australine, a pyrrolizidine alkaloid that inhibits amyloglucosidase and glycoprotein processing

International Nuclear Information System (INIS)

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

1989-01-01

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

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

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MarkéŽta Vaňkov‡á

2016-01-01

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

Pharmacological response of systemically derived focal epileptic lesions

Energy Technology Data Exchange (ETDEWEB)

Remler, M.P.; Sigvardt, K.; Marcussen, W.H.

1986-11-01

Focal epileptic lesions were made in rats by systemic focal epileptogenesis. In this method, a focal lesion of the blood-brain barrier (BBB) is produced by focal alpha irradiation followed by repeated systemic injection of a convulsant drug that cannot cross the normal BBB, resulting in a chronic epileptic focus. Changes in the spike frequency of these foci in response to various drugs was recorded. The controls, saline and chlorpromazine, produced no change. Phenytoin, phenobarbital, chlordiazepoxide, and valproic acid produced the expected decrease in spike frequency. Pentobarbital and diazepam produced a paradoxical increase in spike frequency.

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

Science.gov (United States)

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

2018-06-01

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

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

Science.gov (United States)

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

2018-05-15

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

Target isolation system, high power laser and laser peening method and system using same

Science.gov (United States)

Dane, C. Brent; Hackel, Lloyd A.; Harris, Fritz

2007-11-06

A system for applying a laser beam to work pieces, includes a laser system producing a high power output beam. Target delivery optics are arranged to deliver the output beam to a target work piece. A relay telescope having a telescope focal point is placed in the beam path between the laser system and the target delivery optics. The relay telescope relays an image between an image location near the output of the laser system and an image location near the target delivery optics. A baffle is placed at the telescope focal point between the target delivery optics and the laser system to block reflections from the target in the target delivery optics from returning to the laser system and causing damage.

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

Science.gov (United States)

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

1991-06-01

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

Recent US target-physics-related research in heavy-ion inertial fusion: simulations for tamped targets and for disk experiments in accelerator test facilities

International Nuclear Information System (INIS)

Mark, J.W.K.

1982-01-01

Within the last few years, there have also appeared in the Heavy-Ion Fusion literature several studies of targets which have outer tampers. One-dimensional simulations indicate higher target gains with a judicious amount of tamping. But for these targets, a full investigation has not been carried through in regards to conservative criteria for fluid instabilities as well as reasonable imperfections in target fabrication and illumination symmetry which all affect target ignition and burn. Comparisons of these results with the gain survey of Part I would have to be performed with care. These calculations suggest that experiments relating to high temperature disk heating, as well as beam deposition, focusing and transport can be performed within the context of current design proposals for accelerator test-facilities. Since the test-facilities have lower ion kinetic energy and beam pulse power as compared to reactor drivers, we achieve high-beam intensities at the focal spot by using short focal distance and properly designed beam optics

O-acetylation of the serine-rich repeat glycoprotein GspB is coordinated with accessory Sec transport.

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Ravin Seepersaud

2017-08-01

Full Text Available The serine-rich repeat (SRR glycoproteins are a family of adhesins found in many Gram-positive bacteria. Expression of the SRR adhesins has been linked to virulence for a variety of infections, including streptococcal endocarditis. The SRR preproteins undergo intracellular glycosylation, followed by export via the accessory Sec (aSec system. This specialized transporter is comprised of SecA2, SecY2 and three to five accessory Sec proteins (Asps that are required for export. Although the post-translational modification and transport of the SRR adhesins have been viewed as distinct processes, we found that Asp2 of Streptococcus gordonii also has an important role in modifying the SRR adhesin GspB. Biochemical analysis and mass spectrometry indicate that Asp2 is an acetyltransferase that modifies N-acetylglucosamine (GlcNAc moieties on the SRR domains of GspB. Targeted mutations of the predicted Asp2 catalytic domain had no effect on transport, but abolished acetylation. Acetylated forms of GspB were only detected when the protein was exported via the aSec system, but not when transport was abolished by secA2 deletion. In addition, GspB variants rerouted to export via the canonical Sec pathway also lacked O-acetylation, demonstrating that this modification is specific to export via the aSec system. Streptococci expressing GspB lacking O-acetylated GlcNAc were significantly reduced in their ability bind to human platelets in vitro, an interaction that has been strongly linked to virulence in the setting of endocarditis. These results demonstrate that Asp2 is a bifunctional protein involved in both the post-translational modification and transport of SRR glycoproteins. In addition, these findings indicate that these processes are coordinated during the biogenesis of SRR glycoproteins, such that the adhesin is optimally modified for binding. This requirement for the coupling of modification and export may explain the co-evolution of the SRR

Recurrent Bilateral Focal Myositis.

Science.gov (United States)

Nagafuchi, Hiroko; Nakano, Hiromasa; Ooka, Seido; Takakuwa, Yukiko; Yamada, Hidehiro; Tadokoro, Mamoru; Shimojo, Sadatomo; Ozaki, Shoichi

This report describes a rare case of recurrent bilateral focal myositis and its successful treatment via methotrexate. A 38-year-old man presented myalgia of the right gastrocnemius in May 2005. Magnetic resonance imaging showed very high signal intensity in the right gastrocnemius on short-tau inversion recovery images. A muscle biopsy revealed inflammatory CD4+ cell-dominant myogenic change. Focal myositis was diagnosed. The first steroid treatment was effective. Tapering of prednisolone, however, repeatedly induced myositis relapse, which progressed to multiple muscle lesions of both lower limbs. Initiation of methotrexate finally allowed successful tapering of prednisolone, with no relapse in the past 4 years.

Predictive distractor context facilitates attentional selection of high, but not intermediate and low, salience targets.

Science.gov (United States)

Töllner, Thomas; Conci, Markus; Müller, Hermann J

2015-03-01

It is well established that we can focally attend to a specific region in visual space without shifting our eyes, so as to extract action-relevant sensory information from covertly attended locations. The underlying mechanisms that determine how fast we engage our attentional spotlight in visual-search scenarios, however, remain controversial. One dominant view advocated by perceptual decision-making models holds that the times taken for focal-attentional selection are mediated by an internal template that biases perceptual coding and selection decisions exclusively through target-defining feature coding. This notion directly predicts that search times remain unaffected whether or not participants can anticipate the upcoming distractor context. Here we tested this hypothesis by employing an illusory-figure localization task that required participants to search for an invariant target amongst a variable distractor context, which gradually changed--either randomly or predictably--as a function of distractor-target similarity. We observed a graded decrease in internal focal-attentional selection times--correlated with external behavioral latencies--for distractor contexts of higher relative to lower similarity to the target. Critically, for low but not intermediate and high distractor-target similarity, these context-driven effects were cortically and behaviorally amplified when participants could reliably predict the type of distractors. This interactive pattern demonstrates that search guidance signals can integrate information about distractor, in addition to target, identities to optimize distractor-target competition for focal-attentional selection. © 2014 Wiley Periodicals, Inc.

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

Magnetic confinement system using charged ammonia targets

International Nuclear Information System (INIS)

Porter, G.D.; Bogdanoff, A.

1979-01-01

A system is described for guiding charged laser targets to a predetermined focal spot of a laser along generally arbitrary, and especially horizontal, directions which comprises a series of electrostatic sensors which provide inputs to a computer for real time calculation of position, velocity, and direction of the target along an initial injection trajectory

The haemagglutination activity of equine herpesvirus type 1 glycoprotein C.

Science.gov (United States)

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

2015-01-02

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

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.

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

International Nuclear Information System (INIS)

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

1988-01-01

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

Multi-focal Vision and Gaze Control Improve Navigation Performance

Directory of Open Access Journals (Sweden)

Kolja Kuehnlenz

2008-11-01

Full Text Available Multi-focal vision systems comprise cameras with various fields of view and measurement accuracies. This article presents a multi-focal approach to localization and mapping of mobile robots with active vision. An implementation of the novel concept is done considering a humanoid robot navigation scenario where the robot is visually guided through a structured environment with several landmarks. Various embodiments of multi-focal vision systems are investigated and the impact on navigation performance is evaluated in comparison to a conventional mono-focal stereo set-up. The comparative studies clearly show the benefits of multi-focal vision for mobile robot navigation: flexibility to assign the different available sensors optimally in each situation, enhancement of the visible field, higher localization accuracy, and, thus, better task performance, i.e. path following behavior of the mobile robot. It is shown that multi-focal vision may strongly improve navigation performance.

Flotillins Regulate Focal Adhesions by Interacting with α-Actinin and by Influencing the Activation of Focal Adhesion Kinase

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Antje Banning

2018-04-01

Full Text Available Cell–matrix adhesion and cell migration are physiologically important processes that also play a major role in cancer spreading. In cultured cells, matrix adhesion depends on integrin-containing contacts such as focal adhesions. Flotillin-1 and flotillin-2 are frequently overexpressed in cancers and are associated with poor survival. Our previous studies have revealed a role for flotillin-2 in cell–matrix adhesion and in the regulation of the actin cytoskeleton. We here show that flotillins are important for cell migration in a wound healing assay and influence the morphology and dynamics of focal adhesions. Furthermore, anchorage-independent growth in soft agar is enhanced by flotillins. In the absence of flotillins, especially flotillin-2, phosphorylation of focal adhesion kinase and extracellularly regulated kinase is diminished. Flotillins interact with α-actinin, a major regulator of focal adhesion dynamics. These findings are important for understanding the molecular mechanisms of how flotillin overexpression in cancers may affect cell migration and, especially, enhance metastasis formation.

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

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

2013-02-01

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

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

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Radikov, N

1989-01-01

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

Continuously variable focal length lens

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Adams, Bernhard W; Chollet, Matthieu C

2013-12-17

A material preferably in crystal form having a low atomic number such as beryllium (Z=4) provides for the focusing of x-rays in a continuously variable manner. The material is provided with plural spaced curvilinear, optically matched slots and/or recesses through which an x-ray beam is directed. The focal length of the material may be decreased or increased by increasing or decreasing, respectively, the number of slots (or recesses) through which the x-ray beam is directed, while fine tuning of the focal length is accomplished by rotation of the material so as to change the path length of the x-ray beam through the aligned cylindrical slows. X-ray analysis of a fixed point in a solid material may be performed by scanning the energy of the x-ray beam while rotating the material to maintain the beam's focal point at a fixed point in the specimen undergoing analysis.

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

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Su, Yuting; Xu, Yongjian

2015-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1982-09-15

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

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

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

2013-01-01

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

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

International Nuclear Information System (INIS)

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

2007-01-01

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

CT appearance of focal fatty infiltration of the liver

International Nuclear Information System (INIS)

Halvorsen, R.A.; Korobkin, M.; Ram, P.C.; Thompson, W.M.

1982-01-01

Focal fatty infiltration of the liver is an entity that may be confused with liver metastasis on computed tomography (CT). The imaging results and medical records of 16 patients with CT appearance suggestive of focal fatty liver were reviewed, three of whom had the simultaneous presence of metastitic liver disease. Focal fatty liver often has a distinctive appearance with CT, usually with a nonspherical shape, absence of mass effect, and density close to water. Liver metastases are usually round or oval, and unless cystic or necrotic, they have CT attenuation values closer to normal liver parenchyma than water. A radionuclide liver scan almost always resolves any confusion about the differential diagnosis of focal fatty liver: a well defined focus of photon deficiency is due to neoplasm rather than focal fatty infiltration. Sonography sometimes helps to confirm the CT impression, but may be misleading if the diagnosis of focal or diffuse fatty infiltration is not suspected before the examination

The study of the focal trough in panoramic radiograph

International Nuclear Information System (INIS)

Park, C. S.; Kim, H. P.

1982-01-01

In the study of the focal trough of panoramic radiograph, using the Moritta company Panex EC a series of 48 exposures were taken with the 6-18 brass pins placed in the holes of the plastic model plate, then evaluated by 4 observers. The author analyzed the focal trough defined by the sharpness criteria and calculated the vertical and horizontal magnification range in the corrected focal trough. The results were as follows; 1. Continuous focal trough was not defined in the anterior region using a very high degree of sharpness. 2. As degree of sharpness used in the analysis became less, focal trough was continuous in the anterior and posterior regions, symmetrized bilaterally, and the widths of the focal trough increased more in the posterior region. 3. As sharpness criteria were reduced, the percentage range of image magnification increased in both vertical and horizontal magnification, and especially the percentage range of horizontal magnification was greater than that of vertical magnification.

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

Science.gov (United States)

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

2016-10-02

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

Stability of rotors and focal sources for human atrial fibrillation: focal impulse and rotor mapping (FIRM) of AF sources and fibrillatory conduction.

Science.gov (United States)

Swarup, Vijay; Baykaner, Tina; Rostamian, Armand; Daubert, James P; Hummel, John; Krummen, David E; Trikha, Rishi; Miller, John M; Tomassoni, Gery F; Narayan, Sanjiv M

2014-12-01

Several groups report electrical rotors or focal sources that sustain atrial fibrillation (AF) after it has been triggered. However, it is difficult to separate stable from unstable activity in prior studies that examined only seconds of AF. We applied phase-based focal impulse and rotor mapping (FIRM) to study the dynamics of rotors/sources in human AF over prolonged periods of time. We prospectively mapped AF in 260 patients (169 persistent, 61 ± 12 years) at 6 centers in the FIRM registry, using baskets with 64 contact electrodes per atrium. AF was phase mapped (RhythmView, Topera, Menlo Park, CA, USA). AF propagation movies were interpreted by each operator to assess the source stability/dynamics over tens of minutes before ablation. Sources were identified in 258 of 260 of patients (99%), for 2.8 ± 1.4 sources/patient (1.8 ± 1.1 in left, 1.1 ± 0.8 in right atria). While AF sources precessed in stable regions, emanating activity including spiral waves varied from collision/fusion (fibrillatory conduction). Each source lay in stable atrial regions for 4,196 ± 6,360 cycles, with no differences between paroxysmal versus persistent AF (4,290 ± 5,847 vs. 4,150 ± 6,604; P = 0.78), or right versus left atrial sources (P = 0.26). Rotors and focal sources for human AF mapped by FIRM over prolonged time periods precess ("wobble") but remain within stable regions for thousands of cycles. Conversely, emanating activity such as spiral waves disorganize and collide with the fibrillatory milieu, explaining difficulties in using activation mapping or signal processing analyses at fixed electrodes to detect AF rotors. These results provide a rationale for targeted ablation at AF sources rather than fibrillatory spiral waves. © 2014 Wiley Periodicals, Inc.

Annotating Human P-Glycoprotein Bioassay Data.

Science.gov (United States)

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

2012-08-01

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

Comprehensive Survey on Improved Focality and Penetration Depth of Transcranial Magnetic Stimulation Employing Multi-Coil Arrays

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Xile Wei

2017-11-01

Full Text Available Multi-coil arrays applied in transcranial magnetic stimulation (TMS are proposed to accurately stimulate brain tissues and modulate neural activities by an induced electric field (EF. Composed of numerous independently driven coils, a multi-coil array has alternative energizing strategies to evoke EFs targeting at different cerebral regions. To improve the locating resolution and the stimulating focality, we need to fully understand the variation properties of induced EFs and the quantitative control method of the spatial arrangement of activating coils, both of which unfortunately are still unclear. In this paper, a comprehensive analysis of EF properties was performed based on multi-coil arrays. Four types of planar multi-coil arrays were used to study the relationship between the spatial distribution of EFs and the structure of stimuli coils. By changing coil-driven strategies in a basic 16-coil array, we find that an EF induced by compactly distributed coils decays faster than that induced by dispersedly distributed coils, but the former has an advantage over the latter in terms of the activated brain volume. Simulation results also indicate that the attenuation rate of an EF induced by the 36-coil dense array is 3 times and 1.5 times greater than those induced by the 9-coil array and the 16-coil array, respectively. The EF evoked by the 36-coil dispense array has the slowest decay rate. This result demonstrates that larger multi-coil arrays, compared to smaller ones, activate deeper brain tissues at the expense of decreased focality. A further study on activating a specific field of a prescribed shape and size was conducted based on EF variation. Accurate target location was achieved with a 64-coil array 18 mm in diameter. A comparison between the figure-8 coil, the planar array, and the cap-formed array was made and demonstrates an improvement of multi-coil configurations in the penetration depth and the focality. These findings suggest

Comprehensive Survey on Improved Focality and Penetration Depth of Transcranial Magnetic Stimulation Employing Multi-Coil Arrays.

Science.gov (United States)

Wei, Xile; Li, Yao; Lu, Meili; Wang, Jiang; Yi, Guosheng

2017-11-14

Multi-coil arrays applied in transcranial magnetic stimulation (TMS) are proposed to accurately stimulate brain tissues and modulate neural activities by an induced electric field (EF). Composed of numerous independently driven coils, a multi-coil array has alternative energizing strategies to evoke EFs targeting at different cerebral regions. To improve the locating resolution and the stimulating focality, we need to fully understand the variation properties of induced EFs and the quantitative control method of the spatial arrangement of activating coils, both of which unfortunately are still unclear. In this paper, a comprehensive analysis of EF properties was performed based on multi-coil arrays. Four types of planar multi-coil arrays were used to study the relationship between the spatial distribution of EFs and the structure of stimuli coils. By changing coil-driven strategies in a basic 16-coil array, we find that an EF induced by compactly distributed coils decays faster than that induced by dispersedly distributed coils, but the former has an advantage over the latter in terms of the activated brain volume. Simulation results also indicate that the attenuation rate of an EF induced by the 36-coil dense array is 3 times and 1.5 times greater than those induced by the 9-coil array and the 16-coil array, respectively. The EF evoked by the 36-coil dispense array has the slowest decay rate. This result demonstrates that larger multi-coil arrays, compared to smaller ones, activate deeper brain tissues at the expense of decreased focality. A further study on activating a specific field of a prescribed shape and size was conducted based on EF variation. Accurate target location was achieved with a 64-coil array 18 mm in diameter. A comparison between the figure-8 coil, the planar array, and the cap-formed array was made and demonstrates an improvement of multi-coil configurations in the penetration depth and the focality. These findings suggest that there is a

Focal myositis: A review.

Science.gov (United States)

Devic, P; Gallay, L; Streichenberger, N; Petiot, P

2016-11-01

Amongst the heterogeneous group of inflammatory myopathies, focal myositis stands as a rare and benign dysimmune disease. Although it can be associated with root and/or nerve lesions, traumatic muscle lesions and autoimmune diseases, its triggering factors remain poorly understood. Defined as an isolated inflammatory pseudotumour usually restricted to one skeletal muscle, clinical presentation of focal myositis is that of a rapidly growing solitary mass within a single muscle, usually in the lower limbs. Electromyography shows spontaneous activity associated with a myopathic pattern. MRI reveals a contrast enhanced enlarged muscle appearing hyper-intense on FAT-SAT T2 weighted images. Adjacent structures are spared and there are no calcifications. Serum creatine kinase (CK) levels are usually moderately augmented and biological markers of systemic inflammation are absent in most cases. Pathological histological features include marked variation in fibre size, inflammatory infiltrates mostly composed of T CD4+ lymphocytes and macrophages, degenerating/regenerating fibres and interstitial fibrosis. Differential diagnoses are numerous and include myositis of other origin with focal onset. Steroid treatment should be reserved for patients who present with major pain, nerve lesions, associated autoimmune disease, or elevated C reactive protein or CK. Copyright © 2016 Elsevier B.V. All rights reserved.

Prenatal sonographic diagnosis of focal musculoskeletal anomalies

International Nuclear Information System (INIS)

Ryu, Jung-Kyu; Cho, Jeong-Yeon; Choi, Jong-Sun

2003-01-01

Focal musculoskeletal anomalies vary, and can manifest as part of a syndrome or be accompanied by numerous other conditions such as genetic disorders, karyotype abnormalities, central nervous system anomalies and other skeletal anomalies, lsolated focal musculoskeletal anomaly does, however, also occur; its early prenatal diagnosis is important in deciding prenatal care, and also helps in counseling parents about the postnatal effects of numerous possible associated anomalies. We have encountered 50 cases involving focal musculoskeletal anomalies, including total limb dysplasia [radial ray abnormality (n=3), mesomelic dysplasia (n=1)]; anomalies of the hand [polydactyly (n=8), syndactyly (n=3), ectrodactyly (n=1), clinodactyly (n=6), clenched hand (n=5)]; anomalies of the foot [clubfoot (n=10), rockerbottom foot (n=5), sandal gap deformity (n=1), curly toe (n=2)]; amniotic band syndrome (n=3); and anomalies of the focal spine [block vertebra (n=1), hemivertebra (n=1)]. Among these 50 cases, five [polydactyly (n=1), syndactyly (n=2) and curly toe (n=2) were confirmed by postnatal physical evaluation, two (focal spine anomalies) were diagnosed after postnatal radiologic examination, and the remaining 43 were proven at autopsy. For each condition, we describe the prenatal sonographic findings, and include a brief review

Prenatal sonographic diagnosis of focal musculoskeletal anomalies

Energy Technology Data Exchange (ETDEWEB)

Ryu, Jung-Kyu; Cho, Jeong-Yeon; Choi, Jong-Sun [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2003-12-15

Focal musculoskeletal anomalies vary, and can manifest as part of a syndrome or be accompanied by numerous other conditions such as genetic disorders, karyotype abnormalities, central nervous system anomalies and other skeletal anomalies, lsolated focal musculoskeletal anomaly does, however, also occur; its early prenatal diagnosis is important in deciding prenatal care, and also helps in counseling parents about the postnatal effects of numerous possible associated anomalies. We have encountered 50 cases involving focal musculoskeletal anomalies, including total limb dysplasia [radial ray abnormality (n=3), mesomelic dysplasia (n=1)]; anomalies of the hand [polydactyly (n=8), syndactyly (n=3), ectrodactyly (n=1), clinodactyly (n=6), clenched hand (n=5)]; anomalies of the foot [clubfoot (n=10), rockerbottom foot (n=5), sandal gap deformity (n=1), curly toe (n=2)]; amniotic band syndrome (n=3); and anomalies of the focal spine [block vertebra (n=1), hemivertebra (n=1)]. Among these 50 cases, five [polydactyly (n=1), syndactyly (n=2) and curly toe (n=2) were confirmed by postnatal physical evaluation, two (focal spine anomalies) were diagnosed after postnatal radiologic examination, and the remaining 43 were proven at autopsy. For each condition, we describe the prenatal sonographic findings, and include a brief review.

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

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Maximilian Wei-Lin Popp

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

Intestinal mucus and juice glycoproteins have a liquid crystalline structure

International Nuclear Information System (INIS)

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

1985-01-01

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

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

International Nuclear Information System (INIS)

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

1986-01-01

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

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

Science.gov (United States)

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

2010-11-09

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

Platelet Glycoprotein Ib-IX and Malignancy

Science.gov (United States)

2010-09-01

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

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.

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

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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.

DEPDC5 as a potential therapeutic target for epilepsy.

Science.gov (United States)

Myers, Kenneth A; Scheffer, Ingrid E

2017-06-01

Dishevelled, Egl-10 and Pleckstrin (DEP) domain-containing protein 5 (DEPDC5) is a protein subunit of the GTPase-activating proteins towards Rags 1 (GATOR1) complex. GATOR1 is a recently identified modulator of mechanistic target of rapamycin (mTOR) activity. mTOR is a key regulator of cell proliferation and metabolism; disruption of the mTOR pathway is implicated in focal epilepsy, both acquired and genetic. Tuberous sclerosis is the prototypic mTOR genetic syndrome with epilepsy, however GATOR1 gene mutations have recently been shown to cause lesional and non-lesional focal epilepsy. Areas covered: This review summarizes the mTOR pathway, including regulators and downstream effectors, emphasizing recent developments in the understanding of the complex role of the GATOR1 complex. We review the epilepsy types associated with mTOR overactivity, including tuberous sclerosis, polyhydramnios megalencephaly symptomatic epilepsy, cortical dysplasia, non-lesional focal epilepsy and post-traumatic epilepsy. Currently available mTOR inhibitors are discussed, primarily rapamycin analogs and ATP competitive mTOR inhibitors. Expert opinion: DEPDC5 is an attractive therapeutic target in focal epilepsy, as effects of DEPDC5 agonists would likely be anti-epileptogenic and more selective than currently available mTOR inhibitors. Therapeutic effects might be synergistic with certain existing dietary therapies, including the ketogenic diet.

A three-cell liquid hydrogen target for an extended focal plane polarimeter

International Nuclear Information System (INIS)

Golovanov, L.B.; Chesny, P.; Gheller, J.M.; Guillier, G.; Ladygin, V.P.; Theure, Ph.; Tomasi-Gustafsson, E.

1996-01-01

This article describes the design and working principle of a three-cell liquid hydrogen target produced for the high-energy deuteron polarimeter HYPOM. This target uses liquid helium as a cooling agent. After a general description of the apparatus, tests and operating modes are thoroughly explained. In particular the air controlled self-regulation of helium flow in the cryostat to stabilize the liquid hydrogen level is presented. The main feature of this target is the simplicity of the design as well as its safeness towards any incident. Results of cooling down, filling up of the target and stabilization regime were processed during one experiment of physics at synchrotron Saturne II. (orig.)

Structure-Based Design of Head-Only Fusion Glycoprotein Immunogens for Respiratory Syncytial Virus.

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Jeffrey C Boyington

Full Text Available Respiratory syncytial virus (RSV is a significant cause of severe respiratory illness worldwide, particularly in infants, young children, and the elderly. Although no licensed vaccine is currently available, an engineered version of the metastable RSV fusion (F surface glycoprotein-stabilized in the pre-fusion (pre-F conformation by "DS-Cav1" mutations-elicits high titer RSV-neutralizing responses. Moreover, pre-F-specific antibodies, often against the neutralization-sensitive antigenic site Ø in the membrane-distal head region of trimeric F glycoprotein, comprise a substantial portion of the human response to natural RSV infection. To focus the vaccine-elicited response to antigenic site Ø, we designed a series of RSV F immunogens that comprised the membrane-distal head of the F glycoprotein in its pre-F conformation. These "head-only" immunogens formed monomers, dimers, and trimers. Antigenic analysis revealed that a majority of the 70 engineered head-only immunogens displayed reactivity to site Ø-targeting antibodies, which was similar to that of the parent RSV F DS-Cav1 trimers, often with increased thermostability. We evaluated four of these head-only immunogens in detail, probing their recognition by antibodies, their physical stability, structure, and immunogenicity. When tested in naïve mice, a head-only trimer, half the size of the parent RSV F trimer, induced RSV titers, which were statistically comparable to those induced by DS-Cav1. When used to boost DS-Cav1-primed mice, two head-only RSV F immunogens, a dimer and a trimer, boosted RSV-neutralizing titers to levels that were comparable to those boosted by DS-Cav1, although with higher site Ø-directed responses. Our results provide proof-of-concept for the ability of the smaller head-only RSV F immunogens to focus the vaccine-elicited response to antigenic site Ø. Decent primary immunogenicity, enhanced physical stability, potential ease of manufacture, and potent

Mucus glycoprotein secretion by tracheal explants: effects of pollutants

International Nuclear Information System (INIS)

Last, J.A.; Kaizu, T.

1980-01-01

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

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

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M Kristen Hall

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

Focal Atrichia: A Diagnostic Clue in Female Pattern Hair Loss.

Science.gov (United States)

Olsen, Elise A; Whiting, David A

2017-10-07

Focal atrichia is a common clinical finding in female pattern hair loss whose specificity and histologic findings need further clarification. To determine the frequency of focal atrichia in various types of hair loss and its histologic characteristics in female pattern hair loss. Part 1: Review of 250 consecutive female patients seen with hair loss for the presence of focal atrichia and Part 2: paired biopsies of haired areas vs focal atrichia in 18 subjects with female pattern hair loss RESULTS: Focal atrichia was seen in 46/104 (44%) of women with female pattern hair loss, including 67% of late onset vs 15% of early onset, compared to 3/146 (2%) of those with other hair disorders Biopsy findings of focal atrichia in female pattern hair loss showed primarily a more progressive miniaturization process than that of haired areas of the scalp. Some women with female pattern hair loss may have had concomitant chronic telogen effluvium CONCLUSIONS: When present, focal atrichia is a clinical clue to the diagnosis of female pattern hair loss, particularly late onset subtype. Copyright © 2017. Published by Elsevier Inc.

Dimerization of glycoprotein Ibα is not sufficient to induce platelet clearance.

Science.gov (United States)

Liang, X; Syed, A K; Russell, S R; Ware, J; Li, R

2016-02-01

ESSENTIALS: Many anti-glycoprotein (GP)Ibα antibodies induce platelet clearance in a dimer-dependent manner. Characterization of monoclonal antibodies that bind the mechanosensitive domain (MSD) of GPIbα. An anti-MSD antibody binds two copies of GPIbα in platelets but does not induce platelet clearance. The prevailing clustering model of GPIbα signaling is incorrect or needs revision. The mechanism of platelet clearance is not clear. Many antibodies binding the membrane-distal ligand-binding domain of glycoprotein (GP)Ibα induce rapid clearance of platelets and acute thrombocytopenia, which requires the bifurcated antibody structure. It was thought that binding of these antibodies induced lateral dimerization or clustering of GPIbα in the plasma membrane, which leads to downstream signaling and platelet clearance. However, many antibodies targeting GPIbβ and GPIX, which are associated with GPIbα in the GPIb-IX complex, do not induce platelet clearance, which is in contradiction to the clustering model. To test whether dimerization or clustering of GPIbα is sufficient to transmit the signal that leads to platelet clearance. We have recently raised several mAbs targeting the mechanosensitive domain (MSD) of GPIbα. Binding of these anti-MSD antibodies was characterized with biochemical methods. Their ability to stimulate platelets and induce platelet clearance in mice was assessed. Infusion of anti-MSD antibodies does not cause thrombocytopenia in mice. These antibodies show no detectable effects on platelet activation and aggregation in vitro. Further biochemical investigation showed that the anti-MSD antibody 3D1 binds two copies of GPIbα on the platelet surface. Therefore, lateral dimerization of GPIbα induced by antibody binding is not sufficient to initiate GPIb-IX signaling and induce platelet clearance. Our results suggest that a factor other than or in addition to clustering of GPIbα is required to induce platelet clearance. © 2015 International

Design and synthesis of an antigenic mimic of the Ebola glycoprotein

OpenAIRE

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

2008-01-01

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

Testing of focal plane arrays

International Nuclear Information System (INIS)

Merriam, J.D.

1988-01-01

Problems associated with the testing of focal plane arrays are briefly examined with reference to the instrumentation and measurement procedures. In particular, the approach and instrumentation used as the Naval Ocean Systems Center is presented. Most of the measurements are made with flooded illumination on the focal plane array. The array is treated as an ensemble of individual pixels, data being taken on each pixel and array averages and standard deviations computed for the entire array. Data maps are generated, showing the pixel data in the proper spatial position on the array and the array statistics

Involvement of Leishmania donovani major surface glycoprotein ...

Indian Academy of Sciences (India)

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

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

Science.gov (United States)

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

2018-01-01

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

Bioinformatics Analysis of Envelope Glycoprotein E epitopes of ...

African Journals Online (AJOL)

User

2011-05-02

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

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

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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.

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

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Kamel El Omari

2013-01-01

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

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

Science.gov (United States)

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

2013-01-01

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

7T MRI in focal epilepsy with unrevealing conventional field strength imaging.

Science.gov (United States)

De Ciantis, Alessio; Barba, Carmen; Tassi, Laura; Cosottini, Mirco; Tosetti, Michela; Costagli, Mauro; Bramerio, Manuela; Bartolini, Emanuele; Biagi, Laura; Cossu, Massimo; Pelliccia, Veronica; Symms, Mark R; Guerrini, Renzo

2016-03-01

To assess the diagnostic yield of 7T magnetic resonance imaging (MRI) in detecting and characterizing structural lesions in patients with intractable focal epilepsy and unrevealing conventional (1.5 or 3T) MRI. We conducted an observational clinical imaging study on 21 patients (17 adults and 4 children) with intractable focal epilepsy, exhibiting clinical and electroencephalographic features consistent with a single seizure-onset zone (SOZ) and unrevealing conventional MRI. Patients were enrolled at two tertiary epilepsy surgery centers and imaged at 7T, including whole brain (three-dimensional [3D] T1 -weighted [T1W] fast-spoiled gradient echo (FSPGR), 3D susceptibility-weighted angiography [SWAN], 3D fluid-attenuated inversion recovery [FLAIR]) and targeted imaging (2D T2*-weighted dual-echo gradient-recalled echo [GRE] and 2D gray-white matter tissue border enhancement [TBE] fast spin echo inversion recovery [FSE-IR]). MRI studies at 1.5 or 3T deemed unrevealing at the referral center were reviewed by three experts in epilepsy imaging. Reviewers were provided information regarding the suspected localization of the SOZ. The same team subsequently reviewed 7T images. Agreement in imaging interpretation was reached through consensus-based discussions based on visual identification of structural abnormalities and their likely correlation with clinical and electrographic data. 7T MRI revealed structural lesions in 6 (29%) of 21 patients. The diagnostic gain in detection was obtained using GRE and FLAIR images. Four of the six patients with abnormal 7T underwent epilepsy surgery. Histopathology revealed focal cortical dysplasia (FCD) in all. In the remaining 15 patients (71%), 7T MRI remained unrevealing; 4 of the patients underwent epilepsy surgery and histopathologic evaluation revealed gliosis. 7T MRI improves detection of epileptogenic FCD that is not visible at conventional field strengths. A dedicated protocol including whole brain FLAIR and GRE images at 7T

An efficient shutter-less non-uniformity correction method for infrared focal plane arrays

Science.gov (United States)

Huang, Xiyan; Sui, Xiubao; Zhao, Yao

2017-02-01

The non-uniformity response in infrared focal plane array (IRFPA) detectors has a bad effect on images with fixed pattern noise. At present, it is common to use shutter to prevent from radiation of target and to update the parameters of non-uniformity correction in the infrared imaging system. The use of shutter causes "freezing" image. And inevitably, there exists the problems of the instability and reliability of system, power consumption, and concealment of infrared detection. In this paper, we present an efficient shutter-less non-uniformity correction (NUC) method for infrared focal plane arrays. The infrared imaging system can use the data gaining in thermostat to calculate the incident infrared radiation by shell real-timely. And the primary output of detector except the shell radiation can be corrected by the gain coefficient. This method has been tested in real infrared imaging system, reaching high correction level, reducing fixed pattern noise, adapting wide temperature range.

Focal Length Affects Depicted Shape and Perception of Facial Images.

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Vít Třebický

Full Text Available Static photographs are currently the most often employed stimuli in research on social perception. The method of photograph acquisition might affect the depicted subject's facial appearance and thus also the impression of such stimuli. An important factor influencing the resulting photograph is focal length, as different focal lengths produce various levels of image distortion. Here we tested whether different focal lengths (50, 85, 105 mm affect depicted shape and perception of female and male faces. We collected three portrait photographs of 45 (22 females, 23 males participants under standardized conditions and camera setting varying only in the focal length. Subsequently, the three photographs from each individual were shown on screen in a randomized order using a 3-alternative forced-choice paradigm. The images were judged for attractiveness, dominance, and femininity/masculinity by 369 raters (193 females, 176 males. Facial width-to-height ratio (fWHR was measured from each photograph and overall facial shape was analysed employing geometric morphometric methods (GMM. Our results showed that photographs taken with 50 mm focal length were rated as significantly less feminine/masculine, attractive, and dominant compared to the images taken with longer focal lengths. Further, shorter focal lengths produced faces with smaller fWHR. Subsequent GMM revealed focal length significantly affected overall facial shape of the photographed subjects. Thus methodology of photograph acquisition, focal length in this case, can significantly affect results of studies using photographic stimuli perhaps due to different levels of perspective distortion that influence shapes and proportions of morphological traits.

Prenatal sonographic diagnosis of focal musculoskeletal anomalies

Energy Technology Data Exchange (ETDEWEB)

Ryu, Jung Kyu; Cho, Jeong Yeon; Lee, Young Ho; Kim, Ei Jeong; Chun, Yi Kyeong [Samsung Cheil Hospital, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2002-09-15

Focal musculoskeletal anomalies are various and may be an isolated finding or may be found in conjunction with numerous associations, including genetic syndromes, Karyotype abnormals, central nervous system anomalies and other general musculoskeletal disorders. Early prenatal diagnosis of these focal musculoskeletal anomalies nor only affects prenatal care and postnatal outcome but also helps in approaching other numerous associated anomalies.

Prenatal sonographic diagnosis of focal musculoskeletal anomalies

International Nuclear Information System (INIS)

Ryu, Jung Kyu; Cho, Jeong Yeon; Lee, Young Ho; Kim, Ei Jeong; Chun, Yi Kyeong

2002-01-01

Focal musculoskeletal anomalies are various and may be an isolated finding or may be found in conjunction with numerous associations, including genetic syndromes, Karyotype abnormals, central nervous system anomalies and other general musculoskeletal disorders. Early prenatal diagnosis of these focal musculoskeletal anomalies nor only affects prenatal care and postnatal outcome but also helps in approaching other numerous associated anomalies.

FOCAL CORTICAL DYSPLASIAS: CLINICAL AND ELECTRO-NEUROIMAGING CHARACTERISTICS

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K. Yu. Mukhin

2016-01-01

Full Text Available In spite of a notable advance made in epileptology, resistant epilepsies account for approximately 30 % of all forms of epilepsy particularly in patients with focal seizures. One of the main causes of therapy-resistant focal epilepsies is focal cortical dysplasias (FCD. This term was first introduced by D. Taylor et al. in 1971. FCD belongs to abnormal cortical development. Among all abnormalities of cortical development, FCD in surgically treated children amounts to 75 %. FCD is the most common cause of resistant epilepsy in children and the most frequent reason for diagnosing cryptogenic focal epilepsy with intractable seizures. The author gives a detailed literature review dedicated to FCD as a cause of resistant epilepsy, including the classification and histologic characteristics of FCD, its clinical manifestations and prognosis, and approaches to medical and surgical treatments. 

Multispectral linear array (MLA) focal plane mechanical and thermal design

Science.gov (United States)

Mitchell, A. S.; Kaminski, E. F.

1982-01-01

The mechanical and thermal design of an integrated focal plane subsystem of a Multispectral Linear Array (MLA) instrument is discussed in terms of focal-plane alignment, thermoelastic performance, and thermal requirements. The modular construction and thermal control of the focal plane array are discussed.

25m2 target-aligned heliostat with closed-loop control

CSIR Research Space (South Africa)

Roos, TH

2007-09-01

Full Text Available system making use of a solar tracker has been developed and tested on a 1.252m target-aligned miniheliostat. A tracking accuracy of 3.3 milliradians was obtained. A good focal spot has been obtained with the 252m target-aligned research heliostat....

The semiology of febrile seizures: Focal features are frequent.

Science.gov (United States)

Takasu, Michihiko; Kubota, Tetsuo; Tsuji, Takeshi; Kurahashi, Hirokazu; Numoto, Shingo; Watanabe, Kazuyoshi; Okumura, Akihisa

2017-08-01

To clarify the semiology of febrile seizures (FS) and to determine the frequency of FS with symptoms suggestive of focal onset. FS symptoms in children were reported within 24h of seizure onset by the parents using a structured questionnaire consisting principally of closed-ended questions. We focused on events at seizure commencement, including changes in behavior and facial expression, and ocular and oral symptoms. We also investigated the autonomic and motor symptoms developing during seizures. The presence or absence of focal and limbic features was determined for each patient. The associations of certain focal and limbic features with patient characteristics were assessed. Information was obtained on FS in 106 children. Various events were recorded at seizure commencement. Behavioral changes were observed in 35 children, changes in facial expression in 53, ocular symptoms in 78, and oral symptoms in 90. In terms of events during seizures, autonomic symptoms were recognized in 78, and convulsive motor symptoms were recognized in 68 children. Focal features were evident in 81 children; 38 children had two or more such features. Limbic features were observed in 44 children, 9 of whom had two or more such features. There was no significant relationship between any patient characteristic and the numbers of focal or limbic features. The semiology of FS varied widely among children, and symptoms suggestive of focal onset were frequent. FS of focal onset may be more common than is generally thought. Copyright © 2017 Elsevier Inc. All rights reserved.

Importance of Neutralizing Monoclonal Antibodies Targeting Multiple Antigenic Sites on the Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein To Avoid Neutralization Escape

Energy Technology Data Exchange (ETDEWEB)

Wang, Lingshu; Shi, Wei; Chappell, James D.; Joyce, M. Gordon; Zhang, Yi; Kanekiyo, Masaru; Becker, Michelle M.; van Doremalen, Neeltje; Fischer, Robert; Wang, Nianshuang; Corbett, Kizzmekia S.; Choe, Misook; Mason, Rosemarie D.; Van Galen, Joseph G.; Zhou, Tongqing; Saunders, Kevin O.; Tatti, Kathleen M.; Haynes, Lia M.; Kwong, Peter D.; Modjarrad, Kayvon; Kong, Wing-Pui; McLellan, Jason S.; Denison, Mark R.; Munster, Vincent J.; Mascola, John R.; Graham, Barney S.; Gallagher, Tom

2018-03-07

structurally defined probes for the MERS-CoV spike glycoprotein (S), the target for neutralizing antibodies, single B cells were sorted from a convalescent human and immunized nonhuman primates (NHPs). MAbs produced from paired immunoglobulin gene sequences were mapped to multiple epitopes within and outside the receptor-binding domain (RBD) and protected against lethal MERS infection in a murine model following passive immunization. Importantly, combining MAbs targeting distinct epitopes prevented viral neutralization escape from RBD-directed MAbs. These data suggest that antibody responses to multiple domains on CoV spike protein may improve immunity and will guide future vaccine and therapeutic development efforts.

The mitochondrial translocator protein, TSPO, inhibits HIV-1 envelope glycoprotein biosynthesis via the endoplasmic reticulum-associated protein degradation pathway.

Science.gov (United States)

Zhou, Tao; Dang, Ying; Zheng, Yong-Hui

2014-03-01

The HIV-1 Env glycoprotein is folded in the endoplasmic reticulum (ER), which is necessary for viral entry and replication. Currently, it is still unclear how this process is regulated. The glycoprotein folding in the ER is controlled by the ER-associated protein degradation (ERAD) pathway, which specifically targets misfolded proteins for degradation. Previously, we reported that HIV-1 replication is restricted in the human CD4(+) T cell line CEM.NKR (NKR). To understand this mechanism, we first analyzed cellular protein expression in NKR cells and discovered that levels of the mitochondrial translocator protein TSPO were upregulated by ∼64-fold. Notably, when NKR cells were treated with TSPO antagonist PK-11195, Ro5-4864, or diazepam, HIV restriction was completely disrupted, and TSPO knockdown by short hairpin RNAs (shRNAs) achieved a similar effect. We next analyzed viral protein expression, and, interestingly, we discovered that Env expression was specifically inhibited. Both TSPO knockdown and treatment with TSPO antagonist could restore Env expression in NKR cells. We further discovered that Env proteins were rapidly degraded and that kifunensine, an ERAD pathway inhibitor, could restore Env expression and viral replication, indicating that Env proteins were misfolded and degraded through the ERAD pathway in NKR cells. We also knocked out the TSPO gene in 293T cells using CRISPR/Cas9 (clustered, regularly interspaced, short palindromic repeat [CRISPR]/CRISPR-associated-9) technology and found that TSPO could similarly inhibit Env expression in these cells. Taken together, these results demonstrate that TSPO inhibits Env protein expression through the ERAD pathway and suggest that mitochondria play an important role in regulating the Env folding process. The HIV-1 Env glycoprotein is absolutely required for viral infection, and an understanding of its expression pathway in infected cells will identify new targets for antiretroviral therapies. Env proteins

The flexible engagement of monitoring processes in non-focal and focal prospective memory tasks with salient cues.

Science.gov (United States)

Hefer, Carmen; Cohen, Anna-Lisa; Jaudas, Alexander; Dreisbach, Gesine

2017-09-01

Prospective memory (PM) refers to the ability to remember to perform a delayed intention. Here, we aimed to investigate the ability to suspend such an intention and thus to confirm previous findings (Cohen, Gordon, Jaudas, Hefer, & Dreisbach, 2016) demonstrating the ability to flexibly engage in monitoring processes. In the current study, we presented a perceptually salient PM cue (bold and red) to rule out that previous findings were limited to non-salient and, thus, easy to ignore PM cues. Moreover, we used both a non-focal (Experiment 1) and a focal PM (Experiment 2) cue. In both Experiments, three groups of participants performed an Eriksen flanker task as an ongoing task with an embedded PM task (they had to remember to press the F1 key if a pre-specified cue appeared). Participants were assigned to either a control condition (performed solely the flanker task), a standard PM condition (performed the flanker task along with the PM task), or a PM delayed condition (performed the flanker task but were instructed to postpone their PM task intention). The results of Experiment 1 with the non-focal PM cue closely replicated those of Cohen et al. (2016) and confirmed that participants were able to successfully postpone the PM cue intention without additional costs even when the PM cue was a perceptually salient one. However, when the PM cue was focal (Experiment 2), it was much more difficult for participants to ignore it as evidenced by commission errors and slower latencies on PM cue trials. In sum, results showed that the focality of the PM cue plays a more crucial role in the flexibility of the monitoring process whereas the saliency of the PM cue does not. Copyright © 2017 Elsevier B.V. All rights reserved.

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

DEFF Research Database (Denmark)

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

2001-01-01

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

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

Imaging a Time-variant Earthquake Focal Region along an Interplate Boundary

Science.gov (United States)

Tsuruga, K.; Kasahara, J.; Hasada, Y.; Fujii, N.

2010-12-01

We show a preliminary result of a trial for detecting a time-variant earthquake focal region along an interplate boundary by means of a new imaging method through a numerical simulation. Remarkable seismic reflections from the interplate boundaries of a subducting oceanic plate have been observed in Japan Trench (Mochizuki et al, 2005) and in Nankai Trough (Iidaka et al., 2003). Those strong seismic reflection existing in the current aseismic zones suggest the existence of fluid along the subduction boundary, and it is considered that they closely relate to a future huge earthquake. Seismic ACROSS has a potential to monitor some changes of transfer function along the propagating ray paths, by using an accurately-controlled transmission and receiving of the steady continuous signals repeatedly (Kumazawa et al., 2000). If the physical state in a focal region along the interplate would be changed enough in the time and space, for instance, by increasing or decreasing of fluid flow, we could detect some differences of the amplitude and/or travel-time of the particular reflection phases from the time-variant target region. In this study, we first investigated the seismic characteristics of seismograms and their differences before and after the change of a target region through a numerical simulation. Then, as one of the trials, we attempted to make an image of such time-variant target region by applying a finite-difference back-propagation technique in the time and space to the differences of waveforms (after Kasahara et al., 2010). We here used a 2-D seismic velocity model in the central Japan (Tsuruga et al., 2005), assuming a time-variant target region with a 200-m thickness along a subducting Philippine Sea plate at 30 km in depth. Seismograms were calculated at a 500-m interval for 260 km long by using FDM software (Larsen, 2000), in the case that P- and S-wave velocities (Vp amd Vs) in the target region decreased about 30 % before to after the change (e.g., Vp=3

Comparison of glycoprotein expression between ovarian and colon adenocarcinomas

DEFF Research Database (Denmark)

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

1999-01-01

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

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

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Hana Čipčić Paljetak

2011-01-01

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

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

Science.gov (United States)

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

2012-06-01

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

Focal necrotizing pneumonia is a distinct entity from lung abscess.

Science.gov (United States)

Seo, Hyewon; Cha, Seung-Ick; Shin, Kyung-Min; Lim, Jaekwang; Yoo, Seung-Soo; Lee, Jaehee; Lee, Shin-Yup; Kim, Chang-Ho; Park, Jae-Yong

2013-10-01

'Focal necrotizing pneumonia' was defined as a localized type of necrotizing pneumonia characterized by a single or few cavities of low density without rim enhancement on computed tomography (CT) scan. The purpose of this study was to investigate the clinical features and course of patients with focal necrotizing pneumonia, thereby elucidating its clinical relevance. The present study was conducted retrospectively in patients who had been interpreted as having lung abscess or necrotizing pneumonia on CT scan. Clinical and radiological characteristics were compared between the focal necrotizing pneumonia and lung abscess groups. Overall, 68 patients with focal necrotizing pneumonia (n = 35) or lung abscess (n = 33) were included in the present study. The frequency of risk factors for aspiration was significantly lower in the focal necrotizing group, compared with the lung abscess group (14.3% vs 45.5%, P = 0.005). Compared with lung abscess, focal necrotizing pneumonia was observed more commonly in non-gravity-dependent segments (66% vs 36%, P lung abscess group (31% vs 12%, P = 0.08). However, in terms of treatment outcomes, a similar high rate of success was observed in both groups: 97%, respectively. Compared to lung abscess, focal necrotizing pneumonia occurs more commonly in non-gravity-dependent segments with lower incidence of risk factors for aspiration. Similar to lung abscess, the rate of success for treatment of focal necrotizing pneumonia was high. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

Noninvasive treatment of focal adenomyosis with MR-guided focused ultrasound in two patients

International Nuclear Information System (INIS)

Polina, Laveena; Nyapathy, Vinay; Mishra, Anindita; Yellamanthili, Himabindu; Vallabhaneni, Mythri P

2012-01-01

Adenomyosis is a common benign gynecological disorder presenting with dysmenorrhea, menorrhagia, and pressure symptoms. Magnetic resonance imaging–guided focused ultrasound surgery (MRgFUS) utilizes precisely focused USG waves to generate and maintain high temperatures within the targeted tissue to achieve protein denaturation and coagulative necrosis. The heat generated is monitored using MRI images acquired in real-time in three planes. We present two cases of focal adenomyosis treated with MRgFUS showing good symptomatic relief at 3 and 6 months follow-up

Pseudotyped Lentiviral Vectors for Retrograde Gene Delivery into Target Brain Regions

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Kenta Kobayashi

2017-08-01

Full Text Available Gene transfer through retrograde axonal transport of viral vectors offers a substantial advantage for analyzing roles of specific neuronal pathways or cell types forming complex neural networks. This genetic approach may also be useful in gene therapy trials by enabling delivery of transgenes into a target brain region distant from the injection site of the vectors. Pseudotyping of a lentiviral vector based on human immunodeficiency virus type 1 (HIV-1 with various fusion envelope glycoproteins composed of different combinations of rabies virus glycoprotein (RV-G and vesicular stomatitis virus glycoprotein (VSV-G enhances the efficiency of retrograde gene transfer in both rodent and nonhuman primate brains. The most recently developed lentiviral vector is a pseudotype with fusion glycoprotein type E (FuG-E, which demonstrates highly efficient retrograde gene transfer in the brain. The FuG-E–pseudotyped vector permits powerful experimental strategies for more precisely investigating the mechanisms underlying various brain functions. It also contributes to the development of new gene therapy approaches for neurodegenerative disorders, such as Parkinson’s disease, by delivering genes required for survival and protection into specific neuronal populations. In this review article, we report the properties of the FuG-E–pseudotyped vector, and we describe the application of the vector to neural circuit analysis and the potential use of the FuG-E vector in gene therapy for Parkinson’s disease.

Proximal Focal Femoral Deficiency in Ibadan a Developing ...

African Journals Online (AJOL)

The cultural aversion to amputation in our environment makes it difficult to employ that option of treatment. Proximal focal femoral deficiency in Ibadan a developing country's perspective and a review of the literature. Keywords: Proximal focal femoral deficiency , congenital malformations , limb malformations , lower limb ...

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

Pigment Epithelium-Derived Factor Reduces Apoptosis and Pro-Inflammatory Cytokine Gene Expression in a Murine Model of Focal Retinal Degeneration

Directory of Open Access Journals (Sweden)

Yujuan Wang

2013-10-01

Full Text Available AMD (age-related macular degeneration is a neurodegenerative disease causing irreversible central blindness in the elderly. Apoptosis and inflammation play important roles in AMD pathogenesis. PEDF (pigment epithelium-derived factor is a potent neurotrophic and anti-inflammatory glycoprotein that protects the retinal neurons and photoreceptors against cell death caused by pathological insults. We studied the effects of PEDF on focal retinal lesions in DKO rd8 (Ccl2 −/− /Cx3cr1 −/− on C57BL/6N [Crb1rd8 ] mice, a model for progressive, focal rd (retinal degeneration. First, we found a significant decrease in PEDF transcript expression in DKO rd8 mouse retina and RPE (retinal pigment epithelium than WT (wild-type, C57BL/6N. Next, cultured DKO rd8 RPE cells secreted lower levels of PEDF protein in the media than WT. Then the right eyes of DKO rd8 mice were injected intravitreously with recombinant human PEDF protein (1 μg, followed by a subconjunctival injection of PEDF (3 μg 4 weeks later. The untreated left eyes served as controls. The effect of PEDF was assessed by fundoscopy, ocular histopathology and A2E {[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl-1E,3E,5E,7E-octatetra-enyl]-1-(2-hydroxyethyl-4-[4-methyl-6(2,6,6-trimethyl-1-cyclohexen-1-yl 1E,3E,5E,7E-hexatrienyl]-pyridinium} levels, as well as apoptotic and inflammatory molecules. The PEDF-treated eyes showed slower progression or attenuation of the focal retinal lesions, fewer and/or smaller photoreceptor and RPE degeneration, and significantly lower A2E, relative to the untreated eyes. In addition, lower expression of apoptotic and inflammatory molecules were detected in the PEDF-treated than untreated eyes. Our results establish that PEDF potently stabilizes photoreceptor degeneration via suppression of both apoptotic and inflammatory pathways. The multiple beneficial effects of PEDF represent a novel approach for potential AMD treatment.

Pigment epithelium-derived factor reduces apoptosis and pro-inflammatory cytokine gene expression in a murine model of focal retinal degeneration.

Science.gov (United States)

Wang, Yujuan; Subramanian, Preeti; Shen, Defen; Tuo, Jingsheng; Becerra, S Patricia; Chan, Chi-Chao

2013-11-26

AMD (age-related macular degeneration) is a neurodegenerative disease causing irreversible central blindness in the elderly. Apoptosis and inflammation play important roles in AMD pathogenesis. PEDF (pigment epithelium-derived factor) is a potent neurotrophic and anti-inflammatory glycoprotein that protects the retinal neurons and photoreceptors against cell death caused by pathological insults. We studied the effects of PEDF on focal retinal lesions in DKO rd8 (Ccl2(-/-)/Cx3cr1(-/-) on C57BL/6N [Crb1(rd8)]) mice, a model for progressive, focal rd (retinal degeneration). First, we found a significant decrease in PEDF transcript expression in DKO rd8 mouse retina and RPE (retinal pigment epithelium) than WT (wild-type, C57BL/6N). Next, cultured DKO rd8 RPE cells secreted lower levels of PEDF protein in the media than WT. Then the right eyes of DKO rd8 mice were injected intravitreously with recombinant human PEDF protein (1 μg), followed by a subconjunctival injection of PEDF (3 μg) 4 weeks later. The untreated left eyes served as controls. The effect of PEDF was assessed by fundoscopy, ocular histopathology and A2E {[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetra-enyl]-1-(2-hydroxyethyl)-4-[4-methyl-6(2,6,6-trimethyl-1-cyclohexen-1-yl) 1E,3E,5E,7E-hexatrienyl]-pyridinium} levels, as well as apoptotic and inflammatory molecules. The PEDF-treated eyes showed slower progression or attenuation of the focal retinal lesions, fewer and/or smaller photoreceptor and RPE degeneration, and significantly lower A2E, relative to the untreated eyes. In addition, lower expression of apoptotic and inflammatory molecules were detected in the PEDF-treated than untreated eyes. Our results establish that PEDF potently stabilizes photoreceptor degeneration via suppression of both apoptotic and inflammatory pathways. The multiple beneficial effects of PEDF represent a novel approach for potential AMD treatment.

A Plutonium Ceramic Target for MASHA

International Nuclear Information System (INIS)

Wilk, P A; Shaughnessy, D A; Moody, K J; Kenneally, J M; Wild, J F; Stoyer, M A; Patin, J B; Lougheed, R W; Ebbinghaus, B B; Landingham, R L; Oganessian, Y T; Yeremin, A V; Dmitriev, S N

2004-01-01

We are currently developing a plutonium ceramic target for the MASHA mass separator. The MASHA separator will use a thick plutonium ceramic target capable of tolerating temperatures up to 2000 C. Promising candidates for the target include oxides and carbides, although more research into their thermodynamic properties will be required. Reaction products will diffuse out of the target into an ion source, where they will then be transported through the separator to a position-sensitive focal-plane detector array. Experiments on MASHA will allow us to make measurements that will cement our identification of element 114 and provide for future experiments where the chemical properties of the heaviest elements are studied

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

Energy Technology Data Exchange (ETDEWEB)

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

1978-03-18

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

Why there? Decomposing the choice of target industry

OpenAIRE

Lien, Lasse B.; Klein, Peter G.

2013-01-01

How do diversifying firms chose their target industries? We explore target-industry choice empirically by focusing on the relative importance of target-market characteristics and the focal firm’s resources and capabilities. We avoid some key restrictions in earlier work by using a measure of relatedness that is highly general and flexible, using population-level data, and including measures of resource strength in addition to resource relevance. We find that the match between the acquiring an...

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

Science.gov (United States)

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

2017-11-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2009-03-16

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

DESI focal plate mechanical integration and cooling

Science.gov (United States)

Lambert, A. R.; Besuner, R. W.; Claybaugh, T. M.; Silber, J. H.

2016-08-01

The Dark Energy Spectroscopic Instrument (DESI) is under construction to measure the expansion history of the Universe using the Baryon Acoustic Oscillation technique[1]. The spectra of 40 million galaxies over 14000 sq. deg will be measured during the life of the experiment. A new prime focus corrector for the KPNO Mayall telescope will deliver light to 5000 fiber optic positioners. The fibers in turn feed ten broad-band spectrographs. This paper describes the mechanical integration of the DESI focal plate and the thermal system design. The DESI focal plate is comprised of ten identical petal assemblies. Each petal contains 500 robotic fiber positioners. Each petal is a complete, self-contained unit, independent from the others, with integrated power supply, controllers, fiber routing, and cooling services. The major advantages of this scheme are: (1) supports installation and removal of complete petal assemblies in-situ, without disturbing the others, (2) component production, assembly stations, and test procedures are repeated and parallelizable, (3) a complete, full-scale prototype can be built and tested at an early date, (4) each production petal can be surveyed and tested as a complete unit, prior to integration, from the fiber tip at the focal surface to the fiber slit at the spectrograph. The ten petal assemblies will be installed in a single integration ring, which is mounted to the DESI corrector. The aluminum integration ring attaches to the steel corrector barrel via a flexured steel adapter, isolating the focal plate from differential thermal expansions. The plate scale will be kept stable by conductive cooling of the petal assembly. The guider and wavefront sensors (one per petal) will be convectively cooled by forced flow of air. Heat will be removed from the system at ten liquid-cooled cold plates, one per petal, operating at ambient temperature. The entire focal plate structure is enclosed in an insulating shroud, which serves as a thermal barrier

Focal fatty infiltra- tion and focal fatty sparing of the liver

African Journals Online (AJOL)

Enrique

Department of Radiology. Nelson Mandela School of Health Sciences. Durban. Fig. 1a. Unenhanced CT of the liver in case 1 demonstrates multiple focal low density regions in both lobes of the liver. Region of interest 1 over the fatty left lobe measured 10 HU while region of interest 2 over the right lobe measure 40 HU in.

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

Directory of Open Access Journals (Sweden)

Menzel Diedrik

2011-02-01

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

Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein

Directory of Open Access Journals (Sweden)

Anna-Janina Behrens

2016-03-01

Full Text Available The HIV-1 envelope glycoprotein trimer is covered by an array of N-linked glycans that shield it from immune surveillance. The high density of glycans on the trimer surface imposes steric constraints limiting the actions of glycan-processing enzymes, so that multiple under-processed structures remain on specific areas. These oligomannose glycans are recognized by broadly neutralizing antibodies (bNAbs that are not thwarted by the glycan shield but, paradoxically, target it. Our site-specific glycosylation analysis of a soluble, recombinant trimer (BG505 SOSIP.664 maps the extremes of simplicity and diversity of glycan processing at individual sites and reveals a mosaic of dense clusters of oligomannose glycans on the outer domain. Although individual sites usually minimally affect the global integrity of the glycan shield, we identify examples of how deleting some glycans can subtly influence neutralization by bNAbs that bind at distant sites. The network of bNAb-targeted glycans should be preserved on vaccine antigens.

Rat macrophages: membrane glycoproteins in differentiation and function

NARCIS (Netherlands)

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

2001-01-01

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

3D Registration of mpMRI for Assessment of Prostate Cancer Focal Therapy.

Science.gov (United States)

Orczyk, Clément; Rosenkrantz, Andrew B; Mikheev, Artem; Villers, Arnauld; Bernaudin, Myriam; Taneja, Samir S; Valable, Samuel; Rusinek, Henry

2017-12-01

This study aimed to assess a novel method of three-dimensional (3D) co-registration of prostate magnetic resonance imaging (MRI) examinations performed before and after prostate cancer focal therapy. We developed a software platform for automatic 3D deformable co-registration of prostate MRI at different time points and applied this method to 10 patients who underwent focal ablative therapy. MRI examinations were performed preoperatively, as well as 1 week and 6 months post treatment. Rigid registration served as reference for assessing co-registration accuracy and precision. Segmentation of preoperative and postoperative prostate revealed a significant postoperative volume decrease of the gland that averaged 6.49 cc (P = .017). Applying deformable transformation based on mutual information from 120 pairs of MRI slices, we refined by 2.9 mm (max. 6.25 mm) the alignment of the ablation zone, segmented from contrast-enhanced images on the 1-week postoperative examination, to the 6-month postoperative T2-weighted images. This represented a 500% improvement over the rigid approach (P = .001), corrected by volume. The dissimilarity by Dice index of the mapped ablation zone using deformable transformation vs rigid control was significantly (P = .04) higher at the ablation site than in the whole gland. Our findings illustrate our method's ability to correct for deformation at the ablation site. The preliminary analysis suggests that deformable transformation computed from mutual information of preoperative and follow-up MRI is accurate in co-registration of MRI examinations performed before and after focal therapy. The ability to localize the previously ablated tissue in 3D space may improve targeting for image-guided follow-up biopsy within focal therapy protocols. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

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

DEFF Research Database (Denmark)

Kirkeby, S; Moe, D; Bøg-Hansen, T C

1990-01-01

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

Glycoprotein CD98 as a receptor for colitis-targeted delivery of nanoparticle†

OpenAIRE

Xiao, Bo; Yang, Yang; Viennois, Emilie; Zhang, Yuchen; Ayyadurai, Saravanan; Baker, Mark; Laroui, Hamed; Merlin, Didier

2014-01-01

Treatment strategies for inflammatory bowel disease have been constrained by limited therapeutic efficacy and serious adverse effects owing to a lack of receptor for targeted drug delivery to the inflamed colon. Upon inflammation, CD98 expression is highly elevated in colonic epithelial cells and infiltrating immune cells. To investigate whether CD98 can be used as a colitis-targeted delivery receptor, we constructed CD98 Fab′-bearing quantum dots (QDs)-loaded nanoparticles (Fab′-NPs). The re...

Thermomechanical architecture of the VIS focal plane for Euclid

International Nuclear Information System (INIS)

Martignac, Jerome; Carty, Michael; Tourette, Thierry; Bachet, Damien; Berthe, Michel; Augueres, Jean-Louis; Amiaux, Jerome; Fontignie, Jean; Horeau, Benoit; Renaud, Diana

2014-01-01

One of the main challenges for current and near future space experiments is the increase of focal plane complexity in terms of amount of pixels. In the frame work of the ESA Euclid mission to be launched in 2020, the Euclid Consortium is developing an extremely large and stable focal plane for the VIS instrument. CEA has developed the thermomechanical architecture of that Focal Plane taking into account all the very stringent performance and mission related requirements. The VIS Focal Plane Assembly integrates 36 CCDs (operated at 150 K) connected to their front end electronics (operated at 280 K) as to obtain one of the largest focal plane (0.6 billion pixels) ever built for space application after the GAIA one. The CCDs are CCD273 type specially designed and provided by the e2v company under ESA contract, front end electronics is studied and provided by MSSL. In this paper we first recall the specific requirements that have driven the overall architecture of the VIS-FPA and especially the solutions proposed to cope with the scientific needs of an extremely stable focal plane, both mechanically and thermally. The mechanical structure based on SiC material used for the cold sub assembly supporting the CCDs is detailed. We describe also the modular architecture concept that we have selected taking into account AIT-AIV and programmatic constraints. (authors)

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

Energy Technology Data Exchange (ETDEWEB)

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

2002-08-01

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

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

Science.gov (United States)

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

1992-01-01

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

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

Directory of Open Access Journals (Sweden)

Pilar T. V. Florentino

2018-04-01

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

Uniform irradiation of adjustable target spots in high-power laser driver

International Nuclear Information System (INIS)

Jiang Xiujuan; Li Jinghui; Li Huagang; Li Yang; Lin Zunqi

2011-01-01

For smoothing and shaping the on-target laser patterns flexibly in high-power laser drivers, a scheme has been developed that includes a zoom lens array and two-dimensional smoothing by spectral dispersion (SSD). The size of the target pattern can be controlled handily by adjusting the focal length of the zoom lens array, while the profile of the pattern can be shaped by fine tuning the distance between the target and the focal plane of the principal focusing lens. High-frequency stripes inside the pattern caused by beamlet interference are wiped off by spectral dispersion. Detailed simulations indicate that SSD works somewhat differently for spots of different sizes. For small spots, SSD mainly smooths the intensity modulation of low-to-middle spatial frequency, while for large spots, SSD sweeps the fine speckle structure to reduce nonuniformity of middle-to-high frequency. Spatial spectra of the target patterns are given and their uniformity is evaluated.

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

Science.gov (United States)

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

1985-08-01

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

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

Indian Academy of Sciences (India)

2017-01-11

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

Glycoprotein CD98 as a receptor for colitis-targeted delivery of nanoparticle.

Science.gov (United States)

Xiao, Bo; Yang, Yang; Viennois, Emilie; Zhang, Yuchen; Ayyadurai, Saravanan; Baker, Mark; Laroui, Hamed; Merlin, Didier

2014-03-21

Treatment strategies for inflammatory bowel disease have been constrained by limited therapeutic efficacy and serious adverse effects owing to a lack of receptor for targeted drug delivery to the inflamed colon. Upon inflammation, CD98 expression is highly elevated in colonic epithelial cells and infiltrating immune cells. To investigate whether CD98 can be used as a colitis-targeted delivery receptor, we constructed CD98 Fab'-bearing quantum dots (QDs)-loaded nanoparticles (Fab'-NPs). The resultant Fab'-NPs had desired particle size (~458 nm) with a narrow size distribution and zeta-potential (approximately +19 mV), low cytotoxicity, and excellent fluorescence properties. Electron microscopy images provided direct evidence for the well-dispersed distribution of QDs within spherical Fab'-NPs. Cellular uptake experiments demonstrated that Fab'-NPs were efficiently internalized into Colon-26 and RAW 264.7 cells through the CD98-mediated endocytosis pathway, and showed that the targeting effect of CD98 Fab' markedly increased their cellular uptake efficiency compared with control pegylated QDs-loaded NPs (PEG-NPs). Furthermore, ex vivo studies showed much more effective accumulation of Fab'-NPs in colitis tissue than that of PEG-NPs. These findings suggest that because of inflammation-dependent over-expression of CD98, active colitis-targeted delivery can be accomplished using NPs decorated with CD98 antibody.

Focal cemento-osseous dysplasia: review and a case report.

Science.gov (United States)

Salem, Y M Y; Osman, Y I; Norval, E J G

2010-10-01

Focal cemento-osseous dysplasia is a benign fibro-osseous condition that can be seen in dentate and edentulous patients. It is an asymptomatic lesion and needs no treatment; however follow-up is essential due to the possibility that focal cemento-osseous dysplasia can progress to a condition called florid osseous dysplasia that involves multiple sites. A case report is presented here, along with a review of the differential diagnoses considered in order to reach a final diagnosis of focal cemento-osseous dysplasia.

Germline and somatic mutations in the MTOR gene in focal cortical dysplasia and epilepsy

DEFF Research Database (Denmark)

Møller, Rikke S; Weckhuysen, Sarah; Chipaux, Mathilde

2016-01-01

OBJECTIVE: To assess the prevalence of somatic MTOR mutations in focal cortical dysplasia (FCD) and of germline MTOR mutations in a broad range of epilepsies. METHODS: We collected 20 blood-brain paired samples from patients with FCD and searched for somatic variants using deep-targeted gene panel...... sequencing. Germline mutations in MTOR were assessed in a French research cohort of 93 probands with focal epilepsies and in a diagnostic Danish cohort of 245 patients with a broad range of epilepsies. Data sharing among collaborators allowed us to ascertain additional germline variants in MTOR. RESULTS: We...... detected recurrent somatic variants (p.Ser2215Phe, p.Ser2215Tyr, and p.Leu1460Pro) in the MTOR gene in 37% of participants with FCD II and showed histologic evidence for activation of the mTORC1 signaling cascade in brain tissue. We further identified 5 novel de novo germline missense MTOR variants in 6...

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

NARCIS (Netherlands)

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

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

MDR1 P-glycoprotein transports endogenous opioid peptides

NARCIS (Netherlands)

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

2001-01-01

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

Self-Calibration Method Based on Surface Micromaching of Light Transceiver Focal Plane for Optical Camera

Directory of Open Access Journals (Sweden)

Jin Li

2016-10-01

Full Text Available In remote sensing photogrammetric applications, inner orientation parameter (IOP calibration of remote sensing camera is a prerequisite for determining image position. However, achieving such a calibration without temporal and spatial limitations remains a crucial but unresolved issue to date. The accuracy of IOP calibration methods of a remote sensing camera determines the performance of image positioning. In this paper, we propose a high-accuracy self-calibration method without temporal and spatial limitations for remote sensing cameras. Our method is based on an auto-collimating dichroic filter combined with a surface micromachining (SM point-source focal plane. The proposed method can autonomously complete IOP calibration without the need of outside reference targets. The SM procedure is used to manufacture a light transceiver focal plane, which integrates with point sources, a splitter, and a complementary metal oxide semiconductor sensor. A dichroic filter is used to fabricate an auto-collimation light reflection element. The dichroic filter, splitter, and SM point-source focal plane are integrated into a camera to perform an integrated self-calibration. Experimental measurements confirm the effectiveness and convenience of the proposed method. Moreover, the method can achieve micrometer-level precision and can satisfactorily complete real-time calibration without temporal or spatial limitations.

Natural Products based P-glycoprotein Activators for Improved β-amyloid Clearance in Alzheimer's Disease: An in silico Approach.

Science.gov (United States)

Shinde, Pravin; Vidyasagar, Nikhil; Dhulap, Sivakami; Dhulap, Abhijeet; Hirwani, Raj

2015-01-01

Alzheimer's disease is an age related disorder and is defined to be progressive, irreversible neurodegenerative disease. The potential targets which are associated with the Alzheimer's disease are cholinesterases, N-methyl-D-aspartate receptor, Beta secretase 1, Pregnane X receptor (PXR) and P-glycoprotein (Pgp). P-glycoprotein is a member of the ATP binding cassette (ABC) transporter family, which is an important integral of the blood-brain, blood-cerebrospinal fluid and the blood-testis barrier. Reports from the literature provide evidences that the up-regulation of the efflux pump is liable for a decrease in β -amyloid intracellular accumulation and is an important hallmark in Alzheimer's disease (AD). Thus, targeting β-amyloid clearance by stimulating Pgp could be a useful strategy to prevent Alzheimer's advancement. Currently available drugs provide limited effectiveness and do not assure to cure Alzheimer's disease completely. On the other hand, the current research is now directed towards the development of synthetic or natural based therapeutics which can delay the onset or progression of Alzheimer's disease. Since ancient time medicinal plants such as Withania somnifera, Bacopa monieri, Nerium indicum have been used to prevent neurological disorders including Alzheimer's disease. Till today around 125 Indian medicinal plants have been screened on the basis of ethnopharmacology for their activity against neurological disorders. In this paper, we report bioactives from natural sources which show binding affinity towards the Pgp receptor using ligand based pharmacophore development, virtual screening, molecular docking and molecular dynamics simulation studies for the bioactives possessing acceptable ADME properties. These bioactives can thus be useful to treat Alzheimer's disease.

Interaction between Ebola Virus Glycoprotein and Host Toll-Like Receptor 4 Leads to Induction of Proinflammatory Cytokines and SOCS1 ▿ †

OpenAIRE

Okumura, Atsushi; Pitha, Paula M.; Yoshimura, Akihiko; Harty, Ronald N.

2009-01-01

Ebola virus initially targets monocytes and macrophages, which can lead to the release of proinflammatory cytokines and chemokines. These inflammatory cytokines are thought to contribute to the development of circulatory shock seen in fatal Ebola virus infections. Here we report that host Toll-like receptor 4 (TLR4) is a sensor for Ebola virus glycoprotein (GP) on virus-like particles (VLPs) and that resultant TLR4 signaling pathways lead to the production of proinflammatory cytokines and sup...

Fast multifrequency focal beam analysis for 3D seismic acquisition geometry

NARCIS (Netherlands)

Wei, W.; Fu, L.; Blacquiere, G.

2012-01-01

A method for the efficient computation of multifrequency focal beams for 3D seismic acquisition geometry analysis has been developed. By computing them for all the frequency components of seismic data, single-frequency focal beams can be extended to multifrequency focal beams. However, this

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

Directory of Open Access Journals (Sweden)

A.M. Al-Sulaiman

2017-11-01

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

Quantitative analysis of N-glycans from human alfa-acid-glycoprotein using stable isotope labeling and zwitterionic hydrophilic interaction capillary liquid chromatography electrospray mass spectrometry as tool for pancreatic disease diagnosis

International Nuclear Information System (INIS)

Giménez, Estela; Balmaña, Meritxell; Figueras, Joan; Fort, Esther; Bolós, Carme de; Sanz-Nebot, Victòria; Peracaula, Rosa; Rizzi, Andreas

2015-01-01

candidate structure worth to be corroborated by an extended study including more clinical cases; especially those with chronic pancreatitis and initial stages of pancreatic cancer. Importantly, the results demonstrate that the presented methodology combining an enrichment of a target protein by IAC with isotope coded relative quantitation of N-glycans can be successfully used for targeted glycomics studies. The methodology is assumed being suitable as well for other such studies aimed at finding novel cancer associated glycoprotein biomarkers

Simulation of a conductive shield plate for the focalization of transcranial magnetic stimulation in the rat.

Science.gov (United States)

Gasca, Fernando; Richter, Lars; Schweikard, Achim

2010-01-01

Transcranial Magnetic Stimulation (TMS) in the rat is a powerful tool for investigating brain function. However, the state-of-the-art experiments are considerably limited because the stimulation usually affects undesired anatomical structures. A simulation of a conductive shield plate placed between the coil stimulator and the rat brain during TMS is presented. The Finite Element (FE) method is used to obtain the 3D electric field distribution on a four-layer rat head model. The simulations show that the shield plate with a circular window can improve the focalization of stimulation, as quantitatively seen by computing the three-dimensional half power region (HPR). Focalization with the shield plate showed a clear compromise with the attenuation of the induced field. The results suggest that the shield plate can work as a helpful tool for conducting TMS rat experiments on specific targets.

SU-F-J-160: Clinical Evaluation of Targeting Accuracy in Radiosurgery Using Tractography

Energy Technology Data Exchange (ETDEWEB)

Juh, R; Han, J; Kim, C; Oh, C [Seoul National University Bundang Hospital, Seongnamsi, GyeonggiDo (Korea, Republic of); Suh, T [The catholic university of Korea, Seoul (Korea, Republic of)

2016-06-15

Purpose: Focal radiosurgery is a common treatment modality for trigeminal neuralgia (TN), a neuropathic facial pain condition. Assessment of treatment effectiveness is primarily clinical, given the paucity of investigational tools to assess trigeminal nerve changes. The efficiency of radiosurgery is related to its highly precise targeting. We assessed clinically the targeting accuracy of radiosurgery with Gamma knife. We hypothesized that trigeminal tractography provides more information than 2D-MR imaging, allowing detection of unique, focal changes in the target area after radiosurgery. Methods: Sixteen TN patients (2 females, 4 males, average age 65.3 years) treated with Gamma Knife radiosurgery, 40 Gy/50% isodose line underwent 1.5Tesla MR trigeminal nerve. Target accuracy was assessed from deviation of the coordinates of the target compared with the center of enhancement on post MRI. Radiation dose delivered at the borders of contrast enhancement was evaluated. Results: The median deviation of the coordinates between the intended target and the center of contrast enhancement was within 1mm. The radiation doses fitting within the borders of the contrast enhancement the target ranged from 37.5 to 40 Gy. Trigeminal tractography accurately detected the radiosurgical target. Radiosurgery resulted in 47% drop in FA values at the target with no significant change in FA outside the target, suggesting that radiosurgery primarily affects myelin. Tractography was more sensitive, since FA changes were detected regardless of trigeminal nerve enhancement. Conclusion: The median deviation found in clinical assessment of gamma knife treatment for TN Is low and compatible with its high rate of efficiency. DTI parameters accurately detect the effects of focal radiosurgery on the trigeminal nerve, serving as an in vivo imaging tool to study TN. This study is a proof of principle for further assessment of DTI parameters to understand the pathophysiology of TN and treatment

Position sensitive proportional counters as focal plane detectors

International Nuclear Information System (INIS)

Ford, J.L.C. Jr.

1979-01-01

The rise time and charge division techniques for position decoding with RC-line proportional counters are reviewed. The advantages that these detectors offer as focal plane counters for nuclear spectroscopy performed with magnetic spectrographs are discussed. The theory of operation of proportional counters as position sensing devices is summarized, as well as practical aspects affecting their application. Factors limiting the position and energy resolutions obtainable with a focal plane proportional counter are evaluated and measured position and energy loss values are presented for comparison. Detector systems capable of the multiparameter measurements required for particle identification, background suppression and ray-tracing are described in order to illustrate the wide applicability of proportional counters within complex focal plane systems. Examples of the use of these counters other than with magnetic spectrographs are given in order to demonstrate their usefulness in not only nuclear physics but also in fields such as solid state physics, biology, and medicine. The influence of the new focal plane detector systems on future magnetic spectrograph designs is discussed. (Auth.)

Catalytic transitions in the human MDR1 P-glycoprotein drug binding sites.

Science.gov (United States)

Wise, John G

2012-06-26

Multidrug resistance proteins that belong to the ATP-binding cassette family like the human P-glycoprotein (ABCB1 or Pgp) are responsible for many failed cancer and antiviral chemotherapies because these membrane transporters remove the chemotherapeutics from the targeted cells. Understanding the details of the catalytic mechanism of Pgp is therefore critical to the development of inhibitors that might overcome these resistances. In this work, targeted molecular dynamics techniques were used to elucidate catalytically relevant structures of Pgp. Crystal structures of homologues in four different conformations were used as intermediate targets in the dynamics simulations. Transitions from conformations that were wide open to the cytoplasm to transition state conformations that were wide open to the extracellular space were studied. Twenty-six nonredundant transitional protein structures were identified from these targeted molecular dynamics simulations using evolutionary structure analyses. Coupled movement of nucleotide binding domains (NBDs) and transmembrane domains (TMDs) that form the drug binding cavities were observed. Pronounced twisting of the NBDs as they approached each other as well as the quantification of a dramatic opening of the TMDs to the extracellular space as the ATP hydrolysis transition state was reached were observed. Docking interactions of 21 known transport ligands or inhibitors were analyzed with each of the 26 transitional structures. Many of the docking results obtained here were validated by previously published biochemical determinations. As the ATP hydrolysis transition state was approached, drug docking in the extracellular half of the transmembrane domains seemed to be destabilized as transport ligand exit gates opened to the extracellular space.

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

International Nuclear Information System (INIS)

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

1996-01-01

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

Benign focal liver lesions: discrimination from malignant mimickers.

Science.gov (United States)

Alobaidi, Mohammad; Shirkhoda, Ali

2004-01-01

Focal lesions of the liver often have various imaging characteristics which may be interpreted as either benign or malignant. Understanding the underlying pathophysiology of these liver lesions may lead to characteristic imaging manifestations, which direct the radiologist to the diagnosis. Benign lesions include congenital hepatic cyst, autosomal dominant polycystic disease, hemangioma, focal nodular hyperplasia (FNH), hepatic adenoma, inflammatory pseudotumor, peliosis hepatis, focal fatty infiltration, hamartoma, and infectious processes such as hepatic abscess, echinococcal cyst, and candidiasis. Characteristic imaging features, clinical symptoms, and treatment/prognosis will be discussed. Emphasis will be placed on key reliable features of each disease to develop a method of discriminating these lesions from other benign and malignant disorders.

Actinic Granuloma with Focal Segmental Glomerulosclerosis

Directory of Open Access Journals (Sweden)

Ruedee Phasukthaworn

2016-02-01

Full Text Available Actinic granuloma is an uncommon granulomatous disease, characterized by annular erythematous plaque with central clearing predominately located on sun-damaged skin. The pathogenesis is not well understood, ultraviolet radiation is recognized as precipitating factor. We report a case of a 52-year-old woman who presented with asymptomatic annular erythematous plaques on the forehead and both cheeks persisting for 2 years. The clinical presentation and histopathologic findings support the diagnosis of actinic granuloma. During that period of time, she also developed focal segmental glomerulosclerosis. The association between actinic granuloma and focal segmental glomerulosclerosis needs to be clarified by further studies.

Podoplanin - an emerging cancer biomarker and therapeutic target.

Science.gov (United States)

Krishnan, Harini; Rayes, Julie; Miyashita, Tomoyuki; Ishii, Genichiro; Retzbach, Edward P; Sheehan, Stephanie A; Takemoto, Ai; Chang, Yao-Wen; Yoneda, Kazue; Asai, Jun; Jensen, Lasse; Chalise, Lushun; Natsume, Atsushi; Goldberg, Gary S

2018-03-25

Podoplanin (PDPN) is a transmembrane receptor glycoprotein that is upregulated on transformed cells, cancer associated fibroblasts (CAFs), and inflammatory macrophages that contribute to cancer progression. In particular, PDPN increases tumor cell clonal capacity, epithelial mesenchymal transition (EMT), migration, invasion, metastasis, and inflammation. Antibodies, CAR-T cells, biologics, and synthetic compounds that target PDPN can inhibit cancer progression and septic inflammation in preclinical models. This review describes recent advances in how PDPN may be used as a biomarker and therapeutic target for many types of cancer including glioma, squamous cell carcinoma, mesothelioma, and melanoma. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

a Plutonium Ceramic Target for Masha

Science.gov (United States)

Wilk, P. A.; Shaughnessy, D. A.; Moody, K. J.; Kenneally, J. M.; Wild, J. F.; Stoyer, M. A.; Patin, J. B.; Lougheed, R. W.; Ebbinghaus, B. B.; Landingham, R. L.; Oganessian, Yu. Ts.; Yeremin, A. V.; Dmitriev, S. N.

2005-09-01

We are currently developing a plutonium ceramic target for the MASHA mass separator. The MASHA separator will use a thick plutonium ceramic target capable of tolerating temperatures up to 2000 °C. Promising candidates for the target include oxides and carbides, although more research into their thermodynamic properties will be required. Reaction products will diffuse out of the target into an ion source, where they will then be transported through the separator to a position-sensitive focal-plane detector array. Experiments on MASHA will allow us to make measurements that will cement our identification of element 114 and provide for future experiments where the chemical properties of the heaviest elements are studied.

Natural-focal diseases: mapping experience in Russia.

Science.gov (United States)

Malkhazova, Svetlana M; Mironova, Varvara A; Kotova, Tatiana V; Shartova, Natalia V; Orlov, Dmitry S

2014-06-14

Natural-focal diseases constitute a serious hazard for human health. Agents and vectors of such diseases belong to natural landscapes. The aim of this study is to identify the diversity and geography of natural-focal diseases in Russia and to develop cartographic approaches for their mapping, including mathematical-cartographical modeling. Russian medico-geographical mapping of natural-focal diseases is highly developed regionally and locally but extremely limited at the national level. To solve this problem, a scientific team of the Faculty of Geography at Lomonosov Moscow State University has developed and implemented a project of a medico-geographical Atlas of Russia "Natural-Focal Diseases". The mapping is based on medical statistics data. The Atlas contains a series of maps on disease incidence, long-term dynamics of disease morbidity, etc. In addition, other materials available to the authors were used: mapping of the natural environment, field data, archival materials, analyzed satellite images, etc. The maps are processed using ArcGIS (ESRI) software application. Different methods of rendering of mapped phenomena are used (geographical ranges, diagrams, choropleth maps etc.). A series of analytical, integrated, and synthetic maps shows disease incidence in the population at both the national and regional levels for the last 15 years. Maps of the mean annual morbidity of certain infections and maps of morbidity dynamics and nosological profiles allow for a detailed analysis of the situation for each of 83 administrative units of the Russian Federation. The degree of epidemic hazard in Russia by natural-focal diseases is reflected in a synthetic medico-geographical map that shows the degree of epidemic risks due to such diseases in Russia and allows one to estimate the risk of disease manifestation in a given region. This is the first attempt at aggregation and public presentation of diverse and multifaceted information about natural-focal diseases in Russia

Mapping and ablating stable sources for atrial fibrillation: summary of the literature on Focal Impulse and Rotor Modulation (FIRM).

Science.gov (United States)

Baykaner, Tina; Lalani, Gautam G; Schricker, Amir; Krummen, David E; Narayan, Sanjiv M

2014-09-01

Atrial fibrillation (AF) is the most common sustained arrhythmia and the most common indication for catheter ablation. However, despite substantial technical advances in mapping and energy delivery, ablation outcomes remain suboptimal. A major limitation to AF ablation is that the areas targeted for ablation are rarely of proven mechanistic importance, in sharp contrast to other arrhythmias in which ablation targets demonstrated mechanisms in each patient. Focal impulse and rotor modulation (FIRM) is a new approach to demonstrate the mechanisms that sustain AF ("substrates") in each patient that can be used to guide ablation then confirm elimination of each mechanism. FIRM mapping reveals that AF is sustained by 2-3 rotors and focal sources, with a greater number in patients with persistent than paroxysmal AF, lying within spatially reproducible 2.2 ± 1.4-cm(2) areas in diverse locations. This temporospatial reproducibility, now confirmed by several groups using various methods, changes the concepts regarding AF-sustaining mechanisms, enabling localized rather than widespread ablation. Mechanistically, the role of rotors and focal sources in sustaining AF has been demonstrated by the acute and chronic success of source (FIRM) ablation alone. Clinically, adding FIRM to conventional ablation substantially improves arrhythmia freedom compared with conventional ablation alone, and ongoing randomized trials are comparing FIRM-ablation with and without conventional ablation to conventional ablation alone. In conclusion, ablation of patient-specific AF-sustaining mechanisms (substrates), as exemplified by FIRM, may be central to substantially improving AF ablation outcomes.

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

DEFF Research Database (Denmark)

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

2007-01-01

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

Focal lesions in the central nervous system

International Nuclear Information System (INIS)

Fabrikant, J.I.; Budinger, T.F.; Tobias, C.A.; Born, J.L.

1980-01-01

This report reviews the animal and human studies currently in progress at LBL with heavy-ion beams to induce focal lesions in the central nervous system, and discusses the potential future prospects of fundamental and applied brain research with heavy-ion beams. Methods are being developed for producing discrete focal lesions in the central nervous system using the Bragg ionization peak to investigate nerve pathways and neuroendocrine responses, and for treating pathological disorders of the brain

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

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Vinca Icard

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

A three-cell liquid hydrogen target for an extended focal plane polarimeter

International Nuclear Information System (INIS)

Golovanov, L.B.; Borzounov, Yu.T.; Piskunov, N.M.; Tsvinev, A.P.

1996-01-01

This article describes the design and working principle of a 3-cell liquid hydrogen target produced for the high-energy deuteron polarimeter HYPOM. This target uses liquid Helium as a cooling agent. After a general description of the apparatus, tests and operating modes are thoroughly explained. In particular the air controlled self regulation of Helium flow in the cryostat to stabilize the liquid hydrogen level is presented. (author)

Focal plane detector for QDD spectrography in Institute of Nuclear Study and detector for SMART 2nd focal plane in RIKEN

Energy Technology Data Exchange (ETDEWEB)

Fuchi, Yoshihide [Tokyo Univ., Tanashi (Japan). Inst. for Nuclear Study

1996-09-01

The focal plane detector for QDD spectrography in Institute of Nuclear Study was composed of drift space and a proportional counter tube, and the latter is composed of position detector and two delta E detector for recognizing the particles. In this detector, a uniform parallel electric field can be obtained by placing a guard plate at the same height as that of a drift plate outer place of the detector. On the other hand, the detector for SMART 2nd focal plate in RIKEN is composed of drift space and a single wire proportional counter, and has two cathode read out single wire drift counters set so as to hold the focal plane. (G.K.)

Magnetic electroanatomical mapping for ablation of focal atrial tachycardias.

Science.gov (United States)

Marchlinski, F; Callans, D; Gottlieb, C; Rodriguez, E; Coyne, R; Kleinman, D

1998-08-01

Uniform success for ablation of focal atrial tachycardias has been difficult to achieve using standard catheter mapping and ablation techniques. In addition, our understanding of the complex relationship between atrial anatomy, electrophysiology, and surface ECG P wave morphology remains primitive. The magnetic electroanatomical mapping and display system (CARTO) offers an on-line display of electrical activation and/or signal amplitude related to the anatomical location of the recorded sites in the mapped chamber. A window of electrical interest is established based on signals timed from an electrical reference that usually represents a fixed electrogram recording from the coronary sinus or the atrial appendage. This window of electrical interest is established to include atrial activation prior to the onset of the P wave activity associated with the site of origin of a focal atrial tachycardia. Anatomical and electrical landmarks are defined with limited fluoroscopic imaging support and more detailed global chamber and more focal atrial mapping can be performed with minimal fluoroscopic guidance. A three-dimensional color map representing atrial activation or voltage amplitude at the magnetically defined anatomical sites is displayed with on-line data acquisition. This display can be manipulated to facilitate viewing from any angle. Altering the zoom control, triangle fill threshold, clipping plane, or color range can all enhance the display of a more focal area of interest. We documented the feasibility of using this single mapping catheter technique for localizing and ablating focal atrial tachycardias. In a consecutive series of 8 patients with 9 focal atrial tachycardias, the use of the single catheter CARTO mapping system was associated with ablation success in all but one patient who had a left atrial tachycardia localized to the medial aspect of the orifice of the left atrial appendage. Only low power energy delivery was used in this patient because of the

Uniform laser ablative acceleration of targets at 1014 W/cm2

International Nuclear Information System (INIS)

Obenschain, S.P.; Whitlock, R.R.; McLean, E.A.; Ripin, B.H.; Price, R.H.; Phillion, D.W.; Campbell, E.M.; Rosen, M.D.

1982-01-01

We present the first detailed investigations of the ablative acceleration of planar targets while simultaneously using high irradiance (10 14 W/cm 2 ), large focal diameters (1 mm) and long laser pulse duration (3 nsec). Included are measurements of target preheat, ablation pressures and uniformity achieved under these conditions. Targets were accelerated to high velocities with velocity profile uniformity approaching that required for high gain pellet implosions

Protein kinase C, focal adhesions and the regulation of cell migration

DEFF Research Database (Denmark)

Fogh, Betina S; Multhaupt, Hinke A B; Couchman, John Robert

2014-01-01

in their intracellular compartment. Among these are tyrosine kinases, which have received a great deal of attention, whereas the serine/threonine kinase protein kinase C has received much less. Here the status of protein kinase C in focal adhesions and cell migration is reviewed, together with discussion of its roles...... and adhesion turnover. Focal adhesions, or focal contacts, are widespread organelles at the cell-matrix interface. They arise as a result of receptor interactions with matrix ligands, together with clustering. Recent analysis shows that focal adhesions contain a very large number of protein components...

Management of Localized Prostate Cancer by Focal Transurethral Resection of Prostate Cancer: An Application of Radical TUR-PCa to Focal Therapy.

Science.gov (United States)

Morita, Masaru; Matsuura, Takeshi

2012-01-01

Background. We analyzed radical TUR-PCa against localized prostate cancer. Patients and Methods. Seventy-nine out of 209 patients with prostate cancer in one lobe were studied. Patients' age ranged from 58 to 91 years and preoperative PSA, 0.70 to 17.30 ng/mL. In other 16 additional patients we performed focal TUR-PCa. Patients' age ranged from 51 to 87 years and preoperative PSA, 1.51 to 25.74 ng/mL. Results. PSA failure in radical TUR-PCa was 5.1% during the mean follow-up period of 58.9 months. The actuarial biochemical non-recurrence rate was 98.2% for pT2a and 90.5% for pT2b. Bladder neck contracture occurred in 28 patients (35.4%). In 209 patients, pathological study revealed prostate cancer of the peripheral zone near the neurovascular bundle bilaterally in 25%, unilaterally in 39% and no cancer bilaterally in 35%, suggesting the possibility of focal TUR-PCa. Postoperative PSA of 16 patients treated by focal TUR-PCa was stable between 0.007 and 0.406 ng/mL at 24.2 months' follow-up. No patients suffered from urinary incontinence. Bladder neck contracture developed in only 1 patient and all 5 patients underwent nerve-preserving TUR-PCa did not show erectile dysfunction. Conclusion. Focal TUR-PCa was considered to be a promising option among focal therapies against localized prostate cancer.

Management of Localized Prostate Cancer by Focal Transurethral Resection of Prostate Cancer: An Application of Radical TUR-PCa to Focal Therapy

Directory of Open Access Journals (Sweden)

Masaru Morita

2012-01-01

Full Text Available Background. We analyzed radical TUR-PCa against localized prostate cancer. Patients and Methods. Seventy-nine out of 209 patients with prostate cancer in one lobe were studied. Patients’ age ranged from 58 to 91 years and preoperative PSA, 0.70 to 17.30 ng/mL. In other 16 additional patients we performed focal TUR-PCa. Patients’ age ranged from 51 to 87 years and preoperative PSA, 1.51 to 25.74 ng/mL. Results. PSA failure in radical TUR-PCa was 5.1% during the mean follow-up period of 58.9 months. The actuarial biochemical non-recurrence rate was 98.2% for pT2a and 90.5% for pT2b. Bladder neck contracture occurred in 28 patients (35.4%. In 209 patients, pathological study revealed prostate cancer of the peripheral zone near the neurovascular bundle bilaterally in 25%, unilaterally in 39% and no cancer bilaterally in 35%, suggesting the possibility of focal TUR-PCa. Postoperative PSA of 16 patients treated by focal TUR-PCa was stable between 0.007 and 0.406 ng/mL at 24.2 months’ follow-up. No patients suffered from urinary incontinence. Bladder neck contracture developed in only 1 patient and all 5 patients underwent nerve-preserving TUR-PCa did not show erectile dysfunction. Conclusion. Focal TUR-PCa was considered to be a promising option among focal therapies against localized prostate cancer.

Focal cortical dysplasia – review

International Nuclear Information System (INIS)

Kabat, Joanna; Król, Przemysław

2012-01-01

Focal cortical dysplasia is a malformation of cortical development, which is the most common cause of medically refractory epilepsy in the pediatric population and the second/third most common etiology of medically intractable seizures in adults. Both genetic and acquired factors are involved in the pathogenesis of cortical dysplasia. Numerous classifications of the complex structural abnormalities of focal cortical dysplasia have been proposed – from Taylor et al. in 1971 to the last modification of Palmini classification made by Blumcke in 2011. In general, three types of cortical dysplasia are recognized. Type I focal cortical dysplasia with mild symptomatic expression and late onset, is more often seen in adults, with changes present in the temporal lobe. Clinical symptoms are more severe in type II of cortical dysplasia usually seen in children. In this type, more extensive changes occur outside the temporal lobe with predilection for the frontal lobes. New type III is one of the above dysplasias with associated another principal lesion as hippocampal sclerosis, tumor, vascular malformation or acquired pathology during early life. Brain MRI imaging shows abnormalities in the majority of type II dysplasias and in only some of type I cortical dysplasias. The most common findings on MRI imaging include: focal cortical thickening or thinning, areas of focal brain atrophy, blurring of the gray-white junction, increased signal on T2- and FLAIR-weighted images in the gray and subcortical white matter often tapering toward the ventricle. On the basis of the MRI findings, it is possible to differentiate between type I and type II cortical dysplasia. A complete resection of the epileptogenic zone is required for seizure-free life. MRI imaging is very helpful to identify those patients who are likely to benefit from surgical treatment in a group of patients with drug-resistant epilepsy. However, in type I cortical dysplasia, MR imaging is often normal, and also in both

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

Science.gov (United States)

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

2017-05-19

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

Histidine-rich glycoprotein can prevent development of mouse experimental glioblastoma.

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Maria Kärrlander

Full Text Available Extensive angiogenesis, formation of new capillaries from pre-existing blood vessels, is an important feature of malignant glioma. Several antiangiogenic drugs targeting vascular endothelial growth factor (VEGF or its receptors are currently in clinical trials as therapy for high-grade glioma and bevacizumab was recently approved by the FDA for treatment of recurrent glioblastoma. However, the modest efficacy of these drugs and emerging problems with anti-VEGF treatment resistance welcome the development of alternative antiangiogenic therapies. One potential candidate is histidine-rich glycoprotein (HRG, a plasma protein with antiangiogenic properties that can inhibit endothelial cell adhesion and migration. We have used the RCAS/TV-A mouse model for gliomas to investigate the effect of HRG on brain tumor development. Tumors were induced with platelet-derived growth factor-B (PDGF-B, in the presence or absence of HRG. We found that HRG had little effect on tumor incidence but could significantly inhibit the development of malignant glioma and completely prevent the occurrence of grade IV tumors (glioblastoma.

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

Science.gov (United States)

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

2003-09-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-03-15

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

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

International Nuclear Information System (INIS)

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

2016-01-01

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

Inhibition of the multidrug resistance P-glycoprotein: time for a change of strategy?

Science.gov (United States)

Callaghan, Richard; Luk, Frederick; Bebawy, Mary

2014-04-01

P-glycoprotein (P-gp) is a key player in the multidrug-resistant phenotype in cancer. The protein confers resistance by mediating the ATP-dependent efflux of an astonishing array of anticancer drugs. Its broad specificity has been the subject of numerous attempts to inhibit the protein and restore the efficacy of anticancer drugs. The general strategy has been to develop compounds that either compete with anticancer drugs for transport or act as direct inhibitors of P-gp. Despite considerable in vitro success, there are no compounds currently available to "block" P-gp-mediated resistance in the clinic. The failure may be attributed to toxicity, adverse drug interaction, and numerous pharmacokinetic issues. This review provides a description of several alternative approaches to overcome the activity of P-gp in drug-resistant cells. These include 1) drugs that specifically target resistant cells, 2) novel nanotechnologies to provide high-dose, targeted delivery of anticancer drugs, 3) compounds that interfere with nongenomic transfer of resistance, and 4) approaches to reduce the expression of P-gp within tumors. Such approaches have been developed through the pursuit of greater understanding of resistance mediators such as P-gp, and they show considerable potential for further application.

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

OpenAIRE

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

2017-01-01

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

Genomic Knockout of Endogenous Canine P-Glycoprotein in Wild-Type, Human P-Glycoprotein and Human BCRP Transfected MDCKII Cell Lines by Zinc Finger Nucleases.

Science.gov (United States)

Gartzke, Dominik; Delzer, Jürgen; Laplanche, Loic; Uchida, Yasuo; Hoshi, Yutaro; Tachikawa, Masanori; Terasaki, Tetsuya; Sydor, Jens; Fricker, Gert

2015-06-01

To investigate whether it is possible to specifically suppress the expression and function of endogenous canine P-glycoprotein (cPgp) in Madin-Darby canine kidney type II cells (MDCKII) transfected with hPGP and breast cancer resistance protein (hBCRP) by zinc finger nuclease (ZFN) producing sequence specific DNA double strand breaks. Wild-type, hPGP-transfected, and hBCRP-transfected MDCKII cells were transfected with ZFN targeting for cPgp. Net efflux ratios (NER) of Pgp and Bcrp substrates were determined by dividing efflux ratios (basal-to-apical / apical-to-basal) in over-expressing cell monolayers by those in wild-type ones. From ZFN-transfected cells, cell populations (ko-cells) showing knockout of cPgp were selected based on genotyping by PCR. qRT-PCR analysis showed the significant knock-downs of cPgp and interestingly also cMrp2 expressions. Specific knock-downs of protein expression for cPgp were shown by western blotting and quantitative targeted absolute proteomics. Endogenous canine Bcrp proteins were not detected. For PGP-transfected cells, NERs of 5 Pgp substrates in ko-cells were significantly greater than those in parental cells not transfected with ZFN. Similar result was obtained for BCRP-transfected cells with a dual Pgp and Bcrp substrate. Specific efflux mediated by hPGP or hBCRP can be determined with MDCKII cells where cPgp has been knocked out by ZFN.

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.

Separation and identification of carp pituitary proteins and glycoproteins

Czech Academy of Sciences Publication Activity Database

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

2005-01-01

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

Enzyme activity assay of glycoprotein enzymes based on a boronate affinity molecularly imprinted 96-well microplate.

Science.gov (United States)

Bi, Xiaodong; Liu, Zhen

2014-12-16

Enzyme activity assay is an important method in clinical diagnostics. However, conventional enzyme activity assay suffers from apparent interference from the sample matrix. Herein, we present a new format of enzyme activity assay that can effectively eliminate the effects of the sample matrix. The key is a 96-well microplate modified with molecularly imprinted polymer (MIP) prepared according to a newly proposed method called boronate affinity-based oriented surface imprinting. Alkaline phosphatase (ALP), a glycoprotein enzyme that has been routinely used as an indicator for several diseases in clinical tests, was taken as a representative target enzyme. The prepared MIP exhibited strong affinity toward the template enzyme (with a dissociation constant of 10(-10) M) as well as superb tolerance for interference. Thus, the enzyme molecules in a complicated sample matrix could be specifically captured and cleaned up for enzyme activity assay, which eliminated the interference from the sample matrix. On the other hand, because the boronate affinity MIP could well retain the enzymatic activity of glycoprotein enzymes, the enzyme captured by the MIP was directly used for activity assay. Thus, additional assay time and possible enzyme or activity loss due to an enzyme release step required by other methods were avoided. Assay of ALP in human serum was successfully demonstrated, suggesting a promising prospect of the proposed method in real-world applications.

Autoantibodies to neuronal antigens in children with focal epilepsy and no prima facie signs of encephalitis.

Science.gov (United States)

Borusiak, Peter; Bettendorf, Ulrich; Wiegand, Gert; Bast, Thomas; Kluger, Gerhard; Philippi, Heike; Münstermann, Dieter; Bien, Christian G

2016-07-01

There is increasing awareness of neuronal autoantibodies and their impact on the pathogenesis of epilepsy. We investigated children with focal epilepsy in order to provide an estimate of autoantibody frequency within a pediatric population without prima facie evidence of encephalitis using a broad panel of autoantibodies. This was done to assess the specificity of antibodies and to see whether antibodies might be of modifying influence on the course of focal epilepsies. We searched for autoantibodies in 124 patients with focal epilepsy (1-18 years; mean 10; 6 years). Sera were tested using a broad panel of surface and intracellular antigens. We found autoantibodies in 5/124 patients (4%): high-positive GAD65 antibodies (n = 1), low-positive GAD65 antibodies (N = 1), VGKC complex antibodies not reactive with LGI1 or CASPR2 (n = 3). We did not find any distinctive features distinguishing antibody positive patients from those without antibodies. The antibodies found in this cohort are probably neither disease-specific nor pathogenic. This has been suggested before for these antigenic targets. Moreover, they do not seem to modify disease severity in the antibody-positive epilepsy patients. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Expression of recombinant glycoproteins in mammalian cells: towards an integrative approach to structural biology.

Science.gov (United States)

Aricescu, A Radu; Owens, Raymond J

2013-06-01

Mammalian cells are rapidly becoming the system of choice for the production of recombinant glycoproteins for structural biology applications. Their use has enabled the structural investigation of a whole new set of targets including large, multi-domain and highly glycosylated eukaryotic cell surface receptors and their supra-molecular assemblies. We summarize the technical advances that have been made in mammalian expression technology and highlight some of the structural insights that have been obtained using these methods. Looking forward, it is clear that mammalian cell expression will provide exciting and unique opportunities for an integrative approach to the structural study of proteins, especially of human origin and medically relevant, by bridging the gap between the purified state and the cellular context. Copyright © 2013 Elsevier Ltd. All rights reserved.

Managing focal fields of vector beams with multiple polarization singularities.

Science.gov (United States)

Han, Lei; Liu, Sheng; Li, Peng; Zhang, Yi; Cheng, Huachao; Gan, Xuetao; Zhao, Jianlin

2016-11-10

We explore the tight focusing behavior of vector beams with multiple polarization singularities, and analyze the influences of the number, position, and topological charge of the singularities on the focal fields. It is found that the ellipticity of the local polarization states at the focal plane could be determined by the spatial distribution of the polarization singularities of the vector beam. When the spatial location and topological charge of singularities have even-fold rotation symmetry, the transverse fields at the focal plane are locally linearly polarized. Otherwise, the polarization state becomes a locally hybrid one. By appropriately arranging the distribution of the polarization singularities in the vector beam, the polarization distributions of the focal fields could be altered while the intensity maintains unchanged.

CD147-targeting siRNA inhibits cell-matrix adhesion of human malignant melanoma cells by phosphorylating focal adhesion kinase.

Science.gov (United States)

Nishibaba, Rie; Higashi, Yuko; Su, Juan; Furukawa, Tatsuhiko; Kawai, Kazuhiro; Kanekura, Takuro

2012-01-01

CD147/basigin, highly expressed on the surface of malignant tumor cells including malignant melanoma (MM) cells, plays a critical role in the invasiveness and metastasis of MM. Metastasis is an orchestrated process comprised of multiple steps including adhesion and invasion. Integrin, a major adhesion molecule, co-localizes with CD147/basigin on the cell surface. Using the human MM cell line A375 that highly expresses CD147/basigin, we investigated whether CD147/basigin is involved in adhesion in association with integrin. CD147/basigin was knocked-down using siRNA targeting CD147 to elucidate the role of CD147/basigin. Cell adhesion was evaluated by adhesion assay on matrix-coated plates. The localization of integrin was inspected under a confocal microscope and the expression and phosphorylation of focal adhesion kinase (FAK), a downstream kinase of integrin, were examined by western blot analysis. Silencing of CD147/basigin in A375 cells by siRNA induced the phosphorylation of FAK at Y397. Integrin identified on the surface of parental cells was distributed in a speckled fashion in the cytoplasm of CD147 knockdown cells, resulting in morphological changes from a round to a polygonal shape with pseudopodial protrusions. Silencing of CD147/basigin in A375 cells clearly weakened their adhesiveness to collagen I and IV. Our results suggest that CD147/basigin regulates the adhesion of MM cells to extracellular matrices and of integrin β1 signaling via the phosphorylation of FAK. © 2011 Japanese Dermatological Association.

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

International Nuclear Information System (INIS)

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

1989-01-01

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

SU-E-J-34: Clinical Evaluation of Targeting Accuracy and Tractogrphy Delineation of Radiosurgery

Energy Technology Data Exchange (ETDEWEB)

Juh, R; Suh, T; Kim, Y; Han, J; Kim, C; Oh, C; Kim, D [Seoul National University Bundang Hospital (Korea, Republic of)

2014-06-01

Purpose: Focal radiosurgery is a common treatment modality for trigeminal neuralgia (TN), a neuropathic facial pain condition. Assessment of treatment effectiveness is primarily clinical, given the paucity of investigational tools to assess trigeminal nerve changes. The efficiency of radiosurgery is related to its highly precise targeting. We assessed clinically the targeting accuracy of radiosurgery with Gamma knife. We hypothesized that trigeminal tractography provides more information than 2D-MR imaging, allowing detection of unique, focal changes in the target area after radiosurgery. Methods: Sixteen TN patients (2 females, 4 male, average age 65.3 years) treated with Gamma Knife radiosurgery, 40 Gy/50% isodose line underwent 1.5Tesla MR trigeminal nerve . Target accuracy was assessed from deviation of the coordinates of the target compared with the center of enhancement on post MRI. Radiation dose delivered at the borders of contrast enhancement was evaluated Results: The median deviation of the coordinates between the intended target and the center of contrast enhancement was within 1mm. The radiation doses fitting within the borders of the contrast enhancement the target ranged from 37.5 to 40 Gy. Trigeminal tractography accurately detected the radiosurgical target. Radiosurgery resulted in 47% drop in FA values at the target with no significant change in FA outside the target, suggesting that radiosurgery primarily affects myelin. Tractography was more sensitive, since FA changes were detected regardless of trigeminal nerve enhancement Conclusion: The median deviation found in clinical assessment of gamma knife treatment for TN Is low and compatible with its high rate of efficiency. DTI parameters accurately detect the effects of focal radiosurgery on the trigeminal nerve, serving as an in vivo imaging tool to study TN. This study is a proof of principle for further assessment of DTI parameters to understand the pathophysiology of TN and treatment effects.

Focal vitiligo: long-term follow-up of 52 cases

NARCIS (Netherlands)

Lommerts, J. E.; Schilder, Y.; de Rie, M. A.; Wolkerstorfer, A.; Bekkenk, M. W.

2016-01-01

Focal vitiligo is characterized by depigmented patches located in a small area without a typical segmental distribution. Focal vitiligo is classified as an undetermined type of vitiligo, and a more definitive diagnosis can be made when the lesions have not evolved into non-segmental or segmental

NeuroSeek dual-color image processing infrared focal plane array

Science.gov (United States)

McCarley, Paul L.; Massie, Mark A.; Baxter, Christopher R.; Huynh, Buu L.

1998-09-01

Several technologies have been developed in recent years to advance the state of the art of IR sensor systems including dual color affordable focal planes, on-focal plane array biologically inspired image and signal processing techniques and spectral sensing techniques. Pacific Advanced Technology (PAT) and the Air Force Research Lab Munitions Directorate have developed a system which incorporates the best of these capabilities into a single device. The 'NeuroSeek' device integrates these technologies into an IR focal plane array (FPA) which combines multicolor Midwave IR/Longwave IR radiometric response with on-focal plane 'smart' neuromorphic analog image processing. The readout and processing integrated circuit very large scale integration chip which was developed under this effort will be hybridized to a dual color detector array to produce the NeuroSeek FPA, which will have the capability to fuse multiple pixel-based sensor inputs directly on the focal plane. Great advantages are afforded by application of massively parallel processing algorithms to image data in the analog domain; the high speed and low power consumption of this device mimic operations performed in the human retina.

A Molecular Sensor To Characterize Arenavirus Envelope Glycoprotein Cleavage by Subtilisin Kexin Isozyme 1/Site 1 Protease

Science.gov (United States)

Oppliger, Joel; da Palma, Joel Ramos; Burri, Dominique J.; Khatib, Abdel-Majid; Spiropoulou, Christina F.

2015-01-01

ABSTRACT Arenaviruses are emerging viruses including several causative agents of severe hemorrhagic fevers in humans. The advent of next-generation sequencing technology has greatly accelerated the discovery of novel arenavirus species. However, for many of these viruses, only genetic information is available, and their zoonotic disease potential remains unknown. During the arenavirus life cycle, processing of the viral envelope glycoprotein precursor (GPC) by the cellular subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P) is crucial for productive infection. The ability of newly emerging arenaviruses to hijack human SKI-1/S1P appears, therefore, to be a requirement for efficient zoonotic transmission and human disease potential. Here we implement a newly developed cell-based molecular sensor for SKI-1/S1P to characterize the processing of arenavirus GPC-derived target sequences by human SKI-1/S1P in a quantitative manner. We show that only nine amino acids flanking the putative cleavage site are necessary and sufficient to accurately recapitulate the efficiency and subcellular location of arenavirus GPC processing. In a proof of concept, our sensor correctly predicts efficient processing of the GPC of the newly emergent pathogenic Lujo virus by human SKI-1/S1P and defines the exact cleavage site. Lastly, we employed our sensor to show efficient GPC processing of a panel of pathogenic and nonpathogenic New World arenaviruses, suggesting that GPC cleavage represents no barrier for zoonotic transmission of these pathogens. Our SKI-1/S1P sensor thus represents a rapid and robust test system for assessment of the processing of putative cleavage sites derived from the GPCs of newly discovered arenavirus by the SKI-1/S1P of humans or any other species, based solely on sequence information. IMPORTANCE Arenaviruses are important emerging human pathogens that can cause severe hemorrhagic fevers with high mortality in humans. A crucial step in productive arenavirus

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)

Radiologic manifestations of focal cerebral hyperemia in acute stroke

DEFF Research Database (Denmark)

Olsen, Tom Skyhøj; Skriver, E B; Herning, M

1991-01-01

In 16 acute stroke patients with focal cerebral hyperemia angiography and regional cerebral blood flow (rCBF) were studied 1 to 4 days post stroke. CT was performed twice with and without contrast enhancement 3 +/- 1 days and 16 +/- 4 days post stroke. Angiographic evidence of focal cerebral hype...

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

International Nuclear Information System (INIS)

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

1989-01-01

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

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

OpenAIRE

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

1987-01-01

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

Earthquake focal mechanism forecasting in Italy for PSHA purposes

Science.gov (United States)

Roselli, Pamela; Marzocchi, Warner; Mariucci, Maria Teresa; Montone, Paola

2018-01-01

In this paper, we put forward a procedure that aims to forecast focal mechanism of future earthquakes. One of the primary uses of such forecasts is in probabilistic seismic hazard analysis (PSHA); in fact, aiming at reducing the epistemic uncertainty, most of the newer ground motion prediction equations consider, besides the seismicity rates, the forecast of the focal mechanism of the next large earthquakes as input data. The data set used to this purpose is relative to focal mechanisms taken from the latest stress map release for Italy containing 392 well-constrained solutions of events, from 1908 to 2015, with Mw ≥ 4 and depths from 0 down to 40 km. The data set considers polarity focal mechanism solutions until to 1975 (23 events), whereas for 1976-2015, it takes into account only the Centroid Moment Tensor (CMT)-like earthquake focal solutions for data homogeneity. The forecasting model is rooted in the Total Weighted Moment Tensor concept that weighs information of past focal mechanisms evenly distributed in space, according to their distance from the spatial cells and magnitude. Specifically, for each cell of a regular 0.1° × 0.1° spatial grid, the model estimates the probability to observe a normal, reverse, or strike-slip fault plane solution for the next large earthquakes, the expected moment tensor and the related maximum horizontal stress orientation. These results will be available for the new PSHA model for Italy under development. Finally, to evaluate the reliability of the forecasts, we test them with an independent data set that consists of some of the strongest earthquakes with Mw ≥ 3.9 occurred during 2016 in different Italian tectonic provinces.

Focal airtrapping at expiratory high-resolution CT: comparison with pulmonary function tests

International Nuclear Information System (INIS)

Kauczor, H.U.; Hast, J.; Heussel, C.P.; Mildenberger, P.; Thelen, M.; Schlegel, J.

2000-01-01

This study was undertaken to determine prevalence, extent, and severity of focal airtrapping at expiratory high-resolution CT, and to compare focal airtrapping with age, gender, pulmonary function tests, and blood gas analysis. Two-hundred seventeen patients with and without pulmonary disease underwent paired inspiratory/expiratory high-resolution CT. Six scan pairs with corresponding scan levels were visually assessed for focal - not diffuse - airtrapping using a four-point scale. Pulmonary function tests and blood gas analysis were available for correlation in all patients (mean interval 5 days). Focal airtrapping with lower lung predominance was observed in 80 % of patients. Twenty-six of 26 patients with restrictive lung function impairment exhibited focal airtrapping (mean score 2.4), whereas only 72 of 98 (74 %) patients with obstruction did (mean score 1.5; p < 0.05). Fifty-eight of 70 (83 %) patients with normal lung function (mean score 1.8) and 19 of 23 (83 %) patients with mixed impairment (mean score 1.8) had focal airtrapping. Focal airtrapping showed negative correlations with static lung volumes (-0.27 to -0.37; p < 0.001) in all patients and moderate positive correlations with dynamic parameters (0.3-0.4; p < 0.001) in patients with obstruction. No significant correlations were found with age, gender, and blood gas analysis. Visual assessment of focal - not diffuse - airtrapping at expiratory high-resolution CT does not correlate with physiological evidence of obstruction as derived from pulmonary function tests since the perception of focal airtrapping requires an adequate expiratory increase in lung density. (orig.)

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

Science.gov (United States)

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

2017-06-01

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

DEPDC5 takes a second hit in familial focal epilepsy.

Science.gov (United States)

Anderson, Matthew P

2018-04-30

Loss-of-function mutations in a single allele of the gene encoding DEP domain-containing 5 protein (DEPDC5) are commonly linked to familial focal epilepsy with variable foci; however, a subset of patients presents with focal cortical dysplasia that is proposed to result from a second-hit somatic mutation. In this issue of the JCI, Ribierre and colleagues provide several lines of evidence to support second-hit DEPDC5 mutations in this disorder. Moreover, the authors use in vivo, in utero electroporation combined with CRISPR-Cas9 technology to generate a murine model of the disease that recapitulates human manifestations, including cortical dysplasia-like changes, focal seizures, and sudden unexpected death. This study provides important insights into familial focal epilepsy and provides a preclinical model for evaluating potential therapies.

The Bering Target Tracking Instrumentation

DEFF Research Database (Denmark)

Denver, Troelz; Jørgensen, John Leif; Betto, Maurizio

2003-01-01

The key science instrument on the Bering satellite mission is a relative small telescope with an entrance aperture of 300 mm and a focal length between 500 and 1000 mm. The detection of potential targets is performed by one of the target scanning advanced stellar compasses (ASCs). This procedure...... results in a simple prioritized list of right ascension, declination, proper motion and intensity of each prospective target. The telescope itself has a dedicated ASC Camera Head Unit (CHU) mounted on the secondary mirror, largely co-aligned with the telescope. This CHU accurately determines the telescope......'s pointing direction. To achieve fast tracking over a large solid angle, the telescope pointing is achieved by means of a folding mirror in the optical pathway. When a prospective target approaches the telescope FOV, the ASC on the secondary will guide the folding mirror into position such that the target...

Rasmussen's encephalitis presenting as focal cortical dysplasia

Science.gov (United States)

O'Rourke, D.J.; Bergin, A.; Rotenberg, A.; Peters, J.; Gorman, M.; Poduri, A.; Cryan, J.; Lidov, H.; Madsen, J.; Harini, C.

2014-01-01

Rasmussen's encephalitis is a rare syndrome characterized by intractable seizures, often associated with epilepsia partialis continua and symptoms of progressive hemispheric dysfunction. Seizures are usually the hallmark of presentation, but antiepileptic drug treatment fails in most patients and is ineffective against epilepsia partialis continua, which often requires surgical intervention. Co-occurrence of focal cortical dysplasia has only rarely been described and may have implications regarding pathophysiology and management. We describe a rare case of dual pathology of Rasmussen's encephalitis presenting as a focal cortical dysplasia (FCD) and discuss the literature on this topic. PMID:25667877

Sulforaphane exerts neuroprotective effects via suppression of the inflammatory response in a rat model of focal cerebral ischemia.

Science.gov (United States)

Ma, Li-Li; Xing, Guo-Ping; Yu, Yin; Liang, Hui; Yu, Tian-Xia; Zheng, Wei-Hong; Lai, Tian-Bao

2015-01-01

Inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a promising target for treatment. Sulforaphane exerts protective effects in a rat model of focal cerebral ischemia/reperfusion injury by alleviating brain edema. However, the possible mechanisms of sulforaphane after cerebral ischemia/reperfusion injury have not been fully elucidated. Therefore, in the present study, we investigated the effect of sulforaphane on inflammatory reaction and the potential molecular mechanisms in cerebral ischemia rats. We found that sulforaphane significantly attenuated the blood-brain barrier (BBB) disruption; decreased the levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β; reduced the nitric oxide (NO) levels and inducible nitric oxide synthase (iNOS) activity; inhibited the expression of iNOS and cyclooxygenase-2 (COX-2). In addition, sulforaphane inhibits the expression of p-NF-κB p65 after focal cerebral ischemia-reperfusion injury. Taken together, our results suggest that sulforaphane suppresses the inflammatory response via inhibiting the NF-κB signaling pathway in a rat model of focal cerebral ischemia, and sulforaphane may be a potential therapeutic agent for the treatment of cerebral ischemia injury.

Focal therapy in prostate cancer

NARCIS (Netherlands)

van den Bos, W.

2016-01-01

Interesting developments took place in the treatment of prostate cancer including focal therapy for less aggressive organ-confined prostate cancer. Fortunately, curative treatment is often still an option for patients suffering from the lower staged tumors. In carefully selected patients, the

Gallbladder adenoma with focal adenocarcinoma.

Science.gov (United States)

Ciurea, S; Matei, E; Petrisor, P; Luca, L; Boros, Mirela; Herlea, V; Popescu, I

2008-01-01

The majority of polypoid lesions of the gallbladder are cholesterolosis pseudopolyps. True neoplastic GB polyps are represented mainly by adenomas. The case of a 52-year old male patient with an adenomatous polyp of the GB with focal adenocarcinoma is presented.

Membrane glycoproteins of differentiating skeletal muscle cells

International Nuclear Information System (INIS)

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

1987-01-01

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

Heterogeneity of Focal Adhesions and Focal Contacts in Motile Fibroblasts.

Science.gov (United States)

Gladkikh, Aleena; Kovaleva, Anastasia; Tvorogova, Anna; Vorobjev, Ivan A

2018-01-01

Cell-extracellular matrix (ECM) adhesion is an important property of virtually all cells in multicellular organisms. Cell-ECM adhesion studies, therefore, are very significant both for biology and medicine. Over the last three decades, biomedical studies resulted in a tremendous advance in our understanding of the molecular basis and functions of cell-ECM adhesion. Based on morphological and molecular criteria, several different types of model cell-ECM adhesion structures including focal adhesions, focal complexes, fibrillar adhesions, podosomes, and three-dimensional matrix adhesions have been described. All the subcellular structures that mediate cell-ECM adhesion are quite heterogeneous, often varying in size, shape, distribution, dynamics, and, to a certain extent, molecular constituents. The morphological "plasticity" of cell-ECM adhesion perhaps reflects the needs of cells to sense, adapt, and respond to a variety of extracellular environments. In addition, cell type (e.g., differentiation status, oncogenic transformation, etc.) often exerts marked influence on the structure of cell-ECM adhesions. Although molecular, genetic, biochemical, and structural studies provide important maps or "snapshots" of cell-ECM adhesions, the area of research that is equally valuable is to study the heterogeneity of FA subpopulations within cells. Recently time-lapse observations on the FA dynamics become feasible, and behavior of individual FA gives additional information on cell-ECM interactions. Here we describe a robust method of labeling of FA using plasmids with fluorescent markers for paxillin and vinculin and quantifying the morphological and dynamical parameters of FA.

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

Science.gov (United States)

Latha, M; Pari, L

2005-02-01

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

Systematic study of the focal shift effect in planar plasmonic slit lenses

International Nuclear Information System (INIS)

Hu Bin; Wang Qijie; Zhang Ying

2012-01-01

In this paper, we systematically studied the focal shift effect in planar plasmonic slit lenses. Through theoretical derivations and numerical simulations, we found that there is a focal length shift between the traditional design model and the finite-difference time-domain simulations. The shift is not only dependent on the Fresnel number (FN) of the lens, like traditional dielectric lenses, determined by the lens width and the designed focal length, but also on the surface plasmon polariton (SPPs) interaction on the lens surfaces, dependent on the slit numbers. We also found that the FN-induced focal shift is predominant when FN 1. An approximated theoretical model is presented to estimate the focal shift of plasmonic slit lens with FN < 1. (paper)

Hohlraum targets for HIDIF

International Nuclear Information System (INIS)

Ramis, R.; Ramirez, J.; Meyer-ter-Vehn, J.

2000-01-01

An optimized high gain IFE indirect target design is presented. Beam parameters (5 MJ of 5 GeV Bi + ions in 10-20 ns and focal spot of 3 mm radius) are in agreement to the ones considered recently for the European Study Group on Heavy Ion Driven Inertial Fusion (HIDIF). The energy yield is close to 530 MJ, giving a large enough gain appropriate for industrial energy production. Numerical and analytical modeling are described and discussed. (authors)

Protein kinase C involvement in focal adhesion formation

DEFF Research Database (Denmark)

Woods, A; Couchman, J R

1992-01-01

Matrix molecules such as fibronectin can promote cell attachment, spreading and focal adhesion formation. Although some interactions of fibronectin with cell surface receptors have now been identified, the consequent activation of intracellular messenger systems by cell/matrix interactions have...... still to be elucidated. We show here that the kinase inhibitors H7 and HA1004 reduce focal adhesion and stress fiber formation in response to fibronectin in a dose-dependent manner, and that activators of protein kinase C can promote their formation under conditions where they do not normally form....... Fibroblasts spread within 1h on substrata composed of fibronectin and formed focal adhesions by 3h, as monitored by interference reflection microscopy (IRM) and by labeling for talin, vinculin and integrin beta 1 subunits. In addition, stress fibers were visible. When cells were allowed to spread for 1h...

A 1.3 giga pixels focal plane for GAIA

Science.gov (United States)

Laborie, Anouk; Pouny, Pierre; Vetel, Cyril; Collados, Emmanuel; Rougier, Gilles; Davancens, Robert; Zayer, Igor; Perryman, Michael; Pace, Oscar

2004-06-01

The astrometric mission GAIA is a cornerstone mission of the European Space Agency, due for launch in the 2010 time frame. Requiring extremely demanding performance GAIA calls for the development of an unprecedented large focal plane featuring innovative technologies. For securing the very challenging GAIA development, a significant number of technology activities have been initiated by ESA through a competitive selection process. In this context, an industrial consortium led by EADS-Astrium (France) with e2v technologies (UK) as major subcontractor was selected for the GAIA CCD and Focal Plane Technology Demonstrators programme, which is by far the most significant and the most critical GAIA pre-development for all aspects: science performance, development schedule and cost. This programme has started since August 2002 and will end early 2005 prior to commencement of the GAIA Phase B. While the GAIA payload will host three instruments and related focal planes, the major mission objectives are assigned to the Astrometric (ASTRO) Focal Plane, which is the subject of this presentation.

Cereal n-glycoproteins enrichment by lectin affinity monolithic chromatography

Czech Academy of Sciences Publication Activity Database

Flodrová, Dana; Bobálová, Janette; Laštovičková, Markéta

2016-01-01

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

Focal adhesions, stress fibers and mechanical tension

Energy Technology Data Exchange (ETDEWEB)

Burridge, Keith, E-mail: Keith_Burridge@med.unc.edu [Department of Cell Biology and Physiology, and Lineberger Comprehensive Cancer Center, 12-016 Lineberger, CB#7295, University of North Carolina, Chapel Hill, NC (United States); Guilluy, Christophe, E-mail: christophe.guilluy@univ-nantes.fr [Inserm UMR-S1087, CNRS UMR-C6291, L' institut du Thorax, and Université de Nantes, Nantes (France)

2016-04-10

Stress fibers and focal adhesions are complex protein arrays that produce, transmit and sense mechanical tension. Evidence accumulated over many years led to the conclusion that mechanical tension generated within stress fibers contributes to the assembly of both stress fibers themselves and their associated focal adhesions. However, several lines of evidence have recently been presented against this model. Here we discuss the evidence for and against the role of mechanical tension in driving the assembly of these structures. We also consider how their assembly is influenced by the rigidity of the substratum to which cells are adhering. Finally, we discuss the recently identified connections between stress fibers and the nucleus, and the roles that these may play, both in cell migration and regulating nuclear function. - Highlights: • The different types of stress fiber and focal adhesion are described. • We discuss the controversy about tension and assembly of these structures. • We describe the different models used to investigate assembly of these structures. • The influence of substratum rigidity is discussed. • Stress fiber connections to the nucleus are reviewed.

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

MRI of a family with focal abnormalities of gyration

International Nuclear Information System (INIS)

Muntaner, L.; Perez-Ferron, J.J.; Herrera, M.; Rosell, J.; Taboada, D.; Climent, S.

1997-01-01

Focal abnormalities of gyration (FAG) are developmental disorders that may occur in isolated patients or, as in the case being reported, as part of a familial disorder. Analysis of individuals in a family spanning three generations was carried out using MRI. Abnormalities, present in all members of generations II and III, included focal cortical dysplasia (three patients), focal cortical infolding (two patients) and schizencephaly (one patient); associated minor anomalies, such as white matter abnormalities, were seen in the remaining three members of generations II and III. MRI recognition of FAG in the family being reported proved useful in defining their phenotypical expression and providing proper counselling for individual family members. (orig.). With 6 figs

Concordance of MRI and EEG Focal Slowing in Nonsyndromic Epilepsy

Directory of Open Access Journals (Sweden)

J Gordon Millichap

2013-04-01

Full Text Available Investigators at the Kangwon National University, Korea, and The Epilepsy Center, Lurie Children’s Hospital of Chicago, USA studied the correlation and significance of EEG focal slowing and focal MRI abnormalities in 253 children with nonsyndromic epilepsy.

Focal low-dose rate brachytherapy for the treatment of prostate cancer

Directory of Open Access Journals (Sweden)

Tong WY

2013-09-01

Full Text Available William Y Tong, Gilad Cohen, Yoshiya Yamada Memorial Sloan-Kettering Cancer Center, Department of Radiation Oncology, New York, NY, USA Abstract: Whole-gland low-dose rate (LDR brachytherapy has been a well-established modality of treating low-risk prostate cancer. Treatment in a focal manner has the advantages of reduced toxicity to surrounding organs. Focal treatment using LDR brachytherapy has been relatively unexplored, but it may offer advantages over other modalities that have established experiences with a focal approach. This is particularly true as prostate cancer is being detected at an earlier and more localized stage with the advent of better detection methods and newer imaging modalities. Keywords: prostate cancer, focal, low dose rate, brachytherapy

Glycoprotein component of plant cell walls

International Nuclear Information System (INIS)

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

1984-01-01

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

Quantitative analysis of N-glycans from human alfa-acid-glycoprotein using stable isotope labeling and zwitterionic hydrophilic interaction capillary liquid chromatography electrospray mass spectrometry as tool for pancreatic disease diagnosis

Energy Technology Data Exchange (ETDEWEB)

Giménez, Estela, E-mail: estelagimenez@ub.edu [Department of Analytical Chemistry, University of Barcelona, Diagonal 647, E-08028 Barcelona (Spain); Balmaña, Meritxell [Biochemistry and Molecular Biology Unit, Department of Biology, University of Girona, Campus Montilivi s/n, 17071 Girona (Spain); Figueras, Joan [Department of Surgery, Dr. Josep Trueta University Hospital, IdlBGi, 17007 Girona (Spain); Fort, Esther [Digestive Unit, Dr. Josep Trueta University Hospital, 17007 Girona (Spain); Bolós, Carme de [Gastroesophagic Cancer Research Group, Research Programme in Cancer, Hospital del Mar Medical Research Institute (IMIM), Dr. Aiguader, 88, 08003 Barcelona (Spain); Sanz-Nebot, Victòria [Department of Analytical Chemistry, University of Barcelona, Diagonal 647, E-08028 Barcelona (Spain); Peracaula, Rosa [Biochemistry and Molecular Biology Unit, Department of Biology, University of Girona, Campus Montilivi s/n, 17071 Girona (Spain); Rizzi, Andreas [Institute of Analytical Chemistry, University of Vienna, Währinger Straße 38, A-1090 Vienna (Austria)

2015-03-25

AGP as a candidate structure worth to be corroborated by an extended study including more clinical cases; especially those with chronic pancreatitis and initial stages of pancreatic cancer. Importantly, the results demonstrate that the presented methodology combining an enrichment of a target protein by IAC with isotope coded relative quantitation of N-glycans can be successfully used for targeted glycomics studies. The methodology is assumed being suitable as well for other such studies aimed at finding novel cancer associated glycoprotein biomarkers.

Efficacy and tolerability of high-dose phenobarbital in children with focal seizures.

Science.gov (United States)

Okumura, Akihisa; Nakahara, Eri; Ikeno, Mitsuru; Abe, Shinpei; Igarashi, Ayuko; Nakazawa, Mika; Takasu, Michihiko; Shimizu, Toshiaki

2016-04-01

We retrospectively reviewed the outcomes of children with focal epilepsy treated with oral high-dose phenobarbital. We reviewed data on children (agedphenobarbital (>5 mg/kg/day to maintain a target serum level >40 μg/mL) for at least 6 months. Seizure frequency was evaluated after phenobarbital titration, and 1 and 2 years after high-dose phenobarbital treatment commenced. Treatment was judged effective when seizure frequencies fell by ⩾75%. Seven boys and eight girls were treated. The median age at commencement of high-dose phenobarbital therapy was 30 months. The maximal serum phenobarbital level ranged from 36.5 to 62.9 μg/mL. High-dose PB was effective in seven. In two patients, treatment was transiently effective, but seizure frequency later returned to the baseline. High-dose PB was ineffective in six. No significant association between effectiveness and any clinical variable was evident. Drowsiness was recorded in nine patients, but no patient developed a behavioral problem or hypersensitivity. Oral high-dose phenobarbital was effective in 7 of 15 patients with focal epilepsy and well tolerated. High-dose PB may be useful when surgical treatment is difficult. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Rasmussen's encephalitis presenting as focal cortical dysplasia

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D.J. O'Rourke

2014-01-01

Full Text Available Rasmussen's encephalitis is a rare syndrome characterized by intractable seizures, often associated with epilepsia partialis continua and symptoms of progressive hemispheric dysfunction. Seizures are usually the hallmark of presentation, but antiepileptic drug treatment fails in most patients and is ineffective against epilepsia partialis continua, which often requires surgical intervention. Co-occurrence of focal cortical dysplasia has only rarely been described and may have implications regarding pathophysiology and management. We describe a rare case of dual pathology of Rasmussen's encephalitis presenting as a focal cortical dysplasia (FCD and discuss the literature on this topic.

Chest pain in focal musculoskeletal disorders

DEFF Research Database (Denmark)

Stochkendahl, Mette Jensen; Christensen, Henrik Wulff

2010-01-01

overlapping conditions and syndromes of focal disorders, including Tietze syndrome, costochondritis, chest wall syndrome, muscle tenderness, slipping rib, cervical angina, and segmental dysfunction of the cervical and thoracic spine, have been reported to cause pain. For most of these syndromes, evidence......The musculoskeletal system is a recognized source of chest pain. However, despite the apparently benign origin, patients with musculoskeletal chest pain remain under-diagnosed, untreated, and potentially continuously disabled in terms of anxiety, depression, and activities of daily living. Several...... arises mainly from case stories and empiric knowledge. For segmental dysfunction, clinical features of musculoskeletal chest pain have been characterized in a few clinical trials. This article summarizes the most commonly encountered syndromes of focal musculoskeletal disorders in clinical practice....

Mechanical design and analysis of focal plate for gravity deformation

Science.gov (United States)

Wang, Jianping; Chu, Jiaru; Hu, Hongzhuan; Li, Kexuan; Zhou, Zengxiang

2014-07-01

The surface accuracy of astronomical telescope focal plate is a key indicator to precision stellar observation. To conduct accurate deformation measurement for focal plate in different status, a 6-DOF hexapod platform was used for attitude adjustment. For the small adjustment range of a classic 6-DOF hexapod platform, an improved structural arrangement method was proposed in the paper to achieve ultimate adjustment of the focal plate in horizontal and vertical direction. To validate the feasibility of this method, an angle change model which used ball hinge was set up for the movement and base plate. Simulation results in MATLAB suggested that the ball hinge angle change of movement and base plate is within the range of the limiting angle in the process of the platform plate adjusting to ultimate attitude. The proposed method has some guiding significance for accurate surface measurement of focal plate.

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

DEFF Research Database (Denmark)

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

1996-01-01

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

Polymeric micelles as a drug carrier for tumor targeting

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Neha M Dand

2013-01-01

Full Text Available Polymeric micelle can be targeted to tumor site by passive and active mechanism. Some inherent properties of polymeric micelle such as size in nanorange, stability in plasma, longevity in vivo, and pathological characteristics of tumor make polymeric micelles to be targeted at the tumor site by passive mechanism called enhanced permeability and retention effect. Polymeric micelle formed from the amphiphilic block copolymer is suitable for encapsulation of poorly water soluble, hydrophobic anticancer drugs. Other characteristics of polymeric micelles such as separated functionality at the outer shell are useful for targeting the anticancer drug to tumor by active mechanisms. Polymeric micelles can be conjugated with many ligands such as antibodies fragments, epidermal growth factors, α2 -glycoprotein, transferrine, and folate to target micelles to cancer cells. Application of heat and ultrasound are the alternative methods to enhance drug accumulation in tumoral cells. Targeting using micelles can also be done to tumor angiogenesis which is the potentially promising target for anticancer drugs. This review summarizes about recently available information regarding targeting the anticancer drug to the tumor site using polymeric micelles.

Target-ion source unit ionization efficiency measurement by method of stable ion beam implantation

CERN Document Server

Panteleev, V.N; Fedorov, D.V; Moroz, F.V; Orlov, S.Yu; Volkov, Yu.M

The ionization efficiency is one of the most important parameters of an on-line used target-ion source system exploited for production of exotic radioactive beams. The ionization efficiency value determination as a characteristic of a target-ion source unit in the stage of its normalizing before on-line use is a very important step in the course of the preparation for an on-line experiment. At the IRIS facility (Petersburg Nuclear Physics Institute, Gatchina) a reliable and rather precise method of the target-ion source unit ionization efficiency measurement by the method of stable beam implantation has been developed. The method worked out exploits an off-line mass-separator for the implantation of the ion beams of selected stable isotopes of different elements into a tantalum foil placed inside the Faraday cup in the focal plane of the mass-separator. The amount of implanted ions has been measured with a high accuracy by the current integrator connected to the Faraday cup. After the implantation of needed a...

Sulforaphane exerts neuroprotective effects via suppression of the inflammatory response in a rat model of focal cerebral ischemia

OpenAIRE

Ma, Li-Li; Xing, Guo-Ping; Yu, Yin; Liang, Hui; Yu, Tian-Xia; Zheng, Wei-Hong; Lai, Tian-Bao

2015-01-01

Inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a promising target for treatment. Sulforaphane exerts protective effects in a rat model of focal cerebral ischemia/reperfusion injury by alleviating brain edema. However, the possible mechanisms of sulforaphane after cerebral ischemia/reperfusion injury have not been fully elucidated. Therefore, in the present study, we investigated the effect of sulforaphane on inflammatory reaction and the potent...

A Diverse Panel of Hepatitis C Virus Glycoproteins for Use in Vaccine Research Reveals Extremes of Monoclonal Antibody Neutralization Resistance.

Science.gov (United States)

Urbanowicz, Richard A; McClure, C Patrick; Brown, Richard J P; Tsoleridis, Theocharis; Persson, Mats A A; Krey, Thomas; Irving, William L; Ball, Jonathan K; Tarr, Alexander W

2015-12-23

effective vaccine that generates both T cell responses and neutralizing antibodies is required to eradicate the disease. Regions within the HCV surface glycoproteins E1 and E2 are essential for virus entry and are targets for neutralizing antibodies. Screening of vaccine candidates requires suitable panels of glycoproteins that represent the breadth of neutralization resistance. Use of a standard reference panel for vaccine studies will ensure comparability of data sets, as has become routine for HIV-1. Here, we describe a large panel of patient-derived HCV glycoproteins with an assessment of their neutralization sensitivity to defined monoclonal antibodies, which has enabled us to predict their likely efficacy in the wider HCV-infected population. The panel could also be important for future selection of additional therapeutic antibodies and for vaccine design. Copyright © 2016 Urbanowicz et al.

Charging as a Focal Practice

DEFF Research Database (Denmark)

Bødker, Mads

This position paper reflects on Borgmann’s notion of ‘focal things’ and its applicability in the discourse about interaction with technologies in nature. Using the example of a combined cooking burner and thermoelectric 5W smartphone charger (a BioLite cook stove), this position paper gives...

CT findings of focal organizing pneumonia: correlation with pathologic findings

Energy Technology Data Exchange (ETDEWEB)

Kim, Yang Soo; Kim, Young Goo; Park, Un Sup [College of Medicine, Chungang University, Seoul (Korea, Republic of)

1994-11-15

To evaluate the CT findings of focal organizing pneumonia and to correlate them with pathologic findings to help differentiating from lung cancer. We evaluated radiologic and pathologic findings of five patients with solitary pulmonary nodule which were confirmed as focal organizing pneumonia pathologically. On CT scan, focal organizing pneumonia had irregular margin contacting the pleura in all five cases. The shape of the nodules were spherical to wedge or elliptical and the size from 3.5cm to 5.5cm(average 4.2 cm) in largest diameter. On postcontrast CT scan, all nodules showed enhancement and four cases showed central low density components. Two nodules contained air within the nodule. In four cases, pleural changes such as effusion and/or focal thickening were noted. No lymphadenopathy was found in all cases. Pathologically, the enhancing portion on CT showed findings of organizing pneumonia such as granulation tissue with fibroblast proliferation in alveolar space and interstitial thickening. The central low density areas on CT were due to ischemic necrosis, abscess and exudate, transudate and infiltration of foamy histiocyte. The possibility of focal organizing pneumonia should be considered when peripherally located solitary pulmonary nodule had enhancing component with no combined lymphadenopathy on CT scan.

CT findings of focal organizing pneumonia: correlation with pathologic findings

International Nuclear Information System (INIS)

Kim, Yang Soo; Kim, Young Goo; Park, Un Sup

1994-01-01

To evaluate the CT findings of focal organizing pneumonia and to correlate them with pathologic findings to help differentiating from lung cancer. We evaluated radiologic and pathologic findings of five patients with solitary pulmonary nodule which were confirmed as focal organizing pneumonia pathologically. On CT scan, focal organizing pneumonia had irregular margin contacting the pleura in all five cases. The shape of the nodules were spherical to wedge or elliptical and the size from 3.5cm to 5.5cm(average 4.2 cm) in largest diameter. On postcontrast CT scan, all nodules showed enhancement and four cases showed central low density components. Two nodules contained air within the nodule. In four cases, pleural changes such as effusion and/or focal thickening were noted. No lymphadenopathy was found in all cases. Pathologically, the enhancing portion on CT showed findings of organizing pneumonia such as granulation tissue with fibroblast proliferation in alveolar space and interstitial thickening. The central low density areas on CT were due to ischemic necrosis, abscess and exudate, transudate and infiltration of foamy histiocyte. The possibility of focal organizing pneumonia should be considered when peripherally located solitary pulmonary nodule had enhancing component with no combined lymphadenopathy on CT scan

EEG dynamical correlates of focal and diffuse causes of coma.

Science.gov (United States)

Kafashan, MohammadMehdi; Ryu, Shoko; Hargis, Mitchell J; Laurido-Soto, Osvaldo; Roberts, Debra E; Thontakudi, Akshay; Eisenman, Lawrence; Kummer, Terrance T; Ching, ShiNung

2017-11-15

Rapidly determining the causes of a depressed level of consciousness (DLOC) including coma is a common clinical challenge. Quantitative analysis of the electroencephalogram (EEG) has the potential to improve DLOC assessment by providing readily deployable, temporally detailed characterization of brain activity in such patients. While used commonly for seizure detection, EEG-based assessment of DLOC etiology is less well-established. As a first step towards etiological diagnosis, we sought to distinguish focal and diffuse causes of DLOC through assessment of temporal dynamics within EEG signals. We retrospectively analyzed EEG recordings from 40 patients with DLOC with consensus focal or diffuse culprit pathology. For each recording, we performed a suite of time-series analyses, then used a statistical framework to identify which analyses (features) could be used to distinguish between focal and diffuse cases. Using cross-validation approaches, we identified several spectral and non-spectral EEG features that were significantly different between DLOC patients with focal vs. diffuse etiologies, enabling EEG-based classification with an accuracy of 76%. Our findings suggest that DLOC due to focal vs. diffuse injuries differ along several electrophysiological parameters. These results may form the basis of future classification strategies for DLOC and coma that are more etiologically-specific and therefore therapeutically-relevant.

Tratamento focal e perifocal contra Aëdes aegypti

Directory of Open Access Journals (Sweden)

Milton Moura Lima

1987-06-01

Full Text Available Em quatro bairros da cidade do Rio de Janeiro, foram feitos ensaios de tratamento focal com abate granulado a 1 ppm e perifocal com pó molhável de Sumition a 2,5%. Esses tratamentos foram feitos tanto isoladamente quanto em conjunto e, também, associados à aplicação de inseticida a ultrabaixo volume. Os índices prediais, levantados um mês depois de terminado o trabalho, mostraram que o tratamento focal dispensa qualquer medida auxiliar. O tratamento perifocal mostrou-se inócuo e incapaz de impedir o aparecimento de larvas de Aëdes aegypti e de outros insetos, em pneus pintados, na face externa, com Sumition e com Malation.In four districts of the city of Rio dc Janeiro focal treatment essays with granulated Abate at 1 ppm and perifocal treatment essays with wettable powder of Sumithion at 2,5% were performed. These were made either alone or in combination as well as associated to insecticides applied at ultra low volume. The premise indices obtained one month after the treatments indicates that the focal treatment alone is effective, no other addicional methods being necessary. The perifocal treatment is not effective and did not prevent the development of Aedes aegypti larvae and other insects in tires which had their external surface painted with Sumithion and Malathion.

[Focal myositis: An unknown disease].

Science.gov (United States)

Gallay, L; Streichenberger, N; Benveniste, O; Allenbach, Y

2017-10-01

Focal myositis are inflammatory muscle diseases of unknown origin. At the opposite from the other idiopathic inflammatory myopathies, they are restricted to a single muscle or to a muscle group. They are not associated with extramuscular manifestations, and they have a good prognosis without any treatment. They are characterized by a localized swelling affecting mostly lower limbs. The pseudo-tumor can be painful, but is not associated with a muscle weakness. Creatine kinase level is normal. Muscle MRI shows an inflammation restricted to a muscle or a muscle group. Muscle biopsy and pathological analysis remain necessary for the diagnosis, showing inflammatory infiltrates composed by macrophages and lymphocytes without any specific distribution within the muscle. Focal overexpression of HLA-1 by the muscle fibers is frequently observed. The muscle biopsy permits to rule out differential diagnosis such a malignancy (sarcoma). Spontaneous remission occurs within weeks or months after the first symptoms, relapse is unusual. Copyright © 2017. Published by Elsevier SAS.

Multiple genes encode the major surface glycoprotein of Pneumocystis carinii

DEFF Research Database (Denmark)

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

1993-01-01

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

Theory of the mechanical response of focal adhesions to shear flow

International Nuclear Information System (INIS)

Biton, Y Y; Safran, S A

2010-01-01

The response of cells to shear flow is primarily determined by the asymmetry of the external forces and moments that are sensed by each member of a focal adhesion pair connected by a contractile stress fiber. In the theory presented here, we suggest a physical model in which each member of such a pair of focal adhesions is treated as an elastic body subject to both a myosin-activated contractile force and the shear stress induced by the external flow. The elastic response of a focal adhesion complex is much faster than the active cellular processes that determine the size of the associated focal adhesions and the direction of the complex relative to the imposed flow. Therefore, the complex attains its mechanical equilibrium configuration which may change because of the cellular activity. Our theory is based on the experimental observation that focal adhesions modulate their cross-sectional area in order to attain an optimal shear. Using this assumption, our elastic model shows that such a complex can passively change its orientation to align parallel to the direction of the flow.

Focal decompositions for linear differential equations of the second order

Directory of Open Access Journals (Sweden)

L. Birbrair

2003-01-01

two-points problems to itself such that the image of the focal decomposition associated to the first equation is a focal decomposition associated to the second one. In this paper, we present a complete classification for linear second-order equations with respect to this equivalence relation.

Focal myositis of lower extremity responsive to botulinum A toxin.

Science.gov (United States)

Mitrovic, Josko; Prka, Zeljko; Zic, Rado; Marusic, Srecko; Morovic-Vergles, Jadranka

2014-01-01

Focal myositis is a rare, mostly benign disease (pseudotumor) of skeletal muscle, histopathologically characterized by interstitial myositis and tumorous enlargement of a single muscle. The etiology of focal myositis remains unknown; however, localized myopathy has been postulated to be caused by denervation lesions. This case report describes a patient that presented with clinical, laboratory, electromyoneurography, and magnetic resonance imaging features of focal myositis complicated with intervertebral disk protrusion in the lumbosacral spine affected with radicular distress. In most cases, focal myositic lesions show spontaneous regression, relapses are rare, and long-term prognosis is good. There is a wide spectrum of therapeutic options, from no therapy at all through nonsteroidal antirheumatics and glucocorticoids to radiotherapy, surgical excision, and immunosuppressants. In the patient presented, treatment with glucocorticoids, methotrexate, and surgical excision failed to produce satisfactory results. Clinical improvement, pain relief, and reduction in lower leg volume were only achieved by local infiltration of botulinum A toxin.

Deriving the effective focal plane for the CBM-RICH detector

Energy Technology Data Exchange (ETDEWEB)

Kres, Ievgenii [Wuppertal University (Germany); Collaboration: CBM-Collaboration

2016-07-01

The Compressed Baryonic Matter (CBM) experiment at the future FAIR complex will investigate the phase diagram of strongly interacting matter at high baryon density and moderate temperatures in A+A collisions from 2-11 AGeV (SIS100). A central component of the proposed detector setup is a ring imaging Cherenkov detector (RICH) using CO2 as radiator gas, and a focussing optic with a large spherical mirror. In the present design, the optimal focal plane is approximated using four individual, flat detection surfaces. However, the exact shape and position of the ideal focal plane is subject to further optimization due to effects from tilting the focussing mirror and from momentum dependant deflection of the electron tracks in the magnetic stray field. In this talk, we present a new approach to derive the effective 3-dimensional shape of the focal plane based on a set of Monte Carlo simulations, comparing the ring sharpness at each point of a preliminary focal plane as function of z-position.

METHOD FOR DETERMINATION OF FOCAL PLANE LOCATION OF FOCUSING COMPONENTS

Directory of Open Access Journals (Sweden)

A. I. Ivashko

2017-01-01

Full Text Available Mass-production of different laser systems often requires utilization of the focal spot size method for determination of output laser beam spatial characteristics. The main challenge of this method is high accuracy maintenance of a CCD camera beam profiler in the collecting lens focal plane. The aim of our work is development of new method for placing of photodetector array in the collecting lens focal plane with high accuracy.Proposed technique is based on focusing of several parallel laser beams. Determination of the focal plane position requires only longitudinal translation of the CCD-camera to find a point of laser beams intersection. Continuous-wave (CW diode-pumped laser emitting in the spectral region near 1μm was created to satisfy the requirements of the developed technique. Designed microchip laser generates two stigmatic Gaussian beams with automatically parallel beam axes due to independent pumping of different areas of the one microchip crystal having the same cavity mirrors.It was theoretically demonstrated that developed method provides possibility of the lenses focal plane determination with 1 % accuracy. The microchip laser generates two parallel Gaussian beams with divergence of about 10 mrad. Laser output power can be varied in the range of 0.1–1.5 W by changing the pumping laser diode electrical current. The distance between two beam axes can be changed in the range of 0.5–5.0 mm.We have proposed method for determination of positive lens focal plane location by using of CCDcamera and two laser beams with parallel axes without utilization of additional optical devices. We have developed CW longitudinally diode pumped microchip laser emitting in the 1-μm spectral region that can be used in the measuring instrument that doesn’t require precision mechanical components for determination of focal plane location with 1 % accuracy. The overall dimensions of laser head was 70 × 40 × 40 mm3 and maximum power consumption was

Detection technique of targets for missile defense system

Science.gov (United States)

Guo, Hua-ling; Deng, Jia-hao; Cai, Ke-rong

2009-11-01

Ballistic missile defense system (BMDS) is a weapon system for intercepting enemy ballistic missiles. It includes ballistic-missile warning system, target discrimination system, anti-ballistic-missile guidance systems, and command-control communication system. Infrared imaging detection and laser imaging detection are widely used in BMDS for surveillance, target detection, target tracking, and target discrimination. Based on a comprehensive review of the application of target-detection techniques in the missile defense system, including infrared focal plane arrays (IRFPA), ground-based radar detection technology, 3-dimensional imaging laser radar with a photon counting avalanche photodiode (APD) arrays and microchip laser, this paper focuses on the infrared and laser imaging detection techniques in missile defense system, as well as the trends for their future development.

Stent parameters predict major adverse clinical events and the response to platelet glycoprotein IIb/IIIa blockade: findings of the ESPRIT trial.

Science.gov (United States)

Tcheng, James E; Lim, Ing Haan; Srinivasan, Shankar; Jozic, Joseph; Gibson, C Michael; O'Shea, J Conor; Puma, Joseph A; Simon, Daniel I

2009-02-01

Only limited data describe relationships between stent parameters (length and diameter), adverse events after percutaneous coronary intervention, and effects of platelet glycoprotein IIb/IIIa blockade by stent parameters. In this post hoc analysis of the 1983 patients receiving a stent in the Enhanced Suppression of the Platelet Glycoprotein IIb/IIIa Receptor with Integrilin Therapy randomized percutaneous coronary intervention trial of eptifibatide versus placebo, rates of the major adverse cardiac event (MACE) end point (death, myocardial infarction, urgent target-vessel revascularization, or thrombotic bailout) at 48 hours and 1 year were correlated with stent parameters and then analyzed by randomization to eptifibatide versus placebo. In the placebo group, MACE increased with number of stents implanted, total stent length (by quartiles of or=30 mm), and total stented vessel area (by quartiles of area or=292 mm(2)). By stent parameters, MACE at 48 hours was reduced in the eptifibatide group at stent lengths of 18 to or=30 mm (OR, 0.43; 95% CI, 0.25 to 0.75; P=0.003), stent diameters of >2.5 to <3.5 mm (OR, 0.56; 95% CI, 0.39 to 0.82; P=0.002), and with 2 stents implanted (OR, 0.39; 95% CI, 0.22 to 0.69; P=0.001). In the placebo group, near-linear relationships were observed between both increasing stent length and increasing stented vessel area and MACE at 48 hours and 1 year (all, P<0.001); these gradients were flattened in the eptifibatide group (P=0.005 for stent length). Stent parameters predict MACE after percutaneous coronary intervention. Glycoprotein IIb/IIIa blockade mitigates much of the hazard of increasing procedural complexity.

Focal depth measurement of scanning helium ion microscope

International Nuclear Information System (INIS)

Guo, Hongxuan; Itoh, Hiroshi; Wang, Chunmei; Zhang, Han; Fujita, Daisuke

2014-01-01

When facing the challenges of critical dimension measurement of complicated nanostructures, such as of the three dimension integrated circuit, characterization of the focal depth of microscopes is important. In this Letter, we developed a method for characterizing the focal depth of a scanning helium ion microscope (HIM) by using an atomic force microscope tip characterizer (ATC). The ATC was tilted in a sample chamber at an angle to the scanning plan. Secondary electron images (SEIs) were obtained at different positions of the ATC. The edge resolution of the SEIs shows the nominal diameters of the helium ion beam at different focal levels. With this method, the nominal shapes of the helium ion beams were obtained with different apertures. Our results show that a small aperture is necessary to get a high spatial resolution and high depth of field images with HIM. This work provides a method for characterizing and improving the performance of HIM.

Targeting Herpes Simplex Virus-1 gD by a DNA Aptamer Can Be an Effective New Strategy to Curb Viral Infection

Directory of Open Access Journals (Sweden)

Tejabhiram Yadavalli

2017-12-01

Full Text Available Herpes simplex virus type 1 (HSV-1 is an important factor for vision loss in developed countries. A challenging aspect of the ocular infection by HSV-1 is that common treatments, such as acyclovir, fail to provide effective topical remedies. Furthermore, it is not very clear whether the viral glycoproteins, required for HSV-1 entry into the host, can be targeted for an effective therapy against ocular herpes in vivo. Here, we demonstrate that HSV-1 envelope glycoprotein gD, which is essential for viral entry and spread, can be specifically targeted by topical applications of a small DNA aptamer to effectively control ocular infection by the virus. Our 45-nt-long DNA aptamer showed high affinity for HSV-1 gD (binding affinity constant [Kd] = 50 nM, which is strong enough to disrupt the binding of gD to its cognate host receptors. Our studies showed significant restriction of viral entry and replication in both in vitro and ex vivo studies. In vivo experiments in mice also resulted in loss of ocular infection under prophylactic treatment and statistically significant lower infection under therapeutic modality compared to random DNA controls. Thus, our studies validate the possibility that targeting HSV-1 entry glycoproteins, such as gD, can locally reduce the spread of infection and define a novel DNA aptamer-based approach to control HSV-1 infection of the eye.

Sindbis Virus-Pseudotyped Lentiviral Vectors Carrying VEGFR2-Specific Nanobody for Potential Transductional Targeting of Tumor Vasculature.

Science.gov (United States)

Ahani, Roshank; Roohvand, Farzin; Cohan, Reza Ahangari; Etemadzadeh, Mohammad Hossein; Mohajel, Nasir; Behdani, Mahdi; Shahosseini, Zahra; Madani, Navid; Azadmanesh, Kayhan

2016-11-01

Introduction of selectivity/specificity into viral-based gene delivery systems, such as lentiviral vectors (LVs), is crucial in their systemic administration for cancer gene therapy. The pivotal role of tumor-associated endothelial cells (TAECs) in tumor angiogenesis and overexpression of vascular endothelial growth factor receptor-2 (VEGFR2 or KDR) in TAECs makes them a potent target in cancer treatment. Herein, we report the development of VEGFR2-targeted LVs pseudotyped with chimeric sindbis virus E2 glycoprotein (cSVE2s). For this purpose, either sequence of a VEGFR2-specific nanobody or its natural ligand (VEGF 121 ) was inserted into the binding site of sindbis virus E2 glycoprotein. In silico modeling data suggested that the inserted targeting motifs were exposed in the context of cSVE2s. Western blot analysis of LVs indicated the incorporation of cSVE2s into viral particles. Capture ELISA demonstrated the specificity/functionality of the incorporated cSVE2s. Transduction of 293/KDR (expressing VEGFR2) or 293T cells (negative control) by constructed LVs followed by fluorescent microscopy and flow cytometric analyses indicated selective transduction of 293/KDR cells (30 %) by both targeting motifs compared to 293T control cells (1-2 %). These results implied similar targeting properties of VEGFR2-specific nanobody compared to the VEGF 121 and indicated the potential for transductional targeting of tumor vasculature by the nanobody displaying LVs.

Super-resolution links vinculin localization to function in focal adhesions.

Science.gov (United States)

Giannone, Grégory

2015-07-01

Integrin-based focal adhesions integrate biochemical and biomechanical signals from the extracellular matrix and the actin cytoskeleton. The combination of three-dimensional super-resolution imaging and loss- or gain-of-function protein mutants now links the nanoscale dynamic localization of proteins to their activation and function within focal adhesions.

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

Energy Technology Data Exchange (ETDEWEB)

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

1975-05-01

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

Membership Functions for Fuzzy Focal Elements

Directory of Open Access Journals (Sweden)

Porębski Sebastian

2016-09-01

Full Text Available The paper presents a study on data-driven diagnostic rules, which are easy to interpret by human experts. To this end, the Dempster-Shafer theory extended for fuzzy focal elements is used. Premises of the rules (fuzzy focal elements are provided by membership functions which shapes are changing according to input symptoms. The main aim of the present study is to evaluate common membership function shapes and to introduce a rule elimination algorithm. Proposed methods are first illustrated with the popular Iris data set. Next experiments with five medical benchmark databases are performed. Results of the experiments show that various membership function shapes provide different inference efficiency but the extracted rule sets are close to each other. Thus indications for determining rules with possible heuristic interpretation can be formulated.

Focal epilepsy in the Belgian shepherd

DEFF Research Database (Denmark)

Berendt, Mette; Gulløv, Christina Hedal; Fredholm, Merete

2009-01-01

and deceased) were ascertained through a telephone interview using a standardised questionnaire regarding seizure history and phenomenology. Living dogs were invited to a detailed clinical evaluation. Litters more than five years of age, or where epilepsy was present in all offspring before the age of five......, were included in the calculations of inheritance. results: Out of 199 family members, 66 dogs suffered from epilepsy. The prevalence of epilepsy in the family was 33%. Fifty-five dogs experienced focal seizures with or without secondary generalisation, while four dogs experienced primary generalised...... seizures. In seven dogs, seizures could not be classified. The mode of inheritance of epilepsy was simple Mendelian. CLINICAL SIGNIFICANCE: This study identified that the Belgian shepherd suffers from genetically transmitted focal epilepsy. The seizure phenomenology expressed by family members have...

Generating Isoform-Specific Antibodies : Lessons from Nucleocytoplasmic Glycoprotein Skp1

NARCIS (Netherlands)

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

2015-01-01

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

Direct chemical modification and voltammetric detection of glycans in glycoproteins

Czech Academy of Sciences Publication Activity Database

Trefulka, Mojmír; Paleček, Emil

2014-01-01

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

Irradiation of rat brain reduces P-glycoprotein expression and function

NARCIS (Netherlands)

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

2007-01-01

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

Extensive Focal Epithelial Hyperplasia: A Case Report.

Science.gov (United States)

Mansouri, Zahra; Bakhtiari, Sedigheh; Noormohamadi, Robab

2015-01-01

Focal epithelial hyperplasia (FEH) or Heck's disease is a rare viral infection of the oral mucosa caused by human papilloma virus especially subtypes 13 or 32. The frequency of this disease varies widely from one geographic region and ethnic groups to another. This paper reports an Iranian case of extensive focal epithelial hyperplasia. A 35-year-old man with FEH is described, in whom the lesions had persisted for more than 25 years. The lesion was diagnosed according to both clinical and histopathological features. Dental practitioner should be aware of these types of lesions and histopathological examination together and a careful clinical observation should be carried out for a definitive diagnosis.

Focal splenic masses of the extramedullary hematopoiesis

International Nuclear Information System (INIS)

Incedayi, M.; Sivrioglu, A.

2012-01-01

Full text: Extramedullary hematopoiesis arises from pleuripotential stem cells distributed throughout the body. It is most common in patients with congenital hemolytic anemia, such as thalassemia, sickle cell anemia and hereditary spherocytosis as a response to ineffective red blood cell formation. Although microscopic foci of Extramedullary hematopoiesis are commonly seen in the spleen and liver parenchyma, focal mass-like lesion of extramedullary hematopoiesis in the liver and spleen are rare. We report a case of intrasplenic focal extramedullary hematopoiesis lesions and the imaging features of extramedullary hematopoiesis on computed tomography and magnetic resonance imaging. Extramedullary hematopoiesis should always be considered as a diagnosis in a patient with a known hematological disorder

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

Science.gov (United States)

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

2010-03-01

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

Correlation between Focal Nodular Low Signal Changes in Hoffa’s Fat Pad Adjacent to Anterior Femoral Cartilage and Focal Cartilage Defect Underlying This Region and Its Possible Implication

Directory of Open Access Journals (Sweden)

Chermaine Deepa Antony

2016-01-01

Full Text Available Purpose. This study investigates the association between focal nodular mass with low signal in Hoffa’s fat pad adjacent to anterior femoral cartilage of the knee (FNMHF and focal cartilage abnormality in this region. Method. The magnetic resonance fast imaging employing steady-state acquisition sequence (MR FIESTA sagittal and axial images of the B1 and C1 region (described later of 148 patients were independently evaluated by two reviewers and categorized into four categories: normal, FNMHF with underlying focal cartilage abnormality, FNMHF with normal cartilage, and cartilage abnormality with no FNMHF. Results. There was a significant association (p=0.00 between FNMHF and immediate adjacent focal cartilage abnormality with high interobserver agreement. The absence of focal nodular lesions next to the anterior femoral cartilage has a very high negative predictive value for chondral injury (97.8%. Synovial biopsy of focal nodular lesion done during arthroscopy revealed some fibrocollagenous tissue and no inflammatory cells. Conclusion. We postulate that the FNMHF adjacent to the cartilage defects is a form of normal healing response to the cartilage damage. One patient with FHMHF and underlying cartilage abnormality was rescanned six months later. In this patient, the FNMHF disappeared and normal cartilage was observed in the adjacent region which may support this theory.

Podoplanin - a small glycoprotein with many faces

OpenAIRE

Ugorski, Maciej; Dziegiel, Piotr; Suchanski, Jaroslaw

2016-01-01

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

The design of LMJ focal spots for indirect drive experiments

International Nuclear Information System (INIS)

Le Garrec, B J; Sajer, J M

2008-01-01

LMJ is a 240 high power laser beam facility for achieving laser matter interaction experiments, high energy density science, including the demonstration of fusion ignition through Inertial Confinement. The Laser Integration Line (LIL) facility is currently a 4-beam prototype for LMJ. The intensity I 0 at the focal spot centre drives hydrodynamic and plasma instabilities and the intensity in the wings must be low to go through the laser entrance Hohlraum. A simple model has been developed to compute the LMJ focal spot. The model gives the intensity at the centre as a function of the focal spot area at 3% of the maximum

Focal myositis of the thigh: unusual MR pattern

International Nuclear Information System (INIS)

Llauger, Jaume; Palmer, Jaume; San Roman, Luis; Bague, Silvia; Matias-Guiu, Xavier; Doncel, Antonio

2002-01-01

Focal myositis is a commonly referenced, infrequently reported and poorly documented benign inflammatory pseudotumor which may be misdiagnosed clinically as a malignant tumor. We report the clinicopathologic features and magnetic resonance imaging findings in a case of focal myositis in the thigh of a 55-year-old woman. A different radiologic presentation of this disorder is described. The gross appearance of the lesion, previously undescribed, appears to be rather specific for such a pseudoneoplastic disorder, and correlates very well with the magnetic resonance imaging features. (orig.)

Focal myositis of the thigh: unusual MR pattern

Energy Technology Data Exchange (ETDEWEB)

Llauger, Jaume; Palmer, Jaume; San Roman, Luis [Department of Radiology, Hospital de la Santa Creu i Sant Pau, Barcelona (Spain); Bague, Silvia; Matias-Guiu, Xavier [Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona (Spain); Doncel, Antonio [Department of Orthopedic Surgery, Hospital de la Santa Creu i Sant Pau, Barcelona (Spain)

2002-05-01

Focal myositis is a commonly referenced, infrequently reported and poorly documented benign inflammatory pseudotumor which may be misdiagnosed clinically as a malignant tumor. We report the clinicopathologic features and magnetic resonance imaging findings in a case of focal myositis in the thigh of a 55-year-old woman. A different radiologic presentation of this disorder is described. The gross appearance of the lesion, previously undescribed, appears to be rather specific for such a pseudoneoplastic disorder, and correlates very well with the magnetic resonance imaging features. (orig.)

Expansion characteristics of coronary stents in focal stenoses

Directory of Open Access Journals (Sweden)

Schmidt Wolfram

2017-09-01

Full Text Available The presented experimental in vitro approach was designed to assess the expansion behavior of stent systems in a resistant focal stenosis model with respect to a potential dog-boning effect. Five different stent systems (nominal diameter 3.0 mm were investigated. The focal stenosis was simulated by a stainless steel tube (ID ≤ 1.20 mm. Stent expansion was performed using a proprietary test device consisting of a test chamber with 37 °C water, 2-axis laser scanner and a pressure controller.

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

International Nuclear Information System (INIS)

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

1989-01-01

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

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

Science.gov (United States)

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

1992-07-01

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

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

Science.gov (United States)

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

1995-01-18

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

Determination of the paraxial focal length using Zernike polynomials over different apertures

Science.gov (United States)

Binkele, Tobias; Hilbig, David; Henning, Thomas; Fleischmann, Friedrich

2017-02-01

The paraxial focal length is still the most important parameter in the design of a lens. As presented at the SPIE Optics + Photonics 2016, the measured focal length is a function of the aperture. The paraxial focal length can be found when the aperture approaches zero. In this work, we investigate the dependency of the Zernike polynomials on the aperture size with respect to 3D space. By this, conventional wavefront measurement systems that apply Zernike polynomial fitting (e.g. Shack-Hartmann-Sensor) can be used to determine the paraxial focal length, too. Since the Zernike polynomials are orthogonal over a unit circle, the aperture used in the measurement has to be normalized. By shrinking the aperture and keeping up with the normalization, the Zernike coefficients change. The relation between these changes and the paraxial focal length are investigated. The dependency of the focal length on the aperture size is derived analytically and evaluated by simulation and measurement of a strong focusing lens. The measurements are performed using experimental ray tracing and a Shack-Hartmann-Sensor. Using experimental ray tracing for the measurements, the aperture can be chosen easily. Regarding the measurements with the Shack-Hartmann- Sensor, the aperture size is fixed. Thus, the Zernike polynomials have to be adapted to use different aperture sizes by the proposed method. By doing this, the paraxial focal length can be determined from the measurements in both cases.

Improved image quality for asymmetric double-focal cone-beam SPECT

International Nuclear Information System (INIS)

Cao, Z.J.; Tsui, B.M.W.

1993-01-01

To optimize both spatial resolution and detection efficiency in brain SPECT imaging using a rectangular camera, an asymmetric double-focal cone-beam collimator is proposed with the focal points located near the base plane of the patient's head. To fit the entire head into the field-of-view of the collimator with dimensions of 50cmx40cm and at a radius-of-rotation of 15 cm, the focal lengths of the collimator are 55 and 70 cm, respectively, in the transverse and axial directions. With this geometry, the artifacts in the reconstructed image produced by the Feldkamp algorithm are more severe compared to those in a symmetric cone-beam geometry, due to the larger vertex angle between the top of the head and the base plane. To improve the reconstructed image quality, a fully three-dimensional (3D) reconstruction algorithm developed previously for single-focal cone-beam SPECT was extended to the asymmetric double-focal cone-beam geometry. The algorithm involves nonstationary 2D filtering and a reprojection technique for estimation of the missing data caused by a single-orbit cone-beam geometry. The results from simulation studies with the 3D Defrise slab phantom demonstrated that the fully 3D algorithm provided a much improved image quality in terms of reduced slice-to-slice cross talks and shape elongation compared to that produced by the conventional Feldkamp algorithm

CT and ERCP findings of chronic focal pancreatitis

Energy Technology Data Exchange (ETDEWEB)

Kim, Hee Soo; Lee, Jong Tae; Yoo, Hyung Sik; Kim, Eun Kyeong [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

1996-10-01

To evaluate the major radiologic features of chronic focal pancreatitis in various imaging studies, with special emphasis on CT and ERCP findings. From 1991 to 1995, twelve patients were pathologically proved to be suffering from focal chronic pancreatitis after pancreatico-duodenectomy;for retrospective evaluation, imaging studies were available for eight(seven men, one woman;mean age 58.9{+-}6.6, range 47 to 67). Clinical, surgical, and radiological findings, including CT(n=8), ultrasound(n=7), ERCP(n=8) and UGI(n=3) were analysed. Seven male patients had suffered from chronic alcoholism for between 20 and 50 years. Serum bilirubin levels were normal in eight patients and alkaline phosphatase levels were normal in seven patients. Serum CA 19-9 levels were normal in all five patients who had undergone preoperative evaluation. Seven patients(87.5%) showed focal enlargement without definable margin on CT, and five of the six lesions detectable on ultrasound(83.3%) were ill defined hypoechoic nodules. Dilated side branches within lesions were seen in five of eight patients(83.3%) on CT and ERCP. Double duct signs were observed in siven(87.5%) patients, and dilated intrahepatic ducts in six(75%), with diameters ranging from 5 to 8mm(average:5.42{+-}1.96mm). The average ratio of pancreatic duct caliber to gland width was 0.33{+-}0.19. None of the patients had calcification within the lesion and one case showed intraductal calcification. None showed perivascular fat obliteration around the superior mesenteric artery or celiac axis. The average biductal distance between abnormal common bile duct and the immediately adjacent pancreatic duct was 4.0{+-}1.15mm. One of three cases who under went a UGI examination showed severe luminal narrowing and mucosal thickening in the second protion of the duodenum, another showed double contour, and the other merely showed widening of the C-loop of the duodenum. Chronic focal pancreatitis mostly demonstrated ill defined focal

CT and ERCP findings of chronic focal pancreatitis

International Nuclear Information System (INIS)

Kim, Hee Soo; Lee, Jong Tae; Yoo, Hyung Sik; Kim, Eun Kyeong

1996-01-01

To evaluate the major radiologic features of chronic focal pancreatitis in various imaging studies, with special emphasis on CT and ERCP findings. From 1991 to 1995, twelve patients were pathologically proved to be suffering from focal chronic pancreatitis after pancreatico-duodenectomy;for retrospective evaluation, imaging studies were available for eight(seven men, one woman;mean age 58.9±6.6, range 47 to 67). Clinical, surgical, and radiological findings, including CT(n=8), ultrasound(n=7), ERCP(n=8) and UGI(n=3) were analysed. Seven male patients had suffered from chronic alcoholism for between 20 and 50 years. Serum bilirubin levels were normal in eight patients and alkaline phosphatase levels were normal in seven patients. Serum CA 19-9 levels were normal in all five patients who had undergone preoperative evaluation. Seven patients(87.5%) showed focal enlargement without definable margin on CT, and five of the six lesions detectable on ultrasound(83.3%) were ill defined hypoechoic nodules. Dilated side branches within lesions were seen in five of eight patients(83.3%) on CT and ERCP. Double duct signs were observed in siven(87.5%) patients, and dilated intrahepatic ducts in six(75%), with diameters ranging from 5 to 8mm(average:5.42±1.96mm). The average ratio of pancreatic duct caliber to gland width was 0.33±0.19. None of the patients had calcification within the lesion and one case showed intraductal calcification. None showed perivascular fat obliteration around the superior mesenteric artery or celiac axis. The average biductal distance between abnormal common bile duct and the immediately adjacent pancreatic duct was 4.0±1.15mm. One of three cases who under went a UGI examination showed severe luminal narrowing and mucosal thickening in the second protion of the duodenum, another showed double contour, and the other merely showed widening of the C-loop of the duodenum. Chronic focal pancreatitis mostly demonstrated ill defined focal enlargement and

[Primary focal dystonia: descriptive study of 205 patients].

Science.gov (United States)

Bartolomé, F M; Fanjul, S; Cantarero, S; Hernández, J; García Ruiz, P J

2003-03-01

To describe the clinical and epidemiologic aspects of different types of focal dystonia. A total of 205 patients with primary focal dystonia were studied retrospectively and the following variables were analyzed: gender, age of onset, age at examination, evolution time, history of trauma, association with other movement disorders, fluctuations of dystonic symptoms as well as a family history of dystonia, Parkinson's disease, tremor, and lefthandedness or stuttering. We compared these variables among the different clinical categories of focal dystonia. Those patients with cranial and laryngeal dystonia were significantly older at the onset of symptoms compared with patients with writer's cramp. Males were more prevalent than females in all categories of focal dystonia except for cranial dystonia. Prior history of trauma and association with tremor were more frequent in patients with cervical dystonia than in those with others dystonic categories. Most patients with cranial, cervical and laryngeal dystonia had fluctuations in the intensity of dystonic symptoms, unlike the patients with writer's cramp. There is a caudo-cranial gradient in age of onset and the age of onset increases as the cranial presentation becomes greater. Females are more prevalent in cranial dystonia and there is a preponderance of males in the dystonias with a lower location. The dystonias with cranial distribution frequently present fluctuations of symptoms during the day. Association with other movement disorders, such as tremor, and prior history of trauma, is common in patients with cervical dystonia.

Quantum-Well Infrared Photodetector (QWIP) Focal Plane Assembly

Science.gov (United States)

Jhabvala, Murzy; Jhabvala, Christine A.; Ewin, Audrey J.; Hess, Larry A.; Hartmann, Thomas M.; La, Anh T.

2012-01-01

A paper describes the Thermal Infrared Sensor (TIRS), a QWIP-based instrument intended to supplement the Operational Land Imager (OLI) for the Landsat Data Continuity Mission (LDCM). The TIRS instrument is a far-infrared imager operating in the pushbroom mode with two IR channels: 10.8 and 12 microns. The focal plane will contain three 640x512 QWIP arrays mounted on a silicon substrate. The silicon substrate is a custom-fabricated carrier board with a single layer of aluminum interconnects. The general fabrication process starts with a 4-in. (approx.10-cm) diameter silicon wafer. The wafer is oxidized, a single substrate contact is etched, and aluminum is deposited, patterned, and alloyed. This technology development is aimed at incorporating three large-format infrared detecting arrays based on GaAs QWIP technology onto a common focal plane with precision alignment of all three arrays. This focal plane must survive the rigors of flight qualification and operate at a temperature of 43 K (-230 C) for five years while orbiting the Earth. The challenges presented include ensuring thermal compatibility among all the components, designing and building a compact, somewhat modular system and ensuring alignment to very tight levels. The multi-array focal plane integrated onto a single silicon substrate is a new application of both QWIP array development and silicon wafer scale integration. The Invar-based assembly has been tested to ensure thermal reliability.

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

DEFF Research Database (Denmark)

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

2008-01-01

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

Genetics Home Reference: focal dermal hypoplasia

Science.gov (United States)

... in people with focal dermal hypoplasia is an omphalocele , which is an opening in the wall of ... Dermal Hypoplasia MedlinePlus Encyclopedia: Ectodermal dysplasia MedlinePlus Encyclopedia: Omphalocele General Information from MedlinePlus (5 links) Diagnostic Tests ...

ANUSANSKAR: a 16 channel frontend electronics (FEE) ASIC targeted for silicon pixel array detector based prototype Alice FOCAL

International Nuclear Information System (INIS)

Mukhopadhyay, Sourav; Chandratre, V.B.; Sukhwani, Menka; Pithawa, C.K.; Singaraju, Ramnarayan; Muhuri, Sanjib; Nayak, T.; Khan, S.A.; Saini, Jogendra

2013-01-01

ANUSANSKAR is a 16 channel pulse processing ASIC with analog multiplexed output designed in 0.7 um standard CMOS technology with each channel consisting of CSA, Semi Gaussian pulse shaper, DC cancellation and pedestal control, track and hold, output buffer blocks. The ASIC's analog multiplexed output can be read serially in daisy-chain topology. Testing, characterization and validation of ANUSANSKAR ASIC as readout for prototype ALICE forward calorimeter (FOCAL) has been carried out in PS beam line at CERN with up to 6 GeV of pion and electron beam. This paper describes the ANUSANSKAR ASIC along with the experimental results. (author)

Performance of an Achromatic Focal Plane Mask for Exoplanet Imaging Coronagraphy

Science.gov (United States)

Newman, Kevin; Belikov, Ruslan; Pluzhnik, Eugene; Balasubramanian, Kunjithapatham; Wilson, Dan

2014-01-01

Coronagraph technology combined with wavefront control is close to achieving the contrast and inner working angle requirements in the lab necessary to observe the faint signal of an Earth-like exoplanet in monochromatic light. An important remaining technological challenge is to achieve high contrast in broadband light. Coronagraph bandwidth is largely limited by chromaticity of the focal plane mask, which is responsible for blocking the stellar PSF. The size of a stellar PSF scales linearly with wavelength; ideally, the size of the focal plane mask would also scale with wavelength. A conventional hard-edge focal plane mask has a fixed size, normally sized for the longest wavelength in the observational band to avoid starlight leakage. The conventional mask is oversized for shorter wavelengths and blocks useful discovery space. Recently we presented a solution to the size chromaticity challenge with a focal plane mask designed to scale its effective size with wavelength. In this paper, we analyze performance of the achromatic size-scaling focal plane mask within a Phase Induced Amplitude Apodization (PIAA) coronagraph. We present results from wavefront control around the achromatic focal plane mask, and demonstrate the size-scaling effect of the mask with wavelength. The edge of the dark zone, and therefore the inner working angle of the coronagraph, scale with wavelength. The achromatic mask enables operation in a wider band of wavelengths compared with a conventional hard-edge occulter.

Butterfly Wings Are Three-Dimensional: Pupal Cuticle Focal Spots and Their Associated Structures in Junonia Butterflies.

Science.gov (United States)

Taira, Wataru; Otaki, Joji M

2016-01-01

Butterfly wing color patterns often contain eyespots, which are developmentally determined at the late larval and early pupal stages by organizing activities of focal cells that can later form eyespot foci. In the pupal stage, the focal position of a future eyespot is often marked by a focal spot, one of the pupal cuticle spots, on the pupal surface. Here, we examined the possible relationships of the pupal focal spots with the underneath pupal wing tissues and with the adult wing eyespots using Junonia butterflies. Large pupal focal spots were found in two species with large adult eyespots, J. orithya and J. almana, whereas only small pupal focal spots were found in a species with small adult eyespots, J. hedonia. The size of five pupal focal spots on a single wing was correlated with the size of the corresponding adult eyespots in J. orithya. A pupal focal spot was a three-dimensional bulge of cuticle surface, and the underside of the major pupal focal spot exhibited a hollowed cuticle in a pupal case. Cross sections of a pupal wing revealed that the cuticle layer shows a curvature at a focal spot, and a positional correlation was observed between the cuticle layer thickness and its corresponding cell layer thickness. Adult major eyespots of J. orithya and J. almana exhibited surface elevations and depressions that approximately correspond to the coloration within an eyespot. Our results suggest that a pupal focal spot is produced by the organizing activity of focal cells underneath the focal spot. Probably because the focal cell layer immediately underneath a focal spot is thicker than that of its surrounding areas, eyespots of adult butterfly wings are three-dimensionally constructed. The color-height relationship in adult eyespots might have an implication in the developmental signaling for determining the eyespot color patterns.

Butterfly Wings Are Three-Dimensional: Pupal Cuticle Focal Spots and Their Associated Structures in Junonia Butterflies.

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Wataru Taira

Full Text Available Butterfly wing color patterns often contain eyespots, which are developmentally determined at the late larval and early pupal stages by organizing activities of focal cells that can later form eyespot foci. In the pupal stage, the focal position of a future eyespot is often marked by a focal spot, one of the pupal cuticle spots, on the pupal surface. Here, we examined the possible relationships of the pupal focal spots with the underneath pupal wing tissues and with the adult wing eyespots using Junonia butterflies. Large pupal focal spots were found in two species with large adult eyespots, J. orithya and J. almana, whereas only small pupal focal spots were found in a species with small adult eyespots, J. hedonia. The size of five pupal focal spots on a single wing was correlated with the size of the corresponding adult eyespots in J. orithya. A pupal focal spot was a three-dimensional bulge of cuticle surface, and the underside of the major pupal focal spot exhibited a hollowed cuticle in a pupal case. Cross sections of a pupal wing revealed that the cuticle layer shows a curvature at a focal spot, and a positional correlation was observed between the cuticle layer thickness and its corresponding cell layer thickness. Adult major eyespots of J. orithya and J. almana exhibited surface elevations and depressions that approximately correspond to the coloration within an eyespot. Our results suggest that a pupal focal spot is produced by the organizing activity of focal cells underneath the focal spot. Probably because the focal cell layer immediately underneath a focal spot is thicker than that of its surrounding areas, eyespots of adult butterfly wings are three-dimensionally constructed. The color-height relationship in adult eyespots might have an implication in the developmental signaling for determining the eyespot color patterns.

Focal thyroid incidentalomas identified with whole-body FDG-PET warrant further investigation.

LENUS (Irish Health Repository)

Prichard, R S

2012-02-01

Fluorodeoxyglucose (FDG) whole body positron emission computed tomography (PET-CT) detects clinically occult malignancy. The aim of this study was to assess the prevalence and significance of focal thyroid 18F - fluorodeoxyglucose uptake. A retrospective review of all patients who had FDG PET-CT examinations, in a single tertiary referral centre was performed. PET scan findings and the final pathological diagnosis were collated. 2105 scans were reviewed. Focal uptake was identified in 35 (1.66%) patients. Final surgical histology was available on eight patients, which confirmed papillary carcinoma in four (20%) patients and lymphoma and metastatic disease in two patients respectively. This gave an overall malignancy rate in focal thyroid uptake of at least 33%. Thyroid incidentalomas occurred with a frequency of 2.13%, with an associated malignancy rate of at least 33% in focal thyroid uptake. The high malignancy rate associated with focal thyroid uptake mandates further investigation in medically fit patients.

Identification of a mouse synaptic glycoprotein gene in cultured neurons.

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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.

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

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

2013-09-01

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

Electrostatics, small particles, and laser fusion targets

International Nuclear Information System (INIS)

Hendricks, C.D.

1978-01-01

The success of any Inertial Confinement Fusion system for the production of useful power depends critically on the production of suitable targets. This is true whether the arrangement is that proposed by Nuckolls et al. or some other arrangement. The target must have characteristics such as material composition, structure, and surface finish which are tailored to the laser pulse length, energy, peak and average power and pulse shape. To provide useful power on a continuous basis, it is likely that the repetition rate will be 1.0 to 10 per second. Thus, in a 24 hour running period 864,000 targets may be necessary and one must be placed at the focal point of the laser every tenth of a second. For economic operation it is necessary that the targets be produced at costs of less than $1.00 per target

Regional cerebral blood flow in focal cortical epilepsy

DEFF Research Database (Denmark)

Hougaard, Kristina Dupont; Oikawa, T; Sveinsdottir, E

1976-01-01

Regional cerebral blood flow (rCBF) was studied in ten patients with focal cortical epilepsy. The blood flow was measured by the intra-arterial injection of xenon 133 (133Xe), and the isotope clearance was recorded by a multidetector scintillation camera with 254 detectors. Three patients were....... This finding accords with earlier studies. All nine patients studied in the interictal phase showed, either spontaneously or during activation by intermittent light, focal flow increases in areas presumed to comprise the epileptic focus. These interictal hyperemic foci probably reflect subictal neuronal...

Continuous contour phase plates for tailoring the focal plane irradiance profile

International Nuclear Information System (INIS)

Dixit, S.N.; Rushford, M.C.; Thomas, I.M.; Perry, M.D.

1995-01-01

We present fully continuous phase screens for producing super-Gaussian focal-plane irradiance profiles. Such phase screens are constructed with the assumption of either circular symmetric near-field and far-field profiles or a separable phase screen in Cartesian co-ordinates. In each case, the phase screen is only a few waves deep. Under illumination by coherent light, such phase screens produce high order super-Gaussian profiles in the focal plane with high energy content effects of beam aberrations on the focal profiles and their energy content are also discussed

A case of pathological rib fractures: focal osteolysis or osteoporosis?

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Vrbanić, T S L; Novak, S; Sestan, B; Tudor, A; Gulan, G

2008-03-01

This paper reports on a unique, previously unreported, successful outcome in the case of a patient with focal osteolytic lesions of the ribs as a first sign of osteoporosis. The lesions were detected by chance after acute cough-induced rib fractures were seen on plain chest radiographs. The diagnosis had to be approached as a diagnosis of exclusion since known causes of the osteolytic process had to be eliminated. The authors describe multiple focal osteolytic lesions with rib fractures appearing in a pattern that could be confused with metastases. Laboratory results were normal. Final diagnosis was based on plain radiography, bone scan and bone densitometry. Pharmacomedical treatments for osteoporosis were applied. The patient was observed between the year 2000 and 2005. Five years later radiological and bone scintigraphy revealed resolution of the lesion. We conclude that osteoporosis should be included in the differential diagnosis of asymptomatic focal osteolysis of the ribs with rib fractures as a complication of acute cough. The case suggests that focal osteolytic lesions of the ribs may regress over time and become scintigraphically inactive.

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

Science.gov (United States)