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Sample records for sanna ala-kleme pivi

  1. Tankerlerde Yükleme-Tahliye Operasyon Sisteminin Otomasyonu

    Directory of Open Access Journals (Sweden)

    Murat H. A. ALTUN

    2015-12-01

    Full Text Available Tanker tipi gemiler için yükleme tahliye operasyonları en kritik operasyonlardır. (1 Gemi limanda iken çevre kirliliği, yangın ve patlama riski ile kaza sonucunda doğabilecek zararların büyük ölçeklerde olma olasılığı yükleme-tahliye operasyonlarını kritik hale getirmektedir. (2. Bu kazaların oluşmasındaki nedenlerin başında personelin üzerine düşen ağır iş yükü neticesinde oluşan aşırı yorgunluk gelmektedir.(3 Bu çalışmada, insan hatasını ve doğabilecek operasyonel riskleri en aza indirgemek için yükleme ve tahliye operasyonunun operatör tarafından belirlenecek kriterlere göre çalışan bir otomasyon sisteminin oluşturulması hedeflenmiştir. Bu sistemin oluşturulması için gemi stabilite formüllerinden yararlanılarak oluşturulacak bilgisayar programları kullanılacaktır. Oluşturulan bilgisayar yazılımı sayesinde geminin kargo ve balast tanklarında bulunan mevcut değerler belirli aralıklarla ölçülüp operatör tarafından belirlenen trim, meyil, kargo akış miktarı, basınç ve geminin intakt stabilite kriterleri hiçbir safhada aşılmadan operasyon gerçekleştirilebilecektir. Sistem, otomasyon sistemine bağlı olan kargo ve balast tanklarının valflerini belirlenen kriterlere bağlı kalarak ayarlamaktadır. Tüm bunları yaparken girilen kargo akış miktarı ve basınç değerlerine bağlı olarak kargo pompasının cinsine bağlı olarak devir sayısını ayarlayabilmektedir. Otomasyon sistemi emniyet açısından beklenmedik durumlarda alarm vererek operatörü uyarmaktadır. Alarm sistemi meyil, basınç, intakt stabilite, akış miktarı ve trim değerleri için farklı olarak ayarlanmakla beraber operatörün belirleyeceği periyotlarda susturulmaması neticesinde genel alarm devreye girecek şekilde tasarlanmıştır. Ayrıca geminin fribord ve draft değerleri arasındaki fark hesaplanarak geminin ne kadar yükseldiği ve alçaldığı hesaplanmaktadır. Yap

  2. Notice: PSPB articles by authors with retracted articles at PSPB or other journals: Stapel, Smeesters, and Sanna.

    Science.gov (United States)

    Funder, David

    2014-01-01

    Numerous articles by the social psychologists Diederick Stapel, Dirk Smeesters, and Lawrence Sanna have been retracted in several different journals. The present notice reports the results of an investigation into papers authored or coauthored by these individuals, and published in Personality and Social Psychology Bulletin, that have not been retracted. The status of these papers range from data confirmed as legitimate by coauthors to, in many cases, being unknown as to their legitimacy. Given the lack of information in the latter cases, there is insufficient basis to recommend retraction at this time. Researchers using the results of these papers in their own work are advised to take the information reported in this notice into account.

  3. Characterization of d-boroAla as a Novel Broad Spectrum Antibacterial Agent Targeting d-Ala-d-Ala Ligase

    OpenAIRE

    Putty, Sandeep; Rai, Aman; Jamindar, Darshan; Pagano, Paul; Quinn, Cheryl L.; Mima, Takehiko; Schweizer, Herbert P.; Gutheil, William G.

    2011-01-01

    d-boroAla was previously characterized as an inhibitor of bacterial alanine racemase and d-Ala-d-Ala ligase enzymes [Duncan, K., et al Biochemistry 1989, 28:3541–9]. In the present study, d-boroAla was identified and characterized as an antibacterial agent. d-boroAla has activity against both Gram-positive and Gram-negative organisms, with MICs down to 8 µg/mL. A structure-function study on the alkyl side chain (NH2-CHR-B(OR’)2) revealed that d-boroAla is the most effective agent in a series ...

  4. Towards understanding the tandem mass spectra of protonated oligopeptides. 2: The proline effect in collision-induced dissociation of protonated Ala-Ala-Xxx-Pro-Ala (Xxx = Ala, Ser, Leu, Val, Phe, and Trp).

    Science.gov (United States)

    Bleiholder, Christian; Suhai, Sándor; Harrison, Alex G; Paizs, Béla

    2011-06-01

    The product ion spectra of proline-containing peptides are commonly dominated by y(n) ions generated by cleavage at the N-terminal side of proline residues. This proline effect is investigated in the current work by collision-induced dissociation (CID) of protonated Ala-Ala-Xxx-Pro-Ala (Xxx includes Ala, Ser, Leu, Val, Phe, and Trp) in an electrospray/quadrupole/time-of-flight (QqTOF) mass spectrometer and by quantum chemical calculations on protonated Ala-Ala-Ala-Pro-Ala. The CID spectra of all investigated peptides show a dominant y(2) ion (Pro-Ala sequence). Our computational results show that the proline effect mainly arises from the particularly low threshold energy for the amide bond cleavage N-terminal to the proline residue, and from the high proton affinity of the proline-containing C-terminal fragment produced by this cleavage. These theoretical results are qualitatively supported by the experimentally observed y(2)/b(3) abundance ratios for protonated Ala-Ala-Xxx-Pro-Ala (Xxx = Ala, Ser, Leu, Val, Phe, and Trp). In the post-cleavage phase of fragmentation the N-terminal oxazolone fragment with the Ala-Ala-Xxx sequence and Pro-Ala compete for the ionizing proton for these peptides. As the proton affinity of the oxazolone fragment increases, the y(2)/b(3) abundance ratio decreases.

  5. Engineering an ATP-dependent D-Ala:D-Ala ligase for synthesizing amino acid amides from amino acids.

    Science.gov (United States)

    Miki, Yuta; Okazaki, Seiji; Asano, Yasuhisa

    2017-05-01

    We successfully engineered a new enzyme that catalyzes the formation of D-Ala amide (D-AlaNH 2 ) from D-Ala by modifying ATP-dependent D-Ala:D-Ala ligase (EC 6.3.2.4) from Thermus thermophilus, which catalyzes the formation of D-Ala-D-Ala from two molecules of D-Ala. The new enzyme was created by the replacement of the Ser293 residue with acidic amino acids, as it was speculated to bind to the second D-Ala of D-Ala-D-Ala. In addition, a replacement of the position with Glu performed better than that with Asp with regards to specificity for D-AlaNH 2 production. The S293E variant, which was selected as the best enzyme for D-AlaNH 2 production, exhibited an optimal activity at pH 9.0 and 40 °C for D-AlaNH 2 production. The apparent K m values of this variant for D-Ala and NH 3 were 7.35 mM and 1.58 M, respectively. The S293E variant could catalyze the synthesis of 9.3 and 35.7 mM of D-AlaNH 2 from 10 and 50 mM D-Ala and 3 M NH 4 Cl with conversion yields of 93 and 71.4 %, respectively. This is the first report showing the enzymatic formation of amino acid amides from amino acids.

  6. ALA Pretreatment Improves Waterlogging Tolerance of Fig Plants.

    Directory of Open Access Journals (Sweden)

    Yuyan An

    Full Text Available 5-aminolevulinic acid (ALA, a natural and environmentally friendly plant growth regulator, can improve plant tolerance to various environmental stresses. However, whether ALA can improve plant waterlogging tolerance is unknown. Here, we investigated the effects of ALA pretreatment on the waterlogging-induced damage of fig (Ficus carica Linn. plants, which often suffer from waterlogging stress. ALA pretreatment significantly alleviated stress-induced morphological damage, increased leaf relative water content (RWC, and reduced leaf superoxide anion ([Formula: see text] production rate and malonaldehyde (MDA content in fig leaves, indicating ALA mitigates waterlogging stress of fig plants. We further demonstrated that ALA pretreatment largely promoted leaf chlorophyll content, photosynthetic electron transfer ability, and photosynthetic performance index, indicating ALA significantly improves plant photosynthetic efficiency under waterlogging stress. Moreover, ALA pretreatment significantly increased activities of leaf superoxide dismutase (SOD and peroxidase (POD, root vigor, and activities of root alcohol dehydrogenase (ADH, and lactate dehydrogenase (LDH, indicating ALA also significantly improves antioxidant ability and root function of fig plants under waterlogging stress. Taken together, ALA pretreatment improves waterlogging tolerance of fig plants significantly, and the promoted root respiration, leaf photosynthesis, and antioxidant ability may contribute greatly to this improvement. Our data firstly shows that ALA can improve plant waterlogging tolerance.

  7. Expression of the alaE gene is positively regulated by the global regulator Lrp in response to intracellular accumulation of l-alanine in Escherichia coli.

    Science.gov (United States)

    Ihara, Kohei; Sato, Kazuki; Hori, Hatsuhiro; Makino, Yumiko; Shigenobu, Shuji; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

    2017-04-01

    The alaE gene in Escherichia coli encodes an l-alanine exporter that catalyzes the active export of l-alanine using proton electrochemical potential. In our previous study, alaE expression was shown to increase in the presence of l-alanyl-l-alanine (Ala-Ala). In this study, the global regulator leucine-responsive regulatory protein (Lrp) was identified as an activator of the alaE gene. A promoter less β-galactosidase gene was fused to an alaE upstream region (240 nucleotides). Cells that were lacZ-deficient and harbored this reporter plasmid showed significant induction of β-galactosidase activity (approximately 17-fold) in the presence of 6 mM l-alanine, l-leucine, and Ala-Ala. However, a reporter plasmid possessing a smaller alaE upstream region (180 nucleotides) yielded transformants with strikingly low enzyme activity under the same conditions. In contrast, lrp-deficient cells showed almost no β-galactosidase induction, indicating that Lrp positively regulates alaE expression. We next performed an electrophoretic mobility shift assay (EMSA) and a DNase I footprinting assay using purified hexahistidine-tagged Lrp (Lrp-His). Consequently, we found that Lrp-His binds to the alaE upstream region spanning nucleotide -161 to -83 with a physiologically relevant affinity (apparent K D , 288.7 ± 83.8 nM). Furthermore, the binding affinity of Lrp-His toward its cis-element was increased by l-alanine and l-leucine, but not by Ala-Ala and d-alanine. Based on these results, we concluded that the gene expression of the alaE is regulated by Lrp in response to intracellular levels of l-alanine, which eventually leads to intracellular homeostasis of l-alanine concentrations. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  8. Loss of the Arabidopsis thaliana P4-ATPases ALA6 and ALA7 Impairs Pollen Fitness and Alters the Pollen Tube Plasma Membrane

    Directory of Open Access Journals (Sweden)

    Stephen C McDowell

    2015-04-01

    Full Text Available Members of the P4 subfamily of P-type ATPases are thought to create and maintain lipid asymmetry in biological membranes by flipping specific lipids between membrane leaflets. In Arabidopsis, 7 of the 12 Aminophospholipid ATPase (ALA family members are expressed in pollen. Here we show that double knockout of ALA6 and ALA7 (ala6/7 results in siliques with a ~2-fold reduction in seed set with a high frequency of empty seed positions near the bottom. Seed set was reduced to near zero when plants were grown under a hot/cold temperature stress. Reciprocal crosses indicate that the ala6/7 reproductive deficiencies are due to a defect related to pollen transmission. In-vitro growth assays provide evidence that that ala6/7 pollen tubes are short and slow, with ~2-fold reductions in both maximal growth rate and overall length relative to wild-type. Outcrosses show that when ala6/7 pollen are in competition with wild-type pollen, they have a near 0% success rate in fertilizing ovules near the bottom of the pistil, consistent with ala6/7 pollen having short and slow growth defects. The ala6/7 phenotypes were rescued by the expression of either an ALA6-YFP or GFP-ALA6 fusion protein, which showed localization to both the plasma membrane and highly-mobile endomembrane structures. A mass spectrometry analysis of mature pollen grains revealed significant differences between ala6/7 and wild-type, both in the relative abundance of lipid classes and in the average number of double bonds present in acyl side chains. A change in the properties of the ala6/7 plasma membrane was also indicated by a ~10-fold reduction of labeling by lipophilic FM-dyes relative to wild-type. Together, these results indicate that ALA6 and ALA7 provide redundant activities that function to directly or indirectly change the distribution and abundance lipids in pollen, and support a model in which ALA6 and ALA7 are critical for pollen fitness under normal and temperature-stress conditions.

  9. Photodynamic therapy using aminolevulinic acid (ALA)

    Science.gov (United States)

    Bachor, Ruediger; Reich, Ella D.; Miller, Kurt; Hautmann, Richard E.

    1994-03-01

    Photodynamic therapy (PDT) is a treatment modality for a variety of cancers. Since no ideal photosensitizer is available yet, new photosensitizers are being sought. A new concept of PDT is the use of endogenous photosensitizers. ALA is a metabolite in heme synthesis. It is a precursor of protoporphyrin IX, a potent photosensitizer. After administration of ALA it is transformed by the cells to protoporphyrin IX. The goal of our study was to examine dark toxicity of ALA and its phototoxic potential in two different human cell lines.

  10. American Library Association (ALA no Second Life (SL

    Directory of Open Access Journals (Sweden)

    Richele Grenge Vignoli

    Full Text Available A American Library Association (ALA está inserida no contexto de Realidade Virtual (RV em 3D, por meio de sua atuação no Second Life (SL, com a ALA Island. Esta pesquisa teve como objetivo analisar o atendimento virtual a bibliotecários no SL; identificar produtos e serviços que a ALA oferece no SL e analisar sua infraestrutura. Para a coleta de dados, foi utilizada a análise documental, ação em que a ALA Island foi observada/explorada e estruturada em dados; e o questionário - enviado a uma bibliotecária da ALA Island. Os resultados demonstram que a atuação da ALA no SL tem como propósito central a divulgação de seus projetos, os eventos físicos e os virtuais e o apoio ao bibliotecário em sua vida profissional. A ALA está inserida em diversos recursos da Web 2.0, além do SL, como blogs, wikis, sites de relacionamento, entre outros. Toda a trajetória da ALA foi analisada, assim como as especificidades do seu trabalho realizado para os bibliotecários. Observou-se que o atendimento a bibliotecários no SL é realizado por meio de robôs e indicação de notecards e hiperlinks informativos. No SL, a ALA disponibiliza diversos serviços e produtos aos bibliotecários, como os relacionados com os escritórios, comitês e instituições, além dos serviços e produtos disponíveis no site e no escritório da ALA em Washington-DC e de seus representantes. Os recursos da ALA e do SL, assim como a inserção de bibliotecários em Realidade Virtual (RV precisam ser estudados por meio de pesquisas, para dinamizar e aproximar essa realidade desses profissionais.

  11. Impact of charged amino acid substitution in the transmembrane domain of L-alanine exporter, AlaE, of Escherichia coli on the L-alanine export.

    Science.gov (United States)

    Kim, Seryoung; Ihara, Kohei; Katsube, Satoshi; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

    2017-01-01

    The Escherichia coli alaE gene encodes the L-alanine exporter, AlaE, that catalyzes active export of L-alanine using proton electrochemical potential. The transporter comprises only 149 amino acid residues and four predicted transmembrane domains (TMs), which contain three charged amino acid residues. The AlaE-deficient L-alanine non-metabolizing cells (ΔalaE cells) appeared hypersusceptible to L-alanyl-L-alanine showing a minimum inhibitory concentration (MIC) of 2.5 µg/ml for the dipeptide due to a toxic accumulation of L-alanine. To elucidate the mechanism by which AlaE exports L-alanine, we replaced charged amino acid residues in the TMs, glutamic acid-30 (TM-I), arginine-45 (TM-II), and aspartic acid-84 (TM-III) with their respective charge-conserved amino acid or a net neutral cysteine. The ΔalaE cells producing R45K or R45C appeared hypersusceptible to the dipeptide, indicating that arginine-45 is essential for AlaE activity. MIC of the dipeptide in the ΔalaE cells expressing E30D and E30C was 156 µg/ml and >10,000 µg/ml, respectively, thereby suggesting that a negative charge at this position is not essential. The ΔalaE cells expressing D84E or D84C showed an MIC >10,000 and 78 µg/ml, respectively, implying that a negative charge is required at this position. These results were generally consistent with that of the L-alanine accumulation experiments in intact cells. We therefore concluded that charged amino acid residues (R45 and D84) in the AlaE transmembrane domain play a pivotal role in L-alanine export. Replacement of three cysteine residues at C22, C28 (both in TM-I), and C135 (C-terminal region) with alanine showed only a marginal effect on L-alanine export.

  12. Characterization of the l-alanine exporter AlaE of Escherichia coli and its potential role in protecting cells from a toxic-level accumulation of l-alanine and its derivatives

    OpenAIRE

    Kim, Seryoung; Ihara, Kohei; Katsube, Satoshi; Hori, Hatsuhiro; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

    2015-01-01

    We previously reported that the alaE gene of Escherichia coli encodes the l-alanine exporter AlaE. The objective of this study was to elucidate the mechanism of the AlaE exporter. The minimum inhibitory concentration of l-alanine and l-alanyl-l-alanine in alaE-deficient l-alanine-nonmetabolizing cells MLA301ΔalaE was 4- and >4000-fold lower, respectively, than in the alaE-positive parent cells MLA301, suggesting that AlaE functions as an efflux pump to avoid a toxic-level accumulation of intr...

  13. Protoporphyrin IX fluorescence kinetics and localization after topical application of ALA pentyl ester and ALA on hairless mouse skin with UVB-induced early skin cancer

    NARCIS (Netherlands)

    van den Akker, J. T.; de Bruijn, H. S.; Beijersbergen van Henegouwen, G. M.; Star, W. M.; Sterenborg, H. J.

    2000-01-01

    In order to improve the efficacy of 5-aminolevulinic acid-based (ALA) photodynamic therapy (PDT), different ALA derivatives are presently being investigated. ALA esters are more lipophilic and therefore may have better skin penetration properties than ALA, possibly resulting in enhanced

  14. Characterization of the l-alanine exporter AlaE of Escherichia coli and its potential role in protecting cells from a toxic-level accumulation of l-alanine and its derivatives.

    Science.gov (United States)

    Kim, Seryoung; Ihara, Kohei; Katsube, Satoshi; Hori, Hatsuhiro; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

    2015-08-01

    We previously reported that the alaE gene of Escherichia coli encodes the l-alanine exporter AlaE. The objective of this study was to elucidate the mechanism of the AlaE exporter. The minimum inhibitory concentration of l-alanine and l-alanyl-l-alanine in alaE-deficient l-alanine-nonmetabolizing cells MLA301ΔalaE was 4- and >4000-fold lower, respectively, than in the alaE-positive parent cells MLA301, suggesting that AlaE functions as an efflux pump to avoid a toxic-level accumulation of intracellular l-alanine and its derivatives. Furthermore, the growth of the alaE-deficient mutant derived from the l-alanine-metabolizing strain was strongly inhibited in the presence of a physiological level of l-alanyl-l-alanine. Intact MLA301ΔalaE and MLA301ΔalaE/pAlaE cells producing plasmid-borne AlaE, accumulated approximately 200% and 50%, respectively, of the [(3) H]l-alanine detected in MLA301 cells, suggesting that AlaE exports l-alanine. When 200 mmol/L l-alanine-loaded inverted membrane vesicles prepared from MLA301ΔalaE/pAlaE were placed in a solution containing 200 mmol/L or 0.34 μmol/L l-alanine, energy-dependent [(3) H]l-alanine accumulation occurred under either condition. This energy-dependent uphill accumulation of [(3) H]l-alanine was strongly inhibited in the presence of carbonyl cyanide m-chlorophenylhydrazone but not by dicyclohexylcarbodiimide, suggesting that the AlaE-mediated l-alanine extrusion was driven by proton motive force. Based on these results, physiological roles of the l-alanine exporter are discussed. © 2015 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  15. PARP1 Val762Ala polymorphism reduces enzymatic activity

    International Nuclear Information System (INIS)

    Wang Xiaogan; Wang Zhaoqi; Tong Weimin; Shen Yan

    2007-01-01

    Poly(ADP-ribose) polymerase 1 (PARP1) modifies a variety of nuclear proteins by poly(ADP-ribosyl)ation, and plays diverse roles in molecular and cellular processes. A common PARP1 single nucleotide polymorphism (SNP) at codon 762, resulting in the substitution of alanine (Ala) for valine (Val) in the catalytic domain has been implicated in susceptibility to cancer. To characterize the functional effect of this polymorphism on PARP1, we performed in vitro enzymatic analysis on PARP1-Ala762 and PARP1-Val762. We found that PARP1-Ala762 displayed 57.2% of the activity of PARP1-Val762 for auto-poly(ADP-ribosyl)ation and 61.9% of the activity of PARP1-Val762 for trans-poly(ADP-ribosyl)ation of histone H1. The kinetic characterization revealed that the K m of PARP1-Ala762 was increased to a 1.2-fold of the K m of PARP1-Val762 for trans-poly(ADP-ribosyl)ation. Thus, the PARP1 Val762Ala polymorphism reduces the enzymatic activity of PARP1 by increasing K m . This finding suggests that different levels of poly(ADP-ribosyl)ation by PARP1 might aid in understanding Cancer risk of carriers of the PARP1 Val762Ala polymorphism

  16. The importance of protoporphyrin IX efflux for ALA-PDT dosimetry

    International Nuclear Information System (INIS)

    Milanetto, M C; Imasato, H; Perussi, J R

    2009-01-01

    One of the major advances in PDT is the use of 5-aminolevulinic acid (ALA) to induce the production of an endogenous photosensitizer inside the cells using intracellular enzymatic pathways. ALA is the first intermediate in heme biosynthesis and a precursor of the protoporphyrin IX (PpIX). When activated by light, this efficient photosensitizer accumulated in the target cells can produce cytotoxicity. The aim of this study was to find the best conditions for cell killing using ALA to temporarily increase the concentration of PpIX in two cell lines. It was shown that a considerable efflux of synthesized PpIX occurs. Since this efflux is time-dependent, it is essential to know the optimum time for irradiation after ALA administration. So, the efflux of PpIX from the cells is an important parameter to be considered for ALA-PDT dosimetry

  17. Jüri Ratas: tasulise parkimise ala suurendamine probleeme ei tekita / Jüri Ratas ; interv. Askur Alas

    Index Scriptorium Estoniae

    Ratas, Jüri, 1978-

    2004-01-01

    Tallinna abilinnapea tasulise parkimise ala laiendamisest Tallinna kesklinnas ja sellega kaasnevatest võimalikest probleemidest. Kommenteerib Johannes Pirita. Kaart. Lisa: Rahvaalgatus sõdib tasulise parkimisega

  18. Studying the potential role of ALIS proteins on the functionality of ALA2

    DEFF Research Database (Denmark)

    Lopez Marques, Rosa Laura; Poulsen, Lisbeth Rosager; Meffert, Katharina

    ). Recently we have identified five Cdc50p homologues in Arabidopsis [ALA Interacting Subunit (ALIS) 1 to 5] (1), and demonstrated that these ß-subunits are essential for the functioning of ALA3. We are currently working on a third Arabidopsis P4-ATPase isoform, ALA2. We have shown that this isoform...... is involved in specific translocation of phosphatidylserine analogues. Furthermore, we have found evidence that the substrate specificity is independent of the ß-subunit interacting with this P4-ATPase. ALA2 in combination with ALIS genes complement both the cold and the metal sensitive phenotype caused...... by lack of DRS2 in yeast. Tissue specific expression patterns of ALA2 and ALIS genes indicate that different ALIS isoforms may interact with ALA2 in diverse parts of the plant. At present we are studying the subcellular localization of ALA2 in planta in order to understand better its possible...

  19. Comparison of 18F-FET PET and 5-ALA fluorescence in cerebral gliomas

    International Nuclear Information System (INIS)

    Floeth, Frank Willi; Sabel, Michael; Steiger, Hans Jakob; Ewelt, Christian; Stummer, Walter; Felsberg, Joerg; Reifenberger, Guido; Stoffels, Gabriele; Langen, Karl-Josef; Coenen, Heinz Hubert

    2011-01-01

    The aim of the study was to compare presurgical 18 F-fluoroethyl-L-tyrosine ( 18 F-FET) uptake and Gd-diethylenetriaminepentaacetic acid (DTPA) enhancement on MRI (Gd) with intraoperative 5-aminolevulinic acid (5-ALA) fluorescence in cerebral gliomas. 18 F-FET positron emission tomography (PET) was performed in 30 patients with brain lesions suggestive of diffuse WHO grade II or III gliomas on MRI. PET and MRI data were coregistered to guide neuronavigated biopsies before resection. After oral application of 5-ALA, 38 neuronavigated biopsies were taken from predefined tumour areas that were positive or negative for 18 F-FET or Gd and checked for 5-ALA fluorescence. 18 F-FET uptake with a mean tumour to brain ratio ≥1.6 was rated as positive. Of 38 biopsies, 21 corresponded to high-grade glioma tissue (HGG) of WHO grade III (n = 19) or IV (n = 2) and 17 biopsies to low-grade glioma tissue (LGG) of WHO grade II. In biopsies corresponding to HGG, 18 F-FET PET was positive in 86% (18/21), but 5-ALA and Gd in only 57% (12/21). A mismatch between Gd and 5-ALA was observed in 6 of 21 cases of HGG biopsy samples (3 Gd-positive/5-ALA-negative and 3 Gd-negative/5-ALA-positive). In biopsies corresponding to LGG, 18 F-FET was positive in 41% (7/17), while 5-ALA and Gd were negative in all but one instance. All tumour areas with 5-ALA fluorescence were positive on 18 F-FET PET. There are differences between 18 F-FET and 5-ALA uptake in cerebral gliomas owing to a limited sensitivity of 5-ALA to detect tumour tissue especially in LGG. 18 F-FET PET is more sensitive to detect glioma tissue than 5-ALA fluorescence and should be considered as an additional tool in resection planning. (orig.)

  20. EKSISTENSI DAN MOTIVASI PRAMUWISATA LOKAL PEREMPUAN DI DAYA TARIK WISATA ALAS KEDATON

    Directory of Open Access Journals (Sweden)

    Gusti Ayu Putu Putri Indira Suari

    2017-01-01

    Full Text Available Keberadaan pramuwisata lokal yang seluruhnya berjenis kelamin perempuan menjadi keunikan tersendiri bagi Alas Kedaton sebagai suatu daya tarik wisata. Bertujuan untuk mengetahui eksistensi pramuwisata lokal perempuan di daya tarik wisata Alas Kedaton serta untuk mengetahui motivasi mereka bekerja sebagai pramuwisata lokal perempuan di daya tarik wisata Alas Kedaton. Jenis data yang digunakan adalah data kuantitatif dan kualitatif. Sedangkan sumber data yakni data primer dan sekunder. Data dikumpulkan melalui observasi, wawancara, kuesioner dan dokumentasi. Informan ditentukan secara purposive sampling. Terdapat 45 responden yang dipilih sebagai sampel dengan menggunakan metode simple random sampling. Dan teknik analisis data yang digunakan adalah analisis deskriptif kualitatif dan deskriptif kuantitatif. Hasil menunjukkan bahwa eksistensi pramuwisata lokal perempuan di daya tarik wisata Alas Kedaton dari awal terbentuknya sampai saat ini dapat dikatakan masih eksis. Meskipun jumlah pramuwisata lokal perempuan di daya tarik wisata Alas Kedaton berkurang dibandingkan ketika awal terbentuknya. Sedangkan motivasi mereka bekerja sebagai pramuwisata lokal di daya tarik wisata Alas Kedaton adalah untuk memenuhi beberapa kebutuhan seperti physiological needs, safety and security needs, affiliation or acceptance needs, esteem needs, dan self actualization. Dan rata-rata responden menjawab motivasi mereka bekerja sebagai pramuwisata lokal perempuan di daya tarik wisata Alas Kedaton adalah untuk memenuhi kebutuhan afiliasi atau affiliation or acceptance needs.

  1. Ex-vivo absorption study of lysine R-lipoate salt, a new pharmaceutical form of R-ALA.

    Science.gov (United States)

    Amenta, Francesco; Buccioni, Michela; Ben, Diego Dal; Lambertucci, Catia; Navia, Aleix Martí; Ngouadjeu Ngnintedem, Michael A; Ricciutelli, Massimo; Spinaci, Andrea; Volpini, Rosaria; Marucci, Gabriella

    2018-06-15

    Alpha-lipoic acid (ALA) oral supplements were used in many pathologies associated with increased oxidative stress. Although only R-ALA is considered the biologically active form, R,S-ALA is used in therapeutic applications even showing poor water solubility. The aim of this work was to study the absorption and transport mechanism across the intestinal barrier of new R-ALA stable and water soluble form, consisting in the lysine R-ALA salt, in presence and absence of specific inhibitors of Na + /multivitamin (SMVT) and monocarboxylic acids (MCT). The absorption of a new ALA form was investigated at rat everted sacs in comparison with R-ALA, S-ALA, and R,S-ALA. Results showed that duodenum is the best portion of intestine for ALA forms absorption. The absorption percentage of R-ALA, S-ALA, R,S-ALA, and lysine R-ALA salt was 66%, 43%, 55%, and 70%, respectively. The modest effect of the SMVT inhibitor biotin demonstrated that this transporter system is not principally involved in the absorption of lysine R-lipoate salt across the rat intestinal barrier. On the contrary, the MCT inhibitor octanoic acid significantly reduced the transport of this salt, whit an absorption decrease of R-ALA and lysine R-lipoate salt of 28% and 24%, respectively. Since the highest concentration of these inhibitors did not completely inhibit the absorption of lysine R-lipoate salt, other transport mechanisms probably operate for its intracellular delivery. The new form of ALA, lysine R-lipoate salt, was the most absorbed respect to the other ALA forms demonstrating that this compound is more suitable for oral administration. This new salt could represent a promising candidate for ALA oral supplementation. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. In vivo study of ALA PLGA nanoparticles-mediated PDT for treating cutaneous squamous cell carcinoma

    Science.gov (United States)

    Wang, Xiaojie; Shi, Lei; Huang, Zheng; Wang, Xiuli

    2014-09-01

    Background: Squamous cell carcinoma (SCC) is a common skin cancer and its treatment is still a challenge. Although topical photodynamic therapy (PDT) is effective for treating in situ and superficial SCC, the effectiveness of topical ALA delivery to thick SCC can be limited by its bioavailability. Polylactic-co-glycolic acid nanopartieles (PLGA NPs) might provide a promising ALA delivery strategy. The aim of this study was to evaluate the efficacy of ALA PLGA NPs PDT for the treatment of cutaneous SCC in a mouse model. Methods: ALA loaded PLGA NPs were prepared and characterized. The therapeutic efficacy of ALA PLGA NP mediated PDT in treating UV-induced cutaneous SCC in the mice model were examined. Results: In vivo study showed that ALA PLGA NPs PDT were more effective than free ALA of the same concentration in treating mouse cutaneous SCC. Conclusion: ALA PLGA NPs provides a promising strategy for delivering ALA and treating cutaneous SCC.

  3. Design of PDT protocols using delta-aminolevulinic acid (5ALA)

    Science.gov (United States)

    Jacques, Steven L.; He, Xiao-Yan; Gofstein, Gary

    1993-06-01

    The kinetics of protoporphyrin IX (PPIX) synthesis, bioconversion to other metabolic products, and photobleaching were measured in cell cultures after incubation in media containing the metabolic precursor for heme synthesis, (delta) -aminolevulinic acid (5 ALA). A compartmental model described the kinetics in terms of rate constants for the three processes. The maximum amount of PPIX that can be attained in the cells and the concentration of 5 ALA in the medium that obtains this maximum were determined. Using this information, two dosimetry protocols are outlined which both involve complete photobleaching of the PPIX: (1) the classical acute protocol using maximum 5 ALA to produce maximum PPIX and a light treatment of about 0.5 - 1 hr, and (2) a novel prolonged protocol using continuous low-level 5 ALA delivery to produce only slightly elevated PPIX and an extended light exposure time of over 24 hrs.

  4. Substitution of the Lys linker with the β-Ala linker dramatically decreased the renal uptake of 99mTc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone peptides.

    Science.gov (United States)

    Flook, Adam M; Yang, Jianquan; Miao, Yubin

    2014-11-13

    The purpose of this study was to examine whether the substitution of the Lys linker with the β-Ala could reduce the renal uptake of (99m)Tc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RSD-β-Ala-(Arg(11))CCMSH (1) {c[Arg-Ser-Asp-dTyr-Asp]-β-Ala-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2}, RTD-β-Ala-(Arg(11))CCMSH (2), RVD-β-Ala-(Arg(11))CCMSH (3), RAD-β-Ala-(Arg(11))CCMSH (4), NAD-β-Ala-(Arg(11))CCMSH (5), and EAD-β-Ala-(Arg(11))CCMSH (6) peptides were synthesized and evaluated for their melanocortin 1 (MC1) receptor binding affinities in B16/F1 melanoma cells. The biodistribution of their (99m)Tc-conjugates were determined in B16/F1 melanoma-bearing C57 mice. The substitution of the Lys linker with β-Ala linker dramatically reduced the renal uptake of all six (99m)Tc-peptides. (99m)Tc-4 exhibited the highest melanoma uptake (15.66 ± 6.19% ID/g) and the lowest kidney uptake (20.18 ± 3.86% ID/g) among these (99m)Tc-peptides at 2 h postinjection. The B16/F1 melanoma lesions could be clearly visualized by single photon emission computed tomography (SPECT)/CT using (99m)Tc-4 as an imaging probe.

  5. A study of parallelism of the occlusal plane and ala-tragus line.

    Science.gov (United States)

    Sadr, Katayoun; Sadr, Makan

    2009-01-01

    Orientation of the occlusal plane is one of the most important clinical procedures in prostho-dontic rehabilitation of edentulous patients. The aim of this study was to define the best posterior reference point of ala-tragus line for orientation of occlusal plane for complete denture fabrication. Fifty-three dental students (27 females and 26 males) with complete natural dentition and Angel's Class I occlusal relationship were selected. The subjects were photographed in natural head position while clenching on a Fox plane. After tracing the photographs, the angles between the following lines were measured: the occlusal plane (Fox plane) and the superior border of ala-tragus, the occlusal plane (Fox plane) and the middle of ala-tragus as well as the occlusal plane (Fox plane) and the inferior border of ala-tragus. Descriptive statistics, one sample t-test and independent t-test were used. P value less than 0.05 was considered significant. There was no parallelism between the occlusal plane and ala-tragus line with three different posterior ends and one sample t-test showed that the angles between them were significantly different from zero (pplane. The superior border of the tragus is suggested as the posterior reference for ala-tragus line.

  6. The final story on the ALA3/ALIS1 complex

    DEFF Research Database (Denmark)

    Lopez Marques, Rosa Laura

    The final story on the ALA3/ALIS1 complex. Lisbeth R. Poulsena, Rosa L. López-Marquésa, Alexander Schultza, Stephen C. McDowellb, Juha Okkeric, Dirk Lichtc, Thomas Pomorskic,  Jeffrey F. Harperb, and Michael G. Palmgrena,1 aCentre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National......).              Through a database search we have previously identified five Cdc50p/Lem3p homologues in Arabidopsis (ALIS1-5 for ALA Interacting Subunit)..We investigated the capacity of ALA3, alone and in combination with expressed ALIS proteins, to functionally complement a battery of yeast mutants carrying deletions...... in endogenous P4-ATPases. Our results indicated that ALIS1 functions as a true ß-subunit for the Arabidopsis putative flippase ALA3, being required for ATP-dependent phospholipid transport and for genetic complementation of the yeast P4-ATPase gene Drs2, which is involved in vesicle budding from the late Golgi...

  7. A facile synthesis of δ-aminolevulinic acid (ALA) regio-selectively labeled with 13C and direct observation of enzymatic transformation from ALA to porphobilinogen (PBG)

    International Nuclear Information System (INIS)

    Kurumaya, Katsuyuki; Okazaki, Takeo; Seido, Nobuo; Akasaka, Yuzuru; Kawajiri, Yoshiki; Kajiwara, Masahiro; Kondo, Masao

    1989-01-01

    δ-Aminolevulinic acid (ALA), labeled with 13 C at position 1, 2, 3, 4, or 5, was synthesized from 13 C-labeled glycine, Meldrum's acid, or bromoacetate. The latter compounds were prepared from 13 C-sodium acetate or 13 C-acetic acid. Enzymatic transformation from ALA to porphobilinogen (PBG) was directly observed by 13 C-NMR. (author)

  8. Treating cutaneous squamous cell carcinoma using ALA PLGA nanoparticle-mediated photodynamic therapy in a mouse model

    Science.gov (United States)

    Wang, Xiaojie; Shi, Lei; Tu, Qingfeng; Wang, Hongwei; Zhang, Haiyan; Wang, Peiru; Zhang, Linglin; Huang, Zheng; Wang, Xiuli; Zhao, Feng; Luan, Hansen

    2015-03-01

    Background: Squamous cell carcinoma (SCC) is a common skin cancer and its treatment is still difficult. The aim of this study was to evaluate the effectiveness of nanoparticle (NP)-assisted ALA delivery for topical photodynamic therapy (PDT) of cutaneous SCC. Methods: UV-induced cutaneous SCCs were established in hairless mice. ALA loaded polylactic-co-glycolic acid (PLGA) NPs were prepared and characterized. The kinetics of ALA PLGA NPs-induced protoporphyrin IX (PpIX) fluorescence in SCCs, therapeutic efficacy of ALA NP-mediated PDT, and immune responses were examined. Results: PLGA NPs could enhance PpIX production in SCC. ALA PLGA NP mediated topical PDT was more effective than free ALA of the same concentration in treating cutaneous SCC. Conclusion: PLGA NPs provide a promising strategy for delivering ALA in topical PDT of cutaneous SCC.

  9. Isolated cleft of the ala nasi: A report of seven cases

    Directory of Open Access Journals (Sweden)

    J Rajesh Jinka

    2012-01-01

    Full Text Available Craniofacial clefts other than cleft lip & palate are reported to be 1.4 to 4.9 per 100,000 live births. Of these, clefts of nose are usually associated with other clefts. Isolated cleft of Ala is rare, 0.7% of all clefts reported by Monasterio. In an analysis of photographic records of 3,500 consecutive patients with craniofacial clefts including cleft lip & palate registered with us between 1985- 2012 which were accessed through our data base, 13 patients with nasal clefts were identified, seven out of which had Isolated cleft of the Ala. All were treated by a rotation flap of the Ala with good results with the longest follow up of 14Yrs. The authors have emphasised the rarity of the condition and presented a simple surgical procedure for correction. In the opinion of the authors this very simple procedure which can be performed by the junior surgeon gives a good long term result in the management of cleft Ala.

  10. ALA-PDT mediated DC vaccine for skin squamous cell carcinoma

    Science.gov (United States)

    Ji, Jie; Fan, Zhixia; Zhou, Feifan; Wang, Xiaojie; Shi, Lei; Zhang, Haiyan; Wang, Peiru; Yang, Degang; Zhang, Linglin; Wang, Xiuli; Chen, Wei R.

    2015-03-01

    Dendritic cell (DC) based vaccine has emerged as a promising immunotherapy for cancers. However, most DC vaccines so far have only achieved limited success in cancer treatment. Photodynamic therapy (PDT), an established cancer treatment strategy, can cause immunogenic apoptosis to induce an effective antitumor immune response. In this study, we developed a DC-based cancer vaccine using immunogenic apoptotic tumor cells induced by 5-aminolevulinic acid (ALA) mediated PDT. The maturation of DCs induced by PDT-treated apoptotic cells was evaluated. The anti-tumor immunity of ALA-PDT-DC vaccine was tested with mouse model. We observed the maturations of DCs potentiated by ALA-PDT treated tumor cells, including phenotypic maturation (upregulation of surface expression of MHC-II, DC80, and CD86), and functional maturation (enhanced capability to secret INF-Υ and IL-12). ALA-PDT-DC vaccine mediated by apoptotic cells provided protection against tumor in mice, far stronger than that of DC vaccine obtained from freeze/thaw treated tumor cells. Our results indicate that immunogenic apoptotic tumor cells can be more effective in enhancing DC-based cancer vaccine, which could improve the clinical application of PDT- DC vaccines.

  11. Alpid, kiviktaimla sünnikodu / Terje Alas

    Index Scriptorium Estoniae

    Alas, Terje

    2006-01-01

    Terje Alas Rehemaa aiandus- ja käsitöötalust vahendab muljeid Shveitsi alpi-botaanikaaiast Botanischer Garten Alpinum Schatzalp. Rajajateks Hans Lichtenhahn, Max ja Hans Frei. Nõuandeid alpiaia rajamiseks

  12. Improve efficacy of topical ALA-PDT by calcipotriol through up-regulation of coproporphyrinogen oxidase.

    Science.gov (United States)

    Yang, Deng-Fu; Chen, Jia-Haur; Chiang, Chun-Pin; Huang, Zheng; Lee, Jeng-Woei; Liu, Chung-Ji; Chang, Junn-Liang; Hsu, Yih-Chih

    2014-09-01

    Topical 5-aminolevulinic acid-mediated photodynamic therapy (topical ALA-PDT) is effective for treating oral precancerous lesions. The aim of this in vivo and in vitro study was to examine whether the efficacy of topical ALA-PDT could be further improved by calcipotriol (CAL). Precancerous lesions in the buccal pouch of hamsters were induced by dimethylbenz(a)anthracene (DMBA). Lesions were treated with multiple topical ALA-PDT with or without CAL pretreatment. ALA-induced protoporphyrine IX (PpIX) was monitored by in situ fluorescence measurement. The effect of CAL on heme-related enzymes (CPOX, PPOX, and FECH) were examined in an in vitro model using human squamous cell carcinoma (SCC) cells (SCC4, SAS) using Western blots. Fluorescence spectroscopy revealed that PpIX reached its peak level in precancerous epithelial cells of buccal pouch at 2.5 or 3.5h without or with CAL pretreatment, respectively. Both treatment regimens showed similar response rates, but the complete response was achieved after 5 times of ALA-PDT and 3 times of CAL-ALA-PDT (plevel. Topical CAL can improve the efficacy of ALA-PDT in treating precancerous lesions, likely through the increase in CPOX level and in PpIX production. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Conversion of the agent-oriented domain-specific language ALAS into JavaScript

    Science.gov (United States)

    Sredojević, Dejan; Vidaković, Milan; Okanović, Dušan; Mitrović, Dejan; Ivanović, Mirjana

    2016-06-01

    This paper shows generation of JavaScript code from code written in agent-oriented domain-specific language ALAS. ALAS is an agent-oriented domain-specific language for writing software agents that are executed within XJAF middleware. Since the agents can be executed on various platforms, they must be converted into a language of the target platform. We also try to utilize existing tools and technologies to make the whole conversion process as simple as possible, as well as faster and more efficient. We use the Xtext framework that is compatible with Java to implement ALAS infrastructure - editor and code generator. Since Xtext supports Java, generation of Java code from ALAS code is straightforward. To generate a JavaScript code that will be executed within the target JavaScript XJAF implementation, Google Web Toolkit (GWT) is used.

  14. Properties of myelin altered peptide ligand cyclo(87-99)(Ala91,Ala96)MBP87-99 render it a promising drug lead for immunotherapy of multiple sclerosis.

    Science.gov (United States)

    Deraos, George; Rodi, Maria; Kalbacher, Hubert; Chatzantoni, Kokona; Karagiannis, Fotios; Synodinos, Loukas; Plotas, Panayiotis; Papalois, Apostolos; Dimisianos, Nikolaos; Papathanasopoulos, Panagiotis; Gatos, Dimitrios; Tselios, Theodore; Apostolopoulos, Vasso; Mouzaki, Athanasia; Matsoukas, John

    2015-08-28

    Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system, and it has been established that autoreactive T helper (Th) cells play a crucial role in its pathogenesis. Myelin basic protein (MBP) epitopes are major autoantigens in MS, and the sequence MBP87-99 is an immunodominant epitope. We have previously reported that MBP87-99 peptides with modifications at principal T-cell receptor (TCR) contact sites suppressed the induction of EAE symptoms in rats and SJL/J mice, diverted the immune response from Th1 to Th2 and generated antibodies that did not cross react with the native MBP protein. In this study, the linear and cyclic analogs of the MBP87-99 epitope, namely linear (Ala91,Ala96)MBP87-99 (P2) and cyclo(87-99)(Ala91,Ala96)MBP87-99 (P3), were evaluated for their binding to HLA-DR4, stability to lysosomal enzymes, their effect on cytokine secretion by peripheral blood mononuclear cells (PBMC) derived from MS patients or healthy subjects (controls), and their effect in rat EAE. P1 peptide (wild-type, MBP87-99) was used as control. P2 and P3 did not alter significantly the cytokine secretion by control PBMC, in contrast to P1 that induced moderate IL-10 production. In MS PBMC, P2 and P3 induced the production of IL-2 and IFN-γ, with a simultaneous decrease of IL-10, whereas P1 caused a reduction of IL-10 secretion only. The cellular response to P3 indicated that cyclization did not affect the critical TCR contact sites in MS PBMC. Interestingly, the cyclic P3 analog was found to be a stronger binder to HLA-DR4 compared to linear P2. Moreover, cyclic P3 was more stable to proteolysis compared to linear P2. Finally, both P2 and P3 suppressed EAE induced by an encephalitogenic guinea pig MBP74-85 epitope in Lewis rats whereas P1 failed to do so. In conclusion, cyclization of myelin altered peptide ligand (Ala91,Ala96)MBP87-99 improved binding affinity to HLA-DR4, resistance to proteolysis and antigen-specific immunomodulation

  15. Preparation and preliminary evaluation of 99Tcm-HYNIC-β-Ala-BBN(7-14)NH2

    International Nuclear Information System (INIS)

    Quan Xin; Zhang Yan; Jia Bing; Shi Jiyun; Wang Fan; Zhao Huiyun; Yu Zilin

    2007-01-01

    99 Tc m -HYNIC-β-Ala-BBN(7-14)NH 2 is prepared by choosing Tricine and EDDA as coligands, and the in vitro stability and biodistribution are compared for the two compounds. The results of ITLC and HPLC analyses show that the labeling yield of both compounds is >95%, and the radiochemical purity (RCP) after purification of Sep-Pak C-18 cartridge is >99%. Both of the compounds show pretty good stability in saline and fetal bovine serum, but cysteine challenge assay shows that the stability of 99 Tc m -HYNIC(EDDA)- β-Ala-BBN (7-14) NH 2 is much better than 99 Tc m -HYNIC (Tricine)-β-Ala-BBN (7-14) NH 2 , with the RCP is >95% and 99 Tc m HYNIC (EDDA)-βAla-BBN (7-14)NH 2 and 99 Tc m -HYNIC (Tricine)-β-Ala-BBN(7-14)NH 2 is defined as two-compartment model, with T 1/2α calculated to be 0.27 min and 1.55 min, and T 1/2β calculated to be 18.1 min and 29.7 min, respectively. Biodistribution reveals that the radio uptake of 99 Tc m -HYNIC(Tricine)-β-Ala-BBN(7-14)NH 2 is higher than that of 99 Tc m -HYNIC(EDDA)-β-Ala-BBN(7-14)NH 2 for all of tis- sues at all time points of the experiment. The uptake in kidneys for both compounds is relatively high, as the uptake in livers and intestines for 99 Tc m -HYNIC(Tricine)-β-Ala-BBN(7- 14)NH 2 is significantly higher than that for 99 Tc m -HYNIC(EDDA)-β-Ala-BBN(7-14)NH 2 , which means that 99 Tc m -HYNIC(EDDA)-β-Ala-BBN(7-14)NH 2 is mainly excreted through kidneys, while 99 Tc m -HYNIC(Tricine)-β-Ala-BBN(7-14)NH 2 is excreted through both kidneys and hepatobiliary system. The above data demonstrate that 99 Tc m -HYNIC(EDDA)-β- Ala-BBN(7-14)NH 2 possesses better chemical and biological properties. (authors)

  16. ALA glossary of library and information science

    CERN Document Server

    Levine-Clark, Michael

    2013-01-01

    This fourth edition of ALA Glossary of Library and Information Science presents a thorough yet concise guide to the specific words that describe the materials, processes and systems relevant to the field of librarianship.

  17. The Caenorhabditis elegans interneuron ALA is (also) a high-threshold mechanosensor.

    Science.gov (United States)

    Sanders, Jarred; Nagy, Stanislav; Fetterman, Graham; Wright, Charles; Treinin, Millet; Biron, David

    2013-12-17

    To survive dynamic environments, it is essential for all animals to appropriately modulate their behavior in response to various stimulus intensities. For instance, the nematode Caenorhabditis elegans suppresses the rate of egg-laying in response to intense mechanical stimuli, in a manner dependent on the mechanosensory neurons FLP and PVD. We have found that the unilaterally placed single interneuron ALA acted as a high-threshold mechanosensor, and that it was required for this protective behavioral response. ALA was required for the inhibition of egg-laying in response to a strong (picking-like) mechanical stimulus, characteristic of routine handling of the animals. Moreover, ALA did not respond physiologically to less intense touch stimuli, but exhibited distinct physiological responses to anterior and posterior picking-like touch, suggesting that it could distinguish between spatially separated stimuli. These responses required neither neurotransmitter nor neuropeptide release from potential upstream neurons. In contrast, the long, bilaterally symmetric processes of ALA itself were required for producing its physiological responses; when they were severed, responses to stimuli administered between the cut and the cell body were unaffected, while responses to stimuli administered posterior to the cut were abolished. C. elegans neurons are typically classified into three major groups: sensory neurons with specialized sensory dendrites, interneurons, and motoneurons with neuromuscular junctions. Our findings suggest that ALA can autonomously sense intense touch and is thus a dual-function neuron, i.e., an interneuron as well as a novel high-threshold mechanosensor.

  18. A facile synthesis of. delta. -aminolevulinic acid (ALA) regio-selectively labeled with sup 13 C and direct observation of enzymatic transformation from ALA to porphobilinogen (PBG)

    Energy Technology Data Exchange (ETDEWEB)

    Kurumaya, Katsuyuki; Okazaki, Takeo; Seido, Nobuo; Akasaka, Yuzuru; Kawajiri, Yoshiki; Kajiwara, Masahiro (Meiji College of Pharmacy, Tokyo (Japan)); Kondo, Masao (Institute of Public Health, Tokyo (Japan))

    1989-02-01

    {delta}-Aminolevulinic acid (ALA), labeled with {sup 13}C at position 1, 2, 3, 4, or 5, was synthesized from {sup 13}C-labeled glycine, Meldrum's acid, or bromoacetate. The latter compounds were prepared from {sup 13}C-sodium acetate or {sup 13}C-acetic acid. Enzymatic transformation from ALA to porphobilinogen (PBG) was directly observed by {sup 13}C-NMR. (author).

  19. Vibrational and chiroptical spectroscopic characterization of gamma-turn model cyclic tetrapeptides containing two beta-Ala residues.

    Science.gov (United States)

    Vass, Elemér; Majer, Zsuzsa; Kohalmy, Krisztina; Hollósi, Miklós

    2010-08-01

    The optical spectroscopic characterization of gamma-turns in solution is uncertain and their distinction from beta-turns is often difficult. This work reports systematic ECD and vibrational circular dichroism (VCD) spectroscopic studies on gamma-turn model cyclic tetrapeptides cyclo(Ala-beta-Ala-Pro-beta-Ala) (1), cyclo(Pro-beta-Ala-Pro-beta-Ala) (2) and cyclo(Ala-beta-Ala-Ala-beta-Ala) (3). Conformational analysis performed at the 6-31G(d)/B3LYP level of theory using an adequate PCM solvent model predicted one predominant conformer for 1-3, featuring two inverse gamma-turns. The ECD spectra in ACN of 1 and 2 are characterized by a negative n-->pi* band near 230 nm and a positive pi-->pi* band below 200 nm with a long wavelength shoulder. The ECD spectra in TFE of 1-3 show similar spectra with blue-shifted bands. The VCD spectra in ACN-d(3) of 1 and 2 show a +/-/+/- amide I sign pattern resulting from four uncoupled vibrations in the case of 1 and a sequence of two positive couplets in the case of 2. A -/+/+/- amide I VCD pattern was measured for 3 in TFE-d(2). All three peptides give a positive couplet or couplet-like feature (+/-) in the amide II region. VCD spectroscopy, in agreement with theoretical calculations revealed that low frequency amide I vibrations (at approximately 1630 cm(-1) or below) are indicative of a C(7) H-bonded inverse gamma-turns with Pro in position 2, while gamma-turns encompassing Ala absorb at higher frequency (above 1645 cm(-1)). Copyright 2010 Wiley-Liss, Inc.

  20. Structural, Mechanical, Anisotropic, and Thermal Properties of AlAs in oC12 and hP6 Phases under Pressure

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2018-05-01

    Full Text Available The structural, mechanical, anisotropic, and thermal properties of oC12-AlAs and hP6-AlAs under pressure have been investigated by employing first-principles calculations based on density functional theory. The elastic constants, bulk modulus, shear modulus, Young’s modulus, B/G ratio, and Poisson’s ratio for oC12-AlAs and hP6-AlAs have been systematically investigated. The results show that oC12-AlAs and hP6-AlAs are mechanically stable within the considered pressure. Through the study of lattice constants (a, b, and c with pressure, we find that the incompressibility of oC12-AlAs and hP6-AlAs is the largest along the c-axis. At 0 GPa, the bulk modulus B of oC12-AlAs, hP6-AlAs, and diamond-AlAs are 76 GPa, 75 GPa, and 74 Gpa, respectively, indicating that oC12-AlAs and hP6-AlAs have a better capability of resistance to volume than diamond-AlAs. The pressure of transition from brittleness to ductility for oC12-AlAs and hP6-AlAs are 1.21 GPa and 2.11 GPa, respectively. The anisotropy of Young’s modulus shows that oC12-AlAs and hP6-AlAs have greater isotropy than diamond-AlAs. To obtain the thermodynamic properties of oC12-AlAs and hP6-AlAs, the sound velocities, Debye temperature, and minimum thermal conductivity at considered pressure were investigated systematically. At ambient pressure, oC12-AlAs (463 K and hP6-AlAs (471 K have a higher Debye temperature than diamond-AlAs (433 K. At T = 300 K, hP6-AlAs (0.822 W/cm·K−1 has the best thermal conductivity of the three phases, and oC12-AlAs (0.809 W/cm·K−1 is much close to diamond-AlAs (0.813 W/cm·K−1.

  1. Stanovení celkového obsahu bílkovin, polyfenolů a sacharidů v pivu

    OpenAIRE

    Dostálová, Blanka

    2016-01-01

    Diplomová práce se zabývá analýzami 65 různých piv se zaměřením na nalezení rozdílů mezi českými výčepními pivy, českými ležáky, českými speciálními pivy a zahraničními pivy. U českých piv byly porovnány výsledky analýz mezi skupinou piv nesoucí označení „České pivo“ a mezi skupinou piv bez tohoto označení. V pivech byl stanovován celkový obsah bílkovin, polyfenolů a sacharidů pomocí UV-VIS spektrometrie. V literární rešerši byla popsána historie vaření piva, charakter a druhy českého piva a ...

  2. Surviving the Tremors: ALA in San Francisco.

    Science.gov (United States)

    Wilson Library Bulletin, 1992

    1992-01-01

    Reports on the American Library Association (ALA) 1992 Annual Conference. Highlights include awards given; libraries' futures; bibliographic instruction; NREN (National Research and Education Network); telecommunications; lack of status in librarianship; proposed guidelines for patron behavior; interlibrary loan; the Americans with Disabilities…

  3. Topical application of ALA PDT for the treatment of moderate to severe acne vulgaris

    Science.gov (United States)

    Wang, Xiu-Li; Wang, Hong-Wei; Zhang, Ling-Lin; Su, Lina; Guo, Ming-Xia; Huang, Zheng

    2009-06-01

    Objectives: To evaluate the effectiveness of topical 5-aminolevulinic acid (ALA)- medicated photodynamic therapy (ALA PDT) for the treatment of moderate to severe acne vulgaris. Methods: Sixteen Chinese patients with moderate to severe facial acne were treated with 1-3 courses of ALA PDT. ALA cream (3%) was freshly prepared and applied to acne lesions for 3-4 h. The lesions were irradiated by a 635 nm diode laser at dose levels of 60 - 80 J/cm2 at 100 mW/cm2. Clinical assessments were conducted before and after treatment up to 3 months. Results: All patents showed response to ALA PDT. Complete clearance was seen in 10 patients (62.5%) and partial clearance in 6 patients (37.5%). One case showed recurrence after complete clearance at 2 months and another two showed recurrence after complete clearance at 3 months. However, the number of new lesions were significantly reduced. Adverse effects were minimal. Conclusions: The results of this preliminary clinical study is encouraging. ALA PDT is a simple, safe and useful therapeutic option for the treatment of moderate to severe acne. Further studies to evaluate the treatment with a larger number of patients and for a longer period of follow-up are needed.

  4. Combination therapies in adjuvant with topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

    Science.gov (United States)

    Yang, Deng-Fu; Hsu, Yih-Chih

    2012-03-01

    In Taiwan, oral cancer has becomes the fastest growth male cancer disease due to the betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of people. In order to eliminate the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch precancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when ALA reached its peak level in the lesional epithelial cells after topical application of ALA gel. We found that ALA reached its peak level in precancerous lesions about 2.5 hrs after topical application of ALA gel. The cancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 150 J/cm2 using LED 635 nm fiber-guided light device. Visual examination demonstrated that adjuvant topical ALA -mediated PDT group has shown better therapeutic results in compared to those of non-adjuvant topical ALA-mediated PDT group for DMBA-induced hamster buccal pouch precancerous lesions.

  5. PPAR2Pro12Ala Polymorphism and Human Health

    Directory of Open Access Journals (Sweden)

    Weimin He

    2009-01-01

    Full Text Available The nuclear hormone receptor peroxisome proliferator activated receptor gamma (PPAR is an important transcription factor regulating adipocyte differentiation, lipid and glucose homeostasis, and insulin sensitivity. Numerous genetic mutations of PPAR have been identified and these mutations positively or negatively regulate insulin sensitivity. Among these, a relatively common polymorphism of PPAR, Pro12Ala of PPAR2, the isoform expressed only in adipose tissue has been shown to be associated with lower body mass index, enhanced insulin sensitivity, and resistance to the risk of type 2 diabetes in human subjects carrying this mutation. Subsequent studies in different ethnic populations, however, have revealed conflicting results, suggesting a complex interaction between the PPAR2 Pro12Ala polymorphism and environmental factors such as the ratio of dietary unsaturated fatty acids to saturated fatty acids and/or between the PPAR2 Pro12Ala polymorphism and genetic factors such as polymorphic mutations in other genes. In addition, this polymorphic mutation in PPAR2 is associated with other aspects of human diseases, including cancers, polycystic ovary syndrome, Alzheimer disease and aging. This review will highlight findings from recent studies.

  6. Tornide väljaku müüriäärse ala tulevik endiselt ebaselge / Askur Alas

    Index Scriptorium Estoniae

    Alas, Askur, 1973-

    2004-01-01

    Tallinna linna ja ehitusfirma Restor vaheline tüli linnamüüri äärse maa täisehitamise suhtes Suurtüki kvartalis pole lahendust leidnud. Linnaosavalitsus soovib müüri äärde parki ja tahab algatada ala detaiplaneeringut. Restoril on Plate ja Eppingi torni vahel ridaelamuboksid juba välja ehitatud

  7. Harnessing cellular differentiation to improve ALA-based photodynamic therapy in an artificial skin model

    Science.gov (United States)

    Maytin, Edward; Anand, Sanjay; Sato, Nobuyuki; Mack, Judith; Ortel, Bernhard

    2005-04-01

    During ALA-based photodynamic therapy (PDT), a pro-drug (aminolevulinic acid; ALA) is taken up by tumor cells and metabolically converted to a photosensitizing intermediate (protoporphyrin IX; PpIX). ALA-based PDT, while an emerging treatment modality, remains suboptimal for most cancers (e.g. squamous cell carcinoma of the skin). Many treatment failures may be largely due to insufficient conversion of ALA to PpIX within cells. We discovered a novel way to increase the conversion of ALA to PpIX, by administering agents that can drive terminal differentiation (i.e., accelerate cellular maturation). Terminally-differentiated epithelial cells show higher levels of intracellular PpIX, apparently via increased levels of a rate-limiting enzyme, coproporphyrinogen oxidase (CPO). To study these mechanisms in a three-dimensional tissue, we developed an organotypic model that mimics true epidermal physiology in a majority of respects. A line of rat epidermal keratinocytes (REKs), when grown in raft cultures, displays all the features of a fully-differentiated epidermis. Addition of ALA to the culture medium results in ALA uptake and PpIX synthesis, with subsequent death of keratinocytes upon exposure to blue light. Using this model, we can manipulate cellular differentiation via three different approaches. (1) Vitamin D, a hormone that enhances keratinocyte differentiation; (2) Hoxb13, a nuclear transcription factor that affects the genetically-controlled differentiation program of stratifying cells (3) Hyaluronan, an abundant extracellular matrix molecule that regulates epidermal differentiation. Because the raft cultures contain only a single cell type (no blood, fibroblasts, etc.) the effects of terminal differentiation upon CPO, PpIX, and keratinocyte cell death can be specifically defined.

  8. 0.5% Liposome-encapsulated 5-aminolevulinic acid (ALA) photodynamic therapy for acne treatment.

    Science.gov (United States)

    An, Jee-Soo; Kim, Jeong-Eun; Lee, Dong-Hun; Kim, Byung-Yoon; Cho, Soyun; Kwon, In-Ho; Choi, Won-Woo; Kang, Seong-Min; Won, Chong-Hyun; Chang, Sung-Eun; Lee, Mi-Woo; Choi, Jee-Ho; Moon, Kee-Chan

    2011-02-01

    Photodynamic therapy using topical 5-aminolevulinic acid (ALA) has been successful in treating acne vulgaris, but sun avoidance for at least 48 hours after treatment is necessary due to the risk of post-treatment photosensitivity. Recently, a lower concentration of liposome-encapsulated 5-ALA was introduced to minimize this risk. To evaluate the efficacy and safety of liposome-encapsulated 0.5% 5-ALA in the photodynamic therapy of inflammatory acne and its effects on sebum secretion in Asian skin. Thirteen Korean subjects with inflammatory acne were administered 0.5% ALA spray before photoradiation treatment. Photoradiation was performed at 3.5-6.0 J/cm(2) three times during each of two visits, performed 2 weeks apart. Improvement of acne was evaluated subjectively and objectively based on the Korean Acne Grading System. Sebum secretion was measured quantitatively at each visit. The mean reduction in acne grade at the end of the treatment was 43.2%. Of the patients, 69.2% reported improvements in subjective skin oiliness, but fewer showed objective reductions in sebum secretion as determined by the Sebumeter® SM10. No serious adverse events were observed. Photodynamic therapy using liposome-encapsulated 0.5% 5-ALA improved inflammatory acne with minimal side effects in Asians.

  9. PENGARUH KARAKTERISTIK INDIVIDU TERHADAP SIKAP GOOD FORESTRY GOVERNANCE DI TAMAN NASIONAL ALAS PURWO (The influence of individual characteristic toward attitude to Good Forestry Governance in Alas Purwo National Park

    Directory of Open Access Journals (Sweden)

    Tri Atmojo

    2013-07-01

    Full Text Available ABSTRAK Organisasi taman nasional di Indonesia mengalami berbagai permasalahan di berbagai simpul dan membutuhkan upaya perbaikan kelembagaan. Salah satu upaya pembenahan adalah perbaikan aspek perilaku organisasi yang mengarah kepada pembentukan good forestry governance. Penelitian ini bertujuan mendapatkan data dan penjelasan mengenai pengaruh karakteristik individu orang-orang yang bekerja di Taman Nasional (TN Alas Purwo terhadap sikap good forestry governance (GFG. Penelitian ini dilaksanakan di TN Alas Purwo pada bulan November-Desember 2011 dengan menggunakan metode kuantitatif. Responden diambil secara purposive sampling terhadap personel TN Alas Purwo. Analisis data menggunakan uji regresi sederhana. Hasil penelitian menunjukkan karakteristik individu berpengaruh terhadap sikap good forestry governance. Persamaan regresi yang dihasilkan adalah GFG = 27,449 + 0,463 KI dengan nilai adjusted R2 0,287. Manajemen TN Alas Purwo perlu menaikan kualitas karakteristik individu personel taman nasional dengan melakukan berbagai tindakan manajemen. Implikasi disain organisasi yang tepat untuk tindakan manajemen ini adalah struktur organisasi organik. ABSTRACT In Indonesia, most of national parks have encountered several problems, which need efforts to improve their management. good forestry governance (GFG is one conceptualisation that can be used to improve aspects of organizational behavior in the management of conservation areas. In this research, we obtain data and explanation about influence of the individual characteristic (KI of Alas Purwo National Park with GFG attitude. Using quantitative methods, this study was conducted between November-December  2011. The respondents were staff of Alas Purwo National Park who taken by purposively. We perform data analysis with a simple regression test. The results indicate that the GFG attitude affected individual characteristic. The model is GFG attitude = 27.449 + 0.463 KI with adjusted R2 0,287. We

  10. Growth optimization and characterization of high mobility two-dimensional electron systems in AlAs quantum wells

    Energy Technology Data Exchange (ETDEWEB)

    Dasgupta, Shivaji

    2009-02-15

    In this work two-dimensional electron systems (2DESs) based on AlAs/AlGaAs heterostructures doped with Si are investigated. The electrons are confined in AlAs quantum wells (QWs) sandwiched between AlGaAs buffers. Analytical calculations and simulations for AlAs QWs are presented in the first chapter. The results show a cross-over width, above which the wide (001)-oriented QWs show double valley occupancy and wide (110)-oriented QWs show single valley occupancy. We solve the Schroedinger equation analytically for anisotropic masses. The solution shows the orientation dependence of the elliptical cyclotron orbit due to the anisotropic mass. We also present an introduction to the Landau level crossings based on g{sup *}m{sup *} product. In the next chapter, we present experimental results for the double-valley (001)-oriented AlAs QWs. We present the different structures of the deep AlAs QWs along with the low temperature magnetotransport data for these QWs. Thereafter, we present the results on shallow AlAs QWs. We achieved a mobility of 4.2 x 10{sup 5} cm{sup 2}/Vs at 330 mK for the deep backside doped AlAs QW. For the shallow QWs, we achieved a mobility of2.3 x 10{sup 5} cm{sup 2}/Vs at 330 mK, for a density of 2.9 x 10{sup 11} cm{sup -2}. From the magneto-transport data, we see evidence of the double-valley occupation for the (001)-oriented AlAs wide QWs. In the next chapter, we present experimental results for the single-valley (110)-oriented AlAs QWs. We deduced the donor binding energy and the doping efficiency for this facet from a doping series of double-sided doped QWs. Thereafter, we designed different structures for the (110)-oriented AlAs QWs, which we present along with their respective low temperature magneto-transport data. We measured one of the double-sided doped AlAs QWs at very high magnetic fields and low temperatures, down to 60 mK. At the end of the chapter, we present a spike feature observed in the magneto-transport data of these QWs. This

  11. D2-Thr92Ala, thyroid hormone levels and biochemical hypothyroidism in preeclampsia.

    Science.gov (United States)

    Procopciuc, Lucia Maria; Caracostea, Gabriela; Hazi, Georgeta; Nemeti, Georgiana; Stamatian, Florin

    2017-02-01

    To identify if there is a relationship between the deiodinase D2-Thr92Ala genetic variant, thyroid hormone levels and biochemical hypothyroidism in preeclampsia. We genotyped 125 women with preeclampsia and 131 normal pregnant women using PCR-RFLP. Serum thyroid hormone levels were determined using ELISA. Our study showed higher TSH and FT4 levels and lower FT3 levels in women with preeclampsia compared to normal pregnant women, with statistical significance for women with mild and severe preeclampsia. The risk to develop pregnancy-induced hypertension (PIH), mild or severe preeclampsia was increased in carriers of at least one D2-Ala92 allele. TSH and FT4 levels were significantly higher and FT3 levels were significantly lower in preeclamptic women with severe preeclampsia if they carried the D2-Ala92 allele compared to non-carriers. Pregnant women with PIH and mild preeclampsia, carriers of at least one D2-Ala92 allele, delivered at lower gestational age neonates with a lower birth weight compared to non-carriers, but the results were statistically significant only in severe preeclampsia. The D2-Thr92Ala genetic variant is associated with the severity and the obstetric outcome of preeclampsia, and it also influences thyroid hormone levels. The study demonstrates non-thyroidal biochemical hypothyroidism - as a result of deiodination effects due to D2 genotypes.

  12. Functional characterization of the Thr946Ala SNP at the type 1 diabetes IFIH1 locus.

    Science.gov (United States)

    Zouk, Hana; Marchand, Luc; Li, Quan; Polychronakos, Constantin

    2014-02-01

    The Thr allele at the Thr946Ala non-synonymous single-nucleotide polymorphism (nsSNP) in the IFIH1 gene confers risk for type 1 diabetes (T1D). IFIH1 binds viral double-stranded RNA (dsRNA), inducing a type I interferon (IFN) response. Reports of this nsSNP's role in IFIH1 expression regulation have produced conflicting results and a study evaluating transfected Thr946Ala protein alleles in an artificial system overexpressing IFIH1 shows that the SNP does not affect IFH1 function. In this study, we examine the effects of the Thr946Ala polymorphism on IFN-α response in a cell line that endogenously expresses physiological levels of IFIH1. Eleven lymphoblastoid cell lines (LCLs) homozygous for the major predisposing allele (Thr/Thr) and 6 LCLs homozygous for the minor protective allele (Ala/Ala) were electroporated with the viral dsRNA mimic, poly I:C, in three independent experiments. Media were collected 24 hours later and measured for IFN-α production by ELISA. Basal IFN response is minimal in mock-transfected cells from both genotypes and increases by about 8-fold in cells treated with poly I:C. LCLs with the Ala/Ala genotype have slightly higher IFN-α levels than their Thr/Thr counterparts but this did not reach statistical significance because of the large variability of the IFN response, due mostly to two high outliers (biological, not technical). A larger sample size would be needed to determine whether the Thr946Ala SNP affects the poly I:C-driven IFN-α response. Additionally, the possibility that this nsSNP recognizes viral dsRNA specificities cannot be ruled out. Thus, the mechanism of the observed association of this SNP with T1D remains to be determined.

  13. Potentiation of ALA-PDT antitumor activity in mice using topical DMXAA

    Science.gov (United States)

    Marrero, Allison; Sunar, Ulas; Sands, Theresa; Oseroff, Allan; Bellnier, David

    2009-06-01

    Photodynamic treatment of subcutaneously implanted Colon 26 tumors in BALB/c mice using the aminolevulinic acid (ALA)-induced photosensitizer protoporphyrin IX (PpIX) was shown to be enhanced by the addition of the vascular disrupting agent 5,6-Dimethylxanthenone-4-acetic-acid (DMXAA; Novartis ASA404). DMXAA increases vascular permeability and decreases blood flow in both murine and human tumors. Sufficiently high parenteral DMXAA doses can lead to tumor collapse and necrosis. We have previously reported marked enhancement of antitumor activity when PDT, using either Photofrin or HPPH, is combined with low-dose intraperitoneal DMXAA. We now describe the first attempt to combine topically-applied DMXAA with PDT. For this, DMXAA was applied two hours before PpIX-activating light delivery. PDT with ALA-PDT alone (ALA 20%; 80 J/cm2 delivered at 75 mW/cm2) caused a 39% decrease in tumor volume compared to unirradiated controls. Addition of topical DMXAA to ALA-PDT resulted in a 74% reduction in tumor volume. Diffuse correlation spectroscopy (DCS), a non-invasive blood flow imaging method, is being used to understand the mechanism of this effect and to aid in the proper design of the therapy. For instance, our most recent DCS data suggests that the 2-hour interval between the DMXAA and light applications may not be optimum. This preliminary study suggests a potential role for topical DMXAA in combination with PDT for dermatologic tumors.

  14. Fluorescence spectroscopy of gastrointestinal tumors using δ-ALA

    Science.gov (United States)

    Borisova, E. G.; Vladimirov, B. G.; Angelov, I. G.; Avramov, L. A.

    2007-03-01

    In the recent study delta-aminolevulinic acid/Protoporphyrin IX (δ-ALA/PpIX) is used as fluorescent marker for dysplasia and tumor detection in esophagus and stomach. The δ-ALA is administered per os six hours before measurements at dose 20mg/kg weight. High-power light-emitting diode at 405 nm is used as an excitation source. Special opto-mechanical device is built to use the light guide of standard video-endoscopic system (Olimpus Corp.). Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer (USB4000, OceanOptics Inc.). The fluorescence detected from tumor sites has very complex spectral origins. It consists of autofluorescence, fluorescence from exogenous fluorophores and re-absorption from the chromophores accumulated in the tissue investigated. Mucosa autofluorescence lies at 450-600 nm region. The fluorescence of PpIX is clearly pronounced at the 630-710 nm region. Deep minima in the tumor fluorescence signals are observed in the region 540-575 nm, related to hemoglobin re-absorption. Such high hemoglobin content is an indication of the tumors neovascularisation and it is clearly pronounced in all dysplastic and tumor sites investigated. The lack of fluorescence peaks in the red spectral area for normal mucosa is an indication for selective accumulation of δ-ALA/PpIX only in abnormal sites and gives high contrast when lesion borders are determined from clinicians during video observation in the process of diagnostic procedure. Very good correlation between fluorescence signals and histology examination results of the lesions investigated is achieved.

  15. Characterization of the Ala62Pro polymorphic variant of human cytochrome P450 1A1 using recombinant protein expression

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Heon; Kang, Sukmo [College of Veterinary Medicine, BK21plus Program for Creative Veterinary Science Research, and Research Institute for Veterinary Science, Seoul National University, Seoul (Korea, Republic of); Dong, Mi Sook [School of Life Sciences and Biotechnology, Korea University, Seoul (Korea, Republic of); Park, Jung-Duck [College of Medicine, Chung-Ang University, Seoul (Korea, Republic of); Park, Jinseo; Rhee, Sangkee [College of Agriculture of Life Science, Seoul National University, Seoul (Korea, Republic of); Ryu, Doug-Young, E-mail: dyryu@snu.ac.kr [College of Veterinary Medicine, BK21plus Program for Creative Veterinary Science Research, and Research Institute for Veterinary Science, Seoul National University, Seoul (Korea, Republic of)

    2015-06-15

    Cytochrome P450 (CYP) 1A1 is a heme-containing enzyme involved in detoxification of hydrophobic pollutants. Its Ala62Pro variant has been identified previously. Ala62 is located in α-helix A of CYP1A1. Residues such as Pro and Gly are α-helix breakers. In this study, the Ala62Pro variant was characterized using heterologous expression. E. coli expressing the Ala62Pro variant, and the purified variant protein, had lower CYP (i.e. holoenzyme) contents than their wild-type (WT) equivalents. The CYP variant from E. coli and mammalian cells exhibited lower 7-ethoxyresorufin O-dealkylation (EROD) and benzo[a]pyrene hydroxylation activities than the WT. Enhanced supplementation of a heme precursor during E. coli culture did not increase CYP content in E. coli expressing the variant, but did for the WT. As for Ala62Pro, E. coli expressing an Ala62Gly variant had a lower CYP content than the WT counterpart, but substitution of Ala62 with α-helix-compatible residues such as Ser and Val partially recovered the level of CYP produced. Microsomes from mammalian cells expressing Ala62Pro and Ala62Gly variants exhibited lower EROD activities than those expressing the WT or Ala62Val variant. A region harboring α-helix A has interactions with another region containing heme-interacting residues. Site-directed mutagenesis analyses suggest the importance of interactions between the two regions on holoenzyme expression. Together, these findings suggest that the Ala62Pro substitution leads to changes in protein characteristics and function of CYP1A1 via structural disturbance of the region where the residue is located. - Highlights: • Ala62 is located in α-helix A of the carcinogen-metabolizing enzyme CYP1A1. • Pro acts as an α-helix breaker. • A variant protein of CYP1A1, Ala62Pro, had lower heme content than the wild-type. • The variant of CYP1A1 had lower enzyme activities than the wild-type.

  16. Lifelong imbalanced LA/ALA intake impairs emotional and cognitive behavior via changes in brain endocannabinoid system

    Science.gov (United States)

    Zamberletti, Erica; Piscitelli, Fabiana; De Castro, Valentina; Murru, Elisabetta; Gabaglio, Marina; Colucci, Paola; Fanali, Chiara; Prini, Pamela; Bisogno, Tiziana; Maccarrone, Mauro; Campolongo, Patrizia; Banni, Sebastiano; Rubino, Tiziana; Parolaro, Daniela

    2017-01-01

    Imbalanced dietary n-3 and n-6 PUFA content has been associated with a number of neurological conditions. Endocannabinoids are n-6 PUFA derivatives, whose brain concentrations are sensitive to modifications of fatty acid composition of the diet and play a central role in the regulation of mood and cognition. As such, the endocannabinoid system appears to be an ideal candidate for mediating the effects of dietary fatty acids on mood and cognition. Lifelong administration of isocaloric α-linolenic acid (ALA)-deficient and -enriched diets induced short-term memory deficits, whereas only dietary ALA enrichment altered emotional reactivity in adult male rats compared with animals fed a standard diet that was balanced in ALA/linoleic acid (LA) ratio. In the prefrontal cortex, both diets reduced 2-AG levels and increased MAG lipase expression, whereas only the enriched diet reduced AEA levels, simultaneously increasing FAAH expression. In the hippocampus, an ALA-enriched diet decreased AEA content and NAPE-PLD expression, and reduced 2-AG content while increasing MAG lipase expression. These findings highlight the importance of a diet balanced in fatty acid content for normal brain functions and to support a link between dietary ALA, the brain endocannabinoid system, and behavior, which indicates that dietary ALA intake is a sufficient condition for altering the endocannabinoid system in brain regions modulating mood and cognition. PMID:27903595

  17. Vanalinna, Kalaranna basseini ja Linnahalli vaheline ala / Villem Tomiste

    Index Scriptorium Estoniae

    Tomiste, Villem, 1975-

    2011-01-01

    Detailplaneeringu koostaja Tallinna Linnaplaneerimise Amet, konsultandid AB Kosmos ja K-Projekt. Projekti peamine eesmärk on tuua linn mere äärde. Selleks on loodud jalakäijate ala, kust voolavad läbi autoteed

  18. Delta-aminolevulinic acid dehydratase (ALAD) polymorphism in lead exposed Bangladeshi children and its effect on urinary aminolevulinic acid (ALA)

    Energy Technology Data Exchange (ETDEWEB)

    Tasmin, Saira, E-mail: rimzim1612@yahoo.com [Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Furusawa, Hana [Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Ahmad, Sk. Akhtar [Department of Occupational and Environmental Health, Bangladesh Institute of Health Sciences, 125/1, Darus Salam, Mirpur, Dhaka 1216 (Bangladesh); Faruquee, M.H. [Department of Public Health, State University of Bangladesh, 77 Satmasjid Road, Dhanmondi, Dhaka 1205 (Bangladesh); Watanabe, Chiho [Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

    2015-01-15

    Background and objective: Lead has long been recognized as a harmful environmental pollutant. People in developing countries like Bangladesh still have a higher risk of lead exposure. Previous research has suggested that the delta-aminolevulinic acid dehydratase (ALAD) genotype can modify lead toxicity and individual susceptibility. As children are more susceptible to lead-induced toxicity, this study investigated whether the ALAD genotype influenced urinary excretion of delta-aminolevulinic acid (U-ALA) among children exposed to environmental lead in Bangladesh. Methods: Subjects were elementary schoolchildren from a semi-urban industrialized area in Bangladesh. A total of 222 children were studied. Blood and urine were collected to determine ALAD genotypes, blood lead levels and urinary aminolevulinic acid (U-ALA). Results: The mean BPb level was 9.7 µg/dl for the study children. BPb was significantly positively correlated with hemoglobin (p<0.01). In total, allele frequency for ALAD 1 and 2 was 0.83 and 0.17 respectively. The mean U-ALA concentration was lower in ALAD1-2/2-2 carriers than ALAD1-1 carriers for boys (p=0.001). But for girls, U-ALA did not differ significantly by genotype (p=0.26). When U-ALA was compared by genotype at the same exposure level in a multiple linear regression analysis, boys who were ALAD1-2/2-2 carriers still had a lower level of U-ALA compared to ALAD1-1carriers. Conclusion: This study provides information about the influence of ALAD polymorphism and its association with U-ALA in Bangladeshi children. Our results indicate that the ALAD1-2/2-2 genotype may have a protective effect in terms of U-ALA for environmentally lead exposed boys. - Highlights: • High blood lead level for the environmentally exposed schoolchildren. • BPb was significantly correlated with U-ALA and Hb. • Effect of ALAD genotype on U-ALA is differed by sex. • Lower U-ALA in ALAD2 than ALAD1 carriers only for boys at same exposure.

  19. Comparsion of light dose on topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

    Science.gov (United States)

    Yang, Deng-Fu; Tseng, Meng-Ke; Liu, Chung-Ji; Hsu, Yih-Chih

    2012-03-01

    Oral cancer has becomes the most prominent male cancer disease due to the local betel nut chewing habit combing with smoking and alcohol-drinking lifestyle. In order to minimize the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch cancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 8 to 10 weeks. Precancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA -mediated PDT. We found that ALA reached its peak level in cancerous lesions about 2.5 hrs after topical application of ALA gel. The precancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 75 and 100 J/cm2 using LED 635 nm Wonderlight device. It is suggesting that optimization of the given light dose is critical to the success of PDT results.

  20. Desleucyl-Oritavancin with a Damaged d-Ala-d-Ala Binding Site Inhibits the Transpeptidation Step of Cell-Wall Biosynthesis in Whole Cells of Staphylococcus aureus.

    Science.gov (United States)

    Kim, Sung Joon; Singh, Manmilan; Sharif, Shasad; Schaefer, Jacob

    2017-03-14

    We have used solid-state nuclear magnetic resonance to characterize the exact nature of the dual mode of action of oritavancin in preventing cell-wall assembly in Staphylococcus aureus. Measurements performed on whole cells labeled selectively in vivo have established that des-N-methylleucyl-N-4-(4-fluorophenyl)benzyl-chloroeremomycin, an Edman degradation product of [ 19 F]oritavancin, which has a damaged d-Ala-d-Ala binding aglycon, is a potent inhibitor of the transpeptidase activity of cell-wall biosynthesis. The desleucyl drug binds to partially cross-linked peptidoglycan by a cleft formed between the drug aglycon and its biphenyl hydrophobic side chain. This type of binding site is present in other oritavancin-like glycopeptides, which suggests that for these drugs a similar transpeptidase inhibition occurs.

  1. Preclinical Development of a Subcutaneous ALAS1 RNAi Therapeutic for Treatment of Hepatic Porphyrias Using Circulating RNA Quantification

    Directory of Open Access Journals (Sweden)

    Amy Chan

    2015-01-01

    Full Text Available The acute hepatic porphyrias are caused by inherited enzymatic deficiencies in the heme biosynthesis pathway. Induction of the first enzyme 5-aminolevulinic acid synthase 1 (ALAS1 by triggers such as fasting or drug exposure can lead to accumulation of neurotoxic heme intermediates that cause disease symptoms. We have demonstrated that hepatic ALAS1 silencing using siRNA in a lipid nanoparticle effectively prevents and treats induced attacks in a mouse model of acute intermittent porphyria. Herein, we report the development of ALN-AS1, an investigational GalNAc-conjugated RNAi therapeutic targeting ALAS1. One challenge in advancing ALN-AS1 to patients is the inability to detect liver ALAS1 mRNA in the absence of liver biopsies. We here describe a less invasive circulating extracellular RNA detection assay to monitor RNAi drug activity in serum and urine. A striking correlation in ALAS1 mRNA was observed across liver, serum, and urine in both rodents and nonhuman primates (NHPs following treatment with ALN-AS1. Moreover, in donor-matched human urine and serum, we demonstrate a notable correspondence in ALAS1 levels, minimal interday assay variability, low interpatient variability from serial sample collections, and the ability to distinguish between healthy volunteers and porphyria patients with induced ALAS1 levels. The collective data highlight the potential utility of this assay in the clinical development of ALN-AS1, and in broadening our understanding of acute hepatic porphyrias disease pathophysiology.

  2. The plant P4-ATPase ALA2 is involved in flipping of phosphatidylserine analogues

    DEFF Research Database (Denmark)

    Lopez Marques, Rosa Laura

    The plant P4-ATPase ALA2 is involved in flipping of phosphatidylserine analogues Rosa Laura López-Marqués1, Lisbeth Rosager Poulsen1, Katharina Meffert2, Thomas Pomorski2, Michael Gjedde Palmgren1 1Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation...... physiological function.   1 Poulsen, L.R; López-Marqués, R.L et al. (2008) The Arabidopsis P4-ATPase ALA3 localizes to the Golgi and requires a ß-subunit to function in lipid translocation and secretory vesicle formation. The Plant Cell, vol. 20, 658-676. 2 Gomès, E. et al. (2000) Chilling tolerance...... in Arabidopsis involves ALA1, a member of a new family of putative aminophospholipid translocases. The Plant Cell, vol. 12, 2441-2453....

  3. The plant P4-ATPase ALA2 is involved in flipping of phosphatidylserine analogues

    DEFF Research Database (Denmark)

    Poulsen, Lisbeth Rosager

      The plant P4-ATPase ALA2 is involved in flipping of phosphatidylserine analogues Rosa Laura López-Marqués1, Lisbeth Rosager Poulsen1, Katharina Meffert2, Thomas Pomorski2, Michael Gjedde Palmgren1 1Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation...... physiological function.   1 Poulsen, L.R; López-Marqués, R.L et al. (2008) The Arabidopsis P4-ATPase ALA3 localizes to the Golgi and requires a ß-subunit to function in lipid translocation and secretory vesicle formation. The Plant Cell, vol. 20, 658-676. 2 Gomès, E. et al. (2000) Chilling tolerance...... in Arabidopsis involves ALA1, a member of a new family of putative aminophospholipid translocases. The Plant Cell, vol. 12, 2441-2453....

  4. Modulatory effects of alpha-lipoic acid (ALA) administration on insulin sensitivity in obese PCOS patients.

    Science.gov (United States)

    Genazzani, A D; Shefer, K; Della Casa, D; Prati, A; Napolitano, A; Manzo, A; Despini, G; Simoncini, T

    2018-05-01

    To evaluate the efficacy of alpha-lipoic acid (ALA) administration on hormonal and metabolic parameters of obese PCOS patients. A group of 32 obese PCOS patients were selected after informed consent. 20 patients referred to have first grade relatives with diabetes type I or II. Hormonal and metabolic parameters as well as OGTT were evaluated before and after 12 weeks of ALA integrative administration (400 mg per os every day). ALA administration significantly decreased insulin, glucose, BMI and HOMA index. Hyperinsulinemia and insulin response to OGTT decreased both as maximal response (Δmax) and as AUC. PCOS with diabetes relatives showed the decrease also of triglyceride and GOT. Interestingly in all PCOS no changes occurred on all hormonal parameters involved in reproduction such as LH, FSH, and androstenedione. ALA integrative administration at a low dosage as 400 mg daily improved the metabolic impairment of all PCOS patients especially in those PCOS with familiar diabetes who have a higher grade of risk of NAFLD and predisposition to diabetes.

  5. Proteomics and SSH analyses of ALA-promoted fruit coloration and evidence for the involvement of a MADS-box gene, MdMADS1

    Directory of Open Access Journals (Sweden)

    Xinxin Feng

    2016-11-01

    Full Text Available Skin color is a key quality attribute of fruits and how to improve fruit coloration has long been a major concern. 5-Aminolevulinic acid (ALA, a natural plant growth regulator, can significantly increase anthocyanin accumulation in fruit skin and therefore effectively improve coloration of many fruits, including apple. However, the molecular mechanism how ALA stimulates anthocyanin accumulation in fruit skin remains unknown. Here, we investigated the impact of ALA on apple skin at the protein and mRNA levels. A total of 85 differentially expressed proteins in apple skins between ALA and water treatment (control were identified by complementary gel-based and gel-freeseparation techniques. Most of these differentially expressed proteins were up-regulated by ALA. Function analysis suggested that 87.06% of the ALA-responsive proteins were associated with fruit ripening. To further screen ALA-responsive regulators, we constructed a subtracted cDNA library (tester: ALA treatment; driver: control and obtained 104 differentially expressed unigenes, of which 38 unigenes were indicators for the fruit ripening-related gene. The differentially changed proteins and transcripts did not correspond well at an individual level, but showed similar regulated direction in function at the pathway level. Among the identified fruit ripening-related genes, the expression of MdMADS1, a developmental transcription regulator of fruit ripening, was positively correlated with expression of anthocyanin biosynthetic genes (MdCHS, MdDFR, MdLDOX and MdUFGT in apple skin under ALA treatment. Moreover, overexpression of MdMADS1 enhanced anthocyanin content in transformed apple calli, which was further enhanced by ALA. The anthocyanin content in MdMADS1-silenced calli was less than that in the control with ALA treatment, but higher than that without ALA treatment. These results indicated that MdMADS1 is involved in ALA-induced anthocyanin accumulation. In addition, anthocyanin

  6. The comparison between LAC and ALA

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    Tzu-heng Chiu

    2000-12-01

    Full Text Available A good library association serves its members, improves the librarianship, and helps library institutions achieving their missions. This article describes the history, missions and goals, organization structure, membership, financial sources, professional activities, publication, and website of the Library Association of China (LAC and American Library Association (ALA, respectively. Considering social / cultural / political differences between Taiwan and the United Sates, the author then compares these two library associations from the eight factors mentioned above. At the end, suggestions for the LAC are proposed.[Article content in Chinese

  7. Kampanye Pr Radio Ssfm “Assik Ala Ssfm”

    OpenAIRE

    Putra, Jeffry Septian; Setiabudi, Djoko; Naryoso, Agus

    2013-01-01

    JUDUL : Kampanye PR Radio SSFM “Assik Ala SSFM”NAMA : Jeffry Septian PutraNIM : D2C607024ABSTRAKSIPersaingan radio saat ini semakin ketat, industri media siaran perlu memahamidan mengenali ekspektasi atau apa yang diinginkan para pendengar. Pengelola radioperlu strategi untuk mendapatkan perhatian dari para pendengarnya terlebih dari sisipemasaran yang akan memberikan dampak bagi kelancaran merebut perhatianpendengar. Untuk menciptakan strategi yang tepat dalam membuat mengelola radioagar tet...

  8. DINAMIKA POPULASI MONYET EKOR PANJANG (MACACA FASCICULARIS DI HUTAN WISATA ALAS KEDATON TABANAN

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    I Gede Soma

    2012-11-01

    Full Text Available Overall population dynamic were observed in identified individuals between August andOctober 2008, in large group of long failed macaques in the AlasKedaton, Bali. Totalpopulation was 364 monkeys consisted of 54 (14,8% adult males, 104 (28,6% adultfemales, 164 (45,1% juvenile and 42 (11,5% infant. They were divided into 4 differentsmall social groups i.e., Parking area group, North area group, Centre area group and Southarea group. Ratio of adult male and adult female was 1: 2.Population densitiesof Macaca fascicularisin Alas Kedaton were 30 monkeys / Ha andpopulation natalities were 11, 5%.

  9. Peroxisome proliferator activated receptor gamma polymorphism Pro12Ala in polycystic ovary syndrome (PCOS of South Indian Population

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    Raichel Jacob

    2016-05-01

    Conclusion: PPARγ2 gene Pro12Ala polymorphism was supposed to be susceptible genes in PCOS. The present study demonstrated that there is a statistical difference between the distributions of PPAR gamma Pro12Ala polymorphism in South Indian Population.

  10. Sperm quality after swim up and density gradient centrifugation sperm preparation with supplementation of alpha lipoic acid (ALA): A preliminary study

    Science.gov (United States)

    Lestari, Silvia W.; Lestari, Sarah H.; Pujianto, Dwi A.

    2018-02-01

    Intra uterine insemination (IUI) as one of the treatment for infertility, persists low success rate. A factor that contributes to the unsuccessful of IUI is sperm preparation, performed through Swim-up (SU) and Density Gradient Centrifugation (DGC) methods. Furthermore, studies have shown that Alpha Lipoic Acid (ALA) is a potent antioxidant that could enhance the sperm motility and protect the DNA integrity of the sperm [1]. This study is aimed to re-evaluate the efficiency of the DGC and SU methods in selecting sperm before being transferred for IUI by the supplementation of ALA based on the sperm DNA integrity. Semen samples were obtained from 13 men from partners of women who are infertile (normozoospermia) and underwent IUI. Semen analysis based on the guideline of World Health Organization (WHO) 2010 was performed to measure the sperm motility and velocity, before and after sperm preparation. Then, samples were incubated with Alpha Lipoic Acid (ALA) in 0.625 mg (ALA 1), 1.25 mg (ALA 2) and 2.5 mg (ALA 3). The Sperm Chromatin Dispersion (SCD) test was performed to evaluate the sperm DNA Fragmentation Index (DFI). The percentage of motile sperm was higher in prepared sperm (post-DGC and post-SU) than in whole semen. Furthermore, the percentage of motile sperm was higher in post-DGC compared to post-SU. The level of DFI after the supplementation of ALA was decreased in prepared sperm compared to the whole semen. ALA was proved capable to select the better sperm quality with decreased sperm DNA fragmentation of prepared sperm in the all of DFI category.

  11. Nuclear receptor 5A (NR5A) family regulates 5-aminolevulinic acid synthase 1 (ALAS1) gene expression in steroidogenic cells.

    Science.gov (United States)

    Ju, Yunfeng; Mizutani, Tetsuya; Imamichi, Yoshitaka; Yazawa, Takashi; Matsumura, Takehiro; Kawabe, Shinya; Kanno, Masafumi; Umezawa, Akihiro; Kangawa, Kenji; Miyamoto, Kaoru

    2012-11-01

    5-Aminolevulinic acid synthase 1 (ALAS1) is a rate-limiting enzyme for heme biosynthesis in mammals. Heme is essential for the catalytic activities of P450 enzymes including steroid metabolic enzymes. Nuclear receptor 5A (NR5A) family proteins, steroidogenic factor-1 (SF-1), and liver receptor homolog-1 (LRH-1) play pivotal roles in regulation of steroidogenic enzymes. Recently, we showed that expression of SF-1/LRH-1 induces differentiation of mesenchymal stem cells into steroidogenic cells. In this study, genome-wide analysis revealed that ALAS1 was a novel SF-1-target gene in differentiated mesenchymal stem cells. Chromatin immunoprecipitation and reporter assays revealed that SF-1/LRH-1 up-regulated ALAS1 gene transcription in steroidogenic cells via binding to a 3.5-kb upstream region of ALAS1. The ALAS1 gene was up-regulated by overexpression of SF-1/LRH-1 in steroidogenic cells and down-regulated by knockdown of SF-1 in these cells. Peroxisome proliferator-activated receptor-γ coactivator-1α, a coactivator of nuclear receptors, also strongly coactivated expression of NR5A-target genes. Reporter analysis revealed that peroxisome proliferator-activated receptor-γ coactivator-1α strongly augmented ALAS1 gene transcription caused by SF-1 binding to the 3.5-kb upstream region. Finally knockdown of ALAS1 resulted in reduced progesterone production by steroidogenic cells. These results indicate that ALAS1 is a novel NR5A-target gene and participates in steroid hormone production.

  12. PPARγ Pro12Ala and ACE ID polymorphisms are associated with BMI and fat distribution, but not metabolic syndrome

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    Passaro Angela

    2011-12-01

    Full Text Available Abstract Background Metabolic Syndrome (MetS results from the combined effect of environmental and genetic factors. We investigated the possible association of peroxisome proliferator-activated receptor-γ2 (PPARγ2 Pro12Ala and Angiotensin Converting Enzyme (ACE I/D polymorphisms with MetS and interaction between these genetic variants. Methods Three hundred sixty four unrelated Caucasian subjects were enrolled. Waist circumference, blood pressure, and body mass index (BMI were recorded. Body composition was estimated by impedance analysis; MetS was diagnosed by the NCEP-ATPIII criteria. A fasting blood sample was obtained for glucose, insulin, lipid profile determination, and DNA isolation for genotyping. Results The prevalence of MetS did not differ across PPARγ2 or ACE polymorphisms. Carriers of PPARγ2 Ala allele had higher BMI and fat-mass but lower systolic blood pressure compared with Pro/Pro homozygotes. A significant PPARγ2 gene-gender interaction was observed in the modulation of BMI, fat mass, and blood pressure, with significant associations found in women only. A PPARγ2-ACE risk genotype combination for BMI and fat mass was found, with ACE DD/PPARγ2 Ala subjects having a higher BMI (p = 0.002 and Fat Mass (p = 0.002. Pro12Ala was independently associated with waist circumference independent of BMI and gender. Conclusions Carriers of PPARγ2 Ala allele had higher BMI and fat-mass but not a worse metabolic profile, possibly because of a more favorable adipose tissue distribution. A gene interaction exists between Pro12Ala and ACE I/D on BMI and fat mass. Further studies are needed to assess the contribution of Pro12Ala polymorphism in adiposity distribution.

  13. Challenges for Community-Based Forest Management in the KoloAla Site Manompana

    Science.gov (United States)

    Urech, Zora Lea; Sorg, Jean-Pierre; Felber, Hans Rudolph

    2013-03-01

    Following the IUCN 5th World Congress on Protected Areas in 2003, the then-President of Madagascar decided to increase the area of Madagascar's protected areas from 1.7 to 6 million ha. To combine the aims of protection and timber production, a new concept was developed through the establishment of community-based forest management (CBFM) sites, called KoloAla. However, experience shows that similar management transfers to communities in Madagascar have only been successful in a very few cases. We aimed to explore the success to be expected of this new approach in the particular case of the Manompana corridor at Madagascar's eastern coast. In a first step, the readiness of the corridor's resource users for CBFM has been analysed according to the seven resource users' attributes developed by Ostrom that predict an effective self-organized resource management. In a second step, we explored how KoloAla addresses known challenges of Madagascar's CBFM. Analyses lead in a rather sober conclusion. Although KoloAla attempts to address the goals of poverty alleviation, biodiversity conservation and timber production under a single umbrella, it does so in a rather non-innovative way. Challenges with regard to the state's environmental governance, agricultural inefficiency and thus deforestation remain unsolved.

  14. Evaluation of Partial Cut-out of Sacroiliac Screws From the Sacral Ala Slope via Pelvic Inlet and Outlet View.

    Science.gov (United States)

    Zhang, Jingwei; Hamilton, Ryan; Li, Ming; Ebraheim, Nabil A; He, Xianfeng; Liu, Jiayong; Zhu, Limei

    2015-12-01

    An anatomic and radiographic study of placement of sacroiliac screws. The aim of this study was to quantitatively assess the risk of partial cut-out of sacroiliac screws from the sacral ala slope via inlet and outlet view. The partial cut-out of sacroiliac screws from the superior surface of sacral ala can jeopardize the L5 nerve root, which is difficult to identify on the pelvic inlet and outlet views. Computed tomography images of 60 patients without pelvic ring deformity or injury were used to measure the width (on inlet view) and height (on outlet view) of the sacral ala. The angle of the sacral ala slope was measured on lateral view. According to the measured parameters, the theoretical safe trajectories of screw placement were calculated using inverse trigonometric functions. Under fluoroscopic guidance, a sacroiliac screw was placed close to the midline on both inlet and outlet views, including posterosuperior, posteroinferior, anterosuperior, and anteroinferior regions to the midline. The incidence of screw partial cut-out from the superior surface of sacral ala was identified. The measured widths and heights of the sacral alas were 28.1 ± 2.8 and 29.8 ± 3.1 mm, respectively. The average angle between the superior aspect of the S1 vertebral body and the superior aspect of the sacral ala was 37.2 ± 2.5 degrees. The rate of partial cut-out of the screws from the superior surface of sacral ala slope was 12.5% (5/40) in posterosuperior, 0% (0/40) in posteroinferior, 70% (28/40) in anterosuperior, and 20% (8/40) in anteroinferior. To avoid the risk of partial cut-out from sacroiliac screw placement, more precise description should be added to the conventional description: the sacroiliac screws should be placed at the inferior half portion on outlet view and at the posterior half portion on inlet view. 4.

  15. Association between PPAR-γ2 Pro12Ala genotype and insulin resistance is modified by circulating lipids in Mexican children

    Science.gov (United States)

    Stryjecki, Carolina; Peralta-Romero, Jesus; Alyass, Akram; Karam-Araujo, Roberto; Suarez, Fernando; Gomez-Zamudio, Jaime; Burguete-Garcia, Ana; Cruz, Miguel; Meyre, David

    2016-01-01

    The Pro12Ala (rs1801282) polymorphism in peroxisome proliferator-activated receptor-γ2 (PPAR-γ2) has been convincingly associated with insulin resistance (IR) and type 2 diabetes (T2D) among Europeans, in interaction with a high-fat diet. Mexico is disproportionally affected by obesity and T2D however, whether the Pro12Ala polymorphism is associated with early metabolic complications in this population is unknown. We assessed the association of PPAR-γ2 Pro12Ala with metabolic traits in 1457 Mexican children using linear regression models. Interactions between PPAR-γ2 Pro12Ala and circulating lipids on metabolic traits were determined by adding an interaction term to regression models. We observed a high prevalence of overweight/obesity (49.2%), dyslipidemia (34.9%) and IR (11.1%). We detected nominally significant/significant interactions between lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol), the PPAR-γ2 Pro12Ala genotype and waist-to-hip ratio, fasting insulin, HOMA-IR and IR (9.30 × 10−4  ≤ Pinteraction ≤ 0.04). Post-hoc subgroup analyses evidenced that the association between the PPAR-γ2 Pro12Ala genotype and fasting insulin, HOMA-IR and IR was restricted to children with total cholesterol or LDL-cholesterol values higher than the median (0.02 ≤ P ≤ 0.03). Our data support an association of the Pro12Ala polymorphism with IR in Mexican children and suggest that this relationship is modified by dyslipidemia. PMID:27075119

  16. Effects of Ala-Gln feeding strategies on growth, metabolism, and crowding stress resistance of juvenile Cyprinus carpio var. Jian.

    Science.gov (United States)

    Chen, Xiu-Mei; Guo, Gui-Liang; Sun, Li; Yang, Qiu-Shi; Wang, Gui-Qin; Qin, Gui-Xin; Zhang, Dong-Ming

    2016-04-01

    The present study was conducted to evaluate the effects of different L-alanyl-l-glutamine (Ala-Gln) feeding strategies on the growth performance, metabolism and crowding stress resistance related parameters in juvenile Jian carp (Cyprinus carpio var. Jian) under crowded condition (80 g/L). Juvenile Jian carp (initial weight 26.1 ± 0.6 g) were distributed into five groups which fed with graded concentrations (0% or 1.0%) of Ala-Gln for eight weeks. Control group (I, 0/0) fed with control diet (0% Ala-Gln) throughout the feeding trial. The other four groups employed different control and experimental diet feeding strategies ranging from two weeks control diet fed and two weeks experimental diet (1% Ala-Gln) fed (II, 0/2) to eight weeks experimental diet fed (V, 4/4). Results revealed that Mean weight gain (MEG) under all different feeding strategies of Ala-Gln were significantly higher than that of the control group (p < 0.05), and MEG of group II (201.90%) was even higher than that of group IV (184.70%). Liver glycogen and blood total protein of groups II, III and V were significantly higher than that in groups I and IV (p < 0.05). The highest level of serum thyroxine (10.07 ng/ml), insulin-like growth factor-I (52.40 ng/ml) and insulin (9.73 μ IU/mL) were observed in group V. However, diet supplemented with Ala-Gln did not affect the levels of serum glucose, cortisol and catecholamine in fish. The mRNA expression of GR1a, GR1b and GR2 were also significantly changed in Ala-Gln supplementation groups compared with control group (p < 0.05). After fish intraperitoneally injected with virulent Aeromonas hydrophila, the fish survival rates were significantly increased in all Ala-Gln supplementation groups compared with control group (p < 0.05). Results from the present experiment showed the importance of dietary supplementation of Ala-Gln in benefaction of the growth performance, metabolism and crowding stress resistance in Jian carp breeding. The

  17. Ala from Zeljin: Results of the recent research of folk mythology in Zupa

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    Todorović Ivica

    2011-01-01

    Full Text Available The paper presents the results of the recent ethnological research, conduced in Aleksandrovacka Zupa and other areas. In this paper, the emphasis has been placed on notions on mythical beings, i.e. alas and dragons, which in the context of the materials collected take up one of most prominent positions, indicating the specific nature of the micro-regional unit, but also a symbol of the local identity. Namely, there are recordings of numerous and extremely interesting variations of the myth and ideas on the ala from Zeljin which, as the definitely most exposed mythical entity, is certainly a Zupa-specific property.

  18. 5-ALA Fluorescence Image Guided Resection of Glioblastoma Multiforme: A Meta-Analysis of the Literature

    Directory of Open Access Journals (Sweden)

    Samy Eljamel

    2015-05-01

    Full Text Available Background: Glioblastoma multiforme (GBM is one of the most deadly cancers in humans. Despite recent advances in anti-cancer therapies, most patients with GBM die from local disease progression. Fluorescence image guided surgical resection (FIGR was recently advocated to enhance local control of GBM. This is meta-analyses of 5-aminolevulinic (5-ALA induced FIGR. Materials: Review of the literature produced 503 potential publications; only 20 of these fulfilled the inclusion criteria of this analysis, including a total of 565 patients treated with 5-ALA-FIGR reporting on its outcomes and 800 histological samples reporting 5-ALA-FIGR sensitivity and specificity. Results: The mean gross total resection (GTR rate was 75.4% (95% CI: 67.4–83.5, p < 0.001. The mean time to tumor progression (TTP was 8.1 months (95% CI: 4.7–12, p < 0.001. The mean overall survival gain reported was 6.2 months (95% CI: −1–13, p < 0.001. The specificity was 88.9% (95% CI: 83.9–93.9, p < 0.001 and the sensitivity was 82.6% (95% CI: 73.9–91.9, p < 0.001. Conclusion: 5-ALA-FIGR in GBM is highly sensitive and specific, and imparts significant benefits to patients in terms of improved GTR and TTP.

  19. Structural and functional analysis of the ASM p.Ala359Asp mutant that causes acid sphingomyelinase deficiency.

    Science.gov (United States)

    Acuña, Mariana; Castro-Fernández, Víctor; Latorre, Mauricio; Castro, Juan; Schuchman, Edward H; Guixé, Victoria; González, Mauricio; Zanlungo, Silvana

    2016-10-21

    Niemann-Pick disease (NPD) type A and B are recessive hereditary disorders caused by deficiency in acid sphingomyelinase (ASM). The p.Ala359Asp mutation has been described in several patients but its functional and structural effects in the protein are unknown. In order to characterize this mutation, we modeled the three-dimensional ASM structure using the recent available crystal of the mammalian ASM as a template. We found that the p.Ala359Asp mutation is localized in the hydrophobic core and far from the sphingomyelin binding site. However, energy function calculations using statistical potentials indicate that the mutation causes a decrease in ASM stability. Therefore, we investigated the functional effect of the p.Ala359Asp mutation in ASM expression, secretion, localization and activity in human fibroblasts. We found a 3.8% residual ASM activity compared to the wild-type enzyme, without changes in the other parameters evaluated. These results support the hypothesis that the p.Ala359Asp mutation causes structural alterations in the hydrophobic environment where ASM is located, decreasing its enzymatic activity. A similar effect was observed in other previously described NPDB mutations located outside the active site of the enzyme. This work shows the first full size ASM mutant model describe at date, providing a complete analysis of the structural and functional effects of the p.Ala359Asp mutation over the stability and activity of the enzyme. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Characterization of a TK6-Bcl-xL gly-159-ala Human Lymphoblast Clone

    Energy Technology Data Exchange (ETDEWEB)

    Chyall, L.: Gauny, S.; Kronenberg, A.

    2006-01-01

    TK6 cells are a well-characterized human B-lymphoblast cell line derived from WIL-2 cells. A derivative of the TK6 cell line that was stably transfected to express a mutated form of the anti-apoptotic protein Bcl-xL (TK6-Bcl-xL gly-159- ala clone #38) is compared with the parent cell line. Four parameters were evaluated for each cell line: growth under normal conditions, plating efficiency, and frequency of spontaneous mutation to 6‑thioguanine resistance (hypoxanthine phosphoribosyl transferase locus) or trifluorothymidine resistance (thymidine kinase locus). We conclude that the mutated Bcl-xL protein did not affect growth under normal conditions, plating efficiency or spontaneous mutation frequencies at the thymidine kinase (TK) locus. Results at the hypoxanthine phosphoribosyl transferase (HPRT) locus were inconclusive. A mutant fraction for TK6‑Bcl-xL gly-159-ala clone #38 cells exposed to 150cGy of 160kVp x-rays was also calculated. Exposure to x-irradiation increased the mutant fraction of TK6‑Bcl-xL gly-159-ala clone #38 cells.

  1. Mida suudab muusikateraapia? / Melanie Voigt, Esa Ala-Ruona ; inetrvjueerinud Kristel Kossar

    Index Scriptorium Estoniae

    Voigt, Melanie

    2012-01-01

    Eesti Muusika- ja Teatriakadeemias toimunud Euroopa Muusikateraapia Konföderatsiooni peaassambleel ja sümpoosionil ettekannetega esinenud muusikaterapeudid Malanie Voigt Saksamaalt ja Esa Ala-Ruona Soomest räägivad tööst puuetega lastega ja tööstressist ning heliilmast

  2. Inducible l-Alanine Exporter Encoded by the Novel Gene ygaW (alaE) in Escherichia coli ▿

    Science.gov (United States)

    Hori, Hatsuhiro; Yoneyama, Hiroshi; Tobe, Ryuta; Ando, Tasuke; Isogai, Emiko; Katsumata, Ryoichi

    2011-01-01

    We previously isolated a mutant hypersensitive to l-alanyl-l-alanine from a non-l-alanine-metabolizing Escherichia coli strain and found that it lacked an inducible l-alanine export system. Consequently, this mutant showed a significant accumulation of intracellular l-alanine and a reduction in the l-alanine export rate compared to the parent strain. When the mutant was used as a host to clone a gene(s) that complements the dipeptide-hypersensitive phenotype, two uncharacterized genes, ygaW and ytfF, and two characterized genes, yddG and yeaS, were identified. Overexpression of each gene in the mutant resulted in a decrease in the intracellular l-alanine level and enhancement of the l-alanine export rate in the presence of the dipeptide, suggesting that their products function as exporters of l-alanine. Since ygaW exhibited the most striking impact on both the intra- and the extracellular l-alanine levels among the four genes identified, we disrupted the ygaW gene in the non-l-alanine-metabolizing strain. The resulting isogenic mutant showed the same intra- and extracellular l-alanine levels as observed in the dipeptide-hypersensitive mutant obtained by chemical mutagenesis. When each gene was overexpressed in the wild-type strain, which does not intrinsically excrete alanine, only the ygaW gene conferred on the cells the ability to excrete alanine. In addition, expression of the ygaW gene was induced in the presence of the dipeptide. On the basis of these results, we concluded that YgaW is likely to be the physiologically most relevant exporter for l-alanine in E. coli and proposed that the gene be redesignated alaE for alanine export. PMID:21531828

  3. Introducing ALAS: A Novel Agent-Oriented Programming Language

    Science.gov (United States)

    Mitrović, Dejan; Ivanović, Mirjana; Vidaković, Milan

    2011-09-01

    Agent-oriented programming languages represent a family of programming languages that provide developers with high-level abstractions and constructs necessary for implementing and using agent-related concepts. In this paper a novel agent-oriented programming language for rapid and efficient development of reactive agents, named ALAS, is presented. The simple, but powerful set of language constructs is designed to support the execution of agents in heterogenous environments, and to enable easy employment of advanced agent features, such as mobility and web service integration.

  4. Synthesis of phthalocyanines-ALA conjugates: water-soluble compounds with low aggregation.

    Science.gov (United States)

    de Oliveira, Kleber T; de Assis, Francisco F; Ribeiro, Anderson O; Neri, Claudio R; Fernandes, Adjaci U; Baptista, Mauricio S; Lopes, Norberto P; Serra, Osvaldo A; Iamamoto, Yassuko

    2009-10-16

    Syntheses of two water-soluble phthalocyanines (Pc) containing 5-aminolevulinic acid (ALA) linked to the core structure are described. These compounds were prepared by using original functionalizations, and they present remarkable structural and photophysical features, indicating that they could be applied to photodynamic therapy (PDT).

  5. Stiilne kahetoaline stuudiokorter / Sanna Vatanen

    Index Scriptorium Estoniae

    Vatanen, Sanna

    2007-01-01

    Infoturvajuhi Markus Porvari renoveeritud korter (71 m2) Helsingi kesklinnas 1925. a. ehitatud majas. Korteris on tipptasemel HI-FI tehnika. Vannitoa, sauna ja tualettruumi kavandas Jukka Airas firmast Airas Design. 7. värv. vaadet

  6. Kabja tervishoiu koolitus / Sanna Turu

    Index Scriptorium Estoniae

    Turu, Sanna

    2013-01-01

    Eesti Raskeveohobuse Seltsi poolt 25. mail Raplamaal Piibelehe Puhkekemajas korraldatud koolitusest, kus hobuveterinaar Triin Tohver ja professionaalne sepp Stephan Ernest Saksamaalt tegid põhjaliku ülevaate hobuse kabja tervishoiu teemadel

  7. ALA-based fluorescent diagnosis of malignant oral lesions in the presence of bacterial porphyrin formation

    Science.gov (United States)

    Schleier, P.; Berndt, A.; Zinner, K.; Zenk, W.; Dietel, W.; Pfister, W.

    2006-02-01

    The aminolevulinic acid (5-ALA) -based fluorescence diagnosis has been found to be promising for an early detection and demarcation of superficial oral squamous cell carcinomas (OSCC). This method has previously demonstrated high sensitivity, however this clinical trial showed a specificity of approximately 62 %. This specificity was mainly restricted by tumor detection in the oral cavity in the presence of bacteria. After topical ALA application in the mouth of patients with previously diagnosed OSSC, red fluorescent areas were observed which did not correlate to confirm histological findings. Swabs and plaque samples were taken from 44 patients and cultivated microbiologically. Fluorescence was investigated (OMA-system) from 32 different bacteria strains found naturally in the oral cavity. After ALA incubation, 30 of 32 strains were found to synthesize fluorescent porphyrins, mainly Protoporphyrin IX. Also multiple fluorescent spectra were obtained having peak wavelengths of 636 nm and around 618 nm - 620 nm indicating synthesis of different porphyrins, such as the lipophylic Protoporphyrin IX (PpIX) and hydrophylic porphyrins (water soluble porphyrins, wsp). Of the 32 fluorescent bacterial strains, 18 produced wsp, often in combination with PpIX, and 5 produced solely wsp. These results clarify that ALA-based fluorescence diagnosis without consideration or suppression of bacteria fluorescence may lead to false-positive findings. It is necessary to suppress bacteria fluorescence with suitable antiseptics before starting the procedure. In this study, when specific antiseptic pre-treatment was performed bacterial associated fluorescence was significantly reduced.

  8. Intestinal fatty acid binding protein Ala54Thr polymorphism is associated with peripheral atherosclerosis combined with type 2 diabetes mellitus.

    Science.gov (United States)

    Khattab, Salma A; Abo-Elmatty, Dina M; Ghattas, Maivel H; Mesbah, Noha M; Mehanna, Eman T

    2017-09-01

    Intestinal fatty acid-binding protein 2 (FABP2) is expressed in enterocytes and binds saturated and unsaturated long-chain fatty acids. The FABP2 Ala54Thr polymorphism has been reported to effect lipid metabolism. The aim of the present study was to assess the relationship between this polymorphism and peripheral atherosclerosis combined with type 2 diabetes mellitus (T2DM) in an Egyptian population. The study was performed on 100 T2DM patients with peripheral atherosclerosis and 100 control subjects. The Ala54Thr polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism, whereas serum FABP2 levels were determined using ELISA. Fasting blood glucose, fasting serum insulin concentrations, HbA1c, lipid profile, body mass index (BMI) and systolic and diastolic blood pressure (SBP and DBP, respectively) were determined. There was a higher frequency of the Thr54 allele among the patient group (P = 0.002). In Ala54/Thr54 heterozygotes and carriers of the rare Thr54/Thr54 genotype, there were significant increases in BMI and FABP2. Those with the Thr54/Thr54 genotype had significantly decreased high-density lipoprotein cholesterol (HDL-C) concentrations; in addition, those with the Thr54/Thr54 genotype had significantly higher SBP and DBP than subjects with the Ala54/Ala54 and Ala54/Thr54 genotypes. There was a positive correlation between FABP2 levels and BMI, SBP and DBP, and a negative correlation with HDL-C. The Thr54 allele of the FABP2 Ala54Thr polymorphism was associated with an increased incidence of peripheral atherosclerosis combined with T2DM in the population studied. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  9. Evaluation of glucose metabolism and reproductive hormones in polycystic ovary syndrome on the basis of peroxisome proliferator-activated receptor (PPAR)-gamma2 Pro12Ala genotype.

    Science.gov (United States)

    Tok, E C; Aktas, A; Ertunc, D; Erdal, E M; Dilek, S

    2005-06-01

    Peroxisome proliferator-activated receptor (PPAR)-gamma2 Pro12Ala polymorphism has been suggested as a protective factor for polycystic ovary syndrome (PCOS). In this study, we aimed to investigate metabolic features and reproductive hormones in women with PCOS and compare these features with control women on the basis of Pro12Ala genotype. This study involved 60 randomly selected women with PCOS and 60 controls. Main outcome measures were anthropometric measures, variables of glucose metabolism and reproductive hormones. All the patients were genotyped for Pro12Ala variant of PPAR-gamma2 gene. Patients with Pro12Ala polymorphism were more obese in both groups. Furthermore, they had lower fasting insulin levels, were less insulin-resistant and were less glucose-intolerant as demonstrated by 2 h glucose concentrations. However, there was no difference in reproductive hormone levels on the basis of Pro12Ala genotype. Both control women and women with PCOS had significant differences in glucose metabolism on the basis of PPAR-gamma2 Pro12Ala polymorphism. Pro12Ala variant may break the process that leads to PCOS in susceptible women, instead of being a direct causal relationship between Pro12Ala polymorphism and PCOS.

  10. Valor educativo y generalización del grupo "Alas por la vida" Educational value and generalization of "Alas por la Vida"

    Directory of Open Access Journals (Sweden)

    Alexis Hugo Cantero Ronquillo

    2012-03-01

    Full Text Available En el tratamiento del cáncer de mama, además de la agresión quirúrgica, en ocasiones mutilante, seguida o precedida por las molestias inherentes a los tratamientos oncoespecíficos, a veces persisten "heridas", que aunque invisibles, no siempre cierran totalmente, y afectan durante mucho tiempo, o toda la vida, a un grupo importante de pacientes y familiares cercanos. El proyecto "Alas por la vida" propone nuevas alternativas en el tratamiento de la mujer con cáncer de mama, que puedan prepararla para una nueva etapa, y vivir con el estatus de enferma crónica, que no refleje invalidez en el desempeño de sus funciones, que alcance la recuperación de su equilibrio biopsicosocial, y, consecuentemente, el disfrute de una adecuada calidad de vida. Mediante intercambios entre sobrevivientes de la enfermedad, familiares y profesionales, charlas científicas, sesiones de preguntas y respuestas, reflexiones de operadas en su lucha contra el cáncer de mama y también de sus esposos, así como con actividades socioculturales, etc., se han logrado resultados muy positivos por este grupo, lo que se refleja en encuestas realizadas a tal efecto. El Grupo de Apoyo a Pacientes Mastectomizadas "Alas por la vida", ha resultado ser un instrumento muy útil para elevar la autoestima y mejorar la calidad de vida de las sobrevivientes, que a la vez ha fortalecido y humanizado nuestra lucha contra el cáncer de mama, y se han aglutinando crecientemente más seguidores en esta noble causa, por lo que recomendamos se organicen proyectos similares en todas las provincias del país.In the treatment of beast cancer besides the surgical aggression occasionally mutilating followed or precedes by the molecules inherent to specific oncologic treatments, sometimes the "wounds" persist that although invisibles, not always are totally closed involving for much time or for life to a significant group of patients and close relatives.The project "Alas por la Vida" proposes

  11. Assay for identification of heterozygous single-nucleotide polymorphism (Ala67Thr in human poliovirus receptor gene

    Directory of Open Access Journals (Sweden)

    Shyam Sundar Nandi

    2016-01-01

    Results: A new SNP assay for detection of heterozygous Ala67Thr genotype was developed and validated by testing 150 DNA samples. Heterozygous CD155 was detected in 27.33 per cent (41/150 of DNA samples tested by both SNP detection assay and sequencing. Interpretation & conclusions: The SNP detection assay was successfully developed for identification of Ala67Thr polymorphism in human PVR/CD155 gene. The SNP assay will be useful for large scale screening of DNA samples.

  12. The Pro12Ala polymorphism in the peroxisome proliferator-activated receptor gamma-2 gene (PPARγ2 is associated with increased risk of coronary artery disease: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Zhijun Wu

    Full Text Available BACKGROUND: Contradictory results have been reported regarding the association between Pro12Ala polymorphism of PPARγ2 and coronary artery disease (CAD. We sought to estimate the inconsistent results by performing a comprehensive meta-analysis. METHODS: Studies in English or Chinese publications were identified by screening MEDLINE, Embase, CNKI, Wanfang and CBM. 22 studies including 8948 cases and 14427 controls were selected. A random-effects model was applied to combine the divergent outcomes of the individual studies, while addressing between-study heterogeneity and publication bias. RESULTS: The Pro12Ala polymorphism of control population followed Hardy-Weinberg equilibrium for all studies (P>0.05. Overall, a marginal increased risk of CAD under the recessive genetic model (AlaAla vs ProAla+ProPro: P = 0.04, OR = 1.31, 95%CI 1.01-1.69, P(heterogeneity = 0.67, I(2 = 0% and the homozygote comparison (AlaAla vs ProPro: P = 0.04,OR = 1.30, 95%CI 1.01-1.68, P(heterogeneity = 0.68, I(2 = 0% was observed. In the subgroup analysis by ethnicity, carriers of AlaAla homozygotes had a significant increased risk for CAD among Caucasians (AlaAla vs ProAla+ProPro: P = 0.01, OR = 1.45, 95%CI 1.08-1.96, P(heterogeneity = 0.48, I(2 = 0%; AlaAla vs ProPro: P = 0.02,OR = 1.44, 95%CI 1.07-1.93, P(heterogeneity = 0.46, I(2 = 0%. After dividing into population source, the CAD risk magnitude of hospital-based studies was distinctly strengthened under the recessive model (P = 0.03,OR = 1.85,95%CI 1.07-3.19, P(heterogeneity = 0.87,I(2 = 0% and the homozygote comparison (P = 0.03,OR = 1.83, 95%CI 1.06-3.16, P(heterogeneity = 0.88, I(2 = 0%. There was no observable publication bias as reflected by funnel plot and Egger's linear regression test (t = -0.12, P = 0.91. CONCLUSION: Our results demonstrated that the PPARγ2 Pro12Ala polymorphism might be risk-conferring locus for the progression of CAD among Caucasians, but not among Asians.

  13. Evaluation of labelling conditions, quality control and biodistribution study of 99mTc-5-aminolevulinic acid (5-ALA). A potential liver imaging agent

    International Nuclear Information System (INIS)

    Kalim Ullah Khan; Mohammad Rafi; Samina Roohi; Rizwana Zahoor; Zafar Iqbal; Mushtaq Ahmad

    2014-01-01

    Labelling of 5-aminolevulinic acid (5-ALA) with 99m Tc was achieved by using SnCl 2 ·2H 2 O as reducing agent. Radiochemical purity and labelling efficiency was determined by instant thin layer chromatography/paper chromatography. Efficiency of labelling was dependent on many parameters such as amount of ligand, reducing agent, pH, and time of incubation. 99m Tc labelled 5-ALA remained stable for 24 h in human serum. Tissue biodistribution of 99m Tc-5-ALA was evaluated in Sprague-Dawley rats. Biodistribution study (% ID/g) in rats revealed that 99m Tc-5-ALA was accumulated significantly in liver, spleen, stomach and intestine after half hour, 4 and 24 h. Significant activity was noted in bladder and urine at 4 h. High liver uptake of 99m Tc-5-ALA makes it a promising liver imaging agent. (author)

  14. Peroxisome proliferator-activated receptor-γ (PPARγ) Pro12Ala polymorphism and colorectal cancer (CRC) risk.

    Science.gov (United States)

    Wang, Wei; Shao, Yan; Tang, Shenhua; Cheng, Xianyong; Lian, Haifeng; Qin, Chengyong

    2015-01-01

    The association between the peroxisome proliferator-activated receptor-γ (PPARγ) Pro12Ala polymorphism and colorectal cancer (CRC) risk was inconclusive. We conducted a meta-analysis to evaluate the association between PPARγ Pro12Ala polymorphism and CRC risk. We searched Pubmed, EMBASE, and China National Knowledge Infrastructure databases. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. A total of 17 case-control studies with 12635 and 15803 controls were included in this meta-analysis. Overall, PPARγ Pro12Ala polymorphism was associated with CRC risk (OR = 0.84, 95% CI 0.75-0.94, P = 0.003, I(2) = 35%). In the subgroup analysis by ethnicity, a significant association was found among Caucasians (OR = 0.85, 95% CI 0.75-0.96, P = 0.007, I(2) = 38%) but not among Asians (OR = 0.76, 95% CI 0.51-1.12, P = 0.17, I(2) = 28%). In the subgroup analysis by CRC site, a significant association was found among colon cancer (OR = 0.81, 95% CI 0.66-0.98, P = 0.03, I(2) = 16%) but not among rectal cancer (OR = 0.83, 95% CI 0.57-1.21, P = 0.34, I(2) = 63%). The sensitivity analysis did not influence the result by omitting low-quality studies (OR = 0.76, 95% CI 0.63-0.93, P = 0.006, I(2) = 51%). In conclusion, this meta-analysis suggested that PPARγ Pro12Ala polymorphism was significant associated with CRC risk.

  15. Shifting with the Paradigm: LJ's Picks & Pans for ALA in Disneyland

    Science.gov (United States)

    Berry, John N., III

    2008-01-01

    The feelings of librarians planning for the American Library Association (ALA) conference at Disneyland (aka Anaheim, California, June 26-July 2) range from moderate pleasure to dread. Some remember the joys and difficulties of Orlando, especially the exorbitant cab fares and mediocre restaurants. Others quail at screaming kids and tourists in…

  16. Sadama ala planeering = Harbour area master plan / Ivan Sergejev, Helen Rebane, Karina Niinepuu

    Index Scriptorium Estoniae

    Sergejev, Ivan, 1987-

    2010-01-01

    EKA arhitektuuri ja linnaplaneerimise osakonna IV kursuse 2009-2010 õppeaastal erialase projekteerimise raames kavandatud planeeringu eesmärgiks on tihendada Tallinna sadama ala ning arendada sellest välja mitmekesine ja efektiivne linnaruum

  17. The Pro12Ala Polymorphism of PPAR-γ Gene Is Associated with Sepsis Disease Severity and Outcome in Chinese Han Population

    Directory of Open Access Journals (Sweden)

    Guoda Ma

    2014-01-01

    Full Text Available Peroxisome proliferator-activated receptor-γ (PPAR-γ is a ligand-binding nuclear receptor, and its activation plays a prominent role in regulating the inflammatory response. Therefore, PPAR-γ has been suggested as a candidate gene for sepsis. In the present study, we investigated the association between the Pro12Ala polymorphism of PPAR-γ and sepsis in a Han Chinese population. A total of 308 patients with sepsis and 345 healthy controls were enrolled in this study. Genotyping was performed using the polymerase chain reaction-ligation detection reaction (PCR-LDR method. No significant differences were detected in the allele and genotype distributions of the PPAR-γ Pro12Ala SNP between septic patients and controls (P=0.622 for genotype; P=0.629 for allele. However, stratification by subtypes (sepsis, septic shock, and severe sepsis revealed a statistically significant difference in the frequency of the Ala allele and Ala-carrier genotype between the patients with the sepsis subtype and the healthy controls (P=0.014 for allele and P=0.012, for genotype. Moreover, significant differences were found in the frequency of the Ala allele and genotype between the sepsis survivors and nonsurvivors (all P=0.002. In the survivors, the PPAR-γ Pro12Ala genotype was significantly associated with decreased disease severity and recovery time (all P<0.001. Thus, genetic polymorphism is thought to play a role in the development and outcome of sepsis.

  18. Loss of the Arabidopsis thaliana P₄-ATPase ALA3 reduces adaptability to temperature stresses and impairs vegetative, pollen, and ovule development.

    Directory of Open Access Journals (Sweden)

    Stephen C McDowell

    Full Text Available Members of the P4 subfamily of P-type ATPases are thought to help create asymmetry in lipid bilayers by flipping specific lipids between the leaflets of a membrane. This asymmetry is believed to be central to the formation of vesicles in the secretory and endocytic pathways. In Arabidopsis thaliana, a P4-ATPase associated with the trans-Golgi network (ALA3 was previously reported to be important for vegetative growth and reproductive success. Here we show that multiple phenotypes for ala3 knockouts are sensitive to growth conditions. For example, ala3 rosette size was observed to be dependent upon both temperature and soil, and varied between 40% and 80% that of wild-type under different conditions. We also demonstrate that ala3 mutants have reduced fecundity resulting from a combination of decreased ovule production and pollen tube growth defects. In-vitro pollen tube growth assays showed that ala3 pollen germinated ∼2 h slower than wild-type and had approximately 2-fold reductions in both maximal growth rate and overall length. In genetic crosses under conditions of hot days and cold nights, pollen fitness was reduced by at least 90-fold; from ∼18% transmission efficiency (unstressed to less than 0.2% (stressed. Together, these results support a model in which ALA3 functions to modify endomembranes in multiple cell types, enabling structural changes, or signaling functions that are critical in plants for normal development and adaptation to varied growth environments.

  19. "LJ" Report "Anaheim, ALA 2008": Amid the Fantasy, Doses of Reality

    Science.gov (United States)

    Blumenstein, Lynn; Berry, John; Fialkoff, Francine; Fox, Bette-Lee; Hadro, Josh; Horrocks, Norman; Oder, Norman; Roncevic, Mirela

    2008-01-01

    If the resort city of Anaheim, California, home of Disneyland and its "imagineers," marked a departure from the urban reality of the typical American Library Association (ALA) annual conference, it was impossible, at this 2008 meeting, to avoid urgent library issues. How do libraries maintain their value and cultural presence as users…

  20. Impact of an AlAs window layer upon the optical properties of Al x Ga1-x As photodiodes

    Science.gov (United States)

    Kang, T.; Chen, X. J.; Johnson, E. B.; Christian, J. F.; Lee, K.; Hammig, M. D.

    2016-05-01

    Recently developed advanced scintillators, which have the ability to distinguish gamma-ray interaction events from those that accompany neutron impact, require improved quantum efficiency in the blue to near UV region of the spectrum. We utilize GaAs/Al0.8Ga0.2As photodiode elements as components in a wide band-gap solid-state photomultiplier as a lower-cost, lower logistical burden, and higher quantum efficiency replacement for the photomultiplier tube. An AlAs window layer is employed as a means to increase the diode’s optical performance. Relative to structures absent the window layer, simulations and measurements demonstrate that the AlAs layer produces a spatial coincidence between regions of large drift fields with regions of high photon absorption. In addition to the AlAs layer, secondary ion mass spectrometry measurements show that an unexpected high degree of inter-diffusion of GaAs and AlAs quenches the photon-detection efficiency, a decrease that can be avoided by its post-growth removal. With the AlAs layer, the peak external quantum efficiency of 49% is achieved at 450 nm with 10 V reverse bias, which does not fully deplete the device. Simulations show that full depletion can result in efficiencies exceeding 90%. In order to enhance the optical response, a simple anti-reflective coating layer is designed using the existing passivation layer components that successfully minimizes the reflection at the wavelength range of interest (300 nm-500 nm).

  1. Impact of an AlAs window layer upon the optical properties of AlxGa1−xAs photodiodes

    International Nuclear Information System (INIS)

    Kang, T; Hammig, M D; Chen, X J; Johnson, E B; Christian, J F; Lee, K

    2016-01-01

    Recently developed advanced scintillators, which have the ability to distinguish gamma-ray interaction events from those that accompany neutron impact, require improved quantum efficiency in the blue to near UV region of the spectrum. We utilize GaAs/Al 0.8 Ga 0.2 As photodiode elements as components in a wide band-gap solid-state photomultiplier as a lower-cost, lower logistical burden, and higher quantum efficiency replacement for the photomultiplier tube. An AlAs window layer is employed as a means to increase the diode’s optical performance. Relative to structures absent the window layer, simulations and measurements demonstrate that the AlAs layer produces a spatial coincidence between regions of large drift fields with regions of high photon absorption. In addition to the AlAs layer, secondary ion mass spectrometry measurements show that an unexpected high degree of inter-diffusion of GaAs and AlAs quenches the photon-detection efficiency, a decrease that can be avoided by its post-growth removal. With the AlAs layer, the peak external quantum efficiency of 49% is achieved at 450 nm with 10 V reverse bias, which does not fully deplete the device. Simulations show that full depletion can result in efficiencies exceeding 90%. In order to enhance the optical response, a simple anti-reflective coating layer is designed using the existing passivation layer components that successfully minimizes the reflection at the wavelength range of interest (300 nm–500 nm). (paper)

  2. 5-ALA/PpIX fluorescence detection of gastrointestinal neoplasia

    Science.gov (United States)

    Borisova, Ekaterina G.; Vladimirov, Borislav; Terziev, Ivan; Ivanova, Radina; Avramov, Latchezar

    2009-07-01

    In the recent study delta-ALA/PpIX is used as fluorescent marker for dysplasia and tumor detection in esophagus, stomach and colon. ALA is administered per os six to eight (depending on the lesion location) hours before measurements at dose 20mg/kg weight. High-power light-emitting diode at 405 nm is used as an excitation source. Special opto-mechanical device is built for the LED to use the light guide of standard video-endoscopic system. Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer. The fluorescence detected from tumor sites has very complex spectral origins. It consists of autofluorescence, fluorescence from exogenous fluorophores and re-absorption from the chromophores accumulated in the tissue investigated. Spectral features observed during endoscopic investigations could be distinct as the next regions: 450-630 nm region, where tissue autofluorescence is observed; 630-710 nm region, where fluorescence of PpIX is clearly pronounced; 530-580 nm region, where minima in the autofluorescence signal are observed, related to re-absorption of oxy-hemoglobin in this spectral area. Endogenous and exogenous fluorescence spectra are used to develop simple but effective algorithm, based on dimensionless ratio of the signals at 560 and 635 nm, for differentiation of normal/abnormal gastrointestinal tissues. Very good correlation between fluorescence signals and histology examination of the lesions investigated is achieved.

  3. Feasibility of Raman spectroscopy in vitro after 5-ALA-based fluorescence diagnosis in the bladder

    Science.gov (United States)

    Grimbergen, M. C. M.; van Swol, C. F. P.; van Moorselaar, R. J. A.; Mahadevan-Jansen, A.,; Stone, N.

    2006-02-01

    Photodynamic diagnosis (PDD) has become popular in bladder cancer detection. Several studies have however shown an increased false positive biopsies rate under PDD guidance compared to conventional cystoscopy. Raman spectroscopy is an optical technique that utilizes molecular specific, inelastic scattering of light photons to interrogate biological tissues, which can successfully differentiate epithelial neoplasia from normal tissue and inflammations in vitro. This investigation was performed to show the feasibility of NIR Raman spectroscopy in vitro on biopsies obtained under guidance of 5-ALA induced PPIX fluorescence imaging. Raman spectra of a PPIX solution was measured to obtain a characteristic signature for the photosensitzer without contributions from tissue constituents. Biopsies were obtained from patients with known bladder cancer instilled with 50ml, 5mg 5-ALA two hours prior to trans-urethral resection of tumor (TURT). Additional biopsies were obtained at a fluorescent and non-fluorescent area, snap-frozen in liquid nitrogen and stored at -80 °C. Each biopsy was thawed before measurements (10sec integration time) with a confocal Raman system (Renishaw Gloucestershire, UK). The 830 nm excitation (300mW) source is focused on the tissue by a 20X ultra-long-working-distance objective. Differences in fluorescence background between the two groups were removed by means of a special developed fluorescence subtraction algorithm. Raman spectra from ALA biopsies showed different fluorescence background which can be effectively removed by a fluorescence subtraction algorithm. This investigation shows that the interaction of the ALA induced PPIX with Raman spectroscopy in bladder samples. Combination of these techniques in-vivo may lead to a viable method of optical biopsies in bladder cancer detection.

  4. Alpha lipoic acid (ALA) modulates expression of apoptosis associated proteins in hippocampus of rats exposed during postnatal period to sodium arsenite (NaAsO2).

    Science.gov (United States)

    Dixit, Shilpi; Dhar, Pushpa; Mehra, Raj D

    2015-01-01

    The present study focused on the role of exogenous alpha lipoic acid (ALA) in amelioration of inorganic arsenic ( iAs ) induced effects on apoptosis and apoptosis associated proteins in developing rat hippocampus. NaAsO 2 (1.5/2.0 mg/kg bw) alone or along with ALA (70 mg/kg bw) was administered to rat pups (experimental groups) by intraperitoneal (i.p.) route from postnatal day (PND) 4-15. Controls received no treatment/distilled water/ALA. On PND 16, the animals were perfusion fixed and the brains were processed for paraffin embedding (CV and TUNEL staining) and cryopreservation (immunohistochemistry). The fresh brain tissue was used for Western blotting. Significant increase was observed in TUNEL positive cells and Bax (pro-apoptotic protein) expression in hippocampal sub-regions of iAs alone treated groups, whereas Bcl-2 expression was intensified in animals receiving ALA with iAs . Densitometric analysis (Western blots) revealed optimal restoration of Bax and Bcl-2 ratio in animals receiving ALA with iAs , thereby suggesting the protective role of ALA in iAs induced developmental neurotoxicity.

  5. Light fractionation increases the efficacy of ALA-PDT but not of MAL-PDT: What is the role of (vascular) endothelial cells?

    Science.gov (United States)

    de Bruijn, H. S.; de Vijlder, H. C.; de Haas, E. R. M.; van der Ploeg-van den Heuvel, A.; Kruijt, B.; Poel-Dirks, D.; Sterenborg, H. J. C. M.; ten Hagen, T. L. M.; Robinson, D. J.

    2009-06-01

    Photodynamic therapy (PDT) using protoporpyrin IX (PpIX) precursors like 5-aminolevulinic acid (ALA) or methyl-aminolevulinate (MAL) has shown to be effective in the treatment of various skin diseases. Using ALA we have shown in numerous studies a significantly improved efficacy by applying light fractionation with a long dark interval. In contrast, in the hairless mouse model, the PDT efficacy using MAL is unaffected by adopting this approach. More acute edema is found after ALA-PDT suggesting a difference in response of endothelial cells to PDT. To investigate the role of endothelial cells, cryo-sections of hairless mouse skin after 4 hours of topical MAL or ALA application were stained with a fluorescent endothelial cell marker (CD31). Co-localization of this marker with the PpIX fluorescence was performed using the spectral imaging function of the confocal microscope. We have also used intra-vital confocal microscopy to image the PpIX fluorescence distribution in correlation with the vasculature of live mouse skin. Our results show PpIX fluorescence at depth in cryo-sections of mouse skin after 4 hours of topical application. Co-localization has shown to be difficult due to the changes in tissue organization caused by the staining procedure. As expected we found high PpIX fluorescence levels in the epidermis after both MAL and ALA application using intra-vital microscopy. After ALA application more PpIX fluorescence was found deep in the dermal layer of the skin than after MAL. Furthermore we detected localized fluorescence in unidentified structures that could not be correlated to blood vessels or nerves.

  6. Idiopathic elastosis perforans serpiginosa with satisfactory response after 5-ALA photodynamic therapy.

    Science.gov (United States)

    Alique-García, S; Company-Quiroga, J; Horcajada-Reales, C; Echeverría-García, B; Tardío-Dovao, J C; Borbujo, J

    2018-03-01

    Photodynamic therapy (PDT) involves the use of photochemical reactions mediated through the interaction of photosensitizing agents, light, and oxygen for the treatment of malignant or benign diseases. Topical photosensitizers employed in dermatology are 5-aminolevulinic acid (5 ALA) and methyl aminolevulinate, classically used for the treatment of superficial non-melanoma skin cancer and their precursors. Recently the efficacy of PDT has been introduced in other benign diseases. Elastosis perforans serpiginosa (EPS) is a rare skin disorder characterized by transepidermal elimination of abnormal elastic fibers. Management of this condition is complicated, various methods have been used but with limited success. We report a case of EPS in a 30-yeard-old woman treated with 5 ALA-PDT. After 4 sessions the lesions have almost completely disappeared with no residual side effects. Therefore we present an effective and safe alternative for the treatment of EPS. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Loss of the Arabidopsis thaliana P4-ATPase ALA3 Reduces Adaptability to Temperature Stresses and Impairs Vegetative, Pollen, and Ovule Development

    DEFF Research Database (Denmark)

    McDowell, Stephen C.; Lopez Marques, Rosa Laura; Poulsen, Lisbeth Rosager

    2013-01-01

    , a P4-ATPase associated with the trans-Golgi network (ALA3) was previously reported to be important for vegetative growth and reproductive success. Here we show that multiple phenotypes for ala3 knockouts are sensitive to growth conditions. For example, ala3 rosette size was observed to be dependent...

  8. Meta-analysis of association between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ2 gene and diabetic retinopathy in Caucasians and Asians.

    Science.gov (United States)

    Ma, Jinlan; Li, Yan; Zhou, Fang; Xu, Xiaoyi; Guo, Gang; Qu, Yi

    2012-01-01

    The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ2 (PPARγ2) gene is reported to be associated with diabetes. However, the gene's association with diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) has been investigated in numerous epidemiologic studies with controversial results. This meta-analysis aimed to collectively assess the association of the Pro12Ala polymorphism with DR in T2DM. An electronic literature search was conducted on PubMed, ISI Web of Knowledge, EMBASE, and the China National Knowledge Internet. A dominant model [(Pro/Ala +Ala/Ala) versus Pro/Pro] was used to ensure adequate statistical power. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the fixed effect model. Potential sources of heterogeneity and bias were explored. This meta-analysis included genotype data from 2,720 cases with DR and 2,450 controls free of DR from eight eligible publications. The results showed the Ala allele had a protective effect on DR in T2DM (OR=0.81; 95% CI: 0.68-0.98, p=0.03). There was no significant evidence against homogeneity (I(2)=46%, P(heterogeneity)=0.07). The sensitivity analysis showed a robust association of the Pro12Ala polymorphism with DR in T2DM after a study involving Caucasians that presented a big effect on heterogeneity (OR=0.75; 95% CI: 0.62-0.91, p=0.003) was excluded. Possible ethnic differences in the association of the Pro12Ala single nucleotide polymorphism and DR were demonstrated; a significant association was illustrated in the Caucasian subgroup (OR=0.74; 95% CI: 0.59-0.94, p=0.01) but was not found in the Asian subgroup (OR=0.77; 95% CI: 0.55-1.07, p=0.12). No publication bias was observed. This meta-analysis suggested a significant association exists between the Pro12Ala polymorphism and DR in T2DM with ethnic differences. The Ala allele had a significant protective effect against DR in T2DM.

  9. Arhitektuuribürood pakkusid hipodroomi ala elamukvartaliks ümberehitamiseks julgeid projekte / Hille Tänavsuu

    Index Scriptorium Estoniae

    Tänavsuu, Hille, 1941-2014

    2008-01-01

    Tallinna Hipodroomi ala hoonestamise ideekonkursi võitsid QP Arhitektid (Tõnu Laigu, Koit Ojaliiv, Mari Rass, Asko Uukado) ja Salto Arhitektuuribüroo (Ralf Lõoke, Karli Luik, Maarja Kask). Kommenteerib Endrik Mänd

  10. Gene expression pattern at different time points following ALA-PDT

    International Nuclear Information System (INIS)

    Verwanger, T.; Sanovic, R.; Ruhdorfer, S.; Aberger, F.; Frischauf, A.; Krammer, B.

    2003-01-01

    Full text: The photo sensitizer protoporphyrin IX, endogenously accumulated from the precursor aminolevulinic acid (ALA), is a successful agent in photodynamic tumor therapy. In spite of encouraging clinical results, the basic mechanisms leading to cell death are not fully understood. We therefore set out to analyze the alteration of the gene expression pattern in the squamous cell carcinoma cell line A-431 at different time points after photodynamic treatment with endogenous protoporphyrin IX by cDNA-array technique. Cells were incubated for 16 hours with 100 μg/ml ALA and irradiated with a fluence of 3.5 J/cm 2 resulting in 50 % survival until 8 hours post treatment. RNA was isolated at 1.5, 3, 5 and 8 hours post treatment as well as of 3 controls (untreated, light only and dark), radioactively labelled by reverse transcription with 33P-dCTP and hybridized onto macroarray PCR filters containing PCR products of 2135 genes, which were selected for relevance in tumors, stress response and signal transduction. Verification of observed expression changes was carried out by real time PCR. We found a strong induction of expression of immediate early genes like c-fos as well as decreased expression of genes involved in proliferation like myc and the proliferating cell nuclear antigen (PCNA). (author)

  11. Alpha lipoic acid (ALA modulates expression of apoptosis associated proteins in hippocampus of rats exposed during postnatal period to sodium arsenite (NaAsO2

    Directory of Open Access Journals (Sweden)

    Shilpi Dixit

    2015-01-01

    Full Text Available The present study focused on the role of exogenous alpha lipoic acid (ALA in amelioration of inorganic arsenic (iAs induced effects on apoptosis and apoptosis associated proteins in developing rat hippocampus. NaAsO2 (1.5/2.0 mg/kg bw alone or along with ALA (70 mg/kg bw was administered to rat pups (experimental groups by intraperitoneal (i.p. route from postnatal day (PND 4–15. Controls received no treatment/distilled water/ALA. On PND 16, the animals were perfusion fixed and the brains were processed for paraffin embedding (CV and TUNEL staining and cryopreservation (immunohistochemistry. The fresh brain tissue was used for Western blotting. Significant increase was observed in TUNEL positive cells and Bax (pro-apoptotic protein expression in hippocampal sub-regions of iAs alone treated groups, whereas Bcl-2 expression was intensified in animals receiving ALA with iAs. Densitometric analysis (Western blots revealed optimal restoration of Bax and Bcl-2 ratio in animals receiving ALA with iAs, thereby suggesting the protective role of ALA in iAs induced developmental neurotoxicity.

  12. [Ala12]MCD peptide: a lead peptide to inhibitors of immunoglobulin E binding to mast cell receptors.

    Science.gov (United States)

    Buku, A; Condie, B A; Price, J A; Mezei, M

    2005-09-01

    An effort was made to discover mast cell degranulating (MCD) peptide analogs that bind with high affinity to mast cell receptors without triggering secretion of histamine or other mediators of the allergic reaction initiated by immunoglobulin E (IgE) after mast cell activation. Such compounds could serve as inhibitors of IgE binding to mast cell receptors. An alanine scan of MCD peptide reported previously showed that the analog [Ala12]MCD was 120-fold less potent in histamine-releasing activity and fivefold more potent in binding affinity to mast cell receptors than the parent MCD peptide. Because this analog showed marginal intrinsic activity and good binding affinity it was subsequently tested in the present study as an IgE inhibitor. In contrast to MCD peptide, [Ala12]MCD showed a 50% inhibition of IgE binding to the Fc epsilon RI alpha mast cell receptor by using rat basophilic leukemia (RBL-2H3) mast cells and fluorescence polarization. Furthermore, in a beta-hexosaminidase secretory assay, the peptide also showed a 50% inhibition of the secretion of this enzyme caused by IgE. An attempt was made to relate structural changes and biologic differences between the [Ala12]MCD analog and the parent MCD peptide. The present results show that [Ala12]MCD may provide a base for designing agents to prevent IgE/Fc epsilon RI alpha interactions and, consequently, allergic conditions.

  13. The Short Life and Ignominious Death of ALA Video and Special Projects.

    Science.gov (United States)

    Handman, Gary

    1991-01-01

    Discussion of videocassettes in our culture and the function of video collections in libraries focuses on the creation and demise of a unit sponsored by the American Library Association, the ALA Video and Special Projects. The unit's role is discussed and funding decisions that led to its demise are explained. (LRW)

  14. The Thr92Ala 5′ Type 2 Deiodinase Gene Polymorphism Is Associated with a Delayed Triiodothyronine Secretion in Response to the Thyrotropin-Releasing Hormone–Stimulation Test: A Pharmacogenomic Study

    Science.gov (United States)

    Butler, Peter W.; Smith, Sheila M.; Linderman, Joyce D.; Brychta, Robert J.; Alberobello, Anna Teresa; Dubaz, Ornella M.; Luzon, Javier A.; Skarulis, Monica C.; Cochran, Craig S.; Wesley, Robert A.; Pucino, Frank

    2010-01-01

    Background The common Thr92Ala D2 polymorphism has been associated with changes in pituitary–thyroid axis homeostasis, but published results are conflicting. To investigate the effects of the Thr92Ala polymorphism on intrathyroidal thyroxine (T4) to triiodothyronine (T3) conversion, we designed prospective pharmacogenomic intervention aimed to detect differences in T3 levels after thyrotropin (TSH)-releasing hormone (TRH)–mediated TSH stimulation of the thyroid gland. Methods Eighty-three healthy volunteers were screened and genotyped for the Thr92Ala polymorphism. Fifteen volunteers of each genotype (Thr/Thr, Thr/Ala, and Ala/Ala) underwent a 500 mcg intravenous TRH stimulation test with serial measurements of serum total T3 (TT3), free T4, and TSH over 180 minutes. Results No differences in baseline thyroid hormone levels were seen among the study groups. Compared to the Thr/Thr group, the Ala/Ala group showed a significantly lower TRH-stimulated increase in serum TT3 at 60 minutes (12.07 ± 2.67 vs. 21.07 ± 2.86 ng/dL, p = 0.029). Thr/Ala subjects showed an intermediate response. Compared to Thr/Thr subjects, the Ala/Ala group showed a blunted rate of rise in serum TT3 as measured by mean time to 50% maximum delta serum TT3 (88.42 ± 6.84 vs. 69.56 ± 6.06 minutes, p = 0.028). Subjects attained similar maximal (180 minutes) TRH-stimulated TT3 levels. TRH-stimulated TSH and free T4 levels were not significantly different among the three genotype groups. Conclusions The commonly occurring Thr92Ala D2 variant is associated with a decreased rate of acute TSH-stimulated T3 release from the thyroid consistent with a decrease in intrathyroidal deiodination. These data provide a proof of concept that the Thr92Ala polymorphism is associated with subtle changes in thyroid hormone homeostasis. PMID:21054208

  15. Volikogu kergitas kruntide alghinna Olümpia vastas 240 miljoni kroonini / Askur Alas

    Index Scriptorium Estoniae

    Alas, Askur, 1973-

    2006-01-01

    Tallinna linnavolikogu tõstis 26. jaanuari istungil Juhkentali 1b, 3d ja 3e kruntide avaliku enampakkumise alghinna 78 miljonilt kroonilt 240 miljonile. Kruntidele on lubatud ehitada üks kuni 30-korruseline ning mitu 3-8 korruselist hoonet. Kaart: Ala detailplaneering

  16. Rolled-Up Nanotech: Illumination-Controlled Hydrofluoric Acid Etching of AlAs Sacrificial Layers

    Directory of Open Access Journals (Sweden)

    Costescu Ruxandra

    2009-01-01

    Full Text Available Abstract The effect of illumination on the hydrofluoric acid etching of AlAs sacrificial layers with systematically varied thicknesses in order to release and roll up InGaAs/GaAs bilayers was studied. For thicknesses of AlAs below 10 nm, there were two etching regimes for the area under illumination: one at low illumination intensities, in which the etching and releasing proceeds as expected and one at higher intensities in which the etching and any releasing are completely suppressed. The “etch suppression” area is well defined by the illumination spot, a feature that can be used to create heterogeneously etched regions with a high degree of control, shown here on patterned samples. Together with the studied self-limitation effect, the technique offers a way to determine the position of rolled-up micro- and nanotubes independently from the predefined lithographic pattern.

  17. cDNAs encoding [D-Ala2]deltorphin precursors from skin of Phyllomedusa bicolor also contain genetic information for three dermorphin-related opioid peptides.

    OpenAIRE

    Richter, K; Egger, R; Negri, L; Corsi, R; Severini, C; Kreil, G

    1990-01-01

    We present the structure of four precursors for [D-Ala2]deltorphins I and II as deduced from cDNAs cloned from skin of the frog Phyllomedusa bicolor. These contain the genetic information for one copy of [D-Ala2]deltorphin II and zero, one, or three copies of [D-Ala2]deltorphin I. In each case, the D-alanine of the end product is encoded by a normal GCG codon for L-alanine. In addition, the existence of three peptides related to dermorphin was predicted from the amino acid sequence of the pre...

  18. The miniband spectrum in (AlAs) sub M (GaAs) sub N (111)

    CERN Document Server

    Karavaev, G F; Egunov, R M

    2002-01-01

    The electron states for energies in the conduction band of (AlAs) sub M (GaAs) sub N (111) superlattices with M >= N (N < 10) are considered. The properties of such superlattices are mainly determined by electrons of X-valley in AlAs and L-valley in GaAs. The calculations are carried out on the basis of the envelope-function model of interface band mixing. Miniband spectra, symmetry and localization of wave functions, and also probabilities of the interminiband infrared absorption are defined and analyzed. It is shown that the latter have a significant magnitude not only at light polarization along the superlattice growth axis, but also at normal incidence of a light wave to the surface. The analysis has been normal incidence of a light wave to the surface. The analysis has shown the importance of consideration of X sub 5 -states belonging to the valence band for infrared absorption

  19. CrAs(0 0 1)/AlAs(0 0 1) heterogeneous junction as a spin current diode predicted by first-principles calculations

    International Nuclear Information System (INIS)

    Min, Y.; Yao, K.L.; Liu, Z.L.; Cheng, H.G.; Zhu, S.C.; Gao, G.Y.

    2009-01-01

    We report on first-principles calculations of spin-dependent quantum transport in a CrAs(0 0 1)/AlAs(0 0 1) heterogeneous junction and predict a strong diode effect of charge and spin current. The minority spin current is absolutely inhibited when the bias voltage is applied to the terminals of both CrAs and AlAs. The majority spin current is inhibited when the bias voltage is applied to the terminal of CrAs and 'relaxed' when the bias voltage is applied to the terminal of AlAs. The charge and spin current diode are promising for reprogrammable logic applications in the field of spintronics

  20. The Signatures of the Invisible exhibition in Geneva

    CERN Multimedia

    Patrice Loïez

    2002-01-01

    The artist Paola Pivi with her work at the Signatures of the Invisible exhibition in Geneva during February 2002. This piece with needles suspended on nylon thread 'detects' people as they approach. The exhibition was for art inspired by research carried out at CERN.

  1. Agentes Locales Ambientales (ALAs: Hacia la ciudad sostenible

    Directory of Open Access Journals (Sweden)

    Marín-Herbert, S.

    2013-09-01

    Full Text Available Any action aimed at improving the quality of life in a city through more sustainable urban models, based on a reference framework such as the Local Agenda 21 or the, calls for changes to its inhabitants' behaviour. The ALAs project drives this change by making the city's youngest inhabitants Leaders of Change. They involve others (school friends, family members, neighbours in direct action in their neighbourhood, making the community participate independently in improving the city’s sustainability and quality of life. To the sequence “awareness- raising - action - monitoring - motivation tools such as our Geographical Information System have been added to support the neighbourhood action strategy by monitoring its efficiency and its effectiveness at meeting targets.Partiendo de un marco de referencia, como la Agenda Local 21 (1 o la Carta de Leipzig (2, cualquier acción encaminada a una mejora en la calidad de vida de una ciudad a través de modelos urbanos más sostenibles, requiere una modificación en las conductas de sus habitantes. El proyecto ALAs, motiva este cambio a través del paso directo a la acción liderada por los más jóvenes a través del Sistema Educativo quien mediante un efecto multiplicador (compañeros, familiares, vecinos y a través de la acción directa en sus barrios, consigue fomentar la participación autónoma de la población en la mejora de la sostenibilidad (3y la calidad de vida de su ciudad. A la secuencia “concienciación - acción - medición - motivación se han incorporado herramientas como el GIS que apoyan la estrategia de acción en los barrios controlando su e! cacia y e! ciencia en la consecución de los objetivos.

  2. ALA/LA ameliorates glucose toxicity on HK-2 cells by attenuating oxidative stress and apoptosis through the ROS/p38/TGF-β1 pathway.

    Science.gov (United States)

    Jiang, Mingxia; Zhang, Haifen; Zhai, Lijie; Ye, Bianliang; Cheng, Yin; Zhai, Chengkai

    2017-11-16

    Growing evidence indicates that oxidative stress (OS) plays a pivotal role in Diabetic nephropathy (DN). In a previous study we demonstrated that ALA/LA protected HK-2 cells against high glucose-induced cytotoxicity. So we aimed to establish the glucose injury model of HK-2 cells and investigate the beneficial effects of ALA/LA on high glucose-induced excessive production of TGF-β1 and the possible mechanisms mediating the effects. The expression of OS markers in high glucose-induced HK-2 cells treated with ALA/LA., including the antioxidant enzymes and reactive oxygen species (ROS) production, as well as the apoptosis rate were assayed by ELISA and flow cytometry. The p38/transforming growth factor β 1 (TGF-β 1 ) signal pathway were measured by real-time RT-PCR and western blot. The modeling condition of glucose toxicity on HK-2 cells was at the glucose concentration of 40.9 mM. ALA/LA can significantly increase the activities of antioxidant enzymes and decrease ROS production stimulated by high glucose. The study also found that ALA/LA caused a decrease in the apoptosis rate and TGF-β 1 level of HK-2 cells under high glucose stress through the ROS/p38 pathway. ALA/LA exerts protective effects in vitro through inhibition of ROS generation, down regulation of the activation of the p38MAPK pathway and the expression of TGF-β 1 in HK-2 cells.

  3. Active Listening Attitude Scale (ALAS: Reliability and Validity in a Nationwide Sample of Greek Educators

    Directory of Open Access Journals (Sweden)

    Ntina Kourmousi

    2017-03-01

    Full Text Available The present study examined the Active Listening Attitude Scale (ALAS validity and reliability in a sample of 3955 Greek educators. The sample was randomly split and an exploratory factor analysis (EFA was conducted in the even subsample to evaluate the scale’s construct validity. A confirmatory factor analysis (CFA was performed in the odd subsample to confirm the three-factor model identified by the EFA. The chi square test (χ2 of the model was significant (p < 0.05, due to the large sample size. The root mean square error of approximation (RMSEA, the comparative fit index (CFI and the goodness of fit index (GFI values were 0.079, 0.969 and 0.960, respectively, further supporting the fit of the three-factor model. Cronbach’s alpha coefficient was used to test internal consistency reliability and was satisfactory exceeding 0.72 for ALAS subscales. The intercorrelations of the three subscales were all positive and significant (p < 0.001, ranging from 0.20 to 0.42. Student’s t-tests and the computation of effect sizes revealed that women scored higher on Listening Skill and Conversation Opportunity, while principals and participants trained on mental health promotion scored higher on all three subscales. The analyses confirmed the three-factor model of ALAS and demonstrated its validity and reliability in measuring Greek teachers’ active listening attitudes.

  4. Short-term supplementation of low-dose gamma-linolenic acid (GLA), alpha-linolenic acid (ALA), or GLA plus ALA does not augment LCP omega 3 status of Dutch vegans to an appreciable extent

    NARCIS (Netherlands)

    Fokkema, M R; Brouwer, D A; Hasperhoven, M B; Martini, I A; Muskiet, F A

    Vegans do not consume meat and fish and have therefore low intakes of long chain polyunsaturated fatty acids (LCP). They may consequently have little negative feedback inhibition from dietary LCP on conversion of alpha -linolenic acid (ALA) to the LCP omega 3 eicosapentaenoic (EPA) and

  5. ALA Office for Intellectual Freedom: Who We Are and How We Help Librarians

    Science.gov (United States)

    Pekoll, Kristin

    2015-01-01

    The American Library Association's (ALA's) Office for Intellectual Freedom (OIF) strives to educate librarians and the public about the nature and importance of intellectual freedom in libraries, and it will celebrate its fiftieth anniversary in 2017. Libraries are a forum for information and ideas (under the First Amendment), and librarians are…

  6. PVR/CD155 Ala67Thr Mutation and Cleft Lip/Palate.

    Science.gov (United States)

    Vieira, Alexandre R; Letra, Ariadne; Silva, Renato M; Granjeiro, Jose M; Shimizu, Takehiko; Poletta, Fernando A; Mereb, Juan C; Castilla, Eduardo E; Orioli, Iêda M

    2018-03-01

    The 19q13 locus has been linked to cleft lip and palate by our group and independently by others. Here we fine mapped the region in an attempt to identify an etiological variant that can explain cleft lip and palate occurrence. A total of 2739 individuals born with cleft lip and palate, related to individuals born with cleft lip and palate, and unrelated were studied. We used linkage and association approaches to fine map the interval between D19S714 and D19S433 and genotypes were defined by the use of TaqMan chemistry. We confirmed our previous findings that markers in PVR/CD155 are associated with cleft lip and palate. We studied the mutation Ala67Thr further and calculated its penetrance. We also attempted to detect PVR/CD155 expression in human whole saliva. Our results showed that markers in PVR/CD155 are associated with cleft lip and palate and the penetrance of the Ala67Thr is very low (between 1% and 5%). We could not detect PVR/CD155 expression in adult human whole saliva and PVR/CD155 possibly interacts with maternal infection to predispose children to cleft lip only.

  7. The Caenorhabditis elegans interneuron ALA is (also) a high-threshold mechanosensor

    OpenAIRE

    Sanders, Jarred; Nagy, Stanislav; Fetterman, Graham; Wright, Charles; Treinin, Millet; Biron, David

    2013-01-01

    Background To survive dynamic environments, it is essential for all animals to appropriately modulate their behavior in response to various stimulus intensities. For instance, the nematode Caenorhabditis elegans suppresses the rate of egg-laying in response to intense mechanical stimuli, in a manner dependent on the mechanosensory neurons FLP and PVD. We have found that the unilaterally placed single interneuron ALA acted as a high-threshold mechanosensor, and that it was required for this pr...

  8. HYDROLOGIC MODELLING OF KATSINA-ALA RIVER BASIN: AN EMERGING SCENARIO FROM LAKE NYOS THREAT

    Directory of Open Access Journals (Sweden)

    J. O. Akinyede

    2012-07-01

    Full Text Available Understanding the hydrologic system surrounding crater lakes is of great importance for prevention of flooding damages, conservation of ecological environment, and assessment of socio-economic impact of dam failure on the civilians in the downstream regions. Lake Nyos is a crater lake formed by volcanic activities at the Oku volcanic field on the Cameroon Volcanic Line. It is a freshwater lake with a maximum depth of 200 meter. In 1986, a limnic eruption at the lake emitted 1.6 million tonnes of carbon dioxide from the bottom of saturated water into the air and suffocated up to 1,800 people and 3,500 livestock at nearby villages. The lake waters are held in place by a natural dam composed of loosely consolidated volcanic rock, which is now at the verge of collapse due to accelerated erosion. This study was carried out to determine the flood risks and vulnerability of population and infrastructure along Katsina-Ala drainage basins. The project integrated both satellite images and field datasets into a hydrologic model for Katsina-Ala River Basin and its vicinity including the Lake Nyos. ArcHydro was used to construct a hydrologic database as 'data models' and MIKE SHE was employed to conduct hydrologic simulations. Vulnerable infrastructures, population and socio-economic activities were identified to assist the Federal and State governments in disaster mitigation and management plans. The result of the project provides comprehensive knowledge of hydrologic system of Katsina-Ala drainage basin to mitigate potential future disasters from a potential dam failure and manage water resources against such disasters.

  9. Stabilization of a chitinase from Serratia marcescens by Gly-->Ala and Xxx-->Pro mutations.

    NARCIS (Netherlands)

    Gaseidnes, S.; Synstad, B.; Jia, X.; Kjellesvik, H.; Vriend, G.; Eijsink, V.G.

    2003-01-01

    This paper describes attempts to increase the kinetic stability of chitinase B from Serratia marcescens (ChiB) by the introduction of semi-automatically designed rigidifying mutations of the Gly-->Ala and Xxx-->Pro type. Of 15 single mutants, several displayed significant increases in thermal

  10. Association of PPARG Pro12Ala polymorphism with insulin sensitivity and body mass index in patients with polycystic ovary syndrome.

    Science.gov (United States)

    Baldani, Dinka Pavicic; Skrgatic, Lana; Cerne, Jasmina Z; Ferk, Polonca; Simunic, Velimir; Gersak, Ksenija

    2014-03-01

    Insulin resistance is one of the key factors in the pathogenesis of polycystic ovary syndrome (PCOS). The peroxisome proliferator-activated receptor gamma (PPARG) plays a role in the regulation of insulin sensitivity. The aim of the present study was to establish a possible association of the PPARG Pro12Ala polymorphism with PCOS and its effect on family and personal history, as well as on the metabolic and endocrine parameters in PCOS patients. A total of 151 PCOS patients and 179 healthy women of reproductive age were enrolled. History, body mass index (BMI), waist-to-hip ratio and the presence of phenotypic hyperandrogenism were recorded. Hormonal, metabolic and biochemical profiles were assessed. A molecular analysis for the genetic polymorphism was performed. One third (29.8%) of the PCOS patients were found to be carriers of at least one variant of the Ala allele (X/Ala), while 70.2% carried two wild-type Pro alleles (Pro/Pro), with an equal distribution observed in the control group. The PCOS patients carrying the X/Ala alleles exhibited lower serum fasting insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR) and BMI compared to Pro/Pro carriers. This finding was significant only in the lean PCOS group. The polymorphic genotype exerted no effect on history, hormonal and clinical hyperandrogenism, lipid status or C-reactive protein, leptin, adiponectin, resistin and ghrelin serum levels in women with PCOS. In conclusion, although the PPARG Pro12Ala polymorphism is not a major determinant of PCOS in the Croatian population, it may exert a positive effect on insulin sensitivity and BMI. As these associations were recorded exclusively in the lean group of patients with PCOS, this polymorphism potentially contributes to a protective role against hyperinsulinemia and obesity.

  11. Electron microscopy of GaAs-based structures with InAs and As quantum dots separated by an AlAs barrier

    International Nuclear Information System (INIS)

    Nevedomskiy, V. N.; Bert, N. A.; Chaldyshev, V. V.; Preobrazhenskiy, V. V.; Putyato, M. A.; Semyagin, B. R.

    2013-01-01

    Electron microscopy studies of GaAs-based structures grown by molecular beam epitaxy and containing arrays of semiconductor InAs quantum dots and metal As quantum dots are performed. The array of InAs quantum dots is formed by the Stranski-Krastanov mechanism and consists of vertically coupled pairs of quantum dots separated by a GaAs spacer 10 nm thick. To separate the arrays of semiconductor and metal quantum dots and to prevent diffusion-induced mixing, the array of InAs quantum dots is overgrown with an AlAs barrier layer 5 or 10 nm thick, after which a GaAs layer is grown at a comparatively low temperature (180°C). The array of As quantum dots is formed in an As-enriched layer of the low-temperature GaAs by means of post-growth annealing at 400–760°C for 15 min. It is established that the AlAs barrier layer has a surface profile corresponding to that of a subbarrier layer with InAs quantum dots. The presence of such a profile causes the formation of V-shaped structural defects upon subsequent overgrowth with the GaAs layer. Besides, it was obtained that AlAs layer is thinned over the InAs quantum dots tops. It is shown that the AlAs barrier layer in the regions between the InAs quantum dots effectively prevents the starting diffusion of excess As at annealing temperatures up to 600°C. However, the concentration of mechanical stresses and the reduced thickness of the AlAs barrier layer near the tops of the InAs quantum dots lead to local barrier breakthroughs and the diffusion of As quantum dots into the region of coupled pairs of InAs quantum dots at higher annealing temperatures

  12. Comparison of the crystal structure and function to wild-type and His25Ala mutant human heme oxygenase-1.

    Science.gov (United States)

    Zhou, Wen-Pu; Zhong, Wen-Wei; Zhang, Xue-Hong; Ding, Jian-Ping; Zhang, Zi-Li; Xia, Zhen-Wei

    2009-03-01

    Human heme oxygenase-1 (hHO-1) is a rate-limiting enzyme in heme metabolism. It regulates serum bilirubin level. Site-directed mutagenesis studies indicate that the proximal residue histidine 25 (His25) plays a key role in hHO-1 activity. A highly purified hHO-1 His25Ala mutant was generated and crystallized with a new expression system. The crystal structure of the mutant was determined by X-ray diffraction technology and molecular replacement at the resolution of 2.8 A, and the model of hHO-1 His25Ala mutant was refined. The final crystallographic and free R factors were 0.245 and 0.283, respectively. The standard bond length deviation was 0.007 A, and the standard bond angle deviation was 1.3 degrees . The mutation of His25 to Ala led to an empty pocket underneath the ferric ion in the heme, leading to loss of binding iron ligand. Although this did not cause an overall structural change, the enzymatic activity of the mutant hHO-1 was reduced by 90%. By supplementing imidazole, the HO-1 activity was restored approximately 90% to its normal level. These data suggest that Ala25 remains unchanged in the structure compared to His25, but the important catalytic function of hHO-1 is lost. Thus, it appears that His25 is a crucial residue for proper hHO-1 catalysis.

  13. Design rules for modulation doped AlAs quantum wells

    Science.gov (United States)

    Chung, Yoon Jang; Baldwin, K. W.; West, K. W.; Kamburov, D.; Shayegan, M.; Pfeiffer, L. N.

    AlxGa1-xAs/AlAs/AlxGa1-xAs quantum wells were grown with various barrier compositions ranging from x =0.26 to x =0.8. We investigate the modulation doping characteristics of the samples by magneto-transport measurements. The carrier concentration in the well peaks near the barrier alloy fraction of x =0.26 in the dark and near x =0.38 after illumination with a red LED. This behavior is consistent with the results in a separate study for AlxGa1-xAs/GaAs/AlxGa1-xAs quantum wells in the range of x =0.26 to x =1.0. We show from a charge transfer model that the calculated energy difference between the conduction band offset at the well interface and the donor energy level, ΔEC-ED, coincides for the two types of wells. This implies that, despite the differing positions of the conduction band minimum for the GaAs and AlAs wells, the doping of either well is governed by the electronic properties of the barrier. Based on this knowledge we designed high quality AlAs quantum wells with low (1 x 1011 cm-2) and high (3 x 1011 cm-2) density, and the magneto-transport data show clear signals of the fractional quantum Hall effect (2/3, 3/5, 4/7 for low density and 5/3, 8/5 for high density). Work supported by the NSF (Grants DMR-1305691, ECCS-1508925, and MRSEC DMR-1420541), the DOE Basic Energy Sciences (Grant DE-FG02-00-ER45841), the Gordon and Betty Moore Foundation (Grant GBMF4420), and the Keck Foundation.

  14. Novel Association of WNK4 Gene, Ala589Ser Polymorphism in Essential Hypertension, and Type 2 Diabetes Mellitus in Malaysia

    Directory of Open Access Journals (Sweden)

    Nooshin Ghodsian

    2016-01-01

    Full Text Available With-no-lysine (K Kinase-4 (WNK4 consisted of unique serine and threonine protein kinases, genetically associated with an autosomal dominant form of hypertension. Argumentative consequences have lately arisen on the association of specific single nucleotide polymorphisms of WNK4 gene and essential hypertension (EHT. The aim of this study was to determine the association of Ala589Ser polymorphism of WNK4 gene with essential hypertensive patients in Malaysia. WNK4 gene polymorphism was specified utilizing mutagenically separated polymerase chain reaction (PCR and restriction fragment length polymorphism (RFLP method in 320 subjects including 163 cases and 157 controls. Close relation between Ala589Ser polymorphism and elevated systolic and diastolic blood pressure (SBP and DBP was recognized. Sociodemographic factors including body mass index (BMI, age, the level of fasting blood sugar (FBS, low density lipoprotein (LDL, and triglyceride (TG in the cases and healthy subjects exhibited strong differences (p<0.05. The distribution of allele frequency and genotype of WNK4 gene Ala589Ser polymorphism showed significant differences (p<0.05 between EHT subjects with or without type 2 diabetes mellitus (T2DM and normotensive subjects, statistically. The WNK4 gene variation influences significantly blood pressure increase. Ala589Ser probably has effects on the enzymic activity leading to enhanced predisposition to the disorder.

  15. Surgical strategy for malignant gliomas involving pyramidal tracts guided by functional neuronavigation and 5-ALA fluorescence navigation

    International Nuclear Information System (INIS)

    Sato, Ken-ichi; Ito, Tamio; Seo, Yoshinobu; Sunohara, Tadashi; Maeda, Masana; Sasaki, Takehiko; Nakagawara, Jyoji; Nakamura, Hirohiko

    2009-01-01

    For patients with malignant glioma invading pyramidal tracts, maximal resections are difficult to accomplish while preserving their motor function. We used tractography-integrated functional neuronavigation and 5-aminolevulinic acid (5-ALA) fluorescence-guided resection for removal of malignant gliomas involving pyramidal tract. In this study, we analyzed postoperative motor function and extent of resection in a series of patients who underwent surgery in our department. Ten patients with malignant glioma invading pyramidal tracts underwent radical surgery. To preserve pyramidal tracts, we developed a functional neuronavigation-guided fence-post procedure to avoid the problem of brain shift, a disadvantage of the existing neuronavigation systems. Furthermore we have achieved precise resection of tumors using 5-ALA fluorescence navigation. Intraoperatively, tumor fluorescence was visualized using a modified operating microscope. All fluorescing tumor tissue was resected. Motor function was preserved after appropriate tumor resection in all cases. Postoperatively, improvement of motor weakness was observed in seven patients, whereas transient mild motor weakness occurred in two patients. Gross total removals were accomplished in seven patients, and subtotal removal was accomplished in one patient, and partial removal was accomplished in two patients. Combined use of tractography-integrated functional neuronavigation and 5-ALA fluorescence-guided resection contributes to maximal safe resection of malignant gliomas with pyramidal tract involvement. (author)

  16. The Arabidopsis P4-ATPase ALA3 requires a ß-subunit to function in phospholipid translocation and secretory vesicle formation

    DEFF Research Database (Denmark)

    Lopez Marques, Rosa Laura

    The Arabidopsis P4-ATPase ALA3 requires a ß-subunit to function in phospholipid translocation and secretory vesicle formation   Lisbeth R. Poulsen1, Rosa L. López-Marqués1, Stephen C. McDowell2, Juha Okkeri3, Dirk Licht3, Alexander Schulz1, Thomas Pomorski3,  Jeffrey F. Harper2, and Michael G....... Palmgren1 1Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation, Department of Plant Biology, University of Copenhagen, DK-1871 Frederiksberg C, Denmark 2Biochemistry Department MS200, University of Nevada Reno, NV 89557, USA 3Humboldt-University Berlin, Faculty...... and in inducing membrane curvature, which is a requirement for vesicle formation. We show that Aminophospholipid ATPase3 (ALA3), a member of the P4-ATPase subfamily in the plant Arabidopsis thaliana, localizes to the Golgi apparatus and that genetic lesions of ALA3 result in impaired growth of roots and shoots...

  17. A determination of occlusal plane comparing different levels of the tragus to form ala-tragal line or Camper's line: A photographic study.

    Science.gov (United States)

    Kumar, Sandeep; Garg, Sandeep; Gupta, Seema

    2013-02-01

    The purpose of this study was to determine accurately the part of the tragus to be used to form the Ala-Tragal line or Camper's line in orthognathic profile patients. 150 dentate subjects with age of 18-40 years with orthognathic profile were sampled. Life-size lateral digital photographs of the face with fox plane were taken in natural head position. Different angles between Eye-Ear plane and occlusal plane (OT1-OP), Eye-Ear plane and ala-superior border of tragus (OT1-AT1), Eye-Ear plane and ala-middle border of tragus (OT1-AT2) and Eye-Ear plane and ala-inferior border of tragus (OT1-AT3) were calculated using computer software package, AutoCAD 2004. From the three angles formed by the Eye-ear plane (OT1 or FH plane) and the ala-tragal lines, the one closest to the angle formed between Eye-Ear plane (OT1) and occlusal plane (OP) was used to determine the occlusal plane of orientation. The obtained results were subjected to ANOVA F test, Tukey's Honestly significant difference test, followed by Karl Pearson coefficient of correlation test. P values of less than 0.05 were taken as statistically significant. The mean of base line angle i.e. OT1-OP angle (11.96 ± 4.36) was found to be close to OT1-AT2 angle (13.67 ± 1.93) and OT1-AT3 angle (10.31 ± 2.03), but OT1-OP angle was found to be more closer to OT1-AT3 angle. Comparison of mean angles showed that OT1-OP angle in both males (11.68) and females (12.51) is close to OT1-AT3 angle (males- 11.01, females- 11.95). The line joining from ala to the lower border of the tragus was parallel to the occlusal plane in 53.3% of the subjects. There was no influence of the sex on the level of occlusal plane.

  18. Role of 5-ALA in improving extent of tumour resection in patients with Glioblastoma Multiforme.

    Science.gov (United States)

    Waqas, Muhammad; Khan, Inamullah; Shamim, Muhammad Shahzad

    2017-10-01

    Goal of surgery for patients with Glioblastoma Multiforme (GBM) is gross total resection with no new neurological deficits. Surgical resection is often restricted due the difficulty in differentiating the tumour from surrounding normal brain using either naked eye, or standard intra-operative white light microscopy. GBM uptakes orally administered 5-ALA becomes fluorescent when viewed by a special light, and this property has been used to improve intra-operative tumour identification. This technique should therefore allow better extent of tumour resection. The hypothesis has been tested through several studies and even though most studies are of low quality, they strongly favour the use of 5- ALA in improving the extent of resection when compared to white light microscopy. A systematic review on the topic had a similar conclusion. Few studies have also hinted on a high false negative rate with the use of this technique..

  19. H2O2 mediates ALA-induced glutathione and ascorbate accumulation in the perception and resistance to oxidative stress in Solanum lycopersicum at low temperatures.

    Science.gov (United States)

    Liu, Tao; Hu, Xiaohui; Zhang, Jiao; Zhang, Junheng; Du, Qingjie; Li, Jianming

    2018-02-15

    Low temperature is a crucial factor influencing plant growth and development. The chlorophyll precursor, 5-aminolevulinic acid (ALA) is widely used to improve plant cold tolerance. However, the interaction between H 2 O 2 and cellular redox signaling involved in ALA-induced resistance to low temperature stress in plants remains largely unknown. Here, the roles of ALA in perceiving and regulating low temperature-induced oxidative stress in tomato plants, together with the roles of H 2 O 2 and cellular redox states, were characterized. Low concentrations (10-25 mg·L - 1 ) of ALA enhanced low temperature-induced oxidative stress tolerance of tomato seedlings. The most effective concentration was 25 mg·L - 1 , which markedly increased the ratio of reduced glutathione and ascorbate (GSH and AsA), and enhanced the activities of superoxide dismutase, catalase, ascorbate peroxidase, dehydroascorbate reductase, and glutathione reductase. Furthermore, gene expression of respiratory burst oxidase homolog1 and H 2 O 2 content were upregulated with ALA treatment under normal conditions. Treatment with exogenous H 2 O 2 , GSH, and AsA also induced plant tolerance to oxidative stress at low temperatures, while inhibition of GSH and AsA syntheses significantly decreased H 2 O 2 -induced oxidative stress tolerance. Meanwhile, scavenging or inhibition of H 2 O 2 production weakened, but did not eliminate, GSH- or AsA- induced tomato plant tolerance to oxidative stress at low temperatures. Appropriate concentrations of ALA alleviated the low temperature-induced oxidative stress in tomato plants via an antioxidant system. The most effective concentration was 25 mg·L - 1 . The results showed that H 2 O 2 induced by exogenous ALA under normal conditions is crucial and may be the initial step for perception and signaling transmission, which then improves the ratio of GSH and AsA. GSH and AsA may then interact with H 2 O 2 signaling, resulting in enhanced antioxidant capacity

  20. Thr92Ala polymorphism in the type 2 deiodinase is not associated with T4 dose in athyroid patients or patients with Hashimoto thyroiditis

    NARCIS (Netherlands)

    Heemstra, K. A.; Hoftijzer, H. C.; van der Deure, W. M.; Peeters, R. P.; Fliers, E.; Appelhof, B. C.; Wiersinga, W. M.; Corssmit, E. P. M.; Visser, T. J.; Smit, J. W. A.

    2009-01-01

    SUMMARY Objective: The type 2 deiodinase (D2)-Thr92Ala polymorphism has been associated with decreased D2 activity in some in vitro experiments but not in others. So far no association between the D2-Thr92Ala polymorphism and serum thyroid hormone levels has been observed in humans, but in a recent

  1. Peroxisome proliferator-activated receptor-gamma (PPARgamma) Pro12Ala polymorphism and risk for pediatric obesity

    NARCIS (Netherlands)

    Dedoussis, George V; Vidra, Nikoleta; Butler, Johannah; Papoutsakis, Constantina; Yannakoulia, Mary; Hirschhorn, Joel N; Lyon, Helen N; Vidra, Nikoletta

    BACKGROUND: Variation in the peroxisome-proliferator-activated receptor gamma (PPARgamma) gene has been reported to alter the risk for adiposity in adults. METHODS: We investigated the gender related association between the Pro12Ala variant (rs1801282) in obesity and insulin resistance traits in 794

  2. Tunnustati parimaid üliõpilasteadlasi / Elsa Suuster, Marit Alas, Annely Aleksejev ; küsitlenud Vilma Rauniste

    Index Scriptorium Estoniae

    Putku, Elsa, 1984-

    2009-01-01

    Vestlus üliõpilaste teadustööde riikliku konkursi kolme laureaadiga, kelle uurimistöö oli tehtud Saare maakonnas. Nendeks on Elsa Suuster ja Annely Aleksejev Eesti Maaülikoolist ning Marit Alas Tallinna Ülikoolist

  3. The Ala54Thr Polymorphism of the Fatty Acid Binding Protein 2 Gene Modulates HDL Cholesterol in Mexican-Americans with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Lorena M. Salto

    2015-12-01

    Full Text Available The alanine to threonine amino acid substitution at codon 54 (Ala54Thr of the intestinal fatty acid binding protein (FABP2 has been associated with elevated levels of insulin and blood glucose as well as with dyslipidemia. The aim of this study was to characterize the effect of this FABP2 polymorphism in Mexican-Americans with type 2 diabetes (T2D in the context of a three-month intervention to determine if the polymorphism differentially modulates selected clinical outcomes. For this study, we genotyped 43 participant samples and performed post-hoc outcome analysis of the profile changes in fasting blood glucose, HbA1c, insulin, lipid panel and body composition, stratified by the Ala54Thr polymorphism. Our results show that the Thr54 allele carriers (those who were heterozygous or homozygous for the threonine-encoding allele had lower HDL cholesterol and higher triglyceride levels at baseline compared to the Ala54 homozygotes (those who were homozygous for the alanine-encoding allele. Both groups made clinically important improvements in lipid profiles and glycemic control as a response to the intervention. Whereas the Ala54 homozygotes decreased HDL cholesterol in the context of an overall total cholesterol decrease, Thr54 allele carriers increased HDL cholesterol as part of an overall total cholesterol decrease. We conclude that the Ala54Thr polymorphism of FABP2 modulates HDL cholesterol in Mexican-Americans with T2D and that Thr54 allele carriers may be responsive in interventions that include dietary changes.

  4. Patarei ja Lennusadama ala planeering = Plan for the Patarei Fort and Lennusadam Port Area

    Index Scriptorium Estoniae

    2007-01-01

    Patarei ja Lennusadama ala mahulise planeerimise rahvusvaheline ideevõistlus 2007. aastal. Võistlustööd "Kolm õuna" (I preemia - Sverre Laanjärv, Ivar Lubjak), "Põhi" (II preemia - Tõnu Laanemäe, Jaak-Adam Looveer, Toomas Paaver, kaasautorid Indrek Järve ja Lauri Saar) ja "Kompass" (III preemia - Ott Kadarik ja Villem Tomiste, AB Kosmos)

  5. The Thr92Ala deiodinase type 2 (DIO2) variant is not associated with type 2 diabetes or indices of insulin resistance in the old order of Amish.

    Science.gov (United States)

    Mentuccia, Daniela; Thomas, Matthew J; Coppotelli, Giuseppe; Reinhart, Laurie J; Mitchell, Braxton D; Shuldiner, Alan R; Celi, Francesco S

    2005-11-01

    A common polymorphism of the type 2 deiodinase gene (Thr92Ala DIO2) was found to be associated with insulin resistance in a mixed Caucasian population. The aim of this study was to investigate the association of the Thr92Ala DIO2 variant to indices of insulin resistance in the Old Order Amish. A genotype-phenotype association study was performed at the research clinic in Strasburg, Pennsylvania, and the molecular genetics laboratory at the University of Maryland, Baltimore, Maryland, and the National Institutes of Health, Bethesda, Maryland. A total of 1,268 subjects participated in the Amish Family Diabetes Study. An association among the Thr92Ala DIO2 variant and type 2 diabetes, indices of insulin resistance (HOMA-IR), insulin secretion, free thyroid hormones, and thyrotropin (TSH) was found. No association was found among the Thr92Ala DIO2 variant and type 2 diabetes, impaired glucose tolerance, or body mass index (BMI) in the Amish. In nondiabetics (n = 747), the Ala92 allele tended to be associated with decreased rather then increased insulin secretion. No differences were observed in thyroid hormones or TSH. Contrary to prior findings, the Thr92Ala DIO2 variant tends to be associated with increased rather then decreased insulin sensitivity in the Amish. These findings could be secondary to a different genetic background or to environmental factors specific for this population.

  6. Association of Pro12Ala polymorphism of PPAR-γ2 Gene and diabetic retinopathy in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Yong-Qing Liu

    2013-06-01

    Full Text Available AIM: To observe the relationship between Prol2Ala polymorphism of peroxisome proliferator activated receptor-γ2(PPAR-γ2gene and diabetic retinopathy(DRwith type 2 diabetic mellitus(T2DMof the Han nationality in Shanxi province. METHODS: Totally 90 patients with T2DM were selected into our research, who were at the age of 40 to 70 years old, diabetic duration from 10 to 20 years, blood pressure PPAR-γ2 gene were determined by polymerase chain reaction-restriction fragment length polymorphisms(PCR-RFLPassay in all the patients. RESULTS: PCR results showed that there were 2 alleles and 3 genotypes in the groups. The frequency of genotype PP, PA, AA were 40.0%, 53.3%, 6.7% in NDR group, 70.0%, 30.0%, 0.0% in BDR group, 76.7%, 23.3%, 0% in PDR group, respectively. The allele frequency(χ2=10.208and gene frequency(χ2=10.351were statistically significant(PCONCLUSION: The alanine variant of Prol2Ala polymorphism of PPAR-γ2 gene is associated with DR in type 2 diabetes among the Hans in Shanxi area, and the Ala allele might be a protective factor for the development of diabetic retinopathy.

  7. Spinal antinociceptive effects of [D-Ala2]deltorphin II, a novel and highly selective delta-opioid receptor agonist.

    Science.gov (United States)

    Improta, G; Broccardo, M

    1992-01-01

    Pharmacological assays in isolated tissues and binding tests have recently shown that two peptides, with the sequence Tyr-D-Ala-Phe-Asp-(or Glu)- Val-Val-Gly-NH2, isolated from skin extracts of Phyllomedusa bicolor and named [D-Ala2]deltorphin I and II, respectively, possess a higher affinity and selectivity for delta-opioid receptors than any other known natural compound. Since much evidence supports the role of spinal delta-opioid sites in producing antinociceptive effects, we investigated whether analgesia might be detected by direct spinal cord administration of [D-Ala2]deltorphin II (DADELT II) in the rat. The thermal antinociceptive effects of intrathecal DADELT II and dermorphin, a potent mu-selective agonist, were compared at different postinjection times by means of the tail-flick test. The DADELT II produced a dose-related inhibition of the tail-flick response, which lasted 10-60 min depending on the dose and appeared to be of shorter duration than the analgesia produced in rats after intrathecal injection of dermorphin (20-120 min). The analgesic effect of infused or injected DADELT II was completely abolished by naltrindole, the highly selective delta antagonist. These results confirm the involvement of delta receptors in spinal analgesic activity in the rat.

  8. Thermal conductivity of InAs quantum dot stacks using AlAs strain compensating layers on InP substrate

    International Nuclear Information System (INIS)

    Salman, S.; Folliot, H.; Le Pouliquen, J.; Chevalier, N.; Rohel, T.; Paranthoën, C.; Bertru, N.; Labbé, C.; Letoublon, A.; Le Corre, A.

    2012-01-01

    Highlights: ► The thermal conductivity of InAs on InP (1 1 3)B quantum dots stacks is measured. ► The growth of a close stack of 100 layers of InAs using AlAs strain compensating layers is presented. ► New data on the thermal conductivity of InP n-doped susbtrate are given. - Abstract: The growth and thermal conductivity of InAs quantum dot (QD) stacks embedded in GaInAs matrix with AlAs compensating layers deposited on (1 1 3)B InP substrate are presented. The effect of the strain compensating AlAs layer is demonstrated through Atomic Force Microscopy (AFM) and X-ray diffraction structural analysis. The thermal conductivity (2.7 W/m K at 300 K) measured by the 3ω method reveals to be clearly reduced in comparison with a bulk InGaAs layer (5 W/m K). In addition, the thermal conductivity measurements of S doped InP substrates and the SiN insulating layer used in the 3ω method in the 20–200 °C range are also presented. An empirical law is proposed for the S doped InP substrate, which slightly differs from previously presented results.

  9. Lead and zinc concentrations in plasma, erythrocytes, and urine in relation to ALA-D activity after intravenous infusion of Ca-EDTA.

    OpenAIRE

    Ishihara, N; Shiojima, S; Hasegawa, K

    1984-01-01

    Lead and zinc concentrations in plasma, erythrocytes, and urine, urinary ALA concentration, and ALA-D activity in blood were studied for four hours in two male lead workers during and after a one hour infusion of Ca-EDTA 2Na. Urinary and plasma lead concentrations increased as a result of administering Ca-EDTA 2Na, and the ratios of lead concentrations in plasma to those in urine were greatly increased. The increase of plasma lead concentration was not due to the haemolytic effect of Ca-EDTA ...

  10. Association of the Pro12Ala Polymorphism with the Metabolic Parameters in Women with Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Moushira Zaki

    2017-06-01

    CONCLUSION: The PPARG Pro12Ala polymorphism might contribute to the risk of PCOS and abnormal metabolic parameters and could be considered as a biomarker for early diagnosis and clinic prediction of metabolic complications.

  11. But what about girls? : introduction into girls' studies / Eda Kalmre

    Index Scriptorium Estoniae

    Kalmre, Eda, 1958-

    2012-01-01

    5203 Tutvustus: Entäs tytöt : johdatus tyttötutkimukseen / toimittaneet Karoliina Ojanen, Heta Mulari & Sanna Aaltonen. Tampere : Vastapaino, 2011. (Julkaisuja / Nuorisotutkimusverkosto & Nuorisotutkimusseura ; 113)

  12. Healthy reduced-fat Bologna sausages enriched in ALA and DHA and stabilized with Melissa officinalis extract.

    Science.gov (United States)

    Berasategi, Izaskun; Navarro-Blasco, Iñigo; Calvo, Maria Isabel; Cavero, Rita Yolanda; Astiasarán, Iciar; Ansorena, Diana

    2014-03-01

    Reduced-energy and reduced-fat Bologna products enriched with ω-3 polyunsaturated fatty acids were formulated by replacing the pork back-fat by an oil-in-water emulsion containing a mixture of linseed-algae oil stabilized with a lyophilized Melissa officinalis extract. Healthier composition and lipid profile was obtained: 85 kcal/100 g, 3.6% fat, 0.6 g ALA and 0.44 g DHA per 100 g of product and ω-6/ω-3 ratio of 0.4. Technological and sensory problems were not detected in the new formulations. Reformulation did not cause oxidation problems during 32 days of storage under refrigeration. The results suggest that it is possible to obtain reduced-fat Bologna-type sausages rich in ALA and DHA and stabilized with natural antioxidants, applying the appropriate technology without significant effects on the sensory quality, yielding interesting products from a nutritional point of view. © 2013.

  13. cDNAs encoding [D-Ala2]deltorphin precursors from skin of Phyllomedusa bicolor also contain genetic information for three dermorphin-related opioid peptides.

    Science.gov (United States)

    Richter, K; Egger, R; Negri, L; Corsi, R; Severini, C; Kreil, G

    1990-06-01

    We present the structure of four precursors for [D-Ala2]deltorphins I and II as deduced from cDNAs cloned from skin of the frog Phyllomedusa bicolor. These contain the genetic information for one copy of [D-Ala2]deltorphin II and zero, one, or three copies of [D-Ala2]deltorphin I. In each case, the D-alanine of the end product is encoded by a normal GCG codon for L-alanine. In addition, the existence of three peptides related to dermorphin was predicted from the amino acid sequence of the precursors. These peptides were synthesized with a D-alanine in position 2 and their pharmacological properties were tested. Two of them, [Lys7]dermorphin-OH and [Trp4,Asn7]dermorphin-OH, were found to have roughly the same affinity and selectivity for mu-type opioid receptors as dermorphin.

  14. PPARγ Pro12Ala polymorphism and risk of acute coronary syndrome in a prospective study of Danes

    Directory of Open Access Journals (Sweden)

    Jensen Majken K

    2009-06-01

    Full Text Available Abstract Background Acute coronary syndrome (ACS is a major cause of morbidity and mortality in the western world. Peroxisome proliferator-activated receptor γ (PPARγ plays a key role in the regulation of the energy balance, adipocyte differentiation and lipid biosynthesis. The aim was to investigate if the polymorphism PPARγ2 Pro12Ala, which encodes a less efficient transcription factor, was associated with risk of acute coronary disease and if there were interactions between this polymorphism and factors that modify PPARγ activity, such as alcohol intake, smoking, and use of non-steroidal anti-inflammatory medicine. Methods A case-cohort study including 1031 ACS cases and a sub-cohort of 1703 persons was nested within the population-based prospective study Diet, Cancer and Health of 57,053 individuals. Results Homozygous male variant allele carriers of PPARγ2 Pro12Ala were at higher risk of ACS (HR = 2.12, 95% CI: 1.00–4.48 than homozygous carriers of the Pro-allele. Among men, there was a statistically significant interaction between genotypes and alcohol intake such that homozygous variant allele carriers with a low alcohol intake were at higher risk of ACS (HR = 25.3, CI: 16.5–38.7 compared to homozygous common allele carriers (p for interaction Conclusion In the present study, there were no consistent associations between PPARγ Pro12Ala and risk of ACS, and no consistent interaction with alcohol, BMI, NSAID or smoking in relation to ACS.

  15. Dietary ALA, EPA and DHA have distinct effects on oxylipin profiles in female and male rat kidney, liver and serum.

    Science.gov (United States)

    Leng, Shan; Winter, Tanja; Aukema, Harold M

    2018-04-18

    There is much data on the effects of dietary n-3 fatty acids on tissue fatty acid compositions, but comparable comprehensive data on their oxygenated metabolites (oxylipins) is limited. The effects of providing female and male rats with diets high in α-linolenic acid (ALA), EPA or DHA for 6 weeks on oxylipins and fatty acids in kidney, liver and serum were therefore examined. The oxylipin profile generally reflected fatty acids, but it also revealed unique effects of individual n-3 fatty acids that were not apparent from fatty acid data alone. Dietary ALA increased renal and serum DHA oxylipins even though DHA itself did not increase, while dietary EPA did not increase DHA oxylipins in kidney or liver, suggesting that high EPA may inhibit this conversion. Oxylipin data generally corroborated fatty acid data that indicated that DHA can be retroconverted to EPA and that further retroconversion to ALA is limited. Dietary n-3 fatty acids decreased n-6 fatty acids and their oxylipins (except linoleic acid and its oxylipins), in order of effectiveness of DHA > EPA > ALA, with some exceptions: several arachidonic acid oxylipins modified at carbon 15 were not lower in all three sites, and EPA had a greater effect on 12-hydroxy-eicosatetraenoic acid and its metabolites in the liver. Oxylipins were predominantly higher in males, which was not reflective of fatty acids. Tissue-specific oxylipin profiles, therefore, provide further information on individual dietary n-3 fatty acid and sex effects that may help explain their unique physiological effects and have implications for dietary recommendations. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Functional and Histological Evaluation following Canine Vocal Fold Reconstruction Using Composite Thyroid Ala Perichondrium Flaps.

    Science.gov (United States)

    Hoffman, Matthew R; Glab, Rachel; Gunderson, McLean; Maytag, Allison L; Yang, David T; Jiang, Jack J; Dailey, Seth H

    2015-07-01

    We evaluated the effects of vocal fold reconstruction using a composite thyroid ala perichondrium flap (CTAP) after unilateral vocal fold stripping in beagles. We hypothesized that CTAP would improve glottic closure, decrease phonation threshold pressure, and decrease perturbation. In addition, vocal folds with CTAP would exhibit neovascularization and fat with increased von Willebrand factor (vWF) and smooth muscle actin (SMA), reflecting neoangiogenesis and flap viability. Randomized controlled trial using beagles. University laboratory. Ten beagles underwent unilateral vocal fold stripping. Dogs in the scar-only group (n = 5) were sacrificed at 1 month. Dogs in the CTAP group (n = 5) underwent ipsilateral reconstruction with CTAP at 1 month and were sacrificed at 2 months. Excised larynx experiments evaluated vocal fold vibration using aerodynamic, acoustic, and mucosal wave measurements. Qualitative evaluation of vocal fold morphology and quantitative analysis of elastin, collagen, glycosaminoglycans, vWF, SMA, and hyaluronic acid were performed. Phonation threshold pressure (P = .005), percent jitter (P = .010), percent shimmer (P = .007), and open quotient (P = .007) were lower in the CTAP group. Neovascularization (P = .0079) and fat (P = .1667) occurred more with CTAP, although the difference in fat was not significant. von Willebrand factor was higher with CTAP vs contralateral normal fold (P = .110), although not statistically significant. Smooth muscle actin was higher with CTAP vs contralateral normal fold (P = .038) and scarred vocal folds (P = .022). Composite thyroid ala perichondrium flap restored glottic closure and vibratory periodicity following vocal fold scarring. Additional investigation on biologic response is warranted. Composite thyroid ala perichondrium flap offers an autologous, vascularized implant that can improve both vocal fold structure and function. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

  17. Evaluation of 99mTc-HYNIC-βAla-Bombesin(7-14 as an agent for pancreas tumor detection in mice

    Directory of Open Access Journals (Sweden)

    F.N. Carlesso

    2015-01-01

    Full Text Available Pancreatic adenocarcinoma is important in oncology because of its high mortality rate. Deaths may be avoided if an early diagnosis could be achieved. Several types of tumors overexpress gastrin-releasing peptide receptors (GRPr, including pancreatic cancer cells. Thus, a radiolabeled peptide derivative of gastrin-releasing peptide (GRP may be useful as a specific imaging probe. The purpose of the present study was to evaluate the feasibility of using 99mTc-HYNIC-βAla-Bombesin(7-14 as an imaging probe for Capan-1 pancreatic adenocarcinoma. Xenographic pancreatic tumor was developed in nude mice and characterized by histopathological analysis. Biodistribution studies and scintigraphic images were carried out in tumor-bearing nude mice. The two methods showed higher uptake by pancreatic tumor when compared to muscle (used as control, and the tumor-to-muscle ratio indicated that 99mTc-HYNIC-βAla-Bombesin(7-14 uptake was four-fold higher in tumor cells than in other tissues. Scintigraphic images also showed a clear signal at the tumor site. The present data indicate that 99mTc-HYNIC-βAla-Bombesin(7-14 may be useful for the detection of pancreatic adenocarcinoma.

  18. Implication of the Pro12Ala polymorphism of the PPAR-gamma 2 gene in type 2 diabetes and obesity in the French population

    Directory of Open Access Journals (Sweden)

    Charles Marie-Aline

    2005-03-01

    Full Text Available Abstract Background The Pro12Ala Single Nucleotide Polymorphism (SNP of the Peroxisome Proliferator-Activated Receptor gamma 2 (PPAR-gamma 2 has been associated with insulin resistance and type 2 diabetes (T2D and also inconsistently with obesity. The aim of this study was to evaluate the impact of this SNP with regards to T2D and childhood and adult obesity in the French Caucasian population. Methods We conducted three independent case/control studies encompassing 2126 cases and 1124 controls. Results We found a significant association between PPAR-gamma 2 Pro12Ala SNP and T2D (p = 0.04, OR = 1.37, which was stronger when the T2D cohort was stratified according to the obesity status (p = 0.03, OR = 1.81 in obese T2D subjects. In contrast, there was no association between the Pro12Ala SNP and childhood and adulthood obesity. In normal glucose tolerant obese adults (but not in lean subjects, the Pro12 allele was associated with a significant increase in fasting insulin levels (p = 0.01, and in insulin resistance estimated by the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR (p = 0.003, after adjustment for age, gender and BMI. We didn't detect evidence for an interaction effect between the Pro12Ala SNP and the obesity status with respect to the HOMA-IR index in normal glucose tolerant children, but we found a borderline interaction (p = 0.06 in normal glucose tolerant adults. Conclusion Our results showed that the Pro12Ala polymorphism is not associated with childhood or adult obesity in the French Caucasian population. In contrast, we confirm a contribution of the PPAR-gamma 2 Pro12 allele in the genetic risk forT2D, especially in obese subjects, where this allele worsens insulin resistanceand increases fasting insulin levels.

  19. The effectiveness and cost-effectiveness of intraoperative imaging in high-grade glioma resection; a comparative review of intraoperative ALA, fluorescein, ultrasound and MRI.

    Science.gov (United States)

    Eljamel, M Sam; Mahboob, Syed Osama

    2016-12-01

    Surgical resection of high-grade gliomas (HGG) is standard therapy because it imparts significant progression free (PFS) and overall survival (OS). However, HGG-tumor margins are indistinguishable from normal brain during surgery. Hence intraoperative technology such as fluorescence (ALA, fluorescein) and intraoperative ultrasound (IoUS) and MRI (IoMRI) has been deployed. This study compares the effectiveness and cost-effectiveness of these technologies. Critical literature review and meta-analyses, using MEDLINE/PubMed service. The list of references in each article was double-checked for any missing references. We included all studies that reported the use of ALA, fluorescein (FLCN), IoUS or IoMRI to guide HGG-surgery. The meta-analyses were conducted according to statistical heterogeneity between studies. If there was no heterogeneity, fixed effects model was used; otherwise, a random effects model was used. Statistical heterogeneity was explored by χ 2 and inconsistency (I 2 ) statistics. To assess cost-effectiveness, we calculated the incremental cost per quality-adjusted life-year (QALY). Gross total resection (GTR) after ALA, FLCN, IoUS and IoMRI was 69.1%, 84.4%, 73.4% and 70% respectively. The differences were not statistically significant. All four techniques led to significant prolongation of PFS and tended to prolong OS. However none of these technologies led to significant prolongation of OS compared to controls. The cost/QALY was $16,218, $3181, $6049 and $32,954 for ALA, FLCN, IoUS and IoMRI respectively. ALA, FLCN, IoUS and IoMRI significantly improve GTR and PFS of HGG. Their incremental cost was below the threshold for cost-effectiveness of HGG-therapy, denoting that each intraoperative technology was cost-effective on its own. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. AlaScan: A Graphical User Interface for Alanine Scanning Free-Energy Calculations.

    Science.gov (United States)

    Ramadoss, Vijayaraj; Dehez, François; Chipot, Christophe

    2016-06-27

    Computation of the free-energy changes that underlie molecular recognition and association has gained significant importance due to its considerable potential in drug discovery. The massive increase of computational power in recent years substantiates the application of more accurate theoretical methods for the calculation of binding free energies. The impact of such advances is the application of parent approaches, like computational alanine scanning, to investigate in silico the effect of amino-acid replacement in protein-ligand and protein-protein complexes, or probe the thermostability of individual proteins. Because human effort represents a significant cost that precludes the routine use of this form of free-energy calculations, minimizing manual intervention constitutes a stringent prerequisite for any such systematic computation. With this objective in mind, we propose a new plug-in, referred to as AlaScan, developed within the popular visualization program VMD to automate the major steps in alanine-scanning calculations, employing free-energy perturbation as implemented in the widely used molecular dynamics code NAMD. The AlaScan plug-in can be utilized upstream, to prepare input files for selected alanine mutations. It can also be utilized downstream to perform the analysis of different alanine-scanning calculations and to report the free-energy estimates in a user-friendly graphical user interface, allowing favorable mutations to be identified at a glance. The plug-in also assists the end-user in assessing the reliability of the calculation through rapid visual inspection.

  1. ERCC1 Cys8092Ala and XRCC1 Arg399Gln polymorphisms predict progression-free survival after curative radiotherapy for nasopharyngeal carcinoma.

    Directory of Open Access Journals (Sweden)

    Hekun Jin

    Full Text Available BACKGROUND: Single nucleotide polymorphisms (SNPs in DNA repair genes can alter gene expression and activity and affect response to cancer treatment and, correspondingly, survival. The present study was designed to evaluate the utility of the XRCC1 Arg399Gln and ERCC1 Cys8092Ala SNPs, measured in pretreatment biopsy samples, as predictors of response to radiotherapy in patients with non-metastatic nasopharyngeal carcinoma (NPC. MATERIALS AND METHODS: The study included 75 consecutive patients with stage II-IVA-B NPC. XRCC1 Arg399Glu and ERCC1 Cys8092Ala SNPs were identified from paraffin-embedded biopsy specimens via Sanger sequencing. Expression of p53 and pAkt protein was analyzed by immunohistochemical staining. Potential relationships between genetic polymorphisms and progression-free survival (PFS were analyzed by using a Cox proportional hazards model, the Kaplan-Meier method, and the log-rank test. RESULTS: Multivariate analysis showed that carriers of the ERCC1 8092 Ala/Ala genotype [hazard ratio (HR 1.882; 95% confidence interval (CI 1.031-3.438; P = 0.039] and heavy smokers (≥20 pack-years carrying the XRCC1 Arg/Arg genotype (HR 2.019; 95% CI 1.010-4.036; P = 0.047 had significantly lower PFS rates. Moreover, combined positive expression of p53 and pAkt led to significantly increased PFS in subgroups carrying the XRCC1 Gln allele (HR 7.057; 95% CI 2.073-24.021; P = 0.002 or the ERCC1 Cys allele (HR 2.568; 95% CI 1.056-6.248; P = 0.038. CONCLUSIONS: The ERCC1 Cys8092Ala polymorphism is an independent predictor of response to radiotherapy for NPC, and the XRCC1 Arg399Glu mutation combined with smoking status seems to predict PFS as well. Our results further suggest a possible correlation between these genetic polymorphisms and p53 protein status on survival.

  2. Professor Trechsel : Eesti e-valimiste aeg on liiga lühike / Alexander H. Trechsel ; interv. Askur Alas

    Index Scriptorium Estoniae

    Trechsel, Alexander H.

    2006-01-01

    e-valimistele pühendatud rahvusvahelisel konverentsil esinenud Genfi ülikooli e-demokraatia keskuse juhataja, poliitikateaduste professor Eesti e-valimistest ja e-valimiste tulevikust. Vt. samas: Askur Alas. Konverentsil analüüsiti e-valimiste kogemusi; Eestis hääletas digitaalselt 9317 valijat

  3. THz emission of donor and acceptor doped GaAs/AlGaAs quantum well structures with inserted thin AlAs monolayer

    Science.gov (United States)

    van Dommelen, Paphavee; Daengngam, Chalongrat; Kalasuwan, Pruet

    2018-04-01

    In this paper, we explore THz range optical intersubband transition energies in a donor doped quantum well of a GaAs/AlGaAs system as a function of the insertion position of an AlAs monolayer in the GaAs quantum well. In simulated models, the optical transition energies between electron subband levels 1 and 2 were higher in the doped structure than in the undoped structure. This may be because the envelope wave function of the second electron subband strongly overlapped the envelope wave function of the first electron subband and influenced the optical intersubband transition between the two levels in the THz range. At different levels of bias voltage at the Schottky barrier on the donor doped structure, the electric field in the growth direction of the structure linearly increased the further away the AlAs monolayer was placed from the reference position. We also simulated the optical transition energies between acceptor energy levels of the acceptor doped structure as a function of the insertion position of the AlAs monolayer. The acceptor doped structure induced THz range emission whereas the undoped structure induced mid-IR emission.

  4. The value of polymorphism RRO12ALA gene PPARG in violation of lipid peroxidation and antioxidant protection in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    S. V. Ziablytsev

    2016-09-01

      Resume. The incidence of type 2 diabetes mellitus is increasing in Ukraine and worldwide. The severity of this disease is determined by the number of complications, which are based on lipid peroxidation (LPO. Today, the influence of gene polymorphisms Pro12Ala PPARG on oxidative and antioxidant processes is not in doubt. We studied the association between gene polymorphism Pro12Ala rs1801282 PPARG and intensification of lipid peroxidation and antioxidant systems (AOS in 88 patients with type 2 diabetes, using analysis of variance. In the 12Pro allele carriers male found probable increased intensification of lipid peroxidation than in women, with increasing levels of DC (p=0,034 and MDA (p=0,001. Reducing the enzyme catalase level of AOC in patients with type 2 diabetes was observed in the case of genotype Pro12Pro gene PPARG on 21.7% compared with heterozygotes (F=8,17; p=0,005 and the presence of the allele 12Pro (F=6,28 , p=0,013. Found significantly higher activity of AOC in the form of increasing the level of α-TF (p=0,016 and catalase activity (p=0,034 among male patients with gene polymorphism Pro12Ala PPARG, than homozygotes for allele 12Pro.   Key words: lipid peroxidation; antioxidant system; type 2 diabetes mellitus; polymorphism Pro12Ala rs1801282 of gene PPARG

  5. Evaluation of {sup 99m}Tc-HYNIC-βAla-Bombesin{sub (7-14)} as an agent for pancreas tumor detection in mice

    Energy Technology Data Exchange (ETDEWEB)

    Carlesso, F.N.; Fuscaldi, L.L.; Araujo, R.S.; Teixeira, C.S.; Oliveira, M.C.; Fernandes, S.O.A.; Cassali, G.D.; Reis, D.C.; Barros, A.L.B.; Cardoso, V.N., E-mail: valbertcardoso@yahoo.com.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)

    2015-10-15

    Pancreatic adenocarcinoma is important in oncology because of its high mortality rate. Deaths may be avoided if an early diagnosis could be achieved. Several types of tumors overexpress gastrin-releasing peptide receptors (GRPr), including pancreatic cancer cells. Thus, a radiolabeled peptide derivative of gastrin-releasing peptide (GRP) may be useful as a specific imaging probe. The purpose of the present study was to evaluate the feasibility of using {sup 99m}Tc-HYNIC--βAla-Bombesin{sub (7-14)} as an imaging probe for Capan-1 pancreatic adenocarcinoma. Xenographic pancreatic tumor was developed in nude mice and characterized by histopathological analysis. Biodistribution studies and scintigraphic images were carried out in tumor-bearing nude mice. The two methods showed higher uptake by pancreatic tumor when compared to muscle (used as control), and the tumor-to-muscle ratio indicated that {sup 99m}Tc-HYNIC--βAla-Bombesin{sub (7-14)} uptake was four-fold higher in tumor cells than in other tissues. Scintigraphic images also showed a clear signal at the tumor site. The present data indicate that {sup 99m}Tc-HYNIC--βAla-Bombesin{sub (7-14)} may be useful for the detection of pancreatic adenocarcinoma. (author)

  6. Anomalous giant piezoresistance in AlAs 2D electron systems with antidot lattices.

    Science.gov (United States)

    Gunawan, O; Gokmen, T; Shkolnikov, Y P; De Poortere, E P; Shayegan, M

    2008-01-25

    An AlAs two-dimensional electron system patterned with an antidot lattice exhibits a giant piezoresistance effect at low temperatures, with a sign opposite to the piezoresistance observed in the unpatterned region. We suggest that the origin of this anomalous giant piezoresistance is the nonuniform strain in the antidot lattice and the exclusion of electrons occupying the two conduction-band valleys from different regions of the sample. This is analogous to the well-known giant magnetoresistance effect, with valley playing the role of spin and strain the role of magnetic field.

  7. Relationship between the occlusal plane corresponding to the lateral borders of the tongue and ala-tragus line in edentulous patients.

    Science.gov (United States)

    Ghosn, Carole Abi; Zogheib, Carla; Makzoumé, Joseph E

    2012-09-01

    Definitions of the ala-tragus line (ATL) cause confusion, because the exact points of reference for this line do not agree. This study determined the relationship between the prosthetic occlusal plane (OP) corresponding to the lateral borders of the tongue and ATL which was established by using the inferior border of the ala of the nose and (1) the superior border of the tragus (ATL 1), (2) the tip (ATL 2) and (3) the inferior border of the tragus (ATL 3). Neutral zone moldings using phonation and autopolymerizing acrylic resin were recorded and leveled with the lateral borders of the tongue. Lateral cephalometric radiographs were taken of each subject by a standard method. Tracings were obtained on acetate paper to show the prosthetic OP and the three ATLs. The relationship between the prosthetic OP and each of ATL was measured for each subject. Mean and standard deviation values were then calculated for the relationship. Statistical analysis was performed using repeated measure analysis of variance followed by Bonferroni pairwise comparisons and Student's t-test (α = 0.05). Significant difference was found between the three mean angles (p = 0.001). There was no significant difference between the mean angle (5.00° ± 4.38) formed by OP and ATL 2, and the mean angle (4.90° ± 3.50) formed by OP and ATL 3 (p = 1.00) which revealed the smallest. The findings of this study indicated that ATLs, extending from the inferior border of the ala of the nose to (1) the tip of the tragus of the ear, and (2) the inferior border of the tragus presented the closest relationship to the prosthetic OP corresponding to the lateral borders of the tongue. When the ATL is used for orientation of the OP in denture construction, it would seem preferable to define it as running from the inferior border of the ala of the nose to the tip or to the inferior border of the tragus of the ear.

  8. The Association of PPARγ Pro12Ala and C161T Polymorphisms with Polycystic Ovary Syndrome and Their Influence on Lipid and Lipoprotein Profiles

    Directory of Open Access Journals (Sweden)

    Zohreh Rahimi

    2018-05-01

    Full Text Available Background The aim of present study was to clarify the role of the peroxisome proliferator-activated receptor (PPAR γ Pro12Ala and C161T polymorphisms in the pathogenesis of polycystic ovary syndrome (PCOS and their influence on lipid and lipoprotein profiles of patients. Materials and Methods The present cross-sectional study consisted of 50 women with PCOS, who referred to the Kermanshah University of Medical Sciences Clinic between April and October 2015, and 233 unrelated age-matched healthy women from the same region (West Iran. The PPARγ Pro12Ala and PPARγ C161T polymorphisms were gen- otyped using the polymerase chain reaction-restriction fragment length polymorphism method. Fasting blood sugar (FBS, serum triglycerides (TG, cholesterol, low density lipoprotein- cholesterol (LDL-C, high density lipoprotein- cholesterol (HDL-C and estradiol levels were measured. Results The serum level of estradiol was significantly lower in PCOS patients compared to healthy women. The PPARγ Pro12Ala (CG genotype increased the risk of PCOS 2.96-fold. The frequency of the PPARγ T allele (at C161T was 21% in patients and 17.2% in controls with no significant difference (P=0.52. In all studied individuals, the PPARγ CG geno- type was associated with significantly higher levels of TG. However, significantly lower levels of total cholesterol and LDL-C were observed in PPARγ TT individuals compared with those with the CC genotype. Within the PCOS group, the PPARγ CG genotype was significantly associated with lower levels of estradiol compared with the CC genotype. Also, the CG genotype was significantly associated with higher levels of TG when compared with the CC genotype. Conclusion Our study shows that, unlike PPARγ C161T, PPARγ Pro12Ala is associated with the risk of PCOS. Also, we found that the lipid and lipoprotein profiles significantly vary based on PPARγ Pro12Ala and C161T genotypes.

  9. Kuldlõvid Louise Bourgeois'le, Bruce Naumanile ja Itaalia paviljonile / Reet Varblane

    Index Scriptorium Estoniae

    Varblane, Reet, 1952-

    1999-01-01

    Veneetsia 48. rahvusvahelise kunstibiennaali preemiasaajad, premeeritud tööd, korralduskomitee ja žürii koosseis. Kuldlõvid: Louise Bourgeois, Bruce Nauman, Itaalia paviljon (Monica Bonvicini, Bruna Esposito, Luisa Lambri, Paola Pivi, Grazia Toderi ühisprojekt); kolm rahvusvahelist preemiat: Doug Aitken, Cai Gou-Qiang, Shirin Neshat; žürii tõstis esile: Georges Abeagbo, Eija-Liisa Ahtila, Katarzyna Kozura ? (Kozyra), Lee Bul; UNESCO preemia: Ghada Amer

  10. Long-sustaining response in a patient with non-resectable, distant recurrence of glioblastoma multiforme treated by interstitial photodynamic therapy using 5-ALA: case report.

    Science.gov (United States)

    Stummer, Walter; Beck, Tobias; Beyer, Wolfgang; Mehrkens, Jan Hendrik; Obermeier, Andreas; Etminan, Nima; Stepp, Herbert; Tonn, Jörg-Christian; Baumgartner, Reinhold; Herms, Jochen; Kreth, Friedrich Wilhelm

    2008-03-01

    Glioblastoma multiforme continues to be a devastating disease despite modest improvements in survival achieved at present, and there is an urgent need for innovative treatment concepts. Five-aminolevulinic acid (ALA) is a drug which induces protoporphyrin IX accumulation in malignant gliomas and has been explored for fluorescence-guided resections of these tumors. ALA is also under investigation as a photosensitizer. We report a case of a patient with prior left frontal glioblastoma multiforme treated by surgery, radiation and chemotherapy, who developed a remote lesion in the left insula, which was refractory to secondary treatments. In a compassionate use setting she was treated by oral application of ALA (20 mg/kg bodyweight), and stereotactic phototherapy achieved by positioning four laser diffusors using 3-dimensional irradiation planning, and a 633 nm diode laser. The lesion disappeared 24 h after therapy. Circumferential contrast enhancement was observed at 72 h, which disappeared in the course of subsequent months. Edema resolved completely. The patient is still free of recurrence 56 months after treatment, demonstrating an impressive and long-lasting response to this novel mode of therapy.

  11. Assessment of the Pro12Ala Polymorphism in the PPAR-γ2 Gene among Type 2 Diabetes Patients in a Nigerian Population

    Directory of Open Access Journals (Sweden)

    Godwill Azeh Engwa

    2018-04-01

    Full Text Available The association between the Pro12Ala polymorphism of the PPARγ2 gene, type 2 diabetes (T2D, and obesity in certain ethnic populations has been reported. However, this relationship has not yet been described among diabetes patients in Nigeria. This study investigated the relationship between the Pro12Ala polymorphism in the PPARγ2 gene, obesity, and lipid abnormalities characterizing T2D among patients in Nigeria. This case-control study recruited 73 T2D and 75 non-diabetic (ND patients. Demographic and clinical data were collected and blood glucose levels together with serum lipid profile for patients were measured. Pro12Ala polymorphism in the PPARγ2 gene was genotyped by restriction fragment length-Polymerase Chain Reaction (RFLP-PCR. The PPAR-γ2 gene (amplicon size = 270 base pair was successfully amplified for all samples. Following restriction enzyme digestion and analysis by agarose gel electrophoresis, amplicons from samples showed a band of size 270 bp and were of the wild homozygous Pro/Pro genotype. Ala12 variant was totally absent from the study population. Obesity, estimated using Body Mass Index (BMI and waist circumference (WC, was significantly higher (p < 0.05 in T2D patients compared to the non-diabetic patients. More so, the prevalence of lipid abnormalities; hypercholesterolaemia (TC > 200 mg/dL, hypertriglyceridaemia (TG > 150 mg/dL, high HDL (>100 mg/dL, and low HDL (<50 mg/dL was significantly greater (p < 0.001 in T2D patients compared to non-diabetic patients. Results obtained further indicated lack of significant association between PPAR-γ2 gene polymorphism, T2D, and obesity. However, obesity and dyslipidaemia were strongly associated in T2D patients.

  12. Ala54Thr fatty acid-binding protein 2 (FABP2 polymorphism in recurrent depression: associations with fatty acid concentrations and waist circumference.

    Directory of Open Access Journals (Sweden)

    Roel J T Mocking

    Full Text Available BACKGROUND: Fatty acid (FA-alterations may mediate the mutual association between Major Depressive Disorder (MDD and cardiovascular disease (CVD. However, etiology of observed FA-alterations in MDD and CVD remains largely unclear. An interesting candidate may be a mutation in the fatty acid-binding protein 2 (FABP2-gene, because it regulates dietary FA-uptake. Therefore, we aimed to test the hypotheses that in MDD-patients the FABP2 Ala54Thr-polymorphism would be (I more prevalent than in sex- and age-matched controls, (II associated with observed alterations in FA-metabolism, and (III associated with CVD-risk factor waist circumference. METHODS: We measured concentrations of 29 different erythrocyte FAs, FABP2-genotype, and waist circumference in recurrent MDD-patients and matched never-depressed controls. RESULTS: FABP2-genotype distribution did not significantly differ between the 137 MDD-patients and 73 matched controls. However, patients with the Ala54Thr-polymorphism had (I higher concentrations of especially eicosadienoic acid (C20:2ω6; P=.009 and other 20-carbon FAs, and associated (II lower waist circumference (P=.019. In addition, FABP2-genotype effects on waist circumference in patients seemed (I mediated by its effect on C20:2ω6, and (II different from controls. CONCLUSIONS: Although Ala54Thr-polymorphism distribution was not associated with recurrent MDD, our results indicate that FABP2 may play a role in the explanation of observed FA-alterations in MDD. For Ala54Thr-polymorphism patients, potentially adaptive conversion of increased bioavailable dietary precursors into eicosadienoic acid instead of arachidonic acid might be related to a low waist circumference. Because this is the first investigation of these associations, replication is warranted, preferably by nutrigenetic studies applying lipidomics and detailed dietary assessment.

  13. Photodynamic Detection of Peritoneal Metastases Using 5-Aminolevulinic Acid (ALA

    Directory of Open Access Journals (Sweden)

    Yutaka Yonemura

    2017-03-01

    Full Text Available In the past, peritoneal metastasis (PM was considered as a terminal stage of cancer. From the early 1990s, however, a new comprehensive treatment consisting of cytoreductive surgery and perioperative chemotherapy has been established to improve long-term survival for selected patients with PM. Among prognostic indicators after the treatment, completeness of cytoreduction is the most independent predictors of survival. However, peritoneal recurrence is a main cause of recurrence, even after complete cytoreduction. As a cause of peritoneal recurrence, small PM may be overlooked at the time of cytoreductive surgery (CRS, therefore, development of a new method to detect small PM is desired. Recently, photodynamic diagnosis (PDD was developed for detection of PM. The objectives of this review were to evaluate whether PDD using 5-aminolevulinic acid (ALA could improve detection of small PM.

  14. The use of 5-ALA to assist complete removal of residual non-enhancing part of childhood medulloblastoma

    DEFF Research Database (Denmark)

    Skjøth-Rasmussen, Jane; Bøgeskov, Lars; Sehested, Astrid

    2015-01-01

    . METHODS: The child was pretreated with 3 × 4 mg dexamethasone for 4 days prior to the second surgery. At 5 a.m. on the day of surgery, a freshly prepared solution of 5-ALA (20 mg/kg body weight; Medac, Germany) was given orally. RESULTS: At surgery, through the original opening, the vague red fluorescence...

  15. IL6R Variation Asp358Ala Is a Potential Modifier of Lung Function in Asthma

    Science.gov (United States)

    Hawkins, Gregory A; Robinson, Mac B; Hastie, Annette T; Li, Xingnan; Li, Huashi; Moore, Wendy C; Howard, Timothy D; Busse, William W.; Erzurum, Serpil C.; Wenzel, Sally E.; Peters, Stephen P; Meyers, Deborah A; Bleecker, Eugene R

    2012-01-01

    Background The IL6R SNP rs4129267 has recently been identified as an asthma susceptibility locus in subjects of European ancestry but has not been characterized with respect to asthma severity. The SNP rs4129267 is in linkage disequilibrium (r2=1) with the IL6R coding SNP rs2228145 (Asp358Ala). This IL6R coding change increases IL6 receptor shedding and promotes IL6 transsignaling. Objectives To evaluate the IL6R SNP rs2228145 with respect to asthma severity phenotypes. Methods The IL6R SNP rs2228145 was evaluated in subjects of European ancestry with asthma from the Severe Asthma Research Program (SARP). Lung function associations were replicated in the Collaborative Study on the Genetics of Asthma (CSGA) cohort. Serum soluble IL6 receptor (sIL6R) levels were measured in subjects from SARP. Immunohistochemistry was used to qualitatively evaluate IL6R protein expression in BAL cells and endobronchial biopsies. Results The minor C allele of IL6R SNP rs2228145 was associated with lower ppFEV1 in the SARP cohort (p=0.005), the CSGA cohort (0.008), and in combined cohort analysis (p=0.003). Additional associations with ppFVC, FEV1/FVC, and PC20 were observed. The rs2228145 C allele (Ala358) was more frequent in severe asthma phenotypic clusters. Elevated serum sIL6R was associated with lower ppFEV1 (p=0.02) and lower ppFVC (p=0.008) (N=146). IL6R protein expression was observed in BAL macrophages, airway epithelium, vascular endothelium, and airway smooth muscle. Conclusions The IL6R coding SNP rs2228145 (Asp358Ala) is a potential modifier of lung function in asthma and may identify subjects at risk for more severe asthma. IL6 transsignaling may have a pathogenic role in the lung. PMID:22554704

  16. Usaha Peningkatan Konservasi Mamalia di Taman Nasional Alas Purwo melalui Wisata Safari pada Generasi Muda

    Directory of Open Access Journals (Sweden)

    Dina - Aulia

    2012-05-01

    Full Text Available Abstrak Wisata Safari melalui mammal watching berpotensi mendukung konservasi alam dan meningkatkan kesejahteraan masyarakat setempat. Penelitian ini bertujuan meningkatkan kualitas apresiasi generasi muda tentang pentingnya diversitas dan konservasi mamalia melalui wisata safari di taman Nasional Alas Purwo. Penelitian eksperimental semu (quasi-experimental research design ini menggunakan rancangan acak lengkap dengan dua perlakuan, yaitu kelompok wisatawan dan kelompok kontrol. Penelitian ini melibatkan enam wisatawan sebagai ulangan. Mammal watching berlangsung selama dua hari pada pagi hingga sore hari di tiga lokasi pengamatan yaitu Padang Rumput Sadengan, Pantai Triangulasi, dan Jalur Triangulasi-Pancur. Saat mammal watching wisatawan melihat aktifitas mamalia mencari makan, atraksi brakhiasi, serta menikmati parade senja. Penilaian persepsi awal, peningkatan kualitas apresiasi generasi muda terhadap diversitas dan konservasi serta evaluasi kegiatan secara keseluruhan diperoleh melalui kuesioner. Data berupa jawaban deskriptif dikonversi melalui penilaian kualitas jawaban 0-100. Data numerik dianalisis menggunakan uji T pada α=0,05. Hasil penelitian menunjukkan bahwa persepsi awal wisatawan lebih baik daripada kontrol. Salah satu poin penting sebelum melakukan kegiatan pengamatan satwa mamalia (mammal watching adalah pembekalan. Mammal watching menambah pemahaman mengenai diversitas dan konservasi mammalia di ranah kognitif, afektif, maupun psikomotorik wisatawan. Keseluruhan rangakaian kegiatan wisata safari meliputi pembekalan, pembagian field guide, mammal watching dan evaluasi dapat meningkatkan apresiasi wisatawan. Wisata safari dapat digunakan sebagai sarana penelitian, hiburan untuk wisatawan dan pemasukan bagi taman nasional. Kata kunci: generasi muda, konservasi, mammals watching, Taman Nasional Alas Purwo   Abstract Wildlife Tourism, especially mammals watching, have play an important role to conserve natural resources and

  17. Studies of the common DIO2 Thr92Ala polymorphism and metabolic phenotypes in 7342 Danish white subjects

    DEFF Research Database (Denmark)

    Grarup, Niels; Andersen, Mette K; Andreasen, Camilla H

    2007-01-01

    The type 2 iodothyronine deiodinase (D2) catalyzes the conversion of T(4) to the active form of thyroid hormone, which is a critical regulator of thermogenesis and glucose metabolism. A Thr92Ala polymorphism in the gene encoding D2 (DIO2) has been reported to associate with insulin resistance....

  18. Yan akımlı anaerobik membran biyoreaktör veriminin araştırılması: Sentetik atıksu ve alkollü içki sanayi atıksuyu

    Directory of Open Access Journals (Sweden)

    Nurdan BÜYÜKKAMACI

    2016-06-01

    Full Text Available Yan akımlı anaerobik membran biyoreaktörlerin verimi yüksek kirliliğe sahip atıksular için laboratuvar ölçekli bir sistem kullanılarak irdelenmiştir. Sistem, yukarı akışlı çamur yataklı anaerobik (UASB reaktör ve ultrafiltrasyon (UF membran modülünden oluşturulmuştur. Sistemin verimi öncelikle seyreltilmiş melastan hazırlanan sentetik atıksu ile farklı hidrolik alıkonma süreleri (1-3 gün ve organik yükleme oranlarında (5-15 kg KOİ/m3.day incelenmiştir. Yapılan deneysel çalışmalar neticesinde, maksimum KOİ giderme verimi (%95 7.5 kg KOİ/m3.gün organik yükleme değerinde (KOİgiriş=15.000 mg/L, HRT=2 gün elde edilmiştir. Organik yükleme değeri 15 kg KOİ/m3.gün değerine çıkartıldığında sistem performansı aniden düşmüştür. Daha sonra, besleme suyu bir alkollü içki sanayi atıksuyu ile değiştirilerek gerçek atıksu ile çalışmalar yürütülmüştür. Bu çalışmada, maksimum toplam sistem verimi ve metan gazı oluşumu sırasıyla %88 ve %74 olarak belirlenmiştir.

  19. Application of evolutionary algorithm methods to polypeptide folding: comparison with experimental results for unsolvated Ac-(Ala-Gly-Gly)5-LysH+

    DEFF Research Database (Denmark)

    Damsbo, Martin; Kinnear, Brian S; Hartings, Matthew R

    2004-01-01

    We present an evolutionary method for finding the low-energy conformations of polypeptides. The application, called FOLDAWAY,is based on a generic framework and uses several evolutionary operators as well as local optimization to navigate the complex energy landscape of polypeptides. It maintains...... mobility measurements. It has a flat energy landscape where helical and globular conformations have similar energies. FOLDAWAY locates several large groups of structures not found in previous molecular dynamics simulations for this peptide, including compact globular conformations, which are probably...... two complementary representations of the structures and uses the CHARMM force field for evaluating the energies. The method is applied to unsolvated Met-enkephalin and Ac-(Ala-Gly-Gly)(5)-Lys(+)H(+). Unsolvated Ac-(Ala-Gly-Gly)(5)-Lys(+)H(+) has been the object of recent experimental studies using ion...

  20. Synthesis and Pharmacology of Halogenated δ-Opioid-Selective [D-Ala2]Deltorphin II Peptide Analogues

    Science.gov (United States)

    Pescatore, Robyn; Marrone, Gina F.; Sedberry, Seth; Vinton, Daniel; Finkelstein, Netanel; Katlowitz, Yitzchak E.; Pasternak, Gavril W.; Wilson, Krista R.; Majumdar, Susruta

    2015-01-01

    Deltorphins are naturally occurring peptides produced by the skin of the giant monkey frog (Phyllomedusa bicolor). They are δ-opioid receptor-selective agonists. Herein, we report the design and synthesis of a peptide, Tyr-D-Ala-(pI)Phe-Glu-Ile-Ile-Gly-NH2 3 (GATE3-8), based on the [D-Ala2]deltorphin II template, which is δ-selective in in vitro radioligand binding assays over the μ- and κ-opioid receptors. It is a full agonist in [35S]GTPγS functional assays and analgesic when administered supraspinally to mice. Analgesia of 3 (GATE3-8) is blocked by the selective δ receptor antagonist naltrindole, indicating that the analgesic action of 3 is mediated by the δ-opioid receptor. We have established a radioligand in which 125I isincorporated into 3 (GATE3-8). The radioligand has a KD of 0.1 nM in Chinese hamster ovary (CHO) cells expressing the δ receptor. Additionally, a series of peptides based on 3 (GATE3-8) was synthesized by incorporating various halogens in the para position on the aromatic ring of Phe3. The peptides were characterized for binding affinity at the μ-, δ-, and κ-opioid receptors, which showed a linear correlation between binding affinity and the size of the halogen substituent. These peptides may be interesting tools for probing δ-opioid receptor pharmacology. PMID:25844930

  1. Synthesis and pharmacology of halogenated δ-opioid-selective [d-Ala(2)]deltorphin II peptide analogues.

    Science.gov (United States)

    Pescatore, Robyn; Marrone, Gina F; Sedberry, Seth; Vinton, Daniel; Finkelstein, Netanel; Katlowitz, Yitzchak E; Pasternak, Gavril W; Wilson, Krista R; Majumdar, Susruta

    2015-06-17

    Deltorphins are naturally occurring peptides produced by the skin of the giant monkey frog (Phyllomedusa bicolor). They are δ-opioid receptor-selective agonists. Herein, we report the design and synthesis of a peptide, Tyr-d-Ala-(pI)Phe-Glu-Ile-Ile-Gly-NH2 3 (GATE3-8), based on the [d-Ala(2)]deltorphin II template, which is δ-selective in in vitro radioligand binding assays over the μ- and κ-opioid receptors. It is a full agonist in [(35)S]GTPγS functional assays and analgesic when administered supraspinally to mice. Analgesia of 3 (GATE3-8) is blocked by the selective δ receptor antagonist naltrindole, indicating that the analgesic action of 3 is mediated by the δ-opioid receptor. We have established a radioligand in which (125)I is incorporated into 3 (GATE3-8). The radioligand has a KD of 0.1 nM in Chinese hamster ovary (CHO) cells expressing the δ receptor. Additionally, a series of peptides based on 3 (GATE3-8) was synthesized by incorporating various halogens in the para position on the aromatic ring of Phe(3). The peptides were characterized for binding affinity at the μ-, δ-, and κ-opioid receptors, which showed a linear correlation between binding affinity and the size of the halogen substituent. These peptides may be interesting tools for probing δ-opioid receptor pharmacology.

  2. Verest saab vein : [luuletused] / Mare Osi

    Index Scriptorium Estoniae

    Osi, Mare

    2003-01-01

    Sisu: "Must üü nigu kaaren ..." ; Metamorfoos ; Pettumus ; Skeptiline ; Talisman ; Unetet latsepõli ; Meie kaits ; Sannaõhtu ; "Külmä süä lüüdi lõhki ..." ; "Egäl kevädil ...". Eluloolisi andmeid autori kohta lk. 193

  3. Expanding phenotype of p.Ala140Val mutation in MECP2 in a 4 generation family with X-linked intellectual disability and spasticity.

    Science.gov (United States)

    Lambert, Sophie; Maystadt, Isabelle; Boulanger, Sébastien; Vrielynck, Pascal; Destrée, Anne; Lederer, Damien; Moortgat, Stéphanie

    2016-10-01

    Mutations in MECP2 (MIM #312750), located on Xq28 and encoding a methyl CpG binding protein, are classically associated with Rett syndrome in female patients, with a lethal effect in hemizygous males. However, MECP2 mutations have already been reported in surviving males with severe neonatal-onset encephalopathy, or with X-linked intellectual disability associated with psychosis, pyramidal signs, parkinsonian features and macro-orchidism (PPM-X syndrome; MIM3 #300055). Here we report on the identification of the p.Ala140Val mutation in the MECP2 gene in 4 males and 3 females of a large Caucasian family affected with X-linked intellectual disability. Females present with mild cognitive impairment and speech difficulties. Males have moderate intellectual disability, impaired language development, friendly behavior, slowly progressive spastic paraparesis and dystonic movements of the hands. Two of them show microcephaly. The p.Ala140Val mutation is recurrent, as it was already described in 4 families with X-linked mental retardation and in three sporadic male patients with intellectual disability. We further delineate the phenotype associated with the p.Ala140Val mutation, illustrating a variable expressivity even within a given family, and we compare our patients with previous reported cases in the literature. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Rationally designed chimeric peptide of met-enkephalin and FMRFa-[D-Ala2,p-Cl-Phe4]YFa induce multiple opioid receptors mediated antinociception and up-regulate their expression.

    Science.gov (United States)

    Vats, Ishwar Dutt; Chaudhary, Snehlata; Sharma, Ahuti; Nath, Mahendra; Pasha, Santosh

    2010-07-25

    The physiological role of NPFF/FMRFa family of peptides appears to be complex and exact mechanism of action of these peptides is not yet completely understood. In same line of scrutiny, another analog of YGGFMKKKFMRFamide (YFa), a chimeric peptide of met-enkephalin and FMRFamide, was rationally designed and synthesized which contain D-alanine and p-Cl-phenylalanine residues at 2nd and 4th positions, respectively i.e., Y-(D-Ala)-G-(p-Cl-Phe)-MKKKFMRFamide ([D-Ala(2), p-Cl-Phe(4)]YFa) in order to achieve improved bioavailability and blood brain barrier penetration. Therefore, present study investigates the possible antinociceptive effect of [D-Ala(2), p-Cl-Phe(4)]YFa on intra-peritoneal (i.p.) administration using tail-flick test in rats followed by its opioid receptor(s) specificity using mu, delta and kappa receptor antagonists. Further, its antinociceptive effect was examined during 6 days of chronic i.p. treatment and assessed effect of this treatment on differential expression of opioid receptors. [D-Ala(2), p-Cl-Phe(4)]YFa in comparison to parent peptide YFa, induce significantly higher dose dependent antinociception in rats which was mediated by all three opioid receptors (mu, delta and kappa). Importantly, it induced comparable antinociception in rats throughout the chronic i.p. treatment and significantly up-regulated the overall expression (mRNA and protein) of mu, delta and kappa opioid receptors. Therefore, pharmacological and molecular behavior of [D-Ala(2), p-Cl-Phe(4)]YFa demonstrate that incorporation of D-alanine and p-Cl-phenylalanine residues at appropriate positions in chimeric peptide leads to altered opioid receptor selectivity and enhanced antinociceptive potency, relative to parent peptide. (c) 2010 Elsevier B.V. All rights reserved.

  5. A retrospective review of pain control by a two-step irradiance schedule during topical ALA-photodynamic therapy of non-melanoma skin cancer.

    Science.gov (United States)

    Zeitouni, Nathalie C; Paquette, Anne D; Housel, Joseph P; Shi, Yi; Wilding, Gregory E; Foster, Thomas H; Henderson, Barbara W

    2013-02-01

    Photodynamic therapy (PDT) with topical δ-aminolevulinic acid (ALA) of non-melanoma skin cancers is often associated with treatment-limiting pain. A previous study on basal cell carcinomas (BCCs) at Roswell Park Cancer Institute evaluated a two-step irradiance scheme as a means of minimizing pain, preserving outcomes, and limiting treatment time. We used an initial low irradiance until 90% of the protoporphyrin IX was photobleached, followed by a high irradiance interval until the prescribed fluence was delivered. Success of this pilot investigation motivated integration of the protocol into routine practice. Here, we present a retrospective review of recent clinical experience in a broad patient population. This was a retrospective review of an existing dermatology database. Fourteen caucasion patients-nine men and five women, ages 18-80, with a total of 51 superficial and 73 nodular BCCs, and three Bowen's disease lesions-were included. ALA was applied to each lesion for approximately 4 hours. Lesions received an initial irradiance of 30-50 mW/cm(2) for 20 J/cm(2) , followed by 150 mW/cm(2) for a total fluence of 200-300 J/cm(2) . Pain was assessed using a visual analog scale (VAS). Clinical outcome was determined at 6-12 months. Median VAS scores were 1.0 for both irradiances. Five of 127 lesions required pain control with 1% xylocaine. Pain was strongly influenced by lesion location but not by lesion type, number, or size. Complete responses were achieved in 84.1% of BCCs, which compares favorably with reported results for single ALA-PDT treatments. Two of three Bowen's disease lesions showed a complete response. Complete responses for nodular BCCs were 37%, which are also within the range of reported outcomes. A two-step irradiance protocol in ALA-PDT effectively minimizes pain, maintains excellent clinical outcomes in superficial lesions, and adds minimal treatment time. Copyright © 2013 Wiley Periodicals, Inc.

  6. The association between the FABP2 Ala54Thr variant and the risk of type 2 diabetes mellitus: a meta-analysis based on 11 case-control studies

    OpenAIRE

    Liu, Peng; Yu, Dan; Jin, Xiaoping; Li, Cai; Zhu, Feng; Zheng, Zhou; Lv, Chenlin; He, Xinwei

    2015-01-01

    Fatty acid binding protein 2 (FABP2) Ala54Thr gene polymorphism has been suggested to be associated with the increased risk of developing type 2 diabetes mellitus (T2DM), but some studies show the inconsistent result. The purpose of this meta-analysis is to assess the association between FABP2 Ala54Thr gene polymorphism variants and the T2DM. A total of 7095 subjects in 11 case-control studies were included in this meta-analysis. Under the allele model (T versus A), the pooled OR of Asian sub...

  7. Research of ALA combined with HpD-PDT which induced s180 ascitic tumor cells, death or apoptosis on cytology

    Science.gov (United States)

    Zhu, Jing; Yan, Min; Zhang, Hui-Guo; Li, Enling; Luo, Hongyu

    2005-07-01

    To ascertain the adequate dosage of ALA combined with HpD-PDT which induced tumor cell death or apoptosis on cytology. And to study the different effect of ALA-PDT and HPD-PDT used only. Rat ascitic tumor cells(S180) were randomly divided into several groups and incubated with ALA(20μg/ml 、40μg/ml、80μg/ml 、160μg/ml)、HPD(2.5μg/ml、5μg/ml、10μg/ml)and their combination dosages. 630nm light (total output 2W) was delivered to tumor cells at a constant fluence rate: 200mw/cm2 and a constant irradiated time period: 20 minutes. We set 3 groups (no photosensitizers or no irradiation or neither) to be the control groups. We used inversion microscopy to observe the morphological change of tumor cells and flow cytometry technology to detect the death or apoptosis of tumor cells during the experiment. ..

  8. Biological evaluation of 177Lu-labeled DOTA-Ala(SO3H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH2 for gastrin-releasing peptide receptor-positive prostate tumor targeting

    International Nuclear Information System (INIS)

    Lim, Jae Cheong; Cho, Eun Ha; Kim, Jin Joo; Choi, Sang Mu; Lee, So young; Nam, Sung Soo; Park, Ul Jae; Park, Soo Hyun

    2015-01-01

    Bombesin binds with selectivity and high affinity to a Gastrin-releasing peptide receptor (GRPR), which is highly overexpressed in prostate cancer cells. The present study describes the in vitro and in vivo biological characteristics of DOTA-Ala(SO 3 H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH 2 (DOTA-sBBNA), an antagonist analogue of bombesin peptide for the targeting of GRPR. DOTA-sBBNA was synthesized and labeled with 177 Lu as previously published. A saturation assay on PC-3 human prostate cancer cells revealed that the Kd value of the radiolabeled peptide was 1.88 nM with a maximum binding capacity (Bmax) of 289.3 fmol/10 6 cells. The radio-peptide slowly internalized, and 24.4 ± 0.5% of the total binding was internalized in 4 hr. Biodistribution studies were conducted in healthy and PC-3 xenografted balb/c mice, which showed high uptake and retention of tumor-associated radioactivity in PC-3 xenografted mice. The tumor-to-blood ratio was 126.02 ± 9.36 at 1.5 hr p.i., and was increased to 216.33 ± 61.58 at 24 hr p.i., which means that the radiolabeled peptide was highly accumulated in a tumor and rapidly cleared from the blood pool. The GRPR is also over-expressed in Korean prostate cancer patients. These results suggest that this 177 Lu-labeled peptide has promising characteristics for application in nuclear medicine, namely for the diagnosis and treatment of GRPR over-expressing prostate tumors

  9. Structures of an alanine racemase from Bacillus anthracis (BA0252) in the presence and absence of (R)-1-aminoethylphosphonic acid (l-Ala-P)

    International Nuclear Information System (INIS)

    Au, Kinfai; Ren, Jingshan; Walter, Thomas S.; Harlos, Karl; Nettleship, Joanne E.; Owens, Raymond J.; Stuart, David I.; Esnouf, Robert M.

    2008-01-01

    Structures of BA0252, an alanine racemase from B. anthracis, in the presence and absence of the inhibitor (R)-1-aminoethylphosphonic acid (l-Ala-P) and determined by X-ray crystallography to resolutions of 2.1 and 1.47 Å, respectively, are described. Bacillus anthracis, the causative agent of anthrax, has been targeted by the Oxford Protein Production Facility to validate high-throughput protocols within the Structural Proteomics in Europe project. As part of this work, the structures of an alanine racemase (BA0252) in the presence and absence of the inhibitor (R)-1-aminoethylphosphonic acid (l-Ala-P) have determined by X-ray crystallo@@graphy to resolutions of 2.1 and 1.47 Å, respectively. Difficulties in crystallizing this protein were overcome by the use of reductive methylation. Alanine racemase has attracted much interest as a possible target for anti-anthrax drugs: not only is d-alanine a vital component of the bacterial cell wall, but recent studies also indicate that alanine racemase, which is accessible in the exosporium, plays a key role in inhibition of germination in B. anthracis. These structures confirm the binding mode of l-Ala-P but suggest an unexpected mechanism of inhibition of alanine racemase by this compound and could provide a basis for the design of improved alanine racemase inhibitors with potential as anti-anthrax therapies

  10. Tallinna sadama ümbruse maa-ala renoveerimise ideekonkurss 1996 = The area around the port of Tallinn : contest for renovation ideas 1996 / Veljo Kaasik

    Index Scriptorium Estoniae

    Kaasik, Veljo

    1999-01-01

    Tallinna sadamapiirkonnast. Linnaehituslik ideekava Tallinna kesklinna sadama ümbruse maa-ala renoveerimiseks (ideekonkursi võistlustöö arhitektuurne osa, 1996). Autorid: A. Alver, V. Kaasik, T. Trummal. Kaasautorid: T. Laht, S. Koppel, U. Mets

  11. Thr202Ala in thyA Is a Marker for the Latin American Mediterranean Lineage of the Mycobacterium tuberculosis Complex Rather than Para-Aminosalicylic Acid Resistance

    KAUST Repository

    Feuerriegel, S.

    2010-08-30

    Single nucleotide polymorphisms (SNPs) involved in the development of resistance represent powerful markers for the rapid detection of first- and second-line resistance in clinical Mycobacterium tuberculosis complex (MTBC) isolates. However, the association between particular mutations and phenotypic resistance is not always clear-cut, and phylogenetic SNPs have been misclassified as resistance markers in the past. In the present study, we investigated the utility of a specific polymorphism in thyA (Thr202Ala) as a marker for resistance to para-aminosalicyclic acid (PAS). Sixty-three PAS-susceptible MTBC strains comprising all major phylogenetic lineages, reference strain H37Rv, and 135 multidrug-resistant (MDR) strains from Germany (comprising 8 PAS-resistant isolates) were investigated for the presence of Thr202Ala. In both strain collections, the Thr202Ala SNP was found exclusively in strains of the Latin American Mediterranean (LAM) lineage irrespective of PAS resistance. Furthermore, PAS MICs (0.5 mg/liter) for selected LAM strains (all containing the SNP) and non-LAM strains (not containing the SNP), as well as the results of growth curve analyses performed in liquid 7H9 medium in the presence of increasing PAS concentrations (0 to 2.0 mg/liter), were identical. In conclusion, our data demonstrate that the Thr202Ala polymorphism in thyA is not a valid marker for PAS resistance but, instead, represents a phylogenetic marker for the LAM lineage of the M. tuberculosis complex. These findings challenge some of the previous understanding of PAS resistance and, as a consequence, warrant further in-depth investigations of the genetic variation in PAS-resistant clinical isolates and spontaneous mutants.

  12. Lack of association between the Pro12Ala polymorphism of the PPAR-gamma 2 gene and type 2 diabetes mellitus in the Qatari consanguineous population.

    Science.gov (United States)

    Badii, Ramin; Bener, Abdulbari; Zirie, Mahmoud; Al-Rikabi, Ammar; Simsek, Mehmet; Al-Hamaq, Abdulla O A A; Ghoussaini, Maya; Froguel, Philippe; Wareham, Nick J

    2008-03-01

    Peroxisome proliferators-activated receptor gamma (PPAR gamma) is a nuclear hormone receptor that serves as a master regulator for adipocytes-specific genes contributing to adipocytes differentiation, insulin sensitivity and lipid metabolism. The substitution of proline to alanine at codon 12 of the PPAR gamma 2 gene (Pro12Ala polymorphism) is most widely studied, and the associations with diabetes, obesity, and other clinical parameters have been reported and discussed in several ethnic groups. Among native Qatar ethnicity, however, there is no report about this polymorphism. The aim of this study was to estimate the allele frequency of the Pro12Ala polymorphism of PPAR gamma 2 gene among Qatari population and investigate the association between this polymorphism and obesity or type 2 diabetes. This is a matched case-control study. It was carried out among diabetic patients and healthy subjects at the Primary Healthcare Clinics, and the survey was conducted from February 2003 to March 2006 in Qatari male and female nationals aged 35 to 60 years. The study was based on matched age, sex, and ethnicity of 400 cases (with diabetes) and 450 controls (without diabetes). Face-to-face interviews were based on a questionnaire that included variables such as age, sex, sociodemographic status, body mass index (BMI), and obesity. Their health status was assessed by medical conditions, family history, and blood pressure measurements. The allele frequency of Pro12Ala polymorphism in PPAR gamma 2 gene among Qataris is lower than that in many Caucasian ethnic groups. No association is seen between the Pro12Ala and type 2 Diabetes (0.055 vs 0.059, OR = 1.1311, P = 0.669). Nearly half of the diabetic type 2 patients (48.5%) were obese (BMI > 30) compared to nondiabetic subjects (29.8%) (P Qatar.

  13. GaAs, AlAs, and AlxGa1-xAs: Material parameters for use in research and device applications

    Science.gov (United States)

    Adachi, Sadao

    1985-08-01

    The AlxGa1-xAs/GaAs heterostructure system is potentially useful material for high-speed digital, high-frequency microwave, and electro-optic device applications. Even though the basic AlxGa1-xAs/GaAs heterostructure concepts are understood at this time, some practical device parameters in this system have been hampered by a lack of definite knowledge of many material parameters. Recently, Blakemore has presented numerical and graphical information about many of the physical and electronic properties of GaAs [J. S. Blakemore, J. Appl. Phys. 53, R123 (1982)]. The purpose of this review is (i) to obtain and clarify all the various material parameters of AlxGa1-xAs alloy from a systematic point of view, and (ii) to present key properties of the material parameters for a variety of research works and device applications. A complete set of material parameters are considered in this review for GaAs, AlAs, and AlxGa1-xAs alloys. The model used is based on an interpolation scheme and, therefore, necessitates known values of the parameters for the related binaries (GaAs and AlAs). The material parameters and properties considered in the present review can be classified into sixteen groups: (1) lattice constant and crystal density, (2) melting point, (3) thermal expansion coefficient, (4) lattice dynamic properties, (5) lattice thermal properties, (6) electronic-band structure, (7) external perturbation effects on the band-gap energy, (8) effective mass, (9) deformation potential, (10) static and high-frequency dielectric constants, (11) magnetic susceptibility, (12) piezoelectric constant, (13) Fröhlich coupling parameter, (14) electron transport properties, (15) optical properties, and (16) photoelastic properties. Of particular interest is the deviation of material parameters from linearity with respect to the AlAs mole fraction x. Some material parameters, such as lattice constant, crystal density, thermal expansion coefficient, dielectric constant, and elastic constant

  14. Association of Polymorphous Markers Ala(-9Val of SOD2 Gene and C(-262T of CAT Gene in Patients with Hashimotos’ Thyroiditis and Hypothyroidism

    Directory of Open Access Journals (Sweden)

    A Mkrtumyan

    2008-03-01

    Full Text Available A comparative analysis of distribution of alleles and genotypes of polymorphous markers Ala(-9Val of SOD2 gene and C(-262T of CAT gene was performed. Eighty six patients with Hashimotos’ thyroiditis (HT were enrolled in the study. Significant deferens were found by comparison of alleles and genotypes incidence of polymorphous marker Ala(-9Val of SOD2 gene in HT-patients and in control group. Significant increase of incidence of Val/Val genotype (OR = 15,6; p = 0.04 in HT-patients may reflect a higher risk of HT in Val/Val individuals. This hypothesis may be confirmed by increase of malonic dialdehyde and antithyroid antibodies in Val/Val carriers.

  15. Habitat Dan Perilaku Kangkareng Perut-putih (Anthracoceros Albirostris Convexus Temm. 1832) Di Resort Rowobendo Tn Alas Purwo

    OpenAIRE

    Tarigan, Salvionita BR; Hernowo, Jarwadi Budi

    2016-01-01

    Oriental pied hornbill (Anthracoceros albirostris) is one of hornbill spesies (Bucerotidae) that protected in Indonesia based on Goverment Regulation No. 7/1999. The habitat of oriental pied hornbillin Resort Rowobendo Alas Purwo National Park (APNP) are natural forest and mixed forest plantation. The characteristic of the bird feeding site is a fruiting tree with a thick meat with the shaped is an oval, thin rind, soft, and contain more water and has sweet taste. The characteristic for the b...

  16. HABITAT DAN PERILAKU KANGKARENG PERUT-PUTIH (Anthracoceros albirostris convexus Temm. 1832) DI RESORT ROWOBENDO TN ALAS PURWO

    OpenAIRE

    Salvionita BR Tarigan; Jarwadi Budi Hernowo

    2017-01-01

    Oriental pied hornbill (Anthracoceros albirostris) is one of hornbill spesies (Bucerotidae) that protected in Indonesia based on Goverment Regulation No. 7/1999. The habitat of oriental pied hornbillin Resort Rowobendo Alas Purwo National Park (APNP) are natural forest and mixed forest plantation. The characteristic of the bird feeding site is a fruiting tree with a thick meat with the shaped is an oval, thin rind, soft, and contain more water and has sweet taste. The characteristic for the b...

  17. Structure-activity relationships of the unique and potent agouti-related protein (AGRP)-melanocortin chimeric Tyr-c[beta-Asp-His-DPhe-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH2 peptide template.

    Science.gov (United States)

    Wilczynski, Andrzej; Wilson, Krista R; Scott, Joseph W; Edison, Arthur S; Haskell-Luevano, Carrie

    2005-04-21

    The melanocortin receptor system consists of endogenous agonists, antagonists, G-protein coupled receptors, and auxiliary proteins that are involved in the regulation of complex physiological functions such as energy and weight homeostasis, feeding behavior, inflammation, sexual function, pigmentation, and exocrine gland function. Herein, we report the structure-activity relationship (SAR) of a new chimeric hAGRP-melanocortin agonist peptide template Tyr-c[beta-Asp-His-DPhe-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) that was characterized using amino acids previously reported in other melanocortin agonist templates. Twenty peptides were examined in this study, and six peptides were selected for (1)H NMR and computer-assisted molecular modeling structural analysis. The most notable results include the identification that modification of the chimeric template at the His position with Pro and Phe resulted in ligands that were nM mouse melanocortin-3 receptor (mMC3R) antagonists and nM mouse melanocortin-4 receptor (mMC4R) agonists. The peptides Tyr-c[beta-Asp-His-DPhe-Ala-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) and Tyr-c[beta-Asp-His-DNal(1')-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) resulted in 730- and 560-fold, respectively, mMC4R versus mMC3R selective agonists that also possessed nM agonist potency at the mMC1R and mMC5R. Structural studies identified a reverse turn occurring in the His-DPhe-Arg-Trp domain, with subtle differences observed that may account for the differences in melanocortin receptor pharmacology. Specifically, a gamma-turn secondary structure involving the DPhe(4) in the central position of the Tyr-c[beta-Asp-Phe-DPhe-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) peptide may differentiate the mixed mMC3R antagonist and mMC4R agonist pharmacology.

  18. MOLECULAR DYNAMICS STUDY OF INTERACTIONS OF POLYMYXIN B3 AND ITS ALA-MUTANTS WITH LIPOPOLYSACCHARIDE

    Directory of Open Access Journals (Sweden)

    Lisnyak Yu. V.

    2015-12-01

    Full Text Available Introduction. Emergence of nosocomial bacterial pathogens (especially Gram-negative bacteria with multiple resistance against almost all available antibiotics is a growing medical problem. No novel drugs targeting multidrug-resistant Gram-negative bacteria have been developed in recent years. In this context, there has been greatly renewed interest to cyclic lipodecapeptides polymyxins. Polymyxins exhibit rapid bactericidal activity, they are specific and highly potent against Gramnegative bacteria, but have potential nephrotoxic side effects. So polymyxins are attractive lead compounds to develop analogues with improved microbiological, pharmacological and toxicological properties. A detailed knowledge of the molecular mechanisms of polymyxin interactions with its cell targets is a prerequisite for the purposeful improvement of its therapeutic properties. The primary cell target of a polymyxin is a lipopolysaccharide (LPS in the outer membrane of Gram-negative bacteria. The binding site of polymyxin on LPS has been supposed to be Kdo2-lipid A fragment. Methods. For all molecular modeling and molecular dynamics simulation experiments the YASARA suite of programs was used. Complex of antimicrobial peptide polymyxin В3 (PmB3 with Kdo2-lipid A portion of E. coli lipopolysaccharide was constructed by rigid docking with flexible side chains of the peptide. By alanine scanning of polymyxin В3 bound to LPS followed by simulated annealing minimization of the complexes in explicit water environment, the molecular aspects of PmB3-LPS binding have been studied by 20 ns molecular dynamics simulations at 298 K and pH 7.0. The AMBER03 force field was used with a 1.05 nm force cutoff. To treat long range electrostatic interactions the Particle Mesh Ewald algorithm was used. Results. Ala-mutations of polymyxin’s residues Dab1, Dab3, Dab5, Dab8 and Dab9 in the PmB3-LPS complex caused sustained structural changes resulting in the notable loss in stability of

  19. Preventing pressure sores of the nasal ala after nasotracheal tube intubation: from animal model to clinical application.

    Science.gov (United States)

    Huang, Tze-Ta; Tseng, Chih-En; Lee, Tsan-Mu; Yeh, Jen-Ying; Lai, Yu-Yung

    2009-03-01

    Nasal-ala pressure sores induced by nasotracheal intubation are common complications of oral and maxillofacial surgery, but are easily ignored. To determine whether such sores could be prevented, we studied the effects of a combination of cushioning material in an animal model, and then analyzed the efficacy of this combination clinically. Four pigs received nasotracheal intubation. Each pig received intubation for 4, 8, 12, or 16 hours. Outcomes from pigs undergoing 500-gram-weight compression on each nostril were compared: one nostril received an application of cushioning materials, and the contralateral nostril did not. After the required study period, clinical assessment and further evaluation were performed by measuring pressure-sore dimensions and performing incisional biopsies. Clinical applications of this protective technique were then undertaken. Eight patients who underwent intubation without Soft Liner (GC Co, Tokyo, Japan) and DuoDERM CGF (ConvaTec, Inc, Princeton, NJ) protection, and 10 patients with Soft Liner and DuoDERM protection, were evaluated. The protective efficacy of the cushioning materials was significant in the animal model as well as in clinical practice. Pressure sores were avoided on the protected side, with severe tissue necrosis documented on the control side. We found that the combined use of Soft Liner and DuoDERM reduced the size and severity of nasal-ala pressure sores attributable to nasotracheal intubation during oral and maxillofacial surgery.

  20. 5-ALA induced fluorescent image analysis of actinic keratosis

    Science.gov (United States)

    Cho, Yong-Jin; Bae, Youngwoo; Choi, Eung-Ho; Jung, Byungjo

    2010-02-01

    In this study, we quantitatively analyzed 5-ALA induced fluorescent images of actinic keratosis using digital fluorescent color and hyperspectral imaging modalities. UV-A was utilized to induce fluorescent images and actinic keratosis (AK) lesions were demarcated from surrounding the normal region with different methods. Eight subjects with AK lesion were participated in this study. In the hyperspectral imaging modality, spectral analysis method was utilized for hyperspectral cube image and AK lesions were demarcated from the normal region. Before image acquisition, we designated biopsy position for histopathology of AK lesion and surrounding normal region. Erythema index (E.I.) values on both regions were calculated from the spectral cube data. Image analysis of subjects resulted in two different groups: the first group with the higher fluorescence signal and E.I. on AK lesion than the normal region; the second group with lower fluorescence signal and without big difference in E.I. between two regions. In fluorescent color image analysis of facial AK, E.I. images were calculated on both normal and AK lesions and compared with the results of hyperspectral imaging modality. The results might indicate that the different intensity of fluorescence and E.I. among the subjects with AK might be interpreted as different phases of morphological and metabolic changes of AK lesions.

  1. Evaluation of Acoustic Emission NDE of Composite Crew Module Service Module/Alternate Launch Abort System (CCM SM/ALAS) Test Article Failure Tests

    Science.gov (United States)

    Horne, Michael R.; Madaras, Eric I.

    2010-01-01

    Failure tests of CCM SM/ALAS (Composite Crew Module Service Module / Alternate Launch Abort System) composite panels were conducted during July 10, 2008 and July 24, 2008 at Langley Research Center. This is a report of the analysis of the Acoustic Emission (AE) data collected during those tests.

  2. The cisproline(i - 1)-aromatic(i) interaction: Folding of the Ala-cisPro-Tyr peptide characterized by NMR and theoretical approaches

    Energy Technology Data Exchange (ETDEWEB)

    Nardi, Frederico; Kemmink, Johan; Sattler, Michael; Wade, Rebecca C. [European Molecular Biology Laboratory (Germany)

    2000-05-15

    Cisproline(i-1)-aromatic(i) interactions have been detected in several short peptides in aqueous solution by analysis of anomalous chemical shifts measured by {sup 1}H-NMR spectroscopy. This formation of local structure is of importance for protein folding and binding properties. To obtain an atomic-detail characterisation of the cisproline(i-1)-aromatic(i) interaction in terms of structure, energetics and dynamics, we studied the minimal peptide unit, blocked Ala-cisPro-Tyr, using computational and experimental techniques. Structural database analyses and a systematic search revealed two groups of conformations displaying a cisproline(i-1)-aromatic(i) interaction. These conformations were taken as seeds for molecular dynamics simulations in explicit solvent at 278 K. During a total of 33.6 ns of simulation, all the 'folded' conformations and some 'unfolded' states were sampled. {sup 1}H- and {sup 13}C-chemical shifts and {sup 3}J-coupling constants were measured for the Ala-Pro-Tyr peptide. Excellent agreement was found between all the measured and computed NMR properties, showing the good quality of the force field. We find that under the experimental and simulation conditions, the Ala-cisPro-Tyr peptide is folded 90% of the time and displays two types of folded conformation which we denote 'a' and 'b'. The type a conformations are twice as populated as the type b conformations. The former have the tyrosine ring interacting with the alanine {alpha} proton and are enthalpically stabilised. The latter have the aromatic ring interacting with the proline side chain and are entropically stabilised. The combined and complementary use of computational and experimental techniques permitted derivation of a detailed scenario of the 'folding' of this peptide.

  3. Burnham in Rhodesia kritiese beskouing oor die betroubaarheid ...

    African Journals Online (AJOL)

    Op Nuwejaarsdag 1893 het Frederick Russell. Burnham, na omswerwings in die Ameri- kaanse weste en Mexico, van San Francisco na Durban gereis en kort voor ... king by Pietersburg te verkry, 'n verkenning na Brakpan en die gevangeneming te Sannas- pos. Hier ontsnap Burnham wat hom nou toela op die vernieling ...

  4. The association between the Pro12Ala polymorphism in the PPARg gene and

    DEFF Research Database (Denmark)

    Schow, Trine

    2006-01-01

    The interaction between the Pro12Ala polymorphism in peroxisome-proliferator-activator receptor gamma PPARg -2 and physical activity in the association with obesity (BMI ≥30 kg m-2) was explored in 901 women and 903 men between 30 and 75 years participating in a population survey of cardiovascular...... disease risk factors in Vara, Sweden, (participation rate 81%). Questionnaires and interviews covered physical activity at leisure time (LTPA), smoking habits and socio-economic background, and anthropometric measures were ascertained. Obesity was found in 26% of the women and 20% of the men......: 0.19-5.91). This association was not seen in men or in women women above 50 years, but this risk was prevented already by a moderate level of LTPA. These findings support the emphasis...

  5. L’ensenyament-aprenentatge de la recerca a Llatinoamèrica. Acostament des d’ALAS Costa Rica

    Directory of Open Access Journals (Sweden)

    José Torres Frías

    2018-01-01

    Full Text Available El present text inclou l’anàlisi de treballs presentats en el XXX Congreso Latinoamericano de Sociología ALAS Costa Rica, celebrat el 2015, coordinat per l’Asociación Latinoamericana de Sociología (ALAS. Es prenen en consideració vuit treballs relacionats amb el procés d’ensenyament-aprenentatge de la recerca i es recuperen les principals aportacions que han fet sobre el tema. Es discuteix sobre com s’aborda el procés d’ensenyament-aprenentatge de la recerca en el context llatinoamericà. S’evidencia que, malgrat les diferències contextuals i institucionals, a Llatinoamèrica prevalen problemàtiques compartides sobre formació per a la recerca. Alguns dels principals aspectes que es posen de manifest estan relacionats amb la dificultat que tenen els formadors per desenvolupar el procés d’ensenyament-aprenentatge en el marc de les ciències socials i humanitats. Altres aspectes es vinculen amb l’experiència en recerca del formador mateix, amb l’estil que té per dur a terme la seva pròpia recerca i guiar tesis, i amb l’estil de docència que utilitza. També són un factor de rellevància els estils dels estudiants, així com les creences que tots dos actors tenen sobre la formació per a la recerca. Finalment, l’existència o no d'una cultura de recerca s’aprecia com una problemàtica que cal tenir en compte.

  6. The History of the Foundation of the Iranian National Blood Transfusion Service in 1974 and the Biography of its Founder; Professor Fereydoun Ala.

    Science.gov (United States)

    Azizi, Mohammad Hossein; Nayernouri, Touraj; Bahadori, Moslem

    2015-06-01

    The history of early attempts of blood transfusion in Iran traces back to the 1940s; however, around three decades later in 1974, the Iranian National Blood Transfusion Service (Sazeman-e Melli-e Enteqal-e Khun-e Iran) was founded by the outstanding hematologist, Professor Fereydoun Ala. The main goals of this centralized organization were to collect blood from healthy voluntary donors, to screen the donated blood and to provide various safe blood products based on scientific and ethical standards. In due course, a new era of blood transfusion service in Iran had begun to such a degree that after more than four decades of its activity, it is now considered the best-developed blood service in the eastern Mediterranean region. Here, a brief historical account of the early blood transfusion efforts and the establishment of the modern Iranian National Blood Transfusion Service in Iran is discussed in addition to the life and career of its founder and first director, Professor Fereydoun Ala.

  7. Vanemuislased jagasid oma majja tunnustust

    Index Scriptorium Estoniae

    2010-01-01

    Vanemuise loomenõukogu jagas aastaauhindu. Autospiriti-nimeline draamaauhind läks Maarja Mittile, Torrese-nimelise balletiauhinna sai Colin Thomas Maggs, Kinema-nimelise tehnilise töötaja auhinna sai Jaan Koiduaru, loomenõukogu eripreemia sai trupijuht Eda Hinno ning haldustöötaja müügiassistendi preemia Sanna Pindma. Samuti jagati kolleegipreemiaid

  8. Metal Borohydrides synthesized from metal borides and metal hydrides

    DEFF Research Database (Denmark)

    Sommer, Sanna

    2014-01-01

    Aarhus C, Denmark email: gallafogh@hotmail.com / sanna-sommer@hotmail.com Magnesium boride, MgB2, ball milled with MH (M = Li, Na, Ca) followed by hydrogenation under high hydrogen pressure, readily forms the corresponding metal borohydrides, M(BH4)x (M = Li, Na, Ca) and MgH2 according to reaction scheme...

  9. Phenotype-genotype correlation in Wilson disease in a large Lebanese family: association of c.2299insC with hepatic and of p. Ala1003Thr with neurologic phenotype.

    Directory of Open Access Journals (Sweden)

    Julnar Usta

    Full Text Available Genotype phenotype correlations in Wilson disease (WD are best established in homozygous patients or in compound heterozygous patients carrying the same set of mutations. We determined the clinical phenotype of patients with WD carrying the c.2298_2299insC in Exon 8 (c.2299insC or the p. Ala1003Thr missense substitution in Exon 13 mutations in the homozygous or compound heterozygous state. We investigated 76 members of a single large Lebanese family. Their genotypes were determined, and clinical assessments were carried out for affected subjects. We also performed a literature search retrieving the phenotypes of patients carrying the same mutations of our patients in the homozygous or compound heterozygous state. There were 7 consanguineous marriages in this family and the prevalence of WD was 8.9% and of carriers of ATP7B mutation 44.7%. WD was confirmed in 9 out of 76 subjects. All 9 had the c.2299insC mutation, 5 homozygous and 4-compound heterozygous with p. Ala1003Thr. Six of our patients had hepatic, 2 had neurologic and 1 had asymptomatic phenotype. Based on our data and a literature review, clear phenotypes were reported for 38 patients worldwide carrying the c.2299insC mutation. About 53% of those have hepatic and 29% have neurologic phenotype. Furthermore, there were 10 compound heterozygous patients carrying the p. Ala1003Thr mutation. Among those, 80% having c.2299insC as the second mutation had hepatic phenotype, and all others had neurologic phenotype. We hereby report an association between the c.2299insC mutation and hepatic phenotype and between the p. Ala1003Thr mutation and neurologic phenotype.

  10. In vitro Evaluation of a Bombesin Antagonistic Analogue Conjugated with DOTA-Ala(SO3H)-Aminooctanoyl for Targeting of the Gastrin-releasing Peptide Receptor

    International Nuclear Information System (INIS)

    Lim, Jae Cheong; Cho, Eun Ha; Kim, Jin Joo; Lee, So Young; Choi, Sang Mu

    2014-01-01

    As Bombesin (BBS) binds with high affinity to GRPR, BBS derivatives have been labeled with various radionuclides such as 99 mTc, 111 In, 90 Y, 64 Cu, 177 Lu, 68 Ga, or 18 F and have proved to be successful candidates for peptide receptor radiotherapy (PRRT). In this study, we employed Ala(SO 3 H)-Aminooctanoyl as a linker of BBS antagonistic peptide sequence, Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH 2 , with DOTA to prepare radiolabeled candidates for GRPR targeting. A DOTA-conjugated BBS antagonistic analogue was synthesized and radiolabeled with 177 Lu, and in vitro characteristics on GRPR-overexpressing human prostate tumor cells were evaluated. In conclusion, a novel BBS antagonistic analogue, 177 Lu-DOTA-sBBNA, is a promising candidate for the targeting of GRPR-over-expressing tumors. Further investigations to evaluate its in vivo characteristics and therapeutic efficacy are needed

  11. Deciphering a molecular mechanism of neonatal diabetes mellitus by the chemical synthesis of a protein diastereomer, [D-AlaB8]human proinsulin.

    Science.gov (United States)

    Avital-Shmilovici, Michal; Whittaker, Jonathan; Weiss, Michael A; Kent, Stephen B H

    2014-08-22

    Misfolding of proinsulin variants in the pancreatic β-cell, a monogenic cause of permanent neonatal-onset diabetes mellitus, provides a model for a disease of protein toxicity. A hot spot for such clinical mutations is found at position B8, conserved as glycine within the vertebrate insulin superfamily. We set out to investigate the molecular basis of the aberrant properties of a proinsulin clinical mutant in which residue Gly(B8) is replaced by Ser(B8). Modular total chemical synthesis was used to prepare the wild-type [Gly(B8)]proinsulin molecule and three analogs: [D-Ala(B8)]proinsulin, [L-Ala(B8)]proinsulin, and the clinical mutant [L-Ser(B8)]proinsulin. The protein diastereomer [D-Ala(B8)]proinsulin produced higher folding yields at all pH values compared with the wild-type proinsulin and the other two analogs, but showed only very weak binding to the insulin receptor. The clinical mutant [L-Ser(B8)]proinsulin impaired folding at pH 7.5 even in the presence of protein-disulfide isomerase. Surprisingly, although [L-Ser(B8)]proinsulin did not fold well under the physiological conditions investigated, once folded the [L-Ser(B8)]proinsulin protein molecule bound to the insulin receptor more effectively than wild-type proinsulin. Such paradoxical gain of function (not pertinent in vivo due to impaired secretion of the mutant insulin) presumably reflects induced fit in the native mechanism of hormone-receptor engagement. This work provides insight into the molecular mechanism of a clinical mutation in the insulin gene associated with diabetes mellitus. These results dramatically illustrate the power of total protein synthesis, as enabled by modern chemical ligation methods, for the investigation of protein folding and misfolding. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Hydrogeological Modelling of the Geothermal Waters of Alaşehir in the Continental Rift Zone of the Gediz, Western Anatolia, Turkey

    Science.gov (United States)

    Ӧzgür, Nevzat; Bostancı, Yesim; Anilır Yürük, Ezgi

    2017-12-01

    In western Anatolia, Turkey, the continental rift zones of the Büyük Menderes, Küçük Menderes and Gediz were formed by extensional tectonic features striking E-W generally and representing a great number of active geothermal systems, epithermal mineralizations and volcanic rocks from Middle Miocene to recent. The geothermal waters are associated with the faults which strike preferentially NW-SE and NE-SW and locate diagonal to general strike of the rift zones of the Menderes Massif. These NW-SE and NE-SW striking faults were probably generated by compressional tectonic regimes which leads to the deformation of uplift between two extensional rift zones in the Menderes Massif. The one of these rift zones is Gediz which is distinguished by a great number of geothermal waters such as Alaşehir, Kurşunlu, Çamurlu, Pamukkale and Urganlı. The geothermal waters of Alaşehir form the biggest potential in the rift zone of Gediz with a capacity of about 100 to 200 MWe. Geologically, the gneisses from the basement rocks in the study area which are overlain by an Paleozoic to Mesozoic intercalation of mica schists, quartzites and marbles, a Miocene intercalation of conglomerates, sandstones and clay stones and Plio-Quaternary intercalation of conglomerates, sandstones and clay stones discordantly. In the study area, Paleozoic to Mesozoic quartzites and marbles form the reservoir rocks hydrogeologically. The geothermal waters anions with Na+K>Ca>Mg dominant cations and HCO3>Cl> dominant anions are of Na-HCO3 type and can be considered as partial equilibrated waters. According to the results of geochemical thermometers, the reservoir temperatures area of about 185°C in accordance with measured reservoir temperatures. Stabile isotopes of δ18O versus δ2H of geothermal waters of Alaşehir deviate from the meteoric water line showing an intensive water-rock interaction under high temperature conditions. These data are well correlated with the results of the

  13. Gömülmüs Atom Potansiyeli Kullanarak CuNi Alasımının Moleküler Dinamik Simulasyonu

    Directory of Open Access Journals (Sweden)

    Eşe Ergün AKPINAR

    2009-04-01

    Full Text Available Bu çalısmada, CuNi alasımının moleküler dinamik simulasyonu, Sutton-Chen (SC potansiyeli kullanılarak incelendi. Bu potansiyel Cu, Ni ve CuNi in deneysel bilgilerinin fonksiyon parametrelerine fit edilmesiyle elde edildi. CuNi alasımının kristalizasyon sürecini atomik olarak tanımlamak için, gömülmüs atom yöntemini esas alan sabit basınç, sabit sıcaklık (NPT moleküler dinamik simulasyonu uygulandı. Sıvı fazda iken 4x1011 K/s sogutma hızında sogutulan CuNi alasımının yapısı ve kristallesme olusum yetenegi radyal dagılım fonksiyonuyla incelendi. Simulasyon, üç temel dogrultu boyunca periyodik sınır sartlarını saglayan kübik bir hücrede 1024 atom içeren sistemle gerçeklestirildi. Hareket denklemleri Verlet algoritması kullanılarak sayısal olarak çözüldü. Sogutma deneyi için sıvı hal baslangıcı, katının sıvı sıcaklıgına ısıtılmasıyla elde edildi. Sistem 1300-1550K sıvılasma bölgesi üzerindeki sıcaklıkta eritildi ve homojenize edildi ve hızla oda sıcaklıgına sogutuldu.

  14. Aktivitas Manusia dan Distribusi Banteng (Bos Javanicus D’alton 1832 di Taman Nasional Alas Purwo

    Directory of Open Access Journals (Sweden)

    Muhammad Ali Imron

    2013-01-01

    Full Text Available Human Activities and Distribution of Banteng (Bos Javanicus D’alton 1832 in Alas Purwo National Park This study aims to comprehend whether human activities contribute to the presence of banteng (Bos sundaicus d’Alton 1836 in the Alas Purwo National Park (APNP. We laid continuous strip line transects from centre of human activities to the direction of core area of APNP. Three locations were selected: Sadengan grazing area, Giri Salaka Hinduism praying area, and Kutorejo village; representing low to high human disturbance respectively. We collected both direct and indirect presence of banteng as well as human activities within 20 metre strip lines with 10 metre width. Data were compiled each 100 metres and analyzed with means comparison to observe difference among locations. Correlation analyses were used to assess the relation between distance from centre of human activities, human activities and banteng presence. Regression analysis was used when  significant correlations found. Our non parametric test showed that human disturbances are significantly different among sites (Kruskal Wallis Test; df 2 = 6.220, p< 0.05. In similar tendency but different manner, it is showed that the different levels of human disturbance conveyed significant difference in number of banteng’s tracks (Kruskal Wallis Test; df 2 = 18.888, p< 0.05. The distance from centre of human activities is negatively related to number of human tracks (Spearman rho; r2= -0.307 N= 64, p<0.05* and also to number of banteng’s tracks (Spearman rho, r2= -0.728 N= 30, p<0.05**. The regression analysis showed that number of human tracks explained 18.6% of total variation on number of Banteng’s tracks, while distance from centre of human activities explained 59%.

  15. An insulin receptor mutant (Asp707 → Ala), involved in leprechaunism, is processed and transported to the cell surface but unable to bind insulin

    NARCIS (Netherlands)

    L.M. 't Hart (Leen); D. Lindhout (Dick); G.C.M. van der Zon (Gerard); H. Kayserilli (Hülya); M.Y. Apak (Memnune); W.J. Kleijer (Wim); E.R. van der Vorm (Eric); J.A. Maassen (Johannes)

    1996-01-01

    textabstractWe have identified a homozygous mutation near the carboxyl terminus of the insulin receptor (IR) α subunit from a leprechaun patient, changing Asp707 into Ala. Fibroblasts from this patient had no high affinity insulin binding sites. To examine the effect of the mutation on IR

  16. Motivación y Hábitos de estudio en estudiantes de la Universidad Alas Peruanas, Filial Juliaca

    OpenAIRE

    Quispe Tapia, David

    2017-01-01

    El objetivo de la presente tesis es sustentar la influencia de la motivación en el habito de estudio en los estudiantes de la Universidad Alas Peruana, filial Juliaca. Asimismo, conocer de qué manera influye la motivación intrínseca y la motivación extrínseca en los hábitos de estudio. Los métodos y el estudio corresponde al tipo cualitativo, básico y con un diseño descriptivo correlacional, con una población de estudio de 160 estudiantes de los cuales se obtuvo una muestra ...

  17. Quantitative model calculation of the time-dependent protoporphyrin IX concentration in normal human epidermis after delivery of ALA by passive topical application or lontophoresis

    NARCIS (Netherlands)

    Star, Willem M.; Aalders, Maurice C. G.; Sac, Arnoldo; Sterenborg, Henricus J. C. M.

    2002-01-01

    We present a mathematical layer model to quantitatively calculate the diffusion of 5-aminolevulinic acid (ALA) in the skin in vivo, its uptake into the cells and its conversion to protoporphyrin IX (PpIX) and subsequently to heme. The model is a modification and extension of a recently presented

  18. Evaluation of the hepatic bioconversion of α-linolenic acid (ALA to eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA in rats fed with oils from chia (Salvia hispánica or rosa mosqueta (Rosa rubiginosa

    Directory of Open Access Journals (Sweden)

    Tapia O., G.

    2012-03-01

    Full Text Available The high dietary intake of n-6 fatty acids in relation to n-3 fatty acids generates health disorders, such as cardiovascular diseases, inflammatory diseases and other chronic diseases. The consumption of fish, which is rich in n-3 fatty acids, is low in Latin America and it is necessary to seek other alternatives, such as chia oil (CO or rosa mosqueta oil (RMO, which are rich in α-linolenic acid (ALA, the precursor of the n -3 fatty acids, eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. This study evaluates the hepatic bioconversion of ALA to EPA and DHA and the damage to the liver (histology and transaminase in Sprague- Dawley rats fed different vegetable oils. Four experimental groups (n = 9 animals each group were fed the following dietary supplements for 21 days: a sunflower oil (SFO, b RMO, c CO d olive oil with fish oil added (EPA and DHA (OO/FO. RMO and CO increased the hepatic levels of ALA, EPA and DHA and decreased the n-6/n-3 ratio compared to SFO (p El elevado aporte en la dieta de ácidos grasos omega- 6, en relación a los ácidos grasos omega-3, genera alteraciones de la salud cardiovascular, inflamación y otras patologías crónicas no transmisibles. Por otro lado, el pescado rico en ácidos grasos omega-3 es de bajo consumo en Latinoamérica, siendo necesario buscar otras alternativas de aporte de ácidos grasos omega-3, como lo son el aceite de chía (CO o el de rosa mosqueta (RMO, ricos en ácido α-linolénico (ALA, que es el precursor de los ácidos grasos omega-3, eicosapentaenoico (EPA y docosahexaenoico (DHA. Este trabajo evaluó en forma preliminar la bioconversión hepática del ALA en EPA y DHA y el daño hepático (histología y transaminasas en ratas Sprague-Dawley alimentadas con diferentes aceites vegetales. Se conformaron cuatro grupos experimentales (n = 9 animales por grupo que recibieron durante 21 días: a aceite de girasol (SFO; b RMO, c CO y d aceite de oliva adicionado de aceite de pescado (EPA

  19. PPAR gamma Pro(12)Ala polymorphism and risk of acute coronary syndrome in a prospective study of Danes

    DEFF Research Database (Denmark)

    Vogel, Ulla Birgitte; Segel, Stine; Dethlefsen, Claus

    2009-01-01

    Background: Acute coronary syndrome (ACS) is a major cause of morbidity and mortality in the western world. Peroxisome proliferator-activated receptor gamma (PPAR gamma) plays a key role in the regulation of the energy balance, adipocyte differentiation and lipid biosynthesis. The aim...... was to investigate if the polymorphism PPAR gamma 2 Pro(12)Ala, which encodes a less efficient transcription factor, was associated with risk of acute coronary disease and if there were interactions between this polymorphism and factors that modify PPAR gamma activity, such as alcohol intake, smoking, and use of non...

  20. Ala397Asp mutation of myosin VIIA gene segregating in a Spanish family with type-Ib Usher syndrome.

    Science.gov (United States)

    Espinós, C; Millán, J M; Sánchez, F; Beneyto, M; Nájera, C

    1998-06-01

    In the current study, 12 Spanish families affected by type-I Usher syndrome, that was previously linked to chromosome 11q, were screened for the presence of mutations in the N-terminal coding portion of the motor domain of the myosin VIIA gene by single-strand conformation polymorphism analysis of the first 14 exons. A mutation (Ala397Asp) segregating with the disease was identified, and several polymorphisms were also detected. It is presumed that the other USHIB mutations in these families could be located in the unscreened regions of the gene.

  1. Refractive properties of imidazolium ionic liquids with alanine anion [C n mim][Ala] ( n = 2, 3, 4, 5, 6)

    Science.gov (United States)

    Zhou, Cai-bin; Li, Jing; Yi, Zhe; Ai, Hong-jun

    2017-10-01

    Imidazolium ionic liquids with alanine anion, [C n mim][Ala] ( n = 2, 3, 4, 5, 6), were prepared and characterized. The standard addition method was used to measure refractivity of the synthesized ionic liquids in order to eliminate the effect of water traces in the ionic liquids. The molar refraction and molecular polarizability were also calculated by Lorentz-Lorenz's method. Using liner extrapolation, the semiempirical estimation method for optical properties of other ionic liquids with amino acid anions was established.

  2. SLC6A3 coding variant Ala559Val found in two autism probands alters dopamine transporter function and trafficking.

    Science.gov (United States)

    Bowton, E; Saunders, C; Reddy, I A; Campbell, N G; Hamilton, P J; Henry, L K; Coon, H; Sakrikar, D; Veenstra-VanderWeele, J M; Blakely, R D; Sutcliffe, J; Matthies, H J G; Erreger, K; Galli, A

    2014-10-14

    Emerging evidence associates dysfunction in the dopamine (DA) transporter (DAT) with the pathophysiology of autism spectrum disorder (ASD). The human DAT (hDAT; SLC6A3) rare variant with an Ala to Val substitution at amino acid 559 (hDAT A559V) was previously reported in individuals with bipolar disorder or attention-deficit hyperactivity disorder (ADHD). We have demonstrated that this variant is hyper-phosphorylated at the amino (N)-terminal serine (Ser) residues and promotes an anomalous DA efflux phenotype. Here, we report the novel identification of hDAT A559V in two unrelated ASD subjects and provide the first mechanistic description of its impaired trafficking phenotype. DAT surface expression is dynamically regulated by DAT substrates including the psychostimulant amphetamine (AMPH), which causes hDAT trafficking away from the plasma membrane. The integrity of DAT trafficking directly impacts DA transport capacity and therefore dopaminergic neurotransmission. Here, we show that hDAT A559V is resistant to AMPH-induced cell surface redistribution. This unique trafficking phenotype is conferred by altered protein kinase C β (PKCβ) activity. Cells expressing hDAT A559V exhibit constitutively elevated PKCβ activity, inhibition of which restores the AMPH-induced hDAT A559V membrane redistribution. Mechanistically, we link the inability of hDAT A559V to traffic in response to AMPH to the phosphorylation of the five most distal DAT N-terminal Ser. Mutation of these N-terminal Ser to Ala restores AMPH-induced trafficking. Furthermore, hDAT A559V has a diminished ability to transport AMPH, and therefore lacks AMPH-induced DA efflux. Pharmacological inhibition of PKCβ or Ser to Ala substitution in the hDAT A559V background restores AMPH-induced DA efflux while promoting intracellular AMPH accumulation. Although hDAT A559V is a rare variant, it has been found in multiple probands with neuropsychiatric disorders associated with imbalances in DA neurotransmission

  3. In vitro Evaluation of a Bombesin Antagonistic Analogue Conjugated with DOTA-Ala(SO{sub 3}H)-Aminooctanoyl for Targeting of the Gastrin-releasing Peptide Receptor

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jae Cheong; Cho, Eun Ha; Kim, Jin Joo; Lee, So Young; Choi, Sang Mu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-05-15

    As Bombesin (BBS) binds with high affinity to GRPR, BBS derivatives have been labeled with various radionuclides such as {sup 99}mTc, {sup 111}In, {sup 90}Y, {sup 64}Cu, {sup 177}Lu, {sup 68}Ga, or {sup 18}F and have proved to be successful candidates for peptide receptor radiotherapy (PRRT). In this study, we employed Ala(SO{sub 3}H)-Aminooctanoyl as a linker of BBS antagonistic peptide sequence, Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH{sub 2}, with DOTA to prepare radiolabeled candidates for GRPR targeting. A DOTA-conjugated BBS antagonistic analogue was synthesized and radiolabeled with {sup 177}Lu, and in vitro characteristics on GRPR-overexpressing human prostate tumor cells were evaluated. In conclusion, a novel BBS antagonistic analogue, {sup 177}Lu-DOTA-sBBNA, is a promising candidate for the targeting of GRPR-over-expressing tumors. Further investigations to evaluate its in vivo characteristics and therapeutic efficacy are needed.

  4. A cyclic carbo-isosteric penta-depsipeptide: cyclo(Phe1–d-Ala2–Gly3–Phe4–APO5

    Directory of Open Access Journals (Sweden)

    Stéphanie M. Guéret

    2015-01-01

    Full Text Available The title compound, cyclo(Phe1–d-Ala2–Gly3–Phe4–APO5, C26H32N4O5, is the minor diastereoisomer of a cyclic penta-peptidomimetic analogue containing a novel 2-aminopropyl lactone (APO motif, which displays the same number of atoms as the native amino acid glycine and has a methyl group in place of the carbonyl O atom. The crystal structure presented here allows the analysis of the secondary structure of this unprecedented cyclic carbo-isosteric depsipeptide. The conformation of the central ring is stabilized by an intramolecular N—H...O hydrogen bond between the carbonyl O atom of the first residue (Phe1 and the amide group H atom of the fourth residue (Phe4. Based on the previously reported hydrogen bond and on the values of the torsion angles ϕ and ψ, the loop formed by the first, second, third and fourth residues (Phe1, d-Ala2, Gly3 and Phe4 can be classified as a type II′ β-turn. The loop around the new peptidomimetic motif, on the other hand, resembles an open γ-turn containing a weak N—H...O hydrogen bond between the carbonyl group O atom of the fourth residue (Phe4 and the amide unit H atom of the first residue (Phe1. In the crystal, the peptidomimetic molecules are arranged in chains along the b-axis direction. Within such a chain, the molecules of the structure are linked via N—H...O hydrogen bonds between the amide group H atom of the secondary residue (d-Ala2 and the carboxy unit O atom of the fourth residue (Phe4 in a neighboring molecule. The newly formed methyl stereocentre of the APO peptidomimetic motif (APO5 was obtained as the minor diastereoisomer in a ring-closing reductive amination reaction and adopts an R configuration.

  5. Tessier No. 3 and No. 4 clefts: Sequential treatment in infancy by pre-surgical orthopedic skeletal contraction, comprehensive reconstruction, and novel surgical lengthening of the ala base-canthal distance.

    Science.gov (United States)

    Spolyar, John L; Hnatiuk, Mark; Shaheen, Kenneth W; Mertz, Jennifer K; Handler, Lawrence F; Jarial, Ravinder; Roldán, J Camilo

    2015-09-01

    Repair of facial clefts implies wide tissue mobilization with multi-stage surgical treatment. Authors propose pre-surgical orthopedic correction for naso-oro-ocular clefts and a novel surgical option for Tessier No. 3 cleft. Two male infants, a Tessier No. 3 cleft (age 7 months) and another Tessier No. 4 (age 3 months), were treated with a modified orthopedic Latham device with additional septo-premaxillary molding and observed to age four years. Tessier No. 3 orthopedic measurements were obtained by image corrected cephalometric analysis. Subsequent repair included tissue expansion on Tessier No. 4 and naso-frontal Rieger flap combined with myocutaneous upper lid flap on Tessier No. 3. Orthopedic movements ranged from 18.5 mm in bi-planar to 33 mm in oblique analyses. Tissue margins became aligned with platform normalization. Tissue expansion on Tessier No. 4 improved distances from ala base-lower lid and subalar base-lip. The naso-frontal flap combined with myocutaneous upper lid flap on Tessier No. 3 had similar achievement, but also sufficiently lengthened ala base-canthal distance. Repairs were facilitated by pre-surgical orthopedic correction. The naso-frontal flap combined with an upper lid myocutaneous flap seems viable as a single-stage option to lengthen ala base-canthal distance to advance repair achievement in unilateral Tessier No. 3. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  6. Structural study of the AlP, GaAs and AlAs semiconductors with wurtzite structure

    International Nuclear Information System (INIS)

    Bautista H, A.; Perez A, L.; Pal, U.; Rivas S, J.F.

    2003-01-01

    In this work we present ab initio calculations of optimization geometries, lattice constant and electronic structure for semiconductors wurtzite type, like AIN, CdS, Zn S, Zn Se, Ga N and GaAs. For this, we used the CASTEP program of CERUIS with LDA and GGA approximations, in the framework of Functional Density Theory. The used pseudopotentials are available in that program and were generated using the optimization scheme of Troullier-Martins. With the lattice constant just optimized, we calculate then the X-ray spectra for studied semiconductors.We analyzed the effect of used pseudopotentials on function of the results obtained. Finally, we predicted the geometry and X-ray pattern for AIP, AlAs and GaAs with wurtzite structure, giving evidence about the semiconductor character of these materials. (Author)

  7. Preliminary Validation of a High Docosahexaenoic Acid (DHA) and -Linolenic Acid (ALA) Dietary Oil Blend: Tissue Fatty Acid Composition and Liver Proteome Response in Atlantic Salmon (Salmo salar) Smolts.

    Science.gov (United States)

    Nuez-Ortín, Waldo G; Carter, Chris G; Wilson, Richard; Cooke, Ira; Nichols, Peter D

    2016-01-01

    Marine oils are important to human nutrition as the major source of docosahexaenoic acid (DHA), a key omega-3 long-chain (≥C20) polyunsaturated fatty acid (n-3 LC-PUFA) that is low or lacking in terrestrial plant or animal oils. The inclusion of fish oil as main source of n-3 LC-PUFA in aquafeeds is mostly limited by the increasing price and decreasing availability. Fish oil replacement with cheaper terrestrial plant and animal oils has considerably reduced the content of n-3 LC-PUFA in flesh of farmed Atlantic salmon. Novel DHA-enriched oils with high alpha-linolenic acid (ALA) content will be available from transgenic oilseeds plants in the near future as an alternative for dietary fish oil replacement in aquafeeds. As a preliminary validation, we formulated an oil blend (TOFX) with high DHA and ALA content using tuna oil (TO) high in DHA and the flaxseed oil (FX) high in ALA, and assessed its ability to achieve fish oil-like n-3 LC-PUFA tissue composition in Atlantic salmon smolts. We applied proteomics as an exploratory approach to understand the effects of nutritional changes on the fish liver. Comparisons were made between fish fed a fish oil-based diet (FO) and a commercial-like oil blend diet (fish oil + poultry oil, FOPO) over 89 days. Growth and feed efficiency ratio were lower on the TOFX diet. Fish muscle concentration of n-3 LC-PUFA was significantly higher for TOFX than for FOPO fish, but not higher than for FO fish, while retention efficiency of n-3 LC-PUFA was promoted by TOFX relative to FO. Proteomics analysis revealed an oxidative stress response indicative of the main adaptive physiological mechanism in TOFX fish. While specific dietary fatty acid concentrations and balances and antioxidant supplementation may need further attention, the use of an oil with a high content of DHA and ALA can enhance tissue deposition of n-3 LC-PUFA in relation to a commercially used oil blend.

  8. Preliminary Validation of a High Docosahexaenoic Acid (DHA and -Linolenic Acid (ALA Dietary Oil Blend: Tissue Fatty Acid Composition and Liver Proteome Response in Atlantic Salmon (Salmo salar Smolts.

    Directory of Open Access Journals (Sweden)

    Waldo G Nuez-Ortín

    Full Text Available Marine oils are important to human nutrition as the major source of docosahexaenoic acid (DHA, a key omega-3 long-chain (≥C20 polyunsaturated fatty acid (n-3 LC-PUFA that is low or lacking in terrestrial plant or animal oils. The inclusion of fish oil as main source of n-3 LC-PUFA in aquafeeds is mostly limited by the increasing price and decreasing availability. Fish oil replacement with cheaper terrestrial plant and animal oils has considerably reduced the content of n-3 LC-PUFA in flesh of farmed Atlantic salmon. Novel DHA-enriched oils with high alpha-linolenic acid (ALA content will be available from transgenic oilseeds plants in the near future as an alternative for dietary fish oil replacement in aquafeeds. As a preliminary validation, we formulated an oil blend (TOFX with high DHA and ALA content using tuna oil (TO high in DHA and the flaxseed oil (FX high in ALA, and assessed its ability to achieve fish oil-like n-3 LC-PUFA tissue composition in Atlantic salmon smolts. We applied proteomics as an exploratory approach to understand the effects of nutritional changes on the fish liver. Comparisons were made between fish fed a fish oil-based diet (FO and a commercial-like oil blend diet (fish oil + poultry oil, FOPO over 89 days. Growth and feed efficiency ratio were lower on the TOFX diet. Fish muscle concentration of n-3 LC-PUFA was significantly higher for TOFX than for FOPO fish, but not higher than for FO fish, while retention efficiency of n-3 LC-PUFA was promoted by TOFX relative to FO. Proteomics analysis revealed an oxidative stress response indicative of the main adaptive physiological mechanism in TOFX fish. While specific dietary fatty acid concentrations and balances and antioxidant supplementation may need further attention, the use of an oil with a high content of DHA and ALA can enhance tissue deposition of n-3 LC-PUFA in relation to a commercially used oil blend.

  9. Comment: studies of the Pro12Ala polymorphism of the PPAR-gamma gene in the Danish MONICA cohort: homozygosity of the Ala allele confers a decreased risk of the insulin resistance syndrome

    DEFF Research Database (Denmark)

    Frederiksen, Laura; Brødbaek, Kasper; Fenger, Mogens

    2002-01-01

    with the frequency in the non-IRS group [2.8% (2.1-3.5%); P = 0.02; odds ratio, 0.24 (0.06-0.99)]. Moreover, in the total study population, homozygous carriers of the variant had lower levels of fasting serum triglyceride [1.1 +/- 0.4 mmol/liter (means +/- SD) vs. 1.4 +/- 0.9 mmol/liter; P = 0.04] and a lower...... was examined using PCR-restriction fragment length polymorphism in a phenotypically well characterized population-based sample of 2245 nondiabetic subjects. The study participants were characterized by a number of anthropometric and biochemical measurements and the European Group for the Study of Insulin...... Resistance criteria enabling a classification of the study population in an IRS group and a non-IRS group. The allelic frequency of the Pro12Ala polymorphism in the total study sample was 14% (95% confidence interval, 13-15%). Two hundred ninety-four subjects fulfilled the European Group for the Study...

  10. Analysis of manganese superoxide dismutase (MnSOD: Ala-9Val and glutathione peroxidase (GSH-Px: Pro 197 Leu gene polymorphisms in mood disorders.

    Directory of Open Access Journals (Sweden)

    Birgül Elbozan Cumurcu

    2013-05-01

    Full Text Available We investigated the etiopathogenetic role of manganese superoxide dismutase (MnSOD (Ala-9Val and glutathione peroxidase (GSH-Px (Pro 197 Leu gene polymorphisms in patients diagnosed with major depressive disorder (MDD and bipolar I disorder (BD. Eighty patients with MDD, 82 patients with BD (total 162 patients and 96 healthy controls were enrolled in this study and genotyped using a Real Time-Quantitative Polymer Chain Reaction (RT-qPCR-based method. The patients with BD and MDD and the controls had a similar distribution of the genotypes and alleles in the Ala-9Val MnSOD gene polymorphism. Comparison of the MDD group and control group regarding the Pro197 Leu GSH-Px gene polymorphism revealed similar genotype distribution but different allele distribution. The BD group and control group were similar both for genotypes and for alleles when compared regarding the Pro 197 Leu GSH-Px gene polymorphism. The combined analysis (MDD plus BD also failed to find any association between the Ala-9Val MnSOD and Pro 197 Leu GSH-Px gene polymorphism. Although small statistical power of the current study the significant difference between patients with depression and the control group for the Pro 197 Leu GSH-Px polymorphism indicates that the distribution of these alleles may have a contribution in the physiopathogenesis of depression. One of the limitation of the current study is that the sample size is too small. Understanding of the exact role of Pro 197 LeuGSH-Px polymorphism in the development of depression needs to further studies with more sample size and high statistical power.

  11. MTHFR Glu429Ala and ERCC5 His46His polymorphisms are associated with prognosis in colorectal cancer patients: analysis of two independent cohorts from Newfoundland.

    Directory of Open Access Journals (Sweden)

    Amit A Negandhi

    Full Text Available In this study, 27 genetic polymorphisms that were previously reported to be associated with clinical outcomes in colorectal cancer patients were investigated in relation to overall survival (OS and disease free survival (DFS in colorectal cancer patients from Newfoundland.The discovery and validation cohorts comprised of 532 and 252 patients, respectively. Genotypes of 27 polymorphisms were first obtained in the discovery cohort and survival analyses were performed assuming the co-dominant genetic model. Polymorphisms associated with disease outcomes in the discovery cohort were then investigated in the validation cohort.When adjusted for sex, age, tumor stage and microsatellite instability (MSI status, four polymorphisms were independent predictors of OS in the discovery cohort MTHFR Glu429Ala (HR: 1.72, 95%CI: 1.04-2.84, p = 0.036, ERCC5 His46His (HR: 1.78, 95%CI: 1.15-2.76, p = 0.01, SERPINE1 -675indelG (HR: 0.52, 95%CI: 0.32-0.84, p = 0.008, and the homozygous deletion of GSTM1 gene (HR: 1.4, 95%CI: 1.03-1.92, p = 0.033. In the validation cohort, the MTHFR Glu429Ala polymorphism was associated with shorter OS (HR: 1.71, 95%CI: 1.18-2.49, p = 0.005, although with a different genotype than the discovery cohort (CC genotype in the discovery cohort and AC genotype in the validation cohort. When stratified based on treatment with 5-Fluorouracil (5-FU-based regimens, this polymorphism was associated with reduced OS only in patients not treated with 5-FU. In the DFS analysis, when adjusted for other variables, the TT genotype of the ERCC5 His46His polymorphism was associated with shorter DFS in both cohorts (discovery cohort: HR: 1.54, 95%CI: 1.04-2.29, p = 0.032 and replication cohort: HR: 1.81, 95%CI: 1.11-2.94, p = 0.018.In this study, associations of the MTHFR Glu429Ala polymorphism with OS and the ERCC5 His46His polymorphism with DFS were identified in two colorectal cancer patient cohorts. Our results also suggest

  12. π-Extended Isoindigo-Based Derivative: A Promising Electron-Deficient Building Block for Polymer Semiconductors.

    Science.gov (United States)

    Xu, Long; Zhao, Zhiyuan; Xiao, Mingchao; Yang, Jie; Xiao, Jian; Yi, Zhengran; Wang, Shuai; Liu, Yunqi

    2017-11-22

    The exploration of novel electron-deficient building blocks is a key task for developing high-performance polymer semiconductors in organic thin-film transistors. In view of the situation of the lack of strong electron-deficient building blocks, we designed two novel π-extended isoindigo-based electron-deficient building blocks, IVI and F 4 IVI. Owing to the strong electron-deficient nature and the extended π-conjugated system of the two acceptor units, their copolymers, PIVI2T and PF 4 IVI2T, containing 2,2'-bithiophene donor units, are endowed with deep-lying highest occupied molecular orbital (HOMO)/lowest unoccupied molecular orbital (LUMO) energy levels and strong intermolecular interactions. In comparison to PIVI2T, the fluorinated PF 4 IVI2T exhibits stronger intra- and intermolecular interactions, lower HOMO/LUMO energy levels up to -5.74/-4.17 eV, and more ordered molecular packing with a smaller π-π stacking distance of up to 3.53 Å, resulting in an excellent ambipolar transporting behavior and a promising application in logic circuits for PF 4 IVI2T in ambient with hole and electron mobilities of up to 1.03 and 1.82 cm 2 V -1 s -1 , respectively. The results reveal that F 4 IVI is a promising and strong electron-deficient building unit to construct high-performance semiconducting polymers, which provides an insight into the structure-property relationships for the exploration and molecular engineering of excellent electron-deficient building blocks in the field of organic electronics.

  13. Statistical analysis of wind speed using two-parameter Weibull distribution in Alaçatı region

    International Nuclear Information System (INIS)

    Ozay, Can; Celiktas, Melih Soner

    2016-01-01

    Highlights: • Wind speed & direction data from September 2008 to March 2014 has been analyzed. • Mean wind speed for the whole data set has been found to be 8.11 m/s. • Highest wind speed is observed in July with a monthly mean value of 9.10 m/s. • Wind speed with the most energy has been calculated as 12.77 m/s. • Observed data has been fit to a Weibull distribution and k &c parameters have been calculated as 2.05 and 9.16. - Abstract: Weibull Statistical Distribution is a common method for analyzing wind speed measurements and determining wind energy potential. Weibull probability density function can be used to forecast wind speed, wind density and wind energy potential. In this study a two-parameter Weibull statistical distribution is used to analyze the wind characteristics of Alaçatı region, located in Çeşme, İzmir. The data used in the density function are acquired from a wind measurement station in Alaçatı. Measurements were gathered on three different heights respectively 70, 50 and 30 m between 10 min intervals for five and half years. As a result of this study; wind speed frequency distribution, wind direction trends, mean wind speed, and the shape and the scale (k&c) Weibull parameters have been calculated for the region. Mean wind speed for the entirety of the data set is found to be 8.11 m/s. k&c parameters are found as 2.05 and 9.16 in relative order. Wind direction analysis along with a wind rose graph for the region is also provided with the study. Analysis suggests that higher wind speeds which range from 6–12 m/s are prevalent between the sectors 340–360°. Lower wind speeds, from 3 to 6 m/s occur between sectors 10–29°. Results of this study contribute to the general knowledge about the regions wind energy potential and can be used as a source for investors and academics.

  14. Selgusid kirjanduse aastapreemiate saajad / Rein Veidemann ; komment. Karl Martin Sinijärv, Viivi Luik

    Index Scriptorium Estoniae

    Veidemann, Rein, 1946-

    2006-01-01

    Eesti Kultuurkapitali aastapreemiad: Kristiina Ehini luulekogu "Kaitseala" ja Jürgen Rooste luulekogu "Ilusaks inimeseks", Piret Raud "Sanna ja salakütid", Merle Karusoo näidend "Misjonärid", Madis Kõivu artiklikogumik "Luhta-minek". Tõlkepreemiad tõlkijatele Anu Saluäär, Heili Einasto, Lembi Loigu, Veronika Kivisilla, Risto Järv. Vabaauhind Käbi Laretei. Artiklipreemia Aare Pilv. Venekeelse autori kirjandusauhind Gohar Markosjan-Käsper, Svetlan Semenenko

  15. Meat, milk, saturated fatty acids, the Pro12Ala and C161T polymorphisms of the PPARgamma gene and colorectal cancer risk in Japanese.

    Science.gov (United States)

    Kuriki, Kiyonori; Hirose, Kaoru; Matsuo, Keitaro; Wakai, Kenji; Ito, Hidemi; Kanemitsu, Yukihide; Hirai, Takashi; Kato, Tomoyuki; Hamajima, Nobuyuki; Takezaki, Toshiro; Suzuki, Takeshi; Saito, Toshiko; Tanaka, Rie; Tajima, Kazuo

    2006-11-01

    The peroxisome proliferator-activated receptor gamma (PPARgamma) gene plays important roles in energy homeostasis. To examine interactions between consumption of foods and fatty acids and the Pro12Ala and C161T (His447His) polymorphisms for colorectal cancer, we performed two case-control studies in Japanese. In study 1, there were 128 colorectal cancer cases and 238 non-cancer controls, and in study 2 there were 257 cases and 771 (age- and sex-matched) non-cancer controls. Assessment of food and nutrients consumption in study 1 was via a nine-item questionnaire, while in study 2 assessment of consumption was according to a more detailed semiquantitative food frequency questionnaire. Consumption of foods and fatty acids was divided into low, moderate and high groups. The overall frequency of the Ala allele was frequencies of the Pro/Pro + C/C and Pro/Pro + (C/T + T/T) genotypes were 70-73% and 20-26%, respectively. Compared with subjects with low meat intake and the Pro/Pro + C/C genotype, those with high meat consumption and the same genotype had a stronger increased risk in study 1 [OR, 2.88; 95% CI, 1.14-7.30; P for trend = 0.02], but a positive association with processed meat consumption was greatest in those with the Pro/Pro + (C/T + T/T) genotype (P for trend = 0.05) in study 2. Likewise, high consumption of saturated fatty acids and milk appeared to confer marginal increased risk and stronger decreased risk, respectively, in those with the Pro/Pro and Pro/Pro + C/C genotypes (OR, 1.35 and 0.65; 95% CI, 0.93-1.96 and 0.43-1.00; P for trend = 0.10 and 0.06). Further large-scale studies are needed to determine colorectal cancer risk according to relationships between the PPARgamma gene polymorphisms and dietary intakes of meat, processed meat, milk and saturated fatty acids in Japanese with very low frequency of the Ala allele.

  16. Use of 99mTc-HYNIC-βAla-Bombesina(7-14) peptide for the identification of prostate tumor, LNCaP line, in an experimental model

    International Nuclear Information System (INIS)

    Fuscaldi, Leonardo Lima

    2012-01-01

    Prostate cancer is one of the most prevalent tumors in men, showing high mortality rates. Current diagnostic methods are not able to identify early prostate carcinoma, often resulting in a late diagnosis with established metastasis. Thus, there is by the scientific community an incessant search for diagnostic methods for early assessment of prostate cancer, facilitating the treatment and increasing the chances of cure. In this context, nuclear medicine provides a diagnostic method which can detect tumors at an early stage, because it is based on biochemical and physiological changes of the tissue, such as overexpression of gastrin releasing peptide receptors (GRPr's) by prostate cancer cells. Bombesin, a tetradecapeptide isolated from the frog Bombina bombina, has a high affinity for the GRPr's, since it is analogous to gastrin releasing peptide. Therefore, this study aims to prepare the complex 99m Tc-HYNIC-βAla-Bombesina (7-14) and use it for the identification of prostate tumor, LNCaP line, in an experimental model. For in vitro assays, aliquots of 0.026 MBq of the radiopeptide were incubated with 2x10 6 LNCaP cells in a water bath at 37 deg C, for 1 and 4 hours, with and without prior addition of cold peptide (n=3). Prostate tumors were induced into the upper right flank of male BALB/c nude mice by subcutaneous injection of 5x106 LNCaP cells resuspended in 150 μL of Matrigel:RPMI-1640 medium (1:1). Biodistribution profile (n=5) and scintigraphic images (n=3) were obtained at 1 and 4 hours after intravenous injection of 7.4 MBq of 99m Tc-HYNIC-βAla-Bombesina (7-14) . To assess this, healthy male BALB/c mice and tumor-bearing male BALB/c nude mice with 15, 20 and 25 days of tumor development were used. In vitro study results showed that the fraction of the radiopeptide which bound to LNCaP cells was 2.08 +- 0.30% (1 hour) and 2.44 +- 0.18% (4 hours). From the percentage which was bound, the internalized fractions were 25.64 +- 3.14% (1 hour) and 25.27 +- 2

  17. EDUCACIÓN Y RESILIENCIA: ALAS DE LA TRANSFORMACIÓN SOCIAL

    Directory of Open Access Journals (Sweden)

    Viviana López Torres

    2010-01-01

    Full Text Available Tratándose de un nuevo paradigma de desarrollo, la resiliencia propone que no todas las personas que crecen en condiciones de adversidad, pobreza y desigualdad social serán adultos condenados al fracaso, a la delincuencia o a la locura; por el contrario, este concepto enfatiza en el potencial humano y hace un llamado a la esperanza y a la responsabilidad colectiva en la promoción de cambio social. El presente ensayo parte de una revisión analítica de literatura reciente sobre resiliencia, en el marco del trabajo realizado durante el año 2009 por el grupo "Esperanza y Vida", en la línea de investigación denominada "Resiliencia y contextos psicosociales", perteneciente al programa de Psicología de la Universidad Antonio Nariño (UAN Bogotá, Colombia. Este ejercicio reflexivo tiene como propósito analizar el concepto de resiliencia en el contexto escolar, considerando que este es uno de los primeros contactos de la infancia con la cultura, el lugar en donde las niñas y los niños van a preguntarse cómo funciona el mundo, el sitio donde pueden encontrar respuestas honestas y sugerencias útiles sobre cómo comprenderlo y cómo transformarlo; además, señala cómo acciones pedagógicas fundamentadas en el reconocimiento del estudiante como un agente responsable y activo en el proceso de aprendizaje, favorecen actitudes de compromiso en la promoción de la transformación social positiva.

  18. Two 24-hour Studies of Water Quality in the Ala Wai Canal during March and July, 1994 for the Mamala Bay Study, Pollutant Source Identification Project MB-3, (NODC Accession 0001188)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset focuses on studies of water quality in the Ala Wai Canal in order to determine its role of point and non point source disharge into Mamala Bay. The...

  19. Study of false positives in 5-ALA induced photodynamic diagnosis of bladder carcinoma

    Science.gov (United States)

    Draga, Ronald O. P.; Grimbergen, Matthijs C. M.; Kok, Esther T.; Jonges, Trudy G. N.; Bosch, J. L. H. R.

    2009-02-01

    Photodynamic diagnosis (PDD) is a technique that enhances the detection of tumors during cystoscopy using a photosensitizer which accumulates primarily in cancerous cells and will fluoresce when illuminated by violetblue light. A disadvantage of PDD is the relatively low specificity. In this retrospective study we aimed to identify predictors for false positive findings in PDD. Factors such as gender, age, recent transurethral resection of bladder tumors (TURBT), previous intravesical therapy (IVT) and urinary tract infections (UTIs) were examined for association with the false positive rates in a multivariate analysis. Data of 366 procedures and 200 patients were collected. Patients were instilled with 5-aminolevulinic acid (5-ALA) intravesically and 1253 biopsies were taken from tumors and suspicious lesions. Female gender and TURBT are independent predictors of false positives in PDD. However, previous intravesical therapy with Bacille Calmette-Guérin is also an important predictor of false positives. The false positive rate decreases during the first 9-12 weeks after the latest TURBT and the latest intravesical chemotherapy. Although shortly after IVT and TURBT false positives increase, PDD improves the diagnostic sensitivity and results in more adequate treatment strategies in a significant number of patients.

  20. PENGEMBANGAN MANAJEMEN DAYA TARIK WISATA BERBASIS QUALITY EXPERIENCES DI OBJEK WISATA ALAS KEDATON TABANAN

    Directory of Open Access Journals (Sweden)

    Yayu Indrawati

    2013-12-01

    Full Text Available In the recent days, to understanding the consumers behaviour is becoming a primary concern in marketing.This is also including in tourism marketing particularly tourism destination. The phenomenon of understandingthe consumer taste in tourism is popularly known as quality experience. It has a meaning that when tourist spendstheir money on a certain destination they expect for quality experience. It can be seen on their satisfaction thatappear on their willingness to revisit or giving the positive impression to their friends and relatives. Today, thereis a downward point in tourist destination in the last five years. Previously there were 1500 visitors per day, butlately it is only 10.000 both for international and domestic visitors. It is caused by the raise of competitor’s numberand the tourist responses towards Alas Kedaton site. Such impression comes from its cleanliness, the hospitalityof the staff, the price of entrance fee, and lack of facilities. Other instances are the uncomfortable way to get tothe site, as well as the absence of spiritual facilities for Muslim visitors for praying during their visit to this place.

  1. Similarities and differences in political opinions of Abul A'la Mawdudi and Sayyid Qutb

    Directory of Open Access Journals (Sweden)

    Kostić Ejub Ivan

    2015-01-01

    Full Text Available In the academic literature in the West, Abul A'la Mawdudi and Sayyid Qutb are often referred to as the thinkers who have, through their thinking and activism, set the foundations for radical Islamist ideas which are said to have served as the basis for the emergence of jihadist movements. Moreover, in the West their intellectual heritage and thought have been to a great extent identified as the same. Therefore, the aim of this paper is to show impartially the true nature of their political thought, and in addition to similarities in their thinking identify differences in their development, intellectual approach and activism. This attempt at differentiating opinions of the two Muslim intellectuals comes as a result of insight into the fact that scientists in the West are often inclined to a gross simplification and identifying of Islamic thinkers and movements for the sake of ideologically coloured academic prerequisites, and without deeper analyses. This paper will also provide terminology solutions for certain aspects of Islamic activism.

  2. Biological profile of 99mTc-HYNIC-βAla-NT(8-13) in MDAMB-231 breast cancer cell line

    International Nuclear Information System (INIS)

    Teodoro, Rodrigo; Faintuch, Bluma L.; Wiecek, Danielle P.; Silva, Natanael G.; Vallejo, Natalia M.

    2009-01-01

    Introduction: Neurotensin (NT) is a tridecapeptide involved in several growth-steps of human cancers. Recent studies postulated the role of NT and NT-receptor subtype 1 in breast cancer progression. However, the main drawback of natural NT is its rapid degradation in plasma. In an effort to develop a NT peptide-based radiopharmaceutical for the detection of breast cancer, the aim of this study was the radiolabeling of the double stabilized NT(8-13) peptide using HYNIC as chelating agent. Methods: Conjugated HYNIC-βAla-NT(8-13) was labeled with 99m Tc using tricine and EDDA as coligands. Radiochemical purity was checked by TLC and confirmed by RP-HPLC. 99m Tc-HYNIC-βAla-NT(8-13) (0.1 mL/74 MBq) was administered in Nude mice bearing MDA-MB-231 breast cancer cells and biodistribution studies were carried out at 30 and 90 min postinjection (pi). Blocking evaluation was also conducted by co-injection of 115 nmol of cold NT (8-13) analog. Planar gamma-camera imaging was acquired at the earlier time point studied. Results: Radiochemical purity of the radioconjugate was higher than 99%. Biodistribution studies revealed a very fast accumulation in tumor (1.97±0.18% ID/g, 30 min pi) with a sharply decrease at the later time point studied (0.44±0.02% ID/g). The specificity of the radioconjugate was evaluated with blockade studies. A reduction of 45.94%, 27.73% and 36.39% was found for tumor, large and small intestines, respectively, at 30 min pi. Otherwise, a less impressive blockade was observed for tumor and small intestine (28.68% and 24.90%, respectively) at the later time point studied. Conclusion: The results provide encouraging evidence in the development of radiolabeled NT(8-13) analogues for breast cancer diagnosis. (author)

  3. Studies of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) gene in relation to insulin sensitivity among glucose tolerant caucasians

    DEFF Research Database (Denmark)

    Ek, J; Andersen, G; Urhammer, S A

    2001-01-01

    We examined whether the Pro12-Ala polymorphism of the human peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) gene was related to altered insulin sensitivity among glucose-tolerant subjects or a lower accumulated incidence or prevalence of IGT and Type II (non-insulin-dependent) dia......-insulin-dependent) diabetes mellitus among Scandinavian Caucasians....

  4. Atomic structures of a monolayer of AlAs, GaAs, and InAs on Si(111)

    International Nuclear Information System (INIS)

    Lee, Geunjung; Yoon, Younggui

    2010-01-01

    We study atomic structures of a monolayer of AlAs, GaAs, and InAs on a Si(111) substrate from first-principles. The surface with the stacking sequence of ...SiSiMAsSiAs is energetically more stable than the surface with the stacking sequence of ...SiSiSiAsMAs, where M is Al, Ga, or In. The atomic structure of the three top layers of the low-energy surfaces are quite robust, irrespective of M, and the atomic structure of the AlAsSiAs terminated surface and that of the GaAsSiAs terminated surface are very similar. For the high-energy AsMAs terminated surfaces, the broken local tetrahedral symmetry plays an important role in the atomic structures. The calculated atomic structures of InAs on the Si(111) substrate depart most from the structure of crystalline Si.

  5. Kilde soome proosa kuldajast / Ann-Christine Snickars ; rootsikeelsest käsikirjast tõlkinud Anu Saluäär

    Index Scriptorium Estoniae

    Snickars, Ann-Christine

    2007-01-01

    Soome proosast, mehe ja naise rollist kirjanduses, ajaloo mõjust soome proosale. Näiteid soome prosaistidest Kari Hotakaisest, Frederik Långist, Kjell Westöst, Pirkko Saisiolist, Asko Sahlbergist, Pirjo Hassisest, Monika Fagerholmist, Anja Snellmanist, Leena Landerist, Anna-Leena Härkösest, Mari Möröst, Heidi Köngäsest, Riitta Jalosest, Kreetta Onkelist, Sofi Oksasest, Henrikka Ringbomist, Sanna Tahvasest, Malin Kivelöst, Lars Sundist, Susanne Ringellist ja Petri Tammisest

  6. Impact of dietary precursor ALA versus preformed DHA on fatty acid profiles of eggs, liver and adipose tissue and expression of genes associated with hepatic lipid metabolism in laying hens.

    Science.gov (United States)

    Neijat, M; Eck, P; House, J D

    2017-04-01

    Dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), including alpha-linolenic acid (ALA) and preformed longer chain PUFA (LCPUFA, particularly docosahexaenoic acid, DHA) differ in their egg LCPUFA enrichment efficiency. However, mechanisms leading to these differences are unclear. To this end, omega-3 PUFA contents in different lipid classes, including triacylglycerol (TAG) and total phospholipid (PL) in yolk, liver and adipose, as well as the expression of key hepatic enzymes in lipid metabolism were evaluated in laying hens in response to changes in dietary supply. Seventy Lohmann hens (n=10/treatment) consumed either a control diet (0.03% total omega-3 PUFA), or the control with supplementation (0.20%, 0.40% and 0.60% total omega-3 PUFA) from either flaxseed oil or algal product, as sources of ALA (precursor) or DHA (preformed), respectively. The study was arranged in a completely randomized design, and data were analyzed using the Proc Mixed procedure of SAS. ALA accumulated as a function of intake (PDHA-fed hens. Unlike flaxseed oil, preformed-DHA contributed to greater (P<0.0001) accumulation of LCPUFA in yolk total PL and TAG pool, as well as adipose TAG. This may relate to elevated (P<0.0001) expression of acyl-CoA synthetase (ACSL1). No difference in hepatic EPA level in total lipids was noted between both treatment groups; EPA liver =2.1493x-0.0064; R 2 =0.70, P<0.0001 (x=dietary omega-3 PUFA). The latter result may highlight the role of hepatic EPA in the regulation of LCPUFA metabolism in laying hens. Copyright © 2017. Published by Elsevier Ltd.

  7. Obtención de modelo matemático para el desarrollo del perfil del ala de una aeronave.

    Directory of Open Access Journals (Sweden)

    R. Cabrera Pedroso

    2008-05-01

    Full Text Available El presente trabajo está dirigido a brindar un modelo matemático que permita el cálculo y determinación de una función analítica para la obtención del perfil de un ala de geometría simétrica y variable de una aeronave con el empleo de métodos computacionales. En el artículo se analiza los métodos para la elaboración de sistemas de cálculo basados en modelos matemáticos obtenidos en MATLAB 7.0 e implementados con el software LabVIEW 6.0 a través de programas de diseños asistidos por computadoras en AUTOCAD (AUTOLISP. Los diferentes tópicos abordados dan a los interesados una idea global del desarrollo de esta tecnología computacional y su aplicación a ramas de la mecánica, así como la metodología seguida para obtener el perfil aerodinámico de un ala. También se exponen aspectos generales del empleo de la función AUTOLISP y el código fuente del programa diseñado.Title: Obtaining a mathematical model for the development of an airship wing profile.This article was carried out to obtain a mathematical model that allows the calculation and determination of an analytic function of symmetrical geometry profile and variable. In the article it is analyzed the methods for the elaboration of system of calculations based on mathematical models obtained with the software language LabVIEW 6.0 and it is used to developing the program attended by the computers AUTOCAD (AUTOLISP. The approached topics give to the interested parties a global idea of the development it gives this technology and their application to branches of the mechanical specialties, as well as the followed methodology to obtain the aerofoil profile of a wing. General aspects are also exposed of the employment of the function AUTOLISP and the source code on the sketch program.

  8. Evaluation of the water quality related to the acid mine drainage of an abandoned mercury mine (Alaşehir, Turkey).

    Science.gov (United States)

    Gemici, Unsal

    2008-12-01

    Mobility of metals in water, mine wastes, and stream sediments around the abandoned Alaşehir mercury mine was investigated to evaluate the environmental effects around the area. Mine waters are dominantly acidic with pH values of 2.55 in arid season and 2.70 in wet season and are sulfate rich. Acidity is caused mainly by the oxidation of sulfide minerals. Pyrite is the main acid-producing mineral in the Alaşehir area. Of the major ions, SO(4) shows a notable increase reaching 3981 mg/l, which exceeds the WHO (WHO guidelines for drinking water quality, vol. 2. Health criteria and other supporting information, 1993) and TS (Sular-Içme ve kullanma sulari. Ankara: Türk Standartlari Enstitüsü, 1997) drinking water standard of 250 mg/L. Mine waters have As, Fe, Mn, Ni, and Al with concentrations higher than drinking water standards. Hg concentrations of adit water samples and surface waters draining the mine area are between 0.25 and 0.274 microg/L and are below the WHO (WHO guidelines for drinking water quality, vol. 2. Health criteria and other supporting information, 1993) drinking water standard of 1.0 microg/L. However, the concentrations are above the 0.012 microg/L standard (EPA, Water quality standards. Establishment of numeric criteria for priority toxic pollutants, states' compliance, final rule. Fed. Reg., 40 CFR, Part 131, 57/246, 60847-60916, 1992) used to protect aquatic life. Stream sediment samples have abnormally high values of especially Hg, As, Ni, and Cr metals. Geoaccumulation (Igeo) and pollution index (PI) values are significantly high and denote heavy contamination in stream sediments. The stream sediments derived from the mining area with the surface waters are potentially hazardous to the environment adjacent to the abandoned Hg mine and are in need of remediation.

  9. Biological profile of {sup 99m}Tc-HYNIC-betaAla-NT(8-13) in MDAMB-231 breast cancer cell line

    Energy Technology Data Exchange (ETDEWEB)

    Teodoro, Rodrigo; Faintuch, Bluma L.; Wiecek, Danielle P.; Silva, Natanael G.; Vallejo, Natalia M., E-mail: teodoro_rodrigo@yahoo.com.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Diretoria de Radiofarmacia

    2009-07-01

    Introduction: Neurotensin (NT) is a tridecapeptide involved in several growth-steps of human cancers. Recent studies postulated the role of NT and NT-receptor subtype 1 in breast cancer progression. However, the main drawback of natural NT is its rapid degradation in plasma. In an effort to develop a NT peptide-based radiopharmaceutical for the detection of breast cancer, the aim of this study was the radiolabeling of the double stabilized NT(8-13) peptide using HYNIC as chelating agent. Methods: Conjugated HYNIC-betaAla-NT(8-13) was labeled with {sup 99m}Tc using tricine and EDDA as coligands. Radiochemical purity was checked by TLC and confirmed by RP-HPLC. {sup 99m}Tc-HYNIC-betaAla-NT(8-13) (0.1 mL/74 MBq) was administered in Nude mice bearing MDA-MB-231 breast cancer cells and biodistribution studies were carried out at 30 and 90 min postinjection (pi). Blocking evaluation was also conducted by co-injection of 115 nmol of cold NT (8-13) analog. Planar gamma-camera imaging was acquired at the earlier time point studied. Results: Radiochemical purity of the radioconjugate was higher than 99%. Biodistribution studies revealed a very fast accumulation in tumor (1.97+-0.18% ID/g, 30 min pi) with a sharply decrease at the later time point studied (0.44+-0.02% ID/g). The specificity of the radioconjugate was evaluated with blockade studies. A reduction of 45.94%, 27.73% and 36.39% was found for tumor, large and small intestines, respectively, at 30 min pi. Otherwise, a less impressive blockade was observed for tumor and small intestine (28.68% and 24.90%, respectively) at the later time point studied. Conclusion: The results provide encouraging evidence in the development of radiolabeled NT(8-13) analogues for breast cancer diagnosis. (author)

  10. Lapsen varhaiskasvatussuunnitelma Konneveden kunnalle

    OpenAIRE

    Siekkinen, Sanna

    2017-01-01

    Siekkinen, Sanna. Lapsen varhaiskasvatussuunnitelma Konneveden kunnalle. Pieksämäki, kevät 2017, 65 s., 3 liitettä. Diakonia-ammattikorkeakoulu, Sosiaalialan koulutusohjelma, Sosionomi (AMK) + lastentarhanopettajan kelpoisuus. Opinnäytetyön tavoitteena oli suunnitella, työstää ja kehittää hyvä ja toimiva työväline Konneveden kunnan varhaiskasvatuksen työntekijöiden käyttöön. Valtakunnalliset varhaiskasvatussuunnitelman perusteet on juuri uudistettu ja paikallinen varhaiskasvatussuunni...

  11. Transthyretin Ala36Pro mutation in a Chinese pedigree of familial transthyretin amyloidosis with elevated vitreous and serum vascular endothelial growth factor.

    Science.gov (United States)

    Zou, Xuan; Dong, Fangtian; Zhang, Shuying; Tian, Rong; Sui, Ruifang

    2013-05-01

    The familial transthyretin (TTR) amyloidosis (FTA) demonstrates variable penetrance of clinical features associated with mutations in the plasma thyroid hormone-binding protein TTR gene. The purpose of this study was to assess the ocular features, to analyze vitreous and serum vascular endothelial growth factor (VEGF) levels, and to identify the genetic defect in a Chinese family with TTR FTA. The pedigree of interest was a three-generation family with eleven members. The primary ocular signs were vitreous opacities, beginning from the third or fourth decade, accompanied by retinal vasculitis, hemorrhages, and widespread pinpoint deposits in the peripheral retina. Two patients underwent vitrectomy with marked improvement of visual acuity postoperatively. Vitreous and serum samples for VEGF were analyzed with an enzyme-linked immunosorbent assay (ELISA). Forty-eight healthy adult volunteers were enrolled as a control group for the analysis of serum VEGF. Eight subjects who underwent vitrectomy for a macular epiretinal membrane or macular hole were enrolled as control for the analysis of vitreous VEGF. Both serum and vitreous VEGF levels of patients were raised compared to that of controls. Venous blood was collected from family members and the genomic DNA was extracted. All exons and exon-intron boundaries of the TTR gene were sequenced. A previously-described pathogenic transversion in exon 2 (c.G106C, p.Ala36Pro) was identified. Within this family eight individuals were confirmed as affected. In conclusion, a Chinese family with TTR Ala36Pro associated FTA is characterized by early ocular involvement. Widespread pinpoint lesions indicate RPE lesions caused by TTR deposition. FTA is associated with increased VEGF levels, both in serum and vitreous. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Fabrication of Al/A206–Al2O3 nano/micro composite by combining ball milling and stir casting technology

    International Nuclear Information System (INIS)

    Tahamtan, S.; Halvaee, A.; Emamy, M.; Zabihi, M.S.

    2013-01-01

    Highlights: ► Uniform distribution of alumina particles in molten Al alloy by using MMMC. ► Improvement in wettability of alumina particles with molten Al alloy by using MMMC. ► Porosity content in Al/A206-alumina composite decreased by using MMMC. ► Improvement in tensile strength of Al/A206-alumina composite by using MMMC. ► Decrease in interfacial reaction product by incorporating MMMC in semi-solid state. - Abstract: Al206/5vol.%Al 2 O 3p cast composites were fabricated by the injection of reinforcing particles into molten Al alloy in two different forms, i.e. as Al 2 O 3 particles and milled particulates of alumina with Al and Mg powders. The resultant milled powders (Master Metal Matrix Composite (MMMC)) were then added into the molten Al alloy both in semi-solid state and above liquidus temperature. Effects of powder addition technique, reinforcement particle size and casting temperature on distribution and incorporation of reinforcing particles into molten Al alloy were investigated. Morphology evolution of powders during milling, microscopic examinations of composite and matrix alloy were studied by scanning electron microscopy (SEM). X-ray diffraction (XRD) analysis was also used to determine the possible interaction between powders after ball milling process. Results showed that injection of powders in the form of MMMC leads to considerable improvement in incorporation and distribution of Al 2 O 3p in the Al206 matrix alloy leading to the improvement in tensile properties. Improvement in tensile properties is attributed to the better wetting of Al 2 O 3p by melt as well as removing microchannels and roughness on alumina particles as a consequence of ball milling process

  13. Integration of seismic and petrophysics to characterize reservoirs in "ALA" oil field, Niger Delta.

    Science.gov (United States)

    Alao, P A; Olabode, S O; Opeloye, S A

    2013-01-01

    In the exploration and production business, by far the largest component of geophysical spending is driven by the need to characterize (potential) reservoirs. The simple reason is that better reservoir characterization means higher success rates and fewer wells for reservoir exploitation. In this research work, seismic and well log data were integrated in characterizing the reservoirs on "ALA" field in Niger Delta. Three-dimensional seismic data was used to identify the faults and map the horizons. Petrophysical parameters and time-depth structure maps were obtained. Seismic attributes was also employed in characterizing the reservoirs. Seven hydrocarbon-bearing reservoirs with thickness ranging from 9.9 to 71.6 m were delineated. Structural maps of horizons in six wells containing hydrocarbon-bearing zones with tops and bottoms at range of -2,453 to -3,950 m were generated; this portrayed the trapping mechanism to be mainly fault-assisted anticlinal closures. The identified prospective zones have good porosity, permeability, and hydrocarbon saturation. The environments of deposition were identified from log shapes which indicate a transitional-to-deltaic depositional environment. In this research work, new prospects have been recommended for drilling and further research work. Geochemical and biostratigraphic studies should be done to better characterize the reservoirs and reliably interpret the depositional environments.

  14. Co-Circulation of the Rare CPV-2c with Unique Gln370Arg Substitution, New CPV-2b with Unique Thr440Ala Substitution, and New CPV-2a with High Prevalence and Variation in Heilongjiang Province, Northeast China.

    Directory of Open Access Journals (Sweden)

    Yufei Geng

    Full Text Available To trace evolution of canine parvovirus-2 (CPV-2, a total of 201 stool samples were collected from dogs with diarrhea in Heilongjiang province of northeast China from May 2014 to April 2015. The presence of CPV-2 in the samples was determined by PCR amplification of the VP2 gene (568 bp of CPV-2. The results revealed that 95 samples (47.26% were positive for CPV-2, and they showed 98.8%-100% nucleotide identity and 97.6%-100% amino acid identity. Of 95 CPV-2-positive samples, types new2a (Ser297Ala, new2b (Ser297Ala, and 2c accounted for 64.21%, 21.05%, and 14.74%, respectively. The positive rate of CPV-2 and the distribution of the new2a, new2b and 2c types exhibited differences among regions, seasons, and ages. Immunized dogs accounted for 48.42% of 95 CPV-2-positive samples. Coinfections with canine coronavirus, canine kobuvirus, and canine bocavirus were identified. Phylogenetic analysis revealed that the identified new2a, new2b, and CPV-2c strains in our study exhibited a close relationship with most of the CPV-2 strains from China; type new2a strains exhibited high variability, forming three subgroups; type new2b and CPV-2c strains formed one group with reference strains from China. Of 95 CPV-2 strains, Tyr324Ile and Thr440Ala substitutions accounted for 100% and 64.21%, respectively; all type new2b strains exhibited the Thr440Ala substitution, while the unique Gln370Arg substitution was found in all type 2c strains. Recombination analysis using entire VP2 gene indicated possible recombination events between the identified CPV-2 strains and reference strains from China. Our data revealed the co-circulation of new CPV-2a, new CPV-2b, and rare CPV-2c, as well as potential recombination events among Chinese CPV-2 strains.

  15. Seismic examination for assessment of safety of location of atomic energy objects (by the example of the WWR-K reactor, Ala-Tau village)

    International Nuclear Information System (INIS)

    Belyashova, N.N.

    2001-01-01

    In the Republic of Kazakhstan there are 3 research reactors (the fourth one is temporarily stopped). One of the reactors in 1998 (WWR-K, situated in the Ala Tau village, nearby Almaty city) was conserved because of a number of reasons. Including the reason of the earth crust geological structure insufficient study for the ensuring the seismic safety of the reactor site location. In 1994-1996 a number of geological-geophysical studies was carried out by Kazakhstan specialists confirming the the geological-geophysical conditions in the reactor site location in view of its safety. These condition are meeting to IAEA requirements and up-to-date standards acting in Kazakhstan

  16. Isäksi kasvaminen : Miesten kokemuksia isyydestä esikoisen odotusaikana

    OpenAIRE

    Pitkäranta, Sanna; Haapalainen, Salla; Kivi, Marjo

    2015-01-01

    Oulun ammattikorkeakoulu Hoitotyön koulutusohjelma Tekijät: Salla Haapalainen, Marjo Kivi ja Sanna Pitkäranta Opinnäytetyön nimi: Isäksi kasvaminen. Miesten kokemuksia isyydestä esikoisen odotusaikana Työn ohjaajat: Yliopettaja Hilkka Honkanen ja lehtori Pirjo Juujärvi Työn valmistumislukukausi ja -vuosi: Kevät 2015 Sivumäärä: 32 Opinnäytetyömme tarkoituksena oli kuvata millaisia kokemuksia ja ajatuksia miehillä on isyydestä esikoisen odotusaikana sekä olivatko ne muutt...

  17. Pressure dependence of backbone chemical shifts in the model peptides Ac-Gly-Gly-Xxx-Ala-NH2.

    Science.gov (United States)

    Erlach, Markus Beck; Koehler, Joerg; Crusca, Edson; Kremer, Werner; Munte, Claudia E; Kalbitzer, Hans Robert

    2016-06-01

    For a better understanding of nuclear magnetic resonance (NMR) detected pressure responses of folded as well as unstructured proteins the availability of data from well-defined model systems are indispensable. In this work we report the pressure dependence of chemical shifts of the backbone atoms (1)H(α), (13)C(α) and (13)C' in the protected tetrapeptides Ac-Gly-Gly-Xxx-Ala-NH2 (Xxx one of the 20 canonical amino acids). Contrary to expectation the chemical shifts of these nuclei have a nonlinear dependence on pressure in the range from 0.1 to 200 MPa. The polynomial pressure coefficients B 1 and B 2 are dependent on the type of amino acid studied. The coefficients of a given nucleus show significant linear correlations suggesting that the NMR observable pressure effects in the different amino acids have at least partly the same physical cause. In line with this observation the magnitude of the second order coefficients of nuclei being direct neighbors in the chemical structure are also weakly correlated.

  18. Preoperative predictive factors for hearing preservation in vestibular schwannoma surgery.

    Science.gov (United States)

    Rohit; Piccirillo, Enrico; Jain, Yogesh; Augurio, Angela; Sanna, Mario

    2006-01-01

    We performed a retrospective chart review to evaluate the various predictive factors for postoperative hearing preservation in the surgical management of vestibular schwannoma. Of 792 patients operated on for vestibular schwannoma between April 1987 and July 2002, 107 were candidates for hearing preservation surgery. These patients were divided into group 1 (hearing preserved) and group 2 (hearing not preserved), and both of these groups were evaluated for age, sex, pure tone average, sound discrimination score, tumor size, and auditory brain stem response parameters. A corrected chi2 test and a corrected t-test were used for statistical analysis. Multiple regression analysis was further done to evaluate independent predictive factors, either alone or in combination. The results were evaluated by use of the modified Sanna classification and the guidelines of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS). Preoperative pure tone average and tumor size were the 2 predictive factors in our study. A Pearson correlation test showed that there was no multicollinearity between the factors. On multiple regression analysis by backward elimination of nonsignificant factors, we found that tumor size is an independent predictive factor for postoperative hearing. According to the modified Sanna classification, postoperative hearing was preserved in 11.2% of patients (equivalent to class A of AAO-HNS guidelines). In our series, preoperative pure tone average and tumor size were found to be predictors of postoperative hearing levels.

  19. Two-peaked 5-ALA-induced PpIX fluorescence emission spectrum distinguishes glioblastomas from low grade gliomas and infiltrative component of glioblastomas.

    Science.gov (United States)

    Montcel, Bruno; Mahieu-Williame, Laurent; Armoiry, Xavier; Meyronet, David; Guyotat, Jacques

    2013-04-01

    5-ALA-induced protoporphyrin IX (PpIX) fluorescence enables to guiding in intra-operative surgical glioma resection. However at present, it has yet to be shown that this method is able to identify infiltrative component of glioma. In extracted tumor tissues we measured a two-peaked emission in low grade gliomas and in the infiltrative component of glioblastomas due to multiple photochemical states of PpIX. The second emission peak appearing at 620 nm (shifted by 14 nm from the main peak at 634 nm) limits the sensibility of current methods to measured PpIX concentration. We propose new measured parameters, by taking into consideration the two-peaked emission, to overcome these limitations in sensitivity. These parameters clearly distinguish the solid component of glioblastomas from low grade gliomas and infiltrative component of glioblastomas.

  20. Studies of the Ala/Val98 polymorphism of the hepatocyte nuclear factor-1alpha gene and the relationship to beta-cell function during an OGTT in glucose-tolerant women with and without previous gestational diabetes mellitus

    DEFF Research Database (Denmark)

    Lauenborg, J; Damm, P; Ek, J

    2004-01-01

    In pregnancies complicated by gestational diabetes mellitus (GDM) an increased demand for insulin is not met due to beta-cell dysfunction. An Ala/Val polymorphism at codon 98 of the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene has been associated with decreased serum insulin and C-peptide r...

  1. Structural requirements of acylated Gly-l-Ala-d-Glu analogs for activation of the innate immune receptor NOD2.

    Science.gov (United States)

    Gobec, Martina; Mlinarič-Raščan, Irena; Dolenc, Marija Sollner; Jakopin, Žiga

    2016-06-30

    The fragment of bacterial peptidoglycan muramyl dipeptide (MDP) has long been known for its adjuvant activity, however the underlying mechanism of this action has only recently been elucidated. It is ascribed to its agonist action on the nucleotide-binding oligomerization domain-containing protein 2 (NOD2). In spite of the pressing need for novel adjuvants for human use, this discovery is hampered, by not knowing the structural requirements underlying the immunostimulatory activity. We have investigated how minor modifications of hit compound acyl Gly-L-Ala-D-Glu derivative I modulate the molecular recognition by NOD2. A series of novel desmuramyldipeptides has been designed and synthesized leading to the identification of compound 16, in which the sugar moiety is replaced by a 6-phenylindole moiety, that exhibits the strongest NOD2 activation to date sans the carbohydrate moiety. The results have enabled a deeper understanding of the structural requirements of desmuramylpeptides for NOD2 activation. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. Functional importance of the Ala(116)-Pro(136) region in the calcium-sensing receptor. Constitutive activity and inverse agonism in a family C G-protein-coupled receptor

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Spalding, T A; Burstein, E S

    2000-01-01

    The calcium-sensing receptor (CaR) belongs to family C of the G-protein-coupled receptor superfamily. To date 14 activating mutations in CaR showing increased sensitivity to Ca(2+) have been identified in humans with autosomal dominant hypocalcemia. Four of these activating mutations are found......, suppressed the elevated basal response of the constitutively activated Ca/1a mutants demonstrating inverse agonist activity of CPCCOEt. Taken together, our results demonstrate that the Ala(116)-Pro(136) region is of key importance for the maintenance of the inactive conformation of CaR....

  3. Review of recent publications

    Directory of Open Access Journals (Sweden)

    2012-01-01

    Full Text Available Christine Daigle. Jean-Paul Sartre by Candice Nicolas Anna Marie Sandoval. Toward a Latina Feminism of the Americas: Repression and Resistance in Chicana and Mexicana Literature by Yajaira M. Padilla Ruth Cruickshank. Fin de millénaire French Fiction: The Aesthetics of Crisis by Martine Motard-Noar Sanna Turoma. Brodsky Abroad: Empire, Tourism, Nostalgia by Galya Diment Svetlana Alexievich. Voices from Chernobyl: the Oral History of a Nuclear Disaster by Teresa Polowy Leslie Raymond Williams. A Companion to Gabriel García Márquez by David William Foster

  4. Influencia de la autoeficacia académica y la procrastinación académica sobre el cansancio emocional de estudiantes de la Universidad Alas Peruanas, Lima, 2015

    OpenAIRE

    Gutiérrez Torres, Andrés Martín

    2015-01-01

    Objetivo: determinar cuánta es la influencia de la autoeficacia académica y la procrastinación académica sobre el cansancio emocional de estudiantes de la Universidad Alas Peruanas, Lima, 2015. Metodología: se usó un diseño observacional, transversal, retrospectivo y correlacional-causal. La muestra no probabilística fue de 332 estudiantes de Psicología de una universidad privada de Lima, quienes fueron evaluados con tres instrumentos: Escala de Autoeficacia para Situaciones Académicas, E...

  5. La inteligencia emocional y la gestión educativa según los estudiantes de la especialidad de Farmacia y Bioquímica, Universidad Alas Peruanas, 2014

    OpenAIRE

    Fernández Vila, Albert Luis

    2015-01-01

    La tesis que se presenta se inició con la formulación de la siguiente pregunta: ¿Qué relación existe entre la inteligencia emocional y la gestión educativa según los estudiantes de Farmacia y Bioquímica de la Universidad Alas Peruanas, 2014?, Esta investigación tuvo como objetivo determinar la relación existente entre la inteligencia emocional y la gestión educativa. El método de investigación utilizado fue el cuantitativo de tipo relacional y de diseño descriptivo correlacional. La población...

  6. Pressure dependence of backbone chemical shifts in the model peptides Ac-Gly-Gly-Xxx-Ala-NH{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Erlach, Markus Beck; Koehler, Joerg [University of Regensburg, Institute of Biophysics and Physical Biochemistry and Centre of Magnetic Resonance in Chemistry and Biomedicine (Germany); Crusca, Edson [University of São Paulo, Physics Institute of São Carlos (Brazil); Kremer, Werner [University of Regensburg, Institute of Biophysics and Physical Biochemistry and Centre of Magnetic Resonance in Chemistry and Biomedicine (Germany); Munte, Claudia E. [University of São Paulo, Physics Institute of São Carlos (Brazil); Kalbitzer, Hans Robert, E-mail: hans-robert.kalbitzer@biologie.uni-regensburg.de [University of Regensburg, Institute of Biophysics and Physical Biochemistry and Centre of Magnetic Resonance in Chemistry and Biomedicine (Germany)

    2016-06-15

    For a better understanding of nuclear magnetic resonance (NMR) detected pressure responses of folded as well as unstructured proteins the availability of data from well-defined model systems are indispensable. In this work we report the pressure dependence of chemical shifts of the backbone atoms {sup 1}H{sup α}, {sup 13}C{sup α} and {sup 13}C′ in the protected tetrapeptides Ac-Gly-Gly-Xxx-Ala-NH{sub 2} (Xxx one of the 20 canonical amino acids). Contrary to expectation the chemical shifts of these nuclei have a nonlinear dependence on pressure in the range from 0.1 to 200 MPa. The polynomial pressure coefficients B{sub 1} and B{sub 2} are dependent on the type of amino acid studied. The coefficients of a given nucleus show significant linear correlations suggesting that the NMR observable pressure effects in the different amino acids have at least partly the same physical cause. In line with this observation the magnitude of the second order coefficients of nuclei being direct neighbors in the chemical structure are also weakly correlated.Graphical Abstract.

  7. Cu(II) Binding to the Peptide Ala-His-His, a Chimera of the Canonical Cu(II)-Binding Motifs Xxx-His and Xxx-Zzz-His.

    Science.gov (United States)

    Gonzalez, Paulina; Vileno, Bertrand; Bossak, Karolina; El Khoury, Youssef; Hellwig, Petra; Bal, Wojciech; Hureau, Christelle; Faller, Peter

    2017-12-18

    Peptides and proteins with the N-terminal motifs NH 2 -Xxx-His and NH 2 -Xxx-Zzz-His form well-established Cu(II) complexes. The canonical peptides are Gly-His-Lys and Asp-Ala-His-Lys (from the wound healing factor and human serum albumin, respectively). Cu(II) is bound to NH 2 -Xxx-His via three nitrogens from the peptide and an external ligand in the equatorial plane (called 3N form here). In contrast, Cu(II) is bound to NH 2 -Xxx-Zzz-His via four nitrogens from the peptide in the equatorial plane (called 4N form here). These two motifs are not mutually exclusive, as the peptides with the sequence NH 2 -Xxx-His-His contain both of them. However, this chimera has never been fully explored. In this work, we use a multispectroscopic approach to analyze the Cu(II) binding to the chimeric peptide Ala-His-His (AHH). AHH is capable of forming the 3N- and 4N-type complexes in a pH dependent manner. The 3N form predominates at pH ∼ 4-6.5 and the 4N form at ∼ pH 6.5-10. NMR experiments showed that at pH 8.5, where Cu(II) is almost exclusively bound in the 4N form, the Cu(II)-exchange between AHH or the amidated AHH-NH 2 is fast, in comparison to the nonchimeric 4N form (AAH). Together, the results show that the chimeric AHH can access both Cu(II) coordination types, that minor changes in the second (or further) coordination sphere can impact considerably the equilibrium between the forms, and that Cu kinetic exchange is fast even when Cu-AHH is mainly in the 4N form.

  8. HABITAT DAN PERILAKU KANGKARENG PERUT-PUTIH (Anthracoceros albirostris convexus Temm. 1832 DI RESORT ROWOBENDO TN ALAS PURWO

    Directory of Open Access Journals (Sweden)

    Salvionita BR Tarigan

    2017-04-01

    Full Text Available Oriental pied hornbill (Anthracoceros albirostris is one of hornbill spesies (Bucerotidae that protected in Indonesia based on Goverment Regulation No. 7/1999. The habitat of oriental pied hornbillin Resort Rowobendo Alas Purwo National Park (APNP are natural forest and mixed forest plantation. The characteristic of the bird feeding site is a fruiting tree with a thick meat with the shaped is an oval, thin rind, soft, and contain more water and has sweet taste. The characteristic for the birdresting site is a tree with dense leaf, horizontal withstrong enough branch to withstand oriental pied hornbill. The tree height is about 10-26 m and the diameters  about 29-71 cm. The nesting site characteristic the bird is a tree with diameters about ≥ 50 cm and the height is about ≥10 m. The tree has a hole, main branch that is large and fairly flat with the height of the nest from the ground level of 12-30 m. Behavior of oriental pied hornbill observed are eating, resting, calling, flying and nesting. Keywords: APNP, behavior, habitat, oriental pied hornbill

  9. Variantes polimórficas Ala513Pro y Gly972Arg del gen IRS-1 no se asocian a la diabetes mellitus tipo 2 en un grupo de la población cubana The Ala513Pro and Gly972ARg polymorphous variants of IRS-1 gen are not associated with type diabetes mellitus in a group of the Cuban population

    Directory of Open Access Journals (Sweden)

    Luis Miguel Pérez

    2011-08-01

    Full Text Available Introducción: la diabetes mellitus tipo 2 es una enfermedad heterogénea y multifactorial, que está determinada por factores genéticos y no genéticos. El sustrato 1 del receptor de la insulina (IRS-1 cumple una función fundamental en la transmisión de la señal insulínica, por tanto sus variantes génicas constituyen blancos importantes en el estudio de la susceptibilidad genética a esta enfermedad en las diferentes poblaciones. Objetivo: explorar el papel de las variantes polimórficas Gly972Arg y Ala513Pro del gen IRS-1 en la susceptibilidad genética de la diabetes mellitus tipo 2 en un grupo de la población cubana. Métodos: se determinó la frecuencia de los polimorfismos Gly972Arg y Ala513Pro del IRS-1 en 499 ciudadanos cubanos, con un índice de masa corporal entre 22-30, con edades comprendidas entre los 40 y 70 años: de ellos 272 (54,5 % diabéticos y 227 (45,5 % no diabéticos. Resultados: la frecuencia del alelo Pro513 fue baja (1,2 % y similar para ambos grupos (1,1 % vs. 1,3 % para el grupo de diabéticos y el grupo control, respectivamente. La frecuencia del polimorfismo Gly972Arg fue de 16,2%, superior a la reportada para la mayoría de las poblaciones estudiadas. No se encontraron diferencias significativas en la frecuencia del alelo Arg972 entre el grupo de diabéticos y el grupo control (15,4 % vs. 17,3 %, ni cambios en los niveles de glucemia e insulinemia asociados a la presencia del alelo polimórfico Arg972. Conclusiones: en este grupo de sujetos de la población cubana, las variantes polimórficas Ala513Pro y Gly972Arg del gen IRS-1 no participan en la etiología de la diabetes mellitus tipo 2.Introduction: the type 2 diabetes mellitus is a heterogeneous and multifactor disease determined by genetic and no-genetic factors. The substrate 1 of insulin receptor (IRS-1 has a fundamental function in transmission of insulin signal, thus its genic variants are significant targets in study of genetic susceptibility to

  10. Design Of Polymer Matrix Composite Materials Used For Helicopter Rotor Blades By Finite Element Method

    OpenAIRE

    Karaaslan, Nevzat Hakan

    2007-01-01

    Gelişmiş helikopter rotor paları genellikle kompozit malzemelerden üretilmektedirler ve yapılarında çeşitli hasarlara neden olabilecek yüksek derecede dinamik ve kararsız aerodinamik çevresel yüklerde çalışmaktadırlar. Bu yükleme şartlarına tekrarlı olarak maruz kalınması kompozit rotor pala yüzey kaplamalarında delaminasyon, çatlak vb. hasarlara neden olabilir. Bu tezin amacı, farklı kompozit rotor pala malzemelerinin, sonlu elemanlar yöntemi ile modellenmesi ve döner kanat yüzey kaplamaları...

  11. Las competencias genéricas del estudiante y la influencia en su nivel de emprendimiento en la Facultad de Ciencias Empresariales de la Universidad Alas Peruanas – Filial Tacna

    OpenAIRE

    Eyzaguirre Mazuelos, Néstor Guido

    2014-01-01

    La presente tesis tuvo como objetivo principal determinar la influencia de las competencias genéricas del estudiante sobre su nivel de emprendimiento en la Facultad de Ciencias Empresariales de la Universidad Alas Peruanas – Filial Tacna, en el año 2013; para lo cual, se trabajó con una muestra de 150 estudiantes de las 03 Escuelas Profesionales; se encontró que existe una relación directa y significativa entre los indicadores de las competencias genéricas del estudiante y los indicadores de ...

  12. Uso de las tics en la enseñanza del inglés y rendimiento académico en estudiantes universitarios de la Universidad Alas Peruanas 2015

    OpenAIRE

    Rodas Paredes, Ysabel Misela

    2016-01-01

    El objetivo de la presente investigación es determinar cómo influye el uso de las Tics en el nivel del rendimiento académico del idioma inglés de los estudiantes de la Escuela Profesional de Ingeniería Mecánica de la Universidad Alas Peruanas filial Arequipa. La población estuvo conformada por 455 estudiantes, tanto varones como mujeres, del primer al noveno ciclo de la referida carrera profesional. Para la obtención de los datos usamos una encuesta referida al uso de las Tics por parte de lo...

  13. Crystallization and preliminary X-ray analysis of a d-Ala:d-Ser ligase associated with VanG-type vancomycin resistance

    International Nuclear Information System (INIS)

    Weber, Patrick; Meziane-Cherif, Djalal; Haouz, Ahmed; Saul, Frederick A.; Courvalin, Patrice

    2009-01-01

    The VanG d-alanine:d-serine ligase was crystallized in complex with ADP and diffraction data were collected at 2.35 Å resolution. Acquired VanG-type resistance to vancomycin in Enterococcus faecalis BM4518 arises from inducible synthesis of peptidoglycan precursors ending in d-alanyl-d-serine, to which vancomycin exhibits low binding affinity. VanG, a d-alanine:d-serine ligase, catalyzes the ATP-dependent synthesis of the d-Ala-d-Ser dipeptide, which is incorporated into the peptidoglycan synthesis of VanG-type vancomycin-resistant strains. Here, the purification, crystallization and preliminary crystallographic analysis of VanG in complex with ADP are reported. The crystal belonged to space group P3 1 21, with unit-cell parameters a = b = 116.1, c = 177.2 Å, and contained two molecules in the asymmetric unit. A complete data set has been collected to 2.35 Å resolution from a single crystal under cryogenic conditions using synchrotron radiation

  14. Microstructural features associated with the effect of temperature on the dimensional stability of an automotive Al-A319 alloy

    Directory of Open Access Journals (Sweden)

    Hugo F. Lopez

    2016-05-01

    Full Text Available In this work an automotive Al-A319 was given a solid solution heat treatment (T4 at 753 K (480 °C for 4.5 hours and an ageing treatment (T7 at 513 K (240 °C for various times up to 3.0 h. The alloy in the T4 condition was dilatometrically tested at various temperatures in order to measure its relative dimensional changes. It was found that the dimensional changes are due to both, alloy thermal expansion and nucleation and growth of second phases. In addition, in the T7 condition the alloy strength and ductility were determined as a function of ageing times. Ageing promoted alloy strength but at the expenses of a rather poor alloy ductility (down to 1%. Apparently, Cu rich intermetallic phases and regions provided a brittle path for fracturing. In particular, microstructural characterization using high resolution transmission electron microscopy indicated that not all the Cu in the matrix was dissolved during the T4 treatment. Hence, after ageing (T7 these Cu-rich regions seemed to coarsen into spherical particles.

  15. Obtención de modelo matemático para el desarrollo del perfil del ala de una aeronave. // Obtaining a mathematical model for the development of the profile of the airship wing.

    Directory of Open Access Journals (Sweden)

    R. Cabrera Pedroso

    2008-05-01

    Full Text Available El presente trabajo está dirigido a brindar un modelo matemático que permita el cálculo y determinación de una funciónanalítica para la obtención del perfil de un ala de geometría simétrica y variable de una aeronave con el empleo de métodoscomputacionales. En el artículo se analiza los métodos para la elaboración de sistemas de cálculo basados en modelosmatemáticos obtenidos en MATLAB 7.0 e implementados con el software LabVIEW 6.0 a través de programas de diseñosasistidos por computadoras en AUTOCAD (AUTOLISP. Los diferentes tópicos abordados dan a los interesados una ideaglobal del desarrollo de esta tecnología computacional y su aplicación a ramas de la mecánica, así como la metodologíaseguida para obtener el perfil aerodinámico de un ala. También se exponen aspectos generales del empleo de la funciónAUTOLISP y el código fuente del programa diseñado.Palabras claves: perfil de alas, modelos matemáticos, AutoCAD, AutoLISP, medición experimental.__________________________________________________________________________Abstract.This article was carried out to obtain a mathematical model that allows the calculation and determination of an analyticfunction of symmetrical geometry profile and variable. In the article it is analyzed the methods for the elaboration ofsystem of calculations based on mathematical models obtained with the software language LabVIEW 6.0 and it is used todeveloping the program attended by the computers AUTOCAD (AUTOLISP. The approached topics give to the interestedparties a global idea of the development it gives this technology and their application to branches of the mechanicalspecialties, as well as the followed methodology to obtain the aerofoil profile of a wing. General aspects are also exposedof the employment of the function AUTOLISP and the source code on the sketch program.Key words: Wing profiles, mathematical models, AutoCAD, AutoLISP, experimental measurement.

  16. Retalho em ilha de tubarão: uma técnica cirúrgica reconstrutiva de defeitos localizados na área nasal alar/perialar. Um procedimento simples Shark island pedicle flap for repairing of basal cell carcinoma localized in nasal ala-perialar region: a simple procedure

    Directory of Open Access Journals (Sweden)

    Marisa C André

    2011-08-01

    Full Text Available O Carcinoma Basocelular é a neoplasia cutânea mais frequente. Os autores descrevem uma técnica realizada unicamente num tempo operatório para correção de defeitos na asa do nariz após excisão tumoral. Esta técnica simples permite a correção cirúrgica de defeitos nesta localização possibilitando a reconstrução da anatomia local e a preservação das unidades cosméticas, sem a necessidade de enxertoBasal Cell Carcinoma is the most common skin cancer. We describe a single-staged technique for correction of nasal ala defect after the excision of a basal cell carcinoma. This technique allows correction of surgical defects of the ala rebuilding the original anatomy, maintaining cosmetic units, without need for a graft

  17. Effects of hydrostatic pressure on the electron g|| factor and g-factor anisotropy in GaAs-(Ga, Al)As quantum wells under magnetic fields

    International Nuclear Information System (INIS)

    Porras-Montenegro, N; Duque, C A; Oliveira, L E; Reyes-Gomez, E

    2008-01-01

    The hydrostatic-pressure effects on the electron-effective Lande g || factor and g-factor anisotropy in semiconductor GaAs-Ga 1-x Al x As quantum wells under magnetic fields are studied. The g || factor is computed by considering the non-parabolicity and anisotropy of the conduction band through the Ogg-McCombe effective Hamiltonian, and numerical results are displayed as functions of the applied hydrostatic pressure, magnetic fields, and quantum-well widths. Good agreement between theoretical results and experimental measurements in GaAs-(Ga, Al)As quantum wells for the electron g factor and g-factor anisotropy at low values of the applied magnetic field and in the absence of hydrostatic pressure is obtained. Present results open up new possibilities for manipulating the electron-effective g factor in semiconductor heterostructures.

  18. PENDUGAAN MODEL PERTUMBUHAN DAN BENTUK SEBARAN SPASIAL POPULASI BANTENG (BOS SONDAICUS D'ALTON DI TAMAN NASIONAL ALAS PURWO JAWA TIMUR

    Directory of Open Access Journals (Sweden)

    Yanto Santosa

    2009-12-01

    Full Text Available Population of bulls in the world is decreasing to 80%. On Java and Bali, the habitat of the species has declined by about 20% and 30% respectively (IUCN 2003. In Java, especially in Alas Purwo National Park, the decreasing population of bulls is caused by hunting and degradation of habitat. The estimation of growth bulls population in APNP is increase. The size of population in the beginning is 588 individuals the rate of growth is 0.093 and carrying capacity of habitat is 4772 individuals. The population will reach the carrying capacity by the year of 2126. The pattern of spatial distribution of bulls in APNP based on analysis of chi-square test is grouped (2hit>220.025. The pattern of distribution in low-land forest and platation forest is randomized (20.9752hit20.025, meanwhile it is grouped in coastal forest ecosystem. The pattern of distribution in each type of ecoystem is influenced by the factor of resources (feedings, water, and salty water and predation factor

  19. Effect of fatty acid-binding protein 2 Ala54Thr genotype on weight loss and cardiovascular risk factors after a high-polyunsaturated fat diet in obese patients.

    Science.gov (United States)

    de Luis, Daniel; Aller, Rocio; Izaola, Olatz; Sagrado, Manuel Gonzalez; de la Fuente, Beatriz; Conde, Rosa; Primo, David

    2012-12-01

    It has been found that the expression of fatty acid-binding protein 2 messenger RNA is under dietary control. The aim of our study was to investigate the influence of Thr54 polymorphism in the FABP2 gene on weight loss and secondarily in cardiovascular risk factors and serum adipokine after an enriched polyunsaturated fat hypocaloric diet in obese patients. A sample of 111 obese patients was analyzed. The enriched polyunsaturated fat hypocaloric diet during 3 months' intervention consisted of 1459 kcal, 45.7% carbohydrates, 34.4% lipids, and 19.9% proteins. The distribution of fats was as follows: 21.8% saturated fats, 55.5% monounsaturated fats, and 22.7% polyunsaturated fats. Level of significance was P fat mass (-3.1 ± 3.5 kg), and waist circumference (-3.3 ± 2.1 cm) decreased. In carriers of the Thr54 allele, body mass index (-1.9 ± 1.6 kg/m(2)), weight (- 4.7 ± 1.4 kg), and waist circumference (-3.9 ± 3.7 cm) decreased. These changes were significantly higher in the carriers of the Thr54 allele than noncarriers. Only in the carriers of Thr54 allele, total cholesterol levels (-11.4 ± 20.6 mg/dl), low-density lipoprotein cholesterol levels (-5.4 ± 10.6 mg/dL), insulin (-2.6 ± 3.4 MUI/L), and the level of homeostasis model assessment for insulin sensitivity (-0.9 ± 1.7 U) decreased. Carriers of Thr54 allele have a better metabolic response than obese carriers with Ala54Ala genotype, with a decrease of total cholesterol, low-density lipoprotein cholesterol, insulin levels, leptin levels, and homeostasis model assessment for insulin sensitivity.

  20. In vivo wide-field multispectral dosimeter for use in ALA-PpIX based photodynamic therapy of skin

    Science.gov (United States)

    LaRochelle, Ethan P. M.; Davis, Scott C.; de Souza, Ana Luiza Ribeiro; Pogue, Brian W.

    2017-02-01

    Photodynamic therapy (PDT) for Actinic Kertoses (AK) using aminoluvelinic acid (ALA) is an FDA-approved treatment, which is generally effective, yet response rates vary. The origin of the variability is not well characterized, but may be related to inter-patient variability in the production of protoporphyrin IX (PpIX). While fiber-based point probe systems provide a method for measuring PpIX production, these measurements have demonstrated large spatial and inter-operator variability. Thus, in an effort to improve patient-specific dosimetry and treatment it is important to develop a robust system that accounts for spatial variability and reduces the chance of operator errors. To address this need, a wide-field multispectral imaging system was developed that is capable of quantifying maps of PpIX in both liquid phantoms and in vivo experiments, focusing on high sensitivity light signals. The system uses both red and blue excitation to elicit a fluorescent response at varying skin depths. A ten-position filter wheel with bandpass filters ranging from 635nm to 710nm are used to capture images along the emission band. A linear least-square spectral fitting algorithm provides the ability to decouple background autofluorescence from PpIX fluorescence, which has improved the system sensitivity by an order of magnitude, detecting nanomolar PpIX concentrations in liquid phantoms in the presence of 2% whole blood and 2% intralipid.

  1. Association of the SOD2 polymorphism (Val6Ala and SOD activity with vaso-occlusive crisis and acute splenic sequestration in children with sickle cell anemia

    Directory of Open Access Journals (Sweden)

    Isabela Cristina Cordeiro Farias

    2018-02-01

    Full Text Available The SOD2 polymorphism Val16Ala TàC influences the antioxidative response. This study investigated the association of the SOD2 polymorphism and superoxide dismutase (SOD activity with vaso-occlusive crisis (VOC and acute splenic sequestration (ASS in children with sickle cell anemia (SCA. One hundred ninety-five children aged 1-9 years old were analyzed. The TC and CC genotypes were associated with lower SOD activity compared with the TT genotype (p=0.0321; p=0.0253, respectively. Furthermore, TC/CC were more frequent in patients with VOC or ASS (p=0.0285; p=0.0090, respectively. These results suggest that the SOD2 polymorphism associated with low SOD activity could be involved in SCA physiopathology.

  2. Photoaffinity labeling of opiate (enkephalin) receptor of rat brain plasma membranes with 125I(D-Ala2, p-N3-Phe4-Met5)-enkephalin

    International Nuclear Information System (INIS)

    Yeung, C.W.T.

    1986-01-01

    A photoreactive (D-Ala 2 , p-N 3 -Phe 4 -Met 5 )enkephalin derivative was prepared, iodinated with carrier free 125 I and then purified by high performance liquid chromatography. The purified radioactive photoprobe was monoiodinated at the amino terminal tyrosine residue. This radioactive photoprobe was used to photoaffinity label plasma membranes prepared from rat brain, spinal cord and cerebellum. The photolabeled plasma membranes were analyzed by sodium dodecyl sulfate gel electrophoresis. A 46,000-daltons band was specifically photolabeled in the plasma membranes of brain and spinal cord but not in the plasma membranes from cerebellum. The photolabeling of this band was inhibited by peptides related to enkephalin by not but substance P or gastrin tetrapeptide. These data demonstrate that the labeled 46,000-daltons band is a protein of the opiate (enkephalin)receptor

  3. A new fit-for-purpose model testing framework: Decision Crash Tests

    Science.gov (United States)

    Tolson, Bryan; Craig, James

    2016-04-01

    Decision-makers in water resources are often burdened with selecting appropriate multi-million dollar strategies to mitigate the impacts of climate or land use change. Unfortunately, the suitability of existing hydrologic simulation models to accurately inform decision-making is in doubt because the testing procedures used to evaluate model utility (i.e., model validation) are insufficient. For example, many authors have identified that a good standard framework for model testing called the Klemes Crash Tests (KCTs), which are the classic model validation procedures from Klemeš (1986) that Andréassian et al. (2009) rename as KCTs, have yet to become common practice in hydrology. Furthermore, Andréassian et al. (2009) claim that the progression of hydrological science requires widespread use of KCT and the development of new crash tests. Existing simulation (not forecasting) model testing procedures such as KCTs look backwards (checking for consistency between simulations and past observations) rather than forwards (explicitly assessing if the model is likely to support future decisions). We propose a fundamentally different, forward-looking, decision-oriented hydrologic model testing framework based upon the concept of fit-for-purpose model testing that we call Decision Crash Tests or DCTs. Key DCT elements are i) the model purpose (i.e., decision the model is meant to support) must be identified so that model outputs can be mapped to management decisions ii) the framework evaluates not just the selected hydrologic model but the entire suite of model-building decisions associated with model discretization, calibration etc. The framework is constructed to directly and quantitatively evaluate model suitability. The DCT framework is applied to a model building case study on the Grand River in Ontario, Canada. A hypothetical binary decision scenario is analysed (upgrade or not upgrade the existing flood control structure) under two different sets of model building

  4. Forms of n-3 (ALA, C18:3n-3 or DHA, C22:6n-3) Fatty Acids Affect Carcass Yield, Blood Lipids, Muscle n-3 Fatty Acids and Liver Gene Expression in Lambs.

    Science.gov (United States)

    Ponnampalam, Eric N; Lewandowski, Paul A; Fahri, Fahri T; Burnett, Viv F; Dunshea, Frank R; Plozza, Tim; Jacobs, Joe L

    2015-11-01

    The effects of supplementing diets with n-3 alpha-linolenic acid (ALA) and docosahexaenoic acid (DHA) on plasma metabolites, carcass yield, muscle n-3 fatty acids and liver messenger RNA (mRNA) in lambs were investigated. Lambs (n = 120) were stratified to 12 groups based on body weight (35 ± 3.1 kg), and within groups randomly allocated to four dietary treatments: basal diet (BAS), BAS with 10.7 % flaxseed supplement (Flax), BAS with 1.8 % algae supplement (DHA), BAS with Flax and DHA (FlaxDHA). Lambs were fed for 56 days. Blood samples were collected on day 0 and day 56, and plasma analysed for insulin and lipids. Lambs were slaughtered, and carcass traits measured. At 30 min and 24 h, liver and muscle samples, respectively, were collected for determination of mRNA (FADS1, FADS2, CPT1A, ACOX1) and fatty acid composition. Lambs fed Flax had higher plasma triacylglycerol, body weight, body fat and carcass yield compared with the BAS group (P DHA supplementation increased carcass yield and muscle DHA while lowering plasma insulin compared with the BAS diet (P DHA treatment increased (P DHA concentration. Liver mRNA FADS2 was higher and CPT1A lower in the DHA group (P DHA diet. In summary, supplementation with ALA or DHA modulated plasma metabolites, muscle DHA, body fat and liver gene expression differently.

  5. Simultaneous effects of hydrostatic stress and an electric field on donors in a GaAs-(Ga, Al)As quantum well

    International Nuclear Information System (INIS)

    Morales, A.L.; Montes, A.; Lopez, S.Y.; Duque, C.A.

    2002-01-01

    Theoretical calculations on the influence of both an external electric field and hydrostatic stress on the binding energy and impurity polarizability of shallow-donor impurities in an isolated GaAs-(Ga, Al)As quantum well are presented. A variational procedure within the effective-mass approximation is considered. The pressure-related Γ-X crossover is taken into account. As a general feature, we observe that the binding energy increases as the length of the well decreases. For the low-pressure regime we observe a linearly binding energy behaviour. For the high-pressure regime the simultaneous effects of the barrier height and the applied electric field bend the binding energy curves towards smaller values. For low hydrostatic pressures the impurity polarization remains constant in all cases with an increasing value as the field increases. This constant behaviour shows that the small variations in well width, effective mass, and dielectric constant with pressure do not appreciably affect polarizability. For high hydrostatic pressure, we see a non-linear increase in polarizability, mainly due to the decrease of barrier height as a result of the external pressure, which allows further deformation of the impurity. (author)

  6. Incidencia de la comunicación 360º como estrategia para reducir el índice de morosidad en los pagos académicos de los alumnos de la universidad alas peruanas filial Cajamarca 2016

    OpenAIRE

    Huamán Alva, Ancelmo

    2017-01-01

    La presente investigación tiene como objetivo determinar la incidencia de la comunicación 360° como estrategia para reducir el índice de morosidad en los pagos académicos de los alumnos de la Universidad Alas Peruanas – Filial Cajamarca, 2016. Para ello se identificaron dos variables, la primera estuvo referida a la comunicación 360º con cinco dimensiones: comunicación organizacional, fidelización, relaciones públicas, imagen corporativa y publicidad, la segunda variable fue sobre la morosida...

  7. Structural, elastic, electronic, optical and thermoelectric properties of the Zintl-phase Ae3AlAs3 (Ae = Sr, Ba)

    Science.gov (United States)

    Benahmed, A.; Bouhemadou, A.; Alqarni, B.; Guechi, N.; Al-Douri, Y.; Khenata, R.; Bin-Omran, S.

    2018-05-01

    First-principles calculations were performed to investigate the structural, elastic, electronic, optical and thermoelectric properties of the Zintl-phase Ae3AlAs3 (Ae = Sr, Ba) using two complementary approaches based on density functional theory. The pseudopotential plane-wave method was used to explore the structural and elastic properties whereas the full-potential linearised augmented plane wave approach was used to study the structural, electronic, optical and thermoelectric properties. The calculated structural parameters are in good consistency with the corresponding measured ones. The single-crystal and polycrystalline elastic constants and related properties were examined in details. The electronic properties, including energy band dispersions, density of states and charge-carrier effective masses, were computed using Tran-Blaha modified Becke-Johnson functional for the exchange-correlation potential. It is found that both studied compounds are direct band gap semiconductors. Frequency-dependence of the linear optical functions were predicted for a wide photon energy range up to 15 eV. Charge carrier concentration and temperature dependences of the basic parameters of the thermoelectric properties were explored using the semi-classical Boltzmann transport model. Our calculations unveil that the studied compounds are characterised by a high thermopower for both carriers, especially the p-type conduction is more favourable.

  8. The novel RAF1 mutation p.(Gly361Ala) located outside the kinase domain of the CR3 region in two patients with Noonan syndrome, including one with a rare brain tumor.

    Science.gov (United States)

    Harms, Frederike L; Alawi, Malik; Amor, David J; Tan, Tiong Y; Cuturilo, Goran; Lissewski, Christina; Brinkmann, Julia; Schanze, Denny; Kutsche, Kerstin; Zenker, Martin

    2018-02-01

    Noonan syndrome is characterized by typical craniofacial dysmorphism, postnatal growth retardation, congenital heart defect, and learning difficulties and belongs to the RASopathies, a group of neurodevelopmental disorders caused by germline mutations in genes encoding components of the RAS-MAPK pathway. Mutations in the RAF1 gene are associated with Noonan syndrome, with a high prevalence of hypertrophic cardiomyopathy (HCM). RAF1 mutations cluster in exons encoding the conserved region 2 (CR2), the kinase activation segment of the CR3 domain, and the C-terminus. We present two boys with Noonan syndrome and the identical de novo RAF1 missense variant c.1082G>C/p.(Gly361Ala) affecting the CR3, but located outside the kinase activation segment. The p.(Gly361Ala) mutation has been identified as a RAF1 allele conferring resistance to RAF inhibitors. This amino acid change favors a RAF1 conformation that allows for enhanced RAF dimerization and increased intrinsic kinase activity. Both patients with Noonan syndrome showed typical craniofacial dysmorphism, macrocephaly, and short stature. One individual developed HCM and was diagnosed with a disseminated oligodendroglial-like leptomeningeal tumor (DOLT) of childhood at the age of 9 years. While there is a well-established association of NS with malignant tumors, especially childhood hemato-oncological diseases, brain tumors have rarely been reported in Noonan syndrome. Our data demonstrate that mutation scanning of the entire coding region of genes associated with Noonan syndrome is mandatory not to miss rare variants located outside the known mutational hotspots. © 2017 Wiley Periodicals, Inc.

  9. Characterization of electron clouds in the Cornell Electron Storage Ring Test Accelerator using TE-wave transmission

    International Nuclear Information System (INIS)

    De Santis, S.; Byrd, J.M.; Billing, M.; Palmer, M.; Sikora, J.; Carlson, B.

    2010-01-01

    A relatively new technique for measuring the electron cloud density in storage rings has been developed and successfully demonstrated (S. De Santis, J.M. Byrd, F. Caspers, A. Krasnykh, T. Kroyer, M.T.F. Pivi, and K.G. Sonnad, Phys. Rev. Lett. 100, 094801 (2008).). We present the experimental results of a systematic application of this technique at the Cornell Electron Storage Ring Test Accelerator. The technique is based on the phase modulation of the TE mode transmitted in a synchrotron beam pipe caused by the periodic variation of the density of electron plasma. Because of the relatively simple hardware requirements, this method has become increasingly popular and has been since successfully implemented in several machines. While the principles of this technique are straightforward, quantitative derivation of the electron cloud density from the measurement requires consideration of several effects, which we address in detail.

  10. Delta opioid peptide (D-Ala 2, D-Leu 5) enkephalin: linking hibernation and neuroprotection.

    Science.gov (United States)

    Borlongan, Cesario V; Wang, Yun; Su, Tsung-Ping

    2004-09-01

    Hibernation is a potential protective strategy for the peripheral, as well as for the central nervous system. A protein factor termed hibernation induction trigger (HIT) was found to induce hibernation in summer-active ground squirrels. Purification of HIT yielded an 88-kD peptide that is enriched in winter hibernators. Partial sequence of the 88-kD protein indicates that it may be related to the inhibitor of metalloproteinase. Using opioid receptor antagonists to elucidate the mechanisms of HIT, it was found that HIT targeted the delta opioid receptors. Indeed, delta opioid (D-Ala 2, D-Leu 5) enkephalin (DADLE) was shown to induce hibernation. Specifically, HIT and DADLE were found to prolong survival of peripheral organs, such as the lung, the heart, liver, and kidney preserved en bloc or as a single preparation. In addition, DADLE has been recently demonstrated to promote survival of neurons in the central nervous system. Exposure to DADLE dose-dependently enhanced cell viability of cultured primary rat fetal dopaminergic cells. Subsequent transplantation of these DADLE-treated dopaminergic cells into the Parkinsonian rat brain resulted in a two-fold increase in surviving grafted cells. Interestingly, delivery of DADLE alone protected against dopaminergic depletion in a rodent model of Parkinson s disease. Similarly, DADLE blocked and reversed the dopaminergic terminal damage induced by methamphetamine (METH). Such neuroprotective effects of DADLE against METH neurotoxicity was accompanied by attenuation of mRNA expressions of a tumor necrosis factor p53 and an immediate early gene c-fos. In parallel to these beneficial effects of DADLE on the dopaminergic system, DADLE also ameliorated the neuronal damage induced by ischemia-reperfusion following a transient middle cerebral artery occlusion. In vitro replication of this ischemia cell death by serum-deprivation of PC12 cells revealed that DADLE exerted neuroprotection in a naltrexone-sensitive manner. These

  11. Structures of the a2 ions of Ala-Ala-Ala and Phe-Phe-Phe

    NARCIS (Netherlands)

    Verkerk, U.H.; Zhao, J.; Lau, J.K.-C.; Lam, T.-W.; Hao, Q.; Steill, J.D.; Siu, C.K.; Oomens, J.; Hopkinson, A.C.; Siu, K.W.M.

    2012-01-01

    IRMPD spectra are reported for a2 ions derived from trialanine (AAA) and triphenylalanine (FFF) and compared with spectra calculated by density functional theory at the B3LYP/6-311++G(d,p) level of theory. At low collision energies the cyclic N1-protonated imidazolidinone ion C1 is dominant, but at

  12. Delta-ALA-mediated fluorescence spectroscopy of gastrointestinal tumors: comparison of in vivo and in vitro results

    Science.gov (United States)

    Vladimirov, B.; Borisova, E.; Avramov, L.

    2007-06-01

    The limitations of standard endoscopy for detection of dysplastic changes of mucosa are significant challenge and initiate development of new photodiagnostic techniques, additional to diagnostic possibilities of standard endoscopic equipment. One of the most widely examined optical modalities is the laser- or light-induced fluorescence spectroscopy (LIFS), because of its rapid and highly sensitive response to early biochemical and morphological changes in biological tissues. In the recent study delta-aminolevulinic acid/protoporphyrin IX is used as fluorescent marker for dysplasia and tumor detection in esophagus and stomach. The δ -ALA is administered per os six hours before measurements at dose 20mg/kg weight. High-power light-emitting diode at 405 nm is used as an excitation source. Special opto-mechanical device is built to use the light guide of standard video-endoscopic system. Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer. The fluorescence detected from in vivo tumor sites has very complex spectral origins. It consists of autofluorescence, fluorescence from exogenous fluorophores and re-absorption from the chromophores accumulated in the tissue investigated. Mucosa autofluorescence lies at 450-600 nm region. The fluorescence of PpIX is clearly pronounced at the 630-710 nm region. Deep minima in the tumor fluorescence signals are observed in the region 540-575 nm, related to hemoglobin re-absorption. Such high hemoglobin content is an indication of the tumors vascularization and it is clearly pronounced in all dysplastic and tumor sites investigated. After formalin conservation for in vitro samples hemoglobin absorption is strongly reduced that increases mucous fluorescence signal in green-yellow spectral region. Simultaneously the maxima at 635 nm and 720 nm are reduced.

  13. Anti-arrhythmic peptide N-3-(4-hydroxyphenyl)propionyl Pro-Hyp-Gly-Ala-Gly-OH reduces dispersion of action potential duration during ischemia/reperfusion in rabbit hearts

    DEFF Research Database (Denmark)

    Kjølbye, Anne Louise; Petersen, Jørgen Søberg; Holstein-Rathlou, N.-H.

    2002-01-01

    During ischemia, cardiac gap junctions close and neighboring cells uncouple. This leads to slow conduction, increased dispersion of APD90 (duration from action potential beginning to 90% of repolarization), nonuniform anisotropy, and unidirectional conduction block, all of which favor the induction...... of reentry arrhythmias. It has been suggested that anti-arrhythmic peptides increase gap junction conductance during states of reduced coupling. The aim of this study was to test the effect of the anti-arrhythmic peptide N-3-(4-hydroxyphenyl)propionyl Pro-Hyp-Gly-Ala-Gly-OH (HP-5) (10(-10) ) on dispersion...... of epicardial APD90 during both normokalemic and hypokalemic ischemia/reperfusion in isolated perfused rabbit hearts. HP-5 did not affect average APD90, heart rate, left ventricular contractility (LVP dP/dtmax), or mean coronary flow. HP-5 significantly reduced the epicardial APD dispersion during hypokalemic...

  14. The Effect of Visitor Satisfaction Level on Willingness to Pay at Plengkung, in Alas Purwo National Park

    Directory of Open Access Journals (Sweden)

    Mona Annisa Matondang

    2018-01-01

    Full Text Available One of ecotourism destinations in Indonesia is located in the Plengkung Beach at Alas Purwo National Park, Banyuwangi, East Java. Plengkung is one of the world's best locations for surfing activities which can be equated with Hawaii, Australia and South Africa. It was attract tourists to visit Plengkung. Each investor should pay attention to visitor satisfaction in order to maintain and increase the number of visitors. However, visitor satisfaction could be reflected through the improvement of service quality. The purpose of this study was to measure the level of visitor satisfaction based on service quality at PT Plengkung Indah Wisata and PT Wanasari Pramudita Ananta in Plengkung, to measure the value of ecotourism satisfaction using the willingness to pay (WTP approach and to know the effect of visitor satisfaction level on WTP after doing ecotourism activities. The research was conducted in June-October 2016 with data collection method using quesionnaires, interviews and literature studies. The effect of visitor satisfaction level on WTP of ecotourism activities in Plengkung was analyzed using bivariate correlation analysis (parson correlation coefficient with p-value <0,05. The results showed that PT WPA had better service quality, hence it got higher satisfaction score which is 4,8. The WTP in PT WPA was greater than PT PIW, that is Rp 15.452.370 since PT WPA had a higher level of visitor satisfaction than PT PIW. The correlation test results proved that the level of visitor satisfaction significantly affect the WTP with a value of 0,031.Keyword: ecotourism, visitor satisfaction level, WTP.

  15. Nonconserved Residues Ala287 and Ser290 of the Cryptosporidium hominis Thymidylate Synthase Domain Facilitate Its Rapid Rate of Catalysis

    Energy Technology Data Exchange (ETDEWEB)

    Doan,L.; Martucci, W.; Vargo, M.; Atreya, C.; Anderson, K.

    2007-01-01

    Cryptosporidium hominis TS-DHFR exhibits an unusually high rate of catalysis at the TS domain, at least 10-fold greater than those of other TS enzymes. Using site-directed mutagenesis, we have mutated residues Ala287 and Ser290 in the folate-binding helix to phenylalanine and glycine, respectively, the corresponding residues in human and most other TS enzymes. Our results show that the mutant A287F, the mutant S290G, and the double mutant all have reduced affinities for methylene tetrahydrofolate and reduced rates of reaction at the TS domain. Interestingly, the S290G mutant enzyme had the lowest TS activity, with a catalytic efficiency {approx}200-fold lower than that of the wild type (WT). The rate of conformational change of the S290G mutant is {approx}80 times slower than that of WT, resulting in a change in the rate-limiting step from hydride transfer to covalent ternary complex formation. We have determined the crystal structure of ligand-bound S290G mutant enzyme, which shows that the primary effect of the mutation is an increase in the distance between the TS ligands. The kinetic and crystal structure data presented here provide the first evidence explaining the unusually fast TS rate in C. hominis.

  16. Strategi Pengembangan Wista Mangrove Di “Blok Bedul” Taman Nasional Alas Purwo Kabupaten Banyuwangi Jawa Timur

    Directory of Open Access Journals (Sweden)

    Saifullah Saifullah

    2013-09-01

    Full Text Available Ekowisata dapat dilihat sebagai suatu konsep pengembangan pariwisata berkelanjutan yang bertujuan untuk mendukung upaya-upaya pelestarian lingkungan dan meningkatkan partisipasi masyarakat dalam pengelolaannya. Oleh karena itu diperlukan penelitian tentang strategi pengembangan ekowisata kawasan mangrove untuk mendukung pelestarian lingkungan pesisir yang berkelanjutan. Hasil penelitian menujukan Potensi mangrove yang terdapat di kawasan ini 4 species dari 2 famili yaitu : Rhizophora mucronata, Rhizophora apiculata, Sonneratia alba dan Cariop tagal, selain itu dari hasil studi literatur diketahui bahwa terdapat 24 species dari 12 famili di sepanjang kawasan segara anakan Taman Nasional Alas Purwo. Untuk inventarisasi satwa, dari hasil studi literatur dan pengamatan dilapang terdapat jenis burung air, burung darat, burung pemangsa, mamalia, reptile, pisces dan crustacea. Untuk potensi budaya terdapat upacara petik laut dan sumber air randu telu yang dipercaya dapat menyembuhkan penyakit. Dari hasil analisa kuisioner 47% dari jumlah pengunjung mengetahui tentang ekosistem mangrove. Dan 47% dari responden yang memahami tentang fungsi ekosistem mangrove. Dari pengenalan tentang ekowisata mempunyai nilai-nilai konservasi atau perlindungan, 85% responden memahami hal tersebut. Untuk pemberdayaan masyarakat, 67% memahami ekowisata harus disertai dengan pemberdayaan dan partisipasi masyarakat. Dan 50% responden menyetujui bahwa ekowisata harus memberikan nilai ekonomi kepada masyarakat. Dan untuk persepsi bahwa ekowisata harus dapat memberikan nilai pendidikan kepada pengunjung, 73% responden mengetahuinya. Dari hasil perhitungan menggunakan konsep surplus konsumen didapat total valuasi ekonomi kawasan ekowisata mangrove blok bedul adalah Rp. 88.606.183,00. Nilai ini untuk per 1000 orang dalam kunjungan pertahun. Arahan strategi kebijakan pengembangan antara lain: (a Kelembagaan pengelola ekowisata harus dapat meningkatkan pelayanannya, (b Pengembangan

  17. Using a Fluorescent Cytosine Analogue tC[superscript o] To Probe the Effect of the Y567 to Ala Substitution on the Preinsertion Steps of dNMP Incorporation by RB69 DNA Polymerase

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Shuangluo; Beckman, Jeff; Wang, Jimin; Konigsberg, William H. (Yale)

    2012-10-10

    Residues in the nascent base pair binding pocket (NBP) of bacteriophage RB69 DNA polymerase (RB69pol) are responsible for base discrimination. Replacing Tyr567 with Ala leads to greater flexibility in the NBP, increasing the probability of misincorporation. We used the fluorescent cytosine analogue, 1,3-diaza-2-oxophenoxazine (tC{sup o}), to identify preinsertion step(s) altered by NBP flexibility. When tC{sup o} is the templating base in a wild-type (wt) RB69pol ternary complex, its fluorescence is quenched only in the presence of dGTP. However, with the RB69pol Y567A mutant, the fluorescence of tC{sup o} is also quenched in the presence of dATP. We determined the crystal structure of the dATP/tC{sup o}-containing ternary complex of the RB69pol Y567A mutant at 1.9 {angstrom} resolution and found that the incoming dATP formed two hydrogen bonds with an imino-tautomerized form of tC{sup o}. Stabilization of the dATP/tC{sup o} base pair involved movement of the tC{sup o} backbone sugar into the DNA minor groove and required tilting of the tC{sup o} tricyclic ring to prevent a steric clash with L561. This structure, together with the pre-steady-state kinetic parameters and dNTP binding affinity, estimated from equilibrium fluorescence titrations, suggested that the flexibility of the NBP, provided by the Y567 to Ala substitution, led to a more favorable forward isomerization step resulting in an increase in dNTP binding affinity.

  18. ELASTİK ZEMİNE OTURAN KALIN PLAKLAR İÇİN KAYMA KİLİTLENMESİZ BİR SONLU ELEMAN MODELİ

    OpenAIRE

    ÖZGAN, KORHAN; DALOĞLU, AYŞE T.

    2015-01-01

    Bu çalışmada, kalınlık doğrultusundaki kayma şekil değiştirmelerini dikkate alan 4 düğüm noktalı (PBQ4) ve 8 düğüm noktalı (PBQ8) Mindlin plak elemanlar kullanılarak elastik zemine oturan kalın plakların hesabı incelenmiştir. Küçük plak kalınlıklarında meydana gelen kayma kilitlenmesini önlemek amacıyla her iki tip elemanın plak rijitlik matrisleri tam integrasyon (Tİ) tekniğinin yanı sıra seçilerek azaltılmış integrasyon (SAİ) tekniği de kullanılarak elde edilmektedir. Çeşitli yükleme duruml...

  19. HABITAT DAN PERILAKU ELANG JAWA (Nisaetus bartelsi DI SPTN 1 TEGALDLIMO TAMAN NASIONAL ALAS PURWO, JAWA TIMUR

    Directory of Open Access Journals (Sweden)

    Desy Natalia Sitorus

    2017-05-01

    Full Text Available Javan Hawk-eagle (Nisaetus bartelsi considered as endangered species by IUCN redlist 2015 and protected species by Government Regulation No.7/1999. Alas Purwo National Park (APNP is a conservation area and its one of the natural habitat of Javan Hawk-eagle distribution (endemic species of java. The study was aimed to analysis its habitat and the behavior. Purposive sampling was used on focused observation area base on direct contex with the bird. The habitat analysis was approach with vagetation analysis dan habitat used method. Focal animal sampling used as approach describe to know the daily activities. The result showed that the bird used of natural lowland forest as main habitat and the bird distibute as equal (focused at natural lowland forest. Characteristic of sheltering site of the bird using tree in A strata and B strata, which have horizontal and strong enough branch. The javan hawk-eagle choising at emergent tree for the nesting site, with characteristic of emergent tree, with crown not so dense of the leaf and the position of the tree close to hunting area. Characteristic of hunting areas of the bird is natural lowland forest with diverse and abundant of preys. The bird like preys on mammals such as giant squirrel and bird such as red jungle fowl. The behavior was most often observed was resting in natural lowland forest with five times encounter (58,06%. But the bird also done activities of preening and observing surrounding to focus on seaching food. Hunting activity was observed used perch hunting in natural low land forest in APNP. Keywords: APNP, habitat, javan hawk-eagle

  20. A prevalent amino acid polymorphism at codon 98 (Ala98Val) of the hepatocyte nuclear factor-1alpha is associated with maturity-onset diabetes of the young and younger age at onset of type 2 diabetes in Asian Indians

    DEFF Research Database (Denmark)

    Anuradha, Shekher; Radha, Venkatesan; Deepa, Raj

    2005-01-01

    Among Europeans, mutations in the hepatocyte nuclear factor-1alpha (HNF1alpha) gene are associated with the most common form of maturity-onset diabetes of the young (MODY)3. In Asian Indians, type 2 diabetes occurs earlier and often overlaps with MODY, but the genetics of the latter are unknown....... The aim of this study was to estimate the prevalence of Ala98Val polymorphism of the HNF1alpha gene in different types of diabetes in Asian Indians....

  1. Characterization of electron clouds in the Cornell Electron Storage Ring Test Accelerator using TE-wave transmission

    Directory of Open Access Journals (Sweden)

    S. De Santis

    2010-07-01

    Full Text Available A relatively new technique for measuring the electron cloud density in storage rings has been developed and successfully demonstrated [S. De Santis, J. M. Byrd, F. Caspers, A. Krasnykh, T. Kroyer, M. T. F. Pivi, and K. G. Sonnad, Phys. Rev. Lett. 100, 094801 (2008.PRLTAO0031-900710.1103/PhysRevLett.100.094801]. We present the experimental results of a systematic application of this technique at the Cornell Electron Storage Ring Test Accelerator. The technique is based on the phase modulation of the TE mode transmitted in a synchrotron beam pipe caused by the periodic variation of the density of electron plasma. Because of the relatively simple hardware requirements, this method has become increasingly popular and has been since successfully implemented in several machines. While the principles of this technique are straightforward, quantitative derivation of the electron cloud density from the measurement requires consideration of several effects, which we address in detail.

  2. The critical main-chain length for helix formation in water: determined in a peptide series with alternating Aib and Ala residues exclusively and detected with ECD spectroscopy.

    Science.gov (United States)

    Longo, Edoardo; Moretto, Alessandro; Formaggio, Fernando; Toniolo, Claudio

    2011-10-01

    Critical main-chain length for peptide helix formation in the crystal (solid) state and in organic solvents has been already reported. In this short communication, we describe our results aiming at assessing the aforementioned parameter in water solution. To this goal, we synthesized step-by-step by solution procedures a complete series of N-terminally acetylated, C-terminally methoxylated oligopeptides, characterized only by alternating Aib and Ala residues, from the dimer to the nonamer level. All these compounds were investigated by electronic circular dichroism in the far-UV region in water solution as a function of chemical structure, namely presence/absence of an ester moiety or a negative charge at the C-terminus, and temperature. We find that the critical main-chain lengths for 3(10)- and α-helices, although still formed to a limited extent, in aqueous solution are six and eight residues, respectively. © 2011 Wiley-Liss, Inc.

  3. The growth hormone (GH) response to GH-releasing peptide (His-DTrp-Ala-Trp-DPhe-Lys-NH2), GH-releasing hormone, and thyrotropin-releasing hormone in acromegaly.

    Science.gov (United States)

    Alster, D K; Bowers, C Y; Jaffe, C A; Ho, P J; Barkan, A L

    1993-09-01

    In patients with acromegaly, GH-producing pituitary tumors release GH in response to specific stimuli such as GH-releasing hormone (GHRH) and are also responsive to a variety of nonspecific stimuli, such as TRH or GnRH, and may exhibit paradoxical responses to glucose and dopamine. In healthy humans, the synthetic peptide GH-releasing peptide (GHRP) (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) releases GH by a putative mechanism of action that is independent of GHRH. How these tumors respond to GHRP is not well characterized. We studied the GH responses to GHRH, GHRP, and TRH stimulation in 11 patients with active acromegaly. The peak GH responses to GHRP and GHRH were not correlated (r = 0.57; P = 0.066). In contrast, the peak GH responses to GHRP and TRH were highly correlated (r = 0.95; P < 0.001). In conclusion, in patients with acromegaly, the GH response to GHRP is qualitatively normal and does not appear to depend on GHRH.

  4. Vegetable oils rich in alpha linolenic acid allow a higher accretion of n-3 LCPUFA in the plasma, liver and adipose tissue of the rat

    Directory of Open Access Journals (Sweden)

    Valenzuela, R.

    2014-06-01

    Full Text Available ALA is the precursor of EPA and DHA and its dietary availability is limited. Vegetable oils rich in ALA (48–64% are alternatives for increasing its consumption. The conversion of ALA into EPA and DHA and the ratio (EPA+DHA/ALA was evaluated in different tissues from male Wistar rats fed ALA –rich oils. Four groups (n=12/group were fed for 21 days with oils from: a corn (CO, 3% ALA; b soybean (SO, 6% ALA; c sacha inchi (SIO, 48% ALA and; d chia (ChO, 64% ALA. SO, SIO and ChO significantly increased ALA levels (pALA es precursor de EPA y DHA y sus fuentes dietarias son limitadas. Aceites ricos en ALA (48–64% son una alternativa para incrementar su consumo. En este trabajo se evaluó la conversión de ALA a EPA y DHA, y la relación (EPA+DHA/ALA en tejidos de ratas macho Wistar alimentadas con aceites con alto contenido en ALA. Cuatro grupos (n=12/grupo recibieron durante 21 días aceite de: a maíz (CO, 3% ALA; b soja (SO, 6% ALA; c sacha inchi (SIO, 48% ALA y; d chía (ChO, 64% ALA. SO, SIO y ChO incrementaron ALA (p<0,05 en los tejidos. Solo SIO y ChO incrementaron el EPA y DHA, disminuyendo la relación n-6/n-3 (p<0,05. Se propone SIO y ChO como fuentes de ALA para incrementar EPA y DHA en los tejidos.

  5. Pressure dependence of side chain 13C chemical shifts in model peptides Ac-Gly-Gly-Xxx-Ala-NH2.

    Science.gov (United States)

    Beck Erlach, Markus; Koehler, Joerg; Crusca, Edson; Munte, Claudia E; Kainosho, Masatsune; Kremer, Werner; Kalbitzer, Hans Robert

    2017-10-01

    For evaluating the pressure responses of folded as well as intrinsically unfolded proteins detectable by NMR spectroscopy the availability of data from well-defined model systems is indispensable. In this work we report the pressure dependence of 13 C chemical shifts of the side chain atoms in the protected tetrapeptides Ac-Gly-Gly-Xxx-Ala-NH 2 (Xxx, one of the 20 canonical amino acids). Contrary to expectation the chemical shifts of a number of nuclei have a nonlinear dependence on pressure in the range from 0.1 to 200 MPa. The size of the polynomial pressure coefficients B 1 and B 2 is dependent on the type of atom and amino acid studied. For H N , N and C α the first order pressure coefficient B 1 is also correlated to the chemical shift at atmospheric pressure. The first and second order pressure coefficients of a given type of carbon atom show significant linear correlations suggesting that the NMR observable pressure effects in the different amino acids have at least partly the same physical cause. In line with this observation the magnitude of the second order coefficients of nuclei being direct neighbors in the chemical structure also are weakly correlated. The downfield shifts of the methyl resonances suggest that gauche conformers of the side chains are not preferred with pressure. The valine and leucine methyl groups in the model peptides were assigned using stereospecifically 13 C enriched amino acids with the pro-R carbons downfield shifted relative to the pro-S carbons.

  6. The third serine proteinase with chymotrypsin specificity isolated from Atlantic cod (Gadus morhua) is a type-II elastase

    DEFF Research Database (Denmark)

    Asgeirsson, B; Leth-Larsen, Rikke; Thórólfsson, M

    1998-01-01

    -Ala-Ala-Pro-Phe-p-nitroanilide, but inactive against the typical elastase substrates succinyl-Ala-Ala-Ala-p-nitroanilide and orcein-elastin. Comparison of the kinetic properties of the cod elastase C with bovine chymotrypsin and cod chymotrypsin variants A and B, using succinyl-Ala-Ala-Pro-Phe-p-nitroanilide, showed a lower catalytic...

  7. Survey of Hawksbill Turtle (Eretmochelys imbricate Health Condition in Terms of Parasites and Microbes in Alas Purwo National Park, Indonesia

    Directory of Open Access Journals (Sweden)

    Qurrota A'yunin

    2017-07-01

    Full Text Available Indonesian waters have six types of turtles that can live, spawn and breed. Sea turtle conservation becomes an important and urgent program to be done in order to protect and save sea turtle population in Indonesia. One of the factors that most affect the turtle population is the cause of degradation of pathogenic factors. Alas Purwo National Park, East Java, there is some communities that have activities turtle conservation. Conservation is done by securing and protecting turtle eggs. Turtle eggs that have hatched are released into the sea once it is ready. This study aims was to determine the type of bacteria and fungi that infect hatchlings and environmental factors that influence. This research is descriptive method to Hawksbill turtle (Eretmochelys imbricate is by way of random sampling. Sampling of microbes in sea turtle was conducted using cotton swab method and then microbes was cultured and indentified in laboratory. The results showed The kind of parasites and microbes which were indentified in hatching and adult Hawksbill sea turtles were fungus with genus Aspergillus sp., Geotrichum sp., Fusarium sp., and Gliocladium sp. ; bacteria are Pseudomonas aeruginosa and Enterobacter cloaceae; and parasite is Chelonibia testudinaria barnacles.  The parameter average value of water in pond indicated 28.1 – 29.2°C for temperature, 32 - 34 ‰ for salinity, 7.78 – 8.2 for pH, and 3.86 – 4.21 mg/L for DO.

  8. Whole-Body Docosahexaenoic Acid Synthesis-Secretion Rates in Rats Are Constant across a Large Range of Dietary α-Linolenic Acid Intakes.

    Science.gov (United States)

    Domenichiello, Anthony F; Kitson, Alex P; Metherel, Adam H; Chen, Chuck T; Hopperton, Kathryn E; Stavro, P Mark; Bazinet, Richard P

    2017-01-01

    Docosahexaenoic acid (DHA) is an ω-3 (n-3) polyunsaturated fatty acid (PUFA) thought to be important for brain function. Although the main dietary source of DHA is fish, DHA can also be synthesized from α-linolenic acid (ALA), which is derived from plants. Enzymes involved in DHA synthesis are also active toward ω-6 (n-6) PUFAs to synthesize docosapentaenoic acid n-6 (DPAn-6). It is unclear whether DHA synthesis from ALA is sufficient to maintain brain DHA. The objective of this study was to determine how different amounts of dietary ALA would affect whole-body DHA and DPAn-6 synthesis rates. Male Long-Evans rats were fed an ALA-deficient diet (ALA-D), an ALA-adequate (ALA-A) diet, or a high-ALA (ALA-H) diet for 8 wk from weaning. Dietary ALA concentrations were 0.07%, 3%, and 10% of the fatty acids, and ALA was the only dietary PUFA that differed between the diets. After 8 wk, steady-state stable isotope infusion of labeled ALA and linoleic acid (LA) was performed to determine the in vivo synthesis-secretion rates of DHA and DPAn-6. Rats fed the ALA-A diet had an ∼2-fold greater capacity to synthesize DHA than did rats fed the ALA-H and ALA-D diets, and a DHA synthesis rate that was similar to that of rats fed the ALA-H diet. However, rats fed the ALA-D diet had a 750% lower DHA synthesis rate than rats fed the ALA-A and ALA-H diets. Despite enrichment into arachidonic acid, we did not detect any labeled LA appearing as DPAn-6. Increasing dietary ALA from 3% to 10% of fatty acids did not increase DHA synthesis rates, because of a decreased capacity to synthesize DHA in rats fed the ALA-H diet. Tissue concentrations of DPAn-6 may be explained at least in part by longer plasma half-lives. © 2017 American Society for Nutrition.

  9. Alginate enhances excretion and reduces absorption of strontium and cesium in rats

    International Nuclear Information System (INIS)

    Idota, Yoko; Harada, Hitomi; Tomono, Takumi; Morimoto, Kaori; Kakinuma, Chihaya; Ogihara, Takuo; Kobayashi, Shoko; Miyajima, Chihiro; Kasahara, Fumiyoshi

    2013-01-01

    Alginate (ALA), which is an intercellular polysaccharide associated with brown algae, is used as a food additive, a health food and a medicine. Here, we first examined the adsorption of strontium (Sr) and cesium (Cs) by ALA in vitro, and then evaluated the effects of ALA on absorption and excretion of Sr and Cs in rats, in order to evaluate its potential usefulness for minimizing radiation damage from materials released after a nuclear accident. Both Sr and Cs were concentration-dependently adsorbed by sodium alginate (ALA-Na) in vitro. In rats given diet containing either ALA-Na or calcium alginate (ALA-Ca) for two weeks, the plasma concentration of Sr gradually decreased compared with the controls (normal diet); however, in the case of Cs, the plasma concentration was decreased only in the ALA-Ca group, but not the ALA-Na group. Moreover, we examined the effect of preadministration of diet containing either ALA-Na or ALA-Ca on absorption of Sr and Cs administered orally as the chloride salts to rats. Absorption of both Sr and Cs was reduced in the ALA-Ca group, while absorption of only Sr was reduced in the ALA-Na group. Safety assessments indicated that ALA-Ca is safer than ALA-Na. These results indicate that ALA-Ca reduces absorption and promotes excretion of both Sr and Cs, while ALA-Na does so only for Sr. (author)

  10. Investigation of a potential scintigraphic marker of apoptosis: radioiodinated Z-Val-Ala-DL-Asp(O-methyl)-fluoromethyl ketone

    Energy Technology Data Exchange (ETDEWEB)

    Haberkorn, Uwe E-mail: uwe_haberkorn@med.uni-heidelberg.de; Kinscherf, Ralf; Krammer, Peter H.; Mier, Walter; Eisenhut, Michael

    2001-10-01

    The imaging of apoptosis represents an attractive diagnostic goal in the area of tumor therapy, degenerative diseases and organ transplantation. Since caspases play a key role during the early period of the intracellular signal cascade of cells undergoing apoptosis we considered benzyloxycarbonyl-Val-Ala-DL-Asp(O-methyl)-fluoromethyl ketone [Z-VAD-fmk], a pan-caspase inhibitor, as a potential apoptosis imaging agent. Applying the Tl(TFA){sub 3}/[{sup 131}I]iodide method Z-VAD-fmk was successfully labeled at the benzyloxycarbonyl protecting group. The success of radioiodination, however, depended on the presence of carrier iodide resulting in specific radioactivities of 2.6 GBq/{mu}mol and the formation of a mixture of the 2- and 4-iodophenyl derivative (61%) which could not be separated by HPLC. Uptake measurements were performed with Morris hepatoma cells (MH3924Atk8) which showed expression of the Herpes Simplex Virus thymidine kinase (HSVtk) gene. Apoptosis was induced by treatment of the cells with 25 {mu}M ganciclovir. The TUNEL assay revealed 1.3{+-}0.3 and 23{+-}1.1% apoptotic cells immediately and 24 h after therapy, respectively. A two-fold increase of [{sup 131}I]IZ-VAD-fmk uptake was found at the end of treatment with the HSVtk/suicide system which constantly remained elevated for the following 4 hours. The slow cellular influx and lack of uptake saturation of [{sup 131}I]IZ-VAD-fmk are evidence for simple diffusion as transport mechanism. In addition, the absolute cellular uptake of [{sup 131}I]IZ-VAD-fmk was found to be low. This quality was related to the rather high lipophilicity of [{sup 131}I]IZ-VAD-fmk causing unspecific binding to macromolecules in the medium. Instead of using an inhibitor, synthetic caspase substrates are currently investigated which may accumulate in the apoptotic cell by metabolic trapping thereby enhancing the imaging signal.

  11. 5-aminolevulinic acid-incorporated nanoparticles of methoxy poly(ethylene glycol-chitosan copolymer for photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Chung CW

    2013-02-01

    Full Text Available Chung-Wook Chung,1,* Kyu-Don Chung,2,* Young-Il Jeong,1 Dae Hwan Kang,1 1National Research and Development Center for Hepatobiliary Disease, Pusan National University Yangsan Hospital, Gyeongnam, Republic of Korea; 2Department of Anesthesiology and Pain Medicine, College of Medicine, The Catholic University, Seoul, Republic of Korea*These authors contributed equally to this workPurpose: The aim of this study was to make 5-aminolevulinic acid (5-ALA-incorporated nanoparticles using methoxy polyethylene glycol/chitosan (PEG-Chito copolymer for application in photodynamic therapy for colon cancer cells.Methods: 5-ALA-incorporated (PEG-Chito-5-ALA nanoparticles were prepared by ion complex formation between 5-ALA and chitosan. Protoporphyrin IX accumulation in the tumor cells and phototoxicity induced by PEG-Chito-5-ALA nanoparticles were assessed using CT26 cells in vitro.Results: PEG-Chito-5-ALA nanoparticles have spherical shapes with sizes diameters 200 nm. More specifically, microscopic observation revealed a core-shell structure of PEG-Chito-5-ALA nanoparticles. 1H NMR spectra showed that 5-ALA was incorporated in the core of the nanoparticles. In the absence of light irradiation, all components such as 5-ALA, empty nanoparticles, and PEG-Chito-5-ALA nanoparticles did not affect the viability of cells. However, 5-ALA or PEG-Chito-5-ALA nanoparticles induced tumor cell death under light irradiation, and the viability of tumor cells was dose-dependently decreased according to the increase in irradiation time. In particular, PEG-Chito-5-ALA nanoparticles induced increased phototoxicity and higher protoporphyrin IX accumulation into the tumor cells than did 5-ALA alone. Furthermore, PEG-Chito-5-ALA nanoparticles accelerated apoptosis/necrosis of tumor cells, compared to 5-ALA alone.Conclusion: PEG-Chito-5-ALA nanoparticles showed superior delivery capacity of 5-ALA and phototoxicity against tumor cells. These results show that PEG-Chito-5-ALA

  12. Continuing evolution of canine parvovirus in China: Isolation of novel variants with an Ala5Gly mutation in the VP2 protein.

    Science.gov (United States)

    Wang, Jianke; Lin, Peng; Zhao, Hang; Cheng, Yuening; Jiang, Zhong; Zhu, Hongwei; Wu, Hua; Cheng, Shipeng

    2016-03-01

    Canine parvovirus (CPV) type 2c is a new antigenic variant of CPV-2. Since the year 2000 it has spread to several countries, causing severe hemorrhagic enteritis in dogs. In 2014 and 2015, 58 fecal samples were collected from dogs in Beijing with suspected CPV infection. Regardless of the vaccination status of the dogs, 43 samples were found positive for CPV according to PCR results; i.e., 18, 7, and 18 respectively belonged to antigenic types new CPV-2a, new CPV-2b, and CPV-2c. A phylogenetic tree based on their VP2 gene sequences indicated that the Chinese CPV-2c strains form a separate cluster. In addition to synonymous mutations, the CPV-2c strains also contain a unique coding mutation in VP2 that leads to glycine at residue 5, instead of the highly conserved alanine at this position in all other CPV-2c strains sequenced to date. Using F81 cells, several novel isolates of CPV-2c, each with the Ala5Gly mutation, were obtained. One of these was used to infect experimentally beagle dogs, which subsequently developed the typical clinical symptoms of CPV infection. Hence, it appears that CPV-2c is still evolving in China, a finding that warrants continuous surveying and the eventual adaptation of current vaccines. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Neuroprotective evidence of alpha-lipoic acid and desvenlafaxine on memory deficit in a neuroendocrine model of depression.

    Science.gov (United States)

    de Sousa, Caren Nádia Soares; Meneses, Lucas Nascimento; Vasconcelos, Germana Silva; da Silva Medeiros, Ingridy; Silva, Márcia Calheiros Chaves; Mouaffak, Fayçal; Kebir, Oussama; da Silva Leite, Cláudio Manuel Gonçalves; Patrocinio, Manoel Cláudio Azevedo; Macedo, Danielle; Vasconcelos, Silvânia Maria Mendes

    2018-05-07

    Cognitive impairment is present in patients with depression. We hypothesized that alpha-lipoic acid (ALA) can reduce cognitive impairment, especially when combined to antidepressants. Female mice received vehicle or corticosterone (CORT) 20 mg/kg, s.c. for 14 days. From the 15th to 21st day, the animals were divided in groups: vehicle, CORT, CORT+desvenlafaxine (DVS) 10 or 20 mg/kg, ALA 100 or 200 mg/kg, DVS10+ALA100, DVS20+ALA100, DVS10+ALA200, or DVS20+ALA200. Tail suspension (TST), social interaction (SIT), novel object recognition (NOR), and Y-maze tests were conducted. Acetylcholinesterase activity (AChE) was measured in the prefrontal cortex (PFC), hippocampus (HC), and striatum (ST). CORT caused depressive-like behavior, impairment in SIT, and cognitive deficits. Alpha-lipoic acid and DVS, alone or combined, reversed CORT effect on TST. In the NOR, ALA200 alone, DVS10+ALA100, or DVS10+ALA200 reversed the deficits in short-term memory, while DVS20 alone or DVS20+ALA200 reversed the deficits in long-term memory. In the Y-maze test, ALA200 alone, DVS20+ALA100, or DVS20+ALA200 reversed the deficits caused by CORT in the working memory. CORT increased AChE in the PFC, HC, and ST. ALA200 alone or DVS20+ALA200 reversed this effect in the PFC, while DVS20 or DVS20+ALA100 reversed this effect in the HC. In the ST, DVS10 or 20, alone or combined, and ALA100 reversed the effects of CORT. These results suggest that DVS+ALA, by reversing CORT-induced memory and social deficits, seems to be a promising therapy for the treatment of depression and reversal of cognitive impairment observed in this disorder.

  14. Topical methotrexate pretreatment enhances the therapeutic effect of topical 5-aminolevulinic acid-mediated photodynamic therapy on hamster buccal pouch precancers.

    Science.gov (United States)

    Yang, Deng-Fu; Lee, Jeng-Woei; Chen, Hsin-Ming; Hsu, Yih-Chih

    2014-09-01

    Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is effective for treatment of human oral precancerous lesions. This animal study aimed to assess whether topical methotrexate (MTX) pretreatment could enhance the therapeutic effect of topical ALA-PDT on hamster buccal pouch precancerous lesions. Twenty hamster buccal pouch precancerous lesions were treated with either topical ALA-PDT with topical MTX pretreatment (topical MTX-ALA-PDT group, n = 10) or topical ALA-PDT alone (topical ALA-PDT group, n = 10). The intracellular protoporphyrin IX (PpIX) level in another 12 precancerous lesions (n = 6 for either the topical MTX-ALA or topical ALA group) was monitored by fluorescence spectroscopy. The intracellular PpIX reached its peak level in precancerous lesions 6.5 hours and 2.5 hours after topical ALA application for the topical MTX-ALA group (5.63-fold higher in the lesion than in the normal mucosa) and topical ALA group (2.42-fold higher in the lesion than in the normal mucosa), respectively. The complete response rate of precancerous lesions was 80% for the topical MTX-ALA-PDT group and 70% for the topical ALA-PDT group. In addition, the topical MTX-ALA-PDT group required a significantly lower mean treatment number (2.1 ± 0.6) to achieve complete response than the topical ALA-PDT group (4.4 ± 1.3, p topical MTX-ALA-PDT group had a lower recurrence rate (12.5%) than the topical ALA-PDT group (28.6%). We conclude that topical MTX-pretreatment can increase intracellular PpIX production in hamster buccal pouch precancerous lesions and significantly improves the outcomes of the precancerous lesions treated with topical ALA-PDT. Copyright © 2014. Published by Elsevier B.V.

  15. A New Ala-122-Asn Amino Acid Change Confers Decreased Fitness to ALS-Resistant Echinochloa crus-galli

    Directory of Open Access Journals (Sweden)

    Silvia Panozzo

    2017-11-01

    Full Text Available Gene mutations conferring herbicide resistance may cause pleiotropic effects on plant fitness. Knowledge of these effects is important for managing the evolution of herbicide-resistant weeds. An Echinochloa crus-galli population resistant to acetolactate synthase (ALS herbicides was collected in a maize field in north-eastern Italy and the cross-resistance pattern, resistance mechanism and fitness costs associated to mutant-resistant plants under field conditions in the presence or absence of intra-specific competition were determined. The study reports for the first time the Ala-122-Asn amino-acid change in the ALS gene that confers high levels of cross-resistance to all ALS inhibitors tested. Results of 3-year growth analysis showed that mutant resistant E. crus-galli plants had a delayed development in comparison with susceptible plants and this was registered in both competitive (3, 7, and 20 plants m-2 and non-competitive (spaced plants situations. The number of panicles produced by resistant plants was also lower (about 40% fewer panicles than susceptible plants under no-intraspecific competition. Instead, with the increasing competition level, the difference in panicle production at harvest time decreased until it became negligible at 20 plants m-2. Evaluation of total dry biomass as well as biomass allocation in vegetative parts did not highlight any difference between resistant and susceptible plants. Instead, panicle dry weight was higher in susceptible plants indicating that they allocated more biomass than resistant ones to the reproductive organs, especially in no-competition and in competition situations at lower plant densities. The different fitness between resistant and susceptible phenotypes suggests that keeping the infestation density as low as possible can increase the reproduction success of the susceptible phenotype and therefore contribute to lowering the ratio between resistant and susceptible alleles. If adequately

  16. A New Ala-122-Asn Amino Acid Change Confers Decreased Fitness to ALS-Resistant Echinochloa crus-galli.

    Science.gov (United States)

    Panozzo, Silvia; Scarabel, Laura; Rosan, Valentina; Sattin, Maurizio

    2017-01-01

    Gene mutations conferring herbicide resistance may cause pleiotropic effects on plant fitness. Knowledge of these effects is important for managing the evolution of herbicide-resistant weeds. An Echinochloa crus-galli population resistant to acetolactate synthase (ALS) herbicides was collected in a maize field in north-eastern Italy and the cross-resistance pattern, resistance mechanism and fitness costs associated to mutant-resistant plants under field conditions in the presence or absence of intra-specific competition were determined. The study reports for the first time the Ala-122-Asn amino-acid change in the ALS gene that confers high levels of cross-resistance to all ALS inhibitors tested. Results of 3-year growth analysis showed that mutant resistant E. crus-galli plants had a delayed development in comparison with susceptible plants and this was registered in both competitive (3, 7, and 20 plants m -2 ) and non-competitive (spaced plants) situations. The number of panicles produced by resistant plants was also lower (about 40% fewer panicles) than susceptible plants under no-intraspecific competition. Instead, with the increasing competition level, the difference in panicle production at harvest time decreased until it became negligible at 20 plants m -2 . Evaluation of total dry biomass as well as biomass allocation in vegetative parts did not highlight any difference between resistant and susceptible plants. Instead, panicle dry weight was higher in susceptible plants indicating that they allocated more biomass than resistant ones to the reproductive organs, especially in no-competition and in competition situations at lower plant densities. The different fitness between resistant and susceptible phenotypes suggests that keeping the infestation density as low as possible can increase the reproduction success of the susceptible phenotype and therefore contribute to lowering the ratio between resistant and susceptible alleles. If adequately embedded in a

  17. Climate and drought

    Science.gov (United States)

    McNab, Alan L.

    Drought is a complex phenomenon that can be defined from several perspectives [Wilhite and Glantz, 1987]. The common characteristic and central idea of these perspectives is the straightforward notion of a water deficit. Complexity arises because of the need to specify the part of the hydrologic cycle experiencing the deficit and the associated time period. For example, a long-term deficit in deep groundwater storage can occur simultaneously with a short-term surplus of root zone soil water.Figure 1 [Changnon, 1987] illustrates how the definitions of drought are related to specific components of the hydrologic cycle. The dashed lines indicate the delayed translation of two hypothetical precipitation deficits with respect to runoff, soil moisture, streamflow and groundwater. From this perspective, precipitation can be considered as the carrier of the drought signal, and hydrological processes are among the final indicators that reveal the presence of drought [Hare, 1987; Klemes, 1987].

  18. State-dependent variation in the inhibitory effect of (D-Ala sup 2 , D-Leu sup 5 )-enkephalin on hippocampal serotonin release in ground squirrels

    Energy Technology Data Exchange (ETDEWEB)

    Kramarova, L.I.; Lee, T.F.; Cui, Y.; Wang, L.C.H. (Univ. of Alberta, Edmonton (Canada))

    1990-01-01

    Accumulated evidence has suggested that increased endogenous opioid activities may facilitate the onset of hibernation either directly or possibly through modulation of other neurotransmitter systems. The seasonal change of (D-Ala{sup 2}, D-Leu{sup 5})-enkephalin (DADLE), a {delta} receptor agonist, in modulating K{sup +}-induced ({sup 3}H)-5-hydroxytryptamine (5-HT) release from the hippocampal and hypothalamic slices of euthermic and hibernating Richardsons' ground squirrels was therefore investigated. DADLE had no effect on 5-HT release in the hypothalamic slices but elicited a dose-related inhibition on ({sup 3}H)-5-HT release from the hippocampal slices of the euthermic ground squirrel. The inhibitory effect of DADLE was completely reversed by naloxone, but not by tetrodotoxin. In contrast, DADLE failed to alter the K{sup +}-induced 5-HT release from the hippocampal slices of the hibernating ground squirrel. This state-dependent reduction in responsiveness to an opioid is consistent with the hypothesis that enhanced endogenous opioid activity in the hibernating phase could lead to down regulation of the opioid receptors and minimize its inhibition on hippocampal serotonergic activity. A high 5-HT activity would inhibit midbrain reticular activating system indirectly through non-serotonergic fibers, which in turn facilitate the onset or maintenance of hibernation.

  19. Albumin Redhill (-1 Arg, 320 Ala → Thr): A glycoprotein variant of human serum albumin whose precursor has an aberrant signal peptidase cleavage site

    International Nuclear Information System (INIS)

    Brennan, S.O.; Myles, T.; Peach, R.J.; George, P.M.; Donaldson, D.

    1990-01-01

    Albumin Redhill is an electrophoretically slow genetic variant of human serum albumin that does not bind 63 Ni 2+ and has a molecular mass 2.5 kDa higher than normal albumin. Its inability to bind Ni 2+ was explained by the finding of an additional residue of Arg at position -1. This did not explain the molecular basis of the genetic variation or the increase in apparent molecular mass. Fractionation of tryptic digests on concanavalin A-Sepharose followed by peptide mapping of the bound and unbound fractions and sequence analysis of the glycopeptides identified a mutation of 320 Ala → Thr. This introduces as Asn-Tyr-Thr oligosaccharide attachment sequence centered on Asn-318 and explains the increase in molecular mass. This, however, did not satisfactorily explain the presence of the additional Arg residue at position -1. DNA sequencing of polymerase chain reaction-amplified genomic DNA encoding the prepro sequence of albumin indicated an additional mutation of -2 Arg → Cys. The authors propose that the new Phe-Cys-Arg sequence in the propeptide is an aberrant signal peptidase cleavage site and that the signal peptidase cleaves the propeptide of albumin Redhill in the lumen of the endoplasmic reticulum before it reaches the Golgi vesicles, the site of the diarginyl-specific proalbumin convertase

  20. Thermochemistry of the Dissolution of Dipeptides Containing DL-α-Alanine in Aqueous Solutions of Sodium Dodecyl Sulfate at 298.15 K

    Science.gov (United States)

    Smirnov, V. I.; Badelin, V. G.

    2018-05-01

    Enthalpies of the dissolution of DL-α-alanylglycine (AlaGly), DL-α-alanyl-DL-α-alanine (AlaAla), DL-α-alanyl-DL-α-valine (AlaVal), and DL-α-alanyl-DL-norleucine (AlaNln) in an aqueous solution of sodium dodecyl sulfate (SDS) at SDS concentration of m = 0-0.07 mol kg-1 and temperature T = 298.15 K are measured via calorimetry. The standard values of the enthalpy of dissolution (Δsol H m ) and the transfer of dipeptides (Δtr H m ) from water to aqueous SDS solutions are calculated using the experimental data. The dependences of Δsol H m and Δtr H m the SDS concentration at a constant concentration of dipeptide are established. Thermochemical characteristics of the transfer of AlaGly, AlaAla, AlaVal, and AlaNln in the investigated range of SDS concentrations are compared. The results are interpreted by considering ion-ion, ion-polar, and hydrophobic-hydrophobic interactions between SDS and dipeptide molecules.

  1. The structure and energetic of AlAsn (n = 1-15) clusters: A first-principles study

    International Nuclear Information System (INIS)

    Guo Ling

    2010-01-01

    Geometric structures of AlAs n (n = 1-15) clusters are reported. The binding energy, dissociation energy, stability of these clusters are studied with the three-parameter hybrid generalized gradient approximation (GGA) due to Becke-Lee-Yang-Parr (B3LYP). Ionization potentials, electron affinities, hardness, and static polarizabilities are calculated for the ground-state structures within the same method. The growth pattern for AlAs n (n = 6-15) clusters is Al-substituted pure As n+1 clusters and it keeps the similar frameworks of the most stable As n+1 clusters (for example AlAs 6 , AlAs 7 , AlAs 9 , AlAs 14 and AlAs 15 clusters) or capping the different sides of the low-lying geometry of As n clusters (for example AlAs 8 , AlAs 10 , AlAs 11 , and AlAs 12 clusters). The Al atom prefer to occupy a peripheral position for n n (n = 1-5, 13) clusters. The odd-even oscillations from AlAs n (n = 5-15) in the dissociation energy, the second-order energy differences, the HOMO-LUMO gaps, the electron affinity, and the hardness are more pronounced. The stability analysis based on the energies clearly shows the AlAs n clusters from n = 5 with an even number of valence electrons are more stable than clusters with odd number of valence electrons.

  2. Two Patients with Severe Short Stature due to a FBN1 Mutation (p.Ala1728Val) with a Mild Form of Acromicric Dysplasia.

    Science.gov (United States)

    de Bruin, Christiaan; Finlayson, Courtney; Funari, Mariana F A; Vasques, Gabriela A; Lucheze Freire, Bruna; Lerario, Antonio M; Andrew, Melissa; Hwa, Vivian; Dauber, Andrew; Jorge, Alexander A L

    2016-01-01

    Acromicric dysplasia (AD) and geleophysic dysplasia 2 (GD2) belong to the category of acromelic dysplasia syndromes, consisting of severe short stature, short hands and feet and skin thickening. Both can result from missense mutations in the transforming growth factor beta 5 domain of the fibrillin-1 gene (FBN1). Two patients (P1 age 10, and P2 age 7) from unrelated families presented to their endocrinologist with severe short stature (approx. -4 SDS). They were otherwise asymptomatic and only had mild facial dysmorphisms. Extensive endocrine work-up did not reveal an underlying etiology. Exome sequencing was performed in each family. Exome sequencing identified the presence of the same heterozygous missense variant c.C5183T (p.Ala1728Val) in the FBN1 gene in both P1 and P2. This variant was previously reported in a patient with GD2 and associated cardiac valvulopathy and hepatomegaly. Detailed clinical re-examination, cardiac and skeletal imaging did not reveal any abnormalities in P1 or P2 other than mild hip dysplasia. This report broadens the phenotypic spectrum of growth disorders associated with FBN1 mutations. Identical mutations give rise to a wide phenotypic spectrum, ranging from isolated short stature to a more classic picture of GD2 with cardiac involvement, distinct facial dysmorphisms and various skeletal anomalies. © 2016 S. Karger AG, Basel.

  3. The UCP2 -866G/A, Ala55Val and UCP3 -55C/T polymorphisms are associated with premature coronary artery disease and cardiovascular risk factors in Mexican population.

    Science.gov (United States)

    Gamboa, Ricardo; Huesca-Gómez, Claudia; López-Pérez, Vanessa; Posadas-Sánchez, Rosalinda; Cardoso-Saldaña, Guillermo; Medina-Urrutia, Aida; Juárez-Rojas, Juan Gabriel; Soto, María Elena; Posadas-Romero, Carlos; Vargas-Alarcón, Gilberto

    2018-05-21

    We examined the role of UCP gene polymorphisms as susceptibility markers for premature coronary artery disease (pCAD). The UCP2 Ala55Val (C/T rs660339), UCP2 -866G/A (rs659366), and UCP3 -55C/T (rs1800849) polymorphisms were genotyped in 948 patients with pCAD, and 763 controls. The distribution of the UCP2 A55V (C/T rs660339) and UCP3 -55 (rs1800849) was similar in patients and controls. However, under a recessive model, the UCP2 -866 (rs659366) A allele was associated with increased risk of developing pCAD (OR = 1.43, Pc = 0.003). On the other hand, patients with pCAD and UCP2 A55V (rs660339) TT showed high levels of visceral abdominal fat (VAF) (Pc = 0.002), low levels of subcutaneous abdominal fat (SAF) (Pc = 0.001) and high VAT/SAT ratio (Pc cardiovascular risk factors.

  4. IAA-Ala Resistant3, an evolutionarily conserved target of miR167, mediates Arabidopsis root architecture changes during high osmotic stress

    KAUST Repository

    Kinoshita, Natsuko

    2012-09-01

    The functions of microRNAs and their target mRNAs in Arabidopsis thaliana development have been widely documented; however, roles of stress-responsive microRNAs and their targets are not as well understood. Using small RNA deep sequencing and ATH1 microarrays to profile mRNAs, we identified IAA-Ala Resistant3 (IAR3) as a new target of miR167a. As expected, IAR3 mRNA was cleaved at the miR167a complementary site and under high osmotic stress miR167a levels decreased, whereas IAR3 mRNA levels increased. IAR3 hydrolyzes an inactive form of auxin (indole-3-acetic acid [IAA]-alanine) and releases bioactive auxin (IAA), a central phytohormone for root development. In contrast with the wild type, iar3 mutants accumulated reduced IAA levels and did not display high osmotic stress-induced root architecture changes. Transgenic plants expressing a cleavage-resistant form of IAR3 mRNA accumulated high levels of IAR3 mRNAs and showed increased lateral root development compared with transgenic plants expressing wild-type IAR3. Expression of an inducible noncoding RNA to sequester miR167a by target mimicry led to an increase in IAR3 mRNA levels, further confirming the inverse relationship between the two partners. Sequence comparison revealed the miR167 target site on IAR3 mRNA is conserved in evolutionarily distant plant species. Finally, we showed that IAR3 is required for drought tolerance. © 2012 American Society of Plant Biologists. All rights reserved.

  5. IAA-Ala Resistant3, an evolutionarily conserved target of miR167, mediates Arabidopsis root architecture changes during high osmotic stress

    KAUST Repository

    Kinoshita, Natsuko; Wang, Huan; Kasahara, Hiroyuki; Liu, Jun; MacPherson, Cameron R.; Machida, Yasunori; Kamiya, Yuji; Hannah, Matthew A.; Chuaa, Nam Hai

    2012-01-01

    The functions of microRNAs and their target mRNAs in Arabidopsis thaliana development have been widely documented; however, roles of stress-responsive microRNAs and their targets are not as well understood. Using small RNA deep sequencing and ATH1 microarrays to profile mRNAs, we identified IAA-Ala Resistant3 (IAR3) as a new target of miR167a. As expected, IAR3 mRNA was cleaved at the miR167a complementary site and under high osmotic stress miR167a levels decreased, whereas IAR3 mRNA levels increased. IAR3 hydrolyzes an inactive form of auxin (indole-3-acetic acid [IAA]-alanine) and releases bioactive auxin (IAA), a central phytohormone for root development. In contrast with the wild type, iar3 mutants accumulated reduced IAA levels and did not display high osmotic stress-induced root architecture changes. Transgenic plants expressing a cleavage-resistant form of IAR3 mRNA accumulated high levels of IAR3 mRNAs and showed increased lateral root development compared with transgenic plants expressing wild-type IAR3. Expression of an inducible noncoding RNA to sequester miR167a by target mimicry led to an increase in IAR3 mRNA levels, further confirming the inverse relationship between the two partners. Sequence comparison revealed the miR167 target site on IAR3 mRNA is conserved in evolutionarily distant plant species. Finally, we showed that IAR3 is required for drought tolerance. © 2012 American Society of Plant Biologists. All rights reserved.

  6. Effect of 5-aminolevulinic acid on erythropoiesis: A preclinical in vitro characterization for the treatment of congenital sideroblastic anemia

    International Nuclear Information System (INIS)

    Fujiwara, Tohru; Okamoto, Koji; Niikuni, Ryoyu; Takahashi, Kiwamu; Okitsu, Yoko; Fukuhara, Noriko; Onishi, Yasushi; Ishizawa, Kenichi; Ichinohasama, Ryo; Nakamura, Yukio; Nakajima, Motowo; Tanaka, Tohru; Harigae, Hideo

    2014-01-01

    Highlights: • Treatment with ALA induces erythroid differentiation of K562 cells. • Transportation of ALA into erythroid cells occurs predominantly via SLC36A1. • ALA restores defects in ALAS2 in human iPS cell-derived erythroblasts. • ALA may represent a novel therapeutic option for CSA caused by ALAS2 mutations. - Abstract: Congenital sideroblastic anemia (CSA) is a hereditary disorder characterized by microcytic anemia and bone marrow sideroblasts. The most common form of CSA is attributed to mutations in the X-linked gene 5-aminolevulinic acid synthase 2 (ALAS2). ALAS2 is a mitochondrial enzyme, which utilizes glycine and succinyl-CoA to form 5-aminolevulinic acid (ALA), a crucial precursor in heme synthesis. Therefore, ALA supplementation could be an effective therapeutic strategy to restore heme synthesis in CSA caused by ALAS2 defects. In a preclinical study, we examined the effects of ALA in human erythroid cells, including K562 cells and human induced pluripotent stem cell-derived erythroid progenitor (HiDEP) cells. ALA treatment resulted in significant dose-dependent accumulation of heme in the K562 cell line. Concomitantly, the treatment substantially induced erythroid differentiation as assessed using benzidine staining. Quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis confirmed significant upregulation of heme-regulated genes, such as the globin genes [hemoglobin alpha (HBA) and hemoglobin gamma (HBG)] and the heme oxygenase 1 (HMOX1) gene, in K562 cells. Next, to investigate the mechanism by which ALA is transported into erythroid cells, quantitative RT-PCR analysis was performed on previously identified ALA transporters, including solute carrier family 15 (oligopeptide transporter), member (SLC15A) 1, SLC15A2, solute carrier family 36 (proton/amino acid symporter), member (SLC36A1), and solute carrier family 6 (neurotransmitter transporter), member 13 (SLC6A13). Our analysis revealed that SLC36A1 was abundantly

  7. Effect of 5-aminolevulinic acid on erythropoiesis: A preclinical in vitro characterization for the treatment of congenital sideroblastic anemia

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Tohru [Department of Hematology and Rheumatology, Tohoku University Graduate School, Sendai (Japan); Department of Molecular Hematology/Oncology, Tohoku University Graduate School, Sendai (Japan); Okamoto, Koji; Niikuni, Ryoyu [Department of Hematology and Rheumatology, Tohoku University Graduate School, Sendai (Japan); Takahashi, Kiwamu [SBI Pharmaceuticals Co., Ltd., Tokyo (Japan); Okitsu, Yoko; Fukuhara, Noriko; Onishi, Yasushi [Department of Hematology and Rheumatology, Tohoku University Graduate School, Sendai (Japan); Ishizawa, Kenichi [Department of Hematology and Rheumatology, Tohoku University Graduate School, Sendai (Japan); Clinical Research, Innovation and Education Center, Tohoku University Hospital, Sendai (Japan); Ichinohasama, Ryo [Department of Hematopathology, Tohoku University Graduate School, Sendai (Japan); Nakamura, Yukio [Cell Engineering Division, RIKEN BioResource Center, Tsukuba, Ibaraki (Japan); Nakajima, Motowo; Tanaka, Tohru [SBI Pharmaceuticals Co., Ltd., Tokyo (Japan); Harigae, Hideo, E-mail: harigae@med.tohoku.ac.jp [Department of Hematology and Rheumatology, Tohoku University Graduate School, Sendai (Japan); Department of Molecular Hematology/Oncology, Tohoku University Graduate School, Sendai (Japan)

    2014-11-07

    Highlights: • Treatment with ALA induces erythroid differentiation of K562 cells. • Transportation of ALA into erythroid cells occurs predominantly via SLC36A1. • ALA restores defects in ALAS2 in human iPS cell-derived erythroblasts. • ALA may represent a novel therapeutic option for CSA caused by ALAS2 mutations. - Abstract: Congenital sideroblastic anemia (CSA) is a hereditary disorder characterized by microcytic anemia and bone marrow sideroblasts. The most common form of CSA is attributed to mutations in the X-linked gene 5-aminolevulinic acid synthase 2 (ALAS2). ALAS2 is a mitochondrial enzyme, which utilizes glycine and succinyl-CoA to form 5-aminolevulinic acid (ALA), a crucial precursor in heme synthesis. Therefore, ALA supplementation could be an effective therapeutic strategy to restore heme synthesis in CSA caused by ALAS2 defects. In a preclinical study, we examined the effects of ALA in human erythroid cells, including K562 cells and human induced pluripotent stem cell-derived erythroid progenitor (HiDEP) cells. ALA treatment resulted in significant dose-dependent accumulation of heme in the K562 cell line. Concomitantly, the treatment substantially induced erythroid differentiation as assessed using benzidine staining. Quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis confirmed significant upregulation of heme-regulated genes, such as the globin genes [hemoglobin alpha (HBA) and hemoglobin gamma (HBG)] and the heme oxygenase 1 (HMOX1) gene, in K562 cells. Next, to investigate the mechanism by which ALA is transported into erythroid cells, quantitative RT-PCR analysis was performed on previously identified ALA transporters, including solute carrier family 15 (oligopeptide transporter), member (SLC15A) 1, SLC15A2, solute carrier family 36 (proton/amino acid symporter), member (SLC36A1), and solute carrier family 6 (neurotransmitter transporter), member 13 (SLC6A13). Our analysis revealed that SLC36A1 was abundantly

  8. Enhancement techniques for improving 5-aminolevulinic acid delivery through the skin

    Directory of Open Access Journals (Sweden)

    Li-Wen Zhang

    2011-03-01

    Full Text Available Photodynamic therapy (PDT is a popular technique for skin cancer treatment. Protoporphyrin IX, which is a photosensitizing agent, converted enzymatically from the prodrug 5-aminolevulinic acid (ALA, is used as a photosensitizer in PDT for cancer. However, ALA penetrates with difficulty through intact skin; therefore, improving delivery systems for ALA in the skin will play an important role in ALA-PDT. Enhancement of ALA skin penetration can be achieved by physical methods, such as iontophoresis, laser, microneedles, ultrasound, and by adding chemical penetration enhancers, such as, dimethyl sulfoxide, oleic acid, and others, whereas some researches used lipophilic ALA derivatives and different vehicles to improve the transdermal delivery of ALA. This review introduces several enhancement techniques for increasing ALA permeation through the skin.

  9. 5-Aminolevulinic acid protects against cisplatin-induced nephrotoxicity without compromising the anticancer efficiency of cisplatin in rats in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Yoshio Terada

    Full Text Available Nephrotoxicity is a frequent and major limitation in cisplatin (CDDP-based chemotherapy. 5-Aminolevulinic acid (ALA is widely distributed in animal cells, and it is a precursor of tetrapyrole compounds such as heme that is fundamentally important in aerobic energy metabolism. The aim of this study is to evaluate the protective role of ALA in CDDP-induced acute kidney injury (AKI.We used CDDP-induced AKI rat model and cultured renal tubular cells (NRK-52E. We divided four groups of rats: control, CDDP only, CDDP + ALA(post;(ALA 10 mg/kg + Fe in drinking water after CDDP, CDDP + ALA(pre & post.CDDP increased Cr up to 6.5 mg/dl, BUN up to 230 mg/dl, and ALA significantly reduced these changes. ALA ameliorates CDDP-induced morphological renal damages, and reduced tubular apoptosis evaluated by TUNEL staining and cleaved caspase 3. Protein and mRNA levels of ATP5α, complex(COX IV, UCP2, PGC-1α in renal tissue were significantly decreased by CDDP, and ALA ameliorates reduction of these enzymes. In contrast, Heme Oxigenase (HO-1 level is induced by CDDP treatment, and ALA treatment further up-regulates HO-1 levels. In NRK-52E cells, the CDDP-induced reduction of protein and mRNA levels of mitochondrial enzymes was significantly recovered by ALA + Fe. CDDP-induced apoptosis were ameliorated by ALA + Fe treatment. Furthermore, we evaluated the size of transplantated bladder carcinoma to the rat skin, and ALA did not change the anti cancer effects of CDDP.These data suggested that the protective role of ALA in cisplatin-induced AKI is via protection of mitochondrial viability and prevents tubular apoptosis. Also there are no significant effects of ALA on anticancer efficiency of CDDP in rats. Thus, ALA has the potential to prevent CDDP nephrotoxicity without compromising its anticancer efficacy.

  10. Popmuusika / Janar Ala

    Index Scriptorium Estoniae

    Ala, Janar, 1979-

    2006-01-01

    Uutest heliplaatidest Kode 9 And Spaceape "Memories Of The Future", Nitrous "Dominant Force", Jamelia "Walk With Me", Sparklehorse "dream For Light Years", Mocky "Navy Brown Blues", Pat Metheny & Brad Mehldau, Enigma "A Posteriori"

  11. δ-Aminolevulinic acid cytotoxic effects on human hepatocarcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    De Siervi, Adriana; Vazquez, Elba S; Rezaval, Carolina; Rossetti, María V; Batlle, Alcira M del [Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), Argentine National Research Council (CONICET), Department of Biological Chemistry, FCEN, University of Buenos Aires (Argentina)

    2002-01-01

    Acute Intermittent Porphyria is a genetic disorder of heme metabolism, characterized by increased levels of porphyrin precursors, δ-aminolevulinic acid (ALA) and porphobilinogen (PBG). ALA has been reported to generate reactive oxygen species and to cause oxidative damage to proteins, subcellular structures and DNA. It is known that oxidative stress can induce apoptosis. The aim of this work was to study the cytotoxic effect of ALA on two hepatocarcinoma cell lines. We have determined the impact of ALA on HEP G2 and HEP 3B hepatocarcinoma cell lines survival as measured by the MTT assay. ALA proved to be cytotoxic in both cell lines however; HEP G2 was more sensitive to ALA than HEP 3B. Addition of hemin or glucose diminished ALA cytotoxicity in HEP G2 cells; instead it was enhanced in HEP 3B cells. Because apoptosis is usually associated with DNA fragmentation, the DNA of ALA treated and untreated cells were analyzed. The characteristic pattern of DNA fragmentation ladders was observed in ALA treated cells. To elucidate the mechanisms of ALA induced apoptosis, we examined its effect on p53 expression. No changes in p53 mRNA levels were observed after exposure of both cell lines to ALA for 24 h. CDK2 and CDK4 protein levels were reduced after ALA treatment at physiological concentrations.

  12. δ-Aminolevulinic acid cytotoxic effects on human hepatocarcinoma cell lines

    Directory of Open Access Journals (Sweden)

    del Batlle Alcira M

    2002-03-01

    Full Text Available Abstract Background Acute Intermittent Porphyria is a genetic disorder of heme metabolism, characterized by increased levels of porphyrin precursors, δ-aminolevulinic acid (ALA and porphobilinogen (PBG. ALA has been reported to generate reactive oxygen species and to cause oxidative damage to proteins, subcellular structures and DNA. It is known that oxidative stress can induce apoptosis. The aim of this work was to study the cytotoxic effect of ALA on two hepatocarcinoma cell lines. Results We have determined the impact of ALA on HEP G2 and HEP 3B hepatocarcinoma cell lines survival as measured by the MTT assay. ALA proved to be cytotoxic in both cell lines however; HEP G2 was more sensitive to ALA than HEP 3B. Addition of hemin or glucose diminished ALA cytotoxicity in HEP G2 cells; instead it was enhanced in HEP 3B cells. Because apoptosis is usually associated with DNA fragmentation, the DNA of ALA treated and untreated cells were analyzed. The characteristic pattern of DNA fragmentation ladders was observed in ALA treated cells. To elucidate the mechanisms of ALA induced apoptosis, we examined its effect on p53 expression. No changes in p53 mRNA levels were observed after exposure of both cell lines to ALA for 24 h. CDK2 and CDK4 protein levels were reduced after ALA treatment at physiological concentrations.

  13. δ-Aminolevulinic acid cytotoxic effects on human hepatocarcinoma cell lines

    International Nuclear Information System (INIS)

    De Siervi, Adriana; Vazquez, Elba S; Rezaval, Carolina; Rossetti, María V; Batlle, Alcira M del

    2002-01-01

    Acute Intermittent Porphyria is a genetic disorder of heme metabolism, characterized by increased levels of porphyrin precursors, δ-aminolevulinic acid (ALA) and porphobilinogen (PBG). ALA has been reported to generate reactive oxygen species and to cause oxidative damage to proteins, subcellular structures and DNA. It is known that oxidative stress can induce apoptosis. The aim of this work was to study the cytotoxic effect of ALA on two hepatocarcinoma cell lines. We have determined the impact of ALA on HEP G2 and HEP 3B hepatocarcinoma cell lines survival as measured by the MTT assay. ALA proved to be cytotoxic in both cell lines however; HEP G2 was more sensitive to ALA than HEP 3B. Addition of hemin or glucose diminished ALA cytotoxicity in HEP G2 cells; instead it was enhanced in HEP 3B cells. Because apoptosis is usually associated with DNA fragmentation, the DNA of ALA treated and untreated cells were analyzed. The characteristic pattern of DNA fragmentation ladders was observed in ALA treated cells. To elucidate the mechanisms of ALA induced apoptosis, we examined its effect on p53 expression. No changes in p53 mRNA levels were observed after exposure of both cell lines to ALA for 24 h. CDK2 and CDK4 protein levels were reduced after ALA treatment at physiological concentrations

  14. Impact of the Pro12Ala Polymorphism of the PPAR-Gamma 2 Gene on Metabolic and Clinical Characteristics in the Palestinian Type 2 Diabetic Patients

    Directory of Open Access Journals (Sweden)

    S. Ereqat

    2009-01-01

    Full Text Available Peroxisome proliferators activated receptor-gamma2 (PPARγ2 represents the transcriptional master regulator of adipocyte differentiation and therefore has been suggested as a candidate gene for obesity, insulin resistance, and dyslipidemia. The objective of the study was to investigate for the first time the potential association of the most common variant Pro12Ala (p.P12A substitution of the PPARγ2 gene with body mass index (BMI, blood pressure, fasting plasma glucose, plasma total cholesterol, LDL and HDL cholesterol, and plasma triglyceride in a sample of 202 (138 females and 64 male type 2 diabetic Palestinians. Genotyping of the PPARγ2 p.P12A polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP analysis. The A12 allele was associated with lower fasting plasma glucose (P=.03 but had no influence on blood pressure, BMI, or other metabolic parameters. In obese patients, the p.P12A substitution was associated with elevated total plasma cholesterol levels (P=.02 and a tendency toward increased LDL cholesterol level (P=.06. In conclusion, the p.P12A variant of the PPARγ2 may influence cardiovascular risk through effects on lipid metabolism in obese T2D Palestinian patients.

  15. Single-nucleotide polymorphisms in peroxisome proliferator ...

    Indian Academy of Sciences (India)

    Prakash

    1Molecular Biology Unit, National Institute of Nutrition, Jamai Osmania, Hyderabad 500 .... to stimulate several pro-inflammatory cytokines including ... were found to be lower in Ala carriers (Pro/Ala+Ala/Ala ...... or skeletal muscle; Biochem.

  16. The nuclear debate in Sweden

    International Nuclear Information System (INIS)

    Sandstrom, S.

    1976-01-01

    The current preoccupation with conservation among widespread factions in the Swedish populace dates back to the 1960's. Co-ordinated by a central organisation, Miljocentrum, a variety of environmental protection groups concentrated at first on such things as fluorine in drinking water, colouring matter in foodstuffs, poisonous industrial effluents such as phosphates in detergents and mercury. In the early 1970's attention became more and more directed against nuclear energy, the arguments generally following the same lines as the U.S. debate but with some time lag. Nuclear energy has since become the focal point of environmental protest both among the public and within parliament. Public opposition to a reprocessing plant site at Sannas may lead to a decision to opt for a 'fuel cycle centre' on a site suitable for final disposal of high level radioactive waste. (author)

  17. A novel c.1037C > G (p.Ala346Gly) mutation in TP63 as cause of the ectrodactyly-ectodermal dysplasia and cleft lip/palate (EEC) syndrome

    Science.gov (United States)

    Alves, Leandro Ucela; Pardono, Eliete; Otto, Paulo A.; Mingroni Netto, Regina Célia

    2015-01-01

    Ectrodactyly – ectodermal dysplasia and cleft lip/palate (EEC) syndrome (OMIM 604292) is a rare disorder determined by mutations in the TP63 gene. Most cases of EEC syndrome are associated to mutations in the DNA binding domain (DBD) region of the p63 protein. Here we report on a three-generation Brazilian family with three individuals (mother, son and grandfather) affected by EEC syndrome, determined by a novel mutation c.1037C > G (p.Ala346Gly). The disorder in this family exhibits a broad spectrum of phenotypes: two individuals were personally examined, one presenting the complete constellation of EEC syndrome manifestations and the other presenting an intermediate phenotype; the third affected, a deceased individual not examined personally and referred to by his daughter, exhibited only the split-hand/foot malformation (SHFM). Our findings contribute to elucidate the complex phenotype-genotype correlations in EEC syndrome and other related TP63-mutation syndromes. The possibility of the mutation c.1037C > G being related both to acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome and SHFM is also raised by the findings here reported. PMID:25983622

  18. Alanine aminotransferase variants conferring diverse NUE phenotypes in Arabidopsis thaliana.

    Science.gov (United States)

    McAllister, Chandra H; Good, Allen G

    2015-01-01

    Alanine aminotransferase (AlaAT, E.C. 2.6.1.2), is a pyridoxal-5'-phosphate-dependent (PLP) enzyme that catalyzes the reversible transfer of an amino group from alanine to 2-oxoglutarate to produce glutamate and pyruvate, or vice versa. It has been well documented in both greenhouse and field studies that tissue-specific over-expression of AlaAT from barley (Hordeum vulgare, HvAlaAT) results in a significant increase in plant NUE in both canola and rice. While the physical phenotypes associated with over-expression of HvAlaAT have been well characterized, the role this enzyme plays in vivo to create a more N efficient plant remains unknown. Furthermore, the importance of HvAlaAT, in contrast to other AlaAT enzyme homologues in creating this phenotype has not yet been explored. To address the role of AlaAT in NUE, AlaAT variants from diverse sources and different subcellular locations, were expressed in the wild-type Arabidopsis thaliana Col-0 background and alaat1;2 (alaat1-1;alaat2-1) knockout background in various N environments. The analysis and comparison of both the physical and physiological properties of AlaAT over-expressing transgenic plants demonstrated significant differences between plants expressing the different AlaAT enzymes under different external conditions. This analysis indicates that the over-expression of AlaAT variants other than HvAlaAT in crop plants could further increase the NUE phenotype(s) previously observed.

  19. Low-Centred Polygons and Alas-Like Basins as Geological Markers of Warming Trends Late in Mars' History

    Science.gov (United States)

    Soare, R. J.; Conway, S. J.; Godin, E.; Osinski, G.; Hawkswell, J.; Bina, A.

    2017-12-01

    Expansive assemblages of low/high centred (ice-wedge) polygons and (polygonised) flat-floored thermokarst-basins (alases) are ubiquitous on Earth where the permafrost is continuous, metres to decametres-thick and ice rich, i.e. the Tuktoyaktuk Coastlands of northern Canada and the Yamal Peninsula of eastern Russia. These assemblages are geological bellwethers of transient and on occasion, long-term rises of sub-aerial and thaw-generating mean temperatures, for two principal reasons. First, high-centred (ice-wedge) polygons evolve from low-centred (ice-wedge) polygons when ice wedges that have aggraded and uplift overlying sediments above the elevation datum at the polygon centres, degrade, by thaw, and induce the loss of elevation below that datum. Second, thermokarst terrain comprises sediments whose pore volume is exceeded by the presence of water ice. A thermokarst basin (an alas) forms if and only when this ice undergoes thermal destabilisation and where thaw-generated meltwater is lost by evaporation or drainage. Spatially-associated and morphologically-similar assemblages of polygons and basins are commonplace throughout the mid-latitudes of eastern Utopia Planitia (UP), Mars. Under current conditions of extreme aridity, low atmospheric-pressure and frigid mean-temperatures, the widespread formation of ice-rich terrain by freeze-thaw cycling, let alone of near-surface ice-wedges and/or thermokarst basins, seems implausible. Against this environmental backdrop, sublimation seemingly stands alone in being able to revise ice-rich landscapes. However, multiple strands of data point to the possible periglacial-assemblages (PPAs) being youthful but not current in their formation. First, the sub-regional and dark-toned terrain incised by the PPAs is cratered more densely than would be expected. Second, the PPAs reside at a lower relative and absolute elevation than a light-toned and region-wide latitude-dependent mantle that is generally thought to be very recent in

  20. Content of alpha-linolenic acid in human atrial tissue correlates with plasma levels of alpha-linolenic acid

    DEFF Research Database (Denmark)

    Gu, Jiwei; Eschen, Rikke Bülow; Andreasen, Annette

    and ALA levels were compared by the Pearson correlation coefficient. Results: There was a statistical significant correlation (r=0.54, 95% confidence interval: 0.30-0.71) between levels of ALA in plasma phospholipids and atrial tissue. Conclusion: The content of ALA in plasma phospholipids is a short term...... indicator of intake of ALA and this correlated well with the content of ALA in atrial tissue. Atrial tissue is not readily available but this study shows that determination of plasma phospholipids may be useful to further investigate an antiarrhythmic effect of ALA on AF....

  1. Treatment with α-Lipoic Acid over 16 Weeks in Type 2 Diabetic Patients with Symptomatic Polyneuropathy Who Responded to Initial 4-Week High-Dose Loading

    Directory of Open Access Journals (Sweden)

    Hector Garcia-Alcala

    2015-01-01

    Full Text Available Effective treatment of diabetic sensorimotor polyneuropathy remains a challenge. To assess the efficacy and safety of α-lipoic acid (ALA over 20 weeks, we conducted a multicenter randomized withdrawal open-label study, in which 45 patients with type 2 diabetes and symptomatic polyneuropathy were initially treated with ALA (600 mg tid for 4 weeks (phase 1. Subsequently, responders were randomized to receive ALA (600 mg qd; n=16 or to ALA withdrawal (n=17 for 16 weeks (phase 2. During phase 1, the Total Symptom Score (TSS decreased from 8.9 ± 1.8 points to 3.46 ± 2.0 points. During phase 2, TSS improved from 3.7 ± 1.9 points to 2.5 ± 2.5 points in the ALA treated group (p<0.05 and remained unchanged in the ALA withdrawal group. The use of analgesic rescue medication was higher in the ALA withdrawal group than ALA treated group (p<0.05. In conclusion, in type 2 diabetic patients with symptomatic polyneuropathy who responded to initial 4-week high-dose (600 mg tid administration of ALA, subsequent treatment with ALA (600 mg qd over 16 weeks improved neuropathic symptoms, whereas ALA withdrawal was associated with a higher use of rescue analgesic drugs. This trial is registered with ClinicalTrials.gov Identifier: NCT02439879.

  2. Purification and characterization of elastase from the pyloric caeca of rainbow trout (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Bassompierre, Marc; Nielsen, Henrik Hauch; Børresen, Torger

    1993-01-01

    1. An elastase-like enzyme was purified from the pyloric caeca of rainbow trout by hydrophobic interaction, cation exchange and gel-filtration chromatography. 2. The approximate molecular weight of the elastase was 27 kDa and the isoelectric point was remarkably basic. 3. The pH optimum of this e......1. An elastase-like enzyme was purified from the pyloric caeca of rainbow trout by hydrophobic interaction, cation exchange and gel-filtration chromatography. 2. The approximate molecular weight of the elastase was 27 kDa and the isoelectric point was remarkably basic. 3. The pH optimum...... of this enzyme was 8.0, when assayed with Succinyl-Ala-Ala-Ala-p-Nitroanilide. 4. When assayed with Succinyl-Ala-Ala-Ala-p-Nitroanilide, the enzyme activity had a temperature optimum of 45 degree C, and the enzyme was stable up to this temperature. 5. The trout elastase exhibited a higher specific activity than...... porcine elastase against Succinyl-Ala-Ala-Ala-p-Nitroanilide and elastin-orcein. 6. The trout elastase was inhibited by elastatinal, PMSF, TPCK, SBTI and Bowman-Birk inhibitor....

  3. Parallel β-Sheet Structure of Alanine Tetrapeptide in the Solid State As Studied by Solid-State NMR Spectroscopy.

    Science.gov (United States)

    Asakura, Tetsuo; Horiguchi, Kumiko; Aoki, Akihiro; Tasei, Yugo; Naito, Akira

    2016-09-01

    The structural analysis of alanine oligopeptides is important for understanding the crystalline region in silks from spiders and wild silkworms and also the mechanism of cellular toxicity of human diseases arising from expansion in polyalanine sequences. The atomic-level structures of alanine tripeptide and tetrapeptide with antiparallel β-sheet structures (AP-Ala3 and AP-Ala4, respectively) together with alanine tripeptide with parallel β-sheet structures (P-Ala3) have been determined, but alanine tetrapeptide with a parallel β-sheet structure (P-Ala4) has not been reported yet. In this article, first, we established the preparation protocol of P-Ala4 from more stable AP-Ala4. Second, complete assignments of the (13)C, (15)N, and (1)H solid-state NMR spectra were performed with (13)C- and (15)N-labeled Ala4 samples using several solid-state NMR techniques. Then, the structural constraints were obtained, for example, the amide proton peaks of P-Ala4 in the (1)H double-quantum magic-angle spinning NMR spectrum were heavily overlapped and observed at about 7.4 ppm, which was a much higher field than that of 8.7-9.1 ppm observed for AP-Ala4, indicating that the intermolecular hydrogen-bond lengths across strands (N-H···O═C) were considerably longer for P-Ala4, that is, 2.21-2.34 Å, than those reported for AP-Ala4, that is, 1.8-1.9 Å. The structural model was proposed for P-Ala4 by NMR results and MD calculations.

  4. Determination of Noncovalent Binding Using a Continuous Stirred Tank Reactor as a Flow Injection Device Coupled to Electrospray Ionization Mass Spectrometry

    Science.gov (United States)

    Santos, Inês C.; Waybright, Veronica B.; Fan, Hui; Ramirez, Sabra; Mesquita, Raquel B. R.; Rangel, António O. S. S.; Fryčák, Petr; Schug, Kevin A.

    2015-07-01

    Described is a new method based on the concept of controlled band dispersion, achieved by hyphenating flow injection analysis with ESI-MS for noncovalent binding determinations. A continuous stirred tank reactor (CSTR) was used as a FIA device for exponential dilution of an equimolar host-guest solution over time. The data obtained was treated for the noncovalent binding determination using an equimolar binding model. Dissociation constants between vancomycin and Ac-Lys(Ac)-Ala-Ala-OH peptide stereoisomers were determined using both the positive and negative ionization modes. The results obtained for Ac- L-Lys(Ac)- D-Ala- D-Ala (a model for a Gram-positive bacterial cell wall) binding were in reasonable agreement with literature values made by other mass spectrometry binding determination techniques. Also, the developed method allowed the determination of dissociation constants for vancomycin with Ac- L-Lys(Ac)- D-Ala- L-Ala, Ac- L-Lys(Ac)- L-Ala- D-Ala, and Ac- L-Lys(Ac)- L-Ala- L-Ala. Although some differences in measured binding affinities were noted using different ionization modes, the results of each determination were generally consistent. Differences are likely attributable to the influence of a pseudo-physiological ammonium acetate buffer solution on the formation of positively- and negatively-charged ionic complexes.

  5. Modulation of Colorectal Cancer Risk by Polymorphisms in 51Gln/His, 64Ile/Val, and 148Asp/Glu of APEX Gene; 23Gly/Ala of XPA Gene; and 689Ser/Arg of ERCC4 Gene

    Directory of Open Access Journals (Sweden)

    L. Dziki

    2017-01-01

    Full Text Available Polymorphisms in DNA repair genes may affect the activity of the BER (base excision repair and NER (nucleotide excision repair systems. Using DNA isolated from blood taken from patients (n=312 and a control group (n=320 with CRC, we have analyzed the polymorphisms of selected DNA repair genes and we have demonstrated that genotypes 51Gln/His and 148Asp/Glu of APEX gene and 23Gly/Ala of XPA gene may increase the risk of colorectal cancer. At the same time analyzing the gene-gene interactions, we suggest the thesis that the main factor to be considered when analyzing the impact of polymorphisms on the risk of malignant transformation should be intergenic interactions. Moreover, we are suggesting that some polymorphisms may have impact not only on the malignant transformation but also on the stage of the tumor.

  6. A novel hemoglobin variant found on the α1 chain: Hb KSVGH (HBA1: p.Lys57_Gly58insSerHisGlySerAlaGlnValLys).

    Science.gov (United States)

    Wang, Mei-Chun; Tsai, Kuo-Wang; Chu, Chih-Hsun; Yu, Ming-Sun; Lam, Hing-Chung

    2015-01-01

    Glycosylated hemoglobin (Hb A1C) is a crucial indicator for the long-term control and the diagnosis of diabetes. However, the presence of hemoglobin (Hb) variants may affect the measured value of Hb A1C and result in an abnormal graph trend and inconsistency between the clinical blood sugar test and Hb A1C values. In this study, laboratory data of 41,267 patients with diabetes were collected. The Hb A1C levels and the graph results were examined. We identified 74 cases containing abnormal Hb A1C graph trends. The conducted blood cell counts and capillary Hb electrophoresis were used to analyze Hb variants. We also determined gene variation for the Hb variants by a sequence approach. Fifteen different types of Hb variants were identified in this study. Among these, we found a novel variant in which the α1 subunit of Hb showed an insertion of 24 nucleotides (nts) between the 56th and 57th residues. We named this novel variant Hb Kaohsiung Veterans General Hospital (Hb KSVGH) (HBA1: p.Lys57_Gly58insSerHisGlySerAlaGlnValLys).

  7. Comparison of non-volatile umami components in chicken soup and chicken enzymatic hydrolysate.

    Science.gov (United States)

    Kong, Yan; Yang, Xiao; Ding, Qi; Zhang, Yu-Yu; Sun, Bao-Guo; Chen, Hai-Tao; Sun, Ying

    2017-12-01

    Umami taste is an important part to the taste of chicken. To isolate and identify non-volatile umami compounds, fractions from chicken soup and hydrolysate were prepared and analyzed. Amino acids were analyzed by amino acid analyzer. Organic acids and nucleotides were determined by ultra-performance liquid chromatography. Separation procedures utilizing ultrafiltration, Sephadex G-15 and reversed-phase high-performance liquid chromatography were used to isolate umami taste peptides. Combined with sensory evaluation and LC-Q-TOF-MS, the amino acid sequences of 12 oligopeptides were determined. The amount of taste compounds was higher in chicken enzymatic hydrolysate than that of chicken soup. Eight oligopeptides from chicken enzymatic hydrolysate were identified, including Ala-Asp, Ala-Met, His-Ser, Val-Glu, Ala-Glu, Asp-Ala-Gly, Glu-Asp and Ala-Glu-Ala. Four oligopeptides from chicken soup were identified, including Val-Thr, Ala-His, Ala-Phe and Thr-Glu. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Effects of metal ions on biomass and 5-aminolevulinic acid production in Rhodopseudomonas palustris wastewater treatment.

    Science.gov (United States)

    Liu, Shuli; Zhang, Guangming; Li, Jianzheng; Li, Xiangkun; Zhang, Jie

    2016-01-01

    This work investigated the effects of eight metal ions on Rhodopseudomonas palustris growth and 5-aminolevulinic acid (ALA) yield in wastewater treatment. Results show that metal ions (Mg(2+) of 15 mmol/L, Fe(2+) of 400 μmol/L, Co(2+) of 4 μmol/L, Ni(2+) of 8 μmol/L and Zn(2+) of 4 μmol/L) could effectively improve the chemical oxygen demand (COD) removal, Rp. palustris biomass and ALA yield. The highest ALA yield of 13.1 mg/g-biomass was achieved with Fe(2+) of 400 μmol/L. ALA yields were differentially increased under different metal ions in the following order: Fe(2+) group > Mg(2+) group > Co(2+) group = Ni(2+) group > Zn(2+) group = Mo(2+) group > control. Cu(2+) and Mn(2+) inhibited Rp. palustris growth and ALA production. Mechanism analysis revealed that metal ions changed ALA yields by influencing the activities of ALA synthetase and ALA dehydratase.

  9. Biosynthetic pathways to delta-aminolevulinic acid induced by blue light in the pigment mutant C-2A' of Scenedesmus obliquus

    International Nuclear Information System (INIS)

    Klein, O.; Senger, H.

    1978-01-01

    The X-ray induced mutant C-2A' of Scenedesmus obliquus grows heterotrophically but forms only traces of chlorophyll in the dark. Upon illumination, delta-aminolevulinic acid (ALA) is synthesized and chlorophyll is formed. These processes are blue light dependent and ceased immediately when the cells were transferred back into darkness. Addition of levulinic acid (LA) inhibited the light-dependent formation of chlorophyll and caused accumulation of ALA by competitive inhibition of the ALA dehydratase (EC. 4.2.1.24). By feeding specifically labelled 14 C precursors to the pigment mutant, inhibiting the ALA dehydratase with LA, accumulating, extracting and analyzing the ALA, two pathways leading towards ALA could be established: glycine and succinyl CoA can be condensed to ALA and the 5 carbon skeleton of glutamate can completely be incorporated into ALA via a second pathway. The glycine-succinyl CoA pathway dominated over the glutamate pathway, but both led to chlorophyll formation. (author)

  10. 5-Aminolevulinic Acid-Squalene Nanoassemblies for Tumor Photodetection and Therapy: In Vitro Studies

    Science.gov (United States)

    Babič, Andrej; Herceg, V.; Bastien, E.; Lassalle, H.-P.; Bezdetnaya, L.; Lange, Norbert

    2018-01-01

    Protoporphyrin IX (PpIX) as natural photosensitizer derived from administration of 5-aminolevulinic acid (5-ALA) has found clinical use for photodiagnosis and photodynamic therapy of several cancers. However, broader use of 5-ALA in oncology is hampered by its charge and polarity that result in its reduced capacity for passing biological barriers and reaching the tumor tissue. Advanced drug delivery platforms are needed to improve the biodistribution of 5-ALA. Here, we report a new approach for the delivery of 5-ALA. Squalenoylation strategy was used to covalently conjugate 5-ALA to squalene, a natural precursor of cholesterol. 5-ALA-SQ nanoassemblies were formed by self-assembly in water. The nanoassemblies were monodisperse with average size of 70 nm, polydispersity index of 0.12, and ζ-potential of + 36 mV. They showed good stability over several weeks. The drug loading of 5-ALA was very high at 26%. In human prostate cancer cells PC3 and human glioblastoma cells U87MG, PpIX production was monitored in vitro upon the incubation with nanoassemblies. They were more efficient in generating PpIX-induced fluorescence in cancer cells compared to 5-ALA-Hex at 1.0 to 3.3 mM at short and long incubation times. Compared to 5-ALA, they showed superior fluorescence performance at 4 h which was diminished at 24 h. 5-ALA-SQ presents a novel nano-delivery platform with great potential for the systemic administration of 5-ALA.

  11. Structure determination of a peptide model of the repeated helical domain in Samia cynthia ricini silk fibroin before spinning by a combination of advanced solid-state NMR methods.

    Science.gov (United States)

    Nakazawa, Yasumoto; Asakura, Tetsuo

    2003-06-18

    Fibrous proteins unlike globular proteins, contain repetitive amino acid sequences, giving rise to very regular secondary protein structures. Silk fibroin from a wild silkworm, Samia cynthia ricini, consists of about 100 repeats of alternating polyalanine (poly-Ala) regions of 12-13 residues in length and Gly-rich regions. In this paper, the precise structure of the model peptide, GGAGGGYGGDGG(A)(12)GGAGDGYGAG, which is a typical repeated sequence of the silk fibroin, was determined using a combination of three kinds of solid-state NMR studies; a quantitative use of (13)C CP/MAS NMR chemical shift with conformation-dependent (13)C chemical shift contour plots, 2D spin diffusion (13)C solid-state NMR under off magic angle spinning and rotational echo double resonance. The structure of the model peptide corresponding to the silk fibroin structure before spinning was determined. The torsion angles of the central Ala residue, Ala(19), in the poly-Ala region were determined to be (phi, psi) = (-59 degrees, -48 degrees ) which are values typically associated with alpha-helical structures. However, the torsion angles of the Gly(25) residue adjacent to the C-terminal side of the poly-Ala chain were determined to be (phi, psi) = (-66 degrees, -22 degrees ) and those of Gly(12) and Ala(13) residues at the N-terminal of the poly-Ala chain to be (phi, psi) = (-70 degrees, -30 degrees ). In addition, REDOR experiments indicate that the torsion angles of the two C-terminal Ala residues, Ala(23) and Ala(24), are (phi, psi) = (-66 degrees, -22 degrees ) and those of N-terminal two Ala residues, Ala(13) and Ala(14) are (phi, psi) = (-70 degrees, -30 degrees ). Thus, the local structure of N-terminal and C-terminal residues, and also the neighboring residues of alpha-helical poly-Ala chain in the model peptide is a more strongly wound structure than found in typical alpha-helix structures.

  12. Politics, the Media, and the Right to Know.

    Science.gov (United States)

    Berry, John; And Others

    1992-01-01

    Report on the 1992 American Library Association (ALA) conference discusses featured speakers, political actions of the ALA Council, guidelines on patron behavior, the resignation of ALA Executive Director Linda Crismond, and conference exhibits. Excerpts from an address by new ALA president Marilyn Miller on empowering people through libraries are…

  13. Identification of the enzymatic basis for δ-aminolevulinic acid auxotrophy in a hemA mutant of escherichia coli

    International Nuclear Information System (INIS)

    Avissar, Y.J.; Beale, S.I.

    1989-01-01

    The hemA mutation of Escherichia coli K-12 confers a requirement for δ-aminolevulinic acid (ALA). Cell extract prepared from the hemA strain SASX41B was incapable of producing ALA from either glutamate or glutamyl-tRNA, whereas extract of the hem + strain HB101 formed colorimetrically detectable amounts of ALA and transferred label from 1-[ 14 C]glutamate and 3,4-[ 3 H]glutamyl-tRNA to ALA. Extracts of both strains converted glutamate-1-semialdehyde to ALA and were capable of aminoacylating tRNA Glu . Glutamyl-tRNA formed by extracts of both strains could be converted to ALA by the extract of hem + cells. The extract of hemA cells did not convert glutamyl-tRNA formed by either strain to ALA. However, the hemA cell extract, when supplemented in vitro with glutamyl-tRNA dehydrogenase isolated from Chlorella vulgaris cells, formed about as much ALA as did the unsupplemented hem + cell extract. We conclude from these observations that the enzyme activity that is lacking in the ALA auxotrophic strain carrying the hemA mutation is that of glutamyl-tRNA dehydrogenase

  14. Studies on the decarboxylation of acetolactate in milk products

    OpenAIRE

    Mohr, Britta

    1997-01-01

    The effect of different parameters on the decarboxylation of acetolactate (ALA) to diacetyl and acetoin were studied. The distillation volume and the milk solids concentration had no significant effect on decarboxylation of ALA, whereas breakdown of ALA increased with decreasing pH and increasing temperature. Oxygenation increased diacetyl production from ALA, but diacetyl was lost from the model system. Oxygenation did not have an effect on acetoin production from ALA. Metal ions (Cu2+, Fe2+...

  15. Effect of alpha linolenic acid supplementation on serum prostate specific antigen (PSA): results from the alpha omega trial

    NARCIS (Netherlands)

    Brouwer, Ingeborg A.; Geleijnse, Johanna M.; Klaasen, Veronique M.; Smit, Liesbeth A.; Giltay, Erik J.; de Goede, Janette; Heijboer, Annemieke C.; Kromhout, Daan; Katan, Martijn B.

    2013-01-01

    Alpha linolenic acid (ALA) is the major omega-3 fatty acid in the diet. Evidence on health effects of ALA is not conclusive, but some observational studies found an increased risk of prostate cancer with higher intake of ALA. We examined the effect of ALA supplementation on serum concentrations of

  16. Potential efficacy of a delta 5-aminolevulinic acid thermosetting gel formulation for use in photodynamic therapy of lesions of the gastrointestinal tract.

    Science.gov (United States)

    Bourre, Ludovic; Thibaut, Sonia; Briffaud, Amelie; Lajat, Youenn; Patrice, Thierry

    2002-02-01

    Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX may play a role in the treatment of dysplastic Barrett's oesophagus. An ALA thermosetting gel Pluronic F-127) was developed and evaluated in an in vivo mouse model for potential use in PDT of Barrett's mucosa. In vitro studies of the influence of Pluronic F-127 percentage on thermosetting gel temperature, followed by the influence of ALA concentration on thermosetting temperature and ALA-gel stability as a function of time or temperature were studied. In vivo relationships between ALA doses and fluorescence were studied to determine the optimal concentration. Fluorescence measurement in vivo showed that ALA concentration and time had a nonlinear influence on protoporphyrin IX synthesis. For ALA-gel applications longer than 30 min a plateau fluorescence was reached, the maximum fluorescence being obtained after 4 h whatever the time of contact. The maximum intensity (2824 counts s(-1)) was found with 40 mg mL(-1) ALA-gel, and fluorescence intensities differed with time, reaching a maximum after 3-4 h. ALA-Pluronic F-127 is a suitable formulation for treatment of Barrett's oesophagus, allowing easy application in liquid form at 4 degrees C and good adhesion in the oesophagus in gel form, with efficient diffusion of ALA into treated mucosa. Copyright 2002 Elsevier Science Ltd.

  17. Adjunctive α-lipoic acid reduces weight gain compared with placebo at 12 weeks in schizophrenic patients treated with atypical antipsychotics: a double-blind randomized placebo-controlled study.

    Science.gov (United States)

    Kim, Nam Wook; Song, Yul-Mai; Kim, Eosu; Cho, Hyun-Sang; Cheon, Keun-Ah; Kim, Su Jin; Park, Jin Young

    2016-09-01

    α-Lipoic acid (ALA) has been reported to be effective in reducing body weight in rodents and obese patients. Our previous open trial showed that ALA may play a role in reducing weight gain in patients with schizophrenia on atypical antipsychotics. The present study evaluated the efficacy of ALA in reducing weight and BMI in patients with schizophrenia who had experienced significant weight gain since taking atypical antipsychotics. In a 12-week, double-blind randomized placebo-controlled study, 22 overweight and clinically stable patients with schizophrenia were randomly assigned to receive ALA or placebo. ALA was administered at 600-1800 mg, as tolerated. Weight, BMI, abdomen fat area measured by computed tomography, and metabolic values were determined. Adverse effects were also assessed to examine safety. Overall, 15 patients completed 12 weeks of treatment. There was significant weight loss and decreased visceral fat levels in the ALA group compared with the placebo group. There were no instances of psychopathologic aggravation or severe ALA-associated adverse effects. ALA was effective in reducing weight and abdominal obesity in patients with schizophrenia who had experienced significant weight gain since beginning an atypical antipsychotic regimen. Moreover, ALA was well tolerated throughout this study. ALA might play an important role as an adjunctive treatment in decreasing obesity in patients who take atypical antipsychotics.

  18. A severe connatal form of Pelizaeus Merzbacher disease in a Czech boy caused by a novel mutation (725C>A, Ala242Glu) at the 'jimpy(msd) codon' in the PLP gene.

    Science.gov (United States)

    Seeman, Pavel; Paderova, Katerina; Benes, Vladimir; Sistermans, Erik A

    2002-02-01

    Pelizaeus Merzbacher disease (PMD) is an X-linked recessive disorder of the central nervous system myelination caused by mutations involving the proteolipid protein gene (PLP). Early nystagmus and developmental delay, progressive pyramidal, cerebellar and dystonic signs as well as white matter changes in brain MRI are typical for PMD. The PLP gene can be affected by two major types of mutations. A duplication of the whole PLP gene is the most common mutation and results usually in the milder classical phenotype, whereas point mutations in PLP gene often result in the rarer and more severe connatal form of PMD. The PLP protein is a higly conserved across species and is identical in human, mouse and rat. We describe a 13-year-old Czech boy with an early and severe developmental delay. His maternal uncle died at the age of one year and was also early and severely psychomotoricly retarded. The patient was the first child of healthy unrelated parents born after an uneventful pregnancy and delivery in 1988. Hyperbilirubinemia and bronchopneumonia and early stridor complicated his neonatal period. Diffuse hypotonia, nystagmus, psychomotor retardation, visual and hearing impairment have been observed in the patient since the age of 6 weeks. White matter abnormalities, cortical and periventricular atrophy were detected by MRI at the age of 6 and 11 years, respectively. Despite these signs and results an accurate clinical diagnosis was unclear until the age of 11 years. Last neurological examination in 1999 showed no nystagmus anymore, but extremely dystrophic limbs, truncal deformation, due to severe scoliosis, tetraplegia with hyperreflexia in C5C7 and areflexia L2S2 and positive pyramidal signs. The boy had no visual or speech contact. DNA tests followed the clinical suspicion for PMD. At first, duplication of PLP gene was excluded by quantitative comparative PCR. Direct sequencing of PLP gene detected a novel mutation in exon 6, a missense mutation 725C-->A (Ala242Glu

  19. Inconel 718 süper alaşımının farklı gerilme ve sıcaklıklarda yüksek sıcaklık sürünme davranışının incelenmesi

    Directory of Open Access Journals (Sweden)

    Ergün Subaşı

    2016-04-01

    Full Text Available Bu çalışmada, havacılıkta yaygın olarak kullanılan Inconel 718 süper alaşımının sürünme davranışına sıcaklık ve gerilmenin etkileri incelenmiştir. Deneyler; 750°C, 800°C sıcaklıklarında ve 200-350MPa gerilme aralığında gerçekleştirilmiştir. Deneysel çalışma sonuçlarından, gerilme üssü (n, sürünme hızı (έ ve aktivasyon enerjisi (Q hesaplanmıştır. Hesaplanan sonuçlara göre; sürünme hızlarının artan gerilme ile arttığı, ayrıca sıcaklığın artmasıyla birlikte sürünme hızları çok daha fazla artmaktadır. Aynı şekilde, artan gerilme ile birlikte aktivasyon enerjisi artmaktadır. Deney sonuçlarından elde edilen gerilme üssü değerlerine göre; etkin deformasyon mekanizmasının dislokasyon sürünmesi olduğu tespit edilmiştir. Inconel 718 süper alaşımının kopma sürünme ömrünü tahmin etmek için, Larson Miller grafiği çizilmiştir. Bu grafikle, Inconel 718’in yüksek sıcaklık sürünme ömürleri hesaplanabilir.

  20. Dipeptide model prodrugs for the intestinal oligopeptide transporter. Affinity for and transport via hPepT1 in the human intestinal Caco-2 cell line

    DEFF Research Database (Denmark)

    Nielsen, C U; Andersen, R; Brodin, Birger

    2001-01-01

    -moieties for benzyl alcohol have been shown to maintain affinity for hPepT1. The primary aim of the present study was to investigate if modifications of the benzyl alcohol model drug influence the corresponding D-Glu-Ala and D-Asp-Ala model prodrugs' affinity for hPepT1 in Caco-2 cells. A second aim...... was to investigate the transepithelial transport and hydrolysis parameters for D-Asp(BnO)-Ala and D-Glu(BnO)-Ala across Caco-2 cell monolayers. In the present study, all investigated D-Asp-Ala and D-Glu-Ala model prodrugs retained various degrees of affinity for hPepT1 in Caco-2 cells. These affinities are used....... Transepithelial transport studies performed using Caco-2 cells of D-Asp(BnO)-Ala and D-Glu(BnO)-Ala showed that the K(m) for transepithelial transport was not significantly different for the two compounds. The maximal transport rate of the carrier-mediated flux component does not differ between the two model...

  1. Characterization of Chlamydia MurC-Ddl, a fusion protein exhibiting D-alanyl-D-alanine ligase activity involved in peptidoglycan synthesis and D-cycloserine sensitivity.

    Science.gov (United States)

    McCoy, Andrea J; Maurelli, Anthony T

    2005-07-01

    Recent characterization of chlamydial genes encoding functional peptidoglycan (PG)-synthesis proteins suggests that the Chlamydiaceae possess the ability to synthesize PG yet biochemical evidence for the synthesis of PG has yet to be demonstrated. The presence of D-amino acids in PG is a hallmark of bacteria. Chlamydiaceae do not appear to encode amino acid racemases however, a D-alanyl-D-alanine (D-Ala-D-Ala) ligase homologue (Ddl) is encoded in the genome. Thus, we undertook a genetics-based approach to demonstrate and characterize the D-Ala-D-Ala ligase activity of chlamydial Ddl, a protein encoded as a fusion with MurC. The full-length murC-ddl fusion gene from Chlamydia trachomatis serovar L2 was cloned and placed under the control of the arabinose-inducible ara promoter and transformed into a D-Ala-D-Ala ligase auxotroph of Escherichia coli possessing deletions of both the ddlA and ddlB genes. Viability of the E. coliDeltaddlADeltaddlB mutant in the absence of exogenous D-Ala-D-Ala dipeptide became dependent on the expression of the chlamydial murC-ddl thus demonstrating functional ligase activity. Domain mapping of the full-length fusion protein and site-directed mutagenesis of the MurC domain revealed that the structure of the full fusion protein but not MurC enzymatic activity was required for ligase activity in vivo. Recombinant MurC-Ddl exhibited substrate specificity for D-Ala. Chlamydia growth is inhibited by D-cycloserine (DCS) and in vitro analysis provided evidence for the chlamydial MurC-Ddl as the target for DCS sensitivity. In vivo sensitivity to DCS could be reversed by addition of exogenous D-Ala and D-Ala-D-Ala. Together, these findings further support our hypothesis that PG is synthesized by members of the Chlamydiaceae family and suggest that D-amino acids, specifically D-Ala, are present in chlamydial PG.

  2. Effects of alpha lipoic acid, ascorbic acid-6-palmitate, and fish oil on the glutathione, malonaldehyde, and fatty acids levels in erythrocytes of streptozotocin induced diabetic male rats.

    Science.gov (United States)

    Yilmaz, Okkeş; Ozkan, Yusuf; Yildirim, Mehmet; Oztürk, A Ihsan; Erşan, Yasemin

    2002-01-01

    In this research, it has been aimed to evaluate the improvement effects of alpha lipoic acid (ALA), ascorbic acid-6-palmitate (AA6P), fish oil (FO), and their combination (COM) on some biochemical properties in erythrocytes of streptozotocin (STZ)-induced diabetic male rats. According to experimental results, glutathione (GSH) level in erythrocytes decreased in diabetes (P cholesterol level was high in diabetes and D + ALA groups (P acid raised in diabetes group (P acid in D + FO, D + ALA, and diabetes groups was lower than control (P acid reduced in D + COM and D + FO groups, but its level raised in D + AA6P and D + ALA groups (P acid (LA) elevated in ALA + D, D + AA6P, and diabetes groups, linolenic acid level in diabetes, D + AA6P, and D + FO groups was lower than control (P acid (AA) decreased in D + ALA, D+ AA6P, and diabetes groups (P acid (DHA) increased in D + AA6P and D + COM (P acid level raised in diabetes group, its level reduced in D + ALA and D + FO groups (P acid level in D + ALA and D + FO groups was higher than control (P acid degree was raised by the effects of ALA and FO. Copyright 2002 Wiley-Liss, Inc.

  3. Improving contrast enhancement in magnetic resonance imaging using 5-aminolevulinic acid-induced protoporphyrin IX for high-grade gliomas.

    Science.gov (United States)

    Yamamoto, Junkoh; Kakeda, Shingo; Yoneda, Tetsuya; Ogura, Shun-Ichiro; Shimajiri, Shohei; Tanaka, Tohru; Korogi, Yukunori; Nishizawa, Shigeru

    2017-03-01

    Magnetic resonance imaging (MRI) with a gadolinium-based contrast agent is the gold standard for high-grade gliomas (HGGs). The compound 5-aminolevulinic acid (5-ALA) undergoes a high rate of cellular uptake, particularly in cancer cells. In addition, fluorescence-guided resection with 5-ALA is widely used for imaging HGGs. 5-ALA is water soluble, while protoporphyrin IX (PpIX) is water insoluble. It was speculated whether converting from 5-ALA to PpIX may relatively increase intracellular water content, and consequently, might enhance the T2 signal intensity in HGG. The aim of the present study was to assess whether 5-ALA-induced PpIX enhances the T2 signal intensity in patients with HGGs. A total of 4 patients who were candidates for HGG surgical treatment were prospectively analyzed with preoperative MRI. Patients received oral doses of 5-ALA (20 mg/kg) 3 h prior to anesthesia. At 2.5 h post-5-ALA administration, T2-weighted images (T2WIs) were obtained from all patients. Subsequently, tumors were evaluated via fluorescence using a modified operating microscope. Fluorescent tumor tissues were obtained to analyze the accumulation of 5-ALA-induced PpIX within the tumors, which was confirmed quantitatively by high-performance liquid chromatography (HPLC) analysis. The MRI T2 signal intensity within the tumors was evaluated prior to and following 5-ALA administration. Three glioblastoma multiformes (GBMs) and 1 anaplastic oligodendroglioma (AO) were included in the analysis. Intraoperatively, all GBMs exhibited strong fluorescence of 5-ALA-induced PpIX, whilst no fluorescence was observed in the AO sample. HPLC analysis indicated a higher accumulation of 5-ALA-induced PpIX in the GBM samples compared with the AO sample. In total, 48 regions of interest were identified within the tumors from T2-WIs. In the GBM group, the relative T2 signal intensity value within the tumors following 5-ALA administration was significantly increased compared with the T2 signal

  4. The effects of visual fluorescence marking induced by 5-aminolevulinic acid for endoscopic diagnosis of urinary bladder cancer

    Science.gov (United States)

    Daniltchenko, Dmitri I.; Koenig, Frank; Schnorr, Dietmar; Valdman, Alexander; Al-Shukri, Salman; Loening, Stefan A.

    2003-10-01

    During cystoscopy procedure, fluorescence diagnostics induced by 5-ALA improves visual detection of the bladder cancer. Macroscopic ALA-fluorescence allows visualizing of small flat tumors, carcinoma in situ, true neoplasm margins and dysplasias of the bladder. Following ALA instillation, cystoscopy has been performed under both standard and blue light illumination. Totally, 153 biopsies have been carried out at 53 patients with suspicion of bladder cancer. The results were compared to ALA-fluorescence data. In 13% of the patients, bladder cancer and dysplasia were found out in addition, due to red fluorescence. The sensitivity and specificity of ALA-fluorescence technique aggregated 96% and 52% respectively. The sensitivity and specificity of 5-ALA-fluorescent detection exceeded standard endoscopy under white light on 20%. The new method does not exclude a false positive and a false negative fluorescent luminescence. The ALA-based fluorescence detection system enhances the diagnosis of malignant/dysplastic bladder lesions significantly.

  5. Is docosahexaenoic acid synthesis from α-linolenic acid sufficient to supply the adult brain?

    Science.gov (United States)

    Domenichiello, Anthony F; Kitson, Alex P; Bazinet, Richard P

    2015-07-01

    Docosahexaenoic acid (DHA) is important for brain function, and can be obtained directly from the diet or synthesized in the body from α-linolenic acid (ALA). Debate exists as to whether DHA synthesized from ALA can provide sufficient DHA for the adult brain, as measures of DHA synthesis from ingested ALA are typically <1% of the oral ALA dose. However, the primary fate of orally administered ALA is β-oxidation and long-term storage in adipose tissue, suggesting that DHA synthesis measures involving oral ALA tracer ingestion may underestimate total DHA synthesis. There is also evidence that DHA synthesized from ALA can meet brain DHA requirements, as animals fed ALA-only diets have brain DHA concentrations similar to DHA-fed animals, and the brain DHA requirement is estimated to be only 2.4-3.8 mg/day in humans. This review summarizes evidence that DHA synthesis from ALA can provide sufficient DHA for the adult brain by examining work in humans and animals involving estimates of DHA synthesis and brain DHA requirements. Also, an update on methods to measure DHA synthesis in humans is presented highlighting a novel approach involving steady-state infusion of stable isotope-labeled ALA that bypasses several limitations of oral tracer ingestion. It is shown that this method produces estimates of DHA synthesis that are at least 3-fold higher than brain uptake rates in rats. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Dynamics of absorption, metabolism, and excretion of 5-aminolevulinic acid in human intestinal Caco-2 cells

    Directory of Open Access Journals (Sweden)

    Kei Saito

    2017-09-01

    Full Text Available 5-Aminolevulinic acid (ALA is a precursor for the biosynthesis of porphyrins and heme. Although the oral administration of ALA has been widely applied in clinical settings, the dynamics of its absorption, metabolism, and excretion within enterocytes remain unknown. In this study, after enterocytic differentiation, Caco-2 cells were incubated with 200 µM ALA and/or 100 µM sodium ferrous citrate (SFC for up to 72 h. Both ALA and the combination of ALA and SFC promoted the synthesis of heme, without affecting the expression of genes involved in intestinal iron transport, such as DMT1 and FPN. The enhanced heme synthesis in Caco-2 cells was more pronounced under the effect of the combination of ALA and SFC than under the effect of ALA alone, as reflected by the induced expression of heme oxygenase 1 (HO-1, as well as a reduced protein level of the transcriptional corepressor Bach1. Chromatin immunoprecipitation analysis confirmed Bach1 chromatin occupancy at the enhancer regions of HO-1, which were significantly decreased by the addition of ALA and SFC. Finally, Transwell culture of Caco-2 cells suggested that the administered ALA to the intestinal lumen was partially transported into vasolateral space. These findings enhance our understanding of the absorption and metabolism of ALA in enterocytes, which could aid in the development of a treatment strategy for various conditions such as anemia.

  7. Saponifikasi dan Ekstraksi Satu Tahap untuk Ekstraksi Minyak Tinggi Linoleat dan Linolenat dari Kedelai Varietas Lokal

    OpenAIRE

    Estiasih, Teti; Ahmadi, Kgs; Sunarharum, Wenny Bekti; Kurnain, R. Amilia D

    2011-01-01

    Linoleic acid (LA, C18:2ω-6) and alpha linolenic acid (ALA, C18:3ω-3) were essential polyunsaturated fatty acid (PUFA). The exploration of local varieties of soybean as the sources of LA and ALA is very important to reduce the dependence of LA+ALA import products. However, the local varieties of soybean in Indonesia are limited to be ex- plored as the suorce of LA and ALA. The efficient technique is needed to increase the PUFA (LA and ALA) content of soybean oil. One of the techniques is the ...

  8. Ehitame sotsiaalmaad täis elamuid, siis tulevad põlluelanikud linna? / Triin Talk ; kommenteerinud Endrik Mänd

    Index Scriptorium Estoniae

    Talk, Triin

    2011-01-01

    Tallinna hipodroomi ala detailplaneeringust, millega tahetakse ala muuta korruselamute alaks. Tallinna üldplaneeringus on hipodroomi ala määratud ühiskondlike ja puhkeehitiste alaks, koostatavas rohealade teemaplaneeringus eriotstarbeliseks rohealaks

  9. Parallel studies of His-DTrp-Ala-Trp-DPhe-Lys-NH2 and human pancreatic growth hormone-releasing factor-44-NH2 in rat primary pituitary cell monolayer culture.

    Science.gov (United States)

    Sartor, O; Bowers, C Y; Chang, D

    1985-03-01

    His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GH-RP-6) is a synthetic hexapeptide that specifically releases GH both in vivo and in vitro in pituitary incubates. In this study, for the first time, GH-RP-6 was studied in primary pituitary cell monolayer culture. Parallel studies were performed with human pancreatic GH-releasing factor-44 (hpGRF-44). Culture conditions optimal for GH-RP-6 were not optimal for hpGRF-44. Both peptides released GH in a dose- and time-dependent manner. In this assay system, the ED50 for GH-RP-6 was 9 nM, and the ED50 for hp-GRF-44 was 1.6 nM. Calcium-blocking agents inhibited the GH responses of both peptides as well as basal GH release. Pretreatment with GH-RP-6 decreased the subsequent response to both GH-RP-6 and hpGRF-44. hpGRF-44 down regulated itself but not GH-RP-6. Rat sera potentiated the GH response of hpGRF-44 but not that of GH-RP-6. GH-RP-6 and hpGRF-44 GH responses were additive. These results suggest that GH-RP-6 and hpGRF-44 stimulate GH release via different somatotroph receptors.

  10. A 90-day repeated-dose toxicity study of dietary alpha linolenic acid-enriched diacylglycerol oil in rats.

    Science.gov (United States)

    Bushita, Hiroto; Ito, Yuichi; Saito, Tetsuji; Nukada, Yuko; Ikeda, Naohiro; Nakagiri, Hideaki; Saito, Kazutoshi; Morita, Osamu

    2018-05-31

    Diets supplemented with alpha-linolenic acid (ALA)-enriched diacylglycerol (DAG) oil-which mainly consists of oleic and linolenic, linoleic acids-have potential health benefits in terms of preventing or managing obesity. Although safety of DAG oil has been extensively investigated, toxicity of ALA-DAG oil has not been well understood. Hence, the present study was conducted to clarify the potential adverse effects, if any, of ALA-DAG oil in rats (10/sex/group) fed diets containing 1.375%, 2.75%, or 5.5% ALA-DAG oil for 90 days. Compared to control rats fed rapeseed oil or ALA-triacylglycerol oil (flaxseed oil), rats receiving ALA-DAG oil did not reveal any toxicologically significant treatment-related changes as evaluated by clinical signs, functional observational battery, body weight, food consumption, ophthalmology, urinalysis, hematology, clinical chemistry, organ weight, necropsy and histopathology. The no observed adverse effect levels for dietary exposure to ALA-DAG oil for male and female rats were 2916 and 3326 mg/kg body weight/day, respectively, the highest dose tested. The findings from this study suggest that consumption of ALA-DAG oil is unlikely to cause adverse effects. Copyright © 2018. Published by Elsevier Inc.

  11. Biochemical characterisation of the chlamydial MurF ligase, and possible sequence of the chlamydial peptidoglycan pentapeptide stem.

    Science.gov (United States)

    Patin, Delphine; Bostock, Julieanne; Chopra, Ian; Mengin-Lecreulx, Dominique; Blanot, Didier

    2012-06-01

    Chlamydiaceae are obligate intracellular bacteria that do not synthesise detectable peptidoglycan although they possess an almost complete arsenal of genes encoding peptidoglycan biosynthetic activities. In this paper, the murF gene from Chlamydia trachomatis was shown to be capable of complementing a conditional Escherichia coli mutant impaired in UDP-MurNAc-tripeptide:D-Ala-D-Ala ligase activity. Recombinant MurF from C. trachomatis was overproduced and purified from E. coli. It exhibited ATP-dependent UDP-MurNAc-X-γ-D-Glu-meso-A(2)pm:D-Ala-D-Ala ligase activity in vitro. No significant difference of kinetic parameters was seen when X was L-Ala, L-Ser or Gly. The L-Lys-containing UDP-MurNAc-tripeptide was a poorer substrate as compared to the meso-A(2)pm-containing one. Based on the respective substrate specificities of the chlamydial MurC, MurE, MurF and Ddl enzymes, a sequence L-Ala/L-Ser/Gly-γ-D-Glu-meso-A(2)pm-D-Ala-D-Ala is expected for the chlamydial pentapeptide stem, with Gly at position 1 being less likely.

  12. Alpha-lipoic acid induces sodium iodide symporter expression in TPC-1 thyroid cancer cell line

    International Nuclear Information System (INIS)

    Choi, Hyun-Jeung; Kim, Tae Yong; Ruiz-Llorente, Sergio; Jeon, Min Ji; Han, Ji Min; Kim, Won Gu; Shong, Young Kee; Kim, Won Bae

    2012-01-01

    Introduction: Patients with metastatic thyroid cancers that do not uptake iodine need effective therapeutic option. Differentiation-inducing agents have been tried to restore functional expression of sodium iodide symporter (NIS) without success. Our objective was to assess the effect of alpha-lipoic acid (ALA), known as potential antioxidant, on expression of sodium iodide symporter in thyroid cancer cells. Methods: Human thyroid cancer-derived cell lines, TPC-1, were treated with ALA, and changes in NIS mRNA and protein expression were measured. ALA's effect on NIS gene promoter was evaluated, and functional NIS expression was assessed by iodide uptake assay. Results: Treatment with ALA increased NIS mRNA expression up to ten folds of control dose-dependently after 24 h of exposure. ALA increased NIS promoter activity, and increased iodide uptake by 1.6 fold. ALA induced expression of NIS protein, but had no significant effect on the plasma membrane trafficking. ALA increased phosphorylation of CREB and nuclear translocation of pCREB, and co-treatment of ALA and trichostatin A increased iodide uptake by three folds in TPC-1 cells. Conclusions: ALA is a potential agent to increase NIS transcription in TPC-1. It could be used as an adjunctive agent to increase efficacy of radioiodine therapy if combined with a strategy to increase NIS protein trafficking to cell membrane.

  13. Analysis of the enzymatic properties of a broad family of alanine aminotransferases.

    Directory of Open Access Journals (Sweden)

    Chandra H McAllister

    Full Text Available Alanine aminotransferase (AlaAT has been studied in a variety of organisms due to the involvement of this enzyme in mammalian processes such as non-alcoholic hepatocellular damage, and in plant processes such as C4 photosynthesis, post-hypoxic stress response and nitrogen use efficiency. To date, very few studies have made direct comparisons of AlaAT enzymes and fewer still have made direct comparisons of this enzyme across a broad spectrum of organisms. In this study we present a direct kinetic comparison of glutamate:pyruvate aminotransferase (GPAT activity for seven AlaATs and two glutamate:glyoxylate aminotransferases (GGAT, measuring the K(M values for the enzymes analyzed. We also demonstrate that recombinant expression of AlaAT enzymes in Eschericia coli results in differences in bacterial growth inhibition, supporting previous reports of AlaAT possessing bactericidal properties, attributed to lipopolysaccharide endotoxin recognition and binding. A probable lipopolysaccharide binding region within the AlaAT enzymes, homologous to a region of a lipopolysaccharide binding protein (LBP in humans, was also identified in this study. The AlaAT enzyme differences identified here indicate that AlaAT homologues have differentiated significantly and the roles these homologues play in vivo may also have diverged significantly. Specifically, the differing kinetics of AlaAT enzymes and how this may alter the nitrogen use efficiency in plants is discussed.

  14. Effects of alanyl-glutamine supplementation on the small intestinal mucosa barrier in weaned piglets

    Directory of Open Access Journals (Sweden)

    Shen Xing

    2017-02-01

    Full Text Available Objective The study was to investigate the effects of alanyl-glutamine (Ala-Gln and glutamine (Gln supplementation on the intestinal mucosa barrier in piglets. Methods A total of 180 barrows with initial weight 10.01±0.03 kg were randomly allocated to three treatments, and each treatment consisted of three pens and twenty pigs per pen. The piglets of three groups were fed with control diet [0.62% alanine (Ala], Ala-Gln diet (0.5% Ala-Gln, Gln diet (0.34% Gln and 0.21% Ala, respectively. Results The results showed that in comparison with control diet, dietary Ala-Gln supplementation increased the height of villi in duodenum and jejunum (p<0.05, Gln supplementation increased the villi height of jejunum (p<0.05, Ala-Gln supplementation up-regulated the mRNA expressions of epidermal growth factor receptor and insulin-like growth factor 1 receptor in jejunal mucosa (p<0.05, raised the mRNA expressions of Claudin-1, Occludin, zonula occludens protein-1 (ZO-1 and the protein levels of Occludin, ZO-1 in jejunal mucosa (p<0.05, Ala-Gln supplementation enlarged the number of goblet cells in duodenal and ileal epithelium (p<0.05, Gln increased the number of goblet cells in duodenal epithelium (p<0.05 and Ala-Gln supplementation improved the concentrations of secretory immunoglobulin A and immunoglobulin G in the jejunal mucosa (p<0.05. Conclusion These results demonstrated that dietary Ala-Gln supplementation could maintain the integrity of small intestine and promote the functions of intestinal mucosa barriers in piglets.

  15. Substrate specificity and catalysis by the editing active site of alanyl-tRNA synthetase from Escherichia coli†

    Science.gov (United States)

    Pasman, Zvi; Robey-Bond, Susan; Mirando, Adam C.; Smith, Gregory J.; Lague, Astrid; Francklyn, Christopher S.

    2011-01-01

    Aminoacyl-tRNA synthetases (ARSs) enhance the fidelity of protein synthesis through multiple mechanisms, including hydrolysis of the adenylate and cleavage of misacylated tRNA. Alanyl-tRNA synthetase (AlaRS) limits misacylation with glycine and serine by use of a dedicated editing domain, and a mutation in this activity has been genetically linked to a mouse model of a progressive neurodegenerative disease. Using the free standing P. horikoshii AlaX editing domain complexed with serine as a model and both Ser-tRNAAla and Ala-tRNAAla as substrates, the deacylation activities of the wild type and five different E. coli AlaRS editing site substitution mutants were characterized. The wild type AlaRS editing domain deacylated Ser-tRNAAla with a kcat/KM of 6.6 × 105 M−1 s−1, equivalent to a rate enhancement of 6000 over the rate of enzyme-independent deacylation, but only 12.2-fold greater than the rate with Ala-tRNAAla. While the E664A and T567G substitutions only minimally decreased kcat/KM, Q584H, I667E, and C666A AlaRS were more compromised in activity, with decreases in kcat/KM in the range of 6-, 7.3-, and 15-fold. C666A AlaRS was 1.4-fold more active on Ala-tRNAAla relative to Ser-tRNAAla, providing the only example of a true reversal of substrate specificity and highlighting a potential role of the coordinated zinc in editing substrate specificity. Along with the potentially serious physiological consequences of serine mis-incorporation, the relatively modest specificity of the AlaRS editing domain may provide a rationale for the widespread phylogenetic distribution of AlaX free standing editing domains, thereby contributing a further mechanism to lower concentrations of misacylated tRNAAla. PMID:21241052

  16. Enantioselective Collision-Activated Dissociation of Gas-Phase Tryptophan Induced by Chiral Recognition of Protonated l-Alanine Peptides

    Science.gov (United States)

    Fujihara, Akimasa; Matsuyama, Hiroki; Tajiri, Michiko; Wada, Yoshinao; Hayakawa, Shigeo

    2017-06-01

    Enantioselective dissociation in the gas phase is important for enantiomeric enrichment and chiral transmission processes in molecular clouds regarding the origin of homochirality in biomolecules. Enantioselective collision-activated dissociation (CAD) of tryptophan (Trp) and the chiral recognition ability of l-alanine peptides ( l-Ala n ; n = 2-4) were examined using a linear ion trap mass spectrometer. CAD spectra of gas-phase heterochiral H+( d-Trp)( l-Ala n ) and homochiral H+( l-Trp)( l-Ala n ) noncovalent complexes were obtained as a function of the peptide size n. The H2O-elimination product was observed in CAD spectra of both heterochiral and homochiral complexes for n = 2 and 4, and in homochiral H+( l-Trp)( l-Ala3), indicating that the proton is attached to the l-alanine peptide, and H2O loss occurs from H+( l-Ala n ) in the noncovalent complexes. H2O loss did not occur in heterochiral H+( d-Trp)( l-Ala3), where NH3 loss and (H2O + CO) loss were the primary dissociation pathways. In heterochiral H+( d-Trp)( l-Ala3), the protonation site is the amino group of d-Trp, and NH3 loss and (H2O + CO) loss occur from H+( d-Trp). l-Ala peptides recognize d-Trp through protonation of the amino group for peptide size n = 3. NH3 loss and (H2O + CO) loss from H+( d-Trp) proceeds via enantioselective CAD in gas-phase heterochiral H+( d-Trp)( l-Ala3) at room temperature, whereas l-Trp dissociation was not observed in homochiral H+( l-Trp)( l-Ala3). These results suggest that enantioselective dissociation induced by chiral recognition of l-Ala peptides through protonation could play an important role in enantiomeric enrichment and chiral transmission processes of amino acids.

  17. Exogenous 5-aminolevulenic acid promotes seed germination in Elymus nutans against oxidative damage induced by cold stress.

    Directory of Open Access Journals (Sweden)

    Juanjuan Fu

    Full Text Available The protective effects of 5-aminolevulenic acid (ALA on germination of Elymus nutans Griseb. seeds under cold stress were investigated. Seeds of E. nutans (Damxung, DX and Zhengdao, ZD were pre-soaked with various concentrations (0, 0.1, 0.5, 1, 5, 10 and 25 mg l(-1 of ALA for 24 h before germination under cold stress (5°C. Seeds of ZD were more susceptible to cold stress than DX seeds. Both seeds treated with ALA at low concentrations (0.1-1 mg l(-1 had higher final germination percentage (FGP and dry weight at 5°C than non-ALA-treated seeds, whereas exposure to higher ALA concentrations (5-25 mg l(-1 brought about a dose dependent decrease. The highest FGP and dry weight of germinating seeds were obtained from seeds pre-soaked with 1 mg l(-1 ALA. After 5 d of cold stress, pretreatment with ALA provided significant protection against cold stress in the germinating seeds, significantly enhancing seed respiration rate and ATP synthesis. ALA pre-treatment also increased reduced glutathione (GSH, ascorbic acid (AsA, total glutathione, and total ascorbate concentrations, and the activities of superoxide dismutase (SOD, catalase (CAT, ascorbate peroxidase (APX and glutathione reductase (GR, whereas decreased the contents of malondialdehyde (MDA and hydrogen peroxide (H2O2, and superoxide radical (O2•- release in both germinating seeds under cold stress. In addition, application of ALA increased H+-ATPase activity and endogenous ALA concentration compared with cold stress alone. Results indicate that ALA considered as an endogenous plant growth regulator could effectively protect E. nutans seeds from cold-induced oxidative damage during germination without any adverse effect.

  18. Comparison of Linear and Cyclic His-Ala-Val Peptides in Modulating the Blood-Brain Barrier Permeability: Impact on Delivery of Molecules to the Brain.

    Science.gov (United States)

    Alaofi, Ahmed; On, Ngoc; Kiptoo, Paul; Williams, Todd D; Miller, Donald W; Siahaan, Teruna J

    2016-02-01

    The aim of this study is to evaluate the effect of peptide cyclization on the blood-brain barrier (BBB) modulatory activity and plasma stability of His-Ala-Val peptides, which are derived from the extracellular 1 domain of human E-cadherin. The activities to modulate the intercellular junctions by linear HAV4 (Ac-SHAVAS-NH2), cyclic cHAVc1 (Cyclo(1,8)Ac-CSHAVASC-NH2), and cyclic cHAVc3 (Cyclo(1,6)Ac-CSHAVC-NH2) were compared in in vitro and in vivo BBB models. Linear HAV4 and cyclic cHAVc1 have the same junction modulatory activities as assessed by in vitro MDCK monolayer model and in situ rat brain perfusion model. In contrast, cyclic cHAVc3 was more effective than linear HAV4 in modulating MDCK cell monolayers and in improving in vivo brain delivery of Gd-DTPA on i.v. administration in Balb/c mice. Cyclic cHAVc3 (t1/2 = 12.95 h) has better plasma stability compared with linear HAV4 (t1/2 = 2.4 h). The duration of the BBB modulation was longer using cHAVc3 (2-4 h) compared with HAV4 (brain delivery of IRdye800cw-PEG (25 kDa) as detected by near IR imaging. The result showed that cyclic cHAVc3 peptide had better activity and plasma stability than linear HAV4 peptide. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  19. Perturbed porphyrin biosynthesis contributes to differential herbicidal symptoms in photodynamically stressed rice (Oryza sativa) treated with 5-aminolevulinic acid and oxyfluorfen.

    Science.gov (United States)

    Phung, Thu-Ha; Jung, Sunyo

    2014-11-01

    This paper focuses on the molecular mechanism of deregulated porphyrin biosynthesis in rice plants under photodynamic stress imposed by an exogenous supply of 5-aminolevulinic acid (ALA) and oxyfluorfen (OF). Plants treated with 5 mM ALA or 50 µM OF exhibited differential herbicidal symptoms as characterized by white and brown necrosis, respectively, with substantial increases in cellular leakage and malondialdehyde production. Protoporphyrin IX accumulated to higher levels after 1 day of ALA and OF treatment, whereas it decreased to the control level after 2 days of ALA treatment. Plants responded to OF by greatly decreasing the levels of Mg-protoporphyrin IX (MgProto IX), MgProto IX methyl ester, and protochlorophyllide to levels lower than control, whereas their levels drastically increased 1 day after ALA treatment and then disappeared 2 days after the treatment. Enzyme activity and transcript levels of HEMA1, GSA and ALAD for ALA synthesis greatly decreased in ALA- and OF-treated plants. Transcript levels of PPO1, CHLH, CHLI, and PORB genes involving Mg-porphyrin synthesis continuously decreased in ALA- and OF-treated plants, with greater decreases in ALA-treated plants. By contrast, up-regulation of FC2 and HO2 genes in Fe-porphyrin branch was noticeable in ALA and OF-treated plants 1 day and 2 days after the treatments, respectively. Decreased transcript levels of nuclear-encoded genes Lhcb1, Lhcb6, and RbcS were accompanied by disappearance of MgProto IX in ALA- and OF-treated plants after 2 days of the treatments. Under photodynamic stress imposed by ALA and OF, tight control of porphyrin biosynthesis prevents accumulation of toxic metabolic intermediates not only by down-regulation of their biosynthesis but also by photodynamic degradation. The up-regulation of FC2 and HO2 also appears to compensate for the photodynamic stress-induced damage. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Phage display-derived inhibitor of the essential cell wall biosynthesis enzyme MurF

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    Blewett Ann

    2008-12-01

    Full Text Available Abstract Background To develop antibacterial agents having novel modes of action against bacterial cell wall biosynthesis, we targeted the essential MurF enzyme of the antibiotic resistant pathogen Pseudomonas aeruginosa. MurF catalyzes the formation of a peptide bond between D-Alanyl-D-Alanine (D-Ala-D-Ala and the cell wall precursor uridine 5'-diphosphoryl N-acetylmuramoyl-L-alanyl-D-glutamyl-meso-diaminopimelic acid (UDP-MurNAc-Ala-Glu-meso-A2pm with the concomitant hydrolysis of ATP to ADP and inorganic phosphate, yielding UDP-N-acetylmuramyl-pentapeptide. As MurF acts on a dipeptide, we exploited a phage display approach to identify peptide ligands having high binding affinities for the enzyme. Results Screening of a phage display 12-mer library using purified P. aeruginosa MurF yielded to the identification of the MurFp1 peptide. The MurF substrate UDP-MurNAc-Ala-Glumeso-A2pm was synthesized and used to develop a sensitive spectrophotometric assay to quantify MurF kinetics and inhibition. MurFp1 acted as a weak, time-dependent inhibitor of MurF activity but was a potent inhibitor when MurF was pre-incubated with UDP-MurNAc-Ala-Glu-meso-A2pm or ATP. In contrast, adding the substrate D-Ala-D-Ala during the pre-incubation nullified the inhibition. The IC50 value of MurFp1 was evaluated at 250 μM, and the Ki was established at 420 μM with respect to the mixed type of inhibition against D-Ala-D-Ala. Conclusion MurFp1 exerts its inhibitory action by interfering with the utilization of D-Ala-D-Ala by the MurF amide ligase enzyme. We propose that MurFp1 exploits UDP-MurNAc-Ala-Glu-meso-A2pm-induced structural changes for better interaction with the enzyme. We present the first peptide inhibitor of MurF, an enzyme that should be exploited as a target for antimicrobial drug development.

  1. Porphyrin metabolism in lymphocytes of miners exposed to diesel exhaust at oil shale mine

    Energy Technology Data Exchange (ETDEWEB)

    Muzyka, V.; Bogovski, S.; Lang, I.; Schmidt, N.; Ryazanov, V.; Veidebaum, T. [Laboratory of Environmental Carcinogens, Institute of Experimental and Clinical Medicine, Hiiu 42, Tallinn 11619 (Estonia); Scheepers, P.T.J. [Department of Epidemiology and Biostatistics, University Medical Centre St Radboud, P.O. Box 9101, Nijmegen NL 6500 HB (Netherlands)

    2004-04-25

    The present study was carried out on the evaluation and application of new biomarkers for populations exposed to occupational diesel exhaust at oil shale mines. Since not only genotoxic effects may play an important role in the generation of tumors, the level of porphyrin metabolism was proposed as a biomarker of diesel exhaust exposure effects. The data on determination of 5-aminolevulinic acid (ALA) synthesis and heme formation in lymphocytes from groups of 50 miners exposed to diesel exhaust and 50 unexposed surface workers of oil shale mine are presented. All workers were examined and interviewed using structured questionnaires. The levels of benzene, carbon monoxide and nitric oxides in air as well as concentrations of 1-nitropyrene and elemental carbon in particulate matter were used for evaluation of exposure to diesel exhaust in mine. The levels of ALA and protoporphyrin (PP), activities of ALA synthetase (ALA-S) and ferrochelatase (FC), as well as levels of PP associated with DNA (PP/DNA) were investigated in lymphocytes spectrophotometrically. Significant differences in activity of ALA synthesis and heme formation between exposed miners and surface workers were found (207{+-}23 vs. 166{+-}14 pmol/10{sup 6} lymp./30' for ALA-S and 46.1{+-}3.8 vs. 54.8{+-}4.1 pmol/10{sup 6} lymp./60' for FC activities, respectively, P<0.001). ALA-S activity was higher and ALA accumulated in lymphocytes of exposed miners. Inhibition of FC activity caused PP cellular accumulation and an increase in the PP/DNA level (P<0.05). Tobacco smoking led to the increase of ALA biosynthesis in lymphocytes of both surface and underground smokers. The comparison of data obtained for non-smokers and smokers of both groups of workers has shown a significant difference (P<0.05). The work duration of underground or surface workers did not significantly influence the investigated biochemical parameters. The determination of ALA synthesis in lymphocytes could be a useful biomonitoring

  2. Draamalaborite tuleproov / Janar Ala

    Index Scriptorium Estoniae

    Ala, Janar, 1979-

    2010-01-01

    Cabaret Rhizomes 12. märtsil esietenduvast Päär Pärensoni lavastusest "Ürgne kutse" ja Solarise maa-aluses parklas 15. ja 17. märtsil etenduvast Tamur Tohveri lavastusest "Kas ma olen nüüd elus"

  3. Effects of Dietary L-carnosine and Alpha-lipoic Acid on Growth Performance, Blood Thyroid Hormones and Lipid Profiles in Finishing Pigs

    Directory of Open Access Journals (Sweden)

    Yinghui Bao

    2015-10-01

    Full Text Available The present study was conducted to determine the effects of L-carnosine (LC and/or alpha-lipoic acid (ALA supplementation on growth performance, blood thyroid hormones and lipid profiles in finishing pigs. A total of 40 (Landrace×Yorkshire pigs with an initial body weight of 57.93±3.14 kg were randomly allocated to 4 experimental diets using a 2×2 factorial arrangement with 2 LC supplemental levels (0 or 0.1% and 2 ALA supplemental levels (0 or 0.03% in basal diets. The results showed that pigs fed LC-supplemented diets increased final live weight, average daily gain, and average daily feed intake compared to those of pigs fed without LC-supplemented diets (p0.05. Additionally, LC supplementation increased serum triiodothyronine, thyroxine levels, and ALA supplementation increased serum triiodothyronine levels (p<0.05. Serum total cholesterol and triglycerides levels were significantly decreased in LC and ALA supplemented groups, respectively (p<0.05. Moreover, serum low density lipoprotein cholesterol levels were lower in the ALA-supplemented groups than those of pigs fed without ALA-supplemented diets (p<0.05. However, no significant LC×ALA interaction effect on growth performance, blood thyroid hormones and lipid profiles was found. This study suggested that dietary supplementation of LC resulted in better growth performance compared to that of ALA supplementation. L-carnosine and/or ALA supplementation positively modified blood lipid profiles, which may have the potential to prevent cardiovascular diseases.

  4. The Predominant Pathway of Apoptosis in THP-1 Macrophage-Derived Foam Cells Induced by 5-Aminolevulinic Acid-Mediated Sonodynamic Therapy is the Mitochondria-Caspase Pathway Despite the Participation of Endoplasmic Reticulum Stress

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    Huan Wang

    2014-05-01

    Full Text Available Background: In advanced atherosclerosis, chronic endoplasmic reticulum (ER stress induces foam cells apoptosis and generates inflammatory reactions. Methods: THP-1 macrophage-derived foam cells (FC were incubated with 1 mM 5-aminolevulinic acid (ALA. After ALA mediated sonodynamic therapy (ALA-SDT, apoptosis of FC was assayed by Annexin V-PI staining. Intracellular reactive oxygen species (ROS and mitochondrial membrane potential were detected by staining with CellROX® Green Reagent and jc-1. Pretreatment of FC with N-acetylcysteine (NAC, Z-VAD-FMK or 4-phenylbutyrate (4-PBA, mitochondria apoptotic pathway associated proteins and C/EBP-homologous (CHOP expressions were assayed by wertern blotting. Results: Burst of apoptosis of FC was observed at 5-hour after ALA-SDT with 6-hour incubation of ALA and 0.4 W/cm2 ultrasound. After ALA-SDT, intracellular ROS level increased and mitochondrial membrane potential collapsed. Translocations of cytochrome c from mitochondria into cytosol and Bax from cytosol into mitochondria, cleaved caspase 9, cleaved caspase 3, upregulation of CHOP, as well as downregulation of Bcl-2 after ALA-SDT were detected, which could be suppressed by NAC. Activation of mitochondria-caspase pathway could not be inhibited by 4-PBA. Cleaved caspase 9 and caspase 3 as well as apoptosis induced by ALA-SDT could be inhibited by Z-VAD-FMK. Conclusion: The mitochondria-caspase pathway is predominant in the apoptosis of FC induced by ALA-SDT though ER stress participates in.

  5. Preservation of organic matter in nontronite against iron redox cycling.

    Science.gov (United States)

    Zeng, Q.

    2015-12-01

    It is generally believed that clay minerals can protect organic matter from degradation in redox active environments, but both biotic and abiotic factors can influence the redox process and thus potentially change the clay-organic associations. However, the specific mechanisms involved in this process remain poorly understood. In this study, a model organic compound, 12-Aminolauric acid (ALA) was selected to intercalate into the structural interlayer of nontronite (an iron-rich smectite, NAu-2) to form an ALA-intercalated NAu-2 composite (ALA-NAu-2). Shawanella putrefaciens CN32 and sodium dithionite were used to reduce structural Fe(III) to Fe(II) in NAu-2 and ALA-NAu-2. The bioreduced ALA-NAu-2 was subsequently re-oxidized by air. The rates and extents of bioreduction and air re-oxidation were determined with wet chemistry methods. ALA release from ALA-NAu-2 via redox process was monitored. Mineralogical changes after iron redox cycle were investigated with X-ray diffraction, infrared spectroscopy, and scanning and transmission electron microscopy. At the beginning stage of bioreduction, S. putrefaciens CN32 reduced Fe(III) from the edges of nontronite and preferentially reduced and dissolved small and poorly crystalline particles, and released ALA, resulting a positive correlation between ALA release and iron reduction extent (80%). Because bacteria are the principal agent for mediating redox process in natural environments, our results demonstrated that the structural interlayer of smectite can serve as a potential shelter to protect organic matter from oxidation.

  6. Comparative analysis of the effects of CO2 fractional laser and sonophoresis on human skin penetration with 5-aminolevulinic acid.

    Science.gov (United States)

    Choi, J H; Shin, E J; Jeong, K H; Shin, M K

    2017-11-01

    Successful delivery of a photosensitizer into the skin is an important factor for effective photodynamic therapy (PDT). The effective method to increase drug penetration within short incubation time overcoming skin barrier have been investigated. This study was performed to analyze and compare the effectiveness of ablative fractional laser (FXL) pretreatment and/or sonophoresis for enhancing the penetration of 5-aminolevulinic acid (ALA) into human skin in vivo. Twenty-four identical 1 × 1 cm 2 treatment areas were mapped on the backs of ten healthy male subjects. Each area received FXL pretreatment and/or sonophoresis with different energy settings and ALA incubation times. After treatments, porphyrin fluorescence reflecting the ALA penetration were measured. Application of ablative CO 2 FXL pretreatment resulted to higher fluorescence intensities than the non-treatment group. Incubation times were positively correlated with the increments of ALA penetration. However, increasing pulse energy or combining with sonophoresis did not show additional positive effects on ALA penetration. Ablative CO 2 FXL pretreatment effectively facilitated ALA penetration in human skin in vivo. Ablative CO 2 FXL alone without sonophoresis setting pulse energy of 10 and 20 mJ with more than 60 min of ALA incubation time could be an ideal setting for ALA penetration.

  7. Difference in the structures of alanine tri- and tetra-peptides with antiparallel β-sheet assessed by X-ray diffraction, solid-state NMR and chemical shift calculations by GIPAW.

    Science.gov (United States)

    Asakura, Tetsuo; Yazawa, Koji; Horiguchi, Kumiko; Suzuki, Furitsu; Nishiyama, Yusuke; Nishimura, Katsuyuki; Kaji, Hironori

    2014-01-01

    Alanine oligomers provide a key structure for silk fibers from spider and wild silkworms.We report on structural analysis of L-alanyl-L-alanyl-L-alanyl-L-alanine (Ala)4 with anti-parallel (AP) β-structures using X-ray and solid-state NMR. All of the Ala residues in the (Ala)4 are in equivalent positions, whereas for alanine trimer (Ala)3 there are two alternative locations in a unit cell as reported previously (Fawcett and Camerman, Acta Cryst., 1975, 31, 658-665). (Ala)4 with AP β-structure is more stable than AP-(Ala)3 due to formation of the stronger hydrogen bonds. The intermolecular structure of (Ala)4 is also different from polyalanine fiber structure, indicating that the interchain arrangement of AP β-structure changes with increasing alanine sequencelength. Furthermore the precise (1)H positions, which are usually inaccesible by X-ray diffraction method, are determined by high resolution (1)H solid state NMR combined with the chemical shift calculations by the gauge-including projector augmented wave method. Copyright © 2013 Wiley Periodicals, Inc.

  8. Photodynamic destruction of Porphyromonas gingivalis induced by delta-aminolaevulinic acid

    Science.gov (United States)

    Sieron, Aleksander; Wiczkowski, Andrzej; Adamek, Mariusz; Dyla, Lucja; Mazur, Sebastian; Wierucka-Mlynarczyk, Beata

    2004-09-01

    Photodynamic therapy (PDT) is one of a novel modalities which has recently been exploited to eradicate various microorganisms. In our study we have evaluated bactericidal efficacy of PDT in the presence of 5-δ aminolaevulinic acid (ALA). Porphyromonas gingivalis were incubated with increasing concentration of ALA and subsequently irradiated by progressive light doses. Complete killing effect was obtained for bacteria irradiated with 25J/cm2 in ALA solution final concentration of 1mM, 5mM, 10mM. Statistical analysis has revealed ALA concentration to be a major factor responsible for eradication of bacteria. The latter may be attributable to the known ALA dark toxicity.

  9. Topical methotrexate pretreatment enhances the therapeutic effect of topical 5-aminolevulinic acid-mediated photodynamic therapy on hamster buccal pouch precancers

    OpenAIRE

    Deng-Fu Yang; Jeng-Woei Lee; Hsin-Ming Chen; Yih-Chih Hsu

    2014-01-01

    Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is effective for treatment of human oral precancerous lesions. This animal study aimed to assess whether topical methotrexate (MTX) pretreatment could enhance the therapeutic effect of topical ALA-PDT on hamster buccal pouch precancerous lesions. Methods: Twenty hamster buccal pouch precancerous lesions were treated with either topical ALA-PDT with topical MTX pretreatment (topical MTX-ALA-PDT group, n = 10) or topical A...

  10. EVALUATIONS OF BIOTECHNICAL CONSOLIDATIONS OF SLOPES GULLIES IN OPOKA DUŻA (LUBLIN UPLAND

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    Andrzej Mazur

    2017-10-01

    Full Text Available The studies were carried out in consolidated gullies in Opoka Duża, an anti-erosion biotechnical structure created in 1962-1964. On the basis of the studies it can be stated that the applied gullies buildings appeared to be efficient. Gullies did not deepen and did not increase its dimensions, whereas the Sanna river bed did not require expensive dredging. Accumulation of soil material is mainly observed at the bottoms of the gullies. In 51 years, about 4000 m3 of material accumulated at the bottoms. Hydrotechnical structures efficiently strengthened the erosion thresholds and bottoms of gullies against linear erosion and contributed to the inhibition of the fertile soil material creating more favourable conditions for plants growth. However, application of this type of buildings in gullies should be reduced to a necessary minimum, due to the high cost of maintaining a m3 of soil material and the introduction of additional elements in the landscape.

  11. Interactions of nickel(II) with histones. Stability and solution structure of complexes with CH3CO-Cys-Ala-Ile-His-NH2, a putative metal binding sequence of histone H3.

    Science.gov (United States)

    Bal, W; Lukszo, J; Jezowska-Bojczuk, M; Kasprzak, K S

    1995-01-01

    Nickel(II) compounds are established human carcinogens, but the molecular mechanisms underlying their activity are only partially known. One mechanism may include mediation by nickel of promutagenic oxidative DNA damage that depends on Ni(II) binding to chromatin. To characterize such binding at the histone moiety of chromatin, we synthesized the peptide CH3CO-Cys-Ala-Ile-His-NH2 (L), a model of the evolutionarily conserved motif in histone H3 with expected affinity for transition metals, and evaluated its reactivity toward Ni(II). Combined spectroscopic (UV/vis, CD, NMR) and potentiometric measurements showed that, at physiological pH, mixtures of Ni(II) and L yielded unusual macrochelate complexes, NiL and NiL2, in which the metal cation was bound through Cys and His side chains in a square-planar arrangement. Above pH 9, a NiH-3L complex was formed, structurally analogous to typical square-planar nickel complexes. These complexes are expected to catalyze oxidation reactions, and therefore, coordination of Ni(II) by the L motif in core histone H3 may be a key event in oxidative DNA base damage observed in the process of Ni(II)-induced carcinogenesis.

  12. 5-Aminolevulinic acid-mediated photodynamic therapy for oral cancers and precancers

    Directory of Open Access Journals (Sweden)

    Hsin-Ming Chen

    2012-12-01

    Full Text Available Previous studies have used both systemic and topical 5-aminolevulinic acid (ALA-mediated photodynamic therapy (PDT to treat oral precancers including oral leukoplakia (OL, oral erythroleukoplakia (OEL, and oral verrucous hyperplasia (OVH as well as oral cancers including oral verrucous carcinoma (OVC and oral squamous cell carcinoma (OSCC. Systemic ALA-PDT has been used to treat oral dysplastic lesions and oral cancers with promising clinical outcomes. The efficacy of a regular topical ALA-PDT (fluence rate, 100 mW/cm2; light dose, 100 J/cm2 was tested on an extensive buccal OVC and an enhanced topical ALA-PDT (fluence rate, 200 mW/cm2; light dose, 200 J/cm2 on an early-invasive OSCC; complete regression of the carcinomas was demonstrated after 28 and 18 PDT treatments, respectively. Several previous studies showed relatively good outcomes for OL lesions treated with topical ALA-PDT. However, it was found that the regular topical ALA-PDT is very effective for OVH and OEL lesions but less so for OL lesions. Better PDT outcomes are significantly associated with OVH and OEL lesions with smaller size, pink to red color, epithelial dysplasia, or thinner surface keratin layer. Moreover, the thicker surface keratin layer on the OL lesions is responsible for the relatively poorer PDT outcomes for OL lesions. In addition, both light emitting diode light- and laser light-mediated topical ALA-PDTs are comparative treatment modalities for OVH and OEL lesions. Methotrexate- or vitamin D3-preconditioned prostate or skin carcinoma cells can accumulate more intracellular protoporphyrin IX, resulting in an increased killing of these preconditioned cells by subsequent ALA-PDT. Because chemotherapy can help destroy carcinoma cells and tumor-associated vasculatures and cryotherapy pretreatment may help the diffusion of ALA into lesional epithelial cells, the chemotherapy or cryotherapy-combined topical ALA-PDT may be a new effective PDT alternative for

  13. Role of Natural IgM Autoantibodies (IgM-NAA) and IgM Anti-Leukocyte Antibodies (IgM-ALA) in Regulating Inflammation.

    Science.gov (United States)

    Lobo, Peter I

    2017-01-01

    Natural IgM autoantibodies (IgM-NAA) are rapidly produced to inhibit pathogens and abrogate inflammation mediated by invading microorganisms and host neoantigens. IgM-NAA achieve this difficult task by being polyreactive with low binding affinity but with high avidity, characteristics that allow these antibodies to bind antigenic determinants shared by pathogens and neoantigens. Hence the same clones of natural IgM can bind and mask host neoantigens as well as inhibit microorganisms. In addition, IgM-NAA regulate the inflammatory response via mechanisms involving binding of IgM to apoptotic cells to enhance their removal and binding of IgM to live leukocytes to regulate their function. Secondly, we review how natural IgM prevents autoimmune disorders arising from pathogenic IgG autoantibodies as well as by autoreactive B and T cells that have escaped tolerance mechanisms. Thirdly, using IgM knockout mice, we show that regulatory B and T cells require IgM to effectively regulate inflammation mediated by innate, adaptive and autoimmune mechanisms. It is therefore not surprising why the host positively selects such autoreactive B1 cells that generate protective IgM-NAA, which are also evolutionarily conserved. Fourthly, we show that IgM anti-leukocyte autoantibodies (IgM-ALA) levels and their repertoire can vary in normal humans and disease states and this variation may partly explain the observed differences in the inflammatory response after infection, ischemic injury or after a transplant. Finally we also show how protective IgM-NAA can be rendered pathogenic under non-physiological conditions. IgM-NAA have therapeutic potential. Polyclonal IgM infusions can be used to abrogate ongoing inflammation. Additionally, inflammation arising after ischemic kidney injury, e.g., during high-risk elective cardiac surgery or after allograft transplantation, can be prevented by pre-emptively infusing polyclonal IgM, or DC pretreated ex vivo with IgM, or by increasing in vivo Ig

  14. Lipid metabolic dose response to dietary alpha-linolenic acid in monk parrot (Myiopsitta monachus).

    Science.gov (United States)

    Petzinger, Christina; Heatley, J J; Bailey, Christopher A; Bauer, John E

    2014-03-01

    Monk parrots (Myiopsitta monachus) are susceptible to atherosclerosis, a progressive disease characterized by the formation of plaques in the arteries accompanied by underlying chronic inflammation. The family of n-3 fatty acids, especially eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), have consistently been shown to reduce atherosclerotic risk factors in humans and other mammals. Some avian species have been observed to convert α-linolenic acid (18:3n-3, ALA) to EPA and DHA (Htin et al. in Arch Geflugelk 71:258-266, 2007; Petzinger et al. in J Anim Physiol Anim Nutr, 2013). Therefore, the metabolic effects of including flaxseed oil, as a source of ALA, in the diet at three different levels (low, medium, and high) on the lipid metabolism of Monk parrots was evaluated through measuring plasma total cholesterol (TC), free cholesterol (FC), triacylglycerols (TAG), and phospholipid fatty acids. Feed intake, body weight, and body condition score were also assessed. Thus the dose and possible saturation response of increasing dietary ALA at constant linoleic acid (18:2n-6, LNA) concentration on lipid metabolism in Monk parrots (M. monachus) was evaluated. Calculated esterified cholesterol in addition to plasma TC, FC, and TAG were unaltered by increasing dietary ALA. The high ALA group had elevated levels of plasma phospholipid ALA, EPA, and docosapentaenoic acid (DPAn-3, 22:5n-3). The medium and high ALA groups had suppressed plasma phospholipid 20:2n-6 and adrenic acid (22:4n-6, ADA) compared to the low ALA group. When the present data were combined with data from a previous study (Petzinger et al. in J Anim Physiol Anim Nutr, 2013) a dose response to dietary ALA was observed when LNA was constant. Plasma phospholipid ALA, EPA, DPAn-3, DHA, and total n-3 were positively correlated while 20:2n-6, di-homo-gamma-linoleic acid (20:3n-6Δ7), arachidonic acid (20:4n-6), ADA, and total n-6 were inversely correlated with dietary en% ALA.

  15. Analysis of cell line variation in biochemical production of protoporphyrin IX

    Science.gov (United States)

    Gibbs, Summer L.; Chen, Bin; O'Hara, Julia A.; Hoopes, P. Jack; Hasan, Tayyaba; Pogue, Brian W.

    2006-02-01

    Protoporphyrin IX (PpIX) is produced via the heme synthesis pathway by the cell following administration of aminolevulinic acid (ALA). ALA synthase, the enzyme that produces ALA in the cell from glycine and succinyl-coenzyme A, is inhibited in a feedback mechanism by heme and thus is the rate limiting enzyme in the heme synthesis pathway. Since ALA is administered systemically, the rate limiting step that naturally exists in the cells is bypassed, however it is currently unclear why cells have different rate limiting steps in the ALA-PpIX synthesis pathway, and more specifically which types of cancer cells are most productive. It has been determined that when the same amount of ALA is administered to a wide panel of cancer cells in vitro that vastly differing amounts of PpIX are produced. The steps for the ALA-PpIX pathway occur in and around the mitochondria of the cell, but interestingly no correlation is seen between PpIX production and mitochondrial content of the cell, following ALA administration. However, total cell area shows positive correlation with PpIX production. Administration of the iron chelator, 1,2-dimethyl-3-hydroxy-4-pyridone (L1) in combination with ALA allows the final step in the heme synthesis pathway, conversion of PpIX to heme, to be delayed and thus increases the detectable amount of PpIX in each cell line. The cell lines that have the lowest PpIX production following administration of ALA alone show the largest increase in production following the combined administration of ALA and L1. PpIX fluorescence is thought to be a measure of cellular activity and the goal of the current study was to determine which cell lines would be the most promising targets for fluorescence detection or monitoring response to therapy. The results indicate that the cells with larger size and larger numbers of mitochondria may be good potential targets for this therapy. While this conclusion may appear obvious, it is not universally true, and cellular specific

  16. SU-F-T-674: In Vitro Study of 5-Aminolevulinic Acid-Mediated Photo Dynamic Therapy in Human Cancer Cell Lines

    Energy Technology Data Exchange (ETDEWEB)

    Cvetkovic, D; Wang, B; Gupta, R; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

    2016-06-15

    Purpose: Photodynamic therapy (PTD) is a promising cancer treatment modality. 5-sminolevulinic acid (ALA) is a clinically approved photosensitizer. Here we studied the effect of 5-ALA administration with irradiation on several cell lines in vitro. Methods: Human head and neck (FaDu), lung (A549) and prostate (LNCaP) cancer cells (104/well) were seeded overnight in 96-well plates (Figure 1). 5-ALA at a range from 0.1 to 30.0mg/ml was added to confluent cells 3h before irradiation in 100ul of culture medium. 15MV photon beams from a Siemens Artiste linear accelerator were used to deliver 2 Gy dose in one fraction to the cells. Cell viability was evaluated by WST1 assay. The development of orange color was measured 3h after the addition of WST-1 reagent at 450nm on an Envision Multilabel Reader (Figure 2) and directly correlated to cell number. Control, untreated cells were incubated without 5-ALA. The experiment was performed twice for each cell line. Results: The cell viability rates for the head and neck cancer line are shown in Figure 3. FaDu cell viability was reduced significantly to 36.5% (5-ALA) and 18.1% (5-ALA + RT) only at the highest concentration of 5-ALA, 30mg/ml. This effect was observed in neither A549, nor LNCaP cell line. No toxicity was detected at lower 5-ALA concentrations. Conclusion: Application of 5-ALA and subsequent PDT was found to be cytotoxic at the highest dose of the photosensitizer used in the FaDu head and neck cell line, and their effect was synergistic. Further efforts are necessary to study the potential therapeutic effects of 5-ALA PTD in vitro and in vivo. Our results suggest 5-ALA may improve the efficacy of radiotherapy by acting as a radiomediator in head and neck cancer.

  17. Metal-free Phtalocyanine and 5-Aminolevulenic Acid in Photodynamic Treatment of Human Vascular Cells

    Science.gov (United States)

    Udartseva, Olga O.; Andreeva, Elena R.; Buravkova, Ludmila B.; Tararak, Eduard M.

    2010-05-01

    Originally developed as a tumor therapy, now photodynamic therapy (PDT) may become a useful tool for treatment of cardiovascular diseases. Different cell types are involved in this vascular pathology, and these cells possess different susceptibility to PDT. In this study we screened the effects of two new photosensitizers (PtS and ALA) on human vascular cells. Human macrophages (Mph), aorta endothelial (HAEC) and smooth muscle (SMC) cells were obtained and cultured as described elsewhere. 2-10 ug/ml PtS was added to culture medium 24 h before PDT. ALA was added in 2-10 mM concentration in serum-free culture medium. Then cells were washed carefully and illuminated with 692-nm (PtS) or 633-nm (ALA) light. Cellular viability was measured with MTT-test. Except the case of use 5-10 mM ALA, either photosensitizer accumulation alone or laser illumination alone did not affect cells. Illumination of PtS or ALA-loaded cells (1-20 J/cm2) impaired cellular viability in dose-dependent manner. LD90 for different vascular cells with PtS were as follows: HAEC -1 J/cm2, SMC -2 J/cm2, Mph -5 J/cm2. HAEC and some Mph were unsusceptible to ALA-PDT. SMC LD90 with ALA was 20 J/cm2. Effects of ALA-PDT depended on protoporphyrin IX (PpIX) formation in cells. HAEC didn't accumulate PpIX and were non-sensitive to ALA-PDT. PpIX formation in Mph changed individually according to donor. Illumination of ALA-loaded Mph with low PpIX formation did not affect cells. However LD90 for Mph with high PpIX formation comprised 20 J/cm2. All cell types were more susceptible to PtS-PDT compared to ALA-PDT. Among tested photosensitizers PtS was the most effective one. HAEC were the most susceptible to PtS-PDT.

  18. Brain antioxidant effect of mirtazapine and reversal of sedation by its combination with alpha-lipoic acid in a model of depression induced by corticosterone.

    Science.gov (United States)

    Oliveira, Tatiana de Queiroz; de Sousa, Caren Nádia Soares; Vasconcelos, Germana Silva; de Sousa, Luciene Costa; de Oliveira, Anneheydi Araújo; Patrocínio, Cláudio Felipe Vasconcelos; Medeiros, Ingridy da Silva; Honório Júnior, José Eduardo Ribeiro; Maes, Michael; Macedo, Danielle; Vasconcelos, Silvânia Maria Mendes

    2017-09-01

    Depression is accompanied by activated neuro-oxidative and neuro-nitrosative pathways, while targeting these pathways has clinical efficacy in depression. This study aimed to investigate the effects of mirtazapine (MIRT) alone and combined with alpha-lipoic acid (ALA) against corticosterone (CORT) induced behavioral and oxidative alterations. Male mice received vehicle or CORT 20mg/kg during 14 days. From the 15th to 21st days they were divided in groups administered: vehicle, MIRT 3mg/kg or the combinations MIRT+ALA100 or MIRT+ALA200. On the 21st day of treatment, the animals were subjected to behavioral tests. Twenty-four hours after the last drug administration hippocampus (HC) and striatum (ST) were dissected for the determination reduced glutathione (GSH), lipid peroxidation (LP) and nitrite levels. CORT induced anxiety- and depressive-like behaviors as observed by increased immobility time in the tail suspension test and decreased sucrose consumption. MIRT or MIRT+ALA are effective in reversing anxiety- and depressive-like behaviors induced by CORT. CORT and MIRT alone prolonged sleeping time and this effect was reversed by MIRT+ALA. CORT significantly increased LP, which was reversed by MIRT or MIRT+ALA. Nitrite levels were increased in CORT-treated animals and reversed by MIRT+ALA200 (HC), MIRT or MIRT+ALA (ST). A relative small sample size and lack of a washout period between drug administration and behavioral testing. MIRT or MIRT+ALA reverse CORT-induced anxiety- and depressive-like behaviors probably via their central antioxidant effects. Augmentation of MIRT with ALA may reverse sedation, an important side effect of MIRT. Randomized controlled studies are needed to examine the clinical efficacy of this combination in human depression. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Effects of urea formaldehyde condensation polymer treatment of flaxseed on ruminal digestion and lactation in dairy cows.

    Science.gov (United States)

    Hawkins, A; Yuan, K; Armendariz, C K; Highland, G; Bello, N M; Winowiski, T; Drouillard, J S; Titgemeyer, E C; Bradford, B J

    2013-06-01

    Flaxseed is a potent source of the n-3 fatty acid α-linolenic acid (ALA), yet most ALA is lost during ruminal biohydrogenation when ground flaxseed is fed to ruminants. Heat processing and urea formaldehyde condensation polymer (UFCP) treatment of flaxseed were investigated as possible means of protecting ALA from ruminal degradation. Ground flaxseed (GF), heated ground flaxseed (HGF), or UFCP-treated ground flaxseed (UFCPGF) were incubated for 0, 4, 8, and 12h in 4 ruminally cannulated multiparous lactating Holstein cows. Compared with GF, HGF and UFCPGF decreased ruminal disappearance of dry matter, crude protein, and ALA. Pepsin-digestible protein remaining after 12h of ruminal incubation was greater for UFCPGF and HGF than for GF. Twenty-four lactating Holstein cows (207 ± 37 d in milk, 668 ± 66 kg of body weight, and 1.33 ± 0.56 lactations) were then used in a randomized complete block design experiment with a basal feeding period to assess effects of flaxseed treatment on ALA enrichment of plasma and milk as well as lactational performance. No evidence existed that supplementation of HGF and UFCPGF affected dry matter intake, milk fat content, milk protein content, or energy-corrected milk yield, but UFCPGF marginally decreased milk yield compared with HGF. Plasma concentration of ALA was not affected by treatment. Concentrations of n-3 fatty acids and conjugated linoleic acids in milk fat were increased by UFCPGF relative to HGF, but ALA yield was not affected. Taken together, in situ results suggest that heat-treated flaxseed, with or without UFCP treatment, slowed ruminal disappearance of ALA. Feeding UFCP-treated flaxseed failed to alter ALA content of plasma or milk ALA yield relative to heating alone. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  20. Increased Heme Levels in the Heart Lead to Exacerbated Ischemic Injury.

    Science.gov (United States)

    Sawicki, Konrad Teodor; Shang, Meng; Wu, Rongxue; Chang, Hsiang-Chun; Khechaduri, Arineh; Sato, Tatsuya; Kamide, Christine; Liu, Ting; Naga Prasad, Sathyamangla V; Ardehali, Hossein

    2015-07-31

    Heme is an essential iron-containing molecule for cardiovascular physiology, but in excess it may increase oxidative stress. Failing human hearts have increased heme levels, with upregulation of the rate-limiting enzyme in heme synthesis, δ-aminolevulinic acid synthase 2 (ALAS2), which is normally not expressed in cardiomyocytes. We hypothesized that increased heme accumulation (through cardiac overexpression of ALAS2) leads to increased oxidative stress and cell death in the heart. We first showed that ALAS2 and heme levels are increased in the hearts of mice subjected to coronary ligation. To determine the causative role of increased heme in the development of heart failure, we generated transgenic mice with cardiac-specific overexpression of ALAS2. While ALAS2 transgenic mice have normal cardiac function at baseline, their hearts display increased heme content, higher oxidative stress, exacerbated cell death, and worsened cardiac function after coronary ligation compared to nontransgenic littermates. We confirmed in cultured cardiomyoblasts that the increased oxidative stress and cell death observed with ALAS2 overexpression is mediated by increased heme accumulation. Furthermore, knockdown of ALAS2 in cultured cardiomyoblasts exposed to hypoxia reversed the increases in heme content and cell death. Administration of the mitochondrial antioxidant MitoTempo to ALAS2-overexpressing cardiomyoblasts normalized the elevated oxidative stress and cell death levels to baseline, indicating that the effects of increased ALAS2 and heme are through elevated mitochondrial oxidative stress. The clinical relevance of these findings was supported by the finding of increased ALAS2 induction and heme accumulation in failing human hearts from patients with ischemic cardiomyopathy compared to nonischemic cardiomyopathy. Heme accumulation is detrimental to cardiac function under ischemic conditions, and reducing heme in the heart may be a novel approach for protection against the

  1. 5-aminolevulinic acid-mediated photodynamic therapy and its strain-dependent combined effect with antibiotics on Staphylococcus aureus biofilm.

    Directory of Open Access Journals (Sweden)

    Qing-Zhao Zhang

    Full Text Available Staphylococcus aureus (S. aureus is hard to be eradicated, not only due to the emergence of antibiotic resistant strains but also because of its ability to form biofilm. Antibiotics are the major approach to treating biofilm infections, but their effects are unsatisfactory. One of the potential alternative treatments for controlling biofilm infections is photodynamic therapy (PDT, which requires the administration of photosensitizer, followed by light activation. 5-aminolevulinic acid (ALA, a natural photosensitizer prodrug, presents favorable characteristics, such as easy penetration and rapid clearance. These advantages enable ALA-based PDT (ALA-PDT to be well-tolerated by patients and it can be repeatedly applied without cumulative toxicity or serious side effects. ALA-PDT has been proven to be an effective treatment for multidrug resistant pathogens; however, the study of its effect on S. aureus biofilm is limited. Here, we established our PDT system based on the utilization of ALA and a light-emitting diode, and we tested the effect of ALA-PDT on S. aureus biofilm as well as the combined effect of ALA-PDT and antibiotics on S. aureus biofilm. Our results showed that ALA-PDT has a strong antibacterial effect on S. aureus biofilm, which was confirmed by the confocal laser scanning microscope. We also found that lethal photosensitization occurred predominantly in the upper layer of the biofilm, while the residual live bacteria were located in the lower layer of the biofilm. In addition, the improved bactericidal effect was observed in the combined treatment group but in a strain-dependent manner. Our results suggest that ALA-PDT is a potential alternative approach for future clinical use to treat S. aureus biofilm-associated infections, and some patients may benefit from the combined treatment of ALA-PDT and antibiotics, but drug sensitivity testing should be performed in advance.

  2. The effect of haem biosynthesis inhibitors and inducers on intestinal iron absorption and liver haem biosynthetic enzyme activities

    International Nuclear Information System (INIS)

    Laftah, A.H.; Simpson, R.J.; Peters, T.J.; Raja, K.B.

    2008-01-01

    The relation between haem biosynthesis and intestinal iron absorption is not well understood, we therefore investigated the effect of compounds that alter haem metabolism on duodenal iron absorption. CD1 mice were treated with either an inhibitor (succinyl acetone (SA)) or stimulator (2-allyl-2-isopropylacetamide (AIA)) of haem biosynthesis. 5-Aminolaevulinic acid (ALA) dehydratase and urinary ALA and porphobilinogen (PBG) levels, were determined. Intestinal iron absorption was assayed with in vivo and in vitro techniques. Liver hepcidin (Hamp1) and duodenal iron transporter mRNA levels were measured using RT-PCR. AIA caused increased hepatic ALA synthase (1.6-fold) and ALA dehydratase (1.4-fold, both p < 0.005) activities and increased urinary ALA and PBG excretion (2.1- and 1.4-fold, p < 0.005, p < 0.05, respectively). In vivo intestinal iron absorption was reduced to 49% of control (p < 0.005). Mice treated with SA showed decreased urinary ALA and PBG levels (75 and 55% control, both p < 0.005) and reductions in both ALA synthase and ALA dehydratase activities (77 and 56% control, p < 0.05, p < 0.005, respectively) in the liver. Liver and duodenal haem and cytochrome oxidase levels were not significantly decreased. Iron absorption was enhanced (1.26-fold, p < 0.05) and hepatic Hamp1 mRNA was reduced (53% of control, p < 0.05). In vitro duodenal iron uptake after mice were injected with SA also demonstrated an increase in Fe(III) reduction and uptake (1.27- and 1.41-fold, p < 0.01 respectively). Simultaneous injections of SA and ALA blocked the enhancing effect on iron absorption seen with SA alone. We conclude that alterations in haem biosynthesis can influence iron absorption and in particular, the intermediate ALA seems to be an inhibitor of iron absorption

  3. Alleviation of salt-induced oxidative damage by 5-aminolevulinic acid in wheat seedlings

    Science.gov (United States)

    Genişel, Mucip; Erdal, Serkan

    2016-04-01

    The aim of this study was to elucidate how 5-aminolevulinic acid (ALA), the precursor of chlorophyll compounds, affects the defence mechanisms of wheat seedlings induced by salt stress. To determine the possible stimulative effects of ALA against salinity, 11-day old wheat seedlings were sprayed with ALA at two different concentrations (10 and 20 mg.l-1) and then stressed by exposure to salt (150 mM NaCl). The salt stress led to significant changes in the antioxidant activity. While guaiacol peroxidase activity decreased, the activities of superoxide dismutase, catalase, and ascorbate peroxidase markedly increased under salt stress. Compared to the salt stress alone, the application of ALA beforehand further increased the activity of these enzymes. This study is the first time the effects of ALA have been monitored with regard to protein content and the isoenzyme profiles of the antioxidant enzymes. Although the salt stress reduced both the soluble protein content and protein band intensities, pre-treating with ALA significantly mitigated these stress-induced reductions. The data for the isoenzyme profiles of the antioxidant enzymes paralleled that of the ALA-induced increases in antioxidant activity. As a consequence of the high antioxidant activity in the seedlings pre-treated with ALA, the stress-induced elevations in the reactive oxygen species, superoxide anion, and hydrogen peroxide contents and lipid peroxidation levels were markedly diminished. Taken together, this data demonstrated that pre-treating with ALA confers resistance to salt stress by modulating the protein synthesis and antioxidant activity in wheat seedlings.

  4. Exogenous 5-Aminolevulenic Acid Promotes Antioxidative Defence System, Photosynthesis and Growth in Soybean against Cold Stress

    Directory of Open Access Journals (Sweden)

    Elahe MANAFI

    2015-12-01

    Full Text Available In the present study, the possibility of enhancing cold stress tolerance of young soybean plants (Glycine max [L.] Merr by exogenous application of 5-aminolevulinic acid (ALA was investigated. ALA was applied at various concentrations (0, 0.3, 0.6 and 0.9 mM by seed priming and foliar application method. After ALA treatment, the plants were subjected to cold stress at 10 ± 0.5 °C for 72 h. Cold stress significantly decreased plant growth, relative water content, chlorophyll, photosynthesis and stomatal conductivity, while it increased electrolyte leakage and proline accumulation. ALA at low concentrations (0.3 mM protected plants against cold stress, enhancing plant height, shoot fresh and dry weight, chlorophyll content, photosynthesis, stomatal conductivity as well as relative water content. Increase of electrolyte leakage was also prevented by 0.6 mM ALA. ALA also enhanced superoxide dismutase and catalase activities at 0.6 mM concentration especially under cold stress conditions. Proline increased with increasing in ALA concentration under both temperature conditions. In most cases, application of ALA by spraying method was better than seed priming method. Results showed that ALA, which is considered as an endogenous plant growth regulator, can be used effectively to protect soybean plants from the damaging effects of cold stress, by enhancing the activity of antioxidative enzymes, protecting cell membrane against reactive oxygen species and finally by promoting chlorophyll synthesis, leading to more intense photosynthesis and more carbon fixation, without any adverse effect on the plant growth.

  5. Synthesis of [64Cu]DOTA-ADIBON3-Ala-PEG28-A20FMDV2 via copper-free click chemistry for PET imaging of integrin αvβ6

    International Nuclear Information System (INIS)

    Drishty Satpati; Nadine Bauer; Hausner, S.H.

    2014-01-01

    Catalyst-free click reactions are effective chemical tools for synthesis of radiometal-based radiopharmaceuticals offering advantages towards preparation of non-toxic agents with high specific activity. In the present study the radiotracer [ 64 Cu]DOTA-ADIBON 3 -Ala-PEG 28 -A20FMDV2, [ 64 Cu]3, was synthesized for positron emission tomography imaging of integrin α v β 6 expressing tumors via a strain-promoted click reaction using both a 'pre-click' and 'post-click' approaches. The radiotracer, prepared in >99 % radiochemical yield, was evaluated in vitro (64.6 ± 2.8 % binding to α v β 6 -positive cells vs. v β 6 -negative cells) and in vivo (α v β 6 -positive tumor uptake: 1.52 ± 0.16 % ID/g, 24 h p.i.). While the high initial renal uptake (76.2 ± 10.7 % ID/g at 1 h p.i.) was comparable to a previously reported radiotracer, [ 64 Cu]DOTA-PEG 28 -A20FMDV2, [ 64 Cu]3 showed notably improved renal clearance (11.3 ± 2.5 % ID/g at 24 h p.i.). Thus, the introduction of a chelator-strained alkyne system resulted in improved pharmacokinetics for the present radiotracer, highlighting the attractive prospects of strain-promoted click-based preparations in the construction of radiometalated bioconjugates for targeted molecular imaging and therapy. (author)

  6. Alpha-linolenic acid-enriched diacylglycerol oil does not promote tumor development in tongue and gastrointestinal tract tissues in a medium-term multi-organ carcinogenesis bioassay using male F344 rat.

    Science.gov (United States)

    Honda, Hiroshi; Kawamoto, Taisuke; Doi, Yuko; Matsumura, Shoji; Ito, Yuichi; Imai, Norio; Ikeda, Naohiro; Mera, Yukinori; Morita, Osamu

    2017-08-01

    Alpha-linolenic acid (ALA)-enriched diacylglycerol (DAG) oil is an edible oil enriched with DAG (>80%) and ALA (>50%). The present study investigated whether ALA-DAG oil promotes tumorigenesis in the tongue and gastrointestinal tract, using a rat medium-term multi-organ carcinogenesis bioassay model. Rats were treated with five genotoxic carcinogens to induce multi-organ tumorigenesis until week 4, and from 1 week after withdrawal, fed a semi-synthetic diet (AIN-93G) containing ALA-DAG oil at concentrations of 0, 13,750, 27,500, and 55,000 ppm. Rats fed AIN-93G containing 55,000 ppm ALA-triacylglycerol or a standard basal diet served as reference and negative control groups, respectively. Animals were euthanized at week 30. ALA-DAG oil was shown to have no effects on survival, general condition, body weight, food consumption, or organ weight. More discolored spots were observed in the stomachs of the 13,750- and 55,000-ppm ALA-DAG groups than in those of the control groups; however, there were no differences in the frequency of histopathological findings across groups. There were no meaningful increases in the incidence of pre-neoplastic and neoplastic lesions in the tongue and gastrointestinal tract among the groups. We therefore conclude that ALA-DAG oil does not promote tumor development in the digestive system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Detection of anti-lactoferrin antibodies and anti-myeloperoxidase antibodies in autoimmune hepatitis: a retrospective study.

    Science.gov (United States)

    Tan, Liming; Zhang, Yuhong; Peng, Weihua; Chen, Juanjuan; Li, Hua; Ming, Feng

    2014-01-01

    Anti-lactoferrin antibodies (ALA) and anti-myeloperoxidase antibodies (AMPA) are specific serological markers for autoimmune hepatitis (AIH). The project aimed to detect ALA and AMPA and explore their clinical significances in AIH patients. 59 AIH patients, 217 non AIH patients, and 50 healthy controls were enrolled in this study. ALA and AMPA were detected by ELISA. Antineutropil cytoplasmic antibodies (ANCA) and anti-smooth muscle antibodies (ASMA) were examined by indirect immunofluorescence. Antimitochondrial antibody M2 subtype (AMA-M2), anti-liver kidney microsomal antibody Type 1 (LKM1), anti-liver cytosol antibody Type 1 (LC1), and anti-soluble liver antigen/liver-pancreas antibodies (SLA/LP) were tested by immunoblot. The positivity for ALA was 18.6% in AIH group, only one patient in non-AIH group was positive for ALA; the positivity for AMPA was 59.3% in AIH group, with significant differences (P < 0.01) compared with other groups. The specificities for ALA and AMPA were 99.63% and 97.75%; the sensitivities were 18.64% and 59.32%; and the accuracy rates were 84.97% and 90.80%, respectively. A certain correlation was observed between ALA and SLA/LP, AMPA and ANCA, ASMA in AIH group. ALA and AMPA were associated with AIH, and had high clinical diagnostic value. Co-detection with other relative autoantibodies could play an important role in differential diagnosis of AIH.

  8. Various levels and forms of dietary α-lipoic acid in broiler chickens: Impact on blood biochemistry, stress response, liver enzymes, and antibody titers.

    Science.gov (United States)

    Kim, D W; Mushtaq, M M H; Parvin, R; Kang, H K; Kim, J H; Na, J C; Hwangbo, J; Kim, J D; Yang, C B; Park, B J; Choi, H C

    2015-02-01

    The present experiment was conducted to evaluate the impact of various levels and forms of α-lipoic acid (ALA) on blood biochemistry, immune and stress response, and antibody titers in broiler chickens. The four levels (7.5, 15, 75, and 150 ppm) and 2 sources (powder, P-ALA and encapsulated, E-ALA) of ALA along with negative (C-) and positive control (C+; contains antibiotics) diets consisted of 10 dietary treatments, and these treatments were allocated to 1,200 1-d-old chicks and were replicated 12 times with 10 birds per replicate. Among the blood biochemistry parameters, creatinine levels were almost 3 times lower in E-ALA-supplemented diets compared to the C- diet (0.09 vs. 0.25 mg/dL; PBirds did not respond to infectious bronchitis virus (IBV) vaccination at any observed stage (P>0.05). The concentration of cortisol was reduced in chickens fed ALA-supplemented diets as compared to the C- diet (Pbiochemistry profiles and immune responses and reduced stress in broiler chickens. The encapsulated form of ALA was more effective than the powder form. © 2015 Poultry Science Association Inc.

  9. Topical glycerol monooleate/propylene glycol formulations enhance 5-aminolevulinic acid in vitro skin delivery and in vivo protophorphyrin IX accumulation in hairless mouse skin.

    Science.gov (United States)

    Steluti, Regilene; De Rosa, Fernanda Scarmato; Collett, John; Tedesco, Antônio Cláudio; Bentley, Maria Vitória Lopes Badra

    2005-08-01

    Photodynamic therapy (PDT), a potential therapy for cancer treatment, utilizes exogenously applied or endogenously formed photosensitizers, further activated by light in an appropriate wavelength and dose to induce cell death through free radical formation. 5-Aminolevulinic acid (5-ALA) is a pro-drug which can be converted to the effective photosensitizer, protoporphyrin IX (PpIX). However, the use of 5-ALA in PDT is limited by the low penetration capacity of this highly hydrophilic molecule into appropriate skin layers. In the present study, we propose to increase 5-ALA penetration by using formulations containing glycerol monooleate (GMO), an interesting and useful component of pharmaceutical formulations. Propylene glycol solutions containing different concentrations of GMO significantly increased the in vitro skin permeation/retention of 5-ALA in comparison to control solutions. In vivo studies also showed increased PpIX accumulation in mouse hairless skin, after the use of topical 5-ALA formulations containing GMO in a concentration-dependent manner. The results show that skin 5-ALA penetration and PpIX accumulation, important factors for the success of topical 5-ALA-PDT in skin cancer, are optimized by GMO/propylene glycol formulations.

  10. Regulation of His-dTrp-Ala-Trp-dPhe-Lys-NH2 (GHRP-6)-induced GH secretion in the rat.

    Science.gov (United States)

    Mallo, F; Alvarez, C V; Benitez, L; Burguera, B; Coya, R; Casanueva, F F; Dieguez, C

    1993-01-01

    His-dTrp-Ala-Trp-dPhe,Lys-NH2(GHRP-6) is a synthetic compound that releases GH in a dose-response and specific manner in several species and that may well be related to an endogenous compound of similar structure. The aim of this study was to investigate the in vivo GH responses to GHRP-6 in pentobarbital anesthetized rats. Specifically and in order to avoid the influence of endogenous GHRH and somatostatin secretion we studied the GH responses to GHRP-6 in animals with surgical ablation of the hypothalamus, confirmed by histological assessment, as well as in hypophysectomyzed-transplanted rats bearing two hypophyses under the renal capsule. Since it has been previously reported that rats pretreated with GHRH (10 micrograms/kg i.p. every 12 h for 15 days) rather than saline-treated rats have greater GH responses to acutely administered GHRH, we compared the self-potentiating effect of chronic GH pretreatment with GHRP-6 (10 micrograms/kg i.p. every 12 h). Furthermore we also studied the influence of estrogens, glucocorticoids, free fatty acids (FFA) and bombesin on somatotroph responsiveness to GHRP-6 in intact rats. We found a greater GH response to GHRP-6 in rats that underwent a surgical ablation of the hypothalamus 36 h prior to the test than in sham-operated rats. A direct stimulatory effect of GHRP-6 on in vivo GH secretion was demonstrated by a clear GH response to GHRP-6 in hypophysectomyzed-transplanted rats. In addition, we found a similar response whether the animals were pretreated with GHRH or GHRP-6 over the previous 2 weeks. Finally, we found that both estrogen- and testosterone-treated rats have greater GH responses to GHRP-6 than untreated rats. On the other hand, chronic dexamethasone administration, acute elevation of circulating FFA levels and bombesin administration markedly inhibited GH responses to GHRP-6. In contrast to the effects exerted on GH responses to GHRP-6 estrogen administration led to a decrease in GH responses to GHRH while

  11. The adsorption of amino acids and cations onto goethite: a prebiotic chemistry experiment.

    Science.gov (United States)

    Farias, Ana Paula S F; Carneiro, Cristine E A; de Batista Fonseca, Inês C; Zaia, Cássia T B V; Zaia, Dimas A M

    2016-06-01

    Few prebiotic chemistry experiments have assessed the adsorption of biomolecules by iron oxide-hydroxides. The present work investigated the effects of cations in artificial seawaters on the adsorption of Gly, α-Ala and β-Ala onto goethite, and vice versa. Goethite served to concentrate K and Mg cations from solution; these effects could have played important roles in peptide nucleoside formation. Goethite showed low adsorption of Gly and α-Ala. On the other hand, β-Ala (a non-protein amino acid) was highly adsorbed by goethite. Because Gly and α-Ala are the most common amino acids in living beings, and iron oxide-hydroxides are widespread on Earth, additional iron oxides should be studied. Increased ionic strength in artificial seawaters decreased the adsorption of amino acids by goethite. Because Na was highly abundant in the artificial seawater, it showed the highest effect on amino acid adsorption. β-Ala increased the adsorption of K and Ca by goethite, this effect could have been important for peptide synthesis.

  12. Different dietary omega-3 sources during pregnancy and DHA in the developing rat brain

    Directory of Open Access Journals (Sweden)

    Childs Caroline E.

    2011-09-01

    Full Text Available The essential n-3 fatty acid α-linolenic acid (ALA can be converted into eicosapentaenoic acid (EPA, docosapentaenoic acid (DPA and docosahexaenoic acid (DHA under the action of desaturase and elongase enzymes. Human studies have demonstrated that females convert a higher proportion of ALA into EPA and DHA than males. We have demonstrated that when fed upon an ALA rich diet, female rats have a significantly higher EPA content of plasma and liver lipids than males. When fetal tissues were collected, it was observed that pups from dams fed the ALA rich diet had a comparable brain DHA status to those from dams fed on a salmon-oil based diet, indicating that conversion of ALA to DHA during pregnancy was efficient, and that DHA accumulated in a tissue-specific manner. Similar efficacy of dietary ALA in women during pregnancy would mean that plant n-3 fatty acids would be useful alternatives to preformed EPA and DHA.

  13. Synthesis and Evaluation of ABO3 Perovskites (A=La and B=Mn, Co with Stoichiometric and Over-stoichiometric Ratios of B/A for Catalytic Oxidation of Trichloroethylene

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    Razieh Alagheband

    2018-01-01

    Full Text Available In this contribution, perovskite catalysts (ABO3 were probed that site A and site B were occupied by lanthanum and transition metals of manganese or cobalt, respectively, with stoichiometric ratios as well as 20 % over-stoichiometric ratios of B/A. The perovskite samples were synthesized using a gel-combustion method and characterized by BET, XRD, SEM and O2-TPD analyses. After mounting in a fixed bed reactor, the catalysts were examined in atmospheric pressure conditions at different temperatures for oxidation of 1000 ppm trichloroethylene in the air. Evaluation of over-stoichiometric catalysts activity showed that the increased ratio of B/A in the catalysts compared to the stoichiometric one led to BET surface area, oxygen mobility, and consequently catalytic performance improvement. The lanthanum manganite perovskite with 20 % excess manganese yielded the best catalytic performance among the probed perovskites. Copyright © 2018 BCREC Group. All rights reserved Received: 28th April 2017; Revised: 31st July 2017; Accepted: 4th August 2017; Available online: 22nd January 2018; Published regularly: 2nd April 2018 How to Cite: Alagheband, R., Maghsoodi, S., Kootenaei, A.S., Kianmanesh, H. (2018. Synthesis and Evaluation of ABO3 Perovskites (A=La and B=Mn, Co with Stoichiometric and Over-stoichiometric Ratios of B/A for Catalytic Oxidation of Trichloroethylene. Bulletin of Chemical Reaction Engineering & Catalysis, 13 (1: 47-56 (doi:10.9767/bcrec.13.1.1188.47-56

  14. Redox Thermodynamics of Cytochromes c Subjected to Urea Induced Unfolding

    NARCIS (Netherlands)

    Monari, S.; Ranieri, A.; Di Rocco, G.; van der Zwan, G.; Peressini, S.; Tavagnacco, C.; Millo, D.; Borsari, M.

    2009-01-01

    The thermodynamics of the electron transfer (ET) process for beef heart and yeast cytochromes c and the Lys72Ala/Lys73Ala/Lys79Ala mutant of the latter species subjected to progressive urea-induced unfolding was determined electrochemically. The results indicate the presence of at least three

  15. Nasogastric Tube Placement Errors and Complications in Pediatric Intensive Care Unit: A Case Report

    Directory of Open Access Journals (Sweden)

    Mahin Seyedhejazi

    2011-11-01

    Full Text Available Nasal ala pressure sores are among complications of nasogastric tube in Pediatric Intensive Care Unit (PICU. The severity of the injury is usually minor and easily ignored. However, the complication could be easily avoided. This is a case of nasal ala sore after the place-ment of nasal enteral tube in a pediatric intensive care unit in our center. A 5-month-old female with pulmonary hypertension secondary to bronchiectasis with nasal ala pressure sore were reported. She was hospitalized in pediatric intensive care unit at Tabriz Children Hospital in 2010.After 53 days of PICU hospitalization she had nasal ala sore. Conclusion: We know that nasal ala pressure sores could easily be avoided when preventive procedures were performed during nasogastric tube insertion.

  16. Intraoperative Detection of Superficial Liver Tumors by Fluorescence Imaging Using Indocyanine Green and 5-aminolevulinic Acid.

    Science.gov (United States)

    Kaibori, Masaki; Matsui, Kosuke; Ishizaki, Morihiko; Iida, Hiroya; Okumura, Tadayoshi; Sakaguchi, Tatsuma; Inoue, Kentaro; Ikeura, Tsukasa; Asano, Hiroaki; Kon, Masanori

    2016-04-01

    Indocyanine green (ICG) and the porphyrin precursor 5-aminolevulinic acid (5-ALA) have been approved as fluorescence imaging agents in the clinical setting. This study evaluated the usefulness of fluorescence imaging with both ICG and 5-ALA for intraoperative identification of latent small liver tumors. There were 48 patients who had main tumors within 5 mm of the liver surface. 5-ALA hydrochloride was orally administered to patients 3 h before surgery. ICG had been intravenously injected within 14 days prior to surgery. Intraoperatively, after visual inspection, manual palpation and ultrasonography fluorescence images of the liver surface were obtained with ICG and 5-ALA prior to resection. With ICG, the sensitivity, specificity and accuracy for detecting the preoperatively identified main tumors were 96%, 50% and 94%, respectively. Twelve latent small tumors were newly detected on the liver surface using ICG, five of which proved to be carcinomas. With 5-ALA, the sensitivity, specificity and accuracy for detecting the main tumors were 57%, 100% and 58%, respectively. Five latent small tumors were newly detected using 5-ALA; all were carcinomas. Overall, five new tumors were detected by both ICG and 5-ALA fluorescence imaging; two were hepatocellular carcinomas (HCCs) and three were metastases of colorectal cancer. The sensitivity and specificity of ICG fluorescence imaging for main tumor detection were relatively high and low, respectively, but the opposite was true of 5-ALA imaging. Fluorescence imaging using 5-ALA may provide greater specificity in the detection of surface-invisible malignant liver tumors than using ICG fluorescence imaging alone. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  17. EDUCACIÓN Y RESILIENCIA: ALAS DE LA TRANSFORMACIÓN SOCIAL ( EDUCATION AND RESILIENCE: WINGS OF SOCIAL CHANGE

    Directory of Open Access Journals (Sweden)

    López Torres Viviana

    2010-08-01

    Full Text Available Resumen:Tratándose de un nuevo paradigma de desarrollo, la resiliencia propone que no todas las personas que crecen en condiciones de adversidad, pobreza y desigualdad social serán adultos condenados al fracaso, a la delincuencia o a la locura; por el contrario, este concepto enfatiza en el potencial humano y hace un llamado a la esperanza y a la responsabilidad colectiva en la promoción de cambio social. El presente ensayo parte de una revisión analítica de literatura reciente sobre resiliencia, en el marco del trabajo realizado durante el año 2009 por el grupo “Esperanza y Vida”, en la línea de investigación denominada “Resiliencia y contextos psicosociales”, perteneciente al programa de Psicología de la Universidad Antonio Nariño (UAN Bogotá, Colombia. Este ejercicio reflexivo tiene como propósito analizar el concepto de resiliencia en el contexto escolar, considerando que este es uno de los primeros contactos de la infancia con la cultura, el lugar en donde las niñas y los niños van a preguntarse cómo funciona el mundo, el sitio donde pueden encontrar respuestas honestas y sugerencias útiles sobre cómo comprenderlo y cómo transformarlo; además, señala cómo acciones pedagógicas fundamentadas en el reconocimiento del estudiante como un agente responsable y activo en el proceso de aprendizaje, favorecen actitudes de compromiso en la promoción de la transformación social positiva.Abstract:Being a new development paradigm, resilience suggests that not all people who grow up in conditions of adversity, poverty and social inequality will be adults doomed to failure, delinquency or madness; on the contrary, this concept emphasizes the human potential and calls for hope and collective responsibility in promoting social change. This essay is an analytical review of recent literature on resilience in the context of the work performed during 2009 by the group "Esperanza y Vida" in the line of research called

  18. Experimental and Theoretical Studies of the Structures and Interactions of Vancomycin Antibiotics with Cell Wall Analogues

    International Nuclear Information System (INIS)

    Yang, Zhibo; Vorpagel, Erich R.; Laskin, Julia

    2008-01-01

    Surface-induced dissociation (SID) of the singly protonated complex of vancomycin antibiotic with cell wall peptide analogue (N α , N # var e psilon#-diacetyl-L-Lys-D-Ala-D-Ala) was studied using a 6 T Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FT-ICR MS) specially configured for SID experiments. The binding energy between the vancomycin and the peptide was obtained from the RRKM modeling of the time- and energy resolved fragmentation efficiency curves (TFECs) of the precursor ion and its fragments. Electronic structure calculations of the geometries, proton affinities and binding energies were performed for several model systems including vancomycin (V), vancomycin aglycon (VA), N α , N # var e psilon#-diacetyl-L-Lys-D-Ala-D-Ala, and non-covalent complexes of VA with N-acetyl-D-Ala-D-Ala and N α , N # var e psilon#-diacetyl-L-Lys-D-Ala-D-Ala at the B3LYP/6-31G(d) level of theory. Comparison between the experimental and computational results suggests that the most probable structure of the complex observed in our experiments corresponds to the neutral peptide bound to the vancomycin protonated at the secondary amino group of the N-methyl-leucine residue. The experimental binding energy of 30.9 ± 1.8 kcal/mol is in good agreement with the binding energy of 29.3 ± 2.5 kcal/mol calculated for the model system representing the preferred structure of the complex

  19. Distribution of δ-aminolevulinic acid biosynthetic pathways among phototrophic and related bacteria

    International Nuclear Information System (INIS)

    Avissar, Y.J.; Beale, S.I.; Ormerod, J.G.

    1989-01-01

    Two biosynthetic pathways are known for the universal tetrapyrrole precursor, δ-aminolevulinic acid (ALA): condensation of glycine and succinyl-CoA to form ALA with the loss of C-1 of glycine as CO 2 , and conversion of the intact carbon skeleton of glutamate to ALA in a process requiring tRNA Glu , ATP, Mg 2+ , NADPH, and pyridoxal phosphate. The distribution of the two ALA biosynthetic pathways among various bacterial genera was determined, using cell-free extracts obtained from representative organisms. Evidence for the operation of the glutamate pathway was obtained by the measurement of RNase-sensitive label incorporation from glutamate into ALA using 3,4-[ 3 H]glutamate and 1-[ 14 C]glutamate as substrate. The glycine pathway was indicated by RNase-insensitive incorporation of level from 2-[ 14 C]glycine into ALA. The distribution of the two pathways among the bacteria tested was in general agreement with their previously phylogenetic relationships and clearly indicates that the glutamate pathway is the more ancient process, whereas the glycine pathway probably evolved much later. The glutamate pathway is the more widely utilized one among bacteria, while the glycine pathway is apparently limited to the α subgroup of purple bacteria (including Rhodobacter, Rhodospirillum, and Rhizobium). E. coli was found ALA via the glutamate pathway. The ALA-requiring hemA mutant of E. coli was determined to lack the dehydrogenase activity that utilizes glutamyl-tRNA as a substrate

  20. (R)-α-Lipoic acid inhibits fructose-induced myoglobin fructation and the formation of advanced glycation end products (AGEs) in vitro.

    Science.gov (United States)

    Ghelani, Hardik; Razmovski-Naumovski, Valentina; Pragada, Rajeswara Rao; Nammi, Srinivas

    2018-01-15

    Fructose-mediated protein glycation (fructation) has been linked to an increase in diabetic and cardiovascular complications due to over consumption of high-fructose containing diets in recent times. The objective of the present study is to evaluate the protective effect of (R)-α-lipoic acid (ALA) against fructose-induced myoglobin fructation and the formation of advanced glycation end products (AGEs) in vitro. The anti-glycation activity of ALA was determined using the formation of AGEs fluorescence intensity, iron released from the heme moiety of myoglobin and the level of fructosamine. The fructation-induced myoglobin oxidation was examined using the level of protein carbonyl content and thiol group estimation. The results showed that co-incubation of myoglobin (1 mg/mL), fructose (1 M) and ALA (1, 2 and 4 mM) significantly inhibited the formation of AGEs during the 30 day study period. ALA markedly decreased the levels of fructosamine, which is directly associated with the reduction of AGEs formation. Furthermore, ALA significantly reduced free iron release from myoglobin which is attributed to the protection of myoglobin from fructose-induced glycation. The results also demonstrated a significant protective effect of ALA on myoglobin oxidative damages, as seen from decreased protein carbonyl content and increased protein thiols. These findings provide new insights into the anti-glycation properties of ALA and emphasize that ALA supplementation is beneficial in the prevention of AGEs-mediated diabetic and cardiovascular complications.

  1. Evaluation of Hydrogel Suppositories for Delivery of 5-Aminolevulinic Acid and Hematoporphyrin Monomethyl Ether to Rectal Tumors.

    Science.gov (United States)

    Ye, Xuying; Yin, Huijuan; Lu, Yu; Zhang, Haixia; Wang, Han

    2016-10-12

    We evaluated the potential utility of hydrogels for delivery of the photosensitizing agents 5-aminolevulinic acid (ALA) and hematoporphyrin monomethyl ether (HMME) to rectal tumors. Hydrogel suppositories containing ALA or HMME were administered to the rectal cavity of BALB/c mice bearing subcutaneous tumors of SW837 rectal carcinoma cells. For comparison, ALA and HMME were also administered by three common photosensitizer delivery routes; local administration to the skin and intratumoral or intravenous injection. The concentration of ALA-induced protoporphyrin IX or HMME in the rectal wall, skin, and subcutaneous tumor was measured by fluorescence spectrophotometry, and their distribution in vertical sections of the tumor was measured using a fluorescence spectroscopy system. The concentration of ALA-induced protoporphyrin IX in the rectal wall after local administration of suppositories to the rectal cavity was 9.76-fold (1 h) and 5.8-fold (3 h) higher than in the skin after cutaneous administration. The maximal depth of ALA penetration in the tumor was ~3-6 mm at 2 h after cutaneous administration. Much lower levels of HMME were observed in the rectal wall after administration as a hydrogel suppository, and the maximal depth of tumor penetration was <2 mm after cutaneous administration. These data show that ALA more readily penetrates the mucosal barrier than the skin. Administration of ALA as an intrarectal hydrogel suppository is thus a potential delivery route for photodynamic therapy of rectal cancer.

  2. Protective Role of Alpha Lipoic Acid Against Disorders Induced by Gamma Radiation

    International Nuclear Information System (INIS)

    Abd El Azeem, Kh.N.M.

    2011-01-01

    Ionizing radiation interacts with living cells, causing a variety of biochemical changes depending on exposed and absorbed doses, duration of exposure, interval after exposure and susceptibility of tissues to ionizing radiation. So, it may increase the oxidative stress and damage of body organs. Alpha-lipoic acid (ALA-also known as thioctic acid) appears to be readily absorbed from an oral dose and converts easily to its reduced form, dihydro lipoic acid (DHLA), in many tissues of the body. ALA can neutralize free radicals in both fatty and watery regions of cells. The present study has been designed to evaluate the possible efficiency of ALA as antioxidant and radio-protector against radiation induced oxidative stress in different organs (liver, kidney and heart) in rats through estimation of the activity of markers of serum liver, kidney and heart function, in addition to the histopathological differentiation of these organs by light and electron microscope. Five equal groups were conducted for the study: control, ALA (30 mg/kg body wt), irradiated (each rat was exposed to 6 Gy as a fractionated dose of gamma (γ) radiation), irradiated plus ALA (each rat received ALA for 9 days simultaneously during exposure) and ALA plus irradiation plus ALA groups (each rat received ALA for a week pre-exposure plus 9 days during exposure). Radiation doses were fractionated dose levels of 2 Gy each 3 days to reach accumulative dose of 6 Gy. After 3 days of each exposure rats were sacrificed, except, those left for recovery test one month after last exposure. The results revealed that whole body γ-irradiation of rats induces oxidative stress in liver, kidney and heart obviously manifested by significant elevation in alanine and aspartate transaminase ( ALT and AST), alkaline phosphatase (ALP), urea, creatinine and creatine kinase (CK-MB). ALA treated-irradiated rats showed lower significantly values indicating remarkable improvement in all measured parameters and

  3. Antioxidant effect of erdosteine and lipoic acid in ovarian ischemia-reperfusion injury.

    Science.gov (United States)

    Dokuyucu, R; Karateke, A; Gokce, H; Kurt, R K; Ozcan, O; Ozturk, S; Tas, Z A; Karateke, F; Duru, M

    2014-12-01

    To investigate the effects of erdosteine and alpha lipoic acid (ALA) in a rat model of ovarian ischaemia-reperfusion injury. Forty-eight female Wistar albino rats were separated, at random, into six groups of eight rats. The groups were classified as: sham, torsion, detorsion, detorsion+erdosteine 100mg/kg, detorsion+alpha lipoic acid (ALA) 100mg/kg, and detorsion+erdosteine+ALA. The investigators executing the biochemical and histological analyses were blinded to the randomization until the end of the study. The TOS (Total Oxidant Status) and OSI (Oxidative Stress Index) levels are higher in the Torsion and Detorsion groups when compared with the ones in the Sham group (pOSI and total histological score in the sham, torsion and detorsion groups (r=0.765, pOSI in the rats that received erdosteine and/or ALA were significantly lower compared with the sham, torsion and detorsion groups (pOSI were lower in the detorsion+erdosteine+ALA group compared with the detorsion+erdosteine and detorsion+ALA groups (pmodel; combination treatment had a greater effect than either agent alone. Treatment with erdosteine and/or ALA was found to preserve the loss of reproductive capacity normally observed after ovarian torsion. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Isotopic effects in mechanistic studies of biotransformations of fluorine derivatives of L-alanine catalysed by L-alanine dehydrogenase

    International Nuclear Information System (INIS)

    Szymańska-Majchrzak, Jolanta; Pałka, Katarzyna; Kańska, Marianna

    2017-01-01

    Synthesis of 3-fluoro-[2- 2 H]-L-alanine (3-F-[ 2 H]-L-Ala) in reductive amination of 3-fluoropyruvic acid catalysed by L-alanine dehydrogenase (AlaDH) was described. Fluorine derivative was used to study oxidative deamination catalysed by AlaDH applied kinetic (for 3-F-L-Ala in H 2 O - KIE’s on V max : 1.1; on V max /K M : 1.2; for 3-F-L-Ala in 2 H 2 O – on V max : 1.4; on V max /K M : 2.1) and solvent isotope effect methods (for 3-F-L-Ala - SIE’s on V max : 1.0; on V max /K M : 0.87; for 3-F-[2- 2 H]-L-Ala – on V max : 1.4; on V max /K M : 1.5). Studies explain some details of reaction mechanism. - Highlights: • Synthesis of 3-fluoro-[2- 2 H]-L-alanine was performed. • The reactions were catalysed using the enzyme L-alanine dehydrogenase. • Performed reactions involved fluorinated analogues of L-alanine. • Solvent isotope effects of deuterium were determined. • Kinetic isotope effects were determined for obtained 3-fluoro-L-alanine. • The mechanism of reaction catalysed by L-alanine dehydrogenase was proposed.

  5. Whole body synthesis rates of DHA from α-linolenic acid are greater than brain DHA accretion and uptake rates in adult rats.

    Science.gov (United States)

    Domenichiello, Anthony F; Chen, Chuck T; Trepanier, Marc-Olivier; Stavro, P Mark; Bazinet, Richard P

    2014-01-01

    Docosahexaenoic acid (DHA) is important for brain function, however, the exact amount required for the brain is not agreed upon. While it is believed that the synthesis rate of DHA from α-linolenic acid (ALA) is low, how this synthesis rate compares with the amount of DHA required to maintain brain DHA levels is unknown. The objective of this work was to assess whether DHA synthesis from ALA is sufficient for the brain. To test this, rats consumed a diet low in n-3 PUFAs, or a diet containing ALA or DHA for 15 weeks. Over the 15 weeks, whole body and brain DHA accretion was measured, while at the end of the study, whole body DHA synthesis rates, brain gene expression, and DHA uptake rates were measured. Despite large differences in body DHA accretion, there was no difference in brain DHA accretion between rats fed ALA and DHA. In rats fed ALA, DHA synthesis and accretion was 100-fold higher than brain DHA accretion of rats fed DHA. Also, ALA-fed rats synthesized approximately 3-fold more DHA than the DHA uptake rate into the brain. This work indicates that DHA synthesis from ALA may be sufficient to supply the brain.

  6. Whole body synthesis rates of DHA from α-linolenic acid are greater than brain DHA accretion and uptake rates in adult rats[S

    Science.gov (United States)

    Domenichiello, Anthony F.; Chen, Chuck T.; Trepanier, Marc-Olivier; Stavro, P. Mark; Bazinet, Richard P.

    2014-01-01

    Docosahexaenoic acid (DHA) is important for brain function, however, the exact amount required for the brain is not agreed upon. While it is believed that the synthesis rate of DHA from α-linolenic acid (ALA) is low, how this synthesis rate compares with the amount of DHA required to maintain brain DHA levels is unknown. The objective of this work was to assess whether DHA synthesis from ALA is sufficient for the brain. To test this, rats consumed a diet low in n-3 PUFAs, or a diet containing ALA or DHA for 15 weeks. Over the 15 weeks, whole body and brain DHA accretion was measured, while at the end of the study, whole body DHA synthesis rates, brain gene expression, and DHA uptake rates were measured. Despite large differences in body DHA accretion, there was no difference in brain DHA accretion between rats fed ALA and DHA. In rats fed ALA, DHA synthesis and accretion was 100-fold higher than brain DHA accretion of rats fed DHA. Also, ALA-fed rats synthesized approximately 3-fold more DHA than the DHA uptake rate into the brain. This work indicates that DHA synthesis from ALA may be sufficient to supply the brain. PMID:24212299

  7. Biomonitoring of lead-contaminated Missouri streams with an assay for erythrocyte δ-aminolevulinic acid dehydratase activity in fish blood

    Science.gov (United States)

    Schmitt, C.J.; Wildhaber, M.L.; Hunn, J.B.; Nash, T.; Tieger, M. N.; Steadman, B. L.

    1993-01-01

    The activity of the enzyme δ-aminolevulinic acid dehydratase (ALA-D) in erythrocytes has long been used as a biomarker of lead exposure in humans and waterfowl and, more recently, in fishes. The assay was tested for ALA-D activity in fishes from streams affected by lead in combination with other metals from lead-zinc mining and related activities. Fishes (mostly catostomids) were collected from sites affected by historic and current mining activities, and from sites considered to be unaffected by mining (reference sites). A group of potentially toxic elements was measured in blood and carcass samples of individual fish, as were ALA-D activity, total protein (TP), and hemoglobin (Hb) in blood. Concentrations of mining-related metals (lead, zinc, and cadmium) were significantly greater (P<0.05) in fish blood and carcass at sites affected by historic mining activities than at reference and active mining sites. When analyzed by multiple regression, ALA-D activity, Hb, and TP accounted for 66% of blood-lead and 69% of carcass-lead variability. Differences among species were small. ALA-D activity as a biomarker adequately distinguished sites affected by bioavailable environmental lead. Zinc was the only other metal that affected ALA-D activity; it appeared to ameliorate the inactivation of ALA-D by lead.

  8. Selective Production of 9R-Hydroxy-10E,12Z,15Z-Octadecatrienoic Acid from α-Linolenic Acid in Perilla Seed Oil Hydrolyzate by a Lipoxygenase from Nostoc Sp. SAG 25.82.

    Science.gov (United States)

    Kim, Kyoung-Rok; An, Jung-Ung; Lee, Seon-Hwa; Oh, Deok-Kun

    2015-01-01

    Hydroxy fatty acids (HFAs) derived from omega-3 polyunsaturated fatty acids have been known as versatile bioactive molecules. However, its practical production from omega-3 or omega-3 rich oil has not been well established. In the present study, the stereo-selective enzymatic production of 9R-hydroxy-10E,12Z,15Z-octadecatrienoic acid (9R-HOTE) from α-linolenic acid (ALA) in perilla seed oil (PO) hydrolyzate was achieved using purified recombinant 9R-lipoxygenase (9R-LOX) from Nostoc sp. SAG 25.82. The specific activity of the enzyme followed the order linoleic acid (LA) > ALA > γ-linolenic acid (GLA). A total of 75% fatty acids (ALA and LA) were used as a substrate for 9R-LOX from commercial PO by hydrolysis of Candida rugosa lipase. The optimal reaction conditions for the production of 9R-HOTE from ALA using 9R-LOX were pH 8.5, 15°C, 5% (v/v) acetone, 0.2% (w/v) Tween 80, 40 g/L ALA, and 1 g/L enzyme. Under these conditions, 9R-LOX produced 37.6 g/L 9R-HOTE from 40 g/L ALA for 1 h, with a conversion yield of 94% and a productivity of 37.6 g/L/h; and the enzyme produced 34 g/L 9R-HOTE from 40 g/L ALA in PO hydrolyzate for 1 h, with a conversion yields of 85% and a productivity of 34 g/L/h. The enzyme also converted 9R-hydroxy-10E,12Z-octadecadienoic acid (9R-HODE) from 40 g/L LA for 1.0 h, with a conversion yield of 95% and a productivity of 38.4 g/L. This is the highest productivity of HFA from both ALA and ALA-rich vegetable oil using LOX ever reported. Therefore, our result suggests an efficient method for the production of 9R-HFAs from LA and ALA in vegetable oil using recombinant LOX in biotechnology.

  9. 5-Aminolevulinic Acid-Mediated Sonodynamic Therapy Alleviates Atherosclerosis via Enhancing Efferocytosis and Facilitating a Shift in the Th1/Th2 Balance Toward Th2 Polarization

    Directory of Open Access Journals (Sweden)

    Yang Yang

    2018-05-01

    Full Text Available Background/Aims: We and other groups have demonstrated that 5-aminolevulinic acid (ALA-mediated sonodynamic therapy (ALA-SDT induces macrophage and foam cell apoptosis and stabilizes atherosclerosis (AS plaques in animal models. Lymphocytes also play vital roles in the development of AS. The primary purpose of the present study was to investigate the effects of ALA-SDT on T helper (Th cell fate and function, Th subset differentiation, and atherosclerotic lesion stability. Methods: We utilized ALA-SDT on Western diet-fed apoE-/-mice in vivo and human Jurkat cells in vitro. Hematoxylin and eosin staining and TUNEL assays were used to evaluate the atherosclerotic plaque size and apoptosis within the atheroma. ALA induced cytotoxicity on cultured Jurkat cells was determined with CCK-8 assay. To address the mechanisms, levels of intracellular reactive oxygen species (ROS, mitochondrial membrane potential (MMP, and mitochondrial permeability transition pore (MPTP opening were evaluated by staining with fluorescent probes. Western blot analysis and confocal microscopy were used to analyze the protein levels of caspases, Bax and cytochrome c and the release of cytochrome c. Cell apoptosis and necrosis and phagocytosis were examined by flow cytometry. ELISAs and immunofluorescent staining were used to assess the corresponding cytokine levels and Th subset cell numbers within the atheroma. Results: Our studies revealed that ALA-SDT significantly enhanced CD4+ cell apoptosis and macrophage-mediated phagocytosis and hence reduced the necrotic core size. ALA-SDT activated the mitochondrial apoptotic signaling pathway with minimal necrosis in Jurkat cells. ALA-SDT inhibited the Th1 response and enhanced the Th2 response. These effects of ALA-SDT were mediated primarily through the generation of ROS. Conclusion: ALA-SDT alleviates AS by enhancing cytotoxic effects on Th cells, subsequently stimulating efferocytosis and facilitating a shift in the Th1/Th2

  10. Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea

    Directory of Open Access Journals (Sweden)

    Sol Jae Lee

    2017-07-01

    Full Text Available BackgroundDiabetic cardiac autonomic neuropathy (CAN is one of the important complications of diabetes. It is characterized by reduced heart rate variability (HRV.MethodsIn this randomized, double-blind, placebo-controlled, multicenter trial, 75 patients were randomly assigned to one of two groups. One group (n=41 received α-lipoic acid (ALA at an oral dose of 600 mg/day for the first 12 weeks and then 1,200 mg/day for the next 12 weeks. The other group (n=34 received placebo treatment for 24 weeks. CAN was assessed by measuring HRVs in people with diabetes.ResultsMost of the baseline measures for HRVs were similar between the ALA and placebo groups. Although there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial, we found a positive tendency in some of the HRV parameters of the ALA group. The standard deviations of normal-to-normal RR intervals in the standing position increased by 1.87 ms in the ALA group but decreased by −3.97 ms in the placebo group (P=0.06. The power spectrum of the low frequency (LF band in the standing position increased by 15.77 ms2 in the ALA group, whereas it declined by −15.04 ms2 in the placebo group (P=0.08. The high frequency/LF ratio in the upright position increased by 0.35 in the ALA group, whereas it declined by −0.42 in the placebo group (P=0.06. There were no differences between the two groups regarding rates of adverse events.ConclusionAlthough a slight improvement tendency was seen in HRV in the ALA group, there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial. However, the high oral dose of ALA was well-tolerated.

  11. Retroconversion is a minor contributor to increases in eicosapentaenoic acid following docosahexaenoic acid feeding as determined by compound specific isotope analysis in rat liver.

    Science.gov (United States)

    Metherel, Adam H; Chouinard-Watkins, Raphaël; Trépanier, Marc-Olivier; Lacombe, R J Scott; Bazinet, Richard P

    2017-01-01

    Dietary docosahexaenoic acid (DHA, 22:6n-3) not only increases blood and tissue levels of DHA, but also eicosapentaenoic acid (EPA, 20:5n-3). It is generally believed that this increase is due to DHA retroconversion to EPA, however, a slower conversion of α-linolenic acid (ALA, 18:3n-3) derived EPA to downstream metabolic products (i.e. slower turnover of EPA) is equally plausible. In this study, 21-day old Long Evans rats were weaned onto an ALA only or DHA + ALA diet for 12 weeks. Afterwards, livers were collected and the natural abundance 13 C-enrichment was determined by compound specific isotope analysis (CSIA) of liver EPA by isotope ratio mass-spectrometry and compared to dietary ALA and DHA 13 C-enrichment. Isotopic signatures (per mil, ‰) for liver EPA were not different ( p  > 0.05) between the ALA only diet (-25.89 ± 0.39 ‰, mean ± SEM) and the DHA + ALA diet (-26.26 ± 0.40 ‰), suggesting the relative contribution from dietary ALA and DHA to liver EPA did not change. However, with DHA feeding estimates of absolute EPA contribution from ALA increased 4.4-fold (147 ± 22 to 788 ± 153 nmol/g) compared to 3.2-fold from DHA (91 ± 14 to 382 ± 13 nmol/g), respectively. In conclusion, CSIA of liver EPA in rats following 12-weeks of dietary DHA suggests that retroconversion of DHA to EPA is a relatively small contributor to increases in EPA, and that this increase in EPA is largely coming from elongation/desaturation of ALA.

  12. Dietary HMB and β-alanine co-supplementation does not improve in situ muscle function in sedentary, aged male rats.

    Science.gov (United States)

    Russ, David W; Acksel, Cara; Boyd, Iva M; Maynard, John; McCorkle, Katherine W; Edens, Neile K; Garvey, Sean M

    2015-12-01

    This study evaluated the effects of dietary β-hydroxy-β-methylbutyrate (HMB) combined with β-alanine (β-Ala) in sedentary, aged male rats. It has been suggested that dietary HMB or β-Ala supplementation may mitigate age-related declines in muscle strength and fatigue resistance. A total of 20 aged Sprague-Dawley rats were studied. At age 20 months, 10 rats were administered a control, purified diet and 10 rats were administered a purified diet supplemented with both HMB and β-Ala (HMB+β-Ala) for 8 weeks (approximately equivalent to 3 and 2.4 g per day human dose). We measured medial gastrocnemius (MG) size, force, fatigability, and myosin composition. We also evaluated an array of protein markers related to muscle mitochondria, protein synthesis and breakdown, and autophagy. HMB+β-Ala had no significant effects on body weight, MG mass, force or fatigability, myosin composition, or muscle quality. Compared with control rats, those fed HMB+β-Ala exhibited a reduced (41%, P = 0.039) expression of muscle RING-finger protein 1 (MURF1), a common marker of protein degradation. Muscle from rats fed HMB+β-Ala also exhibited a 45% reduction (P = 0.023) in p70s6K phosphorylation following fatiguing stimulation. These data suggest that HMB+β-Ala at the dose studied may reduce muscle protein breakdown by reducing MURF1 expression, but has minimal effects on muscle function in this model of uncomplicated aging. They do not, however, rule out potential benefits of HMB+β-Ala co-supplementation at other doses or durations of supplementation in combination with exercise or in situations where extreme muscle protein breakdown and loss of mass occur (e.g., bedrest, cachexia, failure-to-thrive).

  13. Effect of alpha linolenic acid supplementation on serum prostate specific antigen (PSA: results from the alpha omega trial.

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    Ingeborg A Brouwer

    Full Text Available Alpha linolenic acid (ALA is the major omega-3 fatty acid in the diet. Evidence on health effects of ALA is not conclusive, but some observational studies found an increased risk of prostate cancer with higher intake of ALA. We examined the effect of ALA supplementation on serum concentrations of prostate-specific antigen (PSA, a biomarker for prostate cancer.The Alpha Omega Trial (ClinicalTrials.gov Identifier: NCT00127452 was a double-blind, placebo-controlled trial of ALA and the fish fatty acids eicosapentanoic acid (EPA and docosahexanoic acid (DHA on the recurrence of cardiovascular disease, using a 2×2 factorial design. Blood was collected at the start and the end of the intervention period. The present analysis included 1622 patients with a history of a myocardial infarction, aged 60-80 years with an initial PSA concentration 4 ng/mL.Mean serum PSA increased by 0.42 ng/mL on placebo (n = 815 and by 0.52 ng/mL on ALA (n = 807, a difference of 0.10 (95% confidence interval: -0.02 to 0.22 ng/mL (P = 0·12. The odds ratio for PSA rising above 4 ng/mL on ALA versus placebo was 1.15 (95% CI: 0.84-1.58.An additional amount of 2 g of ALA per day increased PSA by 0.10 ng/mL, but the confidence interval ranged from -0.02 to 0.22 ng/mL and included no effect. Therefore, more studies are needed to establish whether or not ALA intake has a clinically significant effect on PSA or prostate cancer.ClinicalTrials.gov; Identifier: NCT00127452. URL: http://www.clinicaltrials.gov/ct2/show/NCT00127452.

  14. Potent agonists of growth hormone-releasing hormone. Part I.

    Science.gov (United States)

    Zarandi, M; Serfozo, P; Zsigo, J; Bokser, L; Janaky, T; Olsen, D B; Bajusz, S; Schally, A V

    1992-03-01

    Analogs of the 29 amino acid sequence of growth hormone-releasing hormone (GH-RH) with agmatine (Agm) in position 29 have been synthesized by the solid phase method, purified, and tested in vitro and in vivo. The majority of the analogs contained desaminotyrosine (Dat) in position 1, but a few of them had Tyr1, or N-MeTyr1. Some peptides contained one or more additional L- or D-amino acid substitutions in positions 2, 12, 15, 21, 27, and/or 28. Compared to the natural sequence of GH-RH(1-29)NH2, [Dat1,Ala15]GH-RH(1-28)Agm (MZ-3-191) and [D-Ala2,Ala15]GH-RH(1-28)Agm (MZ-3-201) were 8.2 and 7.1 times more potent in vitro, respectively. These two peptides contained Met27. Their Nle27 analogs, [Dat1,Ala15,Nle27]GH-RH(1-28)Agm(MZ-2-51), prepared previously (9), and [D-Ala2,Ala15,Nle28]GH-RH(1-28)Agm(MZ-3-195) showed relative in vitro potencies of 10.5 and 2.4, respectively. These data indicate that replacement of Met27 by Nle27 enhanced the GH-releasing activity of the analog when the molecule contained Dat1-Ala2 residues at the N-terminus, but peptides containing Tyr1-D-Ala2 in addition to Nle27 showed decreased potencies. Replacement of Ser28 with Asp in multi-substituted analogs of GH-RH(1-28)Agm resulted in a decrease in in vitro potencies compared to the parent compound. Thus, the Ser28-containing MZ-2-51, and [Dat1,Ala15,D-Lys21,Nle27]GH-RH(1-28)Agm, its Asp28 homolog (MZ-3-149), possessed relative activities of 10.5 and 5.6, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. The Pseudomonas aeruginosa antimetabolite L-2-amino-4-methoxy-trans-3-butenoic acid (AMB is made from glutamate and two alanine residues via a thiotemplate-linked tripeptide precursor

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    Nelson eRojas Murcia

    2015-03-01

    Full Text Available The Pseudomonas aeruginosa toxin L-2-amino-4-methoxy-trans-3-butenoic acid (AMB is a non-proteinogenic amino acid which is toxic for prokaryotes and eukaryotes. Production of AMB requires a five-gene cluster encoding a putative LysE-type transporter (AmbA, two nonribosomal peptide synthetases (AmbB and AmbE, and two iron(II/α-ketoglutarate-dependent oxygenases (AmbC and AmbD. Bioinformatics analysis predicts one thiolation (T domain for AmbB and two T domains (T1 and T2 for AmbE, suggesting that AMB is generated by a processing step from a precursor tripeptide assembled on a thiotemplate. Using a combination of ATP-PPi exchange assays, aminoacylation assays, and mass spectrometry-based analysis of enzyme-bound substrates and pathway intermediates, the AmbB substrate was identified to be L-alanine (L-Ala, while the T1 and T2 domains of AmbE were loaded with L-glutamate (L-Glu and L-Ala, respectively. Loading of L-Ala at T2 of AmbE occurred only in the presence of AmbB, indicative of a trans loading mechanism. In vitro assays performed with AmbB and AmbE revealed the dipeptide L-Glu-L-Ala at T1 and the tripeptide L-Ala-L-Glu-L-Ala attached at T2. When AmbC and AmbD were included in the assay, these peptides were no longer detected. Instead, an L-Ala-AMB-L-Ala tripeptide was found at T2. These data are in agreement with a biosynthetic model in which L-Glu is converted into AMB by the action of AmbC, AmbD and tailoring domains of AmbE. The importance of the flanking L-Ala residues in the precursor tripeptide is discussed.

  16. Protoporphyrin IX induced by 5-aminolevulinic acid in bladder cancer cells in voided urine can be extracorporeally quantified using a spectrophotometer.

    Science.gov (United States)

    Nakai, Yasushi; Anai, Satoshi; Onishi, Sayuri; Masaomi, Kuwada; Tatsumi, Yoshihiro; Miyake, Makito; Chihara, Yoshitomo; Tanaka, Nobumichi; Hirao, Yoshihiko; Fujimoto, Kiyohide

    2015-06-01

    We evaluated the feasibility of photodynamic diagnosis of bladder cancer by spectrophotometric analysis of voided urine samples after extracorporeal treatment with 5-aminolevulinic acid (ALA). Sixty-one patients with bladder cancer, confirmed histologically after the transurethral resection of a bladder tumor, were recruited as the bladder cancer group, and 50 outpatients without history of urothelial carcinoma or cancer-related findings were recruited as the control group. Half of the voided urine sample was incubated with ALA (ALA-treated sample), and the rest was incubated without treatment (ALA-untreated sample). For detecting cellular protoporphyrin IX levels, intensity of the samples at the excitation wavelength of 405 nm was measured using a spectrophotometer. The difference between the intensity of the ALA-treated and ALA-untreated samples at 635 nm was calculated. The differences in the bladder cancer group were significantly greater than those in the control group (p spectrophotometer in patients with bladder cancer. Therefore, this cancer detection system has a potential for clinical use. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Bifidobacterium breve with α-linolenic acid alters the composition, distribution and transcription factor activity associated with metabolism and absorption of fat.

    Science.gov (United States)

    Patterson, Elaine; Wall, Rebecca; Lisai, Sara; Ross, R Paul; Dinan, Timothy G; Cryan, John F; Fitzgerald, Gerald F; Banni, Sebastiano; Quigley, Eamonn M; Shanahan, Fergus; Stanton, Catherine

    2017-03-07

    This study focused on the mechanisms that fatty acid conjugating strains - Bifidobacterium breve NCIMB 702258 and Bifidobacterium breve DPC 6330 - influence lipid metabolism when ingested with α-linolenic acid (ALA) enriched diet. Four groups of BALB/c mice received ALA enriched diet (3% (w/w)) either alone or in combination with B. breve NCIMB 702258 or B. breve DPC 6330 (10 9 CFU/day) or unsupplemented control diet for six weeks. The overall n-3 PUFA score was increased in all groups receiving the ALA enriched diet. Hepatic peroxisomal beta oxidation increased following supplementation of the ALA enriched diet with B. breve (P breve NCIMB 702258 was found on the endocannabinoid system (ECS). Liver triglycerides (TAG) were reduced following ALA supplementation, compared with unsupplemented controls (P breve further reduced liver TAG (P < 0.01), compared with the ALA enriched control. These data indicate that the interactions of the gut microbiota with fatty acid metabolism directly affect host health by modulating n-3 PUFA score and the ECS.

  18. Bifidobacterium breve with α-linolenic acid alters the composition, distribution and transcription factor activity associated with metabolism and absorption of fat

    Science.gov (United States)

    Patterson, Elaine; Wall, Rebecca; Lisai, Sara; Ross, R. Paul; Dinan, Timothy G.; Cryan, John F.; Fitzgerald, Gerald F.; Banni, Sebastiano; Quigley, Eamonn M.; Shanahan, Fergus; Stanton, Catherine

    2017-01-01

    This study focused on the mechanisms that fatty acid conjugating strains - Bifidobacterium breve NCIMB 702258 and Bifidobacterium breve DPC 6330 - influence lipid metabolism when ingested with α-linolenic acid (ALA) enriched diet. Four groups of BALB/c mice received ALA enriched diet (3% (w/w)) either alone or in combination with B. breve NCIMB 702258 or B. breve DPC 6330 (109 CFU/day) or unsupplemented control diet for six weeks. The overall n-3 PUFA score was increased in all groups receiving the ALA enriched diet. Hepatic peroxisomal beta oxidation increased following supplementation of the ALA enriched diet with B. breve (P breve NCIMB 702258 was found on the endocannabinoid system (ECS). Liver triglycerides (TAG) were reduced following ALA supplementation, compared with unsupplemented controls (P breve further reduced liver TAG (P < 0.01), compared with the ALA enriched control. These data indicate that the interactions of the gut microbiota with fatty acid metabolism directly affect host health by modulating n-3 PUFA score and the ECS. PMID:28265110

  19. Alanine synthesis from glyceraldehyde and ammonium ion in aqueous solution

    Science.gov (United States)

    Weber, A. L.

    1985-01-01

    The formation of alanine (ala) form C(14)-glyceraldehyde and ammonium phosphate in the presence or absence of a thiol is reported. At ambient temperature, ala synthesis was six times more rapid in the presence of 3-mercaptopropionic acid than in its absence (0.6 and 0.1 percent, respectively, after 60 days). Similarly, the presence of another thiol, N-acetylcysteinate, increased the production of ala, as well as of lactate. The reaction pathway of thiol-catalyzed synthesis of ala, with the lactic acid formed in a bypath, is suggested. In this, dehydration of glyceraldehyde is followed by the formation of hemithioacetal. In the presence of ammonia, an imine is formed, which eventually yields ala. This pathway is consistent with the observation that the rate ratio of ala/lactate remains constant throughout the process. The fact that the reaction takes place under anaerobic conditions in the presence of H2O and with the low concentrations of simple substrates and catalysts makes it an attractive model prebiotic reaction in the process of molecular evolution.

  20. Chronic treatment of (R)-α-lipoic acid reduces blood glucose and lipid levels in high-fat diet and low-dose streptozotocin-induced metabolic syndrome and type 2 diabetes in Sprague-Dawley rats.

    Science.gov (United States)

    Ghelani, Hardik; Razmovski-Naumovski, Valentina; Nammi, Srinivas

    2017-06-01

    (R)- α -lipoic acid ( ALA ), an essential cofactor in mitochondrial respiration and a potential antioxidant, possesses a wide array of metabolic benefits including anti-obesity, glucose lowering, insulin-sensitizing, and lipid-lowering effects. In this study, the curative effects of ALA (100 mg/kg) on a spectrum of conditions related to metabolic syndrome and type 2 diabetes ( T2D ) were investigated in a high-fat diet (HFD)-fed and low-dose streptozotocin (STZ)-induced rat model of metabolic syndrome and T2D . The marked rise in the levels of glucose, triglycerides, total-cholesterol, LDL-cholesterol, and VLDL-cholesterol in the blood of HFD-fed and low-dose STZ-injected rats were significantly reduced by ALA treatment. Furthermore, ALA treatment significantly increased the serum HDL-cholesterol levels and tended to inhibit diabetes-induced weight reduction. Mathematical computational analysis revealed that ALA also significantly improved insulin sensitivity and reduced the risk of atherosclerotic lesions and coronary atherogenesis. This study provides scientific evidence to substantiate the use of ALA to mitigate the glucose and lipid abnormality in metabolic syndrome and T2D .

  1. Entamoeba histolytica acetyl–CoA synthetase: biomarker of acute amoebic liver abscess

    Directory of Open Access Journals (Sweden)

    Lim Boon Huat

    2014-06-01

    Conclusions: This finding suggested the significant role of EhACS as a biomarker for moribund hamsters with acute amoebic liver abscess (ALA infection. It is deemed pertinent that future studies explore the potential roles of EhACS in better understanding the pathogenesis of ALA; and in the development of vaccine and diagnostic tests to control ALA in human populations.

  2. d-Alanine metabolism is essential for growth and biofilm formation of Streptococcus mutans.

    Science.gov (United States)

    Qiu, W; Zheng, X; Wei, Y; Zhou, X; Zhang, K; Wang, S; Cheng, L; Li, Y; Ren, B; Xu, X; Li, Y; Li, M

    2016-10-01

    Part of the d-alanine (d-Ala) metabolic pathway in bacteria involves the conversion of l-alanine to d-Ala by alanine racemase and the formation of d-alanyl-d-alanine by d-alanine-d-alanine ligase, the product of which is involved in cell wall peptidoglycan synthesis. At present, drugs that target the metabolic pathway of d-Ala are already in clinical use - e.g. d-cycloserine (DCS) is used as an antibiotic against Mycobacterium tuberculosis. Streptococcus mutans is the main cariogenic bacterium in the oral cavity. Its d-Ala metabolism-associated enzymes alanine racemase and d-alanine-d-alanine ligase are encoded by the genes smu.1834 and smu.599, respectively, which may be potential targets for inhibitors. In this study, the addition of DCS blocked the d-Ala metabolic pathway in S. mutans, leading to bacterial cell wall defects, significant inhibition of bacterial growth and biofilm formation, and reductions in extracellular polysaccharide production and bacterial adhesion. However, the exogenous addition of d-Ala could reverse the inhibitory effect of DCS. Through the means of drug regulation, our study demonstrated, for the first time, the importance of d-Ala metabolism in the survival and biofilm formation of S. mutans. If the growth of S. mutans can be specifically inhibited by designing drugs that target d-Ala metabolism, then this may serve as a potential new treatment for dental caries. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. The Porphobilinogen Conundrum in Prebiotic Routes to Tetrapyrrole Macrocycles

    Science.gov (United States)

    Taniguchi, Masahiko; Ptaszek, Marcin; Chandrashaker, Vanampally; Lindsey, Jonathan S.

    2017-03-01

    Attempts to develop a credible prebiotic route to tetrapyrroles have relied on enzyme-free recapitulation of the extant biosynthesis, but this process has foundered from the inability to form the pyrrole porphobilinogen ( PBG) in good yield by self-condensation of the precursor δ-aminolevulinic acid ( ALA). PBG undergoes robust oligomerization in aqueous solution to give uroporphyrinogen (4 isomers) in good yield. ALA, PBG, and uroporphyrinogen III are universal precursors to all known tetrapyrrole macrocycles. The enzymic formation of PBG entails carbon-carbon bond formation between the less stable enolate/enamine of one ALA molecule (3-position) and the carbonyl/imine (4-position) of the second ALA molecule; without enzymes, the first ALA reacts at the more stable enolate/enamine (5-position) and gives the pyrrole pseudo-PBG. pseudo-PBG cannot self-condense, yet has one open α-pyrrole position and is proposed to be a terminator of oligopyrromethane chain-growth from PBG. Here, 23 analogues of ALA have been subjected to density functional theoretical (DFT) calculations, but no motif has been identified that directs reaction at the 3-position. Deuteriation experiments suggested 5-(phosphonooxy)levulinic acid would react preferentially at the 3- versus 5-position, but a hybrid condensation with ALA gave no observable uroporphyrin. The results suggest efforts toward a biomimetic, enzyme-free route to tetrapyrroles from ALA should turn away from structure-directed reactions and focus on catalysts that orient the two aminoketones to form PBG in a kinetically controlled process, thereby avoiding formation of pseudo-PBG.

  4. 17β-estradiol increases liver and serum docosahexaenoic acid in mice fed varying levels of α-linolenic acid.

    Science.gov (United States)

    Mason, Julie K; Kharotia, Shikhil; Wiggins, Ashleigh K A; Kitson, Alex P; Chen, Jianmin; Bazinet, Richard P; Thompson, Lilian U

    2014-08-01

    Docosahexaenoic acid (DHA) is considered to be important for cardiac and brain function, and 17β-estradiol (E2) appears to increase the conversion of α-linolenic acid (ALA) into DHA. However, the effect of varying ALA intake on the positive effect of E2 on DHA synthesis is not known. Therefore, the objective of this study was to investigate the effects of E2 supplementation on tissue and serum fatty acids in mice fed a low-ALA corn oil-based diet (CO, providing 0.6 % fatty acids as ALA) or a high ALA flaxseed meal-based diet (FS, providing 11.2 % ALA). Ovariectomized mice were implanted with a slow-release E2 pellet at 3 weeks of age and half the mice had the pellet removed at 7 weeks of age. Mice were then randomized onto either the CO or FS diet. After 4 weeks, the DHA concentration was measured in serum, liver and brain. A significant main effect of E2 was found for liver and serum DHA, corresponding to 25 and 15 % higher DHA in livers of CO and FS rats, respectively, and 19 and 13 % in serum of CO and FS rats, respectively, compared to unsupplemented mice. There was no effect of E2 on brain DHA. E2 results in higher DHA in serum and liver, at both levels of dietary ALA investigated presently, suggesting that higher ALA intake may result in higher DHA in individuals with higher E2 status.

  5. Fractional Ablative Laser Followed by Transdermal Acoustic Pressure Wave Device to Enhance the Drug Delivery of Aminolevulinic Acid: In Vivo Fluorescence Microscopy Study.

    Science.gov (United States)

    Waibel, Jill S; Rudnick, Ashley; Nousari, Carlos; Bhanusali, Dhaval G

    2016-01-01

    Topical drug delivery is the foundation of all dermatological therapy. Laser-assisted drug delivery (LAD) using fractional ablative laser is an evolving modality that may allow for a greater precise depth of penetration by existing topical medications, as well as more efficient transcutaneous delivery of large drug molecules. Additional studies need to be performed using energy-driven methods that may enhance drug delivery in a synergistic manner. Processes such as iontophoresis, electroporation, sonophoresis, and the use of photomechanical waves aid in penetration. This study evaluated in vivo if there is increased efficacy of fractional CO2 ablative laser with immediate acoustic pressure wave device. Five patients were treated and biopsied at 4 treatment sites: 1) topically applied aminolevulinic acid (ALA) alone; 2) fractional ablative CO2 laser and topical ALA alone; 3) fractional ablative CO2 laser and transdermal acoustic pressure wave device delivery system; and 4) topical ALA with transdermal delivery system. The comparison of the difference in the magnitude of diffusion with both lateral spread of ALA and depth diffusion of ALA was measured by fluorescence microscopy. For fractional ablative CO2 laser, ALA, and transdermal acoustic pressure wave device, the protoporphyrin IX lateral fluorescence was 0.024 mm on average vs 0.0084 mm for fractional ablative CO2 laser and ALA alone. The diffusion for the acoustic pressure wave device was an order of magnitude greater. We found that our combined approach of fractional ablative CO2 laser paired with the transdermal acoustic pressure wave device increased the depth of penetration of ALA.

  6. Alpha-lipoic acid attenuates cardiac fibrosis in Otsuka Long-Evans Tokushima Fatty rats

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    Lee Jung Eun

    2012-09-01

    Full Text Available Abstract Background Hyperglycemia leads to cardiac oxidative stress and an imbalance in glucose homeostasis. Diabetic cardiomyopathy is characterised by cardiac hypertrophy and fibrosis. However, the underlying mechanisms of diabetic cardiomyopathy are not fully understood. This study aimed to investigate the effects of alpha-lipoic acid (ALA on cardiac energy metabolism, antioxidant effect, and fibrosis in the hearts of Otsuka Long-Evans Tokushima fatty (OLETF rats. Methods Animals were separated into non-diabetic Long-Evans Tokushima Otsuka (LETO rats and diabetes-prone OLETF rats with or without ALA (200 mg/kg/day administration for 16 weeks. Diabetic cardiomyopathy was assessed by staining with Sirius Red. The effect of ALA on AMPK signalling, antioxidant enzymes, and fibrosis-related genes in the heart of OLETF rats were performed by Western blot analysis or immunohistochemistry. Results Western blot analysis showed that cardiac adenosine monophosphate-activated kinase (AMPK signalling was lower in OLETF rats than in LETO rats, and that ALA treatment increased the signalling in OLETF rats. Furthermore, the low antioxidant activity in OLETF rats was increased by ALA treatment. In addition to increased Sirius red staining of collagen deposits, transforming growth factor-β1 (TGF-β1 and connective tissue growth factor (CTGF were expressed at higher levels in OLETF rat hearts than in LETO rat hearts, and the levels of these factors were decreased by ALA. Conclusions ALA enhances AMPK signalling, antioxidant, and antifibrogenic effect. Theses findings suggest that ALA may have beneficial effects in the treatment of diabetic cardiomyopathy.

  7. Treating cutaneous squamous cell carcinoma using 5-aminolevulinic acid polylactic-co-glycolic acid nanoparticle-mediated photodynamic therapy in a mouse model

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    Wang X

    2015-01-01

    Full Text Available Xiaojie Wang,1,2,* Lei Shi,2,* Qingfeng Tu,2 Hongwei Wang,3 Haiyan Zhang,2 Peiru Wang,2 Linglin Zhang,2 Zheng Huang,4 Feng Zhao,5 Hansen Luan,5 Xiuli Wang2 1Shanghai Skin Diseases Clinical College of Anhui Medical University, 2Shanghai Skin Disease Hospital, 3Huadong Hospital, Fudan University, Shanghai, 4MOE Key Laboratory of OptoElectronic Science and Technology for Medicine, Fujian Normal University, Fuzhou, 5National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, People’s Republic of China *These authors contributed equally to this study Background: Squamous cell carcinoma (SCC is a common skin cancer, and its treatment is still difficult. The aim of this study was to evaluate the effectiveness of nanoparticle (NP-assisted 5-aminolevulinic acid (ALA delivery for topical photodynamic therapy (PDT of cutaneous SCC.Materials and methods: Ultraviolet-induced cutaneous SCCs were established in hairless mice. ALA-loaded polylactic-co-glycolic acid (PLGA NPs were prepared and characterized. The kinetics of ALA PLGA NP-induced protoporphyrin IX fluorescence in SCCs, therapeutic efficacy of ALA NP-mediated PDT, and immune responses were examined.Results: PLGA NPs enhanced protoporphyrin IX production in SCC. ALA PLGA NP-mediated topical PDT was more effective than free ALA of the same concentration in treating cutaneous SCC.Conclusion: PLGA NPs provide a promising strategy for delivering ALA in topical PDT of cutaneous SCC. Keywords: 5-aminolevulinic acid (ALA, polylactic-co-glycolic acid (PLGA, nanoparticles (NPs, cutaneous squamous cell carcinoma (SCC, photodynamic therapy (PDT, microneedling

  8. Alpha linolenic acid in maternal diet halts the lipid disarray due to saturated fatty acids in the liver of mice offspring at weaning.

    Science.gov (United States)

    Shomonov-Wagner, Limor; Raz, Amiram; Leikin-Frenkel, Alicia

    2015-02-26

    Alpha linolenic acid (ALA, 18:3) in maternal diets has been shown to attenuate obesity associated insulin resistance (IR) in adult offspring in mice. The objective in the present study was to detect the early effects of maternal dietary saturated fatty acids (SFA) and their partial substitution with ω-3 ALA, docosa hexenoic acid (DHA,22:6) and eicosapentenoic acid 20:5 (EPA,20:5) on the HOMA index, liver lipids and fatty acid desaturases in the offspring at weaning. 3 month old C57Bl6/J female mice were fed diets containing normal amount of calories but rich in SFA alone or partially replaced with ALA, DHA or EPA before mating, during pregnancy and lactation. Pregnant mice fed SFA produced offspring with the highest HOMA index, liver lipids and desaturase activities. ALA prevented SFA induced lipid increase but DHA and EPA only reduced it by 42% and 31% respectively. ALA, DHA and EPA decreased HOMA index by 84%, 75% and 83% respectively. ALA, DHA and EPA decreased Δ6 and SCD1 desaturase activities about 30%. SFA feeding to mothers predisposes their offspring to develop IR and liver lipid accumulation already at weaning. ω3 fatty acids reduce IR, ALA halts lipid accumulation whereas DHA and EPA only blunt it.ALA and DHA restore the increased SCD1 to normal. These studies suggest that ω-3 fatty acids have different potencies to preclude lipid accumulation in the offspring partially by affecting pathways associated to SCD1 modulation.

  9. Synthesis and immunostimulating properties of novel adamant-1-yl tripeptides.

    Science.gov (United States)

    Ribić, Rosana; Habjanec, Lidija; Vranešić, Branka; Frkanec, Ruža; Tomić, Srđanka

    2012-04-01

    The aim of this work was to prepare L- and D-(adamant-1-yl)-Gly-L-Ala-D-isoGln peptides in order to study their adjuvant (immunostimulating) activities. Adjuvant activity of adamant-1-yl tripeptides was tested in the mouse model using ovalbumin as an antigen and in comparison to the peptidoglycan monomer (PGM; β-D-GlcNAc-(1→4)-D-MurNAc-L-Ala-D-isoGln-mesoDAP(εNH(2) )-D-Ala-D-Ala) and structurally related adamant-2-yl tripeptides. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

  10. Aplicación del módulo de reanimación cardiopulmonar (RCP) básica en recién nacidos en el currículo de enfermería y el aprendizaje de los alumnos de enfermería de la Universidad Alas Peruanas filial Chosica- durante el año académico 2012

    OpenAIRE

    Torres Contreras, Hayder Ronald

    2015-01-01

    El objetivo de la investigación fue determinar la influencia de la aplicación del Módulo Teórico- Práctico en la Atención en Reanimación Cardiopulmonar (RCP) Básica en Recién Nacidos, en el aprendizaje de los estudiantes de la Facultad de Enfermería de la Universidad Alas Peruanas Filial Chosica, Lima Perú 2012. Material y métodos: Estudio es de tipo ex post facto retrospectivo que recoge los resultados de un estudio de tipo pre - experimental, con preprueba y posprueba pre-experimental reali...

  11. Interactions of nickel(II) with histones: enhancement of 2'-deoxyguanosine oxidation by Ni(II) complexes with CH3CO-Cys-Ala-Ile-His-NH2, a putative metal binding sequence of histone H3.

    Science.gov (United States)

    Bal, W; Lukszo, J; Kasprazak, K S

    1996-03-01

    Studies of 2'-deoxyguanosine oxidation by hydrogen peroxide in the presence of CH3CO-Cys-Ala-Ile-His-NH2 (CAIH) and/or NiCl2 have been carried out in 100 mM phosphate buffer (pH 7.4) at 37 degrees C. The dimeric CAIH oxidation product, CAIH disulfide, and its weak, octahedral Ni(II) complex, rather than the monomeric CAIH and its strong, square-planar Ni(II) complex, were found to be major catalysts of 8-oxo-2'-deoxyguanosine (8-oxo-dG) formation. The presence of Ni(II) largely enhanced 8-oxo-dG yield, especially at submillimolar concentrations of H2O2. The reaction was found not to involve detectable amounts of free radicals or Ni(III). These results, together with those published previously [Bal, W. et al. (1995) Chem. Res. Toxicol. 8, 683-692], lay a framework for the detailed investigations of the interactions of histone octamer with Ni(II) and other metal ions. They also suggest that molecular mechanisms of nickel carcinogenesis may involve oxidative damage processes catalyzed by weak Ni(II) complexes with cellular components.

  12. Effect of 5-aminolevulinic acid on kinetics of protoporphyrin IX production in CHO cells.

    Directory of Open Access Journals (Sweden)

    W Warchoł

    2004-07-01

    Full Text Available 5-aminolevulinic acid (ALA is utilized in a photodynamic therapy as a compound capable of augmenting intracellular pool of protoporphyrin IX (PpIX, which exhibits properties of a photosensitizer. The studies were aimed at monitoring accumulation of endogenous protoporphyrin IX in CHO cells under effect of various concentrations of ALA in culture medium and following removal of the compound from the culture medium. Cell content of PpIX was determined following incubation of the cells for 72 h in a culture medium containing different concentration of ALA. Moreover, the cells were preincubated for 2 h in ALA at various concentrations and separated from the compound by medium change and their PpIX content was monitored following incubation. PpIX content was defined by a fluorescent technique under the confocal microscope. In the course of continuous incubation of cells with ALA, biphasic alterations were noted in cellular PpIX concentration. Removal of ALA from the incubation medium resulted at first in a decrease in PpIX content in cells, which was followed by an evidently augmented accumulation of the compound in the cells. The results suggested that in the case of CHO cells, exogenous ALA was not an exclusive source of PpIX synthesis and that alterations in enzyme activities were responsible for production of PpIX.

  13. An evaluation of the Oxoid Biochemical Identification System Campy rapid screening test for Campylobacteraceae and Helicobacter spp.

    Science.gov (United States)

    Hoosain, N; Lastovica, A J

    2009-06-01

    To evaluate the Oxoid Biochemical Identification System (OBIS) Campy test (ID0800M) against Campylobacter; Arcobacter; and other micro-organisms, with similar colonial morphology, for the detection of l-alanine aminopeptidase (l-ALA). The KOH and l-ALA (OBIS and Fluka) tests were carried out on every isolate. The procedures were followed as indicated in the OBIS and Fluka kit instructions. A total of 146 strains of 19 species of Campylobacter, seven strains of Arcobacter butzleri, four Arcobacter butzleri-like strains, 42 strains of 10 species of Helicobacter, 96 Gram-negative and 49 Gram-positive clinical isolates were tested. As expected, Campylobacter and Arcobacter strains were negative, while other Gram-negative bacteria were positive for the l-ALA test. An unexpected finding was that Helicobacter strains, although Gram-negative, were all negative for the l-ALA tests suggesting the absence of l-ALA within this genus. This is a novel finding. The absence of l-ALA was confirmed upon comparison with the available full genomic sequences of Helicobacter on the NCBI database. The OBIS Campy (ID0800M) test kit proved to be rapid and accurate for the presumptive characterization of Campylobacter and Arcobacter. A novel finding was that Helicobacter species also did not have the l-ALA enzyme. The OBIS kit will be useful in diagnostic laboratories for the presumptive diagnosis of Campylobacter, Arcobacter and Helicobacter strains.

  14. Transferred nuclear Overhauser effect analyses of membrane-bound enkephalin analogues by sup 1 H nuclear magnetic resonance: Correlation between activities and membrane-bound conformations

    Energy Technology Data Exchange (ETDEWEB)

    Milon, Alain; Miyazawa, Tatsuo; Higashijima, Tsutomu (Univ. of Tokyo (Japan))

    1990-01-09

    Leu-enkephalin, (D-Ala{sup 2})Leu-enkephalin, and (D-Ala{sup 2})Leu-enkephalinamide (agonists) and (L-Ala{sup 2})Leu-enkephalin (inactive analogue) bind to lipid bilayer consisting of phosphatidylcholine and phosphatidylserine. The conformations that these compounds assume, once bound to perdeuterated phospholipid bilayer, have been shown to be unique, as shown by the transferred nuclear Overhauser effect (TRNOE) of {sup 1}H NMR spectroscopy. In addition, their location in the bilayer was analyzed by TRNOE in the presence of spin-labeled phospholipids. These analyses showed a clear relationship between the activity and the peptide-membrane interaction. The three active peptides, when bound to membranes, adopt the same conformation, characterized by a type II{prime} {beta}-turn around Gly{sup 3}-Phe and a {gamma}-turn around Gly{sup 2} (or D-Ala{sup 2}). The inactive analogue, (L-Ala{sup 2})Leu-enkephalin, displayed a completely different TRNOE pattern corresponding to a different conformation in the membrane-bound state. The tyrosine residue of the active compounds is not inserted into the interior of membrane, but it is inserted into the bilayer for the L-Ala{sup 2} analogue. According to these results, (L-Ala{sup 2})Leu-enkephalin may be explained to be inactive because the mode of binding to the membranes is different from that of active compounds.

  15. 6061 Alüminyum Alaşımının Sürtünme Karıştırma Kaynak Yöntemi ile Kaynak Edilebilirliğinin İncelenmesi

    Directory of Open Access Journals (Sweden)

    İlker EKER

    2009-02-01

    Full Text Available Bu çalışmada sürtünme karıştırma kaynağı yöntemiyle birleştirilen alüminyum döküm levhaların kaynak bölgelerinin değişen parametrelerle mikrosertlik ve mekanik özellikleri incelenmiştir. Kaynak süresince karıştırıcı ucun devir sayısı ve kaynak ilerleme hızı değişken parametreler olarak alınmıştır. Alüminyum alaşımlı levhaların kaynağında SAE 8620 malzeme numaralı sementasyon çeliğinden imal edilmiş karıştırıcı uç kullanılmıştır. Karıştırıcı ucun devir hızı sabitken kaynak ilerleme hızı dört farklı değerde seçilmiştir. Kaynaklı birleştirmelere metalografik ve mekanik testler yapılarak işlem parametrelerinin etkileri araştırılmıştır.

  16. Prostate Cancer in the Metropolitan Washington DC Latino/Hispanic Community; Cultural, Linguistic and Economic Barriers to Care

    Science.gov (United States)

    2001-01-01

    AGVILAR ALARY ALBURQUERQUE ALDAVE ANEWO ALAS ALCADE ALDAYA AMIN ALATORRE ALCAIDA ALDAZ AHUERO ALATRISTE ALCAIDE ALDAZABAL ANUMADA ALA VA ALCALA...ALDEBOT AIBAR ALAVARADO ALCALAN ALDECOA A [NSA ALA VARDO ALCALDE ALDECOCEA AINZ ALAYA ALCAHIZ ALDEIS AIKZA ALAYETO ALCANTA ALDEREGUIA AIRA ALAYO ALCANTAR...ARMADO ARQUELLES ARRIAZOLA ARTEGO ARKAIZ ARQUELLO ARRIBA ARTELLAI( ARKANDARIZ ARQUER ARRIBAS ARTERO ARJ4ARIO ARQUERO ARRIERA ARTESOKA ARMAS ARQUES ARRIERO

  17. Apolar Distal Pocket Mutants of Yeast Cytochrome c Peroxidase: Hydrogen Peroxide Reactivity and Cyanide Binding of the TriAla, TriVal, and TriLeu Variants

    Science.gov (United States)

    Bidwai, Anil K.; Meyen, Cassandra; Kilheeney, Heather; Wroblewski, Damian; Vitello, Lidia B.; Erman, James E.

    2012-01-01

    Three yeast cytochrome c peroxidase (CcP) variants with apolar distal heme pockets have been constructed. The CcP variants have Arg48, Trp51, and His52 mutated to either all alanines, CcP(triAla), all valines, CcP(triVal), or all leucines, CcP(triLeu). The triple mutants have detectable enzymatic activity at pH 6 but the activity is less than 0.02% that of wild-type CcP. The activity loss is primarily due to the decreased rate of reaction between the triple mutants and H2O2 compared to wild-type CcP. Spectroscopic properties and cyanide binding characteristics of the triple mutants have been investigated over the pH stability region of CcP, pH 4 to 8. The absorption spectra indicate that the CcP triple mutants have hemes that are predominantly five-coordinate, high-spin at pH 5 and six-coordinate, low-spin at pH 8. Cyanide binding to the triple mutants is biphasic indicating that the triple mutants have two slowly-exchanging conformational states with different cyanide affinities. The binding affinity for cyanide is reduced at least two orders of magnitude in the triple mutants compared to wild-type CcP and the rate of cyanide binding is reduced by four to five orders of magnitude. Correlation of the reaction rates of CcP and 12 distal pocket mutants with H2O2 and HCN suggests that both reactions require ionization of the reactants within the distal heme pocket allowing the anion to bind the heme iron. Distal pocket features that promote substrate ionization (basic residues involved in base-catalyzed substrate ionization or polar residues that can stabilize substrate anions) increase the overall rate of reaction with H2O2 and HCN while features that inhibit substrate ionization slow the reactions. PMID:23022490

  18. Dietary alpha-Lipoic Acid Alters Piglet Neurodevelopment

    Directory of Open Access Journals (Sweden)

    Austin T Mudd

    2016-05-01

    Full Text Available Introduction: Alpha-lipoic acid (a-LA is an antioxidant shown to ameliorate age-associated impairments of brain and cardiovascular function. Human milk is known to have high antioxidant capacity, however the role of antioxidants in the developing brain is largely uncharacterized. This exploratory study aimed to examine the dose response effects of a-LA on piglet growth and neurodevelopment. Methods: Beginning at 2 d of age, 31 male pigs received one of three diets: control (CONT [0 mg a-LA/100g], low a-LA (LOW [120 mg a-LA/100g], or high a-LA (HIGH [240 mg a-LA/100g]. From 14 to 28 d of age, pigs were subjected to spatial T-maze assessment and macrostructural and microstructural neuroimaging procedures were performed at 31 d of age.Results: No differences due to diet were observed for bodyweight gain or intestinal weight and length. Spatial T-maze assessment did not reveal learning differences due to diet in proportion of correct choices or latency to choice measures. Diffusion tensor imaging revealed decreased (P = 0.01 fractional anisotropy (FA in the internal capsule of HIGH fed pigs compared with both the CONT (P < 0.01 and LOW (P = 0.03 fed pigs, which were not different from one another. Analysis of axial diffusivity (AD within the internal capsule revealed a main effect of diet (P < 0.01 in which HIGH fed piglets exhibited smaller (P < 0.01 rates of diffusion compared with CONT piglets, but HIGH fed piglets were not different (P = 0.12 than LOW fed piglets. Tract-based spatial statistics, a comparison of FA values along white matter tracts, revealed 1,650 voxels where CONT piglets exhibited higher (P < 0.05 values compared with HIGH fed piglets. Conclusion: The lack of differences in intestinal and bodyweight measures among piglets indicate a-LA supplementation does not impact overall growth, regardless of concentration. Additionally, no observed differences between CONT and LOW fed piglets in behavior and neuroimaging measures indicate a

  19. N-terminal diproline and charge group effects on the stabilization of helical conformation in alanine-based short peptides: CD studies with water and methanol as solvent.

    Science.gov (United States)

    Goyal, Bhupesh; Srivastava, Kinshuk Raj; Durani, Susheel

    2017-06-01

    Protein folding problem remains a formidable challenge as main chain, side chain and solvent interactions remain entangled and have been difficult to resolve. Alanine-based short peptides are promising models to dissect protein folding initiation and propagation structurally as well as energetically. The effect of N-terminal diproline and charged side chains is assessed on the stabilization of helical conformation in alanine-based short peptides using circular dichroism (CD) with water and methanol as solvent. A1 (Ac-Pro-Pro-Ala-Lys-Ala-Lys-Ala-Lys-Ala-NH 2 ) is designed to assess the effect of N-terminal homochiral diproline and lysine side chains to induce helical conformation. A2 (Ac-Pro-Pro-Glu-Glu-Ala-Ala-Lys-Lys-Ala-NH 2 ) and A3 (Ac-dPro-Pro-Glu-Glu-Ala-Ala-Lys-Lys-Ala-NH 2 ) with N-terminal homochiral and heterochiral diproline, respectively, are designed to assess the effect of Glu...Lys (i, i + 4) salt bridge interactions on the stabilization of helical conformation. The CD spectra of A1, A2 and A3 in water manifest different amplitudes of the observed polyproline II (PPII) signals, which indicate different conformational distributions of the polypeptide structure. The strong effect of solvent substitution from water to methanol is observed for the peptides, and CD spectra in methanol evidence A2 and A3 as helical folds. Temperature-dependent CD spectra of A1 and A2 in water depict an isodichroic point reflecting coexistence of two conformations, PPII and β-strand conformation, which is consistent with the previous studies. The results illuminate the effect of N-terminal diproline and charged side chains in dictating the preferences for extended-β, semi-extended PPII and helical conformation in alanine-based short peptides. The results of the present study will enhance our understanding on stabilization of helical conformation in short peptides and hence aid in the design of novel peptides with helical structures. Copyright © 2017 European Peptide

  20. Evaluation of Eudragit® Retard Polymers for the Microencapsulation of Alpha-Lipoic Acid.

    Science.gov (United States)

    Pecora, Tiziana M G; Musumeci, Teresa; Musumeci, Lucrezia; Fresta, Massimo; Pignatello, Rosario

    2016-01-01

    Microencapsulation of natural antioxidants in polymeric systems represents a possible strategy for improving the oral bioavailability of compounds that are otherwise poorly soluble. α-lipoic acid (ALA) was microencapsulated with polymethacrylate polymers (blends at various ratios of Eudragit® RS100 and RL100 resins). Microspheres were produced by solvent displacement of an ethanol cosolution of ALA and polymers; the microsuspensions were then freeze-dried, using trehalose as a cryoprotector. Microspheres were characterized in the solid state for micromeritic properties and drug loading, as well as by infrared spectroscopy, powder X-ray diffractometry and differential scanning calorimetry. The antioxidant activity of free and encapsulated ALA was assessed by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. In vitro release studies, performed in simulated gastric (pH 1.2) and intestinal fluid (pH 6.8), showed that, depending on polymer composition and drug-to-polymer ratio, ALA release can be slowed down, compared to the dissolution pattern of the free drug. Solid-state characterization confirmed the chemical stability of ALA in the microspheres, suggesting that ALA did not develop strong interactions with the polymer and was present in an amorphous or a disordered-crystalline state within the polymer network. As indicated by the DPPH assay, the microencapsulation of ALA in Eudragit® Retard matrices did not alter its antioxidant activity. ALA was effectively encapsulated in Eudragit® Retard matrices, showing a chemical stability up to 6 months at room conditions and at 40°C. Moreover, since the drug maintained its antioxidant activity in vitro, the potential application of these microparticulate systems for oral administration would deserve further studies.

  1. A microscopic insight from conformational thermodynamics to functional ligand binding in proteins.

    Science.gov (United States)

    Sikdar, Samapan; Chakrabarti, J; Ghosh, Mahua

    2014-12-01

    We show that the thermodynamics of metal ion-induced conformational changes aid to understand the functions of protein complexes. This is illustrated in the case of a metalloprotein, alpha-lactalbumin (aLA), a divalent metal ion binding protein. We use the histograms of dihedral angles of the protein, generated from all-atom molecular dynamics simulations, to calculate conformational thermodynamics. The thermodynamically destabilized and disordered residues in different conformational states of a protein are proposed to serve as binding sites for ligands. This is tested for β-1,4-galactosyltransferase (β4GalT) binding to the Ca(2+)-aLA complex, in which the binding residues are known. Among the binding residues, the C-terminal residues like aspartate (D) 116, glutamine (Q) 117, tryptophan (W) 118 and leucine (L) 119 are destabilized and disordered and can dock β4GalT onto Ca(2+)-aLA. No such thermodynamically favourable binding residues can be identified in the case of the Mg(2+)-aLA complex. We apply similar analysis to oleic acid binding and predict that the Ca(2+)-aLA complex can bind to oleic acid through the basic histidine (H) 32 of the A2 helix and the hydrophobic residues, namely, isoleucine (I) 59, W60 and I95, of the interfacial cleft. However, the number of destabilized and disordered residues in Mg(2+)-aLA are few, and hence, the oleic acid binding to Mg(2+)-bound aLA is less stable than that to the Ca(2+)-aLA complex. Our analysis can be generalized to understand the functionality of other ligand bound proteins.

  2. Regulation of ion homeostasis by aminolevulinic acid in salt-stressed wheat seedlings

    Energy Technology Data Exchange (ETDEWEB)

    Türk, Hülya, E-mail: hulyaa.turk@hotmail.com [Biology Department, Science Faculty, Ataturk University, Erzurum (Turkey); East Anatolian High Technology Research and Application Center, Ataturk University, Erzurum (Turkey); Genişel, Mucip, E-mail: m.genisel@hotmail.com [Department of Crop and Animal Production, Vocational High School, Agri (Turkey); Erdal, Serkan, E-mail: serkanerdal25@hotmail.com [Biology Department, Science Faculty, Ataturk University, Erzurum (Turkey)

    2016-04-18

    Salinity is regarded as a worldwide agricultural threat, as it seriously limits plant development and productivity. Salt stress reduces water uptake in plants by disrupting the osmotic balance of soil solution. In addition, it creates a damaged metabolic process by causing ion imbalance in cells. In this study, we aim to examine the negative effects of 5-aminolevulinic acid (ALA) (20 mg/l) on the ion balance in wheat seedling leaves exposed to salt stress (150 mM). Sodium is known to be highly toxic for plant cells at high concentrations, and is significantly increased by salt stress. However, it can be reduced by combined application of ALA and salt, compared to salt application alone. On the other hand, while the K{sup +}/Na{sup +} ratio was reduced by salt stress, ALA application changed this ratio in favor of K{sup +}. Manganese, iron, and copper were also able to reduce stress. However, ALA pre-treatment resulted in mineral level increments. Conversely, the stress-induced rise in magnesium, potassium, calcium, phosphorus, zinc, and molybdenum were further improved by ALA application. These data clearly show that ALA has an important regulatory effect of ion balance in wheat leaves.

  3. Developmental changes in circulating IL-8/CXCL8 isoforms in neonates.

    Science.gov (United States)

    Maheshwari, Akhil; Voitenok, Nikolai N; Akalovich, Svetlana; Shaik, Sadiq S; Randolph, David A; Sims, Brian; Patel, Rakesh P; Killingsworth, Cheryl R; Fallon, Michael B; Ohls, Robin K

    2009-04-01

    Interleukin-8 (IL-8/CXCL8) is widely expressed in fetal tissues although inflammatory changes are not seen. Circulating IL-8 is comprised of an endothelial-derived [ala-IL-8](77) isoform and another, more potent [ser-IL-8](72) secreted by most other cells; [ala-IL-8](77) can be converted into [ser-IL-8](72) by proteolytic removal of an N-terminal pentapeptide from [ala-IL-8](77). In this study, we show [ala-IL-8](77) is the predominant circulating isoform of IL-8 in premature neonates but not in term neonates/adults, who have [ser-IL-8](72) as the major isoform. This isoform switch from the less potent [ala-IL-8](77) to [ser-IL-8](72) correlates with a maturational increase in the neutrophil chemotactic potency of plasma IL-8. The emergence of [ser-IL-8](72) as the major isoform is likely due to increased plasma [ala-IL-8](77)-convertase activity and/or changes in the cellular sources of IL-8. Developmental changes in IL-8 isoforms may serve to minimize its inflammatory effects in the fetus and also provide a mechanism to restore its full activity after birth.

  4. Evaluation of erythrocyte delta-amino levulinic acid dehydratase activity as a short-term indicator in fish of a harmful exposure to lead

    Energy Technology Data Exchange (ETDEWEB)

    Hodson, P.V.; Blunt, B.R.; Spry, D.J.; Austen, K.

    1977-04-01

    The activity of erythrocyte delta-amino levulinic acid dehydratase (ALA-D) of fish is easily measured under a variety of experimental conditions. Exposure of rainbow trout (Salmo gairdneri), brook trout (Salvelinus fontinalis), goldfish (Carassius auratus), and pumpkinseeds (Lepomis gibbosus) to lead consistently inhibited ALA-D within 2 wks at concentrations as low as 10, 90, 470, and 90 ..mu..g/l, respectively. In rainbow and brook trout these concentrations were closely related to the published minimum effective concentrations causing sublethal harm. There was a significant linear relationship between ALA-D activity and log of blood lead concentration, between ALA-D activity and log of lead in water, and between blood lead and lead in water. Near lethal exposures to cadmium, copper, zinc, and mercury did not significantly inhibit ALA-D activity. Recovery of ALA-D activity of rainbow trout after transfer from 120 ..mu..g/l lead to clean water occurred in 8 wk. This enzyme provides fast, consistent, specific, and sensitive estimates of lead concentrations causing sublethal harm to fish and may help to relate sources of lead to degree of exposure of fish populations in the field.

  5. Novel approach to control Salmonella enterica by modern biophotonic technology: photosensitization.

    Science.gov (United States)

    Buchovec, I; Vaitonis, Z; Luksiene, Z

    2009-03-01

    Salmonellosis is one of the most common foodborne diseases in the world. The aim of this study was to evaluate the antibacterial efficiency of 5-aminolevulinic acid (ALA) based photosensitization against one of food pathogens Salmonella enterica. Salmonella enterica was incubated with ALA (7.5 mmol l(-1)) for 1-4 h and afterwards illuminated with visible light. The light source used for illumination of S. enterica emitted light lambda = 400 nm with energy density 20 mW cm(-2). The illumination time varied from 0 to 20 min and subsequently a total energy dose reached 0-24 J cm(-2). The data obtained indicate that S. enterica is able to produce endogenous photosensitizer PpIX when incubated with ALA. Remarkable inactivation of micro-organisms can be achieved (6 log) after photosensitization. It is obvious that photosensitization-based inactivation of S. enterica depends on illumination as well as incubation with ALA time. ALA-based photosensitization can be an effective tool against multi-drug resistant Gram-negative bacteria S. enterica serovar Typhimurium. Experimental data and mathematical evaluations support the idea that ALA-based photosensitization can be a useful tool for the development of nonthermal food preservation technology in future.

  6. Variation in the interleukin-6 receptor gene associates with type 2 diabetes in Danish whites

    DEFF Research Database (Denmark)

    Hamid, Yasmin H; Urhammer, Søren A; Jensen, Dorit P

    2004-01-01

    quantitative traits among Danish whites. By applying a recessive genetic model in a case-control study of 1,349 type 2 diabetic patients and 4,596 glucose-tolerant control subjects, we found a significant difference in genotype distribution (P = 0.008) and in allele frequency (Ala-allele 38.3% [95% CI 36.......5-40.1] in diabetic subjects vs. 41.2% [40.2-42.2] in control subjects; P = 0.007). The odds ratio for the Asp/Asp carriers versus Ala/Ala carriers was 1.38 (1.09-1.71). Among 4,251 middle-aged glucose-tolerant subjects, the Asp358Ala polymorphism was not associated with estimates of obesity, post-oral glucose...... tolerance test serum insulin release, or the homeostasis model assessment of insulin resistance index. In conclusion, the Asp358Ala polymorphism of the IL6R associates with type 2 diabetes in Danish whites....

  7. Alamethicin permeabilizes the plasma membrane and mitochondria but not the tonoplast in tobacco (Nicotiana tabacum L. cv Bright Yellow) suspension cells

    DEFF Research Database (Denmark)

    Matic, S.; Geisler, D.A.; Møller, I.M.

    2005-01-01

    remained intact, as indicated by an unaffected tonoplast proton gradient. Low-flux permeabilization of plasma membranes and mitochondria at moderate AlaM concentrations was reversible and did not affect cell vigour. Higher AlaM concentrations induced cell death. After the addition of catalase that removes...... concentrations. Possible uses and limitations of this method for plant cell research are discussed.......The ion channel-forming peptide AlaM (alamethicin) is known to permeabilize isolated mitochondria as well as animal cells. When intact tobacco (Nicotiana tabacum L.) Bright Yellow-2 cells were treated with AlaM, the cells became permeable for low-molecular-mass molecules as shown by induced leakage...

  8. Safety test of a supplement, 5-aminolevulinic acid phosphate with sodium ferrous citrate, in diabetic patients treated with oral hypoglycemic agents

    Directory of Open Access Journals (Sweden)

    Naohide Yamashita

    2014-09-01

    Full Text Available Objective: This study aimed to examine the safety of 5-aminolevulinic acid phosphate (5-ALA with sodium ferrous citrate (SFC in diabetic patients treated with one or more oral hypoglycemic agents (OHAs. Background: Recent intervention studies performed in the USA and Japan have shown that a nutritional supplement of 5-ALA with SFC efficiently reduced blood glucose levels in pre-diabetic population without any adverse events. Thus, it was anticipated that 5-ALA with SFC may potentially be taken as a beneficial supplement by diabetic patients who were being treated with OHA therapy. Nevertheless, it is important to examine its safety and efficacy in diabetic population. Methods: This study was a prospective single-blinded, randomized, placebo-controlled and parallel-group comparison study. Medically treated diabetic patients between the ages of 30 and 75 were recruited from the Tokyo metropolitan area of Japan and 45 subjects were selected after screening. These subjects were randomly assigned to three groups: daily intake of 15mg 5-ALA, 50mg 5-ALA, and a placebo (n=15, respectively. The supplement or placebo was administered for 12 weeks followed by a four week washout period. The primary endpoint was safety and occurrence of hypoglycemic attack, while the secondary endpoint was changes of fasting blood glucose (FBG and hemoglobin A1c (HbA1c. Results: Adverse events related to 5-ALA with SFC were not observed in all the groups. Abnormalities in blood and urine tests were not observed either. Significant decrease in FBG was not detected in all the groups. However, there was a small but significant decrease in HbA1c at 4 and 8 week in the 15 mg 5-ALA group. Significant decrease in HbA1c was not observed in the 50 mg 5-ALA group, although a tendency to decrease after 4 weeks was apparent. Conclusion: 5-ALA with SFC is a safe and potentially beneficial supplement if taken by diabetic patients treated with OHAs.

  9. Kinetics and comparison of δ-aminolevulinic-acid-induced endogenous protoporphyrin-IX in single cell by steady state and multiphoton fluorescence imaging

    Science.gov (United States)

    Ganesan, Singaravelu; Elangovan, Masilamani; Periasamy, Ammasi

    2001-04-01

    Photodynamic Therapy has emerged as a new modality in the treatment of various nonmalignant and malignant diseases. It involves the systemic administration of tumor specific photo-sensitizers with the subsequent application of visible light. This combination causes the generation of cytotoxic species, which damage sensitive targets, producing cell injury and tumor destruction. Although, photofrin is the only photosensitizer currently approved for PDT and tumor detection, its concomitant cutaneous photosensitization poses a significant problem. Hence, δ-aminoleuvulinic acid (δ-ALA) a precursor for the endogenous production of Protoporphyrin IX, through heme biosynthesis pathway, has gained significant importance in the Photodynamic Therapy. Though δ-ALA is present naturally in the cells, exogenous δ-ALA helps to synthesis more of PpIX in the tumor cells, as the fast growing tumor cells take up the administered δ-ALA more than the normal cells. Based on these facts, many invasive studies have been reported on the kinetics of δ-ALA at cellular level by chemical extraction of PpIX from the cells. In the present study we have studied the kinetics of δ-ALA induced PpIX fluorescence from Hela cells by perchloric/Methanol extraction method. However, the amount of PpIX synthesized in the cells at different point of incubation time by noninvasive methods has not been reported. Hence we have also used a noninvasive technique of measuring the kinetics δ-ALA induced PPIX fluorescence from Hela, an epithelial cell derived from human cervical cancer by both single photon (steady state) and multi photon excitation. From the studies it is observed that the δ-ALA induced PpIX is more at 2 hours incubation time for 2 mM of δ-ALA concentration. Further, it is observed that with steady state fluorescence imaging method, the excitation light itself cause the Photodynamic damage, due to the prolonged exposure of the cells than in multi photon excitation, leading to the rounding

  10. The Safety and Tolerability of 5-Aminolevulinic Acid Phosphate with Sodium Ferrous Citrate in Patients with Type 2 Diabetes Mellitus in Bahrain

    Science.gov (United States)

    Al-Saber, Feryal; Aldosari, Waleed; Alselaiti, Mariam; Khalfan, Hesham; Kaladari, Ahmed; Khan, Ghulam; Harb, George; Rehani, Riyadh; Kudo, Sizuka; Koda, Aya; Tanaka, Tohru

    2016-01-01

    Type 2 diabetes mellitus is prevalent especially in Gulf countries and poses serious long-term risks to patients. A multifaceted treatment approach can include nutritional supplements with antioxidant properties such as 5-aminolevulinic acid (5-ALA) with sodium ferrous citrate (SFC). This prospective, randomized, single-blind, placebo-controlled, dose escalating pilot clinical trial assessed the safety of 5-ALA with SFC at doses up to 200 mg 5-ALA/229.42 mg SFC per day in patients living in Bahrain with type 2 diabetes mellitus that was uncontrolled despite the use of one or more antidiabetic drugs. Fifty-three patients (n = 53) from 3 sites at one center were enrolled by Dr. Feryal (Site #01), Dr. Hesham (Site #02), and Dr. Waleed (Site #03) (n = 35, 5-ALA-SFC; n = 18, placebo). There was no significant difference in incidence of adverse events reported, and the most frequent events reported were gastrointestinal in nature, consistent with the known safety profile of 5-ALA in patients with diabetes. No significant changes in laboratory values and no difference in hypoglycemia between patients receiving 5-ALA and placebo were noted. Overall, the current results support that use of 5-ALA-SFC up to 200 mg per day taken as 2 divided doses is safe in patients taking concomitant oral antidiabetic medications and may offer benefits in the diabetic population. This trial is registered with ClinicalTrials.gov NCT02481141. PMID:27738640

  11. Physiological and metabolic effects of 5-aminolevulinic acid for mitigating salinity stress in creeping bentgrass.

    Directory of Open Access Journals (Sweden)

    Zhimin Yang

    Full Text Available The objectives of this study were to determine whether foliar application of a chlorophyll precursor, 5-aminolevulinic acid (ALA, could mitigate salinity stress damages in perennial grass species by regulating photosynthetic activities, ion content, antioxidant metabolism, or metabolite accumulation. A salinity-sensitive perennial grass species, creeping bentgrass (Agrostis stolonifera, was irrigated daily with 200 mM NaCl for 28 d, which were foliar sprayed with water or ALA (0.5 mg L-1 weekly during the experiment in growth chamber. Foliar application of ALA was effective in mitigating physiological damage resulting from salinity stress, as manifested by increased turf quality, shoot growth rate, leaf relative water content, chlorophyll content, net photosynthetic rate, stomatal conductance and transpiration rate. Foliar application of ALA also alleviated membrane damages, as shown by lower membrane electrolyte leakage and lipid peroxidation, which was associated with increases in the activities of antioxidant enzymes. Leaf content of Na+ was reduced and the ratio of K+/Na+ was increased with ALA application under salinity stress. The positive effects of ALA for salinity tolerance were also associated with the accumulation of organic acids (α-ketoglutaric acid, succinic acid, and malic acid, amino acids (alanine, 5-oxoproline, aspartic acid, and γ -aminobutyric acid, and sugars (glucose, fructose, galactose, lyxose, allose, xylose, sucrose, and maltose. ALA-mitigation of physiological damages by salinity could be due to suppression of Na+ accumulation and enhanced physiological and metabolic activities related to photosynthesis, respiration, osmotic regulation, and antioxidant defense.

  12. HepG2 human hepatocarcinomas cells sensitization by endogenous porphyrins

    Science.gov (United States)

    Vonarx-Coinsmann, Veronique; Foultier, Marie-Therese; de Brito, Leonor X.; Morlet, Laurent; Patrice, Thierry

    1995-03-01

    We assessed the ability of the human hepatocarcinoma cell line HepG2 to synthesize PpIX in vitro from exogenous ALA and analyzed ALA-induced toxicity and phototoxicity on this cell line. ALA induced a slight dose-dependent dark toxicity, with 79 and 66% cell survival respectively for ALA 50 and 100 mg/ml after 3-h incubation. Whereas the same treatment followed by laser irradiation (l equals 632 nm, 25 J/sq cm) induced dose-dependent phototoxicity, with 54 and 19% cell survival 24 h after PDT. Whatever the incubation time with ALA, a 3-h delay before light exposure was found optimal to reach a maximal phototoxicity. Photoproducts induced by porphyrin light irradiation absorbed light in the red spectral region at longer wavelengths than did the original porphyrins. The possible enhancement of PDT effects after ALA HepG2 cell incubation was investigated by irradiating cells successively with red light (l equals 632 nm) and light (l equals 650 nm). Total fluence was kept constant at 25 J/sq cm. Phototoxicity was lower when cells were irradiated for increased periods of l equals 650 nm light than with l equals 632 nm light alone. Any photoproducts involved had either a short life or were poorly photoreactive. HepG2 cells, synthesizing enzymes and precursors of endogenous porphyrin synthesis, represent a good in vitro model for experiments using ALA-PpIX-PDT.

  13. Hangar con alas, Los Angeles

    Directory of Open Access Journals (Sweden)

    Editorial, Equipo

    1961-04-01

    Full Text Available Formando parte de su programa, la TWA ha construido recientemente un hangar para servicio y reparaciones de su flota aérea de naves ordinarias y de aviones de reacción en el aeropuerto internacional de Los Angeles (Estados Unidos. El proyecto de esta obra se encargó a la empresa constructora Holmes & Narver, Inc.

  14. Membaca Televisi 'ala Al-Jabiri

    OpenAIRE

    Hamad, Ibnu

    2016-01-01

     Since the New Order Era collapsed and the Reformasi Era had come out, the media freedom reached its climax. The growth of mass media had increased until the amazing number. Unfortunately, this rapid growth didn't base on the idealism, but only for the business purposes. As a consequence, the TV station owners and investors are only emphasizing how many profit they can get, without considering the importance of qualified content of TV program. This article wants to introduce a reading and mak...

  15. Strateegiad konkurentsieelise saavutamiseks / Ruth Alas

    Index Scriptorium Estoniae

    Alas, Ruth, 1960-2018

    1999-01-01

    Personalijuhtimise strateegia: väärtuste loomise ahel, parima säästlikkuse saavutamine, TQM, kvaliteedi ja innovaatilisuse saavutamine. Tabelid. Ilmunud ka: Buhgalterskije Novosti, nr. 4, 1999, lk. 39-45

  16. ALA Salary Survey: Personal Members

    Science.gov (United States)

    American Libraries, 1971

    1971-01-01

    A survey of the members of the American Library Association revealed that the principal salary determinants are academic degree, type of employer and sex. The obvious differences in the earnings of men and women is not only found in the early experience years but any narrowing which does take place in the wage gap seems to take place at the…

  17. Sladkaja voennaja taina / Senta Alas

    Index Scriptorium Estoniae

    Alas, Senta

    2006-01-01

    NATO Norra kõrgeid ametnikke ja Saksa elektroonikakontserni Siemens puudutavast korruptsiooniskandaalist: Siemens Business Service maksis Norra kõrgematele sõjaväelastele 22 miljonit norra krooni, et kindlustada firmale soodsad tellimused

  18. Binding of 14C-5-aminolevulinic acid to a stromal protein from developing pea chloroplasts

    International Nuclear Information System (INIS)

    Thayer, S.S.; Castelfranco, P.A.; Wilkinson, J.; Benson, G.

    1987-01-01

    14 -5-Aminolevulinic acid ( 14 C-ALA) binds to a stromal protein with an apparent molecular weight of 42-43 KD on LDS and non-denaturing gels. The reaction is rapid. Binding is inhibited by sulfhydryl reagents, mM concentrations of levulinic, dihydroxy heptanoic acids and gabaculine, 10 μM N-methylprotoporphyrin. Dicarboxilic acids, such as δKG, Glu, OAA, do not inhibit. Chloramphenicol, ATP, protoporphyrin, anoxia, light, darkness have no effect. The product, once formed, is stable to treatment with 5% conc. HCl in cold acetone. It can be chased in a second incubation with unlabeled ALA, but not with levulinic acid. No activity was detected in the subplastidic membrane fractions. Western blot analysis failed to reveal any homology between the labeled protein and either cytochrome for ALA dehydratase. This ALA-binding protein was not formed in chloroplasts isolated from fully expanded pea leaves. Therefore, it is deemed likely to participate in ALA metabolism during chloroplast development

  19. Genotoxicity evaluation of alpha-linolenic acid-diacylglycerol oil

    Directory of Open Access Journals (Sweden)

    Hiroshi Honda

    Full Text Available The alpha-linolenic acid (ALA-diacylglycerol (DAG oil is an edible oil enriched with DAG (>80% and ALA (>50%. Although DAG oil, which mainly consists of oleic and linoleic acids has no genotoxic concerns, the fatty acid composition could affect the chemical property of DAG. Therefore, the purpose of this study was to evaluate the genotoxicity of ALA-DAG oil using standard genotoxicity tests in accordance with the OECD guidelines. ALA-DAG oil showed negative results in the bacterial reverse mutation test (Ames test and in vitro micronucleus test in cultured Chinese hamster lung cells with and without metabolic activation, and in the in vivo bone marrow micronucleus test in mice. Our results did not show any genotoxicity, suggesting that the fatty acid composition had no deleterious effects. We conclude that ALA-DAG oil had no genotoxicity concerns under the testing conditions. Keywords: Alpha-linolenic acid-rich diacylglycerol, Diacylglycerol, Alpha-linolenic acid, Fatty acid composition, Genotoxicity

  20. Influence of mannosylation on immunostimulating activity of adamant-1-yl tripeptide.

    Science.gov (United States)

    Ribić, Rosana; Habjanec, Lidija; Frkanec, Ruža; Vranešić, Branka; Tomić, Srđanka

    2012-07-01

    The mannosylated derivative of adamant-1-yl tripeptide (D-(Ad-1-yl)Gly-L-Ala-D-isoGln) was prepared to study the effects of mannosylation on adjuvant (immunostimulating) activity. Mannosylated adamant-1-yl tripeptide (Man-OCH(2) CH(Me)CO-D-(Ad-1-yl)Gly-L-Ala-D-isoGln) is a non-pyrogenic, H(2) O-soluble, and non-toxic compound. Adjuvant activity of mannosylated adamantyl tripeptide was tested in the mouse model with ovalbumin as an antigen and in comparison to the parent tripeptide and peptidoglycan monomer (PGM, β-D-GlcNAc-(1→4)-D-MurNAc-L-Ala-D-isoGln-mesoDAP(εNH(2) )-D-Ala-D-Ala), a well-known effective adjuvant. The mannosylation of adamantyl tripeptide caused the amplification of its immunostimulating activity in such a way that it was comparable to that of PGM. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

  1. Verification of radiodynamic therapy by medical linear accelerator using a mouse melanoma tumor model.

    Science.gov (United States)

    Takahashi, Junko; Murakami, Mami; Mori, Takashi; Iwahashi, Hitoshi

    2018-02-09

    Combined treatment with 5-aminolevulinic acid (5-ALA) and X-rays improves tumor suppression in vivo. This is because the accumulated protoporphyrin IX from 5-ALA enhances the generation of ROS by the X-ray irradiation. In the present study, a high-energy medical linear accelerator was used instead of a non-medical low energy X-ray irradiator, which had been previously used. Tumor-bearing mice implanted with B16-BL6 melanoma cells were treated with fractionated doses of irradiation (in total, 20 or 30 Gy), using two types of X-ray irradiator after 5-ALA administration. Suppression of tumor growth was enhanced with X-ray irradiation in combination with 5-ALA treatment compared with X-ray treatment alone, using both medical and non-medical X-ray irradiators. 5-ALA has been used clinically for photodynamic therapy. Thus, "radiodynamic therapy", using radiation from medical linacs as a physical driving force, rather than the light used in photodynamic therapy, may have potential clinical applications.

  2. An empirical investigation of attiribution for success and failure

    OpenAIRE

    Asanakutlu, Tuncer; Sahin, Tezcan Kesmer

    2014-01-01

       Çalışmanın  amacı,  cinsiyet,  kişilik  ve  tanışıklık  durumunun  atfetme  üzerinde  farklılaşmaya  neden   olup   olmadığının   ve   temel   atfetme   hatası   ve   kendine   hizmet   eden   yükleme  yanlılığının   gerçekleşip   gerçekleşmediğinin   tespit   edilmesidir.   Amacın   gerçekleştirilmesi  için   görgül   bir   çalışma   yapılmıştır.   Araştırmada   maksatlı   örnekleme   kullanılmış   olup,  gönüllülük   esasına   bağlı   olarak   katılan   toplam   52   öğrenci   üzerinde  ...

  3. Expression and secretion of Bacillus amyloliquefaciens alpha-amylase by using the yeast pheromone alpha-factor promoter and leader sequence in Saccharomyces cerevisiae.

    OpenAIRE

    Southgate, V J; Steyn, A J; Pretorius, I S; Van Vuuren, H J

    1993-01-01

    Replacement of the regulatory and secretory signals of the alpha-amylase gene (AMY) from Bacillus amylolique-faciens with the complete yeast pheromone alpha-factor prepro region (MF alpha 1p) resulted in increased levels of extracellular alpha-amylase production in Saccharomyces cerevisiae. However, the removal of the (Glu-Ala)2 peptide from the MF alpha 1 spacer region (Lys-Arg-Glu-Ala-Glu-Ala) yielded decreased levels of extracellular alpha-amylase.

  4. Determination of the torsion angles of alanine and glycine residues of model compounds of spider silk (AGG){sub 10} using solid-state NMR methods

    Energy Technology Data Exchange (ETDEWEB)

    Ashida, Jun; Ohgo, Kosuke; Komatsu, Kohei; Kubota, Ayumi; Asakura, Tetsuo [Tokyo University of Agriculture and Technology, Department of Biotechnology (Japan)], E-mail: asakura@cc.tuat.ac.jp

    2003-02-15

    Spiders synthesize several kinds of silk fibers. In the primary structure of spider silk, one of the major ampullate (dragline, frame) silks, spidroin 1, and flagelliform silk (core fibers of adhesive spiral), there are common repeated X-Gly-Gly (X = Ala, Leu, Pro, Tyr, Glu, and Arg) sequences, which are considered to be related to the elastic character of these fibers. In this paper, two dimensional spin diffusion solid-state NMR under off magic angle spinning (OMAS), {sup 13}C chemical shift contour plots, and Rotational Echo DOuble Resonance (REDOR) were applied to determine the torsion angles of one Ala and two kinds of Gly residues in the Ala-Gly-Gly sequence of {sup 13}C=O isotope-labeled (Ala-Gly-Gly){sub 10}. The torsion angles were determined to be ({phi}, {psi}) = (-90 deg., 150 deg.) within an experimental error of {+-}10 deg. for each residue. This conformation is characterized as 3{sub 1} helix which is in agreement with the structure proposed from the X-ray powder diffraction pattern of poly(Ala-Gly-Gly). The 3{sub 1} helix of (Ala-Gly-Gly){sub 10} does not change by formic acid treatment although (Ala-Gly){sub 15} easily changes from the silk I conformation (the structure of Bombyx mori silk fibroin before spinning in the solid state) to silk II conformation (the structure of the silk fiber after spinning) by such treatment. Thus, the 3{sub 1} helix conformation of (Ala-Gly-Gly){sub 10} is considered very stable. Furthermore, the torsion angles of the 16th Leu residue of (Leu-Gly-Gly){sub 10} were also determined as ({phi}, {psi}) = (-90 deg., 150 deg.) and this peptide is also considered to take 3{sub 1} helix conformation.

  5. Mutagenesis of the redox-active disulfide in mercuric ion reductase: Catalysis by mutant enzymes restricted to flavin redox chemistry

    International Nuclear Information System (INIS)

    Distefano, M.D.; Au, K.G.; Walsh, C.T.

    1989-01-01

    Mercuric reductase, a flavoenzyme that possesses a redox-active cystine, Cys 135 Cys 140 , catalyzes the reduction of Hg(II) to Hg(0) by NADPH. As a probe of mechanism, the authors have constructed mutants lacking a redox-active disulfide by eliminating Cys 135 (Ala 135 Cys 140 ), Cys 14 (Cys 135 Ala 140 ), or both (Ala 135 Ala 140 ). Additionally, they have made double mutants that lack Cys 135 (Ala 135 Cys 139 Cys 140 ) or Cys 140 (Cys 135 Cys 139 Ala 140 ) but introduce a new Cys in place of Gly 139 with the aim of constructing dithiol pairs in the active site that do not form a redox-active disulfide. The resulting mutant enzymes all lack redox-active disulfides and are hence restricted to FAD/FADH 2 redox chemistry. Each mutant enzyme possesses unique physical and spectroscopic properties that reflect subtle differences in the FAD microenvironment. Preliminary evidence for the Ala 135 Cys 139 Cys 14 mutant enzyme suggests that this protein forms a disulfide between the two adjacent Cys residues. Hg(II) titration experiments that correlate the extent of charge-transfer quenching with Hg(II) binding indicate that the Ala 135 Cys 140 protein binds Hg(II) with substantially less avidity than does the wild-type enzyme. All mutant mercuric reductases catalyze transhydrogenation and oxygen reduction reactions through obligatory reduced flavin intermediates at rates comparable to or greater than that of the wild-type enzyme. In multiple-turnover assays which monitored the production of Hg(0), two of the mutant enzymes were observed to proceed through at least 30 turnovers at rates ca. 1000-fold slower than that of wild-type mercuric reductase. They conclude that the Cys 135 and Cys 140 thiols serve as Hg(II) ligands that orient the Hg(II) for subsequent reduction by a reduced flavin intermediate

  6. Characterization of serine hydroxymethyltransferase GlyA as a potential source of D-alanine in Chlamydia pneumoniae.

    Science.gov (United States)

    De Benedetti, Stefania; Bühl, Henrike; Gaballah, Ahmed; Klöckner, Anna; Otten, Christian; Schneider, Tanja; Sahl, Hans-Georg; Henrichfreise, Beate

    2014-01-01

    For intracellular Chlamydiaceae, there is no need to withstand osmotic challenges, and a functional cell wall has not been detected in these pathogens so far. Nevertheless, penicillin inhibits cell division in Chlamydiaceae resulting in enlarged aberrant bodies, a phenomenon known as chlamydial anomaly. D-alanine is a unique and essential component in the biosynthesis of bacterial cell walls. In free-living bacteria like Escherichia coli, penicillin-binding proteins such as monofunctional transpeptidases PBP2 and PBP3, the putative targets of penicillin in Chlamydiaceae, cross-link adjacent peptidoglycan strands via meso-diaminopimelic acid and D-Ala-D-Ala moieties of pentapeptide side chains. In the absence of genes coding for alanine racemase Alr and DadX homologs, the source of D-Ala and thus the presence of substrates for PBP2 and PBP3 activity in Chlamydiaceae has puzzled researchers for years. Interestingly, Chlamydiaceae genomes encode GlyA, a serine hydroxymethyltransferase that has been shown to exhibit slow racemization of D- and L-alanine as a side reaction in E. coli. We show that GlyA from Chlamydia pneumoniae can serve as a source of D-Ala. GlyA partially reversed the D-Ala auxotrophic phenotype of an E. coli racemase double mutant. Moreover, purified chlamydial GlyA had racemase activity on L-Ala in vitro and was inhibited by D-cycloserine, identifying GlyA, besides D-Ala ligase MurC/Ddl, as an additional target of this competitive inhibitor in Chlamydiaceae. Proof of D-Ala biosynthesis in Chlamydiaceae helps to clarify the structure of cell wall precursor lipid II and the role of chlamydial penicillin-binding proteins in the development of non-dividing aberrant chlamydial bodies and persistence in the presence of penicillin.

  7. Characterization of serine hydroxymethyltransferase GlyA as a potential source of D-alanine in Chlamydia pneumoniae

    Directory of Open Access Journals (Sweden)

    Stefania eDe Benedetti

    2014-02-01

    Full Text Available For intracellular Chlamydiaceae, there is no need to withstand osmotic challenges, and a functional cell wall has not been detected in these pathogens so far. Nevertheless, penicillin inhibits cell division in Chlamydiaceae resulting in enlarged aberrant bodies, a phenomenon known as chlamydial anomaly.D-alanine is a unique and essential component in the biosynthesis of bacterial cell walls. In free-living bacteria like Escherichia coli, penicillin-binding proteins such as monofunctional transpeptidases PBP2 and PBP3, the putative targets of penicillin in Chlamydiaceae, cross-link adjacent peptidoglycan strands via meso-diaminopimelic acid and D-Ala-D-Ala moieties of pentapeptide side chains. In the absence of genes coding for alanine racemase Alr and DadX homologs, the source of D-Ala and thus the presence of substrates for PBP2 and PBP3 activity in Chlamydiaceae has puzzled researchers for years. Interestingly, Chlamydiaceae genomes encode GlyA, a serine hydroxymethyltransferase that has been shown to exhibit slow racemization of D- and L- alanine as a side reaction in E. coli. We show that GlyA from Chlamydia pneumoniae can serve as a source of D-Ala. GlyA partially reversed the D-Ala auxotrophic phenotype of an E. coli racemase double mutant. Moreover, purified chlamydial GlyA had racemase activity on L-Ala in vitro and was inhibited by D-cycloserine, identifying GlyA, besides D-Ala ligase MurC/Ddl, as an additional target of this competitive inhibitor in Chlamydiaceae. Proof of D-Ala biosynthesis in Chlamydiaceae helps to clarify the structure of cell wall precursor lipid II and the role of chlamydial penicillin-binding proteins in the development of non-dividing aberrant chlamydial bodies and persistence in the presence of penicillin.

  8. Secretion of d-alanine by Escherichia coli.

    Science.gov (United States)

    Katsube, Satoshi; Sato, Kazuki; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

    2016-07-01

    Escherichia coli has an l-alanine export system that protects the cells from toxic accumulation of intracellular l-alanine in the presence of l-alanyl-l-alanine (l-Ala-l-Ala). When a DadA-deficient strain was incubated with 6.0 mM l-Ala-l-Ala, we detected l-alanine and d-alanine using high-performance liquid chromatography (HPLC) analysis at a level of 7.0 mM and 3.0 mM, respectively, after 48 h incubation. Treatment of the culture supernatant with d-amino acid oxidase resulted in the disappearance of a signal corresponding to d-alanine. Additionally, the culture supernatant enabled a d-alanine auxotroph to grow without d-alanine supplementation, confirming that the signal detected by HPLC was authentic d-alanine. Upon introduction of an expression vector harbouring the alanine racemase genes, alr or dadX, the extracellular level of d-alanine increased to 11.5 mM and 8.5 mM, respectively, under similar conditions, suggesting that increased metabolic flow from l-alanine to d-alanine enhanced d-alanine secretion. When high-density DadA-deficient cells preloaded with l-Ala-l-Ala were treated with 20 µM carbonyl cyanide m-chlorophenyl hydrazone (CCCP), secretion of both l-alanine and d-alanine was enhanced ~twofold compared with that in cells without CCCP treatment. In contrast, the ATPase inhibitor dicyclohexylcarbodiimide did not exert such an effect on the l-alanine and d-alanine secretion. Furthermore, inverted membrane vesicles prepared from DadA-deficient cells lacking the l-alanine exporter AlaE accumulated [3H]D-alanine in an energy-dependent manner. This energy-dependent accumulation of [3H]D-alanine was strongly inhibited by CCCP. These results indicate that E. coli has a transport system(s) that exports d-alanine and that this function is most likely modulated by proton electrochemical potential.

  9. Quantitation of alpha-linolenic acid elongation to eicosapentaenoic and docosahexaenoic acid as affected by the ratio of n6/n3 fatty acids

    Directory of Open Access Journals (Sweden)

    Somoza Veronika

    2009-02-01

    Full Text Available Abstract Background Conversion of linoleic acid (LA and alpha-linolenic acid (ALA to their higher chain homologues in humans depends on the ratio of ingested n6 and n3 fatty acids. Design and methods In order to determine the most effective ratio with regard to the conversion of ALA to eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA, human hepatoma cells were incubated with varying ratios of [13C] labeled linoleic acid ([13C]LA- and alpha-linolenic acid ([13C]ALA-methylesters. Regulative cellular signal transduction pathways involved were studied by determinations of transcript levels of the genes encoding delta-5 desaturase (D5D and delta-6 desaturase (D6D, peroxisome proliferator-activated receptor alpha (PPARα and sterol regulatory element binding protein 1c (SREBP-1c. Mitogen-activated protein kinase kinase 1 (MEK1 and mitogen-activated protein kinase kinase kinase 1 (MEKK1 were also examined. Results Maximum conversion was observed in cells incubated with the mixture of [13C]LA/[13C]ALA at a ratio of 1:1, where 0.7% and 17% of the recovered [13C]ALA was converted to DHA and EPA, respectively. Furthermore, differential regulation of enzymes involved in the conversion at the transcript level, dependent on the ratio of administered n6 to n3 fatty acids in human hepatocytes was demonstrated. Conclusion Formation of EPA and DHA was highest at an administered LA/ALA ratio of 1:1, although gene expression of PPARα, SREBP-1c and D5D involved in ALA elongation were higher in the presence of ALA solely. Also, our findings suggest that a diet-induced enhancement of the cell membrane content of highly unsaturated fatty acids is only possible up to a certain level.

  10. Whole-body DHA synthesis-secretion kinetics from plasma eicosapentaenoic acid and alpha-linolenic acid in the free-living rat.

    Science.gov (United States)

    Metherel, Adam H; Domenichiello, Anthony F; Kitson, Alex P; Hopperton, Kathryn E; Bazinet, Richard P

    2016-09-01

    Whole body docosahexaenoic acid (DHA, 22:6n-3) synthesis from α-linolenic acid (ALA, 18:3n-3) is considered to be very low, however, the daily synthesis-secretion of DHA may be sufficient to supply the adult brain. The current study aims to assess whether whole body DHA synthesis-secretion kinetics are different when comparing plasma ALA versus eicosapentaenoic acid (EPA, 20:5n-3) as the precursor. Male Long Evans rats (n=6) were fed a 2% ALA in total fat diet for eight weeks, followed by surgery to implant a catheter into each of the jugular vein and carotid artery and 3h of steady-state infusion with a known amount of (2)H-ALA and (13)C-eicosapentaenoic acid (EPA, 20:5n3). Blood samples were collected at thirty-minute intervals and plasma enrichment of (2)H- and (13)C EPA, n-3 docosapentaenoic acid (DPAn-3, 22:5n-3) and DHA were determined for assessment of synthesis-secretion kinetic parameters. Results indicate a 13-fold higher synthesis-secretion coefficient for DHA from EPA as compared to ALA. However, after correcting for the 6.6 fold higher endogenous plasma ALA concentration, no significant differences in daily synthesis-secretion (nmol/day) of DHA (97.6±28.2 and 172±62), DPAn-3 (853±279 and 1139±484) or EPA (1587±592 and 1628±366) were observed from plasma unesterified ALA and EPA sources, respectively. These results suggest that typical diets which are significantly higher in ALA compared to EPA yield similar daily DHA synthesis-secretion despite a significantly higher synthesis-secretion coefficient from EPA. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Melatonin modulates drug-induced acute porphyria

    Directory of Open Access Journals (Sweden)

    Sandra M. Lelli

    Full Text Available This work investigated the modulation by melatonin (Mel of the effects of the porphyrinogenic drugs 2-allyl-2-isopropylacetamide (AIA and 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine (DDC on oxidative environment, glucose biosynthesis and heme pathway parameters. Administration of Mel before rat intoxication with AIA/DDC showed a clear beneficial effect in all cases. Mel induced decreases of 42% and 35% in the excretion of the hemeprecursors 5-aminolevulinic acid (ALA and porphobilinogen (PBG, respectively, and a 33% decrease in the induction of the heme regulatory enzyme 5-aminolevulinic acid-synthase (ALA-S. The activity of the glucose metabolism enzyme phosphoenolpyruvate carboxykinase (PEPCK, which had been diminished by the porphyrinogenic treatment, was restored by 45% when animals were pre-treated with Mel. Mel abolished the modest decrease in glucose 6-phospatase (G6Pase activity caused by AIA/DDC treatment. The oxidative status of lipids was attenuated by Mel treatment in homogenates by 47%, whereas no statistically significant AIA/DDC-induced increase in thiobarbituric acid reactive substances (TBARS was observed in microsomes after Mel pre-treatment. We hypothesize that Mel may be scavenging reactive species of oxygen (ROS that could be damaging lipids, PEPCK, G6Pase and ferrochelatase (FQ. Additionally, Mel administration resulted in the repression of the key enzyme ALA-S, and this could be due to an increase in glucose levels, which is known to inhibit ALA-S induction. The consequent decrease in levels of the heme precursors ALA and PBG had a beneficial effect on the drug-induced porphyria. The results obtained open the possibility of further research on the use of melatonin as a co-treatment option in acute porphyria. Keywords: Melatonin, Glucose synthesis, Heme pathway, Acute porphyria, Oxidative stress

  12. Recombinant Brucella abortus gene expressing immunogenic protein

    Energy Technology Data Exchange (ETDEWEB)

    Mayfield, J.E.; Tabatabai, L.B.

    1991-06-11

    This patent describes a synthetic recombinant DNA molecule containing a DNA sequence. It comprises a gene of Brucella abortus encoding an immunogenic protein having a molecular weight of approximately 31,000 daltons as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis under denaturing conditions, the protein having an isoelectric point around 4.9, and containing a twenty-five amino acid sequence from its amino terminal end consisting of Gln-Ala-Pro-Thr-Phe-Phe-Arg-Ile-Gly-Thr-Gly-Gly-Thr-Ala-Gly-Thr-Tyr-Tyr-Pro-Ile-Gly-Gly-Leu-Ile-Ala, wherein Gln, Ala, Pro, Thr, Phe, Arg, Ile, Gly, Tyr, and Leu, respectively, represent glutamine, alanine, proline, threonine, phenylalanine, arginine, isolecuine, glycine, tyrosine, and leucine.

  13. Review of dermatology use of 5-aminolevulinic acid photodynamic therapy in China from 1997 to 2013

    Science.gov (United States)

    Wang, Peiru; Zhang, Guolong; Wang, Xiuli

    2015-07-01

    The prodrug 5-aminolevulinic acid (ALA) and its ester derivatives have been used in photodynamic therapy (PDT) in dermatology worldwide. In China, ALA-PDT was first used to treat urethral condylomata acuminata and non-melanoma skin cancers in 1997. A powder formulation of ALA hydrochloride was approved by the Chinese Food and Drug Administration for the treatment of condylomata acuminata in 2007. Large successful experience of treating condylomatas was accumulated compared with Western countries. Meanwhile, numerous clinical studies as well as off-label use of ALAPDT have been carried out in China. To reflect the progress of ALA-PDT in China, several major Chinese and English databases were searched and published data were reviewed in this article.

  14. Design, synthesis and evaluation of a potent substrate analog inhibitor identified by scanning Ala/Phe mutagenesis, mimicking substrate co-evolution, against multidrug-resistant HIV-1 protease

    Energy Technology Data Exchange (ETDEWEB)

    Yedidi, Ravikiran S. [Department of Biochemistry and Molecular Biology, School of Medicine, Wayne State University, Detroit, MI 48201 (United States); Muhuhi, Joseck M. [Department of Chemistry, Wayne State University, Detroit, MI 48202 (United States); Liu, Zhigang [Department of Biochemistry and Molecular Biology, School of Medicine, Wayne State University, Detroit, MI 48201 (United States); Bencze, Krisztina Z. [Department of Chemistry, Fort Hays State University, Hays, KS 67601 (United States); Koupparis, Kyriacos [Department of Biochemistry and Molecular Biology, School of Medicine, Wayne State University, Detroit, MI 48201 (United States); Department of Chemistry, Wayne State University, Detroit, MI 48202 (United States); O’Connor, Carrie E.; Kovari, Iulia A. [Department of Biochemistry and Molecular Biology, School of Medicine, Wayne State University, Detroit, MI 48201 (United States); Spaller, Mark R. [Department of Chemistry, Wayne State University, Detroit, MI 48202 (United States); Kovari, Ladislau C., E-mail: kovari@med.wayne.edu [Department of Biochemistry and Molecular Biology, School of Medicine, Wayne State University, Detroit, MI 48201 (United States)

    2013-09-06

    Highlights: •Inhibitors against MDR HIV-1 protease were designed, synthesized and evaluated. •Lead peptide (6a) showed potent inhibition (IC{sub 50}: 4.4 nM) of MDR HIV-1 protease. •(6a) Showed favorable binding isotherms against NL4-3 and MDR proteases. •(6a) Induced perturbations in the {sup 15}N-HSQC spectrum of MDR HIV-1 protease. •Molecular modeling suggested that (6a) may induce total flap closure inMDR protease. -- Abstract: Multidrug-resistant (MDR) clinical isolate-769, human immunodeficiency virus type-1 (HIV-1) protease (PDB ID: (1TW7)), was shown to exhibit wide-open flaps and an expanded active site cavity, causing loss of contacts with protease inhibitors. In the current study, the expanded active site cavity of MDR769 HIV-1 protease was screened with a series of peptide-inhibitors that were designed to mimic the natural substrate cleavage site, capsid/p2. Scanning Ala/Phe chemical mutagenesis approach was incorporated into the design of the peptide series to mimic the substrate co-evolution. Among the peptides synthesized and evaluated, a lead peptide (6a) with potent activity (IC{sub 50}: 4.4 nM) was identified against the MDR769 HIV-1 protease. Isothermal titration calorimetry data showed favorable binding profile for 6aagainst both wild type and MDR769 HIV-1 protease variants. Nuclear magnetic resonance spectrum of {sup 15}N-labeled MDR769 HIV-1 protease in complex with 6a showed some major perturbations in chemical shift, supporting the peptide induced conformational changes in protease. Modeling analysis revealed multiple contacts between 6a and MDR769 HIV-1 protease. The lead peptide-inhibitor, 6a, with high potency and good binding profile can be used as the basis for developing potent small molecule inhibitors against MDR variants of HIV.

  15. Design, synthesis and evaluation of a potent substrate analog inhibitor identified by scanning Ala/Phe mutagenesis, mimicking substrate co-evolution, against multidrug-resistant HIV-1 protease

    International Nuclear Information System (INIS)

    Yedidi, Ravikiran S.; Muhuhi, Joseck M.; Liu, Zhigang; Bencze, Krisztina Z.; Koupparis, Kyriacos; O’Connor, Carrie E.; Kovari, Iulia A.; Spaller, Mark R.; Kovari, Ladislau C.

    2013-01-01

    Highlights: •Inhibitors against MDR HIV-1 protease were designed, synthesized and evaluated. •Lead peptide (6a) showed potent inhibition (IC 50 : 4.4 nM) of MDR HIV-1 protease. •(6a) Showed favorable binding isotherms against NL4-3 and MDR proteases. •(6a) Induced perturbations in the 15 N-HSQC spectrum of MDR HIV-1 protease. •Molecular modeling suggested that (6a) may induce total flap closure inMDR protease. -- Abstract: Multidrug-resistant (MDR) clinical isolate-769, human immunodeficiency virus type-1 (HIV-1) protease (PDB ID: (1TW7)), was shown to exhibit wide-open flaps and an expanded active site cavity, causing loss of contacts with protease inhibitors. In the current study, the expanded active site cavity of MDR769 HIV-1 protease was screened with a series of peptide-inhibitors that were designed to mimic the natural substrate cleavage site, capsid/p2. Scanning Ala/Phe chemical mutagenesis approach was incorporated into the design of the peptide series to mimic the substrate co-evolution. Among the peptides synthesized and evaluated, a lead peptide (6a) with potent activity (IC 50 : 4.4 nM) was identified against the MDR769 HIV-1 protease. Isothermal titration calorimetry data showed favorable binding profile for 6aagainst both wild type and MDR769 HIV-1 protease variants. Nuclear magnetic resonance spectrum of 15 N-labeled MDR769 HIV-1 protease in complex with 6a showed some major perturbations in chemical shift, supporting the peptide induced conformational changes in protease. Modeling analysis revealed multiple contacts between 6a and MDR769 HIV-1 protease. The lead peptide-inhibitor, 6a, with high potency and good binding profile can be used as the basis for developing potent small molecule inhibitors against MDR variants of HIV

  16. Evaluation of laser therapy and alpha-lipoic acid for the treatment of burning mouth syndrome: a randomized clinical trial.

    Science.gov (United States)

    Barbosa, Natália Guimarães; Gonzaga, Amanda Katarinny Goes; de Sena Fernandes, Luzia Leiros; da Fonseca, Aldilane Gonçalves; Queiroz, Salomão Israel Monteiro Lourenço; Lemos, Telma Maria Araújo Moura; da Silveira, Éricka Janine Dantas; de Medeiros, Ana Miryam Costa

    2018-03-03

    The aim of this study was to evaluate the efficacy of low-level laser therapy (LLLT) and alpha-lipoic acid (ALA) in the treatment of burning mouth syndrome (BMS) and secondary oral burning (SOB) by unstimulated sialometry, symptom assessment, and measurement of salivary TNF-α levels. Forty-four patients were randomized into four treatment groups: BMS/laser (n = 10), BMS/ALA (n = 5), SOB/laser (n = 15), and SOB/ALA (n = 14). The control group consisted of eight healthy female subjects. Unstimulated salivary flow was measured before and after treatment, and the collected saliva was stored at - 20 °C for the analysis of TNF-α. Symptoms were evaluated before and after treatment using a pain visual analog scale. Most patients were women (81.8%) during menopause (72.2%). LLLT and ALA were efficient in increasing salivary flow only in BMS but provided symptom relief in both conditions. TNF-α levels did not differ between patients with BMS and SOB or between those patients and the control group. No differences were observed in posttreatment TNF-α levels in either condition. The results of this study suggest that LLLT and ALA are efficient therapies in reducing burning mouth symptoms, with LLLT being more efficient than ALA.

  17. Mechanism governing heme synthesis reveals a GATA factor/heme circuit that controls differentiation.

    Science.gov (United States)

    Tanimura, Nobuyuki; Miller, Eli; Igarashi, Kazuhiko; Yang, David; Burstyn, Judith N; Dewey, Colin N; Bresnick, Emery H

    2016-02-01

    Metal ion-containing macromolecules have fundamental roles in essentially all biological processes throughout the evolutionary tree. For example, iron-containing heme is a cofactor in enzyme catalysis and electron transfer and an essential hemoglobin constituent. To meet the intense demand for hemoglobin assembly in red blood cells, the cell type-specific factor GATA-1 activates transcription of Alas2, encoding the rate-limiting enzyme in heme biosynthesis, 5-aminolevulinic acid synthase-2 (ALAS-2). Using genetic editing to unravel mechanisms governing heme biosynthesis, we discovered a GATA factor- and heme-dependent circuit that establishes the erythroid cell transcriptome. CRISPR/Cas9-mediated ablation of two Alas2 intronic cis elements strongly reduces GATA-1-induced Alas2 transcription, heme biosynthesis, and surprisingly, GATA-1 regulation of other vital constituents of the erythroid cell transcriptome. Bypassing ALAS-2 function in Alas2 cis element-mutant cells by providing its catalytic product 5-aminolevulinic acid rescues heme biosynthesis and the GATA-1-dependent genetic network. Heme amplifies GATA-1 function by downregulating the heme-sensing transcriptional repressor Bach1 and via a Bach1-insensitive mechanism. Through this dual mechanism, heme and a master regulator collaborate to orchestrate a cell type-specific transcriptional program that promotes cellular differentiation. © 2015 The Authors.

  18. Primary structure of pancreatic polypeptide from four species of Perissodactyla (Przewalski's horse, zebra, rhino, tapir).

    Science.gov (United States)

    Henry, J S; Lance, V A; Conlon, J M

    1991-12-01

    Pancreatic polypeptide (PP) has been purified from extracts of the pancreas of four species of odd-toed ungulates (Perissodactyla): Przewalski's horse, mountain zebra, white rhinoceros, and mountain tapir. The amino acid sequence of Przewalski's horse pancreatic polypeptide was established as Ala-Pro-Met-Glu-Pro-Val-Tyr-Pro-Gly-Asp10-Asn- Ala-Thr-Pro-Glu-Gln-Met-Ala-Gln-Tyr20-Ala-Ala-Glu-Leu-Arg-Arg-Tyr- Ile-Asn-Met30 - Leu-Thr-Arg-Pro-Arg-Tyr.NH2. Zebra PP was identical to Przewalski's horse PP, rhinoceros PP contained three substitutions relative to the horse (Ser for Ala1, Leu for Met3, and Glu for Gln16), and tapir PP contained one substitution relative to the horse (Leu for Met3). On the basis of morphological characteristics and the fossil record, the rhinocerotids are classified with the tapirids in the suborder Ceratomorpha, whereas the horse and zebra belong to a separate suborder, Hippomorpha. On the basis of structural similarity of the PP molecules, however, it would appear that the tapir is more closely related to the horse than to the rhinoceros. These observations provide a further example of the need for extreme caution when inferring taxonomic or phylogenetic relationships between species from the structures of homologous peptides.

  19. Evidence for classification of c.1852_1853AA>GC in MLH1 as a neutral variant for Lynch syndrome

    Directory of Open Access Journals (Sweden)

    Llor Xavier

    2011-01-01

    Full Text Available Abstract Background Lynch syndrome (LS is an autosomal dominant inherited cancer syndrome characterized by early onset cancers of the colorectum, endometrium and other tumours. A significant proportion of DNA variants in LS patients are unclassified. Reports on the pathogenicity of the c.1852_1853AA>GC (p.Lys618Ala variant of the MLH1 gene are conflicting. In this study, we provide new evidence indicating that this variant has no significant implications for LS. Methods The following approach was used to assess the clinical significance of the p.Lys618Ala variant: frequency in a control population, case-control comparison, co-occurrence of the p.Lys618Ala variant with a pathogenic mutation, co-segregation with the disease and microsatellite instability in tumours from carriers of the variant. We genotyped p.Lys618Ala in 1034 individuals (373 sporadic colorectal cancer [CRC] patients, 250 index subjects from families suspected of having LS [revised Bethesda guidelines] and 411 controls. Three well-characterized LS families that fulfilled the Amsterdam II Criteria and consisted of members with the p.Lys618Ala variant were included to assess co-occurrence and co-segregation. A subset of colorectal tumour DNA samples from 17 patients carrying the p.Lys618Ala variant was screened for microsatellite instability using five mononucleotide markers. Results Twenty-seven individuals were heterozygous for the p.Lys618Ala variant; nine had sporadic CRC (2.41%, seven were suspected of having hereditary CRC (2.8% and 11 were controls (2.68%. There were no significant associations in the case-control and case-case studies. The p.Lys618Ala variant was co-existent with pathogenic mutations in two unrelated LS families. In one family, the allele distribution of the pathogenic and unclassified variant was in trans, in the other family the pathogenic variant was detected in the MSH6 gene and only the deleterious variant co-segregated with the disease in both

  20. Protective Effect of Alpha Lipoic Acid on Rat Sciatic Nerve Ischemia Reperfusion Damage

    Directory of Open Access Journals (Sweden)

    Ozan Turamanlar

    2015-06-01

    Full Text Available Background: Alpha lipoic acid is a potent antioxidant that plays numerous roles in human health. This study examined the effect of ALA on rat sciatic nerve ischemia reperfusion damage. Aims: Protective effect of alpha lipoic acid (ALA on sciatic nerve following ischemia-reperfusion in rats was investigated by using light microscopy and biochemical methods. Provided that the protective effect of ALA on sciatic nerve is proven, we think the damage to the sciatic nerve that has already occurred or might occur in patients for various reasons maybe prevented or stopped by giving ALA in convenient doses. Study Design: Animal experiment. Methods: Forty-two adult male Sprague-Dawley rats (250-300 grams were used in this study. Rats were randomly divided into six groups including one control (Group 1, one sham (Group 2, two ischemia-reperfusion (Groups 3 and 4 and two treatment groups (Groups5 and 6. Doses of 60 and 100 mg/kg ALA were given (Group 5 and 6 intra peritoneally twice, 1 and 24 hours before the ischemia to each treatment group. Ischemia was carried out the abdominal aorta starting from the distal part of the renal vein for two hours followed by reperfusion for three hours. In immunohistochemical methods, fibronectin immunoreactivity was analyzed. For biochemical analyses, the tissues were taken in eppendorf microtubes and superoxide dismutase (SOD and glutathione peroxidase (GSHPx enzyme activities as well as malondialdehyde (MDA and nitricoxide (NO levels were measured. Results: Fibronectin was observed to have increased significantly in the ischemia group; on the other hand, it was observed to have decreased in parallel to the doses in the ALA groups. Biochemical studies showed that SOD and GSHPx declined with ischemia-reperfusion, but the activities of these enzymes were increased in the treatment groups in parallel with the dose. It was found that increased MDA levels with ischemia-reperfusion were decreased in parallel with ALA dose