Relationship between general and specific coordination in 8- to 17-year-old male basketball players.

Science.gov (United States)

Kamandulis, Sigitas; Venckūnas, Tomas; Masiulis, Nerijus; Matulaitis, Kestutis; Balciūnas, Mindaugas; Peters, Derek; Skurvydas, Albertas

2013-12-01

The purpose of the present study was to investigate the relationships between general coordination, sport-specific coordination, and sport-specific fitness of 8- to 17-year-old male basketball players. 312 males with training experience ranging from one year in the 8-year-old cohort up to 10 years for the 17-year-olds performed basketball-specific fitness (20 m sprint, Illinois, countermovement jump), general coordination (20 m run with three obstacles), semi-basketball-specific coordination (20 m sprint dribbling two balls, countermovement jump with arm swing) and basketball-specific coordination (Illinois ball dribbling) tests. There were moderate to large correlations between the results of both general and basketball-specific coordination with the results of most basketball-specific coordination tests in all age groups. Correlations between general and basketball-specific coordination were large in four age groups (11-14 yr., r = .52 to r = .76), moderate in five groups (8-10, 15 & 16 yr., r = .37 to r = .46), while not significant in the 17-year-olds. These results suggest that the importance of general coordination for sport-specific skills improvements during a sports-specific skill acquisition phase, remains high at the skill refinement phase, and decreases when sport-specific skills have been mastered to near-perfection.

High IL-17E and low IL-17C dermal expression identifies a fibrosis-specific motif common to morphea and systemic sclerosis.

Directory of Open Access Journals (Sweden)

Paola Adele Lonati

Full Text Available BACKGROUND: High interleukin (IL-17A levels are characteristically found in the skin of systemic sclerosis (SSc individuals. Our aim was to investigate whether the dermal expression of IL-17A and related IL-17 family members (i.e. IL-17C, IL-17E and IL-17F could distinguish fibrotic from healthy skin and could show similarities in SSc and morphea, two disorders with presumed distinct pathogenesis, but characterized by skin fibrosis. METHODS: Biopsies were obtained from the involved skin of 14 SSc, 5 morphea and 8 healthy donors (HD undergoing plastic surgery. Immunohistochemistry/immunofluorescence techniques were coupled to a semi-automated imaging quantification approach to determine the presence of the IL-17 family members in the skin. The in vitro effects induced by the IL-17 family members on fibroblasts from normal and SSc individuals were assessed by ELISA and RIA. RESULTS: Positive cells for each of the IL-17 isoforms investigated were present in the dermis of all the individuals tested, though with variable frequencies. SSc individuals had increased frequency of IL-17A+ (p = 0.0237 and decreased frequency of IL-17F+ (p = 0.0127 and IL-17C+ cells (p = 0.0008 when compared to HD. Similarly, morphea individuals had less frequent IL-17C+ cells (p = 0.0186 in their skin but showed similar number of IL-17A+ and IL-17F+ cells when compared to HD. Finally, IL-17E+ cells were more numerous in morphea (p = 0.0109 and tended to be more frequent in SSc than in HD. Fibroblast production of IL-6, MMP-1 and MCP-1 was enhanced in a dose-dependent manner in the presence of IL-17E and IL-17F, but not in the presence of IL-17C. None of the cytokine tested had significant effect on type I collagen production. Of interest, in SSc the frequency of both IL-17A and IL-17F positive cells increased with disease duration. CONCLUSIONS: The frequency of IL-17A and IL-17F distinguish SSc to morphea individuals while dermal expression of IL-17C (low and IL-17E (high

Synthetic Biology with Cytochromes P450 Using Photosynthetic Chassis

DEFF Research Database (Denmark)

Gnanasekaran, Thiyagarajan

, this modern field of synthetic biology is completely dependent on the nature of the chassis - the host organisms - for its endeavor. Of all the chassis, photosynthetic organisms such as cyanobacteria and plants gains special attention due to the remarkable amount of sunlight that is striking the Earth...... in cyanobacteria and plant chloroplasts for the purpose of light driven synthesis of bioactive compounds by using synthetic biology approaches. As model pathways, in this thesis, the pathway involved in the synthesis of the cyanogenic glucoside dhurrin from Sorghum bicolor, and the pathway involved......Synthetic biology is a rapidly growing engineering discipline in biology. It aims at building novel biological systems that do not exist in nature by selecting the interchangeable standardized biological parts that are already available in the nature, and assembling them in a specific order. Today...

Traceability of synthetic drugs by position-specific deuterium isotope ratio analysis

Energy Technology Data Exchange (ETDEWEB)

Brenna, Elisabetta [Dipartimento di Chimica, Materiali e di Ingegneria Chimica del Politecnico di Milano and Istituto CNR per la Chimica del Riconoscimento Molecolare, Via Mancinelli 7, Milan I-20131 (Italy)], E-mail: elisabetta.brenna@polimi.it; Fronza, Giovanni [Dipartimento di Chimica, Materiali e di Ingegneria Chimica del Politecnico di Milano (Italy) and Instituto CNR per la Chimica del Riconoscimento Molecolare, Via Mancinelli 7, Milan I-20131 (Italy)], E-mail: giovanni.fronza@polimi.it; Fuganti, Claudio [Dipartimento di Chimica, Materiali e di Ingegneria Chimica del Politecnico di Milano (Italy) and Istituto CNR per la Chimica del Riconoscimento Molecolare, Via Mancinelli 7, Milan I-20131 (Italy)

2007-10-10

Samples of fluoxetine of different origin were submitted to natural abundance {sup 2}H NMR spectroscopy. The deuterium content at the various sites of the molecule was found to depend on its synthetic history. Hints on the synthetic procedure can be obtained by comparison with standard compounds, whose synthesis is known. These preliminary results give an idea of the potential of site-specific isotope ratio analysis in the fight against patent infringement and drug counterfeiting.

Traceability of synthetic drugs by position-specific deuterium isotope ratio analysis

International Nuclear Information System (INIS)

Brenna, Elisabetta; Fronza, Giovanni; Fuganti, Claudio

2007-01-01

Samples of fluoxetine of different origin were submitted to natural abundance 2 H NMR spectroscopy. The deuterium content at the various sites of the molecule was found to depend on its synthetic history. Hints on the synthetic procedure can be obtained by comparison with standard compounds, whose synthesis is known. These preliminary results give an idea of the potential of site-specific isotope ratio analysis in the fight against patent infringement and drug counterfeiting

Improved scFv Anti-HIV-1 p17 Binding Affinity Guided from the Theoretical Calculation of Pairwise Decomposition Energies and Computational Alanine Scanning

Directory of Open Access Journals (Sweden)

Panthip Tue-ngeun

2013-01-01

Full Text Available Computational approaches have been used to evaluate and define important residues for protein-protein interactions, especially antigen-antibody complexes. In our previous study, pairwise decomposition of residue interaction energies of single chain Fv with HIV-1 p17 epitope variants has indicated the key specific residues in the complementary determining regions (CDRs of scFv anti-p17. In this present investigation in order to determine whether a specific side chain group of residue in CDRs plays an important role in bioactivity, computational alanine scanning has been applied. Molecular dynamics simulations were done with several complexes of original scFv anti-p17 and scFv anti-p17mutants with HIV-1 p17 epitope variants with a production run up to 10 ns. With the combination of pairwise decomposition residue interaction and alanine scanning calculations, the point mutation has been initially selected at the position MET100 to improve the residue binding affinity. The calculated docking interaction energy between a single mutation from methionine to either arginine or glycine has shown the improved binding affinity, contributed from the electrostatic interaction with the negative favorably interaction energy, compared to the wild type. Theoretical calculations agreed well with the results from the peptide ELISA results.

A synthetic multifunctional mammalian pH sensor and CO2 transgene-control device.

Science.gov (United States)

Ausländer, David; Ausländer, Simon; Charpin-El Hamri, Ghislaine; Sedlmayer, Ferdinand; Müller, Marius; Frey, Olivier; Hierlemann, Andreas; Stelling, Jörg; Fussenegger, Martin

2014-08-07

All metabolic activities operate within a narrow pH range that is controlled by the CO2-bicarbonate buffering system. We hypothesized that pH could serve as surrogate signal to monitor and respond to the physiological state. By functionally rewiring the human proton-activated cell-surface receptor TDAG8 to chimeric promoters, we created a synthetic signaling cascade that precisely monitors extracellular pH within the physiological range. The synthetic pH sensor could be adjusted by organic acids as well as gaseous CO2 that shifts the CO2-bicarbonate balance toward hydrogen ions. This enabled the design of gas-programmable logic gates, provided remote control of cellular behavior inside microfluidic devices, and allowed for CO2-triggered production of biopharmaceuticals in standard bioreactors. When implanting cells containing the synthetic pH sensor linked to production of insulin into type 1 diabetic mice developing diabetic ketoacidosis, the prosthetic network automatically scored acidic pH and coordinated an insulin expression response that corrected ketoacidosis. Copyright © 2014 Elsevier Inc. All rights reserved.

7 CFR 407.17 - Group risk plan for wheat.

Science.gov (United States)

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Group risk plan for wheat. 407.17 Section 407.17..., DEPARTMENT OF AGRICULTURE GROUP RISK PLAN OF INSURANCE REGULATIONS § 407.17 Group risk plan for wheat. The provisions of the Group Risk Plan for Wheat for the 2000 and succeeding crop years are as follows: 1...

P-glycoprotein induction in Caco-2 cells by newly synthetized thioxanthones prevents paraquat cytotoxicity.

Science.gov (United States)

Silva, Renata; Palmeira, Andreia; Carmo, Helena; Barbosa, Daniel José; Gameiro, Mariline; Gomes, Ana; Paiva, Ana Mafalda; Sousa, Emília; Pinto, Madalena; Bastos, Maria de Lourdes; Remião, Fernando

2015-10-01

The induction of P-glycoprotein (P-gp), an ATP-dependent efflux pump, has been proposed as a strategy against the toxicity induced by P-gp substrates such as the herbicide paraquat (PQ). The aim of this study was to screen five newly synthetized thioxanthonic derivatives, a group known to interact with P-gp, as potential inducers of the pump's expression and/or activity and to evaluate whether they would afford protection against PQ-induced toxicity in Caco-2 cells. All five thioxanthones (20 µM) caused a significant increase in both P-gp expression and activity as evaluated by flow cytometry using the UIC2 antibody and rhodamine 123, respectively. Additionally, it was demonstrated that the tested compounds, when present only during the efflux of rhodamine 123, rapidly induced an activation of P-gp. The tested compounds also increased P-gp ATPase activity in MDR1-Sf9 membrane vesicles, indicating that all derivatives acted as P-gp substrates. PQ cytotoxicity was significantly reduced in the presence of four thioxanthone derivatives, and this protective effect was reversed upon incubation with a specific P-gp inhibitor. In silico studies showed that all the tested thioxanthones fitted onto a previously described three-feature P-gp induction pharmacophore. Moreover, in silico interactions between thioxanthones and P-gp in the presence of PQ suggested that a co-transport mechanism may be operating. Based on the in vitro activation results, a pharmacophore model for P-gp activation was built, which will be of further use in the screening for new P-gp activators. In conclusion, the study demonstrated the potential of the tested thioxanthonic compounds in protecting against toxic effects induced by P-gp substrates through P-gp induction and activation.

Effect of sewage sludge and synthetic fertilizer on pH, available N ...

African Journals Online (AJOL)

use

2011-11-21

Nov 21, 2011 ... Key words: Sewage sludge, synthetic fertilizer, pH, N, P, available duration. INTRODUCTION ... nutrient availability of N and P from organic amendments .... likened to 98.8 ton/ha applied in a semi-arid rangeland (Fish, 1995).

A Canadian refiner's perspective of synthetic crudes

International Nuclear Information System (INIS)

Halford, T.L.; McIntosh, A.P.; Rasmussen

1997-01-01

Some of the factors affecting a refiner's choice of crude oil include refinery hardware, particularly gas oil crackers, products slate and product specifications, crude availability, relative crude price and crude quality. An overview of synthetic crude, the use of synthetic crude combined with other crudes and a comparison of synthetic crude with conventional crude oil was given. The two main users of synthetic crude are basically two groups of refiners, those large groups who use synthetic crude combined with other crudes, and a smaller group who run synthetic crude on specially designed units as a sole feed. The effects of changes in fuel legislation were reviewed. It was predicted that the changes will have a mixed impact on the value of synthetic crude, but low sulphur diesel regulations and gasoline sulphur regulations will make current synthetic crudes attractive. The big future change with a negative impact will be diesel cetane increases to reduce engine emissions. This will reduce synthetic crude attractiveness due to distillate yields and quality and high gas oil yields. Similarly, any legislation limiting aromatics in diesel fuel will also make synthetic crudes less attractive. Problems experienced by refiners with hardware dedicated to synthetic crude (salt, naphthenic acid, fouling, quality variations) were also reviewed. 3 tabs

Waterproofing with polymeric geo synthetic barriers (GBR-P) in the manual for the design, construction, management and maintenance of reservoirs

International Nuclear Information System (INIS)

Blanco, M.; Cea, J. C.; Garcia, F.; Sanchez, F. J.; Castillo, F.; Mora, J.; Crespo, M. A.

2010-01-01

This article presents a part of Manual for the Design, Construction, Management and Maintenance of Reservoirs relative to waterproofing with Polymeric Geo synthetic Barriers (GBR-P). the nature materials of geo membranes is studied also theirs characteristics and specifications. (Author) 26 refs.

Gadolinium heteropoly complex K 17[Gd(P 2W 17O 61) 2] as a potential MRI contrast agent

Science.gov (United States)

Sun, Guoying; Feng, Jianghua; Wu, Huifeng; Pei, Fengkui; Fang, Ke; Lei, Hao

2004-10-01

Gadolinium heteropoly complex K17[Gd(P2W17O61)2] has been evaluated by in vitro and in vivo experiments as a potential contrast agent for magnetic resonance imaging (MRI). The thermal analysis and conductivity study indicate that this complex has good thermal stability and wide pH stability range. The T1 relaxivity is 7.59 mM-1 s-1 in aqueous solution and 7.97 mM-1 s-1 in 0.725 mmol l-1 bovine serum albumin (BSA) solution at 25 °C and 9.39 T, respectively. MR imaging of three male Sprague-Dawley rats showed remarkable enhancement in rat liver after intravenous injection, which persisted longer than with Gd-DTPA. The signal intensity increased by 57.1±16.9% during the whole imaging period at 0.082 mmol kg-1dose. Our preliminary in vitro and in vivo studies indicate that K17[Gd(P2W17O61)2] is a potential liver-specific MRI contrast agent.

Circulating FoxP3+ Regulatory T and Interleukin17-Producing Th17 Cells Actively Influence HBV Clearance in De Novo Hepatitis B Virus Infected Patients after Orthotopic Liver Transplantation

Science.gov (United States)

Li, Jin; Yang, Mei; Liu, Yuan; Guo, Xiaodong; Li, Hanwei; Liu, Zhenwen; Zhao, Jingmin

2015-01-01

Objective To longitudinally investigate the role of FoxP3+ Regulatory T cells (Treg) and interleukin17-producing T helper 17 cells (Th17) in De Novo Hepatitis B Virus infection after orthotopic Liver Transplantation (DNHB-OLT), and analyze the possible correlation between these cells and HBV clearance of the disease. Methods We enrolled 12 control cases after orthotopic Liver Transplantation (OLT) and 24 patients, including 12 diagnosed with DNHB-OLT and 12 diagnosed with Acute Hepatitis B Virus infection (AHB), into the study from the liver transplantation and research center at Beijing 302 Hospital. Flow cytometry was used to detect the frequencies of Treg and Th17, and ELISA was applied to detect the concentration of IL6, IL22, TGF-β and IL2 in peripheral blood. We also measured the gene expression level by real time-quantitative PCR and protein expression using immunohistochemistry and western-blot. Furthermore, we divided DNHB-OLT patients into the clearance and non-clearance groups and examined longitudinally Th17, Treg cells at different times. Results The percentage of Treg cells, expression of FoxP3 mRNA and related anti-inflammatory cytokines such as IL2 and TGF-β1 in the DNHB-OLT group were significantly higher than that in the AHB and OLT groups. The percentage of Th17 cells, expression of RORγt mRNA and related pro-inflammatory cytokines such as IL17 and IL22 in the DNHB-OLT group were significantly lower than that in the AHB group, but the levels of these cytokines are very similar to the OLT group. The ratios of Treg to Th17 in the DNHB-OLT group were significantly higher than that in the OLT and AHB groups. Treg frequencies significantly correlated with HBV DNA, whereas IL17 frequencies didn’t significantly correlate with ALT. In DNHB-OLT patients, the clearance group was accompanied by a rapid increase in the Th17 cells during the first 4th week and afterwards continuously decrease to the control group, together with a continuously decrease in

NNS computing facility manual P-17 Neutron and Nuclear Science

International Nuclear Information System (INIS)

Hoeberling, M.; Nelson, R.O.

1993-11-01

This document describes basic policies and provides information and examples on using the computing resources provided by P-17, the Neutron and Nuclear Science (NNS) group. Information on user accounts, getting help, network access, electronic mail, disk drives, tape drives, printers, batch processing software, XSYS hints, PC networking hints, and Mac networking hints is given

Concentration of acrylamide in a polyacrylamide gel affects VP4 gene coding assignment of group A equine rotavirus strains with P[12] specificity

Science.gov (United States)

2010-01-01

Background It is universally acknowledged that genome segment 4 of group A rotavirus, the major etiologic agent of severe diarrhea in infants and neonatal farm animals, encodes outer capsid neutralization and protective antigen VP4. Results To determine which genome segment of three group A equine rotavirus strains (H-2, FI-14 and FI-23) with P[12] specificity encodes the VP4, we analyzed dsRNAs of strains H-2, FI-14 and FI-23 as well as their reassortants by polyacrylamide gel electrophoresis (PAGE) at varying concentrations of acrylamide. The relative position of the VP4 gene of the three equine P[12] strains varied (either genome segment 3 or 4) depending upon the concentration of acrylamide. The VP4 gene bearing P[3], P[4], P[6], P[7], P[8] or P[18] specificity did not exhibit this phenomenon when the PAGE running conditions were varied. Conclusions The concentration of acrylamide in a PAGE gel affected VP4 gene coding assignment of equine rotavirus strains bearing P[12] specificity. PMID:20573245

MicroRNA-17-5p post-transcriptionally regulates p21 expression in irradiated betel quid chewing-related oral squamous cell carcinoma cells

International Nuclear Information System (INIS)

Wu, S.Y.; HungKuang Univ., Taichung; Lin, K.C.; Chiou, J.F.; Taipei Medical Univ. Hospital, Taipei; Taipei Medical Univ. Hospital, Taipei; Taipei Medical Univ. Hospital, Taipei; Jeng, S.C.; Cheng, W.H.; Chang, C.I.; Lin, W.C.; Wu, L.L.; Lee, H.L.; Chen, R.J.

2013-01-01

Background and purpose: Betel nut chewing is associated with oral cavity cancer in Taiwan. OC3 is an oral carcinoma cell line that was established from cells collected from a long-term betel nut chewer who does not smoke. After we found that microRNA-17-5p (miR-17-5p) is induced in OC3 cells, we used this cell line to examine the biological role(s) of this microRNA in response to exposure to ionizing radiation. Materials and methods: A combined SYBR green-based real-time PCR and oligonucleotide ligation assay was used to examine the expression of the miR-17 polycistron in irradiated OC3 cells. The roles of miR-17-5p and p21 were evaluated with specific antisense oligonucleotides (ODN) that were designed and used to inhibit their expression. Expression of the p21 protein was evaluated by Western blotting. The clonogenic assay and annexin V staining were used to evaluate cell survival and apoptosis, respectively. Cells in which miR-17-5p was stably knocked down were used to create ectopic xenografts to evaluate in vivo the role of miR-17-5p. Results: A radiation dose of 5 Gy significantly increased miR-17-5p expression in irradiated OC3 cells. Inhibition of miR-17-5p expression enhanced the radiosensitivity of the OC3 cells. We found that miR-17-5p downregulates radiation-induced p21 expression in OC3 cells and, by using a tumor xenograft model, it was found that p21 plays a critical role in increasing the radiosensitivity of OC3 cells in vitro and in vivo. Conclusion: miR-17-5p is induced in irradiated OC3 cells and it downregulates p21 protein expression, contributing to the radioresistance of OC3 cells. (orig.)

MicroRNA-17-5p post-transcriptionally regulates p21 expression in irradiated betel quid chewing-related oral squamous cell carcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Wu, S.Y. [Taipei Medical Univ., Wan Fang Hospital, Taipei (China). Dept. of Radiation-Oncology; HungKuang Univ., Taichung (China). Dept. of Biotechnology; Lin, K.C. [Taipei Medical Univ., Wan Fang Hospital, Taipei (China). Dept. of Oral and Maxillofacial Surgery; Chiou, J.F. [Taipei Medical Univ., Taipei (China). Dept. of Radiology; Taipei Medical Univ. Hospital, Taipei (China). Dept. of Radiation Oncology; Taipei Medical Univ. Hospital, Taipei (China). Dept. of Hospice and Palliative Center; Taipei Medical Univ. Hospital, Taipei (China). Cancer Center; Jeng, S.C. [Taipei Medical Univ. Hospital, Taipei (China). Dept. of Radiation Oncology; Cheng, W.H.; Chang, C.I. [Taipei Medical Univ., Wan Fang Hospital, Taipei (China). Dept. of Hemato-Ongology; Lin, W.C. [Taipei Medical Univ., Wan Fang Hospital, Taipei (China). Div. of Thoracic Surgery; Wu, L.L. [National Taiwan Univ. Hospital, Taipei (China). Dept. of Ophthalmology; Lee, H.L. [Taipei Medical Univ., Wan Fang Hospital, Taipei (China). Dept. of Radiation-Oncology; Chen, R.J. [National Taiwan Univ. Hospital and National Taiwan Univ., Taipei (China). Dept. of Obstetrics and Gynecology

2013-08-15

Background and purpose: Betel nut chewing is associated with oral cavity cancer in Taiwan. OC3 is an oral carcinoma cell line that was established from cells collected from a long-term betel nut chewer who does not smoke. After we found that microRNA-17-5p (miR-17-5p) is induced in OC3 cells, we used this cell line to examine the biological role(s) of this microRNA in response to exposure to ionizing radiation. Materials and methods: A combined SYBR green-based real-time PCR and oligonucleotide ligation assay was used to examine the expression of the miR-17 polycistron in irradiated OC3 cells. The roles of miR-17-5p and p21 were evaluated with specific antisense oligonucleotides (ODN) that were designed and used to inhibit their expression. Expression of the p21 protein was evaluated by Western blotting. The clonogenic assay and annexin V staining were used to evaluate cell survival and apoptosis, respectively. Cells in which miR-17-5p was stably knocked down were used to create ectopic xenografts to evaluate in vivo the role of miR-17-5p. Results: A radiation dose of 5 Gy significantly increased miR-17-5p expression in irradiated OC3 cells. Inhibition of miR-17-5p expression enhanced the radiosensitivity of the OC3 cells. We found that miR-17-5p downregulates radiation-induced p21 expression in OC3 cells and, by using a tumor xenograft model, it was found that p21 plays a critical role in increasing the radiosensitivity of OC3 cells in vitro and in vivo. Conclusion: miR-17-5p is induced in irradiated OC3 cells and it downregulates p21 protein expression, contributing to the radioresistance of OC3 cells. (orig.)

Biotin-specific synthetic receptors prepared using molecular imprinting

Energy Technology Data Exchange (ETDEWEB)

Piletska, Elena; Piletsky, Sergey; Karim, Kal; Terpetschnig, Ewald; Turner, Anthony

2004-02-16

The composition of new molecularly imprinted polymers (MIPs) specific for biotin was optimised using molecular modelling software. Three functional monomers: methacrylic acid (MAA), 2-(trifluoromethyl)acrylic acid (TFAA) and 2-acrylamido-2-methylpropanesulfonic acid (AMPSA), which demonstrated the highest binding scores with biotin, were tested on their ability to generate specific binding sites. The imprinted polymers were photografted to the surface of polystyrene microspheres in water. The affinity of the synthetic 'receptor' sites was evaluated in binding experiments using horseradish peroxidase-labelled biotin. Good correlation was found between the modelling results and the performance of the materials in the template re-binding study. The dissociation constants for all MIPs were 1.4-16.8 nM, which is sufficient for most analytical applications where biotin is used as a label.

Biotin-specific synthetic receptors prepared using molecular imprinting

International Nuclear Information System (INIS)

Piletska, Elena; Piletsky, Sergey; Karim, Kal; Terpetschnig, Ewald; Turner, Anthony

2004-01-01

The composition of new molecularly imprinted polymers (MIPs) specific for biotin was optimised using molecular modelling software. Three functional monomers: methacrylic acid (MAA), 2-(trifluoromethyl)acrylic acid (TFAA) and 2-acrylamido-2-methylpropanesulfonic acid (AMPSA), which demonstrated the highest binding scores with biotin, were tested on their ability to generate specific binding sites. The imprinted polymers were photografted to the surface of polystyrene microspheres in water. The affinity of the synthetic 'receptor' sites was evaluated in binding experiments using horseradish peroxidase-labelled biotin. Good correlation was found between the modelling results and the performance of the materials in the template re-binding study. The dissociation constants for all MIPs were 1.4-16.8 nM, which is sufficient for most analytical applications where biotin is used as a label

Effects of electro-acupuncture on ovarian P450arom, P450c17α and mRNA expression induced by letrozole in PCOS rats.

Directory of Open Access Journals (Sweden)

Jie Sun

Full Text Available Hyperandrogenism is a core factor in the series of reproductive and endocrine metabolic disorders involved in polycystic ovary syndrome (PCOS. Abnormalities in enzymatic activity and the expression of ovarian granular cell layer P450arom and theca cell P450c17α can lead to an atypical environment of local ovarian hormones, including excessive androgen levels. Rat models prepared with letrozole exhibit similar endocrine and histological changes to those that occur in human PCOS. We used such a model to study the role of electro-acupuncture (EA in regulating ovarian P450arom and P450c17α enzymatic activity and mRNA expression in PCOS rats. Female Sprague Dawley (SD rats aged 42 days were randomly divided into 3 groups (control, PCOS, and PCOS EA consisting of 10 rats each. The PCOS and PCOS EA groups were administered a gavage of 1.0 mg/kg(-1 of letrozole solution once daily for 21 consecutive days. Beginning in the ninth week, the PCOS EA group was administered low-frequency EA treatment daily for 14 consecutive days. After the treatment, we obtained the following results. The estrous cycles were restored in 8 of the 10 rats in the PCOS EA group, and their ovarian morphologies and ultrastructures normalized. The peripheral blood measurements (with ELISA showed significantly decreased androgens (i.e., androstenedione and testosterone with significantly increased estrogens (i.e., estrone, estradiol and increased P450arom with decreased P450C17α. Immunohistochemistry and Western blotting methods showed enhanced expression of ovarian granular cell layer P450arom as well as decreased expression of theca cell layer P450C17α. Fluorescence quantitative PCR methods showed enhanced expression of ovarian granular cell layer P450arom mRNA as well as decreased expression of theca cell layer P450C17α mRNA. These results may help explain the effects of electro-acupuncture in changing the local ovarian hyperandrogenic environment and improving reproductive

Effects of electro-acupuncture on ovarian P450arom, P450c17α and mRNA expression induced by letrozole in PCOS rats.

Science.gov (United States)

Sun, Jie; Jin, Chunlan; Wu, Huangan; Zhao, Jimeng; Cui, Yunhua; Liu, Huirong; Wu, Lingxiang; Shi, Yin; Zhu, Bing

2013-01-01

Hyperandrogenism is a core factor in the series of reproductive and endocrine metabolic disorders involved in polycystic ovary syndrome (PCOS). Abnormalities in enzymatic activity and the expression of ovarian granular cell layer P450arom and theca cell P450c17α can lead to an atypical environment of local ovarian hormones, including excessive androgen levels. Rat models prepared with letrozole exhibit similar endocrine and histological changes to those that occur in human PCOS. We used such a model to study the role of electro-acupuncture (EA) in regulating ovarian P450arom and P450c17α enzymatic activity and mRNA expression in PCOS rats. Female Sprague Dawley (SD) rats aged 42 days were randomly divided into 3 groups (control, PCOS, and PCOS EA) consisting of 10 rats each. The PCOS and PCOS EA groups were administered a gavage of 1.0 mg/kg(-1) of letrozole solution once daily for 21 consecutive days. Beginning in the ninth week, the PCOS EA group was administered low-frequency EA treatment daily for 14 consecutive days. After the treatment, we obtained the following results. The estrous cycles were restored in 8 of the 10 rats in the PCOS EA group, and their ovarian morphologies and ultrastructures normalized. The peripheral blood measurements (with ELISA) showed significantly decreased androgens (i.e., androstenedione and testosterone) with significantly increased estrogens (i.e., estrone, estradiol) and increased P450arom with decreased P450C17α. Immunohistochemistry and Western blotting methods showed enhanced expression of ovarian granular cell layer P450arom as well as decreased expression of theca cell layer P450C17α. Fluorescence quantitative PCR methods showed enhanced expression of ovarian granular cell layer P450arom mRNA as well as decreased expression of theca cell layer P450C17α mRNA. These results may help explain the effects of electro-acupuncture in changing the local ovarian hyperandrogenic environment and improving reproductive and

Effects of Electro-Acupuncture on Ovarian P450arom, P450c17α and mRNA Expression Induced by Letrozole in PCOS Rats

Science.gov (United States)

Wu, Huangan; Zhao, Jimeng; Cui, Yunhua; Liu, Huirong; Wu, Lingxiang; Shi, Yin; Zhu, Bing

2013-01-01

Hyperandrogenism is a core factor in the series of reproductive and endocrine metabolic disorders involved in polycystic ovary syndrome (PCOS). Abnormalities in enzymatic activity and the expression of ovarian granular cell layer P450arom and theca cell P450c17α can lead to an atypical environment of local ovarian hormones, including excessive androgen levels. Rat models prepared with letrozole exhibit similar endocrine and histological changes to those that occur in human PCOS. We used such a model to study the role of electro-acupuncture (EA) in regulating ovarian P450arom and P450c17α enzymatic activity and mRNA expression in PCOS rats. Female Sprague Dawley (SD) rats aged 42 days were randomly divided into 3 groups (control, PCOS, and PCOS EA) consisting of 10 rats each. The PCOS and PCOS EA groups were administered a gavage of 1.0 mg/kg−1 of letrozole solution once daily for 21 consecutive days. Beginning in the ninth week, the PCOS EA group was administered low-frequency EA treatment daily for 14 consecutive days. After the treatment, we obtained the following results. The estrous cycles were restored in 8 of the 10 rats in the PCOS EA group, and their ovarian morphologies and ultrastructures normalized. The peripheral blood measurements (with ELISA) showed significantly decreased androgens (i.e., androstenedione and testosterone) with significantly increased estrogens (i.e., estrone, estradiol) and increased P450arom with decreased P450C17α. Immunohistochemistry and Western blotting methods showed enhanced expression of ovarian granular cell layer P450arom as well as decreased expression of theca cell layer P450C17α. Fluorescence quantitative PCR methods showed enhanced expression of ovarian granular cell layer P450arom mRNA as well as decreased expression of theca cell layer P450C17α mRNA. These results may help explain the effects of electro-acupuncture in changing the local ovarian hyperandrogenic environment and improving reproductive and

Evaluation of a Group A Streptococcus synthetic oligosaccharide as vaccine candidate.

Science.gov (United States)

Kabanova, Anna; Margarit, Immaculada; Berti, Francesco; Romano, Maria R; Grandi, Guido; Bensi, Giuliano; Chiarot, Emiliano; Proietti, Daniela; Swennen, Erwin; Cappelletti, Emilia; Fontani, Paola; Casini, Daniele; Adamo, Roberto; Pinto, Vittoria; Skibinski, David; Capo, Sabrina; Buffi, Giada; Gallotta, Marilena; Christ, William J; Campbell, A Stewart; Pena, John; Seeberger, Peter H; Rappuoli, Rino; Costantino, Paolo

2010-12-10

Bacterial infections caused by Group A Streptococcus (GAS) are a serious health care concern that currently cannot be prevented by vaccination. The GAS cell-wall polysaccharide (GAS-PS) is an attractive vaccine candidate due to its constant expression pattern on different bacterial strains and protective properties of anti-GAS-PS antibodies. Here we report for the first time the immunoprotective efficacy of glycoconjugates with synthetic GAS oligosaccharides as compared to those containing the native GAS-PS. A series of hexa- and dodecasaccharides based on the GAS-PS structure were prepared by chemical synthesis and conjugated to CRM(197). When tested in mice, the conjugates containing the synthetic oligosaccharides conferred levels of immunoprotection comparable to those elicited by the native conjugate. Antisera from immunized rabbits promoted phagocytosis of encapsulated GAS strains. Furthermore we discuss variables that might correlate with glycoconjugate immunogenicity and demonstrate the potential of the synthetic approach that benefits from increased antigen purity and facilitated manufacturing. Copyright © 2010 Elsevier Ltd. All rights reserved.

The construction of a library of synthetic promoters revealed some specific features of strong Streptomyces promoters

DEFF Research Database (Denmark)

Seghezzi, Nicolas; Amar, Patrick; Købmann, Brian

2011-01-01

Streptomyces are bacteria of industrial interest whose genome contains more than 73% of bases GC. In order to define, in these GC-rich bacteria, specific sequence features of strong promoters, a library of synthetic promoters of various sequence composition was constructed in Streptomyces. To do so...... cloned into the promoter-probe plasmid pIJ487 just upstream of the promoter-less aphII gene that confers resistance to neomycin. This synthetic promoter library was transformed into Streptomyces lividans, and the resulting transformants were screened for their ability to grow in the presence of different...... projects. Thirty-eight promoters were sequenced, and the sequences of the 14 weakest and 14 strongest promoters were compared using the WebLogo software with small sample correction. This comparison revealed that the −10 box, the −10 extended motif as well as the spacer of the strong Streptomyces promoters...

Increasing synthetic serum substitute (SSS) concentrations in P1 glucose/phosphate-free medium improves implantation rate: a comparative study.

Science.gov (United States)

Ben-Yosef, D; Yovel, I; Schwartz, T; Azem, F; Lessing, J B; Amit, A

2001-11-01

To assess the comparative efficacy of IVF medium (MediCult, with 5.2 mM glucose) and a glucose/phosphate-free medium, P1 (Irvine Scientific), and to investigate the influence of increasing the serum supplementation (synthetic serum substitute; SSS; Irvine Scientific) to P1 on embryo development and implantation. Patients were randomly assigned to IVF medium (Group 1, cycles n = 172) or P1 supplemented with 10% SSS (Group 2, cycles n = 229) according to the medium scheduled for use on the day of oocyte retrieval. Another 555 IVF consequent cycles (Group 3) were performed using increased SSS concentrations (20%) in P1 medium. In this large series of IVF cycles, we herein demonstrate that significantly higher pregnancy and implantation rates were found when embryos were cultured in glucose/phosphate-free medium P1 supplemented with 20% SSS compared to supplementation with the lower SSS concentration and with IVF medium.

Enamel surface remineralization: Using synthetic nanohydroxyapatite

Directory of Open Access Journals (Sweden)

J Shanti Swarup

2012-01-01

Full Text Available Objective: The purpose of this study was to evaluate the effects of synthetically processed hydroxyapatite particles in remineralization of the early enamel lesions in comparison with 2% sodium fluoride. Materials and Methods: Thirty sound human premolars were divided into nanohydroxyapatite group (n0 = 15 and the sodium fluoride group (n = 15. The specimens were subjected to demineralization before being coated with 10% aqueous slurry of 20 nm nanohydroxyapatite or 2% sodium fluoride. The remineralizing efficacy of the materials was evaluated using surface microhardness (SMH measurements, scanning microscopic analysis and analysis of the Ca/P ratio of the surface enamel. Data analysis was carried out using paired t-test and independent t-test. Results: The results showed that the nanohydroxyapatite group produced a surface morphology close to the biologic enamel, the increase in mineral content (Ca/P ratio was more significant in the nanohydroxyapatite group ( P 0.05. Conclusion: The use of biomimetic nanohydroxyapatite as a remineralizing agent holds promise as a new synthetic enamel biocompatible material to repair early carious lesions.

Use of an immunodominant p17 antigenic fraction of Neospora caninum in detection of antibody response in cattle

Directory of Open Access Journals (Sweden)

Gema Álvarez García

2006-08-01

Full Text Available A Neospora caninum 17 kDa protein fraction (p17 has been described as an immunodominant antigen (IDA under reducing and non-reducing conditions. The aim of the present study was to investigate the diagnostic utility of p17 in cattle. In order to achieve this, p17 was purified by electroelution from whole N. caninum tachyzoite soluble extract and a p17-based Western blot (WB-p17 was developed. The p17 recognition was measured by densitometry and expressed as OD values to check the validity of the WB-p17. A total of 131 sera including sequential samples from naturally- and experimentally-infected calves and breeding cattle were analysed by WB-p17 and compared with IFAT using whole formalin-fixed tachyzoites as a reference test. The results obtained highlight the feasibility of using the N. caninum p17 in a diagnostic test in cattle. Firstly, the assay based on the p-17 antigen discriminated between known positive and negative sera from different cattle populations, breeding cattle and calves. Secondly, the p17 antigen detected fluctuations in the antibody levels and seroconversion in naturally- and experimentally-infected cattle. Significant differences in p-17 antigen recognition were observed between naturally infected aborting and non-aborting cattle, as well as significant antibody fluctuations over time in experimentally infected cattle, which varied between groups. Furthermore, the results obtained with WB-p17 are in accordance with the results obtained with the IFAT, as high agreement values were obtained when all bovine subpopulations were included (kappa = 0.86.

Differential physiological and behavioral cues observed in individuals smoking botanical marijuana versus synthetic cannabinoid drugs.

Science.gov (United States)

Chase, Peter B; Hawkins, Jeff; Mosier, Jarrod; Jimenez, Ernest; Boesen, Keith; Logan, Barry K; Walter, Frank G

2016-01-01

males) was 20 years (IQR 19-24 years) (p = 0.46). In the synthetic cannabinoid group, 94% (15/16) admitted to using synthetic cannabinoids. In the marijuana group, 96% (24/25) admitted to using marijuana. Blood was available for testing in 96% (24/25) of the marijuana group; 21 of these 24 had quantitative levels of THC (mean + SD = 10.7 + 5 ng/mL) and THC-COOH (mean + SD = 57.8 + 3 ng/mL). Blood was available for testing in 63% (10/16) of the synthetic cannabinoid group, with 80% (8/10) of these positive for synthetic cannabinoids. Those in the synthetic cannabinoid group were more frequently confused (7/16 [44%] vs. 0/25 [0%], p ≤ 0.003) and disoriented (5/16 [31%] vs. 0/25 [0%], p ≤ 0.003), and more frequently had incoherent, slurred speech (10/16 [63%] vs. 3/25 [12%], p = 0.0014) and horizontal gaze nystagmus (8/16 [50%] vs. 3/25 [12%], p = 0.01) than those in the marijuana group. Drivers under the influence of synthetic cannabinoids were more frequently impaired with confusion, disorientation, and incoherent, slurred speech than drivers under the influence of marijuana in this population evaluated by DREs.

Group 5 allergens of timothy grass (Phl p 5) bear cross-reacting T cell epitopes with group 1 allergens of rye grass (Lol p 1).

Science.gov (United States)

Müller, W D; Karamfilov, T; Bufe, A; Fahlbush, B; Wolf, I; Jäger, L

1996-04-01

Selected human T cell clones reactive with group 5 allergens of timothy grass (Phl p 5) were cross-stimulated in specific proliferation assays with group 1 allergens of rye grass (Lol p 1). Such interspecies cross-reactivities result obviously from structural motifs presented on defined Phl p 5 fragments as shown with recombinant Phl p 5 products.

Clinical validation of synthetic brain MRI in children: initial experience

Energy Technology Data Exchange (ETDEWEB)

West, Hollie; Leach, James L.; Jones, Blaise V.; Care, Marguerite; Radhakrishnan, Rupa; Merrow, Arnold C.; Alvarado, Enrique; Serai, Suraj D. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States)

2017-01-15

The purpose of this study was to determine the diagnostic accuracy of synthetic MR sequences generated through post-acquisition processing of a single sequence measuring inherent R1, R2, and PD tissue properties compared with sequences acquired conventionally as part of a routine clinical pediatric brain MR exam. Thirty-two patients underwent routine clinical brain MRI with conventional and synthetic sequences acquired (22 abnormal). Synthetic axial T1, T2, and T2 fluid attenuation inversion recovery or proton density-weighted sequences were made to match the comparable clinical sequences. Two exams for each patient were de-identified. Four blinded reviewers reviewed eight patients and were asked to generate clinical reports on each exam (synthetic or conventional) at two different time points separated by a mean of 33 days. Exams were rated for overall and specific finding agreement (synthetic/conventional and compared to gold standard consensus review by two senior reviewers with knowledge of clinical report), quality, and diagnostic confidence. Overall agreement between conventional and synthetic exams was 97%. Agreement with consensus readings was 84% (conventional) and 81% (synthetic), p = 0.61. There were no significant differences in sensitivity, specificity, or accuracy for specific imaging findings involving the ventricles, CSF, brain parenchyma, or vasculature between synthetic or conventional exams (p > 0.05). No significant difference in exam quality, diagnostic confidence, or noise/artifacts was noted comparing studies with synthetic or conventional sequences. Diagnostic accuracy and quality of synthetically generated sequences are comparable to conventionally acquired sequences as part of a standard pediatric brain exam. Further confirmation in a larger study is warranted. (orig.)

Clinical validation of synthetic brain MRI in children: initial experience

International Nuclear Information System (INIS)

West, Hollie; Leach, James L.; Jones, Blaise V.; Care, Marguerite; Radhakrishnan, Rupa; Merrow, Arnold C.; Alvarado, Enrique; Serai, Suraj D.

2017-01-01

The purpose of this study was to determine the diagnostic accuracy of synthetic MR sequences generated through post-acquisition processing of a single sequence measuring inherent R1, R2, and PD tissue properties compared with sequences acquired conventionally as part of a routine clinical pediatric brain MR exam. Thirty-two patients underwent routine clinical brain MRI with conventional and synthetic sequences acquired (22 abnormal). Synthetic axial T1, T2, and T2 fluid attenuation inversion recovery or proton density-weighted sequences were made to match the comparable clinical sequences. Two exams for each patient were de-identified. Four blinded reviewers reviewed eight patients and were asked to generate clinical reports on each exam (synthetic or conventional) at two different time points separated by a mean of 33 days. Exams were rated for overall and specific finding agreement (synthetic/conventional and compared to gold standard consensus review by two senior reviewers with knowledge of clinical report), quality, and diagnostic confidence. Overall agreement between conventional and synthetic exams was 97%. Agreement with consensus readings was 84% (conventional) and 81% (synthetic), p = 0.61. There were no significant differences in sensitivity, specificity, or accuracy for specific imaging findings involving the ventricles, CSF, brain parenchyma, or vasculature between synthetic or conventional exams (p > 0.05). No significant difference in exam quality, diagnostic confidence, or noise/artifacts was noted comparing studies with synthetic or conventional sequences. Diagnostic accuracy and quality of synthetically generated sequences are comparable to conventionally acquired sequences as part of a standard pediatric brain exam. Further confirmation in a larger study is warranted. (orig.)

Activity of Genital Tract Secretions and Synthetic Antimicrobial Peptides against Group B Streptococcus.

Science.gov (United States)

Agarwal, Nidhi; Buckley, Niall; Nakra, Natasha; Gialanella, Philip; Yuan, Weirong; Ghartey, Jeny P

2015-12-01

Genital tract secretions inhibit Escherichia coli (E. coli) through antimicrobial peptides (AMP) secreted by the host and vaginal microbiota. However, there are limited data against group B Streptococcus (GBS). Group B Streptococcus were incubated with cervico-vaginal lavage (CVL) samples from healthy non-pregnant women (n = 12) or synthetic AMP and monitored for bacterial growth using a turbidimetric approach. E. coli inhibitory activity was determined by a colony-forming unit assay. None of the CVL samples inhibited GBS. The human neutrophil peptide-1 and human defensin 5 inhibited GBS growth by ≥80% at concentrations ≥20 μg/mL and ≥50 μg/mL, respectively, while human beta-defensin 2 and LL-37 did not inhibit at highest concentration tested (100 μg/mL). In contrast, all AMP inhibited E. coli. Antimicrobial peptides may protect against E. coli colonization but have more limited activity against GBS. Future studies will focus on augmenting host defense with specific AMP to prevent genitourinary infection with these pathogenic organisms. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Modulation of P-glycoprotein activity by novel synthetic curcumin derivatives in sensitive and multidrug-resistant T-cell acute lymphoblastic leukemia cell lines

International Nuclear Information System (INIS)

Ooko, Edna; Alsalim, Tahseen; Saeed, Bahjat; Saeed, Mohamed E.M.; Kadioglu, Onat; Abbo, Hanna S.; Titinchi, Salam J.J.; Efferth, Thomas

2016-01-01

Background: Multidrug resistance (MDR) and drug transporter P-glycoprotein (P-gp) represent major obstacles in cancer chemotherapy. We investigated 19 synthetic curcumin derivatives in drug-sensitive acute lymphoblastic CCRF–CEM leukemia cells and their multidrug-resistant P-gp-overexpressing subline, CEM/ADR5000. Material and methods: Cytotoxicity was tested by resazurin assays. Doxorubicin uptake was assessed by flow cytometry. Binding modes of compounds to P-gp were analyzed by molecular docking. Chemical features responsible for bioactivity were studied by quantitative structure activity relationship (QSAR) analyses. A 7-descriptor QSAR model was correlated with doxorubicin uptake values, IC 50 values and binding energies. Results: The compounds displayed IC 50 values between 0.7 ± 0.03 and 20.2 ± 0.25 μM. CEM/ADR5000 cells exhibited cross-resistance to 10 compounds, collateral sensitivity to three compounds and regular sensitivity to the remaining six curcumins. Molecular docking studies at the intra-channel transmembrane domain of human P-gp resulted in lowest binding energies ranging from − 9.00 ± 0.10 to − 6.20 ± 0.02 kcal/mol and pKi values from 0.24 ± 0.04 to 29.17 ± 0.88 μM. At the ATP-binding site of P-gp, lowest binding energies ranged from − 9.78 ± 0.17 to − 6.79 ± 0.01 kcal/mol and pKi values from 0.07 ± 0.02 to 0.03 ± 0.03 μM. CEM/ADR5000 cells accumulated approximately 4-fold less doxorubicin than CCRF–CEM cells. The control P-gp inhibitor, verapamil, partially increased doxorubicin uptake in CEM/ADR5000 cells. Six curcumins increased doxorubicin uptake in resistant cells or even exceeded uptake levels compared to sensitive one. QSAR yielded good activity prediction (R = 0.797 and R = 0.794 for training and test sets). Conclusion: Selected derivatives may serve to guide future design of novel P-gp inhibitors and collateral sensitive drugs to combat MDR. - Highlights: • Novel derivatives of curcumin in reversing multidrug

Modulation of P-glycoprotein activity by novel synthetic curcumin derivatives in sensitive and multidrug-resistant T-cell acute lymphoblastic leukemia cell lines

Energy Technology Data Exchange (ETDEWEB)

Ooko, Edna [Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz (Germany); Alsalim, Tahseen; Saeed, Bahjat [Department of Chemistry, College of Education for Pure Sciences, University of Basrah, P.O. Box 49 Basrah, Al Basrah (Iraq); Saeed, Mohamed E.M.; Kadioglu, Onat [Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz (Germany); Abbo, Hanna S. [Department of Chemistry, University of the Western Cape, P/B X17, Bellville, 7535 Cape Town (South Africa); Titinchi, Salam J.J., E-mail: stitinchi@uwc.ac.za [Department of Chemistry, University of the Western Cape, P/B X17, Bellville, 7535 Cape Town (South Africa); Efferth, Thomas, E-mail: efferth@uni-mainz.de [Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz (Germany)

2016-08-15

Background: Multidrug resistance (MDR) and drug transporter P-glycoprotein (P-gp) represent major obstacles in cancer chemotherapy. We investigated 19 synthetic curcumin derivatives in drug-sensitive acute lymphoblastic CCRF–CEM leukemia cells and their multidrug-resistant P-gp-overexpressing subline, CEM/ADR5000. Material and methods: Cytotoxicity was tested by resazurin assays. Doxorubicin uptake was assessed by flow cytometry. Binding modes of compounds to P-gp were analyzed by molecular docking. Chemical features responsible for bioactivity were studied by quantitative structure activity relationship (QSAR) analyses. A 7-descriptor QSAR model was correlated with doxorubicin uptake values, IC{sub 50} values and binding energies. Results: The compounds displayed IC{sub 50} values between 0.7 ± 0.03 and 20.2 ± 0.25 μM. CEM/ADR5000 cells exhibited cross-resistance to 10 compounds, collateral sensitivity to three compounds and regular sensitivity to the remaining six curcumins. Molecular docking studies at the intra-channel transmembrane domain of human P-gp resulted in lowest binding energies ranging from − 9.00 ± 0.10 to − 6.20 ± 0.02 kcal/mol and pKi values from 0.24 ± 0.04 to 29.17 ± 0.88 μM. At the ATP-binding site of P-gp, lowest binding energies ranged from − 9.78 ± 0.17 to − 6.79 ± 0.01 kcal/mol and pKi values from 0.07 ± 0.02 to 0.03 ± 0.03 μM. CEM/ADR5000 cells accumulated approximately 4-fold less doxorubicin than CCRF–CEM cells. The control P-gp inhibitor, verapamil, partially increased doxorubicin uptake in CEM/ADR5000 cells. Six curcumins increased doxorubicin uptake in resistant cells or even exceeded uptake levels compared to sensitive one. QSAR yielded good activity prediction (R = 0.797 and R = 0.794 for training and test sets). Conclusion: Selected derivatives may serve to guide future design of novel P-gp inhibitors and collateral sensitive drugs to combat MDR. - Highlights: • Novel derivatives of curcumin in reversing

Natural and synthetic polymers in fabric and home care applications

Science.gov (United States)

Paderes, Monissa; Ahirwal, Deepak; Fernández Prieto, Susana

2017-07-01

Polymers can be tailored to provide different benefits in Fabric & Home Care formulations depending on the monomers and modifications used, such as avoiding dye transfer inhibition in the wash, modifying the surface of tiles or increasing the viscosity and providing suspension properties to consumer products. Specifically, the rheology modification properties of synthetic and natural polymers are discussed in this chapter. The choice of a polymeric rheology modifier will depend on the formulation ingredients (charges, functional groups), the type and the amount of surfactants, the pH and the desired rheology modification. Natural polymeric rheology modifiers have been traditionally used in the food industry, being xanthan gum one of the most well-known ones. On the contrary, synthetic rheology modifiers are preferably used in paints & coats, textile printing and cleaning products.

The Prion Concept and Synthetic Prions.

Science.gov (United States)

Legname, Giuseppe; Moda, Fabio

2017-01-01

Transmissible spongiform encephalopathies or prion diseases are a group of fatal neurodegenerative diseases caused by unconventional infectious agents, known as prions (PrP Sc ). Prions derive from a conformational conversion of the normally folded prion protein (PrP C ), which acquires pathological and infectious features. Moreover, PrP Sc is able to transmit the pathological conformation to PrP C through a mechanism that is still not well understood. The generation of synthetic prions, which behave like natural prions, is of fundamental importance to study the process of PrP C conversion and to assess the efficacy of therapeutic strategies to interfere with this process. Moreover, the ability of synthetic prions to induce pathology in animals confirms that the pathological properties of the prion strains are all enciphered in abnormal conformations, characterizing these infectious agents. © 2017 Elsevier Inc. All rights reserved.

pClone: Synthetic Biology Tool Makes Promoter Research Accessible to Beginning Biology Students

Science.gov (United States)

Eckdahl, Todd; Cronk, Brian; Andresen, Corinne; Frederick, Paul; Huckuntod, Samantha; Shinneman, Claire; Wacker, Annie; Yuan, Jason

2014-01-01

The Vision and Change report recommended genuine research experiences for undergraduate biology students. Authentic research improves science education, increases the number of scientifically literate citizens, and encourages students to pursue research. Synthetic biology is well suited for undergraduate research and is a growing area of science. We developed a laboratory module called pClone that empowers students to use advances in molecular cloning methods to discover new promoters for use by synthetic biologists. Our educational goals are consistent with Vision and Change and emphasize core concepts and competencies. pClone is a family of three plasmids that students use to clone a new transcriptional promoter or mutate a canonical promoter and measure promoter activity in Escherichia coli. We also developed the Registry of Functional Promoters, an open-access database of student promoter research results. Using pre- and posttests, we measured significant learning gains among students using pClone in introductory biology and genetics classes. Student posttest scores were significantly better than scores of students who did not use pClone. pClone is an easy and affordable mechanism for large-enrollment labs to meet the high standards of Vision and Change. PMID:26086659

Semi-synthetic preparation of the rare, cytotoxic, deep-sea sourced sponge metabolites discorhabdins P and U.

Science.gov (United States)

Grkovic, Tanja; Kaur, Balwinder; Webb, Victoria L; Copp, Brent R

2006-04-01

Semi-synthetic routes to the enzyme inhibitory and potently anti-proliferative marine natural products discorhabdins P and U were developed by one-step methylation reactions of discorhabdins C and B, respectively. Two novel semi-synthetic derivatives of discorhabdin U were also prepared, one of which (6) exhibited significant anti-proliferative activity.

Thermonuclear reaction rate of 17O(p,γ)18F

International Nuclear Information System (INIS)

Fox, C.; Iliadis, C.; Champagne, A.E.; Fitzgerald, R.P.; Longland, R.; Newton, J.; Pollanen, J.; Runkle, R.

2005-01-01

The 17 O(p,γ) 18 F and 17 O(p,α) 14 N reactions have a profound influence on hydrogen-burning nucleosynthesis in a number of stellar sites, including red giants, asymptotic giant branch (AGB) stars, massive stars, and classical novae. Previously evaluated thermonuclear rates for both reactions carry large uncertainties. We investigated the proton-capture reaction on 17 O in the bombarding energy range of E p lab = 180-540 keV. We observed a previously undiscovered resonance at E R lab = 193.2 ± 0.9 keV. The resonance strength amounts to (ωγ) pγ (1.2±0.2)x10 -6 eV. With this value, the uncertainties of the 17 O(p,γ) 18 F reaction rates are reduced by orders of magnitude in the peak temperature range of classical novae (T=0.1-0.4 GK). We also report on a reevaluation of the 17 O(p,γ) 18 F reaction rates at lower temperatures that are pertinent to red giants, AGB stars, or massive stars. The present work establishes the 17 O(p,γ) 18 F reaction rates over a temperature range of T= 0.01-1.5 GK with statistical uncertainties of 10-50%. The new recommended reaction rates deviate from the previously accepted values by an order of magnitude around T≅0.2 GK and by factors of 2-3 at T < 0.1 GK

Acute Intoxications Involving Synthetic Psychoactive Substances

Directory of Open Access Journals (Sweden)

Sergey A. Vasil'ev

2018-01-01

Full Text Available The purpose of this study was to evaluate the effectiveness of a succinic acid derivate, a substrate metabolic agent cytoflavin in patients with acute poisoning with synthetic psychoactive drugs.Materials and methods. A retrospective evaluation of effectiveness of a combined intensive care treatment protocol for 622 patients with acute narcotic poisoning (methadone and synthetic cannabinoids was carried out. All patients were divided into two groups. The main group (112 patients, median age 38.2±12.0 years included patients who, in addition to the basic treatment, received cytoflavin by intravenous drop infusion, 20–40 ml diluted in 400–500 ml of 10% glucose, for 5 days. Patients of the reference group (510 subjects, median age 37.6±14.1 years received treatment according to the «classical scheme». In addition to conventional examination, all patients underwent duplex scanning of cerebral vessels, examination of changes in the cerebral blood circulation and electroencephalogram findings. The severity of somatic disorders was assessed using criteria of the Glasgow coma scale. The severity of the asthenic syndrome was assessed according to the MFI-20 scale.Results. Compared to patients who received a standard therapy, patients of the main group had a significantly more rapid recovery from coma (by 1.5-fold: 23.5±3.1 days, versus 15.1±3.0 days, respectively, P0.05; the duration of psychotic disorders was shorter (by 1.8-fold: 15.5±4.2 hours vs 8.3±2.5 hours., respectively, P0.05, and the intensity of asthenic syndrome (by 2.8-fold: 64.1±3.3 rel. units vs 23.0±4,9 rel. units, respectively, P0.05 was also lower.Conclusion. Inclusion of cytoflavin in a protocol of a complex treatment of patients with synthetic drugs poisoning increased the effectiveness of the therapy. Data demonstrate that inclusion of the drug can be recommended for treatment of acute synthetic narcotic poisoning. 

Shell model description of 16O(p,γ)17F and 16O(p,p)16O reactions

International Nuclear Information System (INIS)

Bennaceur, K.; Michel, N.; Okolowicz, J.; Ploszajczak, M.; Bennaceur, K.; Nowacki, F.; Okolowicz, J.

2000-01-01

We present shell model calculations of both the structure of 17 F and the reactions 16 O(p,γ) 17 F, 16 O(p,p) 16 O. We use the ZBM interaction which provides a fair description of the properties of 16 O and neighbouring nuclei and, in particular it takes account for the complicated correlations in coexisting low-lying states of 16 O. (authors)

Radically altered T cell receptor signaling in glycopeptide-specific T cell hybridoma induced by antigen with minimal differences in the glycan group

DEFF Research Database (Denmark)

Jensen, T; Nielsen, M; Gad, Monika

2001-01-01

A T cell hybridoma raised against the synthetic glycopeptide T(72)(Tn) was used to study whether the initial TCR signaling events are markedly different when the hybridoma is stimulated with glycopeptides closely related to the cognate glycopeptide antigen. T(72)(Tn) has an alpha-D-GalNAc group O......)(alpha-D-GlcNAc), which differs from T(72)(Tn) solely by the orientation of a hydroxy group in the carbohydrate structure, completely failed to induce detectable tyrosine phosphorylation and IL-2 secretion. APC pulsed with S(72)(Tn), which differs from T(72)(Tn) by not having a methyl group in the serine......-linked to the central threonine in the decapeptide VITAFTEGLK, and the hybridoma is known to be highly specific for this carbohydrate group. T(72)(Tn)-pulsed APC induced tyrosine phosphorylation of the TCR-zeta 21- and 23-kDa proteins and the downstream p42/44 MAP kinase and strong IL-2 secretion. APC pulsed with T(72...

17AAG-induced internalisation of HER2-specific Affibody molecules.

Science.gov (United States)

Göstring, Lovisa; Lindegren, Sture; Gedda, Lars

2016-10-01

The geldanamycin derivative 17-allylamino-17-demethoxygeldanamycin (17-AAG) is known to induce internalisation and degradation of the otherwise internalisation-resistant human epidermal growth factor receptor 2 (HER2) receptor. In the present study, 17-AAG was used to increase internalisation of the HER2-specific Affibody molecule ABY-025. The cellular redistribution of halogen-labelled 211 At-ABY-025 and radiometal-labelled 111 In-ABY-025 following treatment with 17-AAG was studied. 17-AAG treatment of SKOV-3 human ovarian carcinoma and SKBR-3 human breast carcinoma cells to some extent shifted the localisation of 111 In-ABY-025 from the cell surface to intracellular compartments in the two cell lines. ABY-025 labelled with the high-linear energy transfer α emitter 211 At was also internalised to a higher degree; however, due to its physiological properties, this nuclide was excreted faster. The results indicate that 17-AAG may be used to facilitate cell-specific intracellular localisation of a suitable cytotoxic or radioactive agent coupled to ABY-025 in HER2-overexpressing cells.

The classification of p-compact groups for p odd

DEFF Research Database (Denmark)

Andersen, Kasper K. S.; Grodal, Jesper Kragh; Møller, Jesper Michael

2008-01-01

A p-compact group, as defined by Dwyer and Wilkerson, is a purely homotopically defined p-local analog of a compact Lie group. It has long been the hope, and later the conjecture, that these objects should have a classification similar to the classification of compact Lie groups. In this paper we...... groups are uniquely determined as p-compact groups by their Weyl groups seen as finite reflection groups over the p-adic integers. Our approach in fact gives a largely self-contained proof of the entire classification theorem for p odd....

Laboratory measurements of P- and S-wave anisotropy in synthetic rocks by 3D printing

Science.gov (United States)

Kong, L.; Ostadhassan, M.; Tamimi, N.; Li, C.; Alexeyev, A.

2017-12-01

Synthetic rocks have been widely used to realize the models with controlled factors in rock physics and geomechanics experiments. Additive manufacturing technology, known as 3D printing, is becoming a popular method to produce the synthetic rocks as the advantages of timesaving, economics, and control. In terms of mechanical properties, the duplicability of 3D printed rock towards a natural rock has been studied whereas the seismic anisotropy still remains unknown as being the key factor in conducting rock physics experiments. This study utilized a 3D printer with gypsum as the ink to manufacture a series of synthetic rocks that have the shapes of octagonal prisms, with half of them printed from lateral and another half from the bottom. An ultrasonic investigation system was set up to measure the P- and S- wave velocities at different frequencies while samples were under dry conditions. The results show the impact of layered property on the P- and S- wave velocities. The measurement results were compared with the predicted results of Hudson model, demonstrating that the synthetic rock from 3D printing is a transverse isotropic model. The seismic anisotropy indicates that the availability of using 3D printed rocks to duplicate natural rocks for the purpose of recreating the experiments of rock physics. Future experiments will be performed on the dependence of seismic anisotropy on fracture geometry and density in 3D printed synthetic rocks.

Purification of dirucotide, a synthetic 17-aminoacid peptide, by ion exchange centrifugal partition chromatography.

Science.gov (United States)

Boudesocque, Leslie; Forni, Luciano; Martinez, Agathe; Nuzillard, Jean-Marc; Giraud, Matthieu; Renault, Jean-Hugues

2017-09-01

Dirucotide is a synthetic drug candidate for the treatment of multiple sclerosis. This 17-aminoacid peptide was successfully purified by ion exchange centrifugal partition chromatography. The optimized conditions involved the biphasic methyl tert-butyl ether/acetonitrile/n-butanol/water (2:1:2:5, v/v) solvent system in the descending mode, the di(2-ethylhexyl)phosphoric acid cation-exchanger with an exchanger (di(2-ethylhexyl)phosphoric acid)/dirucotide mole ratio of 100 and Ca 2+ ions in aqueous solution as displacer. Critical impurities were efficiently eliminated and dirucotide was recovered in high yield and purity (69% and 98%, respectively) and with a productivity of 2.29g per liter of stationary phase per hour. Copyright © 2017 Elsevier B.V. All rights reserved.

Unveiling Collaborative Group Identities in Social Synthetic Environments from Interaction Data

DEFF Research Database (Denmark)

Grappiolo, Corrado

used to simulate aspects of real-life, yet by maintaining a customisable level of control of the phenomena under investigation. Examples of social synthetic environments are theoretical games and cooperative computer games. The proposed framework is composed of two pipelined modules. The first one....... This dissertation successfully leverages on the hypothesis that it is possible to infer the existence of group structures by solely focusing on the ongoing interactions. The limitations of the approach and possible strategies to overcome them are also proposed....

Dissolving mechanism of strain P17 on insoluble phosphorus of yellow-brown soil

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Zhong Chuan-qing

2014-09-01

Full Text Available Strain P17 was a bacterial strain identified as Bacillus megaterium isolated from ground accumulating phosphate rock powder. The fermentation broth of strain P17 and the yellow-brown soil from Nanjing Agricultural University garden were collected to conduct this study. The simulation of fixed insoluble phosphorous forms after applying calcium superphosphate into yellow-brown soil was performed in pots, while available P and total P of soil were extremely positive correlative with those of groundwater. Then the dissolving effect of strain P17 on insoluble P of yellow-brown soil was studied. Results showed that Bacillus megaterium strain P17 had notable solubilizing effect on insoluble phosphates formed when too much water-soluble phosphorous fertilizer used. During 100 days after inoculation, strain P17 was dominant. Until the 120th day, compared with water addition, available P of strain P17 inoculation treated soil increased by 3 times with calcium superphosphate addition. Besides available P, pH, activity of acid and alkaline phosphatase and population of P-solubilizing microbes were detected respectively. P-solubilizing mechanism of P-solubilizing bacteria strain P17 seems to be a synergetic effect of pH decrease, organic acids, phosphatase, etc.

Plant synthetic biology.

Science.gov (United States)

Liu, Wusheng; Stewart, C Neal

2015-05-01

Plant synthetic biology is an emerging field that combines engineering principles with plant biology toward the design and production of new devices. This emerging field should play an important role in future agriculture for traditional crop improvement, but also in enabling novel bioproduction in plants. In this review we discuss the design cycles of synthetic biology as well as key engineering principles, genetic parts, and computational tools that can be utilized in plant synthetic biology. Some pioneering examples are offered as a demonstration of how synthetic biology can be used to modify plants for specific purposes. These include synthetic sensors, synthetic metabolic pathways, and synthetic genomes. We also speculate about the future of synthetic biology of plants. Copyright © 2015 Elsevier Ltd. All rights reserved.

High mobility group protein number17 cross-links primarily to histone H2A in the reconstituted HMG 17 - nucleosome core particle complex

International Nuclear Information System (INIS)

Cook, G.R.; Yau, P.; Yasuda, H.; Traut, R.R.; Bradbury, E.M.

1986-01-01

The neighbor relationship of lamb thymus High Mobility Group (HMG) protein 17 to native HeLa nucleosome core particle histones in the reconstituted complex has been studied. 125 I-labeled HMG 17 was cross-linking to core histones using the protein-protein cross-linking reagent 2-iminothiolane. Specific cross-linked products were separated on a two-dimensional Triton-acid-urea/SDS gel system, located by autoradiography, excised and quantified. Disulfide bonds in the cross links were then cleaved and the protein constituents were identified by SDS gel electrophoresis. HMG 17 cross-linked primarily to histone H2A while lower levels of cross-linking occurred between HMG 17 and the other histones. In contrast, cross-linking between two HMG 17 molecules bound on the same nucleosome was relatively rare. It is concluded that the same nucleosome was relatively rare. It is concluded that H2A comprises part of the HMG 17 binding site but that HMG 17 is sufficiently elongated and mobile to permit cross-linking to the other histones and to a second HMG 17 molecule. These results are in agreement with the current model for the structure of the nucleosome and the proposed binding sites for HMG 17

Protease-sensitive synthetic prions.

Directory of Open Access Journals (Sweden)

David W Colby

2010-01-01

Full Text Available Prions arise when the cellular prion protein (PrP(C undergoes a self-propagating conformational change; the resulting infectious conformer is designated PrP(Sc. Frequently, PrP(Sc is protease-resistant but protease-sensitive (s prions have been isolated in humans and other animals. We report here that protease-sensitive, synthetic prions were generated in vitro during polymerization of recombinant (rec PrP into amyloid fibers. In 22 independent experiments, recPrP amyloid preparations, but not recPrP monomers or oligomers, transmitted disease to transgenic mice (n = 164, denoted Tg9949 mice, that overexpress N-terminally truncated PrP. Tg9949 control mice (n = 174 did not spontaneously generate prions although they were prone to late-onset spontaneous neurological dysfunction. When synthetic prion isolates from infected Tg9949 mice were serially transmitted in the same line of mice, they exhibited sPrP(Sc and caused neurodegeneration. Interestingly, these protease-sensitive prions did not shorten the life span of Tg9949 mice despite causing extensive neurodegeneration. We inoculated three synthetic prion isolates into Tg4053 mice that overexpress full-length PrP; Tg4053 mice are not prone to developing spontaneous neurological dysfunction. The synthetic prion isolates caused disease in 600-750 days in Tg4053 mice, which exhibited sPrP(Sc. These novel synthetic prions demonstrate that conformational changes in wild-type PrP can produce mouse prions composed exclusively of sPrP(Sc.

Automorphism group of nonabelian groups of order p{sup 3}

Energy Technology Data Exchange (ETDEWEB)

Sarmin, Nor Haniza [Department of Mathematical Sciences, Faculty of Science, Universiti Teknologi Malaysia, 81310 UTM Johor Bahru (Malaysia); Barakat, Yasamin [Department of Mathematical Sciences, Faculty of Science, Universiti Teknologi Malaysia, 81310 UTM Johor Bahru, Malaysia and Islamic Azad University-Ahvaz Branch, Ahvaz (Iran, Islamic Republic of)

2014-06-19

Let G be a nonabelian group of order p{sup 3}, where p is a prime number. Then G is a two generated group that its commutator, centre and Frattini subgroup coincide and are of order p. Hence, the quotient group of G over its centre and also Frattini quotient group of G, both are of order p{sup 2}. However, the first mentioned quotient is isomorphic to the inner group of G, which is a normal subgroup of automorphism group of G. Whereas, Frattini quotient group of G is an abelian elementary group that can be considered as a vector space of dimension two over Z{sub p}, the field of integers modulo p. In this paper, we consider to apply these properties of G to characterize the automorphism group of G.

Waterproofing with polymeric geo synthetic barriers (GBR-P) in the manual for the design, construction, management and maintenance of reservoirs; La impermeabilizacion con barreras geosinteticas polimericas (GBR-P) en el manual para el diseno, construccion, explotacion y mantenimiento de balsas

Energy Technology Data Exchange (ETDEWEB)

Blanco, M.; Cea, J. C.; Garcia, F.; Sanchez, F. J.; Castillo, F.; Mora, J.; Crespo, M. A.

2010-07-01

This article presents a part of Manual for the Design, Construction, Management and Maintenance of Reservoirs relative to waterproofing with Polymeric Geo synthetic Barriers (GBR-P). the nature materials of geo membranes is studied also theirs characteristics and specifications. (Author) 26 refs.

Comparative study of hydroxyapatite from eggshells and synthetic hydroxyapatite for bone regeneration.

Science.gov (United States)

Lee, Sang-Woon; Kim, Seong-Gon; Balázsi, Csaba; Chae, Weon-Sik; Lee, Hee-Ok

2012-03-01

The objective of this study was to evaluate the physical properties of synthetic hydroxyapatite (sHA) and hydroxyapatite from eggshells (eHA) by Fourier-transform infrared (FT-IR) and x-ray diffraction (XRD) and to compare the regenerative ability of the bone using sHA and eHA in a rabbit calvarial defect model. FT-IR and XRD were used to compare the physical properties of sHA and eHA. sHA was purchased from Sigma, and eHA was kindly donated from the Hungarian academy of science. Sixteen New Zealand white rabbits were used for the animal study. After the formation of a bilateral parietal bony defect (diameter 8.0 mm), either sHA or eHA was grafted into the defect. The defect in the control was left unfilled. Bone regeneration was evaluated by histomorphometry at 4 and 8 weeks after the operation. The peak broadening of the XRD experiments were in agreement with scanning electron microscope observation; the sHA had a smaller granule size than the eHA. The eHA had impurities phases of CaO (International Center for Diffraction Data (ICDD) 075-0264) and Ca(OH)(2) (ICDD 072-0156). Total new bone was 17.11 ± 10.24% in the control group, 28.81 ± 12.63% in sHA group, and 25.68 ± 10.89% in eHA group at 4 weeks after the operation. The difference was not statistically significant (P > .05). Total new bone at 8 weeks after the operation was 27.50 ± 10.89% in the control group, 38.62 ± 17.42% in sHA group, and 41.99 ± 8.44% in the eHA group. When comparing the sHA group to the control group, the difference was not statistically significant (P > .05). However, the eHA group was significantly different from the control group (P = .038). When comparing the eHA group to the sHA group, the difference was not statistically significant (P > .05). Both types of HA showed higher bone formation than the unfilled control. However, eHA had significantly higher bone formation than the unfilled control at 8 weeks after operation. Copyright © 2012 Elsevier Inc. All rights reserved.

Exploration and pharmacokinetic profiling of phenylalanine based carbamates as novel substance p 1-7 analogues.

Science.gov (United States)

Fransson, Rebecca; Nordvall, Gunnar; Bylund, Johan; Carlsson-Jonsson, Anna; Kratz, Jadel M; Svensson, Richard; Artursson, Per; Hallberg, Mathias; Sandström, Anja

2014-12-11

The bioactive metabolite of Substance P, the heptapeptide SP1-7 (H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH), has been shown to attenuate signs of hyperalgesia in diabetic mice, which indicate a possible use of compounds targeting the SP1-7 binding site as analgesics for neuropathic pain. Aiming at the development of drug-like SP1-7 peptidomimetics we have previously reported on the discovery of H-Phe-Phe-NH2 as a high affinity lead compound. Unfortunately, the pharmacophore of this compound was accompanied by a poor pharmacokinetic (PK) profile. Herein, further lead optimization of H-Phe-Phe-NH2 by substituting the N-terminal phenylalanine for a benzylcarbamate group giving a new type of SP1-7 analogues with good binding affinities is reported. Extensive in vitro as well as in vivo PK characterization is presented for this compound. Evaluation of different C-terminal functional groups, i.e., hydroxamic acid, acyl sulfonamide, acyl cyanamide, acyl hydrazine, and oxadiazole, suggested hydroxamic acid as a bioisosteric replacement for the original primary amide.

[Effects of electroacupuncture of "Guanyuan" (CV 4)-"Zhongji" (CV 3) on ovarian P450 arom and P450c 17alpha expression and relevant sex hormone levels in rats with polycystic ovary syndrome].

Science.gov (United States)

Sun, Jie; Zhao, Ji-meng; Ji, Rong; Liu, Hui-rong; Shi, Yin; Jin, Chun-lan

2013-12-01

To observe the effect of electroacupuncture (EA) on ovarian P 450 arom and P 450 c 17 alpha (aromatases) expression and related sex hormone levels in polycystic ovary syndrome (PCOS) rats. Thirty SD rats were randomly divided into normal control group, model group and EA group (10 rats/group). PCOS model was made by intragastric administration of letrozole at 1 mg/kg per day for consecutive 21 days. "Guanyuan" (CV 4) and "Zhongji" (CV 3) acupoints were stimulated 20 min by EA (2 mA, 2 Hz), once daily for consecutive 14 days. The damp ovarian weight was weighed and the pathological changes of the ovarian tissue were observed after H. E. staining. Ultrastructural changes of the ovarian tissue were observed by transmission electron microscope. Immunohistochemical staining was adopted to detect ovarian follicle granulosa cell P 450 arom and follicle membrane cell P 450 c 17 alpha expression. The contents of estradiol (E 2), estrone (E 1), androstenedione (ASD), testosterone (T), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the ovarian tissue were measured by ELISA. Compared with the normal group, there was a significant increase in the damp weight of both left and right ovarian tissues in the model group (P ovarian weight was remarkably reduced (P ovarian tissue such as thickening of the superficial albugineous coat of the ovary, thinning of the granular cell layer, and disappearance of the intraovular oocytes and coronaradiata under light microscope, and mitochondrion swelling, fracture or disappearance of mitochondrial cristae, and enlargement of the endoplasmic reticulum, etc. after modeling were obviously improved in the EA group. In comparison to the control group, the expression of the follicle granulosa cell P450 arom was significantly down-regulated and that of follicle membrane cell P 450 c 17 alpha was significantly upregulated in the model group (P ovarian tissues (P ovarian E 1 and E2 (P ovarian ASD, T and LH levels were notably

The potential of species-specific tagatose-6-phosphate (T6P) pathway in Lactobacillus casei group for galactose reduction in fermented dairy foods.

Science.gov (United States)

Wu, Qinglong; Shah, Nagendra P

2017-04-01

Residual lactose and galactose in fermented dairy foods leads to several industrial and health concerns. There is very little information pertaining to manufacture of fermented dairy foods that are low in lactose and galactose. In the present study, comparative genomic survey demonstrated the constant presence of chromosome-encoded tagatose-6-phosphate (T6P) pathway in Lactobacillus casei group. Lactose/galactose utilization tests and β-galactosidase assay suggest that PTS Gal system, PTS Lac system and T6P pathway are major contributors for lactose/galactose catabolism in this group of organisms. In addition, it was found than lactose catabolism by Lb. casei group accumulated very limited galactose in the MRS-lactose medium and in reconstituted skim milk, whereas Streptococcus thermophilus and Lb. delbrueckii subsp. bulgaricus (Lb. bulgaricus) strains secreted high amount of galactose extracellularly. Moreover, co-culturing Lb. casei group with Str. thermophilus showed significant reduction in galactose content, while co-culturing Lb. casei group with Lb. bulgaricus showed significant reduction in lactose content but significant increase in galactose content in milk. Overall, the present study highlighted the potential of Lb. casei group for reducing galactose accumulation in fermented milks due to its species-specific T6P pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

Allogeneic stem cell transplant in patients with chronic lymphocytic leukemia with 17p deletion: consult-transplant versus consult- no-transplant analysis.

Science.gov (United States)

Poon, Michelle L; Fox, Patricia S; Samuels, Barry I; O'Brien, Susan; Jabbour, Elias; Hsu, Yvonne; Gulbis, Alison; Korbling, Martin; Champlin, Richard; Abruzzo, Lynne V; Bassett, Roland L; Khouri, Issa F

2015-03-01

Allogeneic stem cell transplant (alloSCT) can overcome the adverse prognosis of chronic lymphocytic leukemia with 17p deletion (17p- CLL). However, its applicability remains unclear. Since 2007, our leukemia service has referred patients with 17p- CLL for alloSCT at presentation. In this study, the outcomes of these patients were reviewed retrospectively to determine whether they underwent alloSCT and why patients did not undergo alloSCT. Fifty-two patients with 17p- CLL who were referred to the transplant service from 2007 to 2010 were identified. Of these patients, 32 (62%) did not undergo alloSCT, mainly because of treatment- or disease-related complications (n = 15). The 2-year post-referral overall survival rates of the alloSCT and non-SCT groups were 64% and 25%, respectively (p = 0.001). These findings suggest that while alloSCT is an effective therapy in patients with 17p- CLL, pre-SCT complications may preclude a significant proportion of patients from undergoing the procedure.

Microdeletion in distal 17p13.1

DEFF Research Database (Denmark)

Zeesman, Susan; Kjaergaard, Susanne; Hove, Hanne Buciek

2012-01-01

Array comparative genomic hybridization has led to the identification of new syndromes by identifying genomic imbalances not detectable by standard karyotyping methods and by allowing correlations with physical findings. Deletions in the 17p13.1 region have been reported in patients with dysmorphic...

Synthetic protease substrate n-benzoyl-L-argininyl-p-nitroanilide activates specific binding of [3H]estradiol to a protein in rat pancreas: relationship of structure to activity

International Nuclear Information System (INIS)

Grossman, A.

1984-01-01

N-benzoyl-L-argininyl-p-nitroanilide (BAN), a synthetic substrate for trypsin-like proteolytic enzymes, is a potent activator of [ 3 H]estradiol-binding to a protein present in rat pancreas. When partially purified, this protein is almost devoid of [ 3 H]estradiol-binding activity in the absence of an endogenous accessory factor. BAN can mimic the natural coligand in this steroid binding reaction. The effect of BAN is specific since a number of derivatives of this substance are inactive or may even inhibit steroid binding. It is unlikely that BAN exerts this stimulatory action indirectly, possibly by preventing proteolytic inactivation of the [ 3 H]estradiol-binding protein, since preincubation of the protein in the absence of BAN resulted neither in reduced rate, nor extent, of steroid binding following BAN addition. Also, a number of protease inhibitors had no effect on the binding reaction. Of those inhibitors tested, only antipain significantly enhanced binding of [ 3 H]estradiol, but only about 20 percent as effectively as BAN. 13 references, 1 figure, 2 tables

Determination of Ca, P, Sr and Mg in the synthetic biomaterial aragonite by NAA

International Nuclear Information System (INIS)

Oudadesse, H.; Derrien, A.C.; Lucas-Girot, A.

2004-01-01

In orthopaedic surgery, synthetic biomaterials encountered a great success. In this work, the 'in-vivo' behaviour of aragonite synthesized in our laboratory was studied. The in vivo experiments have been carried out on femurs sites of nine ovine. Neutron activation analysis was applied to evaluate the ossification kinetics of synthetic aragonite. The content of several elements (Ca, P, Sr and Mg and phosphorous to calcium ratio) were determined versus time after implantation. Results showed that the biomaterial undergoes a lot of transformations during time. The chemical composition of the aragonite was modified and progress to become close to that of an ovine bone. Biological studies assess its biocompatibility. (author)

In Situ Proteolysis for Crystallization of Membrane Bound Cytochrome P450 17A1 and 17A2 Proteins from Zebrafish.

Science.gov (United States)

Lei, Li; Egli, Martin

2016-04-01

Fish and human cytochrome P450 (P450) 17A1 catalyze both steroid 17α-hydroxylation and 17α,20-lyase reactions. Fish P450 17A2 catalyzes only 17α-hydroxylation. Both enzymes are microsomal-type P450s, integral membrane proteins that bind to the membrane through their N-terminal hydrophobic segment, the signal anchor sequence. The presence of this N-terminal region renders expression of full-length proteins challenging or impossible. For some proteins, variable truncation of the signal anchor sequence precludes expression or results in poor expression levels. To crystallize P450 17A1 and 17A2 in order to gain insight into their different activities, we used an alternative N-terminal sequence to boost expression together with in situ proteolysis. Key features of our approach to identify crystallizable P450 fragments were the use of an N-terminal leader sequence, a screen composed of 12 proteases to establish optimal cleavage, variations of protease concentration in combination with an SDS-PAGE assay, and analysis of the resulting fragments using Edman sequencing. Described in this unit are protocols for vector preparation, expression, purification, and in situ proteolytic crystallization of two membrane-bound P450 proteins. Copyright © 2016 John Wiley & Sons, Inc.

Synthetic prions and other human neurodegenerative proteinopathies.

Science.gov (United States)

Le, Nhat Tran Thanh; Narkiewicz, Joanna; Aulić, Suzana; Salzano, Giulia; Tran, Hoa Thanh; Scaini, Denis; Moda, Fabio; Giachin, Gabriele; Legname, Giuseppe

2015-09-02

Transmissible spongiform encephalopathies (TSE) are a heterogeneous group of neurodegenerative disorders. The common feature of these diseases is the pathological conversion of the normal cellular prion protein (PrP(C)) into a β-structure-rich conformer-termed PrP(Sc). The latter can induce a self-perpetuating process leading to amplification and spreading of pathological protein assemblies. Much evidence suggests that PrP(Sc) itself is able to recruit and misfold PrP(C) into the pathological conformation. Recent data have shown that recombinant PrP(C) can be misfolded in vitro and the resulting synthetic conformers are able to induce the conversion of PrP(C) into PrP(Sc)in vivo. In this review we describe the state-of-the-art of the body of literature in this field. In addition, we describe a cell-based assay to test synthetic prions in cells, providing further evidence that synthetic amyloids are able to template conversion of PrP into prion inclusions. Studying prions might help to understand the pathological mechanisms governing other neurodegenerative diseases. Aggregation and deposition of misfolded proteins is a common feature of several neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and other disorders. Although the proteins implicated in each of these diseases differ, they share a common prion mechanism. Recombinant proteins are able to aggregate in vitro into β-rich amyloid fibrils, sharing some features of the aggregates found in the brain. Several studies have reported that intracerebral inoculation of synthetic aggregates lead to unique pathology, which spread progressively to distal brain regions and reduced survival time in animals. Here, we review the prion-like features of different proteins involved in neurodegenerative disorders, such as α-synuclein, superoxide dismutase-1, amyloid-β and tau. Copyright © 2014 Elsevier B.V. All rights reserved.

Hybrid Synthetic Receptors on MOSFET Devices for Detection of Prostate Specific Antigen in Human Plasma.

Science.gov (United States)

Tamboli, Vibha K; Bhalla, Nikhil; Jolly, Pawan; Bowen, Chris R; Taylor, John T; Bowen, Jenna L; Allender, Chris J; Estrela, Pedro

2016-12-06

The study reports the use of extended gate field-effect transistors (FET) for the label-free and sensitive detection of prostate cancer (PCa) biomarkers in human plasma. The approach integrates for the first time hybrid synthetic receptors comprising of highly selective aptamer-lined pockets (apta-MIP) with FETs for sensitive detection of prostate specific antigen (PSA) at clinically relevant concentrations. The hybrid synthetic receptors were constructed by immobilizing an aptamer-PSA complex on gold and subjecting it to 13 cycles of dopamine electropolymerization. The polymerization resulted in the creation of highly selective polymeric cavities that retained the ability to recognize PSA post removal of the protein. The hybrid synthetic receptors were subsequently used in an extended gate FET setup for electrochemical detection of PSA. The sensor was reported to have a limit of detection of 0.1 pg/mL with a linear detection range from 0.1 pg/mL to 1 ng/mL PSA. Detection of 1-10 pg/mL PSA was also achieved in diluted human plasma. The present apta-MIP sensor developed in conjunction with FET devices demonstrates the potential for clinical application of synthetic hybrid receptors for the detection of clinically relevant biomarkers in complex samples.

Inhibitory effects of 131I labeled 17-allylamino-17-demethoxygeldanamycin on breast cancer cell line

International Nuclear Information System (INIS)

Chen Daozhen; Liu Lu; Jiang Xinyu; Huang Ying; Yang Min; Yu Huixin; Luo Shineng; Lin Xiufeng

2007-01-01

Objective: 17-allylamino-17-demethoxygeldanamycin(17-AAG) is a less toxic analogue of geldanamycin (GA) that retains the tumoricidal features of GA. Same as its parent compound, 17-AAG inhibits several signaling pathways through binding to heat shock protein (HSP) 90, which results in destabilization of signaling complexes and degradation of client proteins in a variety of tumor cell growth. Treatment with 17-AAG was effective to inhibit tumor growth and induce apoptosis in colon cancer, glioblastoma, and breast cancer cell lines. This study aimed at exploring the anti-proliferation effects and mechanism of 131 I labeled 17-AAG on human breast cancer cell line MCF-7. Methods: 131 I-17-AAG was prepared by the reaction of 17-AAG with Na 131 I in the presence of hydrogen peroxide. The MCF-7 cells were divided into 5 groups with different additional drugs: group A, dimethyl sulfoxide (DMSO); group B, 370 kBq Na 131 I; group C, 2.5 mg/L 17-AAG; group D, 370 kBq 131 I-17-AAG; group E, 370 kBq 131 I-17-AAG + 2.5 mg/L 17-AAG. 3- (4,5-dimethylthiazol-2-yl)-2,5, diphenylte-trazolium bromide (MTT) assay was used to evaluate the effect of growth inhibition of MCF-7 cells. Cell cycle and apoptosis were analyzed by flow cytometry. The change of the expression of Akt2 mRNA in MCF-7 cells was examined by RT-PCR. Results: The labeling yield of 131 I-17-AAG was 83%. The radiochemical purity of 131 I-17-AAG after purification was 96.6%. The specific activity was 1.48 x 10 5 MBq/μmol. All drugs could significantly inhibit the growth of MCF-7 cells in vitro as the duration lasts longer, especially for group E. After 48 h, sub-G1 peaks detected by flow cytometry were(1.54±0.13)%, (5.72±1.05)%, (12.97±1.44)%, (20.65±1.36)%, (35.39±4.15)% for group A, B, C, D and E, respectively. The experimental groups (B-E) were all significantly higher than the control group (A, all P 131 I-17-AAG could suppress the growth of human breast cancer cell line MCF-7 and hasten the apoptosis. It could

Adsorption of hydrogen sulfide gas on several synthetic zeolites

Energy Technology Data Exchange (ETDEWEB)

Fukui, T; Ise, Y; Boki, K; Tanada, S

1974-07-01

Ten kinds of synthetic zeolites were tested to determine the most suitable adsorbent for H/sub 2/S gas removal by a dry process. Specific surface area with argon gas and H/sub 2/S gas, surface pH, and thermodynamic data of adsorbents were measured. The amounts of H/sub 2/S gas adsorbed on synthetic zeolite adsorbents were affected in terms of the pore sizes of the adsorbents rather than the surface pH and the thermodynamic factors. The adsorbents No. 3, No. 7, and No. 8 showed higher adsorption of H/sub 2/S than the other adsorbents and were the most suitable for practical purposes.

Generation and characterization of polyclonal antibodies specific to N-terminal extension of p85 isoform of ribosomal protein S6 kinase 1 (p85 S6K1

Directory of Open Access Journals (Sweden)

Savinska L. O.

2015-08-01

Full Text Available Aim. Generation of polyclonal antibodies specific to the ribosomal protein S6 kinase isoform – p85S6K1 and directed to the N-terminal (1–23 aa extension of p85S6K1. Methods. Animal immunization with synthetic (1–23 aa peptide, ELISA, Western blot, Immunoprecipitation, immunofluorescent analysis. Results. Polyclonal antibodies have been generated, which specifically recognize only p85 but not p70 isoform of S6K1 in western blot, immunoprecipitation and immunofluorescence analysis. Conclusions. The obtained antibodies can be recommended for studies on the p85S6K1 and other S6K1 isoforms possessing the N-terminal extension – the identification of binding protein partners, analysis of subcellular localization under different physiological conditions, elucidation of the signal transduction pathways involving different S6K1 isoforms.

In vivo evaluation of biofunctionalized implant surfaces with a synthetic peptide (P-15) and its impact on osseointegration. A preclinical animal study.

Science.gov (United States)

Schmitt, Christian M; Koepple, Markus; Moest, Tobias; Neumann, Konrad; Weisel, Tamara; Schlegel, Karl Andreas

2016-11-01

The overall aim of the study was to investigate a biofunctionalized implant surface with electrochemically deposition of hydroxyapatite and the synthetic peptide (P-15) and its effect on osseointegration. Three modified implant types of ANKYLOS ® C/X implants were used; (1) machined implants used as negative control (M, n = 20), (2) implants with the FRIADENT ® plus surface (grit blasted and acid-etched) used as positive control (P, n = 20), and (3) implants with a biomimetic surface consisting of hydroxyapatite and the synthetic 15 aminoacids containing peptide P-15 (BP, n = 40). The implants were randomly inserted in the mandibles of 10 beagle dogs following 4 months after tooth extraction (P1-P4). Three animals were sacrificed 2 and 7 days after implant insertion, respectively, and four animals were sacrificed 6 months post implant insertion. Bone-to-implant contacts (BICs) were analyzed via histomorphometrical analyses at five different region of interests (ROIs); two at the middle part on either side of the implant (ROI 1/4), two at the apical part of the implant at each side (ROI 2/3), and one at the tip of the implant (ROI 5). All implant surfaces showed a high level of osseointegration and osteoconductivity. The cumulative implant survival rate (CSR) was 93.8%, 100% in the M, 85% in the P, and 95% in the BP group. No statistical difference in BICs at ROI 1/4, 2/3, and 5 could be shown between implant types following 2 and 7 days of healing. BIC values increased in all groups over time. After 6 months of healing the BP group showed superiority in BIC in ROI 2/3 (73.2 ± 15.6%) compared to the P (48.3 ± 10.6%) and M group (66.3 ± 30.2%) with a significant difference between BP and P (P = 0.002). It is hypothesized, that the surface biofunctionalization improves peri-implant bone formation and remodeling, leading to an increased bone-to implant contact. However, within the limitations of the study set-up no benefit in the early phase of

Stability of Synthetic Cathinones in Urine.

Science.gov (United States)

Glicksberg, Lindsay; Kerrigan, Sarah

2018-03-01

In this report, we evaluate the concentration, pH, temperature and analyte-dependent effects on cathinone stability in preserved human urine. A total of 22 synthetic cathinones were evaluated at 100 ng/mL and 1,000 ng/mL in pH 4 and pH 8 urine over 6 months. Specimens were stored at -20°C, 4°C, 20°C and 32°C. The stability of synthetic cathinones was highly dependent on urine pH and storage temperature. Cathinones were considerably more stable in acidic urine (pH 4) at low temperature. In alkaline urine (pH 8) at 32°C, significant losses (>20%) were observed within hours for the majority of drugs. In contrast, all drugs were stable in frozen and refrigerated urine at pH 4 for the duration of the study. These results highlight the importance of sample storage and the potential for pre-analytical changes in concentration during routine shipping and handling of specimens. Significant structural influence was also observed. Cathinones bearing a tertiary amine (pyrrolidine group) were significantly more stable than their secondary amine counterparts. The methylenedioxy group also exerted a significant stabilizing effect on both the tertiary and secondary amines. In the absence of the methylenedioxy group, no significant differences in stability were observed between the unsubstituted and ring substituted secondary amines. Half-lives at ambient temperature in pH 8 urine ranged from 9 h (3-fluoromethcathinone) to 4.3 months (methylenedioxypyrovalerone and 3,4-methylenedioxy-α-pyrrolidinobutiophenone), demonstrating the importance of analyte dependence, and the dual stabilizing effect of both the pyrollidine and methylenedioxy groups. Biological evidence may be subjected to a variety of environmental conditions prior to, and during transport to the forensic laboratory. These findings demonstrate the inherent instability of certain cathinone species in biological evidence under some conditions. Moreover, this study highlights the need for quantitative drug findings in

Amine-derived synthetic approach to color-tunable InP/ZnS quantum dots with high fluorescent qualities

International Nuclear Information System (INIS)

Song, Woo-Seuk; Lee, Hye-Seung; Lee, Ju Chul; Jang, Dong Seon; Choi, Yoonyoung; Choi, Moongoo; Yang, Heesun

2013-01-01

High-quality, Cd-free InP quantum dots (QDs) have been conventionally synthesized by exclusively selecting tris(trimethylsilyl)phosphine (P(TMS) 3 ) as a phosphorus (P) precursor, which is problematic from the standpoint of green and economic chemistry. Thus, other synthetic chemistries adopting alternative P sources to P(TMS) 3 have been introduced, however, they could not guarantee the production of satisfactorily fluorescence-efficient, color-pure InP QDs. In this study, the unprecedented controlled synthesis of a series of band-gap-tuned InP QDs is demonstrated through a hot-injection of a far safer and cheaper tris(dimethylamino)phosphine in the presence of a key coordinating solvent of oleylamine that enables successful QD nucleation/growth. Effects of the co-existence of Zn additive, the core growth temperature, and the amount of P source injected on the growth behaviors of InP QD are investigated. After ZnS overcoating by a successive injection of 1-dodecanethiol only, high-fluorescence-quality, green-to-red color emission-tunable core/shell QDs of InP/ZnS are obtained. The fluorescent characteristics of different color-emitting QDs desirably exhibit little fluctuations in quantum yield and emission bandwidth, specifically ranging 51–53 % and 60–64 nm, respectively. Lastly, the utility of the introduction of a secondary shelling process in rendering the QDs are more bright, photostable is also proved.

Amine-derived synthetic approach to color-tunable InP/ZnS quantum dots with high fluorescent qualities

Science.gov (United States)

Song, Woo-Seuk; Lee, Hye-Seung; Lee, Ju Chul; Jang, Dong Seon; Choi, Yoonyoung; Choi, Moongoo; Yang, Heesun

2013-06-01

High-quality, Cd-free InP quantum dots (QDs) have been conventionally synthesized by exclusively selecting tris(trimethylsilyl)phosphine (P(TMS)3) as a phosphorus (P) precursor, which is problematic from the standpoint of green and economic chemistry. Thus, other synthetic chemistries adopting alternative P sources to P(TMS)3 have been introduced, however, they could not guarantee the production of satisfactorily fluorescence-efficient, color-pure InP QDs. In this study, the unprecedented controlled synthesis of a series of band-gap-tuned InP QDs is demonstrated through a hot-injection of a far safer and cheaper tris(dimethylamino)phosphine in the presence of a key coordinating solvent of oleylamine that enables successful QD nucleation/growth. Effects of the co-existence of Zn additive, the core growth temperature, and the amount of P source injected on the growth behaviors of InP QD are investigated. After ZnS overcoating by a successive injection of 1-dodecanethiol only, high-fluorescence-quality, green-to-red color emission-tunable core/shell QDs of InP/ZnS are obtained. The fluorescent characteristics of different color-emitting QDs desirably exhibit little fluctuations in quantum yield and emission bandwidth, specifically ranging 51-53 % and 60-64 nm, respectively. Lastly, the utility of the introduction of a secondary shelling process in rendering the QDs are more bright, photostable is also proved.

Amine-derived synthetic approach to color-tunable InP/ZnS quantum dots with high fluorescent qualities

Energy Technology Data Exchange (ETDEWEB)

Song, Woo-Seuk; Lee, Hye-Seung [Hongik University, Department of Materials Science and Engineering (Korea, Republic of); Lee, Ju Chul; Jang, Dong Seon; Choi, Yoonyoung; Choi, Moongoo [LGE Advanced Research Institute, LG Electronics, Materials and Devices Laboratory (Korea, Republic of); Yang, Heesun, E-mail: hyang@hongik.ac.kr [Hongik University, Department of Materials Science and Engineering (Korea, Republic of)

2013-06-15

High-quality, Cd-free InP quantum dots (QDs) have been conventionally synthesized by exclusively selecting tris(trimethylsilyl)phosphine (P(TMS){sub 3}) as a phosphorus (P) precursor, which is problematic from the standpoint of green and economic chemistry. Thus, other synthetic chemistries adopting alternative P sources to P(TMS){sub 3} have been introduced, however, they could not guarantee the production of satisfactorily fluorescence-efficient, color-pure InP QDs. In this study, the unprecedented controlled synthesis of a series of band-gap-tuned InP QDs is demonstrated through a hot-injection of a far safer and cheaper tris(dimethylamino)phosphine in the presence of a key coordinating solvent of oleylamine that enables successful QD nucleation/growth. Effects of the co-existence of Zn additive, the core growth temperature, and the amount of P source injected on the growth behaviors of InP QD are investigated. After ZnS overcoating by a successive injection of 1-dodecanethiol only, high-fluorescence-quality, green-to-red color emission-tunable core/shell QDs of InP/ZnS are obtained. The fluorescent characteristics of different color-emitting QDs desirably exhibit little fluctuations in quantum yield and emission bandwidth, specifically ranging 51-53 % and 60-64 nm, respectively. Lastly, the utility of the introduction of a secondary shelling process in rendering the QDs are more bright, photostable is also proved.

Clonal Ordering of 17p and 5q Allelic Losses in Barrett Dysplasia and Adenocarcinoma

Science.gov (United States)

Blount, Patricia L.; Meltzer, Stephen J.; Yin, Jing; Huang, Ying; Krasna, Mark J.; Reid, Brian J.

1993-04-01

Both 17p and 5q allelic losses appear to be involved in the pathogenesis or progression of many human solid tumors. In colon carcinogenesis, there is strong evidence that the targets of the 17p and 5q allelic losses are TP53, the gene encoding p53, and APC, respectively. It is widely accepted that 5q allelic losses precede 17p allelic losses in the progression to colonic carcinoma. The data, however, supporting this proposed order are largely based on the prevalence of 17p and 5q allelic losses in adenomas and unrelated adenocarcinomas from different patients. We investigated the order in which 17p and 5q allelic losses developed during neoplastic progression in Barrett esophagus by evaluating multiple aneuploid cell populations from the same patient. Using DNA content flow cytometric cell sorting and polymerase chain reaction, 38 aneuploid cell populations from 14 patients with Barrett esophagus who had high grade dysplasia, cancer or both were evaluated for 17p and 5q allelic losses. 17p allelic losses preceded 5q allelic losses in 7 patients, both 17p and 5q allelic losses were present in all aneuploid populations of 4 patients, and only 17p (without 5q) allelic losses were present in the aneuploid populations of 3 patients. In no patient did we find that a 5q allelic loss preceded a 17p allelic loss. Our data suggest that 17p allelic losses typically occur before 5q allelic losses during neoplastic progression in Barrett esophagus.

Allelic imbalance and fine mapping of the 17p13.3 subregion in sporadic breast carcinomas

DEFF Research Database (Denmark)

Hoff, C; Mollenhauer, J; Waldau, B

2001-01-01

Chromosome arm 17p is frequently altered in a variety of human cancers, especially in breast cancer, and allelic imbalances (AIs) in the region 17p13.1 do not always coincide with mutations in the TP53 gene. A second interval that frequently shows AIs at 17p is the chromosomal band 17p13.3. This ......Chromosome arm 17p is frequently altered in a variety of human cancers, especially in breast cancer, and allelic imbalances (AIs) in the region 17p13.1 do not always coincide with mutations in the TP53 gene. A second interval that frequently shows AIs at 17p is the chromosomal band 17p13...

Study of 17O(p,α)14N reaction via the Trojan Horse Method for application to 17O nucleosynthesis

International Nuclear Information System (INIS)

Sergi, M. L.; Spitaleri, C.; Pizzone, R. G.; Gulino, M.; Cherubini, S.; Crucilla, V.; La Cognata, M.; Lamia, L.; Puglia, S. M. R.; Rapisarda, G. G.; Romano, S.; Tudisco, S.; Tumino, A.; Coc, A.; Burjan, V.; Hons, Z.; Kroha, V.; Hammache, F.; Sereville, N. de; Kiss, G.

2008-01-01

Because of the still present uncertainties on its rate, the 17 O(p,α) 14 N is one of the most important reaction to be studied in order to get more information about the fate of 17 O in different astrophysical scenarios. The preliminary study of the three-body reaction 2 H( 17 O,α 14 N)n is presented here as a first stage of the indirect study of this important 17 O(p,α) 14 N reaction through the Trojan Horse Method (THM)

Immunogenicity Evaluation of A Synthetic Peptide EgP-29aa134-142 from Echinococcus granulosus In BALB /c Strain Mice

Directory of Open Access Journals (Sweden)

Sh. Jafari

2016-02-01

Full Text Available Background: Cystic echinococcosis or hydatid disease is a widely endemic helminthic  zoonotic disease caused by infection with metacestodes the larval stage of the tapeworm Echinococcus granulosus. P-29, a 29-kDa antigen from E. granulosus, is a protoscolex specific component. The immunologic cross reactivity between P-29 and a major diagnostic antigen of E. granulosus (Ag5 indicated that P-29 might be another useful antigen of E. granulosus to be used in diagnosis or in multi epitope vaccines to prevent secondary echinococcosis. In this study, the peptide epitope regions after the identification and synthesis were evaluated in order to determine the effect of stimulating an immune response in a mouse model. Methods: In this study, the p29 antigen epitope regions of the parasite Echinococcus granulosus detected by the IEDB Bioinformatics software and a 8 amino acids sequence were synthesized. BALB/c mice were immunized subcutaneously three times with two weeks interval. Fourteen days after last immunization spleen tissues were extracted and splenocytes were cultured in presence of antigen for 72 hours. Supernatants were collected and used for cytokine assay by Quantikine  ELISA kit. Results: Sandwich ELISA results were analyzed and showed significant difference in IFN-γ but no significant differences observed in levels of two cytokines IL-4, IL-10, between immunized and control groups. Conclusion: This study has assessed the effect of synthetic peptide EgP-29aa134-142 on the immune response and our results showed that the peptide can increase IFN-γ and therefore induce activation of innate Immunity as well as CTL and Th1 response.

Biochemical Characterisation of Phage Pseudomurein Endoisopeptidases PeiW and PeiP Using Synthetic Peptides

OpenAIRE

Schofield, Linley R.; Beattie, Amy K.; Tootill, Catherine M.; Dey, Debjit; Ronimus, Ron S.

2015-01-01

Pseudomurein endoisopeptidases cause lysis of the cell walls of methanogens by cleaving the isopeptide bond Ala-ε-Lys in the peptide chain of pseudomurein. PeiW and PeiP are two thermostable pseudomurein endoisopeptidases encoded by phage ΨM100 of Methanothermobacter wolfei and phages ΨM1 and ΨM2 of Methanothermobacter marburgensis, respectively. A continuous assay using synthetic peptide substrates was developed and used in the biochemical characterisation of recombinant PeiW and PeiP. The a...

De novo duplication of 17p13.1-p13.2 in a patient with intellectual disability and obesity.

Science.gov (United States)

Kuroda, Yukiko; Ohashi, Ikuko; Tominaga, Makiko; Saito, Toshiyuki; Nagai, Jun-Ichi; Ida, Kazumi; Naruto, Takuya; Masuno, Mitsuo; Kurosawa, Kenji

2014-06-01

17p13.1 Deletion encompassing TP53 has been described as a syndrome characterized by intellectual disability and dysmorphic features. Only one case with a 17p13.1 duplication encompassing TP53 has been reported in a patient with intellectual disability, seizures, obesity, and diabetes mellitus. Here, we present a patient with a 17p13.1 duplication who exhibited obesity and intellectual disability, similar to the previous report. The 9-year-old proposita was referred for the evaluation of intellectual disability and obesity. She also exhibited insulin resistance and liver dysfunction. She had wide palpebral fissures, upturned nostrils, a long mandible, short and slender fingers, and skin hyperpigmentation. Array comparative genomic hybridization (array CGH) detected a 3.2 Mb duplication of 17p13.1-p13.2 encompassing TP53, FXR2, NLGN2, and SLC2A4, which encodes the insulin-responsive glucose transporter 4 (GLUT4) associated with insulin-stimulated glucose uptake in adipocytes and muscle. We suggest that 17p13.1 duplication may represent a clinically recognizable condition characterized partially by a characteristic facial phenotype, developmental delay, and obesity. © 2014 Wiley Periodicals, Inc.

Placental transfer and metabolism of 17 alpha-ethynylestradiol-17 beta and estradiol-17 beta in the rhesus monkey

International Nuclear Information System (INIS)

Slikker, W. Jr.; Bailey, J.R.; Newport, D.; Lipe, G.W.; Hill, D.E.

1982-01-01

The synthetic estrogen component of many oral contraceptives, 17 alpha-ethynylestradiol-17 beta (EE2) and the naturally occurring estrogen, estradiol-17 beta (E2) were studied in four pregnant rhesus monkeys (71% term: 108-121 days gestational age). Under ketamine anesthesia, catheters were implanted in the maternal femoral artery and fetal interplacental artery. After simultaneous i.v. administration of [ 3 H]EE2-[ 14 C]E2 to the maternal animal, serial blood samples were drawn from both mother and fetus. The estrogens and metabolites were identified and quantified by the comigration of radioactivity with reference standards in several high-performance liquid chromatography systems and subsequent selective enzyme hydrolysis of the conjugates. Only estrone (E1), E1 sulfate, EE2 and EE2-3 sulfate were observed in the fetal circulation, whereas the major radiolabeled compounds in the maternal circulation consisted of the above plus E2, E1 glucuronide and EE2-3 glucuronide. In order to determine whether the placenta could convert E2 to its metabolite E1, the placentas of three term rhesus monkeys were perfused in situ via the umbilical artery with 120 ml (15 ml/min) of Hanks' balanced salt solution (pH 7.4) containing [ 3 H]E2. High-performance liquid chromatographic analysis of umbilical vein samples revealed that 96% of the E2 was metabolized to E1. These studies indicate that the placenta can metabolize the potent naturally occurring estrogen E2 to the less potent E1. In contrast, the synthetic estrogen EE2 does not undergo this placental metabolic conversion and thus enters the fetal circulation as the parent compound

Amperometric micro pH measurements in oxygenated saliva.

Science.gov (United States)

Chaisiwamongkhol, Korbua; Batchelor-McAuley, Christopher; Compton, Richard G

2017-07-24

An amperometric micro pH sensor has been developed based on the chemical oxidation of carbon fibre surfaces (diameter of 9 μm and length of ca. 1 mm) to enhance the population of surface quinone groups for the measurement of salivary pH. The pH analysis utilises the electrochemically reversible two-electron, two-proton behaviour of surface quinone groups on the micro-wire electrodes. A Nernstian response is observed across the pH range 2-8 which is the pH range of many biological fluids. We highlight the measurement of pH in small volumes of biological fluids without the need for oxygen removal and specifically the micro pH electrode is examined by measuring the pH of commercial synthetic saliva and authentic human saliva samples. The results correspond well with those obtained by using commercial glass pH electrodes on large volume samples.

File list: InP.Bld.50.AllAg.Th17 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Bld.50.AllAg.Th17 mm9 Input control Blood Th17 SRX288138,SRX495621,SRX288137,SR...X220933,SRX172342,SRX1328057,SRX1328056 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.50.AllAg.Th17.bed ...

Cytochrome P450c17 (steroid 17α-hydroxylase/17,20 lyase): cloning of human adrenal and testis cDNAs indicates the same gene is expressed in both tissues

International Nuclear Information System (INIS)

Chung, B.; Picado-Leonard, J.; Haniu, M.; Bienkowski, M.; Hall, P.F.; Shively, J.E.; Miller, W.L.

1987-01-01

P450c17 is the single enzyme mediating both 17α-hydroxylase (steroid 17α-monooxygenase, EC 1.14.99.9) and 17,20 lyase activities in the synthesis of steroid hormones. It has been suggested that different P450c17 isozymes mediate these activities in the adrenal gland and testis. The authors sequenced 423 of the 509 amino acids (83%) of the porcine adrenal enzyme; based on this partial sequence, a 128-fold degenerate 17-mer was synthesized and used to screen a porcine adrenal cDNA library. This yielded a 380-base cloned cDNA, which in turn was used to isolate several human adrenal cDNAs. The longest of these, λ hac 17-2, is 1754 base pairs long and includes the full-length coding region, the complete 3'-untranslated region, and 41 bases of the 5'-untranslated region. This cDNA encodes a protein of 508 amino acids having a predicted molecular weight of 57,379.82. High-stringency screening of a human testicular cDNA library yielded a partial clone containing 1303 identical bases. RNA gel blots and nuclease S1-protection experiments confirm that the adrenal and testicular P450c17 mRNAs are indistinguishable. These data indicate that the testis possesses a P450c17 identical to that in the adrenal. The human amino acid sequence is 66.7% homologous to the corresponding regions of the porcine sequence, and the human cDNA and amino acid sequences are 80.1 and 70.3% homologous, respectively, to bovine adrenal P450c17 cDNA. Both comparisons indicate that a central region comprising amino acid residues 160-268 is hypervariable among these species of P450c17

Lack of adaptation to human tetherin in HIV-1 Group O and P

Science.gov (United States)

2011-01-01

Background HIV-1 viruses are categorized into four distinct groups: M, N, O and P. Despite the same genomic organization, only the group M viruses are responsible for the world-wide pandemic of AIDS, suggesting better adaptation to human hosts. Previously, it has been reported that the group M Vpu protein is capable of both down-modulating CD4 and counteracting BST-2/tetherin restriction, while the group O Vpu cannot antagonize tetherin. This led us to investigate if group O, and the related group P viruses, possess functional anti-tetherin activities in Vpu or another viral protein, and to further map the residues required for group M Vpu to counteract human tetherin. Results We found a lack of activity against human tetherin for both the Vpu and Nef proteins from group O and P viruses. Furthermore, we found no evidence of anti-human tetherin activity in a fully infectious group O proviral clone, ruling out the possibility of an alternative anti-tetherin factor in this virus. Interestingly, an activity against primate tetherins was retained in the Nef proteins from both a group O and a group P virus. By making chimeras between a functional group M and non-functional group O Vpu protein, we were able to map the first 18 amino acids of group M Vpu as playing an essential role in the ability of the protein to antagonize human tetherin. We further demonstrated the importance of residue alanine-18 for the group M Vpu activity. This residue lies on a diagonal face of conserved alanines in the TM domain of the protein, and is necessary for specific Vpu-tetherin interactions. Conclusions The absence of human specific anti-tetherin activities in HIV-1 group O and P suggests a failure of these viruses to adapt to human hosts, which may have limited their spread. PMID:21955466

Lack of adaptation to human tetherin in HIV-1 Group O and P

Directory of Open Access Journals (Sweden)

Haworth Kevin G

2011-09-01

Full Text Available Abstract Background HIV-1 viruses are categorized into four distinct groups: M, N, O and P. Despite the same genomic organization, only the group M viruses are responsible for the world-wide pandemic of AIDS, suggesting better adaptation to human hosts. Previously, it has been reported that the group M Vpu protein is capable of both down-modulating CD4 and counteracting BST-2/tetherin restriction, while the group O Vpu cannot antagonize tetherin. This led us to investigate if group O, and the related group P viruses, possess functional anti-tetherin activities in Vpu or another viral protein, and to further map the residues required for group M Vpu to counteract human tetherin. Results We found a lack of activity against human tetherin for both the Vpu and Nef proteins from group O and P viruses. Furthermore, we found no evidence of anti-human tetherin activity in a fully infectious group O proviral clone, ruling out the possibility of an alternative anti-tetherin factor in this virus. Interestingly, an activity against primate tetherins was retained in the Nef proteins from both a group O and a group P virus. By making chimeras between a functional group M and non-functional group O Vpu protein, we were able to map the first 18 amino acids of group M Vpu as playing an essential role in the ability of the protein to antagonize human tetherin. We further demonstrated the importance of residue alanine-18 for the group M Vpu activity. This residue lies on a diagonal face of conserved alanines in the TM domain of the protein, and is necessary for specific Vpu-tetherin interactions. Conclusions The absence of human specific anti-tetherin activities in HIV-1 group O and P suggests a failure of these viruses to adapt to human hosts, which may have limited their spread.

[Nah-plasmids of IncP-9 group from natural strains of Pseudomonas].

Science.gov (United States)

Levchuk, A A; Bulyga, I M; Izmalkova, T Iu; Sevast'ianovich, Ia R; Kosheleva, I A; Thomas, C M; Titok, M A

2006-01-01

Use of polymerase chain reaction helped to establish that the most frequent among naphthalene utilizing bacteria, isolated on the territory of Belarus, are Nah-plasmids of IncP-9 incompatibility group and those with indefinite systematic belonging. With the help of classical test of incompatibility, restriction and sequence analyses three new subgroups within the IncP-9 group were discovered (zeta, eta and IncP-9-like replicons). Conducting of restriction analysis for amplification products of nahG and nahAc genes allowed us to reveal, in addition to known sequences of stated determinants, two new types of nahG gene. Restriction analysis performed on amplification products of 16S RNA genes (ARDRA method) showed that native hosts of Nah-plasmids of IncP-9 group are not only fluorescent bacteria from genus Pseudomonas (P. fluorescens, P. putida, P. aeruginosa, P. species), but also non-fluorescent bacteria with indefinite specific belonging.

A synthetic interaction screen identifies factors selectively required for proliferation and TERT transcription in p53-deficient human cancer cells.

Directory of Open Access Journals (Sweden)

Li Xie

Full Text Available Numerous genetic and epigenetic alterations render cancer cells selectively dependent on specific genes and regulatory pathways, and represent potential vulnerabilities that can be therapeutically exploited. Here we describe an RNA interference (RNAi-based synthetic interaction screen to identify genes preferentially required for proliferation of p53-deficient (p53- human cancer cells. We find that compared to p53-competent (p53+ human cancer cell lines, diverse p53- human cancer cell lines are preferentially sensitive to loss of the transcription factor ETV1 and the DNA damage kinase ATR. In p53- cells, RNAi-mediated knockdown of ETV1 or ATR results in decreased expression of the telomerase catalytic subunit TERT leading to growth arrest, which can be reversed by ectopic TERT expression. Chromatin immunoprecipitation analysis reveals that ETV1 binds to a region downstream of the TERT transcriptional start-site in p53- but not p53+ cells. We find that the role of ATR is to phosphorylate and thereby stabilize ETV1. Our collective results identify a regulatory pathway involving ETV1, ATR, and TERT that is preferentially important for proliferation of diverse p53- cancer cells.

Engineering Bacteria to Search for Specific Concentrations of Molecules by a Systematic Synthetic Biology Design Method.

Science.gov (United States)

Tien, Shin-Ming; Hsu, Chih-Yuan; Chen, Bor-Sen

2016-01-01

Bacteria navigate environments full of various chemicals to seek favorable places for survival by controlling the flagella's rotation using a complicated signal transduction pathway. By influencing the pathway, bacteria can be engineered to search for specific molecules, which has great potential for application to biomedicine and bioremediation. In this study, genetic circuits were constructed to make bacteria search for a specific molecule at particular concentrations in their environment through a synthetic biology method. In addition, by replacing the "brake component" in the synthetic circuit with some specific sensitivities, the bacteria can be engineered to locate areas containing specific concentrations of the molecule. Measured by the swarm assay qualitatively and microfluidic techniques quantitatively, the characteristics of each "brake component" were identified and represented by a mathematical model. Furthermore, we established another mathematical model to anticipate the characteristics of the "brake component". Based on this model, an abundant component library can be established to provide adequate component selection for different searching conditions without identifying all components individually. Finally, a systematic design procedure was proposed. Following this systematic procedure, one can design a genetic circuit for bacteria to rapidly search for and locate different concentrations of particular molecules by selecting the most adequate "brake component" in the library. Moreover, following simple procedures, one can also establish an exclusive component library suitable for other cultivated environments, promoter systems, or bacterial strains.

Engineering Bacteria to Search for Specific Concentrations of Molecules by a Systematic Synthetic Biology Design Method.

Directory of Open Access Journals (Sweden)

Shin-Ming Tien

Full Text Available Bacteria navigate environments full of various chemicals to seek favorable places for survival by controlling the flagella's rotation using a complicated signal transduction pathway. By influencing the pathway, bacteria can be engineered to search for specific molecules, which has great potential for application to biomedicine and bioremediation. In this study, genetic circuits were constructed to make bacteria search for a specific molecule at particular concentrations in their environment through a synthetic biology method. In addition, by replacing the "brake component" in the synthetic circuit with some specific sensitivities, the bacteria can be engineered to locate areas containing specific concentrations of the molecule. Measured by the swarm assay qualitatively and microfluidic techniques quantitatively, the characteristics of each "brake component" were identified and represented by a mathematical model. Furthermore, we established another mathematical model to anticipate the characteristics of the "brake component". Based on this model, an abundant component library can be established to provide adequate component selection for different searching conditions without identifying all components individually. Finally, a systematic design procedure was proposed. Following this systematic procedure, one can design a genetic circuit for bacteria to rapidly search for and locate different concentrations of particular molecules by selecting the most adequate "brake component" in the library. Moreover, following simple procedures, one can also establish an exclusive component library suitable for other cultivated environments, promoter systems, or bacterial strains.

Use of actin-bound adenosine 5'-diphosphate as a method to determine the specific 32P-radioactivity of the gamma-phosphoryl group of adenosine 5'-triphosphate in a highly compartmentalized cell, the platelet

International Nuclear Information System (INIS)

Verhoeven, A.J.; Cook, C.A.; Holmsen, H.

1988-01-01

Determination of the specific 32 P-radioactivity of cytoplasmic ATP in 32 P-Pi-labeled platelets is complicated by the presence of a large pool of metabolically inactive, granule-stored nucleotides. Moreover, our data show that the specific 32 P-radioactivity of cytoplasmic ATP is severely underestimated when determined in platelets after the complete secretion of granule-stored nucleotides, possibly due to isotopic dilution with granule-stored phosphate. As F-actin-bound ADP is ethanol-insoluble, this pool can be readily separated from the other nucleotide pools in platelets. Here we show that the specific 32 P-radioactivity of F-actin-bound ADP accurately reflects that of the gamma-phosphoryl group of cytoplasmic ATP. During uptake of 32 P-Pi by human platelets the specific 32 P-radioactivity of F-actin-bound ADP equals that of the monoester phosphates of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate, which are in metabolic equilibrium with cytoplasmic ATP. Therefore, this method enables the determination of the specific 32 P-radioactivity of the gamma-phosphoryl group of cytoplasmic ATP in platelets even under short-term labeling conditions

[Relationship between interleukin-17A gene polymorphisms and the susceptibility to childhood asthma].

Science.gov (United States)

Zhong, Fang-Fang; Zou, Yan; Liu, Chun-Yan; Liu, Wen-Jun

2016-12-01

To explore the relationship between polymorphisms of interleukin-17A (IL-17A) gene promoter (-197G/A and -692C/T) and the susceptibility to childhood asthma, to further identify the candidate genes for asthma, and to provide a basis for early prevention of asthma in high-risk children. Sixty-five outpatients or inpatients with childhood asthma between August 2013 and August 2015 were assigned to asthma group. Seventy healthy children within the same period were assigned to control group. Using peripheral venous blood from the two groups, PCR with sequence-specific primers was carried out to determine single nucleotide polymorphisms at positions -197G/A and -692C/T in IL-17A gene promoter. A statistical analysis was used to evaluate differences in genotype and allele frequencies between the two groups. Compared with the control group, the asthma group had significantly higher frequencies of TT genotype (29% vs 16%; P=0.012) and T allele (52% vs 42%; P=0.039) at position -692C/T of IL-17A gene. Children with T allele had 1.413-fold higher risk of childhood asthma than those with C allele (OR=1.413, 95%CI: 1.015-1.917). There were no significant differences in genotype and allele frequencies at position -197G/A in IL-17A gene between the two groups (p>0.05). Polymorphisms at position -692C/T in IL-17A gene promoter is associated with the susceptibility to childhood asthma. Children with -692T allele are more susceptible to childhood asthma. There is no significant relationship between polymorphisms at position -197G/A in IL-17A gene promoter and the susceptibility to childhood asthma.

TSH Response to the Intravenous Administration of Synthetic TRH in Various Thyroid Diseases

Energy Technology Data Exchange (ETDEWEB)

Choi, Sung Jae; Kim, Kwang Won; Lee, Mun Ho [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1980-03-15

Serum TSH levels were ,measured by radioimmunoassay before and after intravenous administration of synthetic thyrotropin-releasing hormone(TRH) to 15 normal subjects and 55 patients with primary thyroid disease (14 patients with euthyroidism, 24 patients with thyrotoxicosis and 17 patients with hypothyroidism) to evaluate pituitary TSH reserve and its diagnostic availability. The observed results were as follows. 1) In normal subjects, serum TSH responses to synthetic TRH were 3.2+-1.0 at 0 min (baseline TSH level), 8.0+-4.0 at 10 min, 11.7+-5.0 at 20 min, 13.7+-7.1 at 80 min, 9.7+-5.0 at 60 min., 5.2+-2.0 at 120 min. and 3.6+-0.4 muU/ml at 180 min. Serum TSH peaked at 20-30 minutes and returned nearly to baseline at 180 minutes. 2) In euthyroid group, serum TSH responses to synthetic TRH were 3.3+-1.6 at 0 min, 8.6+-8.0 at 10 min, 10.9+-8. 5 at 20 min, 12.5+-8.4 at 30 min, 9.0+-5.9 at 60 min, 5.6+-2.6 at 120 min and 3.5+-1.3 muU/ml at 180 min. No significant difference revealed between euthyroid group and normal subjects(p>0.05). 3) In hyperthyroid group, serum TSH responses to synthetic TRH were 1.5+-0.6 at 0 min, 2.2+-0.8 at 10 min., 2.3+-1.0 at 20 min., 2.4+-1.5 at 30 min., 2.1+-1.1 at 60 min,, 1.9+-0.2 at 120 min, and 1. 5+-0.8 muU/ml, at 180 min., No response to TRH showed. 4) In hypothyroid group, mean values of serum TSH response to synthetic TRH were 42.0 at 0 min., 60.6 at 10 min., 124.8 at 20 min., 123.0 at 30 min. 101.6 at 60 min., 64.3 at 120 min. and 15.5 muU/ml at 180 min., Patients with primary hypothyroidism showed an exaggerated TSH response to synthetic TRH despite their high basal TSH. 5) Side effects attending synthetic TRH administration were transient nausea (59.0%), desire to micturate (59.0%), feeling of flushing (19.7%), dizziness (45.9%), metallic taste (9.8%) and headache (19.7%). Any side effect didn't show in 16.4%. These symptoms began almost immediately after TRH intravenous injection and lasted several minutes, and not related

A Computational Model of the Hypothalamic Pituitary Gonadal Axis in Female Fathead Minnows (Pimephales promelas) exposed to 17á-ethynylestradiol and 17â-trenbolone

Science.gov (United States)

Endocrine disrupting chemicals (e.g., estrogens, androgens and their mimics) are known to affect reproduction in fish. 17a-ethynylestradiol is a synthetic estrogen used in birth control pills. 17a-trenbolone is a relatively stable metabolite of trenbolone acetate, a synthetic and...

A Comparison of Degradable Synthetic Polymer Fibers for Anterior Cruciate Ligament Reconstruction

OpenAIRE

Tovar, Nick; Bourke, Sharon; Jaffe, Michael; Murthy, N. Sanjeeva; Kohn, Joachim; Gatt, Charles; Dunn, Michael G.

2010-01-01

We compared mechanical properties, degradation rates, and cellular compatibilities of two synthetic polymer fibers potentially useful as ACL reconstruction scaffolds: poly(desaminotyrosyl-tyrosine dodecyl dodecanedioate)(12,10), p(DTD DD) and poly(L-lactic acid), PLLA. The yield stress of ethylene oxide (ETO) sterilized wet fibers was 150 ± 22 MPa and 87 ± 12 MPa for p(DTD DD) and PLLA, respectively, with moduli of 1.7 ± 0.1 MPa and 4.4 ± 0.43 MPa. Strength and molecular weight retention were...

GPR17: Molecular modeling and dynamics studies of the 3-D structure and purinergic ligand binding features in comparison with P2Y receptors

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Ranghino Graziella

2008-06-01

Full Text Available Abstract Background GPR17 is a G-protein-coupled receptor located at intermediate phylogenetic position between two distinct receptor families: the P2Y and CysLT receptors for extracellular nucleotides and cysteinyl-LTs, respectively. We previously showed that GPR17 can indeed respond to both classes of endogenous ligands and to synthetic compounds active at the above receptor families, thus representing the first fully characterized non-peptide "hybrid" GPCR. In a rat brain focal ischemia model, the selective in vivo knock down of GPR17 by anti-sense technology or P2Y/CysLT antagonists reduced progression of ischemic damage, thus highlighting GPR17 as a novel therapeutic target for stroke. Elucidation of the structure of GPR17 and of ligand binding mechanisms are the necessary steps to obtain selective and potent drugs for this new potential target. On this basis, a 3-D molecular model of GPR17 embedded in a solvated phospholipid bilayer and refined by molecular dynamics simulations has been the first aim of this study. To explore the binding mode of the "purinergic" component of the receptor, the endogenous agonist UDP and two P2Y receptor antagonists demonstrated to be active on GPR17 (MRS2179 and cangrelor were then modeled on the receptor. Results Molecular dynamics simulations suggest that GPR17 nucleotide binding pocket is similar to that described for the other P2Y receptors, although only one of the three basic residues that have been typically involved in ligand recognition is conserved (Arg255. The binding pocket is enclosed between the helical bundle and covered at the top by EL2. Driving interactions are H-bonds and salt bridges between the 6.55 and 6.52 residues and the phosphate moieties of the ligands. An "accessory" binding site in a region formed by the EL2, EL3 and the Nt was also found. Conclusion Nucleotide binding to GPR17 occurs on the same receptor regions identified for already known P2Y receptors. Agonist

Non-structural proteins P17 and P33 are involved in the assembly of the internal membrane-containing virus PRD1

Energy Technology Data Exchange (ETDEWEB)

Karttunen, Jenni; Mäntynen, Sari [Centre of Excellence in Biological Interactions, Department of Biological and Environmental Science and Nanoscience Center, University of Jyväskylä, P.O. Box 35, 40014 Jyväskylä (Finland); Ihalainen, Teemu O. [Stem Cells in Neurological Applications Group, BioMediTech, University of Tampere, Tampere (Finland); Bamford, Jaana K.H. [Centre of Excellence in Biological Interactions, Department of Biological and Environmental Science and Nanoscience Center, University of Jyväskylä, P.O. Box 35, 40014 Jyväskylä (Finland); Oksanen, Hanna M., E-mail: hanna.oksanen@helsinki.fi [Institute of Biotechnology and Department of Biosciences, University of Helsinki, Biocenter 2, P.O. Box 56 (Viikinkaari 5), FIN-00014 Helsinki (Finland)

2015-08-15

Bacteriophage PRD1, which has been studied intensively at the structural and functional levels, still has some gene products with unknown functions and certain aspects of the PRD1 assembly process have remained unsolved. In this study, we demonstrate that the phage-encoded non-structural proteins P17 and P33, either individually or together, complement the defect in a temperature-sensitive GroES mutant of Escherichia coli for host growth and PRD1 propagation. Confocal microscopy of fluorescent fusion proteins revealed co-localisation between P33 and P17 as well as between P33 and the host chaperonin GroEL. A fluorescence recovery after photobleaching assay demonstrated that the diffusion of the P33 fluorescent fusion protein was substantially slower in E. coli than theoretically calculated, presumably resulting from intermolecular interactions. Our results indicate that P33 and P17 function in procapsid assembly, possibly in association with the host chaperonin complex GroEL/GroES. - Highlights: • Two non-structural proteins of PRD1 are involved in the virus assembly. • P17 and P33 complement the defect in GroES of Escherichia coli. • P33 co-localises with GroEL and P17 in the bacterium. • Slow motion of P33 in the bacterium suggests association with cellular components.

A colloidal water-stable MOF as a broad-range fluorescent pH sensor via post-synthetic modification.

Science.gov (United States)

Aguilera-Sigalat, Jordi; Bradshaw, Darren

2014-05-11

We report for the first time the pH-dependent fluorescence of UiO-66-NH2 across the wide range from 1 to 9. By application of a post-synthetic modification (PSM) diazotisation strategy, we synthesized a new material, UiO-66-N=N-ind, which shows increased chemical stability and enhanced sensing up to pH 12.

Intrapartum synthetic oxytocin reduce the expression of primitive reflexes associated with breastfeeding.

Science.gov (United States)

Marín Gabriel, Miguel A; Olza Fernández, Ibone; Malalana Martínez, Ana M; González Armengod, Carmen; Costarelli, Valeria; Millán Santos, Isabel; Fernández-Cañadas Morillo, Aurora; Pérez Riveiro, Pilar; López Sánchez, Francisco; García Murillo, Lourdes

2015-05-01

Several synthetic peptide manipulations during the time surrounding birth can alter the specific neurohormonal status in the newborn brain. This study is aimed at assessing whether intrapartum oxytocin administration has any effect on primitive neonatal reflexes and determining whether such an effect is dose-dependent. A cohort prospective study was conducted at a tertiary hospital. Mother-infant dyads who received intrapartum oxytocin (n=53) were compared with mother-infant dyads who did not receive intrapartum oxytocin (n=45). Primitive neonatal reflexes (endogenous, antigravity, motor, and rhythmic reflexes) were quantified by analyzing videotaped breastfeeding sessions in a biological nurturing position. Two observers blind to the group assignment and the oxytocin dose analyzed the videotapes and assesed the newborn's state of consciousness according to the Brazelton scale. The release of all rhythmic reflexes (p=0.01), the antigravity reflex (p=0.04), and total primitive neonatal reflexes (p=0.02) in the group exposed to oxytocin was lower than in the group not exposed to oxytocin. No correlations were observed between the dose of oxytocin administered and the percentage of primitive neonatal reflexes released (r=0.03; p=0.82). Intrapartum oxytocin administration might inhibit the expression of several primitive neonatal reflexes associated with breastfeeding. This correlation does not seem to be dose-dependent.

7 CFR 29.1166 - Primings (P Group).

Science.gov (United States)

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Primings (P Group). 29.1166 Section 29.1166... REGULATIONS TOBACCO INSPECTION Standards Grades § 29.1166 Primings (P Group). This group consists of round-tipped leaves from the lowest portion of the stalk. Leaves of the P group ripen prematurely as a result...

Synthetic biological networks

International Nuclear Information System (INIS)

Archer, Eric; Süel, Gürol M

2013-01-01

Despite their obvious relationship and overlap, the field of physics is blessed with many insightful laws, while such laws are sadly absent in biology. Here we aim to discuss how the rise of a more recent field known as synthetic biology may allow us to more directly test hypotheses regarding the possible design principles of natural biological networks and systems. In particular, this review focuses on synthetic gene regulatory networks engineered to perform specific functions or exhibit particular dynamic behaviors. Advances in synthetic biology may set the stage to uncover the relationship of potential biological principles to those developed in physics. (review article)

IL-17A, IL-17RC polymorphisms and IL17 plasma levels in Tunisian patients with rheumatoid arthritis

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Chahbi, Mayssa; Haouami, Youssra; Sfar, Imen; Abdelmoula, Leila; Ben Abdallah, Taieb; Gorgi, Yousr

2018-01-01

Background Interleukin-17 (IL-17), a cytokine mainly secreted by Th17 cells, seems to play a significant role in the pathogenesis of rheumatoid arthritis (RA). Functional genetic polymorphisms in IL-17 and its receptor genes can influence either qualitatively or quantitatively their functions. Therefore, we aimed to study the impact of IL17-A and IL17RC polymorphisms on plasma level of IL-17 and RA susceptibility and severity. Methods In this context, IL-17A*rs2275913 and IL-17RC*rs708567 polymorphisms were investigated together with the quantification of IL17 plasma level in 115 RA patients and 91 healthy control subjects matched in age, sex and ethnic origin. Results There were no statistically significant associations between IL-17A and IL-17RC studied polymorphisms and RA susceptibility. In contrast, IL-17A plasma levels were significantly higher in patients (55.07 pg/ml) comparatively to controls (4.75 pg/ml), p<10E-12. A ROC curve was used to evaluate the performance of plasma IL-17 in detecting RA. Given 100% specificity, the highest sensitivity of plasma IL-17A was 61.7% at a cut-off value of 18.25 pg/ml; p < 10E-21, CI = [0.849–0.939]. Analytic results showed that the IgM-rheumatoid factor and anti-CCP antibodies were significantly less frequent in patients with the IL-17RC*A/A genotype than those carrying *G/G and *G/A genotypes; p = 0.013 and p = 0.015, respectively. Otherwise, IL-17 plasma levels’ analysis showed a significant association with the activity of RA (DAS28≥5.1 = 74.71 pg/ml vs. DAS28<5.1 = 11.96 pg/ml), p<10E-6. Conclusion IL-17A*rs2275913 (G/A) and IL-17RC*rs708567 (G/A) polymorphisms did not seem to influence RA susceptibility in Tunisian population. This result agrees with those reported previously. Plasma IL-17A level seems to be predictive of severe RA occurrence. PMID:29584788

Interleukin 17 receptor gene polymorphism in periimplantitis and chronic periodontitis.

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Mahdi Kadkhodazadeh

2013-06-01

Full Text Available Gene polymorphism of cytokines influencing their function has been known as a contributing factor in the pathogenesis of inflammatory diseases of the tooth and implant supporting tissues. The aim of this study was to investigate the association of IL-17R gene polymorphism (rs879576 with chronic periodontitis and periimplantitis in an Iranian population. 73 patients with chronic periodontitis, 37 patients with periimplantitis and 83 periodontally healthy patients were enrolled in this study. 5cc blood was obtained from each subject's arm vein and transferred to tubes containing EDTA. Genomic DNA was extracted using Miller's Salting Out technique. The DNA was transferred into 96 division plates, transported to Kbioscience Institute in United Kingdom and analyzed using the Kbioscience Competitive Allele Specific PCR (KASP technique. Chi-square and Kruskal Wallis tests were used to analyze differences in the expression of genotypes and frequency of alleles in disease and control groups (P-Value less than 0.05 was considered statistically significant. There were no significant differences between periodontitis, periimplantitis with AA, GG, GA genotype of IL-17R gene (P=0.8239. Also comparison of frequency of alleles in SNP rs879576 of IL-17R gene between the chronic periodontitis group and periimplantitis group did not revealed statistically significant differences (P=0.8239. The enigma of IL-17 and its polymorphism-role in periodontitis and periimplantitis is yet to be investigated more carefully throughout further research but this article demonstrates that polymorphism of IL-17R plays no significant role in incidence of chronic periodontitis and Periimplantitis.

Interleukin 17 Receptor Gene Polymorphism in Periimplantitis and Chronic Periodontitis

Directory of Open Access Journals (Sweden)

Mahdi Kadkhodazadeh

2013-05-01

Full Text Available Gene polymorphism of cytokines influencing their function has been known as a contributing factor in the pathogenesis of inflammatory diseases of the tooth and implant supporting tissues. The aim of this study was to investigate the association of IL-17R gene polymorphism (rs879576 with chronic periodontitis and periimplantitis in an Iranian population. 73 patients with chronic periodontitis, 37 patients with periimplantitis and 83 periodontally healthy patients were enrolled in this study. 5cc blood was obtained from each subject’s arm vein and transferred to tubes containing EDTA. Genomic DNA was extracted using Miller's Salting Out technique. The DNA was transferred into 96 division plates, transported to Kbioscience Institute in United Kingdom and analyzed using the Kbioscience Competitive Allele Specific PCR (KASP technique. Chi-square and Kruskal Wallis tests were used to analyze differences in the expression of genotypes and frequency of alleles in disease and control groups (P-Value less than 0.05 was considered statistically significant. There were no significant differences between periodontitis, periimplantitis with AA, GG, GA genotype of IL-17R gene (P=0.8239. Also comparison of frequency of alleles in SNP rs879576 of IL-17R gene between the chronic periodontitis group and periimplantitis group did not revealed statistically significant differences (P=0.8239. The enigma of IL-17 and its polymorphism-role in periodontitis and periimplantitis is yet to be investigated more carefully throughout further research but this article demonstrates that polymorphism of IL-17R plays no significant role in incidence of chronic periodontitis and Periimplantitis.

Increased Th17/Treg Ratio in Poststroke Fatigue

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Xinjing Liu

2015-01-01

Full Text Available Fatigue is a major debilitating symptom after stroke. The biological mechanisms underlying poststroke fatigue (PFS are unknown. We hypothesized that PSF is associated with an alteration in the balance between Th17 and Treg cells. To test this hypothesis we assessed fatigue in 30 stroke survivors using the Fatigue Scale for Motor and Cognitive Functions (FSMC. Peripheral blood was collected for assessment of Th17 and Treg cell populations and measurement of interleukin-10 (IL-10. Participants were dichotomized into severe fatigue n=14 and low-moderate fatigue n=16 groups by K-mean cluster analysis of FSMC scores. There were no group differences in age, gender, stroke type, stroke severity, or time since stroke. Stroke survivors in the severe fatigue group reported greater anxiety p=0.004 and depression p=0.001 than in the low-moderate fatigue group. The ratio of Th17 to Treg cells was significantly increased in the severe fatigue group relative to the mild-moderate fatigue group p=0.035. Serum levels of IL-10 negatively correlated withTh17/Treg ratio (r=-0.408,  p=0.025. Our preliminary findings suggest that an imbalance in the Th17/Treg ratio is associated with the severity of PSF.

Synthetically derived bat influenza A-like viruses reveal a cell type- but not species-specific tropism.

Science.gov (United States)

Moreira, Étori Aguiar; Locher, Samira; Kolesnikova, Larissa; Bolte, Hardin; Aydillo, Teresa; García-Sastre, Adolfo; Schwemmle, Martin; Zimmer, Gert

2016-10-24

Two novel influenza A-like viral genome sequences have recently been identified in Central and South American fruit bats and provisionally designated "HL17NL10" and "HL18NL11." All efforts to isolate infectious virus from bats or to generate these viruses by reverse genetics have failed to date. Recombinant vesicular stomatitis virus (VSV) encoding the hemagglutinin-like envelope glycoproteins HL17 or HL18 in place of the VSV glycoprotein were generated to identify cell lines that are susceptible to bat influenza A-like virus entry. More than 30 cell lines derived from various species were screened but only a few cell lines were found to be susceptible, including Madin-Darby canine kidney type II (MDCK II) cells. The identification of cell lines susceptible to VSV chimeras allowed us to recover recombinant HL17NL10 and HL18NL11 viruses from synthetic DNA. Both influenza A-like viruses established a productive infection in MDCK II cells; however, HL18NL11 replicated more efficiently than HL17NL10 in this cell line. Unlike conventional influenza A viruses, bat influenza A-like viruses started the infection preferentially at the basolateral membrane of polarized MDCK II cells; however, similar to conventional influenza A viruses, bat influenza A-like viruses were released primarily from the apical site. The ability of HL18NL11 or HL17NL10 viruses to infect canine and human cells might reflect a zoonotic potential of these recently identified bat viruses.

Contribution of 194.1 keV Resonance to 17O(p, alpha) 14N Reaction Rate using R Matrix Code

International Nuclear Information System (INIS)

Chafa, A.; Messili, F.Z.; Barhoumi, S.

2009-01-01

Knowledge of the 17 O(p, alpha ) 14 N reaction rates is required for evaluating elemental abundances in a number of hydrogen - burning stellar sites. This reaction is specifically very important for nucleosynthesis of the rare oxygen isotope 17 O. Classical novae are thought to be a major source of 17 O in the Galaxy and produce the short-live radioisotope 18 F whose + decay is followed by a gamma ray emission which could be observed with satellites such as the Integral observatory. As the 17 O(p, alpha) 14 N and 17 O(p, alpha ) 18 F reactions govern the destruction of 17 O and the formation of 1 '8F, their rates are decisive in determining the final abundances of these isotopes. Stellar temperatures of primary importance for nucleosynthesis are typically in the ranges T = 0.01-0.1 GK for red giant, AGB, and massive stars, and T 0.01-0.4 GK for classical nova explosions In recent work, we observed, for the first time, a resonance a 183.3 keV corresponding to level in 18 F at Ex 5789.8 ± 0.3 keV. A new astrophysical parameters of this resonance are found. In this work we study this reaction using numerical code based on R matrix method including the new values of level energy and parameters of 183.3 keV resonance in order to show his contribution to 17 O(p, alpha) 14 N reaction rates. We also use old parameters values of this resonance given in Keiser work for comparison. We show that this resonance predominate the reaction rates in all range of stellar temperature for classical nova explosions. This is in good agreement with our work with experimental method. We also study cross section and differential cross section 17 O(p, alpha ) 14 N reaction with R matrix method

P-glycoprotein confers acquired resistance to 17-DMAG in lung cancers with an ALK rearrangement

International Nuclear Information System (INIS)

Kim, Hee Joung; Lee, Kye Young; Kim, Young Whan; Choi, Yun Jung; Lee, Jung-Eun; Choi, Chang Min; Baek, In-Jeoung; Rho, Jin Kyung; Lee, Jae Cheol

2015-01-01

Because anaplastic lymphoma kinase (ALK) is dependent on Hsp90 for protein stability, Hsp90 inhibitors are effective in controlling growth of lung cancer cells with ALK rearrangement. We investigated the mechanism of acquired resistance to 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), a geldanamycin analogue Hsp90 inhibitor, in H3122 and H2228 non-small cell lung cancer cell lines with ALK rearrangement. Resistant cell lines (H3122/DR-1, H3122/DR-2 and H2228/DR) were established by repeated exposure to increasing concentrations of 17-DMAG. Mechanisms for resistance by either NAD(P)H/quinone oxidoreductase 1 (NQO1), previously known as a factor related to 17-DMAG resistance, or P-glycoprotein (P-gp; ABCB1/MDR1) were queried using RT-PCR, western blot analysis, chemical inhibitors, the MTT cell proliferation/survival assay, and cellular efflux of rhodamine 123. The resistant cells showed no cross-resistance to AUY922 or ALK inhibitors, suggesting that ALK dependency persists in cells with acquired resistance to 17-DMAG. Although expression of NQO1 was decreased in H3122/DR-1 and H3122/DR-2, NQO1 inhibition by dicumarol did not affect the response of parental cells (H2228 and H3122) to 17-DMAG. Interestingly, all resistant cells showed the induction of P-gp at the protein and RNA levels, which was associated with an increased efflux of the P-gp substrate rhodamine 123 (Rho123). Transfection with siRNA directed against P-gp or treatment with verapamil, an inhibitor of P-gp, restored the sensitivity to the drug in all cells with acquired resistance to 17-DMAG. Furthermore, we also observed that the growth-inhibitory effect of 17-DMAG was decreased in A549/PR and H460/PR cells generated to over-express P-gp by long-term exposure to paclitaxel, and these cells recovered their sensitivity to 17-DMAG through the inhibition of P-gp. P-gp over-expression is a possible mechanism of acquired resistance to 17-DMAG in cells with ALK rearrangement. The online

Cloning of synthetic gene including antigens against Urinary Tract Infections in pET28a+ vector

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Zohreh Haghri

2017-12-01

Full Text Available There are many different bacterial infections in the world that patients are suffering from and research teams are trying to find suitable ways to prevent and treat them. Urinary Tract Infections (UTIs are most important infections in the world , and they are more common among women because vaginal cavity is near to urethral opening. The aim of this study is cloning of synthetic gene include antigens against UTIs in pET28a+ vector. Antibiotic resistant has been increasing because of antibiotic overuse recently, so It shows the necessity of developing a vaccine against these infections. There for, it will be imperative to develop a vaccine instead of antibiotics. This infection causes by many organisms, most important of which are Uropathogenic Escherichia coli (UPEC, Proteus mirabilis and Klebsiella pneumoniae Uropathogenic Escherichia .coli is the most important microorganism that causes these infections more than other bacteria, so in developing a vaccine it is the most important one, that have to be considered. The synthetic Gene which was designed against these three bacteria including antigens which are important and common to cause these infections. This gene has involved 1293bp. It was ordered to Gene Ray Biotechnology. Primers were designed by Gene Runner. Gene and pET28a+ vector was checked by SnappGene. Synthetic gene was multiplied by PCR and cloned in pET28a+ vector. Construct was transformed into E. coli TOP10.The clone was confirmed by PCR, Digestion. This data indicates that this gene can be expressed and it might be a vaccine candidate to protect people from these infections in the future.

Current status of synthetic epikeratoplasty.

Science.gov (United States)

Thompson, K P; Hanna, K; Waring, G O; Gipson, I; Liu, Y; Gailitis, R P; Johnson-Wint, B; Green, K

1991-01-01

Many of the deficiencies with human tissue epikeratoplasty might be improved by the use of a suitable synthetic lenticule. Potential biomaterials for epikeratoplasty include collagen (types I, III, or IV), collagen-hydrogel copolymers, bioactive synthetics, and coated hydrogels. The biomaterial must be engineered to achieve strict specifications of optical clarity, support of epithelial migration and adhesion, permeability to solutes, and stability to corneal proteases. Attaching synthetic lenticules to the cornea without cutting Bowman's layer by adhesives, laser welding, or direct adhesion may also improve the efficacy of synthetic epikeratoplasty.

Immunogenicity, reactogenicity, and safety of a P1.7b,4 strain-specific serogroup B meningococcal vaccine given to preteens.

Science.gov (United States)

Hosking, Jamie; Rasanathan, Kumanan; Mow, Florina Chan; Jackson, Catherine; Martin, Diana; O'Hallahan, Jane; Oster, Philipp; Ypma, Ellen; Reid, Stewart; Aaberge, Ingeborg; Crengle, Sue; Stewart, Joanna; Lennon, Diana

2007-11-01

New Zealand (NZ) has experienced a Neisseria meningitidis serogroup B epidemic since 1991. MeNZB, a strain-specific outer membrane vesicle vaccine made using an NZ epidemic strain isolate, NZ98/254 (B:4:P1.7b,4), from two manufacturing sites, the Norwegian Institute of Public Health (NIPH) and Chiron Vaccines (CV; now Novartis), was evaluated for safety, immunogenicity, and reactogenicity in this observer-blind trial with 8- to 12-year-old children. In year 1, cohort A (n = 302) was randomized 4:1 for receipt of NIPH-MeNZB or MenBvac (Norwegian parent vaccine strain 44/76; B:15:P1.7,16). In year 2, cohort B (n = 313) was randomized 4:1 for receipt of CV-MeNZB or NIPH-MeNZB. Participants all received three vaccinations 6 weeks apart. Local and systemic reactions were monitored for 7 days. Seroresponse was defined as a fourfold or greater rise in the serum bactericidal antibody titer from the baseline titer as measured by a serum bactericidal assay. Those with baseline titers of /=1:8 to serorespond. Intention-to-treat (ITT) and per protocol (PP) analyses are presented. In cohort A, 74% (ITT) and 73% (PP) of NIPH-MeNZB recipients demonstrated seroresponses against NZ98/254 after three doses, versus 32% (ITT and PP) of MenBvac recipients. In cohort B, seroresponses against NZ98/254 after three doses occurred in 79% (ITT and PP) of CV-MeNZB versus 75% (ITT) and 76% (PP) of NIPH-MeNZB recipients. Vaccines were tolerable, with no vaccine-related serious adverse events. In conclusion, the NZ strain meningococcal B vaccine (MeNZB) from either manufacturing site was immunogenic against New Zealand epidemic vaccine strain meningococci with no safety concerns when given in three doses to these 8- to 12-year-old children.

The precipitation of magnesium potassium phosphate hexahydrate for P and K recovery from synthetic urine.

Science.gov (United States)

Xu, Kangning; Li, Jiyun; Zheng, Min; Zhang, Chi; Xie, Tao; Wang, Chengwen

2015-09-01

Nutrients recovery from urine to close the nutrient loop is one of the most attractive benefits of source separation in wastewater management. The current study presents an investigation of the thermodynamic modeling of the recovery of P and K from synthetic urine via the precipitation of magnesium potassium phosphate hexahydrate (MPP). Experimental results show that maximum recovery efficiencies of P and K reached 99% and 33%, respectively, when the precipitation process was initiated only through adding dissolvable Mg compound source. pH level and molar ratio of Mg:P were key factors determining the nutrient recovery efficiencies. Precipitation equilibrium of MPP and magnesium sodium phosphate heptahydrate (MSP) was confirmed via precipitates analysis using a Scanning Electron Microscope/Energy Dispersive Spectrometer and an X-ray Diffractometer. Then, the standard solubility products of MPP and MSP in the synthetic urine were estimated to be 10(-12.2 ± 0.0.253) and 10(-11.6 ± 0.253), respectively. The thermodynamic model formulated on chemical software PHREEQC could well fit the experimental results via comparing the simulated and measured concentrations of K and P in equilibrium. Precipitation potentials of three struvite-type compounds were calculated through thermodynamic modeling. Magnesium ammonium phosphate hexahydrate (MAP) has a much higher tendency to precipitate than MPP and MSP in normal urine while MSP was the main inhibitor of MPP in ammonium-removed urine. To optimize the K recovery, ammonium should be removed prior as much as possible and an alternative alkaline compound should be explored for pH adjustment rather than NaOH. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthetic peptides for antibody production

NARCIS (Netherlands)

N.D. Zegers (Netty)

1995-01-01

textabstractSynthetic peptides are useful tools for the generation of antibodies. The use of antibodies as specific reagents in inununochemical assays is widely applied. In this chapter, the application of synthetic peptides for the generation of antibodies is described. The different steps

Immunization with Tc52 or its amino terminal domain adjuvanted with c-di-AMP induces Th17+Th1 specific immune responses and confers protection against Trypanosoma cruzi.

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Marina N Matos

2017-02-01

Full Text Available The development of new adjuvants enables fine modulation of the elicited immune responses. Ideally, the use of one or more adjuvants should result in the induction of a protective immune response against the specific pathogen. We have evaluated the immune response and protection against Trypanosoma cruzi infection in mice vaccinated with recombinant Tc52 or its N- and C-terminal domains (NTc52 and CTc52 adjuvanted either with the STING (Stimulator of Interferon Genes agonist cyclic di-AMP (c-di-AMP, a pegylated derivative of α-galactosylceramide (αGC-PEG, or oligodeoxynucleotides containing unmethylated CpG motifs (ODN-CpG. All groups immunized with the recombinant proteins plus adjuvant: Tc52+c-di-AMP, NTc52+c-di-AMP, CTc52+c-di-AMP, NTc52+c-di-AMP+αGC-PEG, NTc52+CpG, developed significantly higher anti-Tc52 IgG titers than controls. Groups immunized with c-di-AMP and Tc52, NTc52 or CTc52 showed the highest Tc52-specific IgA titers in nasal lavages. All groups immunized with the recombinant proteins plus adjuvant developed a strong specific cellular immune response in splenocytes and lymph node cells with significant differences for groups immunized with c-di-AMP and Tc52, NTc52 or CTc52. These groups also showed high levels of Tc52-specific IL-17 and IFN-γ producing cells, while NTc52+CpG group only showed significant difference with control in IFN-γ producing cells. Groups immunized with c-di-AMP and Tc52, NTc52 or CTc52 developed predominantly a Th17 and Th1immune response, whereas for NTc52+CpG it was a dominant Th1 response. It was previously described that αGC-PEG inhibits Th17 differentiation by activating NKT cells. Thus, in this work we have also included a group immunized with both adjuvants (NTc52+c-di-AMP+αGC-PEG with the aim to modulate the Th17 response induced by c-di-AMP. This group showed a significant reduction in the number of Tc52-specific IL-17 producing splenocytes, as compared to the group NTc52+c-di-AMP, which has

The pH of buffers based on 2-amino-2-hydroxymethyl-1,3-propanediol (`tris') in synthetic sea water

Science.gov (United States)

DelValls, T. A.; Dickson, A. G.

1998-09-01

E.m.f. measurements were made over the temperature range 273.15-318.15 K, and at five salinities from 20 to 40, using the cell Pt( s) H2( g, p°) BH+ and B in synthetic sea water AgCl( s) Ag( s) Pt( s) where p°=101.325 kPa, and BH + and B are the conjugate acid-base pair of 2-amino-2hydroxymethyl-1,3-propanediol ('tris') - each present at a concentration of 0.04 mol kg -1. The results were used to assign pH values based on the 'total' hydrogen ion scale to such buffer solutions based on this acid-base pair. Additional measurements were made over a range of buffer concentrations at a salinity of 35; these were used to calculate the stoichiometric (ionic medium) dissociation constant for 'tris-H +' in synthetic sea water.

TSH Response to the Intravenous Administration of Synthetic TRH in Various Thyroid Diseases

International Nuclear Information System (INIS)

Choi, Sung Jae; Kim, Kwang Won; Lee, Mun Ho

1980-01-01

Serum TSH levels were ,measured by radioimmunoassay before and after intravenous administration of synthetic thyrotropin-releasing hormone(TRH) to 15 normal subjects and 55 patients with primary thyroid disease (14 patients with euthyroidism, 24 patients with thyrotoxicosis and 17 patients with hypothyroidism) to evaluate pituitary TSH reserve and its diagnostic availability. The observed results were as follows. 1) In normal subjects, serum TSH responses to synthetic TRH were 3.2±1.0 at 0 min (baseline TSH level), 8.0±4.0 at 10 min, 11.7±5.0 at 20 min, 13.7±7.1 at 80 min, 9.7±5.0 at 60 min., 5.2±2.0 at 120 min. and 3.6±0.4 μU/ml at 180 min. Serum TSH peaked at 20-30 minutes and returned nearly to baseline at 180 minutes. 2) In euthyroid group, serum TSH responses to synthetic TRH were 3.3±1.6 at 0 min, 8.6±8.0 at 10 min, 10.9±8. 5 at 20 min, 12.5±8.4 at 30 min, 9.0±5.9 at 60 min, 5.6±2.6 at 120 min and 3.5±1.3 μU/ml at 180 min. No significant difference revealed between euthyroid group and normal subjects(p>0.05). 3) In hyperthyroid group, serum TSH responses to synthetic TRH were 1.5±0.6 at 0 min, 2.2±0.8 at 10 min., 2.3±1.0 at 20 min., 2.4±1.5 at 30 min., 2.1±1.1 at 60 min,, 1.9±0.2 at 120 min, and 1. 5±0.8 μU/ml, at 180 min., No response to TRH showed. 4) In hypothyroid group, mean values of serum TSH response to synthetic TRH were 42.0 at 0 min., 60.6 at 10 min., 124.8 at 20 min., 123.0 at 30 min. 101.6 at 60 min., 64.3 at 120 min. and 15.5 μU/ml at 180 min., Patients with primary hypothyroidism showed an exaggerated TSH response to synthetic TRH despite their high basal TSH. 5) Side effects attending synthetic TRH administration were transient nausea (59.0%), desire to micturate (59.0%), feeling of flushing (19.7%), dizziness (45.9%), metallic taste (9.8%) and headache (19.7%). Any side effect didn't show in 16.4%. These symptoms began almost immediately after TRH intravenous injection and lasted several minutes, and not related to

Synthetic peptides for antibody production

NARCIS (Netherlands)

Zegers, N.D.

1995-01-01

Synthetic peptides are useful tools for the generation of antibodies. The use of antibodies as specific reagents in inununochemical assays is widely applied. In this chapter, the application of synthetic peptides for the generation of antibodies is described. The different steps that lead to the

Synthetic biology era: Improving antibiotic's world.

Science.gov (United States)

Guzmán-Trampe, Silvia; Ceapa, Corina D; Manzo-Ruiz, Monserrat; Sánchez, Sergio

2017-06-15

The emergence of antibiotic-resistant pathogen microorganisms is problematic in the context of the current spectrum of available medication. The poor specificity and the high toxicity of some available molecules have made imperative the search for new strategies to improve the specificity and to pursue the discovery of novel compounds with increased bioactivity. Using living cells as platforms, synthetic biology has counteracted this problem by offering novel pathways to create synthetic systems with improved and desired functions. Among many other biotechnological approaches, the advances in synthetic biology have made it possible to design and construct novel biological systems in order to look for new drugs with increased bioactivity. Advancements have also been made in the redesigning of RNA and DNA molecules in order to engineer antibiotic clusters for antibiotic overexpression. As for the production of these antibacterial compounds, yeasts and filamentous fungi as well as gene therapy are utilized to enhance protein solubility. Specific delivery is achieved by creating chimeras using plant genes into bacterial hosts. Some of these synthetic systems are currently in clinical trials, proving the proficiency of synthetic biology in terms of both pharmacological activities as well as an increase in the biosafety of treatments. It is possible that we may just be seeing the tip of the iceberg, and synthetic biology applications will overpass expectations beyond our present knowledge. Copyright © 2017. Published by Elsevier Inc.

A Rapid ELISA Method for 17, 20b-dihydroxy-4-pregenen-3-one (17,20bP Hormone Using Acetylcholinesterase Enzyme as Tracer

Directory of Open Access Journals (Sweden)

M Ebrahimi

2004-06-01

Full Text Available Background: During the past 15 years Enzyme Linked ImmunoSorbent Assay (ELISA has been described as an alternative to radioimmunoassay for steroid detection. In addition to gonads, sperm itself is capable of producing reduced progesterone metabolites. In this study we introduced a method to extend the applicability of previous measures by describing a general preparation procedure for the enzyme label which is applicable to any steroid hormone. Methods: A simple and rapid Enzyme Linked Immunosorbant Assay (ELISA is described and validated for 17,20β- dihydroxy-4-pregnen-3-one (17,20βP. A general procedure for preparation of the acetylcholinesterase labelled steroid is described which is applicable to any steroid. Results: Use of acetylcholinesterase tracer increased the sensitivity of assay so that reliable measurements of each steroid could be achieved with only 10 µl of plasma. ELISA was applied to measure of 17,20βP steroid production by sperm of trout which has sufficient amount of potent and active 20βHSD enzyme to convert 17α-hydroxy-4-pregnen-3-one (17αP substrate to 17,20βP product. The results showed that a clear shift in 17,20βP production was found with increase in substrate concentration in all in vitro incubations. Conclusion: ELISA method presented in this study has greater sensitivity and accuracy compared to previously described method that uses radiolabelled substances. Keywords: Immunoassay, ELISA, Steroids, Hormone, Assay

Synthetic lubrication oil influences on performance and emission characteristic of coated diesel engine fuelled by biodiesel blends

International Nuclear Information System (INIS)

Mohamed Musthafa, M.

2016-01-01

Highlights: • Synthetic lubricant provides the maximum performance benefits. • Synthetic lubricant is capable of retaining satisfactory viscosity. • Synthetic lubricant is to increase the life of the engine. • Improvement in efficiency of the coated engine with synthetic lubrication. • No significant changes in the coated engine emission with synthetic lubricants. - Abstract: In this study, the effects of using synthetic lubricating oil on the performance and exhaust emissions in a low heat rejection diesel engine running on Pongamia methyl ester blends and diesel have been investigated experimentally compared to those obtained from a conventional diesel engine with SAE 40 lubrication oil fuelled by diesel. For this purpose, direct injection diesel engine was converted to Yttria-stabilized zirconia (YSZ) coated engine. The results showed 5–9% increase in engine efficiency and 8–17% decrease in specific fuel consumption, as well as significant improvements in exhaust gas emissions (except NO_X) for all tested fuels (pure diesel, B10 and B20) used in coated engine with synthetic lubricants compared to that of the uncoated engine with SAE 40 lubricant running on diesel fuel.

Specific gravity and antibacterial assays of some synthetic industrial ...

African Journals Online (AJOL)

... naturalcounterpart may contain certain antibacterial agents with similar effects to standard Chloramphenicol used in this work. However, further studies are required to justify the safety of the application of SIEO as antimicrobial agents. Keywords: synthetic fragrance, Staphylococcus aureus, Escherichia coli, human health ...

Synthetic Biology of Polyhydroxyalkanoates (PHA).

Science.gov (United States)

Meng, De-Chuan; Chen, Guo-Qiang

Microbial polyhydroxyalkanoates (PHA) are a family of biodegradable and biocompatible polyesters which have been extensively studied using synthetic biology and metabolic engineering methods for improving production and for widening its diversity. Synthetic biology has allowed PHA to become composition controllable random copolymers, homopolymers, and block copolymers. Recent developments showed that it is possible to establish a microbial platform for producing not only random copolymers with controllable monomers and their ratios but also structurally defined homopolymers and block copolymers. This was achieved by engineering the genome of Pseudomonas putida or Pseudomonas entomophiles to weaken the β-oxidation and in situ fatty acid synthesis pathways, so that a fatty acid fed to the bacteria maintains its original chain length and structures when incorporated into the PHA chains. The engineered bacterium allows functional groups in a fatty acid to be introduced into PHA, forming functional PHA, which, upon grafting, generates endless PHA variety. Recombinant Escherichia coli also succeeded in producing efficiently poly(3-hydroxypropionate) or P3HP, the strongest member of PHA. Synthesis pathways of P3HP and its copolymer P3HB3HP of 3-hydroxybutyrate and 3-hydroxypropionate were assembled respectively to allow their synthesis from glucose. CRISPRi was also successfully used to manipulate simultaneously multiple genes and control metabolic flux in E. coli to obtain a series of copolymer P3HB4HB of 3-hydroxybutyrate (3HB) and 4-hydroxybutyrate (4HB). The bacterial shapes were successfully engineered for enhanced PHA accumulation.

A fluorescent probe which allows highly specific thiol labeling at low pH

DEFF Research Database (Denmark)

Nielsen, Jonas W.; Jensen, Kristine Steen; Hansen, Rosa E.

2012-01-01

and properties of a thiol-specific reagent, fluorescent cyclic activated disulfide (FCAD), which includes the fluorescein moiety as fluorophore and utilizes a variation of thiol-disulfide exchange chemistry. The leaving-group character of FCAD makes it reactive at pH 3, allowing modification at low pH, limiting...

Oculocutaneous albinism in a patient with 17p13.2-pter duplication - a review on the molecular syndromology of 17p13 duplication.

Science.gov (United States)

Kucharczyk, Marzena; Jezela-Stanek, Aleksandra; Gieruszczak-Bialek, Dorota; Kugaudo, Monika; Cieslikowska, Agata; Pelc, Magdalena; Krajewska-Walasek, Malgorzata

2015-06-01

Chromosomal duplications involving 17p13.3 have recently been defined as a new distinctive syndrome with several diagnosed patients. Some variation is known to occur in the breakpoints of the duplicated region and, consequently, in the phenotype as well. We report on a patient, the fifth to our knowledge, a 4-year-old girl with a pure de novo subtelomeric 17p13.2-pter duplication. She presents all of the facial features described so far for this duplication and in addition, a unilateral palmar transversal crease and oculocutaneous albinism which has not been reported previously. A detailed molecular description of the reported aberration and correlation with the observed phenotypical features based on a literature review. We discuss the possible molecular etiology of albinism in regard to the mode of inheritance. The new data provided here may be useful for further genotype correlations in syndromes with oculocutaneous albinism, especially of autosomal dominant inheritance.

p53 specific (auto)immunity in mice

NARCIS (Netherlands)

Lauwen, Marjolein Monique

2008-01-01

Self-tolerance to p53 is a major potential limitation for the activation of the endogenous T-cell repertoire. So far, p53 specific CD8+ and CD4+ T-cell immunity has been described in cancer patients and healthy individuals. However, the restrictions of tolerance on the recruitment of p53 specific T

Sex-specific effects of low-dose gestational estradiol-17β exposure on bone development in porcine offspring

International Nuclear Information System (INIS)

Flöter, Veronika L.; Galateanu, Gabriela; Fürst, Rainer W.; Seidlová-Wuttke, Dana; Wuttke, Wolfgang; Möstl, Erich; Hildebrandt, Thomas B.

2016-01-01

Highlights: • Sex-specific effects and non-monotonic dose responses were demonstrated after low-dose in utero E2 treatment in offspring. • Alterations in bone parameters were found in prepubertal male but not female offspring. • In postpubertal female offspring, cortical and total cross-sectional area were higher at the femoral midpoint. • In utero E2 treatment did neither significantly affect hormone concentrations nor puberty onset in offspring. • The results substantiate the high sensitivity of developing organisms to exogenous estrogens. - Abstract: Estrogens are important for the bone development and health. Exposure to endocrine disrupting chemicals during the early development has been shown to affect the bone phenotype later in life. Several studies have been performed in rodents, while in larger animals that are important to bridge the gap to humans there is a paucity of data. To this end, the pig as large animal model was used in the present study to assess the influence of gestational estradiol-17β (E2) exposure on the bone development of the prepubertal and adult offspring. Two low doses (0.05 and 10 μg E2/kg body weight) referring to the ‘acceptable daily intake’ (ADI) and the ‘no observed effect level’ (NOEL) as stated for humans, and a high-dose (1000 μg E2/kg body weight), respectively, were fed to the sows every day from insemination until delivery. In the male prepubertal offspring, the ADI dose group had a lower strength strain index (p = 0.002) at the proximal tibia compared to controls, which was determined by peripheral quantitative computed tomography. Prepubertal females were not significantly affected. However, there was a higher cortical cross-sectional area (CSA) (p = 0.03) and total CSA (p = 0.02) at the femur midpoint in the adult female offspring of the NOEL dose group as measured by computed tomography. These effects were independent from plasma hormone concentrations (leptin, IGF1, estrogens), which remained

Geo synthetic-reinforced Pavement systems

International Nuclear Information System (INIS)

Zornberg, J. G.

2014-01-01

Geo synthetics have been used as reinforcement inclusions to improve pavement performance. while there are clear field evidence of the benefit of using geo synthetic reinforcements, the specific conditions or mechanisms that govern the reinforcement of pavements are, at best, unclear and have remained largely unmeasured. Significant research has been recently conducted with the objectives of: (i) determining the relevant properties of geo synthetics that contribute to the enhanced performance of pavement systems, (ii) developing appropriate analytical, laboratory and field methods capable of quantifying the pavement performance, and (iii) enabling the prediction of pavement performance as a function of the properties of the various types of geo synthetics. (Author)

The triazine-based porous organic polymer: Novel synthetic strategy for high specific surface area

International Nuclear Information System (INIS)

Park, Jin Kuen

2017-01-01

A new type of microporous polymer has been successively synthesized via a simple polycondensation reaction with the 2,4-diaminotriazine moiety and dianhydride monomer. Diaminotriazine moieties in M1 especially can provide effective branching sites, resulting in high surface areas up to 1150 m"2 /g. In addition, the specific pore structure of the polyimide POP in its solid state can be modified by the surface activation method. Therefore, it can be expected that the resulting material will be a promising candidate for gas storage, and with this synthetic strategy, various type of derivatives will also be optimized

The triazine-based porous organic polymer: Novel synthetic strategy for high specific surface area

Energy Technology Data Exchange (ETDEWEB)

Park, Jin Kuen [Dept. of Chemistry, Hankuk University of Foreign Studies, Yongin (Korea, Republic of)

2017-02-15

A new type of microporous polymer has been successively synthesized via a simple polycondensation reaction with the 2,4-diaminotriazine moiety and dianhydride monomer. Diaminotriazine moieties in M1 especially can provide effective branching sites, resulting in high surface areas up to 1150 m{sup 2} /g. In addition, the specific pore structure of the polyimide POP in its solid state can be modified by the surface activation method. Therefore, it can be expected that the resulting material will be a promising candidate for gas storage, and with this synthetic strategy, various type of derivatives will also be optimized.

Development, evaluation, and laboratory validation of immunoassays for the diagnosis of equine infectious anemia (EIA) using recombinant protein produced from a synthetic p26 gene of EIA virus.

Science.gov (United States)

Singha, Harisankar; Goyal, Sachin K; Malik, Praveen; Khurana, Sandip K; Singh, Raj K

2013-12-01

Equine infectious anemia (EIA)-a retroviral disease caused by equine infectious anemia virus (EIAV)-is a chronic, debilitating disease of horses, mules, and donkeys. EIAV infection has been reported worldwide and is recognized as pathogen of significant economic importance to the horse industry. This disease falls under regulatory control program in many countries including India. Control of EIA is based on identification of inapparent carriers by detection of antibodies to EIAV in serologic tests and "Stamping Out" policy. The current internationally accepted test for diagnosis of EIA is the agar gel immune-diffusion test (AGID), which detects antibodies to the major gag gene (p26) product. The objective of this study was to develop recombinant p26 based in-house immunoassays [enzyme linked immunosorbent assays (ELISA), and AGID] for EIA diagnosis. The synthetic p26 gene of EIAV was expressed in Escherichia coli and diagnostic potential of recombinant p26 protein were evaluated in ELISA and AGID on 7,150 and 1,200 equine serum samples, respectively, and compared with commercial standard AGID kit. The relative sensitivity and specificity of the newly developed ELISA were 100 and 98.6 %, respectively. Whereas, relative sensitivity and specificity of the newly developed AGID were in complete agreement in respect to commercial AGID kit. Here, we have reported the validation of an ELISA and AGID on large number of equine serum samples using recombinant p26 protein produced from synthetic gene which does not require handling of pathogenic EIAV. Since the indigenously developed reagents would be economical than commercial diagnostic kit, the rp26 based-immunoassays could be adopted for the sero-diagnosis and control of EIA in India.

Radioimmunoassay for the middle region of human parathyroid hormone: comparison of two radioiodinated synthetic peptides

International Nuclear Information System (INIS)

Sharp, M.E.; Marx, S.J.

1985-01-01

Two synthetic peptides were evaluated to develop radioligands for midregion-specific radioimmunoassay (RIA) of human parathyroid hormone (hPTH). Both radioligands were tested using three anti-PTH sera of proven clinical utility. While each of these midregion-directed antisera showed unique specificity, they all reacted with high affinity with both radioligands and none of them discriminated significantly between the two synthetic midregion peptides. Analysis of data on the relation of serum calcium and hPTH midregion immunoreactivity showed a useful separation of groups (all nonazotemic) with primary hyperparathyroidism, secondary hyperparathyroidism, primary hypoparathyroidism and secondary hypoparathyroidism. (Auth.)

New alkali metal diphosphates how materials to preserve the security of the environment: CsNaCu(P2O7), Rb2Cu(P2O7) and CsNaCo(P2O7) synthesis and crystal structure determination

Science.gov (United States)

Chernyatieva, Anastasiya; Filatova, Alyona; Spiridonova, Dariya; Krivovichev, Sergey

2013-04-01

tetrahedra and P2O7 groups. The structure of the [Co(P2O7)]2-framework in more detail. The phosphate groups and tetrahedra coordinate cobalt ions form topology. This is a unique 4-coordination topology, where Co and P2O7 groups in the structure are topologically equivalent. References CHERNYATIEVA, A. P., KRIVOVICHEV, S. V., SPIRIDONOVA, D. V. (2008): International conference «Inorganic Materials» Dresden (2008) P3 - 143. CHERNYATIEVA, A. P, SPIRIDONOVA, D. V., KRIVOVICHEV, S. V. The crystal structures of two new synthetic compounds CsNaCu(P2O7) and Rb2Cu(P2O7), Acta Mineralogica-Petrographica (2012) Vol.7, p.25 EL MAADI, A., BOUKHARI, A., HOLT, E.M. (1995) Journal of Alloys Compounds, 223: 13-17. HUANG, Q., HWU, S. J., MO, X. H. (2001): Angewandte Chemie - International Edition, 40: 1690-1693.

Rational Diversification of a Promoter Providing Fine-Tuned Expression and Orthogonal Regulation for Synthetic Biology

Science.gov (United States)

Blount, Benjamin A.; Weenink, Tim; Vasylechko, Serge; Ellis, Tom

2012-01-01

Yeast is an ideal organism for the development and application of synthetic biology, yet there remain relatively few well-characterised biological parts suitable for precise engineering of this chassis. In order to address this current need, we present here a strategy that takes a single biological part, a promoter, and re-engineers it to produce a fine-graded output range promoter library and new regulated promoters desirable for orthogonal synthetic biology applications. A highly constitutive Saccharomyces cerevisiae promoter, PFY1p, was identified by bioinformatic approaches, characterised in vivo and diversified at its core sequence to create a 36-member promoter library. TetR regulation was introduced into PFY1p to create a synthetic inducible promoter (iPFY1p) that functions in an inverter device. Orthogonal and scalable regulation of synthetic promoters was then demonstrated for the first time using customisable Transcription Activator-Like Effectors (TALEs) modified and designed to act as orthogonal repressors for specific PFY1-based promoters. The ability to diversify a promoter at its core sequences and then independently target Transcription Activator-Like Orthogonal Repressors (TALORs) to virtually any of these sequences shows great promise toward the design and construction of future synthetic gene networks that encode complex “multi-wire” logic functions. PMID:22442681

Rational diversification of a promoter providing fine-tuned expression and orthogonal regulation for synthetic biology.

Science.gov (United States)

Blount, Benjamin A; Weenink, Tim; Vasylechko, Serge; Ellis, Tom

2012-01-01

Yeast is an ideal organism for the development and application of synthetic biology, yet there remain relatively few well-characterised biological parts suitable for precise engineering of this chassis. In order to address this current need, we present here a strategy that takes a single biological part, a promoter, and re-engineers it to produce a fine-graded output range promoter library and new regulated promoters desirable for orthogonal synthetic biology applications. A highly constitutive Saccharomyces cerevisiae promoter, PFY1p, was identified by bioinformatic approaches, characterised in vivo and diversified at its core sequence to create a 36-member promoter library. TetR regulation was introduced into PFY1p to create a synthetic inducible promoter (iPFY1p) that functions in an inverter device. Orthogonal and scalable regulation of synthetic promoters was then demonstrated for the first time using customisable Transcription Activator-Like Effectors (TALEs) modified and designed to act as orthogonal repressors for specific PFY1-based promoters. The ability to diversify a promoter at its core sequences and then independently target Transcription Activator-Like Orthogonal Repressors (TALORs) to virtually any of these sequences shows great promise toward the design and construction of future synthetic gene networks that encode complex "multi-wire" logic functions.

Early recurrence in standard-risk medulloblastoma patients with the common idic(17)(p11.2) rearrangement

Science.gov (United States)

Bien-Willner, Gabriel A.; López-Terrada, Dolores; Bhattacharjee, Meena B.; Patel, Kayuri U.; Stankiewicz, Paweł; Lupski, James R.; Pfeifer, John D.; Perry, Arie

2012-01-01

Medulloblastoma is diagnosed histologically; treatment depends on staging and age of onset. Whereas clinical factors identify a standard- and a high-risk population, these findings cannot differentiate which standard-risk patients will relapse and die. Outcome is thought to be influenced by tumor subtype and molecular alterations. Poor prognosis has been associated with isochromosome (i)17q in some but not all studies. In most instances, molecular investigations document that i17q is not a true isochromosome but rather an isodicentric chromosome, idic(17)(p11.2), with rearrangement breakpoints mapping within the REPA/REPB region on 17p11.2. This study explores the clinical utility of testing for idic(17)(p11.2) rearrangements using an assay based on fluorescent in situ hybridization (FISH). This test was applied to 58 consecutive standard- and high-risk medulloblastomas with a 5-year minimum of clinical follow-up. The presence of i17q (ie, including cases not involving the common breakpoint), idic(17)(p11.2), and histologic subtype was correlated with clinical outcome. Overall survival (OS) and disease-free survival (DFS) were consistent with literature reports. Fourteen patients (25%) had i17q, with 10 (18%) involving the common isodicentric rearrangement. The presence of i17q was associated with a poor prognosis. OS and DFS were poor in all cases with anaplasia (4), unresectable disease (7), and metastases at presentation (10); however, patients with standard-risk tumors fared better. Of these 44 cases, tumors with idic(17)(p11.2) were associated with significantly worse patient outcomes and shorter mean DFS. FISH detection of idic(17)(p11.2) may be useful for risk stratification in standard-risk patients. The presence of this abnormal chromosome is associated with early recurrence of medulloblastoma. PMID:22573308

Synthetic properties of models of globular clusters

Energy Technology Data Exchange (ETDEWEB)

Angeletti, L; Dolcetta, R; Giannone, P. (Rome Univ. (Italy). Osservatorio Astronomico)

1980-05-01

Synthetic and projected properties of models of globular clusters have been computed on the basis of stellar evolution and time changes of the dynamical cluster structure. Clusters with five and eight stellar groups (each group consisting of stars with the same mass) were studied. Mass loss from evolved stars was taken into account. Observational features were obtained at ages of 10-19 x 10/sup 9/ yr. The basic importance of the horizontal- and asymptotic-branch stars was pointed out. A comparison of the results with observed data of M3 is discussed with the purpose of obtaining general indications rather than a specific fit.

Synthetic properties of models of globular clusters

International Nuclear Information System (INIS)

Angeletti, L.; Dolcetta, R.; Giannone, P.

1980-01-01

Synthetic and projected properties of models of globular clusters have been computed on the basis of stellar evolution and time changes of the dynamical cluster structure. Clusters with five and eight stellar groups (each group consisting of stars with the same mass) were studied. Mass loss from evolved stars was taken into account. Observational features were obtained at ages of 10-19 x 10 9 yr. The basic importance of the horizontal- and asymptotic-branch stars was pointed out. A comparison of the results with observed data of M3 is discussed with the purpose of obtaining general indications rather than a specific fit. (orig.)

Synthetic Biology and Personalized Medicine

Science.gov (United States)

Jain, K.K.

2013-01-01

Synthetic biology, application of synthetic chemistry to biology, is a broad term that covers the engineering of biological systems with structures and functions not found in nature to process information, manipulate chemicals, produce energy, maintain cell environment and enhance human health. Synthetic biology devices contribute not only to improve our understanding of disease mechanisms, but also provide novel diagnostic tools. Methods based on synthetic biology enable the design of novel strategies for the treatment of cancer, immune diseases metabolic disorders and infectious diseases as well as the production of cheap drugs. The potential of synthetic genome, using an expanded genetic code that is designed for specific drug synthesis as well as delivery and activation of the drug in vivo by a pathological signal, was already pointed out during a lecture delivered at Kuwait University in 2005. Of two approaches to synthetic biology, top-down and bottom-up, the latter is more relevant to the development of personalized medicines as it provides more flexibility in constructing a partially synthetic cell from basic building blocks for a desired task. PMID:22907209

Inactive Gingipains from P. gingivalis Selectively Skews T Cells toward a Th17 Phenotype in an IL-6 Dependent Manner

Directory of Open Access Journals (Sweden)

Jan Potempa

2017-04-01

Full Text Available Gingipain cysteine proteases are considered key virulence factors of Porphyromonas gingivalis. They significantly influence antibacterial and homeostatic functions of macrophages, neutrophils, the complement system, and cytokine networks. Recent data indicate the role of P. gingivalis in T cell differentiation; however, the involvement of gingipains in this process remains elusive. Therefore, the aim of this study was to investigate the contribution of danger signals triggered by the gingipains on the generation of Th17 cells, which play a key role in protection against bacterial diseases but may cause chronic inflammation and bone resorption. To this end we compared the effects of the wild-type strain of P. gingivalis (W83 with its isogenic mutant devoid of gingipain activity (ΔKΔRAB, and bacterial cells pretreated with a highly-specific inhibitor of gingipains activity (KYTs. Antigen presenting cells (APCs, both professional (dendritic cells, and non-professional (gingival keratinocytes, exposed to viable bacteria expressed high amounts of cytokines (IL-6, IL-21, IL-23. These cytokines are reported to either stimulate or balance the Th17-dependent immune response. Surprisingly, cells infected with P. gingivalis devoid of gingipain activity showed increased levels of all tested cytokines compared to bacteria with fully active enzymes. The effect was dependent on both the reduction of cytokine proteolysis and the lack of cross-talk with other bacterial virulence factors, including LPS and fimbriae that induce de novo synthesis of cytokines. The profile of lymphocyte T differentiation from naive T cells showed enhanced generation of Th17 in response to bacteria with inactive gingipains. Moreover, we found that gingipain-dependent induction of Th17 cells was highly specific, since other T cell-subsets remained unchanged. Finally, inhibition of IL-6 signaling in dendritic cells led to a significant depletion of the Th17 population. Cumulatively

Inactive Gingipains from P. gingivalis Selectively Skews T Cells toward a Th17 Phenotype in an IL-6 Dependent Manner.

Science.gov (United States)

Glowczyk, Izabela; Wong, Alicia; Potempa, Barbara; Babyak, Olena; Lech, Maciej; Lamont, Richard J; Potempa, Jan; Koziel, Joanna

2017-01-01

Gingipain cysteine proteases are considered key virulence factors of Porphyromonas gingivalis . They significantly influence antibacterial and homeostatic functions of macrophages, neutrophils, the complement system, and cytokine networks. Recent data indicate the role of P. gingivalis in T cell differentiation; however, the involvement of gingipains in this process remains elusive. Therefore, the aim of this study was to investigate the contribution of danger signals triggered by the gingipains on the generation of Th17 cells, which play a key role in protection against bacterial diseases but may cause chronic inflammation and bone resorption. To this end we compared the effects of the wild-type strain of P. gingivalis (W83) with its isogenic mutant devoid of gingipain activity (ΔKΔRAB), and bacterial cells pretreated with a highly-specific inhibitor of gingipains activity (KYTs). Antigen presenting cells (APCs), both professional (dendritic cells), and non-professional (gingival keratinocytes), exposed to viable bacteria expressed high amounts of cytokines (IL-6, IL-21, IL-23). These cytokines are reported to either stimulate or balance the Th17-dependent immune response. Surprisingly, cells infected with P. gingivalis devoid of gingipain activity showed increased levels of all tested cytokines compared to bacteria with fully active enzymes. The effect was dependent on both the reduction of cytokine proteolysis and the lack of cross-talk with other bacterial virulence factors, including LPS and fimbriae that induce de novo synthesis of cytokines. The profile of lymphocyte T differentiation from naive T cells showed enhanced generation of Th17 in response to bacteria with inactive gingipains. Moreover, we found that gingipain-dependent induction of Th17 cells was highly specific, since other T cell-subsets remained unchanged. Finally, inhibition of IL-6 signaling in dendritic cells led to a significant depletion of the Th17 population. Cumulatively, this study

Platelet factor-4 and its p17-70 peptide inhibit myeloma proliferation and angiogenesis in vivo

International Nuclear Information System (INIS)

Yang, Longjiang; Du, Juan; Hou, Jian; Jiang, Hua; Zou, Jianfeng

2011-01-01

Angiogenesis plays an important role in the development of multiple myeloma (MM). The interaction between MM cells and the bone marrow microenvironment stimulates the proliferation and migration of endothelial progenitor cells (EPCs). Vascular endothelial growth factor (VEGF) contributes to the formation of new blood vessels by actively recruiting circulating EPCs. The production of proangiogenic and antiangiogenic factors is also dysregulated in MM. Platelet factor 4 (PF4) is a potent angiostatic cytokine that inhibits angiogenesis and tumor growth in several animal models. In this study, we stably transfected human myeloma cell lines with the PF4 gene or the sequence encoding its more potent p17-70 peptide and investigated the effects of PF4 and p17-70 on angiogenesis and tumor growth in vitro and in a SCID-rab myeloma model. PF4 and p17-70 significantly attenuated VEGF production, both in vitro and in vivo. In a migration study using a Transwell system, PF4 or p17-70 markedly suppressed the migration of co-cultured human endothelial progenitor cells. PF4 or p17-70 also caused a significant reduction in microvessel densities in myeloma xenografts and markedly reduced the tumor volume in the SCID mice. Kaplan-Meier analysis demonstrated that PF4 and p17-70 significantly extended the overall survival of SCID mice bearing human myeloma xenografts. Our findings indicate that PF4 or p17-70 could be valuable in combating multiple myeloma by disrupting tumor angiogenesis

EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF); Scientific Opinion on Flavouring Group Evaluation 17, Revision 3 (FGE.17Rev3): Pyrazine derivatives from chemical group 24

DEFF Research Database (Denmark)

Larsen, John Christian; Nørby, Karin Kristiane; Beltoft, Vibe Meister

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate 28 flavouring substances in the Flavouring Group Evaluation 17, including seven additional substances considered in this Revision 3, using the Procedure......-activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. The Panel concluded that 24 substances [FL-no: 14.057, 14.081, 14.083, 14.084, 14.086, 14.087, 14.091, 14.097, 14.099, 14.101, 14.102, 14.108, 14.109, 14.111, 14.112, 14.113, 14.122, 14...... substances, the specifications for the materials of commerce have also been considered and for one substance [FL-no: 14.102], the composition of mixture has not been specified sufficiently....

EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF); Scientific Opinion on Flavouring Group Evaluation 17, Revision 2 (FEG.17Rev2): Pyrazine derivatives from chemical group 24

DEFF Research Database (Denmark)

Larsen, John Christian; Nørby, Karin Kristiane; Beltoft, Vibe Meister

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate 21 flavouring substances in the Flavouring Group Evaluation 17, Revision 2, using the Procedure in Commission Regulation (EC) No 1565/2000. From the in vitro...... substance [FL-no: 14.051] no intake data are available preventing it from being evaluated through the Procedure. The remaining 18 substances were evaluated through a stepwise approach that integrates information on structure-activity relationships, intake from current uses, toxicological threshold...... intake, estimated on the basis of the MSDI approach. For the remaining substance [FL-no: 14.052] additional toxicity data are required. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered and for two substances...

Rheumatoid arthritis patients exhibit impaired Candida albicans-specific Th17 responses.

Science.gov (United States)

Bishu, Shrinivas; Su, Ee Wern; Wilkerson, Erich R; Reckley, Kelly A; Jones, Donald M; McGeachy, Mandy J; Gaffen, Sarah L; Levesque, Marc C

2014-02-11

Accumulating data implicate the CD4+ T cell subset (Th17 cells) in rheumatoid arthritis (RA). IL-17 is an inflammatory cytokine that induces tumor necrosis factor (TNF)α, IL-1β and IL-6, all of which are targets of biologic therapies used to treat RA. RA patients are well documented to experience more infections than age-matched controls, and biologic therapies further increase the risk of infection. The Th17/IL-17 axis is vital for immunity to fungi, especially the commensal fungus Candida albicans. Therefore, we were prompted to examine the relationship between RA and susceptibility to C. albicans because of the increasing interest in Th17 cells and IL-17 in driving autoimmunity, and the advent of new biologics that target this pathway. We analyzed peripheral blood and saliva from 48 RA and 33 healthy control subjects. To assess C. albicans-specific Th17 responses, PBMCs were co-cultured with heat-killed C. albicans extract, and IL-17A levels in conditioned supernatants were measured by ELISA. The frequency of Th17 and Th1 cells was determined by flow cytometry. As a measure of IL-17A-mediated effector responses, we evaluated C. albicans colonization rates in the oral cavity, salivary fungicidal activity and levels of the antimicrobial peptide β-defensin 2 (BD2) in saliva. Compared to controls, PBMCs from RA subjects exhibited elevated baseline production of IL-17A (P = 0.004), although they had similar capacity to produce IL-17A in response to Th17 cell differentiating cytokines (P = 0.91). However RA PBMCs secreted less IL-17A in response to C. albicans antigens (P = 0.006). Significantly more RA patients were colonized with C. albicans in the oral cavity than healthy subjects (P = 0.02). Concomitantly, RA saliva had reduced concentrations of salivary BD2 (P = 0.02). Nonetheless, salivary fungicidal activity was preserved in RA subjects (P = 0.70). RA subjects exhibit detectable impairments in oral immune responses to C. albicans, a

T Helper 17 Promotes Induction of Antigen-Specific Gut-Mucosal Cytotoxic T Lymphocytes following Adenovirus Vector Vaccination

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Masahisa Hemmi

2017-11-01

Full Text Available Few current vaccines can establish antigen (Ag-specific immune responses in both mucosal and systemic compartments. Therefore, development of vaccines providing defense against diverse infectious agents in both compartments is of high priority in global health. Intramuscular vaccination of an adenovirus vector (Adv has been shown to induce Ag-specific cytotoxic T lymphocytes (CTLs in both systemic and gut-mucosal compartments. We previously found that type I interferon (IFN signaling is required for induction of gut-mucosal, but not systemic, CTLs following vaccination; however, the molecular mechanism involving type I IFN signaling remains unknown. Here, we found that T helper 17 (Th17-polarizing cytokine expression was down-regulated in the inguinal lymph nodes (iLNs of Ifnar2−/− mice, resulting in the reduction of Ag-specific Th17 cells in the iLNs and gut mucosa of the mice. We also found that prior transfer of Th17 cells reversed the decrease in the number of Ag-specific gut-mucosal CTLs in Ifnar2−/− mice following Adv vaccination. Additionally, prior transfer of Th17 cells into wild-type mice enhanced the induction of Ag-specific CTLs in the gut mucosa, but not in systemic compartments, suggesting a gut mucosa-specific mechanism where Th17 cells regulate the magnitude of vaccine-elicited Ag-specific CTL responses. These data suggest that Th17 cells translate systemic type I IFN signaling into a gut-mucosal CTL response following vaccination, which could promote the development of promising Adv vaccines capable of establishing both systemic and gut-mucosal protective immunity.

Identification of novel peptide ligands for the cancer-specific receptor mutation EFGRvIII using a mixture-based synthetic combinatorial library

DEFF Research Database (Denmark)

Denholt, Charlotte Lund; Hansen, Paul Robert; Pedersen, Nina

2009-01-01

We report here, the design and synthesis of a positional scanning synthetic combinatorial library for the identification of novel peptide ligands targeted against the cancer-specific epidermal growth factor tyrosine kinase receptor mutation variant III (EGFRvIII). This receptor is expressed in se...

A facile synthetic route to poly(p-phenylene terephthalamide) with dual functional groups.

Science.gov (United States)

Du, Shuming; Wang, Wenbin; Yan, Yan; Zhang, Jie; Tian, Ming; Zhang, Liqun; Wan, Xinhua

2014-09-07

Claisen rearrangement reaction was employed for the first time to obtain a novel PPTA bearing reactive allyl and hydroxyl groups which may act as a sizing agent of Kevlar fibers to improve the interface structure and interfacial adhesion of rubber or epoxy based composites.

The Impact of MicroRNA-223-3p on IL-17 Receptor D Expression in Synovial Cells.

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Nozomu Moriya

Full Text Available Rheumatoid arthritis (RA is an autoimmune inflammatory disease affecting joints. Elevated plasma levels of microRNA-223-3p (miR-223-3p in patients with RA are implicated in the pathogenesis of the disease. This study aimed to analyze the functional role of miR-223-3p in the pathogenesis of RA by overexpressing miR-223-3p in synovial cell lines.Arthritis was induced in the RA model of SKG mice by injection of ß-glucan. The histopathologic features of joints were examined using hematoxylin and eosin and immunohistochemical staining. Plasma levels of miRNA were determined by panel real-time PCR analysis. Target genes of the differentially expressed miRNAs in SKG mice were analyzed using miRNA target prediction algorithms. The dual-luciferase reporter system was used to evaluate the relationship between miR-223-3p and IL-17 receptor D (IL-17RD. The activity of miR-223-3p was analyzed by transfection of plasmid vectors overexpressing miR-223-3p into IL-17RD-expressing NIH3T3 and MH7A cell lines. Il6 and Il17rd mRNA expression was analyzed by quantitative real-time PCR. IL-17RD protein expression was analyzed by western blot analysis.We identified 17 upregulated miRNAs (fold change > 2.0 in plasma of SKG mice injected with ß-glucan relative to untreated SKG mice. Il17rd was identified as the candidate target gene of miR-223-3p using five miRNA target prediction algorithms. The transfection of plasmid vectors overexpressing miR-223-3p into NIH3T3 and MH7A cells resulted in the downregulation of Il17rd expression and upregulation of Il6 expression. Expression of miR-223-3p and Il6 mRNA in MH7A cells was upregulated; however, that of Il17rd mRNA was downregulated following TNF-α stimulation. IL-17RD expression in synovial tissues from SKG mice and RA patients was inversely correlated with the severity of arthritis.This study is the first to demonstrate that miR-223-3p downregulates IL-17RD in both mouse and human cells; miR-223-3p may contribute to

Avian Reovirus Protein p17 Functions as a Nucleoporin Tpr Suppressor Leading to Activation of p53, p21 and PTEN and Inactivation of PI3K/AKT/mTOR and ERK Signaling Pathways.

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Wei-Ru Huang

Full Text Available Avian reovirus (ARV protein p17 has been shown to regulate cell cycle and autophagy by activation of p53/PTEN pathway; nevertheless, it is still unclear how p53 and PTEN are activated by p17. Here, we report for the first time that p17 functions as a nucleoporin Tpr suppressor that leads to p53 nuclear accumulation and consequently activates p53, p21, and PTEN. The nuclear localization signal (119IAAKRGRQLD128 of p17 has been identified for Tpr binding. This study has shown that Tpr suppression occurs by p17 interacting with Tpr and by reducing the transcription level of Tpr, which together inhibit Tpr function. In addition to upregulation of PTEN by activation of p53 pathway, this study also suggests that ARV protein p17 acts as a positive regulator of PTEN. ARV p17 stabilizes PTEN by stimulating phosphorylation of cytoplasmic PTEN and by elevating Rak-PTEN association to prevent it from E3 ligase NEDD4-1 targeting. To activate PTEN, p17 is able to promote β-arrestin-mediated PTEN translocation from the cytoplasm to the plasma membrane via a Rock-1-dependent manner. The accumulation of p53 in the nucleus induces the PTEN- and p21-mediated downregulation of cyclin D1 and CDK4. Furthermore, Tpr and CDK4 knockdown increased virus production in contrast to depletion of p53, PTEN, and LC3 reducing virus yield. Taken together, our data suggest that p17-mediated Tpr suppression positively regulates p53, PTEN, and p21 and negatively regulates PI3K/AKT/mTOR and ERK signaling pathways, both of which are beneficial for virus replication.

pBAM1: an all-synthetic genetic tool for analysis and construction of complex bacterial phenotypes

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Arévalo-Rodríguez Miguel

2011-02-01

Full Text Available Abstract Background Since publication in 1977 of plasmid pBR322, many breakthroughs in Biology have depended on increasingly sophisticated vector platforms for analysis and engineering of given bacterial strains. Although restriction sites impose a certain format in the procedures for assembling cloned genes, every attempt thus far to standardize vector architecture and nomenclature has ended up in failure. While this state of affairs may still be tolerable for traditional one-at-a-time studies of single genes, the onset of systems and synthetic biology calls for a simplification -along with an optimization- of the currently unwieldy pool of genetic tools. Results The functional DNA sequences present in the natural bacterial transposon Tn5 have been methodically edited and refactored for the production of a multi-purpose genetic tool named pBAM1, which allows a range of manipulations in the genome of Gram-negative bacteria. This all-synthetic construct enhances the power of mini-transposon vectors for either de-construction or re-construction of phenotypes á la carte by incorporating features inspired in systems engineering: modularity, re-usability, minimization, and compatibility with other genetic tools. pBAM1 bears an streamlined, restriction site-freed and narrow-host range replication frame bearing the sequences of R6K oriV, oriT and an ampicillin resistance marker. These go along with a business module that contains a host-independent and hyperactive transposition platform for in vivo or in vitro insertion of desired DNA into the genome of the target bacterium. All functional sequences were standardized for a straightforward replacement by equivalent counterparts, if required. pBAM1 can be delivered into recipient cells by either mating or electroporation, producing transposon insertion frequencies of 1.8 × 10-3 and 1.02 × 10-7, respectively in the soil bacterium Pseudomonas putida. Analyses of the resulting clones revealed a 100% of

Indole and synthetic derivative activate chaperone expression to reduce polyQ aggregation in SCA17 neuronal cell and slice culture models

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Kung PJ

2014-10-01

Full Text Available Pin-Jui Kung,1,* Yu-Chen Tao,1,* Ho-Chiang Hsu,1 Wan-Ling Chen,1 Te-Hsien Lin,1 Donala Janreddy,2 Ching-Fa Yao,2 Kuo-Hsuan Chang,3 Jung-Yaw Lin,1 Ming-Tsan Su,1 Chung-Hsin Wu,1 Guey-Jen Lee-Chen,1 Hsiu-Mei Hsieh-Li1 1Department of Life Science, 2Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan; 3Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan *These authors contributed equally to this work Abstract: In spinocerebellar ataxia type 17 (SCA17, the expansion of a translated CAG repeat in the TATA box binding protein (TBP gene results in a long polyglutamine (polyQ tract in the TBP protein, leading to intracellular accumulation of aggregated TBP and cell death. The molecular chaperones act in preventing protein aggregation to ameliorate downstream harmful events. In this study, we used Tet-On SH-SY5Y cells with inducible SCA17 TBP/Q79-green fluorescent protein (GFP expression to test indole and synthetic derivative NC001-8 for neuroprotection. We found that indole and NC001-8 up-regulated chaperone expression to reduce polyQ aggregation in neuronal differentiated TBP/Q79 cells. The effects on promoting neurite outgrowth and on reduction of aggregation on Purkinje cells were also confirmed with cerebellar primary and slice cultures of SCA17 transgenic mice. Our results demonstrate how indole and derivative NC001-8 reduce polyQ aggregation to support their therapeutic potentials in SCA17 treatment. Keywords: spinocerebellar ataxia type 17, TATA box binding protein, polyQ aggregation, indole and derivative, therapeutics

The Baseplate of Lactobacillus delbrueckii Bacteriophage Ld17 Harbors a Glycerophosphodiesterase.

Science.gov (United States)

Cornelissen, Anneleen; Sadovskaya, Irina; Vinogradov, Evgeny; Blangy, Stéphanie; Spinelli, Silvia; Casey, Eoghan; Mahony, Jennifer; Noben, Jean-Paul; Dal Bello, Fabio; Cambillau, Christian; van Sinderen, Douwe

2016-08-05

Glycerophosphodiester phosphodiesterases (GDPDs; EC 3.1.4.46) typically hydrolyze glycerophosphodiesters to sn-glycerol 3-phosphate (Gro3P) and their corresponding alcohol during patho/physiological processes in bacteria and eukaryotes. GDPD(-like) domains were identified in the structural particle of bacterial viruses (bacteriophages) specifically infecting Gram-positive bacteria. The GDPD of phage 17 (Ld17; GDPDLd17), representative of the group b Lactobacillus delbrueckii subsp. bulgaricus (Ldb)-infecting bacteriophages, was shown to hydrolyze, besides the simple glycerophosphodiester, two complex surface-associated carbohydrates of the Ldb17 cell envelope: the Gro3P decoration of the major surface polysaccharide d-galactan and the oligo(glycerol phosphate) backbone of the partially glycosylated cell wall teichoic acid, a minor Ldb17 cell envelope component. Degradation of cell wall teichoic acid occurs according to an exolytic mechanism, and Gro3P substitution is presumed to be inhibitory for GDPDLd17 activity. The presence of the GDPDLd17 homotrimer in the viral baseplate structure involved in phage-host interaction together with the dependence of native GDPD activity, adsorption, and efficiency of plating of Ca(2+) ions supports a role for GDPDLd17 activity during phage adsorption and/or phage genome injection. In contrast to GDPDLd17, we could not identify any enzymatic activity for the GDPD-like domain in the neck passage structure of phage 340, a 936-type Lactococcus lactis subsp. lactis bacteriophage. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Antimicrobial activity of new porphyrins of synthetic and natural origin

Science.gov (United States)

Gyulkhandanyan, Grigor V.; Ghazaryan, Robert K.; Paronyan, Marina H.; Ulikhanyan, Ghukas I.; Gyulkhandanyan, Aram G.; Sahakyan, Lida A.

2012-03-01

Antimicrobial photodynamic inactivation has been successfully used against Gram (+) microorganisms, but most of the photosensitizers (PSs) on Gram (-) bacteria acts weakly. PSs are the natural or synthetic origin dyes, mainly porphyrins. We have synthesized more than 100 new cationic porphyrins and metalloporphyrins with different functional groups (hydroxyethyl, butyl, allyl, methallyl) and metals (cobalt, iron, copper, zinc, silver and other); from the nettle have also been purified pheophytin (a+b) and pheophytin (a) and have synthesized their Ag-and Zn-metalloporphyrins. It was found that in the dark (cytotoxic) mode, the most highly efficiency against microorganisms showed Agmetalloporphyrins of both types of porphyrins (synthetic and natural). Metalloporphyrin of natural origin Ag-pheophytin (a + b) is a strong antibacterial agent and causes 100% death as the Gram (+) microorganisms (St. aureus and MRSA) and the Gram (-) microorganisms (E.coli and Salmonella). It is established that for the destruction of Gram (+) and Gram (-) microorganisms in photodynamic mode cationic water-soluble synthetic metalloporphyrins, especially Zn-TBut4PyP, many times more effective than pheophytins. In vivo conditions on mice established that the best therapeutic activity against various strains of the microorganism St. aureus has the synthetic metalloporphyrin Ag-TBut4PyP. It is significantly more efficient than known drug "Chlorophyllipt" (2.5-3 times) and leads the survival rate of animals up to 50-60%.

Use of specific radioimmunoassays to determine the renal clearance rates of estrone and 17. beta. -estradiol during the menstrual cycle. [Tritium tracer techniques

Energy Technology Data Exchange (ETDEWEB)

Wright, K.; Collins, D.C.; Preedy, J.R.K.

1978-11-01

Specific RIAs requiring ether extraction only were established for estrone and 17..beta..-estradiol both in plasma and in urine from the nonpregnant female. These assays were used to measure the renal clearance rates of estrone and of 17..beta..-estradiol in eight ambulatory women in the follicular and in the luteal phases of the menstrual cycle. The mean (+-SE) for the renal clearance rate of estrone was 0.71 +- 0.058 ml/min in the follicular phase and 1.26 +- 0.35 ml/min in the luteal phase. The mean (+-SE) renal clearance rate of 17..beta..-estradiol was 0.44 +- 0.055 ml/min in the follicular phase and 0.29 +- 0.043 ml/min in the luteal phase. There was no significant difference in the renal clearance rates of either estrone or of 17..beta..-estradiol between the follicular and luteal phases of the cycle. The renal clearances of estrone and 17..beta..-estradiol were highly correlated (r = 0.84; P < 0.01). The renal clearance rate of estrone was significantly greater than that of 17..beta..-estradiol in both phases of the cycle (P < 0.01).

Quality of life in mucopolysaccharidoses: construction of a specific measure using the focus group technique.

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Oliveira, M R; Schwartz, I; Costa, L S; Maia, H; Ribeiro, M; Guerreiro, L B; Acosta, A; Rocha, N S

2018-01-15

To describe the perceptions of patients, their caregivers, and their healthcare providers to the development of a new specific instrument for assessment of the quality of life (QoL) in patients with mucopolysaccharidoses (MPS) using a qualitative focus group (FG) design. FGs were held in two Brazilian states (Rio Grande do Sul and Rio de Janeiro). Three versions of the new instrument were developed, each for a different age group: children (age 8-12 years), adolescents (age 13-17), and adults (age ≥ 18). The FGs mostly confirmed the relevance of items. All FGs unanimously agreed on the facets: School, Happiness, Life Prospects, Religiosity, Pain, Continuity of Treatment, Trust in Treatment, Relationship with Family, Relationship with Healthcare Providers, Acceptance, and Meaning of Life. The overall concept of QoL (as proposed by the WHO-World Health Organization) and its facets apply to this patient population. However, other specific facets-particularly concerning clinical manifestations and the reality of the disease-were suggested, confirming the need for the development of a specific QoL instrument for MPS.

Detection of autoimmune antibodies in localized scleroderma by synthetic oligonucleotide antigens

DEFF Research Database (Denmark)

Samuelsen, Simone; Jørgensen, Christian Damsgaard; Mellins, Elizabeth D

2018-01-01

In this study, we developed a series of synthetic oligonucleotides that allowed us to investigate the details on the antigen recognition by autoimmune antibodies in localized scleroderma subjects. Besides dramatically improved analytical specificity of the assay, our data suggests a potential...... linking for antibodies to DNA to the biological status of disease state in localized scleroderma. Moreover, introducing chemical modifications into short synthetic deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) molecules completely changed the binding titers of corresponding antibodies...... and their clinical relevance. The strongest observed effect was registered for the localized scleroderma skin damage index (LoSDI) on the IgG antibodies to TC dinucleotide-rich double-stranded antigen (p

ATF4-Induced Metabolic Reprograming Is a Synthetic Vulnerability of the p62-Deficient Tumor Stroma.

Science.gov (United States)

Linares, Juan F; Cordes, Thekla; Duran, Angeles; Reina-Campos, Miguel; Valencia, Tania; Ahn, Christopher S; Castilla, Elias A; Moscat, Jorge; Metallo, Christian M; Diaz-Meco, Maria T

2017-12-05

Tumors undergo nutrient stress and need to reprogram their metabolism to survive. The stroma may play a critical role in this process by providing nutrients to support the epithelial compartment of the tumor. Here we show that p62 deficiency in stromal fibroblasts promotes resistance to glutamine deprivation by the direct control of ATF4 stability through its p62-mediated polyubiquitination. ATF4 upregulation by p62 deficiency in the stroma activates glucose carbon flux through a pyruvate carboxylase-asparagine synthase cascade that results in asparagine generation as a source of nitrogen for stroma and tumor epithelial proliferation. Thus, p62 directly targets nuclear transcription factors to control metabolic reprogramming in the microenvironment and repress tumorigenesis, and identifies ATF4 as a synthetic vulnerability in p62-deficient tumor stroma. Copyright © 2017 Elsevier Inc. All rights reserved.

The effects of cigarette smoking on prostate-specific antigen in two different age groups.

Science.gov (United States)

Koc, Gokhan; Akgul, Korhan; Yilmaz, Yuksel; Dirik, Alper; Un, Sitki

2013-01-01

We investigate the effects of cigarette smoking on prostate-specific antigen (PSA) using 2 different age groups. The study was carried out between January 2007 and October 2011 with men; the 2 sets of age groups were: 25 to 35 years and 50 to 70 years old. The participants were divided into 4 groups. Of the 25 to 35 age range, smokers were Group 1, and non-smokers were Group 2; of the 50 to 70 age range, smokers were Group 3 and non-smokers Group 4. In addition, for the 50 to 70 age group, the International Prostate Symptom Score was completed, digital rectal examination was performed, and transabdominal prostate volume was measured. We wanted to see whether prostate-specific antigen (PSA) levels showed a difference between the 2 age groups. There were 114 patients in Group 1, 82 in Group 2, 90 in Group 3, and 102 in Group 4. The mean PSA level was 0.7 ± 0.28 ng/mL for Group 1, and 0.6 ± 0.27 ng/mL for Group 2 (p = 0.27), and there was no statistically significant difference between the 2 groups. The mean PSA was 2.5 ± 1.8 ng/mL for Group 3, and 2.1 ± 2.0 ng/mL (p = 0.59) for Group 4, and there was no statistically significant difference between the these 2 age groups. Cigarette smoking effects various hormone levels. Different from previous studies, the PSA level was higher in smokers compared to nonsmokers, although it was not statistically significant. Our study is limited by the small numbers in our study groups and the lack of PSA velocity data.

Measurement of the {sup 15}O(2p,{gamma}){sup 17}Ne cross section by Coulomb dissociation of {sup 17}Ne

Energy Technology Data Exchange (ETDEWEB)

Marganiec, Justyna [ExtreMe Matter Institute EMMI, GSI Darmstadt, Darmstadt (Germany); Aumann, Thomas; Heil, Michael; Plag, Ralf; Wamers, Felix [Kernreaktionen und Nuklear Astrophysik, GSI Darmstadt, Darmstadt (Germany)

2010-07-01

For the production of proton-rich nuclei during the rp process two-proton capture plays an important role. This process can bridge long-lived waiting points which otherwise hamper the mass flow between CNO material and the FeNi mass region. One of these waiting points is {sup 15}O. The three-body radiative capture can proceed sequentially or directly from the three-body continuum. The rate of the {sup 15}O(2p,{gamma}){sup 17}Ne reaction obtained using the two-successive-proton-capture model has been discussed in J. Goerres et al. (Phys. Rev. C 51, 392, 1995). The role of continuum states ({sup 15}O+2p) for the rate calculation has been demonstrated in L.V Grigorenko, M.V. Zhukov (Phys. Rev. C 72, 015803, 2005). It has been suggested that the reaction rate can be enhanced by a few orders of magnitude by taking into account the three-body continuum. In order to verify these calculations, we have deduced the {sup 15}O(2p,{gamma}){sup 17}Ne cross section by studying the time-reversed process, the Coulomb dissociation of {sup 17}Ne, at the LAND/R{sup 3}B setup at GSI, using a {sup 17}Ne secondary beam from the fragment separator FRS.

Screening for HIV-related PTSD: Sensitivity and specificity of the 17 ...

African Journals Online (AJOL)

This study assessed the sensitivity and specificity of the 17-item Post traumatic Stress Diagnostic Scale (PDS), a self-report instrument, in the detection of HIVrelated PTSD. An adapted version of the PTSD module of the Composite International Diagnostic Interview (CIDI) served as the gold standard. Method: 85 HIV-positive ...

Engineering of synthetic, stress-responsive yeast promoters

DEFF Research Database (Denmark)

Rajkumar, Arun Stephen; Liu, Guodong; Bergenholm, David

2016-01-01

Advances in synthetic biology and our understanding of the rules of promoter architecture have led to the development of diverse synthetic constitutive and inducible promoters in eukaryotes and prokaryotes. However, the design of promoters inducibleby specific endogenous or environmental conditions...

Automated radiofrequency-based US measurement of common carotid intima-media thickness in RA patients treated with synthetic vs synthetic and biologic DMARDs.

Science.gov (United States)

Naredo, Esperanza; Möller, Ingrid; Corrales, Alfonso; Bong, David A; Cobo-Ibáñez, Tatiana; Corominas, Hector; Garcia-Vivar, Ma Luz; Macarrón, Pilar; Navio, Teresa; Richi, Patricia; Iagnocco, Annamaria; Garrido, Jesús; Martínez-Hernández, David

2013-02-01

To compare the carotid intima-media thickness (IMT) assessed with automated radiofrequency-based US in RA patients treated with synthetic vs synthetic and biologic DMARDs and controls. Ninety-four RA patients and 94 sex- and age-matched controls were prospectively recruited at seven centres. Cardiovascular (CV) risk factors and co-morbidities, RA characteristics and therapy were recorded. Common carotid artery (CCA)-IMT was assessed in RA patients and controls with automated radiofrequency-based US by the same investigator at each centre. Forty-five (47.9%) RA patients had been treated with synthetic DMARDs and 49 (52.1%) with synthetic and biologic DMARDs. There were no significant differences between the RA patients and controls in demographics, CV co-morbidities and CV disease. There were significantly more smokers among RA patients treated with synthetic and biologic DMARDs (P = 0.036). Disease duration and duration of CS and synthetic DMARD therapy was significantly longer in RA patients treated with synthetic and biologic DMARDs (P radiofrequency-based measurement of CCA-IMT can discriminate between RA patients treated with synthetic DMARDs vs RA patients treated with synthetic and biologic DMARDs.

Molecular Imaging in Synthetic Biology, and Synthetic Biology in Molecular Imaging.

Science.gov (United States)

Gilad, Assaf A; Shapiro, Mikhail G

2017-06-01

Biomedical synthetic biology is an emerging field in which cells are engineered at the genetic level to carry out novel functions with relevance to biomedical and industrial applications. This approach promises new treatments, imaging tools, and diagnostics for diseases ranging from gastrointestinal inflammatory syndromes to cancer, diabetes, and neurodegeneration. As these cellular technologies undergo pre-clinical and clinical development, it is becoming essential to monitor their location and function in vivo, necessitating appropriate molecular imaging strategies, and therefore, we have created an interest group within the World Molecular Imaging Society focusing on synthetic biology and reporter gene technologies. Here, we highlight recent advances in biomedical synthetic biology, including bacterial therapy, immunotherapy, and regenerative medicine. We then discuss emerging molecular imaging approaches to facilitate in vivo applications, focusing on reporter genes for noninvasive modalities such as magnetic resonance, ultrasound, photoacoustic imaging, bioluminescence, and radionuclear imaging. Because reporter genes can be incorporated directly into engineered genetic circuits, they are particularly well suited to imaging synthetic biological constructs, and developing them provides opportunities for creative molecular and genetic engineering.

Membrane polypeptide in rabbit erythrocytes associated with the inhibition of L-lactate transport by a synthetic anhydride of lactic acid

International Nuclear Information System (INIS)

Donovan, J.A.; Jennings, M.L.

1985-01-01

The synthetic lactyl anhydride isobutylcarbonyl lactyl anhydride (iBCLA), a selective and potent inhibitor of L-(+)-lactate transport in rabbit erythrocytes, reduces the chemical labeling of a 40-50-kdalton polypeptide by tritiated 4,4'-diisothiocyanato-2,2'-dihydrostilbenedisulfonate ([ 3 H]H 2 DIDS). iBCLA does so in a dose-dependent manner at concentrations that strongly inhibit lactate-lactate exchange but not chloride-phosphate exchange. These labeling experiments and inhibition reversal studies using iBCLA, p-(chloro-mercuri)benzenesulfonic acid (pCMBS), and dithiothreitol (DDT) suggest that iBCLA does not act at sulfhydryl groups but at or near an amino group that is near a disulfide linkage in the polypeptide which catalyzes lactate transport. These experiments support the association between specific monocarboxylate transport and a 40-50-kdalton membrane-bound polypeptide of the rabbit erythrocyte

Word selection affects perceptions of synthetic biology

Directory of Open Access Journals (Sweden)

Tonidandel Scott

2011-07-01

Full Text Available Abstract Members of the synthetic biology community have discussed the significance of word selection when describing synthetic biology to the general public. In particular, many leaders proposed the word "create" was laden with negative connotations. We found that word choice and framing does affect public perception of synthetic biology. In a controlled experiment, participants perceived synthetic biology more negatively when "create" was used to describe the field compared to "construct" (p = 0.008. Contrary to popular opinion among synthetic biologists, however, low religiosity individuals were more influenced negatively by the framing manipulation than high religiosity people. Our results suggest that synthetic biologists directly influence public perception of their field through avoidance of the word "create".

Labeling of amino acids and peptides with isotopic oxygen as followed by 17O-N.M.R

International Nuclear Information System (INIS)

Steinschneider, A.; Burgar, M.I.; Buku, A.; Fiat, D.

1981-01-01

17 O was introduced into the respective α- and γ-COOH groups of Boc-Gly and Boc-Glu by saponification of the corresponding O-methyl esters with 1 N NaOH in H 2 17 O. Other 17 O enriched Boc-amino acids were prepared by acid catalyzed exchange into the amino acid α-COOH group followed by t-butyloxycarbonylation with t-butyl S-4, 6-dimethylpyrimidin-2-ylthio carbonate. Final enrichment, by approximately three orders of magnitude over natural abundance, was 60-100% of the possible maximum. The synthesis of [ 17 O]-Gly-Ala, [ 17 O]-Gly-Leu and [ 17 O]-Gly-Glu by DCC/HBT mediated coupling of Boc-Gly-[ 17 O]-α-COOH with amino acid-O-t-butyl esters followed by deprotection with HCL/EtOAc proceeded without undue loss of the isotope. Boc-[ 17 O]-Pro-Leu-Gly-NH 2 was prepared by a similar procedure. [Tyr 2 - 17 O]-, Pro 7 - 17 O]- and [Gly 4 - 17 O]-oxytocin were synthesized using solid phase support. 17 O-chemical shifts of synthetic intermediates and of the final products were as expected for each functional group. Linewith data correlate with the molecular weights of the compounds prepared. (author)

Justifying group-specific common morality.

Science.gov (United States)

Strong, Carson

2008-01-01

Some defenders of the view that there is a common morality have conceived such morality as being universal, in the sense of extending across all cultures and times. Those who deny the existence of such a common morality often argue that the universality claim is implausible. Defense of common morality must take account of the distinction between descriptive and normative claims that there is a common morality. This essay considers these claims separately and identifies the nature of the arguments for each claim. It argues that the claim that there is a universal common morality in the descriptive sense has not been successfully defended to date. It maintains that the claim that there is a common morality in the normative sense need not be understood as universalist. This paper advocates the concept of group specific common morality, including country-specific versions. It suggests that both the descriptive and the normative claims that there are country-specific common moralities are plausible, and that a country-specific normative common morality could provide the basis for a country's bioethics.

Synthetic Lipoproteins as Carriers for Drug Delivery.

Science.gov (United States)

Huang, Gangliang; Liu, Yang; Huang, Hualiang

2016-01-01

Synthetic lipoprotein is an effective carrier of targeted delivery for drugs. It has the very small size, good biocompatibility, suitable half-life, and specific lipoprotein receptorbinding capacity. Compared with the traditional natural lipoprotein, synthetic lipoprotein not only retains the original biological characteristics and functions, but also exhibits the excellent characteristics in drug delivery. Herein, the advantages, development, applications, and prospect of synthetic lipoproteins as drug carriers were summarized.

Detection and cellular localisation of the synthetic soluble macromolecular drug carrier pHPMA

Energy Technology Data Exchange (ETDEWEB)

Kissel, Maria; Peschke, Peter; Strunz, Anke M.; Kuehnlein, Rainer; Debus, Juergen [Department of Radiation Oncology, E0505, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Subr, Vladimir; Ulbrich, Karel [Institute of Macromolecular Chemistry, Prague (Czech Republic); Friedrich, Eckhard [Division of Biology, University of Koblenz-Landau, Landau (Germany)

2002-08-01

Synthetic macromolecules such as copolymers of N-(2-hydroxypropyl)methacrylamide (pHPMA) are potential carriers for the delivery of drugs owing to their ability to passively accumulate in solid tumours [enhanced permeation and retention (EPR) effect]. To gain further knowledge about the biodistribution and the cellular localisation, poly(HPMA) was prepared for labelling by introducing biotin molecules. Biotinylated pHPMA (5 mol%) was intravenously injected into tumour-bearing rats and the accumulation of biotin-pHPMA was visualised using a streptavidin-alkaline phosphatase technique at day 7 post injection. In spite of the high solubility of pHPMA copolymers and the lack of attachment to cell structures, the biotinylated polymer could be easily detected in tissues fixed in 10% paraformaldehyde-phosphate buffer at 4 C for 48 h. While biotin-pHPMA could be detected intracytoplasmically in liver and spleen, a predominantly interstitial localisation was observed within the anaplastic prostate carcinoma (Dunning R3327-AT1). How biotin as a label influences the biodistribution of poly(HPMA) was assessed by scintigraphy, autoradiography and histology comparing homopolymer poly(HPMA) with biotin-pHPMA. The organ distribution patterns of the two polymers correlated well, except with respect to kidney. It is assumed that the accumulation of biotin-pHPMA in the distal tubuli is due to a biotin transporter in the brush border membrane. The technique presented is useful for a more comprehensive understanding of the biodistribution of soluble macromolecules. (orig.)

Detection and cellular localisation of the synthetic soluble macromolecular drug carrier pHPMA

International Nuclear Information System (INIS)

Kissel, Maria; Peschke, Peter; Strunz, Anke M.; Kuehnlein, Rainer; Debus, Juergen; Subr, Vladimir; Ulbrich, Karel; Friedrich, Eckhard

2002-01-01

Synthetic macromolecules such as copolymers of N-(2-hydroxypropyl)methacrylamide (pHPMA) are potential carriers for the delivery of drugs owing to their ability to passively accumulate in solid tumours [enhanced permeation and retention (EPR) effect]. To gain further knowledge about the biodistribution and the cellular localisation, poly(HPMA) was prepared for labelling by introducing biotin molecules. Biotinylated pHPMA (5 mol%) was intravenously injected into tumour-bearing rats and the accumulation of biotin-pHPMA was visualised using a streptavidin-alkaline phosphatase technique at day 7 post injection. In spite of the high solubility of pHPMA copolymers and the lack of attachment to cell structures, the biotinylated polymer could be easily detected in tissues fixed in 10% paraformaldehyde-phosphate buffer at 4 C for 48 h. While biotin-pHPMA could be detected intracytoplasmically in liver and spleen, a predominantly interstitial localisation was observed within the anaplastic prostate carcinoma (Dunning R3327-AT1). How biotin as a label influences the biodistribution of poly(HPMA) was assessed by scintigraphy, autoradiography and histology comparing homopolymer poly(HPMA) with biotin-pHPMA. The organ distribution patterns of the two polymers correlated well, except with respect to kidney. It is assumed that the accumulation of biotin-pHPMA in the distal tubuli is due to a biotin transporter in the brush border membrane. The technique presented is useful for a more comprehensive understanding of the biodistribution of soluble macromolecules. (orig.)

The Role of Neutrophils in the Induction of Specific Th1 and Th17 during Vaccination against Tuberculosis.

Science.gov (United States)

Trentini, Monalisa M; de Oliveira, Fábio M; Kipnis, André; Junqueira-Kipnis, Ana P

2016-01-01

Mycobacterium tuberculosis causes tuberculosis (TB), a disease that killed more than 1.5 million people worldwide in 2014, and the Bacillus Calmette Guérin (BCG) vaccine is the only currently available vaccine against TB. However, it does not protect adults. Th1 and Th17 cells are crucial for TB control, as well as the neutrophils that are directly involved in DC trafficking to the draining lymph nodes and the activation of T lymphocytes during infection. Although several studies have shown the importance of neutrophils during M. tuberculosis infection, none have shown its role in the development of a specific response to a vaccine. The vaccine mc(2)-CMX was shown to protect mice against M. tuberculosis challenge, mainly due to specific Th1 and Th17 cells. This study evaluated the importance of neutrophils in the generation of the Th1- and Th17-specific responses elicited by this vaccine. The vaccine injection induced a neutrophil rich lesion with a necrotic central area. The IL-17 KO mice did not generate vaccine-specific Th1 cells. The vaccinated IL-22 KO mice exhibited Th1- and Th17-specific responses. Neutrophil depletion during vaccination abrogated the induction of Th1-specific responses and prohibited the bacterial load reduction observed in the vaccinated animals. The results show, for the first time, the role of neutrophils in the generation of specific Th1 and Th17 cells in response to a tuberculosis vaccine.

Synthesis, radiometric determination of functional groups, complexation

International Nuclear Information System (INIS)

Pompe, S.; Bubner, M.; Schmeide, K.; Heise, K.H.; Bernhard, G.; Nitsche, H.

2000-01-01

The interaction behavior of humic acids with uranium(VI) and the influence of humic substances on the migration behavior of uranium was investigated. A main focus of this work was the synthesis of four different humic acid model substances and their characterization and comparison to the natural humic acid from Aldrich. A radiometric method for the determination of humic acid functional groups was applied in addition to conventional methods for the determination of the functionality of humic acids. The humic acid model substances show functional and structural properties comparable to natural humic acids. Modified humic acids with blocked phenolic OH were synthesized to determine the influence of phenolic OH groups on the complexation behavior of humic acids. A synthesis method for 14 C-labeled humic acids with high specific activity was developed. The complexation behavior of synthetic and natural humic acids with uranium(VI) was investigated by X-ray absorption spectroscopy, laser-induced fluorescence spectroscopy and FTIR spectroscopy. The synthetic model substances show an interaction behavior with uranium(VI) that is comparable to natural humic acids. This points to the fact that the synthetic humic acids simulate the functionality of their natural analogues very well. For the first time the influence of phenolic OH groups on the complexation behavior of humic acids was investigated by applying a modified humic acid with blocked phenolic OH groups. The formation of a uranyl hydroxy humate complex was identified by laserspectroscopic investigations of the complexation of Aldrich humic acid with uranium(VI) at pH 7. The migration behavior of uranium in a sandy aquifer system rich is humic substances was investigated in column experiments. A part of uranium migrates non-retarded through the sediment, bound to humic colloids. The uranium migration behavior is strongly influenced by the kinetically controlled interaction processes of uranium with the humic colloids

WHO Working Group on Technical Specifications for Manufacture and Evaluation of Yellow Fever Vaccines, Geneva, Switzerland, 13-14 May 2009.

Science.gov (United States)

Ferguson, Morag; Shin, Jinho; Knezevic, Ivana; Minor, Philip; Barrett, Alan

2010-12-06

In May 2009, WHO convened a meeting of Working Group on Technical Specifications for Manufacturing and Evaluating Yellow Fever (YF) Vaccines, Geneva, Switzerland to initiate revision of the WHO Recommendations (formerly, Requirements) for YF vaccine published in WHO Technical Report Series number 872 (1998). The Working Group, consisting of experts from academia, industry, national regulatory authorities and national control laboratories, reviewed the latest issues of safety, efficacy and quality of YF vaccines and agreed that (i) the revision should focus on live attenuated YF vaccine virus 17D lineage; and that (ii) nonclinical and clinical guidelines for new vaccines prepared from 17D lineage be developed. Copyright © 2010. Published by Elsevier Ltd.. All rights reserved.

Synthetic biology and occupational risk.

Science.gov (United States)

Howard, John; Murashov, Vladimir; Schulte, Paul

2017-03-01

Synthetic biology is an emerging interdisciplinary field of biotechnology that involves applying the principles of engineering and chemical design to biological systems. Biosafety professionals have done an excellent job in addressing research laboratory safety as synthetic biology and gene editing have emerged from the larger field of biotechnology. Despite these efforts, risks posed by synthetic biology are of increasing concern as research procedures scale up to industrial processes in the larger bioeconomy. A greater number and variety of workers will be exposed to commercial synthetic biology risks in the future, including risks to a variety of workers from the use of lentiviral vectors as gene transfer devices. There is a need to review and enhance current protection measures in the field of synthetic biology, whether in experimental laboratories where new advances are being researched, in health care settings where treatments using viral vectors as gene delivery systems are increasingly being used, or in the industrial bioeconomy. Enhanced worker protection measures should include increased injury and illness surveillance of the synthetic biology workforce; proactive risk assessment and management of synthetic biology products; research on the relative effectiveness of extrinsic and intrinsic biocontainment methods; specific safety guidance for synthetic biology industrial processes; determination of appropriate medical mitigation measures for lentiviral vector exposure incidents; and greater awareness and involvement in synthetic biology safety by the general occupational safety and health community as well as by government occupational safety and health research and regulatory agencies.

Frequency of chromosome 17 aneuploidy in primary and recurrent pterygium by interphase-fluorescence in situ hybridization.

Science.gov (United States)

Kamis, Umit; Kerimoglu, Hurkan; Ozkagnici, Ahmet; Acar, Hasan

2006-01-01

To investigate chromosome 17 numerical aberrations by using fluorescence in situ hybridization (FISH) in pterygia and to find out whether there is any association between chromosome 17 aneuploidy and recurrent pterygia. Pterygium tissue samples were taken from 21 patients by surgical excision. Eighteen of them had primary and 3 had recurrent pterygium. Peripheral whole blood interphase cells obtained from 11 healthy subjects were assigned as control group. The cells from pterygium tissue and peripheral blood were incubated with a hypotonic solution and fixed in order to obtain interphase nuclei. FISH analysis with chromosome-17-specific alpha-satellite DNA probe was performed on both the interphase nuclei of pterygium tissue (of patients) and peripheral whole blood cells of controls. The mean percentage of chromosome 17 aneuploidy was 4.71% for the pterygia group and 4.41% for the controls. No significant difference of chromosome 17 aneuploidy was observed between the patients and the controls. When the group of patients with recurrences was compared with the group without recurrences, there was a significant difference in the frequency of chromosome 17 aneuploidy (U = 17, p = 0.029). Chromosome 17 aneuploidy is probably not an important factor in the formation of pterygium, but it may be related to recurrence.

Specific collaborative group intervention for patients with medically unexplained symptoms in general practice: a cluster randomized controlled trial.

Science.gov (United States)

Schaefert, R; Kaufmann, C; Wild, B; Schellberg, D; Boelter, R; Faber, R; Szecsenyi, J; Sauer, N; Guthrie, E; Herzog, W

2013-01-01

Patients with medically unexplained symptoms (MUS) are frequent in primary care and substantially impaired in their quality of life (QoL). Specific training of general practitioners (GPs) alone did not demonstrate sustained improvement at later follow-up in current reviews. We evaluated a collaborative group intervention. We conducted a cluster randomized controlled trial. Thirty-five GPs recruited 304 MUS patients (intervention group: 170; control group: 134). All GPs were trained in diagnosis and management of MUS (control condition). Eighteen randomly selected intervention GPs participated in training for a specific collaborative group intervention. They conducted 10 weekly group sessions and 2 booster meetings in their practices, together with a psychosomatic specialist. Six and 12 months after baseline, QoL was assessed with the Short-Form 36. The primary outcome was the physical composite score (PCS), and the secondary outcome was the mental composite score (MCS). At 12 months, intention-to-treat analyses showed a significant between-group effect for the MCS (p = 0.023) but not for the PCS (p = 0.674). This effect was preceded by a significant reduction of somatic symptom severity (15-item somatic symptom severity scale of the Patient Health Questionnaire, PHQ-15) at 6 months (p = 0.008) that lacked significance at 12 months (p = 0.078). As additional between-group effects at 12 months, per-protocol analyses showed less health anxiety (Whiteley-7; p = 0.038) and less psychosocial distress (PHQ; p = 0.024); GP visits were significantly (p = 0.042) reduced in the intervention group. Compared to pure GP training, collaborative group intervention achieved a progressive, clinically meaningful improvement in mental but not physical QoL. It could bridge gaps between general practice and mental health care. Copyright © 2012 S. Karger AG, Basel.

By Targeting Stat3 microRNA-17-5p Promotes Cardiomyocyte Apoptosis in Response to Ischemia Followed by Reperfusion

Directory of Open Access Journals (Sweden)

Weijie Du

2014-08-01

Full Text Available Background: Several studies have confirmed the role of microRNAs in regulating ischemia/reperfusion-induced cardiac injury (I/R-I. MiR-17-5p has been regarded as an oncomiR in the development of cancer. However, its potential role in cardiomyocytes has not been exploited. The aim of this study is to investigate the role of miR-17-5p in I/R-I and the underlying mechanism through targeting Stat3, a key surviving factor in cardiomyocytes. Methods: MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromide assay was used to detect the cell viability. ELISA and TUNEL were performed to measure apoptosis of neonatal rat ventricular cardiomyocytes (NRVCs. Infarct area was estimated by TTC (triphenyltetrazolium chloride and Evans blue staining. Western blot analysis was employed to detect the Stat3 and p-Stat3 levels and real-time RT-PCR was used to quantify miR-17-5p level. Results: The miR-17-5p level was significantly up-regulated in I/R-I mice and in NRVCs under oxidative stress. Overexpression of miR-17-5p aggravated cardiomyocyte injury with reduced cell viability and enhanced apoptotic cell death induced by H2O2, whereas inhibition of miR-17-5p by its antisense AMO-17-5p abrogated the deleterious changes. Moreover, the locked nucleic acid-modified antisense (LNA-anti-miR-17-5p markedly decreased the infarct area and apoptosis induced by I/R-I in mice. Furthermore, overexpression of miR-17-5p diminished the p-Stat3 level in response to H2O2. The results from Western blot analysis and luciferase reporter gene assay confirmed Stat3 as a target gene for miR-17-5p. Conclusion: Upregulation of miR-17-5p promotes apoptosis induced by oxidative stress via targeting Stat3, accounting partially for I/R-I.

Large-scale production and study of a synthetic G protein-coupled receptor: Human olfactory receptor 17-4

Science.gov (United States)

Cook, Brian L.; Steuerwald, Dirk; Kaiser, Liselotte; Graveland-Bikker, Johanna; Vanberghem, Melanie; Berke, Allison P.; Herlihy, Kara; Pick, Horst; Vogel, Horst; Zhang, Shuguang

2009-01-01

Although understanding of the olfactory system has progressed at the level of downstream receptor signaling and the wiring of olfactory neurons, the system remains poorly understood at the molecular level of the receptors and their interaction with and recognition of odorant ligands. The structure and functional mechanisms of these receptors still remain a tantalizing enigma, because numerous previous attempts at the large-scale production of functional olfactory receptors (ORs) have not been successful to date. To investigate the elusive biochemistry and molecular mechanisms of olfaction, we have developed a mammalian expression system for the large-scale production and purification of a functional OR protein in milligram quantities. Here, we report the study of human OR17-4 (hOR17-4) purified from a HEK293S tetracycline-inducible system. Scale-up of production yield was achieved through suspension culture in a bioreactor, which enabled the preparation of >10 mg of monomeric hOR17-4 receptor after immunoaffinity and size exclusion chromatography, with expression yields reaching 3 mg/L of culture medium. Several key post-translational modifications were identified using MS, and CD spectroscopy showed the receptor to be ≈50% α-helix, similar to other recently determined G protein-coupled receptor structures. Detergent-solubilized hOR17-4 specifically bound its known activating odorants lilial and floralozone in vitro, as measured by surface plasmon resonance. The hOR17-4 also recognized specific odorants in heterologous cells as determined by calcium ion mobilization. Our system is feasible for the production of large quantities of OR necessary for structural and functional analyses and research into OR biosensor devices. PMID:19581598

The Effects of Synthetic Cannabinoids on Alveolar-Arterial Oxygen Gradient

Directory of Open Access Journals (Sweden)

Egemen Kucuk

2016-09-01

Full Text Available Aim: Synthetic cannabinoids are chemicals that produce several marijuana-like effects in humans. Aim of this study is to investigate the effects of synthetic cannabinoids on to alveolar-arterial oxygen gradient. Material and Method: A total of 112 patients, who admitted directly to emergency clinic with synthetic cannabinoid usage, were determined between February 2014 and August 2014. Blood gases of 41 patients were determined as arterial blood gases on room air, and included in to study. Patients were evaluated according to age, sex, decade, partial pressure of arterial oxygen, partial pressure of arterial carbon dioxide, pH, bicarbonate, metabolic status, age consistent expected alveolar-arterial oxygen gradient and calculated alveolar-arterial oxygen gradient. Results: Synthetic cannabinoid using was higher in males, mean age of patients was 23.32±6.14 years. Number of patients in the third decade were significantly higher than the other decades. The calculated alveolar-arterial oxygen gradient value of patients was significantly higher than age consistent expected alveolar-arterial oxygen gradient value. Respiratory acidosis, was significantly higher than the other types of the metabolic disorders. The best cutoff point for calculated alveolar-arterial oxygen gradient was 12.70, with sensitivity of 90% and specifity of 85%. Area under curve was 0.70 for calculated alveolar-arterial oxygen gradient. Discussion: The value of alveolar-arterial oxygen gradient has been increased due to synthetic cannabinoid usage. This can be used as a supportive parameter in the diagnosis of synthetic cannabinoid usage.

miR-17-5p targets the p300/CBP-associated factor and modulates androgen receptor transcriptional activity in cultured prostate cancer cells

International Nuclear Information System (INIS)

Gong, Ai-Yu; Eischeid, Alex N; Xiao, Jing; Zhao, Jian; Chen, Dongqing; Wang, Zhao-Yi; Young, Charles YF; Chen, Xian-Ming

2012-01-01

Androgen receptor (AR) signalling is critical to the initiation and progression of prostate cancer (PCa). Transcriptional activity of AR involves chromatin recruitment of co-activators, including the p300/CBP-associated factor (PCAF). Distinct miRNA expression profiles have been identified in PCa cells during the development and progression of the disease. Whether miRNAs regulate PCAF expression in PCa cells to regulate AR transcriptional activity is still unclear. Expression of PCAF was investigated in several PCa cell lines by qRT-PCR, Western blot, and immunocytochemistry. The effects of PCAF expression on AR-regulated transcriptional activity and cell growth in PCa cells were determined by chromatin immunoprecipitation, reporter gene construct analysis, and MTS assay. Targeting of PCAF by miR-17-5p was evaluated using the luciferase reporter assay. PCAF was upregulated in several PCa cell lines. Upregulation of PCAF promoted AR transcriptional activation and cell growth in cultured PCa cells. Expression of PCAF in PCa cells was associated with the downregulation of miR-17-5p. Targeting of the 3’-untranslated region of PCAF mRNA by miR-17-5p caused translational suppression and RNA degradation, and, consequently, modulation of AR transcriptional activity in PCa cells. PCAF is upregulated in cultured PCa cells, and upregulation of PCAF is associated with the downregulation of miR-17-5p. Targeting of PCAF by miR-17-5p modulates AR transcriptional activity and cell growth in cultured PCa cells

Oestrous synchronization and fertility in cycling Damascus does using the synthetic prostaglandin F2α, iliren

International Nuclear Information System (INIS)

Zarkawi, M.

2008-01-01

To assess the effect of synthetic prostaglandin F2α (PGF2α) Iliren, on oestrous synchronisation and other related parameters, 9 intact indigenous Damascus does each were either intramuscularly injected twice with 2 ml of synthetic prostaglandin F2α, Iliren (0.3 mg Tiaprost) at an interval of 12 d (P) or served as control (C) with no treatments. Doses in group P responded to the treatment and exhibited oestrus at an average of 96 h; whereas, does in group C exhibited oestrus at an average of 199 h after bucks introduction. The treatment had no significant effect (P>0.05) on duration of pregnancy, fecundity rate of does, birth or weaning weight of kids at 3 months of age. At the second injection of PGF2α, there were active corpora lutea formed in some ovaries of the does treated with Iliren as indicated by the high concentration of progesterone. It could be concluded that it is possible to use the synthetic prostaglandin F2α, Iliren, at a dose of 2 ml (0.3 mg Tiaprost) given twice at an interval of 12 d for oestrous synchronisation in local Damascus does during the breeding season with no adverse effect on the reproductive or growth parameters. (author)

Microbial transformation of synthetic estrogen 17 alpha-ethinylestradiol

Czech Academy of Sciences Publication Activity Database

Cajthaml, Tomáš; Křesinová, Zdena; Svobodová, Kateřina; Sigler, Karel; Řezanka, Tomáš

2009-01-01

Roč. 157, č. 12 (2009), s. 3325-3335 ISSN 0269-7491 R&D Projects: GA MŠk LC06066; GA AV ČR KJB600200613 Institutional research plan: CEZ:AV0Z50200510 Keywords : 17 alpha-Ethinylestradiol * Microbial biodegradation * Ligninolytic fungi Subject RIV: EE - Microbiology, Virology Impact factor: 3.426, year: 2009

Duplication of 17(p11.2p11.2) in a male child with autism and severe language delay.

Science.gov (United States)

Nakamine, Alisa; Ouchanov, Leonid; Jiménez, Patricia; Manghi, Elina R; Esquivel, Marcela; Monge, Silvia; Fallas, Marietha; Burton, Barbara K; Szomju, Barbara; Elsea, Sarah H; Marshall, Christian R; Scherer, Stephen W; McInnes, L Alison

2008-03-01

Duplications of 17(p11.2p11.2) have been associated with various behavioral manifestations including attention deficits, obsessive-compulsive symptoms, autistic traits, and language delay. We are conducting a genetic study of autism and are screening all cases for submicroscopic chromosomal abnormalities, in addition to standard karyotyping, and fragile X testing. Using array-based comparative genomic hybridization analysis of data from the Affymetrix GeneChip(R) Human Mapping Array set, we detected a duplication of approximately 3.3 Mb on chromosome 17p11.2 in a male child with autism and severe expressive language delay. The duplication was confirmed by measuring the copy number of genomic DNA using quantitative polymerase chain reaction. Gene expression analyses revealed increased expression of three candidate genes for the Smith-Magenis neurobehavioral phenotype, RAI1, DRG2, and RASD1, in transformed lymphocytes from Case 81A, suggesting gene dosage effects. Our results add to a growing body of evidence suggesting that duplications of 17(p11.2p11.2) result in language delay as well as autism and related phenotypes. As Smith-Magenis syndrome is also associated with language delay, a gene involved in acquisition of language may lie within this interval. Whether a parent of origin effect, gender of the case, the presence of allelic variation, or changes in expression of genes outside the breakpoints influence the resultant phenotype remains to be determined. (c) 2007 Wiley-Liss, Inc.

The duplication 17p13.3 phenotype

DEFF Research Database (Denmark)

Curry, Cynthia J; Rosenfeld, Jill A; Grant, Erica

2013-01-01

. Older patients were often overweight. Three variant phenotypes included cleft lip/palate (CLP), split hand/foot with long bone deficiency (SHFLD), and a connective tissue phenotype resembling Marfan syndrome. The duplications in patients with clefts appear to disrupt ABR, while the SHFLD phenotype......Chromosome 17p13.3 is a gene rich region that when deleted is associated with the well-known Miller-Dieker syndrome. A recently described duplication syndrome involving this region has been associated with intellectual impairment, autism and occasional brain MRI abnormalities. We report 34...... was associated with duplication of BHLHA9 as noted in two recent reports. The connective tissue phenotype did not have a convincing critical region. Our experience with this large cohort expands knowledge of this diverse duplication syndrome....

Monoclonal antibodies against a synthetic peptide from human immunodeficiency virus type 1 Nef protein

DEFF Research Database (Denmark)

Steinaa, L; Wulff, A M; Saermark, T

1994-01-01

Monoclonal antibodies against a synthetic peptide (aa 138-152) from HIV-1 Nef protein were produced and characterized. Three hybridoma lines producing monoclonal antibodies (MAbs) against the synthetic peptide were generated by fusion between P3-X63 Ag8.653 myeloma cells and BALB/c splenocytes from...... mice immunized with the synthetic peptide coupled to keyhole limpet hemocyanin (KLH). The hybridomas were screened and selected by ELISA with the peptide coupled to bovine serum albumin (BSA) immobilized to the polystyrene surface and specificity for the peptide was confirmed by competitive ELISA...... with the peptide free in solution. The reactions of the MAbs with a 5-aa motif (WCYKL) included in the sequence were examined with synthetic peptides and two of the MAbs reacted with the motif. The recognitions of recombinant full-length Nef protein were also tested. One MAb reacted with the protein in both ELISA...

Chagas disease-specific antigens: characterization of epitopes in CRA/FRA by synthetic peptide mapping and evaluation by ELISA-peptide assay.

Science.gov (United States)

Bottino, Carolina G; Gomes, Luciano P; Pereira, José B; Coura, José R; Provance, David William; De-Simone, Salvatore G

2013-12-03

The identification of epitopes in proteins recognized by medically relevant antibodies is useful for the development of peptide-based diagnostics and vaccines. In this study, epitopes in the cytoplasmic repetitive antigen (CRA) and flagellar repetitive antigen (FRA) proteins from Trypanosoma cruzi were identified using synthetic peptide techniques and pooled sera from Chagasic patients. The epitopes were further assayed with an ELISA assay based on synthetic peptides. Twenty-two overlapping synthetic peptides representing the coding sequence of the T. cruzi CRA and FRA proteins were assessed by a Spot-synthesis array analysis using sera donated by patients with Chagas disease. Shorter peptides were selected that represented the determined epitopes and synthesized by solid phase synthesis to evaluate the patterns of cross-reactivities and discrimination through an ELISA-diagnostic assay. The peptide Spot-synthesis array successfully identified two IgG antigenic determinants in the CRA protein and four in FRA. Bioinformatics suggested that the CRA antigens were unique to T. cruzi while the FRA antigen showed similarity with sequences present within various proteins from Leishmania sp. Subsequently, shorter peptides representing the CRA-1, CRA-2 and FRA-1 epitopes were synthesized by solid phase synthesis and assayed by an ELISA-diagnostic assay. The CRA antigens gave a high discrimination between Chagasic, Leishmaniasis and T. cruzi-uninfected serum. A sensitivity and specificity of 100% was calculated for CRA. While the FRA antigen showed a slightly lower sensitivity (91.6%), its specificity was only 60%. The epitopes recognized by human anti-T. cruzi antibodies have been precisely located in two biomarkers of T. cruzi, CRA and FRA. The results from screening a panel of patient sera through an ELISA assay based on peptides representing these epitopes strongly suggest that the sequences from CRA would be useful for the development of diagnostic reagents that could

Living GenoChemetics by hyphenating synthetic biology and synthetic chemistry in vivo.

Science.gov (United States)

Sharma, Sunil V; Tong, Xiaoxue; Pubill-Ulldemolins, Cristina; Cartmell, Christopher; Bogosyan, Emma J A; Rackham, Emma J; Marelli, Enrico; Hamed, Refaat B; Goss, Rebecca J M

2017-08-09

Marrying synthetic biology with synthetic chemistry provides a powerful approach toward natural product diversification, combining the best of both worlds: expediency and synthetic capability of biogenic pathways and chemical diversity enabled by organic synthesis. Biosynthetic pathway engineering can be employed to insert a chemically orthogonal tag into a complex natural scaffold affording the possibility of site-selective modification without employing protecting group strategies. Here we show that, by installing a sufficiently reactive handle (e.g., a C-Br bond) and developing compatible mild aqueous chemistries, synchronous biosynthesis of the tagged metabolite and its subsequent chemical modification in living culture can be achieved. This approach can potentially enable many new applications: for example, assay of directed evolution of enzymes catalyzing halo-metabolite biosynthesis in living cells or generating and following the fate of tagged metabolites and biomolecules in living systems. We report synthetic biological access to new-to-nature bromo-metabolites and the concomitant biorthogonal cross-coupling of halo-metabolites in living cultures.Coupling synthetic biology and chemical reactions in cells is a challenging task. The authors engineer bacteria capable of generating bromo-metabolites, develop a mild Suzuki-Miyaura cross-coupling reaction compatible with cell growth and carry out the cross-coupling chemistry in live cell cultures.

Symptoms 10-17 years after breast cancer radiotherapy data from the randomised SWEBCG91-RT trial

International Nuclear Information System (INIS)

Lundstedt, Dan; Gustafsson, Magnus; Malmstroem, Per; Johansson, Karl-Axel; Alsadius, David; Sundberg, Agnetha; Wilderaeng, Ulrica; Holmberg, Erik; Anderson, Harald; Steineck, Gunnar; Karlsson, Per

2010-01-01

Background: Postoperative radiotherapy decreases the risk for local recurrence and improves overall survival in women with breast cancer. We have limited information on radiotherapy-induced symptoms 10-17 years after therapy. Material and methods: Between 1991 and 1997, women with lymph node-negative breast cancer were randomised in a Swedish multi-institutional trial to breast conserving surgery with or without postoperative radiotherapy. In 2007, 10-17 years after randomisation, the group included 422 recurrence-free women. We collected data with a study-specific questionnaire on eight pre-selected symptom groups. Results: For six symptom groups (oedema in breast or arm, erysipelas, heart symptoms, lung symptoms, rib fractures, and decreased shoulder mobility) we found similar occurrence in both groups. Excess occurrence after radiotherapy was observed for pain in the breast or in the skin, reported to occur 'occasionally' by 38.1% of survivors having undergone radiotherapy and surgery versus 24.0% of those with surgery alone (absolute difference 14.1%; p = 0.004) and at least once a week by 10.3% of the radiotherapy group versus 1.7% (absolute difference 8.6%; p = 0.001). Daily life and analgesic use did not differ between the groups. Conclusions: Ten to 17 years after postoperative radiotherapy 1 in 12 women had weekly pain that could be attributed to radiotherapy. The symptoms did not significantly affect daily life and thus the reduced risk for local recurrence seems to outweigh the risk for long-term symptoms for most women.

Hydrogen speciation in synthetic quartz

Science.gov (United States)

Aines, R.D.; Kirby, S.H.; Rossman, G.R.

1984-01-01

The dominant hydrogen impurity in synthetic quartz is molecular H2O. H-OH groups also occur, but there is no direct evidence for the hydrolysis of Si-O-Si bonds to yield Si-OH HO-Si groups. Molecular H2O concentrations in the synthetic quartz crystals studied range from less than 10 to 3,300 ppm (H/Si), and decrease smoothly by up to an order of magnitude with distance away from the seed. OH- concentrations range from 96 to 715 ppm, and rise smoothly with distance away from the seed by up to a factor of three. The observed OH- is probably all associated with cationic impurities, as in natural quartz. Molecular H2O is the dominant initial hydrogen impurity in weak quartz. The hydrolytic weakening of quartz may be caused by the transformation H2O + Si-O-Si ??? 2SiOH, but this may be a transitory change with the SiOH groups recombining to form H2O, and the average SiOH concentration remaining very low. Synthetic quartz is strengthened when the H2O is accumulated into fluid inclusions and cannot react with the quartz framework. ?? 1984 Springer-Verlag.

Detection of extracellular neutrophil elastase in hamster lungs after intratracheal instillation of E. coli lipopolysaccharide using a fluorogenic, elastase-specific, synthetic substrate.

Science.gov (United States)

Rudolphus, A.; Stolk, J.; van Twisk, C.; van Noorden, C. J.; Dijkman, J. H.; Kramps, J. A.

1992-01-01

Repeated intratracheal instillations of E. coli lipopolysaccharide (LPS) in hamster lungs cause an influx of polymorphonuclear leukocytes (PMNs) into the alveolar walls, with concomitant development of severe emphysema. It has been suggested that elastase, released by these PMNs, is involved in the development of emphysema. This study demonstrates the release of elastase from recruited PMNs in cryostat sections of hamster lungs, after being treated once, twice, or thrice with LPS, intratracheally. Elastase activity was visualized using two elastase-specific synthetic substrates, to which a methoxynaphthylamine (MNA) group had been bound covalently. Liberated MNA, when made insoluble by coupling with 5-nitrosalicylaldehyde, fluoresces strongly. The authors observed that the interval between start of incubation and appearance of fluorescence and the intensity of fluorescence correlated with the number of LPS administrations. Fluorescence was observed to be located in or in close vicinity to alveolar walls. No fluorescence was observed in sections of untreated hamsters. Liberation of MNA from synthetic substrates was delayed strongly by the addition of a recombinant secretory leukocyte proteinase inhibitor or a substituted cephalosporin neutrophil elastase inhibitor. The authors conclude that LPS-mediated PMN influx into the lung is accompanied by release of elastase from these cells and speculate that this PMN-elastase is involved in the development of LPS-mediated emphysema. Images Figure 1 Figure 2 Figure 3 PMID:1632460

Interim Report on the Investigation of the Fresh Properties of Synthetic Fiber-Reinforced Concrete for the Richardson Landing Casting Field

Science.gov (United States)

2017-04-01

ER D C/ G SL S R- 17 -1 Interim Report on the Investigation of the Fresh Properties of Synthetic Fiber - Reinforced Concrete for the...default. ERDC/GSL SR-17-1 April 2017 Interim Report on the Investigation of the Fresh Properties of Synthetic Fiber - Reinforced Concrete for... reinforced concrete mixtures containing 3-, 2-, and 1-lb(s)/yd3, respectively, of synthetic (polypropylene) fiber into the current mixture proportion

Synthetic biology: an emerging engineering discipline.

Science.gov (United States)

Cheng, Allen A; Lu, Timothy K

2012-01-01

Over the past decade, synthetic biology has emerged as an engineering discipline for biological systems. Compared with other substrates, biology poses a unique set of engineering challenges resulting from an incomplete understanding of natural biological systems and tools for manipulating them. To address these challenges, synthetic biology is advancing from developing proof-of-concept designs to focusing on core platforms for rational and high-throughput biological engineering. These platforms span the entire biological design cycle, including DNA construction, parts libraries, computational design tools, and interfaces for manipulating and probing synthetic circuits. The development of these enabling technologies requires an engineering mindset to be applied to biology, with an emphasis on generalizable techniques in addition to application-specific designs. This review aims to discuss the progress and challenges in synthetic biology and to illustrate areas where synthetic biology may impact biomedical engineering and human health.

Synthetic Self-Assembled Materials in Biological Environments

NARCIS (Netherlands)

Versluis, F.; van Esch, J.H.; Eelkema, R.

2016-01-01

<p>Synthetic self-assembly has long been recognized as an excellent approach for the formation of ordered structures on the nanoscale. Although the development of synthetic self-assembling materials has often been inspired by principles observed in nature (e.g., the assembly of lipids, DNA,

Annotating novel genes by integrating synthetic lethals and genomic information

Directory of Open Access Journals (Sweden)

Faty Mahamadou

2008-01-01

Full Text Available Abstract Background Large scale screening for synthetic lethality serves as a common tool in yeast genetics to systematically search for genes that play a role in specific biological processes. Often the amounts of data resulting from a single large scale screen far exceed the capacities of experimental characterization of every identified target. Thus, there is need for computational tools that select promising candidate genes in order to reduce the number of follow-up experiments to a manageable size. Results We analyze synthetic lethality data for arp1 and jnm1, two spindle migration genes, in order to identify novel members in this process. To this end, we use an unsupervised statistical method that integrates additional information from biological data sources, such as gene expression, phenotypic profiling, RNA degradation and sequence similarity. Different from existing methods that require large amounts of synthetic lethal data, our method merely relies on synthetic lethality information from two single screens. Using a Multivariate Gaussian Mixture Model, we determine the best subset of features that assign the target genes to two groups. The approach identifies a small group of genes as candidates involved in spindle migration. Experimental testing confirms the majority of our candidates and we present she1 (YBL031W as a novel gene involved in spindle migration. We applied the statistical methodology also to TOR2 signaling as another example. Conclusion We demonstrate the general use of Multivariate Gaussian Mixture Modeling for selecting candidate genes for experimental characterization from synthetic lethality data sets. For the given example, integration of different data sources contributes to the identification of genetic interaction partners of arp1 and jnm1 that play a role in the same biological process.

Chemical modification and pH dependence of kinetic parameters to identify functional groups in a glucosyltransferase from Strep. Mutans

International Nuclear Information System (INIS)

Bell, J.E.; Leone, A.; Bell, E.T.

1986-01-01

A glucosyltransferase, forming a predominantly al-6 linked glucan, was partially purified from the culture filtrate of S. mutans GS-5. The kinetic properties of the enzyme, assessed using the transfer of 14 C glucose from sucrose into total glucan, were studied at pH values from pH 3.5 to 6.5. From the dependence of km on pH, a group with pKa = 5.5 must be protonated to maximize substrate binding. From plots of V/sub max/ vs pH two groups, with pKa's of 4.5 and 5.5 were indicated. The results suggest the involvement of either two carboxyl groups (one protonated, one unprotonated in the native enzyme) or a carboxyl group (unprotonated) and some other protonated group such as histidine, cysteine. Chemical modification studies showed that Diethylyrocarbonate (histidine specific) had no effect on enzyme activity while modification with p-phydroxy-mercuribenzoate or iodoacetic acid (sulfhydryl reactive) and carbodimide reagents (carboxyl specific) resulted in almost complete inactivation. Activity loss was dependent upon time of incubation and reagent concentration. The disaccharide lylose, (shown to be an inhibitor of the enzyme with similar affinity to sucrose) offers no protection against modification by the sulfhydryl reactive reagents

Development of [3H]2-Carboxy-4,6-dichloro-1H-indole-3-propionic Acid ([3H]PSB-12150): A Useful Tool for Studying GPR17

Science.gov (United States)

2014-01-01

The recently described synthetic GPR17 agonist 2-carboxy-4,6-dichloro-1H-indole-3-propionic acid (1) was prepared in tritium-labeled form by catalytic hydrogenation of the corresponding propenoic acid derivative 8 with tritium gas. The radioligand [3H]PSB-12150 (9) was obtained with a specific activity of 17 Ci/mmol (629 GBq/mmol). It showed specific and saturable binding to a single binding site in membrane preparations from Chinese hamster ovary cells recombinantly expressing the human GPR17. A competition assay procedure was established, which allows the determination of ligand binding affinities. PMID:24900835

Development of [(3)H]2-Carboxy-4,6-dichloro-1H-indole-3-propionic Acid ([(3)H]PSB-12150): A Useful Tool for Studying GPR17.

Science.gov (United States)

Köse, Meryem; Ritter, Kirsten; Thiemke, Katharina; Gillard, Michel; Kostenis, Evi; Müller, Christa E

2014-04-10

The recently described synthetic GPR17 agonist 2-carboxy-4,6-dichloro-1H-indole-3-propionic acid (1) was prepared in tritium-labeled form by catalytic hydrogenation of the corresponding propenoic acid derivative 8 with tritium gas. The radioligand [(3)H]PSB-12150 (9) was obtained with a specific activity of 17 Ci/mmol (629 GBq/mmol). It showed specific and saturable binding to a single binding site in membrane preparations from Chinese hamster ovary cells recombinantly expressing the human GPR17. A competition assay procedure was established, which allows the determination of ligand binding affinities.

Fine specificity and cross-reactions of monoclonal antibodies to group B streptococcal capsular polysaccharide type III

DEFF Research Database (Denmark)

Pincus, Seth H; Moran, Emily; Maresh, Grace

2012-01-01

) is considered the dominant "protective" immune mediator. Here we study the fine specificity and potential host reactivity of a panel of well-characterized murine monoclonal Abs against the type III CPS by examining the binding of the Abs to intact and neuraminidase-digested GBS, purified CPS, synthetic...

Synthetic biology, inspired by synthetic chemistry.

Science.gov (United States)

Malinova, V; Nallani, M; Meier, W P; Sinner, E K

2012-07-16

The topic synthetic biology appears still as an 'empty basket to be filled'. However, there is already plenty of claims and visions, as well as convincing research strategies about the theme of synthetic biology. First of all, synthetic biology seems to be about the engineering of biology - about bottom-up and top-down approaches, compromising complexity versus stability of artificial architectures, relevant in biology. Synthetic biology accounts for heterogeneous approaches towards minimal and even artificial life, the engineering of biochemical pathways on the organismic level, the modelling of molecular processes and finally, the combination of synthetic with nature-derived materials and architectural concepts, such as a cellular membrane. Still, synthetic biology is a discipline, which embraces interdisciplinary attempts in order to have a profound, scientific base to enable the re-design of nature and to compose architectures and processes with man-made matter. We like to give an overview about the developments in the field of synthetic biology, regarding polymer-based analogs of cellular membranes and what questions can be answered by applying synthetic polymer science towards the smallest unit in life, namely a cell. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Rodolicoite and grattarolaite, intermediates in the thermal transformation of synthetic P-doped ferrihydrite

Science.gov (United States)

Pieczara, Gabriela; Borkiewicz, Olaf; Manecki, Maciej

2017-04-01

Rodolicoite FePO4 and grattarolaite Fe3PO7, naturally occurring anhydrous iron(III) phosphates have been identified in coal samples derived from Santa Barbara lignite mine, as final products of the progressive thermal conversion and oxidation of vivianite Fe32+(PO4)2•8H2O to amorphous phase [1]. In natural environment however, the conversion steps of amorphous phase into these nanominerals are extremely difficult to identify. We propose to fill this gap by utilizing the nanoparticles of synthetic P-doped ferrihydrite Fe5HO8•4H2O as a source of amorphous hydrated iron(III) phosphate. This phase, at certain conditions, undergoes thermal conversion to rodolicoite and grattarolaite. Synthetic anhydrous iron(III) phosphate analogs of berlinite AlPO4 and α- quartz, particularly rodolicoite, receive a lot of attention in mineral sciences partly because of their geologic importance and partly because of their prospective applications as raw material for lithium iron phosphate batteries LiFePO4[2]. In this case, potential presence of impurities and intermediates during thermal synthesis or oxidation steps of rodolicoite is inexpedient. Thus, the main goal of this research was to characterize the products of thermal transformation of P-doped ferrihydrite. Ferrihydrite synthesized in the presence of phosphate PO43- was used. P-ferrihydrites were synthesized by precipitation from aqueous solutions of Fe2(SO4)3 and K2HPO4 at pH 8.2. The thermal transformation experiments were carried out using ferrihydrites with various P/Fe ratios (0.00, 0.20, 0.50 and 1.00) at various heating temperatures. All samples were characterized by XRD, FTIR, SEM and differential thermal analysis prior and after the experiments. The results indicate that the presence of phosphate not only stabilizes the structure of ferrihydrite but also controls its thermal transformation to hematite α-Fe2O3 in more complex manner. Pure ferrihydrite transforms immediately to hematite at the temperature below

Trace analysis of 61 natural and synthetic progestins in river water and sewage effluents by ultra-high performance liquid chromatography-tandem mass spectrometry.

Science.gov (United States)

Shen, Xiaoyan; Chang, Hong; Sun, Dezhi; Wang, Linxia; Wu, Fengchang

2018-04-15

A broad number of natural and synthetic progestins are widely used in human and veterinary therapies. Although progestins exhibit adverse effects in aquatic organisms, information about environmental occurrence and fate have been limited to several compounds, hampering the accuracy of risk assessments of the compounds. In this study, a selective and sensitive analytical method was established to simultaneously determine 19 natural and 42 synthetic progestins in environmental waters, and the synthetic progestins included 19-nortestosterone, 17α-hydroxyprogesterone and progesterone derivatives. All of the target compounds were effectively separated using an HSS T3 column, and the recoveries for effluent and river samples were 80-115% and 75-105%, respectively. The detection limits for the 61 analytes were in the range of 0.05-0.60 ng/L and 0.03-0.40 ng/L for the effluent and river samples, respectively. The developed method is applied to analyze the target progestogens in sewage effluent and river water samples from Beijing. The detected concentrations of natural progesterone metabolites (3α-hydroxy-5β-tetrahydroprogesterone) were up to 63 times higher than those of the parent compound. Of the three groups of synthetic progestins, the progesterone derivatives were detected for the first time and had the highest concentrations followed by the 19-nortestosterone and 17α-hydroxyprogesterone derivatives. In contrast to previous studies, the predominant derivative compounds of 19-nortestosterone were found to be 19-nortestosterone, gestodene and mifepristone, and those of 17α-hydroxyprogesterone were 6-epi-medroxy progesterone 17-acetate and melengestrol acetate. The toxicities and environmental risk of these emerging progestins deserves more attention in the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of Calcium and Phosphorus Ratios in Feed on the Specific Radioactivity of 32P Recovered in Excreta and Blood Plasma by Growing Broiler Chicks

International Nuclear Information System (INIS)

Al-Masri, M.R.

1998-01-01

32 P was injected into male broiler chicks aged 14 days. The experiment lasted until day 29. During the experiment specific radioactivity of 32 P recovered in excreta and in plasma were quantitatively evaluated at different Ca:P ratios (I=1:1; II=1.5:1; III=2:1; IV=2.5:1) in four groups given experimental diets. The phosphorus content was the same in all groups. Specific radioactivity of 32 P in excreta and in plasma amounted to (Bq/mg P):614, 588, 193 and 180; and 928, 964, 1103 and 1136 in groups(I,II,III and IV ) respectively. Widening of the Ca:P ratio in the feed decreased the radio of 32 P specific radioactivity in excreta to 32 P specific radioactivity in plasma

SU-F-J-109: Generate Synthetic CT From Cone Beam CT for CBCT-Based Dose Calculation

Energy Technology Data Exchange (ETDEWEB)

Wang, H; Barbee, D; Wang, W; Pennell, R; Hu, K; Osterman, K [Department of Radiation Oncology, NYU Langone Medical Center, New York, NY (United States)

2016-06-15

Purpose: The use of CBCT for dose calculation is limited by its HU inaccuracy from increased scatter. This study presents a method to generate synthetic CT images from CBCT data by a probabilistic classification that may be robust to CBCT noise. The feasibility of using the synthetic CT for dose calculation is evaluated in IMRT for unilateral H&N cancer. Methods: In the training phase, a fuzzy c-means classification was performed on HU vectors (CBCT, CT) of planning CT and registered day-1 CBCT image pair. Using the resulting centroid CBCT and CT values for five classified “tissue” types, a synthetic CT for a daily CBCT was created by classifying each CBCT voxel to obtain its probability belonging to each tissue class, then assigning a CT HU with a probability-weighted summation of the classes’ CT centroids. Two synthetic CTs from a CBCT were generated: s-CT using the centroids from classification of individual patient CBCT/CT data; s2-CT using the same centroids for all patients to investigate the applicability of group-based centroids. IMRT dose calculations for five patients were performed on the synthetic CTs and compared with CT-planning doses by dose-volume statistics. Results: DVH curves of PTVs and critical organs calculated on s-CT and s2-CT agree with those from planning-CT within 3%, while doses calculated with heterogeneity off or on raw CBCT show DVH differences up to 15%. The differences in PTV D95% and spinal cord max are 0.6±0.6% and 0.6±0.3% for s-CT, and 1.6±1.7% and 1.9±1.7% for s2-CT. Gamma analysis (2%/2mm) shows 97.5±1.6% and 97.6±1.6% pass rates for using s-CTs and s2-CTs compared with CT-based doses, respectively. Conclusion: CBCT-synthesized CTs using individual or group-based centroids resulted in dose calculations that are comparable to CT-planning dose for unilateral H&N cancer. The method may provide a tool for accurate dose calculation based on daily CBCT.

SU-F-J-109: Generate Synthetic CT From Cone Beam CT for CBCT-Based Dose Calculation

International Nuclear Information System (INIS)

Wang, H; Barbee, D; Wang, W; Pennell, R; Hu, K; Osterman, K

2016-01-01

Purpose: The use of CBCT for dose calculation is limited by its HU inaccuracy from increased scatter. This study presents a method to generate synthetic CT images from CBCT data by a probabilistic classification that may be robust to CBCT noise. The feasibility of using the synthetic CT for dose calculation is evaluated in IMRT for unilateral H&N cancer. Methods: In the training phase, a fuzzy c-means classification was performed on HU vectors (CBCT, CT) of planning CT and registered day-1 CBCT image pair. Using the resulting centroid CBCT and CT values for five classified “tissue” types, a synthetic CT for a daily CBCT was created by classifying each CBCT voxel to obtain its probability belonging to each tissue class, then assigning a CT HU with a probability-weighted summation of the classes’ CT centroids. Two synthetic CTs from a CBCT were generated: s-CT using the centroids from classification of individual patient CBCT/CT data; s2-CT using the same centroids for all patients to investigate the applicability of group-based centroids. IMRT dose calculations for five patients were performed on the synthetic CTs and compared with CT-planning doses by dose-volume statistics. Results: DVH curves of PTVs and critical organs calculated on s-CT and s2-CT agree with those from planning-CT within 3%, while doses calculated with heterogeneity off or on raw CBCT show DVH differences up to 15%. The differences in PTV D95% and spinal cord max are 0.6±0.6% and 0.6±0.3% for s-CT, and 1.6±1.7% and 1.9±1.7% for s2-CT. Gamma analysis (2%/2mm) shows 97.5±1.6% and 97.6±1.6% pass rates for using s-CTs and s2-CTs compared with CT-based doses, respectively. Conclusion: CBCT-synthesized CTs using individual or group-based centroids resulted in dose calculations that are comparable to CT-planning dose for unilateral H&N cancer. The method may provide a tool for accurate dose calculation based on daily CBCT.

Technical Assessment: Synthetic Biology

Science.gov (United States)

2015-01-01

Pfizer, Bausch & Lomb, Coca - Cola , and other Fortune 500 companies 8 Data estimated by the... financial prize for ideas to drive forward the production of a sensor relying on synthetic organisms that can detect exposure to 500 specific chemicals

Thermal and structural characterization of synthetic and natural nanocrystalline hydroxyapatite

International Nuclear Information System (INIS)

Sofronia, Ancuta M.; Baies, Radu; Anghel, Elena M.; Marinescu, Cornelia A.; Tanasescu, Speranta

2014-01-01

The aim of this work was to study the thermal stability on heating and to obtain the processing parameters of synthetic and bone-derived hydroxyapatite over temperatures between room temperature and 1400 °C by thermal analysis (thermogravimetry (TG)/differential scanning calorimetry (DSC) and thermo-mechanical analysis—TMA). Structural and surface modifications related to samples origin and calcination temperature were investigated by Fourier transformed infrared (FTIR) and Raman spectroscopy, X-ray diffraction (XRD) and BET method. FTIR spectra indicated that the organic constituents and carbonate are no longer present in the natural sample calcined at 800 °C. Raman spectra highlighted the decomposition products of the hydroxyapatite. The calcination treatment modifies the processes kinetics of the synthetic samples, being able to isolate lattice water desorption processes of decarbonization and the dehydroxylation processes. Shrinkage of calcined synthetic sample increases by 10% compared to uncalcined synthetic powder. From the TMA correlated with TG analysis and heat capacity data it can be concluded that sintering temperature of the synthetic samples should be chosen in the temperature range of the onset of dehydroxylation and the temperature at which oxyapatite decomposition begins. - Highlights: • Specific surface area of HA powder was reduced from 19.2 to 9.5 m 2 /g by calcination. • Raman spectra indicate the presence of B-type CO 3 group in HA synthetic samples. • The onset temperature of HA densification and dehydroxylation processes correspond. • Calcination of HA influences reactions kinetics with consequences on densification. • Shrinkage of calcined HA sample increases by 10% with respect to uncalcined sample

Thermal and structural characterization of synthetic and natural nanocrystalline hydroxyapatite

Energy Technology Data Exchange (ETDEWEB)

Sofronia, Ancuta M. [Ilie Murgulescu Institute of Physical Chemistry of the Romanian Academy, 060021 Bucharest (Romania); Baies, Radu [National Research Institute for Electrochemistry and Condensed Matter, 300224 Timisoara (Romania); Anghel, Elena M. [Ilie Murgulescu Institute of Physical Chemistry of the Romanian Academy, 060021 Bucharest (Romania); Marinescu, Cornelia A., E-mail: alcorina@chimfiz.icf.ro [Ilie Murgulescu Institute of Physical Chemistry of the Romanian Academy, 060021 Bucharest (Romania); Tanasescu, Speranta [Ilie Murgulescu Institute of Physical Chemistry of the Romanian Academy, 060021 Bucharest (Romania)

2014-10-01

The aim of this work was to study the thermal stability on heating and to obtain the processing parameters of synthetic and bone-derived hydroxyapatite over temperatures between room temperature and 1400 °C by thermal analysis (thermogravimetry (TG)/differential scanning calorimetry (DSC) and thermo-mechanical analysis—TMA). Structural and surface modifications related to samples origin and calcination temperature were investigated by Fourier transformed infrared (FTIR) and Raman spectroscopy, X-ray diffraction (XRD) and BET method. FTIR spectra indicated that the organic constituents and carbonate are no longer present in the natural sample calcined at 800 °C. Raman spectra highlighted the decomposition products of the hydroxyapatite. The calcination treatment modifies the processes kinetics of the synthetic samples, being able to isolate lattice water desorption processes of decarbonization and the dehydroxylation processes. Shrinkage of calcined synthetic sample increases by 10% compared to uncalcined synthetic powder. From the TMA correlated with TG analysis and heat capacity data it can be concluded that sintering temperature of the synthetic samples should be chosen in the temperature range of the onset of dehydroxylation and the temperature at which oxyapatite decomposition begins. - Highlights: • Specific surface area of HA powder was reduced from 19.2 to 9.5 m{sup 2}/g by calcination. • Raman spectra indicate the presence of B-type CO{sub 3} group in HA synthetic samples. • The onset temperature of HA densification and dehydroxylation processes correspond. • Calcination of HA influences reactions kinetics with consequences on densification. • Shrinkage of calcined HA sample increases by 10% with respect to uncalcined sample.

Novel polyketones with pendant imidazolium groups as nanodispersants of hydrophobic antibiotics

NARCIS (Netherlands)

Araya-Hermosilla, Esteban; Orellana, Sandra L.; Toncelli, Claudio; Picchioni, Francesco; Moreno-Villoslada, Ignacio

2015-01-01

In this work, we present a new method to nanodisperse the pH-sensitive antibiotics oxolinic acid and flumequine by the use of a pH-sensitive synthetic polyketone derivative with amphiphilic characteristics. The pH-sensitive polymer bears imidazolium residues on pendant groups as weak acids, and its

Culture-specific programs for children and adults from minority groups who have asthma.

Science.gov (United States)

McCallum, Gabrielle B; Morris, Peter S; Brown, Ngiare; Chang, Anne B

2017-08-22

studies ranged from very low to low. For our primary outcome (asthma exacerbations during follow-up), the quality of evidence was low for all outcomes. In adults, use of a culture-specific programme, compared to generic programmes or usual care did not significantly reduce the number of participants from two studies with 294 participants for: exacerbations with one or more exacerbations during follow-up (odds ratio (OR) 0.80, 95% confidence interval (CI) 0.50 to 1.26), hospitalisations over 12 months (OR 0.83, 95% CI 0.31 to 2.22) and exacerbations requiring oral corticosteroids (OR 0.97, 95% CI 0.55 to 1.73). However, use of a culture-specific programme, improved asthma quality of life scores in 280 adults from two studies (mean difference (MD) 0.26, 95% CI 0.17 to 0.36) (although the MD was less then the minimal important difference for the score). In children, use of a culture-specific programme was superior to generic programmes or usual care in reducing severe asthma exacerbations requiring hospitalisation in two studies with 305 children (rate ratio 0.48, 95% CI 0.24 to 0.95), asthma control in one study with 62 children and QoL in three studies with 213 children, but not for the number of exacerbations during follow-up (OR 1.55, 95% CI 0.66 to 3.66) or the number of exacerbations (MD 0.18, 95% CI -0.25 to 0.62) among 100 children from two studies. The available evidence showed that culture-specific education programmes for adults and children from minority groups are likely effective in improving asthma-related outcomes. This review was limited by few studies and evidence of very low to low quality. Not all asthma-related outcomes improved with culture-specific programs for both adults and children. Nevertheless, while modified culture-specific education programs are usually more time intensive, the findings of this review suggest using culture-specific asthma education programmes for children and adults from minority groups. However, more robust RCTs are needed to

17,20β-P and cortisol are the main in vitro metabolites of 17-hydroxy-progesterone produced by spermiating testes of Micropogonias furnieri (Desmarest, 1823 (Perciformes: Sciaenidae

Directory of Open Access Journals (Sweden)

Denise Vizziano Cantonnet

Full Text Available The aim was to investigate the major C21 steroids produced by spermiating white croaker Micropogonias furnieri (Sciaenidae in order to establish the potential mediator of gamete maturation in males of this species. The testes steroid production at the spawning season was identified incubating the 3H-17-hydroxy-4-pregnene-3,20-dione precursor through thin layer chromatography, high pressure liquid chromatography, enzymatic oxydation, acetylation and immunochemistry analyses. 17,20β-Dihydroxy-4-pregnen-3-one (17,20β-P and 11β,17,21-Trihydroxy-4-pregnene-3,20-dione (cortisol were the main metabolites produced. Contrary to what we expected, 17,20β,21-Trihydroxy-4-pregnen-3-one was not detected. Circulating levels of 17,20β-P were undetectable in immature testes and in those at the first spermatogenesis stages, while a clear increase was observed during the whole spermatogenesis and spermiation phases (from undetectable to 1047 pg mL-1. In vitro studies together with plasma detection suggest that 17,20β-P is a good steroid candidate involved in M. furnieri testes maturation. The role of cortisol during late phases of testes development needs further studies.

Philosophy of Systems and Synthetic Biology

DEFF Research Database (Denmark)

Green, Sara

2017-01-01

This entry aims to clarify how systems and synthetic biology contribute to and extend discussions within philosophy of science. Unlike fields such as developmental biology or molecular biology, systems and synthetic biology are not easily demarcated by a focus on a specific subject area or level...... of organization. Rather, they are characterized by the development and application of mathematical, computational, and synthetic modeling strategies in response to complex problems and challenges within the life sciences. Proponents of systems and synthetic biology often stress the necessity of a perspective...... that goes beyond the scope of molecular biology and genetic engineering, respectively. With the emphasis on systems and interaction networks, the approaches explicitly engage in one of the oldest philosophical discussions on the relationship between parts and wholes, or between reductionism and holism...

The kinome of Phytophthora infestans reveals oomycete-specific innovations and links to other taxonomic groups

Directory of Open Access Journals (Sweden)

Ah-Fong Audrey MV

2010-12-01

Full Text Available Abstract Background Oomycetes are a large group of economically and ecologically important species. Its most notorious member is Phytophthora infestans, the cause of the devastating potato late blight disease. The life cycle of P. infestans involves hyphae which differentiate into spores used for dispersal and host infection. Protein phosphorylation likely plays crucial roles in these stages, and to help understand this we present here a genome-wide analysis of the protein kinases of P. infestans and several relatives. The study also provides new insight into kinase evolution since oomycetes are taxonomically distant from organisms with well-characterized kinomes. Results Bioinformatic searches of the genomes of P. infestans, P. ramorum, and P. sojae reveal they have similar kinomes, which for P. infestans contains 354 eukaryotic protein kinases (ePKs and 18 atypical kinases (aPKs, equaling 2% of total genes. After refining gene models, most were classifiable into families seen in other eukaryotes. Some ePK families are nevertheless unusual, especially the tyrosine kinase-like (TKL group which includes large oomycete-specific subfamilies. Also identified were two tyrosine kinases, which are rare in non-metazoans. Several ePKs bear accessory domains not identified previously on kinases, such as cyclin-dependent kinases with integral cyclin domains. Most ePKs lack accessory domains, implying that many are regulated transcriptionally. This was confirmed by mRNA expression-profiling studies that showed that two-thirds vary significantly between hyphae, sporangia, and zoospores. Comparisons to neighboring taxa (apicomplexans, ciliates, diatoms revealed both clade-specific and conserved features, and multiple connections to plant kinases were observed. The kinome of Hyaloperonospora arabidopsidis, an oomycete with a simpler life cycle than P. infestans, was found to be one-third smaller. Some differences may be attributable to gene clustering, which

[Analysis of clinical features and allergic status of asthmatic patients with positive serum mycosis-specific IgE].

Science.gov (United States)

Mou, Yan; Ye, Ling; Gong, Ying; Zhang, Zhi-feng; Jin, Mei-ling

2013-08-01

To improve understanding of the clinical characteristics and diagnosis of allergic bronchopulmonary mycosis (ABPM). We retrospectively analyzed the clinical data, including clinical symptoms, laboratory tests, pulmonary function tests and chest CT imaging of 95 asthmatic patients with positive serum mycosis-specific IgE from January 2010 to September 2012 in Zhongshan Hospital Affiliated to Fudan University. Of the 95 patients, 59 cases met the diagnostic criteria of ABPM. There were 34 males and 25 females, with a mean age of (53 ± 4) years and a duration of asthma for (21 ± 4) years. Thirty-six cases showed mycosis hypersensitivity (MH). There were 10 males and 26 females, with a mean age of (46 ± 6) years and a duration of asthma for (16 ± 5) years. Clinical symptoms such as wheeze (52 vs 21, χ(2) = 11.159, P = 0.001), cough (54 vs 27, χ(2) = 4.859, P = 0.030) and expectoration (43 vs 9, χ(2) = 25.731, P = 0.000) were more common in the ABPM group compared to the MH group.In the ABPM group, 58 were A. fumigatus-specific IgE antibody positive, 34 Penicillium-specific IgE antibody positive and 1 only Penicillium-specific IgE antibody positive.While in the MH group, 15 were A.fumigatus-specific IgE antibody positive, 24 Penicillium-specific IgE antibody positive and 17 only Penicillium-specific IgE antibody positive.In the ABPM group, the percentage of positive fumigatus-specific IgE antibody was higher (58 vs 15, χ(2) = 24.500, P = 0.000), while the percentages of dermatophagoides pteronyssinus(21 vs 20, χ(2) = 3.632, P = 0.045) and Dermatophagoides farinae(17 vs 21, χ(2) = 8.118, P = 0.004) were lower. Total serum IgE [(4395 ± 1437) IU/ml vs (276 ± 133) IU/ml, T = 4.384, P = 0.000], peripheral eosinophil percentage[(12.56 ± 1.20)% vs (1.30 ± 0.15)%, t = 8.175, P = 0.000] and count [(2.09 ± 0.43)×10(9)/L vs (0.19 ± 0.04)×10(9)/L, t = 7.032, P = 0.000] were higher in the ABPM group as compared to the MH group.FEV1% slightly declined in the ABPM

Promising Tools in Prostate Cancer Research: Selective Non-Steroidal Cytochrome P450 17A1 Inhibitors

Science.gov (United States)

Bonomo, Silvia; Hansen, Cecilie H.; Petrunak, Elyse M.; Scott, Emily E.; Styrishave, Bjarne; Jørgensen, Flemming Steen; Olsen, Lars

2016-07-01

Cytochrome P450 17A1 (CYP17A1) is an important target in the treatment of prostate cancer because it produces androgens required for tumour growth. The FDA has approved only one CYP17A1 inhibitor, abiraterone, which contains a steroidal scaffold similar to the endogenous CYP17A1 substrates. Abiraterone is structurally similar to the substrates of other cytochrome P450 enzymes involved in steroidogenesis, and interference can pose a liability in terms of side effects. Using non-steroidal scaffolds is expected to enable the design of compounds that interact more selectively with CYP17A1. Therefore, we combined a structure-based virtual screening approach with density functional theory (DFT) calculations to suggest non-steroidal compounds selective for CYP17A1. In vitro assays demonstrated that two such compounds selectively inhibited CYP17A1 17α-hydroxylase and 17,20-lyase activities with IC50 values in the nanomolar range, without affinity for the major drug-metabolizing CYP2D6 and CYP3A4 enzymes and CYP21A2, with the latter result confirmed in human H295R cells.

Using the 5 P Relay in Task Groups

Science.gov (United States)

Stanley, Paula Helen

2006-01-01

This article describes the 5 P Relay, a group exercise that can increase the effectiveness of task groups. The 5 P Relay is based on the principles and concepts of the Invitational Model, which emphasizes the importance of assessing the effectiveness or health of five aspects of an organization's environment: people, places, programs, processes,…

Radioimmunoassay of 17α-alkalyted anabolic steroids

International Nuclear Information System (INIS)

Hampl, R.; Picha, J.; Chundela, B.

1978-01-01

A method for the detection of anabolic 17α-alkylated androstane derivatives in both plasma and urine is described and evaluated. The goat and rabbit antisera against 17α-Methyltestosteron-3-carboxymethyloxim-Rinderserum albumin were raised and compared using [ 3 H]methandrostenolone as a tracer. 22 Steroids including 10 potent synthetic anabolics were tested for their cross-reaction with these antisera. (orig.) [de

miR-146a modulates autoreactive Th17 cell differentiation and regulates organ-specific autoimmunity.

Science.gov (United States)

Li, Bo; Wang, Xi; Choi, In Young; Wang, Yu-Chen; Liu, Siyuan; Pham, Alexander T; Moon, Heesung; Smith, Drake J; Rao, Dinesh S; Boldin, Mark P; Yang, Lili

2017-10-02

Autoreactive CD4 T cells that differentiate into pathogenic Th17 cells can trigger autoimmune diseases. Therefore, investigating the regulatory network that modulates Th17 differentiation may yield important therapeutic insights. miR-146a has emerged as a critical modulator of immune reactions, but its role in regulating autoreactive Th17 cells and organ-specific autoimmunity remains largely unknown. Here, we have reported that miR-146a-deficient mice developed more severe experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS). We bred miR-146a-deficient mice with 2D2 T cell receptor-Tg mice to generate 2D2 CD4 T cells that are deficient in miR-146a and specific for myelin oligodendrocyte glycoprotein (MOG), an autoantigen in the EAE model. miR-146a-deficient 2D2 T cells induced more severe EAE and were more prone to differentiate into Th17 cells. Microarray analysis revealed enhancements in IL-6- and IL-21-induced Th17 differentiation pathways in these T cells. Further study showed that miR-146a inhibited the production of autocrine IL-6 and IL-21 in 2D2 T cells, which in turn reduced their Th17 differentiation. Thus, our study identifies miR-146a as an important molecular brake that blocks the autocrine IL-6- and IL-21-induced Th17 differentiation pathways in autoreactive CD4 T cells, highlighting its potential as a therapeutic target for treating autoimmune diseases.

Prediction of novel synthetic pathways for the production of desired chemicals

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Park Jin

2010-03-01

Full Text Available Abstract Background There have been several methods developed for the prediction of synthetic metabolic pathways leading to the production of desired chemicals. In these approaches, novel pathways were predicted based on chemical structure changes, enzymatic information, and/or reaction mechanisms, but the approaches generating a huge number of predicted results are difficult to be applied to real experiments. Also, some of these methods focus on specific pathways, and thus are limited to expansion to the whole metabolism. Results In the present study, we propose a system framework employing a retrosynthesis model with a prioritization scoring algorithm. This new strategy allows deducing the novel promising pathways for the synthesis of a desired chemical together with information on enzymes involved based on structural changes and reaction mechanisms present in the system database. The prioritization scoring algorithm employing Tanimoto coefficient and group contribution method allows examination of structurally qualified pathways to recognize which pathway is more appropriate. In addition, new concepts of binding site covalence, estimation of pathway distance and organism specificity were taken into account to identify the best synthetic pathway. Parameters of these factors can be evolutionarily optimized when a newly proven synthetic pathway is registered. As the proofs of concept, the novel synthetic pathways for the production of isobutanol, 3-hydroxypropionate, and butyryl-CoA were predicted. The prediction shows a high reliability, in which experimentally verified synthetic pathways were listed within the top 0.089% of the identified pathway candidates. Conclusions It is expected that the system framework developed in this study would be useful for the in silico design of novel metabolic pathways to be employed for the efficient production of chemicals, fuels and materials.

Th1-Th17 Ratio as a New Insight in Rheumatoid Arthritis Disease.

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Bazzazi, Hadi; Aghaei, Mehrdad; Memarian, Ali; Asgarian-Omran, Hossein; Behnampour, Nasser; Yazdani, Yaghoub

2018-02-01

The Th17, Th1 and dual Th17/Th1 cells are important players in rheumatoid arthritis (RA) disease. To assess their roles, the frequency and impact of these cells were investigated in patients with different disease activity. In 14 new cases and 41 established RA patients in comparison with 22 healthy controls, the percentages of Th17, Th1 and dual Th17/Th1 cells were determined by flow-cytometry and their correlations were investigated with disease activity score (DAS28). Moreover, serum levels of IL-6 and IL-17 as inducer and functional cytokines for Th17 were investigated. Finally, serum levels of anti citrullinated protein antibody (ACPA) and rheumatoid factor (RF) were assessed. Percentage of Th17 cells in RA patients were increased in comparison with healthy controls (pTh1 cells in RA patients were less than healthy group (pTh17/Th1 cell only in new cases of RA were more than healthy control groups (pTh1/Th17 ratio in RA patients is statistically different with healthy control group (pTh1/Th17 ratio in RA patient suggested a new paradigm in the field of autoimmune disease and indicated that imbalance or plasticity between these subsets can be important in progress, diagnosis and therapy of RA disease.

Individual versus group female-specific cognitive behavior therapy for alcohol use disorder.

Science.gov (United States)

Epstein, Elizabeth E; McCrady, Barbara S; Hallgren, Kevin A; Gaba, Ayorkor; Cook, Sharon; Jensen, Noelle; Hildebrandt, Thomas; Holzhauer, Cathryn Glanton; Litt, Mark D

2018-05-01

To test group-based Female-Specific Cognitive Behavioral Therapy (G-FS-CBT) for women with Alcohol Use Disorder (AUD) against an individual Female-Specific Cognitive Behavioral Therapy (I-FS-CBT). This aims of this paper are to describe G-FS-CBT development, content, feasibility, acceptability, group process, engagement in treatment, and within- and post-treatment outcomes. Women with AUD (n=155) were randomly assigned to 12 manual-guided sessions of G-FS-CBT or I-FS-CBT; 138 women attended at least one treatment session. Women in G-FS-CBT attended fewer sessions (M=7.6) than women in I-FS-CBT (M=9.7; p<.001). Women in both conditions reported high satisfaction with the treatments. Independent coders rated high fidelity of delivery of both G-FS-CBT and I-FS-CBT. Therapeutic alliance with the therapist was high in both conditions, with I-FS-CBT being slightly but significantly higher than G-FS-CBT. In the first six weeks of treatment, women in both treatment conditions significantly reduced their percent drinking days (PDD) and percent heavy days drinking (PHD) by equivalent amounts, maintained through the rest of treatment and the 12month follow up with no treatment condition effects. Women reported significant improvement in all but one of the secondary outcomes during treatment; gains made during treatment in depression, anxiety, autonomy, and interpersonal problems were maintained during the follow-up period, while gains made during treatment in use of coping skills, self-efficacy for abstinence, self-care, and sociotropy deteriorated over follow up but remained improved compared to baseline. Findings support the feasibility, acceptability, and efficacy of a group format for female-specific CBT for AUD, a new 12-session, single gender, community friendly, group therapy with programming specifically for women. Similar, positive outcomes for individual and group treatment formats were found for drinking, mood, coping skills, self-confidence, interpersonal

Data-driven approach for creating synthetic electronic medical records

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Moniz Linda

2010-10-01

Full Text Available Abstract Background New algorithms for disease outbreak detection are being developed to take advantage of full electronic medical records (EMRs that contain a wealth of patient information. However, due to privacy concerns, even anonymized EMRs cannot be shared among researchers, resulting in great difficulty in comparing the effectiveness of these algorithms. To bridge the gap between novel bio-surveillance algorithms operating on full EMRs and the lack of non-identifiable EMR data, a method for generating complete and synthetic EMRs was developed. Methods This paper describes a novel methodology for generating complete synthetic EMRs both for an outbreak illness of interest (tularemia and for background records. The method developed has three major steps: 1 synthetic patient identity and basic information generation; 2 identification of care patterns that the synthetic patients would receive based on the information present in real EMR data for similar health problems; 3 adaptation of these care patterns to the synthetic patient population. Results We generated EMRs, including visit records, clinical activity, laboratory orders/results and radiology orders/results for 203 synthetic tularemia outbreak patients. Validation of the records by a medical expert revealed problems in 19% of the records; these were subsequently corrected. We also generated background EMRs for over 3000 patients in the 4-11 yr age group. Validation of those records by a medical expert revealed problems in fewer than 3% of these background patient EMRs and the errors were subsequently rectified. Conclusions A data-driven method was developed for generating fully synthetic EMRs. The method is general and can be applied to any data set that has similar data elements (such as laboratory and radiology orders and results, clinical activity, prescription orders. The pilot synthetic outbreak records were for tularemia but our approach may be adapted to other infectious

Data-driven approach for creating synthetic electronic medical records.

Science.gov (United States)

Buczak, Anna L; Babin, Steven; Moniz, Linda

2010-10-14

New algorithms for disease outbreak detection are being developed to take advantage of full electronic medical records (EMRs) that contain a wealth of patient information. However, due to privacy concerns, even anonymized EMRs cannot be shared among researchers, resulting in great difficulty in comparing the effectiveness of these algorithms. To bridge the gap between novel bio-surveillance algorithms operating on full EMRs and the lack of non-identifiable EMR data, a method for generating complete and synthetic EMRs was developed. This paper describes a novel methodology for generating complete synthetic EMRs both for an outbreak illness of interest (tularemia) and for background records. The method developed has three major steps: 1) synthetic patient identity and basic information generation; 2) identification of care patterns that the synthetic patients would receive based on the information present in real EMR data for similar health problems; 3) adaptation of these care patterns to the synthetic patient population. We generated EMRs, including visit records, clinical activity, laboratory orders/results and radiology orders/results for 203 synthetic tularemia outbreak patients. Validation of the records by a medical expert revealed problems in 19% of the records; these were subsequently corrected. We also generated background EMRs for over 3000 patients in the 4-11 yr age group. Validation of those records by a medical expert revealed problems in fewer than 3% of these background patient EMRs and the errors were subsequently rectified. A data-driven method was developed for generating fully synthetic EMRs. The method is general and can be applied to any data set that has similar data elements (such as laboratory and radiology orders and results, clinical activity, prescription orders). The pilot synthetic outbreak records were for tularemia but our approach may be adapted to other infectious diseases. The pilot synthetic background records were in the 4

Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicentre study.

Science.gov (United States)

O'Brien, Susan; Jones, Jeffrey A; Coutre, Steven E; Mato, Anthony R; Hillmen, Peter; Tam, Constantine; Österborg, Anders; Siddiqi, Tanya; Thirman, Michael J; Furman, Richard R; Ilhan, Osman; Keating, Michael J; Call, Timothy G; Brown, Jennifer R; Stevens-Brogan, Michelle; Li, Yunfeng; Clow, Fong; James, Danelle F; Chu, Alvina D; Hallek, Michael; Stilgenbauer, Stephan

2016-10-01

The TP53 gene, encoding tumour suppressor protein p53, is located on the short arm of chromosome 17 (17p). Patients with 17p deletion (del17p) chronic lymphocytic leukaemia have poor responses and survival after chemoimmunotherapy. We assessed the activity and safety of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase, in relapsed or refractory patients with del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma. We did a multicentre, international, open-label, single-arm study at 40 sites in the USA, Canada, Europe, Australia, and New Zealand. Patients (age ≥18 years) with previously treated del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma received oral ibrutinib 420 mg once daily until progressive disease or unacceptable toxicity. The primary endpoint was overall response in the all-treated population per International Workshop on Chronic Lymphocytic Leukaemia 2008 response criteria modified for treatment-related lymphocytosis. Preplanned exploratory analyses were progression-free survival, overall survival, sustained haematological improvement, and immunological improvement. Patient enrolment is complete, but follow-up is ongoing. Treatment discontinuation owing to adverse events, unacceptable toxicity, or death were collected as a single combined category. This study is registered with ClinicalTrials.gov, number NCT01744691. Between Jan 29, 2013, and June 19, 2013, 145 patients were enrolled. The all-treated population consisted of 144 patients with del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma who received at least one dose of study drug, with a median age of 64 years (IQR 57-72) and a median of two previous treatments (IQR 1-3). At the prespecified primary analysis after a median follow-up of 11·5 months (IQR 11·1-13·8), 92 (64%, 95% CI 56-71) of 144 patients had an overall response according to independent review committee assessment; 119 patients (83%, 95% CI 76-88) had an overall

Ships as salient objects in synthetic aperture radar imaginary

CSIR Research Space (South Africa)

Schwegmann, Colin P

2016-07-01

Full Text Available The widespread access to Synthetic Aperture Radar data has created a need for more precise ship extraction, specifically in low-to-medium resolution imagery. While Synthetic Aperture Radar pixel resolution is improving for a large swaths...

Suppression of atherosclerosis by synthetic REV-ERB agonist

Energy Technology Data Exchange (ETDEWEB)

Sitaula, Sadichha [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Billon, Cyrielle [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States); Kamenecka, Theodore M.; Solt, Laura A. [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Burris, Thomas P., E-mail: burristp@slu.edu [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States)

2015-05-08

The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. - Highlights: • Synthetic REV-ERB agonist treatment reduced atherosclerosis in a mouse model. • Pharmacological activation of REV-ERB decreased M1 macrophage polarization. • Pharmacological activation of REV-ERB increased M2 macrophage polarization.

Mechanism of Cytochrome P450 17A1-Catalyzed Hydroxylase and Lyase Reactions

DEFF Research Database (Denmark)

Bonomo, Silvia; Jorgensen, Flemming Steen; Olsen, Lars

2017-01-01

Cytochrome P450 17A1 (CYP17A1) catalyzes C17 hydroxylation of pregnenolone and progesterone and the subsequent C17–C20 bond cleavage (lyase reaction) to form androgen precursors. Compound I (Cpd I) and peroxo anion (POA) are the heme-reactive species underlying the two reactions. We have characte...... the concept that the selectivity of the steroidogenic CYPs is ruled by direct interactions with the enzyme, in contrast to the selectivity of drug-metabolizing CYPs, where the reactivity of the substrates dominates....... characterized the reaction path for both the hydroxylase and lyase reactions using density functional theory (DFT) calculations and the enzyme–substrate interactions by molecular dynamics (MD) simulations. Activation barriers for positions subject to hydroxylase reaction have values close to each other and span...

Studies on the specificity of immunological reactions of synthetic and natural Thomsen-Friedenreich antigens

International Nuclear Information System (INIS)

Hoeppner, W.

1982-01-01

A number of derivatives of disaccharide β-D-Gal-(1,3)-D-GalNAc, the carbohydrate component of T-antigen, and four different synthetic antigens having this disaccharide structure have been investigated. The immunological reactions with native human antibodies and rabbit immune antibodies have been studied in the haemagglutination inhibition test and in RIA. The findings are relevant to the use of synthetic carbohydrate antigens as model substances for immunological studies. (orig./MG) [de

A rapid and convenient method for specific 11C-labelling of synthetic polypeptides containing methionine

International Nuclear Information System (INIS)

Laengstroem, B.; Sjoeberg, S.; Ragnarsson, U.

1981-01-01

11 C-labelling of methionine residues in a synthetic peptide via the preparation of the corresponding protected, pure homocysteine peptide has been investigated. Complete deprotection of the peptide and specific methylation of the homocysteine residue can be performed in one step in liquid ammonia. As a first application of this method the synthesis of the tripeptide, Z-Gly-L-Hcy(Bzl)-Gly-O-Bzl, and its conversion to Gly-Met-Gly and the corresponding labelled Gly-([ 11 C]-methyl)-Met-Gly, is reported. Starting with the protected peptide the labelling was performed in 20 +- 5 min (starting with 11 CO 2 ), yielding the labelled peptide in 92 +- 5 % radiochemical yield. Analyses and preparative LC can be performed within 6 min. (author)

Mapping Spaces, Centralizers, and p-Local Finite Groups of Lie Type

DEFF Research Database (Denmark)

Laude, Isabelle

We study the space of maps from the classifying space of a finite p-group to theBorel construction of a finite group of Lie type G in characteristic p acting on itsbuilding. The first main result is a description of the homology with Fp-coefficients,showing that the mapping space, up to p...... between a finite p-group and theuncompleted classifying space of the p-local finite group coming from a finite groupof Lie type in characteristic p, providing some of the first results in this uncompletedsetting.......-completion, is a disjoint union indexedover the group homomorphism up to conjugation of classifying spaces of centralizersof p-subgroups in the underlying group G. We complement this description bydetermining the actual homotopy groups of the mapping space. These resultstranslate to descriptions of the space of maps...

Multiply-Imputed Synthetic Data: Advice to the Imputer

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Loong Bronwyn

2017-12-01

Full Text Available Several statistical agencies have started to use multiply-imputed synthetic microdata to create public-use data in major surveys. The purpose of doing this is to protect the confidentiality of respondents’ identities and sensitive attributes, while allowing standard complete-data analyses of microdata. A key challenge, faced by advocates of synthetic data, is demonstrating that valid statistical inferences can be obtained from such synthetic data for non-confidential questions. Large discrepancies between observed-data and synthetic-data analytic results for such questions may arise because of uncongeniality; that is, differences in the types of inputs available to the imputer, who has access to the actual data, and to the analyst, who has access only to the synthetic data. Here, we discuss a simple, but possibly canonical, example of uncongeniality when using multiple imputation to create synthetic data, which specifically addresses the choices made by the imputer. An initial, unanticipated but not surprising, conclusion is that non-confidential design information used to impute synthetic data should be released with the confidential synthetic data to allow users of synthetic data to avoid possible grossly conservative inferences.

Specific heat of filled skutterudite PrOs4P12

International Nuclear Information System (INIS)

Matsuhira, Kazuyuki; Doi, Yoshihiro; Wakeshima, Makoto; Hinatsu, Yukio; Kihou, Kunihiro; Sekine, Chihiro; Shirotani, Ichimin

2005-01-01

We report the specific heat of filled skutterudite compounds PrOs 4 P 12 and LaOs 4 P 12 down to 1.8K. The specific heat divided by temperature C(T)/T in PrOs 4 P 12 shows a shoulder around 13K. This shoulder is caused by a Schottky anomaly due to a crystalline electric field effect. The electronic specific heat coefficients γ of PrOs 4 P 12 and LaOs 4 P 12 are estimated to be 56.5 and 21.6mJ/K 2 mol, respectively. The value of γ in PrOs 4 P 12 is 2.6 times larger than that in LaOs 4 P 12

On classification of finite groups with four generators, three of which having orders p,p,q (p

International Nuclear Information System (INIS)

Yacoub, K.R.

1984-03-01

Finite groups with two independent generators attracted the attention of authors for several years. The author, having started on such groups in his PhD Thesis in 1953, discussed later on the existence and the structure of finite groups with three generators, one being of arbitrary order and the other two having given orders [Pub. Math. Debrecen, 11, 32-38(1964), 13, 9-16(1966)] and others. Recently, the author started the problem of finite groups with four generators a,b,c and d when b,c and d have the same odd prime order p. It is the object of the present paper to deal with a similar problem when the given orders are p, p and q with p q together with the particular case when m is an element of set containing p,q will be kept to a further discussion. The present paper consists actually of two main parts, the first deals with the case p does not divide q-1 while the second deals with the case p divides q-1. (author)

Identification of group specific motifs in Beta-lactamase family of proteins

Directory of Open Access Journals (Sweden)

Saxena Akansha

2009-12-01

Full Text Available Abstract Background Beta-lactamases are one of the most serious threats to public health. In order to combat this threat we need to study the molecular and functional diversity of these enzymes and identify signatures specific to these enzymes. These signatures will enable us to develop inhibitors and diagnostic probes specific to lactamases. The existing classification of beta-lactamases was developed nearly 30 years ago when few lactamases were available. DLact database contain more than 2000 beta-lactamase, which can be used to study the molecular diversity and to identify signatures specific to this family. Methods A set of 2020 beta-lactamase proteins available in the DLact database http://59.160.102.202/DLact were classified using graph-based clustering of Best Bi-Directional Hits. Non-redundant (> 90 percent identical protein sequences from each group were aligned using T-Coffee and annotated using information available in literature. Motifs specific to each group were predicted using PRATT program. Results The graph-based classification of beta-lactamase proteins resulted in the formation of six groups (Four major groups containing 191, 726, 774 and 73 proteins while two minor groups containing 50 and 8 proteins. Based on the information available in literature, we found that each of the four major groups correspond to the four classes proposed by Ambler. The two minor groups were novel and do not contain molecular signatures of beta-lactamase proteins reported in literature. The group-specific motifs showed high sensitivity (> 70% and very high specificity (> 90%. The motifs from three groups (corresponding to class A, C and D had a high level of conservation at DNA as well as protein level whereas the motifs from the fourth group (corresponding to class B showed conservation at only protein level. Conclusion The graph-based classification of beta-lactamase proteins corresponds with the classification proposed by Ambler, thus there is

Realistic Vendor-Specific Synthetic Ultrasound Data for Quality Assurance of 2-D Speckle Tracking Echocardiography: Simulation Pipeline and Open Access Database.

Science.gov (United States)

Alessandrini, Martino; Chakraborty, Bidisha; Heyde, Brecht; Bernard, Olivier; De Craene, Mathieu; Sermesant, Maxime; D'Hooge, Jan

2018-03-01

Two-dimensional (2-D) echocardiography is the modality of choice in the clinic for the diagnosis of cardiac disease. Hereto, speckle tracking (ST) packages complement visual assessment by the cardiologist by providing quantitative diagnostic markers of global and regional cardiac function (e.g., displacement, strain, and strain-rate). Yet, the reported high vendor-dependence between the outputs of different ST packages raises clinical concern and hampers the widespread dissemination of the ST technology. In part, this is due to the lack of a solid commonly accepted quality assurance pipeline for ST packages. Recently, we have developed a framework to benchmark ST algorithms for 3-D echocardiography by using realistic simulated volumetric echocardiographic recordings. Yet, 3-D echocardiography remains an emerging technology, whereas the compelling clinical concern is, so far, directed to the standardization of 2-D ST only. Therefore, by building upon our previous work, we present in this paper a pipeline to generate realistic synthetic sequences for 2-D ST algorithms. Hereto, the synthetic cardiac motion is obtained from a complex electromechanical heart model, whereas realistic vendor-specific texture is obtained by sampling a real clinical ultrasound recording. By modifying the parameters in our pipeline, we generated an open-access library of 105 synthetic sequences encompassing: 1) healthy and ischemic motion patterns; 2) the most common apical probe orientations; and 3) vendor-specific image quality from seven different systems. Ground truth deformation is also provided to allow performance analysis. The application of the provided data set is also demonstrated in the benchmarking of a recent academic ST algorithm.

Synthetic cannabinoid: prevalence, mechanisms of addiction development, mental disorders associated with the use of synthetic cannabinoid

Directory of Open Access Journals (Sweden)

Antsyborov A.V.

2017-04-01

Full Text Available according to the authors among the new psychoactive substances, the number of which is growing every year, despite the measures aimed at the obstacles to their dissemination there discovered the most frequent violations of psychotic conditions associated with use of synthetic cannabinoid in clinical practice. On the black market, they are distributed through online shops, under the guise of herbal mixtures for Smoking. When ingested, this group of drugs at the peak of intoxication raises a number of mental (different according to the depth of impaired consciousness, auditory and visual hallucinations, panic attacks, acute psychotic paranoid disorders, catatonic stupor, polar affective disorders, acute polythematic delusional symptoms and somatic disorders (disorders of heart rhythm and conduction, acute ischemic disorders, hypertension, depression of respiratory activity, violation of thermoregulation, development of acute renal failure, vomiting, expressed cephalgia, clinic of hypokalemia. In the reviewed literature and authors own observations there have been discovered some cases of mental addiction development to synthetic cannabinoids. The analysis of new literature data and own clinical observations helped the authors to compare the psychotropic effects caused by this group of drugs, relative to other known surfactants. The toxic effects of CSC on the body greatly exceeds the use of plant cannabinoids, and it has almost the same effects as the synthetic cathinone’s. The speed of formation of psychological dependence is lower compared to synthetic cathinone. Developing current strategies for diagnosis, treatment, and rehabilitation of patients who use synthetic cannabinoids remains an important task for practical healthcare.

An experimental study on the antitumor effect of 131I-17-AAG in vitro and in vivo

International Nuclear Information System (INIS)

Tu Wenyong; Liu Lu; Chen Daozhen; Huang Ying; Yin Weidong

2009-01-01

The objective of this study was to observe the antitumor effect of 131 I-17-allylamino-17-demethoxygeldanamycin ( 131 I-17-AAG) in vitro/in vivo and explore its antitumor mechanism with a view to its potential therapeutic application. 131 I-17-AAG was prepared by the reaction of 17-AAG with Na [ 131 I] in the presence of hydrogen peroxide. The effects of 131 17-AAG on cell growth inhibition and cell cycle distribution in vitro were studied in BEL-7402 cells lines. Following BEL-7402 tumor implantation by subcutaneous xenografts into nude mice, the reagents were injected through the tail vein, and the tumor volume was measured and analyzed. At the end of the experiment, tumor specimens were processed for histopathological analysis. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was used to investigate apoptosis. The expression change of Akt2 was tested by Western-blot analysis. Methyl-thiazolyl-tetrazolium assay showed inhibition rates of 27.7±5.3%, 57.3±4.3%, and 63.7±3.1%, in Na 131 I group, 17-AAG group, and 131 I-17-AAG group, respectively. The inhibition rate in the 131 I-17-AAG group differed significantly between Na 131 I group and 17-AAG group (F=229.49, P 131 I group, 17-AAG group, and 131 I-17-AAG group, respectively. Following infusion for 32 days, the tumor volumes in the 131 I-17-AAG group were significantly smaller than those in the DMSO group (F=24.18, P 131 I group (F=20.68, P 131 I-17-AAG inhibited the proliferation of tumor cells and induced apoptosis. The expression of Akt2 in 131 I-17-AAG was significantly lower than that in the DMSO group or 131 I group. 131 I-17-AAG can effectively inhibit the growth of BEL-7402 tumor cells in vitro and in vivo. 131 I-17-AAG is a promising agent for the treatment of BEL-7402 cell tumor. (author)

Trabecular bone structural parameters evaluated using dental cone-beam computed tomography: cellular synthetic bones.

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Ho, Jung-Ting; Wu, Jay; Huang, Heng-Li; Chen, Michael Y c; Fuh, Lih-Jyh; Hsu, Jui-Ting

2013-11-09

This study compared the adequacy of dental cone beam computed tomography (CBCT) and micro computed tomography (micro-CT) in evaluating the structural parameters of trabecular bones. The cellular synthetic bones in 4 density groups (Groups 1-4: 0.12, 0.16, 0.20, and 0.32 g/cm3) were used in this study. Each group comprised 8 experimental specimens that were approximately 1 cm3. Dental CBCT and micro-CT scans were conducted on each specimen to obtain independent measurements of the following 4 trabecular bone structural parameters: bone volume fraction (BV/TV), specific bone surface (BS/BV), trabecular thickness (Tb.Th.), and trabecular separation (Tb.Sp.). Wilcoxon signed ranks tests were used to compare the measurement variations between the dental CBCT and micro-CT scans. A Spearman analysis was conducted to calculate the correlation coefficients (r) of the dental CBCT and micro-CT measurements. Of the 4 groups, the BV/TV and Tb.Th. measured using dental CBCT were larger compared with those measured using micro-CT. By contrast, the BS/BV measured using dental CBCT was significantly less compared with those measured using micro-CT. Furthermore, in the low-density groups (Groups 1 and 2), the Tb.Sp. measured using dental CBCT was smaller compared with those measured using micro-CT. However, the Tb.Sp. measured using dental CBCT was slightly larger in the high-density groups (Groups 3 and 4) than it was in the low density groups. The correlation coefficients between the BV/TV, BS/BV, Tb.Th., and Tb.Sp. values measured using dental CBCT and micro-CT were 0.9296 (p < .001), 0.8061 (p < .001), 0.9390 (p < .001), and 0.9583 (p < .001), respectively. Although the dental CBCT and micro-CT approaches exhibited high correlations, the absolute values of BV/TV, BS/BV, Tb.Th., Tb.Sp. differed significantly between these measurements. Additional studies must be conducted to evaluate using dental CBCT in clinical practice.

Aluminum Exchangeable and Phosphorous Availability on Ultisol Using Humic Substance and Synthetic ……………..…. Sugeng Winarso and Abdullah Taufiq

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Sugeng Winarso

2011-09-01

Full Text Available Humic substance (HS extracted from composted agricultural waste contains organic acids that potential for an acid soil amandement. Functional group of COOH and OH in synthetically organic acid is higher than in HS originated from composted agricultural waste. Addition of synthetically organic acid to the HS may increase its functional group and therefore it will increase effectiveness in detoxifying aluminum (Al and desorpting phosphorus (P from an acid soil. Objective of reseach was to determine effect of synthetic organic acid addition to HS extracted from composted organic matter in desorpting P and detoxify Al. Research was conducted at Soil Laboratory of Agricultural Faculty of Jember University from February to May 2010. Treatment consisted of combination of four levels of HS concentration extracted from composted rice straw (0; 1,000; 2,000; and 5,000 mg kg-1 with two kind of synthetic organic acid: ethylenediaminetetraacetic acid (EDTA and acetic acid (CH3COOH at concentration of 5 mM. The treatment laid out in a randomized complete by design with three replications. Ultisol collected from Kentrong Banten was used in this research. Observation consisted of pH, Al and P concentration in the suspension at 0, 1, 2, 3, and 4 weeks after incubation. The result showed that EDTA or acetic acid treatment at concentration of 5 mM effectively increased soil pH and decreased exchangeable Al (exch-Al. However, EDTA was more reactive and having higher capability in increasing pH and detoxifying exch-Al than acetic acid. Humic substance extracted from composted rice straw at concentration of 1,000 to 5,000 mg kg-1 also effectively increased soil pH, decreased exch-Al, and increased P availability during a 4 weeks incubation period. The HS effect in Al detoxification and P desorption in acid soil could be boosted by addition of EDTA or acetic acid synthetic

Epitope and functional specificity of monoclonal antibodies to mouse gamma interferon: the synthetic peptide approach

International Nuclear Information System (INIS)

Russell, J.K.; Hayes, M.P.; Carter, J.M.; Torres, B.A.; Dunn, B.M.; Johnson, H.M.

1986-01-01

Four anti-recombinant mouse gamma interferon (α-IFNγ) monoclonal antibodies were generated using hamster spleen cells. Binding of 125 I-IFNγ by these protein A-bound antibodies was specifically blocked by cold IFNγ. Binding by three of these antibodies was also blocked by a synthetic peptide corresponding to the N-terminal 1-39 amino acids of IFNγ, while a corresponding C-terminal (95-133) peptide had no effect on binding. One of the N-terminal specific monoclonal antibodies inhibited both the antiviral and macrophage priming (for tumor cell killing) activities of IFNγ, while the other two had no effect on either biological function. Blocking experiments with cold IFNγ and N-terminal peptide suggest that the epitope specificities of the monoclonal antibodies could be determined by the conformational or topographic structure of IFNγ. Polyclonal antibodies to either the N-terminal or C-terminal peptides also inhibited both the antiviral and macrophage priming activities of IFNγ. All of the antibodies that inhibited IFNγ function also blocked binding of IFNγ to membrane receptor on cells, while antibodies that did not inhibit function also did not block binding. The data suggest that both the N-terminal and C-terminal domains of IFNγ play an important role in its antiviral and macrophage priming functions, possibly in a cooperative manner

Synthesis of [14α, 15α-3H]-17α-cyanomethyl-17β-hydroxyestra-4.9-diene-3-one - a specifically tritium labelled gestagen

International Nuclear Information System (INIS)

Roemer, J.; Wagner, H.

1978-05-01

Synthesis of [14α, 15α- 3 H 2 ]-17α-cyanomethyl-17β-hydroxyestra-4.9-diene-3-one from quantitativly tritiated [14α, 15α- 3 H 2 ]-3-methoxyestra-1,3,5(10),8-tetraene-17β-ol is described. The determination of the radiochemical purity and chemical yield was carried out by thin-layer chromatography. Preparative thin-layer chromatography was used for purifying the final product. By-products formed in the course of synthesis could be detected by determining and comparing specific activities of the intermediate products. Radiolytic investigations revealed the instability of the tritium labelled dienone system. (author)

Peptide/protein-polymer conjugates: synthetic strategies and design concepts.

Science.gov (United States)

Gauthier, Marc A; Klok, Harm-Anton

2008-06-21

This feature article provides a compilation of tools available for preparing well-defined peptide/protein-polymer conjugates, which are defined as hybrid constructs combining (i) a defined number of peptide/protein segments with uniform chain lengths and defined monomer sequences (primary structure) with (ii) a defined number of synthetic polymer chains. The first section describes methods for post-translational, or direct, introduction of chemoselective handles onto natural or synthetic peptides/proteins. Addressed topics include the residue- and/or site-specific modification of peptides/proteins at Arg, Asp, Cys, Gln, Glu, Gly, His, Lys, Met, Phe, Ser, Thr, Trp, Tyr and Val residues and methods for producing peptides/proteins containing non-canonical amino acids by peptide synthesis and protein engineering. In the second section, methods for introducing chemoselective groups onto the side-chain or chain-end of synthetic polymers produced by radical, anionic, cationic, metathesis and ring-opening polymerization are described. The final section discusses convergent and divergent strategies for covalently assembling polymers and peptides/proteins. An overview of the use of chemoselective reactions such as Heck, Sonogashira and Suzuki coupling, Diels-Alder cycloaddition, Click chemistry, Staudinger ligation, Michael's addition, reductive alkylation and oxime/hydrazone chemistry for the convergent synthesis of peptide/protein-polymer conjugates is given. Divergent approaches for preparing peptide/protein-polymer conjugates which are discussed include peptide synthesis from synthetic polymer supports, polymerization from peptide/protein macroinitiators or chain transfer agents and the polymerization of peptide side-chain monomers.

Synthetic Biology: Engineering Living Systems from Biophysical Principles.

Science.gov (United States)

Bartley, Bryan A; Kim, Kyung; Medley, J Kyle; Sauro, Herbert M

2017-03-28

Synthetic biology was founded as a biophysical discipline that sought explanations for the origins of life from chemical and physical first principles. Modern synthetic biology has been reinvented as an engineering discipline to design new organisms as well as to better understand fundamental biological mechanisms. However, success is still largely limited to the laboratory and transformative applications of synthetic biology are still in their infancy. Here, we review six principles of living systems and how they compare and contrast with engineered systems. We cite specific examples from the synthetic biology literature that illustrate these principles and speculate on their implications for further study. To fully realize the promise of synthetic biology, we must be aware of life's unique properties. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Effect of pH and dilution rate on specific production rate of extra cellular metabolites by Lactobacillus salivarius UCO_979C in continuous culture.

Science.gov (United States)

Valenzuela, Javier Ferrer; Pinuer, Luis; Cancino, Apolinaria García; Yáñez, Rodrigo Bórquez

2015-08-01

The effect of pH and dilution rate on the production of extracellular metabolites of Lactobacillus salivarius UCO_979 was studied. The experiments were carried out in continuous mode, with chemically defined culture medium at a temperature of 37 °C, 200 rpm agitation and synthetic air flow of 100 ml/min. Ethanol, acetic acid, formic acid, lactic acid and glucose were quantified through HPLC, while exopolysaccharide (EPS) was extracted with ethanol and quantified through the Dubois method. The results showed no linear trends for the specific production of lactic acid, EPS, acetic acid and ethanol, while the specific glucose consumption and ATP production rates showed linear trends. There was a metabolic change of the strain for dilution rates below 0.3 h(-1). The pH had a significant effect on the metabolism of the strain, which was evidenced by a higher specific glucose consumption and increased production of ATP at pH 6 compared with that obtained at pH 7. This work shows not only the metabolic capabilities of L. salivarius UCO_979C, but also shows that it is possible to quantify some molecules associated with its current use as gastrointestinal probiotic, especially regarding the production of organic acids and EPS.

Autism-specific covariation in perceptual performances: "g" or "p" factor?

Science.gov (United States)

Meilleur, Andrée-Anne S; Berthiaume, Claude; Bertone, Armando; Mottron, Laurent

2014-01-01

Autistic perception is characterized by atypical and sometimes exceptional performance in several low- (e.g., discrimination) and mid-level (e.g., pattern matching) tasks in both visual and auditory domains. A factor that specifically affects perceptive abilities in autistic individuals should manifest as an autism-specific association between perceptual tasks. The first purpose of this study was to explore how perceptual performances are associated within or across processing levels and/or modalities. The second purpose was to determine if general intelligence, the major factor that accounts for covariation in task performances in non-autistic individuals, equally controls perceptual abilities in autistic individuals. We asked 46 autistic individuals and 46 typically developing controls to perform four tasks measuring low- or mid-level visual or auditory processing. Intelligence was measured with the Wechsler's Intelligence Scale (FSIQ) and Raven Progressive Matrices (RPM). We conducted linear regression models to compare task performances between groups and patterns of covariation between tasks. The addition of either Wechsler's FSIQ or RPM in the regression models controlled for the effects of intelligence. In typically developing individuals, most perceptual tasks were associated with intelligence measured either by RPM or Wechsler FSIQ. The residual covariation between unimodal tasks, i.e. covariation not explained by intelligence, could be explained by a modality-specific factor. In the autistic group, residual covariation revealed the presence of a plurimodal factor specific to autism. Autistic individuals show exceptional performance in some perceptual tasks. Here, we demonstrate the existence of specific, plurimodal covariation that does not dependent on general intelligence (or "g" factor). Instead, this residual covariation is accounted for by a common perceptual process (or "p" factor), which may drive perceptual abilities differently in autistic and

Autism-specific covariation in perceptual performances: "g" or "p" factor?

Directory of Open Access Journals (Sweden)

Andrée-Anne S Meilleur

Full Text Available Autistic perception is characterized by atypical and sometimes exceptional performance in several low- (e.g., discrimination and mid-level (e.g., pattern matching tasks in both visual and auditory domains. A factor that specifically affects perceptive abilities in autistic individuals should manifest as an autism-specific association between perceptual tasks. The first purpose of this study was to explore how perceptual performances are associated within or across processing levels and/or modalities. The second purpose was to determine if general intelligence, the major factor that accounts for covariation in task performances in non-autistic individuals, equally controls perceptual abilities in autistic individuals.We asked 46 autistic individuals and 46 typically developing controls to perform four tasks measuring low- or mid-level visual or auditory processing. Intelligence was measured with the Wechsler's Intelligence Scale (FSIQ and Raven Progressive Matrices (RPM. We conducted linear regression models to compare task performances between groups and patterns of covariation between tasks. The addition of either Wechsler's FSIQ or RPM in the regression models controlled for the effects of intelligence.In typically developing individuals, most perceptual tasks were associated with intelligence measured either by RPM or Wechsler FSIQ. The residual covariation between unimodal tasks, i.e. covariation not explained by intelligence, could be explained by a modality-specific factor. In the autistic group, residual covariation revealed the presence of a plurimodal factor specific to autism.Autistic individuals show exceptional performance in some perceptual tasks. Here, we demonstrate the existence of specific, plurimodal covariation that does not dependent on general intelligence (or "g" factor. Instead, this residual covariation is accounted for by a common perceptual process (or "p" factor, which may drive perceptual abilities differently in

pTRA - A reporter system for monitoring the intracellular dynamics of gene expression.

Science.gov (United States)

Wagner, Sabine G; Ziegler, Martin; Löwe, Hannes; Kremling, Andreas; Pflüger-Grau, Katharina

2018-01-01

The presence of standardised tools and methods to measure and represent accurately biological parts and functions is a prerequisite for successful metabolic engineering and crucial to understand and predict the behaviour of synthetic genetic circuits. Many synthetic gene networks are based on transcriptional circuits, thus information on transcriptional and translational activity is important for understanding and fine-tuning the synthetic function. To this end, we have developed a toolkit to analyse systematically the transcriptional and translational activity of a specific synthetic part in vivo. It is based on the plasmid pTRA and allows the assignment of specific transcriptional and translational outputs to the gene(s) of interest (GOI) and to compare different genetic setups. By this, the optimal combination of transcriptional strength and translational activity can be identified. The design is tested in a case study using the gene encoding the fluorescent mCherry protein as GOI. We show the intracellular dynamics of mRNA and protein formation and discuss the potential and shortcomings of the pTRA plasmid.

Identification of an intracellular protein that specifically interacts with photoaffinity-labeled oncogenic p21 protein

International Nuclear Information System (INIS)

Lee, G.; Ronai, Z.A.; Pincus, M.R.; Brandt-Rauf, P.W.; Weinstein, I.B.; Murphy, R.B.; Delohery, T.M.; Nishimura, S.; Yamaizumi, Z.

1989-01-01

An oncogenic 21-kDa (p21) protein (Harvey RAS protein with Val-12) has been covalently modified with a functional reagent that contains a photoactivatable aromatic azide group. This modified p21 protein has been introduced quantitatively into NIH 3T3 cells using an erythrocyte-mediated fusion technique. The introduced p21 protein was capable of inducing enhanced pinocytosis and DNA synthesis in the recipient cells. To identify the putative intracellular protein(s) that specifically interact with modified p21 protein, the cells were pulsed with [ 35 S]methionine at selected times after fusion and then UV-irradiated to activate the azide group. The resulting nitrene covalently binds to amino acid residues in adjacent proteins, thus linking the p21 protein to these proteins. The cells were then lysed, and the lysate was immunoprecipitated with the anti-p21 monoclonal antibody Y13-259. The immunoprecipitate was analyzed by SDS/PAGE to identify p21 - protein complexes. By using this technique, the authors found that three protein complexes of 51, 64, and 82 kDa were labeled specifically and reproducibly. The most prominent band is the 64-kDa protein complex that shows a time-dependent rise and fall, peaking within a 5-hr period after introduction of the p21 protein the cells. These studies provide evidence that in vitro the p21 protein becomes associated with a protein whose mass is about 43 kDa. They suggest that the formation of this complex may play a role in mediating early events involved with cell transformation induced by RAS oncogenes

Members of Glycosyl-Hydrolase Family 17 of A. fumigatus Differentially Affect Morphogenesis

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Nicolas Millet

2018-01-01

Full Text Available Cell wall biosynthesis and remodeling are essential for fungal growth and development. In the fungal pathogen Aspergillus fumigatus, the β(1,3glucan is the major cell wall polysaccharide. This polymer is synthesized at the plasma membrane by a transmembrane complex, then released into the parietal space to be remodeled by enzymes, and finally incorporated into the pre-existing cell wall. In the Glycosyl-Hydrolases family 17 (GH17 of A. fumigatus, two β(1,3glucanosyltransferases, Bgt1p and Bgt2p, have been previously characterized. Disruption of BGT1 and BGT2 did not result in a phenotype, but sequence comparison and hydrophobic cluster analysis showed that three other genes in A. fumigatus belong to the GH17 family, SCW4, SCW11, and BGT3. In constrast to Δbgt1bgt2 mutants, single and multiple deletion of SCW4, SCW11, and BGT3 showed a decrease in conidiation associated with a higher conidial mortality and an abnormal conidial shape. Moreover, mycelium was also affected with a slower growth, stronger sensitivity to cell wall disturbing agents, and altered cell wall composition. Finally, the synthetic interactions between Bgt1p, Bgt2p, and the three other members, which support a functional cooperation in cell-wall assembly, were analyzed. Our data suggest that Scw4p, Scw11p, and Bgt3p are essential for cell wall integrity and might have antagonistic and distinct functions to Bgt1p and Bgt2p.

Members of Glycosyl-Hydrolase Family 17 of A. fumigatus Differentially Affect Morphogenesis

Science.gov (United States)

Millet, Nicolas; Latgé, Jean-Paul; Mouyna, Isabelle

2018-01-01

Cell wall biosynthesis and remodeling are essential for fungal growth and development. In the fungal pathogen Aspergillus fumigatus, the β(1,3)glucan is the major cell wall polysaccharide. This polymer is synthesized at the plasma membrane by a transmembrane complex, then released into the parietal space to be remodeled by enzymes, and finally incorporated into the pre-existing cell wall. In the Glycosyl-Hydrolases family 17 (GH17) of A. fumigatus, two β(1,3)glucanosyltransferases, Bgt1p and Bgt2p, have been previously characterized. Disruption of BGT1 and BGT2 did not result in a phenotype, but sequence comparison and hydrophobic cluster analysis showed that three other genes in A. fumigatus belong to the GH17 family, SCW4, SCW11, and BGT3. In constrast to Δbgt1bgt2 mutants, single and multiple deletion of SCW4, SCW11, and BGT3 showed a decrease in conidiation associated with a higher conidial mortality and an abnormal conidial shape. Moreover, mycelium was also affected with a slower growth, stronger sensitivity to cell wall disturbing agents, and altered cell wall composition. Finally, the synthetic interactions between Bgt1p, Bgt2p, and the three other members, which support a functional cooperation in cell-wall assembly, were analyzed. Our data suggest that Scw4p, Scw11p, and Bgt3p are essential for cell wall integrity and might have antagonistic and distinct functions to Bgt1p and Bgt2p. PMID:29385695

EXTINCTION IN THE COMA OF COMET 17P/HOLMES

International Nuclear Information System (INIS)

Lacerda, Pedro; Jewitt, David

2012-01-01

On 2007 October 29, the outbursting comet 17P/Holmes passed within 0.''79 of a background star. We recorded the event using optical, narrowband photometry and detect a 3%-4% dip in stellar brightness bracketing the time of closest approach to the comet nucleus. The detected dimming implies an optical depth τ ≈ 0.04 at 1.''5 from the nucleus and an optical depth toward the nucleus center τ n d = 0.006 ± 0.002 at α = 16° phase angle. Our measurements place the most stringent constraints on the extinction optical depth of any cometary coma.

EXTINCTION IN THE COMA OF COMET 17P/HOLMES

Energy Technology Data Exchange (ETDEWEB)

Lacerda, Pedro [Astrophysics Research Centre, Queen' s University Belfast, Belfast BT7 1NN (United Kingdom); Jewitt, David, E-mail: lacerda.pedro@gmail.com [Department of Earth and Space Sciences, University of California Los Angeles (UCLA), 595 Charles Young Drive, Los Angeles, CA 90095-1567 (United States)

2012-11-20

On 2007 October 29, the outbursting comet 17P/Holmes passed within 0.''79 of a background star. We recorded the event using optical, narrowband photometry and detect a 3%-4% dip in stellar brightness bracketing the time of closest approach to the comet nucleus. The detected dimming implies an optical depth {tau} Almost-Equal-To 0.04 at 1.''5 from the nucleus and an optical depth toward the nucleus center {tau}{sub n} < 13.3. At the time of our observations, the coma was optically thick only within {rho} {approx}< 0.''01 from the nucleus. By combining the measured extinction and the scattered light from the coma, we estimate a dust red albedo p{sub d} = 0.006 {+-} 0.002 at {alpha} = 16 Degree-Sign phase angle. Our measurements place the most stringent constraints on the extinction optical depth of any cometary coma.

Fourier analysis of a new P1 synthetic acceleration for Sn transport equations

International Nuclear Information System (INIS)

Turcksin, B.; Ragusa, J. C.

2010-10-01

In this work, is derived a new P1 synthetic acceleration scheme (P1SA) for the S N transport equation and analyze its convergence properties through the means of a Fourier analysis. The Fourier analysis is carried out for both continuous (i.e., not spatially discretized) S N equations and linear discontinuous Fem discretization. We show, thanks to the continuous analysis, that the scheme is unstable when the anisotropy is important (μ - >0.5). However, the discrete analysis shows that when cells are large in comparison to the mean free path, the spectral radius decreases and the acceleration scheme becomes effective, even for highly anisotropic scattering. In charged particles transport, scattering is highly anisotropic and mean free paths are very small and, thus, this scheme could be of interest. To use the P1SA when cells are small and anisotropy is important, the scheme is modified by altering the update of the accelerated flux or by using either K transport sweeps before the application of P1SA. The update scheme performs well as long as μ - - ≥0.9, the modified update scheme is unstable. The multiple transport sweeps scheme is convergent with an arbitrary μ - but the spectral radius increases when scattering is isotropic. When anisotropic increases, the frequency of use of the acceleration scheme needs to be decreased. Even if the P1SA is used less often, the spectral radius is significantly smaller when compared with a method that does not use it for high anisotropy (μ - ≥0.5). It is interesting to notice that using P1SA every two iterations gives the same spectral radius than the update method when μ - ≥0.5 but it is much less efficient when μ - <0.5. (Author)

Characterization of the human T cell response to rye grass pollen allergens Lol p 1 and Lol p 5.

Science.gov (United States)

Burton, M D; Papalia, L; Eusebius, N P; O'Hehir, R E; Rolland, J M

2002-12-01

Knowledge of dominant T cell epitopes of major allergens recognized by allergic individuals is required to improve efficacy and safety of allergen immunotherapy. Rye grass pollen (RGP) is the most important source of seasonal aeroallergens in temperate climates and Lol p 1 and Lol p 5 are the two major IgE-reactive allergens. This study aimed to characterize the T cell response to these allergens using a large panel of RGP-sensitive individuals. Short-term RGP-specific T cell lines (TCL) were generated from 38 RGP-sensitive subjects and stimulated with Lol p 1 and/or Lol p 5 allergens and synthetic 20-mer peptides. Proliferative responses were determined by 3H-thymidine uptake and IL-5 and IFN-gamma in culture supernatants analysed by ELISA. Of 17 subjects tested for reactivity to both allergens 16 (94%) responded to Lol p 1 and/or Lol p 5, establishing these as major T cell-reactive allergens. Sites of T cell reactivity were spread throughout the allergen molecules but regions of high reactivity were found. For Lol p 1 these spanned residues 19-38, 109-128, 154-173, 190-209, and for Lol p 5 37-56, 100-119, 145-164, 154-173, 190-209, 217-236 and 226-245. IL-5 and IFN-gamma were produced by T cells cultured with proliferation-inducing peptides. T cell responses to RGP major allergens have been extensively characterized, providing fundamental information for developing T cell-targeted immunotherapy for RGP allergy.

Breckinridge Project, initial effort. Report III, Volume 2. Specifications

Energy Technology Data Exchange (ETDEWEB)

None

1982-01-01

Report III, Volume 2 contains those specifications numbered K through Y, as follows: Specifications for Compressors (K); Specifications for Piping (L); Specifications for Structures (M); Specifications for Insulation (N); Specifications for Electrical (P); Specifications for Concrete (Q); Specifications for Civil (S); Specifications for Welding (W); Specifications for Painting (X); and Specifications for Special (Y). The standard specifications of Bechtel Petroleum Incorporated have been amended as necessary to reflect the specific requirements of the Breckinridge Project and the more stringent specifications of Ashland Synthetic Fuels, Inc. These standard specifications are available for the Initial Effort (Phase Zero) work performed by all contractors and subcontractors.

Solvothermal synthesis of InP quantum dots and their enhanced luminescent efficiency by post-synthetic treatments.

Science.gov (United States)

Byun, Ho-June; Lee, Ju Chul; Yang, Heesun

2011-03-01

InP quantum dots (QDs) were solvothermally synthesized by using a greener phosphorus source of P(N(CH(3))(2))(3) instead of highly toxic P(TMS)(3) widely used, and subsequently subjected to a size-sorting processing. While as-grown QDs showed an undetectably low emission intensity, post-synthetic treatments such as photo-etching, photo-radiation, and photo-assisted ZnS shell coating gave rise to a substantial increase in emission efficiency due to the effective removal and passivation of surface states. The emission efficiency of the photo-etched QDs was further enhanced by a consecutive UV photo-radiation, attributable to the photo-oxidation at QD surface. Furthermore, a relatively thick ZnS shell on the surface of InP QDs that were surface-modified with hydrophilic ligands beforehand was photochemically generated in an aqueous solution at room temperature. The resulting InP/ZnS core/shell QDs, emitting from blue to red wavelengths, were more efficient than the above photo-treated InP QDs, and their luminescent properties (emission bandwidth and quantum yield) were comparable to those of InP QDs synthesized with P(TMS)(3). Structural, size, and compositional analyses on InP/ZnS QDs were also conducted to elucidate their core/shell structure. Copyright © 2010 Elsevier Inc. All rights reserved.

Synthetic Genetic Targeting of Genome Instability in Cancer

International Nuclear Information System (INIS)

Sajesh, Babu V.; Guppy, Brent J.; McManus, Kirk J.

2013-01-01

Cancer is a leading cause of death throughout the World. A limitation of many current chemotherapeutic approaches is that their cytotoxic effects are not restricted to cancer cells, and adverse side effects can occur within normal tissues. Consequently, novel strategies are urgently needed to better target cancer cells. As we approach the era of personalized medicine, targeting the specific molecular defect(s) within a given patient’s tumor will become a more effective treatment strategy than traditional approaches that often target a given cancer type or sub-type. Synthetic genetic interactions are now being examined for their therapeutic potential and are designed to target the specific genetic and epigenetic phenomena associated with tumor formation, and thus are predicted to be highly selective. In general, two complementary approaches have been employed, including synthetic lethality and synthetic dosage lethality, to target aberrant expression and/or function associated with tumor suppressor genes and oncogenes, respectively. Here we discuss the concepts of synthetic lethality and synthetic dosage lethality, and explain three general experimental approaches designed to identify novel genetic interactors. We present examples and discuss the merits and caveats of each approach. Finally, we provide insight into the subsequent pre-clinical work required to validate novel candidate drug targets

Characterization of the binding of the Ptychodiscus brevis neurotoxin T17 to sodium channels in rat brain synaptosomes

International Nuclear Information System (INIS)

Poli, M.A.

1985-01-01

The lipid-soluble polyether neurotoxins isolated from the marine dinoflagellate Ptychodiscus brevis (formerly Gymnodinium breve) have been determined to bind to a unique receptor site associated with the voltage-sensitive sodium channel in rat brain synaptosomes. Reduction of the C 42 aldehyde function of T34 to the alcohol function of T17 using NaB 3 H 4 yielded 3 H-T17 with a specific activity of 15 Ci;/mmol. Using this specific probe, binding to sodium channels was measured at 4 0 CC, 22 0 C, and 37 0 C. Rosenthal analysis of the binding data yielded a K/sub d/ of 2.9 nM and B/sub max/ of 6.8 pmoles 3 H-T17 per mg of synaptosomal protein at 4 0 C. Both K/sub d/ and B/sub max/ were found to be temperature dependent. Depolarization of the synaptosomes by osmotic lysis resulted in the loss of 34% of the available receptor sites, with no decrease in binding affinity. Unlabeled T17, T34, and synthetic T17 (reduced T34) were equipotent in their ability to displace 3 H-T17 from its specific receptor site. Competition experiments using natural toxin probes specific for sites I-IV on the voltage-sensitive sodium channel demonstrate that 3 H-T17 does not bind to any of the previously-described neurotoxin receptor sites. A fifth site is proposed

Characterization of the binding of the Ptychodiscus brevis neurotoxin T17 to sodium channels in rat brain synaptosomes

Energy Technology Data Exchange (ETDEWEB)

Poli, M.A.

1985-01-01

The lipid-soluble polyether neurotoxins isolated from the marine dinoflagellate Ptychodiscus brevis (formerly Gymnodinium breve) have been determined to bind to a unique receptor site associated with the voltage-sensitive sodium channel in rat brain synaptosomes. Reduction of the C/sub 42/ aldehyde function of T34 to the alcohol function of T17 using NaB/sup 3/H/sub 4/ yielded /sup 3/H-T17 with a specific activity of 15 Ci;/mmol. Using this specific probe, binding to sodium channels was measured at 4/sup 0/CC, 22/sup 0/C, and 37/sup 0/C. Rosenthal analysis of the binding data yielded a K/sub d/ of 2.9 nM and B/sub max/ of 6.8 pmoles /sup 3/H-T17 per mg of synaptosomal protein at 4/sup 0/C. Both K/sub d/ and B/sub max/ were found to be temperature dependent. Depolarization of the synaptosomes by osmotic lysis resulted in the loss of 34% of the available receptor sites, with no decrease in binding affinity. Unlabeled T17, T34, and synthetic T17 (reduced T34) were equipotent in their ability to displace /sup 3/H-T17 from its specific receptor site. Competition experiments using natural toxin probes specific for sites I-IV on the voltage-sensitive sodium channel demonstrate that /sup 3/H-T17 does not bind to any of the previously-described neurotoxin receptor sites. A fifth site is proposed.

The Trojan Horse Method as a tool to investigate low-energy resonances: the 18O(p, α)15N and 17O(p, α)14N cases

International Nuclear Information System (INIS)

La Cognata, M.; Sergi, M. L.; Spitaleri, C.; Cherubini, S.; Gulino, M.; Kiss, G.; Lamia, L.; Pizzone, R. G.; Romano, S.; Mukhamedzhanov, A.; Goldberg, V.; Tribble, R.; Coc, A.; Hammache, F.; Sereville, N. de; Irgaziev, B.; Tumino, A.

2010-01-01

The 18 O(p, α) 15 N and 17 O(p, α) 14 N reactions are of primary importance in several as-trophysical scenarios, including nucleosynthesis inside Asymptotic Giant Branch stars and oxygen and nitrogen isotopic ratios in meteorite grains. They are also key reactions to understand exotic systems such as R-Coronae Borealis stars and novae. Thus, the measurement of their cross sections in the low energy region can be crucial to reduce the nuclear uncertainty on theoretical predictions, because the resonance parameters are poorly determined. The Trojan Horse Method, in its newly developed form particularly suited to investigate low-energy resonances, has been applied to the 2 H( 18 O, α 15 N)n and 2 H( 17 O, α 14 N)n reactions to deduce the 18 O(p, α) 15 N and 17 O(p, α) 14 N cross sections at low energies. Resonances in the 18 O(p, α) 15 N and 17 O(p, α) 14 N excitation functions have been studied and the resonance parameters deduced.

GRP1 PH Domain, Like AKT1 PH Domain, Possesses a Sentry Glutamate Residue Essential for Specific Targeting to Plasma Membrane PI(3,4,5)P3

Science.gov (United States)

Pilling, Carissa; Landgraf, Kyle E.; Falke, Joseph J.

2011-01-01

During the appearance of the signaling lipid PI(3,4,5)P3, an important subset of pleckstrin homology (PH) domains target signaling proteins to the plasma membrane. To ensure proper pathway regulation, such PI(3,4,5)P3-specific PH domains must exclude the more prevalant, constitutive plasma membrane lipid PI(4,5)P2 and bind the rare PI(3,4,5)P3 target lipid with sufficiently high affinity. Our previous study of the E17K mutant of protein kinase B (AKT1) PH domain, together with evidence from Carpten et al (1), revealed that the native AKT1 E17 residue serves as a sentry glutamate that excludes PI(4,5)P2, thereby playing an essential role in specific PI(3,4,5)P3 targeting (2). The sentry glutamate hypothesis proposes that an analogous sentry glutamate residue is a widespread feature of PI(3,4,5)P3-specific PH domains, and that charge reversal mutation at the sentry glutamate position will yield both increased PI(4,5)P2 affinity and constitutive plasma membrane targeting. To test this hypothesis the present study investigates the E345 residue, a putative sentry glutamate, of General Receptor for Phosphoinositides 1 (GRP1) PH domain. The results show that incorporation of the E345K charge reversal mutation into GRP1 PH domain enhances PI(4,5)P2 affinity 8-fold and yields constitutive plasma membrane targeting in cells, reminiscent of the effects of the E17K mutation in AKT1 PH domain. Hydrolysis of plasma membrane PI(4,5)P2 releases E345K GRP1 PH domain into the cytoplasm and the efficiency of this release increases when target Arf6 binding is disrupted. Overall, the findings provide strong support for the sentry glutamate hypothesis and suggest that the GRP1 E345K mutation will be linked to changes in cell physiology and human pathologies, as demonstrated for AKT1 E17K (1, 3). Analysis of available PH domain structures suggests that a lone glutamate residue (or, in some cases an aspartate) is a common, perhaps ubiquitous, feature of PI(3,4,5)P3-specific binding

Synergistic Synthetic Biology: Units in Concert

Science.gov (United States)

Trosset, Jean-Yves; Carbonell, Pablo

2013-01-01

Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications. PMID:25022769

Synergistic Synthetic Biology: Units in Concert

International Nuclear Information System (INIS)

Trosset, Jean-Yves; Carbonell, Pablo

2013-01-01

Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications.

Organic synthetic dye degradation by modified pinhole discharge

Czech Academy of Sciences Publication Activity Database

Božic' Lončaric', A.; Koprivanac, N.; Šunka, Pavel; Člupek, Martin; Babický, Václav

2004-01-01

Roč. 54, suppl.C (2004), C958-C963 ISSN 0011-4626. [Symposium on Plasma Physics and Technology /21st/. Praha, 14.06.2004-17.06.2004] R&D Projects: GA ČR GA202/02/1026 Keywords : organic synthetic Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 0.292, year: 2004

Stem cell markers (cytokeratin 17 and cytokeratin 19 in scarring and nonscarring alopecia

Directory of Open Access Journals (Sweden)

Dalia El Sakka

2016-01-01

Full Text Available Background: Alopecia is one of the most important hair follicle (HF disorders, which is divided into scarring (cicatricial and nonscarring (noncicatricial types. Objective: The aim of this study is to investigate the expression of stem cell (SC markers such as cytokeratin (CK 17 and CK19 in scarring and nonscarring alopecia. Materials and Methods: Thirty patients with scalp alopecia (15 with scarring alopecia and 15 without together with ten healthy volunteers were included in this study. Biopsies were taken from all participants and stained for CK17 and CK19 using immunohistochemistry. Results: There was a statistically significant difference between the nonscarring group and the control group with regard to CK17 expression in the outer layers of the HFs (P = 0.00 and CK19 staining of the inner layers of the HFs (P = 0.008. There was a statistically significant difference between the scarring and the control groups regarding CK17 expression in the outer (P = 0.00 and the inner layers (P = 0.00 of the HFs and CK19 expression in the inner layers of the HFs (P = 0.00. CK17 expression in the outer layers (P = 0.02 and the inner layers of the HFs (P = 0.00 together with CK19 expression in the inner layers of the HFs (P = 0.00 showed statistically significant differences between scarring and nonscarring alopecia groups. Conclusions: The presence of SC markers (CK17 and CK19 in the HFs was affected in both scarring and nonscarring alopecia, but the defect in scarring alopecia is more evident than that of nonscarring alopecia. The persistence of SC markers in some types of scarring alopecia could give a hope for the recovery of these lesions. Further studies are recommended to clarify the benefit from using HF SCs in the treatment of alopecia.

Stem Cell Markers (Cytokeratin 17 and Cytokeratin 19) in Scarring and Nonscarring Alopecia

Science.gov (United States)

El Sakka, Dalia; Gaber, Mohamed Abdel Wahed; Abdou, Asmaa Gaber; Wahed, Moshira Abdel; Saleh, Ahmed Abdel-Wahab; Shehata, Walla

2016-01-01

Background: Alopecia is one of the most important hair follicle (HF) disorders, which is divided into scarring (cicatricial) and nonscarring (noncicatricial) types. Objective: The aim of this study is to investigate the expression of stem cell (SC) markers such as cytokeratin (CK) 17 and CK19 in scarring and nonscarring alopecia. Materials and Methods: Thirty patients with scalp alopecia (15 with scarring alopecia and 15 without) together with ten healthy volunteers were included in this study. Biopsies were taken from all participants and stained for CK17 and CK19 using immunohistochemistry. Results: There was a statistically significant difference between the nonscarring group and the control group with regard to CK17 expression in the outer layers of the HFs (P = 0.00) and CK19 staining of the inner layers of the HFs (P = 0.008). There was a statistically significant difference between the scarring and the control groups regarding CK17 expression in the outer (P = 0.00) and the inner layers (P = 0.00) of the HFs and CK19 expression in the inner layers of the HFs (P = 0.00). CK17 expression in the outer layers (P = 0.02) and the inner layers of the HFs (P = 0.00) together with CK19 expression in the inner layers of the HFs (P = 0.00) showed statistically significant differences between scarring and nonscarring alopecia groups. Conclusions: The presence of SC markers (CK17 and CK19) in the HFs was affected in both scarring and nonscarring alopecia, but the defect in scarring alopecia is more evident than that of nonscarring alopecia. The persistence of SC markers in some types of scarring alopecia could give a hope for the recovery of these lesions. Further studies are recommended to clarify the benefit from using HF SCs in the treatment of alopecia. PMID:27761086

Immunoexpression of Th17-related cytokines in oral lichen planus.

Science.gov (United States)

Monteiro, Bárbara Vanessa de Brito; Pereira, Joabe Dos Santos; Nonaka, Cassiano F W; Godoy, Gustavo P; da Silveira, Éricka J D; Miguel, Márcia Cristina da Costa

2015-07-01

A recently described lineage of lymphocytes, Th17 cells, has been associated with inflammatory and autoimmune diseases. The aim of this article was to assess the immunoexpression of cytokines related to this lineage, interleukin-17 (IL-17) and IL-23 and in reticular and erosive oral lichen planus (OLP). The sample included 41 cases of OLP (23 reticular and 18 erosive) and 10 cases of inflammatory fibrous hyperplasia (IFH). Lymphocytes exhibiting cytoplasmic immunostaining were counted. Epithelial immunostaining was also evaluated. There was no statistical differences in the number of IL-17 and IL-23 lymphocytes between the OLP (55.40 and 48.40, respectively) and IFH (39.30 and 44.40, respectively). A significantly higher number of IL-23 lymphocytes was found in erosive OLP group (63.80) when compared with reticular (41.40) and IFH lesions (44.40) (P=0.019). Furthermore, epithelial immunopositivity for IL-17 and IL-23 was higher in OLP lesions than in IFH (P=0.012 and P=0.011, respectively). A significantly higher number of IL-23 lymphocytes in erosive OLP and the strong epithelial immunopositivity for IL-23 and IL-17 in OLP group could suggest an important participation of TCD4 Th17 response in this disorder.

Do group-specific equations provide the best estimates of stature?

Science.gov (United States)

Albanese, John; Osley, Stephanie E; Tuck, Andrew

2016-04-01

An estimate of stature can be used by a forensic anthropologist with the preliminary identification of an unknown individual when human skeletal remains are recovered. Fordisc is a computer application that can be used to estimate stature; like many other methods it requires the user to assign an unknown individual to a specific group defined by sex, race/ancestry, and century of birth before an equation is applied. The assumption is that a group-specific equation controls for group differences and should provide the best results most often. In this paper we assess the utility and benefits of using group-specific equations to estimate stature using Fordisc. Using the maximum length of the humerus and the maximum length of the femur from individuals with documented stature, we address the question: Do sex-, race/ancestry- and century-specific stature equations provide the best results when estimating stature? The data for our sample of 19th Century White males (n=28) were entered into Fordisc and stature was estimated using 22 different equation options for a total of 616 trials: 19th and 20th Century Black males, 19th and 20th Century Black females, 19th and 20th Century White females, 19th and 20th Century White males, 19th and 20th Century any, and 20th Century Hispanic males. The equations were assessed for utility in any one case (how many times the estimated range bracketed the documented stature) and in aggregate using 1-way ANOVA and other approaches. This group-specific equation that should have provided the best results was outperformed by several other equations for both the femur and humerus. These results suggest that group-specific equations do not provide better results for estimating stature while at the same time are more difficult to apply because an unknown must be allocated to a given group before stature can be estimated. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Synthetic 6B di-, tri-, and tetrasaccharide-protein conjugates contain pneumococcal type 6A and 6B common and 6B-specific epitopes that elicit protective antibodies in mice

NARCIS (Netherlands)

Vliegenthart, J.F.G.; Jansen, W.T.M.; Hogenboom, S.; Thijssen, M.J.L.; Kamerling, J.P.; Verhoef, J.; Snippe, H.; Verheul, A.F.M.

2001-01-01

The immunogenicity and protective capacity of Streptococcus pneumoniae 6B capsular polysaccharide (PS)-derived synthetic phosphate-containing disaccharide (Rha-ribitol-P-), trisaccharide (ribitol-P-Gal-Glc-), and tetrasaccharide (Rha-ribitol-P-Gal-Glc-)-protein conjugates in rabbits and mice were

Natural - synthetic - artificial!

DEFF Research Database (Denmark)

Nielsen, Peter E

2010-01-01

The terms "natural," "synthetic" and "artificial" are discussed in relation to synthetic and artificial chromosomes and genomes, synthetic and artificial cells and artificial life.......The terms "natural," "synthetic" and "artificial" are discussed in relation to synthetic and artificial chromosomes and genomes, synthetic and artificial cells and artificial life....

UTILIZING SYNTHETIC VISIBLE SPECTRA TO EXPLORE THE PHYSICAL BASIS FOR THE CLASSIFICATION OF LAMBDA BOÖTIS STARS

Energy Technology Data Exchange (ETDEWEB)

Cheng, Kwang-Ping; Johnson, Dustin M.; Tarbell, Erik S.; Romo, Christopher A. [California State University, Fullerton CA (United States); Neff, James E. [College of Charleston, Charleston, SC (United States); Gray, Richard O. [Appalachian State University, Boone, NC (United States); Corbally, Christopher J. [Vatican Observatory, Tucson, AZ (United States)

2017-01-01

Since the peculiar nature of Lambda Boötis was first noticed in 1943, the Lambda Boo stars have been recognized as a group of peculiar A-type stars. They are Population I dwarfs that show deficiencies of iron-peak elements (up to 2 dex), but have near-solar C, N, O, and S abundances. In a previous paper, we used both observed and synthetic ultraviolet spectra to demonstrate that the C i 1657 Å/Al ii 1671 Å equivalent width ratio can help distinguish between Lambda Boo stars and other metal-weak stars hotter than 8000 K. In this paper, using observed and synthetic visible (4000–6800 Å) spectra, we demonstrate that the C i 5052.17 Å/Mg ii 4481 Å equivalent width ratio can be used as a quantitative diagnostic for cooler Lambda Boo stars.

The Pseudomonas aeruginosa pirA gene encodes a second receptor for ferrienterobactin and synthetic catecholate analogues.

Science.gov (United States)

Ghysels, Bart; Ochsner, Urs; Möllman, Ute; Heinisch, Lothar; Vasil, Michael; Cornelis, Pierre; Matthijs, Sandra

2005-05-15

Actively secreted iron chelating agents termed siderophores play an important role in the virulence and rhizosphere competence of fluorescent pseudomonads, including Pseudomonas aeruginosa which secretes a high affinity siderophore, pyoverdine, and the low affinity siderophore, pyochelin. Uptake of the iron-siderophore complexes is an active process that requires specific outer membrane located receptors, which are dependent of the inner membrane-associated protein TonB and two other inner membrane proteins, ExbB and ExbC. P. aeruginosa is also capable of using a remarkable variety of heterologous siderophores as sources of iron, apparently by expressing their cognate receptors. Illustrative of this feature are the 32 (of which 28 putative) siderophore receptor genes observed in the P. aeruginosa PAO1 genome. However, except for a few (pyoverdine, pyochelin, enterobactin), the vast majority of P. aeruginosa siderophore receptor genes still remain to be characterized. Ten synthetic iron chelators of catecholate type stimulated growth of a pyoverdine/pyochelin deficient P. aeruginosa PAO1 mutant under condition of severe iron limitation. Null mutants of the 32 putative TonB-dependent siderophore receptor encoding genes engineered in the same genetic background were screened for obvious deficiencies in uptake of the synthetic siderophores, but none showed decreased growth stimulation in the presence of the different siderophores. However, a double knock-out mutant of ferrienterobactin receptor encoding gene pfeA (PA 2688) and pirA (PA0931) failed to be stimulated by 4 of the tested synthetic catecholate siderophores whose chemical structures resemble enterobactin. Ferric-enterobactin also failed to stimulate growth of the double pfeA-pirA mutant although, like its synthetic analogues, it stimulated growth of the corresponding single mutants. Hence, we confirmed that pirA represents a second P. aeruginosa ferric-enterobactin receptor. The example of these two

Identification of an intracellular protein that specifically interacts with photoaffinity-labeled oncogenic p21 protein.

Science.gov (United States)

Lee, G; Ronai, Z A; Pincus, M R; Brandt-Rauf, P W; Murphy, R B; Delohery, T M; Nishimura, S; Yamaizumi, Z; Weinstein, I B

1989-11-01

An oncogenic 21-kDa (p21) protein (Harvey RAS protein with Val-12) has been covalently modified with a functional reagent that contains a photoactivatable aromatic azide group. This modified p21 protein has been introduced quantitatively into NIH 3T3 cells using an erythrocyte-mediated fusion technique. The introduced p21 protein was capable of inducing enhanced pinocytosis and DNA synthesis in the recipient cells. To identify the putative intracellular protein(s) that specifically interact with the modified p21 protein, the cells were pulsed with [35S]methionine at selected times after fusion and then UV-irradiated to activate the azide group. The resulting nitrene covalently binds to amino acid residues in adjacent proteins, thus linking the p21 protein to these proteins. The cells were then lysed, and the lysate was immunoprecipitated with the anti-p21 monoclonal antibody Y13-259. The immunoprecipitate was analyzed by SDS/PAGE to identify p21-protein complexes. By using this technique, we found that three protein complexes of 51, 64, and 82 kDa were labeled specifically and reproducibly. The most prominent band is the 64-kDa protein complex that shows a time-dependent rise and fall, peaking within a 5-hr period after introduction of the p21 protein into the cells. These studies provide evidence that in vitro the p21 protein becomes associated with a protein whose mass is about 43 kDa. We suggest that the formation of this complex may play a role in mediating early events involved with cell transformation induced by RAS oncogenes.

Circulating endothelial progenitor cells, Th1/Th2/Th17-related cytokines, and endothelial dysfunction in resistant hypertension.

Science.gov (United States)

Magen, Eli; Feldman, Arie; Cohen, Ziona; Alon, Dora Ben; Minz, Evegeny; Chernyavsky, Alexey; Linov, Lina; Mishal, Joseph; Schlezinger, Menacham; Sthoeger, Zev

2010-02-01

A possible link between chronic vascular inflammation and arterial hypertension is now an object of intensive studies. To compare Th1/Th2/Th17 cells-related cytokines, circulating endothelial progenitor cells (EPC), and endothelial function in subjects with resistant arterial hypertension (RAH) and controlled arterial hypertension (CAH). Blood pressure was measured by electronic sphygmomanometer. EPC were identified as CD34+/CD133+/kinase insert domain receptor (KDR)+ cells by flow cytometry. Th1/Th2/Th17 cells-related cytokines were identified using the Human Th1/Th2/Th17 Cytokines MultiAnalyte ELISArray Kit. Endothelium-dependent (FMD) vasodilatation of brachial artery was measured by Doppler ultrasound scanning. RAH group (n = 20) and CAH group (n = 20) and 17 healthy individuals (control group) were recruited. In the RAH group, lower blood levels of EPC number (42.4 +/- 16.7 cells/mL) and EPC% (0.19 +/- 0.08%) were observed than in the CAH group (93.1 +/- 88.7 cells/mL; P = 0.017; 0.27 +/- 0.17; P = 0.036) and control group (68.5 +/- 63.6 cells/mL; P < 0.001; 0.28 +/- 0.17%; P = 0.003), respectively. Plasma transforming growth factor-beta1 levels were significantly higher in the RAH group (1767 +/- 364 pg/mL) than in the CAH group (1292 +/- 349; P < 0.001) and in control group (1203 +/- 419 pg/mL; P < 0.001). In the RAH group, statistically significant negative correlation was observed between systolic blood pressure and EPC% (r = -0.72, P < 0.01). FMD in the RAH group was significantly lower (5.5 +/- 0.8%) than in the CAH group (9.2 +/- 1.4; P < 0.001) and in healthy controls (10.1 +/- 1.1%; P < 0.001). RAH is characterized by reduced circulating EPC, substantial endothelial dysfunction, and increased plasma transforming growth factor-beta1 levels.

US Competitiveness in Synthetic Biology.

Science.gov (United States)

Gronvall, Gigi Kwik

2015-01-01

Synthetic biology is an emerging technical field that aims to make biology easier to engineer; the field has applications in strategically important sectors for the US economy. While the United States currently leads in synthetic biology R&D, other nations are heavily investing in order to boost their economies, which will inevitably diminish the US leadership position. This outcome is not entirely negative--additional investments will expand markets--but it is critical that the US government take steps to remain competitive: There are applications from which the US population and economy may benefit; there are specific applications with importance for national defense; and US technical leadership will ensure that US experts have a leading role in synthetic biology governance, regulation, and oversight. Measures to increase competitiveness in S&T generally are broadly applicable for synthetic biology and should be pursued. However, the US government will also need to take action on fundamental issues that will affect the field's development, such as countering anti-GMO (genetically modified organism) sentiments and anti-GMO legislation. The United States should maintain its regulatory approach so that it is the product that is regulated, not the method used to create a product. At the same time, the United States needs to ensure that the regulatory framework is updated so that synthetic biology products do not fall into regulatory gaps. Finally, the United States needs to pay close attention to how synthetic biology applications may be governed internationally, such as through the Nagoya Protocol of the Convention on Biological Diversity, so that beneficial applications may be realized.

PrP P102L and Nearby Lysine Mutations Promote Spontaneous In Vitro Formation of Transmissible Prions.

Science.gov (United States)

Kraus, Allison; Raymond, Gregory J; Race, Brent; Campbell, Katrina J; Hughson, Andrew G; Anson, Kelsie J; Raymond, Lynne D; Caughey, Byron

2017-11-01

Accumulation of fibrillar protein aggregates is a hallmark of many diseases. While numerous proteins form fibrils by prion-like seeded polymerization in vitro , only some are transmissible and pathogenic in vivo To probe the structural features that confer transmissibility to prion protein (PrP) fibrils, we have analyzed synthetic PrP amyloids with or without the human prion disease-associated P102L mutation. The formation of infectious prions from PrP molecules in vitro has required cofactors and/or unphysiological denaturing conditions. Here, we demonstrate that, under physiologically compatible conditions without cofactors, the P102L mutation in recombinant hamster PrP promoted prion formation when seeded by minute amounts of scrapie prions in vitro Surprisingly, combination of the P102L mutation with charge-neutralizing substitutions of four nearby lysines promoted spontaneous prion formation. When inoculated into hamsters, both of these types of synthetic prions initiated substantial accumulation of prion seeding activity and protease-resistant PrP without transmissible spongiform encephalopathy (TSE) clinical signs or notable glial activation. Our evidence suggests that PrP's centrally located proline and lysine residues act as conformational switches in the in vitro formation of transmissible PrP amyloids. IMPORTANCE Many diseases involve the damaging accumulation of specific misfolded proteins in thread-like aggregates. These threads (fibrils) are capable of growing on the ends by seeding the refolding and incorporation of the normal form of the given protein. In many cases such aggregates can be infectious and propagate like prions when transmitted from one individual host to another. Some transmitted aggregates can cause fatal disease, as with human iatrogenic prion diseases, while other aggregates appear to be relatively innocuous. The factors that distinguish infectious and pathogenic protein aggregates from more innocuous ones are poorly understood

Cytochrome P450-mediated metabolism of the synthetic cannabinoids UR-144 and XLR-11

DEFF Research Database (Denmark)

Nielsen, Line Marie; Holm, Niels Bjerre; Olsen, Lars

2016-01-01

In recent years, synthetic cannabinoids have emerged in the illicit drug market, in particular via the Internet, leading to abuse of these drugs. There is currently limited knowledge about the specific enzymes involved in the metabolism of these drugs. In this study, we investigated the cytochrome...... of UR-144 and XLR-11, while inhibition of the other CYP enzymes in HLM had only minor effects. Thus, CYP3A4 is the major contributor to the CYP mediated metabolism of UR-144 and XLR-11 with minor contributions from CYP1A2. Users of UR-144 and XLR-11 are thus subject to the influence of potential drug-drug...... interactions, if they are concomitantly medicated with CYP3A4 inducers (e.g. some antiepileptics) or inhibitors (e.g. some antifungal drugs). Copyright © 2015 John Wiley & Sons, Ltd....

Production of DNA polymerase by recombinant pET-17b/Pfu-Pol ...

African Journals Online (AJOL)

Although this enzyme has been produced worldwide, there is no reported cloning or production of polymerases in Egypt. In the current work, plasmid coding Pfu polymerase enzyme (pET-17b/Pfu-Pol) was transformed into E. coli Top10. The plasmid coding Pfu- polymerase was confirmed by restriction analysis using HindIII ...

Maximization of integral outlet quantities of an axisymmetric synthetic jet actuator based on a loudspeaker

Czech Academy of Sciences Publication Activity Database

Kordík, Jozef; Trávníček, Zdeněk

2016-01-01

Roč. 114, March (2016), č. článku 02152. ISSN 2101-6275. [International Conference on Experimental Fluid Mechanics /10./. Praha, 17.11.2015-20.11.2015] R&D Projects: GA ČR GA14-08888S Institutional support: RVO:61388998 Keywords : synthetic jet * synthetic jet actuator * resonance Subject RIV: JU - Aeronautics, Aerodynamics, Aircrafts

Synthetic Biology and the Translational Imperative.

Science.gov (United States)

Heidari Feidt, Raheleh; Ienca, Marcello; Elger, Bernice Simone; Folcher, Marc

2017-12-18

Advances at the interface between the biological sciences and engineering are giving rise to emerging research fields such as synthetic biology. Harnessing the potential of synthetic biology requires timely and adequate translation into clinical practice. However, the translational research enterprise is currently facing fundamental obstacles that slow down the transition of scientific discoveries from the laboratory to the patient bedside. These obstacles including scarce financial resources and deficiency of organizational and logistic settings are widely discussed as primary impediments to translational research. In addition, a number of socio-ethical considerations inherent in translational research need to be addressed. As the translational capacity of synthetic biology is tightly linked to its social acceptance and ethical approval, ethical limitations may-together with financial and organizational problems-be co-determinants of suboptimal translation. Therefore, an early assessment of such limitations will contribute to proactively favor successful translation and prevent the promising potential of synthetic biology from remaining under-expressed. Through the discussion of two case-specific inventions in synthetic biology and their associated ethical implications, we illustrate the socio-ethical challenges ahead in the process of implementing synthetic biology into clinical practice. Since reducing the translational lag is essential for delivering the benefits of basic biomedical research to society at large and promoting global health, we advocate a moral obligation to accelerating translational research: the "translational imperative."

Synthetic multicellular oscillatory systems: controlling protein dynamics with genetic circuits

International Nuclear Information System (INIS)

Koseska, Aneta; Volkov, Evgenii; Kurths, Juergen

2011-01-01

Synthetic biology is a relatively new research discipline that combines standard biology approaches with the constructive nature of engineering. Thus, recent efforts in the field of synthetic biology have given a perspective to consider cells as 'programmable matter'. Here, we address the possibility of using synthetic circuits to control protein dynamics. In particular, we show how intercellular communication and stochasticity can be used to manipulate the dynamical behavior of a population of coupled synthetic units and, in this manner, finely tune the expression of specific proteins of interest, e.g. in large bioreactors.

MicroRNA-181a-5p Impedes IL-17-Induced Nonsmall Cell Lung Cancer Proliferation and Migration through Targeting VCAM-1

Directory of Open Access Journals (Sweden)

Yang Cao

2017-05-01

Full Text Available Aim: The contribution of the inflammatory mediator interleukin-17 (IL-17 in nonsmall cell lung cancer (NSCLC malignancy has been reported in the literature. MicroRNA-181a-5p (miR-181a-5p acts as a tumor suppressor which can regulate target gene at the posttranscriptional level. Our study aimed to investigate the interaction between IL-17 and miR-181a-5p in NSCLC. Methods: 35 patients with NSCLC and 24 COPD controls were selected and examined in our study. In vitro, H226 and H460 cell lines were exposed to different doses (20, 40, 60, and 80 ng/mL of IL-17 to examine the effect of IL-17 on miR-181a-5p and vascular cell adhesion molecule 1 (VCAM-1 expression. MiR-181 mimic and miR-181a-5p inhibitor were transfected to explore the regulation of VCAM-1 as well as tumor cell proliferation and migration. Results: miR-181a-5p expression was downregulated, and IL-17 and VCAM-1 expression was upregulated in NSCLC tissues. Furthermore, IL-17 decreased miR-181a-5p expression but increased VCAM-1 expression in H226 and H460 cells. MiR-181 regulated VCAM-1 expression through binding to 3’-UTR sequence. MiR-181 attenuated tumor cell proliferation and migration. IL-17 modulated miR-181a-5p expression through activating NF-κB but not Stat3. Conclusion: Taken together, our data show the regulation of VCAM-1 expression by miR-181a-5p under IL-17 exposure, predicting a potential way for counteracting cancer metastasis.

Career exploration in young people: Study with specific groups

Directory of Open Access Journals (Sweden)

Ana Daniela Silva

2015-07-01

Full Text Available This work presents two studies of career exploration with specific groups of youth, using the Career Exploration Survey (CES. The first study compares the career exploration process of 136 foster-care youth and 186 youth living with their families, using the One-Way MANOVA. In the second study we analyzed the process of career exploration of 323 young people in vocational education, comparing it with the 208 regular education using the T-Test. Implications for career intervention with specific groups will be taken based on the results.

Full-thickness skin graft vs. synthetic mesh in the repair of giant incisional hernia: a randomized controlled multicenter study.

Science.gov (United States)

Clay, L; Stark, B; Gunnarsson, U; Strigård, K

2018-04-01

Repair of large incisional hernias includes the implantation of a synthetic mesh, but this may lead to pain, stiffness, infection and enterocutaneous fistulae. Autologous full-thickness skin graft as on-lay reinforcement has been tested in eight high-risk patients in a proof-of-concept study, with satisfactory results. In this multicenter randomized study, the use of skin graft was compared to synthetic mesh in giant ventral hernia repair. Non-smoking patients with a ventral hernia > 10 cm wide were randomized to repair using an on-lay autologous full-thickness skin graft or a synthetic mesh. The primary endpoint was surgical site complications during the first 3 months. A secondary endpoint was patient comfort. Fifty-three patients were included. Clinical evaluation was performed at a 3-month follow-up appointment. There were fewer patients in the skin graft group reporting discomfort: 3 (13%) vs. 12 (43%) (p = 0.016). Skin graft patients had less pain and a better general improvement. No difference was seen regarding seroma; 13 (54%) vs. 13 (46%), or subcutaneous wound infection; 5 (20%) vs. 7 (25%). One recurrence appeared in each group. Three patients in the skin graft group and two in the synthetic mesh group were admitted to the intensive care unit. No difference was seen for the primary endpoint short-term surgical complication. Full-thickness skin graft appears to be a reliable material for ventral hernia repair producing no more complications than when using synthetic mesh. Patients repaired with a skin graft have less subjective abdominal wall symptoms.

A Comparison of Natural (D-α-tocopherol) and Synthetic (DL-α-tocopherol Acetate) Vitamin E Supplementation on the Growth Performance, Meat Quality and Oxidative Status of Broilers.

Science.gov (United States)

Cheng, K; Niu, Y; Zheng, X C; Zhang, H; Chen, Y P; Zhang, M; Huang, X X; Zhang, L L; Zhou, Y M; Wang, T

2016-05-01

The present study was conducted to compare the supplementation of natural (D-α-tocopherol) and synthetic (DL-α-tocopherol acetate) vitamin E on the growth performance, meat quality, muscular antioxidant capacity and genes expression related to oxidative status of broilers. A total of 144 1 day-old Arbor Acres broiler chicks were randomly allocated into 3 groups with 6 replicates of 8 birds each. Birds were given a basal diet (control group), and basal diet supplemented with either 20 IU D-α-tocopherol or DL-α-tocopherol acetate for 42 days, respectively. The results indicated that treatments did not alter growth performance of broilers (p>0.05). Compared with the control group, concentration of α-tocopherol in the breast muscle was increased by the supplementation of vitamin E (pnatural vitamin E group (pnatural vitamin E group (pnatural rather than synthetic vitamin E reduced MDA accumulation in the thigh (pnatural nor synthetic vitamin E supplementation altered muscular mRNA abundance of genes related to oxidative stress (p>0.05). It was concluded that vitamin E supplementation, especially the natural vitamin E, can enhance the retention of muscular α-tocopherol, improve meat quality and muscular antioxidant capacity of broilers.

Contribution of soil-32P, fertilizer-32P and VA mycorrhizal fungi to phosphorus nutrition of corn plant

International Nuclear Information System (INIS)

Feng Gu; Yang Maoqiu; Bai Dengsha; Huang Quansheng

1997-01-01

32 P labelled fertilizer and five synthetic phosphates (dicalcium phosphate, octocalcium phosphate, iron phosphate, aluminium phosphate and apatite), which were used to simulate inorganic phosphates such as Ca 2 -P, Ca 8 -P, Fe P , Al-P and Ca 10 -P in calcareous soil, were applied to corn plants inoculating with and without vesicular-arbuscular (VA) mycorrhizal fungi in a calcareous soil. The results showed that VA mycorrhizal fungi and dicalcium phosphate, octocalcium phosphate, iron phosphate, aluminium phosphate promoted growth and increased phosphorus content of corn plant. The four synthetic phosphates except apatite had higher contributions to corn plant growth than VA mycorrhizal fungi. Contributions of fertilizer-P, soil-P and synthetic phosphates to phosphorus nutrition of corn plant were in order of synthetic phosphates (except apatite) > soil- P > fertilizer-P. Inoculating with VA mycorrhizal fungi increased the contribution of soil-P and decreased the contribution of synthetic phosphates, but did not affect the contribution of fertilizer-P

Prognostic significance of del 17p, ZAP-70 and CD38 as ...

African Journals Online (AJOL)

This study analyzed 40 recently diagnosed, untreated B-CLL patients for CD38 and ZAP-70 expression by flow cytometry and for del 17p by conventional cytogenetics (CCG) and by fluorescence in situ hybridization (FISH) technique to evaluate their effect on the clinical course of CLL and as risk factors for disease ...

Immunomodulating activities of soluble synthetic polymer-bound drugs.

Science.gov (United States)

Ríhová, Blanka

2002-09-13

The introduction of a synthetic material into the body always affects different body systems, including the defense system. Synthetic polymers are usually thymus-independent antigens with only a limited ability to elicit antibody formation or to induce a cellular immune response against them. However, there are many other ways that they influence or can be used to influence the immune system of the host. Low-immunogenic water-soluble synthetic polymers sometimes exhibit significant immunomodulating activity, mainly concerning the activation/suppression of NK cells, LAK cells and macrophages. Some of them, such as poly(ethylene glycol) and poly[N-(2-hydroxypropyl)methacrylamide], can be used as effective protein carriers, as they are able to reduce the immunogenicity of conjugated proteins and/or to reduce non-specific uptake of liposome/nanoparticle-entrapped drugs and other therapeutic agents. Recently, the development of vaccine delivery systems prepared from biodegradable and biocompatible water-soluble synthetic polymers, microspheres, liposomes and/or nanoparticles has received considerable attention, as they can be tailored to meet the specific physical, chemical, and immunogenic requirements of a particular antigen and some of them can also act as adjuvants. Copyright 2002 Elsevier Science B.V.

On the structure of Selmer groups of $p$-ordinary modular forms over $\\mathbf{Z}_p$-extensions

OpenAIRE

Kidwell, Keenan

2016-01-01

We prove analogues of the major algebraic results of Greenberg-Vatsal for Selmer groups of $p$-ordinary newforms over $\\mathbf{Z}_p$-extensions which may be neither cyclotomic nor anticyclotomic, under a number of technical hypotheses, including a cotorsion assumption on the Selmer groups. The main complication which arises in our work is the possible presence of finite primes which can split completely in the $\\mathbf{Z}_p$-extension being considered, resulting in the local cohomology groups...

Dopaminergic Neuron-Specific Deletion of p53 Gene Attenuates Methamphetamine Neurotoxicity.

Science.gov (United States)

Lu, Tao; Kim, Paul P; Greig, Nigel H; Luo, Yu

2017-08-01

p53 plays an essential role in the regulation of cell death in dopaminergic (DA) neurons and its activation has been implicated in the neurotoxic effects of methamphetamine (MA). However, how p53 mediates MA neurotoxicity remains largely unknown. In this study, we examined the effect of DA-specific p53 gene deletion in DAT-p53KO mice. Whereas in vivo MA binge exposure reduced locomotor activity in wild-type (WT) mice, this was significantly attenuated in DAT-p53KO mice and associated with significant differences in the levels of the p53 target genes BAX and p21 between WT and DAT-p53KO. Notably, DA-specific deletion of p53 provided protection of substantia nigra pars reticulata (SNpr) tyrosine hydroxylase (TH) positive fibers following binge MA, with DAT-p53KO mice having less decline of TH protein levels in striatum versus WT mice. Whereas DAT-p53KO mice demonstrated a consistently higher density of TH fibers in striatum compared to WT mice at 10 days after MA exposure, DA neuron counts within the substantia nigra pars compacta (SNpc) were similar. Finally, supportive of these results, administration of a p53-specific inhibitor (PFT-α) provided a similarly protective effect on MA binge-induced behavioral deficits. Neither DA specific p53 deletion nor p53 pharmacological inhibition affected hyperthermia induced by MA binge. These findings demonstrate a specific contribution of p53 activation in behavioral deficits and DA neuronal terminal loss by MA binge exposure.

Microdeletions of chromosome 17p13.3 markers in an unselected survey of probands with type I lissencephaly

Energy Technology Data Exchange (ETDEWEB)

Giannakoudis, J.; Wrisch, A.; Farber, C. [and others

1994-09-01

Type I lissencephaly (MIM No.247200, McKusick, 1992), a brain malformation characterized by a smooth cerebral surface, exhibits a four-layered cortex and leads to mental retardation and other neurological anomalies. Lissencephaly, type I occurs either isolated (ILS) or in association with dysmorphic facial features (Miller-Dieker syndrome, MDS). Microdeletions were detected within a 350 kb critical segment in 17p13.3 in about 13% of patients with ILS and about 90% with MDS. Most of these patients were selected for molecular analysis, however, by an already known abnormal karyotype. Therefore, the diagnostic value of microsatellite and VNTR markers to identify deletions in unselected ILS/MDS patients is still unknown. We have tested the respective significance of a novel (CA)17 VNDR element (D17S379) and of the VNTR marker YNZ22 (D17S5) to identify deletions in an unselected survey of 28 ILS/MDS patients. For D17S379, 50% of our patients were heterozygous, while 46% were uninformative with respect to segregation of alleles within their family. One patient (3.6%) was shown to be deleted for a paternal allele. PCR for D17S5, which maps proximal to the ILS region, disclosed a deletion in 3 patients (10.7%), including the one seen also by D17S379. Altogether, 75% were heterozygous and only 14% uninformative for this locus. Our results suggest that the combined PCR analysis for two of the most significant markers within the ILS/MDS region disclose a deletion in about 10% of unselected patients with features of type I lissencephaly. The low frequency of deletions detected may reflect different mutation mechanisms, genetic heterogeneity, the need for more densely spaced markers around the critical region, and/or more strict clinical criteria for defining the study group.

A Naturalistic Comparison of Group Transdiagnostic Behaviour Therapy (TBT) and Disorder-Specific Cognitive Behavioural Therapy Groups for the Affective Disorders.

Science.gov (United States)

Gros, Daniel F; Merrifield, Colleen; Rowa, Karen; Szafranski, Derek D; Young, Lisa; McCabe, Randi E

2018-05-29

Transdiagnostic psychotherapies are designed to apply the same underlying treatment principles across a set of psychiatric disorders, without significant tailoring to specific diagnoses. Several transdiagnostic psychotherapy protocols have been developed recently, each of which has its own strengths and weaknesses. One promising treatment is Transdiagnostic Behaviour Therapy (TBT), in that it is one of the few transdiagnostic treatments to date shown to be effective in patients with depressive and anxiety disorders. However, TBT has only been investigated via individual psychotherapy. The present study investigated the effectiveness of a group protocol for TBT, compared with disorder-specific group psychotherapies, in a naturalistic setting. 109 participants with various diagnoses of affective disorders completed either group TBT (n = 37) or a disorder-specific group psychotherapy (n = 72). Measures included assessments of psychiatric symptomatology and transdiagnostic impairment at baseline and post-treatment. Overall, participants in the TBT group demonstrated significant improvements across all measures. When compared with disorder-specific groups, no statistical differences were observed between groups across symptoms; however, participants in the TBT group demonstrated roughly twice the treatment effect sizes in transdiagnostic impairment compared with participants in the disorder-specific groups. In addition, when participants from the most well-represented diagnosis and disorder-specific treatment (social anxiety disorder) were investigated separately, participants in the TBT group demonstrated significantly larger improvements in comorbid depressive symptoms than participants in the disorder-specific treatment. Pending replication and additional comparison studies, group TBT may provide an effective group treatment option for patients with affective disorders.

What is the best frontline therapy for patients with CLL and 17p deletion?

Science.gov (United States)

Badoux, Xavier C; Keating, Michael J; Wierda, William G

2011-03-01

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease with significant variation in disease progression, response to therapy, and survival outcome. Deletions of 17p or mutations of TP53 have been identified as one of the poorest prognostic factors, being predictive of short time for disease progression, lack of response to therapy, short response duration, and short overall survival. The treatment of patients with CLL has improved significantly with the development of chemoimmunotherapy, but this benefit was not pronounced in patients with 17p deletion. We compare various treatment strategies used in these patients, including FCR-like chemoimmunotherapy, alemtuzumab, other antibody combinations, or novel targeted therapies with promising results. Allogeneic stem cell transplantation offers the possibility for long-term disease control in these patients and should be considered early in younger, transplant-eligible patients. The current state of therapy is far from optimal and resources should be applied to studying therapeutic options for patients who have CLL with loss of p53 function.

Shock compression of synthetic opal

International Nuclear Information System (INIS)

Inoue, A; Okuno, M; Okudera, H; Mashimo, T; Omurzak, E; Katayama, S; Koyano, M

2010-01-01

Structural change of synthetic opal by shock-wave compression up to 38.1 GPa has been investigated by using SEM, X-ray diffraction method (XRD), Infrared (IR) and Raman spectroscopies. Obtained information may indicate that the dehydration and polymerization of surface silanole due to high shock and residual temperature are very important factors in the structural evolution of synthetic opal by shock compression. Synthetic opal loses opalescence by 10.9 and 18.4 GPa of shock pressures. At 18.4 GPa, dehydration and polymerization of surface silanole and transformation of network structure may occur simultaneously. The 4-membered ring of TO 4 tetrahedrons in as synthetic opal may be relaxed to larger ring such as 6-membered ring by high residual temperature. Therefore, the residual temperature may be significantly high at even 18.4 GPa of shock compression. At 23.9 GPa, opal sample recovered the opalescence. Origin of this opalescence may be its layer structure by shock compression. Finally, sample fuse by very high residual temperature at 38.1 GPa and the structure closes to that of fused SiO 2 glass. However, internal silanole groups still remain even at 38.1 GPa.

Shock compression of synthetic opal

Science.gov (United States)

Inoue, A.; Okuno, M.; Okudera, H.; Mashimo, T.; Omurzak, E.; Katayama, S.; Koyano, M.

2010-03-01

Structural change of synthetic opal by shock-wave compression up to 38.1 GPa has been investigated by using SEM, X-ray diffraction method (XRD), Infrared (IR) and Raman spectroscopies. Obtained information may indicate that the dehydration and polymerization of surface silanole due to high shock and residual temperature are very important factors in the structural evolution of synthetic opal by shock compression. Synthetic opal loses opalescence by 10.9 and 18.4 GPa of shock pressures. At 18.4 GPa, dehydration and polymerization of surface silanole and transformation of network structure may occur simultaneously. The 4-membered ring of TO4 tetrahedrons in as synthetic opal may be relaxed to larger ring such as 6-membered ring by high residual temperature. Therefore, the residual temperature may be significantly high at even 18.4 GPa of shock compression. At 23.9 GPa, opal sample recovered the opalescence. Origin of this opalescence may be its layer structure by shock compression. Finally, sample fuse by very high residual temperature at 38.1 GPa and the structure closes to that of fused SiO2 glass. However, internal silanole groups still remain even at 38.1 GPa.

Shock compression of synthetic opal

Energy Technology Data Exchange (ETDEWEB)

Inoue, A; Okuno, M; Okudera, H [Department of Earth Sciences, Kanazawa University Kanazawa, Ishikawa, 920-1192 (Japan); Mashimo, T; Omurzak, E [Shock Wave and Condensed Matter Research Center, Kumamoto University, Kumamoto, 860-8555 (Japan); Katayama, S; Koyano, M, E-mail: okuno@kenroku.kanazawa-u.ac.j [JAIST, Nomi, Ishikawa, 923-1297 (Japan)

2010-03-01

Structural change of synthetic opal by shock-wave compression up to 38.1 GPa has been investigated by using SEM, X-ray diffraction method (XRD), Infrared (IR) and Raman spectroscopies. Obtained information may indicate that the dehydration and polymerization of surface silanole due to high shock and residual temperature are very important factors in the structural evolution of synthetic opal by shock compression. Synthetic opal loses opalescence by 10.9 and 18.4 GPa of shock pressures. At 18.4 GPa, dehydration and polymerization of surface silanole and transformation of network structure may occur simultaneously. The 4-membered ring of TO{sub 4} tetrahedrons in as synthetic opal may be relaxed to larger ring such as 6-membered ring by high residual temperature. Therefore, the residual temperature may be significantly high at even 18.4 GPa of shock compression. At 23.9 GPa, opal sample recovered the opalescence. Origin of this opalescence may be its layer structure by shock compression. Finally, sample fuse by very high residual temperature at 38.1 GPa and the structure closes to that of fused SiO{sub 2} glass. However, internal silanole groups still remain even at 38.1 GPa.

Misconceptions of Synthetic Biology: Lessons from an Interdisciplinary Summer School

DEFF Research Database (Denmark)

Verseux, Cyprien; G Acevedo-Rocha, Carlos; Chizzolini, Fabio

2016-01-01

In 2014, an international group of scholars from various fields analysed the "societal dimensions" of synthetic biology in an interdisciplinary summer school. Here, we report and discuss the biologists' observations on the general perception of synthetic biology by non-biologists who took part...... in this event. Most attendees mainly associated synthetic biology with contributions from the best-known public figures of the field, rarely mentioning other scientists. Media extrapolations of those contributions appeared to have created unrealistic expectations and irrelevant fears that were widely...... disconnected from the current research in synthetic biology. Another observation was that when debating developments in synthetic biology, semantics strongly mattered: depending on the terms used to present an application of synthetic biology, attendees reacted in radically different ways. For example, using...

Paper-based synthetic gene networks.

Science.gov (United States)

Pardee, Keith; Green, Alexander A; Ferrante, Tom; Cameron, D Ewen; DaleyKeyser, Ajay; Yin, Peng; Collins, James J

2014-11-06

Synthetic gene networks have wide-ranging uses in reprogramming and rewiring organisms. To date, there has not been a way to harness the vast potential of these networks beyond the constraints of a laboratory or in vivo environment. Here, we present an in vitro paper-based platform that provides an alternate, versatile venue for synthetic biologists to operate and a much-needed medium for the safe deployment of engineered gene circuits beyond the lab. Commercially available cell-free systems are freeze dried onto paper, enabling the inexpensive, sterile, and abiotic distribution of synthetic-biology-based technologies for the clinic, global health, industry, research, and education. For field use, we create circuits with colorimetric outputs for detection by eye and fabricate a low-cost, electronic optical interface. We demonstrate this technology with small-molecule and RNA actuation of genetic switches, rapid prototyping of complex gene circuits, and programmable in vitro diagnostics, including glucose sensors and strain-specific Ebola virus sensors.

Paper-based Synthetic Gene Networks

Science.gov (United States)

Pardee, Keith; Green, Alexander A.; Ferrante, Tom; Cameron, D. Ewen; DaleyKeyser, Ajay; Yin, Peng; Collins, James J.

2014-01-01

Synthetic gene networks have wide-ranging uses in reprogramming and rewiring organisms. To date, there has not been a way to harness the vast potential of these networks beyond the constraints of a laboratory or in vivo environment. Here, we present an in vitro paper-based platform that provides a new venue for synthetic biologists to operate, and a much-needed medium for the safe deployment of engineered gene circuits beyond the lab. Commercially available cell-free systems are freeze-dried onto paper, enabling the inexpensive, sterile and abiotic distribution of synthetic biology-based technologies for the clinic, global health, industry, research and education. For field use, we create circuits with colorimetric outputs for detection by eye, and fabricate a low-cost, electronic optical interface. We demonstrate this technology with small molecule and RNA actuation of genetic switches, rapid prototyping of complex gene circuits, and programmable in vitro diagnostics, including glucose sensors and strain-specific Ebola virus sensors. PMID:25417167

A novel synthetic peptide microarray assay detects Chlamydia species-specific antibodies in animal and human sera.

Science.gov (United States)

Sachse, Konrad; Rahman, Kh Shamsur; Schnee, Christiane; Müller, Elke; Peisker, Madlen; Schumacher, Thomas; Schubert, Evelyn; Ruettger, Anke; Kaltenboeck, Bernhard; Ehricht, Ralf

2018-03-16

Serological analysis of Chlamydia (C.) spp. infections is still mainly based on micro-immunofluorescence and ELISA. To overcome the limitations of conventional serology, we have designed a novel microarray carrying 52 synthetic peptides representing B-cell epitopes from immunodominant proteins of all 11 chlamydial species. The new assay has been validated using monospecific mouse hyperimmune sera. Subsequently, serum samples from cattle, sheep and humans with a known history of chlamydial infection were examined. For instance, the specific humoral response of sheep to treatment with a C. abortus vaccine has been visualized against a background of C. pecorum carriership. In samples from humans, dual infection with C. trachomatis and C. pneumoniae could be demonstrated. The experiments revealed that the peptide microarray assay was capable of simultaneously identifying specific antibodies to each Chlamydia spp. The actual assay represents an open platform test that can be complemented through future advances in Chlamydia proteome research. The concept of the highly parallel multi-antigen microarray proven in this study has the potential to enhance our understanding of antibody responses by defining not only a single quantitative response, but also the pattern of this response. The added value of using peptide antigens will consist in unprecedented serodiagnostic specificity.

Quantitative measurement of pathogen specific human memory T cell repertoire diversity using a CDR3β-specific microarray

Directory of Open Access Journals (Sweden)

Gorski Jack

2007-09-01

Full Text Available Abstract Background Providing quantitative microarray data that is sensitive to very small differences in target sequence would be a useful tool in any number of venues where a sample can consist of a multiple related sequences present in various abundances. Examples of such applications would include measurement of pseudo species in viral infections and the measurement of species of antibodies or T cell receptors that constitute immune repertoires. Difficulties that must be overcome in such a method would be to account for cross-hybridization and for differences in hybridization efficiencies between the arrayed probes and their corresponding targets. We have used the memory T cell repertoire to an influenza-derived peptide as a test case for developing such a method. Results The arrayed probes were corresponded to a 17 nucleotide TCR-specific region that distinguished sequences differing by as little as a single nucleotide. Hybridization efficiency between highly related Cy5-labeled subject sequences was normalized by including an equimolar mixture of Cy3-labeled synthetic targets representing all 108 arrayed probes. The same synthetic targets were used to measure the degree of cross hybridization between probes. Reconstitution studies found the system sensitive to input ratios as low as 0.5% and accurate in measuring known input percentages (R2 = 0.81, R = 0.90, p 0.05. Conclusion This novel strategy appears to be robust and can be adapted to any situation where complex mixtures of highly similar sequences need to be quantitatively resolved.

Annular Impinging Jet Controlled by Radial Synthetic Jets

Czech Academy of Sciences Publication Activity Database

Trávníček, Zdeněk; Tesař, Václav; Broučková, Zuzana; Peszyński, K.

2014-01-01

Roč. 35, 16-17 (2014), s. 1450-1461 ISSN 0145-7632 R&D Projects: GA ČR GA14-08888S; GA AV ČR(CZ) IAA200760801 Institutional support: RVO:61388998 Keywords : impinging jet * hybrid synthetic jet * flow control Subject RIV: JU - Aeronautics, Aerodynamics, Aircrafts Impact factor: 0.814, year: 2014 http://dx.doi.org/10.1080/01457632.2014.889467

P-R-R Study Technique, Group Counselling And Gender Influence ...

African Journals Online (AJOL)

Read-Recall (P-R-R) study technique and group counselling on the academic performance of senior secondary school students. The objectives of this study were to determine the effect of Group Counselling combined with P-R-R study ...

The Utility of Synthetic-based Approach of Writing among Iranian EFL Learners

Directory of Open Access Journals (Sweden)

Nasrin Derakhshandeh

2014-05-01

Full Text Available The present study intends to examine the utility of synthetic-based approach versus traditional approaches of writing among Iranian EFL learners. To achieve this end, ninety students at Upper-Intermediate level were randomly chosen from the English population of Kish and Gooyesh English Institutes. The students were divided into three groups. Group1 was asked to do a writing task based on product-based approach. A writing task based on process-oriented approach was administered to Group2; later on, Group 3 was invited to write a composition to assess their performance based on synthetic-based approach. The result of the t test and two-way ANOVA revealed that the students performed better in writing using synthetic approach rather than traditional approaches to writing.

Anti-tumor effect of 131I labeled 17-allylamino-17-demethoxygeldanamycin on human non-small cell lung cancer in xenograft-bearing nude mice

International Nuclear Information System (INIS)

Sun Jin; Liu Lu; Zhu Xiaoli; Chen Daozhen; Gao Wen; Jiang Xinyu; Huang Ying

2008-01-01

Objective: 17-allylamino-17-demethoxygeldanamycin (17-AAG) has been developed as a novel heat shock protein 90 (HSP90) inhibitor being used in clinical trials. HSP90 is known as a molecular target for tumor therapy. The goal of this study was to investigate the inhibitive effects of 131 I labeled 17-AAG on human non-small cell lung cancer in xenograft-bearing nude mice. Methods: 17-AAG was labeled with 131 I. Twenty-eight BALB/c nude mice bearing H460 human non-small cell lung carcinoma tumor xenograft were randomly divided into seven groups, one control group and six treatment groups according to the route of administration (via tail vein injection or intratumoral injection) and the doses of injected radio-activity (5.5 MBq x 2 with 8 d interval, 11.0 MBq and 5.5 MBq). Two additional mice were treated with intratumoral injection of Na 131 I solution that was served as seintigraphic imaging controls. In each group two mice underwent scintigraphy at 2 h, 6 h, 24 h, 2 d, 3 d, 7 d, 10 d and 16 d. After 16 d the tumor inhibition rate was calculated. Then all of the mice were sacrificed and the tumor tissues were obtained for histological examination and immunohistochemical assay. Results: Persistent accumulation of 131 I-17-AAG in the tumors was seen on seintigraphic images. Tumor inhibiting effect was demonstrated in all treatment groups with varying degrees. The highest tumor inhibition rate (86.77 ± 4.57)% was shown in the group with interval intratumoral injection (5.5 MBq x 2). There was no significant difference of tumor inhibition rates between 5.5 MBq x 2 group (via tail vein injection) and 11.0 MBq group( via tail vein injection, q=1.67, P>0.05). While among the other treatment groups, there was significant difference in tumor inhibition rates( q=3.16-24.34, all P 131 I-17-AAG may effectively inhibit the tumor growth and expression of HSP90α antigen expression in non-small cell lung cancer bearing nude mice. The more prominent anti-tumor effect may be

Biochemical and immunological characterization of recombinant allergen Lol p 1.

Science.gov (United States)

Tamborini, E; Faccini, S; Lidholm, J; Svensson, M; Brandazza, A; Longhi, R; Groenlund, H; Sidoli, A; Arosio, P

1997-11-01

Pollen from perennial rye grass (Lolium perenne), a major cause of type-I allergy worldwide, contains a complex mixture of allergenic proteins among which Lol p 1 is one of the most important. We describe the expression, purification and characterization of a recombinant Lol p 1 overproduced in Escherichia coli. The recombinant allergen, expressed in high yields and purified in milligram amounts, bound to specific IgE antibodies from human sera, induced histamine release from sensitized human basophils, and elicited rabbit antisera that recognize specifically recombinant Lol p 1 and natural Lol p 1 of pollen extract. Recombinant Lol p 1 was used to develop ImmunoCAP assays for analysis of 150 sera that were Radioallergosorbent test positive to L. perenne pollen. In 130 of them (87%) the assay detected a significant level of IgE antibodies to Lol p 1, reaching on average 37% of the level obtained with a test for IgE to the whole grass pollen extract. To map epitopes on Lol p 1, we produced three deletion mutants [des-(116-240)-Lol p 1, des-(1-88)-Lol p 1 and des-(133-189)-Lol p 1], which were efficiently expressed in bacteria. These all showed a strong reactivity with the specific rabbit IgG antibodies, but lacked most or all the allergenic properties of recombinant Lol p 1. A study of the antigenic structure of Lol p 1 was performed using the three deletion mutants and a set of 17-18-residue overlapping synthetic peptides covering the whole allergen sequence. The results indicate that human IgE and rabbit IgG antibodies bind to distinct regions of Lol p 1, and that at least some important IgE epitopes are mainly conformational. The findings suggest that recombinant allergens constitute useful reagents for further development of serological diagnosis of allergy, and that it should be possible to produce immunogenic fragments of allergenic proteins without allergenic properties.

A computational model of the hypothalamic - pituitary - gonadal axis in female fathead minnows (Pimephales promelas exposed to 17α-ethynylestradiol and 17β-trenbolone

Directory of Open Access Journals (Sweden)

Lazorchak James M

2011-05-01

Full Text Available Abstract Background Endocrine disrupting chemicals (e.g., estrogens, androgens and their mimics are known to affect reproduction in fish. 17α-ethynylestradiol is a synthetic estrogen used in birth control pills. 17β-trenbolone is a relatively stable metabolite of trenbolone acetate, a synthetic androgen used as a growth promoter in livestock. Both 17α-ethynylestradiol and 17β-trenbolone have been found in the aquatic environment and affect fish reproduction. In this study, we developed a physiologically-based computational model for female fathead minnows (FHM, Pimephales promelas, a small fish species used in ecotoxicology, to simulate how estrogens (i.e., 17α-ethynylestradiol or androgens (i.e., 17β-trenbolone affect reproductive endpoints such as plasma concentrations of steroid hormones (e.g., 17β-estradiol and testosterone and vitellogenin (a precursor to egg yolk proteins. Results Using Markov Chain Monte Carlo simulations, the model was calibrated with data from unexposed, 17α-ethynylestradiol-exposed, and 17β-trenbolone-exposed FHMs. Four Markov chains were simulated, and the chains for each calibrated model parameter (26 in total converged within 20,000 iterations. With the converged parameter values, we evaluated the model's predictive ability by simulating a variety of independent experimental data. The model predictions agreed with the experimental data well. Conclusions The physiologically-based computational model represents the hypothalamic-pituitary-gonadal axis in adult female FHM robustly. The model is useful to estimate how estrogens (e.g., 17α-ethynylestradiol or androgens (e.g., 17β-trenbolone affect plasma concentrations of 17β-estradiol, testosterone and vitellogenin, which are important determinants of fecundity in fish.

Comet 17P/Holmes: Possibility of a CO driven explosion

Science.gov (United States)

Kossacki, Konrad J.; Szutowicz, Slawomira

2011-04-01

This work is a continuation of our previous paper about brightening of Comet 17P/Holmes (Kossacki, K.J., Szutowicz, S. [2010]. Icarus 207, 320-340). In that paper we presented results of simulations indicating that the nonuniform crystallization of amorphous water ice itself is probably not sufficient for an explosion. In the present work we investigate the possibility that the explosion is caused by a rapid sublimation of the CO ice leading to the rise of gas pressure above the tensile strength of the nucleus. We simulated evolution of a model nucleus in the orbit of Comet 17P/Holmes. The nucleus is composed of water ice, carbon monoxide ice and dust and has the shape of an elongated ellipsoid. The simulations include crystallization of amorphous ice in the nucleus, changes of the dust mantle thickness, and sublimation of the CO ice. In our model CO is mantling grains composed of dust and amorphous water ice. Orientation of the nuclear spin axis in space is the same as derived in Moreno et al. (Moreno, F., Ortiz, J.L., Santos-Sanz, P., Morales, N., Vidal-Nunez, M.J., Lara, L.M., Gutierrez, P.J. [2008]. Astrophys. J. 677, L63-L66) for Comet Holmes during recent brightening event. Hence, the angle between the orbital and the equatorial planes of the comet is I = 95°, and the cometocentric solar longitude at perihelion is Φ = 210°. The calculations are performed for the south pole being the sub-solar point close to time of the outburst. Our computations indicate, that the CO pressure within the comet nucleus can rise to high values. When the layer between the dust mantle and the crystallization front of the amorphous water ice is very fine grained, few microns in radius, the CO pressure within the nucleus can exceed 10 kPa. This value is the lowest estimate for the tensile strength of the nucleus of Comet Holmes (Reach, W.T., Vaubaillon, J., Lisse, C.M., Holloway, M., Rho, J. [2010]. Icarus 208, 276-292). Hence, when the gas pressure reaches this value the nucleus

3D analysis of the TCR/pMHCII complex formation in monkeys vaccinated with the first peptide inducing sterilizing immunity against human malaria.

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Manuel A Patarroyo

Full Text Available T-cell receptor gene rearrangements were studied in Aotus monkeys developing high antibody titers and sterilizing immunity against the Plasmodium falciparum malaria parasite upon vaccination with the modified synthetic peptide 24112, which was identified in the Merozoite Surface Protein 2 (MSP-2 and is known to bind to HLA-DRbeta1*0403 molecules with high capacity. Spectratyping analysis showed a preferential usage of Vbeta12 and Vbeta6 TCR gene families in 67% of HLA-DRbeta1*0403-like genotyped monkeys. Docking of peptide 24112 into the HLA-DRbeta1*0401-HA peptide-HA1.7TCR complex containing the VDJ rearrangements identified in fully protected monkeys showed a different structural signature compared to nonprotected monkeys. These striking results show the exquisite specificity of the TCR/pMHCII complex formation needed for inducing sterilizing immunity and provide important hints for a logical and rational methodology to develop multiepitopic, minimal subunit-based synthetic vaccines against infectious diseases, among them malaria.

Synthetic biology between technoscience and thing knowledge.

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Gelfert, Axel

2013-06-01

Synthetic biology presents a challenge to traditional accounts of biology: Whereas traditional biology emphasizes the evolvability, variability, and heterogeneity of living organisms, synthetic biology envisions a future of homogeneous, humanly engineered biological systems that may be combined in modular fashion. The present paper approaches this challenge from the perspective of the epistemology of technoscience. In particular, it is argued that synthetic-biological artifacts lend themselves to an analysis in terms of what has been called 'thing knowledge'. As such, they should neither be regarded as the simple outcome of applying theoretical knowledge and engineering principles to specific technological problems, nor should they be treated as mere sources of new evidence in the general pursuit of scientific understanding. Instead, synthetic-biological artifacts should be viewed as partly autonomous research objects which, qua their material-biological constitution, embody knowledge about the natural world-knowledge that, in turn, can be accessed via continuous experimental interrogation. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Change of Plasma Interleukin-17 Level in Patients with Extranodal NK/T-Cell Lymphoma and Its Clinical Significance].

Science.gov (United States)

Shang, Chun-Xiang; Ma, Ji-Cheng; Nan, Zheng; Li, Ye; He, Wen-Cai; Pan, Xian-Ying

2017-06-01

To investigate the clinical significance of interleukin-17 (IL-17) level in patients with extranodal NK/T-cell lymphoma(ENKTL). Eighty patients with nasal ENKTL who received radiotherapy, chemotherapy or radiotherapy combined with chemotherapy from January 2011 to January 2012 were enrolled in the study. Eighty healthy volunteers were selected as the controls (control group). About 5 ml of peripheral blood was collected from all patients and controls. IL-17 level was determined by ELISA. The age, sex, ECOG score, B symptoms, LDH level, lymph node involvment, Ann Arbor stage, IPI, KPI, peripheral blood lymphocyte and lymph node metastasis, number of lymphocytes and monocytes in peripheral blood were recorded. All patients were followed up for 3 year progression-free survival (PFS) and overall survival (OS). The average IL-17 level in patients with ENKTL was 6.48 pg/ml and the average concentration of IL-17 in control group was 0.56 pg/ml (PKPI, lymphocyte count and monocyte cell count. The sensitivity and specificity of IL-17 were 74.5% and 73.7% respectively, and the optimal threshold was 3.49 pg/ml and AUC was 0.799 (95% CI: 0.688-0.909) (P<0.01). The PFS and OS were longer in the patients with IL-17≤3.49 pg/ml and longer in the patients without lymph node involvement and Ann Arbor I. Multivariate analysis showed that independent predictors of PFS and OS in patients with ENKTL were plasma IL-17 levels and age (P<0.05). ENKTL patients with different clinical characteristics have different levels of IL-17, the different level of IL-17 has different effects on prognosis of patients with ENKTL.

Controlled polymer synthesis--from biomimicry towards synthetic biology.

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Pasparakis, George; Krasnogor, Natalio; Cronin, Leroy; Davis, Benjamin G; Alexander, Cameron

2010-01-01

The controlled assembly of synthetic polymer structures is now possible with an unprecedented range of functional groups and molecular architectures. In this critical review we consider how the ability to create artificial materials over lengthscales ranging from a few nm to several microns is generating systems that not only begin to mimic those in nature but also may lead to exciting applications in synthetic biology (139 references).

Distal hindlimb kinematics of galloping Thoroughbred racehorses on dirt and synthetic racetrack surfaces.

Science.gov (United States)

Symons, J E; Garcia, T C; Stover, S M

2014-03-01

The effect of racetrack surface (dirt or synthetic) on distal hindlimb kinematics of racehorses running at competition speeds is not known. To compare distal hindlimb and hoof kinematics during stance of breezing (unrestrained gallop) racehorses between dirt and synthetic surfaces. Two-dimensional kinematic video analysis of 5 Thoroughbred racehorses galloping at high speeds (12-17 m/s) on a dirt racetrack and a synthetic racetrack. The positions of kinematic markers applied to the left hindlimb were recorded at 500 Hz. Position, velocity and acceleration of joint angles and hoof translation during stance were calculated in the sagittal plane. Peak translational and angular kinematic values were compared between the dirt and synthetic race surfaces using mixed model analyses of covariance. Maximum and heel-strike metatarsophalangeal (fetlock) angles were greater (Pdirt surface than on the synthetic surface. Maximum fetlock angle occurred earlier during stance on the dirt surface (Pdirt surface (Pdirt surface than on a synthetic surface. Synthetic race surfaces may mitigate risk of injury to hindlimb fetlock structures by reducing fetlock hyperextension and associated strains in fetlock support structures. Differences in hoof slide may contribute to different distal hindlimb kinematics between surfaces. © 2013 EVJ Ltd.

Axisymmetric Synthetic Jet Actuators with Large Streamwise Dimensions

Czech Academy of Sciences Publication Activity Database

Kordík, Jozef; Trávníček, Zdeněk

2013-01-01

Roč. 51, č. 12 (2013), s. 2862-2877 ISSN 0001-1452 R&D Projects: GA ČR GPP101/12/P556; GA ČR(CZ) GCP101/11/J019 Institutional support: RVO:61388998 Keywords : synthetic jet * synthetic jet actuator * resonance frequency Subject RIV: BK - Fluid Dynamics Impact factor: 1.165, year: 2013 http://arc.aiaa.org/doi/abs/10.2514/1.J052504

Synthetic Cannabinoids

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Aslihan Okan Ibiloglu

2017-09-01

Full Text Available Synthetic cannabinoids which is a subgroup of cannabinoids are commonly used for recreational drug use throughout the whole world. Although both marijuana and synthetic cannabinoids stimulate the same receptors, cannabinoid receptor 1 (CB1 and cannabinoid receptor 2 (CB2, studies have shown that synthetic cannabinoids are much more potent than marijuana. The longer use of synthetic cannabinoids can cause severe physical and psychological symptoms that might even result in death, similar to many known illicit drugs. Main treatment options mostly involve symptom management and supportive care. The aim of this article is to discuss clinical and pharmacological properties of the increasingly used synthetic cannabinoids. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2017; 9(3.000: 317-328

Age‑specific Serum Prostate Specific Antigen Ranges Among ...

African Journals Online (AJOL)

ethnic differences.[16] Although similar studies have been presented for a number of different groups of men and few studies have looked at the pattern of serum PSA among Nigerians[17‑20] but no such studies on normal serum PSA ranges and the age‑specific pattern have been carried out among healthy Nigerian men.

Determination and analysis of site-specific 125I decay-induced DNA double-strand break end-group structures.

Science.gov (United States)

Datta, Kamal; Weinfeld, Michael; Neumann, Ronald D; Winters, Thomas A

2007-02-01

End groups contribute to the structural complexity of radiation-induced DNA double-strand breaks (DSBs). As such, end-group structures may affect a cell's ability to repair DSBs. The 3'-end groups of strand breaks caused by gamma radiation, or oxidative processes, under oxygenated aqueous conditions have been shown to be distributed primarily between 3'-phosphoglycolate and 3'-phosphate, with 5'-phosphate ends in both cases. In this study, end groups of the high-LET-like DSBs caused by 125I decay were investigated. Site-specific DNA double-strand breaks were produced in plasmid pTC27 in the presence or absence of 2 M DMSO by 125I-labeled triplex-forming oligonucleotide targeting. End-group structure was assessed enzymatically as a function of the DSB end to serve as a substrate for ligation and various forms of end labeling. Using this approach, we have demonstrated 3'-hydroxyl (3'-OH) and 3'-phosphate (3'-P) end groups and 5'-ends (> or = 42%) terminated by phosphate. A 32P postlabeling assay failed to detect 3'-phosphoglycolate in a restriction fragment terminated by the 125I-induced DNA double-strand break, and this is likely due to restricted oxygen diffusion during irradiation as a frozen aqueous solution. Even so, end-group structure and relative distribution varied as a function of the free radical scavenging capacity of the irradiation buffer.

Asperger syndrome in a boy with a balanced de novo translocation: t(17;19)(p13.3;p11)

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-04-10

The cause of Asperger syndrome is unknown. It is classified as a form of childhood autism. Familial aggregation in infantile autism has been reported. Asperger syndrome has also been considered as being genetically transmitted and certain of its characteristics have tended to occur in other relatives, especially in the fathers. We describe a 10-year-old boy with a clinical diagnosis of Asperger syndrome and a balanced de novo translocation (t(17;19)9p13.3;p11). His parents are not consanguineous and are healthy, as are his three brothers. 5 refs.

Antigen-Specific Th17 Cells Are Primed by Distinct and Complementary Dendritic Cell Subsets in Oropharyngeal Candidiasis.

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Kerstin Trautwein-Weidner

2015-10-01

Full Text Available Candida spp. can cause severe and chronic mucocutaneous and systemic infections in immunocompromised individuals. Protection from mucocutaneous candidiasis depends on T helper cells, in particular those secreting IL-17. The events regulating T cell activation and differentiation toward effector fates in response to fungal invasion in different tissues are poorly understood. Here we generated a Candida-specific TCR transgenic mouse reactive to a novel endogenous antigen that is conserved in multiple distant species of Candida, including the clinically highly relevant C. albicans and C. glabrata. Using TCR transgenic T cells in combination with an experimental model of oropharyngeal candidiasis (OPC we investigated antigen presentation and Th17 priming by different subsets of dendritic cells (DCs present in the infected oral mucosa. Candida-derived endogenous antigen accesses the draining lymph nodes and is directly presented by migratory DCs. Tissue-resident Flt3L-dependent DCs and CCR2-dependent monocyte-derived DCs collaborate in antigen presentation and T cell priming during OPC. In contrast, Langerhans cells, which are also present in the oral mucosa and have been shown to prime Th17 cells in the skin, are not required for induction of the Candida-specific T cell response upon oral challenge. This highlights the functional compartmentalization of specific DC subsets in different tissues. These data provide important new insights to our understanding of tissue-specific antifungal immunity.

Small constrained SP1-7 analogs bind to a unique site and promote anti-allodynic effects following systemic injection in mice.

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Jonsson, A; Fransson, R; Haramaki, Y; Skogh, A; Brolin, E; Watanabe, H; Nordvall, G; Hallberg, M; Sandström, A; Nyberg, F

2015-07-09

Previous results have shown that the substance P (SP) N-terminal fragment SP1-7 may attenuate hyperalgesia and produce anti-allodynia in animals using various experimental models for neuropathic pain. The heptapeptide was found to induce its effects through binding to and activating specific sites apart from any known neurokinin or opioid receptor. Furthermore, we have applied a medicinal chemistry program to develop lead compounds mimicking the effect of SP1-7. The present study was designed to evaluate the pharmacological effect of these compounds using the mouse spared nerve injury (SNI) model of chronic neuropathic pain. Also, as no comprehensive screen with the aim to identify the SP1-7 target has yet been performed we screened our lead compound H-Phe-Phe-NH2 toward a panel of drug targets. The extensive target screen, including 111 targets, did not reveal any hit for the binding site among a number of known receptors or enzymes involved in pain modulation. Our animal studies confirmed that SP1-7, but also synthetic analogs thereof, possesses anti-allodynic effects in the mouse SNI model of neuropathic pain. One of the lead compounds, a constrained H-Phe-Phe-NH2 analog, was shown to exhibit a significant anti-allodynic effect. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

The effects of 17β-estradiol plus drospirenone on anthropometric and biochemical measures of adiposity in menopausal women.

Science.gov (United States)

Karakus, Mesut; Gelisgen, Remise; Topcuoglu, Ata; Guralp, Onur; Topcuoglu, Deniz; Simsek, Gonul; Uludag, Seyfettin; Uzun, Hafize

2012-11-01

To assess whether there are changes on anthropometric and biochemical measures of adiposity in pre- and postmenopausal women and in the latter before and after 6 months treatment with 17β-estradiol plus drospirenone. Twenty postmenopausal and 20 premenopausal women were enrolled in a prospective comparative study. Postmenopausal women received 1 mg 17β-estradiol plus 2 mg drospirenone daily for 6 months. Measurements of body mass index (BMI), waist/hip ratio and plasmatic levels of insulin, glucose, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride, leptin, adiponectin, orexin-A, glucagon-like peptide-1 (GLP-1) and ghrelin were performed in premenopausal (group 1) and postmenopausal women and in the latter before (group 2a) and after (group 2b) 6 months treatment with 17β-estradiol plus drospirenone. No significant changes in BMIs, insulin and glucose were observed between group 1 and 2a; and group 2a and 2b. GLP-1 levels were significantly increased in group 1 compared to group 2a (p = 0.035). Leptin levels were significantly increased (p = 0.001) and GLP-1 levels were significantly decreased (p = 0.021) in group 2b compared to group 2a. HDL was significantly decreased while LDL and triglyceride levels were significantly increased in group 2a compared to group 1. (p = 0.030, p = 0.001, p = 0.020; respectively) LDL was significantly decreased (p = 0.010) in group 2b compared to group 2a. GLP-1 had a positive correlation with orexin-A (p correlation with leptin (p = 0.008, r = -0.345). Leptin was significantly higher and GLP-1 was significantly lower in women receiving 17β-estradiol plus drospirenone treatment. GLP-1 levels were significantly lower after the menopause compared to premenopausal levels. Orexin-A and GLP-1 were positively correlated.

Angels and demons: Th17 cells represent a beneficial response, while neutrophil IL-17 is associated with poor prognosis in squamous cervical cancer.

Science.gov (United States)

Punt, Simone; Fleuren, Gert Jan; Kritikou, Eva; Lubberts, Erik; Trimbos, J Baptist; Jordanova, Ekaterina S; Gorter, Arko

2015-01-01

The role of interleukin (IL)-17 in cancer remains controversial. In view of the growing interest in the targeting of IL-17, knowing its cellular sources and clinical implications is crucial. In the present study, we unraveled the phenotype of IL-17 expressing cells in cervical cancer using immunohistochemical double and immunofluorescent triple stainings. In the tumor stroma, IL-17 was found to be predominantly expressed by neutrophils (66%), mast cells (23%), and innate lymphoid cells (8%). Remarkably, T-helper 17 (Th17) cells were a minor IL-17 expressing population (4%). A similar distribution was observed in the tumor epithelium. The Th17 and granulocyte fractions were confirmed in head and neck, ovarian, endometrial, prostate, breast, lung, and colon carcinoma. An above median number of total IL-17 expressing cells was an independent prognostic factor for poor disease-specific survival in early stage disease ( p = 0.016). While a high number of neutrophils showed at trend toward poor survival, the lowest quartile of mast cells correlated with poor survival ( p = 0.011). IL-17 expressing cells and neutrophils were also correlated with the absence of vaso-invasion ( p < 0.01). IL-17 was found to increase cell growth or tightness of cervical cancer cell lines, which may be a mechanism for tumorigenesis in early stage disease. These data suggest that IL-17, primarily expressed by neutrophils, predominantly promotes tumor growth, correlated with poor prognosis in early stage disease. Strikingly, a high number of Th17 cells was an independent prognostic factor for improved survival ( p = 0.026), suggesting Th17 cells are part of a tumor suppressing immune response.

BNN27, a 17-Spiroepoxy Steroid Derivative, Interacts With and Activates p75 Neurotrophin Receptor, Rescuing Cerebellar Granule Neurons from Apoptosis.

Science.gov (United States)

Pediaditakis, Iosif; Kourgiantaki, Alexandra; Prousis, Kyriakos C; Potamitis, Constantinos; Xanthopoulos, Kleanthis P; Zervou, Maria; Calogeropoulou, Theodora; Charalampopoulos, Ioannis; Gravanis, Achille

2016-01-01

Neurotrophin receptors mediate a plethora of signals affecting neuronal survival. The p75 pan-neurotrophin receptor controls neuronal cell fate after its selective activation by immature and mature isoforms of all neurotrophins. It also exerts pleiotropic effects interacting with a variety of ligands in different neuronal or non-neuronal cells. In the present study, we explored the biophysical and functional interactions of a blood-brain-barrier (BBB) permeable, C17-spiroepoxy steroid derivative, BNN27, with p75 NTR receptor. BNN27 was recently shown to bind to NGF high-affinity receptor, TrkA. We now tested the p75 NTR -mediated effects of BNN27 in mouse Cerebellar Granule Neurons (CGNs), expressing p75 NTR , but not TrkA receptors. Our findings show that BNN27 physically interacts with p75 NTR receptors in specific amino-residues of its extracellular domain, inducing the recruitment of p75 NTR receptor to its effector protein RIP2 and the simultaneous release of RhoGDI in primary neuronal cells. Activation of the p75 NTR receptor by BNN27 reverses serum deprivation-induced apoptosis of CGNs resulting in the decrease of the phosphorylation of pro-apoptotic JNK kinase and of the cleavage of Caspase-3, effects completely abolished in CGNs, isolated from p75 NTR null mice. In conclusion, BNN27 represents a lead molecule for the development of novel p75 NTR ligands, controlling specific p75 NTR -mediated signaling of neuronal cell fate, with potential applications in therapeutics of neurodegenerative diseases and brain trauma.

Phylogenetic resolution and habitat specificity of members of the Photobacterium phosphoreum species group.

Science.gov (United States)

Ast, Jennifer C; Dunlap, Paul V

2005-10-01

Substantial ambiguity exists regarding the phylogenetic status of facultatively psychrophilic luminous bacteria identified as Photobacterium phosphoreum, a species thought to be widely distributed in the world's oceans and believed to be the specific bioluminescent light-organ symbiont of several deep-sea fishes. Members of the P. phosphoreum species group include luminous and non-luminous strains identified phenotypically from a variety of different habitats as well as phylogenetically defined lineages that appear to be evolutionarily distinct. To resolve this ambiguity and to begin developing a meaningful knowledge of the geographic distributions, habitats and symbiotic relationships of bacteria in the P. phosphoreum species group, we carried out a multilocus, fine-scale phylogenetic analysis based on sequences of the 16S rRNA, gyrB and luxABFE genes of many newly isolated luminous strains from symbiotic and saprophytic habitats, together with previously isolated luminous and non-luminous strains identified as P. phosphoreum from these and other habitats. Parsimony analysis unambiguously resolved three evolutionarily distinct clades, phosphoreum, iliopiscarium and kishitanii. The tight phylogenetic clustering within these clades and the distinct separation between them indicates they are different species, P. phosphoreum, Photobacterium iliopiscarium and the newly recognized 'Photobacterium kishitanii'. Previously reported non-luminous strains, which had been identified phenotypically as P. phosphoreum, resolved unambiguously as P. iliopiscarium, and all examined deep-sea fishes (specimens of families Chlorophthalmidae, Macrouridae, Moridae, Trachichthyidae and Acropomatidae) were found to harbour 'P. kishitanii', not P. phosphoreum, in their light organs. This resolution revealed also that 'P. kishitanii' is cosmopolitan in its geographic distribution. Furthermore, the lack of phylogenetic variation within 'P. kishitanii' indicates that this facultatively

Dual lineage-specific expression of Sox17 during mouse embryogenesis

DEFF Research Database (Denmark)

Choi, Eunyoung; Kraus, Marine R C; Lemaire, Laurence A

2012-01-01

Sox17 is essential for both endoderm development and fetal hematopoietic stem cell (HSC) maintenance. While endoderm-derived organs are well known to originate from Sox17-expressing cells, it is less certain whether fetal HSCs also originate from Sox17-expressing cells. By generating a Sox17(GFPC...

Precision control of recombinant gene transcription for CHO cell synthetic biology.

Science.gov (United States)

Brown, Adam J; James, David C

2016-01-01

The next generation of mammalian cell factories for biopharmaceutical production will be genetically engineered to possess both generic and product-specific manufacturing capabilities that may not exist naturally. Introduction of entirely new combinations of synthetic functions (e.g. novel metabolic or stress-response pathways), and retro-engineering of existing functional cell modules will drive disruptive change in cellular manufacturing performance. However, before we can apply the core concepts underpinning synthetic biology (design, build, test) to CHO cell engineering we must first develop practical and robust enabling technologies. Fundamentally, we will require the ability to precisely control the relative stoichiometry of numerous functional components we simultaneously introduce into the host cell factory. In this review we discuss how this can be achieved by design of engineered promoters that enable concerted control of recombinant gene transcription. We describe the specific mechanisms of transcriptional regulation that affect promoter function during bioproduction processes, and detail the highly-specific promoter design criteria that are required in the context of CHO cell engineering. The relative applicability of diverse promoter development strategies are discussed, including re-engineering of natural sequences, design of synthetic transcription factor-based systems, and construction of synthetic promoters. This review highlights the potential of promoter engineering to achieve precision transcriptional control for CHO cell synthetic biology. Copyright © 2015. Published by Elsevier Inc.

Anisotropic evaluation of synthetic surgical meshes.

Science.gov (United States)

Saberski, E R; Orenstein, S B; Novitsky, Y W

2011-02-01

The material properties of meshes used in hernia repair contribute to the overall mechanical behavior of the repair. The anisotropic potential of synthetic meshes, representing a difference in material properties (e.g., elasticity) in different material axes, is not well defined to date. Haphazard orientation of anisotropic mesh material can contribute to inconsistent surgical outcomes. We aimed to characterize and compare anisotropic properties of commonly used synthetic meshes. Six different polypropylene (Trelex(®), ProLite™, Ultrapro™), polyester (Parietex™), and PTFE-based (Dualmesh(®), Infinit) synthetic meshes were selected. Longitudinal and transverse axes were defined for each mesh, and samples were cut in each axis orientation. Samples underwent uniaxial tensile testing, from which the elastic modulus (E) in each axis was determined. The degree of anisotropy (λ) was calculated as a logarithmic expression of the ratio between the elastic modulus in each axis. Five of six meshes displayed significant anisotropic behavior. Ultrapro™ and Infinit exhibited approximately 12- and 20-fold differences between perpendicular axes, respectively. Trelex(®), ProLite™, and Parietex™ were 2.3-2.4 times. Dualmesh(®) was the least anisotropic mesh, without marked difference between the axes. Anisotropy of synthetic meshes has been underappreciated. In this study, we found striking differences between elastic properties of perpendicular axes for most commonly used synthetic meshes. Indiscriminate orientation of anisotropic mesh may adversely affect hernia repairs. Proper labeling of all implants by manufacturers should be mandatory. Understanding the specific anisotropic behavior of synthetic meshes should allow surgeons to employ rational implant orientation to maximize outcomes of hernia repair.

Dose Specification and Quality Assurance of Radiation Therapy Oncology Group Protocol 95-17; a Cooperative Group Study of Iridium-192 Breast Implants as Sole Therapy

International Nuclear Information System (INIS)

Ibbott, Geoffrey S.; Hanson, W.F.; O'Meara, Elizabeth; Kuske, Robert R.; Arthur, Douglas; Rabinovitch, Rachel; White, Julia; Wilenzick, Raymond M.; Harris, Irene; Tailor, Ramesh C.

2007-01-01

Purpose: The Radiation Therapy Oncology Group (RTOG) protocol 95-17 was a Phase I/II trial to evaluate multicatheter brachytherapy as the sole method of adjuvant breast radiotherapy for Stage I/II breast carcinoma after breast-conserving surgery. Low- or high-dose-rate sources were allowed. Dose prescription and treatment evaluation were based on recommendations in the International Commission on Radiation Units and Measurements (ICRU), Report 58 and included the parameters mean central dose (MCD), average peripheral dose, dose homogeneity index (DHI), and the dimensions of the low- and high-dose regions. Methods and Materials: Three levels of quality assurance were implemented: (1) credentialing of institutions was required before entering patients into the study; (2) rapid review of each treatment plan was conducted before treatment; and (3) retrospective review was performed by the Radiological Physics Center in conjunction with the study chairman and RTOG dosimetry staff. Results: Credentialing focused on the accuracy of dose calculation algorithm and compliance with protocol guidelines. Rapid review was designed to identify and correct deviations from the protocol before treatment. The retrospective review involved recalculation of dosimetry parameters and review of dose distributions to evaluate the treatment. Specifying both central and peripheral doses resulted in uniform dose distributions, with a mean dose homogeneity index of 0.83 ± 0.06. Conclusions: Vigorous quality assurance resulted in a high-quality study with few deviations; only 4 of 100 patients were judged as representing minor variations from protocol, and no patient was judged as representing major deviation. This study should be considered a model for quality assurance of future trials

[Asu(1,7)E-CT, an analog of eel calcitonin. A comparative study in man with reference to other synthetic calcitonins].

Science.gov (United States)

Caniggia, A; Nuti, R; Vattimo, A; Galli, M; Turchetti, V; Franci, B; Martorelli, T; Righi, G

1983-04-28

(Asu) E-CT is a deaminodicarba-analog of the synthetic eel-calcitonin (E-CT) that shows specific activity and the potency reasonably high in comparison with that of the most potent natural hormone. The structure of its molecule indicates that the disulphide bond in calcitonins is not essential for the biological activity but only for the maintenance of the specific conformation by forming an intramolecular bridge. The instability of calcitonins should mainly be attributed to the presence of the disulfide bond and (Asu)E-CT proved to be more stable "in vitro" than native calcitonins. The more prolonged hypocalcemic effect of E-CT and its aminosuberic analog (Asu)E-CT has been accounted for to a greater stability of and persistence at the receptor site. (Asu) E-CT has been largely studied in Japan on experimental animals and successfully used in the treatment of hypercalcemia in man. On the contrary investigations on human administration of this analog are very scarce. The present paper reports studies carried out in normal subjects and Paget's disease patients to investigate the effects of (Asu)E-CT in man in comparison with the effects of synthetic human calcitonin (H-CT) and synthetic salmon calcitonin (S-CT). Two different experimental procedures have been used: 1) rapid intravenous injection of (Asu)E-CT (80 MRC. U.) or respectively of H-CT and S-CT (100 MRC. U.) in 15 subjects (7 normals and 8 with Paget's disease); 2) slow 7 days continuous subcutaneous infusion of similar daily amounts of (Asu)E-CT, H-CT and S-CT administered by a microjet pump device in 21 subjects (7 normals and 14 with Paget's disease). The intravenous administration of (Asu)E-CT induced a rapid and persistent decrease in total plasma calcium, ionized calcium and plasma phosphate that was more evident in Paget's disease patients than in normal subjects. No clearly cut differences have been observed with the hypocalcemic and hypophosphatemic effect of H-CT and S-CT administered

[From synthetic biology to synthetic humankind].

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Nouvel, Pascal

2015-01-01

In this paper, we propose an historical survey of the expression "synthetic biology" in order to identify its main philosophical components. The result of the analysis is then used to investigate the meaning of the notion of "synthetic man". It is shown that both notions share a common philosophical background that can be summed up by the short but meaningful assertion: "biology is technology". The analysis allows us to distinguish two notions that are often confused in transhumanist literature: the notion of synthetic man and the notion of renewed man. The consequences of this crucial distinction are discussed. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Effect of interleukin-17A on stemness of hepatoma cell lines

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LI Kexin

2017-06-01

Full Text Available ObjectiveTo investigate the effect of interleukin-17A (IL-17A on stemness of human hepatoma cell lines Hep 3B, MHCC97H, and MHCC97L and the association between IL-17A and the progression of liver cancer. MethodsHuman hepatoma cell lines Hep 3B, MHCC97H, and MHCC97L were selected, and in vitro 3D sphere formation assay was used to analyze the effect of IL-17A on sphere formation ability. The control group with common culture solution and the experimental group with 50 ng/ml IL-17A were established. Real-time cellular analysis was used to determine the effect of IL-17A on the proliferation and migration of hepatoma cells with enhanced sphere formation ability; quantitative real-time PCR was used to measure the changes in the mRNA expression of IL-17A receptors IL-17RA and IL-17RC and stemness-related genes SOX2, NANOG, OCT4, and BMI1 in hepatoma cells with enhanced sphere formation ability; Western blot was used to measure the expression of epithelial-mesenchymal transition-related proteins E-cadherin, N-cadherin, and vimentin. The t-test was used for comparison of continuous doota betwwen groups. ResultsWith the presence of 50 ng/ml IL-17A and 500 inoculated cells, Hep 3B cells had a significant increase in the number of spheres formed (113.0±10.3 vs 180.0±7.2, t=5.533, P＜0.001, while MHCC97H and MHCC97L cells showed no significant changes (t=1.087 and 0.279, P=0.325 and 0785. The analysis showed that IL-17A promoted the proliferation and migration of Hep 3B cells with an increased number of spheres formed. After the addition of 50 ng/ml IL-17A, there was an increase in the mRNA expression of IL-17A receptors IL-17RA and IL-17RC over the time of treatment; Hep 3B cells showed significant increases in the mRNA expression of stemness-related genes SOX2 (t=4.749, P=0.042, NANOG (t=19.600, P=0.003, OCT4 (t=37.310, P＜0.001, and BMI1 (t=16.810, P=0.004. Western blot showed no significant change in the expression of the epithelium

Mutants of the major ryegrass pollen allergen, Lol p 5, with reduced IgE-binding capacity: candidates for grass pollen-specific immunotherapy.

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Swoboda, Ines; De Weerd, Nicole; Bhalla, Prem L; Niederberger, Verena; Sperr, W R; Valent, Peter; Kahlert, Helga; Fiebig, Helmut; Verdino, Petra; Keller, Walter; Ebner, Christof; Spitzauer, Susanne; Valenta, Rudolf; Singh, Mohan B

2002-01-01

More than 400 million individuals are sensitized to grass pollen allergens. Group 5 allergens represent the most potent grass pollen allergens recognized by more than 80 % of grass pollen allergic patients. The aim of our study was to reduce the allergenic activity of group 5 allergens for specific immunotherapy of grass pollen allergy. Based on B- and T-cell epitope mapping studies and on sequence comparison of group 5 allergens from different grasses, point mutations were introduced by site-directed mutagenesis in highly conserved sequence domains of Lol p 5, the group 5 allergen from ryegrass. We obtained Lol p 5 mutants with low IgE-binding capacity and reduced allergenic activity as determined by basophil histamine release and by skin prick testing in allergic patients. Circular dichroism analysis showed that these mutants exhibited an overall structural fold similar to the recombinant Lol p 5 wild-type allergen. In addition, Lol p 5 mutants retained the ability to induce proliferation of group 5 allergen-specific T cell lines and clones. Our results demonstrate that a few point mutations in the Lol p 5 sequence yield mutants with reduced allergenic activity that represent potential vaccine candidates for immunotherapy of grass pollen allergy.

Highly luminescent core-shell InP/ZnX (X = S, Se) quantum dots prepared via a phosphine synthetic route.

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Mordvinova, Natalia; Vinokurov, Alexander; Kuznetsova, Tatiana; Lebedev, Oleg I; Dorofeev, Sergey

2017-01-24

Here we report a simple method for the creation of highly luminescent core-shell InP/ZnX (X = S, Se) quantum dots (QDs) on the basis of a phosphine synthetic route. In this method a Zn precursor was added to the reaction mixture at the beginning of the synthesis to form an In(Zn)P alloy structure, which promoted the formation of a ZnX shell. Core-shell InP/ZnX QDs exhibit highly intensive emission with a quantum yield over 50%. The proposed method is primarily important for practical applications. Advantages of this method compared to the widely used SILAR technique are discussed. We further demonstrate that the SILAR approach consisting of consequent addition of Zn and chalcogen precursors to pre-prepared non-doped InP colloidal nanoparticles is not quite suitable for shell growth without the addition of special activator agents or the use of very reactive precursors.

Cloning, Expression, and Immunogenicity of Fimbrial-F17A Subunit Vaccine against Escherichia coli Isolated from Bovine Mastitis

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Wei Chen

2017-01-01

Full Text Available There is a need to identify and select new promising immunodominant antigens that have the ability to provide protective immunity against E. coli causing bovine mastitis. Recently we showed that f17a was found to be the most prevalent and crucial virulent factor among the pathogenic E. coli isolated from bovine mastitis. Here, in this report, the recombinant F17A based subunit vaccine adjuvant with MF59 was tested for immunogenicity against E. coli in a murine model. The vaccinated mice did not show any abnormal behavioral changes and histopathological lesions after vaccination. The specific antibody level against F17A was significantly higher in MF59-adjuvant-group, and also lasted for longer duration with a significant (P<0.01 production level of IgG1 and IgG2a. Moreover, we noted higher survival rate in mice injected with F17A-MF59-adjuvant group after challenging with the clinical E. coli strain. Our findings of bacterial clearance test revealed that elimination rate from liver, spleen, and kidney in MF59-adjuvant-group was significantly higher than the control group. Finally, the proportion of CD4+T cells was increased, while CD8+ was decreased in MF59-adjuvant group. In conclusion, the current study reveals the capability of F17A-MF59 as a potential vaccine candidate against pathogenic E. coli causing mastitis in dairy animals.

Fluorescence in situ hybridization of TP53 for the detection of chromosome 17 abnormalities in myelodysplastic syndromes.

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Sánchez-Castro, Judit; Marco-Betés, Víctor; Gómez-Arbonés, Xavier; García-Cerecedo, Tomás; López, Ricard; Talavera, Elisabeth; Fernández-Ruiz, Sara; Ademà, Vera; Marugan, Isabel; Luño, Elisa; Sanzo, Carmen; Vallespí, Teresa; Arenillas, Leonor; Marco Buades, Josefa; Batlle, Ana; Buño, Ismael; Martín Ramos, María Luisa; Blázquez Rios, Beatriz; Collado Nieto, Rosa; Vargas, Ma Teresa; González Martínez, Teresa; Sanz, Guillermo; Solé, Francesc

2015-01-01

Conventional G-banding cytogenetics (CC) detects chromosome 17 (chr17) abnormalities in 2% of patients with de novo myelodysplastic syndromes (MDS). We used CC and fluorescence in situ hybridization (FISH) (LSI p53/17p13.1) to assess deletion of 17p in 531 patients with de novo MDS from the Spanish Group of Hematological Cytogenetics. FISH detected - 17 or 17p abnormalities in 13 cases (2.6%) in whom no 17p abnormalities were revealed by CC: 0.9% of patients with a normal karyotype, 0% in non-informative cytogenetics, 50% of patients with a chr17 abnormality without loss of 17p and 4.7% of cases with an abnormal karyotype not involving chr17. Our results suggest that applying FISH of 17p13 to identify the number of copies of the TP53 gene could be beneficial in patients with a complex karyotype. We recommend using FISH of 17p13 in young patients with a normal karyotype or non-informative cytogenetics, and always in isolated del(17p).

Molecular Epidemiology of Group A Rotaviruses in Water Sources and Selected Raw Vegetables in Southern Africa

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van Zyl, W. B.; Page, N. A.; Grabow, W. O. K.; Steele, A. D.; Taylor, M. B.

2006-01-01

Group A rotaviruses (RVs) are the most important cause of acute viral gastroenteritis in infants and young children. In this study raw and treated drinking water supplies at plants in two geographic areas, as well as selected irrigation water and corresponding raw vegetables in three regions of southern Africa, were screened for the presence of RVs using molecular techniques. Group A RVs were detected in 11.8% of partially treated and 1.7% of finally treated drinking water samples and in 14% of irrigation water samples and 1.7% of corresponding raw vegetable samples. Type-specific reverse transcriptase-PCR and sequence analysis revealed the presence of multiple types (G1, G2, G8, and G9) in irrigation water and single types (G1 or G3) in raw and treated drinking water. Group A RVs detected in all samples consisted of mixed P types (P[4], P[6], P[8], and P[9]), with P[6] predominating. The detection of types G8, G9, and P[6] reflects the emergence of these types in clinical infections. The similarity of environmental types to those in patients with clinical RV infections confirms the value of wastewater screening as a tool for assessing RVs circulating in communities, with the benefit of detecting types that cause both clinical and subclinical infections. The results provide new information on RV types in water and related environments and identify the potential risk of waterborne transmission. In addition, the presence of RVs in drinking water underlines shortcomings in quality specifications. These data provide valuable information regarding the prevalence of RVs in environmental sources, with important implications for vaccine development. PMID:16820443

Rhinovirus-induced VP1-specific Antibodies are Group-specific and Associated With Severity of Respiratory Symptoms

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Katarzyna Niespodziana

2015-01-01

Interpretation: Our results demonstrate that increases of antibodies towards the VP1 N-terminus are group-specific and associated with severity of respiratory symptoms and suggest that it may be possible to develop serological tests for identifying causative RV groups.

Chiral separation of synthetic vicinal diol compounds by capillary zone electrophoresis with borate buffer and beta-cyclodextrin as buffer additive.

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Zhao, Yan; Yang, Xingbin; Jiang, Ru; Sun, Xiaoli; Liu, Wenmin; Zhang, Shengyong

2006-05-01

The investigation on capillary electrophoretic enantioseparation of six synthetic compounds containing vicinal diol groups has been undertaken to acquire the optimum conditions using native beta-cyclodextrin (beta-CD) as chiral selector and borate as a background electrolyte. The separation was carried out in an uncoated capillary (58.5 cm x 75 microm i.d., effective length 48.5 cm) and the effects of several important factors were investigated in detail. The results showed that beta-CD as a chiral selector exhibited good enantioselectivity and that the enantioseparation was greatly influenced by the structure of the diols, the borate concentration and the buffer pH. The optimum performance was obtained for the chiral vicinal diols under the conditions of 200 mM borate buffer of pH 9.8 containing 1.7% beta-CD at an applied voltage of 15 kV and a capillary temperature of 20 degrees C. Under the conditions, four diols were baseline separated with fast analysis time and the good theoretical plate numbers (above 10 x 10(4)) and favorable migration-time reproducibilities (RSDs below 3.0%) were obtained. The separation results were satisfactory.