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Sample records for antigen dramatically improves

  1. MHC class II-associated invariant chain linkage of antigen dramatically improves cell-mediated immunity induced by adenovirus vaccines

    DEFF Research Database (Denmark)

    Holst, Peter Johannes; Mandrup Jensen, Camilla Maria; Orskov, Cathrine

    2008-01-01

    The ideal vaccine induces a potent protective immune response, which should be rapidly induced, long-standing, and of broad specificity. Recombinant adenoviral vectors induce potent Ab and CD8+ T cell responses against transgenic Ags within weeks of administration, and they are among the most...... potent and versatile Ag delivery vehicles available. However, the impact of chronic infections like HIV and hepatitis C virus underscore the need for further improvements. In this study, we show that the protective immune response to an adenovirus-encoded vaccine Ag can be accelerated, enhanced......, broadened, and prolonged by tethering of the rAg to the MHC class II-associated invariant chain (Ii). Thus, adenovirus-vectored vaccines expressing lymphocytic choriomeningitis virus (LCMV)-derived glycoprotein linked to Ii increased the CD4+ and CD8+ T cell stimulatory capacity in vitro and in vivo...

  2. A method to dramatically improve subcarrier tracking

    Science.gov (United States)

    Hurd, William J.; Aguirre, Sergio

    1988-01-01

    A method is presented for achieving a dramatic improvement in phase tracking of square wave subcarriers or other square waves. The method is to set the amplitude of the phase quadrature reference signal to zero except near the zero crossings of the input signal. Without changing the loop bandwidth, the variance of the phase error can be reduced to approximately W sigma(sub 0)(2), where sigma (sub 0)(2) is the phase error variance without windowing, and W is the fraction of cycle in which the reference signal has a nonzero value. Simulation results confirm the analysis and establish minimum W versus signal-to-noise ratio. Typically, the window can be made so narrow as to achieve a phase error variance of 1.5 sigma(sub 0)(4).

  3. Microalloying Boron Carbide with Silicon to Achieve Dramatically Improved Ductility.

    Science.gov (United States)

    An, Qi; Goddard, William A

    2014-12-01

    Boron carbide (B4C) is a hard material whose value for extended engineering applications such as body armor; is limited by its brittleness under impact. To improve the ductility while retaining hardness, we used density functional theory to examine modifying B4C ductility through microalloying. We found that replacing the CBC chain in B4C with Si-Si, denoted as (B11Cp)-Si2, dramatically improves the ductility, allowing a continuous shear to a large strain of 0.802 (about twice of B4C failure strain) without brittle failure. Moreover, (B11C)-Si2 retains low density and high hardness. This ductility improvement arises because the Si-Si linkages enable the icosahedra accommodate additional shear by rotating instead of breaking bonds.

  4. A case of Lewis-Sumner syndrome showing dramatic improvement after plasma exchange.

    Science.gov (United States)

    Park, Young-Eun; Yook, Ji-Won; Kim, Dae-Seong

    2010-07-01

    We report a patient with Lewis-Sumner syndrome (LSS) who showed an improvement only with plasma exchange (PE). The patient, 32-yr old man, had progressive multifocal motor-sensory deficits with persistent, multiple conduction blocks and marked slowing of NCVs. Nerve pathology supported a diagnosis of demyelinating neuropathy by revealing marked loss of myelinated fibers with inter- and intrafascicular variation. Although the patient was refractory to treatment with corticosteroid and intravenous immunoglobulin, PE produced a dramatic improvement. Our experience strongly proposes that PE should be tried for refractory LSS.

  5. Critical success factors simplified implementing the powerful drivers of dramatic business improvement

    CERN Document Server

    Howell, Marvin T

    2010-01-01

    Critical-to-success factors (CSFs) have become essential elements to strategic planning and no business can achieve consistent success without effectively adopting them. To take full advantage of CSFs, however, an organization must first understand what they are and how they can be used to drive organizational initiatives and processes. Critical Success Factors Simplified: Implementing the Powerful Drivers of Dramatic Business Improvement provides a concise manual on CSFs that will teach you how to identify and select the right CSFs, measure their impact, and adjust them as needed to reach your goals.

  6. Dramatic improvement of pyoderma gangrenosum with infliximab in a patient with PAPA syndrome.

    Science.gov (United States)

    Stichweh, Dorothee S; Punaro, Marilynn; Pascual, Virginia

    2005-01-01

    Infliximab, a chimeric antitumor necrosis factor alpha monoclonal antibody (anti-TNF alpha), has been recently shown to have a beneficial effect on pyoderma gangrenosum associated with inflammatory bowel disease. Patients with the syndromic triad of pyogenic sterile arthritis, pyoderma gangrenosum, and acne, an autoinflammatory process caused by mutations in the CD2 binding protein-1 (CD2BP1) gene, can have severe pyoderma gangrenosum. We describe a 14-year-old patient with this syndrome who was unresponsive to multiple therapies. A dramatic improvement in his pyoderma gangrenosum was observed after one infusion of infliximab, and a second infusion led to its resolution. Our observation extends the therapeutic use of infliximab to this component of PAPA syndrome.

  7. SAFETY IMPROVES DRAMATICALLY IN FLUOR HANFORD SOIL AND GROUNDWATER REMEDIATION PROJECT

    Energy Technology Data Exchange (ETDEWEB)

    GERBER MS

    2007-12-05

    This paper describes dramatic improvements in the safety record of the Soil and Groundwater Remediation Project (SGRP) at the Hanford Site in southeast Washington state over the past four years. During a period of enormous growth in project work and scope, contractor Fluor Hanford reduced injuries, accidents, and other safety-related incidents and enhanced a safety culture that earned the SGRP Star Status in the Department of Energy's (DOE's) Voluntary Protection Program (VPP) in 2007. This paper outlines the complex and multi-faceted work of Fluor Hanford's SGRP and details the steps taken by the project's Field Operations and Safety organizations to improve safety. Holding field safety meetings and walkdowns, broadening safety inspections, organizing employee safety councils, intensively flowing down safety requirements to subcontractors, and adopting other methods to achieve remarkable improvement in safety are discussed. The roles of management, labor and subcontractors are detailed. Finally, SGRP's safety improvements are discussed within the context of overall safety enhancements made by Fluor Hanford in the company's 11 years of managing nuclear waste cleanup at the Hanford Site.

  8. Dramatic improvement of anti-SS-A/Ro-associated interstitial lung disease after immunosuppressive treatment.

    Science.gov (United States)

    Paola, Caramaschi; Giuliana, Festi; Giovanni, Orsolini; Cristian, Caimmi; Domenico, Biasi

    2016-07-01

    The aim of the study was to report three patients affected by interstitial lung disease associated with positive anti-SS-A/Ro autoantibody who showed a dramatic improvement after immunosuppressive treatment. Medical charts were reviewed to obtain clinical data, laboratory parameters, lung function tests, high-resolution computed tomography results and response to immunosuppressive treatment. The three patients showed a clinical picture of a lung-dominant connective tissue disease characterized by a sudden onset with dyspnea, cough and subtle extrathoracic features together with positive anti-SS-A/Ro antibody and weak titer antinuclear antibodies. All three patients responded favorably to immunosuppressive therapy: Two cases were treated with a combination of corticosteroid and cyclophosphamide followed by mycophenolate mofetil; in the third patient, clinical benefit was obtained after rituximab was added to corticosteroid and immunosuppressant drug. In spite of an abrupt onset with significant lung function impairment, all three patients had a favorable clinical response to immunosuppressive therapy. This report may be useful in making therapeutic decisions in case of interstitial lung disease associated with anti-SS-A antibody.

  9. A Case of Lewis-Sumner Syndrome Showing Dramatic Improvement after Plasma Exchange

    OpenAIRE

    Park, Young-Eun; Yook, Ji-Won; Kim, Dae-Seong

    2010-01-01

    We report a patient with Lewis-Sumner syndrome (LSS) who showed an improvement only with plasma exchange (PE). The patient, 32-yr old man, had progressive multifocal motor-sensory deficits with persistent, multiple conduction blocks and marked slowing of NCVs. Nerve pathology supported a diagnosis of demyelinating neuropathy by revealing marked loss of myelinated fibers with inter- and intrafascicular variation. Although the patient was refractory to treatment with corticosteroid and intraven...

  10. Transglycosylated stevia and hesperidin as pharmaceutical excipients: dramatic improvement in drug dissolution and bioavailability.

    Science.gov (United States)

    Uchiyama, Hiromasa; Tozuka, Yuichi; Imono, Masaaki; Takeuchi, Hirofumi

    2010-10-01

    The capability of transglycosylated materials, α-glycosyltransferase-treated stevia (Stevia-G) and α-glycosyl hesperidin (Hsp-G), to enhance the bioavailability of poorly water-soluble drugs was investigated. Spray-dried particles (SDPs) of drug/transglycosylated material, such as, flurbiprofen (FP)/Stevia-G, probucol (PRO)/Stevia-G, FP/Hsp-G, and PRO/Hsp-G were prepared. All SDPs showed pronounced improvement in both dissolution rate and apparent drug solubility. The amount of dissolved PRO was significantly improved to that of untreated PRO crystals when prepared as SDPs of PRO/Stevia-G or PRO/Hsp-G. There was no cytotoxicity to Caco-2 cells at levels of 10% Stevia-G or Hsp-G solution. Values for the area under the plasma concentration-time curve (AUC) of untreated PRO, SDPs of PRO/Hsp-G and PRO/Stevia-G after oral administration to rats were 4.94±2.06, 26.08±4.52 and 48.79±9.97μgh/mL, respectively. Interestingly, AUC values in cases of the FP system were in the order of untreated FPStevia-GStevia-G, a newly investigated material for this purpose, was found to have good potential for use as a pharmaceutical excipient.

  11. Dramatic improvement in dissolution rate of albendazole by a simple, one-step, industrially scalable technique

    Directory of Open Access Journals (Sweden)

    Saeed Ghanbarzadeh

    2016-01-01

    Full Text Available Low solubility and dissolution rate are the primary challenges in the drug development which substantially impact the oral absorption and bioavailability of drugs. Due to the poor water solubility, Albendazole (ABZ is poorly absorbed from the gastrointestinal tract and shows low oral bioavailability (5% which is a major disadvantage for the systemic use of ABZ. To improve the solubility and dissolution rate of ABZ, different classes of hydrophilic excipients such as sugars (lactose, sucrose, and glucose, polyols (mannitol and sorbitol, ionic surfactant (sodium lauryl sulfate and non-ionic surfactant (Cremophor A25 were co-spray dried with ABZ. The crystallinity changes in the processed drug were characterized by differential scanning calorimetry and X-Ray diffraction methods were used to interpret the enhanced solubility and dissolution rate of the drug. Results showed that the solubility and dissolution rate of ABZ were increased 1.8-2.6 folds and 3-25 folds, respectively. Unexpectedly, SLS decreased the solubility index of drug powder even lower than the unprocessed drug which was attributed to drug-SLS ionic interaction as depicted from Fourier transform infrared spectroscopy. It was concluded that by applying the facile, one-step, industrially scalable technique and the use of small amounts of excipient (only 4% of the formulation, a great improvement (21 folds in dissolution rate of ABZ was achieved. This finding may be used in the pharmaceutical industries for the formulation of therapeutically efficient dosage forms of class II and IV drugs classified in biopharmaceutical classification system.

  12. Dramatic enhancement of genome editing by CRISPR/Cas9 through improved guide RNA design.

    Science.gov (United States)

    Farboud, Behnom; Meyer, Barbara J

    2015-04-01

    Success with genome editing by the RNA-programmed nuclease Cas9 has been limited by the inability to predict effective guide RNAs and DNA target sites. Not all guide RNAs have been successful, and even those that were, varied widely in their efficacy. Here we describe and validate a strategy for Caenorhabditis elegans that reliably achieved a high frequency of genome editing for all targets tested in vivo. The key innovation was to design guide RNAs with a GG motif at the 3' end of their target-specific sequences. All guides designed using this simple principle induced a high frequency of targeted mutagenesis via nonhomologous end joining (NHEJ) and a high frequency of precise DNA integration from exogenous DNA templates via homology-directed repair (HDR). Related guide RNAs having the GG motif shifted by only three nucleotides showed severely reduced or no genome editing. We also combined the 3' GG guide improvement with a co-CRISPR/co-conversion approach. For this co-conversion scheme, animals were only screened for genome editing at designated targets if they exhibited a dominant phenotype caused by Cas9-dependent editing of an unrelated target. Combining the two strategies further enhanced the ease of mutant recovery, thereby providing a powerful means to obtain desired genetic changes in an otherwise unaltered genome.

  13. Primary extranodal non-Hodgkin's lymphoma of the lung presenting with bilateral, patchy infiltrates dramatically improving after corticosteroid therapy.

    Science.gov (United States)

    Boon, E S; Graal, M B; van Noord, J A

    1993-10-01

    A 63-year-old man was admitted to the hospital with fever and bilateral, peripheral infiltrates. Infectious disease and malignancy seemed to be excluded by fiberoptic diagnostic procedures. Subsequently, respiratory insufficiency developed, making open lung biopsy impossible. The diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP) was strongly considered and treatment with corticosteroids was started; this led to dramatic clinical and radiologic improvement for a short time. Eventually, an open lung biopsy specimen disclosed primary extranodal non-Hodgkin's lymphoma of T-cell origin, immunoblastic, of high-grade malignancy according to the Kiel classification. After the first course of chemotherapy, total respiratory insufficiency developed and the patient died. This case is unique in a patient without AIDS.

  14. [A case of Wernicke-Korsakoff syndrome with dramatic improvement in consciousness immediately after intravenous infusion of thiamine].

    Science.gov (United States)

    Kikuchi, A; Chida, K; Misu, T; Okita, N; Nomura, H; Konno, H; Takase, S; Takeda, A; Itoyama, Y

    2000-01-01

    A 68-year-old man was hospitalized on March 4, 1998 for disturbances in consciousness. In 1995, he had received proximal subtotal gastrectomy and reconstructive surgery of the jejunal interposition for gastric cancer. Thereafter he had been taking enough food without the habit of taking liquor. In October 1997, his short term memory was becoming gradually worse. On February 12, 1998, he suffered from numbness in the feet, and then dysphagia, unsteady gait, and diplopia developed gradually. On February 26, brain MRI showed no abnormalities. On March 3, he had a fever of 38.5 degrees C and his consciousness became unclear. Neurological examination revealed semi-coma, total ophthalmoplegia, and absence of doll's eye movement. Deep tendon reflexes were absent. The serum thiamine level was 9 ng/ml (normal range: 20-50). Brain MRI demonstrated symmetrical high intensity lesions in the periaqueductal area of the midbrain, dorsomedial nuclei of bilateral thalami, and vestibular nuclei. About 30 seconds after intravenous infusion of thiamine, his consciousness improved dramatically, but returned to semi-coma after about two minutes. Wernicke-Korsakoff syndrome usually occurs acutely. In the present case, however, the disease showed slow onset, chronic progression, and then rapid worsening after fever. Reconstructive surgery of the jejunal interposition might have caused the slow onset of Wernicke-Korsakoff syndrome, and fever might have facilitated the rapid progression of the disease. An immediate high concentration of thiamine modifies the kinetics of acetylcholine receptor ion channels, thereby maintaining wakefulness, and the level of consciousness may change dramatically.

  15. Bariatric surgery prior to total joint arthroplasty may not provide dramatic improvements in post-arthroplasty surgical outcomes.

    Science.gov (United States)

    Inacio, Maria C S; Paxton, Elizabeth W; Fisher, David; Li, Robert A; Barber, Thomas C; Singh, Jasvinder A

    2014-07-01

    This study compared the total joint arthroplasty (TJA) surgical outcomes of patients who had bariatric surgery prior to TJA to TJA patients who were candidates but did not have bariatric surgery. Patients were retrospectively grouped into: Group 1 (n = 69), those with bariatric surgery >2 years prior to TJA, Group 2 (n = 102), those with surgery within 2 years of TJA, and Group 3 (n = 11,032), those without bariatric surgery. In Group 1, 2.9% (95% CI 0.0-6.9%) had complications within 1 year compared to 5.9% (95% CI 1.3%-10.4%) in Group 2, and 4.1% (95% CI 3.8%-4.5%) in Group 3. Ninety-day readmission (7.2%, 95% CI 1.1%-13.4%) and revision density (3.4/100 years of observation) was highest in Group 1. Bariatric surgery prior to TJA may not provide dramatic improvements in post-operative TJA surgical outcomes.

  16. Improvement of immunodetection of bacterial spore antigen by ultrasonic cavitation.

    Science.gov (United States)

    Borthwick, Kathryn A J; Love, Tracey E; McDonnell, Martin B; Coakley, W Terence

    2005-11-15

    Ultrasonic cavitation was employed to enhance sensitivity of bacterial spore immunoassay detection, specifically, enzyme-linked immunosorbent assay (ELISA) and resonant mirror (RM) sensing. Bacillus spore suspensions were exposed to high-power ultrasound in a tubular sonicator operated at 267 kHz in both batch and flow modes. The sonicator was designed to deliver high output power and is in a form that can be cooled efficiently to avoid thermal denaturation of antigen. The 30-s batch and cooled flow (0.3 mL/min) sonication achieved an approximately 20-fold increase in ELISA sensitivity compared to unsonicated spores by ELISA. RM sensing of sonicated spores achieved detection sensitivity of approximately 10(6) spores/mL, whereas unsonicated spores were undetectable at the highest concentration tested. Improvements in detection were associated with antigen released from the spores. Equilibrium temperature increase in the tubular sonicator was limited to 14 K after 30 min and was maintained for 6 h with cooling and flow (0.3 mL/min). The work described here demonstrates the utility of the tubular sonicator for the improvement in the sensitivity of the detection of spores and its suitability as an in-line component of a rapid detection system.

  17. Immune control of tumors by antigen presentation improvement.

    Science.gov (United States)

    Remedi, María Mónica; Bonacci, Gustavo; Vides, Miguel Angel; Donadio, Ana Carolina

    2003-01-01

    Tumor cells cannot activate T lymphocytes, since they do not usually express major histocompatibility complex (MHC) class II molecules. Thus, tumor antigens can only be presented indirectly to T cells through professional antigen-presenting cells (APC). In our laboratory, we have treated a tumor cell line (Tu1-A) - derived from an induced rat mammary sarcoma - in order to increase the expression of MHC class I and class II molecules. In our tumor model, the transference of these induced cells into normal rats generated a tumor mass that exhibited a lower tumor growth rate and an earlier regression as compared to those observed in rats inoculated with wild-type Tu1-A cells. This earlier tumor regression was associated with the development of an antigen-specific immune response. 85-87% of the rats in both groups rejected the tumor and were alive at day 60 after tumor cell inoculation. However, in rats treated with wild-type cells the rejection was delayed and took place after tumor ulceration. Rats that had rejected tumors were rechallenged with wild-type cells in order to assay the presence of a long-lived antitumor immunity. All the animals were resistant to the second tumor challenge. We conclude that the development of a specific immune response could be achieved by the superexpression of MHC molecules on tumor cells or when tumor ulceration promotes APC to take up necrotic cells and tumor antigens are presented to T lymphocytes.

  18. A dramatic, objective antiandrogen withdrawal response: case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Litwin Alan

    2008-11-01

    Full Text Available Abstract Antiandrogen withdrawal response is an increasingly recognized entity in patients with metastatic prostate cancer. To our knowledge, there have been no reports describing a durable radiologic improvement along with prostate-specific antigen (PSA with discontinuation of the antiandrogen agent bicalutamide. We report a case in which a dramatic decline of serum PSA levels associated with a dramatic improvement in radiologic disease was achieved with bicalutamide discontinuation.

  19. Creative Dramatics. Beginnings Workshop.

    Science.gov (United States)

    Gabriel, Julia; Sidlovskaya, Olga; Stotter, Ruth; Haugen, Kirsten; Leithold, Naomi

    2000-01-01

    Presents five articles on using creative dramatics in early childhood education: (1) "Drama: A Rehearsal for Life" (Julia Gabriel); (2) "Fairy Tales Enhance Imagination and Creative Thinking" (Olga Sidlovskaya); (3) "Starting with a Story" (Ruth Stotter); (4) "Using Creative Dramatics to Include All…

  20. Poly(2,5-dimercapto-1,3,4-thiadiazole) as a Cathode for Rechargeable Lithium Batteries with Dramatically Improved Performance

    KAUST Repository

    Gao, Jie

    2012-05-29

    Organosulfur compounds with multiple thiol groups are promising for high gravimetric energy density electrochemical energy storage. We have synthesized a poly(2,5-dimercapto-1,3,4-thiadiazole) (PDMcT)/poly(3,4-ethylenedioxythiophene) (PEDOT) composite cathode for lithium-ion batteries with a new method and investigated its electrochemical behavior by charge/discharge cycles and cyclic voltammetry (CV) in an ether-based electrolyte. Based on a comparison of the electrochemical performance with a carbonate-based electrolyte, we found a much higher discharge capacity, but also a very attractive cycling performance of PDMcT by using a tetra(ethylene glycol) dimethyl ether (TEGDME)-based electrolyte. The first discharge capacity of the as-synthesized PDMcT/PEDOT composite approached 210 mAh g -1 in the TEGDME-based electrolyte. CV results clearly show that the redox reactions of PDMcT are highly reversible in this TEGDME-based electrolyte. The reversible capacity remained around 120 mAh g -1 after 20 charge/discharge cycles. With improved cycling performance and very low cost, PDMcT could become a very promising cathode material when combined with a TEGDME-based electrolyte. The poor capacity in the carbonate-based electrolyte is a consequence of the irreversible reaction of the DMcT monomer and dimer with the solvent, emphasizing the importance of electrolyte chemistry when studying molecular-based battery materials. The nature of the electrolyte has a dramatic effect on the performance of poly(2,5-dimercapto-1,3,4-thiadiazole) (PDMcT) as a cathode material in lithium-ion batteries. Whereas the use of an ethylene/diethyl carbonate (EC/DEC)-based electrolyte resulted in very poor performance, the use of a tetra(ethylene glycol) dimethyl ether (TEGDME)-based electrolyte dramatically improved the performance in terms of both the discharge capacity and capacity retention (see scheme). Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Deglycosylation of Toxocara excretory-secretory antigens improves the specificity of the serodiagnosis for human toxocariasis.

    Science.gov (United States)

    Roldán, W H; Elefant, G R; Ferreira, A W

    2015-11-01

    Serodiagnosis of human toxocariasis is difficult in tropical areas where other helminthiasis are endemic. Many studies have shown that glycans from helminths may be the responsible for cross-reactions in the immunoassays. In this study, we have evaluated the deglycosylation of the Toxocara canis excretory-secretory (TES) antigens for the detection of IgG antibodies using a panel of 228 serum samples (58 patients with toxocariasis, 75 patients with other helminth infections and 95 healthy individuals) by ELISA and Western blot assays. Our results showed that the deglycosylation of TES antigens resulted in a single fraction of 26 kDa (dTES) and was able to detect IgG antibodies with a sensitivity and specificity of 100% in both above-mentioned assays. The rate of cross-reactions, observed in ELISA with TES (13·3%), was significantly reduced (5·3%) when the dTES antigens were used. Likewise, the cross-reactivity observed with the fractions of 32, 55 and 70 kDa of the TES antigens was totally eliminated when the dTES were used in the Western blot. All these results showed that the deglycosylation of the TES antigens really improves the specificity of the serodiagnosis of human toxocariasis in endemic areas for helminth infections.

  2. Idiopathic Facial Aseptic Granuloma in a 13-Year-Old Boy Dramatically Improved with Oral Doxycycline and Topical Metronidazole: Evidence for a Link with Childhood Rosacea

    Directory of Open Access Journals (Sweden)

    Camille Orion

    2016-07-01

    Full Text Available Idiopathic facial aseptic granuloma (IFAG is a rare, benign pediatric dermatological lesion that occurs in children between 8 months and 13 years of age. The pathogenesis of IFAG is still unclear but it is likely to be associated with granulomatous rosacea in childhood. Here we describe a case of IFAG in a 13-year-old boy who showed a dramatic response to oral doxycycline and topical metronidazole, which supports the hypothesis that IFAG may belong to the spectrum of rosacea.

  3. Combining BRAF inhibitor and anti PD-L1 antibody dramatically improves tumor regression and anti tumor immunity in an immunocompetent murine model of anaplastic thyroid cancer.

    Science.gov (United States)

    Brauner, Eran; Gunda, Viswanath; Vanden Borre, Pierre; Zurakowski, David; Kim, Yon Seon; Dennett, Kate Virginia; Amin, Salma; Freeman, Gordon James; Parangi, Sareh

    2016-03-29

    The interaction of programmed cell death-1 and its ligand is widely studied in cancer. Monoclonal antibodies blocking these molecules have had great success but little is known about them in thyroid cancer. We investigated the role of PD-L1 in thyroid cancer with respect to BRAF mutation and MAP kinase pathway activity and the effect of anti PD-L1 antibody therapy on tumor regression and intra-tumoral immune response alone or in combination with BRAF inhibitor (BRAFi). BRAFV600E cells showed significantly higher baseline expression of PD-L1 at mRNA and protein levels compared to BRAFWT cells. MEK inhibitor treatment resulted in a decrease of PD-L1 expression across all cell lines. BRAFi treatment decreased PD-L1 expression in BRAFV600E cells, but paradoxically increased its expression in BRAFWT cells. BRAFV600E mutated patients samples had a higher level of PD-L1 mRNA compared to BRAFWT (p=0.015). Immunocompetent mice (B6129SF1/J) implanted with syngeneic 3747 BRAFV600E/WT P53-/- murine tumor cells were randomized to control, PLX4720, anti PD-L1 antibody and their combination. In this model of aggressive thyroid cancer, control tumor volume reached 782.3±174.6mm3 at two weeks. The combination dramatically reduced tumor volume to 147.3±60.8, compared to PLX4720 (439.3±188.4 mm3, P=0.023) or PD-L1 antibody (716.7±62.1, Panti PD-L1 treatment potentiates the effect of BRAFi on tumor regression and intensifies anti tumor immune response in an immunocompetent model of ATC. Clinical trials of this therapeutic combination may be of benefit in patients with ATC.

  4. Why were alternating-current-driven electrochemiluminescence properties from Ru(bpy)3(2+) dramatically improved by the addition of titanium dioxide nanoparticles?

    Science.gov (United States)

    Tsuneyasu, Shota; Ichihara, Kazuki; Nakamura, Kazuki; Kobayashi, Norihisa

    2016-06-28

    Electrochemiluminescence (ECL) is a phenomenon in which light is emitted from the excited state of a redox-active material generated by electrochemical reactions. Among light-emitting devices, ECL devices have various advantages in terms of structure and ease of fabrication, and therefore, they are expected to be next-generation emitting devices. In this study, we introduced rutile-type titanium dioxide nanoparticles (TiO2 NPs) in a Ru(ii)-complex-based electrolyte to improve the emission properties of an alternating current (AC)-driven ECL device. The properties of the ECL device with TiO2 NPs were greatly improved (emission luminescence, 165 cd m(-2); half-life time, 1000 s) compared to a previously reported AC-driven ECL device without nanoparticles. To determine how TiO2 NPs helped in achieving high emission luminescence and long-term stability, we measured the optical and electrochemical properties of the Ru(bpy)3(2+)-based ECL solution in detail. The PL intensity of Ru(bpy)3(2+) was increased by adding TiO2 NPs, which indicated that the suppression of non-radiative quenching of the complex's excited states could improve the ECL intensity. With respect to the enhanced stability, electron transfers between Ru(bpy)3(2+) and TiO2 were suggested by detailed electrochemical measurements. These electron transfers occurred from the reduced Ru(bpy)3(2+) species to the TiO2, and subsequently, from the TiO2 to the oxidized Ru(bpy)3(2+) species. Such electron transfers are thought to improve the balance of the redox reactions in the ECL device, leading to long-term stability.

  5. Co-injection of a targeted, reversibly masked endosomolytic polymer dramatically improves the efficacy of cholesterol-conjugated small interfering RNAs in vivo.

    Science.gov (United States)

    Wong, So C; Klein, Jason J; Hamilton, Holly L; Chu, Qili; Frey, Christina L; Trubetskoy, Vladimir S; Hegge, Julia; Wakefield, Darren; Rozema, David B; Lewis, David L

    2012-12-01

    Effective in vivo delivery of small interfering (siRNA) has been a major obstacle in the development of RNA interference therapeutics. One of the first attempts to overcome this obstacle utilized intravenous injection of cholesterol-conjugated siRNA (chol-siRNA). Although studies in mice revealed target gene knockdown in the liver, delivery was relatively inefficient, requiring 3 daily injections of 50 mg/kg of chol-siRNA to obtain measurable reduction in gene expression. Here we present a new delivery approach that increases the efficacy of the chol-siRNA over 500-fold and allows over 90% reduction in target gene expression in mice and, for the first time, high levels of gene knockdown in non-human primates. This improved efficacy is achieved by the co-injection of a hepatocyte-targeted and reversibly masked endosomolytic polymer. We show that knockdown is absolutely dependent on the presence of hepatocyte-targeting ligand on the polymer, the cognate hepatocyte receptor, and the cholesterol moiety of the siRNA. Importantly, we provide evidence that this increase in efficacy is not dependent on interactions between the chol-siRNA with the polymer prior to injection or in the bloodstream. The simplicity of the formulation and efficacy of this mode of siRNA delivery should prove beneficial in the use of siRNA as a therapeutic.

  6. Zscan4 promotes genomic stability during reprogramming and dramatically improves the quality of iPS cells as demonstrated by tetraploid complementation

    Institute of Scientific and Technical Information of China (English)

    Jing Jiang; Wenjian Lv; Xiaoying Ye; Lingbo Wang; Man Zhang; Hui Yang; Maja Okuka

    2013-01-01

    Induced pluripotent stem (iPS) cells generated using Yamanaka factors have great potential for use in autologous cell therapy.However,genomic abnormalities exist in human iPS cells,and most mouse iPS cells are not fully pluripotent,as evaluated by the tetraploid complementation assay (TCA); this is most likely associated with the DNA damage response (DDR) occurred in early reprogramming induced by Yamanaka factors.In contrast,nuclear transfer can faithfully reprogram somatic cells into embryonic stem (ES) cells that satisfy the TCA.We thus hypothesized that factors involved in oocyte-induced reprogramming may stabilize the somatic genome during reprogramming,and improve the quality of the resultant iPS cells.To test this hypothesis,we screened for factors that could decrease DDR signals during iPS cell induction.We determined that Zscan4,in combination with the Yamanaka factors,not only remarkably reduced the DDR but also markedly promoted the efficiency of iPS cell generation.The inclusion of Zscan4 stabilized the genomic DNA,resulting in p53 downregulation.Furthermore,Zscan4 also enhanced telomere lengthening as early as 3 days post-infection through a telomere recombination-based mechanism.As a result,iPS cells generated with addition of Zscan4 exhibited longer telomeres than classical iPS cells.Strikingly,more than 50%of iPS cell lines (11/19) produced via this "Zscan4 protocol" gave rise to live-borne all-iPS cell mice as determined by TCA,compared to 1/12 for lines produced using the classical Yamanaka factors.Our findings provide the first demonstration that maintaining genomic stability during reprogramming promotes the generation of high quality iPS cells.

  7. Zscan4 promotes genomic stability during reprogramming and dramatically improves the quality of iPS cells as demonstrated by tetraploid complementation.

    Science.gov (United States)

    Jiang, Jing; Lv, Wenjian; Ye, Xiaoying; Wang, Lingbo; Zhang, Man; Yang, Hui; Okuka, Maja; Zhou, Chikai; Zhang, Xuan; Liu, Lin; Li, Jinsong

    2013-01-01

    Induced pluripotent stem (iPS) cells generated using Yamanaka factors have great potential for use in autologous cell therapy. However, genomic abnormalities exist in human iPS cells, and most mouse iPS cells are not fully pluripotent, as evaluated by the tetraploid complementation assay (TCA); this is most likely associated with the DNA damage response (DDR) occurred in early reprogramming induced by Yamanaka factors. In contrast, nuclear transfer can faithfully reprogram somatic cells into embryonic stem (ES) cells that satisfy the TCA. We thus hypothesized that factors involved in oocyte-induced reprogramming may stabilize the somatic genome during reprogramming, and improve the quality of the resultant iPS cells. To test this hypothesis, we screened for factors that could decrease DDR signals during iPS cell induction. We determined that Zscan4, in combination with the Yamanaka factors, not only remarkably reduced the DDR but also markedly promoted the efficiency of iPS cell generation. The inclusion of Zscan4 stabilized the genomic DNA, resulting in p53 downregulation. Furthermore, Zscan4 also enhanced telomere lengthening as early as 3 days post-infection through a telomere recombination-based mechanism. As a result, iPS cells generated with addition of Zscan4 exhibited longer telomeres than classical iPS cells. Strikingly, more than 50% of iPS cell lines (11/19) produced via this "Zscan4 protocol" gave rise to live-borne all-iPS cell mice as determined by TCA, compared to 1/12 for lines produced using the classical Yamanaka factors. Our findings provide the first demonstration that maintaining genomic stability during reprogramming promotes the generation of high quality iPS cells.

  8. In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination.

    Science.gov (United States)

    Bonifaz, Laura C; Bonnyay, David P; Charalambous, Anna; Darguste, Dara I; Fujii, Shin-Ichiro; Soares, Helena; Brimnes, Marie K; Moltedo, Bruno; Moran, Thomas M; Steinman, Ralph M

    2004-03-15

    The prevention and treatment of prevalent infectious diseases and tumors should benefit from improvements in the induction of antigen-specific T cell immunity. To assess the potential of antigen targeting to dendritic cells to improve immunity, we incorporated ovalbumin protein into a monoclonal antibody to the DEC-205 receptor, an endocytic receptor that is abundant on these cells in lymphoid tissues. Simultaneously, we injected agonistic alpha-CD40 antibody to mature the dendritic cells. We found that a single low dose of antibody-conjugated ovalbumin initiated immunity from the naive CD4+ and CD8+ T cell repertoire. Unexpectedly, the alphaDEC-205 antigen conjugates, given s.c., targeted to dendritic cells systemically and for long periods, and ovalbumin peptide was presented on MHC class I for 2 weeks. This was associated with stronger CD8+ T cell-mediated immunity relative to other forms of antigen delivery, even when the latter was given at a thousand times higher doses. In parallel, the mice showed enhanced resistance to an established rapidly growing tumor and to viral infection at a mucosal site. By better harnessing the immunizing functions of maturing dendritic cells, antibody-mediated antigen targeting via the DEC-205 receptor increases the efficiency of vaccination for T cell immunity, including systemic and mucosal resistance in disease models.

  9. In Vivo Targeting of Antigens to Maturing Dendritic Cells via the DEC-205 Receptor Improves T Cell Vaccination

    Science.gov (United States)

    Bonifaz, Laura C.; Bonnyay, David P.; Charalambous, Anna; Darguste, Dara I.; Fujii, Shin-Ichiro; Soares, Helena; Brimnes, Marie K.; Moltedo, Bruno; Moran, Thomas M.; Steinman, Ralph M.

    2004-01-01

    The prevention and treatment of prevalent infectious diseases and tumors should benefit from improvements in the induction of antigen-specific T cell immunity. To assess the potential of antigen targeting to dendritic cells to improve immunity, we incorporated ovalbumin protein into a monoclonal antibody to the DEC-205 receptor, an endocytic receptor that is abundant on these cells in lymphoid tissues. Simultaneously, we injected agonistic α-CD40 antibody to mature the dendritic cells. We found that a single low dose of antibody-conjugated ovalbumin initiated immunity from the naive CD4+ and CD8+ T cell repertoire. Unexpectedly, the αDEC-205 antigen conjugates, given s.c., targeted to dendritic cells systemically and for long periods, and ovalbumin peptide was presented on MHC class I for 2 weeks. This was associated with stronger CD8+ T cell–mediated immunity relative to other forms of antigen delivery, even when the latter was given at a thousand times higher doses. In parallel, the mice showed enhanced resistance to an established rapidly growing tumor and to viral infection at a mucosal site. By better harnessing the immunizing functions of maturing dendritic cells, antibody-mediated antigen targeting via the DEC-205 receptor increases the efficiency of vaccination for T cell immunity, including systemic and mucosal resistance in disease models. PMID:15024047

  10. An improved haemolytic plaque assay for the detection of cells secreting antibody to bacterial antigens

    DEFF Research Database (Denmark)

    Barington, T; Heilmann, C

    1992-01-01

    Recent advances in the development of conjugate polysaccharide vaccines for human use have stimulated interest in the use of assays detecting antibody-secreting cells (AbSC) with specificity for bacterial antigens. Here we present improved haemolytic plaque-forming cell (PFC) assays detecting Ab......SC with specificity for tetanus and diphtheria toxoid as well as for Haemophilus influenzae type b and pneumococcal capsular polysaccharides. These assays were found to be less time consuming, more economical and yielded 1.9-3.4-fold higher plaque numbers than traditional Jerne-type PFC assays. In the case of anti......-polysaccharide AbSC of the IgG isotype, the increase was as high as 7.4-11.8 times. Evidence is presented that the pronounced improvement in the detection of the latter is due to the presence of aggregating anti-IgG antibody from the beginning of the assay. It is proposed that in the case of low affinity of anti...

  11. Optical Refrigeration for Dramatically Improved Cryogenic Technology

    Science.gov (United States)

    2015-01-24

    DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour... LANL )  by  a  team  led  by  TDF’s  CEO  [RIE95].    Two  technical  challenges   were  addressed  and  overcome  in...cooling  of  fluoride  glass  at   LANL  in  1995.    In  2009,  optical   refrigerators   cooled   below  

  12. Hospitality Ethical Growth via Dramatic English

    Directory of Open Access Journals (Sweden)

    Cherif Haberih

    2014-09-01

    Full Text Available The objective of this research is to find scalable data and statistics for realistic rendering of Ethical and Dramatic English gradual growth based on Thai students within the Hospitality and Tourism Industry. We also intend to prove that Dramatic English serves English improvements for Thai students. Furthermore we intend to better understand students' behaviors and ethical growth processes based on cultural, social, personal and psychological background through Dramatic English for Hospitality Industry. Universities and Educational Organizations today are involved in complex tasks. With the burst of communication through Medias and an ever increasing student’s demand for higher quality education and services, having a competitive advantage is seen as a necessary tool. Education has evolved and its business approach requires a modern and inadequate solution. As of today, Thailand is in need of a new generation of tools applied to modernize the current educational system, and emphasize on new methods.

  13. Bortezomib improves progression-free survival in multiple myeloma patients overexpressing preferentially expressed antigen of melanoma

    Institute of Scientific and Technical Information of China (English)

    Qin Yazhen; Lu Jin; Bao Li; Zhu Honghu; Li Jinlan; Li Lingdi; Lai Yueyun

    2014-01-01

    Background Significant efforts have been made to identify factors that differentiate patients treated with novel therapies,such as bortezomib in multiple myeloma (MM).The exact expression pattern and prognostic value of the cancer/testis antigen preferentially expressed antigen of melanoma (PRAME) in MM are unknown and were explored in this study.Methods The transcript level of PRAME was detected in bone marrow specimens from 100 newly diagnosed MM patients using real-time quantitative polymerase chain reaction,and the prognostic value of PRAME was determined through retrospective survival analysis.PRAME expression higher than the upper limit of normal bone marrow was defined as PRAME overexpression or PRAME (+).Results Sixty-two patients (62.0%) overexpressed PRAME.PRAME overexpression showed no prognostic significance to either overall survival (n=100) or progression-free survival (PFS,n=96,all P >0.05) of patients.The patients were also categorized according to regimens with or without bortezomib.PRAME overexpression tended to be associated with a lower two-year PFS rate in patients treated with non-bortezomib-containing regimens (53.5% vs.76.9%,P=0.071).By contrast,it was not associated with the two-year PFS rate in patients with bortezomib-containing regimens (77.5% vs.63.9%,P >0.05).When the patients were categorized into PRAME (+) and PRAME (-) groups,treatment with bortezomib-containing regimens predicted a higher two-year PFS rate in PRAME (+) patients (77.5% vs.53.5%,P=0.027) but showed no significant effect on two-year PFS rate in PRAME (-) patients (63.9% vs.76.9%,P >0.05).Conclusion PRAME overexpression might be an adverse prognostic factor of PFS in MM patients treated with non-bortezomib-containing regimens.Bortezomib improves PFS in patients overexpressing PRAME.

  14. Development of influenza A(H7N9) candidate vaccine viruses with improved hemagglutinin antigen yield in eggs

    Science.gov (United States)

    Ridenour, Callie; Johnson, Adam; Winne, Emily; Hossain, Jaber; Mateu-Petit, Guaniri; Balish, Amanda; Santana, Wanda; Kim, Taejoong; Davis, Charles; Cox, Nancy J; Barr, John R; Donis, Ruben O; Villanueva, Julie; Williams, Tracie L; Chen, Li-Mei

    2015-01-01

    Background The emergence of avian influenza A(H7N9) virus in poultry causing zoonotic human infections was reported on March 31, 2013. Development of A(H7N9) candidate vaccine viruses (CVV) for pandemic preparedness purposes was initiated without delay. Candidate vaccine viruses were derived by reverse genetics using the internal genes of A/Puerto/Rico/8/34 (PR8). The resulting A(H7N9) CVVs needed improvement because they had titers and antigen yields that were suboptimal for vaccine manufacturing in eggs, especially in a pandemic situation. Methods Two CVVs derived by reverse genetics were serially passaged in embryonated eggs to improve the hemagglutinin (HA) antigen yield. The total viral protein and HA antigen yields of six egg-passaged CVVs were determined by the BCA assay and isotope dilution mass spectrometry (IDMS) analysis, respectively. CVVs were antigenically characterized by hemagglutination inhibition (HI) assays with ferret antisera. Results Improvement of total viral protein yield was observed for the six egg-passaged CVVs; HA quantification by IDMS indicated approximately a twofold increase in yield of several egg-passaged viruses as compared to that of the parental CVV. Several different amino acid substitutions were identified in the HA of all viruses after serial passage. However, HI tests indicated that the antigenic properties of two CVVs remained unchanged. Conclusions If influenza A(H7N9) viruses were to acquire sustained human-to-human transmissibility, the improved HA yield of the egg-passaged CVVs generated in this study could expedite vaccine manufacturing for pandemic mitigation. PMID:25962412

  15. Dramatizing Nonfiction with Emerging Readers.

    Science.gov (United States)

    Putnam, Lynne

    1991-01-01

    Presents scenarios from a kindergarten classroom in which dramatization is used extensively in conjunction with nonfiction books. Shows how the children acted out topics that ranged from the Pilgrims' first Thanksgiving to the life of Dr. Martin Luther King, Jr., showing that they were able to develop rich representations of nonfiction materials.…

  16. Learning through Dramatic Story Presentation

    Science.gov (United States)

    Tindall, Evie

    2012-01-01

    The use of story with dramatic presentation approaches produces an engaging and powerful instructional choice for today's adult ESL educators. Two engaging and timed-tested approaches are Reader's Theater and Tableau Vivant. Both provide English language learners with content tailored to their abilities in addition to numerable opportunities to…

  17. Little Eyolf and dramatic tradition

    Directory of Open Access Journals (Sweden)

    Roland Lysell

    2015-02-01

    Full Text Available The article criticises an Ibsen tradition who has seen the last scene of Little Eyolf as a reconciliation. Instead, the article discusses the improbability of a happy marriage characterised by social engagement. The play is open but it is hardly probable that Rita, with her erotic desire, and Allmers, whose desire has turned into metaphysics, can be happy together. The arguments refer to inner criteria and the constantly present dramatic tradition.

  18. Improved immunogenicity of novel baculovirus-derived Theileria parva p67 subunit antigens

    NARCIS (Netherlands)

    Kaba, S.A.; Schaap, D.; Roode, E.C.; Nene, V.; Musoke, A.J.; Vlak, J.M.; Oers, van M.M.

    2004-01-01

    East Coast fever (ECF) in cattle is caused by the tick-borne protozoan parasite Theileria parva. The major sporozoite surface antigen of T parva (p67) is an important candidate for inclusion in a subunit vaccine. Recently, we reported the expression and production of different parts of p67 as fusion

  19. Proteasomal targeting and minigene repetition improve cell-surface presentation of a transfected, modified melanoma tumour antigen

    DEFF Research Database (Denmark)

    Rasmussen, A B; Zocca, M-B; Bonefeld, C M;

    2004-01-01

    Melanoma antigen recognized by T cell 1 (MART-1) is regarded as a candidate peptide for vaccination against malignant melanoma, and it is of importance to develop strategies to improve the vaccine-elicited T-cell activation towards MART-1. T-cell activation is, among other determinants, dependent......-surface presentation of the epitope and propose both these approaches as potential strategies in DNA vaccines to increase MART-1-specific T-cell activation.......Melanoma antigen recognized by T cell 1 (MART-1) is regarded as a candidate peptide for vaccination against malignant melanoma, and it is of importance to develop strategies to improve the vaccine-elicited T-cell activation towards MART-1. T-cell activation is, among other determinants, dependent...... on the density of specific major histocompatibility complex-peptide complexes on the surface of the antigen-presenting cell. In this study, we explored the cell-surface presentation of a substituted MART-1 peptide encoded by transfected minigenes. We investigated the potential of proteasomal targeting compared...

  20. Methionine enkephalin (MENK) improved the functions of bone marrow-derived dendritic cells (BMDCs) loaded with antigen.

    Science.gov (United States)

    Li, Weiwei; Meng, Jingjuan; Li, Xuan; Hua, Hui; Yiming, Meng; Wang, Qiushi; Wang, Enhua; Shan, Fengping

    2012-09-01

    The aim of this investigation is to look at whether MENK could improve antitumor effect of CD8+T cell elicited by BMDCs. We investigated the effects of MENK on the differentiation, maturation, and functions of murine BMDC loaded with Rac-1 antigens (RG) and CTL of tumor specific immune response elicited by the BMDC in vitro and in vivo. The production of cytokine IL-12 and TNF-α secreted by BMDCs in the presence of MENK was assayed with ELISA and key surface markers of CD40, CD86, CD83 and MHC-II on the BMDCs were analyzed with use of flow cytometry (FCM). In addition, the activities to induce CD8+ T cell proliferation, along with displayed cytotoxicity of the CD8+T cells(CTL) by the BMDCs after treatment with MENK were determined with use of FCM as well as MTS. Our results indicated that MENK induced phenotypic and functional maturation of BMDC loaded with RG antigen, as evidenced by higher level of expression of key surface markers and more production of cytokines. Subsequently, the BMDC activated by MENK intensified immune responses mounted by CTL, resulting in stronger antitumor activity. Our results suggest that MENK could be working as an effective immune adjuvant in vaccine preparation for cancer fight and other immune related diseases. We concluded that MENK could be a positive immune modulator in the improved functions of BMDCs loaded with antigen as well as in CD8+T cell mediated anti-tumor responses.

  1. [Case of continuous trans-arterial calcium gluconate infusion using a direct arterial sphygmomanometry line that exhibited dramatic improvement of chemical burns on the fingers caused by hydrofluoric acid].

    Science.gov (United States)

    Miyamoto, Kazuyuki; Shimizu, Makiko; Tanaka, Kotaro; Minemura, Atsuko; Tamatsukuri, Tatsuro; Miyake, Yasufumi; Aruga, Tohru

    2014-12-01

    Hydrofluoric acid (HFA) is commonly used and many injuries occur on the upper extremities following exposure to HFA. The use of calcium gluconate (CG) -containing gel or local injections of CG are widely used for the initial treatment of HFA exposure. However, severe pain continues in some cases despite the treatment. There was a report that trans-arterial CG infusion could improve HFA burns, however, such treatment is not an established clinical procedure. A 30-year-old male presented at our hospital with severe pain in his left thumb. He had been cleaning tiles with an HFA-containing detergent. We diagnosed him with a chemical burn due to HFA exposure. Local CG injections were tried several times, but his terrible pain continued. Therefore, a direct arterial sphygmomanometry line was inserted from the left radial artery, and continuous transarterial CG injection was performed. His terrible pain dramatically improved. Direct arterial sphygmomanometry systems are widely used in the critical care field to monitor the hemodynamics and ICU staffs are used to dealing with it. Moreover, continuous saline infusion prevents the tube obstruction. Continuous CG infusion from a direct arterial sphygmomanometry line is simple and safe way to administer CG in HFA burns.

  2. Controlled and targeted release of antigens by intelligent shell for improving applicability of oral vaccines.

    Science.gov (United States)

    Zhang, Lei; Zeng, Zhanzhuang; Hu, Chaohua; Bellis, Susan L; Yang, Wendi; Su, Yintao; Zhang, Xinyan; Wu, Yunkun

    2016-01-01

    Conventional oral vaccines with simple architecture face barriers with regard to stimulating effective immunity. Here we describe oral vaccines with an intelligent phase-transitional shielding layer, poly[(methyl methacrylate)-co-(methyl acrylate)-co-(methacrylic acid)]-poly(D,L-lactide-co-glycolide) (PMMMA-PLGA), which can protect antigens in the gastro-intestinal tract and achieve targeted vaccination in the large intestine. With the surface immunogenic protein (SIP) from group B Streptococcus (GBS) entrapped as the antigen, oral administration with PMMMA-PLGA (PTRBL)/Trx-SIP nanoparticles stimulated robust immunity in tilapia, an animal with a relatively simple immune system. The vaccine succeeded in protecting against Streptococcus agalactiae, a pathogen of worldwide importance that threatens human health and is transmitted in water with infected fish. After oral vaccination with PTRBL/Trx-SIP, tilapia produced enhanced levels of SIP specific antibodies and displayed durability of immune protection. 100% of the vaccinated tilapia were protected from GBS infection, whereas the control groups without vaccines or vaccinated with Trx-SIP only exhibited respective infection rates of 100% or >60% within the initial 5 months after primary vaccination. Experiments in vivo demonstrated that the recombinant antigen Trx-SIP labeled with FITC was localized in colon, spleen and kidney, which are critical sites for mounting an immune response. Our results revealed that, rather than the size of the nanoparticles, it is more likely that the negative charge repulsion produced by ionization of the carboxyl groups in PMMMA shielded the nanoparticles from uptake by small intestinal epithelial cells. This system resolves challenges arising from gastrointestinal damage to antigens, and more importantly, offers a new approach applicable for oral vaccination.

  3. Improvement of antigen detection efficiency with the use of two-dimensional photonic crystal as a substrate

    Science.gov (United States)

    Dovzhenko, Dmitriy; Terekhin, Vladimir; Vokhmincev, Kirill; Sukhanova, Alyona; Nabiev, Igor

    2017-01-01

    Multiplex detection of different antigens in human serum in order to reveal diseases at the early stage is of interest nowadays. There are a lot of biosensors, which use the fluorescent labels for specific detection of analytes. For instance, common method for detection of antigens in human serum samples is enzyme-linked immunosorbent assay (ELISA). One of the most effective ways to improve the sensitivity of this detection method is the use of a substrate that could enhance the fluorescent signal and make it easier to collect. Two-dimensional (2D) photonic crystals are very suitable structures for these purposes because of the ability to enhance the luminescent signal, control the light propagation and perform the analysis directly on its surface. In our study we have calculated optimal parameters for 2D-dimensional photonic crystal consisting of the array of silicon nano-rods, fabricated such photonic crystal on a silicon substrate using reactive ion etching and showed the possibility of its efficient application as a substrate for ELISA detection of human cancer antigens.

  4. Conjugating influenza a (H1N1) antigen to n-trimethylaminoethylmethacrylate chitosan nanoparticles improves the immunogenicity of the antigen after nasal administration.

    Science.gov (United States)

    Liu, Qingfeng; Zheng, Xiaoyao; Zhang, Chi; Shao, Xiayan; Zhang, Xi; Zhang, Qizhi; Jiang, Xinguo

    2015-11-01

    As one of the most serious infectious respiratory diseases, influenza A (H1N1) is a great threat to human health, and it has created an urgent demand for effective vaccines. Nasal immunization can induce both systemic and mucosal immune responses against viruses, and it can serve as an ideal route for vaccination. However, the low immunogenicity of antigens on nasal mucosa is a high barrier for the development of nasal vaccines. In this study, we covalently conjugated an influenza A (H1N1) antigen to the surface of N-trimethylaminoethylmethacrylate chitosan (TMC) nanoparticles (H1N1-TMC/NP) through thioester bonds to increase the immunogenicity of the antigen after nasal administration. SDS-PAGE revealed that most of the antigen was conjugated on TMC nanoparticles, and an in vitro biological activity assay confirmed the stability of the antigen after conjugation. After three nasal immunizations, the H1N1-TMC/NP induced significantly higher levels of serum IgG and mucosal sIgA compared with free antigen. A hemagglutination inhibition assay showed that H1N1-TMC/NP induced much more protective antibodies than antigen-encapsulated nanoparticles or alum-precipitated antigen (I.M.). In the mechanistic study, H1N1-TMC/NP was shown to stimulate macrophages to produce IL-1β and IL-6 and to stimulate spleen lymphocytes to produce IL-2 and IFN-γ. These results indicated that H1N1-TMC/NP may be an effective vaccine against influenza A (H1N1) viruses for use in nasal immunization.

  5. A Francisella tularensis live vaccine strain that improves stimulation of antigen-presenting cells does not enhance vaccine efficacy.

    Directory of Open Access Journals (Sweden)

    Deanna M Schmitt

    Full Text Available Vaccination is a proven strategy to mitigate morbidity and mortality of infectious diseases. The methodology of identifying and testing new vaccine candidates could be improved with rational design and in vitro testing prior to animal experimentation. The tularemia vaccine, Francisella tularensis live vaccine strain (LVS, does not elicit complete protection against lethal challenge with a virulent type A Francisella strain. One factor that may contribute to this poor performance is limited stimulation of antigen-presenting cells. In this study, we examined whether the interaction of genetically modified LVS strains with human antigen-presenting cells correlated with effectiveness as tularemia vaccine candidates. Human dendritic cells infected with wild-type LVS secrete low levels of proinflammatory cytokines, fail to upregulate costimulatory molecules, and activate human T cells poorly in vitro. One LVS mutant, strain 13B47, stimulated higher levels of proinflammatory cytokines from dendritic cells and macrophages and increased costimulatory molecule expression on dendritic cells compared to wild type. Additionally, 13B47-infected dendritic cells activated T cells more efficiently than LVS-infected cells. A deletion allele of the same gene in LVS displayed similar in vitro characteristics, but vaccination with this strain did not improve survival after challenge with a virulent Francisella strain. In vivo, this mutant was attenuated for growth and did not stimulate T cell responses in the lung comparable to wild type. Therefore, stimulation of antigen-presenting cells in vitro was improved by genetic modification of LVS, but did not correlate with efficacy against challenge in vivo within this model system.

  6. Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer Cells

    Directory of Open Access Journals (Sweden)

    Claudia Schlimper

    2012-01-01

    Full Text Available Adoptive therapy of malignant diseases with cytokine-induced killer (CIK cells showed promise in a number of trials; the activation of CIK cells from cancer patients towards their autologous cancer cells still needs to be improved. Here, we generated CIK cells ex vivo from blood lymphocytes of colorectal cancer patients and engineered those cells with a chimeric antigen receptor (CAR with an antibody-defined specificity for carcinoembryonic antigen (CEA. CIK cells thereby gained a new specificity as defined by the CAR and showed increase in activation towards CEA+ colon carcinoma cells, but less in presence of CEA− cells, indicated by increased secretion of proinflammatory cytokines. Redirected CIK activation was superior by CAR-mediated CD28-CD3ζ than CD3ζ signaling only. CAR-engineered CIK cells from colon carcinoma patients showed improved activation against their autologous, primary carcinoma cells from biopsies resulting in more efficient tumour cell lysis. We assume that adoptive therapy with CAR-modified CIK cells shows improved selectivity in targeting autologous tumour lesions.

  7. Long-term Prostate-specific Antigen Velocity in Improved Classification of Prostate Cancer Risk and Mortality

    DEFF Research Database (Denmark)

    Ørsted, David Dynnes; Bojesen, Stig E; Kamstrup, Pia R;

    2013-01-01

    BACKGROUND: It remains unclear whether adding long-term prostate-specific antigen velocity (PSAV) to baseline PSA values improves classification of prostate cancer (PCa) risk and mortality in the general population. OBJECTIVE: To determine whether long-term PSAV improves classification of PCa risk...... classification was assessed using the net reclassification index (NRI). RESULTS: Age-adjusted hazard ratios for PCa risk and mortality were 2.7-5.3 and 2.3-3.4, respectively, for long-term PSAV when added to models already including baseline PSA values. For PCa risk and mortality, adding long-term PSAV to models....... Correspondingly, inappropriately reclassified were 49 of 10 000 men with PCa and 1658 of 10 000 men with no PCa. CONCLUSIONS: Long-term PSAV in addition to baseline PSA value improves classification of PCa risk and mortality. Applying long-term PSAV nationwide, the ratio of appropriately to inappropriately...

  8. Improved proliferation of antigen-specific cytolytic T lymphocytes using a multimodal nanovaccine

    Directory of Open Access Journals (Sweden)

    Li B

    2016-11-01

    Full Text Available Bo Li,1,2 Michael Siuta,1 Vanessa Bright,1,2 Dmitry Koktysh,3,4 Brittany K Matlock,5 Megan E Dumas,1 Meiying Zhu,1 Alex Holt,1 Donald Stec,3,6 Shenglou Deng,7 Paul B Savage,7 Sebastian Joyce,8,9 Wellington Pham1,2,6,10–12 1Institute of Imaging Science, Vanderbilt University School of Medicine, 2Department of Radiology and Radiological Sciences, 3Department of Chemistry, Vanderbilt University, 4Vanderbilt Institute of Nanoscale Science and Engineering, 5Vanderbilt Flow Cytometry Shared Resource, Vanderbilt University, 6Vanderbilt Institute of Chemical Biology, 7Department of Chemistry and Biochemistry, Brigham Young University, 8Department of Pathology, Microbiology and Immunology, Vanderbilt University, 9Veterans Administration Tennessee Valley Healthcare System, 10Department of Biomedical Engineering, 11Vanderbilt Ingram Cancer Center, 12Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA Abstract: The present study investigated the immunoenhancing property of our newly designed nanovaccine, that is, its ability to induce antigen-specific immunity. This study also evaluated the synergistic effect of a novel compound PBS-44, an α-galactosylceramide analog, in boosting the immune response induced by our nanovaccine. The nanovaccine was prepared by encapsulating ovalbumin (ova and an adjuvant within the poly(lactic-co-glycolic acid nanoparticles. Quantitative analysis of our study data showed that the encapsulated vaccine was physically and biologically stable; the core content of our nanovaccine was found to be released steadily and slowly, and nearly 90% of the core content was slowly released over the course of 25 days. The in vivo immunization studies exhibited that the nanovaccine induced stronger and longer immune responses compared to its soluble counterpart. Similarly, intranasal inhalation of the nanovaccine induced more robust antigen-specific CD8+ T cell response than intraperitoneal injection of nanovaccine

  9. A combined approach of human leukocyte antigen ligandomics and immunogenicity analysis to improve peptide-based cancer immunotherapy.

    Science.gov (United States)

    Peper, Janet Kerstin; Stevanović, Stefan

    2015-10-01

    The breakthrough development of immune checkpoint inhibitors as clinically effective novel therapies demonstrates the potential of cancer immunotherapy. The identification of suitable targets for specific immunotherapy, however, remains a challenging task. Most peptides previously used for vaccination in clinical trials were able to elicit strong immunological responses but failed with regard to clinical benefit. This might, at least partly, be caused by an inadequate peptide selection, usually derived from established tumor-associated antigens which are not necessarily presented as human leukocyte antigen (HLA) ligands. Recently, HLA ligandome analysis revealed cancer-associated peptides, which have been used in clinical trials showing encouraging impact on survival. To improve peptide-based cancer immunotherapy, our group established a combined approach of HLA ligandomics and immunogenicity analysis for the identification of vaccine peptides. This approach is based on the identification of naturally presented HLA ligands on tumor samples, the selection of tumor-associated/tumor-specific HLA ligands and their subsequent testing for immunogenicity in vitro. In this review, we want to present our pipeline for the identification of vaccine peptides, focusing on ovarian cancer, and want to discuss differences to other approaches. Furthermore, we want to give a short outlook of a potential multi-peptide vaccination trial using the novel identified peptides.

  10. Dramatic response to infliximab in refractory neurosarcoidosis

    Directory of Open Access Journals (Sweden)

    Chintamaneni Sreekanth

    2010-01-01

    Full Text Available Sarcoidosis is a systemic disease characterized by noncaseating granulomas in the involved organs. Neurologic manifestations involving the central and/or peripheral nervous system occur in about 5% of patients. Neurosarcoidosis is often refractory to conventional treatment and therefore more effective treatment options are needed. While the etiology of the disease is still unknown, there is now a better understanding of its pathogenesis on a molecular level. It is clear that tumor necrosis factor-α (TNFα plays a pivotal role in the development of the granulomas and it is believed to be a key cytokine involved in the pathogenesis of the disease. Taking advantage of this better understanding of disease pathogenesis, anti-TNFα agents are being increasingly used to treat refractory sarcoidosis. We report a patient with refractory neurosarcoidosis who showed dramatic improvement in the clinical and radiological manifestations following treatment with infliximab; he suffered a relapse upon discontinuation of the medication.

  11. Dramatic weight loss with rufinamide.

    Science.gov (United States)

    Mourand, Isabelle; Crespel, Arielle; Gelisse, Philippe

    2013-01-01

    Rufinamide (RUF) is a novel antiepileptic drug considered as second-line therapy in the treatment of Lennox-Gastaut syndrome. Treatment-emergent adverse events (AEs) have consisted mainly of drowsiness, irritability, vomiting, and loss of appetite. RUF is considered as a "weight-neutral" drug. We found clinically significant weight loss in 7 of 15 consecutive adult patients (47%; 3 male, 4 female, aged 18-31 years) treated with RUF as add-on therapy (800-2,400 mg/day: 23.5-57.1 mg/kg/day). The body mass index (BMI) decreased by 7.3-18.7%. Two patients were obese class I before RUF. Five patients (71%) were underweight before RUF (mild in one case, moderate in two cases, and severe in two cases). Four of these patients stopped RUF because of this adverse effect. RUF was recommenced in two patients using a lower and slower dosing strategy; one patient showed improvement in seizure control and no weight loss but RUF was re-stopped in the second patient because of continued weight loss. Despite of weight loss, RUF was continued in two other patients because it reduced seizure activity. We primarily related weight loss to reduced food intake, that is, loss of appetite and nausea, although in two patients no obvious loss of appetite was reported. RUF can cause clinically significant weight loss in adult patients, even at low dose. This AE can affect patients who are already underweight. There is a possibility that lower starting doses and slower escalation might minimize weight loss, but further information is required to determine whether this is the case.

  12. Gamma irradiated antigen extracts improves the immune response and protection in experimental toxoplasmosis

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Andrea da; Galisteo Junior, Andres Jimenez; Andrade Junior, Heitor Franco de, E-mail: andreacosta@usp.br [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Instituto de Medicina Tropical; Zorgi, Nahiara Estevez [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Instituto de Ciencias Biomedicas; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2015-07-01

    We aimed to use ionizing radiation on soluble extracts of T. gondii tachyzoites (AgTg) and tested the ability of these extracts to induce immunity in BALB/c mice against a challenge. T. gondii RH strain AgTg was irradiated with Co-60 at 0.25 to 4 kGy and were affected after 1 kGy, as evidenced by a progressive high molecular weight protein aggregates and no loss in antigenicity, as detected by immunoblotting, except after 4kGy. BALB/c mice were immunized with biweekly doses of 03 s.c. native or irradiated AgTg without adjuvants; the anti-T.gondii IgG production was detected by ELISA, and higher levels and avidity were detected in mice immunized with 1.5 kGy AgTg compared to controls (p<0.05). Mice immunized with native AgTg exhibited spleen CD19{sup +} B, CD3{sup +}CD4{sup +} or CD3{sup +}CD8{sup +} T cell proliferation levels of 5%, while 1.5 kGy-immunized mice exhibited spleen cell proliferation levels of 12.2%, primarily for CD19{sup +} or CD3{sup +}CD8{sup +} lymphocytes and less evidently for CD3{sup +}CD4{sup +} (8.8%) helper T lymphocytes. All cells from control mice showed little to no proliferation when stimulated with AgTg. These cells secreted more IFN-γ in the 1.5 kGy AgTg-immunized group (p<0.05). BALB/c mice immunized with 1.5 kGy and challenged with different strains of T. gondii were partially protected, as evidenced by survival after RH virulent strain challenge (p<0.0001) but also after ME-49 strain challenge: the brain cyst numbers (p<0.05) and the levels of T. gondii DNA measured by real-time PCR (p<0.05) decreased compared to non-immunized controls. (author)

  13. A new adenovirus based vaccine vector expressing an Eimeria tenella derived TLR agonist improves cellular immune responses to an antigenic target.

    Directory of Open Access Journals (Sweden)

    Daniel M Appledorn

    Full Text Available BACKGROUND: Adenoviral based vectors remain promising vaccine platforms for use against numerous pathogens, including HIV. Recent vaccine trials utilizing Adenovirus based vaccines expressing HIV antigens confirmed induction of cellular immune responses, but these responses failed to prevent HIV infections in vaccinees. This illustrates the need to develop vaccine formulations capable of generating more potent T-cell responses to HIV antigens, such as HIV-Gag, since robust immune responses to this antigen correlate with improved outcomes in long-term non-progressor HIV infected individuals. METHODOLOGY/PRINCIPAL FINDINGS: In this study we designed a novel vaccine strategy utilizing an Ad-based vector expressing a potent TLR agonist derived from Eimeria tenella as an adjuvant to improve immune responses from a [E1-]Ad-based HIV-Gag vaccine. Our results confirm that expression of rEA elicits significantly increased TLR mediated innate immune responses as measured by the influx of plasma cytokines and chemokines, and activation of innate immune responding cells. Furthermore, our data show that the quantity and quality of HIV-Gag specific CD8(+ and CD8(- T-cell responses were significantly improved when coupled with rEA expression. These responses also correlated with a significantly increased number of HIV-Gag derived epitopes being recognized by host T cells. Finally, functional assays confirmed that rEA expression significantly improved antigen specific CTL responses, in vivo. Moreover, we show that these improved responses were dependent upon improved TLR pathway interactions. CONCLUSION/SIGNIFICANCE: The data presented in this study illustrate the potential utility of Ad-based vectors expressing TLR agonists to improve clinical outcomes dependent upon induction of robust, antigen specific immune responses.

  14. Introducing Dramatic Inquiry as Visual Art Education

    Science.gov (United States)

    Rhoades, Mindi; Daiello, Vittoria S.

    2016-01-01

    This article defines dramatic inquiry, exploring its possible contributions to discourses on subjectivity, embodied pedagogy, and relational knowing in art education. As a communal, ensemble endeavor emerging from the discipline of drama education, dramatic inquiry offers strategies for enhancing arts education's critical inquiries by facilitating…

  15. Refinement of molecular approaches to improve the chance of identification of hematopoietic-restricted minor histocompatibility antigens.

    NARCIS (Netherlands)

    Rijke, B. de; Horssen-Zoetbrood, A. van; Veenbergen, S.; Fredrix, H.; Witte, T.J.M. de; Kemenade, E van de Wiel-van; Dolstra, H.

    2008-01-01

    Minor histocompatibility antigens (mHAgs) constitute the target antigens of the T cell-mediated graft-versus-leukemia response after HLA-identical allogeneic stem cell transplantation (SCT). Several human mHAgs have been identified, but only a few are selectively expressed by hematopoietic cells rep

  16. The porcine circovirus type 1 capsid gene promoter improves antigen expression and immunogenicity in a HIV-1 plasmid vaccine

    Directory of Open Access Journals (Sweden)

    Burger Marieta

    2011-02-01

    Full Text Available Abstract Background One of the promising avenues for development of vaccines against Human immunodeficiency virus type 1 (HIV-1 and other human pathogens is the use of plasmid-based DNA vaccines. However, relatively large doses of plasmid must be injected for a relatively weak response. We investigated whether genome elements from Porcine circovirus type 1 (PCV-1, an apathogenic small ssDNA-containing virus, had useful expression-enhancing properties that could allow dose-sparing in a plasmid vaccine. Results The linearised PCV-1 genome inserted 5' of the CMV promoter in the well-characterised HIV-1 plasmid vaccine pTHgrttnC increased expression of the polyantigen up to 2-fold, and elicited 3-fold higher CTL responses in mice at 10-fold lower doses than unmodified pTHgrttnC. The PCV-1 capsid gene promoter (Pcap alone was equally effective. Enhancing activity was traced to a putative composite host transcription factor binding site and a "Conserved Late Element" transcription-enhancing sequence previously unidentified in circoviruses. Conclusions We identified a novel PCV-1 genome-derived enhancer sequence that significantly increased antigen expression from plasmids in in vitro assays, and improved immunogenicity in mice of the HIV-1 subtype C vaccine plasmid, pTHgrttnC. This should allow significant dose sparing of, or increased responses to, this and other plasmid-based vaccines. We also report investigations of the potential of other circovirus-derived sequences to be similarly used.

  17. Racial differences in hypogonadal improvement and prostate-specific antigen levels in hypogonadal men treated with testosterone replacement therapy

    Directory of Open Access Journals (Sweden)

    Robert M. Coward

    2010-12-01

    Full Text Available PURPOSE: To observe hypogonadal men undergoing testosterone replacement therapy (TRT and assess racial differences in hypogonadal improvement and prostate-specific antigen (PSA levels. MATERIALS AND METHODS: In a retrospective analysis, 75 hypogonadal men were followed for an average 34 months after initiating TRT. Total testosterone and PSA levels were assessed every 6 months, and patients diagnosed with prostatitis or prostate cancer during treatment were excluded. RESULTS: For 16 African American men, the average age at diagnosis of hypogonadism was 53.5 years, compared with 57.8 years in 59 Caucasian men (p = NS. Pre- and post-treatment testosterone was 219 ng/dL and 310 ng/dL in African American men, and 247 ng/dL and 497 ng/dL in Caucasian men (p = NS. Symptomatic response was 81% in African American men and 93% in Caucasian men (p = NS. Baseline PSA level was 1.32 ng/mL in African American men and 1.27 ng/mL in Caucasian men, and there was no significant difference in PSA between racial groups at 6-month intervals, although there was a small decreasing trend in the PSA of African Americans compared with Caucasians. CONCLUSIONS: Hypogonadal African American men have a similar normalization of testosterone and symptomatic response as hypogonadal Caucasian men, and PSA levels remain stable over time in both groups. In this hypogonadal cohort, in contrast to studies of eugonadal men, higher PSA levels in African Americans were not observed.

  18. [Improvement of sensitivity in the second generation HCV core antigen assay by a novel concentration method using polyethylene glycol (PEG)].

    Science.gov (United States)

    Higashimoto, Makiko; Takahashi, Masahiko; Jokyu, Ritsuko; Syundou, Hiromi; Saito, Hidetsugu

    2007-11-01

    A HCV core antigen (Ag) detection assay system, Lumipulse Ortho HCV Ag has been developed and is commercially available in Japan with a lower detection level limit of 50 fmol/l, which is equivalent to 20 KIU/ml in PCR quantitative assay. HCV core Ag assay has an advantage of broader dynamic range compared with PCR assay, however the sensitivity is lower than PCR. We developed a novel HCV core Ag concentration method using polyethylene glycol (PEG), which can improve the sensitivity five times better than the original assay. The reproducibility was examined by consecutive five-time measurement of HCV patients serum, in which the results of HCV core Ag original and concentrated method were 56.8 +/- 8.1 fmol/l (mean +/- SD), CV 14.2% and 322.9 +/- 45.5 fmol/l CV 14.0%, respectively. The assay results of HCV negative samples in original HCV core Ag were all 0.1 fmol/l and the results were same even in the concentration method. The results of concentration method were 5.7 times higher than original assay, which was almost equal to theoretical rate as expected. The assay results of serially diluted samples were also as same as expected data in both original and concentration assay. We confirmed that the sensitivity of HCV core Ag concentration method had almost as same sensitivity as PCR high range assay in the competitive assay study using the serially monitored samples of five HCV patients during interferon therapy. A novel concentration method using PEG in HCV core Ag assay system seems to be useful for assessing and monitoring interferon treatment for HCV.

  19. Combined hepatitis C virus (HCV) antigen-antibody detection assay does not improve diagnosis for seronegative individuals with occult HCV infection.

    Science.gov (United States)

    Quiroga, Juan A; Castillo, Inmaculada; Pardo, Margarita; Rodríguez-Iñigo, Elena; Carreño, Vicente

    2006-12-01

    A combined hepatitis C virus (HCV) antigen-antibody assay was evaluated for 115 seronegative individuals with occult HCV infection. The assay was reactive in one patient and negative to weakly reactive in three others (all four gave indeterminate results by supplemental assay) but failed to detect HCV in the remaining patients. Despite increased sensitivity the combined assay does not improve serodiagnosis of occult HCV infection.

  20. Combined Hepatitis C Virus (HCV) Antigen-Antibody Detection Assay Does Not Improve Diagnosis for Seronegative Individuals with Occult HCV Infection▿

    OpenAIRE

    Quiroga, Juan A.; Castillo, Inmaculada; Pardo, Margarita; Rodríguez-Iñigo, Elena; CARREÑO, VICENTE

    2006-01-01

    A combined hepatitis C virus (HCV) antigen-antibody assay was evaluated for 115 seronegative individuals with occult HCV infection. The assay was reactive in one patient and negative to weakly reactive in three others (all four gave indeterminate results by supplemental assay) but failed to detect HCV in the remaining patients. Despite increased sensitivity the combined assay does not improve serodiagnosis of occult HCV infection.

  1. The Art of Reading: Dramatizing Literacy

    Science.gov (United States)

    Ortlieb, Evan; Cramer, Neva; Cheek, Earl, Jr.

    2007-01-01

    The art of reading refers to the act of representing and interpreting text through oral dramatic reading. To the dismay of many teachers, reading is becoming a "lost art." Students are expected to apply specific literacy techniques rather than use their imagination to learn to enact text. Based on a study of the reading perceptions of natural oral…

  2. The Psychodrama-Social Dramatics Separation.

    Science.gov (United States)

    Klepac, Richard L.

    Social dramatics is a therapeutic and educational program that can act as a mirror to reflect images of the self in action with others. It is the modality for experiential learning to correct social dysfunction by providing models for imitation, opportunities to practice and develop individual forms from that model, and risk free environments for…

  3. Nietzsche contra Burke: The Melodrama in Dramatism.

    Science.gov (United States)

    Desilet, Gregory

    1989-01-01

    Examines Kenneth Burke's and Friedrich Nietzsche's similar understanding of the hortatory nature of language-using, weighed against their radically differing conceptions of the negative, which allows a distinction between two genres of dramatism, and illustrates contrasting orientations toward symbolic activity in general. (SR)

  4. Fusion to green fluorescent protein improves expression levels of Theileria parva sporozoite surface antigen p67 in insect cells

    NARCIS (Netherlands)

    Kaba, S.A.; Nene, V.; Musoke, A.J.; Vlak, J.M.; Oers, van M.M.

    2002-01-01

    East Coast fever (ECF) is a fatal disease of cattle caused by the protozoan parasite Theileria parva. The development of a subunit vaccine, based on the sporozoite-specific surface antigen p67, has been hampered by difficulties in achieving high-level expression of recombinant p67 in a near-authenti

  5. Care initiation area yields dramatic results.

    Science.gov (United States)

    2009-03-01

    The ED at Gaston Memorial Hospital in Gastonia, NC, has achieved dramatic results in key department metrics with a Care Initiation Area (CIA) and a physician in triage. Here's how the ED arrived at this winning solution: Leadership was trained in and implemented the Kaizen method, which eliminates redundant or inefficient process steps. Simulation software helped determine additional space needed by analyzing arrival patterns and other key data. After only two days of meetings, new ideas were implemented and tested.

  6. Dramatic reduction of culture time of Mycobacterium tuberculosis

    Science.gov (United States)

    Ghodbane, Ramzi; Raoult, Didier; Drancourt, Michel

    2014-02-01

    Mycobacterium tuberculosis culture, a critical technique for routine diagnosis of tuberculosis, takes more than two weeks. Here, step-by-step improvements in the protocol including a new medium, microaerophlic atmosphere or ascorbic-acid supplement and autofluorescence detection dramatically shortened this delay. In the best case, primary culture and rifampicin susceptibility testing were achieved in 72 hours when specimens were inoculated directly on the medium supplemented by antibiotic at the beginning of the culture.

  7. Cotton domestication: dramatic changes in a single cell

    Directory of Open Access Journals (Sweden)

    Strasburg Jared L

    2010-11-01

    Full Text Available Abstract Investigations on the nature of genetic changes underpinning plant domestication have begun to shed light on the evolutionary history of crops and can guide improvements to modern cultivars. A recent study focused on cotton fiber cells tracks the dramatic genome-wide changes in gene expression during development that have accompanied selection for increased fiber yield and quality. See Research article: http://www.biomedcentral.com/1741-7007/8/139

  8. On the Dramatic Features in Robert Browning’s Poems of Dramatic Monologue

    Institute of Scientific and Technical Information of China (English)

    杜玉文

    2014-01-01

    This paper explored the three dramatic features intrinsic in Robert Browning’s poems of dramatic monologue, name-ly, the employment of first-person point of view, the use of irony, and the intricate psychological exploration and vivid character-ization. Such features are crucial in the successful presentation of various human nature and experience with profundity, making his poems an enduring classic in the English literature.

  9. Microalloying Boron Carbide with Silicon to Achieve Dramatically Improved Ductility

    Science.gov (United States)

    2014-11-18

    Fracture Toughness in Nanostructured Diamond−SiC Composites. Appl . Phys. Lett. 2004, 84, 1356−1358. (8) Sigl, L. S.; Mataga, P. A.; Dalgleish, B. J...Commun. 2012, 3, 1052. (11) Sezer, A. O.; Brand , J. I. Chemical Vapor Deposition of Boron Carbide. Mater. Sci. Eng., B 2001, 79, 191−202. (12) Thevenot...23) Johnson, G. R.; Holmquist, T. J. Response of Boron Carbide Subjected to Large Strains, High Strain Rates, and High Pressures. J. Appl . Phys. 1999

  10. Targeting hepatitis B virus antigens to dendritic cells by heat shock protein to improve DNA vaccine potency

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate a novel DNA vaccination based upon expression of the HBV e antigen fused to a heat shock protein (HSP) as a strategy to enhance DNA vaccine potency.METHODS: A pCMV-HBeAg-HSP DNA vaccine and a control DNA vaccine were generated. Mice were immunized with these different construct. Immune responses were measured 2 wk after a second immunization by a T cell response assay, CTL cytotoxicity assay, and an antibody assay in C57BL/6 and BALB/c mice. CT26-HBeAg tumor cell challenge test in vivo was performed in BALB/c mice to monitor anti-tumor immune responses.RESULTS: In the mice immunized with pCMV-HBe-HSP DNA, superior CTL activity to target HBV-positive target cells was observed in comparison with mice immunized with pCMV-HBeAg (44% ± 5% vs 30% ± 6% in E: T > 50:1, P < 0.05). ELISPOT assays showed a stronger T-cell response from mice immunized with pCMV-HBe-HSP than that from pCMV-HBeAg immunized animals when stimulated either with MHC class Ⅰ or class Ⅱ epitopes derived from HBeAg (74% ± 9% vs 31% ± 6%, P < 0.01). ELISA assays revealed an enhanced HBeAg antibody response from mice immunized with pCMV-HBe-HSP than from those immunized with pCMV-HBeAg. The lowest tumor incidence and the slowest tumor growth were observed in mice immunized with pCMV-HBe-HSP when challenged with CT26-HBeAg.CONCLUSION: The results of this study demonstrate a broad enhancement of antigen-specific CD4+ helper,CD8+ cytotoxic T-cell, and B-cell responses by a novel DNA vaccination strategy. They also proved a stronger antigen-specific immune memory, which may be superior to currently described HBV DNA vaccination strategies for the treatment of chronic HBV infection.

  11. The Transformational Qualities of Dramatic Arts

    Directory of Open Access Journals (Sweden)

    Laura Gardner Salazar

    2014-05-01

    Full Text Available During the International Drama and Education Association (IDEA Congress in Kenya in 1998, the life of two educators crossed roads. Although both are from different geographical contexts (Colombia and the United States, they have shared the same passion: to encourage in their societies the implementation of dramatic arts in different educational settings (schools, universities, communities so children and adults could develop to their fullest, thus enabling them to participate actively in building a more democratic society. Fifteen years after this encounter, they met again in the 2013 IDEA Congress in Paris to reflect on their efforts during their life spans. Through examining their drama practices, they discuss how this human expression functions as a critical thinking art form, changing players, audiences, and communities. Lessons derived from their experiences might be useful for a new generation of transformational drama leaders.

  12. Mutual helper effect in copulsing of dendritic cells with 2 antigens: a novel approach for improvement of dendritic-based vaccine efficacy against tumors and infectious diseases simultaneously.

    Science.gov (United States)

    Shojaeian, Jaleh; Jeddi-Tehrani, Mahmood; Dokouhaki, Pouneh; Mahmoudi, Ahmad Reza; Ghods, Roya; Bozorgmehr, Mahmood; Nikoo, Shohreh; Bayat, Ali Ahmad; Akhondi, Mohammad Mehdi; Ostadkarampour, Mahyar; Rezania, Simin; Zarnani, Amir Hassan

    2009-05-01

    To develop an efficient dendritic cell (DC)-based immunotherapy protocol, we examined whether simultaneous pulsing of DCs with a given antigen and a third-party antigen could enhance their antigen presentation capacity. Purified splenic DCs of Balb/c mice were pulsed separately with immunoglobulin G, ovalbumin, conalbumin, P15 peptide of Mycobacterium tuberculosis, and prostate-specific antigen or double combinations of the aforementioned antigens. In some settings, DCs pulsed with 1 antigen were mixed equally with those pulsed with another antigen. Antigen-pulsed DCs were injected into the footpad of syngeneic mice and proliferation of whole, CD4 and CD8 depleted lymph node cells was measured after restimulation with cognate antigen. Antigen-specific production of interferon-gamma (IFNgamma) was tested in culture supernatants. Frequency of responding lymph node cells was determined by IFNgamma enzyme-linked immunosorbent spot assay. Our results showed that copulsing of DCs with 2 unrelated antigens increased the capacity of DCs to induce antigen-specific T-cell proliferation against both antigens up to 16-fold. Injection of 2 populations of DCs each pulsed with a different antigen, increased proliferation of primed T cells significantly as well. Both CD4 and CD8 depleted populations showed vigorous proliferative response in copulsing system. In addition, copulsing of DCs with 2 antigens resulted in higher frequency of antigen-specific responding cells and significantly more IFNgamma production. Our results clearly showed that unrelated peptides and proteins could be used to enhance efficacy of DC-based vaccines and in this system, each antigen served to help the other one, a condition that we termed as "mutual helper effect."

  13. Improving Mycobacterium bovis bacillus Calmette-Guerin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells.

    Directory of Open Access Journals (Sweden)

    Manjunatha M Venkataswamy

    Full Text Available Recombinant Mycobacterium bovis bacillus Calmette-Guèrin (rBCG has been explored as a vector for vaccines against HIV because of its ability to induce long lasting humoral and cell mediated immune responses. To maximize the potential for rBCG vaccines to induce effective immunity against HIV, various strategies are being employed to improve its ability to prime CD8+ T cells, which play an important role in the control of HIV infections. In this study we adopted a previously described approach of incorporating glycolipids that activate CD1d-restricted natural killer T (NKT cells to enhance priming of CD8+ T cells by rBCG strains expressing an SIV Gag antigen (rBCG-SIV gag. We found that the incorporation of the synthetic NKT activating glycolipid α-galactosylceramide (α-GC into rBCG-SIV gag significantly enhanced CD8+ T cell responses against an immunodominant Gag epitope, compared to responses primed by unmodified rBCG-SIV gag. The abilities of structural analogues of α-GC to enhance CD8+ T cell responses to rBCG were compared in both wild type and partially humanized mice that express human CD1d molecules in place of mouse CD1d. These studies identified an α-GC analogue known as 7DW8-5, which has previously been used successfully as an adjuvant in non-human primates, as a promising compound for enhancing immunogenicity of antigens delivered by rBCG.vectors. Our findings support the incorporation of synthetic glycolipid activators of NKT cells as a novel approach to enhance the immunogenicity of rBCG-vectored antigens for induction of CD8+ T cell responses. The glycolipid adjuvant 7DW8-5 may be a promising candidate for advancing to non-human primate and human clinical studies for the development of HIV vaccines based on rBCG vectors.

  14. Improving Mycobacterium bovis Bacillus Calmette-Guèrin as a Vaccine Delivery Vector for Viral Antigens by Incorporation of Glycolipid Activators of NKT Cells

    Science.gov (United States)

    Kharkwal, Shalu S.; Carreño, Leandro J.; Johnson, Alison J.; Kunnath-Velayudhan, Shajo; Liu, Zheng; Bittman, Robert; Jervis, Peter J.; Cox, Liam R.; Besra, Gurdyal S.; Wen, Xiangshu; Yuan, Weiming; Tsuji, Moriya; Li, Xiangming; Ho, David D.; Chan, John; Lee, Sunhee; Frothingham, Richard; Haynes, Barton F.; Panas, Michael W.; Gillard, Geoffrey O.; Sixsmith, Jaimie D.; Korioth-Schmitz, Birgit; Schmitz, Joern E.; Larsen, Michelle H.; Jacobs, William R.; Porcelli, Steven A.

    2014-01-01

    Recombinant Mycobacterium bovis bacillus Calmette-Guèrin (rBCG) has been explored as a vector for vaccines against HIV because of its ability to induce long lasting humoral and cell mediated immune responses. To maximize the potential for rBCG vaccines to induce effective immunity against HIV, various strategies are being employed to improve its ability to prime CD8+ T cells, which play an important role in the control of HIV infections. In this study we adopted a previously described approach of incorporating glycolipids that activate CD1d-restricted natural killer T (NKT) cells to enhance priming of CD8+ T cells by rBCG strains expressing an SIV Gag antigen (rBCG-SIV gag). We found that the incorporation of the synthetic NKT activating glycolipid α-galactosylceramide (α-GC) into rBCG-SIV gag significantly enhanced CD8+ T cell responses against an immunodominant Gag epitope, compared to responses primed by unmodified rBCG-SIV gag. The abilities of structural analogues of α-GC to enhance CD8+ T cell responses to rBCG were compared in both wild type and partially humanized mice that express human CD1d molecules in place of mouse CD1d. These studies identified an α-GC analogue known as 7DW8-5, which has previously been used successfully as an adjuvant in non-human primates, as a promising compound for enhancing immunogenicity of antigens delivered by rBCG.vectors. Our findings support the incorporation of synthetic glycolipid activators of NKT cells as a novel approach to enhance the immunogenicity of rBCG-vectored antigens for induction of CD8+ T cell responses. The glycolipid adjuvant 7DW8-5 may be a promising candidate for advancing to non-human primate and human clinical studies for the development of HIV vaccines based on rBCG vectors. PMID:25255287

  15. Improving influenza virological surveillance in Europe: strain-based reporting of antigenic and genetic characterisation data, 11 European countries, influenza season 2013/14

    Science.gov (United States)

    Broberg, Eeva; Hungnes, Olav; Schweiger, Brunhilde; Prosenc, Katarina; Daniels, Rod; Guiomar, Raquel; Ikonen, Niina; Kossyvakis, Athanasios; Pozo, Francisco; Puzelli, Simona; Thomas, Isabelle; Waters, Allison; Wiman, Åsa; Meijer, Adam

    2016-01-01

    Influenza antigenic and genetic characterisation data are crucial for influenza vaccine composition decision making. Previously, aggregate data were reported to the European Centre for Disease Prevention and Control by European Union/European Economic Area (EU/EEA) countries. A system for collecting case-specific influenza antigenic and genetic characterisation data was established for the 2013/14 influenza season. In a pilot study, 11 EU/EEA countries reported through the new mechanism. We demonstrated feasibility of reporting strain-based antigenic and genetic data and ca 10% of influenza virus-positive specimens were selected for further characterisation. Proportions of characterised virus (sub)types were similar to influenza virus circulation levels. The main genetic clades were represented by A/StPetersburg/27/2011(H1N1)pdm09 and A/Texas/50/2012(H3N2). A(H1N1)pdm09 viruses were more prevalent in age groups (by years) < 1 (65%; p = 0.0111), 20–39 (50%; p = 0.0046) and 40–64 (55%; p = 0.00001) while A(H3N2) viruses were most prevalent in those ≥ 65 years (62%*; p = 0.0012). Hospitalised patients in the age groups 6–19 years (67%; p = 0.0494) and ≥ 65 years (52%; p = 0.0005) were more frequently infected by A/Texas/50/2012 A(H3N2)-like viruses compared with hospitalised cases in other age groups. Strain-based reporting enabled deeper understanding of influenza virus circulation among hospitalised patients and substantially improved the reporting of virus characterisation data. Therefore, strain-based reporting of readily available data is recommended to all reporting countries within the EU/EEA. PMID:27762211

  16. Affinity improvement of a therapeutic antibody by structure-based computational design: generation of electrostatic interactions in the transition state stabilizes the antibody-antigen complex.

    Directory of Open Access Journals (Sweden)

    Masato Kiyoshi

    Full Text Available The optimization of antibodies is a desirable goal towards the development of better therapeutic strategies. The antibody 11K2 was previously developed as a therapeutic tool for inflammatory diseases, and displays very high affinity (4.6 pM for its antigen the chemokine MCP-1 (monocyte chemo-attractant protein-1. We have employed a virtual library of mutations of 11K2 to identify antibody variants of potentially higher affinity, and to establish benchmarks in the engineering of a mature therapeutic antibody. The most promising candidates identified in the virtual screening were examined by surface plasmon resonance to validate the computational predictions, and to characterize their binding affinity and key thermodynamic properties in detail. Only mutations in the light-chain of the antibody are effective at enhancing its affinity for the antigen in vitro, suggesting that the interaction surface of the heavy-chain (dominated by the hot-spot residue Phe101 is not amenable to optimization. The single-mutation with the highest affinity is L-N31R (4.6-fold higher affinity than wild-type antibody. Importantly, all the single-mutations showing increase affinity incorporate a charged residue (Arg, Asp, or Glu. The characterization of the relevant thermodynamic parameters clarifies the energetic mechanism. Essentially, the formation of new electrostatic interactions early in the binding reaction coordinate (transition state or earlier benefits the durability of the antibody-antigen complex. The combination of in silico calculations and thermodynamic analysis is an effective strategy to improve the affinity of a matured therapeutic antibody.

  17. Immunotherapy of acute leukemia by chimeric antigen receptor-modified lymphocytes using an improved Sleeping Beauty transposon platform.

    Science.gov (United States)

    Magnani, Chiara F; Turazzi, Nice; Benedicenti, Fabrizio; Calabria, Andrea; Tenderini, Erika; Tettamanti, Sarah; Giordano Attianese, Greta M P; Cooper, Laurence J N; Aiuti, Alessandro; Montini, Eugenio; Biondi, Andrea; Biagi, Ettore

    2016-08-09

    Chimeric antigen receptor (CAR)-modified T-cell adoptive immunotherapy is a remarkable therapeutic option proven effective in the treatment of hematological malignancies. In order to optimize cell manufacturing, we sought to develop a novel clinical-grade protocol to obtain CAR-modified cytokine-induced killer cells (CIKs) using the Sleeping Beauty (SB) transposon system. Administration of irradiated PBMCs overcame cell death of stimulating cells induced by non-viral transfection, enabling robust gene transfer together with efficient T-cell expansion. Upon single stimulation, we reached an average of 60% expression of CD123- and CD19- specific 3rd generation CARs (CD28/OX40/TCRzeta). Furthermore, modified cells displayed persistence of cell subsets with memory phenotype, specific and effective lytic activity against leukemic cell lines and primary blasts, cytokine secretion, and proliferation. Adoptive transfer of CD123.CAR or CD19.CAR lymphocytes led to a significant anti-tumor response against acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) disseminated diseases in NSG mice. Notably, we found no evidence of integration enrichment near cancer genes and transposase expression at the end of the differentiation. Taken all together, our findings describe a novel donor-derived non-viral CAR approach that may widen the repertoire of available methods for T cell-based immunotherapy.

  18. CRACC-targeting Fc-fusion protein induces activation of NK cells and DCs and improves T cell immune responses to antigenic targets.

    Science.gov (United States)

    Aldhamen, Yasser A; Rastall, David P W; Chen, Weimin; Seregin, Sergey S; Pereira-Hicks, Cristiane; Godbehere, Sarah; Kaminski, Norbert E; Amalfitano, Andrea

    2016-06-08

    The CD2-like receptor activating cytotoxic cell (CRACC) receptor is a member of the SLAM family of receptors that are found on several types of immune cells. We previously demonstrated that increasing the abundance of the adaptor protein EAT-2 during vaccination enhanced innate and adaptive immune responses to vaccine antigens. Engagement of the CRACC receptor in the presence of the EAT-2 adaptor generally results in immune cell activation, while activating CRACC signaling in cells that lack EAT-2 adaptor inhibits their effector and regulatory functions. As EAT-2 is the only SAP adaptor that interacts with the CRACC receptor, we hypothesized that technologies that specifically modulate CRACC signaling during vaccination may also improve antigen specific adaptive immune responses. To test this hypothesis, we constructed a CRACC-targeting Fc fusion protein and included it in vaccination attempts. Indeed, mice co-vaccinated with the CRACC-Fc fusion protein and an adenovirus vaccine expressing the HIV-Gag protein had improved Gag-specific T cell responses, as compared to control mice. These responses are characterized by increased numbers of Gag-specific tetramer+ CD8+ T cells and increases in production of IFNγ, TNFα, and IL2, by Gag-specific CD8+ T cells. Moreover, our results revealed that use of the CRACC-Fc fusion protein enhances vaccine-elicited innate immune responses, as characterized by increased dendritic cells (DCs) maturation and IFNγ production from NK cells. This study highlights the importance of CRACC signaling during the induction of an immune response generally, and during vaccinations specifically, and also lends insight into the mechanisms underlying our prior results noting EAT-2-dependent improvements in vaccine efficacy.

  19. Maverick Comet Splits during Dramatic Outburst

    Science.gov (United States)

    1996-01-01

    New ESO Observations of P/Schwassmann-Wachmann 3 A few months ago, Periodic Comet Schwassmann-Wachmann 3 underwent a dramatic and completely unexpected, thousand-fold brightening. At that time, the cause for this interesting event was unknown. However, observations with the two largest ESO telescopes have now shown that the ``dirty snowball'' nucleus of this comet has recently split into at least four individual pieces [1]. There is little doubt that the outburst and the splitting event(s) are closely related and that the greatly increased dust and gas production is due to ``fresh'' material of the icy cometary nucleus becoming exposed to the surrounding space for the first time. A Comet with a Troubled History Comet Schwassmann-Wachmann 3 was discovered on May 2, 1930, on a photographic plate obtained at the Hamburg Observatory (Germany) by two astronomers at this institution, Arnold Schwassmann and Arthur Arno Wachmann. The subsequent observations showed that the comet moved in an elliptical orbit with a revolution period of somewhat more than 5 years. Great efforts were expended to observe the comet during the next returns, but it was not recovered until nearly 50 years and eight revolutions later, when its faint image was found of a plate obtained in August 1979 with a telescope at the Perth Observatory in Western Australia. It was missed in 1984, but was sighted again in 1989 and most recently in 1994. Thus this comet has only been observed during four out of thirteen approaches since 1930. While this may be partly due to a less advantageous location in the sky at some returns, it is also a strong indication that the comet behaves unpredictably and must have a quite variable brightness. For the sake of convenience this comet is often referred to as ``SW-3'' by professional astronomers. Recent orbital calculations have shown that it was inserted into the present, short-period orbit by the strong gravitational pull of Jupiter during several, relatively close

  20. Combination of autoantibodies against NY-ESO-1 and viral capsid antigen immunoglobulin A for improved detection of nasopharyngeal carcinoma.

    Science.gov (United States)

    Peng, Yu-Hui; Xu, Yi-Wei; Qiu, Si-Qi; Hong, Chao-Qun; Zhai, Tian-Tian; Li, En-Min; Xu, Li-Yan

    2014-09-01

    Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Southern China and Southeast Asia, and early detection remains a challenge. Autoantibodies have been found to precede the manifestations of symptomatic cancer by several months to years, making their identification of particular relevance for early detection. In the present study, the diagnostic value of serum autoantibodies against NY-ESO-1 in NPC patients was evaluated. The study included 112 patients with NPC and 138 normal controls. Serum levels of autoantibodies against NY-ESO-1 and classical Epstein-Barr virus marker, viral capsid antigen immunoglobulin A (VCA-IgA), were measured by enzyme-linked immunosorbent assay. Measurement of autoantibodies against NY-ESO-1 and VCA-IgA demonstrated a sensitivity/specificity of 42.9/94.9% [95% confidence interval (CI), 33.7-52.6/89.4-97.8%] and 55.4/95.7% (95% CI, 45.7-64.7/90.4-98.2%), respectively. The area under receiver operating characteristic curve for autoantibodies against NY-ESO-1 (0.821; 95% CI, 0.771-0.871) was marginally lower than that for VCA-IgA (0.860; 95% CI, 0.810-0.910) in NPC. The combination of autoantibodies against NY-ESO-1 and VCA-IgA yielded an enhanced sensitivity of 80.4% (95% CI, 71.6-87.0%) and a specificity of 90.6% (95% CI, 84.1-94.7%). Moreover, detection of autoantibodies against NY-ESO-1 could differentiate early-stage NPC patients from normal controls. Our results suggest that autoantibodies against NY-ESO-1 may serve as a potential biomarker, as a supplement to VCA-IgA, for the screening and diagnosis of NPC.

  1. Dramatic Advance in Quality in Flexographic Printing

    Directory of Open Access Journals (Sweden)

    Jochen Richter

    2004-12-01

    Full Text Available The enormous changes in flexography printing in recent years concerning the printing quality achievable cannot generally be ascribed to a single revolutionary invention, but are the result of continuous developments to the complete system. Thus the direct drive technology in all machine types and its associated advantages in terms of printing length corrections has become established since drupa 2000. The race for ever finer raster rolls has also been completed to the benefit of improvements in bowl geometry and in ceramic surfaces. Clearly improved colour transfer behaviour has become feasible as a result. In a closely intermeshed system such as flexography printing this naturally has to have an effect on the printing colours used. Further improvements in bonding agents and pigment concentrations now allow users to print ever thinner colour layers while maintaining all of the required authenticities.Furthermore, it has become possible to reduce additional disturbing characteristics in the UV colour area, such as the unpleasant odour. While the digital imaging of printing plates has primarily been improved in terms of economic efficiency by the use of up to eight parallel laser beams, extreme improvements in the system are noticeable especially in the area of directly engraved printing moulds. Whereas many still dismissed directly engraved polymer plates at the last drupa as a laboratory system, the first installation was recently placed on the market a mere three years later. A further noteworthy innovation of recent years that has reached market maturity is thin sleeve technology, which combines the advantages of a photopolymer plate with a round imaged printing mould. There are no high sleeve costs for each printing mould, except for one-off cost for an adapter sleeve. To conclude, it can be said that although flexography printing has experienced many new features in the time between drupa 2000 and today, it still has enormous potential for

  2. Using dramatic role-play to develop emotional aptitude

    Directory of Open Access Journals (Sweden)

    Russell Dinapoli

    2009-12-01

    Full Text Available As university educators, we need to prepare students for the transition from the information age to what Daniel H. Pink (2005 calls the conceptual age, which is governed by artistry, empathy and emotion, by including in the curricula activities that stimulate both hemispheres of the brain. This can be done by promoting activities that energize what Daniel Goleman (1995 refers to as emotional intelligence, and it further maintains that, as Paul Ekman (2003 suggests, the ability to detect feelings improves communication. Recognizing the need to include in the curricula procedures that help develop students’ right brain aptitudes and enhance their communication skills, I have endeavoured to introduce dramatic scene study as a sustained activity in my English for Specific Purposes courses at the Universidad de Valencia. My aim was to energize the students’ creative and emotional aptitudes, as well as to dynamize effective teamwork. This article sustains that dramatic role-play, based on scripted scene study and related improvisational activities, is one way of achieving this.

  3. Antigen Export Reduces Antigen Presentation and Limits T Cell Control of M. tuberculosis.

    Science.gov (United States)

    Srivastava, Smita; Grace, Patricia S; Ernst, Joel D

    2016-01-13

    Persistence of Mycobacterium tuberculosis results from bacterial strategies that manipulate host adaptive immune responses. Infected dendritic cells (DCs) transport M. tuberculosis to local lymph nodes but activate CD4 T cells poorly, suggesting bacterial manipulation of antigen presentation. However, M. tuberculosis antigens are also exported from infected DCs and taken up and presented by uninfected DCs, possibly overcoming this blockade of antigen presentation by infected cells. Here we show that the first stage of this antigen transfer, antigen export, benefits M. tuberculosis by diverting bacterial proteins from the antigen presentation pathway. Kinesin-2 is required for antigen export and depletion of this microtubule-based motor increases activation of antigen-specific CD4 T cells by infected cells and improves control of intracellular infection. Thus, although antigen transfer enables presentation by bystander cells, it does not compensate for reduced antigen presentation by infected cells and represents a bacterial strategy for CD4 T cell evasion.

  4. In Vivo Synthesis of Cyclic-di-GMP Using a Recombinant Adenovirus Preferentially Improves Adaptive Immune Responses against Extracellular Antigens.

    Science.gov (United States)

    Alyaqoub, Fadel S; Aldhamen, Yasser A; Koestler, Benjamin J; Bruger, Eric L; Seregin, Sergey S; Pereira-Hicks, Cristiane; Godbehere, Sarah; Waters, Christopher M; Amalfitano, Andrea

    2016-02-15

    There is a compelling need for more effective vaccine adjuvants to augment induction of Ag-specific adaptive immune responses. Recent reports suggested the bacterial second messenger bis-(3'-5')-cyclic-dimeric-guanosine monophosphate (c-di-GMP) acts as an innate immune system modulator. We recently incorporated a Vibrio cholerae diguanylate cyclase into an adenovirus vaccine, fostering production of c-di-GMP as well as proinflammatory responses in mice. In this study, we recombined a more potent diguanylate cyclase gene, VCA0848, into a nonreplicating adenovirus serotype 5 (AdVCA0848) that produces elevated amounts of c-di-GMP when expressed in mammalian cells in vivo. This novel platform further improved induction of type I IFN-β and activation of innate and adaptive immune cells early after administration into mice as compared with control vectors. Coadministration of the extracellular protein OVA and the AdVCA0848 adjuvant significantly improved OVA-specific T cell responses as detected by IFN-γ and IL-2 ELISPOT, while also improving OVA-specific humoral B cell adaptive responses. In addition, we found that coadministration of AdVCA0848 with another adenovirus serotype 5 vector expressing the HIV-1-derived Gag Ag or the Clostridium difficile-derived toxin B resulted in significant inhibitory effects on the induction of Gag and toxin B-specific adaptive immune responses. As a proof of principle, these data confirm that in vivo synthesis of c-di-GMP stimulates strong innate immune responses that correlate with enhanced adaptive immune responses to concomitantly administered extracellular Ag, which can be used as an adjuvant to heighten effective immune responses for protein-based vaccine platforms against microbial infections and cancers.

  5. Improved Detection of Invasive Pulmonary Aspergillosis Arising during Leukemia Treatment Using a Panel of Host Response Proteins and Fungal Antigens.

    Directory of Open Access Journals (Sweden)

    Allan R Brasier

    Full Text Available Invasive pulmonary aspergillosis (IPA is an opportunistic fungal infection in patients undergoing chemotherapy for hematological malignancy, hematopoietic stem cell transplant, or other forms of immunosuppression. In this group, Aspergillus infections account for the majority of deaths due to mold pathogens. Although early detection is associated with improved outcomes, current diagnostic regimens lack sensitivity and specificity. Patients undergoing chemotherapy, stem cell transplantation and lung transplantation were enrolled in a multi-site prospective observational trial. Proven and probable IPA cases and matched controls were subjected to discovery proteomics analyses using a biofluid analysis platform, fractionating plasma into reproducible protein and peptide pools. From 556 spots identified by 2D gel electrophoresis, 66 differentially expressed post-translationally modified plasma proteins were identified in the leukemic subgroup only. This protein group was rich in complement components, acute-phase reactants and coagulation factors. Low molecular weight peptides corresponding to abundant plasma proteins were identified. A candidate marker panel of host response (9 plasma proteins, 4 peptides, fungal polysaccharides (galactomannan, and cell wall components (β-D glucan were selected by statistical filtering for patients with leukemia as a primary underlying diagnosis. Quantitative measurements were developed to qualify the differential expression of the candidate host response proteins using selective reaction monitoring mass spectrometry assays, and then applied to a separate cohort of 57 patients with leukemia. In this verification cohort, a machine learning ensemble-based algorithm, generalized pathseeker (GPS produced a greater case classification accuracy than galactomannan (GM or host proteins alone. In conclusion, Integration of host response proteins with GM improves the diagnostic detection of probable IPA in patients

  6. Improved quantification of HIV-1-infected CD4+ T cells using an optimised method of intracellular HIV-1 gag p24 antigen detection.

    Science.gov (United States)

    Yang, Hongbing; Yorke, Elisabeth; Hancock, Gemma; Clutton, Genevieve; Sande, Nellia; Angus, Brian; Smyth, Redmond; Mak, Johnson; Dorrell, Lucy

    2013-05-31

    The capacity of CD8+ T cells to inhibit HIV-1 replication in vitro strongly correlates with virus control in vivo. Post-hoc evaluations of HIV-1 vaccine candidates suggest that this immunological parameter is a promising benchmark of vaccine efficacy. Large-scale analysis of CD8+ T cell antiviral activity requires a rapid, robust and economical assay for accurate quantification of HIV-1 infection in primary CD4+ T cells. Detection of intracellular HIV-1 p24 antigen (p24 Ag) by flow cytometry is one such method but it is thought to be less sensitive and quantitative than p24 Ag ELISA. We report that fixation and permeabilisation of HIV-infected cells using paraformaldehyde/50% methanol/Nonidet P-40 instead of a conventional paraformaldehyde/saponin-based protocol improved their detection across multiplicities of infection (MOI) ranging from 10(-2) to 8×10(-5), and by nearly two-fold (pp24 Ag release during culture, thus validating its use as a measure of productive infection. We were also able to quantify infection with a panel of HIV-1 isolates representing the major clades. The protocol described here is rapid and cost-effective compared with ELISA and thus could be a useful component of immune monitoring of HIV-1 vaccines and interventions to reduce viral reservoirs.

  7. Decidedly Dramatic! The Power of Creative Drama in Social Studies

    Science.gov (United States)

    Pieczura, Michelle

    2013-01-01

    Creative dramatics, a highly effective method for integrating arts education into core curriculum, produces a positive and lasting impact on student learning, in terms of creative and critical thinking, language development, listening, comprehension, retention, cooperation, and empathy and awareness of others. Creative dramatics not only has the…

  8. Expression, purification, and improved antigenic specificity of a truncated recombinant bp26 protein of Brucella melitensis M5-90: a potential antigen for differential serodiagnosis of brucellosis in sheep and goats.

    Science.gov (United States)

    Liu, Wen-xing; Hu, Sen; Qiao, Zu-jian; Chen, Wei-ye; Liu, Lin-tao; Wang, Fang-kun; Hua, Rong-hong; Bu, Zhi-gao; Li, Xiang-rui

    2011-01-01

    Antibodies produced in animals vaccinated using live attenuated vaccines against Brucella spp. are indistinguishable using current conventional serological tests from those produced in infected animals. One potential approach is to develop marker vaccines in which specific genes have been deleted from parental vaccine strains that show good immunogenicity and vaccine efficacy. Corresponding methods of detection for antibodies raised by the marker vaccine should also be developed. A specific fragment of the bp26 gene of Brucella melitensis M5-90 was cloned into vector pQE32 to construct the recombinant plasmid (pQE32-rΔbp26). It was used to transform Escherichia coli M15 (pREP4) host cells, which expressed the rΔbp26 protein. Subsequently, the recombinant protein was purified by immobilized metal affinity chromatography and size-exclusion chromatography. The results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the purified rΔbp26 protein was represented by only one band, with a molecular weight of 14 kDa, and it showed good antigenic specificity on western blot and enzyme-linked immunosorbent assay (ELISA). The purified rΔbp26 protein was intended to be used as an antigen to develop a novel ELISA to differentiate animals vaccinated with bp26 mutants of Brucella spp. from those infected naturally and those vaccinated with the parental vaccine strains.

  9. Oncogenic cancer/testis antigens

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Andersen, Mads H; Ditzel, Henrik J

    2015-01-01

    Recent developments have set the stage for immunotherapy as a supplement to conventional cancer treatment. Consequently, a significant effort is required to further improve efficacy and specificity, particularly the identification of optimal therapeutic targets for clinical testing. Cancer....../testis antigens are immunogenic, highly cancer-specific, and frequently expressed in various types of cancer, which make them promising candidate targets for cancer immunotherapy, including cancer vaccination and adoptive T-cell transfer with chimeric T-cell receptors. Our current understanding of tumor...... immunology and immune escape suggests that targeting oncogenic antigens may be beneficial, meaning that identification of cancer/testis antigens with oncogenic properties is of high priority. Recent work from our lab and others provide evidence that many cancer/testis antigens, in fact, have oncogenic...

  10. Dramatically enhanced electrical breakdown strength in cellulose nanopaper

    Science.gov (United States)

    Huang, Jianwen; Zhou, Yuanxiang; Zhou, Zhongliu; Liu, Rui

    2016-09-01

    Electrical breakdown behaviors of nanopaper prepared from nanofibrillated cellulose (NFC) were investigated. Compared to conventional insulating paper made from micro softwood fibers, nanopaper has a dramatically enhanced breakdown strength. Breakdown field of nanopaper is 67.7 kV/mm, whereas that of conventional paper is only 20 kV/mm. Air voids in the surface of conventional paper are observed by scanning electron microscope (SEM). Further analyses using mercury intrusion show that pore diameter of conventional paper is around 1.7 μ m , while that of nanopaper is below 3 nm. Specific pore size of nanopaper is determined to be approximately 2.8 nm by the gas adsorption technique. In addition, theoretical breakdown strengths of nanopaper and conventional paper are also calculated to evaluate the effect of pore size. It turns out that theoretical values agree well with experimental data, indicating that the improved strength in nanopaper is mainly attributed to the decreased pore size. Due to its outstanding breakdown strength, this study indicates the suitability of nanopaper for electrical insulation in ultra-high voltage convert transformers and other electrical devices.

  11. Dramatically enhanced electrical breakdown strength in cellulose nanopaper

    Directory of Open Access Journals (Sweden)

    Jianwen Huang

    2016-09-01

    Full Text Available Electrical breakdown behaviors of nanopaper prepared from nanofibrillated cellulose (NFC were investigated. Compared to conventional insulating paper made from micro softwood fibers, nanopaper has a dramatically enhanced breakdown strength. Breakdown field of nanopaper is 67.7 kV/mm, whereas that of conventional paper is only 20 kV/mm. Air voids in the surface of conventional paper are observed by scanning electron microscope (SEM. Further analyses using mercury intrusion show that pore diameter of conventional paper is around 1.7 μm, while that of nanopaper is below 3 nm. Specific pore size of nanopaper is determined to be approximately 2.8 nm by the gas adsorption technique. In addition, theoretical breakdown strengths of nanopaper and conventional paper are also calculated to evaluate the effect of pore size. It turns out that theoretical values agree well with experimental data, indicating that the improved strength in nanopaper is mainly attributed to the decreased pore size. Due to its outstanding breakdown strength, this study indicates the suitability of nanopaper for electrical insulation in ultra-high voltage convert transformers and other electrical devices.

  12. Improved cell mediated immune responses after successful re-vaccination of non-responders to the hepatitis B virus surface antigen (HBsAg) vaccine using the combined hepatitis A and B vaccine.

    Science.gov (United States)

    Nyström, Jessica; Cardell, Kristina; Björnsdottir, Thora Björg; Fryden, Aril; Hultgren, Catharina; Sällberg, Matti

    2008-11-01

    We successfully re-vaccinated hepatitis B virus (HBV) vaccine non-responders using a double dose of the combined hepatitis A virus (HAV) and HBV vaccine. The hope was to improve priming of hepatitis B surface antigen (HBsAg)-specific cell mediated immune response (CMI) by an increased antigen dose and a theoretical adjuvant-effect from the local presence of a HAV-specific CMI. A few non-responders had a detectable HBsAg-specific CMI before re-vaccination. An in vitro detectable HBsAg-specific CMI was primed equally effective in non-responders (58%) as in first time vaccine recipients (68%). After the third dose a weak, albeit significant, association was observed between the magnitude of HBsAg-specific proliferation and anti-HBs levels. This regimen improves the priming of HBsAg-specific CMIs and antibodies.

  13. Strategies for the identification of T cell-recognized tumor antigens in hematological malignancies for improved graft-versus-tumor responses after allogeneic blood and marrow transplantation.

    Science.gov (United States)

    Zilberberg, Jenny; Feinman, Rena; Korngold, Robert

    2015-06-01

    Allogeneic blood and marrow transplantation (allo-BMT) is an effective immunotherapeutic treatment that can provide partial or complete remission for patients with hematological malignancies. Mature donor T cells in the donor inoculum play a central role in mediating graft-versus-tumor (GVT) responses by destroying residual tumor cells that persist after conditioning regimens. Alloreactivity towards minor histocompatibility antigens (miHA), which are varied tissue-related self-peptides presented in the context of major histocompatibility complex (MHC) molecules on recipient cells, some of which may be shared on tumor cells, is a dominant factor for the development of GVT. Potentially, GVT can also be directed to tumor-associated antigens or tumor-specific antigens that are more specific to the tumor cells themselves. The full exploitation of allo-BMT, however, is greatly limited by the development of graft-versus-host disease (GVHD), which is mediated by the donor T cell response against the miHA expressed in the recipient's cells of the intestine, skin, and liver. Because of the significance of GVT and GVHD responses in determining the clinical outcome of patients, miHA and tumor antigens have been intensively studied, and one active immunotherapeutic approach to separate these two responses has been cancer vaccination after allo-BMT. The combination of these two strategies has an advantage over vaccination of the patient without allo-BMT because his or her immune system has already been exposed and rendered unresponsive to the tumor antigens. The conditioning for allo-BMT eliminates the patient's existing immune system, including regulatory elements, and provides a more permissive environment for the newly developing donor immune compartment to selectively target the malignant cells. Utilizing recent technological advances, the identities of many human miHA and tumor antigenic peptides have been defined and are currently being evaluated in clinical and basic

  14. Strategies for the Identification of T Cell–Recognized Tumor Antigens in Hematological Malignancies for Improved Graft-versus-Tumor Responses after Allogeneic Blood and Marrow Transplantation

    Science.gov (United States)

    Zilberberg, Jenny; Feinman, Rena; Korngold, Robert

    2015-01-01

    Allogeneic blood and marrow transplantation (allo-BMT) is an effective immunotherapeutic treatment that can provide partial or complete remission for patients with hematological malignancies. Mature donor T cells in the donor inoculum play a central role in mediating graft-versus-tumor (GVT) responses by destroying residual tumor cells that persist after conditioning regimens. Alloreactivity towards minor histocompatibility antigens (miHA), which are varied tissue-related self-peptides presented in the context of major histocompatibility complex (MHC) molecules on recipient cells, some of which may be shared on tumor cells, is a dominant factor for the development of GVT. Potentially, GVT can also be directed to tumor-associated antigens or tumor-specific antigens that are more specific to the tumor cells themselves. The full exploitation of allo-BMT, however, is greatly limited by the development of graft-versus-host disease (GVHD), which is mediated by the donor T cell response against the miHA expressed in the recipient’s cells of the intestine, skin, and liver. Because of the significance of GVT and GVHD responses in determining the clinical outcome of patients, miHA and tumor antigens have been intensively studied, and one active immunotherapeutic approach to separate these two responses has been cancer vaccination after allo-BMT. The combination of these two strategies has an advantage over vaccination of the patient without allo-BMT because his or her immune system has already been exposed and rendered unresponsive to the tumor antigens. The conditioning for allo-BMT eliminates the patient’s existing immune system, including regulatory elements, and provides a more permissive environment for the newly developing donor immune compartment to selectively target the malignant cells. Utilizing recent technological advances, the identities of many human miHA and tumor antigenic peptides have been defined and are currently being evaluated in clinical and basic

  15. Grieg: Songs and dramatic works with orchestra. / Alan Blyth

    Index Scriptorium Estoniae

    Blyth, Alan

    1993-01-01

    Uuest heliplaadist "Grieg: Songs and dramatic works with orchestra. Barbara Bonney, Randi Stene, Hakan Hagegard, Ruth Tellefsen, Gothenburg Symphony Chorus and Orchestra, Neeme Järvi." CD 437 519 - 2GH

  16. The Effects of Dramatization on English Literature Comprehension

    Institute of Scientific and Technical Information of China (English)

    周思菡; 周思蕊

    2014-01-01

    The article discusses the role that the dramatization of English literature plays in addressing two major difficulties in English literary work comprehension for intermediate English learners in China, namely the linguistic difficulty and the cultural misunderstanding. By taking the dramatization of British writer Jane Austin’s masterpiece Pride and Prejudice as a case study, the first part of the essay examines the role of dramatization in tackling linguistic difficulties based on the interactive reading model de-veloped by David E. Rumelhart(1977) while the second part analyzes how an integral framework for understanding target culture is constructed through the process of dramatization with a reference to Galloway’s(1992) four-stage approach to a cultural read-ing of authentic materials.

  17. Video Taping and Abnormal Psychology: Dramatized Clinical Interviews.

    Science.gov (United States)

    Lyons, Michael J.; And Others

    1984-01-01

    Students in an abnormal psychology course worked in teams to produce dramatizations of diagnostic interviews and then presented them in class. Positive and negative aspects of the activity are discussed. (RM)

  18. Drug Overdose Deaths Climb Dramatically in U.S.

    Science.gov (United States)

    ... Drug Overdose Deaths Climb Dramatically in U.S. Prescription painkillers and heroin lead the increase, latest government data ... fatalities linked to the illicit use of prescription painkillers, new government statistics reveal. Drug overdose deaths increased ...

  19. Theodramatic Rehearsal: Fighting Self-Deception through the Dramatic Imagination

    Directory of Open Access Journals (Sweden)

    Brett Vaden

    2014-03-01

    Full Text Available This paper seeks to appropriate the insights of dramatic theology for Christian psychology and soul care. According to Kevin Vanhoozer, Scripture is the ‘script’ for human beings’ fitting participation in the acts and deeds of God in the world (i.e., ‘theodrama’. Keeping with this dramatic paradigm, the author will explore what ‘rehearsal’ might entail by drawing from a branch of psychotherapy called ‘psychodrama.’ The main question to be addressed in this appropriation of dramatic theology is, “How might dramatic rehearsal combat self-deception?” The author will only begin to answer this question, but in the attempt it is hoped that further reflection and clarity will be induced.

  20. Novel Prostate Specific Antigen plastic antibody designed withcharged binding sites for an improved protein binding and itsapplication in a biosensor of potentiometric transduction

    OpenAIRE

    Rebelo, Tânia S. C. R.; Santos, C.; Costa-Rodrigues, J.; Fernandes, M. H.; Noronha, João P. C.; Sales, M. Goreti F.

    2014-01-01

    This work shows that the synthesis of protein plastic antibodies tailored with selected charged monomersaround the binding site enhances protein binding. These charged receptor sites are placed over a neutralpolymeric matrix, thus inducing a suitable orientation the protein reception to its site. This is confirmed bypreparing control materials with neutral monomers and also with non-imprinted template. This concepthas been applied here to Prostate Specific Antigen (PSA), the protein of choice...

  1. Prime-boost bacillus Calmette-Guérin vaccination with lentivirus-vectored and DNA-based vaccines expressing antigens Ag85B and Rv3425 improves protective efficacy against Mycobacterium tuberculosis in mice.

    Science.gov (United States)

    Xu, Ying; Yang, Enzhuo; Wang, Jianguang; Li, Rui; Li, Guanghua; Liu, Guoyuan; Song, Na; Huang, Qi; Kong, Cong; Wang, Honghai

    2014-10-01

    To prevent the global spread of tuberculosis (TB), more effective vaccines and vaccination strategies are urgently needed. As a result of the success of bacillus Calmette-Guérin (BCG) in protecting children against miliary and meningeal TB, the majority of individuals will have been vaccinated with BCG; hence, boosting BCG-primed immunity will probably be a key component of future vaccine strategies. In this study, we compared the ability of DNA-, protein- and lentiviral vector-based vaccines that express the antigens Ag85B and Rv3425 to boost the effects of BCG in the context of immunity and protection against Mycobacterium tuberculosis in C57BL/6 mice. Our results demonstrated that prime-boost BCG vaccination with a lentiviral vector expressing the antigens Ag85B and Rv3425 significantly enhanced immune responses, including T helper type 1 and CD8(+) cytotoxic T lymphocyte responses, compared with DNA- and protein-based vaccines. However, lentivirus-vectored and DNA-based vaccines greatly improved the protective efficacy of BCG against M. tuberculosis, as indicated by a lack of weight loss and significantly reduced bacterial loads and histological damage in the lung. Our study suggests that the use of lentiviral or DNA vaccines containing the antigens Ag85B and Rv3425 to boost BCG is a good choice for the rational design of an efficient vaccination strategy against TB.

  2. Dramatic interactions: theater work and the formation of learning communities.

    Science.gov (United States)

    Meath-Lang, B

    1997-04-01

    This article examines the relationship of theater and dramatic study to models of learning communities in promoting identity, diversity, and culture. Theater is an example of how learning community can be achieved and levels of theater use in education are presented as ways in which educators can create ensemble and foster community. Strategies for developing learning communities using the performing arts are provided.

  3. Aspects of dramatic communication: action, non-action, interaction

    NARCIS (Netherlands)

    Stelleman, J.

    2011-01-01

    This study is aimed at describing the dramatic means of important transitional (in the sense of innovative) Russian dramas, such as Chekhovian, Symbolist (Blok) and Absurdist (D. Charms) Drama. The reduction of action and plot, the 'disturbed' communication, the alienation of man and the conveying o

  4. On Dramatizing: The Right to Write the Play.

    Science.gov (United States)

    Koste, V. Glasgow

    1995-01-01

    Defines "adaptation" as the transformational process of taking a narrative work and dramatizing it. Stresses the importance of knowing what to leave out and knowing what to leave in. Suggests thinking of "adopting" rather than "adapting." States that artistic freedom is the playwright's right. Emphasizes the…

  5. Sublingual administration of an adenovirus serotype 5 (Ad5)-based vaccine confirms Toll-like receptor agonist activity in the oral cavity and elicits improved mucosal and systemic cell-mediated responses against HIV antigens despite preexisting Ad5 immunity.

    Science.gov (United States)

    Appledorn, Daniel M; Aldhamen, Yasser A; Godbehere, Sarah; Seregin, Sergey S; Amalfitano, Andrea

    2011-01-01

    HIV/AIDS continue to devastate populations worldwide. Recent studies suggest that vaccines that induce beneficial immune responses in the mucosal compartment may improve the efficacy of HIV vaccines. Adenovirus serotype 5 (Ad5)-based vectors remain a promising platform for the development of effective vaccines. In an effort to improve the efficacy of Ad5-based vaccines, even in the presence of preexisting Ad5 immunity, we evaluated the potential for an Ad5-based HIV vaccine to induce antigen-specific immune responses following sublingual (s.l.) administration, a route not previously tested in regard to Ad-based vaccines. s.l. vaccination with an Ad5-based HIV-Gag vaccine resulted in a significant induction of Gag-specific cytotoxic T-lymphocyte (CTL) responses in both the systemic and the mucosal compartment. We also show that s.l. immunization not only avoided preexisting Ad5 immunity but also elicited a broad repertoire of antigen-specific CTL clones. Additionally, we confirm for the first time that oral delivery of a vaccine expressing a potent Toll-like receptor (TLR) agonist can stimulate innate immune responses through induction of cytokines and chemokines and activation of NK cells, NKT cells, and macrophages in vivo. These results positively correlated with improved antigen-specific CTL responses. These results could be achieved both in Ad5-naïve mice and in mice with preexisting immunity to Ad5. The simplicity of the s.l. vaccination regimen coupled with augmentation of TLR-dependent pathways active in the oral cavity makes s.l. delivery a promising method for HIV vaccine development specifically, as well as for many other vaccine applications in general.

  6. Dramatic changes in electronic structure revealed by fractionally charged nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, Aron J. [Department of Chemistry, Lensfield Rd., University of Cambridge, Cambridge CB2 1EW (United Kingdom); Mori-Sánchez, Paula, E-mail: paula.mori@uam.es [Departamento de Química, Universidad Autónoma de Madrid, 28049 Madrid (Spain)

    2014-01-28

    Discontinuous changes in the electronic structure upon infinitesimal changes to the Hamiltonian are demonstrated. These are revealed in one and two electron molecular systems by full configuration interaction (FCI) calculations when the realm of the nuclear charge is extended to be fractional. FCI electron densities in these systems show dramatic changes in real space and illustrate the transfer, hopping, and removal of electrons. This is due to the particle nature of electrons seen in stretched systems and is a manifestation of an energy derivative discontinuity at constant number of electrons. Dramatic errors of density functional theory densities are seen in real space as this physics is missing from currently used approximations. The movements of electrons in these simple systems encapsulate those in real physical processes, from chemical reactions to electron transport and pose a great challenge for the development of new electronic structure methods.

  7. Dramatic changes in electronic structure revealed by fractionally charged nuclei

    Science.gov (United States)

    Cohen, Aron J.; Mori-Sánchez, Paula

    2014-01-01

    Discontinuous changes in the electronic structure upon infinitesimal changes to the Hamiltonian are demonstrated. These are revealed in one and two electron molecular systems by full configuration interaction (FCI) calculations when the realm of the nuclear charge is extended to be fractional. FCI electron densities in these systems show dramatic changes in real space and illustrate the transfer, hopping, and removal of electrons. This is due to the particle nature of electrons seen in stretched systems and is a manifestation of an energy derivative discontinuity at constant number of electrons. Dramatic errors of density functional theory densities are seen in real space as this physics is missing from currently used approximations. The movements of electrons in these simple systems encapsulate those in real physical processes, from chemical reactions to electron transport and pose a great challenge for the development of new electronic structure methods.

  8. Superexpression of tuberculosis antigens in plant leaves.

    Science.gov (United States)

    Dorokhov, Yuri L; Sheveleva, Anna A; Frolova, Olga Y; Komarova, Tatjana V; Zvereva, Anna S; Ivanov, Peter A; Atabekov, Joseph G

    2007-05-01

    Recent developments in genetic engineering allow the employment of plants as factories for 1/foreign protein production. Thus, tuberculosis (TB) ESAT6 antigen was expressed in different plant systems, but the level of vaccine protein accumulation was extremely low. We describe the technology for superexpression of TB vaccine proteins (Ag85B, ESAT6, and ESAT6:Ag85B fusion) in plant leaves which involves: (i) construction of tobacco mosaic virus-based vectors with the coat protein genes substituted by those for TB antigens; (ii) Agrobacterium-mediated delivery to plant leaf tissues of binary vectors containing the cDNA copy of the vector virus genome; and (iii) replication of virus vectors in plant cells under conditions suppressing the virus-induced gene silencing. This technology enables efficient production of the TB vaccine proteins in plants; in particular, the level of Ag85B antigen accumulation was not less than 800 mg/kg of fresh leaves. Expression of TB antigens in plant cells as His(6)-tagged proteins promoted their isolation and purification by Ni-NTA affinity chromatography. Deletion of transmembrane domains from Ag85B caused a dramatic increase in its intracellular stability. We propose that the strategy of TB antigens superproduction in a plant might be used as a basis for the creation of prophylactic and therapeutic vaccine against TB.

  9. Improved cytotoxic T-lymphocyte immune responses to a tumor antigen by vaccines co-expressing the SLAM-associated adaptor EAT-2.

    Science.gov (United States)

    Aldhamen, Y A; Seregin, S S; Kousa, Y A; Rastall, D P W; Appledorn, D M; Godbehere, S; Schutte, B C; Amalfitano, A

    2013-10-01

    The signaling lymphocytic activation molecule-associated adaptor Ewing's sarcoma's-activated transcript 2 (EAT-2) is primarily expressed in dendritic cells, macrophages and natural killer cells. Including EAT-2 in a vaccination regimen enhanced innate and adaptive immune responses toward pathogen-derived antigens, even in the face of pre-existing vaccine immunity. Herein, we investigate whether co-vaccinations with two recombinant Ad5 (rAd5) vectors, one expressing the carcinoembryonic antigen (CEA) and one expressing EAT-2, can induce more potent CEA-specific cytotoxic T lymphocyte (CTL) and antitumor activity in the therapeutic CEA-expressing MC-38 tumor model. Our results suggest that inclusion of EAT-2 significantly alters the kinetics of Th1-biasing proinflammatory cytokine and chemokine responses, and enhances anti-CEA-specific CTL responses. As a result, rAd5-EAT2-augmented rAd5-CEA vaccinations are more efficient in eliminating CEA-expressing target cells as measured by an in vivo CTL assay. Administration of rAd5-EAT2 vaccines also reduced the rate of growth of MC-38 tumor growth in vivo. Also, an increase in MC-38 tumor cell apoptosis (as measured by hematoxylin and eosin staining, active caspase-3 and granzyme B levels within the tumors) was observed. These data provide evidence that more efficient, CEA-specific effector T cells are generated by rAd5 vaccines expressing CEA, when augmented by rAd5 vaccines expressing EAT-2, and this regimen may be a promising approach for cancer immunotherapy in general.

  10. LATERAL FLOW ASSAY FOR CRYPTOCOCCAL ANTIGEN: AN IMPORTANT ADVANCE TO IMPROVE THE CONTINUUM OF HIV CARE AND REDUCE CRYPTOCOCCAL MENINGITIS-RELATED MORTALITY.

    Science.gov (United States)

    Vidal, Jose E; Boulware, David R

    2015-09-01

    AIDS-related cryptococcal meningitis continues to cause a substantial burden of death in low and middle income countries. The diagnostic use for detection of cryptococcal capsular polysaccharide antigen (CrAg) in serum and cerebrospinal fluid by latex agglutination test (CrAg-latex) or enzyme-linked immunoassay (EIA) has been available for over decades. Better diagnostics in asymptomatic and symptomatic phases of cryptococcosis are key components to reduce mortality. Recently, the cryptococcal antigen lateral flow assay (CrAg LFA) was included in the armamentarium for diagnosis. Unlike the other tests, the CrAg LFA is a dipstick immunochromatographic assay, in a format similar to the home pregnancy test, and requires little or no lab infrastructure. This test meets all of the World Health Organization ASSURED criteria (Affordable, Sensitive, Specific, User friendly, Rapid/robust, Equipment-free, and Delivered). CrAg LFA in serum, plasma, whole blood, or cerebrospinal fluid is useful for the diagnosis of disease caused by Cryptococcus species. The CrAg LFA has better analytical sensitivity for C. gattii than CrAg-latex or EIA. Prevention of cryptococcal disease is new application of CrAg LFA via screening of blood for subclinical infection in asymptomatic HIV-infected persons with CD4 counts < 100 cells/mL who are not receiving effective antiretroviral therapy. CrAg screening of leftover plasma specimens after CD4 testing can identify persons with asymptomatic infection who urgently require pre-emptive fluconazole, who will otherwise progress to symptomatic infection and/or die.

  11. LATERAL FLOW ASSAY FOR CRYPTOCOCCAL ANTIGEN: AN IMPORTANT ADVANCE TO IMPROVE THE CONTINUUM OF HIV CARE AND REDUCE CRYPTOCOCCAL MENINGITIS-RELATED MORTALITY

    Science.gov (United States)

    VIDAL, Jose E.; BOULWARE, David R.

    2015-01-01

    SUMMARY AIDS-related cryptococcal meningitis continues to cause a substantial burden of death in low and middle income countries. The diagnostic use for detection of cryptococcal capsular polysaccharide antigen (CrAg) in serum and cerebrospinal fluid by latex agglutination test (CrAg-latex) or enzyme-linked immunoassay (EIA) has been available for over decades. Better diagnostics in asymptomatic and symptomatic phases of cryptococcosis are key components to reduce mortality. Recently, the cryptococcal antigen lateral flow assay (CrAg LFA) was included in the armamentarium for diagnosis. Unlike the other tests, the CrAg LFA is a dipstick immunochromatographic assay, in a format similar to the home pregnancy test, and requires little or no lab infrastructure. This test meets all of the World Health Organization ASSURED criteria (Affordable, Sensitive, Specific, User friendly, Rapid/robust, Equipment-free, and Delivered). CrAg LFA in serum, plasma, whole blood, or cerebrospinal fluid is useful for the diagnosis of disease caused by Cryptococcus species. The CrAg LFA has better analytical sensitivity for C. gattii than CrAg-latex or EIA. Prevention of cryptococcal disease is new application of CrAg LFA via screening of blood for subclinical infection in asymptomatic HIV-infected persons with CD4 counts < 100 cells/mL who are not receiving effective antiretroviral therapy. CrAg screening of leftover plasma specimens after CD4 testing can identify persons with asymptomatic infection who urgently require pre-emptive fluconazole, who will otherwise progress to symptomatic infection and/or die. PMID:26465368

  12. LATERAL FLOW ASSAY FOR CRYPTOCOCCAL ANTIGEN: AN IMPORTANT ADVANCE TO IMPROVE THE CONTINUUM OF HIV CARE AND REDUCE CRYPTOCOCCAL MENINGITIS-RELATED MORTALITY

    Directory of Open Access Journals (Sweden)

    Jose E. VIDAL

    2015-09-01

    Full Text Available SUMMARYAIDS-related cryptococcal meningitis continues to cause a substantial burden of death in low and middle income countries. The diagnostic use for detection of cryptococcal capsular polysaccharide antigen (CrAg in serum and cerebrospinal fluid by latex agglutination test (CrAg-latex or enzyme-linked immunoassay (EIA has been available for over decades. Better diagnostics in asymptomatic and symptomatic phases of cryptococcosis are key components to reduce mortality. Recently, the cryptococcal antigen lateral flow assay (CrAg LFA was included in the armamentarium for diagnosis. Unlike the other tests, the CrAg LFA is a dipstick immunochromatographic assay, in a format similar to the home pregnancy test, and requires little or no lab infrastructure. This test meets all of the World Health Organization ASSURED criteria (Affordable, Sensitive, Specific, User friendly, Rapid/robust, Equipment-free, and Delivered. CrAg LFA in serum, plasma, whole blood, or cerebrospinal fluid is useful for the diagnosis of disease caused by Cryptococcusspecies. The CrAg LFA has better analytical sensitivity for C. gattii than CrAg-latex or EIA. Prevention of cryptococcal disease is new application of CrAg LFA via screening of blood for subclinical infection in asymptomatic HIV-infected persons with CD4 counts < 100 cells/mL who are not receiving effective antiretroviral therapy. CrAg screening of leftover plasma specimens after CD4 testing can identify persons with asymptomatic infection who urgently require pre-emptive fluconazole, who will otherwise progress to symptomatic infection and/or die.

  13. Authoring for Engagement in Interactive Dramatic Experiences for Learning

    DEFF Research Database (Denmark)

    Schoenau-Fog, Henrik; Bruni, Luis Emilio; Khalil, Faysal Fuad

    2013-01-01

    ’s control over communicating a theme. To address this problem, this paper contributes a method for organizing narrative events in a free-roaming virtual environment. The Interactive Dramatic Experience Model (IDEM) retains the freedom of navigation while maintaining the possibility to construct various...... coherent narratives that enable the theme to be communicated. This may be of particular relevance when using digital, interactive, and representational technologies in the mediation of ethically relevant and socially responsible themes. In order to explore the use of the IDEM, we have developed...

  14. Stuttering therapy in 1837 and a young boy's dramatic experience.

    Science.gov (United States)

    Preus, A

    1994-01-01

    This is a historical account of the first known case of stuttering therapy in Norway. In his autobiography, school administrator and politician Nils Hertzberg relates how he in 1837 as a 10-year-old boy travelled on horseback, skis and by boat across Norway from west to east and back in order to receive therapy from a travelling German speech teacher C.F. Bansmann. The article provides extracts from the exciting and dramatic journey, describes Bansmann's method and offers some comments on stuttering and stuttering therapy.

  15. Dramatic response to levetiracetam in post-ischaemic Holmes’ tremor

    Science.gov (United States)

    Striano, P; Elefante, Andrea; Coppola, Antonietta; Tortora, Fabio; Zara, Federico; Minetti, Carlo

    2009-01-01

    Holmes’ tremor refers to an unusual combination of rest, postural and kinetic tremor of extremities. Common causes of Holmes’ tremor include stroke, trauma, vascular malformations and multiple sclerosis, with lesions involving the thalamus, brain stem or cerebellum. Although some drugs (eg, levodopa and dopaminergic drugs, clonazepam and propranolol) have been occasionally reported to give some benefit, medical treatment of Holmes’ tremor is unsatisfactory, and many patients require thalamic surgery to achieve satisfactory control. We report a patient in whom post-ischaemic Holmes’ tremor dramatically responded to levetiracetam treatment. PMID:21686707

  16. Dramatic regression of presumed acquired retinal astrocytoma with photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Samuray Tuncer

    2014-01-01

    Full Text Available Photodynamic therapy (PDT has been used for treatment of various intraocular tumors including choroidal hemangioma, vasoproliferative tumor, amelanotic choroidal melanoma and choroidal neovascular membrane due to choroidal osteoma. This case report documents the effect of PDT for a presumed acquired retinal astrocytoma. A 42-year-old female with a juxtapapillary acquired astrocytoma was treated with a single session of PDT using standard parameters. The tumor showed dramatic regression over 6 months into a fibrotic scar. It remained regressed and stable with 20/20 vision after 51 months of follow-up. We believe that PDT can be used as a primary treatment for acquired retinal astrocytoma.

  17. MAGE-A Antigens and Cancer Immunotherapy

    Science.gov (United States)

    Zajac, Paul; Schultz-Thater, Elke; Tornillo, Luigi; Sadowski, Charlotte; Trella, Emanuele; Mengus, Chantal; Iezzi, Giandomenica; Spagnoli, Giulio C.

    2017-01-01

    MAGE-A antigens are expressed in a variety of cancers of diverse histological origin and germinal cells. Due to their relatively high tumor specificity, they represent attractive targets for active specific and adoptive cancer immunotherapies. Here, we (i) review past and ongoing clinical studies targeting these antigens, (ii) analyze advantages and disadvantages of different therapeutic approaches, and (iii) discuss possible improvements in MAGE-A-specific immunotherapies. PMID:28337438

  18. Bacterial fermentation of recombinant major wasp allergen Antigen 5 using oxygen limiting growth conditions improves yield and quality of inclusion bodies.

    Science.gov (United States)

    Kischnick, Stefanie; Weber, Bernhard; Verdino, Petra; Keller, Walter; Sanders, Ernst A; Anspach, F Birger; Fiebig, Helmut; Cromwell, Oliver; Suck, Roland

    2006-06-01

    A process for bacterial expression and purification of the recombinant major wasp allergen Antigen 5 (Ves v 5) was developed to produce protein for diagnostic and therapeutic applications for type 1 allergic diseases. Special attention was focused on medium selection, fermentation conditions, and efficient refolding procedures. A soy based medium was used for fermentation to avoid peptone from animal origin. Animal-derived peptone required the use of isopropyl-beta-D-thiogalactopyranoside (IPTG) for the induction of expression. In the case of soy peptone, a constitutive expression was observed, suggesting the presence of a component that mimics IPTG. Batch cultivation at reduced stirrer speed caused a reduced biomass due to oxygen limitation. However, subsequent purification and processing of inclusion bodies yielded significantly higher amount of product. Furthermore, the protein composition of the inclusion bodies differed. Inclusion bodies were denatured and subjected to diafiltration. Detailed monitoring of diafiltration enabled the determination of the transition point. Final purification was conducted using cation-exchange and size-exclusion chromatography. Purified recombinant Ves v 5 was analyzed by RP-HPLC, CD-spectroscopy, SDS-PAGE, and quantification ELISA. Up to 15 mg highly purified Ves v 5 per litre bioreactor volume were obtained, with endotoxin concentrations less than 20 EU mg(-1) protein and high comparability to the natural counterpart. Analytical results confirm the suitability of the recombinant protein for diagnostic and clinical applications. The results clearly demonstrate that not only biomass, but especially growth conditions play a key role in the production of recombinant Ves v 5. This has an influence on inclusion body formation, which in turn influences the renaturation rate and absolute product yield. This might also be true for other recombinant proteins that accumulate as inclusion bodies in Escherichia coli.

  19. Eosinofil Sel Penyaji Antigen

    Directory of Open Access Journals (Sweden)

    Safari Wahyu Jatmiko

    2015-04-01

    Full Text Available Sel eosinofil merupakan jenis sel lekosit yang terlibat dalam berbagai patogenesis penyakit. Sel eosinofil pada awalnya dikenal sebagai sel efektor  dari sistem imunitas alamiah. Akan tetapi, kemampuan sel eosinofil dalam memfagositosis patogen menimbulkan dugaan bahwa sel eosinofil ikut berperan sebagai sel penyaji antigen. Hal ini dianalogikan dengan sel makrofag dan sel dendritik yang bisa memfagositosis dan menyajikan antigen sebagai hasil dari degradasi patogen yang difagositosis. Untuk menjawab permasalahan ini, penulis melakukan penelusuran artikel tentang eosinofil sebagai sel penyaji antigen melalui US National Library of Medicine National Institute of Healthdengan kata kunci eoshinophil dan antigen presenting cell. Hasil penelusuran adalah ditemukannya 10 artikel yang relevan dengan topik. Hasil dari sintesis kesepuluh jurnal tersebut adalah sel eosinofil mampu berperan sebagai sel penyaji antigen yang profesional (professionalantigenpresentng cell

  20. Media and identification processes: a ritual and dramatic construction

    Directory of Open Access Journals (Sweden)

    Salomé Sola-Morales

    2016-07-01

    Full Text Available The present theoretical paper analyzes the way mediatic communication construct identifications. The thesis proposed is that the media configure ritually and dramatically identifications made by individuals and groups. First of all, we show the limitations of the concept of “identity” and we propose to use “identification” instead. Second, we explore the extent of social drama theory and role theory and we open it to new theoretical challenges and perspectives. Thirdly, it is shown that the concept of "ritual" is very useful to understand and interpret the identity construction through the media. All this leads us to conclude that both the theatricality and rituality are key to understanding the processes of identification that individuals and groups make in relation to the media.

  1. New therapies for hereditary angioedema: disease outlook changes dramatically.

    Science.gov (United States)

    Frank, Michael M; Jiang, Haixiang

    2008-01-01

    Hereditary angioedema (HAE) is an autosomal dominant disease associated with episodic attacks of nonpitting edema that may affect any external or mucosal body surface. Attacks most often affect the extremities, causing local swelling, the GI tract, leading to severe abdominal pain, and the mouth and throat, at times causing asphyxiation. Most patients with HAE have low levels of the plasma serine protease inhibitor C1 inhibitor. The edema in these patients is caused by unregulated generation of bradykinin. Effective chronic therapy of patients with impeded androgens or plasmin inhibitors has been available for decades, but in the United States, we do not have therapy for acute attacks. Five companies have completed or are in the process of conducting phase 3 clinical trials, double-blind, placebo-controlled studies of products designed to terminate acute attacks or to be used in prophylaxis. Two companies, Lev Pharmaceuticals and CSL Behring, have preparations of C1 inhibitor purified from plasma that have been used in Europe for decades (trade names Cinryze and Berinert P, respectively). One company, Pharming, has developed a recombinant C1 inhibitor preparation. One company, Dyax, is testing a kallikrein inhibitor (ecallantide), and one company, Jerini, is completing testing of a bradykinin type 2 receptor antagonist (Icatibant). Although little has been published thus far, all of these products may prove effective. It is likely that HAE treatment will change dramatically within the next few years.

  2. The Ifugao Alim: Chanted Narrated Dramatic Discourse in Ritual

    Directory of Open Access Journals (Sweden)

    Rosario Bona de Santos

    2013-06-01

    Full Text Available This paper, by way of introducing the little-known Ifugao alim, gives the readers an idea of what has been written about it by Ifugao and non-Ifugao writers and scholars, and recounts my own discovery and study of it. It will focus on the Piwong alim, which was the topic of my dissertation (Rosario de Santos del Rosario 2003, and which I recorded during a live performance in 1975 in Piwong, Hingyon, during the ritual called hongan di tagu—a prestige ritual of the kadangyan, for the welfare of a sick woman. In particular, the paper discusses the Piwong alim’s significance, structure, content and voice, and presents illustrations, through excerpts, which give the reader an insight into its ideological direction and unique aesthetics. The Piwong alim uses a mix of ritual genres, external and internal narration and dramatic character dialogues and monologues.The alim has been considered, by varied Ifugaos, as the crown jewel of its elaborate ritual; a sociological charter; and a magical myth that brings wellbeing.

  3. Historical sampling reveals dramatic demographic changes in western gorilla populations

    Directory of Open Access Journals (Sweden)

    Guschanski Katerina

    2011-04-01

    Full Text Available Abstract Background Today many large mammals live in small, fragmented populations, but it is often unclear whether this subdivision is the result of long-term or recent events. Demographic modeling using genetic data can estimate changes in long-term population sizes while temporal sampling provides a way to compare genetic variation present today with that sampled in the past. In order to better understand the dynamics associated with the divergences of great ape populations, these analytical approaches were applied to western gorillas (Gorilla gorilla and in particular to the isolated and Critically Endangered Cross River gorilla subspecies (G. g. diehli. Results We used microsatellite genotypes from museum specimens and contemporary samples of Cross River gorillas to infer both the long-term and recent population history. We find that Cross River gorillas diverged from the ancestral western gorilla population ~17,800 years ago (95% HDI: 760, 63,245 years. However, gene flow ceased only ~420 years ago (95% HDI: 200, 16,256 years, followed by a bottleneck beginning ~320 years ago (95% HDI: 200, 2,825 years that caused a 60-fold decrease in the effective population size of Cross River gorillas. Direct comparison of heterozygosity estimates from museum and contemporary samples suggests a loss of genetic variation over the last 100 years. Conclusions The composite history of western gorillas could plausibly be explained by climatic oscillations inducing environmental changes in western equatorial Africa that would have allowed gorilla populations to expand over time but ultimately isolate the Cross River gorillas, which thereafter exhibited a dramatic population size reduction. The recent decrease in the Cross River population is accordingly most likely attributable to increasing anthropogenic pressure over the last several hundred years. Isolation of diverging populations with prolonged concomitant gene flow, but not secondary admixture, appears

  4. Liven up Your Student Dramatics with Commedia dell' Arte.

    Science.gov (United States)

    Potter, Jonathan

    1980-01-01

    Suggests using the ancient Commedia dell' Arte technique of establishing characters and a plot and then allowing the actors to create their own play. Indicates that this improves student performances even in more traditional plays. (TJ)

  5. Comparison of E and NS1 antigens capture ELISA to detect dengue viral antigens from mosquitoes

    Directory of Open Access Journals (Sweden)

    Day-Yu Chao

    2015-01-01

    Interpretation & conclusion: With the future potential of antigen capture ELISA to be used in the resource deprived regions, the study showed that E-ELISA has similar sensitivity and antigen stability as NS1 Ag kit to complement the current established virological surveillance in human. The improvement of the sensitivity in detecting DENV-3/4 will be needed to incorporate this method into routine mosquito surveillance system.

  6. Identification of protective antigens for vaccination against systemic salmonellosis

    Directory of Open Access Journals (Sweden)

    Dirk eBumann

    2014-08-01

    Full Text Available There is an urgent medical need for improved vaccines with broad serovar coverage and high efficacy against systemic salmonellosis. Subunit vaccines offer excellent safety profiles but require identification of protective antigens, which remains a challenging task. Here, I review crucial properties of Salmonella antigens that might help to narrow down the number of potential candidates from more than 4000 proteins encoded in Salmonella genomes, to a more manageable number of 50-200 most promising antigens. I also discuss complementary approaches for antigen identification and potential limitations of current pre-clinical vaccine testing.

  7. Dramatically improved RNA in situ hybridization signals using LNA-modified probes

    DEFF Research Database (Denmark)

    Thomsen, Rune; Nielsen, Peter Stein; Jensen, Torben Heick

    2005-01-01

    In situ detection of RNA by hybridization with complementary probes is a powerful technique. Probe design is a critical parameter in successful target detection. We have evaluated the efficiency of fluorescent DNA oligonucleotides modified to contain locked nucleic acid (LNA) residues. This incre...... the nucleus/ nucleolus of wild-type cells. LNA-based probes should be readily applicable to a diverse array of cells and tissue samples....

  8. Dramatic Enhancement of Genome Editing by CRISPR/Cas9 Through Improved Guide RNA Design

    OpenAIRE

    Farboud, B; Meyer,BJ

    2015-01-01

    © 2015 by the Genetics Society of America.Success with genome editing by the RNA-programmed nuclease Cas9 has been limited by the inability to predict effective guide RNAs and DNA target sites. Not all guide RNAs have been successful, and even those that were, varied widely in their efficacy. Here we describe and validate a strategy for Caenorhabditis elegans that reliably achieved a high frequency of genome editing for all targets tested in vivo. The key innovation was to design guide RNAs w...

  9. President Obama and Education: The Possibility for Dramatic Improvements in Teaching and Learning

    Science.gov (United States)

    Darling-Hammond, Linda

    2009-01-01

    From the unique perspective gained heading Obama's education policy transition team, Darling-Hammond describes President Obama's commitment to making the education of every child a collective responsibility and reviews the major tenets of the new administration's plans for education. She reflects on the importance of suggested policy changes,…

  10. Increasing magnetite contents of polymeric magnetic particles dramatically improves labeling of neural stem cell transplant populations.

    Science.gov (United States)

    Adams, Christopher F; Rai, Ahmad; Sneddon, Gregor; Yiu, Humphrey H P; Polyak, Boris; Chari, Divya M

    2015-01-01

    Safe and efficient delivery of therapeutic cells to sites of injury/disease in the central nervous system is a key goal for the translation of clinical cell transplantation therapies. Recently, 'magnetic cell localization strategies' have emerged as a promising and safe approach for targeted delivery of magnetic particle (MP) labeled stem cells to pathology sites. For neuroregenerative applications, this approach is limited by the lack of available neurocompatible MPs, and low cell labeling achieved in neural stem/precursor populations. We demonstrate that high magnetite content, self-sedimenting polymeric MPs [unfunctionalized poly(lactic acid) coated, without a transfecting component] achieve efficient labeling (≥90%) of primary neural stem cells (NSCs)-a 'hard-to-label' transplant population of major clinical relevance. Our protocols showed high safety with respect to key stem cell regenerative parameters. Critically, labeled cells were effectively localized in an in vitro flow system by magnetic force highlighting the translational potential of the methods used.

  11. Improved humoral and cellular immune responses against the gp120 V3 loop of HIV-1 following genetic immunization with a chimeric DNA vaccine encoding the V3 inserted into the hepatitis B surface antigen

    DEFF Research Database (Denmark)

    Fomsgaard, A; Nielsen, H V; Bryder, K

    1998-01-01

    with the HIV MN gp160 envelope plasmid induced a slow and low titred anti-MN V3 antibody response at 12 weeks post-inoculation (p.i.) and a late appearing (7 weeks), weak and variable CTL response. In contrast, DNA vaccination with the HBsAg-encoding plasmid induced a rapid and high titred anti-HBsAg antibody...... response and a uniform strong anti-HBs CTL response already 1 week p.i. in all mice. DNA vaccination with the chimeric MN V3/HBsAg plasmid elicited humoral responses against both viruses within 3-6 weeks which peaked at 6-12 weeks and remained stable for at least 25 weeks. In addition, specific CTL......-2d-restricted cytotoxic T lymphocyte (CTL) epitope. In an attempt to improve the immunogenicity of V3 in DNA vaccines, a plasmid expressing MN V3 as a fusion protein with the highly immunogenic middle (pre-S2 + S) surface antigen of hepatitis B virus (HBsAg) was constructed. Epidermal inoculation...

  12. Improved humoral and cellular immune response against the gp120 V3 loop of HIV-1 following genetic immunization with a chimeric DNA vaccine encoding the V3 inserted into the hepatites B surface antigen

    DEFF Research Database (Denmark)

    Fomsgaard, A.; Nielsen, H.V.; Bryder, K.

    1998-01-01

    MN gp160 envelope plasmid induced a slow and low titred anti-MN V3 antibody response at 12 weeks post-inoculation (p.i.) and a late appearing (7 weeks), weak and variable CTL response. In contrast, DNA vaccination with the HBsAg-encoding plasmid induced a rapid and high titred anti-HBsAg antibody...... response and a uniform strong anti-HBs CTL response already 1 week p.i. in all mice. DNA vaccination with the chimeric MN V2/HBsAg plasmid elicited humoral responses against both viruses within 3-6 weeks which peaked at 6-12 weeks and remained stable for at least 25 weeks. In addition, specific CTL......-2d-restricted cytotoxic T lymphocyte (CTL) epitope. In an attempt to improve the immunogenicity of V3 in DNA vaccines, a plasmid expressing MN V3 as a fusion protein with the highly immunogenic middle (pre-S2+S) surface antigen of hepatitis B virus (HBsAg) was constructed. Epidermal inoculation...

  13. Novel use of a radiolabelled antibody against stage specific embryonic antigen for the detection of occult abscesses in mammals

    Science.gov (United States)

    Thakur, Madhukar L.

    1990-01-01

    The invention discloses improved reagents containing antibodies against stage specific embryonic antigen-1 antibodies and improved methods for detection of occult abscess and inflammation using the improved reagents.

  14. Immune Responses and Protective Efficacy Induced by 85B Antigen and Early Secreted Antigenic Target-6 kDa Antigen Fusion Protein Secreted by Recombinant Bacille Calmette-Guérin

    Institute of Scientific and Technical Information of China (English)

    Changhong SHI; Xiaowu WANG; Hai ZHANG; Zhikai XU; Yuan LI; Lintian YUAN

    2007-01-01

    In an attempt to improve immune responses and protective efficacy, we constructed two recombinant bacille Calmette-Guérin (rBCG) strains expressing an 85B antigen (Ag85B) and early secreted antigenic target-6 kDa antigen (ESAT6) of Mycobacterium tuberculosis (MTB) fusion protein. Both rBCG strains have the same protein insertion but in a different order (Ag85B-ESAT6 and ESAT6-Ag85B). The cultured supernatant of rBCG strains and the sera from the mice immunized with the fusion protein Ag85B-ESAT6 or ESAT6-Ag85B formed a band with a fraction size of 37 kDa, equalivalent to the sum of Ag85B and ESAT6. Six weeks after BALB/c mice were immunized with BCG or rBCG, spleen lymphocytes showed significant proliferation in response to culture filtrate protein of MTB. Compared with the BCG group, mice vaccinated with rBCG elicited a high level increase of immunoglobulin G antibodies to culture filtrate protein in the serum. The γ-interferon levels in the lymphocyte culture medium supernatants increased remarkably in the rBCG1 group, significantly higher than that of the BCG immunized group (P<0.05). Four weeks after vaccination, mice were infected with M. tuberculosis H37Rv and a dramatic reduction in the numbers of MTB colony forming units in the spleens and lungs was observed in the two rBCG immunization groups.Although these rBCG strains were more immunogenic, their protective effect was comparable to the classical BCG strain, and there were no significant differences between two rBCG groups (P>0.05).

  15. The use of high-throughput DNA sequencing in the investigation of antigenic variation: application to Neisseria species.

    Directory of Open Access Journals (Sweden)

    John K Davies

    Full Text Available Antigenic variation occurs in a broad range of species. This process resembles gene conversion in that variant DNA is unidirectionally transferred from partial gene copies (or silent loci into an expression locus. Previous studies of antigenic variation have involved the amplification and sequencing of individual genes from hundreds of colonies. Using the pilE gene from Neisseria gonorrhoeae we have demonstrated that it is possible to use PCR amplification, followed by high-throughput DNA sequencing and a novel assembly process, to detect individual antigenic variation events. The ability to detect these events was much greater than has previously been possible. In N. gonorrhoeae most silent loci contain multiple partial gene copies. Here we show that there is a bias towards using the copy at the 3' end of the silent loci (copy 1 as the donor sequence. The pilE gene of N. gonorrhoeae and some strains of Neisseria meningitidis encode class I pilin, but strains of N. meningitidis from clonal complexes 8 and 11 encode a class II pilin. We have confirmed that the class II pili of meningococcal strain FAM18 (clonal complex 11 are non-variable, and this is also true for the class II pili of strain NMB from clonal complex 8. In addition when a gene encoding class I pilin was moved into the meningococcal strain NMB background there was no evidence of antigenic variation. Finally we investigated several members of the opa gene family of N. gonorrhoeae, where it has been suggested that limited variation occurs. Variation was detected in the opaK gene that is located close to pilE, but not at the opaJ gene located elsewhere on the genome. The approach described here promises to dramatically improve studies of the extent and nature of antigenic variation systems in a variety of species.

  16. World-Wide Effort Produces Dramatic "Movie" of Cosmic Jet

    Science.gov (United States)

    2001-05-01

    Astronomers using a world-wide collection of radio telescopes, including the National Science Foundation's Very Long Baseline Array (VLBA) of the National Radio Astronomy Observatory (NRAO), have made a dramatic "movie" of a voracious, superdense neutron star repeatedly spitting out subatomic particles at nearly the speed of light into two narrow jets as it pulls material from a companion star. The movie shows these jets ejecting clouds of hot plasma that are then "zapped" by pulses of energy in the jets as they move away from the neutron star. Frame from Radio-Telescope 'Movie' of Scorpius X-1 "We have directly measured the speed of energy flow in a cosmic jet for the first time," said Ed Fomalont, an astronomer at the NRAO in Charlottesville, Virginia. Fomalont worked with Barry Geldzahler and Charles Bradshaw of George Mason University in Fairfax, Virginia. The astronomers used the VLBA, the NSF's Very Large Array (VLA) and the Green Bank 140-foot telescope, along with radio telescopes from the European VLBI Network, Australia, Japan and South Africa to record the double-star system's eruptions continuously for 56 hours. "This study is going to be extremely valuable in helping us understand a phenomenon that we see throughout the universe," Fomalont said. Cosmic jets of superfast particles are ejected from the cores of numerous galaxies. On a smaller scale, similar jets are ejected from binary-star systems closer to home, in our own Milky Way Galaxy. While the jets from galaxy cores are thought to be powered by supermassive black holes millions of times more massive than the Sun, the closer "microquasars" are powered by much smaller black holes or by neutron stars only a few times more massive than the sun. "Studying one of the closer, smaller examples will help us understand how they all work, including the bigger ones," Geldzahler said. "The jets coming from distant galaxies are harder to study because of their much greater distance and the slowness of their

  17. Intractable chronic motor tics dramatically respond to Clerodendrum inerme (L) Gaertn.

    Science.gov (United States)

    Fan, Pi-Chuan; Huang, Wei-Jan; Chiou, Lih-Chu

    2009-07-01

    Tics are characterized by involuntary, sudden, rapid, repetitive, nonrhythmic, stereotyped movements or phonic productions. Those who suffer from either motor or phonic tics, but not both, for more than 1 year are diagnosed with chronic tic disorder. Several pharmacological interventions have been proposed for the treatment of tic disorder. Dopamine D2 receptor blockers and dopamine depletors are thought to be the most effective ones clinically. However, such treatments are suboptimal in terms of effectiveness and side effects, such as body weight gain and extrapyramidal symptoms. We report on a 13-year-old girl, with chronic motor tic disorder refractory to multiple anti-tic therapies, who showed dramatic improvement and remission after taking the crude leaf extract of Clerodendrum inerme (L) Gaertn. No side effects were observed during a follow-up of more than 2 years. To the best of our knowledge, this is the first report on the anti-tic effect of Clerodendrum inerme.

  18. Harnessing Dendritic Cells for Tumor Antigen Presentation

    Energy Technology Data Exchange (ETDEWEB)

    Nierkens, Stefan [Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 28, Nijmegen 6525 GA (Netherlands); Janssen, Edith M., E-mail: edith.janssen@cchmc.org [Division of Molecular Immunology, Cincinnati Children' s Hospital Research Foundation, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229 (United States)

    2011-04-26

    Dendritic cells (DC) are professional antigen presenting cells that are crucial for the induction of anti-tumor T cell responses. As a consequence, research has focused on the harnessing of DCs for therapeutic interventions. Although current strategies employing ex vivo-generated and tumor-antigen loaded DCs have been proven feasible, there are still many obstacles to overcome in order to improve clinical trial successes and offset the cost and complexity of customized cell therapy. This review focuses on one of these obstacles and a pivotal step for the priming of tumor-specific CD8{sup +} and CD4{sup +} T cells; the in vitro loading of DCs with tumor antigens.

  19. Dramatic increase in fatigue life in hierarchical graphene composites.

    Science.gov (United States)

    Yavari, F; Rafiee, M A; Rafiee, J; Yu, Z-Z; Koratkar, N

    2010-10-01

    We report the synthesis and fatigue characterization of fiberglass/epoxy composites with various weight fractions of graphene platelets infiltrated into the epoxy resin as well as directly spray-coated on to the glass microfibers. Remarkably only ∼0.2% (with respect to the epoxy resin weight and ∼0.02% with respect to the entire laminate weight) of graphene additives enhanced the fatigue life of the composite in the flexural bending mode by up to 1200-fold. By contrast, under uniaxial tensile fatigue conditions, the graphene fillers resulted in ∼3-5-fold increase in fatigue life. The fatigue life increase (in the flexural bending mode) with graphene additives was ∼1-2 orders of magnitude superior to those obtained using carbon nanotubes. In situ ultrasound analysis of the nanocomposite during the cyclic fatigue test suggests that the graphene network toughens the fiberglass/epoxy-matrix interface and prevents the delamination/buckling of the glass microfibers under compressive stress. Such fatigue-resistant hierarchical materials show potential to improve the safety, reliability, and cost effectiveness of fiber-reinforced composites that are increasingly the material of choice in the aerospace, automotive, marine, sports, biomedical, and wind energy industries.

  20. Socio-dramatic affective-relational intervention for adolescents with asperger syndrome & high functioning autism: pilot study.

    Science.gov (United States)

    Lerner, Matthew D; Mikami, Amori Yee; Levine, Karen

    2011-01-01

    This study examined the effectiveness of a novel intervention called 'socio-dramatic affective-relational intervention' (SDARI), intended to improve social skills among adolescents with Asperger syndrome and high functioning autism diagnoses. SDARI adapts dramatic training activities to focus on in vivo practice of areas of social skill deficit among this population. SDARI was administered as a six-week summer program in a community human service agency. Nine SDARI participants and eight age- and diagnosis-group matched adolescents not receiving SDARI were compared on child- and parent-report of social functioning at three week intervals beginning six weeks prior to intervention and ending six weeks post-intervention. Hierarchical Linear Modeling (HLM) was used to estimate growth trends between groups to assess treatment outcomes and post-treatment maintenance. Results indicated significant improvement and post-treatment maintenance among SDARI participants on several measures of child social functioning. Implications for practice and research are discussed.

  1. Cancer/testis antigens: novel tools for discerning aggressive and non-aggressive prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Takumi Shiraishi; Robert H Getzenberg; Prakash Kulkarni

    2012-01-01

    The introduction of serum prostate-specific antigen (PSA) in the 1980s has dramatically altered and benefited the initial diagnosis of prostate cancer.However,the widespread use of PSA testing has resulted in overdetection and overtreatment of potentially indolent disease.Thus,a clinical dilemma today in the management of prostate cancer is to discern men with aggressive disease who need definitive treatment from men whose disease are not lethal.Although several serum and tissue biomarkers have been evaluated during the past decade,improved markers are still needed to enhance the accuracy,with which patients at risk can be discerned and treated more aggressively.The cancer/testis antigens (CTAs) are a group of proteins that are restricted to the testis in the normal adult,but are aberrantly expressed in several types of cancers.Because of their restricted expression pattern,the CTAs represent attractive biomarker candidates for cancer diagnosis/prognosis.Furthermore,several studies to date have reported the differential expression of CTAs in prostate cancer.Here,we review recent developments that demonstrate the potential of the CTAs as biomarkers to discern the aggressive phenotype of prostate cancer.

  2. Yeast surface display of a noncovalent MHC class II heterodimer complexed with antigenic peptide.

    Science.gov (United States)

    Boder, Eric T; Bill, Jerome R; Nields, Andrew W; Marrack, Philippa C; Kappler, John W

    2005-11-20

    Microbial protein display technologies have enabled directed molecular evolution of binding and stability properties in numerous protein systems. In particular, dramatic improvements to antibody binding affinity and kinetics have been accomplished using these tools in recent years. Examples of successful application of display technologies to other immunological proteins have been limited to date. Herein, we describe the expression of human class II major histocompatibility complex allele (MHCII) HLA-DR4 on the surface of Saccharomyces cerevisiae as a noncovalently associated heterodimer. The yeast-displayed MHCII is fully native as assessed by binding of conformationally specific monoclonal antibodies; failure of antibodies specific for empty HLA-DR4 to bind yeast-displayed protein indicates antigenic peptide is bound. This report represents the first example of a noncovalent protein dimer displayed on yeast and of successful display of wild-type MHCII. Results further point to the potential for using yeast surface display for engineering and analyzing the antigen binding properties of MHCII.

  3. Dramatic Photosynthesis.

    Science.gov (United States)

    Carlsson, Britta

    2003-01-01

    Presents a creative way to teach photosynthesis. Revolves around the growth of a lily planted and stored in the classroom. Combines the concepts of particle theory, transformation, and changes of phase and mass in a holistic approach. The six-step teaching sequence is founded on the notions of challenge, variation, and drama. (Author/NB)

  4. Rho kinase inhibitor Y-27632 and Accutase dramatically increase mouse embryonic stem cell derivation.

    Science.gov (United States)

    Zhang, Peng; Wu, Xinglong; Hu, Chunchao; Wang, Pengbo; Li, Xiangyun

    2012-01-01

    Although it has been 30 yr since the development of derivation methods for mouse embryonic stem (ES) cells, the biology of derivation of ES cells is poorly understood and the efficiency varies dramatically between cell lines. Recently, the Rho kinase inhibitor Y-27632 and the cell dissociation reagent Accutase were reported to significantly inhibit apoptosis of human ES cells during passaging. Therefore, in the current study, C57BL/6×129/Sv mouse blastocysts were used to evaluate the effect of the combination of the two reagents instead of using the conventional 129 line in mouse ES cell derivation. The data presented in this study suggests that the combination of Y-27632 and Accutase significantly increases the efficiency of mouse ES cell derivation; furthermore, no negative side effects were observed with Y-27632 and Accutase treatment. The newly established ES cell lines retain stable karyotype, surface markers expression, formed teratomas, and contributed to viable chimeras and germline transmission by tetraploid complementation assay. In addition, Y-27632 improved embryoid body formation of ES cells. During ES cell microinjection, Y-27632 prevented the formation of dissociation-induced cell blebs and facilitates the selection and the capture of intact cells. The methods presented in this study clearly demonstrate that inhibition of Rho kinase with Y-27632 and Accutase dissociation improve the derivation efficiently and reproducibility of mouse ES cell generation which is essential for reducing variability in the results obtained from different cell lines.

  5. "I Did Not Wash My Feet with that Woman": Using Dramatic Performance to Teach Biblical Studies

    Science.gov (United States)

    Torbett, David

    2010-01-01

    The student dramatic performance is an effective way for undergraduates to learn biblical studies. In this article I will give an example of a dramatic performance assignment that I developed over a number of courses and used most recently and most successfully in an undergraduate course in the Hebrew Bible at a small liberal arts college in the…

  6. Enhancing Creative Dramatic Play and Story Reenactments in a Primary Grade Classroom.

    Science.gov (United States)

    Schierholt, Carla G.

    A classroom research project in Alaska explored what role dramatic play and story reenactments have as a teaching/learning method for young childrens' development. A review of the literature identified several common elements that helped teachers elicit successful dramatic story reenactments: choosing a familiar book or story; encouraging…

  7. Guiding the Noticing: Using a Dramatic Performance Experience to Promote Tellability in Narrative Writing

    Science.gov (United States)

    Clark, Shanetia

    2012-01-01

    In this article, the author describes her use of dramatic performance to promote tellability in narrative writing within a seventh and eighth grade English and language arts classroom. By experiencing dramatic performance, the students were able to actively and physically perform the writing process: brainstorming, drafting, revising, and editing.…

  8. The Effectiveness of Creative Dramatics and Storytelling in a Library Setting

    Science.gov (United States)

    Amato, Anthony; And Others

    1973-01-01

    This 2-year study involving 298 grade school pupils investigates the comparative effectiveness of creative dramatics and storytelling. While the results indicate neither had an effect on children's interests and reading achievement, there is indication that storytelling may have more influence than creative dramatics on self-image and empathy.…

  9. The Impact of Dramatic Play Centre on Promoting the Development of Children's Early Writing Skills

    Science.gov (United States)

    Ihmeideh, Fathi

    2015-01-01

    The purpose of this study is to examine the impact of dramatic play centre (DPC) on promoting the development of children's early writing skills in the Jordanian context. It also intends to investigate the forms of children's writing skills that emerge through the use of dramatic play. Observations and interviews were conducted to obtain…

  10. On the Major Dramatic Conftict of Shakespeare's the Merchant of Venice

    Institute of Scientific and Technical Information of China (English)

    蒋文

    2000-01-01

    "The Merchant of Venice", a master piece with humanist idea by William Shakespeare, presents readers a dramatic conflict between friendship and greediness, love and cruelty.This essay illustrates briefly how this conflict is created, developed and dramatized. At the same time, the root causes for this conflict is analysed.

  11. Cancer testis antigen and immunotherapy

    Directory of Open Access Journals (Sweden)

    Krishnadas DK

    2013-04-01

    Full Text Available Deepa Kolaseri Krishnadas, Fanqi Bai, Kenneth G Lucas Department of Pediatrics, Division of Hematology/Oncology, University of Louisville, KY, USA Abstract: The identification of cancer testis (CT antigens has been an important advance in determining potential targets for cancer immunotherapy. Multiple previous studies have shown that CT antigen vaccines, using both peptides and dendritic cell vaccines, can elicit clinical and immunologic responses in several different tumors. This review details the expression of melanoma antigen family A, 1 (MAGE-A1, melanoma antigen family A, 3 (MAGE-A3, and New York esophageal squamous cell carcinoma-1 (NY-ESO-1 in various malignancies, and presents our current understanding of CT antigen based immunotherapy. Keywords: cancer testis antigens, immunotherapy, vaccine

  12. An Automated Micro-Total Immunoassay System for Measuring Cancer-Associated α2,3-linked Sialyl N-Glycan-Carrying Prostate-Specific Antigen May Improve the Accuracy of Prostate Cancer Diagnosis

    Science.gov (United States)

    Ishikawa, Tomokazu; Yoneyama, Tohru; Tobisawa, Yuki; Hatakeyama, Shingo; Kurosawa, Tatsuo; Nakamura, Kenji; Narita, Shintaro; Mitsuzuka, Koji; Duivenvoorden, Wilhelmina; Pinthus, Jehonathan H.; Hashimoto, Yasuhiro; Koie, Takuya; Habuchi, Tomonori; Arai, Yoichi; Ohyama, Chikara

    2017-01-01

    The low specificity of the prostate-specific antigen (PSA) for early detection of prostate cancer (PCa) is a major issue worldwide. The aim of this study to examine whether the serum PCa-associated α2,3-linked sialyl N-glycan-carrying PSA (S2,3PSA) ratio measured by automated micro-total immunoassay systems (μTAS system) can be applied as a diagnostic marker of PCa. The μTAS system can utilize affinity-based separation involving noncovalent interaction between the immunocomplex of S2,3PSA and Maackia amurensis lectin to simultaneously determine concentrations of free PSA and S2,3PSA. To validate quantitative performance, both recombinant S2,3PSA and benign-associated α2,6-linked sialyl N-glycan-carrying PSA (S2,6PSA) purified from culture supernatant of PSA cDNA transiently-transfected Chinese hamster ovary (CHO)-K1 cells were used as standard protein. Between 2007 and 2016, fifty patients with biopsy-proven PCa were pair-matched for age and PSA levels, with the same number of benign prostatic hyperplasia (BPH) patients used to validate the diagnostic performance of serum S2,3PSA ratio. A recombinant S2,3PSA- and S2,6PSA-spiked sample was clearly discriminated by μTAS system. Limit of detection of S2,3PSA was 0.05 ng/mL and coefficient variation was less than 3.1%. The area under the curve (AUC) for detection of PCa for the S2,3PSA ratio (%S2,3PSA) with cutoff value 43.85% (AUC; 0.8340) was much superior to total PSA (AUC; 0.5062) using validation sample set. Although the present results are preliminary, the newly developed μTAS platform for measuring %S2,3PSA can achieve the required assay performance specifications for use in the practical and clinical setting and may improve the accuracy of PCa diagnosis. Additional validation studies are warranted. PMID:28241428

  13. Serologic responses to somatic O and colonization-factor antigens of enterotoxigenic Escherichia coli in travelers.

    Science.gov (United States)

    Deetz, T R; Evans, D J; Evans, D G; DuPont, H L

    1979-07-01

    To improve the retrospective diagnoses of enterotoxigenic Escherichia coli (ETEC) as a cause of travelers' diarrhea, as well as to determine the presence of colonization-factor antigens in these infections, a study of serologic responses to antigens of ETEC was done. Paired sera from 60 United States students in Cholula, Puebla, Mexico, were analyzed for rises in titer of antibody to heat-labile toxin, eight somatic antigen O serogroups associated with ETEC, and two colonization-factor antigens, CFA/I and CFA/II. Only 9% had a response to O antigens, while 20% had responses to the colonization-factor antigens. Response to the colonization-factor antigens correlated significantly with response to the heat-labile toxin and with culture evidence of ETEC infection. Serologic studies confirmed that colonization-factor antigen has a role in naturally acquired cases of travelers' diarrhea and that it can be used as an additional determinant of infection with ETEC.

  14. Antigen antibody interactions

    CERN Document Server

    DeLisi, Charles

    1976-01-01

    1. 1 Organization of the Immune System One of the most important survival mechanisms of vertebrates is their ability to recognize and respond to the onslaught of pathogenic microbes to which they are conti- ously exposed. The collection of host cells and molecules involved in this recognition­ 12 response function constitutes its immune system. In man, it comprises about 10 cells 20 (lymphocytes) and 10 molecules (immunoglobulins). Its ontogenic development is c- strained by the requirement that it be capable of responding to an almost limitless variety of molecular configurations on foreign substances, while simultaneously remaining inert to those on self components. It has thus evolved to discriminate, with exquisite precision, between molecular patterns. The foreign substances which induce a response, called antigens, are typically large molecules such as proteins and polysaccharides. The portions of these with which immunoglobulins interact are called epitopes or determinants. A typical protein epitope m...

  15. Dramatic capability of the story of Amir Hasanak the vizier in Tarikh-e Beyhaghi

    Directory of Open Access Journals (Sweden)

    پروین گلی زاده

    2010-12-01

    Full Text Available Literary adaptation is recasting literary books such as novels, short stories, or even poems in a new form such as films, stage plays, or even video games. Persian literature abounds with dramatic events. There are many fascinating narratives such as Shahnameh of Ferdowsi, Khmseh of Nezami, Mathnavi of Rumi, and Tarikh-e Beyhaghi of Beyhaghi, which have the dramatic capacity of literary adaptation. In this paper, the writer examines the dramatic capability of “The execution of Amir Hasanak the vizier”. The structure and artistic aspects of the story will be studied in the light of the elements of drama. Keywords: Beyhaghi, Hasanak, narration, dialogue, suspense

  16. Antigenic Variation in Bacterial Pathogens.

    Science.gov (United States)

    Palmer, Guy H; Bankhead, Troy; Seifert, H Steven

    2016-02-01

    Antigenic variation is a strategy used by a broad diversity of microbial pathogens to persist within the mammalian host. Whereas viruses make use of a minimal proofreading capacity combined with large amounts of progeny to use random mutation for variant generation, antigenically variant bacteria have evolved mechanisms which use a stable genome, which aids in protecting the fitness of the progeny. Here, three well-characterized and highly antigenically variant bacterial pathogens are discussed: Anaplasma, Borrelia, and Neisseria. These three pathogens display a variety of mechanisms used to create the structural and antigenic variation needed for immune escape and long-term persistence. Intrahost antigenic variation is the focus; however, the role of these immune escape mechanisms at the population level is also presented.

  17. Radioimmunoassays of hidden viral antigens

    Energy Technology Data Exchange (ETDEWEB)

    Neurath, A.R. (Lindsley F. Kimbell Research Inst., New York, NY); Strick, N.; Baker, L.; Krugman, S.

    1982-07-01

    Antigens corresponding to infectious agents may be present in biological specimens only in a cryptic form bound to antibodies and, thus, may elude detection. We describe a solid-phase technique for separation of antigens from antibodies. Immune complexes are precipitated from serum by polyethylene glycol, dissociated with NaSCN, and adsorbed onto nitrocellulose or polystyrene supports. Antigens remain topographically separated from antibodies after removal of NaSCN and can be detected with radiolabeled antibodies. Genomes from viruses immobilized on nitrocellulose can be identified by nucleic acid hybridization. Nanogram quantities of sequestered hepatitis B surface and core antigens and picogram amounts of hepatitis B virus DNA were detected. Antibody-bound adenovirus, herpesvirus, and measles virus antigens were discerned by the procedure.

  18. Radioimmunoassays of hidden viral antigens.

    Science.gov (United States)

    Neurath, A R; Strick, N; Baker, L; Krugman, S

    1982-01-01

    Antigens corresponding to infectious agents may be present in biological specimens only in a cryptic form bound to antibodies and, thus, may elude detection. We describe a solid phase technique for separation of antigens from antibodies. Immune complexes are precipitated from serum by polyethylene glycol, dissociated with NaSCN, and adsorbed onto nitrocellulose or polystyrene supports. Antigens remain topographically separated from antibodies after removal of NaSCN and can be detected with radiolabeled antibodies. Genomes from viruses immobilized on nitrocellulose can be identified by nucleic acid hybridization. Nanogram quantities of sequestered hepatitis B surface and core antigens and picogram amounts of hepatitis B virus DNA were detected. Antibody-bond adenovirus, herpesvirus, and measles virus antigens were discerned by the procedure. Images PMID:6956871

  19. Neurocognitive impairment in dramatic personalities: histrionic, narcissistic, borderline, and antisocial disorders.

    Science.gov (United States)

    Burgess, J W

    1992-06-01

    Thirty-seven patients with personalities in the dramatic cluster (DSM-III-R histrionic, narcissistic, borderline, and antisocial) and 40 controls matched for age and gender were evaluated on 16 neurocognitive variables. The evaluation screened for deficits in functions of attention, memory, language, abstraction, and behavior planning/sequencing. Analysis of variance revealed significant deficits in neurocognitive performance among patients with dramatic personalities, particularly in subtests requiring multi-step, multi-element associative operations.

  20. A Case of Aripiprazole-Induced Tardive Dyskinesia with Dramatic Evolution

    OpenAIRE

    Edwige Heitzmann; Hervé Javelot; Luisa Weiner; Bruno Michel

    2016-01-01

    Aripiprazole is reported to be a good clinical safety profile antipsychotic. However, recent data suggest that the risk of tardive dyskinesia could be higher than initially thought. We report the case of aripiprazole-induced tardive dyskinesia with dramatic evolution in a patient with several risk factors, including older age and exposure to antipsychotic over a period longer than six months. This case and its dramatic evolution, associated with other cases recently published, suggest reconsi...

  1. COLONOSCOPY AND CARCINOEMBRYONIC ANTIGEN VARIATIONS

    Directory of Open Access Journals (Sweden)

    Rita G SOUSA

    2014-03-01

    Full Text Available Context Colonoscopy is essential for synchronous and metachronous cancer detection. Carcinoembryonic antigen is a colorectal cancer tumor marker, important as a follow-up tool in patients with previous colorectal cancer. False-positive carcinoembryonic antigen elevation results in multiples exams and in patient anxiety. In literature, there is reference to transient carcinoembryonic antigen increase with colonoscopy. Objective To evaluate the influence of bowel preparation and colonoscopy in carcinoembryonic antigen blood levels. Methods We prospectively studied subjects that underwent routine colonoscopy in our institution. Blood samples were collected (1 before bowel cleaning, (2 before colonoscopy and (3 immediately after colonoscopy. Blood carcinoembryonic antigen levels were determined by “Sandwich” immunoassay. The statistical methods used were the paired t-test and ANOVA. Results Thirty-seven patients (22M/15F were included; age range 28-84 (mean 56 years. Mean carcinoembryonic antigen values were 1.9, 2 and 1.8 for (1, (2 and (3, respectively. An increase in value (2 compared with (1 was observed in 20/37 patients (P = 0.018, mainly in younger patients and in patients requiring more endoluminal interventions. In 29/37 patients, the CEA value decreased from (2 to (3 (P = 1.3x10-7. Conclusions A trend for carcinoembryonic antigen increase after bowel cleaning was observed, especially in younger patients and in patients with more endoluminal interventions, but without clinical meaning.

  2. Permeability enhancers dramatically increase zanamivir absolute bioavailability in rats: implications for an orally bioavailable influenza treatment.

    Directory of Open Access Journals (Sweden)

    Eric H Holmes

    Full Text Available We have demonstrated that simple formulations composed of the parent drug in combination with generally regarded as safe (GRAS permeability enhancers are capable of dramatically increasing the absolute bioavailability of zanamivir. This has the advantage of not requiring modification of the drug structure to promote absorption, thus reducing the regulatory challenges involved in conversion of an inhaled to oral route of administration of an approved drug. Absolute bioavailability increases of up to 24-fold were observed when Capmul MCM L8 (composed of mono- and diglycerides of caprylic/capric acids in glycerol was mixed with 1.5 mg of zanamivir and administered intraduodenally to rats. Rapid uptake (t(max of 5 min and a C(max of over 7200 ng/mL was achieved. Variation of the drug load or amount of enhancer demonstrated a generally linear variation in absorption, indicating an ability to optimize a formulation for a desired outcome such as a targeted C(max for enzyme saturation. No absorption enhancement was observed when the enhancer was given 2 hr prior to drug administration, indicating, in combination with the observed tmax, that absorption enhancement is temporary. This property is significant and aligns well with therapeutic applications to limit undesirable drug-drug interactions, potentially due to the presence of other poorly absorbed polar drugs. These results suggest that optimal human oral dosage forms of zanamivir should be enteric-coated gelcaps or softgels for intraduodenal release. There continues to be a strong need and market for multiple neuraminidase inhibitors for influenza treatment. Creation of orally available formulations of inhibitor drugs that are currently administered intravenously or by inhalation would provide a significant improvement in treatment of influenza. The very simple GRAS formulation components and anticipated dosage forms would require low manufacturing costs and yield enhanced convenience. These results

  3. The Effect of Dramatized Instruction on Speaking Ability of Imam Ali University EFL Learners

    Directory of Open Access Journals (Sweden)

    Sadegh Khosronejad

    2013-09-01

    Full Text Available Teaching language as a second or foreign language, undoubtedly, is so demanding and seeking to find methods for facilitating this prominent practice whets the appetite of any practitioner who works in this field. Research shows that using drama in the classroom as a means of teaching helps students learn socially, academically, and developmentally. This study was an attempt to determine the effect of dramatized instruction on the speaking ability of EFL learners of Imam Ali University. Sixty EFL male students at the intermediate level participated in the study. Their age range was 19-22. Two instruments were utilized in this study; pretest, and posttest.  The data were analyzed through t-test. The data analysis indicated that the mean scores of the experimental group students (M = 72.80 were significantly different (3.29>2; df = 58 from the control group students (M = 65.39. In other words, the experimental group outperformed the control group in the posttest significantly. Moreover, the findings indicated that dramatized instruction does have a great effect on the speaking skills. This study supported the idea of effectiveness of dramatized instruction on developing speaking skill and the teachers can help the learners at lower levels promote their speaking skill through dramatized instruction in EFL classes. Key words: Drama, Dramatized Instruction, Conventional Methods

  4. Comparable quality attributes of hepatitis E vaccine antigen with and without adjuvant adsorption-dissolution treatment.

    Science.gov (United States)

    Zhang, Yue; Li, Min; Yang, Fan; Li, Yufang; Zheng, Zizheng; Zhang, Xiao; Lin, Qingshan; Wang, Ying; Li, Shaowei; Xia, Ningshao; Zhang, Jun; Zhao, Qinjian

    2015-01-01

    Most vaccines require adjuvants for antigen stabilization and immune potentiation. Aluminum-based adjuvants are the most widely used adjuvants for human vaccines. Previous reports demonstrated the preservation of antigen conformation and other antigen characteristics after recovery from adjuvanted Hepatitis B and human papillomavirus vaccines. In this study, we used a combination of various physiochemical and immunochemical methods to analyze hepatitis E vaccine antigen quality attributes after recovery from adjuvants. All biochemical and biophysical methods showed similar characteristics of the p239 protein after recovery from adjuvanted vaccine formulation compared to the antigen in solution which never experienced adsorption/desorption process. Most importantly, we demonstrated full preservation of key antigen epitopes post-recovery from adjuvanted vaccine using a panel of murine monoclonal antibodies as exquisite probes. Antigenicity of p239 was probed with a panel of 9 mAbs using competition/blocking ELISA, surface plasmon resonance and sandwich ELISA methods. These multifaceted analyses demonstrated the preservation of antigen key epitopes and comparable protein thermal stability when adsorbed on adjuvants or of the recovered antigen post-dissolution treatment. A better understanding of the antigen conformation in adjuvanted vaccine will enhanced our knowledge of antigen-adjuvant interactions and facilitate an improved process control and development of stable vaccine formulation.

  5. Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination.

    Science.gov (United States)

    Mahan, Alison E; Jennewein, Madeleine F; Suscovich, Todd; Dionne, Kendall; Tedesco, Jacquelynne; Chung, Amy W; Streeck, Hendrik; Pau, Maria; Schuitemaker, Hanneke; Francis, Don; Fast, Patricia; Laufer, Dagna; Walker, Bruce D; Baden, Lindsey; Barouch, Dan H; Alter, Galit

    2016-03-01

    Antibody effector functions, such as antibody-dependent cellular cytotoxicity, complement deposition, and antibody-dependent phagocytosis, play a critical role in immunity against multiple pathogens, particularly in the absence of neutralizing activity. Two modifications to the IgG constant domain (Fc domain) regulate antibody functionality: changes in antibody subclass and changes in a single N-linked glycan located in the CH2 domain of the IgG Fc. Together, these modifications provide a specific set of instructions to the innate immune system to direct the elimination of antibody-bound antigens. While it is clear that subclass selection is actively regulated during the course of natural infection, it is unclear whether antibody glycosylation can be tuned, in a signal-specific or pathogen-specific manner. Here, we show that antibody glycosylation is determined in an antigen- and pathogen-specific manner during HIV infection. Moreover, while dramatic differences exist in bulk IgG glycosylation among individuals in distinct geographical locations, immunization is able to overcome these differences and elicit antigen-specific antibodies with similar antibody glycosylation patterns. Additionally, distinct vaccine regimens induced different antigen-specific IgG glycosylation profiles, suggesting that antibody glycosylation is not only programmable but can be manipulated via the delivery of distinct inflammatory signals during B cell priming. These data strongly suggest that the immune system naturally drives antibody glycosylation in an antigen-specific manner and highlights a promising means by which next-generation therapeutics and vaccines can harness the antiviral activity of the innate immune system via directed alterations in antibody glycosylation in vivo.  .

  6. Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination.

    Directory of Open Access Journals (Sweden)

    Alison E Mahan

    2016-03-01

    Full Text Available Antibody effector functions, such as antibody-dependent cellular cytotoxicity, complement deposition, and antibody-dependent phagocytosis, play a critical role in immunity against multiple pathogens, particularly in the absence of neutralizing activity. Two modifications to the IgG constant domain (Fc domain regulate antibody functionality: changes in antibody subclass and changes in a single N-linked glycan located in the CH2 domain of the IgG Fc. Together, these modifications provide a specific set of instructions to the innate immune system to direct the elimination of antibody-bound antigens. While it is clear that subclass selection is actively regulated during the course of natural infection, it is unclear whether antibody glycosylation can be tuned, in a signal-specific or pathogen-specific manner. Here, we show that antibody glycosylation is determined in an antigen- and pathogen-specific manner during HIV infection. Moreover, while dramatic differences exist in bulk IgG glycosylation among individuals in distinct geographical locations, immunization is able to overcome these differences and elicit antigen-specific antibodies with similar antibody glycosylation patterns. Additionally, distinct vaccine regimens induced different antigen-specific IgG glycosylation profiles, suggesting that antibody glycosylation is not only programmable but can be manipulated via the delivery of distinct inflammatory signals during B cell priming. These data strongly suggest that the immune system naturally drives antibody glycosylation in an antigen-specific manner and highlights a promising means by which next-generation therapeutics and vaccines can harness the antiviral activity of the innate immune system via directed alterations in antibody glycosylation in vivo.  .

  7. A Case of Aripiprazole-Induced Tardive Dyskinesia with Dramatic Evolution

    Science.gov (United States)

    Heitzmann, Edwige; Weiner, Luisa; Michel, Bruno

    2016-01-01

    Aripiprazole is reported to be a good clinical safety profile antipsychotic. However, recent data suggest that the risk of tardive dyskinesia could be higher than initially thought. We report the case of aripiprazole-induced tardive dyskinesia with dramatic evolution in a patient with several risk factors, including older age and exposure to antipsychotic over a period longer than six months. This case and its dramatic evolution, associated with other cases recently published, suggest reconsidering the real risk of tardive dyskinesia associated with aripiprazole, particularly in the elderly. PMID:27818825

  8. A Case of Aripiprazole-Induced Tardive Dyskinesia with Dramatic Evolution

    Directory of Open Access Journals (Sweden)

    Edwige Heitzmann

    2016-01-01

    Full Text Available Aripiprazole is reported to be a good clinical safety profile antipsychotic. However, recent data suggest that the risk of tardive dyskinesia could be higher than initially thought. We report the case of aripiprazole-induced tardive dyskinesia with dramatic evolution in a patient with several risk factors, including older age and exposure to antipsychotic over a period longer than six months. This case and its dramatic evolution, associated with other cases recently published, suggest reconsidering the real risk of tardive dyskinesia associated with aripiprazole, particularly in the elderly.

  9. Analysis of a novel cathepsin B circulating antigen and its response to drug treatment in Trichinella-infected mice.

    Science.gov (United States)

    Zhan, Jian-hua; Yao, Jian-ping; Liu, Wei; Hu, Xu-chu; Wu, Zhong-dao; Zhou, Xing-wang

    2013-09-01

    In this paper, we cloned a novel full-length cDNA that encodes a Trichinella spiralis cathepsin B-like protease gene (TsCPB) using 3'-RACE PCR. The recombinant mature TsCPB protein (rTsCPB) was then expressed in an Escherichia coli expression system and purified with Ni-affinity chromatography. Real-time quantitative PCR revealed that TsCPB was expressed across all development stages of the parasite but had the highest expression level during the adult stage. Furthermore, rTsCPB was detected in Trichinella excretory-secretory products with anti-rTsCPB rabbit polyclonal antibodies. Interestingly, rTsCPB was strongly recognized by the T. spiralis-infected sera in Western blotting, implying that TsCPB protein appeared in the peripheral blood of Trichinella-infected mice as circulating antigens (CAg). We then analyzed the dynamic levels of TsCPB CAg and its antibodies in T. spiralis-infected sera by using an improved double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) and indirect ELISA, respectively. The results showed that TsCPB CAg can be detected much earlier compared to antibody detection in Trichinella-infected mice. In addition, we monitored the effects of albendazole drug therapy (a dosage of 370 mg/kg body weight, twice a day) on T. spiralis-infected mice by detecting the levels of TsCPB CAg and its antibody in the sera of drug-treated mice. The results showed that the levels of CAg dramatically decreased after successful drug treatment, while the antibody level remained unchanged. Overall, the novel Trichinella antigen TsCPB could be a promising novel circulating antigen molecule for the detection of Trichinella infection and for monitoring the efficacy of drug treatment of trichinellosis.

  10. Improvement of an enzyme-linked immunosorbent assay for equine herpesvirus type 4 by using a synthetic-peptide 24-mer repeat sequence of glycoprotein G as an antigen.

    Science.gov (United States)

    Bannai, Hiroshi; Nemoto, Manabu; Tsujimura, Koji; Yamanaka, Takashi; Maeda, Ken; Kondo, Takashi

    2016-02-01

    To increase the sensitivity of an enzyme-linked immunosorbent assay (ELISA) for equine herpesvirus type 4 (EHV-4) that uses a 12-mer peptide of glycoprotein G (gG4-12-mer: MKNNPIYSEGSL) [4], we used a longer peptide consisting of a 24-mer repeat sequence (gG4-24-mer: MKNNPIYSEGSLMLNVQHDDSIHT) as an antigen. Sera of horses experimentally infected with EHV-4 reacted much more strongly to the gG4-24-mer peptide than to the gG4-12-mer peptide. We used peptide ELISAs to test paired sera from horses naturally infected with EHV-4 (n=40). gG4-24-mer ELISA detected 37 positive samples (92.5%), whereas gG4-12-mer ELISA detected only 28 (70.0%). gG4-24-mer ELISA was much more sensitive than gG4-12-mer ELISA.

  11. T Cells as Antigen Carriers for Anti-tumor Vaccination.

    Science.gov (United States)

    Traversari, Catia; Russo, Vincenzo

    2016-01-01

    The exploitation of the physiologic processing and presenting machinery of dendritic cells (DCs) by in vivo loading of tumor-associated antigens may improve the immunogenic potential and clinical efficacy of DC-based cancer vaccines. The approach developed by our group was based on the clinical observation that some patients treated with the infusion of donor lymphocytes transduced to express the HSV-TK suicide gene for relapse of hematologic malignancies, after allogeneic hematopoietic stem cell transplantation, developed a T cell-mediated immune response specifically directed against the HSV-TK gene product.We demonstrated that lymphocytes genetically modified to express HSV-TK as well as self/tumor antigens, acting as antigen carriers, efficiently target DCs in vivo in tumor-bearing mice. The infusion of TRP-2-transduced lymphocytes induced the establishment of protective immunity and long-term memory in tumor-bearing mice by cross-presentation of the antigen mediated by the CD11c(+)CD8a(+) DCs subset. A similar approach was applied in a clinical setting. Ten patients affected by MAGE-3(+) metastatic melanoma were treated with autologous lymphocytes retrovirally transduced to express the MAGE-3 tumor antigen. In three patients, the treatment led to the increase of MAGE-3 specific CD8+ and CD4+ effectors and the development of long-term memory, which ultimately correlated with a favorable clinical outcome. Transduced lymphocytes represent an efficient way for in vivo loading of tumor-associated antigens of DCs.

  12. Erotic Language as Dramatic Action in Plays by Lyly and Shakespeare

    Science.gov (United States)

    Knoll, Gillian

    2012-01-01

    This study closely examines the language of desire in the dramatic works of John Lyly and William Shakespeare, and argues that contemplative and analytical speeches about desire function as modes of action in their plays. Erotic speeches do more than express desire in a purely descriptive or perlocutionary capacity distinct from the action of the…

  13. The Devil and his Dramatic Function in Calderon’s Autos Sacramentales

    Directory of Open Access Journals (Sweden)

    Luis Iglesias Feijoo

    2014-05-01

    Full Text Available In some Calderón’s autos sacramentales the character of the Devil draws the plot and establishes the dramatic action as a demiurge. He elaborates plans and strategies to confuse the Man, but he always fails. This function approaches the autos to the metatheater. Finally certain parallels with Shakespeare are suggested.

  14. Athenian and Shakespearean Tragedies in Oceania: Teaching Dramatic Literatures in Fiji

    Science.gov (United States)

    Anae, Nicole

    2013-01-01

    This paper presents a theorised classroom-based narrative discussing the author's interdisciplinary approach to the teaching of English dramatic literatures--in particular, Sophocles' "Oedipus the King" and Shakespeare's "Macbeth"--to i-Taukei, Indo-Fijian and Pacific Islander tertiary students at a South Pacific university.…

  15. Examining Young Children's Perception toward Augmented Reality-Infused Dramatic Play

    Science.gov (United States)

    Han, Jeonghye; Jo, Miheon; Hyun, Eunja; So, Hyo-jeong

    2015-01-01

    Amid the increasing interest in applying augmented reality (AR) in educational settings, this study explores the design and enactment of an AR-infused robot system to enhance children's satisfaction and sensory engagement with dramatic play activities. In particular, we conducted an exploratory study to empirically examine children's perceptions…

  16. Creating Intersubjectivity during Socio-Dramatic Play at an Australian Kindergarten

    Science.gov (United States)

    Whitington, Victoria; Floyd, Irene

    2009-01-01

    Socio-dramatic play (SDP) creates a zone of proximal development in which optimum cognitive development occurs. To participate successfully in this kind of play children and their partners must create shared meaning, or what is referred to in the socio-cultural literature as intersubjectivity. Based on intersubjectivity and SDP, this study…

  17. Engaging in Dramatic Activities in English as a Foreign Language Classes at the University Level

    Science.gov (United States)

    Algarra Carrasco, Victoria

    2012-01-01

    In this article, we discuss how, through dramatic activities, fiction and reality can work together to help the English as a Foreign language learner communicate in a more personal and meaningful way. The kind of activities proposed are designed to help engender a space where students can personally engage with each other in an atmosphere that is…

  18. Art-House Cinema, Avant-Garde Film, and Dramatic Modernism

    Science.gov (United States)

    Cardullo, Bert

    2011-01-01

    In this article, the author talks about art-house cinema, avant-garde film, and dramatic modernism. He believes that the most important modes of film practice are art-house cinema and the avant-garde, both of which contrast with the classical Hollywood mode of film practice. While the latter is characterized by its commercial imperative, corporate…

  19. Lord Kelvin and the Age-of-the-Earth Debate: A Dramatization.

    Science.gov (United States)

    Stinner, Art; Tecihman, Jurgen

    2003-01-01

    Presents a dramatization of a fictitious debate about the age of the earth that takes place at the Royal Institution, London, England, in the year 1872 among Sir William Thomson, T.H. Huxley, Sir Charles Lyell, and Hermann von Helmholtz. (Contains 17 references.) (Author/YDS)

  20. The Effect of Literacy Intervention in Preschool Children's Dramatic Play on Literacy Behaviors.

    Science.gov (United States)

    Johnson, Emily A.

    This study on the effect of participation in field trips as a literacy intervention in play investigated how preschool children incorporated the literacy behaviors emphasized during the field trips into their play activities. Authentic literacy materials were included in two dramatic play centers before and after 15 children participated in…

  1. Didactique du francais langue seconde, dramatisation, et theatre (French Second Language Teaching, Dramatization, and Theater).

    Science.gov (United States)

    Fancy, Alex

    1991-01-01

    Use of dramatics in French second language education is advocated with theoretical and practical arguments, and a four-stage approach to language acquisition through theater is proposed. The approach is based on activities of a bilingual theater troupe that offers Mount Allison University (New Brunswick) students an opportunity to participate in…

  2. Rapid profiling of the antigen regions recognized by serum antibodies using massively parallel sequencing of antigen-specific libraries.

    KAUST Repository

    Domina, Maria

    2014-12-04

    There is a need for techniques capable of identifying the antigenic epitopes targeted by polyclonal antibody responses during deliberate or natural immunization. Although successful, traditional phage library screening is laborious and can map only some of the epitopes. To accelerate and improve epitope identification, we have employed massive sequencing of phage-displayed antigen-specific libraries using the Illumina MiSeq platform. This enabled us to precisely identify the regions of a model antigen, the meningococcal NadA virulence factor, targeted by serum antibodies in vaccinated individuals and to rank hundreds of antigenic fragments according to their immunoreactivity. We found that next generation sequencing can significantly empower the analysis of antigen-specific libraries by allowing simultaneous processing of dozens of library/serum combinations in less than two days, including the time required for antibody-mediated library selection. Moreover, compared with traditional plaque picking, the new technology (named Phage-based Representation OF Immuno-Ligand Epitope Repertoire or PROFILER) provides superior resolution in epitope identification. PROFILER seems ideally suited to streamline and guide rational antigen design, adjuvant selection, and quality control of newly produced vaccines. Furthermore, this method is also susceptible to find important applications in other fields covered by traditional quantitative serology.

  3. Rapid profiling of the antigen regions recognized by serum antibodies using massively parallel sequencing of antigen-specific libraries.

    Directory of Open Access Journals (Sweden)

    Maria Domina

    Full Text Available There is a need for techniques capable of identifying the antigenic epitopes targeted by polyclonal antibody responses during deliberate or natural immunization. Although successful, traditional phage library screening is laborious and can map only some of the epitopes. To accelerate and improve epitope identification, we have employed massive sequencing of phage-displayed antigen-specific libraries using the Illumina MiSeq platform. This enabled us to precisely identify the regions of a model antigen, the meningococcal NadA virulence factor, targeted by serum antibodies in vaccinated individuals and to rank hundreds of antigenic fragments according to their immunoreactivity. We found that next generation sequencing can significantly empower the analysis of antigen-specific libraries by allowing simultaneous processing of dozens of library/serum combinations in less than two days, including the time required for antibody-mediated library selection. Moreover, compared with traditional plaque picking, the new technology (named Phage-based Representation OF Immuno-Ligand Epitope Repertoire or PROFILER provides superior resolution in epitope identification. PROFILER seems ideally suited to streamline and guide rational antigen design, adjuvant selection, and quality control of newly produced vaccines. Furthermore, this method is also susceptible to find important applications in other fields covered by traditional quantitative serology.

  4. Original encounter with antigen determines antigen-presenting cell imprinting of the quality of the immune response in mice.

    Directory of Open Access Journals (Sweden)

    Valérie Abadie

    Full Text Available BACKGROUND: Obtaining a certain multi-functionality of cellular immunity for the control of infectious diseases is a burning question in immunology and in vaccine design. Early events, including antigen shuttling to secondary lymphoid organs and recruitment of innate immune cells for adaptive immune response, determine host responsiveness to antigens. However, the sequence of these events and their impact on the quality of the immune response remain to be elucidated. Here, we chose to study Modified Vaccinia virus Ankara (MVA which is now replacing live Smallpox vaccines and is proposed as an attenuated vector for vaccination strategies against infectious diseases. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed in vivo mechanisms triggered following intradermal (i.d. and intramuscular (i.m. Modified Vaccinia virus Ankara (MVA administration. We demonstrated significant differences in the antigen shuttling to lymphoid organs by macrophages (MPhis, myeloid dendritic cells (DCs, and neutrophils (PMNs. MVA i.d. administration resulted in better antigen distribution and more sustained antigen-presenting cells (APCs recruitment into draining lymph nodes than with i.m. administration. These APCs, which comprise both DCs and MPhis, were differentially involved in T cell priming and shaped remarkably the quality of cytokine-producing virus-specific T cells according to the entry route of MVA. CONCLUSIONS/SIGNIFICANCE: This study improves our understanding of the mechanisms of antigen delivery and their consequences on the quality of immune responses and provides new insights for vaccine development.

  5. Chemokine programming dendritic cell antigen response: part I - select chemokine programming of antigen uptake even after maturation.

    Science.gov (United States)

    Park, Jaehyung; Wu, Cindy T; Bryers, James D

    2013-05-01

    Here, we report on the successful programming of dendritic cells (DCs) using selectively applied mixtures of chemokines as a novel protocol for engineering vaccine efficiency. Antigen internalization by DCs is a pivotal step in antigen uptake/presentation for bridging innate and adaptive immunity and in exogenous gene delivery used in vaccine strategies. Contrary to most approaches to improve vaccine efficiency, active enhancement of antigen internalization by DCs as a vaccine strategy has been less studied because DCs naturally down-regulate antigen internalization upon maturation. Whereas chemokines are mainly known as signal proteins that induce leucocyte chemotaxis, very little research has been carried out to identify any additional effects of chemokines on DCs following maturation. Here, immature DCs are pre-treated with select chemokines before intentional maturation using lipopolysaccharide (LPS). When pre-treated with a mixture of CCL3 and CCL19 in a 7 : 3 ratio, then matured with LPS, chemokine pre-treated DCs exhibited 36% higher antigen uptake capacity than immature DCs and 27% higher antigen-processing capacity than immature DCs treated only with LPS. Further, CCL3 : CCL19 (7 : 3) pre-treatment of DCs modulated MHC molecule expression and secretion of various cytokines of DCs. Collectively, DC programming was feasible using a specific chemokine combination and these results provide a novel strategy for enhancing DC-based vaccine efficiency. In Part II, we report on the phenotype changes and antigen presentation capacity of chemokine pre-treated murine bone marrow-derived DCs examined in long-term co-culture with antigen-specific CD4(+) T cells.

  6. Red blood cells as innovative antigen carrier to induce specific immune tolerance.

    Science.gov (United States)

    Cremel, Magali; Guérin, Nathalie; Horand, Françoise; Banz, Alice; Godfrin, Yann

    2013-02-25

    The route of administration, the dose of antigen as well as the type of antigen-presenting cells (APCs) targeted are important factors to induce immune tolerance. Despite encouraging results obtained in animal models, intravenous injection of soluble antigen is unsuccessful in human clinical trials on autoimmune disease due to inefficient antigen delivery. To improve antigen delivery, we used mouse red blood cells (RBCs) as antigen vehicles to specifically target APCs which are responsible for removal of senescent RBCs after phagocytosis. In this study, we demonstrated that antigen-delivery by RBCs induced a strong decrease in the humoral response compared with the ovalbumin (OVA) free form in mice. In addition, OVA-loaded RBC treated with [bis(sulphosuccinimidyl)] suberate (BS3), a chemical compound known to enhance RBC phagocytosis, induced an inhibition of antigen-specific T cell responses and an increase in the percentage of regulatory T cells. The state of tolerance induced is long lasting, antigen-specific and sufficiently robust to withstand immunization with antigen mixed with cholera toxin adjuvant. This RBC strategy, which does not abolish the immune system, constitutes an attractive approach for induction of tolerance compared to systemic immunosuppressant therapies already in use.

  7. New Concepts in Tumor Antigens: Their Significance in Future Immunotherapies for Tumors

    Institute of Scientific and Technical Information of China (English)

    Fan Yang; Xiao-Feng Yang

    2005-01-01

    The identification and molecular characterization of self-antigens expressed by human malignancies that are capable of elicitation of anti-tumor immune responses in patients have been an active field in tumor immunology.More than 2,000 tumor antigens have been identified, and most of these antigens are self-antigens. These significant progresses have led to the renaissance of tumor immunology and studies on anti-tumor immunotherapy.However, despite of the progress in the identification of self-tumor antigens, current antigen-specific immunotherapies for tumors are far less satisfied than expected, which reflects the urgent need to improve our understanding on self-tumor antigens. In order to develop more effective antigen specific anti-tumor immunotherapies and to monitor the responses to these immunotherapies in patients with tumors, many important fundamental questions need to be addressed. We propose for the first time that the studies in addressing the characteristics of self-tumor antigens and autoantigens are grouped as a new subject termed "antigenology". In this brief review, we would outline the progress in the identification of tumor antigens in solid tumors and hematologic malignancies, and overview the new concepts and principles of antigenology and their significance for future immunotherapies to these malignancies. Cellular & Molecular Immunology.

  8. Sensitivity improvement of a sandwich-type ELISA immunosensor for the detection of different prostate-specific antigen isoforms in human serum using electrochemical impedance spectroscopy and an ordered and hierarchically organized interfacial supramolecular architecture.

    Science.gov (United States)

    Gutiérrez-Zúñiga, Gabriela Guadalupe; Hernández-López, José Luis

    2016-01-01

    A gold millielectrode (GME) functionalized with a mixed (16-MHA + EG3SH) self-assembled monolayer (SAM) was used to fabricate an indirect enzyme-linked immunosorbent assay (ELISA) immunosensor for the sensitive detection of prostate-specific antigen (PSA), a prostate cancer (PCa) biomarker, in human serum samples. To address and minimize the issue of non-specific protein adsorption, an organic matrix (amine-PEG3-biotin/avidin) was assembled on the previously functionalized electrode surface to build up an ordered and hierarchically organized interfacial supramolecular architecture: Au/16-MHA/EG3SH/amine-PEG3-biotin/avidin. The electrode was then exposed to serum samples at different concentrations of a sandwich-type immunocomplex molecule ((Btn)Ab-AgPSA-(HRP)Ab), and its interfacial properties were characterized using electrochemical impedance spectroscopy (EIS). Calibration curves for polarization resistance (RP) and capacitance (1/C) vs. total and free PSA concentrations were obtained and their analytical quality parameters were determined. This approach was compared with results obtained from a commercially available ELISA immunosensor. The results obtained in this work showed that the proposed immunosensor can be successfully applied to analyze serum samples of patients representative of the Mexican population.

  9. Dramatic Decline of Respiratory Illness Among US Military Recruits After the Renewed Use of Adenovirus Vaccines

    Science.gov (United States)

    2014-10-01

    Naval Health Research Center Dramatic Decline of Respiratory Illness Among US Military Recruits After the Renewed Use of Adenovirus Vaccines ...Renewed Use of Adenovirus Vaccines Jennifer M. Radin,1,2 Anthony W. Hawksworth,1 Patrick J. Blair,1 Dennis J. Faix,3 Rema Raman,4 Kevin L. Russell,5...hiatus, oral vaccines against adenovirus types 4 (Ad4) and 7 (Ad7) were again produced and administered to US military recruits. This study examined the

  10. Discrimination, developmental science, and the law: addressing dramatic shifts in civil rights jurisprudence.

    Science.gov (United States)

    Levesque, Roger J R

    2014-01-01

    The civil rights movement fostered dramatic shifts in legal responses to discrimination based on race, gender, and a host of other group characteristics. The legal system now evinces yet another dramatic shift, as it moves from considering difference to focusing on neutrality, from efforts that seek to counter subjugation to those that adopt a "color-blind" approach. The shifting approach already has reached laws regulating responses to the group that spurred massive civil rights reform: minority youth. The shift requires a different body of empirical evidence to address it and a new look at equality jurisprudence. This article notes the need to turn to the current understanding of prejudice and discrimination for guidance, and uses, as illustration, developmental science to shed light on the development, manifestation, and alleviation of invidious discrimination. Using that understanding, the analysis details how the legal system can benefit from that research and better address discrimination in light of dramatic changes in law. The article articulates the need to address discrimination by recognizing and enlisting the law's inculcative powers through multiple sites of inculcation, ranging from families, schools, health and justice systems to religious and community groups. The discussion concludes with brief suggestions for reform benefiting from understandings of prejudice and its expression.

  11. Identification of Antigenic Proteins of the Nosocomial Pathogen Klebsiella pneumoniae

    Science.gov (United States)

    Hoppe, Sebastian; Bier, Frank F.; von Nickisch-Rosenegk, Markus

    2014-01-01

    The continuous expansion of nosocomial infections around the globe has become a precarious situation. Key challenges include mounting dissemination of multiple resistances to antibiotics, the easy transmission and the growing mortality rates of hospital-acquired bacterial diseases. Thus, new ways to rapidly detect these infections are vital. Consequently, researchers around the globe pursue innovative approaches for point-of-care devices. In many cases the specific interaction of an antigen and a corresponding antibody is pivotal. However, the knowledge about suitable antigens is lacking. The aim of this study was to identify novel antigens as specific diagnostic markers. Additionally, these proteins might be aptly used for the generation of vaccines to improve current treatment options. Hence, a cDNA-based expression library was constructed and screened via microarrays to detect novel antigens of Klebsiella pneumoniae, a prominent agent of nosocomial infections well-known for its extensive antibiotics resistance, especially by extended-spectrum beta-lactamases (ESBL). After screening 1536 clones, 14 previously unknown immunogenic proteins were identified. Subsequently, each protein was expressed in full-length and its immunodominant character examined by ELISA and microarray analyses. Consequently, six proteins were selected for epitope mapping and three thereof possessed linear epitopes. After specificity analysis, homology survey and 3d structural modelling, one epitope sequence GAVVALSTTFA of KPN_00363, an ion channel protein, was identified harboring specificity for K. pneumoniae. The remaining epitopes showed ambiguous results regarding the specificity for K. pneumoniae. The approach adopted herein has been successfully utilized to discover novel antigens of Campylobacter jejuni and Salmonella enterica antigens before. Now, we have transferred this knowledge to the key nosocomial agent, K. pneumoniae. By identifying several novel antigens and their linear

  12. Concepts and applications for influenza antigenic cartography

    Science.gov (United States)

    Cai, Zhipeng; Zhang, Tong; Wan, Xiu-Feng

    2011-01-01

    Influenza antigenic cartography projects influenza antigens into a two or three dimensional map based on immunological datasets, such as hemagglutination inhibition and microneutralization assays. A robust antigenic cartography can facilitate influenza vaccine strain selection since the antigenic map can simplify data interpretation through intuitive antigenic map. However, antigenic cartography construction is not trivial due to the challenging features embedded in the immunological data, such as data incompleteness, high noises, and low reactors. To overcome these challenges, we developed a computational method, temporal Matrix Completion-Multidimensional Scaling (MC-MDS), by adapting the low rank MC concept from the movie recommendation system in Netflix and the MDS method from geographic cartography construction. The application on H3N2 and 2009 pandemic H1N1 influenza A viruses demonstrates that temporal MC-MDS is effective and efficient in constructing influenza antigenic cartography. The web sever is available at http://sysbio.cvm.msstate.edu/AntigenMap. PMID:21761589

  13. Collaboration Takes Center Stage: Interactive Teaching through a Schoolwide Focus on the Performing Arts Leads to Dramatic Improvements in Learning

    Science.gov (United States)

    Williamson, Jeff; Zimmerman, Diane

    2009-01-01

    In the Old Adobe Union School District in Petaluma, California, the school staff's goal is to assure that all teachers make the fundamental shift from teacher-centric to learner-centric thinking. For them, this is what distinguishes great teachers from good teachers. They believe this level of expertise takes years to develop and that schools play…

  14. A Study of Effect of Dramatic Activities on Improving English Communicative Speaking Skill of Grade 11th Students

    Science.gov (United States)

    Iamsaard, Prisana; Kerdpol, Sakon

    2015-01-01

    This paper aimed to reexamine the current EFL communicative speaking skill in high school level in Thailand due to the coming of the entry to ASEAN at the end of the year 2015. Thai students need to be well prepared for workforce in the future since English is used as the working language in ASEAN. The purposes of this paper were to study the…

  15. Gallium arsenide exposure impairs processing of particulate antigen by macrophages: modification of the antigen reverses the functional defect.

    Science.gov (United States)

    Hartmann, Constance B; McCoy, Kathleen L

    2004-06-11

    Gallium arsenide (GaAs), a semiconductor used in the electronics industry, causes systemic immunosuppression in animals. The chemical's impact on macrophages to process the particulate antigen, sheep red blood cells (SRBC), for a T cell response in culture was examined after in vivo exposure of mice. GaAs-exposed splenic macrophages were defective in activating SRBC-primed lymph node T cells that could not be attributed to impaired phagocytosis. Modified forms of SRBC were generated to examine the compromised function of GaAs-exposed macrophages. SRBC were fixed to maintain their particulate nature and subsequently delipidated with detergent. Delipidation of intact SRBC was insufficient to restore normal antigen processing in GaAs-exposed macrophages. However, chemically exposed cells efficiently processed soluble sheep proteins. These findings suggest that the problem may lie in the release of sequestered sheep protein antigens, which then could be effectively cleaved to peptides. Furthermore, opsonization of SRBC with IgG compensated for the macrophage processing defect. The influence of signal transduction and phagocytosis via Fcgamma receptors on improved antigen processing could be dissociated. Immobilized anti-Fcgamma receptor antibody activated macrophages to secrete a chemokine, but did not enhance processing of unmodified SRBC by GaAs-exposed macrophages. Restoration of normal processing of particulate SRBC by chemically exposed macrophages involved phagocytosis through Fcgamma receptors. Hence, initial immune responses may be very sensitive to GaAs exposure, and the chemical's immunosuppression may be averted by opsonized particulate antigens.

  16. Identification of Antigenic Proteins from Lichtheimia corymbifera for Farmer’s Lung Disease Diagnosis

    Science.gov (United States)

    Rognon, Bénédicte; Barrera, Coralie; Monod, Michel; Valot, Benoit; Roussel, Sandrine; Quadroni, Manfredo; Jouneau, Stephane; Court-Fortune, Isabelle; Caillaud, Denis; Fellrath, Jean-Marc; Dalphin, Jean-Charles; Reboux, Gabriel; Millon, Laurence

    2016-01-01

    The use of recombinant antigens has been shown to improve both the sensitivity and the standardization of the serological diagnosis of Farmer’s lung disease (FLD). The aim of this study was to complete the panel of recombinant antigens available for FLD serodiagnosis with antigens of Lichtheimia corymbifera, known to be involved in FLD. L. corymbifera proteins were thus separated by 2D electrophoresis and subjected to western blotting with sera from 7 patients with FLD and 9 healthy exposed controls (HEC). FLD-associated immunoreactive proteins were identified by mass spectrometry based on a protein database specifically created for this study and subsequently produced as recombinant antigens. The ability of recombinant antigens to discriminate patients with FLD from controls was assessed by ELISA performed with sera from FLD patients (n = 41) and controls (n = 43) recruited from five university hospital pneumology departments of France and Switzerland. Forty-one FLD-associated immunoreactive proteins from L. corymbifera were identified. Six of them were produced as recombinant antigens. With a sensitivity and specificity of 81.4 and 77.3% respectively, dihydrolipoyl dehydrogenase was the most effective antigen for discriminating FLD patients from HEC. ELISA performed with the putative proteasome subunit alpha type as an antigen was especially specific (88.6%) and could thus be used for FLD confirmation. The production of recombinant antigens from L. corymbifera represents an additional step towards the development of a standardized ELISA kit for FLD diagnosis. PMID:27490813

  17. THE LYMPH SELF ANTIGEN REPERTOIRE

    Directory of Open Access Journals (Sweden)

    Laura eSantambrogio

    2013-12-01

    Full Text Available The lymphatic fluid originates from the interstitial fluid which bathes every parenchymal organ and reflects the omic composition of the tissue from which it originates in its physiological or pathological signature. Several recent proteomic analyses have mapped the proteome-degradome and peptidome of this immunologically relevant fluid pointing to the lymph as an important source of tissue-derived self-antigens. A vast array of lymph-circulating peptides have been mapped deriving from a variety of processing pathways including caspases, cathepsins, MMPs, ADAMs, kallikreins, calpains and granzymes, among others. These self peptides can be directly loaded on circulatory dendritic cells and expand the self-antigenic repertoire available for central and peripheral tolerance.

  18. Dramatic role of critical current anisotropy on flux avalanches in MgB2 films.

    Science.gov (United States)

    Albrecht, J; Matveev, A T; Strempfer, J; Habermeier, H-U; Shantsev, D V; Galperin, Y M; Johansen, T H

    2007-03-16

    Anisotropic penetration of magnetic flux in MgB(2) films grown on vicinal sapphire substrates is investigated using magneto-optical imaging. Regular penetration above 10 K proceeds more easily along the substrate surface steps, the anisotropy of the critical current being 6%. At lower temperatures the penetration occurs via abrupt dendritic avalanches that preferentially propagate perpendicular to the surface steps. This inverse anisotropy in the penetration pattern becomes dramatic very close to 10 K where all flux avalanches propagate in the strongest pinning direction. The observed behavior is fully explained using a thermomagnetic model of the dendritic instability.

  19. Dramatic changes in the magnetic coupling mechanism for La-doped CaMnO3.

    Science.gov (United States)

    Granado, E; Moreno, N O; Martinho, H; García, A; Sanjurjo, J A; Torriani, I; Rettori, C; Neumeier, J J; Oseroff, S B

    2001-06-01

    The exchange interactions in polycrystalline samples of Ca1-xLaxMnO3 (0.00< or =x< or =0.05) are studied by means of Raman scattering and electron paramagnetic resonance. Dramatic reductions in the spin-phonon interactions and magnetic correlations are observed for La doping levels as small as approximately 2%-3%. These results show that the charge carriers play an important role in the overall exchange coupling in the electron-doped manganites, even at very low doping levels.

  20. USUAL ERRATIC PHENOMENON AND DRAMATIC OUTCOME A CASE REPORT OF PHENYTOIN TOXICITY

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    Ketan L

    2014-11-01

    Full Text Available Phenytoin is still one of the most commonly used antiepileptic drugs in clinical practice around the globe. It has a range of familiar prejudicious and side effects, which have been reported formerly including ataxia, dizziness, visual disturbance, nystagmus, diplopia and cognitive dysfunctions amongst others. Here we are reporting a rare case of phenytoin toxicity presenting dramatically as a behavioural disorder resulting from underlying primary adverse effects of phenytoin, which were clinically overlooked. Discontinuation of phenytoin resulted in remission of side effects as well as the secondary behavioural manifestations.

  1. Dramatic Response of a Case ofRecurrent Basal Cell Carcinoma toSystemic Chemotherapy

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    Mohammad Mohammadianpanah

    2010-10-01

    Full Text Available Basal cell carcinoma (BCC is the most common cancer among humans, and the standard treatment is surgery. Other modalities are reserved as a second line of treatment. Topical chemotherapy may be used in primary BCC. Systemic chemotherapy has no role in the primary treatment of BCC, although it may be efficacious in metastatic cases. We report the case of a patient with persistent recurrent BCC following multiple surgeries and radiotherapy, who achieved a dramatic response with a cisplatinand 5-flourouracil chemotherapy regimen.

  2. Gorham-Stout Disease of the Skull Base With Hearing Loss: Dramatic Recovery and Antiangiogenic Therapy.

    Science.gov (United States)

    Nozawa, Akifumi; Ozeki, Michio; Kuze, Bunya; Asano, Takahiko; Matsuoka, Kentaro; Fukao, Toshiyuki

    2016-05-01

    Gorham-Stout disease (GSD) is a rare disorder of unknown etiology. We present a 6-year-old male with GSD involving the skull base who presented with recurrent cerebrospinal fluid (CSF) rhinorrhea, severe hearing loss, and facial palsy secondary to cerebellar herniation into the internal auditory canal. After 2 months of treatment with pegylated interferon (IFN) α-2b (50 μg/week), his hearing recovered dramatically. Two years later, new bone formation appeared radiologically and IFN was switched to sirolimus. One year after the switch, CSF rhinorrhea disappeared. Antiangiogenic therapy might inhibit proliferation of vascular endothelial cells in osteolytic lesions and lead to new bone formation.

  3. Popular culture and romantic sensibility: Mário de Andrade's dramatic dances

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    Maria Laura Viveiros de Castro Cavalcanti

    2006-01-01

    Full Text Available The text examines the notion of dramatic dances in the work of the Brazilian modernist writer Mário de Andrade (1893-1945 and investigates the reasons bumba-meu-boi (the ox merriment, or ox-dance - a widespread and popular Brazilian festivity - was so extremely valued by the author. It analyzes the connections found in the use of an ethnographic perspective, a romantic view of popular culture, and the pursuit of authenticity in the construction of aesthetical forms by andradian modernism.

  4. Bacterial phospholipide antigens and their taxonomic significance.

    Science.gov (United States)

    Karalnik, B V; Razbash, M P; Akhmetova, E A

    1981-01-01

    The investigation of interrelationships between the phospholipides of various microorganisms (33 strains of corynebacteria, mycobacteria and staphylococci) using crossed antibody neutralization reactions with phospholipide antigenic erythrocyte diagnostic was used for the assessment of the degree of antigenic propinquity and antigenic differences between the phospholipides of bacteria of the same species, genus, and of different genera. The role of the determinants of the corresponding (their own) and "foreign" genera in the antigenic differences between the phospholipides of the microorganisms investigated was established. On the basis of the results obtained the conclusion has been drawn that the method of assessment of antigenic interrelationships between phospholipides can be used for the study of some taxonomic problems.

  5. [HLA antigens in juvenile rheumatoid arthritis].

    Science.gov (United States)

    Rumba, I V; Sochnev, A M; Kukaĭne, E M; Burshteĭn, A M; Benevolenskaia, L I

    1990-01-01

    Antigens of I class HLA system (locus A and B) were investigated in 67 patients of Latvian nationality suffering from juvenile rheumatoid arthritis (JRA). Associations of HLA antigens with juvenile rheumatoid arthritis partially coincided with the ones revealed earlier. Typing established an increased incidence of antigen B27 (p less than 0.01) and gaplotype A2, B40 (p less than 0.01). Antigen B15 possessed a protective action with respect to JRA. Interlocus combinations demonstrated a closer association with the disease than a single antigen. The authors also revealed markers of various clinico-anatomical variants of JRA.

  6. Stable solid-phase Rh antigen.

    Science.gov (United States)

    Yared, M A; Moise, K J; Rodkey, L S

    1997-12-01

    Numerous investigators have attempted to isolate the Rh antigens in a stable, immunologically reactive form since the discovery of the Rh system over 56 years ago. We report here a successful and reproducible approach to solubilizing and adsorbing the human Rh antigen(s) to a solid-phase matrix in an antigenically active form. Similar results were obtained with rabbit A/D/F red blood cell antigens. The antigen preparation was made by dissolution of the red blood cell membrane lipid followed by fragmentation of the residual cytoskeleton in an EDTA solution at low ionic strength. The antigenic activity of the soluble preparations was labile in standard buffers but was stable in zwitterionic buffers for extended periods of time. Further studies showed that the antigenic activity of these preparations was enhanced, as was their affinity for plastic surfaces, in the presence of acidic zwitterionic buffers. Adherence to plastic surfaces at low pH maintained antigenic reactivity and specificity for antibody was retained. The data show that this approach yields a stable form of antigenically active human Rh D antigen that could be used in a red blood cell-free assay for quantitative analysis of Rh D antibody and for Rh D antibody immunoadsorption and purification.

  7. Common antigens between hydatid cyst and cancers

    Directory of Open Access Journals (Sweden)

    Shima Daneshpour

    2016-01-01

    Full Text Available Background: Different research groups reported a negative correlation between cancers and parasitical infections. As an example, the prevalence of a hydatid cyst among patients with cancer was significantly lower than its prevalence among normal population. Tn antigens exist both in cancer and hydatid cyst. This common antigen may be involved in the effect of parasite on cancer growth. So in this work, common antigens between hydatid cyst and cancers have been investigated. Materials and Methods: Different hydatid cyst antigens including hydatid fluid, laminated and germinal layer antigens, and excretory secretory antigens of protoscolices were run in SDS PAGE and transferred to NCP paper. In western immunoblotting, those antigens were probed with sera of patients with different cancer and also sera of non-cancer patients. Also, cross reaction among excretory secretory products of cancer cells and antisera raised against different hydatid cyst antigen was investigated. Results: In western immunoblotting, antisera raised against laminated and germinal layers of hydatid cyst reacted with excretory secretory products of cancer cells. Also, a reaction was detected between hydatid cyst antigens and sera of patients with some cancers. Conclusion: Results of this work emphasize existence of common antigens between hydatid cyst and cancers. More investigation about these common antigens is recommended.

  8. Common antigens between hydatid cyst and cancers

    Science.gov (United States)

    Daneshpour, Shima; Bahadoran, Mehran; Hejazi, Seyed Hossein; Eskandarian, Abas Ali; Mahmoudzadeh, Mehdi; Darani, Hossein Yousofi

    2016-01-01

    Background: Different research groups reported a negative correlation between cancers and parasitical infections. As an example, the prevalence of a hydatid cyst among patients with cancer was significantly lower than its prevalence among normal population. Tn antigens exist both in cancer and hydatid cyst. This common antigen may be involved in the effect of parasite on cancer growth. So in this work, common antigens between hydatid cyst and cancers have been investigated. Materials and Methods: Different hydatid cyst antigens including hydatid fluid, laminated and germinal layer antigens, and excretory secretory antigens of protoscolices were run in SDS PAGE and transferred to NCP paper. In western immunoblotting, those antigens were probed with sera of patients with different cancer and also sera of non-cancer patients. Also, cross reaction among excretory secretory products of cancer cells and antisera raised against different hydatid cyst antigen was investigated. Results: In western immunoblotting, antisera raised against laminated and germinal layers of hydatid cyst reacted with excretory secretory products of cancer cells. Also, a reaction was detected between hydatid cyst antigens and sera of patients with some cancers. Conclusion: Results of this work emphasize existence of common antigens between hydatid cyst and cancers. More investigation about these common antigens is recommended. PMID:26962511

  9. A dramatic increase of C1q protein in the CNS during normal aging.

    Science.gov (United States)

    Stephan, Alexander H; Madison, Daniel V; Mateos, José María; Fraser, Deborah A; Lovelett, Emilie A; Coutellier, Laurence; Kim, Leo; Tsai, Hui-Hsin; Huang, Eric J; Rowitch, David H; Berns, Dominic S; Tenner, Andrea J; Shamloo, Mehrdad; Barres, Ben A

    2013-08-14

    The decline of cognitive function has emerged as one of the greatest health threats of old age. Age-related cognitive decline is caused by an impacted neuronal circuitry, yet the molecular mechanisms responsible are unknown. C1q, the initiating protein of the classical complement cascade and powerful effector of the peripheral immune response, mediates synapse elimination in the developing CNS. Here we show that C1q protein levels dramatically increase in the normal aging mouse and human brain, by as much as 300-fold. This increase was predominantly localized in close proximity to synapses and occurred earliest and most dramatically in certain regions of the brain, including some but not all regions known to be selectively vulnerable in neurodegenerative diseases, i.e., the hippocampus, substantia nigra, and piriform cortex. C1q-deficient mice exhibited enhanced synaptic plasticity in the adult and reorganization of the circuitry in the aging hippocampal dentate gyrus. Moreover, aged C1q-deficient mice exhibited significantly less cognitive and memory decline in certain hippocampus-dependent behavior tests compared with their wild-type littermates. Unlike in the developing CNS, the complement cascade effector C3 was only present at very low levels in the adult and aging brain. In addition, the aging-dependent effect of C1q on the hippocampal circuitry was independent of C3 and unaccompanied by detectable synapse loss, providing evidence for a novel, complement- and synapse elimination-independent role for C1q in CNS aging.

  10. Robert Browning’s Dramatic Monologue as a Medium of Intransigence

    Directory of Open Access Journals (Sweden)

    Sintija Čuljat

    2012-12-01

    Full Text Available Probing the dramatic monologue mould of Robert Browning (1812-1899 has maintained a long tradition of portraying this poet as an experimenter and pursuer of the Victorian representation de-norming process. Browning’s narrative verse employs ambiguation through syntactic rendition of his dramatic personae who voice their minds beyond the restraints of dialogic turn-taking and divulge their impulses through verbal dominance. Browning’s bicentenary seems a most auspicious moment to creatively explore the tenacity of his discordant narrative vein in literary translation. Browning’s fixation on engendering a poetic form that would fully sustain the self-projecting techniques of his protagonists resulted in the employment of narrative verse whose dialogic nature is undermined and embedded in his creations’ monologues. The poet utilizes innuendoes which originate not only from the pool of poetic references but also from the syntactic realizations disclosing a disparity between the speakers’ intentions and their verbal acts. Their interlocutors are being gradually drawn into a puzzling locutionary display.

  11. Mosquito Passage Dramatically Changes var Gene Expression in Controlled Human Plasmodium falciparum Infections.

    Science.gov (United States)

    Bachmann, Anna; Petter, Michaela; Krumkamp, Ralf; Esen, Meral; Held, Jana; Scholz, Judith A M; Li, Tao; Sim, B Kim Lee; Hoffman, Stephen L; Kremsner, Peter G; Mordmüller, Benjamin; Duffy, Michael F; Tannich, Egbert

    2016-04-01

    Virulence of the most deadly malaria parasite Plasmodium falciparum is linked to the variant surface antigen PfEMP1, which is encoded by about 60 var genes per parasite genome. Although the expression of particular variants has been associated with different clinical outcomes, little is known about var gene expression at the onset of infection. By analyzing controlled human malaria infections via quantitative real-time PCR, we show that parasite populations from 18 volunteers expressed virtually identical transcript patterns that were dominated by the subtelomeric var gene group B and, to a lesser extent, group A. Furthermore, major changes in composition and frequency of var gene transcripts were detected between the parental parasite culture that was used to infect mosquitoes and Plasmodia recovered from infected volunteers, suggesting that P. falciparum resets its var gene expression during mosquito passage and starts with the broad expression of a specific subset of var genes when entering the human blood phase.

  12. Stabilizing Cloud Feedback Dramatically Expands the Habitable Zone of Tidally Locked Planets

    CERN Document Server

    Yang, Jun; Abbot, Dorian S

    2013-01-01

    The habitable zone (HZ) is the circumstellar region where a planet can sustain surface liquid water. Searching for terrestrial planets in the HZ of nearby stars is the stated goal of ongoing and planned extrasolar planet surveys. Previous estimates of the inner edge of the HZ were based on one-dimensional radiative-convective models. The most serious limitation of these models is the inability to predict cloud behavior. Here we use global climate models with sophisticated cloud schemes to show that due to a stabilizing cloud feedback, tidally locked planets can be habitable at twice the stellar flux found by previous studies. This dramatically expands the HZ and roughly doubles the frequency of habitable planets orbiting red dwarf stars. At high stellar flux, strong convection produces thick water clouds near the substellar location that greatly increase the planetary albedo and reduce surface temperatures. Higher insolation produces stronger substellar convection and therefore higher albedo, making this phen...

  13. Publications on Peripheral Nerve Injuries during World War I: A Dramatic Increase in Knowledge.

    Science.gov (United States)

    Koehler, Peter J

    2016-01-01

    Publications from French (Jules Tinel and Chiriachitza Athanassio-Bénisty), English (James Purves-Stewart, Arthur Henry Evans and Hartley Sidney Carter), German (Otfrid Foerster and Hermann Oppenheim) and American (Charles Harrison Frazier and Byron Stookey) physicians from both sides of the front during World War I (WWI) contributed to a dramatic increase in knowledge about peripheral nerve injuries. Silas Weir Mitchell's original experience with respect to these injuries, and particularly causalgia, during the American Civil War was further expanded in Europe during WWI. Following the translation of one of his books, he was referred to mainly by French physicians. During WWI, several French books were in turn translated into English, which influenced American physicians, as was observed in the case of Byron Stookey. The establishment of neurological centres played an important role in the concentration of experience and knowledge. Several eponyms originated during this period (including the Hoffmann-Tinel sign and the Froment sign). Electrodiagnostic tools were increasingly used.

  14. Selections of reality: applying Burke's dramatism to a harm reduction program.

    Science.gov (United States)

    Järvinen, Margaretha; Miller, Gale

    2014-09-01

    Kenneth Burke's dramatistic perspective is applied to accounts told by staff members working in methadone maintenance treatment centres in Copenhagen, Denmark. As a harm reduction strategy, methadone maintenance is designed to reduce the costs and dangers of chronic long-term drug use by providing substitution (methadone) treatment to users. Burke's dramatistic perspective calls attention to the recurring relationships among rhetorical elements within accounts of social reality. The elements form a pentad: scene, purpose, agent, agency and acts. Our analysis examines how the ideal of governmentality is constructed by staff members to justify and criticize the operations of the Copenhagen methadone maintenance program. For Burke, social criticism involves rearranging pentadic elements to produce new meanings and justify alternative actions. We discuss how Burke's perspective might be developed by sociologists as a critical dramatism of social policies and programs.

  15. On the potentially dramatic history of the super-Earth rho 55 Cancri e

    CERN Document Server

    Hansen, Brad

    2015-01-01

    We demonstrate that tidal evolution of the inner planet (`e') of the system orbiting the star rho 55 Cancri could have led to passage through two secular resonances with other planets in the system. The consequence of this evolution is excitation of both the planetary eccentricity and inclination relative to the original orbital plane. The large mass ratio between the innermost planet and the others means that these excitations can be of substantial amplitude and can have dramatic consequences for the system organisation. Such evolution can potentially explain the large observed mutual inclination between the innermost and outermost planets in the system, and implies that tidal heating could have substantially modified the structure of planet e, and possibly reduced its mass by Roche lobe overflow. Similar inner secular resonances may be found in many multiple planet systems and suggest that many of the innermost planets in these systems could have suffered similar evolutions.

  16. On the potentially dramatic history of the super-Earth ρ 55 Cancri e

    Science.gov (United States)

    Hansen, Bradley M. S.; Zink, Jonathon

    2015-07-01

    We demonstrate that tidal evolution of the inner planet (`e') of the system orbiting the star ρ 55 Cancri could have led to passage through two secular resonances with other planets in the system. The consequence of this evolution is excitation of both the planetary eccentricity and inclination relative to the original orbital plane. The large mass ratio between the innermost planet and the others means that these excitations can be of substantial amplitude and can have dramatic consequences for the system organization. Such evolution can potentially explain the large observed mutual inclination between the innermost and outermost planets in the system, and implies that tidal heating could have substantially modified the structure of planet e, and possibly reduced its mass by Roche lobe overflow. Similar inner secular resonances may be found in many multiple planet systems and suggest that many of the innermost planets in these systems could have suffered similar evolutions.

  17. Polypeptone induces dramatic cell lysis in ura4 deletion mutants of fission yeast.

    Directory of Open Access Journals (Sweden)

    Yuzy Matsuo

    Full Text Available Polypeptone is widely excluded from Schizosaccharomyces pombe growth medium. However, the reasons why polypeptone should be avoided have not been documented. Polypeptone dramatically induced cell lysis in the ura4 deletion mutant when cells approached the stationary growth phase, and this phenotype was suppressed by supplementation of uracil. To determine the specificity of this cell lysis phenotype, we created deletion mutants of other genes involved in de novo biosynthesis of uridine monophosphate (ura1, ura2, ura3, and ura5. Cell lysis was not observed in these gene deletion mutants. In addition, concomitant disruption of ura1, ura2, ura3, or ura5 in the ura4 deletion mutant suppressed cell lysis, indicating that cell lysis induced by polypeptone is specific to the ura4 deletion mutant. Furthermore, cell lysis was also suppressed when the gene involved in coenzyme Q biosynthesis was deleted. This is likely because Ura3 requires coenzyme Q for its activity. The ura4 deletion mutant was sensitive to zymolyase, which mainly degrades (1,3-beta-D glucan, when grown in the presence of polypeptone, and cell lysis was suppressed by the osmotic stabiliser, sorbitol. Finally, the induction of cell lysis in the ura4 deletion mutant was due to the accumulation of orotidine-5-monophosphate. Cell wall integrity was dramatically impaired in the ura4 deletion mutant when grown in the presence of polypeptone. Because ura4 is widely used as a selection marker in S. pombe, caution needs to be taken when evaluating phenotypes of ura4 mutants.

  18. Beech leaf colonization by the endophyte Apiognomonia errabunda dramatically depends on light exposure and climatic conditions.

    Science.gov (United States)

    Bahnweg, G; Heller, W; Stich, S; Knappe, C; Betz, G; Heerdt, C; Kehr, R D; Ernst, D; Langebartels, C; Nunn, A J; Rothenburger, J; Schubert, R; Wallis, P; Müller-Starck, G; Werner, H; Matyssek, R; Sandermann Jr, H

    2005-11-01

    Ozone and light effects on endophytic colonization by Apiognomonia errabunda of adult beech trees (Fagus sylvatica) and their putative mediation by internal defence compounds were studied at the Kranzberg Forest free-air ozone fumigation site. A. errabunda colonization was quantified by "real-time PCR" (QPCR). A. errabunda-specific primers allowed detection without interference by DNA from European beech and several species of common genera of plant pathogenic fungi, such as Mycosphaerella, Alternaria, Botrytis, and Fusarium. Colonization levels of sun and shade leaves of European beech trees exposed either to ambient or twice ambient ozone regimes were determined. Colonization was significantly higher in shade compared to sun leaves. Ozone exhibited a marginally inhibitory effect on fungal colonization only in young leaves in 2002. The hot and dry summer of 2003 reduced fungal colonization dramatically, being more pronounced than ozone treatment or sun exposure. Levels of soluble and cell wall-bound phenolic compounds were approximately twice as high in sun than in shade leaves. Acylated flavonol 3- O-glycosides with putatively high UV-B shielding effect were very low in shade canopy leaves. Ozone had only a minor influence on secondary metabolites in sun leaves. It slightly increased kaempferol 3- O-glucoside levels exclusively in shade leaves. The frequently prominent hydroxycinnamic acid derivative, chlorogenic acid, was tested for its growth inhibiting activity against Apiognomonia and showed an IC50 of approximately 8 mM. Appearance of Apiognomonia-related necroses strongly correlated with the occurrence of the stress metabolite, 3,3',4,4'-tetramethoxybiphenyl. Infection success of Apiognomonia was highly dependent on light exposure, presumably affected by the endogenous levels of constitutive phenolic compounds. Ozone exerted only minor modulating effects, whereas climatic factors, such as pronounced heat periods and drought, were dramatically overriding.

  19. BIOCHEMICAL STUDIES ON SO-CALLED SYPHILIS ANTIGEN.

    Science.gov (United States)

    Noguchi, H; Bronfenbrenner, J

    1911-01-01

    of tissue is very variable. (c) Substances Soluble in Ether, Alcohol, and Aceton.-In this group are found varying amounts of fatty acids, both saturated and unsaturated, some neutral fats, cholesterin and many unidentified lipoidal bodies. This group causes either hemolysis or inhibition, of hemolysis. In other words, it is anticomplementary as well as hemolytic in the majority of preparations. At the same time, in some preparations it is, to a certain extent, antigenic. This great variation in the amounts of these substances in given extracts renders their presence in the antigen preparation undesirable. It is not denied, however, that, when added in adequate quantities, some of these substances may improve the activity of the antigenic lipoids. (d) Substances Insoluble in Aceton.-This group of substances consists of phosphatids. The best known among them is, of course, lecithin. Besides lecithin, however, there must be various other phosphatids present in this fraction. It will be noticed that the precipitate formed by mixing the ethereal solution with aceton contains a certain amount of lipoids insoluble in ether as well as in alcohol. Before the fractionation in aceton, all lipoids were soluble in ether or ethyl alcohol. Further analytical work on the nature of the phosphatids contained in this fraction is necessary. This fraction, in general, is more constant in amount in the various liver extracts. Biologically considered, it is the most important. It is usually non-hemolytic, frequently anticomplementary, but much more strongly antigenic than the other fractions. The antigenic strength varies with different preparations, being almost absent in the extracts derived from fatty livers. An aceton insoluble fraction may be strongly antigenic without any other auxiliary effects, or may be accompanied by an anticomplementary property. This fraction does not cause the so-called non-specific reaction with an active human serum. For these reasons it is recommended (as

  20. Honokiol nanosuspensions: preparation, increased oral bioavailability and dramatically enhanced biodistribution in the cardio-cerebro-vascular system.

    Science.gov (United States)

    Han, Meihua; Yu, Xin; Guo, Yifei; Wang, Yanhong; Kuang, Haixue; Wang, Xiangtao

    2014-04-01

    Honokiol is a phytochemical component with multiple pharmacological activities, but Honokiol's wider use has been restricted by its poor solubility. Using bovine serum albumin and polyvinylpyrrolidone as stabilisers in a solvent precipitation-ultrasonication method, Honokiol nanosuspensions were prepared with a mean particle size of 116.2 nm (±2 nm), a zeta potential of -44.7 mV (±1.7 mV) and a high drug payload of 50.4 ± 0.6% (w/w). X-ray powder diffraction and differential scanning calorimetry indicated that Honokiol was in an amorphous state in the nanosuspensions, in contrast with bulk Honokiol powder. Honokiol was released faster in vitro from nanosuspensions with no burst release, and the highest 98% cumulative release was after 60 h. Honokiol nanosuspensions improved the oral bioavailability of Honokiol in in vivo studies in rats with a 3.94-fold Cmax and a 2.2-fold AUC(0-t). Remarkably, in contrast to oral administration, intraperitoneal administration of Honokiol nanosuspensions could dramatically alter the biodistribution of Honokiol, resulting in a much higher drug level and tissue bioavailability in the blood, heart and brain, benefitting the treatment of cardio-cerebro-vascular diseases.

  1. Antigenic structures stably expressed by recombinant TGEV-derived vectors.

    Science.gov (United States)

    Becares, Martina; Sanchez, Carlos M; Sola, Isabel; Enjuanes, Luis; Zuñiga, Sonia

    2014-09-01

    Coronaviruses (CoVs) are positive-stranded RNA viruses with potential as immunization vectors, expressing high levels of heterologous genes and eliciting both secretory and systemic immune responses. Nevertheless, its high recombination rate may result in the loss of the full-length foreign gene, limiting their use as vectors. Transmissible gastroenteritis virus (TGEV) was engineered to express porcine reproductive and respiratory syndrome virus (PRRSV) small protein domains, as a strategy to improve heterologous gene stability. After serial passage in tissue cultures, stable expression of small PRRSV protein antigenic domains was achieved. Therefore, size reduction of the heterologous genes inserted in CoV-derived vectors led to the stable expression of antigenic domains. Immunization of piglets with these TGEV vectors led to partial protection against a challenge with a virulent PRRSV strain, as immunized animals showed reduced clinical signs and lung damage. Further improvement of TGEV-derived vectors will require the engineering of vectors with decreased recombination rate.

  2. Human Leukocyte Antigen Diversity: A Southern African Perspective

    Directory of Open Access Journals (Sweden)

    Mqondisi Tshabalala

    2015-01-01

    Full Text Available Despite the increasingly well-documented evidence of high genetic, ethnic, and linguistic diversity amongst African populations, there is limited data on human leukocyte antigen (HLA diversity in these populations. HLA is part of the host defense mechanism mediated through antigen presentation to effector cells of the immune system. With the high disease burden in southern Africa, HLA diversity data is increasingly important in the design of population-specific vaccines and the improvement of transplantation therapeutic interventions. This review highlights the paucity of HLA diversity data amongst southern African populations and defines a need for information of this kind. This information will support disease association studies, provide guidance in vaccine design, and improve transplantation outcomes.

  3. ANTIGEN MG7 IN GASTRIC CANCER AND GASTRIC PRECANCEROUS LESIONS

    Institute of Scientific and Technical Information of China (English)

    郭冬丽; 宁佩芳; 袁媛

    2004-01-01

    Objective: To study the dynamic change and its diagnostic significance of MG7 expression in the process of gastric cancer development. Methods: The expression level of antigen MG7 was determined by immunohistochemistry method in 406 cases of gastric mucosa. The classification of intestinal metaplasia of gastric mucosa was determined by histochemistry method in 82 cases. Results: The positive rate of MG7 expression in normal gastric mucosa, intestinal metaplasia and dysplasia of gastric mucosa and gastric cancer were increased gradually (P<0.01). The positive rate of MG7 expression in superficial gastritis, atrophic gastritis and gastric cancer were increased on sequence (P<0.01). The positive rate of antigen MG7 expression in type Ⅲ intestinal metaplasia of gastric mucosa had significant difference,compared with that in type Ⅰ an Ⅱ intestinal metaplasia (P<0.05). Conclusion: MG7 antigen had close relationship with gastric cancer. Type Ⅲ intestinal metaplasia, atrophic gastritis and dysplasia should be followed up in order to improve the early detection of gastric cancer. MG7 antigen had great clinical value in the dynamic follow-up of gastric precursors.

  4. [Antigenic relationships between Debaryomyces strains (author's transl)].

    Science.gov (United States)

    Aksoycan, N

    1980-01-01

    The results of the agglutinations between homologous and heterologous Debaryomyces strains and their agglutinating sera are shown in table I. According to these findings, D. hansenii and D. marama are antigenically different from other Debaryomyces strains in this genus. In a previous study Aksoycan et al. have shown a common antigenic factor between D. hansenii, D. marama strains and Salmonella 0:7 antigen. This factor was not present in other six strains of Debaryomyces. These results also show that D. tamarii does not have any antigenic relationship with the other seven species of Debaryomyces in this genus.

  5. In Vitro Generation of Antigen-Specific T Cells from Induced Pluripotent Stem Cells of Antigen-Specific T Cell Origin.

    Science.gov (United States)

    Kaneko, Shin

    2016-01-01

    Induced pluripotent stem (iPS) cells derived from T lymphocyte (T-iPS cells) preserve the T cell receptor (TCR) α and β gene rearrangements identical to the original T cell clone. Re-differentiated CD8 single positive αβ T cells from the T-iPS cells exhibited antigen-specific cytotoxicity, improved proliferative response, and elongation of telomere indicating rejuvenation of antigen specific T cell immunity in vitro. To regenerate antigen specific cytotoxic T lymphocytes (CTL), first, we have optimized a method for reprogramming-resistant CD8 T cell clones into T-iPS cells by using sendaiviral vectors. Second, we have optimized stepwise differentiation methods for inducing hematopoietic progenitor cells, T cell progenitors, and functionally matured CD8 single positive CTL. These protocols provide useful in vitro tools and models both for research of antigen-specific T cell immunotherapy and for research of normal and pathological thymopoiesis.

  6. Blastogenic response of human lymphocytes to early antigen(s) of human cytomegalovirus.

    OpenAIRE

    Waner, J L; Kong, N; Biano, S

    1983-01-01

    The lymphocytes of asymptomatic, seropositive donors demonstrated blastogenic responses to early antigens of human cytomegalovirus whether or not antibodies to early antigens were detectable. The lymphocytes of six of nine patients with active cytomegalovirus infections gave stimulation indexes of greater than or equal to 2.00 with antigens of productively infected cells, whereas only two patients demonstrated comparable stimulation indexes with early antigens. Four patients with stimulation ...

  7. A computational framework for influenza antigenic cartography.

    Directory of Open Access Journals (Sweden)

    Zhipeng Cai

    Full Text Available Influenza viruses have been responsible for large losses of lives around the world and continue to present a great public health challenge. Antigenic characterization based on hemagglutination inhibition (HI assay is one of the routine procedures for influenza vaccine strain selection. However, HI assay is only a crude experiment reflecting the antigenic correlations among testing antigens (viruses and reference antisera (antibodies. Moreover, antigenic characterization is usually based on more than one HI dataset. The combination of multiple datasets results in an incomplete HI matrix with many unobserved entries. This paper proposes a new computational framework for constructing an influenza antigenic cartography from this incomplete matrix, which we refer to as Matrix Completion-Multidimensional Scaling (MC-MDS. In this approach, we first reconstruct the HI matrices with viruses and antibodies using low-rank matrix completion, and then generate the two-dimensional antigenic cartography using multidimensional scaling. Moreover, for influenza HI tables with herd immunity effect (such as those from Human influenza viruses, we propose a temporal model to reduce the inherent temporal bias of HI tables caused by herd immunity. By applying our method in HI datasets containing H3N2 influenza A viruses isolated from 1968 to 2003, we identified eleven clusters of antigenic variants, representing all major antigenic drift events in these 36 years. Our results showed that both the completed HI matrix and the antigenic cartography obtained via MC-MDS are useful in identifying influenza antigenic variants and thus can be used to facilitate influenza vaccine strain selection. The webserver is available at http://sysbio.cvm.msstate.edu/AntigenMap.

  8. A computational framework for influenza antigenic cartography.

    Science.gov (United States)

    Cai, Zhipeng; Zhang, Tong; Wan, Xiu-Feng

    2010-10-07

    Influenza viruses have been responsible for large losses of lives around the world and continue to present a great public health challenge. Antigenic characterization based on hemagglutination inhibition (HI) assay is one of the routine procedures for influenza vaccine strain selection. However, HI assay is only a crude experiment reflecting the antigenic correlations among testing antigens (viruses) and reference antisera (antibodies). Moreover, antigenic characterization is usually based on more than one HI dataset. The combination of multiple datasets results in an incomplete HI matrix with many unobserved entries. This paper proposes a new computational framework for constructing an influenza antigenic cartography from this incomplete matrix, which we refer to as Matrix Completion-Multidimensional Scaling (MC-MDS). In this approach, we first reconstruct the HI matrices with viruses and antibodies using low-rank matrix completion, and then generate the two-dimensional antigenic cartography using multidimensional scaling. Moreover, for influenza HI tables with herd immunity effect (such as those from Human influenza viruses), we propose a temporal model to reduce the inherent temporal bias of HI tables caused by herd immunity. By applying our method in HI datasets containing H3N2 influenza A viruses isolated from 1968 to 2003, we identified eleven clusters of antigenic variants, representing all major antigenic drift events in these 36 years. Our results showed that both the completed HI matrix and the antigenic cartography obtained via MC-MDS are useful in identifying influenza antigenic variants and thus can be used to facilitate influenza vaccine strain selection. The webserver is available at http://sysbio.cvm.msstate.edu/AntigenMap.

  9. Dramatic regression and bleeding of a duodenal GIST during preoperative imatinib therapy: case report and review

    Directory of Open Access Journals (Sweden)

    Schwandner Thilo

    2010-06-01

    Full Text Available Abstract Background Gastrointestinal stromal tumors (GISTs are the most common mesenchymal tumors of the digestive tract. The majority of GISTs is located in the stomach. Only 3-5% of GISTs are located in the duodenum associated with an increased risk of gastrointestinal bleeding as primary manifestation. With response rates of up to 90%, but complications like bleeding due to tumor necrosis in 3%, imatinib mesylate dramatically altered the pre- and postoperative therapy for GIST patients. Case presentation A 58-year-old female patient presented with acute upper gastrointestinal bleeding 2 weeks after a giant GIST of the duodenum had been diagnosed. Neoadjuvant imatinib therapy had been initiated to achieve a tumor downsizing prior to surgery. During emergency laparotomy a partial duodenopancreatectomy was performed to achieve a complete resection of the mass. Histology revealed a high-malignancy GIST infiltrating the duodenal wall. Adjuvant imatinib therapy was initiated. At follow-up (19 months the patient is still alive and healthy. Conclusion Giant GISTs of the duodenum are rare and - in contrast to other localizations - harbour a higher risk of serious bleeding as primary manifestation. Tumor necrosis and tumor bleeding are rare but typical adverse effects of imatinib therapy especially during treatment of high-malignancy GIST. In GIST patients with increased risk of tumor bleeding neoadjuvant imatinib therapy should thoroughly be performed during hospitalization. In cases of duodenal GIST primary surgery should be considered as treatment alternative.

  10. Combination of clopidogrel and everolimus dramatically reduced the development of transplant arteriosclerosis in murine aortic allografts.

    Science.gov (United States)

    Eckl, Sebastian; Heim, Christian; Abele-Ohl, Silke; Hoffmann, Julia; Ramsperger-Gleixner, Martina; Weyand, Michael; Ensminger, Stephan M

    2010-09-01

    Our group has shown that platelet inhibition with clopidogrel, an antagonist of the P2Y12 adenosine diphosphate receptor on platelets, reduced the formation of transplant arteriosclerosis. The aim of this study was to investigate whether a combination of cyclosporin or everolimus with clopidogrel has a beneficial effect on the development of transplant arteriosclerosis. Fully MHC mismatched C57Bl/6 (H2(b)) donor aortas were transplanted into CBA.J (H2(k)) recipients and mice received either clopidogrel alone (1 mg/kg/day) or in combination with cyclosporin (2 mg/kg/day) or everolimus (0.05 mg/kg/day). Grafts were analysed by histology and morphometry on day 30 after transplantation. In mice treated with clopidogrel alone, transplant arteriosclerosis was significantly reduced [intima proliferation 56 +/- 11% vs. 81 +/- 7% (control)/n = 7]. Daily application of everolimus reduced the development of transplant arteriosclerosis compared with untreated controls [intima proliferation of 29 +/- 9% vs. 81 +/- 7% (control)/n = 7]. Strikingly, combination of clopidogrel and everolimus almost abolished the formation of transplant arteriosclerosis [intima proliferation: 11 +/- 8% vs. 81 +/- 7% (control)/n = 7]. By contrast, combination of cyclosporin and clopidogrel compared with clopidogrel alone showed no additive effect. These results demonstrate that combination of platelet- and mammalian target of Rapamycin-inhibition can dramatically reduce the development of transplant arteriosclerosis.

  11. Zeolite molecular sieves have dramatic acid-base effects on enzymes in nonaqueous media.

    Science.gov (United States)

    Fontes, Nuno; Partridge, Johann; Halling, Peter J; Barreiros, Susana

    2002-02-05

    Zeolite molecular sieves very commonly are used as in situ drying agents in reaction mixtures of enzymes in nonaqueous media. They often affect enzyme behavior, and this has been interpreted in terms of altered hydration. Here, we show that zeolites can also have dramatic acid-base effects on enzymes in low water media, resulting from their cation-exchange ability. Initial rates of transesterification catalyzed by cross-linked crystals of subtilisin were compared in supercritical ethane, hexane, and acetonitrile with water activity fixed by pre-equilibration. Addition of zeolite NaA (4 A powder) still caused remarkable rate enhancements (up to 20-fold), despite the separate control of hydration. In the presence of excess of an alternative solid-state acid-base buffer, however, zeolite addition had no effect. The more commonly used Merck molecular sieves (type 3 A beads) had similar but somewhat smaller effects. All zeolites have ion-exchange ability and can exchange H+ for cations such as Na+ and K+. These exchanges will tend to affect the protonation state of acidic groups in the protein and, hence, enzymatic activity. Zeolites pre-equilibrated in aqueous suspensions of varying pH-pNa gave very different enzyme activities. Their differing basicities were demonstrated directly by equilibration with an indicator dissolved in toluene. The potential of zeolites as acid-base buffers for low-water media is discussed, and their ability to overcome pH memory is demonstrated.

  12. Papain-templated Cu nanoclusters: assaying and exhibiting dramatic antibacterial activity cooperating with H₂O₂.

    Science.gov (United States)

    Miao, Hong; Zhong, Dan; Zhou, Zinan; Yang, Xiaoming

    2015-12-07

    Herein, papain-functionalized Cu nanoclusters (CuNCs@Papain) were originally synthesized in aqueous solution together with a quantum yield of 14.3%, and showed obviously red fluorescence at 620 nm. Meanwhile, their corresponding fluorescence mechanism was fully elucidated by fluorescence spectroscopy, HR-TEM, FTIR spectroscopy, and XPS. Subsequently, the as-prepared CuNCs were employed as probes for detecting H2O2. Using CuNCs as probes, H2O2 was determined in the range from 1 μM to 50 μM based on a linear decrease of fluorescence intensity as well as a detection limit of 0.2 μM with a signal-to-noise ratio of 3. More significantly, it has been proved that CuNCs could convert H2O2 to ˙OH, which exhibited dramatic antibacterial activity. Both in vitro and in vivo experiments were performed to validate their antibacterial activity against Gram-positive/negative bacteria and actual wound infection, suggesting their potential for serving as one type of promising antibacterial material.

  13. STABILIZING CLOUD FEEDBACK DRAMATICALLY EXPANDS THE HABITABLE ZONE OF TIDALLY LOCKED PLANETS

    Energy Technology Data Exchange (ETDEWEB)

    Yang Jun; Abbot, Dorian S. [Department of the Geophysical Sciences, University of Chicago, 5734 South Ellis Avenue, Chicago, IL 60637 (United States); Cowan, Nicolas B., E-mail: abbot@uchicago.edu [Center for Interdisciplinary Exploration and Research in Astrophysics (CIERA) and Department of Physics and Astronomy, Northwestern University, 2131 Tech Drive, Evanston, IL 60208 (United States)

    2013-07-10

    The habitable zone (HZ) is the circumstellar region where a planet can sustain surface liquid water. Searching for terrestrial planets in the HZ of nearby stars is the stated goal of ongoing and planned extrasolar planet surveys. Previous estimates of the inner edge of the HZ were based on one-dimensional radiative-convective models. The most serious limitation of these models is the inability to predict cloud behavior. Here we use global climate models with sophisticated cloud schemes to show that due to a stabilizing cloud feedback, tidally locked planets can be habitable at twice the stellar flux found by previous studies. This dramatically expands the HZ and roughly doubles the frequency of habitable planets orbiting red dwarf stars. At high stellar flux, strong convection produces thick water clouds near the substellar location that greatly increase the planetary albedo and reduce surface temperatures. Higher insolation produces stronger substellar convection and therefore higher albedo, making this phenomenon a stabilizing climate feedback. Substellar clouds also effectively block outgoing radiation from the surface, reducing or even completely reversing the thermal emission contrast between dayside and nightside. The presence of substellar water clouds and the resulting clement surface conditions will therefore be detectable with the James Webb Space Telescope.

  14. Lipidomics reveals dramatic lipid compositional changes in the maturing postnatal lung

    Energy Technology Data Exchange (ETDEWEB)

    Dautel, Sydney E.; Kyle, Jennifer E.; Clair, Geremy CD; Sontag, Ryan L.; Weitz, Karl K.; Shukla, Anil K.; Nguyen, Son N.; Kim, Young-Mo; Zink, Erika M.; Luders, Teresa; Frevert, Charles; Gharib, Sina A.; Laskin, Julia; Carson, James P.; Metz, Thomas O.; Corley, Richard A.; Ansong, Charles K.

    2017-02-01

    Lung immaturity is a major cause of morbidity and mortality in premature infants. Understanding the molecular mechanisms driving normal lung development could provide insights on how to ameliorate disrupted development. While transcriptomic and proteomic analyses of normal lung development have been previously reported, characterization of changes in the lipidome is lacking. Lipids play significant roles in the lung, such as dipalmitoylcholine in pulmonary surfactant; however, many of the roles of specific lipid species in normal lung development, as well as in disease states, are not well defined. In this study, we used liquid chromatography-mass spectrometry (LC-MS/MS) to investigate the murine lipidome during normal postnatal lung development. Lipidomics analysis of lungs from post-natal day 7, day 14 and 6-8 week mice (adult) identified 928 unique lipids across 21 lipid subclasses, with dramatic alterations in the lipidome across developmental stages. Our data confirmed previously recognized aspects of post-natal lung development and revealed several insights, including in sphingolipid-mediated apoptosis, inflammation and energy storage/usage. Complementary proteomics, metabolomics and chemical imaging corroborated these observations. This multi-omic view provides a unique resource and deeper insight into normal pulmonary development.

  15. Regulatory Bodies: Dramatic Creativity, Control and the Commodity of Lady Audley's Secret

    Directory of Open Access Journals (Sweden)

    Kate Mattacks

    2009-04-01

    Full Text Available 'Lady Audley's Secret' resonates with a sense of theatricality grounded in the eponymous heroine's propensity for visual tactics to attract an audience. Repositioning the dramatic exchange between actress and audience within the domestic sphere sensitised the reader to the question of diagnosing morally degenerative artificiality whilst involving the reader in the complicit act of encouraging Lady Audley's performance through consumer demand. This complex relationship between consumerism, theatre and society saw Lady Audley's figure assume an iconic status, but little has been written on the creative interplay between the novel and the theatre itself. Beginning with the way in which aspiring actresses used Lady Audley as a model to display their histrionic variety, I argue that the theatre used her character to engage with the complex connections between drama and commodity culture. Her autophagy in favour of a false identity provided a model for actresses to visualise self-commodification whilst highlighting the tension between the material practices of the theatre and the materiality of commodity culture. The drive for regulation of the theatrical medium finds its locus in the licensing text/published acting edition of William E. Suter's 'Lady Audley's Secret' (1863. Here I move to show how Suter's adaptation functioned as a site where the state regulation of the theatre was explored and contested. These unauthorised images of Lady Audley's containment came to symbolise not only the regulatory processes of licensing and copyright, but also the creative exploitation of a commodity culture critiqued through the dehumanised form of Braddon's original heroine.

  16. Samuel Beckett's "Rockaby": dramatizing the plight of the solitary elderly at life's end.

    Science.gov (United States)

    Groninger, Hunter; Childress, Marcia Day

    2007-01-01

    Irish playwright Samuel Beckett's spare, compact, and provocative play Rockaby (1981) is a study in old age, isolation, and disengagement from life. In it, an elderly woman rocks in a chair while the audience hears a distant voice remembering her lifelong search for human contact or communion. The play dramatizes the woman's intense physical and psychological isolation and the last sputterings of her impulse to narrate. Such radical isolation may be a necessary precondition for a person relinquishing the narrating that Beckett equates with being, and surrendering unto death. Despite its apparent simplicity, the play powerfully explores the nature of aging in contemporary society, quality-of-life issues for the frail, solitary elderly in our communities and health-care institutions, and how the elderly prepare for life's end in a death-denying culture. Rockaby is thus a text that can help clinicians and other caregivers appreciate the predicament of solitary elderly persons nearing life's end and better understand how we all must manage one day the lonely, self-abnegating yet also paradoxically self-assertive act of dying.

  17. A poorly known high-latitude parasitoid wasp community: unexpected diversity and dramatic changes through time.

    Directory of Open Access Journals (Sweden)

    Jose Fernandez-Triana

    Full Text Available Climate change will have profound and unanticipated effects on species distributions. The pace and nature of this change is largely unstudied, especially for the most diverse elements of terrestrial communities--the arthropods--here we have only limited knowledge concerning the taxonomy and the ecology of these groups. Because Arctic ecosystems have already experienced significant increases in temperature over the past half century, shifts in community structure may already be in progress. Here we utilise collections of a particularly hyperdiverse insect group--parasitoid wasps (Hymenoptera; Braconidae; Microgastrinae--at Churchill, Manitoba, Canada in the early and mid-twentieth century to compare the composition of the contemporary community to that present 50-70 years ago. Morphological and DNA barcoding results revealed the presence of 79 species of microgastrine wasps in collections from Churchill, but we estimate that 20% of the local fauna awaits detection. Species composition and diversity between the two time periods differ significantly; species that were most common in historic collections were not found in contemporary collections and vice versa. Using barcodes we compared these collections to others from across North America; contemporary Churchill species are most affiliated with more south-western collections, while historic collections were more affiliated with eastern collections. The past five decades has clearly seen a dramatic change of species composition within the area studied coincident with rising temperature.

  18. Dramatic Expression in Opera, and Its Implications for Conversational Agents. Chapter 7

    Science.gov (United States)

    Johnson, W. Lewis

    2007-01-01

    This article has discussed principles, techniques, and methods of dramatic portrayal in opera, and their application to the development of embodied conversational agents. Investigations such as this complement studies of natural human behavior, and offer insights as to how to make such behavior understandable and interesting when adapted for use by embodied conversational agents. However, one should use caution in applying such lessons. The unique characteristics of computer-based media are still being identified and explored. In any case, one must always be careful about applying principles blindly to any artistic form. Such principles are post-hoc analysis of the intuitive skill of great artists; this was as true in Aristotle's day as it is today. We should not let structural principles stand in the way of injecting creativity into the design of ECAs. Opera at its best possesses an element of magic that is difficult to describe, much less analytically reconstruct. We can only hope to achieve a similar result with conversational agents.

  19. Systemic Lupus Erythematosus and Bullous Pemphigoid with Dramatic Response to Dapsone

    Science.gov (United States)

    Maggio, Maria Cristina; Corsello, Giovanni; Prinzi, Eugenia; Cimaz, Rolando

    2017-01-01

    Patient: Female, 11 Final Diagnosis: Bullous pemphigoid in systemic lupus erythematosus Symptoms: Bullous lupus • photosensitive rash • synovitis Medication:— Clinical Procedure: Pharmacological treatment Specialty: Rheumatology Objective: Unusual clinical course Background: Bullous pemphigoid is an autoimmune blistering disease, with relapses, isolated or associated with other autoimmune diseases such as systemic lupus erythematosus (SLE). Joint manifestations rapidly respond to small or moderate doses of corticosteroids, whereas skin manifestations usually respond to antimalarial drugs. Case Report: We describe the clinical case of an 11-year-old girl with SLE. She showed bullous skin lesions with arthralgia, mild proteinuria, resolved after steroid treatment. At the tapering of her prednisone dose, the patient had new skin lesions requiring an increased dose of prednisone. She started dapsone at the dosage of 1 mg/kg/day, maintaining low dose prednisone; this treatment was successfully followed by the dramatic disappearance of skin lesions and limb pain. Conclusions: Bullous skin lesions can represent the first clinical presentation of pediatric SLE and could influence the treatment and the outcome of these patients. This case showed an atypical course as both skin manifestations and arthritis promptly and persistently resolved with dapsone without the use of high-dose glucocorticoids. Only a few cases of patients with SLE associated with bullous pemphigoid have been reported in the literature, and very few in the pediatric population. PMID:28352068

  20. Dramatic variations in emergent wetland area in China's largest freshwater lake, Poyang Lake

    Science.gov (United States)

    Mei, Xuefei; Dai, Zhijun; Fagherazzi, Sergio; Chen, Jiyu

    2016-10-01

    Freshwater wetlands are important ecosystems experiencing rapid degradation around the world. As much as 64% of world's wetland area has been lost since 1900; the situation is even more serious in Asia, where land reclamation and anthropogenic modifications of rivers are increasing the rate of wetland disappearance. In this study, we provide a first complete estimation of daily Emergent Wetland Area (EWA) in Poyang Lake, China's largest freshwater lake, from 1955 to 2012. A wavelet analysis indicates a strong periodicity in the monthly EWA time series with two oscillations having a period of 12 and 60-72 months, respectively. A dramatic increase in mean annual EWA is detected since 2003, when the Three Gorges Dam (TGD) was completed, mainly due to the seasonal drying of 1078 km2 of wetlands in October. It is found that the timing of wetland emergence during the dry season has been anticipated of one month, from November to October, since the establishment of TGD. It is argued that a significant increase in wetland exposure and an observable shift in the seasonal timing of flooding and drying will seriously degrade the wetland system and threaten the endangered migratory birds that inhabit it unless effective countermeasures are implemented.

  1. Analysing the development of TV news programmes: from information to dramatization

    Directory of Open Access Journals (Sweden)

    Maribel Rodríguez Fidalgo, Ph.D.

    2010-01-01

    Full Text Available Abstract: The TV news programme is the backbone of all television networks, be they national, regional or local. These types of programmes have been changing over the time. The essence of the information is being modified and has adopted a new format. Based on these principles, this research analyses the evolution of the language used on the Spanish TV news programmes, from their origins until today. This research has been carried out in three different phases: late 1980s, the 1990s and recent years. These stages were thoroughly examined through surveys applied to representative samples of the population. The results showed that TV news programmes have been acquiring a changing narrative style throughout time: they began using an “objective” narrative, followed by a mediated type, and finally dramatized narrative which uses shocking visual content and aims to achieve audience’s sensibilization and identification with news’ protagonists. The spectacularization of information has become the identitary feature of the current TV news programmes as a response to the need of reaching higher audience ratings.

  2. Patterns and potential drivers of dramatic changes in Tibetan lakes, 1972-2010.

    Directory of Open Access Journals (Sweden)

    Yingkui Li

    Full Text Available Most glaciers in the Himalayas and the Tibetan Plateau are retreating, and glacier melt has been emphasized as the dominant driver for recent lake expansions on the Tibetan Plateau. By investigating detailed changes in lake extents and levels across the Tibetan Plateau from Landsat/ICESat data, we found a pattern of dramatic lake changes from 1970 to 2010 (especially after 2000 with a southwest-northeast transition from shrinking, to stable, to rapidly expanding. This pattern is in distinct contrast to the spatial characteristics of glacier retreat, suggesting limited influence of glacier melt on lake dynamics. The plateau-wide pattern of lake change is related to precipitation variation and consistent with the pattern of permafrost degradation induced by rising temperature. More than 79% of lakes we observed on the central-northern plateau (with continuous permafrost are rapidly expanding, even without glacial contributions, while lakes fed by retreating glaciers in southern regions (with isolated permafrost are relatively stable or shrinking. Our study shows the limited role of glacier melt and highlights the potentially important contribution of permafrost degradation in predicting future water availability in this region, where understanding these processes is of critical importance to drinking water, agriculture, and hydropower supply of densely populated areas in South and East Asia.

  3. Atmospheric drying as the main driver of dramatic glacier wastage in the southern Indian Ocean

    Science.gov (United States)

    Favier, V.; Verfaillie, D.; Berthier, E.; Menegoz, M.; Jomelli, V.; Kay, J. E.; Ducret, L.; Malbéteau, Y.; Brunstein, D.; Gallée, H.; Park, Y.-H.; Rinterknecht, V.

    2016-09-01

    The ongoing retreat of glaciers at southern sub-polar latitudes is particularly rapid and widespread. Akin to northern sub-polar latitudes, this retreat is generally assumed to be linked to warming. However, no long-term and well-constrained glacier modeling has ever been performed to confirm this hypothesis. Here, we model the Cook Ice Cap mass balance on the Kerguelen Islands (Southern Indian Ocean, 49°S) since the 1850s. We show that glacier wastage during the 2000s in the Kerguelen was among the most dramatic on Earth. We attribute 77% of the increasingly negative mass balance since the 1960s to atmospheric drying associated with a poleward shift of the mid-latitude storm track. Because precipitation modeling is very challenging for the current generation of climate models over the study area, models incorrectly simulate the climate drivers behind the recent glacier wastage in the Kerguelen. This suggests that future glacier wastage projections should be considered cautiously where changes in atmospheric circulation are expected.

  4. Dramatic Increases of Soil Microbial Functional Gene Diversity at the Treeline Ecotone of Changbai Mountain.

    Science.gov (United States)

    Shen, Congcong; Shi, Yu; Ni, Yingying; Deng, Ye; Van Nostrand, Joy D; He, Zhili; Zhou, Jizhong; Chu, Haiyan

    2016-01-01

    The elevational and latitudinal diversity patterns of microbial taxa have attracted great attention in the past decade. Recently, the distribution of functional attributes has been in the spotlight. Here, we report a study profiling soil microbial communities along an elevation gradient (500-2200 m) on Changbai Mountain. Using a comprehensive functional gene microarray (GeoChip 5.0), we found that microbial functional gene richness exhibited a dramatic increase at the treeline ecotone, but the bacterial taxonomic and phylogenetic diversity based on 16S rRNA gene sequencing did not exhibit such a similar trend. However, the β-diversity (compositional dissimilarity among sites) pattern for both bacterial taxa and functional genes was similar, showing significant elevational distance-decay patterns which presented increased dissimilarity with elevation. The bacterial taxonomic diversity/structure was strongly influenced by soil pH, while the functional gene diversity/structure was significantly correlated with soil dissolved organic carbon (DOC). This finding highlights that soil DOC may be a good predictor in determining the elevational distribution of microbial functional genes. The finding of significant shifts in functional gene diversity at the treeline ecotone could also provide valuable information for predicting the responses of microbial functions to climate change.

  5. Dramatic increases of soil microbial functional gene diversity at the treeline ecotone of Changbai Mountain

    Directory of Open Access Journals (Sweden)

    Congcong Shen

    2016-07-01

    Full Text Available The elevational and latitudinal diversity patterns of microbial taxa have attracted great attention in the past decade. Recently, the distribution of functional attributes has been in the spotlight. Here, we report a study profiling soil microbial communities along an elevation gradient (500 to 2200 m on Changbai Mountain. Using a comprehensive functional gene microarray (GeoChip 5.0, we found that microbial functional gene richness exhibited a dramatic increase at the treeline ecotone, but the bacterial taxonomic and phylogenetic diversity based on 16S rRNA gene sequencing did not exhibit such a similar trend. However, the β-diversity (compositional dissimilarity among sites for both bacterial taxa and functional genes was similar, showing significant elevational distance-decay patterns which presented increased dissimilarity with elevation. The bacterial taxonomic diversity/structure was strongly influenced by soil pH, while the functional gene diversity/structure was significantly correlated with soil dissolved organic carbon (DOC. This finding highlights that soil DOC may be a good predictor in determining the elevational distribution of microbial functional genes. The finding of significant shifts in functional gene diversity at the treeline ecotone could also provide valuable information for predicting the responses of microbial functions to climate change.

  6. Who gets custody now? Dramatic changes in children's living arrangements after divorce.

    Science.gov (United States)

    Cancian, Maria; Meyer, Daniel R; Brown, Patricia R; Cook, Steven T

    2014-08-01

    This article reexamines the living arrangements of children following their parents' divorce, using Wisconsin Court Records, updating an analysis that showed relatively small but significant increases in shared custody in the late 1980s and early 1990s. These changes have accelerated markedly in the intervening years: between 1988 and 2008, the proportion of mothers granted sole physical custody fell substantially, the proportion of parents sharing custody increased dramatically, and father-sole custody remained relatively stable. We explore changes in the correlates of alternative custody outcomes, showing that some results from the earlier analysis still hold (for example, cases with higher total family income are more likely to have shared custody), but other differences have lessened (shared-custody cases have become less distinctive as they have become more common). Despite the considerable changes in marriage and divorce patterns over this period, we do not find strong evidence that the changes in custody are related to changes in the characteristics of families experiencing a divorce; rather, changes in custody may be the result of changes in social norms and the process by which custody is determined.

  7. Lord Kelvin and the Age-of-the-Earth Debate: A Dramatization

    Science.gov (United States)

    Stinner, Art; Teichmann, Jürgen

    This is a dramatization of a fictitious debate about the age of the earth that takes place in the Royal Institution, London, England, in the year 1872. The debate is among Sir William Thomson (later Kelvin), T.H. Huxley (Darwin's Bulldog), Sir Charles Lyell, and Hermann von Helmholtz. In 1862 Thomson published his celebrated and widely studied The Secular Cooling of the Earth that raised the post-Darwinian debate of the age of the earth above the level of popular controversy. He entered the debate with all the arrogance of a newly established science of the century, namely the recently drafted laws of thermodynamics. The debate is partly based on a lively exchange of comments and arguments that occurred between T.H. Huxley and William Thomson, starting in 1868, when Thomson addressed the Glasgow Geological Society. This long public discussion also involved the ideas and the work of geologist Charles Lyell and those of the celebrated German physicist Hermann von Helmholtz. The confrontation is between the unyielding physicists and the insecure biologists and geologists who required a much longer time for the age of the earth than the physicists were prepared to give them. However, the debate ends on a conciliatory note, suggesting that perhaps Sir William's storehouse of creation may contain a hereto undiscovered source of energy that is more bountiful than gravitational energy.

  8. Fermentation study for the production of hepatitis B virus pre-S2 antigen by the methylotrophic yeast Hansenula polymorpha.

    Science.gov (United States)

    de Roubin, M R; Bastien, L; Shen, S H; Groleau, D

    1991-10-01

    Various physico-chemical parameters have been studied in order to improve the production of hepatitis B virus pre-S2 antigen (middle surface antigen) by the methylotrophic yeast Hansenula polymorpha. Antigen production was done in two steps: first, production of cells on glycerol (Phase 1), followed by induction of antigen expression with methanol (Phase 2). Dense cultures of H. polymorpha, equivalent to 35-40 g/l (dry weight), were readily obtained in small fermenters using minimal medium containing glycerol as carbon source. Antigen expression in this minimal medium, after induction with methanol, was however, low and never exceeded 1.6 mg/l of culture. Antigen production was greatly enhanced by adding complex organic nitrogen sources along with methanol at induction time; yeast extract was the best of all the sources tested. In shake flasks, antigen production was proportional to yeast extract concentration up to 7% (w/v) yeast extract, it became clear the the nutritional conditions for good antigen expression were different from those for good biomass production. The effects of yeast extract were reproduced in small fermenters: antigen levels reached 8-9 mg/l in medium containing 6% (w/v) yeast extract during induction with methanol. The mechanisms of yeast extract's effects are still unknown but are probably nutritional. The recombinant H. polymorpha strain produced both periplasmic and intracellular antigen. The periplasmic antigen was shown to be present as 20-22-nm particles and was therefore immunogenic. Immunoblotting indicated that part of the pre-S2 antigen was present as a 24-kDa degradation product. These studies have led to a 140-fold increase in volumetric productivity of antigen and to a 4.6-fold increase in specific production.

  9. Two-dimensional periodic relief grating as a versatile platform for selective immunosorbent assay and visualizing of antigens.

    Science.gov (United States)

    Chen, Jem-Kun; Zhou, Gang-Yan; Huang, Chih-Feng; Chang, Jia-Yaw

    2013-04-24

    In this study, we fabricated a nanopillar array of silicon oxide, involving very-large-scale integration (VLSI) and reactive ion etching (RIE), as two-dimensional periodic relief gratings (2DPRGs) on Si surfaces. Antihuman ALB was successively oriented on the pillar surface of 2DPRG modified protein G as an optical detector that is specific for targeted antigen. The antibody modified 2DPRG alone produces insignificant structure change, but upon immunocapture of antigens, the antigen filling in the 2DPRG leads to a dramatic change of the pillar scale. Binding of the antibodies to the 2DPRG occurs in a way that still allows them to function and selectively bind antigen. The performance of the sensor was evaluated by capturing HRP-human ALB on the antibody-modified 2DPRG and measuring the effective refractive index (neff) resulting from the attachment of antigens. The neff values of the 2DPRG are found to relate with the pillar scale of the 2DPRG, generated by antigen coupling, resulting in color change from pure green to orange, observed by the naked eye along an incident angle of 10-20°. Moreover, we calculated the filling factors inside the 2DPRG with effective-medium theory to verify the pillar structure changes. This technique eliminates much of the surface modifications and the secondary immunochemical or enzyme-linked steps that are common in immunoassays. Such films have potential applications as optical biosensors.

  10. Antigen/Antibody Analyses in Leishmaniasis.

    Science.gov (United States)

    1983-09-01

    antibodies in human sera with antigens of protozoan parasites . It was found that enzyme substrate reactions had distinct advantages over typical...autoradiographic procedures. Analyses of various sera identified a number of antigens of protozoan parasites which may be useful in discriminating infections

  11. Virosomes for antigen and DNA delivery

    NARCIS (Netherlands)

    Daemen, T; de Mare, A; Bungener, L; de Jonge, J; Huckriede, A; Wilschut, J

    2005-01-01

    Specific targeting and delivery as well as the display of antigens on the surface of professional antigen-presenting cells (APCs) are key issues in the design and development of new-generation vaccines aimed at the induction of both humoral and cell-mediated immunity. Prophylactic vaccination agains

  12. Protein antigen delivery by gene gun-mediated epidermal antigen incorporation (EAI).

    Science.gov (United States)

    Scheiblhofer, Sandra; Ritter, Uwe; Thalhamer, Josef; Weiss, Richard

    2013-01-01

    The gene gun technology can not only be employed for efficient transfer of gene vaccines into upper layers of the skin, but also for application of protein antigens. As a tissue rich in professional antigen presenting cells, the skin represents an attractive target for immunizations. In this chapter we present a method for delivery of the model antigen ovalbumin into the skin of mice termed epidermal antigen incorporation and describe in detail how antigen-specific proliferation in draining lymph nodes can be followed by flow cytometry.

  13. Tumor antigens as related to pancreatic cancer.

    Science.gov (United States)

    Chu, T M; Holyoke, E D; Douglass, H O

    1980-01-01

    Data are presented suggesting the presence of pancreas tumor-associated antigens. Slow progress has been made during the past few years in the identification of pancreatic tumor antigens that may be of clinical usefulness and it seems unlikely that many of the practical problems now being faced in identification and isolation of these antigens and in development of a specific, sensitive assay will be solved by conventional immunochemical approaches. The study of antigen and/or antibody purified from immune complexes in the host and the application of leukocyte adherence inhibition techniques to immunodiagnosis of pancreatic cancer are among the new approaches that may provide effective alternatives in the study of pancreatic tumor antigens.

  14. Increased Abundance of M Cells in the Gut Epithelium Dramatically Enhances Oral Prion Disease Susceptibility.

    Science.gov (United States)

    Donaldson, David S; Sehgal, Anuj; Rios, Daniel; Williams, Ifor R; Mabbott, Neil A

    2016-12-01

    Many natural prion diseases of humans and animals are considered to be acquired through oral consumption of contaminated food or pasture. Determining the route by which prions establish host infection will identify the important factors that influence oral prion disease susceptibility and to which intervention strategies can be developed. After exposure, the early accumulation and replication of prions within small intestinal Peyer's patches is essential for the efficient spread of disease to the brain. To replicate within Peyer's patches, the prions must first cross the gut epithelium. M cells are specialised epithelial cells within the epithelia covering Peyer's patches that transcytose particulate antigens and microorganisms. M cell-development is dependent upon RANKL-RANK-signalling, and mice in which RANK is deleted only in the gut epithelium completely lack M cells. In the specific absence of M cells in these mice, the accumulation of prions within Peyer's patches and the spread of disease to the brain was blocked, demonstrating a critical role for M cells in the initial transfer of prions across the gut epithelium in order to establish host infection. Since pathogens, inflammatory stimuli and aging can modify M cell-density in the gut, these factors may also influence oral prion disease susceptibility. Mice were therefore treated with RANKL to enhance M cell density in the gut. We show that prion uptake from the gut lumen was enhanced in RANKL-treated mice, resulting in shortened survival times and increased disease susceptibility, equivalent to a 10-fold higher infectious titre of prions. Together these data demonstrate that M cells are the critical gatekeepers of oral prion infection, whose density in the gut epithelium directly limits or enhances disease susceptibility. Our data suggest that factors which alter M cell-density in the gut epithelium may be important risk factors which influence host susceptibility to orally acquired prion diseases.

  15. Dramatic Decomposition Weakening of Simulated Faults in Carrara Marble at Seismic Slip-rates

    Science.gov (United States)

    Han, R.; Shimamoto, T.; Hirose, T.; Ree, J.

    2005-12-01

    Evolution of fault-zone strength and its weakening mechanisms during an earthquake are critical for understanding of earthquake rupture process. We report dramatic weakening of dry simulated faults in Carrara marble at seismic slip-rates, with frictional coefficient as low as 0.04 (probably the lowest record as rock friction). Calcite decomposition was confirmed by in-situ CO2 detection and other methods and the weakening may require new weakening mechanisms other than currently suggested ones such as frictional melting, thermal pressurization and silica gel formation. We conducted rotary-shear friction experiments on Carrara marble at slip-rates (V) of 0.09-1.24 m/s and normal stresses (σn) of 2.5-13.4 MPa. For preventing a thermal fracturing and applying a high normal load, we used solid cylindrical specimens jacketed with aluminum tubes. Narrow gap was left between the two aluminum tubes to avoid metal-to-metal contact. Our main results can be summarized as follows: (1) Slip weakening occurs in all experiments except for the runs at the lowest V (0.09 m/s); (2) Steady-state friction coefficient (μss) decreases as slip-rate and normal load increase; (3) At the highest V (1.13-1.24 m/s) and σn = 7.3 MPa, the average friction coefficient of initial peak friction (μp) is 0.61 (± 0.02), but the average μss is 0.04! (± 0.01) which is much lower than μp; (4) Decrease in average temperature of sliding surfaces corresponds to increase in friction, and strength recovery occurs very rapidly and completely upon cooling of specimens; (5) XRD and EPMA data show that the gouge for the specimens at V > 0.09 m/s is composed of calcite, lime (CaO) and/or hydrated lime (Ca(OH)2); (6) CO2 gas was detected with sensors during the weakening; (7) Decomposed calcite forms a fault zone consisting of ultrafine-grained gouge, but no melt or amorphous material was identified by optical microscopy or XRD analysis. Calcite decomposition clearly indicates that temperature in the fault

  16. Dramatic reduction of dimensionality in large biochemical networks owing to strong pair correlations

    Science.gov (United States)

    Dworkin, Michael; Mukherjee, Sayak; Jayaprakash, Ciriyam; Das, Jayajit

    2012-01-01

    Large multi-dimensionality of high-throughput datasets pertaining to cell signalling and gene regulation renders it difficult to extract mechanisms underlying the complex kinetics involving various biochemical compounds (e.g. proteins and lipids). Data-driven models often circumvent this difficulty by using pair correlations of the protein expression levels to produce a small number (fewer than 10) of principal components, each a linear combination of the concentrations, to successfully model how cells respond to different stimuli. However, it is not understood if this reduction is specific to a particular biological system or to nature of the stimuli used in these experiments. We study temporal changes in pair correlations, described by the covariance matrix, between concentrations of different molecular species that evolve following deterministic mass-action kinetics in large biologically relevant reaction networks and show that this dramatic reduction of dimensions (from hundreds to less than five) arises from the strong correlations between different species at any time and is insensitive to the form of the nonlinear interactions, network architecture, and to a wide range of values of rate constants and concentrations. We relate temporal changes in the eigenvalue spectrum of the covariance matrix to low-dimensional, local changes in directions of the system trajectory embedded in much larger dimensions using elementary differential geometry. We illustrate how to extract biologically relevant insights such as identifying significant timescales and groups of correlated chemical species from our analysis. Our work provides for the first time, to our knowledge, a theoretical underpinning for the successful experimental analysis and points to a way to extract mechanisms from large-scale high-throughput datasets. PMID:22378749

  17. New Radar Altimeter Missions are Providing a Dramatically Sharper Image of Global Marine Tectonics

    Science.gov (United States)

    Sandwell, D. T.; Müller, D.; Garcia, E.; Matthews, K. J.; Smith, W. H. F.; Zaron, E.; Zhang, S.; Bassett, D.; Francis, R.

    2015-12-01

    Marine gravity, derived from satellite radar altimetry, is a powerful tool for mapping tectonic structures, especially in the deep ocean basins where the topography remains unmapped by ships or is buried by thick sediment. The ability to infer seafloor tectonics from space was first demonstrated in 1978 using Seasat altimeter data but the spatial coverage was incomplete because of the short three-month lifetime of the satellite. Most ocean altimeters have repeat ground tracks with spacings of hundreds of kilometers so they do not resolve tectonic structures. Adequate altimeter coverage became available in 1995 when the United States Navy declassified the Geosat radar altimeter data and the ERS-1 altimeter completed a 1-year mapping phase. These mid-1990's altimeter-derived images of the ocean basins remained static for 15 years because there were no new non-repeat altimeter missions. This situation changed dramatically in 2010 when CryoSat-2, with its advanced radar altimeter, was launched into a non-repeat orbit and continues to collect data until perhaps 2020. In addition the Jason-1 altimeter was placed into a 14-month geodetic phase at the end of its lifetime. More recently the 1.5 times higher precision measurements from the AltiKa altimeter aboard the SARAL spacecraft began to drift away from its 35-day repeat trackline. The Chinese HY-2 altimeter is scheduled to begin a dense mapping phase in early 2016. Moreover in 2020 we may enjoy significantly higher resolution maps of the ocean basins from the planned SWOT altimeter mission with its advanced swath mapping ability. All of this new data will provide a much sharper image of the tectonics of the deep ocean basins and continental margins. During this talk we will tour of the new tectonic structures revealed by CryoSat-2 and Jason-1 and speculate on the tectonic views of the ocean basins in 2020 and beyond.

  18. Angiotensin I-converting enzyme mutation (Trp1197Stop causes a dramatic increase in blood ACE.

    Directory of Open Access Journals (Sweden)

    Andrew B Nesterovitch

    Full Text Available BACKGROUND: Angiotensin-converting enzyme (ACE metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling. Elevated ACE levels may be associated with an increased risk for different cardiovascular or respiratory diseases, including asthma. Previously, a molecular mechanism underlying a 5-fold familial increase of blood ACE was discovered: Pro1199Leu substitution enhanced the cleavage-secretion process. Carriers of this mutation were Caucasians from Europe (mostly Dutch or had European roots. METHODOLOGY/PRINCIPAL FINDINGS: We have found a family of African-American descent whose affected members' blood ACE level was increased 13-fold over normal. In affected family members, codon TGG coding for Trp1197 was substituted in one allele by TGA (stop codon. As a result, half of ACE expressed in these individuals had a length of 1196 amino acids and lacked a transmembrane anchor. This ACE mutant is not trafficked to the cell membrane and is directly secreted out of cells; this mechanism apparently accounts for the high serum ACE level seen in affected individuals. A haplotype of the mutant ACE allele was determined based on 12 polymorphisms, which may help to identify other carriers of this mutation. Some but not all carriers of this mutation demonstrated airflow obstruction, and some but not all have hypertension. CONCLUSIONS/SIGNIFICANCE: We have identified a novel Trp1197Stop mutation that results in dramatic elevation of serum ACE. Since blood ACE elevation is often taken as a marker of disease activity (sarcoidosis and Gaucher diseases, it is important for clinicians and medical scientists to be aware of alternative genetic causes of elevated blood ACE that are not apparently linked to disease.

  19. Urbanization dramatically altered the water balances of a paddy field dominated basin in Southern China

    Directory of Open Access Journals (Sweden)

    L. Hao

    2015-02-01

    Full Text Available Rice paddy fields provide important ecosystem services (e.g., food production, water retention, carbon sequestration to a large population globally. However, these benefits are declining as a result of rapid environmental and socioeconomic transformations characterized by population growth, urbanization, and climate change in many Asian countries. This case study examined the responses of streamflow and watershed water balances to the decline of rice paddy fields due to urbanization in the Qinhuai River Basin in southern China where massive industrialization has occurred in the region during the past three decades. We found that streamflow increased by 58% and evapotranspiration (ET decreased by 23% during 1986–2013 as a result of an increase in urban areas of three folds and reduction of rice paddy field by 27%. Both highflows and lowflows increased significantly by about 28% from 2002 to 2013. The increases in streamflow were consistent with the decreases in ET and leaf area index monitored by independent remote sensing MODIS data. The reduction in ET and increase in streamflow was attributed to the large cropland conversion that overwhelmed the effects of regional climate warming and climate variability. Converting traditional rice paddy fields to urban use dramatically altered land surface conditions from a water-dominated to a human-dominated landscape, and thus was considered as one of the extreme types of contemporary hydrologic disturbances. The ongoing large-scale urbanization in the rice paddy-dominated regions in the humid southern China, and East Asia, will likely elevate stormflow volume, aggravate flood risks, and intensify urban heat island effects. Understanding the linkage between land use change and changes in hydrological processes is essential for better management of urbanizing watersheds.

  20. Investigation of the dramatic changes in lake level of the Bosten Lake in northwestern China

    Science.gov (United States)

    Guo, Mengjing; Wu, Wei; Zhou, Xiaode; Chen, Yongmin; Li, Jing

    2015-01-01

    Bosten Lake, located in the arid region of northwest China, is the largest inland freshwater lake in China. Water resources in Bosten Lake are of great importance for the regional drinking water supply, agricultural irrigation, and economic development of Xinjiang province. In this study, the dynamics of the lake level in Bosten Lake were investigated from 1956 to 2010. We found that the lake level experienced three different periods of change due to the combined influences of climate variation and human activities. Generally, the lake level has shown a significant downward trend since the first observation started in 1956 and dropped to its lowest level in 1987. Thereafter, the lake level presented a continuous upward trend and rose to its highest value in 2002. Then, the level decreased dramatically from 2002 to 2010. A water balance model and the climate elasticity method were used to estimate the reasons for the lake level changes of Bosten Lake. The results showed that an increase in lake evaporation led to the continuous decrease in lake level from 1958 to 1987. Then, human-controlled lake outflow and increasing lake inflow together led to the increase in lake level from 1988 to 2002. During 2003 to 2010, the emergency project of transferring water to Tarim River led to the increase in lake outflow, while the lake inflow obviously decreased because of a decrease in precipitation. These factors resulted in a sharp decrease in the lake level from 2003 to 2010. The changes in lake level indicate changes in available water resources from Bosten Lake. This reason for the analysis of the change in lake level in this study is to support the water resources management of Bosten Lake.

  1. The role of Pacific water in the dramatic retreat of arctic sea ice during summer 2007

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jinlun; MI ke Steele; Rebecca Woodgate

    2008-01-01

    A model study is conducted to examine the role of Pacific water in the dramatic retreat of arctic sea ice during summer 2007. The model generally agrees with the observations in showing considerable seasonal and intcrannual variability of the Pacific water inflow at Bering Strait in response to changes in atmospheric circulation.During summer 2007 anomalously strong southerly winds over the Pacific sector of the Arctic Ocean strengthen the ocean circulation and bring more Pacific water into the Arctic than the recent (2000-2006) average. The simulated summer (3 months )2007 mean Pacific water inflow at Bering Strait is 1.2 Sv, which is the highest in the past three decades of the simulation and is 20% higher than the recent average. Particularly, the Pacific water inflow in September 2007 is about 0.5 Sv or 50% above the 2000-2006 average. The strengthened warm Pacific water inflow carries an additional 1.0 × 1020 Joules of heat into the Arctic, enough to melt an additional 0. 5 m of ice over the whole Chukchi Sea. In the model the extra summer oceanic heat brought in by the Pacific water mainly stays in the Chukchi and Beaufort region, contributing to the wanning of surface waters in that region. The heat is in constant contact with the ice cover in the region in July through September. Thus the Pacific water plays a role in ice melting in the Chukchi and Beaufort region all summer long in 2007, likely contributing to up to 0.5 m per month additional ice melting in some area of that region.

  2. Expression and immunogenicity of novel subunit enterovirus 71 VP1 antigens

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Juan [China-US Vaccine Research Center, The First Affiliated Hospital, Nanjing Medical University (China); Department of Microbiology and Immunology, Nanjing Medical University (China); Wang, Shixia [China-US Vaccine Research Center, The First Affiliated Hospital, Nanjing Medical University (China); Department of Medicine, University of Massachusetts Medical School (United States); Gan, Weihua [Department of Pediatrics, The Second Affiliated Hospital, Nanjing Medical University (China); Zhang, Wenhong [Department of Infectious Diseases, Huashan Hospital, Fudan University (China); Ju, Liwen [School of Public Health, Fudan University (China); Huang, Zuhu [Department of Infectious Diseases, The First Affiliated Hospital, Nanjing Medical University (China); China-US Vaccine Research Center, The First Affiliated Hospital, Nanjing Medical University (China); Lu, Shan, E-mail: shan.lu@umassmed.edu [Department of Infectious Diseases, The First Affiliated Hospital, Nanjing Medical University (China); China-US Vaccine Research Center, The First Affiliated Hospital, Nanjing Medical University (China); Department of Medicine, University of Massachusetts Medical School (United States)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer EV71 is a major emerging infectious disease in many Asian countries. Black-Right-Pointing-Pointer Inactivated EV71 vaccines are in clinical studies but their safety and efficacy are unknown. Black-Right-Pointing-Pointer Developing subunit based EV71 vaccines is significant and novel antigen design is needed. Black-Right-Pointing-Pointer DNA immunization is an efficient tool to test the immunogenicity of VP1 based EV71 vaccines. Black-Right-Pointing-Pointer Multiple VP1 antigens are developed showing immunogenic potential. -- Abstract: Hand, foot, and mouth disease (HFMD) is a common viral illness in young children. HFMD is caused by viruses belonging to the enterovirus genus of the picornavirus family. Recently, enterovirus 71 (EV71) has emerged as a virulent agent for HFMD with severe clinical outcomes. In the current report, we conducted a pilot antigen engineering study to optimize the expression and immunogenicity of subunit VP1 antigen for the design of EV71 vaccines. DNA immunization was adopted as a simple technical approach to test different designs of VP1 antigens without the need to express VP1 protein in vitro first. Our studies indicated that the expression and immunogenicity of VP1 protein can be improved with alternated VP1 antigen designs. Data presented in the current report revealed novel pathways to optimize the design of VP1 antigen-based EV71 vaccines.

  3. Tetravalent neutralizing antibody response against four dengue serotypes by a single chimeric dengue envelope antigen.

    Science.gov (United States)

    Apt, Doris; Raviprakash, Kanakatte; Brinkman, Alice; Semyonov, Andrey; Yang, Shumin; Skinner, Craig; Diehl, Lori; Lyons, Richard; Porter, Kevin; Punnonen, Juha

    2006-01-16

    We employed DNA shuffling and screening technologies to develop a single recombinant dengue envelope (E) antigen capable of inducing neutralizing antibodies against all four antigenically distinct dengue serotypes. By DNA shuffling of codon-optimized dengue 1-4 E genes, we created a panel of novel chimeric clones expressing C-terminal truncated E antigens that combined epitopes from all four dengue serotypes. DNA vaccines encoding these novel chimeras induced multivalent T cell and neutralizing antibody responses against all four dengue serotypes in mice. By contrast, a mixture of four unshuffled, parental DNA vaccines failed to produce tetravalent neutralizing antibodies in mice. The neutralizing antibody titers for some of these antigens could be further improved by extending the sequences to express full-length pre-membrane and envelope proteins. The chimeric antigens also protected mice against a lethal dengue-2 virus challenge. These data demonstrate that DNA shuffling and associated screening can lead to the selection of multi-epitope antigens against closely related dengue virus serotypes and suggest a broad utility for these technologies in optimizing vaccine antigens.

  4. Intestinal Calcium Absorption Decreases Dramatically After Gastric Bypass Surgery Despite Optimization of Vitamin D Status.

    Science.gov (United States)

    Schafer, Anne L; Weaver, Connie M; Black, Dennis M; Wheeler, Amber L; Chang, Hanling; Szefc, Gina V; Stewart, Lygia; Rogers, Stanley J; Carter, Jonathan T; Posselt, Andrew M; Shoback, Dolores M; Sellmeyer, Deborah E

    2015-08-01

    Roux-en-Y gastric bypass (RYGB) surgery has negative effects on bone, mediated in part by effects on nutrient absorption. Not only can RYGB result in vitamin D malabsorption, but the bypassed duodenum and proximal jejunum are also the predominant sites of active, transcellular, 1,25(OH)2 D-mediated calcium (Ca) uptake. However, Ca absorption occurs throughout the intestine, and those who undergo RYGB might maintain sufficient Ca absorption, particularly if vitamin D status and Ca intake are robust. We determined the effects of RYGB on intestinal fractional Ca absorption (FCA) while maintaining ample 25OHD levels (goal ≥30 ng/mL) and Ca intake (1200 mg daily) in a prospective cohort of 33 obese adults (BMI 44.7 ± 7.4 kg/m(2)). FCA was measured preoperatively and 6 months postoperatively with a dual stable isotope method. Other measures included calciotropic hormones, bone turnover markers, and BMD by DXA and QCT. Mean 6-month weight loss was 32.5 ± 8.4 kg (25.8% ± 5.2% of preoperative weight). FCA decreased from 32.7% ± 14.0% preoperatively to 6.9% ± 3.8% postoperatively (p < 0.0001), despite median (interquartile range) 25OHD levels of 41.0 (33.1 to 48.5) and 36.5 (28.8 to 40.4) ng/mL, respectively. Consistent with the FCA decline, 24-hour urinary Ca decreased, PTH increased, and 1,25(OH)2 D increased (p ≤ 0.02). Bone turnover markers increased markedly, areal BMD decreased at the proximal femur, and volumetric BMD decreased at the spine (p < 0.001). Those with lower postoperative FCA had greater increases in serum CTx (ρ = -0.43, p = 0.01). Declines in FCA and BMD were not correlated over the 6 months. In conclusion, FCA decreased dramatically after RYGB, even with most 25OHD levels ≥30 ng/mL and with recommended Ca intake. RYGB patients may need high Ca intake to prevent perturbations in Ca homeostasis, although the approach to Ca supplementation needs further study. Decline in FCA could contribute to

  5. New approaches with different types of circulating cathodic antigen for the diagnosis of patients with low Schistosoma mansoni load.

    Directory of Open Access Journals (Sweden)

    Rafaella Grenfell

    Full Text Available BACKGROUND: Schistosomiasis mansoni is a debilitating and sometimes fatal disease. Accurate diagnosis plays a key role in patient management and infection control. However, currently available parasitological methods are laborious and lack sensitivity. The selection of target antigen candidates has turned out to be a promising tool for the development of more sensitive diagnostic methods. In our previous investigations, the use of crude antigens led to false-positive results. Recently, focus has been given to highly purified Schistosoma mansoni antigens, especially to circulating antigens. METHOD: Thus, our main goal was to test different types of circulating cathodic antigen glycoprotein (CCA, as "crude antigen," the protein chain of recombinant CCA and two individual peptides. These schistosome proteins/peptides were tested in a new diagnostic method employing immunomagnetic separation based on the improvement of antigen-antibody binding. PRINCIPAL FINDINGS: Use of recombinant CCA as a diagnostic antigen allowed us to develop a diagnostic assay with high sensitivity and specificity with no false-negative results. Interestingly, the "crude antigen" worked as a good marker for control of cure after praziquantel treatment. CONCLUSIONS/SIGNIFICANCE: Our new diagnostic method was superior to enzyme-linked immunosorbent assay in diagnosing low endemicity patients.

  6. Digestibility and antigenicity of β-lactoglobulin as affected by heat, pH and applied shear.

    Science.gov (United States)

    Rahaman, Toheder; Vasiljevic, Todor; Ramchandran, Lata

    2017-02-15

    Processing induced conformational changes can modulate digestibility of food allergens and thereby their antigenicity. Effect of different pH (3, 5, 7), temperature (room temperature, 120°C) and shear (0s(-1), 1000s(-1)) on simulated gastrointestinal digestibility of β-lg and post digestion antigenic characteristics have been studied. At all pH levels unheated β-lg showed resistance to peptic digestion with high antigenic value while it was fairly susceptible to pancreatin with moderate reduction in antigenicity. Heating at 120°C significantly improved both peptic and pancreatic digestion attributed to structural alterations that resulted in much lower antigenicity; the level of reduction being pH dependant. The lowest antigenicity was recorded at pH 5. Shearing (1000s(-1)) had a minor impact reducing digestibility and thereby enhancing antigenicity of unheated β-lg at pH 5 and 7 slightly; however in conjunction with heating (120°C) it reduced antigenicity further irrespective of the pH. Overall, treatment at pH 5, 120°C and 1000s(-1) could potentially reduce post digestion antigenicity of β-lg.

  7. Strategy for eliciting antigen-specific CD8+ T cell-mediated immune response against a cryptic CTL epitope of merkel cell polyomavirus large T antigen

    Directory of Open Access Journals (Sweden)

    Gomez Bianca P

    2012-10-01

    Full Text Available Abstract Background Merkel cell carcinoma (MCC is a relatively new addition to the expanding category of oncovirus-induced cancers. Although still comparably rare, the number of cases has risen dramatically in recent years. Further complicating this trend is that MCC is an extremely aggressive neoplasm with poor patient prognosis and limited treatment options for advanced disease. The causative agent of MCC has been identified as the merkel cell polyomavirus (MCPyV. The MCPyV-encoded large T (LT antigen is an oncoprotein that is theorized to be essential for virus-mediated tumorigenesis and is therefore, an excellent MCC antigen for the generation of antitumor immune responses. As a foreign antigen, the LT oncoprotein avoids the obstacle of immune tolerance, which normally impedes the development of antitumor immunity. Ergo, it is an excellent target for anti-MCC immunotherapy. Since tumor-specific CD8+ T cells lead to better prognosis for MCC and numerous other cancers, we have generated a DNA vaccine that is capable of eliciting LT-specific CD8+ T cells. The DNA vaccine (pcDNA3-CRT/LT encodes the LT antigen linked to a damage-associated molecular pattern, calreticulin (CRT, as it has been demonstrated that the linkage of CRT to antigens promotes the induction of antigen-specific CD8+ T cells. Results The present study shows that DNA vaccine-induced generation of LT-specific CD8+ T cells is augmented by linking CRT to the LT antigen. This is relevant since the therapeutic effects of the pcDNA3-CRT/LT DNA vaccine is mediated by LT-specific CD8+ T cells. Mice vaccinated with the DNA vaccine produced demonstrably more LT-specific CD8+ T cells. The DNA vaccine was also able to confer LT-specific CD8+ T cell-mediated protective and therapeutic effects to prolong the survival of mice with LT-expressing tumors. In the interest of determining the LT epitope which most MCC-specific CD8+ T cells recognize, we identified the amino acid sequence of the

  8. Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation

    Science.gov (United States)

    Hattori, Takamitsu; Lai, Darson; Dementieva, Irina S.; Montaño, Sherwin P.; Kurosawa, Kohei; Zheng, Yupeng; Akin, Louesa R.; Świst-Rosowska, Kalina M.; Grzybowski, Adrian T.; Koide, Akiko; Krajewski, Krzysztof; Strahl, Brian D.; Kelleher, Neil L.; Ruthenburg, Alexander J.; Koide, Shohei

    2016-01-01

    Antibodies have a well-established modular architecture wherein the antigen-binding site residing in the antigen-binding fragment (Fab or Fv) is an autonomous and complete unit for antigen recognition. Here, we describe antibodies departing from this paradigm. We developed recombinant antibodies to trimethylated lysine residues on histone H3, important epigenetic marks and challenging targets for molecular recognition. Quantitative characterization demonstrated their exquisite specificity and high affinity, and they performed well in common epigenetics applications. Surprisingly, crystal structures and biophysical analyses revealed that two antigen-binding sites of these antibodies form a head-to-head dimer and cooperatively recognize the antigen in the dimer interface. This “antigen clasping” produced an expansive interface where trimethylated Lys bound to an unusually extensive aromatic cage in one Fab and the histone N terminus to a pocket in the other, thereby rationalizing the high specificity. A long-neck antibody format with a long linker between the antigen-binding module and the Fc region facilitated antigen clasping and achieved both high specificity and high potency. Antigen clasping substantially expands the paradigm of antibody–antigen recognition and suggests a strategy for developing extremely specific antibodies. PMID:26862167

  9. Intravenous application of an anticalin dramatically lowers plasma digoxin levels and reduces its toxic effects in rats

    Energy Technology Data Exchange (ETDEWEB)

    Eyer, Florian, E-mail: Florian.Eyer@mac.com [Department of Toxicology, Klinikum rechts der Isar, Munich (Germany); Steimer, Werner [Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Munich (Germany); Nitzsche, Thomas [Munich Center for Integrated Protein Science (CIPS-M), Freising-Weihenstephan (Germany); Lehrstuhl für Biologische Chemie, Technische Universität München, Freising-Weihenstephan (Germany); Jung, Nicole; Neuberger, Heidi [Department of Toxicology, Klinikum rechts der Isar, Munich (Germany); Müller, Christine [Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Munich (Germany); Schlapschy, Martin [Munich Center for Integrated Protein Science (CIPS-M), Freising-Weihenstephan (Germany); Lehrstuhl für Biologische Chemie, Technische Universität München, Freising-Weihenstephan (Germany); Zilker, Thomas [Department of Toxicology, Klinikum rechts der Isar, Munich (Germany); Skerra, Arne [Munich Center for Integrated Protein Science (CIPS-M), Freising-Weihenstephan (Germany); Lehrstuhl für Biologische Chemie, Technische Universität München, Freising-Weihenstephan (Germany)

    2012-09-15

    Lipocalins tailored with high affinity for prescribed ligands, so-called anticalins, constitute promising candidates as antidotes. Here, we present an animal study to investigate both pharmacokinetic and clinical effects of an anticalin specific for the digitalis compound digoxin. Intravenous digoxin (2.5–50 μg/kg/min) was administered to rats until first changes in the ECG occurred (dose finding study) or a priori for 30 min (kinetic study). The anticalin DigA16(H86N), dubbed DigiCal, was administered intravenously at absolute doses of 1, 5, 10 and 20 mg, while the control group received isotonic saline. Hemodynamic changes, several ECG parameters and digoxin concentration in plasma were monitored at given time intervals. After DigiCal administration free digoxin concentration in plasma ultrafiltrate declined dramatically within 1 min to the presumably non-toxic range. There was also a significant and DigiCal dose-dependent effect on longer survival, less ECG alterations, arrhythmia, and improved hemodynamics. Infusion of a lower digoxin dose (2.5 μg/kg/min) resulted in a more sustained reduction of free digoxin in plasma after DigiCal administration compared to a higher digoxin dose (25 μg/kg/min), whereas ECG and hemodynamic parameters did not markedly differ, reflecting the known relative insensitivity of rats towards digoxin toxicity. Notably, we observed a re-increase of free digoxin in plasma some time after bolus administration of DigiCal, which was presumably due to toxin redistribution from tissue in combination with the relatively fast renal clearance of the rather small protein antidote. We conclude that anticalins with appropriately engineered drug-binding activities and, possibly, prolonged plasma half-life offer prospects for next-generation antidotal therapy. -- Highlights: ► We provide an advanced model of digoxin toxicity in rats. ► We report on binding of digoxin to a novel designed anticalin. ► We report on pharmacokinetics of digoxin

  10. Crude antigens of Fasciola hepatica and Fasciola gigantica using ELISA test: a comparative study

    Directory of Open Access Journals (Sweden)

    Gaur S.N.S

    2008-05-01

    Full Text Available Background: Fasciolosis is a worldwide disease with major economic and public health consequences. Early detection of the infection is important for the prevention and control of the disease. ELISA allows for early detection of fasciolosis in man and animals. Fasciolosis is caused by Fasciola hepatica and F. gigantica in man and domestic animals respectively. These two species have many similar morphological characteristics. In this study, the crude antigens of these two species are investigated by ELISA test. Methods: The excretory-secretory and somatic antigens of two species were prepared from adult flukes collected from the bile ducts of sheep and stored at -20oC. For the preparation of the antisera, the antigens were injected to laboratory-bred rabbits. Each rabbit received five injections at intervals of seven days, starting with 0.5 ml and ending with 2.5 ml. Ten days after the last injection, the rabbits were bled, and serum samples separated and stored at -20oC. The reaction between homologous and heterologous antigens and antisera was tested by ELISA and optical densities were recorded.Results: Excretory- secretory and somatic antigens of each species showed a strong positive reaction with the antisera of the other species. In a homologous combination of antigens and antisera, a stronger reaction was observed compared to the heterologous combination, therefore many antigenic materials of both species are the same.Conclusion: The differences of these crude antigenic materials of F. hepatica and F. gigantica are insufficient to prevent cross reaction of two species by ELISA. Further investigations are recommended for the identification, detection and purification of antigenic material of each species to improve the specificity of this assay.

  11. Learning to Lead against the Grain: Dramatizing the Emotional Toll of Teacher Leadership

    Science.gov (United States)

    Cranston, Jerome; Kusanovich, Kristin

    2015-01-01

    Tremendous research on teacher leadership over the last decade has revealed both the prevalence of and the imperatives for a model teaching force that can actively participate in school improvement (Harrison & Killion, 2007; Katzenmeyer & Moller, 2001; Leithwood & Riehl, 2003). The highly participative teacher leader paradigm is so…

  12. Antigen-specific memory B cell development.

    Science.gov (United States)

    McHeyzer-Williams, Louise J; McHeyzer-Williams, Michael G

    2005-01-01

    Helper T (Th) cell-regulated B cell immunity progresses in an ordered cascade of cellular development that culminates in the production of antigen-specific memory B cells. The recognition of peptide MHC class II complexes on activated antigen-presenting cells is critical for effective Th cell selection, clonal expansion, and effector Th cell function development (Phase I). Cognate effector Th cell-B cell interactions then promote the development of either short-lived plasma cells (PCs) or germinal centers (GCs) (Phase II). These GCs expand, diversify, and select high-affinity variants of antigen-specific B cells for entry into the long-lived memory B cell compartment (Phase III). Upon antigen rechallenge, memory B cells rapidly expand and differentiate into PCs under the cognate control of memory Th cells (Phase IV). We review the cellular and molecular regulators of this dynamic process with emphasis on the multiple memory B cell fates that develop in vivo.

  13. Platelet antigens and antibodies. Literature review

    Directory of Open Access Journals (Sweden)

    N. V. Mineeva

    2014-07-01

    Full Text Available Platelet antigens structure, role of platelet antibodies in the pathogenesis of various clinical conditions, characteristic of modern antibodies detection methods are presented in this article.

  14. Platelet antigens and antibodies. Literature review

    Directory of Open Access Journals (Sweden)

    N. V. Mineeva

    2013-01-01

    Full Text Available Platelet antigens structure, role of platelet antibodies in the pathogenesis of various clinical conditions, characteristic of modern antibodies detection methods are presented in this article.

  15. Reverse immunoediting: When immunity is edited by antigen.

    Science.gov (United States)

    Merlo, Anna; Santa, Silvia Dalla; Dolcetti, Riccardo; Zanovello, Paola; Rosato, Antonio

    2016-07-01

    Immune selective pressure occurring during cancer immunoediting shapes tumor features revealed at clinical presentation. However, in the "Escape" phase, the tumor itself has the chance to influence the immunological response. Therefore, the capacity of the immune response to sculpt the tumor characteristics is only one side of the coin and even the opposite is likely true, i.e. that an antigen can shape the immune response in a sort of "reverse immunoediting". This reciprocal modeling probably occurs continuously, whenever the immune system encounters a tumor/foreign antigen, and can be operative in the pathogen/immune system interplay, thus possibly permeating the protective immunity as a whole. In line with this view, the characterization of a T cell response as well as the design of both active and passive immunotherapy strategies should also take into account all Ag features (type, load and presentation). Overall, we suggest that the "reverse immunoediting" hypothesis could help to dissect the complex interplay between antigens and the immune repertoire, and to improve the outcome of immunotherapeutic approaches, where T cell responses are manipulated and reprogrammed.

  16. Physiological level production of antigen-specific human immunoglobulin in cloned transchromosomic cattle.

    Directory of Open Access Journals (Sweden)

    Akiko Sano

    Full Text Available Therapeutic human polyclonal antibodies (hpAbs derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc cattle carrying a human artificial chromosome (HAC comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH and kappa-chain (hIGK germline loci (named as κHAC are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO. However, B lymphocyte development in these Tc cattle is compromised, and the overall production of hpAbs is low. Here, we report the construction of an improved HAC, designated as cKSL-HACΔ, by incorporating all of the human immunoglobulin germline loci into the HAC. Furthermore, for avoiding the possible human-bovine interspecies incompatibility between the human immunoglobulin mu chain protein (hIgM and bovine transmembrane α and β immunoglobulins (bIgα and bIgβ in the pre-B cell receptor (pre-BCR complex, we partially replaced (bovinized the hIgM constant domain with the counterpart of bovine IgM (bIgM that is involved in the interaction between bIgM and bIgα/Igβ; human IgM bovinization would also improve the functionality of hIgM in supporting B cell activation and proliferation. We also report the successful production of DKO Tc cattle carrying the cKSL-HACΔ (cKSL-HACΔ/DKO, the dramatic improvement of B cell development in these cattle and the high level production of hpAbs (as measured for the human IgG isotype in the plasma. We further demonstrate that, upon immunization by tumor immunogens, high titer tumor immunogen-specific human IgG (hIgG can be produced from such Tc cattle.

  17. Physiological level production of antigen-specific human immunoglobulin in cloned transchromosomic cattle.

    Science.gov (United States)

    Sano, Akiko; Matsushita, Hiroaki; Wu, Hua; Jiao, Jin-An; Kasinathan, Poothappillai; Sullivan, Eddie J; Wang, Zhongde; Kuroiwa, Yoshimi

    2013-01-01

    Therapeutic human polyclonal antibodies (hpAbs) derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc) cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH) and kappa-chain (hIGK) germline loci (named as κHAC) are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO). However, B lymphocyte development in these Tc cattle is compromised, and the overall production of hpAbs is low. Here, we report the construction of an improved HAC, designated as cKSL-HACΔ, by incorporating all of the human immunoglobulin germline loci into the HAC. Furthermore, for avoiding the possible human-bovine interspecies incompatibility between the human immunoglobulin mu chain protein (hIgM) and bovine transmembrane α and β immunoglobulins (bIgα and bIgβ) in the pre-B cell receptor (pre-BCR) complex, we partially replaced (bovinized) the hIgM constant domain with the counterpart of bovine IgM (bIgM) that is involved in the interaction between bIgM and bIgα/Igβ; human IgM bovinization would also improve the functionality of hIgM in supporting B cell activation and proliferation. We also report the successful production of DKO Tc cattle carrying the cKSL-HACΔ (cKSL-HACΔ/DKO), the dramatic improvement of B cell development in these cattle and the high level production of hpAbs (as measured for the human IgG isotype) in the plasma. We further demonstrate that, upon immunization by tumor immunogens, high titer tumor immunogen-specific human IgG (hIgG) can be produced from such Tc cattle.

  18. Metacomprehension for educationally relevant materials: dramatic effects of encoding-retrieval interactions.

    Science.gov (United States)

    Thomas, Ayanna K; McDaniel, Mark A

    2007-04-01

    As the metacomprehension literature has grown, important discoveries pertinent to education havebeen made. For example, as students are better able to assess their knowledge and implement appropriate study strategies, presumably their acquisition and retention of course material improves. Accordingly, we consider the metacomprehension literature with an emphasis on factors that impact metacomprehension accuracy. Several studies have demonstrated that metacomprehension prediction accuracy will improve to the extent that people engage in enriched-encoding activities. More recently, research by Thomas and McDaniel (in press) has suggested that enriched-encoding manipulations interact with retrieval to impact both retention and metacomprehension and, in turn, the effectiveness of controlling subsequent study. Thus, matching enriched-encoding activities with the criterial test plays a critical role in metacomprehension accuracy and control of studying.

  19. A proposal to speed translation of healthcare research into practice: dramatic change is needed.

    Science.gov (United States)

    Kessler, Rodger; Glasgow, Russell E

    2011-06-01

    Efficacy trials have generated interventions to improve health behaviors and biomarkers. However, these efforts have had limited impact on practice and policy. It is suggested that key methodologic and contextual issues have contributed to this state of affairs. Current research paradigms generally have not provided the answers needed for more probable and more rapid translation. A major shift is proposed to produce research with more rapid clinical, public health, and policy impact.

  20. Presentation of antigen by B cells subsets. Pt. 2. The role of CD5 B cells in the presentation of antigen to antigen-specific T cells

    Energy Technology Data Exchange (ETDEWEB)

    Zimecki, Michal [Polish Academy of Sciences, Wroclaw (Poland). Institute of Immunology and Experimental Therapy; Kapp, Judith A. [Emory Univ., Atlanta, GA (United States). School of Medicine

    1994-12-31

    We demonstrate that peritoneal B cells have a much higher ability to present antigen to antigen-specific T cell lines splenic B cells. Presentation of antigen by B cells is abrogated or drastically reduced after removal of Lyb-5{sup +} cells from the population of splenic or peritoneal B cells. Peritoneal B cells, precultured for 7 days prior to the antigen presentation assay, retain their antigen presenting cell (APC) function. Enrichment for CD5{sup +} cells in the peritoneal B cell population results in a more effective antigen presentation. Lastly, stimulation of B cells via CD5 antigen, by treatment of cells with anti-CD5 antibodies or cross-linking of CD5 receptors, enhances APC function of these cells. The results indicate, both indirectly and directly, that CD5{sup +} B cells play a predominant role in the presentation of conventional antigens to antigen-specific T cells. (author). 30 refs, 6 tabs.

  1. Social insect genomes exhibit dramatic evolution in gene composition and regulation while preserving regulatory features linked to sociality

    DEFF Research Database (Denmark)

    Simola, Daniel F.; Wissler, Lothar; Donahue, Greg;

    2013-01-01

    Genomes of eusocial insects code for dramatic examples of phenotypic plasticity and social organization. We compared the genomes of seven ants, the honeybee, and various solitary insects to examine whether eusocial lineages share distinct features of genomic organization. Each ant lineage contain...

  2. TAR (Theatre as Representation) as a Provocative Teaching Tool in School Administration: A Dramatized Inclusive Classroom Scenario

    Science.gov (United States)

    Meyer, Matthew J.; Young, David C.

    2013-01-01

    The following dramatized classroom scenario depicts a teacher struggling with the nature of an inclusive learning environment, with instructional leadership and supervision of instruction as the theoretical and practical backdrop. The purpose of this article is to demonstrate how the use of a TAR (theatre as representation) case study can be used…

  3. The Development of Evaluation Model for Internal Quality Assurance System of Dramatic Arts College of Bunditpattanasilpa Institute

    Science.gov (United States)

    Sinthukhot, Kittisak; Srihamongkol, Yannapat; Luanganggoon, Nuchwana; Suwannoi, Paisan

    2013-01-01

    The research purpose was to develop an evaluation model for the internal quality assurance system of the dramatic arts College of Bunditpattanasilpa Institute. The Research and Development method was used as research methodology which was divided into three phases; "developing the model and its guideline", "trying out the actual…

  4. The Effects of Triptolide on HLA Antigens Expression of Corneal Epithelial Cells Induced by Interferon-γin Vitro

    Institute of Scientific and Technical Information of China (English)

    Qi Zhao; Yiezi Liu; Quanfu Li

    2000-01-01

    Objective: To observe the effects of immunosuppressants triptolide (TL) and cyclosporine A (CSA) on HLA antigens expression induced by interferon-γ(INF -γ) in vitro.Method: By using an indirect immunofluorescent method and analysing with ACAS-570, the abnormal HLA antigen expression of cultured corneal epithelial cells was induced by INF-γ. After incubation with one of the immunosuppressants (CSA, TL) for 72 hrs, the amount of HLA-A BC and HLA-DR antigens was measured.Result: There was no significant difference ( P > 0.05) between the group with CSA and the positive control group without CSA. In contrast to CSA, TL dramatically inhibited INF-γ induced expression of HLA antigens of corneal epithelial cells (P<0.001), compared with the control group without TL.Conclusion: TL had direct inhibition on the expression of HLA-ABCand HLA-DR antigens induced by INF-γin vitro, while CSA had no obvious inhibition. Eye Science 2000; 16:34 ~ 37.

  5. Tandem CAR T cells targeting HER2 and IL13Rα2 mitigate tumor antigen escape.

    Science.gov (United States)

    Hegde, Meenakshi; Mukherjee, Malini; Grada, Zakaria; Pignata, Antonella; Landi, Daniel; Navai, Shoba A; Wakefield, Amanda; Fousek, Kristen; Bielamowicz, Kevin; Chow, Kevin K H; Brawley, Vita S; Byrd, Tiara T; Krebs, Simone; Gottschalk, Stephen; Wels, Winfried S; Baker, Matthew L; Dotti, Gianpietro; Mamonkin, Maksim; Brenner, Malcolm K; Orange, Jordan S; Ahmed, Nabil

    2016-08-01

    In preclinical models of glioblastoma, antigen escape variants can lead to tumor recurrence after treatment with CAR T cells that are redirected to single tumor antigens. Given the heterogeneous expression of antigens on glioblastomas, we hypothesized that a bispecific CAR molecule would mitigate antigen escape and improve the antitumor activity of T cells. Here, we created a CAR that joins a HER2-binding scFv and an IL13Rα2-binding IL-13 mutein to make a tandem CAR exodomain (TanCAR) and a CD28.ζ endodomain. We determined that patient TanCAR T cells showed distinct binding to HER2 or IL13Rα2 and had the capability to lyse autologous glioblastoma. TanCAR T cells exhibited activation dynamics that were comparable to those of single CAR T cells upon encounter of HER2 or IL13Rα2. We observed that TanCARs engaged HER2 and IL13Rα2 simultaneously by inducing HER2-IL13Rα2 heterodimers, which promoted superadditive T cell activation when both antigens were encountered concurrently. TanCAR T cell activity was more sustained but not more exhaustible than that of T cells that coexpressed a HER2 CAR and an IL13Rα2 CAR, T cells with a unispecific CAR, or a pooled product. In a murine glioblastoma model, TanCAR T cells mitigated antigen escape, displayed enhanced antitumor efficacy, and improved animal survival. Thus, TanCAR T cells show therapeutic potential to improve glioblastoma control by coengaging HER2 and IL13Rα2 in an augmented, bivalent immune synapse that enhances T cell functionality and reduces antigen escape.

  6. The efficacy of high-dose penicillin for community-acquired pneumonia diagnosed by pneumococcal urine antigen test.

    Science.gov (United States)

    Oka, Hideaki; Ueda, Atsuhisa; Watanuki, Yuji; Tsukiji, Jun; Kuroda, Hideyo; Akashi, Syunsuke; Hirai, Yoshihiro; Fuyuki, Toshiharu; Kaneko, Takeshi; Ishigatsubo, Yoshiaki

    2009-04-01

    We analyzed the efficacy of both the Streptococcus pneumoniae urine antigen test as a quick diagnostic tool and the administration of high-dose penicillin in response to a positive S. pneumoniae urine antigen test. We conducted a retrospective analysis of 48 cases of pneumococcal pneumonia, in which the patients were treated with high-dose penicillin. All the cases were diagnosed by a positive urine antigen test. Treatment with high-dose penicillin was effective in 43 of the 48 patients. This treatment was also effective in 12 of 16 culture-confirmed cases with low susceptibility to penicillin. Eleven patients who were positive for the S. pneumoniae urine antigen test but culture-negative showed clinical improvement with high-dose penicillin. Pneumonia caused by S. pneumoniae appeared to be treated safely and effectively with high-dose penicillin based on positive results of the urine antigen test, as penicillin resistance was unlikely to be a problem.

  7. Expression and Antigenic Evaluation of VacA Antigenic Fragment of Helicobacter Pylori

    Directory of Open Access Journals (Sweden)

    Leila Hasanzadeh

    2013-07-01

    Full Text Available Objective(s: Helicobacter pylori, a human specific gastric pathogen is a causative agent of chronic active gastritis. The vacuolating cytotoxin (VacA is an effective virulence factor involved in gastric injury. The aim of this study was to construct a recombinant protein containing antigenic region of VacA gene and determine its antigenicity.   Materials and Methods: The antigenic region of VacA gene was detected by bioinformatics methods. The polymerase chain reaction method was used to amplify a highly antigenic region of VacA gene from chromosomal DNA of H. pylori. The eluted product was cloned into the prokaryotic expression vector pET32a. The target protein was expressed in the Escherichia coli BL21 (DE3 pLysS. The bacteria including pET32a-VacA plasmids were induced by IPTG. The antigenicity was finally studied by western blotting using sera of 15 H. pylori infected patients after purification. Results: Enzyme digestion analysis, PCR and DNA sequencing results showed that the target gene was inserted correctly into the recombinant vector. The expressed protein was purified successfully via affinity chromatography. Data indicated that antigenic region of VacA protein from Helicobacter pylori was recognized by all 15 patient’s sera. Conclusion : Our data showed that antigenic region of VacA protein can be expressed by in E. co.li. This protein was recognized by sera patients suffering from H. pylori infection. the recombinant protein has similar epitopes and close antigenic properties to the natural form of this antigen. Recombinant antigenic region of VacA protein also seems to be a promising antigen for protective and serologic diagnosis .

  8. Development of Yersinia pestis F1 antigen-loaded microspheres vaccine against plague

    Directory of Open Access Journals (Sweden)

    Huang SS

    2014-02-01

    immunization of BALB/c mice. The study results show that the greatest survival was observed in the group of mice immunized with one dose of F1 antigen-loaded PLGA/PEG microspheres, and two doses of F1 antigen in Al(OH3 vaccine (100%. In vivo vaccination studies also demonstrated that F1 vaccines microspheres had a protective ability; its steady-state IgG immune protection in mice plasma dramatic increased from 2 weeks (18,764±3,124 to 7 weeks (126,468±19,176 after vaccination. These findings strongly suggest that F1-antigen loaded microspheres vaccine offer a new therapeutic strategy in optimizing the vaccine incorporation and delivery properties of these potential vaccine targeting carriers.Keywords: PLGA, immunological, protective responses

  9. Tumor-Associated Antigens for Specific Immunotherapy of Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kiessling, Andrea [Biologics Safety and Disposition, Preclinical Safety, Translational Sciences, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Werk Klybeck, Klybeckstraße 141, Basel CH-4057 (Switzerland); Wehner, Rebekka [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Füssel, Susanne [Department of Urology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Bachmann, Michael [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Wirth, Manfred P. [Department of Urology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Schmitz, Marc, E-mail: marc.schmitz@tu-dresden.de [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany)

    2012-02-22

    Prostate cancer (PCa) is the most common noncutaneous cancer diagnosis and the second leading cause of cancer-related deaths among men in the United States. Effective treatment modalities for advanced metastatic PCa are limited. Immunotherapeutic strategies based on T cells and antibodies represent interesting approaches to prevent progression from localized to advanced PCa and to improve survival outcomes for patients with advanced disease. CD8{sup +} cytotoxic T lymphocytes (CTLs) efficiently recognize and destroy tumor cells. CD4{sup +} T cells augment the antigen-presenting capacity of dendritic cells and promote the expansion of tumor-reactive CTLs. Antibodies mediate their antitumor effects via antibody-dependent cellular cytotoxicity, activation of the complement system, improving the uptake of coated tumor cells by phagocytes, and the functional interference of biological pathways essential for tumor growth. Consequently, several tumor-associated antigens (TAAs) have been identified that represent promising targets for T cell- or antibody-based immunotherapy. These TAAs comprise proteins preferentially expressed in normal and malignant prostate tissues and molecules which are not predominantly restricted to the prostate, but are overexpressed in various tumor entities including PCa. Clinical trials provide evidence that specific immunotherapeutic strategies using such TAAs represent safe and feasible concepts for the induction of immunological and clinical responses in PCa patients. However, further improvement of the current approaches is required which may be achieved by combining T cell- and/or antibody-based strategies with radio-, hormone-, chemo- or antiangiogenic therapy.

  10. Heterosubtypic protection against pathogenic human and avian influenza viruses via in vivo electroporation of synthetic consensus DNA antigens.

    Directory of Open Access Journals (Sweden)

    Dominick J Laddy

    Full Text Available BACKGROUND: The persistent evolution of highly pathogenic avian influenza (HPAI highlights the need for novel vaccination techniques that can quickly and effectively respond to emerging viral threats. We evaluated the use of optimized consensus influenza antigens to provide broad protection against divergent strains of H5N1 influenza in three animal models of mice, ferrets, and non-human primates. We also evaluated the use of in vivo electroporation to deliver these vaccines to overcome the immunogenicity barrier encountered in larger animal models of vaccination. METHODS AND FINDINGS: Mice, ferrets and non-human primates were immunized with consensus plasmids expressing H5 hemagglutinin (pH5HA, N1 neuraminidase (pN1NA, and nucleoprotein antigen (pNP. Dramatic IFN-gamma-based cellular immune responses to both H5 and NP, largely dependent upon CD8+ T cells were seen in mice. Hemaggutination inhibition titers classically associated with protection (>1:40 were seen in all species. Responses in both ferrets and macaques demonstrate the ability of synthetic consensus antigens to induce antibodies capable of inhibiting divergent strains of the H5N1 subtype, and studies in the mouse and ferret demonstrate the ability of synthetic consensus vaccines to induce protection even in the absence of such neutralizing antibodies. After challenge, protection from morbidity and mortality was seen in mice and ferrets, with significant reductions in viral shedding and disease progression seen in vaccinated animals. CONCLUSIONS: By combining several consensus influenza antigens with in vivo electroporation, we demonstrate that these antigens induce both protective cellular and humoral immune responses in mice, ferrets and non-human primates. We also demonstrate the ability of these antigens to protect from both morbidity and mortality in a ferret model of HPAI, in both the presence and absence of neutralizing antibody, which will be critical in responding to the

  11. Blockade of LFA-1 augments in vitro differentiation of antigen-induced Foxp3+ Treg cells

    Science.gov (United States)

    Verhagen, Johan; Wraith, David C.

    2014-01-01

    Adoptive transfer of antigen-specific, in vitro-induced Foxp3+ Treg (iTreg) cells protects against autoimmune disease. To generate antigen-specific iTreg cells at high purity, however, remains a challenge. Whereas polyclonal T cell stimulation with anti-CD3 and anti-CD28 antibody yields Foxp3+ iTreg cells at a purity of 90–95%, antigen-induced iTreg cells typically do not exceed a purity of 65–75%, even in a TCR-transgenic model. In a similar vein to thymic Treg cell selection, iTreg cell differentiation is influenced not only by antigen recognition and the availability of TGF-β but also by co-factors including costimulation and adhesion molecules. In this study, we demonstrate that blockade of the T cell integrin Leukocyte Function-associated Antigen-1 (LFA-1) during antigen-mediated iTreg cell differentiation augments Foxp3 induction, leading to approximately 90% purity of Foxp3+ iTreg cells. This increased efficacy not only boosts the yield of Foxp3+ iTreg cells, it also reduces contamination with activated effector T cells, thus improving the safety of adoptive transfer immunotherapy. PMID:25108241

  12. Non-cytolytic antigen clearance in DNA-vaccinated mice with electropotation

    Institute of Scientific and Technical Information of China (English)

    Jin-liang PENG; Yong-gang ZHAO; Jun-hua MAI; Wen-ka PANG; Wei GUO; Guang-ming CHEN; Guo-yu MO; Gui-rong RAO; Yu-hong XU

    2007-01-01

    Aim: To explore the potential of electroporation (EP)-mediated hepatitis B virus (HBV) DNA vaccination for the treatment of chronic HBV infection. Methods: BALB/c mice were vaccinated with HBV DNA vaccine encoding for the HBV preS2-S antigen, combined with or without EP. HBV surface antigen expression plasmid was administered into mice liver via a hydrodynamic injection to mimic HBV infection. The clearance of antigen in the serum and liver was detected by ELISA assay and immunohistochemical staining. The histopathology of the liver tissues was examined by HE staining and serum alanine aminotransferase assay.Results: The immunogenicity ofHBV DNA vaccine encoding for the HBV preS2-S antigen can be improved by EP-mediated vaccine delivery. The elicited immune responses can indeed reduce the expression of HBV surface antigen (HBsAg) in hepatocytes of the mouse model that was transfected to express HBsAg using the hydrodynamic injection method. The antigen clearance process did not cause significant toxicity to liver tissue, suggesting a non-cytolytic mechanism. Conclusion: The EP-aided DNA vaccination may have potential in mediating viral clearance in chronic hepatitis B patients.

  13. Potential Target Antigens for a Universal Vaccine in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Renee Vermeij

    2010-01-01

    Full Text Available The prognosis of epithelial ovarian cancer (EOC, the primary cause of death from gynaecological malignancies, has only modestly improved over the last decades. Immunotherapeutic treatment using a cocktail of antigens has been proposed as a “universal” vaccine strategy. We determined the expression of tumor antigens in the context of MHC class I expression in 270 primary tumor samples using tissue microarray. Expression of tumor antigens p53, SP17, survivin, WT1, and NY-ESO-1 was observed in 120 (48.0%, 173 (68.9%, 208 (90.0%, 129 (56.3%, and 27 (11.0% of 270 tumor specimens, respectively. In 93.2% of EOC, at least one of the investigated tumor antigens was (overexpressed. Expression of MHC class I was observed in 78.1% of EOC. In 3 out 4 primary tumors, (overexpression of a tumor antigen combined with MHC class I was observed. These results indicate that a multiepitope vaccine, comprising these antigens, could serve as a universal therapeutic vaccine for the vast majority of ovarian cancer patients.

  14. Antigen cross-presentation of immune complexes.

    Science.gov (United States)

    Platzer, Barbara; Stout, Madeleine; Fiebiger, Edda

    2014-01-01

    The ability of dendritic cells (DCs) to cross-present tumor antigens has long been a focus of interest to physicians, as well as basic scientists, that aim to establish efficient cell-based cancer immune therapy. A prerequisite for exploiting this pathway for therapeutic purposes is a better understanding of the mechanisms that underlie the induction of tumor-specific cytotoxic T-lymphocyte (CTL) responses when initiated by DCs via cross-presentation. The ability of humans DC to perform cross-presentation is of utmost interest, as this cell type is a main target for cell-based immunotherapy in humans. The outcome of a cross-presentation event is guided by the nature of the antigen, the form of antigen uptake, and the subpopulation of DCs that performs presentation. Generally, CD8α(+) DCs are considered to be the most potent cross-presenting DCs. This paradigm, however, only applies to soluble antigens. During adaptive immune responses, immune complexes form when antibodies interact with their specific epitopes on soluble antigens. Immunoglobulin G (IgG) immune complexes target Fc-gamma receptors on DCs to shuttle exogenous antigens efficiently into the cross-presentation pathway. This receptor-mediated cross-presentation pathway is a well-described route for the induction of strong CD8(+) T cell responses. IgG-mediated cross-presentation is intriguing because it permits the CD8(-) DCs, which are commonly considered to be weak cross-presenters, to efficiently cross-present. Engaging multiple DC subtypes for cross-presentation might be a superior strategy to boost CTL responses in vivo. We here summarize our current understanding of how DCs use IgG-complexed antigens for the efficient induction of CTL responses. Because of its importance for human cell therapy, we also review the recent advances in the characterization of cross-presentation properties of human DC subsets.

  15. Dramatic and sustained responsiveness of pulmonary Langerhans cell histiocytosis-associated pulmonary hypertension to vasodilator therapy

    Science.gov (United States)

    May, Adam; Kane, Garvan; Yi, Eunhee; Frantz, Robert; Vassallo, Robert

    2014-01-01

    Pulmonary Langerhans cell histiocytosis (PLCH) is an uncommon diffuse lung disease characterized by the abnormal accumulation of Langerhans' cells around small airways and other distal lung compartments. Although pulmonary hypertension (PH) is a frequent complication of PLCH, the role of advanced PH therapies for PLCH-related PH is not well-established. We describe a PLCH patient with severe, disease-related PH that responded unexpectedly well to advanced PH therapy with sustained improvement over a 10 year follow-up period. This case indicates that PLCH-associated PH may, in certain instances, be highly responsive to advanced PH therapies and emphasizes the importance of trialing these therapies among patients with PLCH-related PH. PMID:26029568

  16. Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators

    Directory of Open Access Journals (Sweden)

    Signe Tandrup Schmidt

    2016-03-01

    Full Text Available The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens for which no effective vaccines exist. The subunit vaccine technology exploits pathogen subunits as antigens, e.g., recombinant proteins or synthetic peptides, allowing for highly specific immune responses against the pathogens. However, such antigens are usually not sufficiently immunogenic to induce protective immunity, and they are often combined with adjuvants to ensure robust immune responses. Adjuvants are capable of enhancing and/or modulating immune responses by exposing antigens to antigen-presenting cells (APCs concomitantly with conferring immune activation signals. Few adjuvant systems have been licensed for use in human vaccines, and they mainly stimulate humoral immunity. Thus, there is an unmet demand for the development of safe and efficient adjuvant systems that can also stimulate cell-mediated immunity (CMI. Adjuvants constitute a heterogeneous group of compounds, which can broadly be classified into delivery systems or immunostimulators. Liposomes are versatile delivery systems for antigens, and they can carefully be customized towards desired immune profiles by combining them with immunostimulators and optimizing their composition, physicochemical properties and antigen-loading mode. Immunostimulators represent highly diverse classes of molecules, e.g., lipids, nucleic acids, proteins and peptides, and they are ligands for pattern-recognition receptors (PRRs, which are differentially expressed on APC subsets. Different formulation strategies might thus be required for incorporation of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the

  17. Added value of antigen ELISA in the diagnosis of neurocysticercosis in resource poor settings.

    Directory of Open Access Journals (Sweden)

    Sarah Gabriël

    Full Text Available BACKGROUND: Neurocysticercosis (NCC is the most common cause of acquired epilepsy in Taenia solium endemic areas, primarily situated in low-income countries. Diagnosis is largely based upon the "Del Brutto diagnostic criteria" using the definitive/probable/no NCC diagnosis approach. Neuroimaging and specific T. solium cysticercosis antibody detection results are at the mainstay of this diagnosis, while antigen detection in serum has never been included. This study aimed at evaluating the addition of antigen detection as a major diagnostic criterion, especially in areas where neuroimaging is absent. METHODS: The B158/B60 monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA for the detection of circulating cysticercus antigen was carried out retrospectively on serum samples collected during a hospital-based study from 83 people with epilepsy (PWE in an endemic area. RESULTS: The addition of antigen results as a major criterion allowed the correct diagnosis of definitive NCC in 10 out of 17 patients as opposed to 0/17 without antigen results in the absence of neuroimaging. A sensitivity of 100% and a specificity of 84% were determined for the diagnosis of active NCC using antigen ELISA. While the use of a higher cutoff improves the specificity of the test to 96%, it decreases its sensitivity to 83%. CONCLUSIONS: In areas where neuroimaging is absent, NCC diagnosis according to the existing criteria is problematic. Taking into account its limitations for diagnosis of inactive NCC, antigen detection can be of added value for diagnosing NCC in PWE by supporting diagnostic and treatment decisions. Therefore, we recommend a revision of the "Del Brutto diagnostic criteria" for use in resource poor areas and suggest the inclusion of serum antigen detection as a major criterion.

  18. Metal based nanoparticles as cancer antigen delivery vehicles for macrophage based antitumor vaccine.

    Science.gov (United States)

    Chattopadhyay, Sourav; Dash, Sandeep Kumar; Mandal, Debasis; Das, Balaram; Tripathy, Satyajit; Dey, Aditi; Pramanik, Panchanan; Roy, Somenath

    2016-02-10

    In the present study, we would like to evaluate the efficacy of modified metal oxide nanoparticles (NPs) as cancer antigen delivery vehicles for macrophage (MФs) based antitumor vaccine. The cobalt oxide nanoparticles (CoO NPs) were promising tools for delivery of antigens to antigen presenting cells and have induced an antitumor immune response. Synthesized CoO NPs were modified by N-phosphonomethyliminodiacetic acid (PMIDA), facilitated the conjugation of lysate antigen, i.e. cancer antigen derived from lysis of cancer cells. The cancer cell lysate antigen conjugated PMIDA-CoO NPs (Ag-PMIDA-CoO NPs) successfully activated macrophage (MФ) evident by the increasing the serum IFN-γ and TNF-α level. Immunization of mice with the Ag-PMIDA-CoO NPs constructed an efficient immunological adjuvant induced anticancer IgG responses, and increased the antibody dependent cellular cytotoxicity (ADCC) response than only lysate antigen treated group to combat the cancer cell. The nanocomplexes enhanced the anticancer CD4(+)T cell response in mice. The result showed that Ag-PMIDA-CoO NPs can stimulate the immune responses over only lysate antigens, which are the most important findings in this study. These NP-mediated Ag deliveries may significantly improve the anticancer immune response by activating MФs and may act as adjuvant and will balance the pro-inflammatory and anti-inflammatory immunoresponse. The crosstalk between the activated MФ with other immune competent cells will be monitored by measuring the cytokines which illustrate the total immunological network setups.

  19. Seroreactivity of Salmonella-infected cattle herds against a fimbrial antigen in comparison with lipopolysaccharide antigens

    DEFF Research Database (Denmark)

    Hoorfar, Jeffrey; Lind, Peter; Bell, M.M.

    1996-01-01

    The IgG seroreaction of Salmonella-infected cattle herds against a fimbrial antigen (SEF14) was compared with that against lipopolysaccharide (LPS) antigens. Sera from 23 dairy herds (n = 205) from an island with no occurrence of salmonellosis, four herds (n = 303) with recent outbreaks of S...

  20. The antigenic relationship between Brettanomyces-Debaryomyces strains and the Salmonella cholerae-suis O antigen.

    Science.gov (United States)

    Aksoycan, N; Sağanak, I; Wells, G

    1978-01-01

    The immune sera for Brettanomyces lambicus, B. claussenii, Debaryomyces hansenii and D. marama agglutinated Salmonella cholerae-suis (0:6(2), 7). The immune serum for S. cholerae-suis agglutinated B. lambicus, B. clausenni, D. hansenii and D. marama. Absorption and agglutination cross-tested demonstrated common antigen factor(s) in the tested yeasts and Salmonella 0:7 antigen.

  1. Antigen presentation by MHC-dressed cells

    Directory of Open Access Journals (Sweden)

    Masafumi eNakayama

    2015-01-01

    Full Text Available Professional antigen presenting cells (APCs such as conventional dendritic cells (DCs process protein antigens to MHC-bound peptides and then present the peptide-MHC complexes to T cells. In addition to this canonical antigen presentation pathway, recent studies have revealed that DCs and non-APCs can acquire MHC class I (MHCI and/or MHC class II (MHCII from neighboring cells through a process of cell-cell contact-dependent membrane transfer called trogocytosis. These MHC-dressed cells subsequently activate or regulate T cells via the preformed antigen peptide-MHC complexes without requiring any further processing. In addition to trogocytosis, intercellular transfer of MHCI and MHCII can be mediated by secretion of membrane vesicles such as exosomes from APCs, generating MHC-dressed cells. This review focuses on the physiological role of antigen presentation by MHCI- or MHCII-dressed cells, and also discusses differences and similarities between trogocytosis and exosome-mediated transfer of MHC.

  2. Dramatic reduction of surface recombination by in situ surface passivation of silicon nanowires.

    Science.gov (United States)

    Dan, Yaping; Seo, Kwanyong; Takei, Kuniharu; Meza, Jhim H; Javey, Ali; Crozier, Kenneth B

    2011-06-08

    Nanowires have unique optical properties and are considered as important building blocks for energy harvesting applications such as solar cells. However, due to their large surface-to-volume ratios, the recombination of charge carriers through surface states reduces the carrier diffusion lengths in nanowires a few orders of magnitude, often resulting in the low efficiency (a few percent or less) of nanowire-based solar cells. Reducing the recombination by surface passivation is crucial for the realization of high-performance nanosized optoelectronic devices but remains largely unexplored. Here we show that a thin layer of amorphous silicon (a-Si) coated on a single-crystalline silicon nanowire, forming a core-shell structure in situ in the vapor-liquid-solid process, reduces the surface recombination nearly 2 orders of magnitude. Under illumination of modulated light, we measure a greater than 90-fold improvement in the photosensitivity of individual core-shell nanowires, compared to regular nanowires without shell. Simulations of the optical absorption of the nanowires indicate that the strong absorption of the a-Si shell contributes to this effect, but we conclude that the effect is mainly due to the enhanced carrier lifetime by surface passivation.

  3. 4-1BB Costimulation Ameliorates T Cell Exhaustion Induced by Tonic Signaling of Chimeric Antigen Receptors

    Science.gov (United States)

    Long, Adrienne H.; Haso, Waleed M.; Shern, Jack F.; Wanhainen, Kelsey M.; Murgai, Meera; Ingaramo, Maria; Smith, Jillian P.; Walker, Alec J.; Kohler, M. Eric; Venkateshwara, Vikas R.; Kaplan, Rosandra N.; Patterson, George H.; Fry, Terry J.; Orentas, Rimas J.; Mackall, Crystal L.

    2015-01-01

    Chimeric antigen receptors (CARs) targeting CD19 have mediated dramatic anti-tumor responses in hematologic malignancies, but tumor regression has rarely occurred using CARs targeting other antigens. It remains unknown whether the impressive effects of CD19 CARs relate to greater susceptibility of hematologic malignancies to CAR therapies, or superior functionality of the CD19 CAR itself. We discovered that tonic CAR CD3ζ phosphorylation, triggered by antigen-independent clustering of CAR scFvs, can induce early exhaustion of CAR T cells that limits anti-tumor efficacy. Such activation is present to varying degrees in all CARs studied, with the exception of the highly effective CD19 CAR. We further identify that CD28 costimulation augments, while 4-1BB costimulation ameliorates, exhaustion induced by persistent CAR signaling. Our results provide biological explanations for the dramatic anti-tumor effects of CD19 CARs and for the observations that CD19.BBz CAR T cells are more persistent than CD19.28z CAR T cells in clinical trials. PMID:25939063

  4. Dramatic decline in fertility marks changes in reproductive behavior in Bangladesh.

    Science.gov (United States)

    1995-01-01

    A summary is given of data from the 1993-94 Bangladesh Demographic and Health Survey. Fertility declined from 6.3 births per woman during the 1970s to 4.3 during 1989-91 and finally 3.4 births during 1991-93, which was a 21% decline in a 2-year period. A validation study in the Matlab area confirmed the decline. The decline is attributed to increases in age at first marriage, increases in age at first birth, and, mostly, increases in contraceptive usage. Family planning use increased from 8% in 1975 to 45% during 1993-94. Almost 40% of all contraceptive use was the pill. 8% used sterilization, 5% used periodic abstinence, and 5% used injection. 3% of married relied on condoms for contraception, and 3% practiced withdrawal. Under 2% relied on the IUD or male sterilization. A slight shift has occurred away from permanent methods to spacing methods, which are less effective. This shift is a concern, given that 48% of women reported a desire to stop childbearing. Almost 50% of women reported having heard or seen family planning messages in the month preceding the survey. Under-5 child mortality declined from 180 deaths per 1000 births during 1979-83 to 133 during 1989-93. 60% of children 12-23 months old were fully immunized, which reflects a considerable increase since 1989. Maternal health has not made the same improvements as child health. Almost 75% did not receive any prenatal care, and 96% of births were home deliveries. Under 10% of deliveries were with trained medical personnel.

  5. Antigenic typing Polish isolates of canine parvovirus

    Energy Technology Data Exchange (ETDEWEB)

    Mizak, B. [National Veterinary Research Institute, Pulawy (Poland); Plucienniczak, A. [Polish Academy ofd Sciences. Microbiology and Virology Center, Lodz (Poland)

    1995-12-31

    Polish strains of canine parvovirus isolated between 1982 and 1993 were examined to determine the extent to which the virus has evolved antigenically and genetically over eleven years. Two CPV isolates obtained in Warsaw in 1982 and Pulawy in 1993, were examined using monoclonal antibody typing, restriction analysis and sequencing VP-2 protein gene. Five other isolates from Warsaw and Pulawy were tested with the panel of monoclonal antibodies specific to CPV-2, CPV-2a and common for canine parvovirus, feline panleukopenia virus and milk enteritis virus. Results of the studies demonstrated that all isolates tested represented CPV-2a antigenic type. Rapid antigenic strain replacement recorded by Parrish and Senda in the U.S.A and Japan was not confirmed in Poland. (author). 30 refs, 2 tabs.

  6. ESL / EFL / SLE THROUGH DRAMA AS QUALITY-ORIENTED EDUCATION: BRAIN RESEARCH, DRAMATIC METHODS AND LANGUAGE ACQUISITION

    Institute of Scientific and Technical Information of China (English)

    JoyceA.Wilkinson

    2001-01-01

    This paper traces evidence from neurobehavioural researchshowing how language functions occur in the brain and supportthe efficacy of drama as a methodology in all language learning.According to Pribram’s holographic view of the brain, move-ment is integral to the transference of vocabulary from the poste-rior convexity to the frontal cortex where words are transformedinto meaning via pragmatic processing mechanisms and then pro-duced as language in the midbrain motor structure which is alsothe center of emotion. Drama is movement with emotion. Words which become amplified with meaning during the dramat-ic process traverse neuronal pathways from the lexicographic,posterior brain to the right forebrain and converge in vocal ex-pression in the centrencephalic mechanism. Without such move-ment, meaning and output do not occur. Words impregnatedwith meaning in the emotional movement of the dramatic processparallel drama-language movements within the brain so thatlearning becomes deeply embedded, retained and easily recalled.Tested drama methods which reinforce or imprint such intra-brain language functions are briefly reviewed as is selected drama-language research supporting the drama-brain-language concep-tual framework of holistic language learning theory. It is arguedthat learning a second language as well as a first languagethrough drama, the language art form which imbues the narra-tive and language structures of any culture, constitutes qualityeducation.

  7. MODELS OF THE SPEECH PORTRAIT AND THE LINGVOPSYCHOLOGICAL PORTRAIT OF DRAMATIC CHARACTERS IN A.P. CHEKHOV'S PLAY "UNCLE VANYA"

    Directory of Open Access Journals (Sweden)

    Jiang Zhiyan

    2016-01-01

    Full Text Available This article highlights the problem of the models of the speech portrait and portraying the dramatic characters by studying the lingvopsychological lexicon in terms of a lingvopsychology. In spite of the fact that today a large number of works on the speech portrait was published, poorly studied a problem of the speech portrait of the dramatic characters of Chekhov's play. Moreover, the researchers did not find an effective approach to the description and analysis of the speech portrait of the dramatic character of Chekhov's play. Thus, in our study, we have created firstly the model for the study of the speech portrait of Chekhov's play (based on the play "Uncle Vanya", taking into account the linguistic culture and lingvopsychology. The lingvopsychological portrait consists of the lingvopsychological lexicons that reflect a mental state and a mental activity, in our opinion. Through the research object of a psychology we use the linguistic research methods, carrying out of a comparison analysis the semantiс fields which form lingvopsychological lexicons in the mental state and the mental activity. In the psychosematic fields manifest the opposition of the semantic fields of the lingvopsychological lexicons by the mental state: about passive and active, about pessimism and the optimism. In addition, the estimated-semantic and moral-semantic field of a mental state can reveal the lingvopsychological portrait. Opposition of the semantic fields by the mental activity make up the lingvopsychological lexicons: love ‒ hate, envy, like ‒ bother.

  8. Multivalent Chromosomal Expression of the Clostridium botulinum Serotype A Neurotoxin Heavy-Chain Antigen and the Bacillus anthracis Protective Antigen in Lactobacillus acidophilus

    Science.gov (United States)

    Klaenhammer, Todd R.

    2016-01-01

    ABSTRACT Clostridium botulinum and Bacillus anthracis produce potent toxins that cause severe disease in humans. New and improved vaccines are needed for both of these pathogens. For mucosal vaccine delivery using lactic acid bacteria, chromosomal expression of antigens is preferred over plasmid-based expression systems, as chromosomal expression circumvents plasmid instability and the need for antibiotic pressure. In this study, we constructed three strains of Lactobacillus acidophilus NCFM expressing from the chromosome (i) the nontoxic host receptor-binding domain of the heavy chain of Clostridium botulinum serotype A neurotoxin (BoNT/A-Hc), (ii) the anthrax protective antigen (PA), and (iii) both the BoNT/A-Hc and the PA. The BoNT/A-Hc vaccine cassette was engineered to contain the signal peptide from the S-layer protein A from L. acidophilus and a dendritic-cell-targeting peptide. A chromosomal region downstream of lba0889 carrying a highly expressed enolase gene was selected for insertion of the vaccine cassettes. Western blot analysis confirmed the heterologous expression of the two antigens from plasmid and chromosome locations. Stability assays demonstrated loss of the vaccine cassettes from expression plasmids without antibiotic maintenance. RNA sequencing showed high expression of each antigen and that insertion of the vaccine cassettes had little to no effect on the transcription of other genes in the chromosome. This study demonstrated that chromosomal integrative recombinant strains are promising vaccine delivery vehicles when targeted into high-expression chromosomal regions. Levels of expression match high-copy-number plasmids and eliminate the requirement for antibiotic selective maintenance of recombinant plasmids. IMPORTANCE Clostridium botulinum and Bacillus anthracis produce potent neurotoxins that pose a biochemical warfare concern; therefore, effective vaccines against these bacteria are required. Chromosomal expression of antigens is

  9. Using Creative Dramatics to Foster Conceptual Learning in a Science Enrichment Program

    Science.gov (United States)

    Hendrix, Rebecca Compton

    This study made analysis of how the integration of creative drama into a science enrichment program enhanced the learning of elementary school students' understanding of sound physics and solar energy. The study also sought to determine if student attitudes toward science could be improved with the inclusion of creative drama as an extension to a well-known science inquiry program. The qualitative portion of this study explored the treatment groups' perceptions of how the use of creative drama helped them to learn science. A treatment group of fourth and fifth grade students were taught using the Full Option Science System (FOSS) kit in sound physics and solar energy with the inclusion of creative drama, while a control group of fourth and fifth grade students were taught using only the FOSS kit. The quantitative data analysis revealed that the students who were taught science with the inclusion of creative drama showed greater understanding of the science content than the students in the control group taught without the inclusion of creative drama. Both groups and grade levels in this study showed a slight decline in science attitudes from pre to post survey. Although the overall change was small it was statistically significant. The conclusion from this data is that the inclusion of creative drama in a science inquiry science program does not increase student's attitudes toward learning science any better than inquiry based instruction without creative drama. The drama treatment group students reported that they enjoyed participating in creative drama activities and generally viewed the creative drama intervention as a fun way to learn more about science. The students indicated that the creative drama activities helped them to remember and think about science. The researcher concluded that creative drama when used as an extension to an inquiry science program increases student understanding of science content better than the use of a science inquiry program alone

  10. A Dramatic Increase in Seismic Observations in the Central and Eastern US

    Science.gov (United States)

    Woodward, R.; Busby, R.; Simpson, D.; Alvarez, M.; Vernon, F.

    2009-05-01

    The USArray Transportable Array (TA) is a network of 400 seismograph stations that is systematically moving west-to-east across the contiguous United States. The TA is part of the National Science Foundation's multi- disciplinary EarthScope program. The TA has already occupied over 700 stations in the western US, and is continuing its multi-year migration towards the Atlantic coast before heading for Alaska. The stations use a grid-like deployment with 70 km separation between stations. At any given time there are approximately 400 stations operational, occupying a nominal 800 km by 2000 km "footprint." Each station is operated for two years. TA stations consist of three component broadband seismometers, with a few sites in the westernmost United States also including three component strong motion instruments. The instruments are installed about two meters below the surface, in thermally stable vaults. All stations transmit continuous data in near-real-time, and the data are freely distributed through the IRIS Data Management Center. TA stations can be upgraded to incorporate high frequency or strong motion instrument. Organizations can also "adopt" stations after installation by reimbursing the cost of the hardware, so that the stations become permanent. The TA is presently operating in the swath of the country extending from Texas to Montana. From 2010 to 2013 the TA will occupy ~800 sites in the central and eastern US. The array will be centered on the New Madrid, MO region during the bicentennial of the 1811-1812 earthquakes. During the TA deployment every existing or planned nuclear plant in the eastern US will be within 70 km of at least four new seismic stations. Thus, this station deployment in the eastern half of the US presents an unprecedented opportunity for improving source characterization, modeling the regional velocity and attenuation structure, and mapping seismic zones down to low magnitude thresholds. We will provide an overview of TA

  11. Antigenic variation of Streptococcus mutans colonizing gnotobiotic rats.

    Science.gov (United States)

    Bratthall, D; Gibbons, R J

    1975-12-01

    Strains of Streptococcus mutans representative of serotypes b and d exhibited antigenic variation in both the oral cavity and in the intestinal canal of gnotobiotic rats. Laboratory-maintained cultures did not vary. The antigenic alterations observed were: (i) loss of detectable levels of both weakly reacting "strain" antigens and the type antigen; (ii) decreased production of the type antigen; (ii) production of altered type antigen; and (iv) production of an antigen not possessed by the parent strain. Immunization of animals before monoinfection with S. mutans strain Bob-1 (serotype d) appeared to increase the rate of emergence of antigenically altered mutants in the intestinal canal, and more diversely altered isolates were obtained. Antigenic variation may account in part for the variation noted by several investigators in attempting to immunize animals against S. mutans-induced dental caries.

  12. Properties of glycolipid-enriched membrane rafts in antigen presentation.

    Science.gov (United States)

    Rodgers, William; Smith, Kenneth

    2005-01-01

    Presentation of antigen to T cells represents one of the central events in the engagement of the immune system toward the defense of the host against pathogens. Accordingly, understanding the mechanisms by which antigen presentation occurs is critical toward our understanding the properties of host defense against foreign antigen, as well as insight into other features of the immune system, such as autoimmune disease. The entire antigen-presentation event is complex, and many features of it remain poorly understood. However, recent studies have provided evidence showing that glycolipid-enriched membrane rafts are important for efficient antigen presentation; the studies suggest that one such function of rafts is trafficking of antigen-MHC II complexes to the presentation site on the surface of the antigen-presenting cell. Here, we present a critical discussion of rafts and their proposed functions in antigen presentation. Emerging topics of rafts and antigen presentation that warrant further investigation are also highlighted.

  13. Classification of human leukocyte antigen (HLA) supertypes

    DEFF Research Database (Denmark)

    Wang, Mingjun; Claesson, Mogens H

    2014-01-01

    Identification of new antigenic peptides, derived from infectious agents or cancer cells, which bind to human leukocyte antigen (HLA) class I and II molecules, is of importance for the development of new effective vaccines capable of activating the cellular arm of the immune response. However...... this complexity is to group thousands of different HLA molecules into several so-called HLA supertypes: a classification that refers to a group of HLA alleles with largely overlapping peptide binding specificities. In this chapter, we focus on the state-of-the-art classification of HLA supertypes including HLA...

  14. Identification of sVSG117 as an immunodiagnostic antigen and evaluation of a dual-antigen lateral flow test for the diagnosis of human African trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    Lauren Sullivan

    2014-07-01

    Full Text Available The diagnosis of human African trypanosomiasis (HAT caused by Trypanosoma brucei gambiense relies mainly on the Card Agglutination Test for Trypanosomiasis (CATT. There is no immunodiagnostic for HAT caused by T. b. rhodesiense. Our principle aim was to develop a prototype lateral flow test that might be an improvement on CATT.Pools of infection and control sera were screened against four different soluble form variant surface glycoproteins (sVSGs by ELISA and one, sVSG117, showed particularly strong immunoreactivity to pooled infection sera. Using individual sera, sVSG117 was shown to be able to discriminate between T. b. gambiense infection and control sera by both ELISA and lateral flow test. The sVSG117 antigen was subsequently used with a previously described recombinant diagnostic antigen, rISG65, to create a dual-antigen lateral flow test prototype. The latter was used blind in a virtual field trial of 431 randomized infection and control sera from the WHO HAT Specimen Biobank.In the virtual field trial, using two positive antigen bands as the criterion for infection, the sVSG117 and rISG65 dual-antigen lateral flow test prototype showed a sensitivity of 97.3% (95% CI: 93.3 to 99.2 and a specificity of 83.3% (95% CI: 76.4 to 88.9 for the detection of T. b. gambiense infections. The device was not as good for detecting T. b. rhodesiense infections using two positive antigen bands as the criterion for infection, with a sensitivity of 58.9% (95% CI: 44.9 to 71.9 and specificity of 97.3% (95% CI: 90.7 to 99.7. However, using one or both positive antigen band(s as the criterion for T. b. rhodesiense infection improved the sensitivity to 83.9% (95% CI: 71.7 to 92.4 with a specificity of 85.3% (95% CI: 75.3 to 92.4. These results encourage further development of the dual-antigen device for clinical use.

  15. Improving DNA vaccine performance through vector design.

    Science.gov (United States)

    Williams, James A

    2014-01-01

    DNA vaccines are a rapidly deployed next generation vaccination platform for treatment of human and animal disease. DNA delivery devices, such as electroporation and needle free jet injectors, are used to increase gene transfer. This results in higher antigen expression which correlates with improved humoral and cellular immunity in humans and animals. This review highlights recent vector and transgene design innovations that improve DNA vaccine performance. These new vectors improve antigen expression, increase plasmid manufacturing yield and quality in bioreactors, and eliminate antibiotic selection and other potential safety issues. A flowchart for designing synthetic antigen transgenes, combining antigen targeting, codon-optimization and bioinformatics, is presented. Application of improved vectors, of antibiotic free plasmid production, and cost effective manufacturing technologies will be critical to ensure safety, efficacy, and economically viable manufacturing of DNA vaccines currently under development for infectious disease, cancer, autoimmunity, immunotolerance and allergy indications.

  16. [Presence of Australia antigen in blood donors].

    Science.gov (United States)

    Gota, F

    1980-01-01

    The differential diagnosis of type A and B viral hepatitis is discussed and guidelines for the prevention of post-transfusional hospital hepatitis are proposed. Methods for the immunological demonstration of HBs antigen are illustrated, together with the respective positivity percentages in blood donors.

  17. HLA antigens and asthma in Greeks.

    Science.gov (United States)

    Apostolakis, J; Toumbis, M; Konstantopoulos, K; Kamaroulias, D; Anagnostakis, J; Georgoulias, V; Fessas, P; Zervas, J

    1996-04-01

    HLA-A and -B antigens were determined in a group of 76 Greek asthmatic patients: 35 children (1.5-15 years) and 41 adults (18-73 years). The results were compared to those of 400 healthy unrelated controls from the same population. The standard NIH lymphocytotoxicity test was applied. When all 76 patients were compared to the controls, a statistically significant lower frequency of HLA-B5 and -B35 antigens was noted. When adults were analysed alone, an increased frequency of HLA-B8 was found. On the other hand, in the asthmatic children sub-group, the HLA-A10 antigen was significantly higher and the HLA-B5 was significantly lower than in the controls. These data imply that different HLA antigens may be involved in the pathogenesis of several clinical forms of asthma and that, in order to study the role of immunogenetic factor(s) in the pathogenesis of this disease, more adequate grouping criteria are needed.

  18. Prostate-specific antigen (PSA) blood test

    Science.gov (United States)

    Prostate-specific antigen; Prostate cancer screening test; PSA ... special steps are needed to prepare for this test. ... Reasons for a PSA test: This test may be done to screen for prostate cancer. It is also used to follow people after prostate cancer ...

  19. A NEW SYNTHETIC FUNCTIONALIZED ANTIGEN CARRIER

    NARCIS (Netherlands)

    DRIJFHOUT, JW; BLOEMHOFF, W

    1991-01-01

    A new synthetic functionalized antigen carrier is described. It consists of a core of seven branched lysine residues, of which each of the four N-terminal lysine residues contains two N-(S-acetylmercaptoacetyl)-glutamyl residues. After removal of the protecting S-acetyl groups affording eight thiol

  20. STAINING OF VACCINIA ANTIGEN BY IMMUNOURANIUM TECHNIQUE,

    Science.gov (United States)

    An attempt to follow morphologically the development of vaccinia antigen in helium-lanthanum ( HeLa ) cells is reported. The conversion of rabbit...antisera to vaccinia virus and the preparation of vaccinia-infected HeLa cells for electron microscopy are described. With specific staining, viral

  1. Activation and dramatically increased cytolytic activity of tumor specific T lymphocytes after radio-frequency ablation in patients with hepatocellular carcinoma and colorectal liver metastases

    Institute of Scientific and Technical Information of China (English)

    Johannes H(a)nsler; Thadd(a)us Till Wissniowski; Detlef Schuppan; Astrid Witte; Thomas Bernatik; Eckhart Georg Hahn; Deike Strobel

    2006-01-01

    AIM: To assess if a specific cytotoxic T cell response can be induced in patients with malignant liver tumors treated with radio-frequency ablation (RFA).METHODS: Six Patients with liver metastases of colorectal cancer and 6 with hepatocellular carcinoma (HCC)underwent RFA. Blood was sampled before, 4 and 8 wk after RFA. Test antigens were autologous liver and tumor lysate obtained from each patient by biopsy. Peripheral T cell activation was assessed by an interferon gamma (IFNγ) secretion assay and flow cytometry. T cells were double-stained for CD4/CD8 and IFNγ to detect cytotoxic T cells. The ratio of IFNγ positive and IFNγ negative T cells was determined as the stimulation index (SI). To assess cytolytic activity, T cells were co-incubated with human CaCo colorectal cancer and HepG2 HCC cells and release of cytosolic adenylate kinase was measured by a luciferase assay.RESULTS: Before RFA SI was 0.021 (±0.006) for CD4+and 0.022 (±0.004) for CD8+T cells against nonmalignant liver tissue and 0.018 (±0.005) for CD4+ and 0.021(±0.004) for CD8+ cells against autologous tumor tissue.Four weeks after RFA SI against tumor tissue increased to 0.109 (±0.005) for CD4+ and 0.11 (±0.012) for CD8+T cells against HCC, and to 0.115 (±0.031) for CD4+ and 0.15 (±0.02) for CD8+ cells for colorectal metastases (P <0.0001). No increased SI was observed with nonmalignant tumor tissue at all time points. Before RFA cytolytic activity against the respective cancer cells was low with 2.62 (±0.37) relative luminescence units (RLU), but rose more than 100 fold 4 and 8 wk after RFA. Spontaneous release was <2% of maximum release in all experiments.CONCLUSION: Patients with primary and secondary tumors of the liver show a significant tumor-specific cytotoxic T-cell stimulation with a dramatically increased tumor specific cytolytic activity of CD8+ T cells after RFA.

  2. Leukemia Associated Antigens: Their Dual Role as Biomarkers and Immunotherapeutic Targets for Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Michael Schmitt

    2007-01-01

    Full Text Available Leukemia associated antigens (LAAs are being increasingly identified by methods such as cytotoxic T-lymphocyte (CTL cloning, serological analysis of recombinant cDNA expression libraries (SEREX and mass spectrometry (MS. In additional, large scale screening techniques such as microarray, single nucleotide polymorphisms (SNPs, serial analysis of gene expression (SAGE and 2-dimensional gel electrophoresis (2-DE have expanded our understanding of the role that tumor antigens play in the biological processes which are perturbed in acute myeloid leukemia (AML. It has become increasingly apparent that these antigens play a dual role, not only as targets for immunotherapy, but also as biomarkers of disease state, stage, response to treatment and survival. We need biomarkers to enable the identification of the patients who are most likely to benefit from specific treatments (conventional and/or novel and to help clinicians and scientists improve clinical end points and treatment design. Here we describe the LAAs identified in AML, to date, which have already been shown to play a dual role as biomarkers of AML disease.Abbreviations: AML: acute myeloid leukemia; APL: acute promyelocytic leukemia; ATRA: all-trans-retinoic acid; B-CLL: B-cell chronic lymphocytic leukemia; CT: cancer-testis; CTL: cytotoxic T-lymphocyte; FAB: French-American-British; HI: hypusination inhibitors; HSP: heat shock protein; ITD: internal tandem duplication; LAA: leukemia associated antigen; MDS: myelodysplastic syndrome; MGEA6: meningioma antigen 6; MPD: myeloproliferative disease; MS: mass spectrometry; NK: natural killer; PRAME: preferentially expressed antigen of melanoma; PRTN3: proteinase 3; RAGE-1: renal antigen 1; RHAMM: receptor for hyaluronic acid-mediated motility; RQ-PCR: real-time PCR; SAGE: serial analysis of gene expression; SCT: stem cell transplant; SEREX: serological analysis of recombinant cDNA expression libraries; SNPs: single nucleotide polymorphisms; UPD

  3. Rational antigen modification as a strategy to upregulate or downregulate antigen recognition.

    Science.gov (United States)

    Abrams, S I; Schlom, J

    2000-02-01

    Recent and rapid advances in our understanding of the cellular and molecular mechanisms of antigen recognition by CD8(+) and CD4(+) T lymphocytes have led to the birth of possibilities for site-directed, rational modification of cognate antigenic determinants. This immunologic concept has vast biomedical implications for regulation of host immunity against the pathogenesis of diverse disease processes. The upregulation of antigen-specific T-cell responses by 'agonistic' peptides would be most desirable in response to invasive pathogenic challenges, such as infectious and neoplastic disease, while the downregulation of antigen-specific T-cell responses by 'antagonistic' peptides would be most efficacious during inappropriate pathologic consequences, such as autoimmunity. The capacity to experimentally manipulate intrinsic properties of cognate peptide ligands to appropriately alter the nature, course and potency of cellular immune interactions has important potential in both preventive and therapeutic clinical paradigms.

  4. Induction of Oral Tolerance with Transgenic Plants Expressing Antigens for Prevention/Treatment of Autoimmune, Allergic and Inflammatory Diseases.

    Science.gov (United States)

    Ma, Shengwu; Liao, Yu-Cai; Jevnikar, Anthony M

    2015-01-01

    The prevalence and incidence of autoimmune and allergic diseases have increased dramatically over the last several decades, especially in the developed world. The treatment of autoimmune and allergic diseases is typically with the use of non-specific immunosuppressive agents that compromise the integrity of the host immune system and therefore, increase the risk of infections. Antigenspecific immunotherapy by reinstating immunological tolerance towards self antigens without compromising immune functions is a much desired goal for the treatment of autoimmune and allergic diseases. Mucosal administration of antigen is a long-recognized method of inducing antigen-specific immune tolerance known as oral tolerance, which is viewed as having promising potential in the treatment of autoimmune and allergic diseases. Plant-based expression and delivery of recombinant antigens provide a promising new platform to induce oral tolerance, having considerable advantages including reduced cost and increased safety. Indeed, in recent years the use of tolerogenic plants for oral tolerance induction has attracted increasing attention, and considerable progress has been made. This review summarizes recent advances in using plants to deliver tolerogens for induction of oral tolerance in the treatment of autoimmune, allergic and inflammatory diseases.

  5. Dengue viruses cluster antigenically but not as discrete serotypes

    NARCIS (Netherlands)

    L. Katzelnick (Leah); J.M. Fonville (Judith); G.D. Gromowski (Gregory D.); J.B. Arriaga (Jose Bustos); A. Green (Angela); S.L. James (Sarah ); L. Lau (Louis); M. Montoya (Magelda); C. Wang (Chunling); L.A. Van Blargan (Laura A.); C.A. Russell (Colin); H.M. Thu (Hlaing Myat); T.C. Pierson (Theodore C.); P. Buchy (Philippe); J.G. Aaskov (John G.); J.L. Muñoz-Jordán (Jorge L.); N. Vasilakis (Nikos); R.V. Gibbons (Robert V.); R.B. Tesh (Robert B.); A.D.M.E. Osterhaus (Albert); R.A.M. Fouchier (Ron); A. Durbin (Anna); C.P. Simmons (Cameron P.); E.C. Holmes (Edward C.); E. Harris (Eva); S.S. Whitehead (Stephen S.); D.J. Smith (Derek James)

    2015-01-01

    textabstractThe four genetically divergent dengue virus (DENV) types are traditionally classified as serotypes. Antigenic and genetic differences among the DENV types influence disease outcome, vaccine-induced protection, epidemic magnitude, and viral evolution.We scharacterized antigenic diversity

  6. Cysteine proteases as potential antigens in antiparasitic DNA vaccines

    DEFF Research Database (Denmark)

    Jørgensen, Louise von Gersdorff; Buchmann, Kurt

    2011-01-01

    En litteraturgennemgang af muligheder for at bruge cystein proteaser som antigener i antiparasitære vacciner.......En litteraturgennemgang af muligheder for at bruge cystein proteaser som antigener i antiparasitære vacciner....

  7. Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators

    DEFF Research Database (Denmark)

    Schmidt, Signe Tandrup; Foged, Camilla; Korsholm, Karen Smith

    2016-01-01

    be classified into delivery systems or immunostimulators. Liposomes are versatile delivery systems for antigens, and they can carefully be customized towards desired immune profiles by combining them with immunostimulators and optimizing their composition, physicochemical properties and antigen-loading mode......The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens...... of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the specific PRR expression profile of the target APCs. Here, we review state-of-the-art formulation approaches employed for the inclusion of immunostimulators and subunit...

  8. Synthetic oligonucleotide antigens modified with locked nucleic acids detect disease specific antibodies

    Science.gov (United States)

    Samuelsen, Simone V.; Solov’yov, Ilia A.; Balboni, Imelda M.; Mellins, Elizabeth; Nielsen, Christoffer Tandrup; Heegaard, Niels H. H.; Astakhova, Kira

    2016-01-01

    New techniques to detect and quantify antibodies to nucleic acids would provide a significant advance over current methods, which often lack specificity. We investigate the potential of novel antigens containing locked nucleic acids (LNAs) as targets for antibodies. Particularly, employing molecular dynamics we predict optimal nucleotide composition for targeting DNA-binding antibodies. As a proof of concept, we address a problem of detecting anti-DNA antibodies that are characteristic of systemic lupus erythematosus, a chronic autoimmune disease with multiple manifestations. We test the best oligonucleotide binders in surface plasmon resonance studies to analyze binding and kinetic aspects of interactions between antigens and target DNA. These DNA and LNA/DNA sequences showed improved binding in enzyme-linked immunosorbent assay using human samples of pediatric lupus patients. Our results suggest that the novel method is a promising tool to create antigens for research and point-of-care monitoring of anti-DNA antibodies. PMID:27775006

  9. Synthetic oligonucleotide antigens modified with locked nucleic acids detect disease specific antibodies

    Science.gov (United States)

    Samuelsen, Simone V.; Solov'Yov, Ilia A.; Balboni, Imelda M.; Mellins, Elizabeth; Nielsen, Christoffer Tandrup; Heegaard, Niels H. H.; Astakhova, Kira

    2016-10-01

    New techniques to detect and quantify antibodies to nucleic acids would provide a significant advance over current methods, which often lack specificity. We investigate the potential of novel antigens containing locked nucleic acids (LNAs) as targets for antibodies. Particularly, employing molecular dynamics we predict optimal nucleotide composition for targeting DNA-binding antibodies. As a proof of concept, we address a problem of detecting anti-DNA antibodies that are characteristic of systemic lupus erythematosus, a chronic autoimmune disease with multiple manifestations. We test the best oligonucleotide binders in surface plasmon resonance studies to analyze binding and kinetic aspects of interactions between antigens and target DNA. These DNA and LNA/DNA sequences showed improved binding in enzyme-linked immunosorbent assay using human samples of pediatric lupus patients. Our results suggest that the novel method is a promising tool to create antigens for research and point-of-care monitoring of anti-DNA antibodies.

  10. The Hamster Model for Identification of Specific Antigens of Taenia solium Tapeworms

    Directory of Open Access Journals (Sweden)

    Alicia Ochoa-Sánchez

    2011-01-01

    Full Text Available Humans acquire taeniasis by ingesting pork meat infected with Taenia solium cysticerci, which are the only definitive hosts of the adult stage (tapeworm and responsible for transmitting the human and porcine cysticercosis. Hence, detection of human tapeworm carriers is a key element in the development of viable strategies to control the disease. This paper presents the identification of specific antigens using sera from hamsters infected with T. solium tapeworms analyzed by western blot assay with crude extracts (CEs and excretion-secretion antigens (E/S Ag obtained from T. solium cysticerci and tapeworms and extracts from other helminthes as controls. The hamster sera infected with T. solium tapeworms recognized specific bands of 72, 48, 36, and 24 kDa, in percentages of 81, 81, 90, and 88%, respectively, using the T. solium tapeworms E/S Ag. The antigens recognized by these hamster sera could be candidates to improve diagnosis of human T. solium taeniasis.

  11. Rapid diagnosis of typhoid fever by enzyme-linked immunosorbent assay detection of Salmonella serotype typhi antigens in urine.

    Science.gov (United States)

    Fadeel, Moustafa Abdel; Crump, John A; Mahoney, Frank J; Nakhla, Isabelle A; Mansour, Adel M; Reyad, Baheia; El Melegi, Dawlat; Sultan, Yehia; Mintz, Eric D; Bibb, William F

    2004-03-01

    We developed and evaluated an enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies to capture somatic antigen 9 (O9), flagellar antigen d (Hd), and the Vi capsular polysaccharide antigen (Vi) from the urine of persons with and without typhoid fever. Sequential urine samples were collected from 44 patients with blood culture-confirmed typhoid fever and from two control groups. The first control group included patients with brucellosis (n = 12) and those with clinically diagnosed, non-typhoid, acute, febrile illness (n = 27). The second control group was a sample of healthy volunteer laboratory workers (n = 11). When assessed relative to date of fever onset, sensitivity was highest during the first week for all three antigens: Vi was detected in the urine of nine (100%) patients, O9 in 4 (44%) patients, and Hd in 4 (44%) patients. Sequential testing of two urine samples from the same patient improved test sensitivity. Combined testing for Vi with O9 and Hd produced a trend towards increased sensitivity without compromising specificity. The specificity for Vi exceeded 90% when assessed among both febrile and healthy control subjects, but was only 25% when assessed among patients with brucellosis. Detection of urinary Vi antigen with this ELISA shows promise for the diagnosis of typhoid fever, particularly when used within the first week after fever onset. However, positive reactions for Vi antigen in patients with brucellosis must be understood before urinary Vi antigen detection can be developed further as a useful rapid diagnostic test.

  12. New Approaches with Different Types of Circulating Cathodic Antigen for the Diagnosis of Patients with Low Schistosoma mansoni Load

    Science.gov (United States)

    Grenfell, Rafaella; Harn, Donald A.; Tundup, Smanla; Da'dara, Akram; Siqueira, Liliane; Coelho, Paulo Marcos Zech

    2013-01-01

    Background Schistosomiasis mansoni is a debilitating and sometimes fatal disease. Accurate diagnosis plays a key role in patient management and infection control. However, currently available parasitological methods are laborious and lack sensitivity. The selection of target antigen candidates has turned out to be a promising tool for the development of more sensitive diagnostic methods. In our previous investigations, the use of crude antigens led to false-positive results. Recently, focus has been given to highly purified Schistosoma mansoni antigens, especially to circulating antigens. Method Thus, our main goal was to test different types of circulating cathodic antigen glycoprotein (CCA), as “crude antigen,” the protein chain of recombinant CCA and two individual peptides. These schistosome proteins/peptides were tested in a new diagnostic method employing immunomagnetic separation based on the improvement of antigen–antibody binding. Principal Findings Use of recombinant CCA as a diagnostic antigen allowed us to develop a diagnostic assay with high sensitivity and specificity with no false-negative results. Interestingly, the “crude antigen” worked as a good marker for control of cure after praziquantel treatment. Conclusions/Significance Our new diagnostic method was superior to enzyme-linked immunosorbent assay in diagnosing low endemicity patients. PMID:23469295

  13. Enhancing blockade of Plasmodium falciparum erythrocyte invasion: assessing combinations of antibodies against PfRH5 and other merozoite antigens.

    Directory of Open Access Journals (Sweden)

    Andrew R Williams

    Full Text Available No vaccine has yet proven effective against the blood-stages of Plasmodium falciparum, which cause the symptoms and severe manifestations of malaria. We recently found that PfRH5, a P. falciparum-specific protein expressed in merozoites, is efficiently targeted by broadly-neutralizing, vaccine-induced antibodies. Here we show that antibodies against PfRH5 efficiently inhibit the in vitro growth of short-term-adapted parasite isolates from Cambodia, and that the EC(50 values of antigen-specific antibodies against PfRH5 are lower than those against PfAMA1. Since antibody responses elicited by multiple antigens are speculated to improve the efficacy of blood-stage vaccines, we conducted detailed assessments of parasite growth inhibition by antibodies against PfRH5 in combination with antibodies against seven other merozoite antigens. We found that antibodies against PfRH5 act synergistically with antibodies against certain other merozoite antigens, most notably with antibodies against other erythrocyte-binding antigens such as PfRH4, to inhibit the growth of a homologous P. falciparum clone. A combination of antibodies against PfRH4 and basigin, the erythrocyte receptor for PfRH5, also potently inhibited parasite growth. This methodology provides the first quantitative evidence that polyclonal vaccine-induced antibodies can act synergistically against P. falciparum antigens and should help to guide the rational development of future multi-antigen vaccines.

  14. Creative Sound Dramatics

    Science.gov (United States)

    Hendrix, Rebecca; Eick, Charles

    2014-01-01

    Sound propagation is not easy for children to understand because of its abstract nature, often best represented by models such as wave drawings and particle dots. Teachers Rebecca Hendrix and Charles Eick wondered how science inquiry, when combined with an unlikely discipline like drama, could produce a better understanding among their…

  15. Comparison of Schistosoma mansoni soluble cercarial antigens and soluble egg antigens for serodiagnosing schistosome infections.

    Directory of Open Access Journals (Sweden)

    Huw Smith

    Full Text Available A Schistosoma mansoni cercarial antigen preparation (cercarial transformation fluid--SmCTF was evaluated for detection of anti-schistosome antibodies in human sera in 4 collaborating laboratories. The performance of SmCTF was compared with that of S. mansoni egg antigens (SmSEA in an indirect enzyme-immunoassay (ELISA antigen assay, the latter being used routinely in 3 of the 4 participating laboratories to diagnose S. mansoni and S. haematobium infections. In the fourth laboratory the performance of SmCTF was compared with that of S. japonicum egg antigens (SjSEA in ELISA for detection of anti-S. japonicum antibodies. In all 4 laboratories the results given by SmCTF in ELISA were very similar to those given by the antigen preparation routinely used in the respective laboratory to detect anti-schistosome antibodies in human infection sera. In so far as the ELISA results from SmCTF are thus so little different from those given by schistosome egg antigens and also cheaper to produce, the former is a potentially useful new diagnostic aid for schistosomiasis.

  16. Mapping antigenic motifs in the trypomastigote small surface antigen from Trypanosoma cruzi.

    Science.gov (United States)

    Balouz, Virginia; Cámara, María de Los Milagros; Cánepa, Gaspar E; Carmona, Santiago J; Volcovich, Romina; Gonzalez, Nicolás; Altcheh, Jaime; Agüero, Fernán; Buscaglia, Carlos A

    2015-03-01

    The trypomastigote small surface antigen (TSSA) is a mucin-like molecule from Trypanosoma cruzi, the etiological agent of Chagas disease, which displays amino acid polymorphisms in parasite isolates. TSSA expression is restricted to the surface of infective cell-derived trypomastigotes, where it functions as an adhesin and engages surface receptors on the host cell as a prerequisite for parasite internalization. Previous results have established TSSA-CL, the isoform encoded by the CL Brener clone, as an appealing candidate for use in serology-based diagnostics for Chagas disease. Here, we used a combination of peptide- and recombinant protein-based tools to map the antigenic structure of TSSA-CL at maximal resolution. Our results indicate the presence of different partially overlapping B-cell epitopes clustering in the central portion of TSSA-CL, which contains most of the polymorphisms found in parasite isolates. Based on these results, we assessed the serodiagnostic performance of a 21-amino-acid-long peptide that spans TSSA-CL major antigenic determinants, which was similar to the performance of the previously validated glutathione S-transferase (GST)-TSSA-CL fusion molecule. Furthermore, the tools developed for the antigenic characterization of the TSSA antigen were also used to explore other potential diagnostic applications of the anti-TSSA humoral response in Chagasic patients. Overall, our present results provide additional insights into the antigenic structure of TSSA-CL and support this molecule as an excellent target for molecular intervention in Chagas disease.

  17. Antigenic community between Schistosoma mansoni and Biomphalaria glabrata: on the search of candidate antigens for vaccines

    Directory of Open Access Journals (Sweden)

    N Chacón

    2002-10-01

    Full Text Available We have previously confirmed the presence of common antigens between Schistosoma mansoni and its vector, Biomphalaria glabrata. Cross-reactive antigens may be important as possible candidates for vaccine and diagnosis of schistosomiasis. Sera from outbred mice immunized with a soluble Biomphalaria glabrata antigen (SBgA of non-infected B. glabrata snails recognized molecules of SBgA itself and S. mansoni AWA by Western blot. Recognition of several molecules of the SBgA were inhibited by pre-incubation with AWA (16, 30, 36, 60 and 155 kDa. The only specific molecule of AWA, inhibited by SBgA, was a 120 kDa protein. In order to determine which epitopes of SBgA were glycoproteins, the antigen was treated with sodium metaperiodate and compared with non-treated antigen. Molecules of 140, 60 and 24 kDa in the SBgA appear to be glycoproteins. Possible protective effects of the SBgA were evaluated immunizing outbred mice in two different experiments using Freund's Adjuvant. In the first one (12 mice/group, we obtained a significant level of protection (46% in the total worm load, with a high variability in worm recovery. In the second experiment (22 mice/group, no significant protection was observed, neither in worm load nor in egg production per female. Our results suggest that SBgA constitutes a rich source of candidate antigens for diagnosis and prophylactic studies.

  18. Characterization of the carbohydrate components of Taenia solium oncosphere proteins and their role in the antigenicity.

    Science.gov (United States)

    Arana, Yanina; Verastegui, Manuela; Tuero, Iskra; Grandjean, Louis; Garcia, Hector H; Gilman, Robert H

    2013-10-01

    This study examines the carbohydrate composition of Taenia solium whole oncosphere antigens (WOAs), in order to improve the understanding of the antigenicity of the T. solium. Better knowledge of oncosphere antigens is crucial to accurately diagnose previous exposure to T. solium eggs and thus predict the development of neurocysticercosis. A set of seven lectins conjugates with wide carbohydrate specificity were used on parasite fixations and somatic extracts. Lectin fluorescence revealed that D-mannose, D-glucose, D-galactose and N-acetyl-D-galactosamine residues were the most abundant constituents of carbohydrate chains on the surface of T. solium oncosphere. Lectin blotting showed that posttranslational modification with N-glycosylation was abundant while little evidence of O-linked carbohydrates was observed. Chemical oxidation and enzymatic deglycosylation in situ were performed to investigate the immunoreactivity of the carbohydrate moieties. Linearizing or removing the carbohydrate moieties from the protein backbones did not diminish the immunoreactivity of these antigens, suggesting that a substantial part of the host immune response against T. solium oncosphere is directed against the peptide epitopes on the parasite antigens. Finally, using carbohydrate probes, we demonstrated for the first time that the presence of several lectins on the surface of the oncosphere was specific to carbohydrates found in intestinal mucus, suggesting a possible role in initial attachment of the parasite to host cells.

  19. Synthetic antigens reveal dynamics of BCR endocytosis during inhibitory signaling.

    Science.gov (United States)

    Courtney, Adam H; Bennett, Nitasha R; Zwick, Daniel B; Hudon, Jonathan; Kiessling, Laura L

    2014-01-17

    B cells detect foreign antigens through their B cell antigen receptor (BCR). The BCR, when engaged by antigen, initiates a signaling cascade. Concurrent with signaling is endocytosis of the BCR complex, which acts to downregulate signaling and facilitate uptake of antigen for processing and display on the cell surface. The relationship between signaling and BCR endocytosis is poorly defined. Here, we explore the interplay between BCR endocytosis and antigens that either promote or inhibit B cell activation. Specifically, synthetic antigens were generated that engage the BCR alone or both the BCR and the inhibitory co-receptor CD22. The lectin CD22, a member of the Siglec family, binds sialic acid-containing glycoconjugates found on host tissues, inhibiting BCR signaling to prevent erroneous B cell activation. At low concentrations, antigens that can cocluster the BCR and CD22 promote rapid BCR endocytosis; whereas, slower endocytosis occurs with antigens that bind only the BCR. At higher antigen concentrations, rapid BCR endocytosis occurs upon treatment with either stimulatory or inhibitory antigens. Endocytosis of the BCR, in response to synthetic antigens, results in its entry into early endocytic compartments. Although the CD22-binding antigens fail to activate key regulators of antigen presentation (e.g., Syk), they also promote BCR endocytosis, indicating that inhibitory antigens can be internalized. Together, our observations support a functional role for BCR endocytosis in downregulating BCR signaling. The reduction of cell surface BCR levels in the absence of B cell activation should raise the threshold for BCR subsequent activation. The ability of the activating synthetic antigens to trigger both signaling and entry of the BCR into early endosomes suggests strategies for targeted antigen delivery.

  20. Sharing the burden: antigen transport and firebreaks in immune responses

    OpenAIRE

    Handel, Andreas; Yates, Andrew; Pilyugin, Sergei S.; Antia, Rustom

    2008-01-01

    Communication between cells is crucial for immune responses. An important means of communication during viral infections is the presentation of viral antigen on the surface of an infected cell. Recently, it has been shown that antigen can be shared between infected and uninfected cells through gap junctions, connexin-based channels, that allow the transport of small molecules. The uninfected cell receiving antigen can present it on its surface. Cells presenting viral antigen are detected and ...

  1. Maturation of recombinant hepatitis B virus surface antigen particles.

    Science.gov (United States)

    Zhao, Qinjian; Wang, Yang; Freed, Daniel; Fu, Tong-Ming; Gimenez, Juan A; Sitrin, Robert D; Washabaugh, Michael W

    2006-01-01

    The major surface antigen of Hepatitis B virus (HBsAg) is a cysteine-rich, lipid-bound protein with 226 amino acids. Recombinant HBsAg (rHBsAg) with associated lipids can self-assemble into 22-nm immunogenic spherical particles, which are used in licensed Hepatitis B vaccines. Little is known about the structural evolvement or maturation upon assembly beyond an elevated level of disulfide formation. In this paper, we further characterized the maturation of HBsAg particles with respect to their degree of cross-linking, morphological changes, and changes in conformational flexibility. The lipid-containing rHBsAg particles undergo KSCN- and heat-induced maturation by formation of additional intra- and inter-molecular disulfide bonds. Direct measurements with atomic force microscopy (AFM) revealed morphological changes upon maturation through KSCN-induced and heat-/storage-incurred oxidative refolding. Particle uniformity and regularity was greatly improved, and protrusions formed by the protein subunits were more prominent on the surface of the mature particles. Decreased conformational flexibility in the mature rHBsAg particles was demonstrated by millisecond-scale unfolding kinetics in the presence of an environment-sensitive conformation probe. Both the accessible hydrophobic cavities under native conditions and the changeable hydrophobic cavities upon denaturant-induced unfolding showed substantial decrease upon maturation of the rHBsAg particles. These changes in the structural properties may be critical for the antigenicity and immuno-genicity of this widely-used vaccine component.

  2. Immunity to intracellular Salmonella depends on surface-associated antigens.

    Directory of Open Access Journals (Sweden)

    Somedutta Barat

    Full Text Available Invasive Salmonella infection is an important health problem that is worsening because of rising antimicrobial resistance and changing Salmonella serovar spectrum. Novel vaccines with broad serovar coverage are needed, but suitable protective antigens remain largely unknown. Here, we tested 37 broadly conserved Salmonella antigens in a mouse typhoid fever model, and identified antigen candidates that conferred partial protection against lethal disease. Antigen properties such as high in vivo abundance or immunodominance in convalescent individuals were not required for protectivity, but all promising antigen candidates were associated with the Salmonella surface. Surprisingly, this was not due to superior immunogenicity of surface antigens compared to internal antigens as had been suggested by previous studies and novel findings for CD4 T cell responses to model antigens. Confocal microscopy of infected tissues revealed that many live Salmonella resided alone in infected host macrophages with no damaged Salmonella releasing internal antigens in their vicinity. In the absence of accessible internal antigens, detection of these infected cells might require CD4 T cell recognition of Salmonella surface-associated antigens that could be processed and presented even from intact Salmonella. In conclusion, our findings might pave the way for development of an efficacious Salmonella vaccine with broad serovar coverage, and suggest a similar crucial role of surface antigens for immunity to both extracellular and intracellular pathogens.

  3. Antigen-specific active immunotherapy for ovarian cancer

    NARCIS (Netherlands)

    Leffers, N.; Daemen, T.; Helfrich, W.; Boezen, H. M.; Cohlen, B. J.; Melief, Cornelis; Nijman, H. W.

    2010-01-01

    BACKGROUND: Despite advances in chemotherapy, prognosis of ovarian cancer remains poor. Antigen-specific active immunotherapy aims to induce a tumour-antigen-specific anti-tumour immune responses as an alternative treatment for ovarian cancer. OBJECTIVES: To assess feasibility of antigen-specific ac

  4. 21 CFR 660.40 - Hepatitis B Surface Antigen.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Hepatitis B Surface Antigen. 660.40 Section 660.40...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Hepatitis B Surface Antigen § 660.40 Hepatitis B Surface Antigen. (a) Proper name and definition. The proper name of this...

  5. Simian virus 40 DNA replication correlates with expression of a particular subclass of T antigen in a human glial cell line.

    Science.gov (United States)

    Deminie, C A; Norkin, L C

    1990-08-01

    Immunocytochemistry and in situ hybridization were used to identify simian virus 40 (SV40) large T-antigen expression and viral DNA replication in individual cells of infected semipermissive human cell lines. SV40 infection aborts before T-antigen expression in many cells of each of the human cell lines examined. In all but one of the human cell lines, most of the T-antigen-producing cells replicated viral DNA. However, in the A172 line of human glial cells only a small percentage of the T-antigen-expressing cells replicated viral DNA. Since different structural and functional classes of T antigen can be recognized with anti-T monoclonal antibodies, we examined infected A172 cells with a panel of 10 anti-T monoclonal antibodies to determine whether viral DNA replication might correlate with the expression of a particular epitope of T antigen. One anti-T monoclonal antibody, PAb 100, did specifically recognize that subset of A172 cells which replicated SV40 DNA. The percentage of PAb 100-reactive A172 cells was dramatically increased by the DNA synthesis inhibitors hydroxyurea and aphidicolin. Removal of the hydroxyurea was followed by an increase in the percentage of cells replicating viral DNA corresponding to the increased percentage reactive with PAb 100. The pattern of SV40 infection in A172 cells was not altered by infection with viable viral mutants containing lesions in the small t protein, the agnoprotein, or the enhancer region. Finally, in situ hybridization was used to show that the percentage of human cells expressing T antigen was similar to the percentage transcribing early SV40 mRNA. Thus, the block to T-antigen expression in human cells is at a stage prior to transcription of early SV40 mRNA.

  6. Specific serum IgG, but not IgA, antibody against purified Opisthorchis viverrini antigen associated with hepatobiliary disease and cholangiocarcinoma.

    Science.gov (United States)

    Pinlaor, Porntip; Pongsamart, Porntip; Hongsrichan, Nuttanan; Sangka, Arunnee; Srilunchang, Thitima; Mairiang, Eimorn; Sithithaworn, Paiboon; Pinlaor, Somchai

    2012-03-01

    Opisthorchiasis caused by Opisthorchis viverrini infection induces hepatobiliary disease (HBD)-associated cholangiocarcinoma (CCA) via a chronic inflammatory immune response. Here, we evaluated specific IgG and IgA antibodies against different fractions of O. viverrini antigen in residents from an endemic community in Northeast Thailand with varying hepatobiliary abnormalities. Crude somatic O. viverrini antigen was purified into three fractions (viz., P1, P2 and P3) by gel infiltration chromatography and these served as antigens for detection of fluke-specific IgG and IgA antibodies by enzyme-linked immunosorbent assay (ELISA). The results revealed fluke-specific IgG and IgA antibody levels-against these antigens from subjects with O. viverrini-positive HBD-higher than in subjects with O. viverrini-negative HBD. Interestingly, the rank of fluke-specific IgG (and not IgA) antibody levels against crude extract and P1 antigens was CCA>severe HBD>mild HBD>healthy individuals. Purified antigens reduced cross-reactivity with other parasites compared to the crude antigen. Multiple linear regression analysis showed that HBD status was significantly associated with the liver fluke-specific IgG antibody against purified antigens. These results suggest that purified O. viverrini-antigen improves serodiagnosis for the evaluation of opisthorchiasis-associated HBD, and may be useful in the screening of opisthorchiasis in subjects at risk of developing CCA.

  7. High affinity antigen recognition of the dual specific variants of herceptin is entropy-driven in spite of structural plasticity.

    Directory of Open Access Journals (Sweden)

    Jenny Bostrom

    Full Text Available The antigen-binding site of Herceptin, an anti-human Epidermal Growth Factor Receptor 2 (HER2 antibody, was engineered to add a second specificity toward Vascular Endothelial Growth Factor (VEGF to create a high affinity two-in-one antibody bH1. Crystal structures of bH1 in complex with either antigen showed that, in comparison to Herceptin, this antibody exhibited greater conformational variability, also called "structural plasticity". Here, we analyzed the biophysical and thermodynamic properties of the dual specific variants of Herceptin to understand how a single antibody binds two unrelated protein antigens. We showed that while bH1 and the affinity-improved bH1-44, in particular, maintained many properties of Herceptin including binding affinity, kinetics and the use of residues for antigen recognition, they differed in the binding thermodynamics. The interactions of bH1 and its variants with both antigens were characterized by large favorable entropy changes whereas the Herceptin/HER2 interaction involved a large favorable enthalpy change. By dissecting the total entropy change and the energy barrier for dual interaction, we determined that the significant structural plasticity of the bH1 antibodies demanded by the dual specificity did not translate into the expected increase of entropic penalty relative to Herceptin. Clearly, dual antigen recognition of the Herceptin variants involves divergent antibody conformations of nearly equivalent energetic states. Hence, increasing the structural plasticity of an antigen-binding site without increasing the entropic cost may play a role for antibodies to evolve multi-specificity. Our report represents the first comprehensive biophysical analysis of a high affinity dual specific antibody binding two unrelated protein antigens, furthering our understanding of the thermodynamics that drive the vast antigen recognition capacity of the antibody repertoire.

  8. Identification of antigen-specific human monoclonal antibodies using high-throughput sequencing of the antibody repertoire.

    Science.gov (United States)

    Liu, Ju; Li, Ruihua; Liu, Kun; Li, Liangliang; Zai, Xiaodong; Chi, Xiangyang; Fu, Ling; Xu, Junjie; Chen, Wei

    2016-04-22

    High-throughput sequencing of the antibody repertoire provides a large number of antibody variable region sequences that can be used to generate human monoclonal antibodies. However, current screening methods for identifying antigen-specific antibodies are inefficient. In the present study, we developed an antibody clone screening strategy based on clone dynamics and relative frequency, and used it to identify antigen-specific human monoclonal antibodies. Enzyme-linked immunosorbent assay showed that at least 52% of putative positive immunoglobulin heavy chains composed antigen-specific antibodies. Combining information on dynamics and relative frequency improved identification of positive clones and elimination of negative clones. and increase the credibility of putative positive clones. Therefore the screening strategy could simplify the subsequent experimental screening and may facilitate the generation of antigen-specific antibodies.

  9. An enzyme-linked immunosorbent assay, using an EDTA-extracted antigen for the serology of Haemophilus pleuropneumoniae.

    Science.gov (United States)

    Nicolet, J; Paroz, P; Krawinkler, M; Baumgartner, A

    1981-12-01

    An enzyme-linked immunosorbent assay (ELISA) was proposed as an alternative to the complement-fixation test (CF) for the detection of antibodies of Haemophilus pleuropneumoniae, agent of the pleuropneumonia in pigs. In tests done with different antigen-extraction procedures (including Tween 20, sodium dodecyl sulfate, aqueous phenol, sonification, and heat treatment at 120 C), ethylenediaminetetraacetic acid (EDTA) provided a satisfactorily reactive antigen. Chromatography purification on Sephacryl S200 improved the specificity of this antigen. Using hyperimmune rabbit sera, we investigated the specificity and the sensitivity of the ELISA with the EDTA-purified antigen of the different serotypes of H pleuropneumoniae on selected swine sera in herds with confirmed H pleuropneumoniae infection, from specific-pathogen-free animals showing doubtful CF reactions. The ELISA proved to be highly specific and more sensitive than the CF test. Furthermore, evidence of cross-reactions with H parasuis, a common bacteria isolated in swine populations, was not found.

  10. Recovery of antigenically reactive HIV-2 cores.

    Science.gov (United States)

    Chrystie, I L; Almeida, J D

    1989-03-01

    Negative staining studies of human immunodeficiency virus (HIV) have been hampered by the fragile nature of the particles. Although detergent treatment is capable of releasing cores from HIV-2 particles, these are unstable and do not retain morphological integrity. Addition of glutaraldehyde will stabilise these structures but, if used at too high a concentration, will destroy their antigenicity. This study shows that if both detergent and glutaraldehyde are used in correct proportions, antigenically reactive cores can be recovered from HIV-2 cell cultures. More specifically we show that a mixture of 0.1% Nonidet P40 and 0.1% glutaraldehyde produces preparations of HIV-2 cores that are suitable for immune electron microscopy. These cores reacted positively, that is, formed immune complexes, with both human HIV-2 antisera and a mouse monoclonal antibody that, although directed against p24 (HIV-1), reacts also with p25 (HIV-2).

  11. Tumor Immunity by Hydrophobic Bearing Antigens

    Science.gov (United States)

    2004-07-01

    protooncogene; TAL, tumor-associated lymphocyte; Perf, perforn, MRT, mean fluorescence intensity; IFN-g= Interferon gamma , FS= Forward scatter; Key words...Badovinac, V. P., T vinnereim, A. R., and Harty, J. T, Regulation of antigen-specific CD8+ Tcell homeostasis by perforin and interferon - gamma . Science...Cancer Res 2003; 63: 2535-45, 17. Zanussi, S., Vaceher, E., Caffau, C., et al. Interferon - gamma secretion and perforinexpression are impaired in CD8+ T

  12. Study of serum Helicobacter pylori soluble antigen

    Institute of Scientific and Technical Information of China (English)

    吴勤动; 朱永良

    2002-01-01

    Objective:to explore a new serological method for detecting Helicobacter pylori(H.pylori) infection.Methods:Serum soluble antigen of H.pylori was detected by using avidin-biotin ELISA technique to evaluate the status of H.pylori infection and for comparison with rapid urease test(RUT).histologic examination and serology,Results:The sensitivity,specificity,positive predictive value and negative predictive value were 77.46% ,91.07%,91.67% and 76.12%,respectively.The prevalence rate of werum H. pylori soluble antigen in 138 patients undergong endoscopy was similar to the rate obtained by 14 C-UBT methods(P>0.05).Conclusions:The detection of serum H.pylori soluble antigen(HpSAg) could be used as a new serological method which is accurate,and convenient,not affected by the memorizing raction of serum antibody;is more sensitive,more specific and suitable for dinical diagriosis,and evaluation of eradication and for follow-up of H.pylori as well as for detection in children and pregnant women.

  13. Study of serum Helicobacter pylori soluble antigen

    Institute of Scientific and Technical Information of China (English)

    吴勤动; 朱永良

    2002-01-01

    Objective: to explore a new serological method for detecting Helicobac ter pylori ( H. pylori ) infection. Methods: Serum soluble antigen of H. p ylor i was detected by using avidin-biotin ELISA technique to evaluate the status of H. pylori infection and for comparison with rapid urease test ( RUT ), histo logi c examination and serology. Results: The sensitivity, specificity, positive pred ictive value and negative predictive value were 77.46%, 91.07%, 91.67% a nd 76.12 %, respectively. The prevalence rate of serum H. pylori soluble antigen in 138 patients undergoing endoscopy was similar to the rate obtained by 14 C-UBT met hods ( P>0.05 ). Conclusions: The detection of serum H. pylori solub le antigen( HpSAg) could be used as a new serological method which is accurate, and convenie nt, not affected by the memorizing reaction of serum antibody; is more sensitive , m ore specific and suitable for clinical diagnosis, and evaluation of eradication and for follow-up of H. pylori as well as for detection in children and pre gnant women.

  14. Chimeric Antigen Receptor T Cell Therapy in Hematology.

    Science.gov (United States)

    Ataca, Pınar; Arslan, Önder

    2015-12-01

    It is well demonstrated that the immune system can control and eliminate cancer cells. Immune-mediated elimination of tumor cells has been discovered and is the basis of both cancer vaccines and cellular therapies including hematopoietic stem cell transplantation. Adoptive T cell transfer has been improved to be more specific and potent and to cause less off-target toxicity. Currently, there are two forms of engineered T cells being tested in clinical trials: T cell receptor (TCR) and chimeric antigen receptor (CAR) modified T cells. On 1 July 2014, the United States Food and Drug Administration granted 'breakthrough therapy' designation to anti-CD19 CAR T cell therapy. Many studies were conducted to evaluate the benefits of this exciting and potent new treatment modality. This review summarizes the history of adoptive immunotherapy, adoptive immunotherapy using CARs, the CAR manufacturing process, preclinical and clinical studies, and the effectiveness and drawbacks of this strategy.

  15. Limited antigenic variation in the Trypanosoma cruzi candidate vaccine antigen TSA-1.

    Science.gov (United States)

    Knight, J M; Zingales, B; Bottazzi, M E; Hotez, P; Zhan, B

    2014-12-01

    Chagas disease (American trypanosomiasis caused by Trypanosoma cruzi) is one of the most important neglected tropical diseases in the Western Hemisphere. The toxicities and limited efficacies of current antitrypanosomal drugs have prompted a search for alternative technologies such as a therapeutic vaccine comprised of T. cruzi antigens, including a recombinant antigen encoding the N-terminal 65 kDa portion of Trypomastigote surface antigen-1 (TSA-1). With at least six known genetically distinct T. cruzi lineages, variability between the different lineages poses a unique challenge for the development of broadly effective therapeutic vaccine. The variability across the major lineages in the current vaccine candidate antigen TSA-1 has not previously been addressed. To assess the variation in TSA-1, we cloned and sequenced TSA-1 from several different T. cruzi strains representing three of the most clinically relevant lineages. Analysis of the different alleles showed limited variation in TSA-1 across the different strains and fit with the current theory for the evolution of the different lineages. Additionally, minimal variation in known antigenic epitopes for the HLA-A 02 allele suggests that interlineage variation in TSA-1 would not impair the range and efficacy of a vaccine containing TSA-1.

  16. Conformational dynamics and antigenicity in the disordered malaria antigen merozoite surface protein 2.

    Directory of Open Access Journals (Sweden)

    Christopher A MacRaild

    Full Text Available Merozoite surface protein 2 (MSP2 of Plasmodium falciparum is an abundant, intrinsically disordered protein that is GPI-anchored to the surface of the invasive blood stage of the malaria parasite. Recombinant MSP2 has been trialled as a component of a malaria vaccine, and is one of several disordered proteins that are candidates for inclusion in vaccines for malaria and other diseases. Nonetheless, little is known about the implications of protein disorder for the development of an effective antibody response. We have therefore undertaken a detailed analysis of the conformational dynamics of the two allelic forms of MSP2 (3D7 and FC27 using NMR spectroscopy. Chemical shifts and NMR relaxation data indicate that conformational and dynamic properties of the N- and C-terminal conserved regions in the two forms of MSP2 are essentially identical, but significant variation exists between and within the central variable regions. We observe a strong relationship between the conformational dynamics and the antigenicity of MSP2, as assessed with antisera to recombinant MSP2. Regions of increased conformational order in MSP2, including those in the conserved regions, are more strongly antigenic, while the most flexible regions are minimally antigenic. This suggests that modifications that increase conformational order may offer a means to tune the antigenicity of MSP2 and other disordered antigens, with implications for vaccine design.

  17. Conformational Dynamics and Antigenicity in the Disordered Malaria Antigen Merozoite Surface Protein 2

    Science.gov (United States)

    Andrew, Dean; Krishnarjuna, Bankala; Nováček, Jiří; Žídek, Lukáš; Sklenář, Vladimír; Richards, Jack S.; Beeson, James G.; Anders, Robin F.; Norton, Raymond S.

    2015-01-01

    Merozoite surface protein 2 (MSP2) of Plasmodium falciparum is an abundant, intrinsically disordered protein that is GPI-anchored to the surface of the invasive blood stage of the malaria parasite. Recombinant MSP2 has been trialled as a component of a malaria vaccine, and is one of several disordered proteins that are candidates for inclusion in vaccines for malaria and other diseases. Nonetheless, little is known about the implications of protein disorder for the development of an effective antibody response. We have therefore undertaken a detailed analysis of the conformational dynamics of the two allelic forms of MSP2 (3D7 and FC27) using NMR spectroscopy. Chemical shifts and NMR relaxation data indicate that conformational and dynamic properties of the N- and C-terminal conserved regions in the two forms of MSP2 are essentially identical, but significant variation exists between and within the central variable regions. We observe a strong relationship between the conformational dynamics and the antigenicity of MSP2, as assessed with antisera to recombinant MSP2. Regions of increased conformational order in MSP2, including those in the conserved regions, are more strongly antigenic, while the most flexible regions are minimally antigenic. This suggests that modifications that increase conformational order may offer a means to tune the antigenicity of MSP2 and other disordered antigens, with implications for vaccine design. PMID:25742002

  18. Expression, purification and antigenicity of Neospora caninum-antigens using silkworm larvae targeting for subunit vaccines.

    Science.gov (United States)

    Otsuki, Takahiro; Dong, Jinhua; Kato, Tatsuya; Park, Enoch Y

    2013-02-18

    Infection of Neospora caninum causes abortion in cattle, which has a serious worldwide impact on the economic performance of the dairy and beef industries. Now, inexpensive and efficacious vaccines are required to protect cattle from neosporosis in livestock industry. In this study, N. caninum surface antigen 1 (SAG1) and SAG1-related sequence 2 (SRS2) were expressed in hemolymph of silkworm larvae as a soluble form. Expressed SAG1 and SRS2 clearly showed antigenicity against N. caninum-positive sera of cow. SAG1 and SRS2 were purified to near homogeneity from hemolymph of silkworm larvae using anti-FLAG M2 antibody agarose: approximately 1.7 mg of SAG1 from 10 silkworm larvae and 370 μg of SRS2 from 17 silkworm larvae. Mice that were injected by antigens induced antibodies against SAG1 and SRS2. This study indicates that it is possible that this silkworm expression system leads to a large-scale production of N. caninum-antigens with biological function and low production cost. Bombyx mori nucleopolyhedrovirus (BmNPV) bacmid expression system paves the way to produce largely and rapidly these recombinant antigens for its application to subunit vaccines against neosporosis in cattle.

  19. The Doppler effect is not what you think it is: dramatic pitch change due to dynamic intensity change.

    Science.gov (United States)

    McBeath, Michael K; Neuhoff, John G

    2002-06-01

    Historically, auditory pitch has been considered to be a function of acoustic frequency, with only a small effect being due to absolute intensity. Yet we found that when tones are Doppler shifted so that frequency drops, the pitch dramatically rises and falls, closely following the pattern of dynamic intensity change. We show that continuous intensity change can produce pitch variation comparable to a frequency change approaching an octave. This effect opposes and is an order of magnitude larger than the well-known effect of discrete intensity change in the frequency range employed. We propose that the perceptual interaction of continuous changes in pitch and loudness reflects a natural correlation between changes in frequency and intensity that is neurally encoded to facilitate the parsing and processing of meaningful acoustic patterns.

  20. Moses revisited. August Strindberg’s and Edvard Munch’s dramatic use of the figure of Moses

    Directory of Open Access Journals (Sweden)

    Camilla Storskog

    2011-06-01

     1903 and Den fri Kjærligheds By (The City of Free Love, ca. 1905. In the first case, the focus is on the examination of Moses as an archetypical character. Analogies are subsequently drawn between the biblical hero and other dramatic characters in the production of the Swedish playwright, such as Gustav Vasa or Birger jarl. In the latter case, I outline the strategy for a parodic reuse of the biblical source in Munch’s invention of a modern Moses created to mock his fellow painter and maestro Christian Krohg and the bohemian ideal of free love. Although the qualities of the Moses character take on different and opposite meanings in the two authors, it is of interest that the issue of a return to the common heritage of biblical culture should make itself evident in the years following both Strindberg’s and Munch’s farewell to the secular milieus of the Bohème.

  1. Biostratigraphic evidence of dramatic Holocene uplift of Robinson Crusoe Island, Juan Fernández Ridge, SE Pacific Ocean

    Directory of Open Access Journals (Sweden)

    P. Sepúlveda

    2014-09-01

    Full Text Available A study of the biostratigraphy and sedimentology of Holocene deposits on Robinson Crusoe Island (RCI on the Juan Fernández Ridge (JFR indicates that a~dramatic but localized uplift occurred since 8000 BP, at a rate of about 8.5 mm yr−1. In fact, supratidal flats and sand layers with marine gastropods (mostly Nerita sp. are now exposed ca. 70 m a.s.l., and covered by transitional dunes. The last volcanic activity on RCI occurred at ca. 0.8 Ma (active hotspot located 280 km further west and there is no sign of a compensating bulge that explains this uplift, isobaths of the sea floor instead suggesting general subsidence. However, modeling indicates that large-scale landslides followed by isostatic rebound are a viable explanation, partially reflected in the low-resolution bathymetry of the area.

  2. Biostratigraphic evidence of dramatic Holocene uplift of Robinson Crusoe Island, Juan Fernández Ridge, SE Pacific Ocean

    Science.gov (United States)

    Sepúlveda, P.; Le Roux, J. P.; Lara, L. E.; Orozco, G.; Astudillo, V.

    2014-09-01

    A study of the biostratigraphy and sedimentology of Holocene deposits on Robinson Crusoe Island (RCI) on the Juan Fernández Ridge (JFR) indicates that a~dramatic but localized uplift occurred since 8000 BP, at a rate of about 8.5 mm yr-1. In fact, supratidal flats and sand layers with marine gastropods (mostly Nerita sp.) are now exposed ca. 70 m a.s.l., and covered by transitional dunes. The last volcanic activity on RCI occurred at ca. 0.8 Ma (active hotspot located 280 km further west) and there is no sign of a compensating bulge that explains this uplift, isobaths of the sea floor instead suggesting general subsidence. However, modeling indicates that large-scale landslides followed by isostatic rebound are a viable explanation, partially reflected in the low-resolution bathymetry of the area.

  3. Dramatis persona in poetical and practical approach of dramatic text in 17th century French theory of theatre

    Directory of Open Access Journals (Sweden)

    Michał Bajer

    2009-01-01

    Full Text Available The idea of the dramatis persona posited by the first French theatre theorists of the Richelieu circle, Jean Chapelain and Jules de la Mesnardiere, emerges as a quite literał implementation of the Aristotelian concepts unfolded in the sixth and fifteenth chapter of his Poetics. In a later period, the third of the aforementioned group of authors, François Hédelin d’Aubignac, dismisses the Aristotelian categories, erecting his theory upon the elements adopted from the Roman theory of rhetoric. The analysis of the Persona in classical drama theory allows to reconstruct the relation between these two 17th century dramatic approaches. The former is the traditional perspective relying on the postulations of the Aristotelian theory. The latter, which is a practical grasp, is new to the 17th century’s dramatic mindset, and was formulated by abbé d’Aubignac. Whereas the axis of poetics is the structural analysis of a work of art, it is the functioning of that work of art in the theatrical process of communication between the stage and the audience that remains the core interest of the practical approach. In this process, the rhetorical effect of presence of the dramatis persona should by created in the imagination of the spectator-auditor. The subject of analysis is common to both perspectives and the discrepancies concem merely aspects of its description. Therefore poetics and practice are neither competitive nor mutually exclusive, but can both legitimately coexist in the description of the very same work of art.

  4. Enhanced discrimination of malignant from benign pancreatic disease by measuring the CA 19-9 antigen on specific protein carriers.

    Directory of Open Access Journals (Sweden)

    Tingting Yue

    Full Text Available The CA 19-9 assay detects a carbohydrate antigen on multiple protein carriers, some of which may be preferential carriers of the antigen in cancer. We tested the hypothesis that the measurement of the CA 19-9 antigen on individual proteins could improve performance over the standard CA 19-9 assay. We used antibody arrays to measure the levels of the CA 19-9 antigen on multiple proteins in serum or plasma samples from patients with pancreatic adenocarcinoma or pancreatitis. Sample sets from three different institutions were examined, comprising 531 individual samples. The measurement of the CA 19-9 antigen on any individual protein did not improve upon the performance of the standard CA 19-9 assay (82% sensitivity at 75% specificity for early-stage cancer, owing to diversity among patients in their CA 19-9 protein carriers. However, a subset of cancer patients with no elevation in the standard CA 19-9 assay showed elevations of the CA 19-9 antigen specifically on the proteins MUC5AC or MUC16 in all sample sets. By combining measurements of the standard CA 19-9 assay with detection of CA 19-9 on MUC5AC and MUC16, the sensitivity of cancer detection was improved relative to CA 19-9 alone in each sample set, achieving 67-80% sensitivity at 98% specificity. This finding demonstrates the value of measuring glycans on specific proteins for improving biomarker performance. Diagnostic tests with improved sensitivity for detecting pancreatic cancer could have important applications for improving the treatment and management of patients suffering from this disease.

  5. Enteric trimethyl chitosan nanoparticles containing hepatitis B surface antigen for oral delivery.

    Science.gov (United States)

    Farhadian, Asma; Dounighi, Naser Mohammadpour; Avadi, Mohammadreza

    2015-01-01

    Oral vaccination is the preferred route of immunization. However, the degradative condition of the gastrointestinal tract and the higher molecular size of peptides pose major challenges in developing an effective oral vaccination system. One of the most excellent methods used in the development of oral vaccine delivery system relies on the entrapment of the antigen in polymeric nanoparticles. In this work, trimethyl chitosan (TMC) nanoparticles were fabricated using ionic gelation teqnique by interaction hydroxypropyl methylcellulose phthalate (HPMCP), a pH-sensitive polymer, with TMC and the utility of the particles in the oral delivery of hepatitis B surface antigen (HBsAg) was evaluated employing solutions that simulated gastric and intestinal conditions. The particle size, morphology, zeta potential, loading capacity, loading efficiency, in vitro release behavior, structure, and morphology of nanoparticles were evaluated, and the activity of the loaded antigen was assessed. Size of the optimized TMC/HPMCP nanoparticles and that of the antigen-loaded nanoparticles were 85 nm and 158 nm, respectively. Optimum loading capacity (76.75%) and loading efficiency (86.29%) were achieved at 300 µg/mL concentration of the antigen. SEM images revealed a spherical shape as well as a smooth and near-homogenous surface of nanoparticles. Results of the in vitro release studies showed that formulation with HPMCP improved the acid stability of the TMC nanoparticles as well as their capability to preserve the loaded HBsAg from gastric destruction. The antigen showed good activity both before and after loading. The results suggest that TMC/HPMCP nanoparticles could be used in the oral delivery of HBsAg vaccine.

  6. Identification and Analysis of Immunodominant Antigens for ELISA-Based Detection of Theileria annulata

    Science.gov (United States)

    Bakırcı, Serkan; Tait, Andrew; Kinnaird, Jane; Eren, Hasan

    2016-01-01

    Tropical or Mediterranean theileriosis, caused by the protozoan parasite Theileria annulata, remains an economically important bovine disease in North Africa, Southern Europe, India, the Middle East and Asia. The disease affects mainly exotic cattle and imposes serious constraints upon livestock production and breed improvement programmes. While microscopic and molecular methods exist which are capable of detecting T. annulata during acute infection, the identification of animals in the carrier state is more challenging. Serological tests, which detect antibodies that react against parasite-encoded antigens, should ideally have the potential to identify carrier animals with very high levels of sensitivity and specificity. However, assays developed to date have suffered from a lack of sensitivity and/or specificity and it is, therefore, necessary to identify novel parasite antigens, which can be developed for this purpose. In the present study, genes encoding predicted antigens were bioinformatically identified in the T. annulata genome. These proteins, together with a panel of previously described antigens, were assessed by western blot analysis for immunoreactivity, and this revealed that four novel candidates and five previously described antigens were recognised by immune bovine serum. Using a combination of immunoprecipitation and mass spectrophotometric analysis, an immunodominant protein (encoded by TA15705) was identified as Ta9, a previously defined T cell antigen. Western blotting revealed another of the five proteins in the Ta9 family, TA15710, also to be an immunodominant protein. However, validation by Enzyme-Linked Immunosorbent Assay indicated that due to either allelic polymorphism or differential immune responses of individual hosts, none of the novel candidates can be considered ideal for routine detection of T. annulata-infected/carrier animals. PMID:27270235

  7. Multiantigen print immunoassay for comparison of diagnostic antigens for Taenia solium cysticercosis and taeniasis.

    Science.gov (United States)

    Handali, Sukwan; Klarman, Molly; Gaspard, Amanda N; Noh, John; Lee, Yeuk-Mui; Rodriguez, Silvia; Gonzalez, Armando E; Garcia, Hector H; Gilman, Robert H; Tsang, Victor C W; Wilkins, Patricia P

    2010-01-01

    One of the best-characterized tests for the diagnosis of neurocysticercosis is the enzyme-linked immunoelectrotransfer blot assay, developed at the CDC, which uses lentil lectin-purified glycoproteins (LLGPs) extracted from Taenia solium cysticerci. The purification of the LLGP antigens has been difficult to standardize, and the polyacrylamide gel system used for the immunoblot assay is not easily transferable to other laboratories. In this study, we developed a multiantigen printing immunoassay (MAPIA) to compare the performance of multiple recombinant Taenia solium proteins with the potential for the detection of cysticercosis and taeniasis. We prepared MAPIA strips using six cysticercosis and two taeniasis diagnostic proteins and compared the performance of the proteins with sera collected from defined cysticercosis and taeniasis cases. Of the six cysticercosis antigens, rT24H performed well in detecting cases with two or more viable cysts in the brain (sensitivity and specificity, 97% and 99.4%, respectively); the use of a combination of cysticercosis antigens did not improve the sensitivity of the test and decreased the specificity. None of the antigens could differentiate the different clinical presentations of cysticercosis. Both of the taeniasis antigens (rES33 and rES38) had the same sensitivity of 99.4% and specificities of 93.9% and 94.5%, respectively. Some cross-reactivity against rES33 and rES38 was found, especially with sera from cases infected with Schistosoma mansoni. We conclude that MAPIA is a simple and effective tool that may be used to compare antibody responses to different cysticercosis and taeniasis antigens and, in this case, may be useful for the rapid detection of T. solium cases.

  8. Dramatic decrease in prevalence of soil-transmitted helminths and new insights into intestinal protozoa in children living in the Chaco region, Bolivia.

    Science.gov (United States)

    Macchioni, Fabio; Segundo, Higinio; Gabrielli, Simona; Totino, Valentina; Gonzales, Patricia Rojas; Salazar, Esteban; Bozo, Ricardo; Bartoloni, Alessandro; Cancrini, Gabriella

    2015-04-01

    We assessed the prevalence of intestinal parasites among 268 2-12-year-old children living in rural areas, small villages, and semi-urban areas of the Chaco region, south-eastern Bolivia. The overall parasitism was 69%. Only protozoa, helminths, or co-infections were observed in 89.2%, 5.9%, or 4.9% of the positive children, respectively. A significant progressive increase in overall parasite prevalence was found when passing from rural areas to small villages and semi-urban areas. The most commonly found species were Entamoeba coli (38.4%), Giardia intestinalis (37.7%), and Blastocystis spp. (16%). Hymenolepis nana was the most prevalent helminth (5.6%), followed by Ascaris lumbricoides and hookworms (1.5% and 0.4%) evidenced only in rural areas and in villages. Molecular diagnostics identified Blastocystis subtypes 9 and 2, and 5 infections by Entamoeba histolytica and 4 by Entamoeba dispar. The dramatic decrease in prevalence of soil-transmitted helminths with respect to that observed about 20 years ago (> 40%) evidences the success of the preventive chemotherapy intervention implemented in 1986. Health education and improved sanitation should be intensified to control protozoan infections.

  9. Modulation of antigenicity of mycelial antigens during developmental cycle of Karnal bunt (Tilletia indica) of wheat.

    Science.gov (United States)

    Rai, G; Kumar, A; Singh, A; Garg, G K

    2000-05-01

    Indirect enzyme linked immunosorbent assays (ELISA) were developed using polyclonal antibodies against soluble cytoplasmic (SCA) and insoluble cell wall antigens (ICWA) for monitoring modulation of mycelial antigens during growth cycle of T. indica. With SCA, continuous decrease in ELISA reactivity was observed in maturing fungus cultures, suggesting that SCA were expressed predominantly during early vegetative phase and their decreasing role was apparent as the fungus matures possibly towards sporogenous mycelium. In case of ICWA, the reaction profile showed an increase up to exponential phase of growth probably due to increase in the cell division and branching of mycelium. But later, ICWA antibody reactivity was decreased which may be due to conversion of mycelial phase to sporogenous phase, a quiescent stage of growth. Characterization of changes in antigenic configuration during developmental cycle of Tilletia indica by these antibodies could prove to be useful in identification of developmentally related and virulence marker(s).

  10. Genetic diversity and antigenicity variation of Babesia bovis merozoite surface antigen-1 (MSA-1) in Thailand.

    Science.gov (United States)

    Tattiyapong, Muncharee; Sivakumar, Thillaiampalam; Takemae, Hitoshi; Simking, Pacharathon; Jittapalapong, Sathaporn; Igarashi, Ikuo; Yokoyama, Naoaki

    2016-07-01

    Babesia bovis, an intraerythrocytic protozoan parasite, causes severe clinical disease in cattle worldwide. The genetic diversity of parasite antigens often results in different immune profiles in infected animals, hindering efforts to develop immune control methodologies against the B. bovis infection. In this study, we analyzed the genetic diversity of the merozoite surface antigen-1 (msa-1) gene using 162 B. bovis-positive blood DNA samples sourced from cattle populations reared in different geographical regions of Thailand. The identity scores shared among 93 msa-1 gene sequences isolated by PCR amplification were 43.5-100%, and the similarity values among the translated amino acid sequences were 42.8-100%. Of 23 total clades detected in our phylogenetic analysis, Thai msa-1 gene sequences occurred in 18 clades; seven among them were composed of sequences exclusively from Thailand. To investigate differential antigenicity of isolated MSA-1 proteins, we expressed and purified eight recombinant MSA-1 (rMSA-1) proteins, including an rMSA-1 from B. bovis Texas (T2Bo) strain and seven rMSA-1 proteins based on the Thai msa-1 sequences. When these antigens were analyzed in a western blot assay, anti-T2Bo cattle serum strongly reacted with the rMSA-1 from T2Bo, as well as with three other rMSA-1 proteins that shared 54.9-68.4% sequence similarity with T2Bo MSA-1. In contrast, no or weak reactivity was observed for the remaining rMSA-1 proteins, which shared low sequence similarity (35.0-39.7%) with T2Bo MSA-1. While demonstrating the high genetic diversity of the B. bovis msa-1 gene in Thailand, the present findings suggest that the genetic diversity results in antigenicity variations among the MSA-1 antigens of B. bovis in Thailand.

  11. Brain-state classification and a dual-state decoder dramatically improve the control of cursor movement through a brain-machine interface

    Science.gov (United States)

    Sachs, Nicholas A.; Ruiz-Torres, Ricardo; Perreault, Eric J.; Miller, Lee E.

    2016-02-01

    Objective. It is quite remarkable that brain machine interfaces (BMIs) can be used to control complex movements with fewer than 100 neurons. Success may be due in part to the limited range of dynamical conditions under which most BMIs are tested. Achieving high-quality control that spans these conditions with a single linear mapping will be more challenging. Even for simple reaching movements, existing BMIs must reduce the stochastic noise of neurons by averaging the control signals over time, instead of over the many neurons that normally control movement. This forces a compromise between a decoder with dynamics allowing rapid movement and one that allows postures to be maintained with little jitter. Our current work presents a method for addressing this compromise, which may also generalize to more highly varied dynamical situations, including movements with more greatly varying speed. Approach. We have developed a system that uses two independent Wiener filters as individual components in a single decoder, one optimized for movement, and the other for postural control. We computed an LDA classifier using the same neural inputs. The decoder combined the outputs of the two filters in proportion to the likelihood assigned by the classifier to each state. Main results. We have performed online experiments with two monkeys using this neural-classifier, dual-state decoder, comparing it to a standard, single-state decoder as well as to a dual-state decoder that switched states automatically based on the cursor’s proximity to a target. The performance of both monkeys using the classifier decoder was markedly better than that of the single-state decoder and comparable to the proximity decoder. Significance. We have demonstrated a novel strategy for dealing with the need to make rapid movements while also maintaining precise cursor control when approaching and stabilizing within targets. Further gains can undoubtedly be realized by optimizing the performance of the individual movement and posture decoders.

  12. New diagnostic antigens for early trichinellosis: the excretory-secretory antigens of Trichinella spiralis intestinal infective larvae.

    Science.gov (United States)

    Sun, Ge Ge; Liu, Ruo Dan; Wang, Zhong Quan; Jiang, Peng; Wang, Li; Liu, Xiao Lin; Liu, Chun Yin; Zhang, Xi; Cui, Jing

    2015-12-01

    The excretory-secretory (ES) antigens from Trichinella spiralis muscle larvae (ML) are the most commonly used diagnostic antigens for trichinellosis, but anti-Trichinella IgG antibodies cannot be detected until 2-3 weeks after infection; there is an obvious window period between Trichinella infection and antibody positivity. Intestinal infective larvae (IIL) are the first invasive stage during Trichinella infection, and their ES antigens are firstly exposed to the immune system and might be the early diagnostic markers of trichinellosis. The aim of this study was to evaluate the early diagnostic values of IIL ES antigens for trichinellosis. The IIL were collected from intestines of infected mice at 6 h postinfection (hpi), and IIL ES antigens were prepared by incubation for 18 h. Anti-Trichinella IgG antibodies in mice infected with 100 ML were detectable by ELISA with IIL ES antigens as soon as 10 days postinfection (dpi), but ELISA with ML ES antigens did not permit detection of infected mice before 12 dpi. When the sera of patients with trichinellosis at 19 dpi were assayed, the sensitivity (100 %) of ELISA with IIL ES antigens was evidently higher than 75 % of ELISA with ML ES antigens (P < 0.05) The specificity (96.86 %) of ELISA with IIL ES antigens was also higher than 89.31 % of ELISA with ML ES antigens (P < 0.05). The IIL ES antigens provided a new source of diagnostic antigens and could be considered as a potential early diagnostic antigen for trichinellosis.

  13. Cowpox virus employs a two-pronged strategy to outflank MHCI antigen presentation.

    Science.gov (United States)

    McCoy, William H; Wang, Xiaoli; Yokoyama, Wayne M; Hansen, Ted H; Fremont, Daved H

    2013-09-01

    Smallpox decimated humanity for thousands of years before being eradicated by vaccination, a success facilitated by the fact that humans are the only host of variola virus. In contrast, other orthopoxviruses such as cowpox virus can infect a variety of mammalian species, although its dominant reservoir appears to be rodents. This difference in host specificity suggests that cowpox may have developed promiscuous immune evasion strategies to facilitate zoonosis. Recent experiments have established that cowpox can disrupt MHCI antigen presentation during viral infection of both human and murine cells, a process enabled by two unique proteins, CPXV012 and CPXV203. While CPXV012 inhibits antigenic peptide transport from the cytosol to the ER, CPXV203 blocks MHCI trafficking to the cell surface by exploiting the KDEL-receptor recycling pathway. Our recent investigations of CPXV203 reveal that it binds a diverse array of classical and non-classical MHCI proteins with dramatically increased affinities at the lower pH of the Golgi relative to the ER, thereby providing mechanistic insight into how it works synergistically with KDEL receptors to block MHCI surface expression. The strategy used by cowpox to both limit peptide supply and disrupt trafficking of fully assembled MHCI acts as a dual-edged sword that effectively disables adaptive immune surveillance of infected cells.

  14. Targeting dendritic cells in lymph node with an antigen peptide-based nanovaccine for cancer immunotherapy.

    Science.gov (United States)

    Qian, Yuan; Jin, Honglin; Qiao, Sha; Dai, Yanfeng; Huang, Chuan; Lu, Lisen; Luo, Qingming; Zhang, Zhihong

    2016-08-01

    The design of peptide-based subunit vaccine formulations for the direct delivery of tumor antigen peptides (Aps) to dendritic cells (DCs) localized within draining lymph nodes (DLNs) is challenging. Mature DCs (mDCs) are abundantly distributed within DLNs but have dramatically reduced endocytic uptake and antigen-processing abilities, so their role as potential vaccine targets has been largely overlooked. Here we report an ultra-small biocompatible nanovaccine (α-Ap-FNP) functionalized by avidly targeting delivery of Ap via the scavenger receptor class B1 (SR-B1) pathway to mDCs. The self-assembly, small size (∼30 nm), SR-B1-targeting and optical properties of α-Ap-FNP resulted in its efficient Ap loading, substantial LN accumulation, targeting of mDCs and enhanced Ap presentation, and fluorescence trafficking, respectively. We also demonstrate that the α-Ap-FNP can be either used alone or encapsulated with CpG oligodeoxynucleotide as a prophylactic and therapeutic vaccine. Thus, the excellent properties of α-Ap-FNP provide it potential for clinical applications as a potent nanovaccine for cancer immunotherapy.

  15. Positive and negative regulation of antigen receptor signaling by the Shc family of protein adapters.

    Science.gov (United States)

    Finetti, Francesca; Savino, Maria Teresa; Baldari, Cosima T

    2009-11-01

    The Shc adapter family includes four members that are expressed as multiple isoforms and participate in signaling by a variety of cell-surface receptors. The biological relevance of Shc proteins as well as their variegated function, which relies on their highly conserved modular structure, is underscored by the distinct and dramatic phenotypic alterations resulting from deletion of individual Shc isoforms both in the mouse and in two model organisms, Drosophila melanogaster and Caenorhabditis elegans. The p52 isoform of ShcA couples antigen and cytokine receptors to Ras activation in both lymphoid and myeloid cells. However, the recognition of the spectrum of activities of p52ShcA in the immune system has been steadily expanding in recent years to other fundamental processes both at the cell and organism levels. Two other Shc family members, p66ShcA and p52ShcC/Rai, have been identified recently in T and B lymphocytes, where they antagonize survival and attenuate antigen receptor signaling. These developments reveal an unexpected and complex interplay of multiple Shc proteins in lymphocytes.

  16. Overlapping antigenic repertoires of variant antigens expressed on the surface of erythrocytes infected by Plasmodium falciparum

    DEFF Research Database (Denmark)

    Giha, H A; Staalsoe, T; Dodoo, D;

    1999-01-01

    Antibodies against variable antigens expressed on the surface of Plasmodium falciparum-infected erythrocytes are believed to be important for protection against malaria. A target for these antibodies is the P. falciparum erythrocyte membrane protein 1, PfEMP1, which is encoded by around 50 var...... genes and undergoes clonal variation. Using agglutination and mixed agglutination tests and flow cytometry to analyse the recognition of variant antigens on parasitized erythrocytes by plasma antibodies from individuals living in Daraweesh in eastern Sudan, an area of seasonal and unstable malaria...

  17. Protamine-based nanoparticles as new antigen delivery systems.

    Science.gov (United States)

    González-Aramundiz, José Vicente; Peleteiro Olmedo, Mercedes; González-Fernández, África; Alonso Fernández, María José; Csaba, Noemi Stefánia

    2015-11-01

    The use of biodegradable nanoparticles as antigen delivery vehicles is an attractive approach to overcome the problems associated with the use of Alum-based classical adjuvants. Herein we report, the design and development of protamine-based nanoparticles as novel antigen delivery systems, using recombinant hepatitis B surface antigen as a model viral antigen. The nanoparticles, composed of protamine and a polysaccharide (hyaluronic acid or alginate), were obtained using a mild ionic cross-linking technique. The size and surface charge of the nanoparticles could be modulated by adjusting the ratio of the components. Prototypes with optimal physicochemical characteristics and satisfactory colloidal stability were selected for the assessment of their antigen loading capacity, antigen stability during storage and in vitro and in vivo proof-of-concept studies. In vitro studies showed that antigen-loaded nanoparticles induced the secretion of cytokines by macrophages more efficiently than the antigen in solution, thus indicating a potential adjuvant effect of the nanoparticles. Finally, in vivo studies showed the capacity of these systems to trigger efficient immune responses against the hepatitis B antigen following intramuscular administration, suggesting the potential interest of protamine-polysaccharide nanoparticles as antigen delivery systems.

  18. Detection of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens

    Directory of Open Access Journals (Sweden)

    Vojdani Aristo

    2009-05-01

    Full Text Available Abstract Background Despite the first documented case of food allergy to cooked food in 1921 by Prausnitz and Kustner, all commercial food antigens are prepared from raw food. Furthermore, all IgE and IgG antibodies against dietary proteins offered by many clinical laboratories are measured against raw food antigens. Methods We developed an enzyme-linked immunosorbent assay for the measurement of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens. Sera with low or high reactivity to modified food antigens were subjected to myelin basic protein, oxidized low density lipoprotein, and advanced glycation end products (AGE such as AGE-human serum albumin and AGE-hemoglobin. Results Compared to raw food antigens, IgE antibodies showed a 3–8-fold increase against processed food antigens in 31% of the patients. Similarly, IgG, IgA and IgM antibodies against modified food antigens overall were found at much higher levels than antibody reactions against raw food antigens. Almost every tested serum with high levels of antibodies against modified food antigens showed very high levels of antibodies against myelin basic protein, oxidized low density lipoprotein, AGE-human serum albumin and AGE-hemoglobin. Conclusion We conclude that the determination of food allergy, intolerance and sensitivity would be improved by testing IgE, IgG, IgA and IgM antibodies against both raw and processed food antigens. Antibodies against modified food antigens, by reacting with AGEs and tissue proteins, may cause perturbation in degenerative and autoimmune diseases such as diabetes, atherosclerosis, inflammation, autoimmunity, neurodegeneration and neuroautoimmunity.

  19. Stable antigen is most effective for eliciting CD8+ T-cell responses after DNA vaccination and infection with recombinant vaccinia virus in vivo.

    Science.gov (United States)

    Schliehe, Christopher; Bitzer, Annegret; van den Broek, Maries; Groettrup, Marcus

    2012-09-01

    The induction of strong CD8(+) T-cell responses against infectious diseases and cancer has remained a major challenge. Depending on the source of antigen and the infectious agent, priming of CD8(+) T cells requires direct and/or cross-presentation of antigenic peptides on major histocompatibility complex (MHC) class I molecules by professional antigen-presenting cells (APCs). However, both pathways show distinct preferences concerning antigen stability. Whereas direct presentation was shown to efficiently present peptides derived from rapidly degraded proteins, cross-presentation is dependent on long-lived antigen species. In this report, we analyzed the role of antigen stability on DNA vaccination and recombinant vaccinia virus (VV) infection using altered versions of the same antigen. The long-lived nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV) can be targeted for degradation by N-terminal fusion to ubiquitin or, as we show here, to the ubiquitin-like modifier FAT10. Direct presentation by cells either transfected with NP-encoding plasmids or infected with recombinant VV in vitro was enhanced in the presence of short-lived antigens. In vivo, however, the highest induction of NP-specific CD8(+) T-cell responses was achieved in the presence of long-lived NP. Our experiments provide evidence that targeting antigens for proteasomal degradation does not improve the immunogenicity of DNA vaccines and recombinant VVs. Rather, it is the long-lived antigen that is superior for the efficient activation of MHC class I-restricted immune responses in vivo. Hence, our results suggest a dominant role for antigen cross-priming in DNA vaccination and recombinant VV infection.

  20. A single point in protein trafficking by Plasmodium falciparum determines the expression of major antigens on the surface of infected erythrocytes targeted by human antibodies.

    Science.gov (United States)

    Chan, Jo-Anne; Howell, Katherine B; Langer, Christine; Maier, Alexander G; Hasang, Wina; Rogerson, Stephen J; Petter, Michaela; Chesson, Joanne; Stanisic, Danielle I; Duffy, Michael F; Cooke, Brian M; Siba, Peter M; Mueller, Ivo; Bull, Peter C; Marsh, Kevin; Fowkes, Freya J I; Beeson, James G

    2016-11-01

    Antibodies to blood-stage antigens of Plasmodium falciparum play a pivotal role in human immunity to malaria. During parasite development, multiple proteins are trafficked from the intracellular parasite to the surface of P. falciparum-infected erythrocytes (IEs). However, the relative importance of different proteins as targets of acquired antibodies, and key pathways involved in trafficking major antigens remain to be clearly defined. We quantified antibodies to surface antigens among children, adults, and pregnant women from different malaria-exposed regions. We quantified the importance of antigens as antibody targets using genetically engineered P. falciparum with modified surface antigen expression. Genetic deletion of the trafficking protein skeleton-binding protein-1 (SBP1), which is involved in trafficking the surface antigen PfEMP1, led to a dramatic reduction in antibody recognition of IEs and the ability of human antibodies to promote opsonic phagocytosis of IEs, a key mechanism of parasite clearance. The great majority of antibody epitopes on the IE surface were SBP1-dependent. This was demonstrated using parasite isolates with different genetic or phenotypic backgrounds, and among antibodies from children, adults, and pregnant women in different populations. Comparisons of antibody reactivity to parasite isolates with SBP1 deletion or inhibited PfEMP1 expression suggest that PfEMP1 is the dominant target of acquired human antibodies, and that other P. falciparum IE surface proteins are minor targets. These results establish SBP1 as part of a critical pathway for the trafficking of major surface antigens targeted by human immunity, and have key implications for vaccine development, and quantifying immunity in populations.

  1. Alphavirus replicon particles acting as adjuvants promote CD8+ T cell responses to co-delivered antigen.

    Science.gov (United States)

    Thompson, Joseph M; Whitmore, Alan C; Staats, Herman F; Johnston, Robert E

    2008-08-05

    Alphavirus replicon particles induce strong antibody and CD8+ T cell responses to expressed antigens in numerous experimental systems. We have recently demonstrated that Venezuelan equine encephalitis virus replicon particles (VRP) possess adjuvant activity for systemic and mucosal antibody responses. In this report, we demonstrate that VRP induced an increased and balanced serum IgG subtype response to co-delivered antigen, with simultaneous induction of antigen-specific IgG1 and IgG2a antibodies, and increased both systemic and mucosal antigen-specific CD8+ T cell responses, as measured by an IFN-gamma ELISPOT assay. Additionally, VRP further increased antigen-specific T cell immunity in an additive fashion following co-delivery with the TLR ligand, CpG DNA. VRP infection led to recruitment of CD8+ T cells into the mucosal compartment, possibly utilizing the mucosal homing receptor, as this integrin was upregulated on CD8+ T cells in the draining lymph node of VRP-infected animals, where VRP-infected dendritic cells reside. This newly recognized ability of VRP to mediate increased T cell response towards co-delivered antigen provides the potential to both define the molecular basis of alphavirus-induced immunity, and improve alphavirus-based vaccines.

  2. Tissue polypeptide antigen activity in cerebrospinal fluid

    DEFF Research Database (Denmark)

    Bach, F; Söletormos, Georg; Dombernowsky, P

    1991-01-01

    in the CSF and neurological clinical function. TPpA concentrations decreased in parallel with the clinical response and increased prior to CNS disease progression. As a marker for CNS metastases, the level of TPpA in the CSF in breast cancer patients appears to be superior to the level of protein, lactate......Tissue polypeptide antigen (TPpA) in the cerebrospinal fluid (CSF) was measured in 59 consecutive breast cancer patients with suspected central nervous system (CNS) metastases. Subsequently, we determined that 13 patients had parenchymal brain metastases, 10 had leptomeningeal carcinomatosis...

  3. Biofunctionalizing nanofibers with carbohydrate blood group antigens.

    Science.gov (United States)

    Barr, Katie; Kannan, Bhuvaneswari; Korchagina, Elena; Popova, Inna; Ryzhov, Ivan; Henry, Stephen; Bovin, Nicolai

    2016-11-01

    A rapid and simple method of biofunctionalising nylon, cellulose acetate, and polyvinyl butyral electrospun nanofibers with blood group glycans was achieved by preparing function-spacer-lipid constructs and simply contacting them to fibers with a piezo inkjet printer. A series of water dispersible amphipathic glycan-spacer constructs were synthesized representing a range ABO and related blood group antigens. After immediate contact of the amphipathic glycan-spacer constructs with nanofiber surfaces they self-assembled and were detectable by enzyme immunoassays with high sensitivity and specificity.

  4. Studies on the Antigenic Relationship among Phleboviruses

    Science.gov (United States)

    1982-01-01

    was easily differentiated by this method. Rift Valley fever virus was shown to be antigenically related to Candiru, Frijoles , Karimabad and Punta... Frijoles VP-161A HS(3) _-90% plaque reduction were recorded as positive. Gabek Forest Sud An 754-61 RS(3) Gordil Dak An B 496d MAF(4) Icoaraci Be An...10 10 0 0 80 0 0 2,60 0 40 0 0 CHILIBRE ង ង ង ង ង ង ង ង ង ង 1,280 ង ង ង FRIJOLES 0 0 0 0 0 0 0 0 0 0 0 10,240 0 0 GABEK

  5. Papain-templated Cu nanoclusters: assaying and exhibiting dramatic antibacterial activity cooperating with H2O2

    Science.gov (United States)

    Miao, Hong; Zhong, Dan; Zhou, Zinan; Yang, Xiaoming

    2015-11-01

    Herein, papain-functionalized Cu nanoclusters (CuNCs@Papain) were originally synthesized in aqueous solution together with a quantum yield of 14.3%, and showed obviously red fluorescence at 620 nm. Meanwhile, their corresponding fluorescence mechanism was fully elucidated by fluorescence spectroscopy, HR-TEM, FTIR spectroscopy, and XPS. Subsequently, the as-prepared CuNCs were employed as probes for detecting H2O2. Using CuNCs as probes, H2O2 was determined in the range from 1 μM to 50 μM based on a linear decrease of fluorescence intensity as well as a detection limit of 0.2 μM with a signal-to-noise ratio of 3. More significantly, it has been proved that CuNCs could convert H2O2 to &z.rad;OH, which exhibited dramatic antibacterial activity. Both in vitro and in vivo experiments were performed to validate their antibacterial activity against Gram-positive/negative bacteria and actual wound infection, suggesting their potential for serving as one type of promising antibacterial material.Herein, papain-functionalized Cu nanoclusters (CuNCs@Papain) were originally synthesized in aqueous solution together with a quantum yield of 14.3%, and showed obviously red fluorescence at 620 nm. Meanwhile, their corresponding fluorescence mechanism was fully elucidated by fluorescence spectroscopy, HR-TEM, FTIR spectroscopy, and XPS. Subsequently, the as-prepared CuNCs were employed as probes for detecting H2O2. Using CuNCs as probes, H2O2 was determined in the range from 1 μM to 50 μM based on a linear decrease of fluorescence intensity as well as a detection limit of 0.2 μM with a signal-to-noise ratio of 3. More significantly, it has been proved that CuNCs could convert H2O2 to &z.rad;OH, which exhibited dramatic antibacterial activity. Both in vitro and in vivo experiments were performed to validate their antibacterial activity against Gram-positive/negative bacteria and actual wound infection, suggesting their potential for serving as one type of promising

  6. Protective antibody titres and antigenic competition in multivalent Dichelobacter nodosus fimbrial vaccines using characterised rDNA antigens.

    Science.gov (United States)

    Raadsma, H W; O'Meara, T J; Egerton, J R; Lehrbach, P R; Schwartzkoff, C L

    1994-03-01

    The relationship between K-agglutination antibody titres and protection against experimental challenge with Dichelobacter nodosus, the effect of increasing the number of D. nodosus fimbrial antigens, and the importance of the nature of additional antigens in multivalent vaccines on antibody response and protection against experimental challenge with D. nodosus were examined in Merino sheep. A total of 204 Merino sheep were allocated to one of 12 groups, and vaccinated with preparations containing a variable number of rDNA D. nodosus fimbrial antigens. The most complex vaccine contained ten fimbrial antigens from all major D. nodosus serogroups, while the least complex contained a single fimbrial antigen. In addition to D. nodosus fimbrial antigens, other bacterial rDNA fimbrial antigens (Moraxella bovis Da12d and Escherichia coli K99), and bovine serum albumin (BSA) were used in some vaccines. Antibody titres to fimbrial antigens and BSA were measured by agglutination and ELISA tests, respectively. Antibody titres were determined on five occasions (Weeks 0, 3, 6, 8, and 11 after primary vaccination). All sheep were exposed to an experimental challenge with virulent isolates of D. nodosus from either serogroup A or B, 8 weeks after primary vaccination. For D. nodosus K-agglutinating antibody titres, a strong negative correlation between antibody titre and footrot lesion score was observed. This relationship was influenced by the virulence of the challenge strain. Increasing the number of fimbrial antigens in experimental rDNA D. nodosus fimbrial vaccines resulted in a linear decrease in K-agglutinating antibody titres to individual D. nodosus serogroups. Similarly, a linear decrease in protection to challenge with homologous serogroups was observed as the number of D. nodosus fimbrial antigens represented in the vaccine increased. The reduction in antibody titres in multicomponent vaccines is thought to be due to antigenic competition. The level of competition

  7. Fcγ receptor antigen targeting potentiates cross-presentation by human blood and lymphoid tissue BDCA-3+ dendritic cells.

    Science.gov (United States)

    Flinsenberg, Thijs W H; Compeer, Ewoud B; Koning, Dan; Klein, Mark; Amelung, Femke J; van Baarle, Debbie; Boelens, Jaap Jan; Boes, Marianne

    2012-12-20

    The reactivation of human cytomegalovirus (HCMV) poses a serious health threat to immune compromised individuals. As a treatment strategy, dendritic cell (DC) vaccination trials are ongoing. Recent work suggests that BDCA-3(+) (CD141(+)) subset DCs may be particularly effective in DC vaccination trials. BDCA-3(+) DCs had however been mostly characterized for their ability to cross-present antigen from necrotic cells. We here describe our study of human BDCA-3(+) DCs in elicitation of HCMV-specific CD8(+) T-cell clones. We show that Fcgamma-receptor (FcγR) antigen targeting facilitates antigen cross-presentation in several DC subsets, including BDCA-3(+) DCs. FcγR antigen targeting stimulates antigen uptake by BDCA-1(+) rather than BDCA-3(+) DCs. Conversely, BDCA-3(+) DCs and not BDCA-1(+) DCs show improved cross-presentation by FcγR targeting, as measured by induced release of IFNγ and TNF by antigen-specific CD8(+) T cells. FcγR-facilitated cross-presentation requires antigen processing in both an acidic endosomal compartment and by the proteasome, and did not induce substantial DC maturation. FcγRII is the most abundantly expressed FcγR on both BDCA-1(+) and BDCA-3(+) DCs. Furthermore we show that BDCA-3(+) DCs express relatively more stimulatory FcγRIIa than inhibitory FcγRIIb in comparison with BDCA-1(+) DCs. These studies support the exploration of FcγR antigen targeting to BDCA-3(+) DCs for human vaccination purposes.

  8. Dramatic change in a young woman’s perception of her diabetes and remarkable reduction in HbA1c after an individual course of Guided Self-Determination

    DEFF Research Database (Denmark)

    Prip, Anne; Christiansen, Anette Wendelboe; Zoffmann, Vibeke

    2015-01-01

    -attendance and psychosocial distress. She managed to change her perception of diabetes dramatically and improved her glycaemic control. Considering the complexity of her case, we explored how she achieved these changes. A GSD-trained nurse delivered the intervention, which involves reflection sheets and advanced professional...... communication. Glycated hemoglobin was reported in the patient's record and an interview conducted by external interviewers was analysed thematically, indicating that a four-stage process of empowerment had taken place: 'focusing on life prior to numbers', 'unpacking a heavy burden', 'breaking out of isolation...

  9. Antigen-induced and non-antigen-induced histamine release from rat mast cells sensitized with mouse antiserum.

    Directory of Open Access Journals (Sweden)

    Kurose,Masao

    1981-10-01

    Full Text Available Marked IgE-mediated histamine release from rat mast cells sensitized in vitro with mouse antiserum occurs in the presence of added Ca++ and phosphatidylserine (PS, although a considerable degree of antigen-induced histamine release which may utilize intracellular or cell-bound calcium is also observed. The decay in the responsiveness to Ca++ of the sensitized cells stimulated by antigen in Ca++-free medium in the presence of PS is relatively slow, and maximum release is produced by Ca++ added 1 min after antigen. Histamine release also occurs when Ca++ is added after PS in the absence of antigen to the sensitized cells suspended in Ca++-free medium. Unlike the antigen-induced release, the intensity of this non-antigen-induced release varies depending on both mast-cell and antiserum pools. A heat-labile factor(s, which is different from antigen-specific IgE antibody and is also contained in normal mouse serum, is involved in this reaction. In the antigen-nondependent (PS + Ca++-induced release, no decay in the responsiveness to Ca++ is observed after PS addition. Both the antigen-induced and non-antigen-induced release are completed fairly rapidly and are dependent of temperature, pH and energy.

  10. Immunoliposome-PCR: a generic ultrasensitive quantitative antigen detection system

    Directory of Open Access Journals (Sweden)

    He Junkun

    2012-06-01

    Full Text Available Abstract Background The accurate quantification of antigens at low concentrations over a wide dynamic range is needed for identifying biomarkers associated with disease and detecting protein interactions in high-throughput microarrays used in proteomics. Here we report the development of an ultrasensitive quantitative assay format called immunoliposome polymerase chain reaction (ILPCR that fulfills these requirements. This method uses a liposome, with reporter DNA encapsulated inside and biotin-labeled polyethylene glycol (PEG phospholipid conjugates incorporated into the outer surface of the liposome, as a detection reagent. The antigenic target is immobilized in the well of a microplate by a capture antibody and the liposome detection reagent is then coupled to a biotin-labeled second antibody through a NeutrAvidin bridge. The liposome is ruptured to release the reporter DNA, which serves as a surrogate to quantify the protein target using real-time PCR. Results A liposome detection reagent was prepared, which consisted of a population of liposomes ~120 nm in diameter with each liposome possessing ~800 accessible biotin receptors and ~220 encapsulated reporters. This liposome detection reagent was used in an assay to quantify the concentration of carcinoembryonic antigen (CEA in human serum. This ILPCR assay exhibited a linear dose–response curve from 10-10 M to 10-16 M CEA. Within this range the assay coefficient of variance was Conclusions The ILPCR assay has several advantages over other immuno-PCR methods. The reporter DNA and biotin-labeled PEG phospholipids spontaneously incorporate into the liposomes as they form, simplifying preparation of the detection reagent. Encapsulation of the reporter inside the liposomes allows nonspecific DNA in the assay medium to be degraded with DNase I prior to quantification of the encapsulated reporter by PCR, which reduces false-positive results and improves quantitative accuracy. The ability to

  11. Antigen presentation for priming T cells in central system.

    Science.gov (United States)

    Dasgupta, Shaoni; Dasgupta, Subhajit

    2017-01-01

    Generation of myelin antigen-specific T cells is a major event in neuroimmune responses that causes demyelination. The antigen-priming of T cells and its location is important in chronic and acute inflammation. In autoimmune multiple sclerosis, the effector T cells are considered to generate in periphery. However, the reasons for chronic relapsing-remitting events are obscure. Considering mechanisms, a feasible aim of research is to investigate the role of antigen-primed T cells in lupus cerebritis. Last thirty years of investigations emphasize the relevance of microglia and infiltrated dendritic cells/macrophages as antigen presenting cells in the central nervous system. The recent approach towards circulating B-lymphocytes is an important area in the context. Here, we analyze the existing findings on antigen presentation in the central nervous system. The aim is to visualize signaling events of myelin antigen presentation to T cells and lead to the strategy of future goals on immunotherapy research.

  12. Human Ia-like antigens in non-lymphoid organs.

    Science.gov (United States)

    Koyama, K; Fukunishi, T; Barcos, M; Tanigaki, N; Pressman, D

    1979-01-01

    Human Ia-like antigens in liver and kidney were shown by the immunofluorescence assay to be present mostly in the endothelial-mesenchymal cells of these organs. The parenchymal cells apparently contained no human Ia-like antigens. The antigens in liver and kidney were purified and shown to have the same subunit structure as human Ia-like antigens of cultured B-lymphoid cells. The human Ia-like antigens in non-lymphoid organs, not only in liver and kidney but also in testis, heart, muscle and brain, carried all the xenoantigenic characteristics of human Ia-like antigens expressed on lymphoid cells of B-cell lineage. Images Figure 1 PMID:389786

  13. Tissue distribution of histo-blood group antigens

    DEFF Research Database (Denmark)

    Ravn, V; Dabelsteen, Erik

    2000-01-01

    carrier carbohydrate chains. Histo-blood group antigens are found in most epithelial tissues. Meanwhile, several factors influence the type, the amount, and the histological distribution of histoblood group antigens, i.e. the ABO, Lewis, and saliva-secretor type of the individual, and the cell- and tissue......The introduction of immunohistochemical techniques and monoclonal antibodies to specific carbohydrate epitopes has made it possible to study in detail the tissue distribution of histo-blood group antigens and related carbohydrate structures. The present paper summarizes the available data...... concerning the histological distribution of histo-blood group antigens and their precursor structures in normal human tissues. Studies performed have concentrated on carbohydrate antigens related to the ABO, Lewis, and TTn blood group systems, i.e. histo-blood group antigens carried by type 1, 2, and 3 chain...

  14. Strategies to enhance immunogenicity of cDNA vaccine encoded antigens by modulation of antigen processing

    NARCIS (Netherlands)

    Platteel, Anouk C M; Marit de Groot, A; Andersen, Peter; Ovaa, Huib; Kloetzel, Peter M; Mishto, Michele; Sijts, Alice J A M

    2016-01-01

    Most vaccines are based on protective humoral responses while for intracellular pathogens CD8(+) T cells are regularly needed to provide protection. However, poor processing efficiency of antigens is often a limiting factor in CD8(+) T cell priming, hampering vaccine efficacy. The multistage cDNA va

  15. Mycobacterium leprae antigens involved in human immune responses. I. Identification of four antigens by monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Britton, W.J.; Hellqvist, L.; Basten, A.; Raison, R.L.

    1985-12-01

    Four distinct antigens were identified in soluble sonicates of Mycobacterium leprae by using a panel of 11 monoclonal antibodies. Cross-reactivity studies with other mycobacterial species were conducted by using ELISA and immunoblot assays, and demonstrated that determinants on two of the antigens were present in many mycobacteria, whereas the other two were limited in distribution. Competitive inhibition experiments with radiolabeled monoclonal antibodies showed cross-inhibition between antibodies identifying two of the four antigenicbands. These two bands, of M/sub tau/ 4.5 to 6 KD and 30 to 40 KD, were resistant to protease treatment after immunoblotting. In contrast the two other bands of 16 and 70 KD were protease-sensitive. Although all four bands reacted with some human lepromatous leprosy sera in immunoblots, the 4.5 to 6 KD and 30 to 40 KD bands were most prominent. Lepromatous leprosy sera also inhibited the binding of radiolabeled monoclonal antibodies to each of the four antigens, with the mean titer causing 50% inhibition being higher for antibodies reacting with the 4.5 to 6 KD and 30 to 40 KD bands. These findings indicated that all four antigens were involved in the human B cell response to M. leprae.

  16. Immunologic aspect of ovarian cancer and p53 as tumor antigen

    Directory of Open Access Journals (Sweden)

    van der Burg SH

    2005-09-01

    Full Text Available Abstract Ovarian cancer represents the fifth leading cause of death from all cancers for women. During the last decades overall survival has improved due to the use of new chemotherapy schedules. Still, the majority of patients die of this disease. Research reveals that ovarian cancer patients exhibit significant immune responses against their tumor. In this review the knowledge obtained thus far on the interaction of ovarian cancer tumor cells and the immune system is discussed. Furthermore the role of p53 as tumor antigen and its potential role as target antigen in ovarian cancer is summarized. Based on the increased knowledge on the role of the immune system in ovarian cancer major improvements are to be expected of immunotherapy based treatment of this disease.

  17. Home in the heat: dramatic seasonal variation in home range of desert golden eagles informs management for renewable energy development

    Science.gov (United States)

    Braham, Melissa; Miller, Tricia A.; Duerr, Adam E.; Lanzone, Michael; Fesnock, Amy; LaPre, Larry; Driscoll, Daniel; Katzner, Todd Eli

    2015-01-01

    Renewable energy is expanding quickly with sometimes dramatic impacts to species and ecosystems. To understand the degree to which sensitive species may be impacted by renewable energy projects, it is informative to know how much space individuals use and how that space may overlap with planned development. We used global positioning system–global system for mobile communications (GPS-GSM) telemetry to measure year-round movements of golden eagles (Aquila chrysaetos) from the Mojave Desert of California, USA. We estimated monthly space use with adaptive local convex hulls to identify the temporal and spatial scales at which eagles may encounter renewable energy projects in the Desert Renewable Energy Conservation Plan area. Mean size of home ranges was lowest and least variable from November through January and greatest in February–March and May–August. These monthly home range patterns coincided with seasonal variation in breeding ecology, habitat associations, and temperature. The expanded home ranges in hot summer months included movements to cooler, prey-dense, mountainous areas characterized by forest, grasslands, and scrublands. Breeding-season home ranges (October–May) included more lowland semi-desert and rock vegetation. Overlap of eagle home ranges and focus areas for renewable energy development was greatest when eagle home ranges were smallest, during the breeding season. Golden eagles in the Mojave Desert used more space and a wider range of habitat types than expected and renewable energy projects could affect a larger section of the regional population than was previously thought.

  18. Satellite monitoring of dramatic changes at Hawai'i's only alpine lake: Lake Waiau on Mauna Kea volcano

    Science.gov (United States)

    Patrick, Matthew R.; Kauahikaua, James P.

    2015-01-01

    Lake Waiau is a small, typically 100-meter-long lake, located near the summit of Mauna Kea volcano, on the Island of Hawaiʻi. It is Hawaiʻi’s only alpine lake and is considered sacred in Hawaiian cultural tradition. Over the past few years, the lake has diminished in size, and, by October 2013, surface water had almost completely disappeared from the lake. In this study, we use high-resolution satellite images and aerial photographs to document recent changes at the lake. Based on our reconstructions covering the past 200 years, the historical lake surface area has typically ranged from 5,000 to 7,000 square meters, but in 2010 a dramatic plunge in lake area ensued. The lake area rebounded significantly in early 2014, following heavy winter storms. This near disappearance of the lake, judging from analysis of visitor photographs and field reports, appears to be highly unusual, if not unprecedented, in the historical record. The unusually low water levels in the lake are consistent with a recent severe drought in Hawaiʻi.

  19. 英美戏剧对白与口语学习%English Dramatic Dialogue and Oral English Learning

    Institute of Scientific and Technical Information of China (English)

    陈爱勤; 张光仕

    2012-01-01

    Oral English is considered as one of the most difficult courses.Many college graduates,after learning English for more than ten years,still cannot speak English fluently,and have an unbalanced development in listening,speaking,reading and writing.There are many factors which may hinder students' oral English development.Using dramatic dialogues as teaching material,through the positive transfer of such some aspects as attention,perceptiveness,imagination,etc.and students' own positive behavior,students can overcome difficulties in learning oral English,and effectively master oral English.%英语口语是最难学的课程之一,许多大学毕业生,学了十多年的英语,在听、说、读、写方面仍然发展不平衡,英语口语不流利。影响其口语能力的因素很多。通过戏剧对白中注意力、感知力、想象力等方面的有效迁移以及学生自己的积极行为,学生们可以克服学习困难,真正有效地掌握英语口语。

  20. Intact neurobehavioral development and dramatic impairments of procedural-like memory following neonatal ventral hippocampal lesion in rats.

    Science.gov (United States)

    Lecourtier, L; Antal, M-C; Cosquer, B; Schumacher, A; Samama, B; Angst, M-J; Ferrandon, A; Koning, E; Cassel, J-C; Nehlig, A

    2012-04-05

    Neonatal ventral hippocampal lesions (NVHL) in rats are considered a potent developmental model of schizophrenia. After NVHL, rats appear normal during their preadolescent time, whereas in early adulthood, they develop behavioral deficits paralleling symptomatic aspects of schizophrenia, including hyperactivity, hypersensitivity to amphetamine (AMPH), prepulse and latent inhibition deficits, reduced social interactions, and spatial working and reference memory alterations. Surprisingly, the question of the consequences of NVHL on postnatal neurobehavioral development has not been addressed. This is of particular importance, as a defective neurobehavioral development could contribute to impairments seen in adult rats. Therefore, at several time points of the early postsurgical life of NVHL rats, we assessed behaviors accounting for neurobehavioral development, including negative geotaxis and grip strength (PD11), locomotor coordination (PD21), and open-field (PD25). At adulthood, the rats were tested for anxiety levels, locomotor activity, as well as spatial reference memory performance. Using a novel task, we also investigated the consequences of the lesions on procedural-like memory, which had never been tested following NVHL. Our results point to preserved neurobehavioral development. They also confirm the already documented locomotor hyperactivity, spatial reference memory impairment, and hyperresponsiveness to AMPH. Finally, our rseults show for the first time that NVHL disabled the development of behavioral routines, suggesting dramatic procedural memory deficits. The presence of procedural memory deficits in adult rats subjected to NHVL suggests that the lesions lead to a wider range of cognitive deficits than previously shown. Interestingly, procedural or implicit memory impairments have also been reported in schizophrenic patients.

  1. Flux dependent MeV self-ion-induced effects on Au nanostructures: dramatic mass transport and nanosilicide formation.

    Science.gov (United States)

    Ghatak, J; Umananda Bhatta, M; Sundaravel, B; Nair, K G M; Liou, Sz-Chian; Chen, Cheng-Hsuan; Wang, Yuh-Lin; Satyam, P V

    2008-08-13

    We report a direct observation of dramatic mass transport due to 1.5 MeV Au(2+) ion impact on isolated Au nanostructures of average size ≈7.6 nm and height ≈6.9 nm that are deposited on Si(111) substrate under high flux (3.2 × 10(10)-6.3 × 10(12) ions cm(-2) s(-1)) conditions. The mass transport from nanostructures was found to extend up to a distance of about 60 nm into the substrate, much beyond their size. This forward mass transport is compared with the recoil implantation profiles using SRIM simulation. The observed anomalies with theory and simulations are discussed. At a given energy, the incident flux plays a major role in mass transport and its redistribution. The mass transport is explained on the basis of thermal effects and the creation of rapid diffusion paths in the nanoscale regime during the course of ion irradiation. The unusual mass transport is found to be associated with the formation of gold silicide nano-alloys at subsurfaces. The complexity of the ion-nanostructure interaction process is discussed with a direct observation of melting (in the form of spherical fragments on the surface) phenomena. Transmission electron microscopy, scanning transmission electron microscopy, and Rutherford backscattering spectroscopy methods have been used.

  2. Dramatic decrease of pelagic carbonate production by nannoplankton across the Early Toarcian anoxic event (T-OAE)

    Science.gov (United States)

    Mattioli, Emanuela; Pittet, Bernard; Petitpierre, Laurent; Mailliot, Samuel

    2009-02-01

    In this account we present estimates of nannofossil fluxes in four sections and one borehole all belonging to the Early Jurassic western Tethys. This study aims to map the distribution of pelagic carbonate production across the Early Toarcian anoxic event (T-OAE), and to understand which environmental parameters did control such production. Our results indicate important changes in carbonate production by nannoplankton occurring within the western Tethys and its variations through time. Nannofossil fluxes (specimens per m 2 per year) are extremely low during the T-OAE in all the studied settings. Higher fluxes are encountered in the westernmost part of the Tethys Ocean before the T-OAE, whilst pelagic carbonate production shifted towards the northern margin of the Tethys after the recovery from anoxic conditions. The dramatic decrease in nannoplankton production during the T-OAE has been interpreted in previous works as a biocalcification crisis related to high pCO 2 in the atmosphere/hydrosphere system. Although a high pCO 2 may have lowered the carbonate saturation state of Early Jurassic oceans and finally hampered biocalcification, we speculate that the most important effects of CO 2 increase were indirect, and affected pelagic producers via changes on climate and sea-level. Namely, it seems that precipitation/evaporation budgets and continental runoff that controlled nutrient levels and salinity in surface oceanic waters were important factors for pelagic biocalcifiers.

  3. “Postdramatic” Tendencies in the German Dramatic Art at the End of XX — Beginning of XXI Centuries

    Directory of Open Access Journals (Sweden)

    Sharypina T. A.

    2014-01-01

    Full Text Available Disintegration and integration processes of German culture of the end of XX and beginning of XXI are analyzed by giving examples of stage interpretations of mythological plots in theatres of present-day Germany. It is stated that pluralism and multidimensionality of the spiritual experience of modern cultural workers, both writers (such as V. Braun, S. Schutz, B. Strauss etc. and leading producers (D. Dorn, S. Nubling and others contribute to the drawing up of a special syncretic style of theatre staging, first of all with the use of the ancient material which is appropriate for it. Ancient myth, as one of the steadiest constants of the European literature, gives a universal key to the interpretation of various cultural and ethic-aesthetic phenomena that are irredundant to nothing else. There is a sociocultural context in which German spectators nowadays try to comprehend these dramaturgy phenomena; and there is a genuine stage director interpretations of them (in Aachen City Theatre, Dramatic Theatre of Hannover, Munich Chamber Theatre etc. that not only lead to the decanonization of the classic model, but also pinpoint problematique of these performances.

  4. Dramatic Changes in Thermoelectric Power of Germanium under Pressure: Printing n–p Junctions by Applied Stress

    Science.gov (United States)

    Korobeinikov, Igor V.; Morozova, Natalia V.; Shchennikov, Vladimir V.; Ovsyannikov, Sergey V.

    2017-03-01

    Controlled tuning the electrical, optical, magnetic, mechanical and other characteristics of the leading semiconducting materials is one of the primary technological challenges. Here, we demonstrate that the electronic transport properties of conventional single-crystalline wafers of germanium may be dramatically tuned by application of moderate pressures. We investigated the thermoelectric power (Seebeck coefficient) of p– and n–type germanium under high pressure to 20 GPa. We established that an applied pressure of several GPa drastically shifts the electrical conduction to p–type. The p–type conduction is conserved across the semiconductor-metal phase transition at near 10 GPa. Upon pressure releasing, germanium transformed to a metastable st12 phase (Ge-III) with n–type semiconducting conductivity. We proposed that the unusual electronic properties of germanium in the original cubic-diamond-structured phase could result from a splitting of the “heavy” and “light” holes bands, and a related charge transfer between them. We suggested new innovative applications of germanium, e.g., in technologies of printing of n–p and n–p–n junctions by applied stress. Thus, our work has uncovered a new face of germanium as a ‘smart’ material.

  5. Osteopontin promotes dendritic cell maturation and function in response to HBV antigens

    Directory of Open Access Journals (Sweden)

    Cui GY

    2015-06-01

    HBV antigens. In addition, OPN deficiency in DCs reduced the HBV antigen-induced inflammatory response in the liver of mice. Importantly, OPN administration significantly promoted the maturation of DCs from CHB patients in vitro.Conclusion: These findings suggested that OPN could improve the maturation and functioning of DCs in the immune response to HBV antigens, which might be useful to further improve the effect of DC vaccine. Keywords: osteopontin, dendritic cells, hepatitis B virus

  6. Suppression of autophagy and antigen presentation by Mycobacterium tuberculosis PE_PGRS47.

    Science.gov (United States)

    Saini, Neeraj K; Baena, Andres; Ng, Tony W; Venkataswamy, Manjunatha M; Kennedy, Steven C; Kunnath-Velayudhan, Shajo; Carreño, Leandro J; Xu, Jiayong; Chan, John; Larsen, Michelle H; Jacobs, William R; Porcelli, Steven A

    2016-08-15

    Suppression of major histocompatibility complex (MHC) class II antigen presentation is believed to be among the major mechanisms used by Mycobacterium tuberculosis to escape protective host immune responses. Through a genome-wide screen for the genetic loci of M. tuberculosis that inhibit MHC class II-restricted antigen presentation by mycobacteria-infected dendritic cells, we identified the PE_PGRS47 protein as one of the responsible factors. Targeted disruption of the PE_PGRS47 (Rv2741) gene led to attenuated growth of M. tuberculosis in vitro and in vivo, and a PE_PGRS47 mutant showed enhanced MHC class II-restricted antigen presentation during in vivo infection of mice. Analysis of the effects of deletion or over-expression of PE_PGRS47 implicated this protein in the inhibition of autophagy in infected host phagocytes. Our findings identify PE_PGRS47 as a functionally relevant, non-redundant bacterial factor in the modulation of innate and adaptive immunity by M. tuberculosis, suggesting strategies for improving antigen presentation and the generation of protective immunity during vaccination or infection.

  7. Construction and Expression of a Single Chain Antibody Mimicing Human Ovarian Cancer Antigen CA125

    Institute of Scientific and Technical Information of China (English)

    Aidong Li; Zheng Li; Yinghong Wang; Yongming Zhang; Jie Ma

    2006-01-01

    One concept for immune therapy of cancer involves induction of antigen mimic antibodies to trigger the immune response against tumor cells. Anti-idiotypic antibodies directed against the antigen-binding site of antibodies specific for tumor antigen may functionally and even structurally mimic antigen and induce anti-anti-idiotypic immune response. Monoclonal antibody WJ02 is one of such anti-idiotypic antibodies, which contains internal image of CA125. In order to improve the immunospecificity of mAb WJ02, we constructed a single chain of mAb WJ02 in Vl-linker-Vh orientation. The scFv-WJ02 could be expressed and secreted in the recombinant Pichia pastoris system. The secreted scFv protein with a molecular weight of 30 kD retained the biological activity of mAb WJ02, which was proved by a direct binding assay and inhibition experiment. Our results indicated that the scFv-WJ02 could be used as a possible tool for idiotypic therapy against ovarian cancer, which might enhance the possibility of eliminating nonspecific responses induced by mAb WJ02.

  8. Mesoporous silica nanoparticles as antigen carriers and adjuvants for vaccine delivery

    Science.gov (United States)

    Mody, Karishma T.; Popat, Amirali; Mahony, Donna; Cavallaro, Antonino S.; Yu, Chengzhong; Mitter, Neena

    2013-05-01

    Vaccines have been at the forefront of improving human health for over two centuries. The challenges faced in developing effective vaccines flow from complexities associated with the immune system and requirement of an efficient and safe adjuvant to induce a strong adaptive immune response. Development of an efficient vaccine formulation requires careful selection of a potent antigen, efficient adjuvant and route of delivery. Adjuvants are immunological agents that activate the antigen presenting cells (APCs) and elicit a strong immune response. In the past decade, the use of mesoporous silica nanoparticles (MSNs) has gained significant attention as potential delivery vehicles for various biomolecules. In this review, we aim to highlight the potential of MSNs as vaccine delivery vehicles and their ability to act as adjuvants. We have provided an overview on the latest progress on synthesis, adsorption and release kinetics and biocompatibility of MSNs as next generation antigen carriers and adjuvants. A comprehensive summary on the ability of MSNs to deliver antigens and elicit both humoral and cellular immune responses is provided. Finally, we give insight on fundamental challenges and some future prospects of these nanoparticles as adjuvants.

  9. Structural and Computational Biology in the Design of Immunogenic Vaccine Antigens

    Directory of Open Access Journals (Sweden)

    Lassi Liljeroos

    2015-01-01

    Full Text Available Vaccination is historically one of the most important medical interventions for the prevention of infectious disease. Previously, vaccines were typically made of rather crude mixtures of inactivated or attenuated causative agents. However, over the last 10–20 years, several important technological and computational advances have enabled major progress in the discovery and design of potently immunogenic recombinant protein vaccine antigens. Here we discuss three key breakthrough approaches that have potentiated structural and computational vaccine design. Firstly, genomic sciences gave birth to the field of reverse vaccinology, which has enabled the rapid computational identification of potential vaccine antigens. Secondly, major advances in structural biology, experimental epitope mapping, and computational epitope prediction have yielded molecular insights into the immunogenic determinants defining protective antigens, enabling their rational optimization. Thirdly, and most recently, computational approaches have been used to convert this wealth of structural and immunological information into the design of improved vaccine antigens. This review aims to illustrate the growing power of combining sequencing, structural and computational approaches, and we discuss how this may drive the design of novel immunogens suitable for future vaccines urgently needed to increase the global prevention of infectious disease.

  10. Thermodynamics of antibody-antigen interaction revealed by mutation analysis of antibody variable regions.

    Science.gov (United States)

    Akiba, Hiroki; Tsumoto, Kouhei

    2015-07-01

    Antibodies (immunoglobulins) bind specific molecules (i.e. antigens) with high affinity and specificity. In order to understand their mechanisms of recognition, interaction analysis based on thermodynamic and kinetic parameters, as well as structure determination is crucial. In this review, we focus on mutational analysis which gives information about the role of each amino acid residue in antibody-antigen interaction. Taking anti-hen egg lysozyme antibodies and several anti-small molecule antibodies, the energetic contribution of hot-spot and non-hot-spot residues is discussed in terms of thermodynamics. Here, thermodynamics of the contribution from aromatic, charged and hydrogen bond-forming amino acids are discussed, and their different characteristics have been elucidated. The information gives fundamental understanding of the antibody-antigen interaction. Furthermore, the consequences of antibody engineering are analysed from thermodynamic viewpoints: humanization to reduce immunogenicity and rational design to improve affinity. Amino acid residues outside hot-spots in the interface play important roles in these cases, and thus thermodynamic and kinetic parameters give much information about the antigen recognition. Thermodynamic analysis of mutant antibodies thus should lead to advanced strategies to design and select antibodies with high affinity.

  11. Immune responses and protective efficacy induced by 85B antigen and early secreted antigenic target-6 kDa antigen fusion protein secreted by recombinant bacille Calmette-Guérin.

    Science.gov (United States)

    Shi, Changhong; Wang, Xiaowu; Zhang, Hai; Xu, Zhikai; Li, Yuan; Yuan, Lintian

    2007-04-01

    In an attempt to improve immune responses and protective efficacy, we constructed two recombinant bacille Calmette-Guérin (rBCG) strains expressing an 85B antigen (Ag85B) and early secreted antigenic target-6 kDa antigen (ESAT6) of Mycobacterium tuberculosis (MTB) fusion protein. Both rBCG strains have the same protein insertion but in a different order (Ag85B-ESAT6 and ESAT6-Ag85B). The cultured supernatant of rBCG strains and the sera from the mice immunized with the fusion protein Ag85B-ESAT6 or ESAT6-Ag85B formed a band with a fraction size of 37 kDa, equalivalent to the sum of Ag85B and ESAT6. Six weeks after BALB/c mice were immunized with BCG or rBCG, spleen lymphocytes showed significant proliferation in response to culture filtrate protein of MTB. Compared with the BCG group, mice vaccinated with rBCG elicited a high level increase of immunoglobulin G antibodies to culture filtrate protein in the serum. The gamma-interferon levels in the lymphocyte culture medium supernatants increased remarkably in the rBCG1 group, significantly higher than that of the BCG immunized group (p0.05).

  12. Glycoconjugates as target antigens in peripheral neuropathies

    Directory of Open Access Journals (Sweden)

    Ljubica Suturkova

    2014-12-01

    Full Text Available Identification and characterization of antigens present at the human peripheral nerve is a great challenge in the field of neuroimmunology. The latest investigations are focused on the understanding of the biology of glycoconjugates present at the peripheral nerve, and their immunological reactivity. Increased titers of antibodies that recognize carbohydrate determinants of glycoconjugates (glycolipids and glycoproteins are associated with distinct neuropathic syndromes. There is considerable cross-reactivity among anti-ganglioside antibodies, resulting from shared oligosaccharide epitopes, possibly explaining the overlap in syndromes observed in many affected patients. Sera from patients with neuropathies (GBS, chronic inflammatory demielynating polyneuropathy - CIDP, multifocal motor neuropathy - MMN, cross-react with glycoproteins isolated from human peripheral nerve and from Campylobacter jejuni O:19. The frequency of occurrence of antibodies against these glycoproteins is different, depending of the type of neuropathy. Identification of the cross-reactive glycoproteins and possible additional auto antigens could be useful in laboratory evaluation of peripheral neuropathies and help to develop a more effective therapeutic approach.

  13. Antigen epitope of Helicobacter pylorivacuolating cytotoxin A

    Institute of Scientific and Technical Information of China (English)

    Xiu-Li Liu; Shu-Qin Li; Chun-Jie Liu; Hao-Xia Tao; Zhao-Shan Zhang

    2004-01-01

    AIM: To construct and select antigen epitopes of vacuolating cytotoxin A (VacA) for nontoxic VacA vaccine against Helicobacter pylori (H pylori) infection.METHODS: Eleven VacA epitopes were predicted according to VacA antigenic bioinformatics. Three candidates of VacA epitope were constructed through different combined epitopes. The candidate was linked with E. coli heat-labile enterotoxin B (LTB) by a linker of 7 amino acids, and cloned into plasmid pQE-60 in which fusion LTB-VacA epitope was efficiently expressed. To test the antigencity of the candidate, 6 BALB/c mice were treated with the fusion LTB-VacA epitope through intraperitoneal injection. To explore the ability of inhibiting the toxicity of VacA, cantiserum against the candidate was used to counteract VacA that induced HeLa cells to produce cell vacuoles in vitro.RESULTS: Serum IgG against the candidate was induced in the BALB/c mice. In vitro, the three antisera against the candidate efficiently counteracted the toxicity of VacA, and decreased the number of cell vacuoles by 14.17%, 20.20%and 30.41% respectively.CONCLUSION: Two of the three candidates, LZ-VacA1and LZ-VacA2, can be used to further study the mechanism of vacuolating toxicity of VacA, and to construct nontoxic VacA vaccine against H pylori infection.

  14. Immunoregulation by Taenia crassiceps and Its Antigens

    Directory of Open Access Journals (Sweden)

    Alberto N. Peón

    2013-01-01

    Full Text Available Taenia crassiceps is a cestode parasite of rodents (in its larval stage and canids (in its adult stage that can also parasitize immunocompromised humans. We have studied the immune response elicited by this helminth and its antigens in mice and human cells, and have discovered that they have a strong capacity to induce chronic Th2-type responses that are primarily characterized by high levels of Th2 cytokines, low proliferative responses in lymphocytes, an immature and LPS-tolerogenic profile in dendritic cells, the recruitment of myeloid-derived suppressor cells and, specially, alternatively activated macrophages. We also have utilized the immunoregulatory capabilities of this helminth to successfully modulate autoimmune responses and the outcome of other infectious diseases. In the present paper, we review the work of others and ourselves with regard to the immune response induced by T. crassiceps and its antigens, and we compare the advances in our understanding of this parasitic infection model with the knowledge that has been obtained from other selected models.

  15. Detection of peste des petits ruminants virus antigen using immunofiltration and antigen-competition ELISA methods.

    Science.gov (United States)

    Raj, G Dhinakar; Rajanathan, T M C; Kumar, C Senthil; Ramathilagam, G; Hiremath, Geetha; Shaila, M S

    2008-06-22

    Peste des petits ruminants (PPR) is one of the most economically important diseases affecting sheep and goats in India. An immunofiltration-based test has been developed using either mono-specific serum/monoclonal antibodies (mAb) prepared against a recombinant truncated nucleocapsid protein of rinderpest virus (RPV) cross-reactive with PPR virus. This method consists of coating ocular swab eluate from suspected animals onto a nitrocellulose membrane housed in a plastic module, which is allowed to react with suitable dilutions of a mAb or a mono-specific polyclonal antibody. The antigen-antibody complex formed on the membrane is then detected by protein A-colloidal gold conjugate, which forms a pink colour. In the immunofiltration test, concordant results were obtained using either PPRV mAb or mono-specific serum. Another test, an antigen-competition ELISA which relies on the competition between plate-coated recombinant truncated 'N' protein of RPV and the PPRV 'N' protein present in ocular swab eluates (sample) for binding to the mono-specific antibody against N protein of RPV (in liquid phase) was developed. The cut-off value for this test was established using reverse transcription polymerase chain reaction (RT-PCR) positive and negative oculo-nasal swab samples. Linear correlation between percent inhibition (PI) values in antigen-competition ELISA and virus infectivity titres was 0.992. Comparison of the immunofiltration test with the antigen-competition ELISA yielded a sensitivity of 80% and specificity of 100%. These two tests can serve as a screening (immunofiltration) and confirmatory (antigen-competition ELISA) test, respectively, in the diagnosis of PPR in sheep or goats.

  16. Antigen-Experienced CD4lo T Cells Are Linked to Deficient Contraction of the Immune Response in Autoimmune Diabetes

    Directory of Open Access Journals (Sweden)

    Sean Linkes

    2010-01-01

    Full Text Available Following proper activation, naïve “CD4lo” T cells differentiate into effector T cells with enhanced expression of CD4 -“CD4hi” effectors. Autoimmune diabetes-prone NOD mice display a unique set of antigen-experienced “CD4lo” T cells that persist after primary stimulation. Here, we report that a population of such cells remained after secondary and tertiary TCR stimulation and produced cytokines upon antigenic challenge. However, when NOD blasts were induced in the presence of rIL-15, the number of antigen-experienced “CD4lo” T cells was significantly reduced. Clonal contraction, mediated in part by CD95-dependent activation-induced cell death (AICD, normally regulates the accumulation of “CD4hi” effectors. Interestingly, CD95 expression was dramatically reduced on the AICD-resistant NOD “CD4lo” T cells. Thus, while autoimmune disease has often been attributed to the engagement of robust autoimmunity, we suggest that the inability to effectively contract the immune response distinguishes benign autoimmunity from progressive autoimmune diseases that are characterized by chronic T cell-mediated inflammation.

  17. СAPSULAR ANTIGEN OF YERSINIA PESTIS

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    L. A. Kadnikova

    2015-01-01

    Full Text Available Plague is a zoonosis caused by gram-negative bacteria Yersinia pestis, which, as a rule, is transmitted to humans from septicemic rodents by the bites of infected fleas. This microbe killed more people than all of the wars in the human history. Y. pestis circulation in the natural plague foci is ensured by the whole number of pathogenicity factors with differing functional orientation. This review is devoted to one of them, Y. pestis capsular antigen (F1 or Caf1. The history of its discovery and studying of its genetic control, biosynthesis, isolation and purification, and physicochemical properties are reviewed. Its roles in plague pathogenesis and its application as a main component of plague vaccines are also discussed. Y. pestis capsule under light microscopy is visually amorphous, while high-resolution electron microscopy displays the structure formed from separate fimbria-like cords up to 200 nm long, diverging from the bacterial surface in different directions. At 37°C Y. pestis produce 800–1000 times more capsular antigen than at 28°C. Genes coding for 17.6-kD Caf1 protein, which contains 170 amino acids, are located in caf1 operon of pFra plasmid. Analysis of caf1 operon nucleotide sequence testified its close phylogenetic relationship with the gene clusters coding for pilus adhesins that were secreted with the help of chaperone/usher systems in enterobacteria including six additional adhesins in Y. pestis. Y. pestis multiplication within macrophages is the obligatory stage of plague pathogenesis, and the plague pathogen virulence correlates not with resistance to phagocyte ingesting but with bacterial ability to survive and multiply within phagolysosomes of phagocytes due to neutralization of antibacterial functions of eukaryotic cells. The capsule formed out of the Caf1 aggregates protects Y. pestis from ingestion by naïve host’s phagocytes and prevents from initiation of the alternative pathway of the complement system

  18. Cancer-germline antigen vaccines and epigenetic enhancers

    DEFF Research Database (Denmark)

    Gjerstorff, Morten Frier; Burns, Jorge; Ditzel, Henrik Jorn

    2010-01-01

    can be achieved using epigenetic modifiers. AREAS COVERED IN THIS REVIEW: We provide an overview of the potential of CG antigens as targets for cancer immunotherapy, including advantages and disadvantages. We also discuss the current state of development of CG antigen vaccines, and the potential...... synergistic effect of combining CG antigen immunotherapeutic strategies with epigenetic modifiers. WHAT THE READER WILL GAIN: The reader will gain an overview of the past, present and future role of CG antigens in cancer immunotherapy. TAKE HOME MESSAGE: Chemoimmunotherapy using epigenetic drugs and CG...

  19. Bayesian nonparametric clustering in phylogenetics: modeling antigenic evolution in influenza.

    Science.gov (United States)

    Cybis, Gabriela B; Sinsheimer, Janet S; Bedford, Trevor; Rambaut, Andrew; Lemey, Philippe; Suchard, Marc A

    2017-01-18

    Influenza is responsible for up to 500,000 deaths every year, and antigenic variability represents much of its epidemiological burden. To visualize antigenic differences across many viral strains, antigenic cartography methods use multidimensional scaling on binding assay data to map influenza antigenicity onto a low-dimensional space. Analysis of such assay data ideally leads to natural clustering of influenza strains of similar antigenicity that correlate with sequence evolution. To understand the dynamics of these antigenic groups, we present a framework that jointly models genetic and antigenic evolution by combining multidimensional scaling of binding assay data, Bayesian phylogenetic machinery and nonparametric clustering methods. We propose a phylogenetic Chinese restaurant process that extends the current process to incorporate the phylogenetic dependency structure between strains in the modeling of antigenic clusters. With this method, we are able to use the genetic information to better understand the evolution of antigenicity throughout epidemics, as shown in applications of this model to H1N1 influenza. Copyright © 2017 John Wiley & Sons, Ltd.

  20. MHC structure and function – antigen presentation. Part 1

    Science.gov (United States)

    Goldberg, Anna Carla; Rizzo, Luiz Vicente

    2015-01-01

    The setting for the occurrence of an immune response is that of the need to cope with a vast array of different antigens from both pathogenic and non-pathogenic sources. When the first barriers against infection and innate defense fail, adaptive immune response enters the stage for recognition of the antigens by means of extremely variable molecules, namely immunoglobulins and T-cell receptors. The latter recognize the antigen exposed on cell surfaces, in the form of peptides presented by the HLA molecule. The first part of this review details the central role played by these molecules, establishing the close connection existing between their structure and their antigen presenting function. PMID:25807245

  1. A Mycobacterium tuberculosis Dormancy Antigen Differentiates Latently Infected Bacillus Calmette–Guérin-vaccinated Individuals

    Directory of Open Access Journals (Sweden)

    Delfina Peña

    2015-08-01

    Full Text Available IFN-γ release assays (IGRAs are better indicators of Mycobacterium tuberculosis infection than the tuberculin skin test (TST in Bacillus Calmette–Guérin (BCG-vaccinated populations. However, IGRAs do not discriminate active and latent infections (LTBI and no gold standard for LTBI diagnosis is available. Thus, since improved tests to diagnose M. tuberculosis infection are required, we assessed the efficacy of several M. tuberculosis latency antigens. BCG-vaccinated healthy donors (HD and tuberculosis (TB patients were recruited. QuantiFERON-TB Gold In-Tube, TST and clinical data were used to differentiate LTBI. IFN-γ production against CFP-10, ESAT-6, Rv2624c, Rv2626c and Rv2628 antigens was tested in peripheral blood mononuclear cells. LTBI subjects secreted significantly higher IFN-γ levels against Rv2626c than HD. Additionally, Rv2626c peptide pools to which only LTBI responded were identified, and their cumulative IFN-γ response improved LTBI discrimination. Interestingly, whole blood stimulation with Rv2626c allowed the discrimination between active and latent infections, since TB patients did not secrete IFN-γ against Rv2626c, in contrast to CFP-10 + ESAT-6 stimulation that induced IFN-γ response from both LTBI and TB patients. ROC analysis confirmed that Rv2626c discriminated LTBI from HD and TB patients. Therefore, since only LTBI recognizes specific epitopes from Rv2626c, this antigen could improve LTBI diagnosis, even in BCG-vaccinated people.

  2. Do FY antigens act as minor histocompatibility antigens in the graft-versus-host disease paradigm after human leukocyte antigen-identical sibling hematopoietic stem cell transplantation?

    Science.gov (United States)

    Sellami, Mohamed Hichem; Chaabane, Manel; Kaabi, Houda; Torjemane, Lamia; Ladeb, Saloua; Ben Othmane, Tarek; Hmida, Slama

    2012-03-01

    FY antigens are candidate minor histocompatibility antigens relevant to renal allograft rejection, but no data have been reported about their role in graft-versus-host disease (GVHD) incidence after human leukocyte antigen (HLA)-identical siblings hematopoietic stem cell transplantation (HSCT). The aim of this study was to examine the effect of donor/recipient disparity at FY antigens on the incidence of GVHD in Tunisian patients receiving an HLA-identical HSCT. This work enrolled 105 Tunisian pairs of recipients and their HLA-identical sibling donors of HSCs. FY genotyping was performed with the polymerase chain reaction-sequence-specific primer method and donor/recipient disparity for these antigens was analyzed at two levels: incompatibility and nonidentity. The case-control analyses showed no significant correlation between FY disparity and the incidence of either acute or chronic GVHD. Sample size calculation showed that 572 cases and 1716 controls would be necessary to be able to detect a significant association with 80% power and two-sided type I error level of 5% (α=0.05). The lack of association in the studied cohort may be explained by the low immunogenicity of FY antigens in HSCT context, compared with other antigens such as HA-1 and CD31.

  3. Dramatic mass loss in extreme high-elevation areas of a western Himalayan glacier: observations and modeling

    Science.gov (United States)

    Zhao, Huabiao; Yang, Wei; Yao, Tandong; Tian, Lide; Xu, Baiqing

    2016-08-01

    Rapid climate change at high elevations has accelerated glacier retreat in the Himalayas and Tibetan Plateau. However, due to the lack of long-term glaciological measurements, there are still uncertainties regarding when the mass loss began and what the magnitude of mass loss is at such high elevations. Based on in situ glaciological observations during the past 9 years and a temperature-index mass balance model, this study investigates recent mass loss of the Naimona’nyi Glacier in the western Himalayas and reconstructs a 41-year (1973/74–2013/14) equilibrium line altitude (ELA) and glacier-wide mass loss. The result indicates that even at 6000 m above sea level (a.s.l.), the annual mass loss reaches ~0.73 m water equivalent (w.e.) during the past 9 years. Concordant with the abrupt climate shift in the end of 1980s, the ELA has dramatically risen from ~5969 ± 73 m a.s.l. during 1973/74–1988/89 to ~6193 ± 75 m a.s.l. during 1989/90–2013/14, suggesting that future ice cores containing uninterrupted climate records could only be recovered at least above 6200 m a.s.l. in the Naimona’nyi region. The glacier-wide mass balance over the past 41 years is averaged to be approximately ‑0.40 ± 0.17 m w.e., exhibiting a significant increase in the decadal average from ‑0.01 ± 0.15 to ‑0.69 ± 0.21 m w.e.

  4. Barremian-Aptian rudist shells record dramatic shallow-water sea-surface temperature changes in the Tethyan Ocean

    Science.gov (United States)

    Huck, Stefan; Heimhofer, Ulrich

    2016-04-01

    The dramatic and stepwise emplacement of large igneous provinces is generally accepted as primary driver of Cretaceous Oceanic Anoxic Events (OAEs). Although excess output of volcanically induced greenhouse gases should have promoted "super greenhouse phases", several studies provide evidence for transient Cretaceous "cold snaps", particularly during the Barremian-Aptian stage. To date, reconstructions of Cretaceous sea surface temperatures (SSTs) are predominantly based either on δ18O analyses of pristine foraminiferal calcite or on crenarchaeotal membrane lipid distributions (TEX86) in pelagic deposits. Both types of proxies provide at best estimates of mean annual SSTs of open ocean settings. In order to better understand the dynamics of Cretaceous global warmth and the impact of fluctuating SSTs on carbonate platform ecosystems, the current study aims at reconstructing the stratigraphic and spatial evolution of subtropical shallow-marine sea-surface temperatures. Well-preserved low-Mg calcite rudist shells hold a strong potential to act as archives for the reconstruction of Cretaceous palaeoclimatic and palaeoenvironmental conditions, as ontogenetic isotopic and trace element variability of these shells also resolve sub-annual (seasonal) temperature fluctuations (Steuber et al., 2005). In the context of the current study, high-resolution sclerochemistry (δ18O, Mg contents) has been performed on rudists derived from chemostratigraphically (87Sr/86Sr, δ13C) well-constrained Barremian-Aptian carbonate platform settings in the subtropical Tethyan realm (France, Croatia, Spain, Portugal). The outcome of this work will be of significance both for those studying the triggering factors of oceanic anoxic events and the palaeoecology of rudist bivalves. Steuber, T., Rauch, M., Masse, J.-P., Graaf, J., Malkoc, M. (2005) Low-latitude seasonality of Cretaceous temperatures in warm and cold episodes. Nature 437: 1341-1344.

  5. Biostratigraphic evidence for dramatic Holocene uplift of Robinson Crusoe Island, Juan Fernández Ridge, SE Pacific Ocean

    Science.gov (United States)

    Sepúlveda, P.; Le Roux, J. P.; Lara, L. E.; Orozco, G.; Astudillo, V.

    2015-03-01

    Hotspot oceanic islands typically experience subsidence due to several processes related to migration of the oceanic plate away from the mantle plume and surface flexural loading. However, many other processes can interrupt subsidence, some of which may be associated with catastrophic events. A study of the biostratigraphy and sedimentology of Holocene deposits on Robinson Crusoe Island (RCI) on the Juan Fernández Ridge (JFR) indicated that dramatic uplift has occurred since 8000 years BP, at a rate of about 8.5mm yr-1. This is evidenced by supratidal flats with tepee structures and sand layers containing marine gastropods (mostly Nerita sp.) that are now exposed ca. 70 m a.s.l. The active hotspot is located 280 km further west and the last volcanic activity on RCI occurred at ca. 800 000 years BP. Long-term subsidence is evidenced by deep submerged marine abrasion terraces at RCI. As no direct evidence was found for the existence of a compensating bulge generated by the present hotspot upon which RCI would be situated, it must be concluded that subsidence in the wake of the mantle plume beneath the migrating plate was interrupted by very rapid uplift, but on a scale that did not fully compensate for the previous subsidence. This can be attributed to large-scale landslides followed by isostatic rebound, although this is only vaguely reflected in the low-resolution bathymetry of the area. To determine if this mechanism produced the uplift, a detailed bathymetric survey of the area will be required. If such a survey confirms this hypothesis, it may have implications for the short-term dynamics of vertical variations of oceanic edifices and their related effects on ecosystems and human population.

  6. Genetic disruption of both tryptophan hydroxylase genes dramatically reduces serotonin and affects behavior in models sensitive to antidepressants.

    Directory of Open Access Journals (Sweden)

    Katerina V Savelieva

    Full Text Available The neurotransmitter serotonin (5-HT plays an important role in both the peripheral and central nervous systems. The biosynthesis of serotonin is regulated by two rate-limiting enzymes, tryptophan hydroxylase-1 and -2 (TPH1 and TPH2. We used a gene-targeting approach to generate mice with selective and complete elimination of the two known TPH isoforms. This resulted in dramatically reduced central 5-HT levels in Tph2 knockout (TPH2KO and Tph1/Tph2 double knockout (DKO mice; and substantially reduced peripheral 5-HT levels in DKO, but not TPH2KO mice. Therefore, differential expression of the two isoforms of TPH was reflected in corresponding depletion of 5-HT content in the brain and periphery. Surprisingly, despite the prominent and evolutionarily ancient role that 5-HT plays in both vertebrate and invertebrate physiology, none of these mutations resulted in an overt phenotype. TPH2KO and DKO mice were viable and normal in appearance. Behavioral alterations in assays with predictive validity for antidepressants were among the very few phenotypes uncovered. These behavioral changes were subtle in the TPH2KO mice; they were enhanced in the DKO mice. Herein, we confirm findings from prior descriptions of TPH1 knockout mice and present the first reported phenotypic evaluations of Tph2 and Tph1/Tph2 knockout mice. The behavioral effects observed in the TPH2 KO and DKO mice strongly confirm the role of 5-HT and its synthetic enzymes in the etiology and treatment of affective disorders.

  7. ADNP/NAP dramatically increase microtubule end-binding protein-Tau interaction: a novel avenue for protection against tauopathy.

    Science.gov (United States)

    Ivashko-Pachima, Y; Sayas, C Laura; Malishkevich, A; Gozes, I

    2017-01-24

    Activity-dependent neuroprotective protein (ADNP), vital for brain formation and cognitive function, is mutated in autism and linked to neurodegenerative/psychiatric diseases. An eight-amino-acid peptide snippet of ADNP, NAP (NAPVSIPQ), identified as a smallest active fragment, includes the SxIP microtubule (MT) end-binding protein (EB) association motif, and enhances ADNP-EB3 interaction. Depletion of EB1 or EB3 abolishes NAP protection against zinc intoxication. Furthermore, NAP enhances Tau-MT interaction, and Tau regulates the localization and function of EB1 and EB3 in developing neuronal cells. Here, we asked how NAP (ADNP) enhances Tau-MT interactions and whether this is mediated by EBs. We showed, for we believe the first time, that NAP augmented endogenous EB1 comet density in the N1E-115 neuroblastoma neuronal model. This finding was substantiated by cell transfection with fluorescent EB1 and live cell imaging. NAP increased comet amounts, length and speed. At the molecular level, NAP enhanced EB3 homodimer formation, while decreasing EB1-EB3 heterodimer content and driving EB1- and EB3-Tau interactions (dramatic 20-fold increases), leading to recruitment of EB1/EB3 and Tau to MTs under zinc intoxication. Our previous results showed that while NAP protected neuronal-like cells against oxidative stress, it did not protect NIH3T3 fibroblasts. Here, NAP did not protect NIH3T3 cells against zinc intoxication, unless these cells were transfected with Tau. Interestingly, other MT associated proteins (MAPs) may replace Tau, thus, EB-Tau (MAPs) interaction is identified as a novel target for endogenous ADNP neuroprotection, and a future target for drug development, with NAP as a prototype.Molecular Psychiatry advance online publication, 24 January 2017; doi:10.1038/mp.2016.255.

  8. Facts on the fragmentation of antigens in presenting cells, on the association of antigen fragments with MHC molecules in cell-free systems, and speculation on the cell biology of antigen processing

    DEFF Research Database (Denmark)

    Werdelin, O; Mouritsen, S; Petersen, B L;

    1988-01-01

    The processing of a protein antigen is a multi-step event taking place in antigen-presenting cells. Processing is a prerequisite for the recognition of most antigens by T lymphocytes. The antigen is ingested by endocytosis, transported to an acid cellular compartment and subjected to proteolytic ...

  9. A universal computational model for predicting antigenic variants of influenza A virus based on conserved antigenic structures

    Science.gov (United States)

    Peng, Yousong; Wang, Dayan; Wang, Jianhong; Li, Kenli; Tan, Zhongyang; Shu, Yuelong; Jiang, Taijiao

    2017-01-01

    Rapid determination of the antigenicity of influenza A virus could help identify the antigenic variants in time. Currently, there is a lack of computational models for predicting antigenic variants of some common hemagglutinin (HA) subtypes of influenza A viruses. By means of sequence analysis, we demonstrate here that multiple HA subtypes of influenza A virus undergo similar mutation patterns of HA1 protein (the immunogenic part of HA). Further analysis on the antigenic variation of influenza A virus H1N1, H3N2 and H5N1 showed that the amino acid residues’ contribution to antigenic variation highly differed in these subtypes, while the regional bands, defined based on their distance to the top of HA1, played conserved roles in antigenic variation of these subtypes. Moreover, the computational models for predicting antigenic variants based on regional bands performed much better in the testing HA subtype than those did based on amino acid residues. Therefore, a universal computational model, named PREDAV-FluA, was built based on the regional bands to predict the antigenic variants for all HA subtypes of influenza A viruses. The model achieved an accuracy of 0.77 when tested with avian influenza H9N2 viruses. It may help for rapid identification of antigenic variants in influenza surveillance. PMID:28165025

  10. A Role For Mitochondria In Antigen Processing And Presentation.

    Science.gov (United States)

    Bonifaz, Lc; Cervantes-Silva, Mp; Ontiveros-Dotor, E; López-Villegas, Eo; Sánchez-García, Fj

    2014-09-23

    Immune synapse formation is critical for T lymphocyte activation, and mitochondria have a role in this process, by localizing close to the immune synapse, regulating intracellular calcium concentration, and providing locally required ATP. The interaction between antigen presenting cells (APCs) and T lymphocytes is a two-way signaling process. However, the role of mitochondria in antigen presenting cells during this process remains unknown. For APCs to be able to activate T lymphocytes, they must first engage in an antigen-uptake, -processing, and -presentation process. Here we show that HEL-loaded B lymphocytes, as a type of APCs, undergo a small but significant mitochondrial depolarization by 1-2 h following antigen exposure thus suggesting an increase in their metabolic demands. Inhibition of ATP synthase (oligomycin) or mitochondrial Ca(2+) uniporter (MCU) (Ruthenium red) had no effect on antigen uptake. Therefore, antigen processing and antigen presentation were further analyzed. Oligomycin treatment reduced the amount of specific MHC-peptide complexes but not total MHC II on the cell membrane of B lymphocytes which correlated with a decrease in antigen presentation. However, oligomycin also reduced antigen presentation by B lymphocytes that endogenously express HEL and by B lymphocytes loaded with the HEL48-62 peptide, although to a lesser extent. ATP synthase inhibition and MCU inhibition had a clear inhibitory effect on antigen processing (DQ-OVA). Taking together these results suggest that ATP synthase and MCU are relevant for antigen processing and presentation. Finally, APCs mitochondria were found to re-organize towards the APC-T immune synapse. This article is protected by copyright. All rights reserved.

  11. Lactobacillus rhamnosus GG secreting an antigen and Interleukin-2 translocates across the gastrointestinal tract and induces an antigen specific immune response.

    Science.gov (United States)

    Kandasamy, Matheswaran; Selvakumari Jayasurya, Anita; Moochhala, Shabbir; Huat Bay, Boon; Kun Lee, Yuan; Mahendran, Ratha

    2011-10-01

    Lactobacillus rhamnosus strain GG (LGG) is a probiotic organism. In this present study, LGG that express the green fluorescence protein (LGG-GFP) and IL-2 and GFP as a fusion protein (LGG-IL-2-GFP) were used to examine bacterial uptake and the immune response induced by oral immunization. Using TEM to examine the intestinal tissue, the Lactobacilli were localized in M cells and in venules. After oral immunization, most of the bacteria were excreted in feces only a small fraction (0.15%) was retained in the intestine at 48 hr. However, more LGG-IL-2-GFP was found in the MLN and spleen than LGG-GFP. The loop ligation method was used to evaluate LGG uptake and both LGG-GFP and LGG-IL-2-GFP were found to translocate at the same rate. Analysis of LGG internalization in J774 macrophage cells indicated that IL-2 increased survival of LGG and this may explain the increased presence of these bacteria in the MLN for a longer period. After oral immunization, specific mucosal antibody production as well as GFP specific CTL activity was demonstrated. IL-2 co-expression with GFP further enhanced antibody production and CTL activity. In conclusion, Lactobacillus rhamnosus GG expressing an antigen could generate an effective immune response to the antigen and IL-2 improved the response generated probably by increasing LGG expressing antigen survival in immune cells.

  12. Crystallization and preliminary X-ray analysis of the low-affinity complex between human leukocyte antigen-G (HLA-G) and leukocyte Ig-like receptor B2 (LILRB2).

    Science.gov (United States)

    Shiroishi, Mitsunori; Maenaka, Katsumi

    2009-01-01

    Human leukocyte antigen-G (HLA-G) is a nonclassical MHC class I (MHCI) molecule that is expressed mainly on placenta trophoblast cells. Leukocyte Ig-like receptor B2 (LILRB2) is a human inhibitory immune receptor that recognizes HLA-G with a higher affinity than any other MHCI although this interaction is only in the microM range. The interaction between HLA-G and LILRB2 seems to play a dominant role in the escape of the fetus from the maternal immune response. Here we report the crystallization and x-ray analysis of the LILRB2/HLA-G complex. The extracellular domains of HLA-G and LILRB2 were expressed in Escherichia coli, refolded and purified. The initial crystallization trials using novel PEG-based screening sets provided crystals of the LILRB2/HLA-G complex with 40-50% PEG400 as the precipitant. These crystals belong to space group P3(1)21 (a=b=81.4 A, c=186.7 A, gamma=120 degrees ). Dehydration of the crystals by soaking them in a solution containing a higher concentration of PEG400 dramatically improved the resolution and also the mosaicity.

  13. Three-day dendritic cells for vaccine development: Antigen uptake, processing and presentation

    Directory of Open Access Journals (Sweden)

    Schendel Dolores J

    2010-09-01

    Full Text Available Abstract Background Antigen-loaded dendritic cells (DC are capable of priming naïve T cells and therefore represent an attractive adjuvant for vaccine development in anti-tumor immunotherapy. Numerous protocols have been described to date using different maturation cocktails and time periods for the induction of mature DC (mDC in vitro. For clinical application, the use of mDC that can be generated in only three days saves on the costs of cytokines needed for large scale vaccine cell production and provides a method to produce cells within a standard work-week schedule in a GMP facility. Methods In this study, we addressed the properties of antigen uptake, processing and presentation by monocyte-derived DC prepared in three days (3d mDC compared with conventional DC prepared in seven days (7d mDC, which represent the most common form of DC used for vaccines to date. Results Although they showed a reduced capacity for spontaneous antigen uptake, 3d mDC displayed higher capacity for stimulation of T cells after loading with an extended synthetic peptide that requires processing for MHC binding, indicating they were more efficient at antigen processing than 7d DC. We found, however, that 3d DC were less efficient at expressing protein after introduction of in vitro transcribed (ivtRNA by electroporation, based on published procedures. This deficit was overcome by altering electroporation parameters, which led to improved protein expression and capacity for T cell stimulation using low amounts of ivtRNA. Conclusions This new procedure allows 3d mDC to replace 7d mDC for use in DC-based vaccines that utilize long peptides, proteins or ivtRNA as sources of specific antigen.

  14. Chemotactic migration of T cells towards dendritic cells promotes the detection of rare antigens.

    Directory of Open Access Journals (Sweden)

    Renske M A Vroomans

    Full Text Available In many immunological processes chemoattraction is thought to play a role in guiding cells to their sites of action. However, based on in vivo two-photon microscopy experiments in the absence of cognate antigen, T cell migration in lymph nodes (LNs has been roughly described as a random walk. Although it has been shown that dendritic cells (DCs carrying cognate antigen in some circumstances attract T cells chemotactically, it is currently still unclear whether chemoattraction of T cells towards DCs helps or hampers scanning. Chemoattraction towards DCs could on the one hand help T cells to rapidly find DCs. On the other hand, it could be deleterious if DCs become shielded by a multitude of attracted yet non-specific T cells. Results from a recent simulation study suggested that the deleterious effect dominates. We re-addressed the question whether T cell chemoattraction towards DCs is expected to promote or hamper the detection of rare antigens using the Cellular Potts Model, a formalism that allows for dynamic, flexible cellular shapes and cell migration. Our simulations show that chemoattraction of T cells enhances the DC scanning efficiency, leading to an increased probability that rare antigen-specific T cells find DCs carrying cognate antigen. Desensitization of T cells after contact with a DC further improves the scanning efficiency, yielding an almost threefold enhancement compared to random migration. Moreover, the chemotaxis-driven migration still roughly appears as a random walk, hence fine-tuned analysis of cell tracks will be required to detect chemotaxis within microscopy data.

  15. Chemotactic migration of T cells towards dendritic cells promotes the detection of rare antigens.

    Science.gov (United States)

    Vroomans, Renske M A; Marée, Athanasius F M; de Boer, Rob J; Beltman, Joost B

    2012-01-01

    In many immunological processes chemoattraction is thought to play a role in guiding cells to their sites of action. However, based on in vivo two-photon microscopy experiments in the absence of cognate antigen, T cell migration in lymph nodes (LNs) has been roughly described as a random walk. Although it has been shown that dendritic cells (DCs) carrying cognate antigen in some circumstances attract T cells chemotactically, it is currently still unclear whether chemoattraction of T cells towards DCs helps or hampers scanning. Chemoattraction towards DCs could on the one hand help T cells to rapidly find DCs. On the other hand, it could be deleterious if DCs become shielded by a multitude of attracted yet non-specific T cells. Results from a recent simulation study suggested that the deleterious effect dominates. We re-addressed the question whether T cell chemoattraction towards DCs is expected to promote or hamper the detection of rare antigens using the Cellular Potts Model, a formalism that allows for dynamic, flexible cellular shapes and cell migration. Our simulations show that chemoattraction of T cells enhances the DC scanning efficiency, leading to an increased probability that rare antigen-specific T cells find DCs carrying cognate antigen. Desensitization of T cells after contact with a DC further improves the scanning efficiency, yielding an almost threefold enhancement compared to random migration. Moreover, the chemotaxis-driven migration still roughly appears as a random walk, hence fine-tuned analysis of cell tracks will be required to detect chemotaxis within microscopy data.

  16. Comparison of three antigen preparations to detect Trichinellosis in live swine using IgG-ELISA.

    Science.gov (United States)

    Tattiyapong, Muncharee; Chaisri, Urai; Vongpakorn, Montakan; Anantaphruti, Malinee T; Dekumyoy, Paron

    2011-11-01

    A swine infected with Trichinella spiralis is a source of transmission to human through consumption of raw or improperly cooked pork. Detection of larvae is suitable for carcasses, so that pigs in households or farms can be examined serologically for trichinellosis. This study compared antigens, crude (CAg), excretory-secretory (ESAg) and surface (SAg), for their potential use in IgG-ELISA. Serum samples were collected from 5 experimentally infected swine with T. spiralis (pTs), 147 positive cases of 9 other parasitic infections, 12 mixed infections of other parasites, and 35 normal controls. At the same 100% sensitivity, specificity of tests was in a range of 98-77%. ESAg was the best source of antigen with specificity of 98.3% at cut-off value of 0.439. False positives included coccidiasis (1/86) and mixed infections (2/39). For CAg, trichuriasis (2/11), coccidiasis (5/86), and mixed infections (8/39) gave cross-reactions and some of these samples had OD values far above cut-off value of 0.332. Cross-reactions of SAg were Oesophagostomum spp-like GI-nematode infection (1/1), unidentified GI-nematode infections (2/3), trichuriasis (5/11), coccidiasis (29/86) and mixed infections (4/39). Thus, ESAg has the highest potential in serodiagnosis, with antibody to T. spiralis in pigs being detected at the earliest 16 day post-infection. However, crude antigen demonstrated a good specificity at 91.8%, and this antigen has a potential to be used as a detection of choice for swine trichinellosis, but the antigen preparation must be improved for higher specificity.

  17. Ether lipid vesicle-based antigens impart protection against experimental listeriosis

    Directory of Open Access Journals (Sweden)

    Ansari MA

    2012-06-01

    Full Text Available Mairaj Ahmed Ansari,1 Swaleha Zubair,2 Saba Tufail,1 Ejaj Ahmad,1 Mohsin Raza Khan,1 Zainuddin Quadri,1 Mohammad Owais,11Interdisciplinary Biotechnology Unit, 2Women's College, Aligarh Muslim University, Aligarh, UP, IndiaBackground: Incidence of food-borne infections from Listeria monocytogenes, a parasite that has adapted intracellular residence to avoid antibody onslaught, has increased dramatically in the past few years. The apparent lack of an effective vaccine that is capable of evoking the desired cytotoxic T cell response to obliterate this intracellular pathogen has encouraged the investigation of alternate prophylactic strategies. It should also be noted that Archaebacteria (Archae lipid-based adjuvants enhance the efficacy of subunit vaccines. In the present study, the adjuvant properties of archaeosomes (liposomes prepared from total polar lipids of archaebacteria, Halobacterium salinarum combined with immunogenic culture supernatant antigens of L. monocytogenes have been exploited in designing a vaccine candidate against experimental listeriosis in murine model.Methods: Archaeosome-entrapped secretory protein antigens (SAgs of L. monocytogenes were evaluated for their immunological responses and tendency to deplete bacterial burden in BALB/c mice challenged with sublethal listerial infection. Various immunological studies involving cytokine profiling, lymphocyte proliferation assay, detection of various surface markers (by flowcytometric analysis, and antibody isotypes (by enzyme-linked immunosorbent assay were used for establishing the vaccine potential of archaeosome-entrapped secretory proteins.Results: Immunization schedule involving archaeosome-encapsulated SAgs resulted in upregulation of Th1 cytokine production along with boosted memory in BALB/c mice. It also showed protective effect by reducing listerial burden in various vital organs (liver and spleen of the infected mice. However, the soluble form of the antigens (SAgs

  18. Engineering antigen-specific immunological tolerance.

    Energy Technology Data Exchange (ETDEWEB)

    Kontos, Stephan; Grimm, Alizee J.; Hubbell, Jeffrey A.

    2015-05-01

    Unwanted immunity develops in response to many protein drugs, in autoimmunity, in allergy, and in transplantation. Approaches to induce immunological tolerance aim to either prevent these responses or reverse them after they have already taken place. We present here recent developments in approaches, based on engineered peptides, proteins and biomaterials, that harness mechanisms of peripheral tolerance both prophylactically and therapeutically to induce antigenspecific immunological tolerance. These mechanisms are based on responses of B and T lymphocytes to other cells in their immune environment that result in cellular deletion or ignorance to particular antigens, or in development of active immune regulatory responses. Several of these approaches are moving toward clinical development, and some are already in early stages of clinical testing.

  19. Antigen processing of glycoconjugate vaccines; the polysaccharide portion of the pneumococcal CRM(197) conjugate vaccine co-localizes with MHC II on the antigen processing cell surface.

    Science.gov (United States)

    Lai, Zengzu; Schreiber, John R

    2009-05-21

    Pneumococcal (Pn) polysaccharides (PS) are T-independent (TI) antigens and do not induce immunological memory or antibodies in infants. Conjugation of PnPS to the carrier protein CRM(197) induces PS-specific antibody in infants, and memory similar to T-dependent (Td) antigens. Conjugates have improved immunogenicity via antigen processing and presentation of carrier protein with MHC II and recruitment of T cell help, but the fate of the PS attached to the carrier is unknown. To determine the location of the PS component of PnPS-CRM(197) in the APC, we separately labeled PS and protein and tracked their location. The PS of types 14-CRM(197) and 19F-CRM(197) was specifically labeled by Alexa Fluor 594 hydrazide (red). The CRM(197) was separately labeled red in a reaction that did not label PS. Labeled antigens were incubated with APC which were fixed, permeabilized and incubated with anti-MHC II antibody labeled green by Alexa Fluor 488, followed by confocal microscopy. Labeled CRM(197) was presented on APC surface and co-localized with MHC II (yellow). Labeled unconjugated 14 or 19F PS did not go to the APC surface, but PS labeled 14-CRM(197) and 19F-CRM(197) was internalized and co-localized with MHC II. Monoclonal antibody to type 14 PS bound to intracellular type 14 PS and PS-CRM(197). Brefeldin A and chloroquine blocked both CRM(197) and PS labeled 14-CRM(197) and 19F-CRM(197) from co-localizing with MHC II. These data suggest that the PS component of the CRM(197) glycoconjugate enters the endosome, travels with CRM(197) peptides to the APC surface and co-localizes with MHC II.

  20. Germinal center reaction: antigen affinity and presentation explain it all.

    Science.gov (United States)

    Oropallo, Michael A; Cerutti, Andrea

    2014-07-01

    The selection and expansion of B cells undergoing affinity maturation in the germinal center is a hallmark of humoral immunity. A recent paper in Nature provides new insights into the relationships between the affinity of the immunoglobulin receptor for antigen, the ability of B cells to present antigen to T cells, and the processes of selection, mutation, and clonal expansion in the germinal center.

  1. Protein antigen adsorption to the DDA/TDB liposomal adjuvant

    DEFF Research Database (Denmark)

    Hamborg, Mette; Jorgensen, Lene; Bojsen, Anders Riber;

    2013-01-01

    Understanding the nature of adjuvant-antigen interactions is important for the future design of efficient and safe subunit vaccines, but remains an analytical challenge. We studied the interactions between three model protein antigens and the clinically tested cationic liposomal adjuvant composed...

  2. 21 CFR 866.3402 - Plasmodium species antigen detection assays.

    Science.gov (United States)

    2010-04-01

    ... is a device that employs antibodies for the detection of specific malaria parasite antigens.... These devices are used for testing specimens from individuals who have signs and symptoms consistent with malaria infection. The detection of these antigens aids in the clinical laboratory diagnosis...

  3. Pneumocystis carinii from pigs and humans are antigenically distinct

    DEFF Research Database (Denmark)

    Christensen, C B; Settnes, Osvald Peter; Bille-Hansen, Vivi;

    1996-01-01

    The antigens of Pneumocystis carinii cysts isolated from pigs and humans were compared by the Western immunoblotting technique. Convalescent pig serum reacted with two antigens (approximately 78 kDa and 32.5 kDa) of porcine P. carinii cysts, whereas convalescent serum from humans did not react wi...

  4. Expression of Treponema pallidum Antigens in Escherichia coli

    Science.gov (United States)

    Walfield, Alan M.; Hanff, Philip A.; Lovett, Michael A.

    1982-04-01

    Treponema pallidum DNA was cloned in a bacteriophage. Clones were screened for expression of Treponema pallidum antigens by an in situ radio-immunoassay on nitrocellulose, with the use of subsequent reactions with syphilitic serum and radioiodinated Staphylococcus aureus protein A. One clone, which gave a strong signal, codes for at least seven antigens that react specifically with human antibodies to Treponema pallidum.

  5. Antigen Loss Variants: Catching Hold of Escaping Foes

    Science.gov (United States)

    Vyas, Maulik; Müller, Rolf; Pogge von Strandmann, Elke

    2017-01-01

    Since mid-1990s, the field of cancer immunotherapy has seen steady growth and selected immunotherapies are now a routine and preferred therapeutic option of certain malignancies. Both active and passive cancer immunotherapies exploit the fact that tumor cells express specific antigens on the cell surface, thereby mounting an immune response specifically against malignant cells. It is well established that cancer cells typically lose surface antigens following natural or therapy-induced selective pressure and these antigen-loss variants are often the population that causes therapy-resistant relapse. CD19 and CD20 antigen loss in acute lymphocytic leukemia and chronic lymphocytic leukemia, respectively, and lineage switching in leukemia associated with mixed lineage leukemia (MLL) gene rearrangements are well-documented evidences in this regard. Although increasing number of novel immunotherapies are being developed, majority of these do not address the control of antigen loss variants. Here, we review the occurrence of antigen loss variants in leukemia and discuss the therapeutic strategies to tackle the same. We also present an approach of dual-targeting immunoligand effectively retargeting NK cells against antigen loss variants in MLL-associated leukemia. Novel immunotherapies simultaneously targeting more than one tumor antigen certainly hold promise to completely eradicate tumor and prevent therapy-resistant relapses. PMID:28286501

  6. Acid test: lipid antigens get into the groove.

    Science.gov (United States)

    Kronenberg, Mitchell; Sullivan, Barbara A

    2008-06-01

    How do CD1 molecules load lipid antigens? In this issue of Immunity, Relloso et al. (2008) uncover how lysosomal pH targets amino acids in CD1b, causing it to open and attain a conformation more receptive to lipid antigens.

  7. Immunochemical analysis of Taenia taeniaeformis antigens expressed in Escherichia coli.

    Science.gov (United States)

    Bowtell, D D; Saint, R B; Rickard, M D; Mitchell, G F

    1986-12-01

    Previously we reported the isolation of several Escherichia coli clones expressing fragments of Taenia taeniaeformis antigens as beta-galactosidase fused proteins (Bowtell, Saint, Rickard & Mitchell, 1984). Here we describe the isolation of additional antigen-expressing clones from a larval cDNA library and the assignment of these clones to 7 antigen families. These were isolated with a polyspecific rabbit antiserum raised to the oncosphere. Since this serum was capable of reacting with a large number of antigens, it was important to develop techniques for rapidly determining the identity of the native T. taeniaeformis molecule corresponding to a cloned antigen gene. These included active immunization of rabbits with fused proteins and several techniques involving affinity purification on immobilized fused proteins. The reactivity of the antigen-positive clones with sera from humans infected with related parasites was also assessed. Finally, immunization of mice with several fused proteins failed to protect against subsequent infection, although antigens previously identified as candidate host-protective antigens (Bowtell, Mitchell, Anders, Lightowlers & Rickard, 1983) have yet to be identified in the expression library.

  8. Self-assembled PEG-b-PDPA-b-PGEM copolymer nanoparticles as protein antigen delivery vehicles to dendritic cells: preparation, characterization and cellular uptake

    Science.gov (United States)

    Li, Pan; Zhou, Junhui; Huang, Pingsheng; Zhang, Chuangnian; Wang, Weiwei; Li, Chen; Kong, Deling

    2017-01-01

    Antigen uptake by dendritic cells (DCs) is a key step for initiating antigen-specific T cell immunity. In the present study, novel synthetic polymeric nanoparticles were prepared as antigen delivery vehicles to improve the antigen uptake by DCs. Well-defined cationic and acid-responsive copolymers, monomethoxy poly(ethylene glycol)-block-poly(2-(diisopropyl amino) ethyl methacrylate)-block-poly(2-(guanidyl) ethyl methacrylate) (mPEG-b-PDPA-b-PGEM, PEDG) were synthesized by reversible addition-fragmentation chain transfer polymerization of 2-(diisopropylamino)ethyl methacrylate) and N-(tert-butoxycarbonyl) amino ethyl methacrylate monomers, followed by deprotection of tert-butyl protective groups and guanidinylation of obtained primary amines. 1H NMR, 13C NMR and GPC results indicated the successful synthesis of well-defined PEDG copolymers. PEDG copolymers could self-assemble into nanoparticles in aqueous solution, which were of cationic surface charges and showed acid-triggered disassembly contributed by PGEM and PDPA moieties, respectively. Significantly, PEDG nanoparticles could effectively condense with negatively charged model antigen ovalbumin (OVA) to form OVA/PEDG nanoparticle formulations with no influence on its secondary and tertiary structures demonstrating by far-UV circular dichroism and UV–vis spectra. In vitro antigen cellular uptake by bone marrow DCs (BMDCs) indicated using PEDG nanoparticles as antigen delivery vehicles could significantly improve the antigen uptake efficiency of OVA compared with free OVA or the commercialized Alum adjuvant. Moreover, as the surface cationic charges of OVA/PEDG nanoparticle formulations reduced, the uptake efficiency decreased correspondingly. Collectively, our work suggests that guanidinylated, cationic and acid-responsive PEDG nanoparticles represent a new kind of promising antigen delivery vehicle to DCs and hold great potential to serve as immunoadjuvants in the development of vaccines. PMID:28149525

  9. Why did watermills not have a dramatic effect on the Anthropocene sediment record of the Zwalm River, Belgium?

    Science.gov (United States)

    Notebaert, Bastiaan; D'Haese, Wouter

    2016-04-01

    Different studies demonstrated the dramatic effects of watermills on fluvial geomorphology in the Eastern US. Damming of floodplains and milldam lakes increased sediment deposition. Several authors attribute most of the so called post settlement legacy sediment to those milldam lakes. In Europe the role of milldams in the anthropogenic increased floodplain deposition rates during the last 1000 to 2000 years has gotten little attention until now. Therefore we studied the influence of watermills on Holocene floodplain deposition in the Zwalm catchment, Belgium. The Zwalm River is located in western part of the Belgian loess belt in an undulating landscape that had intensive agriculture for most of the last 2000 years. In total 9 watermills were present along the 17 km long main channel during the 19th century, while many were also present on tributaries. Historical records date several of the mills to the 10th century AD, although they might be older, and most of them remain to some degree active today. The influence of watermills on floodplain deposits was tested through coring transects of the Holocene deposits. Detailed transects were performed pairwise upstream and downstream 5 watermills. Samples were taken for grain size analysis using laser diffraction. A possible influence on floodplain topography was tested on a 5 m resolution DTM. Holocene floodplain architecture is similar to other floodplains in the region: a basal early to mid-Holocene peat and gyttja layer is covered by a fine grained sediment layer of more than 5 m thickness. The change between both can be attributed to increased soil erosion due to human land use, and can be considered to be the local legacy sediment. Comparison of transects upstream and downstream mills shows no significant difference in total Holocene or legacy sediment thickness. Texture analysis indicates that floodplain sediments are significant coarser downstream the mills.F Floodplains are not significant steeper around mills

  10. Complex Antigens Drive Permissive Clonal Selection in Germinal Centers.

    Science.gov (United States)

    Kuraoka, Masayuki; Schmidt, Aaron G; Nojima, Takuya; Feng, Feng; Watanabe, Akiko; Kitamura, Daisuke; Harrison, Stephen C; Kepler, Thomas B; Kelsoe, Garnett

    2016-03-15

    Germinal center (GC) B cells evolve toward increased affinity by a Darwinian process that has been studied primarily in genetically restricted, hapten-specific responses. We explored the population dynamics of genetically diverse GC responses to two complex antigens-Bacillus anthracis protective antigen and influenza hemagglutinin-in which B cells competed both intra- and interclonally for distinct epitopes. Preferred VH rearrangements among antigen-binding, naive B cells were similarly abundant in early GCs but, unlike responses to haptens, clonal diversity increased in GC B cells as early "winners" were replaced by rarer, high-affinity clones. Despite affinity maturation, inter- and intraclonal avidities varied greatly, and half of GC B cells did not bind the immunogen but nonetheless exhibited biased VH use, V(D)J mutation, and clonal expansion comparable to antigen-binding cells. GC reactions to complex antigens permit a range of specificities and affinities, with potential advantages for broad protection.

  11. Mosaic VSGs and the scale of Trypanosoma brucei antigenic variation.

    Directory of Open Access Journals (Sweden)

    James P J Hall

    Full Text Available A main determinant of prolonged Trypanosoma brucei infection and transmission and success of the parasite is the interplay between host acquired immunity and antigenic variation of the parasite variant surface glycoprotein (VSG coat. About 0.1% of trypanosome divisions produce a switch to a different VSG through differential expression of an archive of hundreds of silent VSG genes and pseudogenes, but the patterns and extent of the trypanosome diversity phenotype, particularly in chronic infection, are unclear. We applied longitudinal VSG cDNA sequencing to estimate variant richness and test whether pseudogenes contribute to antigenic variation. We show that individual growth peaks can contain at least 15 distinct variants, are estimated computationally to comprise many more, and that antigenically distinct 'mosaic' VSGs arise from segmental gene conversion between donor VSG genes or pseudogenes. The potential for trypanosome antigenic variation is probably much greater than VSG archive size; mosaic VSGs are core to antigenic variation and chronic infection.

  12. The global antigenic diversity of swine influenza A viruses

    DEFF Research Database (Denmark)

    Lewis, Nicola S; Russell, Colin A; Langat, Pinky;

    2016-01-01

    Swine influenza presents a substantial disease burden for pig populations worldwide and poses a potential pandemic threat to humans. There is considerable diversity in both H1 and H3 influenza viruses circulating in swine due to the frequent introductions of viruses from humans and birds coupled...... with geographic segregation of global swine populations. Much of this diversity is characterized genetically but the antigenic diversity of these viruses is poorly understood. Critically, the antigenic diversity shapes the risk profile of swine influenza viruses in terms of their epizootic and pandemic potential....... Here, using the most comprehensive set of swine influenza virus antigenic data compiled to date, we quantify the antigenic diversity of swine influenza viruses on a multi-continental scale. The substantial antigenic diversity of recently circulating viruses in different parts of the world adds...

  13. Tumor Antigen-Derived Peptides Delivery for Cancer Immunotherapy.

    Science.gov (United States)

    Wenxue, Ma

    2014-02-05

    Tumor antigenic peptides therapeutics is a promising field for cancer immunotherapy. Benefits include the ease and rapid synthesis of antigenic peptides and capacity for modifications. In the past years, many peptide-based cancer vaccines have been tested in clinical trials with a limited success because of the difficulties associated with peptide stability and delivery approaches, consequently, resulting in inefficient antigen presentation and low response rates in patients with cancer. The development of suitable and efficient vaccine carrier systems still remains a major challenge. This article aims to describe a new delivery approach for tumor antigenic peptides and rationales of dendritic cells (DCs)-based vaccination. In order to elicit enhanced immune responses, poly(DL-lactide-co-glycolide) (PLGA), which has been approved by the US Food and Drug Administration (FDA) for the use of drug delivery, diagnostics and other applications of clinical and basic science research were employed for the formulation of making nanoparticles (NPs) while delivering tumor antigenic peptides.

  14. Antibodies anti granulocytic antigens in IBD: from microscopic morphology to antigenic specificity

    Directory of Open Access Journals (Sweden)

    A. Montanelli

    2011-09-01

    Full Text Available Objective: ANCA (p-ANCA and x-ANCA have been documented to occur in many inflammatory disorders. The specific ANCA antigens and the clinical correlation of a positive ANCA test in these disorders are still for the most part obscure. The aim of the present study was to investigate the prevalence of and the target antigens for ANCA in patients with IBD. Methods: 104 patients (67 age between 3-18 years, mean age 8+3 and 37 age between 25-70 years, mean age 48+15 clinically and hystopathologically diagnosed as: 67 ulcerative colitis, 16 Crohn’ disease, 21 other colitis (7 indeterminate colitis were enrolled in our study. ANCA were determined by ELISA and IIF methods. Results: We observed a good performance in terms of sensibility and specificity of ANCA, and a good correlation between the two methods used; as regard ELISA determination the antigen frequently found in our cases was lactoferrin (60%. Conclusions: Is still unclear the role of these “minor antigens” in the diagnosis and pathogenesis of IBD, but is clear that only morphologic evaluation is no more sufficient.

  15. Antigen-specific regulatory T cells and low dose of IL-2 in treatment of type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Minh N. Pham

    2016-01-01

    Full Text Available Regulatory T cells (Tregs play an important role in preventing effector T-cell (Teff targeting of self-antigens that can lead to tissue destruction in autoimmune settings, including type 1 diabetes (T1D. Autoimmunity is caused in part by an imbalance between Teff and Tregs. Early attempts to treat with immunosuppressive agents have led to serious side effects, thus requiring a more targeted approach. Low-dose IL-2 (LD IL-2 can provide immuno-regulation with few side effects by preferentially acting on Tregs to drive tolerance. The concept of LD IL-2 as a therapeutic approach is supported by data in mouse models where autoimmunity is cured and further strengthened by success in human clinical studies in Hepatitis C Virus (HCV induced vasculitis, chronic graft vs host disease (GVHD and Alopecia areata (AA. Treatment will require identification of a safe therapeutic window, which is a difficult task given that patients are reported to have deficient or defective IL-2 production or signalling and have experienced mild activation of NK cells and eosinophils with LD IL-2 therapy. In T1D, a LD IL-2 clinical trial concluded that Tregs can be safely expanded in humans; however, the study was not designed to address efficacy. Antigen-specific therapies have also aimed at regulation of the autoimmune response, but have been filled with disappointment despite an extensive list of diverse islet antigens tested in humans. This approach could be enhanced through the addition of LD IL-2 to the antigenic treatment regimen to improve the frequency and function of antigen-specific Tregs, without global immunosuppression. Here we will discuss the use of LD IL-2 and islet antigen to enhance antigen-specific Tregs in T1D and focus on what is known about their immunological impact, their safety and potential efficacy, and need for better methods to identify therapeutic effectiveness.

  16. Antigenic Relationships among Human Pathogenic Orientia tsutsugamushi Isolates from Thailand.

    Directory of Open Access Journals (Sweden)

    Sarah L James

    2016-06-01

    Full Text Available Scrub typhus is a common cause of undiagnosed febrile illness in certain tropical regions, but can be easily treated with antibiotics. The causative agent, Orientia tsutsugamushi, is antigenically variable which complicates diagnosis and efforts towards vaccine development.This study aimed to dissect the antigenic and genetic relatedness of O. tsutsugamushi strains and investigate sero-diagnostic reactivities by titrating individual patient sera against their O. tsutsugamushi isolates (whole-cell antigen preparation, in homologous and heterologous serum-isolate pairs from the same endemic region in NE Thailand. The indirect immunofluorescence assay was used to titrate Orientia tsutsugamushi isolates and human sera, and a mathematical technique, antigenic cartography, was applied to these data to visualise the antigenic differences and cross-reactivity between strains and sera. No functional or antigen-specific analyses were performed. The antigenic variation found in clinical isolates was much less pronounced than the genetic differences found in the 56kDa type-specific antigen genes. The Karp-like sera were more broadly reactive than the Gilliam-like sera.Antigenic cartography worked well with scrub typhus indirect immunofluorescence titres. The data from humoral responses suggest that a Karp-like strain would provide broader antibody cross-reactivity than a Gilliam-like strain. Although previous exposure to O. tsutsugamushi could not be ruled out, scrub typhus patient serum antibody responses were characterised by strong homologous, but weak heterologous antibody titres, with little evidence for cross-reactivity by Gilliam-like sera, but a broader response from some Karp-like sera. This work highlights the importance of antigenic variation in O. tsutsugamushi diagnosis and determination of new serotypes.

  17. Strategies for designing and monitoring malaria vaccines targeting diverse antigens

    Directory of Open Access Journals (Sweden)

    Alyssa E Barry

    2014-07-01

    Full Text Available After more than 50 years of intensive research and development, only one malaria vaccine candidate, RTS,S, has progressed to Phase 3 clinical trials. Despite only partial efficacy, this candidate is now forecast to become the first licensed malaria vaccine. Hence, more efficacious second-generation malaria vaccines that can significantly reduce transmission are urgently needed. This review will focus on a major obstacle hindering development of effective malaria vaccines: parasite antigenic diversity. Despite extensive genetic diversity in leading candidate antigens, vaccines have been and continue to be formulated using recombinant antigens representing only one or two strains. These vaccine strains represent only a small fraction of the diversity circulating in natural parasite populations, leading to escape of non-vaccine strains and challenging investigators’ abilities to measure strain-specific efficacy in vaccine trials. Novel strategies are needed to overcome antigenic diversity in order for vaccine development to succeed. Many studies have now catalogued the global diversity of leading Plasmodium falciparum and Plasmodium vivax vaccine antigens. In this review, we describe how population genetic approaches can be applied to this rich data source to predict the alleles that best represent antigenic diversity, polymorphisms that contribute to it, and to identify key polymorphisms associated with antigenic escape. We also suggest an approach to summarise the known global diversity of a given antigen to predict antigenic diversity, how to select variants that best represent the strains circulating in natural parasite populations and how to investigate the strain-specific efficacy of vaccine trials. Use of these strategies in the design and monitoring of vaccine trials will not only shed light on the contribution of genetic diversity to the antigenic diversity of malaria, but will also maximise the potential of future malaria vaccine

  18. Antigenic Relationships among Human Pathogenic Orientia tsutsugamushi Isolates from Thailand

    Science.gov (United States)

    Nawtaisong, Pruksa; Tanganuchitcharnchai, Ampai; Smith, Derek J.; Day, Nicholas P. J.; Paris, Daniel H.

    2016-01-01

    Background Scrub typhus is a common cause of undiagnosed febrile illness in certain tropical regions, but can be easily treated with antibiotics. The causative agent, Orientia tsutsugamushi, is antigenically variable which complicates diagnosis and efforts towards vaccine development. Methodology/Principal Findings This study aimed to dissect the antigenic and genetic relatedness of O. tsutsugamushi strains and investigate sero-diagnostic reactivities by titrating individual patient sera against their O. tsutsugamushi isolates (whole-cell antigen preparation), in homologous and heterologous serum-isolate pairs from the same endemic region in NE Thailand. The indirect immunofluorescence assay was used to titrate Orientia tsutsugamushi isolates and human sera, and a mathematical technique, antigenic cartography, was applied to these data to visualise the antigenic differences and cross-reactivity between strains and sera. No functional or antigen-specific analyses were performed. The antigenic variation found in clinical isolates was much less pronounced than the genetic differences found in the 56kDa type-specific antigen genes. The Karp-like sera were more broadly reactive than the Gilliam-like sera. Conclusions/Significance Antigenic cartography worked well with scrub typhus indirect immunofluorescence titres. The data from humoral responses suggest that a Karp-like strain would provide broader antibody cross-reactivity than a Gilliam-like strain. Although previous exposure to O. tsutsugamushi could not be ruled out, scrub typhus patient serum antibody responses were characterised by strong homologous, but weak heterologous antibody titres, with little evidence for cross-reactivity by Gilliam-like sera, but a broader response from some Karp-like sera. This work highlights the importance of antigenic variation in O. tsutsugamushi diagnosis and determination of new serotypes. PMID:27248711

  19. Potentiation of anthrax vaccines using protective antigen-expressing viral replicon vectors.

    Science.gov (United States)

    Wang, Hai-Chao; An, Huai-Jie; Yu, Yun-Zhou; Xu, Qing

    2015-02-01

    DNA vaccines require improvement for human use because they are generally weak stimulators of the immune system in humans. The efficacy of DNA vaccines can be improved using a viral replicon as vector to administer antigen of pathogen. In this study, we comprehensively evaluated the conventional non-viral DNA, viral replicon DNA or viral replicon particles (VRP) vaccines encoding different forms of anthrax protective antigen (PA) for specific immunity and protective potency against anthrax. Our current results clearly suggested that these viral replicon DNA or VRP vaccines derived from Semliki Forest virus (SFV) induced stronger PA-specific immune responses than the conventional non-viral DNA vaccines when encoding the same antigen forms, which resulted in potent protection against challenge with the Bacillus anthracis strain A16R. Additionally, the naked PA-expressing SFV replicon DNA or VRP vaccines without the need for high doses or demanding particular delivery regimens elicited robust immune responses and afforded completely protective potencies, which indicated the potential of the SFV replicon as vector of anthrax vaccines for use in clinical application. Therefore, our results suggest that these PA-expressing SFV replicon DNA or VRP vaccines may be suitable as candidate vaccines against anthrax.

  20. Prostate-specific antigen (PSA) screening: has the pendulum swung too far?

    Institute of Scientific and Technical Information of China (English)

    Jason M Phillips; E David Crawford

    2011-01-01

    @@ Prostate-specific antigen (PSA) along with digital rectal exam has been the standard for prostate cancer screening in the United States for the past 20 years.1 During this time period,the improved detection of prostate cancer decreased related mortality more than 30%? In fact,metastases and their comorbidities have decreased more than 75% since the early 1990s,resulting in a higher incidence of early organ-confined disease.While it is clear that prostate cancer mortality statistics have improved,it is unclear whether men are overscreened.

  1. The Functions of Dramatic Elements in John Donne's Poems%论约翰·邓恩诗中的戏剧成分

    Institute of Scientific and Technical Information of China (English)

    何静静

    2007-01-01

    诗歌的戏剧化倾向变得越来越重要,便于诗人传达诗歌奇妙的艺术情感,使得诗歌易在读者中产生共鸣.这里主要介绍了玄虚派代表诗人约翰·邓恩诗中所运用的一些戏剧表现手法以及这些戏剧因素在传达诗歌的戏剧艺术效果方面所起到的作用.%Dramatic tendency in poetry is vital in achieving startling artistic effects among readers. This paper mainly points out the dramatic devices applied in the Metaphysical poet John Donne's poems and how they function in actualizing the dramatization of poems.

  2. Clinical significance of variations in levels of Epstein-Barr Virus (EBV) antigen and adaptive immune response during chronic active EBV infection in children.

    Science.gov (United States)

    Xing, Yan; Song, Hong Mei; Wei, Min; Liu, Yu; Zhang, Yu Hua; Gao, Li

    2013-01-01

    Pediatric patients were recruited to analyze differences in Epstein-Barr virus (EBV) copy numbers and adaptive immune reactions in children with chronic active vs acute EBV infection (CAEBVI vs AEBVI), as well as to examine the relationship between these parameters and the pathogenesis of CAEBVI. Fluorescent qPCR was used to assess EBV-DNA levels, while ELISA, antibody affinity, flow cytometry, and heterophil agglutination (HA) assays were used to evaluate patient EBV-adaptive humoral and cellular immunity. Lastly, ELISPOT was employed to assess interferon (IFN)-γ secretory functions of EBV-specific cytotoxic T-lymphocytes (CTL) as a marker of subject EBV-specific adaptive cellular immunity. The results indicated that, compared with AEBVI patients or normal children, there was a dramatic elevation in viral copy levels, viral capsid antigen (VCA)-IgA, early antigen (EA)-IgA, and EA-IgG, but a lack of EBV nuclear antigen (EBNA)-IgG and a negative HA in CAEBVI patients (p EBV-specific CTL function compared with normal children (p EBV antigen availability and in both the adaptive humoral and cellular immune responses in patients with CAEBVI, and that these outcomes may be associated with the chronic active re-infection process itself associated with CAEBVI.

  3. Tumor antigens for cancer immunotherapy: therapeutic potential of xenogeneic DNA vaccines

    Directory of Open Access Journals (Sweden)

    Srinivasan Roopa

    2004-04-01

    Full Text Available Abstract Preclinical animal studies have convincingly demonstrated that tumor immunity to self antigens can be actively induced and can translate into an effective anti-tumor response. Several of these observations are being tested in clinical trials. Immunization with xenogeneic DNA is an attractive approach to treat cancer since it generates T cell and antibody responses. When working in concert, these mechanisms may improve the efficacy of vaccines. The use of xenogeneic DNA in overcoming immune tolerance has been promising not only in inbred mice with transplanted tumors but also in outbred canines, which present with spontaneous tumors, as in the case of human. Use of this strategy also overcomes limitations seen in other types of cancer vaccines. Immunization against defined tumor antigens using a xenogeneic DNA vaccine is currently being tested in early phase clinical trials for the treatment of melanoma and prostate cancers, with proposed trials for breast cancer and Non-Hodgkin's Lymphoma.

  4. Recent Advance in Antigen-Specific Immunotherapy for Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Norimitsu Kadowaki

    2011-01-01

    Full Text Available Relapse after chemotherapy is inevitable in the majority of patients with acute myeloid leukemia (AML. Thus, it is necessary to develop novel therapies that have different antileukemic mechanisms. Recent advances in immunology and identification of promising leukemia-associated antigens open the possibilities for eradicating minimal residual diseases by antigen-specific immunotherapy after chemotherapy. Several methods have been pursued as immunotherapies for AML: peptide vaccines, granulocyte-macrophage colony-stimulating factor-secreting tumor vaccines, dendritic cell vaccines, and adoptive T cell therapy. Whereas immunogenicity and clinical outcomes are improving in these trials, severe adverse events were observed in highly avid engineered T cell therapies, indicating the importance of the balance between effectiveness and side effects in advanced immunotherapy. Such progress in inducing antitumor immune responses, together with strategies to attenuate immunosuppressive factors, will establish immunotherapy as an important armament to combat AML.

  5. Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators

    DEFF Research Database (Denmark)

    Schmidt, Signe Tandrup; Foged, Camilla; Korsholm, Karen Smith;

    2016-01-01

    for which no effective vaccines exist. The subunit vaccine technology exploits pathogen subunits as antigens, e.g., recombinant proteins or synthetic peptides, allowing for highly specific immune responses against the pathogens. However, such antigens are usually not sufficiently immunogenic to induce......The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens...... been licensed for use in human vaccines, and they mainly stimulate humoral immunity. Thus, there is an unmet demand for the development of safe and efficient adjuvant systems that can also stimulate cell-mediated immunity (CMI). Adjuvants constitute a heterogeneous group of compounds, which can broadly...

  6. Plasma lipid-bound sialic acid and carcinoembryonic antigen in cancer patients.

    Science.gov (United States)

    Dnistrian, A M; Schwartz, M K

    1981-10-01

    We evaluated lipid-bound sialic acid as a "marker" in cancer patients and assessed the individual and combined value of lipid-bound sialic acid and carcinoembryonic antigen determinations in these patients. Plasma was sampled from 62 normal subjects and 125 cancer patients. Lipid-bound sialic acid was determined by the resorcinol method after total lipid extraction and isolation of the sialolipid fraction from plasma. Neither marker was increased in many breast cancer patients. Carcinoembryonic antigen was increased more commonly and to a greater degree in colon cancer patients and seems to be the preferred marker. Both markers were increased in lung cancer patients and their combined evaluation improved the rate of detection. Lipid-bound sialic acid was increased in more patients with leukemias, lymphomas, Hodgkin's disease, and melanomas, suggesting that it may be a useful biochemical marker in these types of cancer.

  7. Prostate-specific antigen testing accuracy in community practice

    Directory of Open Access Journals (Sweden)

    Adams-Cameron Meg

    2002-10-01

    Full Text Available Abstract Background Most data on prostate-specific antigen (PSA testing come from urologic cohorts comprised of volunteers for screening programs. We evaluated the diagnostic accuracy of PSA testing for detecting prostate cancer in community practice. Methods PSA testing results were compared with a reference standard of prostate biopsy. Subjects were 2,620 men 40 years and older undergoing (PSA testing and biopsy from 1/1/95 through 12/31/98 in the Albuquerque, New Mexico metropolitan area. Diagnostic measures included the area under the receiver-operating characteristic curve, sensitivity, specificity, and likelihood ratios. Results Cancer was detected in 930 subjects (35%. The area under the ROC curve was 0.67 and the PSA cutpoint of 4 ng/ml had a sensitivity of 86% and a specificity of 33%. The likelihood ratio for a positive test (LR+ was 1.28 and 0.42 for a negative test (LR-. PSA testing was most sensitive (90% but least specific (27% in older men. Age-specific reference ranges improved specificity in older men (49% but decreased sensitivity (70%, with an LR+ of 1.38. Lowering the PSA cutpoint to 2 ng/ml resulted in a sensitivity of 95%, a specificity of 20%, and an LR+ of 1.19. Conclusions PSA testing had fair discriminating power for detecting prostate cancer in community practice. The PSA cutpoint of 4 ng/ml was sensitive but relatively non-specific and associated likelihood ratios only moderately revised probabilities for cancer. Using age-specific reference ranges and a PSA cutpoint below 4 ng/ml improved test specificity and sensitivity, respectively, but did not improve the overall accuracy of PSA testing.

  8. Case of rhesus antigen weak D type 4.2. (DAR category detection

    Directory of Open Access Journals (Sweden)

    L. L. Golovkina

    2015-01-01

    Full Text Available Serological methods of Rhesus antigens identification in humans cannot identify D-antigen variants. In this article the serological characteristics of Rhesus antigen D weak type 4.2. (Category DAR are described.

  9. Advances in alloimmune thrombocytopenia: perspectives on current concepts of human platelet antigens, antibody detection strategies, and genotyping.

    Science.gov (United States)

    Hayashi, Tomoya; Hirayama, Fumiya

    2015-07-01

    Alloimmunisation to platelets leads to the production of antibodies against platelet antigens and consequently to thrombocytopenia. Numerous molecules located on the platelet surface are antigenic and induce immune-mediated platelet destruction with symptoms that can be serious. Human platelet antigens (HPA) cause thrombocytopenias, such as neonatal alloimmune thrombocytopenia, post-transfusion purpura, and platelet transfusion refractoriness. Thirty-four HPA are classified into 28 systems. Assays to identify HPA and anti-HPA antibodies are critically important for preventing and treating thrombocytopenia caused by anti-HPA antibodies. Significant progress in furthering our understanding of HPA has been made in the last decade: new HPA have been discovered, antibody-detection methods have improved, and new genotyping methods have been developed. We review these advances and discuss issues that remain to be resolved as well as future prospects for preventing and treating immune thrombocytopenia.

  10. Intranasal immunization with influenza antigens conjugated with cholera toxin subunit B stimulates broad spectrum immunity against influenza viruses.

    Science.gov (United States)

    Li, Junwei; Arévalo, Maria T; Chen, Yanping; Posadas, Olivia; Smith, Jacob A; Zeng, Mingtao

    2014-01-01

    Frequent mutation of influenza viruses keep vaccinated and non-vaccinated populations vulnerable to new infections, causing serious burdens to public health and the economy. Vaccination with universal influenza vaccines would be the best way to effectively protect people from infection caused by mismatched or unforeseen influenza viruses. Presently, there is no FDA approved universal influenza vaccine. In this study, we expressed and purified a fusion protein comprising of influenza matrix 2 protein ectodomain peptides, a centralized influenza hemagglutinin stem region, and cholera toxin subunit B. Vaccination of BALB/c mice with this novel artificial antigen resulted in potent humoral immune responses, including induction of specific IgA and IgG, and broad protection against infection by multiple influenza viruses. Furthermore, our results demonstrated that when used as a mucosal antigen, cholera toxin subunit B improved antigen-stimulated T cell and memory B cell responses.

  11. Recognition of antigen-specific B-cell receptors from chronic lymphocytic leukemia patients by synthetic antigen surrogates.

    Science.gov (United States)

    Sarkar, Mohosin; Liu, Yun; Morimoto, Jumpei; Peng, Haiyong; Aquino, Claudio; Rader, Christoph; Chiorazzi, Nicholas; Kodadek, Thomas

    2014-12-18

    In patients with chronic lymphocytic leukemia (CLL), a single neoplastic antigen-specific B cell accumulates and overgrows other B cells, leading to immune deficiency. CLL is often treated with drugs that ablate all B cells, leading to further weakening of humoral immunity, and a more focused therapeutic strategy capable of targeting only the pathogenic B cells would represent a significant advance. One approach to this would be to develop synthetic surrogates of the CLL antigens allowing differentiation of the CLL cells and healthy B cells in a patient. Here, we describe nonpeptidic molecules capable of targeting antigen-specific B cell receptors with good affinity and selectivity using a combinatorial library screen. We demonstrate that our hit compounds act as synthetic antigen surrogates and recognize CLL cells and not healthy B cells. Additionally, we argue that the technology we developed can be used to identify other classes of antigen surrogates.

  12. CD4+ T cell-mediated presentation of non-infectious HIV-1virion antigens to HIV-specific CD8+ T cells

    Institute of Scientific and Technical Information of China (English)

    XU Jian-qing; Franco Lori; Julianna Lisziewicz

    2006-01-01

    Background The mechanism of chronic immune activation and impairment of HIV-specific immune responses during chronic infection is not fully understood. However, it is known that high immune activation leads to more rapid progression to AIDS. We hypothesize that CD4+ T cell-mediated viral antigen presentation contributes to this pathologic immune activation in HIV-infected individuals.Methods HIV-specific T cells, responding to noninfectious HIV-1 virions as antigen, were measured by flow cytometric assays. These experimental conditions reflect the in vivo condition where noninfectious HIV-1 represents more than 99% of the antigens.Results CD4+ T cells purified from HIV-infected individuals were capable of cross presenting exogenous noninfectious HIV-1 virions to HIV-1-specific CD8+ T cells. Cross presentation required the entry of HIV-1 to CD4+ T cells and antigen translocation from endoplasmic reticulum to the Golgi complex. Blocking CD4+mediated activation of HIV-specific CD8+ T cells and redirecting the viral antigens to antigen presenting cells improved HIV-specific T cell responses.Conclusions One possible cause of chronic immune activation and impairment of HIV-1 specific T cell responses is represented by HIV-1 harboring CD4+ T cells cross presenting HIV-1 antigen to activate CD8+ T cells. This new mechanism provides the first evidence that cross presentation of noninfectious HIV-1. Virions play a role in the immunopathogenesis of HIV-1 infection.

  13. T-cell receptor gene therapy targeting melanoma-associated antigen-A4 inhibits human tumor growth in non-obese diabetic/SCID/γcnull mice.

    Science.gov (United States)

    Shirakura, Yoshitaka; Mizuno, Yukari; Wang, Linan; Imai, Naoko; Amaike, Chisaki; Sato, Eiichi; Ito, Mamoru; Nukaya, Ikuei; Mineno, Junichi; Takesako, Kazutoh; Ikeda, Hiroaki; Shiku, Hiroshi

    2012-01-01

    Adoptive cell therapy with lymphocytes that have been genetically engineered to express tumor-reactive T-cell receptors (TCR) is a promising approach for cancer immunotherapy. We have been exploring the development of TCR gene therapy targeting cancer/testis antigens, including melanoma-associated antigen (MAGE) family antigens, that are ideal targets for adoptive T-cell therapy. The efficacy of TCR gene therapy targeting MAGE family antigens, however, has not yet been evaluated in vivo. Here, we demonstrate the in vivo antitumor activity in immunodeficient non-obese diabetic/SCID/γc(null) (NOG) mice of human lymphocytes genetically engineered to express TCR specific for the MAGE-A4 antigen. Polyclonal T cells derived from human peripheral blood mononuclear cells were transduced with the αβ TCR genes specific for MAGE-A4, then adoptively transferred into NOG mice inoculated with MAGE-A4 expressing human tumor cell lines. The transferred T cells maintained their effector function in vivo, infiltrated into tumors, and inhibited tumor growth in an antigen-specific manner. The combination of adoptive cell therapy with antigen peptide vaccination enhanced antitumor activity, with improved multifunctionality of the transferred cells. These data suggest that TCR gene therapy with MAGE-A4-specific TCR is a promising strategy to treat patients with MAGE-A4-expressing tumors; in addition, the acquisition of multifunctionality in vivo is an important factor to predict the quality of the T-cell response during adoptive therapy with human lymphocytes.

  14. Development of the ECODAB into a relational database for Escherichia coli O-antigens and other bacterial polysaccharides.

    Science.gov (United States)

    Rojas-Macias, Miguel A; Ståhle, Jonas; Lütteke, Thomas; Widmalm, Göran

    2015-03-01

    Escherichia coli O-antigen database (ECODAB) is a web-based application to support the collection of E. coli O-antigen structures, polymerase and flippase amino acid sequences, NMR chemical shift data of O-antigens as well as information on glycosyltransferases (GTs) involved in the assembly of O-antigen polysaccharides. The database content has been compiled from scientific literature. Furthermore, the system has evolved from being a repository to one that can be used for generating novel data on its own. GT specificity is suggested through sequence comparison with GTs whose function is known. The migration of ECODAB to a relational database has allowed the automation of all processes to update, retrieve and present information, thereby, endowing the system with greater flexibility and improved overall performance. ECODAB is freely available at http://www.casper.organ.su.se/ECODAB/. Currently, data on 169 E. coli unique O-antigen entries and 338 GTs is covered. Moreover, the scope of the database has been extended so that polysaccharide structure and related information from other bacteria subsequently can be added, for example, from Streptococcus pneumoniae.

  15. Atomic structure of anthrax protective antigen pore elucidates toxin translocation.

    Science.gov (United States)

    Jiang, Jiansen; Pentelute, Bradley L; Collier, R John; Zhou, Z Hong

    2015-05-28

    Anthrax toxin, comprising protective antigen, lethal factor, and oedema factor, is the major virulence factor of Bacillus anthracis, an agent that causes high mortality in humans and animals. Protective antigen forms oligomeric prepores that undergo conversion to membrane-spanning pores by endosomal acidification, and these pores translocate the enzymes lethal factor and oedema factor into the cytosol of target cells. Protective antigen is not only a vaccine component and therapeutic target for anthrax infections but also an excellent model system for understanding the mechanism of protein translocation. On the basis of biochemical and electrophysiological results, researchers have proposed that a phi (Φ)-clamp composed of phenylalanine (Phe)427 residues of protective antigen catalyses protein translocation via a charge-state-dependent Brownian ratchet. Although atomic structures of protective antigen prepores are available, how protective antigen senses low pH, converts to active pore, and translocates lethal factor and oedema factor are not well defined without an atomic model of its pore. Here, by cryo-electron microscopy with direct electron counting, we determine the protective antigen pore structure at 2.9-Å resolution. The structure reveals the long-sought-after catalytic Φ-clamp and the membrane-spanning translocation channel, and supports the Brownian ratchet model for protein translocation. Comparisons of four structures reveal conformational changes in prepore to pore conversion that support a multi-step mechanism by which low pH is sensed and the membrane-spanning channel is formed.

  16. Standardization and characterization of antigens for the diagnosis of aspergillosis.

    Science.gov (United States)

    Stopiglia, Cheila Denise Ottonelli; Arechavala, Alicia; Carissimi, Mariana; Sorrentino, Julia Medeiros; Aquino, Valério Rodrigues; Daboit, Tatiane Caroline; Kammler, Luana; Negroni, Ricardo; Scroferneker, Maria Lúcia

    2012-04-01

    The aim of this study was to develop and characterize antigens for the diagnosis of aspergillosis. Nine strains of Aspergillus species Aspergillus fumigatus , Aspergillus flavus , and Aspergillus niger were grown in Sabouraud and Smith broth to produce exoantigens. The antigens were tested by immunodiffusion against sera from patients with aspergillosis and other systemic mycoses. The protein fraction of the antigens was detected by SDS-PAGE; Western blot and representative bands were assessed by mass spectrometry coupled to a nano Acquity UltraPerformance LC and analyzed by the Mascot search engine. Concurrently, all sera were tested with Platelia Aspergillus EIA. The most reactive antigens to sera from patients infected by A. fumigatus were produced by A. fumigatus MG2 Sabouraud and pooled A. fumigatus Sabouraud samples, both with a sensitivity of 93% and specificity of 100% and 97%, respectively. Aspergillus niger and A. flavus antigens were reactive against A. niger and A. flavus sera, each one with a sensitivity and specificity of 100%. Two proteins, probably responsible for antigenic activity, β-glucosidase in A. fumigatus and α-amylase in A. niger were attained. The commercial kit had a specificity of 22%, sensitivity of 100%, positive predictive value of 48%, and negative predictive value of 100%. The antigens produced showed high sensitivity and specificity and can be exploited for diagnostics of aspergilloma.

  17. Molecular mimics of the tumour antigen MUC1.

    Directory of Open Access Journals (Sweden)

    Tharappel C James

    Full Text Available A key requirement for the development of cancer immunotherapy is the identification of tumour-associated antigens that are differentially or exclusively expressed on the tumour and recognized by the host immune system. However, immune responses to such antigens are often muted or lacking due to the antigens being recognized as "self", and further complicated by the tumour environment and regulation of immune cells within. In an effort to circumvent the lack of immune responses to tumour antigens, we have devised a strategy to develop potential synthetic immunogens. The strategy, termed mirror image phage display, is based on the concept of molecular mimicry as demonstrated by the idiotype/anti-idiotype paradigm in the immune system. Here as 'proof of principle' we have selected molecular mimics of the well-characterised tumour associated antigen, the human mucin1 protein (MUC1 from two different peptide phage display libraries. The putative mimics were compared in structure and function to that of the native antigen. Our results demonstrate that several of the mimic peptides display T-cell stimulation activity in vitro when presented by matured dendritic cells. The mimic peptides and the native MUC1 antigenic epitopes can cross-stimulate T-cells. The data also indicate that sequence homology and/or chemical properties to the original epitope are not the sole determining factors for the observed immunostimulatory activity of the mimic peptides.

  18. Antigenic variation with a twist--the Borrelia story.

    Science.gov (United States)

    Norris, Steven J

    2006-06-01

    A common mechanism of immune evasion in pathogenic bacteria and protozoa is antigenic variation, in which genetic or epigenetic changes result in rapid, sequential shifts in a surface-exposed antigen. In this issue of Molecular Microbiology, Dai et al. provide the most complete description to date of the vlp/vsp antigenic variation system of the relapsing fever spirochaete, Borrelia hermsii. This elaborate, plasmid-encoded system involves an expression site that can acquire either variable large protein (vlp) or variable small protein (vsp) surface lipoprotein genes from 59 different archival copies. The archival vlp and vsp genes are arranged in clusters on at least five different plasmids. Gene conversion occurs through recombination events at upstream homology sequences (UHS) found in each gene copy, and at downstream homology sequences (DHS) found periodically among the vlp/vsp archival genes. Previous studies have shown that antigenic variation in relapsing fever Borrelia not only permits the evasion of host antibody responses, but can also result in changes in neurotropism and other pathogenic properties. The vlsE antigenic variation locus of Lyme disease spirochaetes, although similar in sequence to the relapsing fever vlp genes, has evolved a completely different antigenic variation mechanism involving segmental recombination from a contiguous array of vls silent cassettes. These two systems thus appear to represent divergence from a common precursor followed by functional convergence to create two distinct antigenic variation processes.

  19. Soluble Plasmodium falciparum antigens contain carbohydrate moieties important for immune reactivity

    DEFF Research Database (Denmark)

    Jakobsen, P H; Theander, T G; Jensen, J B;

    1987-01-01

    The importance of carbohydrate moieties for the antigenicity of purified soluble Plasmodium falciparum antigens from the asexual blood stage was tested. Digestion of the soluble antigens with alpha-D-galactosidase clearly affected the ability of the antigen to react with malaria-immune sera from ....... The results might have important implications for the strategy of developing a malaria vaccine.......The importance of carbohydrate moieties for the antigenicity of purified soluble Plasmodium falciparum antigens from the asexual blood stage was tested. Digestion of the soluble antigens with alpha-D-galactosidase clearly affected the ability of the antigen to react with malaria-immune sera from...

  20. Microglial MHC antigen expression after ischemic and kainic acid lesions of the adult rat hippocampus

    DEFF Research Database (Denmark)

    Finsen, B.R.; Jørgensen, Martin Balslev; Diemer, Nils Henrik

    1993-01-01

    Leukocyte common antigen, macrophages, blood-brain barrier, neural degeneration, fascia dentata, neuropathology......Leukocyte common antigen, macrophages, blood-brain barrier, neural degeneration, fascia dentata, neuropathology...

  1. Oxygen as a stimulant: Dramatic reduction of sewage sludge volumes; Sauerstoff als Stimulanz: Der Klaerschlammanfall laesst sich dramatisch verringern

    Energy Technology Data Exchange (ETDEWEB)

    Croissant, B. [OWAS Odenwaelder Wasser- und Abwasser-Service GmbH, Erbach (Germany); Stark, O. [Stark-Consult, Duesseldorf (Germany)

    2002-10-01

    Sludge volumes can be reduced significantly by optimising the biological processes in a sewage plant. During a trial period of eight months, a 45 percent reduction was achieved on average. Secondary effects were improved carbon and nitrate reduction. [German] Durch eine Optmierung der biologischen Prozesse in der Klaeranlage ist moeglich, den Ueberschussschlammanfall deutlich zu senken. Ueber einen Zeitraum von acht Monaten konnte der mittlere Schlammanfall um 45 Prozent reduziert werden. Sekundaere Effekte des Verfahrens waren eine verbesserte Kohlenstoffablauf- und Nitratablaufkonzentration. (orig.)

  2. Monocytic HLA DR antigens in schizophrenic patients.

    Science.gov (United States)

    Krause, Daniela; Wagner, Jenny; Matz, Judith; Weidinger, Elif; Obermeier, Michael; Riedel, Michael; Gruber, Rudolf; Schwarz, Markus; Mueller, Norbert

    2012-01-01

    A genetic association of specific human leukocyte antigens (HLA) DR genes and schizophrenia has recently been shown. These HLA play a fundamental role in the control of immune responses. Furthermore infectious agents have been proposed to be involved in the pathogenesis of schizophrenia. In this study we investigated the rate of HLA DR positive monocytes in schizophrenic patients compared to controls with a special focus on the adaption to in vitro stimulation with toll-like receptor ligands. Patients with schizophrenia and matched controls were included. For each individual, we evaluated the rate of HLA DR positive monocytes (either incubated at 37 °C or after stimulation with lipopolysaccharide or Poly I:C). We found a significantly higher percentage of schizophrenic patients with elevated HLA DR positive cells (p=0.045) as compared to controls. The adjustment rate from baseline levels of monocytic HLA DR positive cells to stimulation with Poly I:C was significantly lower in schizophrenic patients (p=0.038). The increased monocytic HLA DR in schizophrenic patients and the maladjustment of their monocytic HLA DR levels to an infectious stimulus might be a sign for a disturbed monocytic immune balance in schizophrenic individuals.

  3. Immunofluorescence antigen mapping for hereditary epidermolysis bullosa

    Directory of Open Access Journals (Sweden)

    Raghavendra Rao

    2012-01-01

    Full Text Available Epidermolysis bullosa (EB is a group of inherited, mechanobullous disorders that are caused by mutations in the structural proteins in the epidermis or dermoepidermal junction. Characteristic clinical picture is the presence of blisters at trauma prone areas of the body, which develops at or soon after birth. Availability of specific monoclonal antibodies against the target proteins together with advances in the molecular genetics have led to the revision in the classification of EB. Now four major types of EB are recognized depending upon the level of blister and the location of target protein: EB simplex (epidermolytic, junctional EB (lucidolytic, dystrophic EB (dermolytic and Kindler′s syndrome (mixed cleavage plane. The laboratory tests not only help to confirm the diagnosis of EB but are also an important tool to classify (and subtype EB. These include immunofluorescence antigen mapping (IFM, transmission electron microscopy (TEM and mutation analysis. IFM is the most preferred method for final diagnosis of EB worldwide. It is relatively easy to perform and results can be obtained rapidly. This article describes the technicalities and significance of IFM in various types of EB.

  4. Engineering less immunogenic and antigenic FVIII proteins

    Science.gov (United States)

    Pratt, Kathleen P.

    2017-01-01

    The development of neutralizing antibodies against blood coagulation factor VIII (FVIII), referred to clinically as “inhibitors”, is the most challenging and deleterious adverse event to occur following intravenous infusions of FVIII to treat hemophilia A. Inhibitors occlude FVIII surfaces that must bind to activated phospholipid membranes, the serine proteinase factor IXa, and other components of the ‘intrinsic tenase complex’ in order to carry out its important role in accelerating blood coagulation. Inhibitors develop in up to one of every three patients, yet remarkably, a substantial majority of severe hemophilia A patients, who circulate no detectable FVIII antigen or activity, acquire immune tolerance to FVIII during initial infusions or else after intensive FVIII therapy to overcome their inhibitor. The design of less immunogenic FVIII proteins through identification and modification (“de-immunization”) of immunodominant T-cell epitopes is an important goal. For patients who develop persistent inhibitors, modification of B-cell epitopes through substitution of surface-exposed amino acid side chains and/or attachment of bulky moieties to interfere with FVIII attachment to antibodies and memory B cells is a promising approach. Both experimental and computational methods are being employed to achieve these goals. Future therapies for hemophilia A, as well as other monogenic deficiency diseases, are likely to involve administration of less immunogenic proteins in conjunction with other novel immunotherapies to promote a regulatory cellular environment promoting durable immune tolerance. PMID:26566286

  5. Hepatitis B Virus e Antigen Variants

    Directory of Open Access Journals (Sweden)

    2005-01-01

    Full Text Available More than 300 million people worldwide are chronically infected with hepatitis B virus (HBV. Considering the very short generation time for a virus, and the high error rate associated with the reverse transcription step of HBV replication, decades of HBV infection are probably equivalent to million years of human evolution. The most important selective force during the natural course of HBV infection appears to be the immune response. The development of anti-HBe antibody in hepatitis B patients usually correlates with reduction of HBV viremia. As a consequence, escape mutants of anti-HBe are selected. The core promoter mutants express less HBe antigen (HBeAg through transcriptional down regulation, while precore mutants express truncated products. We recently identified additional mutations that modulate HBeAg translation initiation, proteolytic cleavage, and secondary structure maintenance through a disulfide bond. The core promoter mutants have been associated with the development of fulminant hepatitis during acute infection and liver cancer during chronic infection. Consistent with their enhanced pathogenicity, core promoter mutants were found to replicate at up to 10-fold higher levels in transfected human hepatoma cells than the wild-type virus. Moreover, some core promoter mutants are impaired in virion secretion due to missense mutations in the envelope gene. These virological properties may help explain enhanced pathogenicity of core promoter mutants in vivo.

  6. Isolation and purification of antigenic components of Cryptococcus.

    Science.gov (United States)

    Wozniak, Karen L; Levitz, Stuart M

    2009-01-01

    The encapsulated fungal pathogens Cryptococcus neoformans and Cryptococcus gattii are significant agents of life-threatening infections, particularly in persons with suppressed cell-mediated immunity. This chapter provides detailed methodology for the purification of two of the major antigen fractions of C. neoformans: glucuronoxylomannan (GXM) and mannoprotein (MP). GXM is the primary component of the polysaccharide capsule, which is the major cryptococcal virulence factor. In contrast, MPs have been identified as key antigens that stimulate T-cell responses. Purification of GXM and MP should assist investigators studying the antigenic, biochemical, and virulence properties of Cryptococcus species.

  7. Simple mucin-type carbohydrate antigens in major salivary glands

    DEFF Research Database (Denmark)

    Therkildsen, M H; Mandel, U; Thorn, J

    1994-01-01

    -defined monoclonal antibodies (MAb) on frozen and paraffin-embedded normal salivary gland tissue from 22 parotid, 14 submandibular, six sublingual, and 13 labial glands to elucidate the simple mucin-type glycosylation pattern in relation to cyto- and histodifferentiation. The investigated carbohydrate structures......Simple mucin-type carbohydrate antigens Tn, sialosyl-Tn and T are often markers of neoplastic transformation and have very limited expression in normal tissues. We performed an immunohistological study of simple mucin-type carbohydrate antigens, including H and A variants, with well...... antigens indicates that these structures may be of value as markers of salivary gland tumors....

  8. Alanine mutagenesis of the primary antigenic escape residue cluster, c1, of apical membrane antigen 1.

    Science.gov (United States)

    Dutta, Sheetij; Dlugosz, Lisa S; Clayton, Joshua W; Pool, Christopher D; Haynes, J David; Gasser, Robert A; Batchelor, Adrian H

    2010-02-01

    Antibodies against apical membrane antigen 1 (AMA1) inhibit invasion of Plasmodium merozoites into red cells, and a large number of single nucleotide polymorphisms on AMA1 allow the parasite to escape inhibitory antibodies. The availability of a crystal structure makes it possible to test protein engineering strategies to develop a monovalent broadly reactive vaccine. Previously, we showed that a linear stretch of polymorphic residues (amino acids 187 to 207), localized within the C1 cluster on domain 1, conferred the highest level of escape from inhibitory antibodies, and these were termed antigenic escape residues (AER). Here we test the hypothesis that immunodampening the C1 AER will divert the immune system toward more conserved regions. We substituted seven C1 AER of the FVO strain Plasmodium falciparum AMA1 with alanine residues (ALA). The resulting ALA protein was less immunogenic than the native protein in rabbits. Anti-ALA antibodies contained a higher proportion of cross-reactive domain 2 and domain 3 antibodies and had higher avidity than anti-FVO. No overall enhancement of cross-reactive inhibitory activity was observed when anti-FVO and anti-ALA sera were compared for their ability to inhibit invasion. Alanine mutations at the C1 AER had shifted the immune response toward cross-strain-reactive epitopes that were noninhibitory, refuting the hypothesis but confirming the importance of the C1 cluster as an inhibitory epitope. We further demonstrate that naturally occurring polymorphisms that fall within the C1 cluster can predict escape from cross-strain invasion inhibition, reinforcing the importance of the C1 cluster genotype for antigenic categorization and allelic shift analyses in future phase 2b trials.

  9. Responses of synovial fluid and peripheral blood mononuclear cells to bacterial antigens and autologous antigen presenting cells.

    Science.gov (United States)

    Klasen, I S; Melief, M J; Swaak, T J; Severijnen, A J; Hazenberg, M P

    1993-01-01

    The specificity of T cells in the inflamed joints of patients with rheumatoid arthritis (RA) has been the subject of much study. Bacterial antigens are suspect in the aetiology of rheumatic diseases. The responsiveness of the mononuclear cell fraction of peripheral blood and synovial fluid of patients with RA and of patients with rheumatic diseases other than RA to bacterial antigens such as cell wall fragments of the anaerobic intestinal flora, cell wall fragments of Streptococcus pyogenes, intestinal flora derived peptidoglycan polysaccharide complexes, the 65 kilodalton protein of Mycobacterium tuberculosis, and muramyldipeptide was investigated. No significant difference in response was found to all these bacterial antigens in the synovial fluid of patients with RA compared with the responses in patients with other rheumatic diseases. The highest responsiveness in the synovial fluid of the patients with RA was to the streptococcal cell wall fragments and to the 65 kilodalton protein. Higher responses to several bacterial antigens in the synovial fluid of patients with RA were found compared with peripheral blood from the same patient group. The antigen presenting cell population of the synovial fluid in patients with RA and the patients with other rheumatic diseases was found to be stimulatory for autologous peripheral blood T cells even in the absence of antigen. This suggests an important role for the synovial antigen presenting cell in the aetiology of inflammatory joint diseases. PMID:8447692

  10. Characterization of O-antigen delivered by Generalized Modules for Membrane Antigens (GMMA) vaccine candidates against nontyphoidal Salmonella.

    Science.gov (United States)

    De Benedetto, G; Alfini, R; Cescutti, P; Caboni, M; Lanzilao, L; Necchi, F; Saul, A; MacLennan, C A; Rondini, S; Micoli, F

    2017-01-11

    Invasive nontyphoidal Salmonella disease (iNTS) is a leading cause of death and morbidity in Africa. The most common pathogens are Salmonella enterica serovars Typhimurium and Enteritidis. The O-antigen portion of their lipopolysaccharide is a target of protective immunity and vaccines targeting O-antigen are currently in development. Here we investigate the use of Generalized Modules for Membrane Antigens (GMMA) as delivery system for S. Typhimurium and S. Enteritidis O-antigen. Gram-negative bacteria naturally shed outer membrane in a blebbing process. By deletion of the tolR gene, the level of shedding was greatly enhanced. Further genetic modifications were introduced into the GMMA-producing strains in order to reduce reactogenicity, by detoxifying the lipid A moiety of lipopolysaccharide. We found that genetic mutations can impact on expression of O-antigen chains. All S. Enteritidis GMMA characterized had an O-antigen to protein w/w ratio higher than 0.6, while the ratio was 0.7 for S. Typhimurium ΔtolR GMMA, but decreased to less than 0.1 when further mutations for lipid A detoxification were introduced. Changes were also observed in O-antigen chain length and level and/or position of O-acetylation. When tested in mice, the GMMA induced high levels of anti-O-antigen-specific IgG functional antibodies, despite variation in density and O-antigen structural modifications. In conclusion, simplicity of manufacturing process and low costs of production, coupled with encouraging immunogenicity data, make GMMA an attractive strategy to further investigate for the development of a vaccine against iNTS.

  11. Prostate-specific antigen (PSA) velocity: a test of controversial benefit in the era of increased prostate cancer screening

    Institute of Scientific and Technical Information of China (English)

    Michael S Borofsky; Danil V Makarov

    2011-01-01

    @@ Determining the need for prostate biopsy remains one of the most controversial questions in urology.Over the past 10 years, practice guidelines have changed dramatically, especially among asymptomatic men with low prostate-specific antigen (PSA) and negative digital rectal exam.Thompson et al.Found that nearly 15% of men with PSA <4.0 had evidence of prostate cancer on biopsy;1 however, the clinical significance of these tumors is unclear.PSAvelocity (PSAV) has been suggested as a measurement to discriminate between aggressive and indolent cancers.Both the NCCN2 and AUA3 guidelines recommend considering prostate biopsy for men with PSA <4.0 and high PSAV (0.35 and 0.4 ng/ml/year, respectively); however, a recent article by Vickers et al.4 has called these recommendations into question, suggesting that PSAV adds little predictive accuracy to the standard risk factor assessment for prostate cancer.

  12. Presensitization to Ascaris antigens promotes induction of mite-specific IgE upon mite antigen inhalation in mice

    Directory of Open Access Journals (Sweden)

    Mayu Suzuki

    2016-01-01

    Conclusions: We demonstrated that the immunization of naïve mice with Ascaris antigens induced production of antibodies and differentiation of Th2 cells, which were cross-reactive to HDM antigens, and accelerated induction of serum HDM-specific IgE upon subsequent airway exposure to HDM antigens in mice. These results suggest that sensitization to HDM towards IgE-mediated allergic diseases is faster in individuals with a previous history of Ascaris infection than in those without presensitization to Ascaris.

  13. Use of Recombinant Antigens for the Diagnosis of Invasive Candidiasis

    Directory of Open Access Journals (Sweden)

    Ana Laín

    2008-01-01

    Full Text Available Invasive candidiasis is a frequent and often fatal complication in immunocompromised and critically ill patients. Unfortunately, the diagnosis of invasive candidiasis remains difficult due to the lack of specific clinical symptoms and a definitive diagnostic method. The detection of antibodies against different Candida antigens may help in the diagnosis. However, the methods traditionally used for the detection of antibodies have been based on crude antigenic fungal extracts, which usually show low-reproducibility and cross-reactivity problems. The development of molecular biology techniques has allowed the production of recombinant antigens which may help to solve these problems. In this review we will discuss the usefulness of recombinant antigens in the diagnosis of invasive candidiasis.

  14. The Antigen Presenting Cells Instruct Plasma Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Wei eXu

    2014-01-01

    Full Text Available The professional antigen presenting cells (APCs, including many subsets of dendritic cells and macrophages, not only mediate prompt but nonspecific response against microbes, but also bridge the antigen-specific adaptive immune response through antigen presentation. In the latter, typically activated B cells acquire cognate signals from T helper cells in the germinal center of lymphoid follicles to differentiate into plasma cells, which generate protective antibodies. Recent advances have revealed that many APC subsets provide not only signal 1 (the antigen, but also signal 2 to directly instruct the differentiation process of plasma cells in a T cell-independent manner. Herein, the different signals provided by these APC subsets to direct B cell proliferation, survival, class switching and terminal differentiation are discussed. We furthermore propose that the next generation of vaccines for boosting antibody response could be designed by targeting APCs.

  15. Immune activation by casein dietary antigens in bipolar disorder

    NARCIS (Netherlands)

    Severance, E.G.; Dupont, D.; Dickerson, F.B.; Stallings, C.R.; Origoni, A.E.; Krivogorsky, B.; Yang, S.; Haasnoot, W.; Yolken, R.H.

    2010-01-01

    Objectives: Inflammation and other immune processes are increasingly linked to psychiatric diseases. Antigenic triggers specific to bipolar disorder are not yet defined. We tested whether antibodies to bovine milk caseins were associated with bipolar disorder, and whether patients recognized differe

  16. The Synthesis of a Novel Phosphorus Containing Antigen

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Antigen 12, containing a phosphonyl peptide hapten with free C-terminal carboxylic group, was synthesized by 11 reaction steps. The design of the hapten was based on the transition state of peptide hydrolysis catalyzed by carboxypeptidase A.

  17. Antigen-specific lymphocyte transformation in patients with recent yersiniosis.

    Science.gov (United States)

    Vuento, R

    1983-04-01

    Lymphocyte transformation in patients with recent yersiniosis was studied. A micromethod using washed blood cells and Yersinia enterocolitica antigen was employed. The washed blood cells were incubated in the presence of various dilutions of heat-treated whole bacteria; these proved as antigen superior to gentamicin- or formalin-treated bacteria. Patients with recent yersiniosis had a significantly higher response against Yersinia antigen as compared to 20 healthy controls, who had either no response or a low response. No difference could be observed in responses against PPD or streptokinase-streptodornase, or in the mitogen responses between these two groups. A marked cross-reaction was observed between Yersinia and Escherichia coli antigen. The results show that patients with recent yersiniosis develop lymphocyte transformation response against Yersinia. Lymphocyte transformation test can be used in the study of host responses against infecting Yersinia in patients with different clinical pictures of yersiniosis.

  18. ABO blood group antigens in oral mucosa. What is new?

    DEFF Research Database (Denmark)

    Dabelsteen, Erik

    2002-01-01

    which represent secondary gene products. They are synthesized in a stepwise fashion from a precursor by the action of different glycosyltransferases. In non-keratinized oral mucosa, a sequential elongation of the carbohydrates is associated with differentiation of epithelial cells, resulting...... in expression of precursors on basal cells and A/B antigens on spinous cells. Reduction or complete deletion of A/B antigen expression in oral carcinomas has been reported, a phenotypic change that is correlated with invasive and metastatic potential of the tumours and with the mortality rates of the patients....... Disappearance of the antigens is ascribed to the absence of A or B transferase gene expression. Several studies have shown that loss of A and B antigen expression is associated with increased cell motility, invasion in matrigel, and tumourigenecity in syngenic animals. In vivo studies of human oral wound...

  19. Chlamydia trachomatis antigen in female genital tract infection

    Directory of Open Access Journals (Sweden)

    Badrinath S

    1996-01-01

    Full Text Available Thirty cases of female genital tract infection were investigated for the presence of Chlamydia trachomatis antigen. Endocervical swabs obtained were subjected to antigen detection by enzyme immunoassay. Rabbit antiserum to chlamydial lipopolysaccharide was used in a card test. Anti rabbit immunoglobulin G conjugated to alkaline phosphatase with a chromogenic substrate 5 bromo-4 chloro-3-indolyl phosphate and nitro blue tetrazolium were used for the enzymatic reaction. Chlamydial antigen could be detected in four out of thirty samples (13.3%. In contrast direct immunofluorescence detected 5 cases (16.6%. Although less sensitive, enzyme immunoassay can be used as a rapid diagnostic tool in detecting Chlamydia trachomatis antigen in genital infections.

  20. Instability of induction cooker (electromagnetic stove) antigen retrieval in immunohistochemistry.

    Science.gov (United States)

    Ding, Wei; Zheng, Xiang-Yi

    2012-03-01

    An induction cooker is a modern electric cooker that takes electromagnetic induction principle to heat. As it has high efficiency, no open flame, and is safe and convenient, more and more laboratories use it as an antigen retrieval heating tool in immunohistochemistry. We found that there was still some instability with the induction cooker, because with certain antigens the power change influenced the results of immunohistochemistry staining, showing weaker staining intensity or decreased number of positive cells, but which were not entirely negative. For some antigens, it had no influence on results. The instability of this heating tool for antigen retrieval was caused partly by negligent operators, and which may influence the experimental results and the pathologic diagnosis.