The change in serum Thiol/Disulphide homeostasis after transrectal ultrasound guided prostate biopsy

PubMed Central

Tokgöz, Hüsnü; Taş, Selim; Giray, Özlem; Yalçınkaya, Soner; Tokgöz, Özlem; Koca, Cemile; Savaş, Murat; Erel, Özcan

2017-01-01

ABSTRACT Objectives The aim of this prospective clinical study was to investigate variations in a novel oxidative stress marker (thiol/disulphide homeostasis) in men who underwent transrectal ultrasound guided prostate biopsy (TRUSB). Materials and Methods A total of 22 men undergoing TRUSB of the prostate were enrolled in the study. Patients with abnormal digital rectal examination and/or total prostate specific antigen (PSA) over 4ng/mL underwent TRUSB with 12 cores. Serum samples were obtained before and just after the procedure to evaluate the possible changes in thiol/disulphide homeostasis. Mean age, total PSA and free PSA, prostate volume and histopathological data were also recorded. Results Mean age of the study population was 65.05±8.89 years. Significant decreases in native and total thiol levels were documented after the biopsy procedure. However, serum disulphide levels and disulphide/native thiol, disulphide/total thiol and native/total thiol ratios did not significantly change after TRUSB. No correlation was observed between oxidative parameters and total PSA and free PSA levels, prostate volume and histopathology of the prostate. However, mean patient age was significantly correlated with mean native and total thiol levels. Conclusion Significant decreases in serum native and total thiol levels related to the prostate biopsy procedure suggest that TRUSB causes acute oxidative stress in the human body. Since our trial is the first in the current literature to investigate these oxidative stress markers in urology practice, additional studies are warranted. PMID:28128906

The change in serum Thiol/Disulphide homeostasis after transrectal ultrasound guided prostate biopsy.

PubMed

Tokgöz, Hüsnü; Taş, Selim; Giray, Özlem; Yalçınkaya, Soner; Tokgöz, Özlem; Koca, Cemile; Savaş, Murat; Erel, Özcan

2017-01-01

The aim of this prospective clinical study was to investigate variations in a novel oxidative stress marker (thiol/disulphide homeostasis) in men who underwent transrectal ultrasound guided prostate biopsy (TRUSB). A total of 22 men undergoing TRUSB of the prostate were enrolled in the study. Patients with abnormal digital rectal examination and/or total prostate specific antigen (PSA) over 4ng/mL underwent TRUSB with 12 cores. Serum samples were obtained before and just after the procedure to evaluate the possible changes in thiol/disulphide homeostasis. Mean age, total PSA and free PSA, prostate volume and histopathological data were also recorded. Mean age of the study population was 65.05±8.89 years. Significant decreases in native and total thiol levels were documented after the biopsy procedure. However, serum disulphide levels and disulphide/native thiol, disulphide/total thiol and native / total thiol ratios did not significantly change after TRUSB. No correlation was observed between oxidative parameters and total PSA and free PSA levels, prostate volume and histopathology of the prostate. However, mean patient age was significantly correlated with mean native and total thiol levels. Significant decreases in serum native and total thiol levels related to the prostate biopsy procedure suggest that TRUSB causes acute oxidative stress in the human body. Since our trial is the first in the current literature to investigate these oxidative stress markers in urology practice, additional studies are warranted. Copyright® by the International Brazilian Journal of Urology.

Evaluation of Dynamic Disulphide/Thiol Homeostasis in Silica Exposed Workers

PubMed Central

Gündüzöz, Meşide; Bal, Ceylan; Büyükşekerci, Murat; Neşelioğlu, Salim; Nadir Öziş, Türkan; İritaş, Servet; Kara, Halil; Erel, Özcan

2017-01-01

Background: Oxidative stress is implicated as one of the main molecular mechanism underlying silicosis. Aims: In this study, our aim was to asses the redox status in occupationally silica-exposed workers, by evaluating the dynamic thiol-disulphide homeostasis. Study Design: Case-control study. Methods: Thirty-six male workers occupationally exposed to silica particles and 30 healthy volunteers, working as office workers were included to the study. Posteroanterior chest radiographs and pulmonary function tests of both groups were evaluated. Also serum thiol disulphide levels were measured using the spectrophotometric method described by Erel and Neşelioğlu. Results: Among the 36 workers that underwent pulmonary function tests 6 (17%) had obstructive, 7 (19%) had restrictive, 6 (17%) had obstructive and restrictive signs whereas 17 (47%) had no signs. The mean PFTs results of silica-exposed workers were significantly lower than control subjects. The serum disulphide levels of silica-exposed workers were significantly higher than control subjects (23.84±5.89 μmol/L and 21.18±3.44 μmol/L, respectively p=0.02). Conclusion: The serum disulphide levels, a biomarker of oxidative stress, are found to be higher in silica-exposed workers. PMID:28418335

A four-disulphide-bridged toxin, with high affinity towards voltage-gated K+ channels, isolated from Heterometrus spinnifer (Scorpionidae) venom.

PubMed

Lebrun, B; Romi-Lebrun, R; Martin-Eauclaire, M F; Yasuda, A; Ishiguro, M; Oyama, Y; Pongs, O; Nakajima, T

1997-11-15

A new toxin, named HsTX1, has been identified in the venom of Heterometrus spinnifer (Scorpionidae), on the basis of its ability to block the rat Kv1.3 channels expressed in Xenopus oocytes. HsTX1 has been purified and characterized as a 34-residue peptide reticulated by four disulphide bridges. HsTX1 shares 53% and 59% sequence identity with Pandinus imperator toxin1 (Pi1) and maurotoxin, two recently isolated four-disulphide-bridged toxins, whereas it is only 32-47% identical with the other scorpion K+ channel toxins, reticulated by three disulphide bridges. The amidated and carboxylated forms of HsTX1 were synthesized chemically, and identity between the natural and the synthetic amidated peptides was proved by mass spectrometry, co-elution on C18 HPLC and blocking activity on the rat Kv1.3 channels. The disulphide bridge pattern was studied by (1) limited reduction-alkylation at acidic pH and (2) enzymic cleavage on an immobilized trypsin cartridge, both followed by mass and sequence analyses. Three of the disulphide bonds are connected as in the three-disulphide-bridged scorpion toxins, and the two extra half-cystine residues of HsTX1 are cross-linked, as in Pi1. These results, together with those of CD analysis, suggest that HsTX1 probably adopts the same general folding as all scorpion K+ channel toxins. HsTX1 is a potent inhibitor of the rat Kv1.3 channels (IC50 approx. 12 pM). HsTX1 does not compete with 125I-apamin for binding to its receptor site on rat brain synaptosomal membranes, but competes efficiently with 125I-kaliotoxin for binding to the voltage-gated K+ channels on the same preparation (IC50 approx. 1 pM).

The Role of zinc in the disulphide stress-regulated anti-sigma factor RsrA from Streptomyces coelicolor.

PubMed

Li, Wei; Bottrill, Andrew R; Bibb, Maureen J; Buttner, Mark J; Paget, Mark S B; Kleanthous, Colin

2003-10-17

The regulation of disulphide stress in actinomycetes such as Streptomyces coelicolor is known to involve the zinc-containing anti-sigma factor RsrA that binds and inactivates the redox-regulated sigma factor sigmaR. However, it is not known how RsrA senses disulphide stress nor what role the metal ion plays. Using in vitro assays, we show that while zinc is not required for sigmaR binding it is required for functional anti-sigma factor activity, and that it plays a critical role in modulating the reactivity of RsrA cysteine thiol groups towards oxidation. Apo-RsrA is easily oxidised and, while the Zn-bound form is relatively resistant, the metal ion is readily expelled when the protein is treated with strong oxidants such as diamide. We also show, using a combination of proteolysis and mass spectrometry, that the first critical disulphide to form in RsrA involves Cys11 and one of either Cys41 or Cys44, all previously implicated in metal binding. Circular dichroism spectroscopy was used to follow structural changes during oxidation of RsrA, which indicated that concomitant with formation of this critical disulphide bond is a major restructuring of the protein where its alpha-helical content increases. Our data demonstrate that RsrA can only bind sigmaR in the reduced state and that this state is stabilised by zinc. Redox stress induces disulphide bond formation amongst zinc-ligating residues, expelling the metal ion and stabilising a structure incapable of binding the sigma factor.

Mutational analysis of RsrA, a zinc-binding anti-sigma factor with a thiol-disulphide redox switch.

PubMed

Paget, M S; Bae, J B; Hahn, M Y; Li, W; Kleanthous, C; Roe, J H; Buttner, M J

2001-02-01

In the Gram-positive bacterium, Streptomyces coelicolor A3(2), expression of the thioredoxin system is modulated by a sigma factor called sigmaR in response to changes in the cytoplasmic thiol-disulphide status, and the activity of sigmaR is controlled post-translationally by an anti-sigma factor, RsrA. In vitro, the anti-sigma factor activity of RsrA, which contains seven cysteines, correlates with its thiol-disulphide redox status. Here, we investigate the function of RsrA in vivo. A constructed rsrA null mutant had very high constitutive levels of disulphide reductase activity and sigmaR-dependent transcription, confirming that RsrA is a negative regulator of sigmaR and a key sensor of thiol-disulphide status. Targeted mutagenesis revealed that three of the seven cysteines in RsrA (C11, C41 and C44) were essential for anti-sigma factor activity and that a mutant RsrA protein containing only these three cysteines was active and still redox sensitive in vivo. We also show that RsrA is a metalloprotein, containing near-stoichiometric amounts of zinc. On the basis of these data, we propose that a thiol-disulphide redox switch is formed between two of C11, C41 and C44, and that all three residues play an essential role in anti-sigma factor activity in their reduced state, perhaps by acting as ligands for zinc. Unexpectedly, rsrA null mutants were blocked in sporulation, probably as a consequence of an increase in the level of free sigmaR.

Role of disulphide bonds in a thermophilic serine protease aqualysin I from Thermus aquaticus YT-1.

PubMed

Sakaguchi, Masayoshi; Takezawa, Makoto; Nakazawa, Rie; Nozawa, Kazutaka; Kusakawa, Taro; Nagasawa, Takeshi; Sugahara, Yasusato; Kawakita, Masao

2008-05-01

A thermophilic serine protease, Aqualysin I, from Thermus aquaticus YT-1 has two disulphide bonds, which are also found in a psychrophilic serine protease from Vibrio sp. PA-44 and a proteinase K-like enzyme from Serratia sp. at corresponding positions. To understand the significance of these disulphide bonds in aqualysin I, we prepared mutants C99S, C194S and C99S/C194S (WSS), in which Cys69-Cys99, Cys163-Cys194 and both of these disulphide bonds, respectively, were disrupted by replacing Cys residues with Ser residues. All mutants were expressed stably in Escherichia coli. The C99S mutant was 68% as active as the wild-type enzyme at 40 degrees C in terms of k(cat) value, while C194S and WSS were only 6 and 3%, respectively, as active, indicating that disulphide bond Cys163-Cys194 is critically important for maintaining proper catalytic site conformation. Mutants C194S and WSS were less thermostable than wild-type enzyme, with a half-life at 90 degrees C of 10 min as compared to 45 min of the latter and with transition temperatures on differential scanning calorimetry of 86.7 degrees C and 86.9 degrees C, respectively. Mutant C99S was almost as stable as the wild-type aqualysin I. These results indicate that the disulphide bond Cys163-Cys194 is more important for catalytic activity and conformational stability of aqualysin I than Cys67-Cys99.

Inhibition of Urease Enzyme Production and some Other Virulence Factors Expression in Proteus mirabilis by N-Acetyl Cysteine and Dipropyl Disulphide.

PubMed

Abdel-Baky, Rehab Mahmoud; Ali, Mohamed Abdullah; Abuo-Rahma, Gamal El-Din Ali A; AbdelAziz, Neveen

2017-01-01

Proteus mirabilis is one of the important pathogens that colonize the urinary tract and catheters resulting in various complications, such as blockage of the catheters and the formation of infective stones. In this study we evaluated the effect of N-acetyl cysteine (NAC) and dipropyl disulphide on some virulence factors expressed by a Proteus mirabilis strain isolated from a catheterized patient. Antibacterial activity of both compounds was determined by broth microdilution method. Their effect on different types of motility was determined by LB medium with variable agar content and sub-MIC of each drug. Their effect on adherence and mature biofilms was tested by tissue culture plate assay. Inhibitory effect on urease production was determined and supported by molecular docking studies. The minimum inhibitory concentration (MIC) of NAC and dipropyl disulphide was 25 mM and 100 mM, respectively. Both compounds decreased the swarming ability and biofilm formation of the tested isolate in a dose-dependent manner. NAC had higher urease inhibitory activity (IC50 249 ±0.05 mM) than that shown by dipropyl disulphide (IC 50 10±0.2 mM). Results were supported by molecular docking studies which showed that NAC and dipropyl disulphide interacted with urease enzyme with binding free energy of -4.8 and -8.528 kcal/mol, respectively. Docking studies showed that both compounds interacted with Ni ion and several amino acids (His-138, Gly-279, Cysteine-321, Met-366 and His-322) which are essential for the enzyme activity. NAC and dipropyl disulphide could be used in the control of P. mirabilis urinary tract infections.

Defining the disulphide stress response in Streptomyces coelicolor A3(2): identification of the sigmaR regulon.

PubMed

Paget, M S; Molle, V; Cohen, G; Aharonowitz, Y; Buttner, M J

2001-11-01

In the Gram-positive, antibiotic-producing bacterium Streptomyces coelicolor A3(2), the thiol-disulphide status of the hyphae is controlled by a novel regulatory system consisting of a sigma factor, sigmaR, and its cognate anti-sigma factor, RsrA. Oxidative stress induces intramolecular disulphide bond formation in RsrA, which causes it to lose affinity for sigmaR, thereby releasing sigmaR to activate transcription of the thioredoxin operon, trxBA. Here, we exploit a preliminary consensus sequence for sigmaR target promoters to identify 27 new sigmaR target genes and operons, thereby defining the global response to disulphide stress in this organism. Target genes related to thiol metabolism encode a second thioredoxin (TrxC), a glutaredoxin-like protein and enzymes involved in the biosynthesis of the low-molecular-weight thiol-containing compounds cysteine and molybdopterin. In addition, the level of the major actinomycete thiol buffer, mycothiol, was fourfold lower in a sigR null mutant, although no candidate mycothiol biosynthetic genes were identified among the sigmaR targets. Three sigmaR target genes encode ribosome-associated products (ribosomal subunit L31, ppGpp synthetase and tmRNA), suggesting that the translational machinery is modified by disulphide stress. The product of another sigmaR target gene was found to be a novel RNA polymerase-associated protein, RbpA, suggesting that the transcriptional machinery may also be modified in response to disulphide stress. We present DNA sequence evidence that many of the targets identified in S. coelicolor are also under the control of the sigmaR homologue in the actinomycete pathogen Mycobacterium tuberculosis.

Dynamic Thiol/Disulphide Homeostasis in Children and Adolescents with Non-Autoimmune Subclinical Hypothyroidism

PubMed Central

Uçaktürk, Seyit Ahmet; Alışık, Murat; Uğur, Çağatay; Elmaoğulları, Selin; Mengen, Eda; Erel, Özcan

2018-01-01

Objective To evaluate the thiol/disulphide homeostasis in children with non-autoimmune subclinical hypothyroidism (SHT). Subjects and Methods Thiol/disulphide homeosta sis, involving native thiol (SH), disulphide (SS), and total thiol (SS + SH), was evaluated in 60 children and adolescents who were negative for thyroid auto-antibodies (anti-thyroid peroxidase, anti-thyroglobulin) and had a thyroid-stimulating hormone (TSH) value of > 5 mIU/L, and in 40 sex- and age-matched healthy control subjects who were negative for thyroid autoantibodies and had normal TSH levels. Lipid profiles and urine iodine levels were also determined. Results SH (466 ± 32.8 vs. 462 ± 32.1 μmol/L p = 0.59), SH + SS (508 ± 34.0 vs. 506 ± 32.7 μmol/L, p = 0.81), SS (21 ± 5.5 vs. 22 ± 5.8 μmol/L, p = 0.41), SS/SH (4.5 ± 1.2 vs. 4.8 ± 1.3%, p = 0.36), SS/SH + SS (4.1 ± 1.0 vs. 4.3 ± 1.1%, p = 0.36) and SH/SH + SS (91 ± 2.1 vs. 91 ± 2.1%, p = 0.31) levels were similar in children with SHT and control subjects (p > 0.05). There was no difference between total cholesterol, triglyceride, and low-density lipoprotein levels in SHT patients and controls. No difference was detected between the patients with or without iodine deficiency in the SHT group in terms of thiol/disulphide homeostasis parameters. Conclusion The status of dynamic thiol/disulphide homeostasis did not change in children and adolescents with non-autoimmune SHT. Future studies are needed for the evaluation of oxidative stress in patients with long-standing non-autoimmune SHT. PMID:29402856

Molecular beam epitaxy of quasi-freestanding transition metal disulphide monolayers on van der Waals substrates: a growth study

NASA Astrophysics Data System (ADS)

Hall, Joshua; Pielić, Borna; Murray, Clifford; Jolie, Wouter; Wekking, Tobias; Busse, Carsten; Kralj, Marko; Michely, Thomas

2018-04-01

Based on an ultra-high vacuum compatible two-step molecular beam epitaxy synthesis with elemental sulphur, we grow clean, well-oriented, and almost defect-free monolayer islands and layers of the transition metal disulphides MoS2, TaS2 and WS2. Using scanning tunneling microscopy and low energy electron diffraction we investigate systematically how to optimise the growth process, and provide insight into the growth and annealing mechanisms. A large band gap of 2.55 eV and the ability to move flakes with the scanning tunneling microscope tip both document the weak interaction of MoS2 with its substrate consisting of graphene grown on Ir(1 1 1). As the method works for the synthesis of a variety of transition metal disulphides on different substrates, we speculate that it could be of great use for providing hitherto unattainable high quality monolayers of transition metal disulphides for fundamental spectroscopic investigations.

Hydrogen sulphide protects against NSAID-enteropathy through modulation of bile and the microbiota

PubMed Central

Blackler, Rory W; Motta, Jean-Paul; Manko, Anna; Workentine, Matthew; Bercik, Premysl; Surette, Michael G; Wallace, John L

2015-01-01

Background and Purpose Hydrogen sulphide is an important mediator of gastrointestinal mucosal defence. The use of non-steroidal anti-inflammatory drugs (NSAIDs) is significantly limited by their toxicity in the gastrointestinal tract. Particularly concerning is the lack of effective preventative or curative treatments for NSAID-induced intestinal damage and bleeding. We evaluated the ability of a hydrogen sulphide donor to protect against NSAID-induced enteropathy. Experimental Approach Intestinal ulceration and bleeding were induced in Wistar rats by oral administration of naproxen. The effects of suppression of endogenous hydrogen sulphide synthesis or administration of a hydrogen sulphide donor (diallyl disulphide) on naproxen-induced enteropathy was examined. Effects of diallyl disulphide on small intestinal inflammation and intestinal microbiota were also assessed. Bile collected after in vivo naproxen and diallyl disulphide administration was evaluated for cytotoxicity in vitro using cultured intestinal epithelial cells. Key Results Suppression of endogenous hydrogen sulphide synthesis by β-cyano-L-alanine exacerbated naproxen-induced enteropathy. Diallyl disulphide co-administration dose-dependently reduced the severity of naproxen-induced small intestinal damage, inflammation and bleeding. Diallyl disulphide administration attenuated naproxen-induced increases in the cytotoxicity of bile on cultured enterocytes, and prevented or reversed naproxen-induced changes in the intestinal microbiota. Conclusions and Implications Hydrogen sulphide protects against NSAID-enteropathy in rats, in part reducing the cytotoxicity of bile and preventing NSAID-induced dysbiosis. PMID:25297699

Both the stroma and thylakoid lumen of tobacco chloroplasts are competent for the formation of disulphide bonds in recombinant proteins.

PubMed

Bally, Julia; Paget, Eric; Droux, Michel; Job, Claudette; Job, Dominique; Dubald, Manuel

2008-01-01

Plant chloroplasts are promising vehicles for recombinant protein production, but the process of protein folding in these organelles is not well understood in comparison with that in prokaryotic systems, such as Escherichia coli. This is particularly true for disulphide bond formation which is crucial for the biological activity of many therapeutic proteins. We have investigated the capacity of tobacco (Nicotiana tabacum) chloroplasts to efficiently form disulphide bonds in proteins by expressing in this plant cell organelle a well-known bacterial enzyme, alkaline phosphatase, whose activity and stability strictly depend on the correct formation of two intramolecular disulphide bonds. Plastid transformants have been generated that express either the mature enzyme, localized in the stroma, or the full-length coding region, including its signal peptide. The latter has the potential to direct the recombinant alkaline phosphatase into the lumen of thylakoids, giving access to this even less well-characterized organellar compartment. We show that the chloroplast stroma supports the formation of an active enzyme, unlike a normal bacterial cytosol. Sorting of alkaline phosphatase to the thylakoid lumen occurs in the plastid transformants translating the full-length coding region, and leads to larger amounts and more active enzyme. These results are compared with those obtained in bacteria. The implications of these findings on protein folding properties and competency of chloroplasts for disulphide bond formation are discussed.

Colloidal synthesis of biocompatible iron disulphide nanocrystals.

PubMed

Santos-Cruz, J; Nuñez-Anita, R E; Mayén-Hernández, S A; Martínez-Alvarez, O; Acosta-Torres, L S; de la Fuente-Hernández, J; Campos-González, E; Vega-González, M; Arenas-Arrocena, M C

2018-08-01

The aim of this research was to synthesis biocompatible iron disulphide nanocrystals at different reaction temperatures using the colloidal synthesis methodology. Synthesis was conducted at the 220-240 °C range of reaction temperatures at intervals of 5 °C in an inert argon atmosphere. The toxicity of iron disulphide nanocrystals was evaluated in vitro using mouse fibroblast cell line. Two complementary assays were conducted: the first to evaluate cell viability of the fibroblast via an MTT assay and the second to determine the preservation of fibroblast nuclei integrity through DAPI staining, which labels nuclear DNA in fluorescence microscopes. Through TEM and HRTEM, we observed a cubic morphology of pyrite iron disulphide nanocrystals ranging in sizes 25-50 nm (225 °C), 50-70 nm (230 °C) and >70 nm (235 °C). Through X-ray diffraction, we observed a mixture of pyrite and pyrrohotite in the samples synthesized at 225 °C and 240 °C, showing the best photocatalytic activity at 80% and 65%, respectively, for the degradation of methylene blue after 120 minutes. In all experimental groups, iron disulphide nanocrystals were biocompatible, i.e. no statistically significant differences were observed between experimental groups as shown in a one-way ANOVA and Tukey's test. Based on all of these results, we recommend non-cytotoxic semiconductor iron sulphide nanocrystals for biomedical applications.

Immunoglobulin subunits of murine B lymphocytes: structure and associations with other membrane proteins.

PubMed Central

Vogel, L; Haustein, D

1989-01-01

The Ig subunit structure of murine B lymphocytes was studied by employing different radiolabelling techniques in combination with chemical cross-linking. The main membrane structure of IgM was a half molecule that was disulphide-linked to proteins with MW 30,000, 45,000 and 55,000, respectively. Small amounts of mu 2L2, microL disulphide-linked to a protein with MW 50,000, and free microL were also detected. The main IgD structures were half molecules disulphide-linked to two proteins with MW 14,000 and two proteins with MW 16,000. Furthermore, IgD half molecules disulphide-linked to a protein with MW 16,000 and free half molecules could be demonstrated. Labelling with hydrophobic reagents showed that all Ig molecules and the protein with MW 50,000, linked to microL, penetrated the lipid bilayer, whereas the other IgM- and IgD-linked proteins probably did not. Additional proteins which were associated exclusively with IgM were detected by chemical cross-linking. These findings offer new possibilities for the investigation of the function(s) of antigen receptors on B cells. Images Figure 1 Figure 2 Figure 4 Figure 5 PMID:2787780

Covalent chromatography. Preparation of fully active papain from dried papaya latex

PubMed Central

Brocklehurst, Keith; Carlsson, Jan; Kierstan, Marek P. J.; Crook, Eric M.

1973-01-01

1. A Sepharose–(glutathione–2-pyridyl disulphide) conjugate has been prepared. 2. Its use in a new type of chromatography, covalent chromatography by thiol–disulphide interchange, is described. 3. With this technique, papain containing 1 intact catalytic site [thiol with high reactivity towards 2,2′-dipyridyl disulphide (2-Py-S-S-2-Py) at pH4] per mol of protein is readily prepared both from dried papaya latex and from commercial 2×crystallized partially active papain. 4. The catalysis of the hydrolysis of α-N-benzoyl-l-arginine ethyl ester at pH6.0, 25.0°C, I=0.3 by fully active papain thus prepared is characterized by Km=18.2±<0.1mm and kcat.=16.4±0.5s−1. PMID:4733241

Synthesis, Characterisation, and Evaluation of a Cross-Linked Disulphide Amide-Anhydride-Containing Polymer Based on Cysteine for Colonic Drug Delivery

PubMed Central

Lim, Vuanghao; Peh, Kok Khiang; Sahudin, Shariza

2013-01-01

The use of disulphide polymers, a low redox potential responsive delivery, is one strategy for targeting drugs to the colon so that they are specifically released there. The objective of this study was to synthesise a new cross-linked disulphide-containing polymer based on the amino acid cysteine as a colon drug delivery system and to evaluate the efficiency of the polymers for colon targeted drug delivery under the condition of a low redox potential. The disulphide cross-linked polymers were synthesised via air oxidation of 1,2-ethanedithiol and 3-mercapto-N-2-(3-mercaptopropionamide)-3-mercapto propionic anhydride (trithiol monomers) using different ratio combinations. Four types of polymers were synthesised: P10, P11, P151, and P15. All compounds synthesised were characterised by NMR, IR, LC-MS, CHNS analysis, Raman spectrometry, SEM-EDX, and elemental mapping. The synthesised polymers were evaluated in chemical reduction studies that were performed in zinc/acetic acid solution. The suitability of each polymer for use in colon-targeted drug delivery was investigated in vitro using simulated conditions. Chemical reduction studies showed that all polymers were reduced after 0.5–1.0 h, but different polymers had different thiol concentrations. The bacterial degradation studies showed that the polymers were biodegraded in the anaerobic colonic bacterial medium. Degradation was most pronounced for polymer P15. This result complements the general consensus that biodegradability depends on the swellability of polymers in an aqueous environment. Overall, these results suggest that the cross-linked disulphide-containing polymers described herein could be used as coatings for drugs delivered to the colon. PMID:24351841

Reactions of l-ergothioneine and some other aminothiones with 2,2′- and 4,4′-dipyridyl disulphides and of l-ergothioneine with iodoacetamide. 2-Mercaptoimidazoles, 2- and 4-thiopyridones, thiourea and thioacetamide as highly reactive neutral sulphur nucleophiles

PubMed Central

Carlsson, Jan; Kierstan, Marek P. J.; Brocklehurst, Keith

1974-01-01

1. The reactions of 2,2′- and 4,4′-dipyridyl disulphide (2-Py–S–S–2-Py and 4-Py–S–S–4-Py) with l-ergothioneine (2-mercapto-l-histidine betaine), 2-mercaptoimidazole, 1-methyl-2-mercaptoimidazole, thiourea, thioacetamide, 2-thiopyridone (Py–2-SH) and 4-thiopyridone (Py–4-SH) were investigated spectrophotometrically in the pH range approx. 1–9. 2. These reactions involve two sequential reversible thiol–disulphide interchanges. 3. The reaction of l-ergothioneine with 2-Py–S–S–2-Py and/or with the l-ergothioneine–Py–2-SH mixed disulphide, both of which provide Py–2-SH, is characterized by at least three reactive protonic states. This provides definitive evidence that neutral l-ergothioneine is a reactive nucleophile, particularly towards the highly electrophilic protonated disulphides. 4. A similar situation appears to obtain in the reactions of l-ergothioneine and Py–2-SH with 4-Py–S–S–4-Py and in the reactions of the other 2-mercaptoimidazoles, thiourea and Py–4-SH with 2-Py–S–S–2-Py. The nucleophilic reactivity of Py–4-SH suggests that general base catalysis provided by the disulphide in a cyclic or quasi-cyclic transition state is not necessary to generate nucleophilic reactivity in the other amino-thiones whose geometry could permit such catalysis. 5. The existence of a positive deuterium isotope effect in the l-ergothioneine–2-Py–S–S–2-Py system at pH6–7 provides no evidence for general base catalysis but is in accord with a mechanism involving specific acid catalysis and post-transition-state proton transfer. 6. The pH-dependences of the overall equilibrium positions of the various thiol–disulphide interchanges are described. 7. Reaction of thioacetamide with a stoicheiometric quantity of 2-Py–S–S–2-Py at pH1 provides 2 molecules of Py–2-SH per molecule of thioacetamide and elemental sulphur; these findings can be accounted for by thiol–disulphide interchange to provide a thioacetamide–Py–2-SH mixed disulphide followed by fragmentation to provide CH3CN, S and Py–2-SH. 8. Provision of high reactivity in the neutral forms of the members of this series of sulphur nucleophiles by electron donation by the amino group is compared with the well known α effect that provides enhanced nucleophilicity in compounds containing an electronegative atom adjacent to the nucleophilic atom. 9. The decrease in the u.v. absorption of l-ergothioneine at 257nm consequent on transformation of its aminothione moiety into an S-alkyl-2-mercaptoimidazole moiety provides a convenient method of following the alkylation of l-ergothioneine by iodoacetamide. 10. The pH dependence of the extinction coefficient of l-ergothioneine at 257nm is described by ε257={8×103/(1+Ka/[H+]} +6×103m−1·cm−1 in which pKa=10.8. 11. In the pH range 3–11 the reaction is characterized by two reactive protonic states (X and XH). 12. The X state, reaction of the ionized 2-mercaptoimidazole moiety of the l-ergothioneine dianion with neutral iodoacetamide, is characterized by the second-order rate constant 4.0m−1·s−1 (25.0°C, I=0.05). The XH state, characterized by the second-order rate constant 0.03m−1·s−1, is interpreted as reaction of the thione form of the neutral 2-mercaptoimidazole moiety of the l-ergothioneine monoanion with neutral iodoacetamide. 13. The XH state of the alkylation reaction does not exhibit a deuterium isotope effect. PMID:4463944

Transform analysis of the resonance Raman excitation profile of lycopene

NASA Astrophysics Data System (ADS)

Hoskins, L. C.

1992-10-01

The resonance Raman excitation profiles (RREPs) of the ν 1, ν 2 and ν 3 vibrations of lycopene in acetone, ethyl alcohol, toluene and carbon disulphide solvents have been analyzed using the transform method for calculating resonance Raman excitation profiles. The tests show excellent agreement between the calculated and observed profiles for the ν 2 and ν 3 RREPs, but greater difference between experiment and theory occurs for the ν 1 RREP, especially in carbon disulphide solvent.

Engineering and introduction of de novo disulphide bridges in organophosphorus hydrolase enzyme for thermostability improvement.

PubMed

Farnoosh, Gholamreza; Khajeh, Khosro; Latifi, Ali Mohammad; Aghamollaei, Hossein

2016-12-01

The organophosphorus hydrolase (OPH) has been used to degrade organophosphorus chemicals, as one of the most frequently used decontamination methods. Under chemical and thermal denaturing conditions, the enzyme has been shown to unfold. To utilize this enzyme in various applications, the thermal stability is of importance. The engineering of de novo disulphide bridges has been explored as a means to increase the thermal stability of enzymes in the rational method of protein engineering. In this study, Disulphide by Design software, homology modelling and molecular dynamics simulations were used to select appropriate amino acid pairs for the introduction of disulphide bridge to improve protein thermostability. The thermostability of the wild-type and three selected mutant enzymes were evaluated by half-life, delta G inactivation (ΔGi) and structural studies (fluorescence and far-UV CD analysis). Data analysis showed that half-life of A204C/T234C and T128C/E153C mutants were increased up to 4 and 24 min, respectively; however, for the G74C/A78C mutant, the half-life was decreased up to 9 min. For the T128C/E124C mutant, both thermal stability and Catalytic efficiency (kcat) were also increased. The half-life and ΔGi results were correlated to the obtained information from structural studies by circular dichroism (CD) spectrometry and extrinsic fluorescence experiments; as rigidity increased in A204C/T2234C and T128C/E153C mutants, half-life and ΔGi also increased. For G74C/A78C mutant, these parameters decreased due to its higher flexibility. The results were submitted a strong evidence for the possibility to improve the thermostability of OPH enzyme by introducing a disulphide bridge after bioinformatics design, even though this design would not be always successful.

Delpech and the origins of occupational psychiatry.

PubMed Central

O'Flynn, R R; Waldron, H A

1990-01-01

Auguste-Louis Delpech (1818-80) has been remembered principally as the author of the first detailed description of the serious consequences of exposure to carbon disulphide. A close reading of his work suggests that his reputation has been seriously undervalued. The subsequent development of occupational psychiatry, with its emphasis on the distinction between the organic and the functional, may be traced through publications on carbon disulphide. It is argued that a contemporary approach to occupational psychiatry is long overdue. PMID:2183876

High-yield exfoliation of tungsten disulphide nanosheets by rational mixing of low-boiling-point solvents

NASA Astrophysics Data System (ADS)

Sajedi-Moghaddam, Ali; Saievar-Iranizad, Esmaiel

2018-01-01

Developing high-throughput, reliable, and facile approaches for producing atomically thin sheets of transition metal dichalcogenides is of great importance to pave the way for their use in real applications. Here, we report a highly promising route for exfoliating two-dimensional tungsten disulphide sheets by using binary combination of low-boiling-point solvents. Experimental results show significant dependence of exfoliation yield on the type of solvents as well as relative volume fraction of each solvent. The highest yield was found for appropriate combination of isopropanol/water (20 vol% isopropanol and 80 vol% water) which is approximately 7 times higher than that in pure isopropanol and 4 times higher than that in pure water. The dramatic increase in exfoliation yield can be attributed to perfect match between the surface tension of tungsten disulphide and binary solvent system. Furthermore, solvent molecular size also has a profound impact on the exfoliation efficiency, due to the steric repulsion.

Submicrodeterminations of thiols, disulphides and thiol esters in serum by using o-hydroxymercuribenzoic acid and dithiofluorescein

PubMed Central

Wroński, Mieczysław

1967-01-01

1. Methods are described for selective estimation of thiols, disulphides and thiol esters in standard solutions and in serum. The methods are based on the reaction with the excess of o-hydroxymercuribenzoic acid (HMB) in alkaline solution with subsequent addition of dithiofluorescein in excess and determination of the extinction at 588mμ. The sensitivity of the methods amounts to 1·5×10−9g.equiv. in 5ml. of final solution. Of results obtained on standard solutions 80% have the errors within the range ±4%. 2. It has been found that serum contains an unidentified substance (substance X) producing green complexes with dithiofluorescein which undergo decomposition on addition of formaldehyde. The correction for substance X must be estimated in a separate sample and taken into account. The concentration of substance X can be calculated from extinctions measured at 588mμ and 635mμ in the presence of dithiofluorescein in excess. 3. The selective determination of thiols and disulphides is based on different reaction rates with formaldehyde. The complexes between HMB and cysteine can be selectively decomposed by formaldehyde, and free glutathione can be selectively removed by formaldehyde in the presence of protein thiols. 4. Thiols are determined in the presence of triethylamine, thiols plus disulphides in the presence of triethylamine and sulphite, and thiols plus thiol esters in the presence of dimethylamine, with subsequent addition of ammonium sulphate. PMID:6049936

Tyrosine phosphorylation of P-selectin in intact platelets and in a disulphide-linked complex with immunoprecipitated pp60c-src.

PubMed Central

Modderman, P W; von dem Borne, A E; Sonnenberg, A

1994-01-01

P-selectin is a 140 kDa membrane glycoprotein found in secretory granules of platelets and endothelial cells where it is rapidly translocated to the plasma membrane upon cell activation. It then functions as a receptor for various types of leucocytes. Metabolic labelling of resting platelets with 32Pi showed that P-selectin is primarily phosphorylated on serine residues, although some tyrosine phosphorylation was observed as well. However, tyrosine phosphorylation of P-selectin was greatly stimulated by treatment with the permeating phosphatase inhibitor, pervanadate. When P-selectin immunoprecipitates were incubated with [gamma-32P]ATP (in vitro kinase assay), a fraction of P-selectin was phosphorylated on its tyrosine residues by a co-precipitated kinase. P-selectin phosphorylated in vitro co-migrated with 140 kDa surface-labelled 125I-P-selectin during SDS/PAGE under reducing conditions. Under non-reducing conditions, however, phosphorylated P-selectin was disulphide-linked to unknown protein(s) in a 205 kDa complex. In vitro kinase assays of the most abundant platelet tyrosine kinase, pp60c-src, demonstrated the presence of similar 140 and 205 kDa phosphorylated proteins in SDS/PAGE under reducing and non-reducing conditions respectively. Extraction and reprecipitation studies with proteins phosphorylated in vitro indicated that P-selectin and pp60c-src form a 205 kDa 1:1 disulphide-linked complex. In the complex, pp60c-src autophosphorylation is inhibited and P-selectin is phosphorylated on tyrosine residues. As protein disulphides in the cytoplasm of intact cells are extremely rare, our results suggest that P-selectin and pp60c-src, which co-localize in platelet dense granules, may be non-covalently associated and spontaneously form disulphide bridges during lysis. In addition, the observed tyrosine phosphorylation of P-selectin in intact platelets suggests that its function might be regulated by phosphorylation by pp60c-src. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:7514867

Computer simulations reveal changes in the conformational space of the transcriptional regulator MosR upon the formation of a disulphide bond and in the collective motions that regulate its DNA-binding affinity

PubMed Central

Câmara, Amanda Souza

2018-01-01

M. tuberculosis oxidation sense Regulator (MosR) is a transcriptional regulator from Mycobacterium tuberculosis. It senses the environment oxidation and regulates the expression of a secreted oxidoreductase, thus defending the bacilli against oxidative stress from the phagosome. While most of the members of the Multiple antibiotics resistance Regulator (MarR) family are ligand-responsive, MosR may dissociate from its DNA site upon formation of an intrachain disulphide bond. However, the structure of MosR in its oxidized state is not known, and it is not clear how the formation of this disulphide bond would lead to the conformational changes required for dissociation of the DNA. Nonetheless, MosR presents two crystallographically resolved conformations in its reduced state: bound and unbound to DNA. We managed to simulate MosR unbound to the DNA, both in the presence and in the absence of the disulphide bond. Our results indicate that this disulphide bond precludes the N-terminal residues from adopting a conformation that stands in-between the helix α1 and the DNA binding domain (DBD) from the other chain. Once this conformation is achieved in the reduced state, this DBD detaches from the dimerization domain and becomes more flexible, being able to perform motions with higher amplitude and higher degree of collectivity. Only then, MosR may achieve a conformation where its recognition helices fit into the major grooves of its DNA site. The analysis of the collective motions performed by MosR, during the different situations sampled by the molecular dynamics (MDs), was only possible by the method of filtering harmonic modes with specific frequencies. The frequency of the collective motions performed by the DBD of MosR in the reduced state to achieve a DNA-binding conformation is in the range of 20 to 50 MHz, but it may be associated to more sporadic events since it requires the combination of a suitable conformation of the N-terminal residues. PMID:29470546

Computer simulations reveal changes in the conformational space of the transcriptional regulator MosR upon the formation of a disulphide bond and in the collective motions that regulate its DNA-binding affinity.

PubMed

Câmara, Amanda Souza; Horjales, Eduardo

2018-01-01

M. tuberculosis oxidation sense Regulator (MosR) is a transcriptional regulator from Mycobacterium tuberculosis. It senses the environment oxidation and regulates the expression of a secreted oxidoreductase, thus defending the bacilli against oxidative stress from the phagosome. While most of the members of the Multiple antibiotics resistance Regulator (MarR) family are ligand-responsive, MosR may dissociate from its DNA site upon formation of an intrachain disulphide bond. However, the structure of MosR in its oxidized state is not known, and it is not clear how the formation of this disulphide bond would lead to the conformational changes required for dissociation of the DNA. Nonetheless, MosR presents two crystallographically resolved conformations in its reduced state: bound and unbound to DNA. We managed to simulate MosR unbound to the DNA, both in the presence and in the absence of the disulphide bond. Our results indicate that this disulphide bond precludes the N-terminal residues from adopting a conformation that stands in-between the helix α1 and the DNA binding domain (DBD) from the other chain. Once this conformation is achieved in the reduced state, this DBD detaches from the dimerization domain and becomes more flexible, being able to perform motions with higher amplitude and higher degree of collectivity. Only then, MosR may achieve a conformation where its recognition helices fit into the major grooves of its DNA site. The analysis of the collective motions performed by MosR, during the different situations sampled by the molecular dynamics (MDs), was only possible by the method of filtering harmonic modes with specific frequencies. The frequency of the collective motions performed by the DBD of MosR in the reduced state to achieve a DNA-binding conformation is in the range of 20 to 50 MHz, but it may be associated to more sporadic events since it requires the combination of a suitable conformation of the N-terminal residues.

Comparative distribution of sulphur, thiols and disulphides in the porcine stratum corneum.

PubMed

Meyer, W; Zschemisch, N H; Lehmann, H; Busche, R; Kunz, U

2005-01-01

Biochemical, histochemical and cytochemical analyses were used to determine the sulphur contents and the thiol and disulphide distribution in the stratum corneum (SC) of the wild boar (WB), a large domestic pig breed (DP) and the Goettingen miniature pig (GMP). The sulphur contents (% DW) were different in the three animal types (WB: 1.70-1.38 body, 0.54 ear; DP: 0.84-0.53 body, 0.50 ear; GMP: 2.28-2.51 body, 2.66 ear). The results of the histochemical analysis of SH- and -S-S- groups were clear, and densitometrical extinctions were highest in most body regions of the GMP for thiols and disulphides, followed by the DP for thiols, and the WB for disulphides. Absolute SC thickness was highest in the body of the GMP (62-80 mum), and generally lowest in the ear (20-38 mum) of all animal types. Relative SC thickness was the same for all animals in the body (40-66%), but lower in the ear (30%). Only -S-S- concentrations were correlated with SC thickness, and primarily in the GMP. Cytochemical analysis showed that high sulphur concentrations were obvious particularly in the CCE of corneal cells in the DP, as compared to the cytoplasm. Intracellular sulphur distribution was homogenous in the WB, and in the GMP, although in the latter at a higher concentration level. The results indicate breed-related effects on keratinisation in porcine corneal cells. Only the SC of the outer side of the ear of DP females is recommended as a model for humans.

N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why.

PubMed

Aldini, Giancarlo; Altomare, Alessandra; Baron, Giovanna; Vistoli, Giulio; Carini, Marina; Borsani, Luisa; Sergio, Francesco

2018-05-09

The main molecular mechanisms explaining the well-established antioxidant and reducing activity of N-acetylcysteine (NAC), the N-acetyl derivative of the natural amino acid l-cysteine, are summarised and critically reviewed. The antioxidant effect is due to the ability of NAC to act as a reduced glutathione (GSH) precursor; GSH is a well-known direct antioxidant and a substrate of several antioxidant enzymes. Moreover, in some conditions where a significant depletion of endogenous Cys and GSH occurs, NAC can act as a direct antioxidant for some oxidant species such as NO 2 and HOX. The antioxidant activity of NAC could also be due to its effect in breaking thiolated proteins, thus releasing free thiols as well as reduced proteins, which in some cases, such as for mercaptoalbumin, have important direct antioxidant activity. As well as being involved in the antioxidant mechanism, the disulphide breaking activity of NAC also explains its mucolytic activity which is due to its effect in reducing heavily cross-linked mucus glycoproteins. Chemical features explaining the efficient disulphide breaking activity of NAC are also explained.

High performance asymmetric supercapacitor based on molybdenum disulphide/graphene foam and activated carbon from expanded graphite.

PubMed

Masikhwa, Tshifhiwa M; Madito, Moshawe J; Bello, Abdulhakeem; Dangbegnon, Julien K; Manyala, Ncholu

2017-02-15

Molybdenum disulphide which has a graphene-like single layer structure has excellent mechanical and electrical properties and unique morphology, which might be used with graphene foam as composite in supercapacitor applications. In this work, Molybdenum disulphide (MoS 2 )/graphene foam (GF) composites with different graphene foam loading were synthesized by the hydrothermal process to improve on specific capacitance of the composites. Asymmetric supercapacitor device was fabricated using the best performing MoS 2 /GF composite and activated carbon derived from expanded graphite (AEG) as positive and negative electrodes, respectively, in 6M KOH electrolyte. The asymmetric MoS 2 /GF//AEG device exhibited a maximum specific capacitance of 59Fg -1 at a current density of 1Ag -1 with maximum energy and power densities of 16Whkg -1 and 758Wkg -1 , respectively. The supercapacitor also exhibited a good cyclic stability with 95% capacitance retention over 2000 constant charge-discharge cycles. The results obtained demonstrate the potential of MoS 2 /GF//AEG as a promising material for electrochemical energy storage application. Copyright © 2016 Elsevier Inc. All rights reserved.

Disulphide bond exchange inhibited by air - kinetic and thermodynamic products in a library of macrocyclic cysteine derivatives.

PubMed

Cholewiak, Agnieszka; Dobrzycki, Łukasz; Jurczak, Janusz; Ulatowski, Filip

2018-04-04

In this paper we present the synthesis and reactivity of dithiols comprising of two cysteine moieties attached to a dipicolinic acid core. Oxidation of these thiols provides oligomeric macrocycles. Monomers with 13-membered rings are kinetic products which are, however, strained and readily transform into higher oligomers under basic conditions or elevated temperature via a disulphide exchange reaction. Dimers, which are the most stable thermodynamic products, equilibrate only under inert conditions with thiolate as a catalyst. Under aerobic conditions, the thiols are oxidised before the equilibrium is reached.

The roles of protein disulphide isomerase family A, member 3 (ERp57) and surface thiol/disulphide exchange in human spermatozoa-zona pellucida binding.

PubMed

Wong, Chi-Wai; Lam, Kevin K W; Lee, Cheuk-Lun; Yeung, William S B; Zhao, Wei E; Ho, Pak-Chung; Ou, Jian-Ping; Chiu, Philip C N

2017-04-01

Are multimeric sperm plasma membrane protein complexes, ERp57 and sperm surface thiol content involved in human spermatozoa-zona pellucida (ZP) interaction? ERp57 is a component of a multimeric spermatozoa-ZP receptor complex involved in regulation of human spermatozoa-ZP binding via up-regulation of sperm surface thiol content. A spermatozoon acquires its fertilization capacity within the female reproductive tract by capacitation. Spermatozoa-ZP receptor is suggested to be a composite structure that is assembled into a functional complex during capacitation. Sperm surface thiol content is elevated during capacitation. ERp57 is a protein disulphide isomerase that modulates the thiol-disulphide status of proteins. The binding ability and components of protein complexes in extracted membrane protein fractions of spermatozoa were studied. The roles of capacitation, thiol-disulphide reagent treatments and ERp57 on sperm functions and sperm surface thiol content were assessed. Spermatozoa were obtained from semen samples from normozoospermic men. Human oocytes were obtained from an assisted reproduction programme. Blue native polyacrylamide gel electrophoresis, western ligand blotting and mass spectrometry were used to identify the components of solubilized ZP/ZP3-binding complexes. The localization and expression of sperm surface thiol and ERp57 were studied by immunostaining and sperm surface protein biotinylation followed by western blotting. Sperm functions were assessed by standard assays. Several ZP-binding complexes were isolated from the cell membrane of capacitated spermatozoa. ERp57 was a component of one of these complexes. Capacitation significantly increased the sperm surface thiol content, acrosomal thiol distribution and ERp57 expression on sperm surface. Sperm surface thiol and ERp57 immunoreactivity were localized to the acrosomal region of spermatozoa, a region responsible for ZP-binding. Up-regulation of the surface thiol content or ERp57 surface expression in vitro stimulated ZP-binding capacity of human spermatozoa. Blocking of ERp57 function by specific antibody or inhibitors against ERp57 reduced the surface thiol content and ZP-binding capacity of human spermatozoa. N/A. The mechanisms by which up-regulation of surface thiol content stimulates spermatozoa-ZP binding have not been depicted. Thiol-disulphide exchange is a crucial event in capacitation. ERp57 modulates the event and the subsequent fertilization process. Modulation of the surface thiol content of the spermatozoa of subfertile men may help to increase fertilization rate in assisted reproduction. This work was supported by The Hong Kong Research Grant Council Grant HKU764611 and HKU764512M to P.C.N.C. The authors have no competing interests. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Savicalin, a lipocalin from hemocytes of the soft tick, Ornithodoros savignyi.

PubMed

Cheng, Paul H; Mans, Ben J; Neitz, Albert W H; Gaspar, Anabella R M

2010-11-01

Savicalin, is a lipocalin found in the hemocytes of the soft tick, Ornithodoros savignyi. It could be assigned to the tick lipocalin family based on BLAST analysis. Savicalin is the first non-salivary gland lipocalin described in ticks. The mature sequence is composed of 188 amino acids with a molecular mass of 21481.9 Da. A homolog for savicalin was found in a whole body EST-library from a related soft tick O. porcinus, while other tick salivary gland derived lipocalins retrieved from the non-redundant sequence database are more distantly related. Homology modeling supports the inclusion of savicalin into the lipocalin family. The model as well as multiple alignments suggests the presence of five disulphide bonds. Two conserved disulphide bonds are found in hard and soft tick lipocalins. A third disulphide bond is shared with the TSGP4-clade of leukotriene C4 binding soft tick lipocalins and a fourth is shared with a lipocalin from the hard tick Ixodes scapularis. The fifth disulphide bond is unique and links strands D-E. Phylogenetic analysis showed that savicalin is a distant relative of salivary gland derived lipocalins, but groups within a clade that is possibly non-salivary gland derived. It lacks the biogenic amine-binding motif associated with tick histamine and serotonin binding proteins. Expression profiles indicate that savicalin is found in hemocytes, midgut and ovaries, but not in the salivary glands. Up-regulation occurs in hemocytes after bacterial challenge and in midguts and ovaries after feeding. Given its tissue distribution and up-regulation of expression, it is possible that this lipocalin functions in tick development after feeding or in an anti-microbial capacity.

Association of a Polymorphism in the BIRC6 Gene with Pseudoexfoliative Glaucoma

PubMed Central

Ayub, Humaira; Micheal, Shazia; Akhtar, Farah; Khan, Muhammad Imran; Bashir, Shaheena; Waheed, Nadia K.; Ali, Mahmood; Schoenmaker-Koller, Frederieke E.; Shafique, Sobia; Qamar, Raheel; den Hollander, Anneke I.

2014-01-01

Recently an association was observed between alleles in genes of the unfolded protein response pathway and primary open angle glaucoma (POAG). The goal of the current study is to investigate the role of these two genes, protein disulphide isomerase A member 5 (PDIA5) and baculoviral IAP repeat containing 6 (BIRC6), in different forms of glaucoma. 278 patients with POAG, 132 patients with primary angle closure glaucoma (PACG) and 135 patients with pseudoexfoliative glaucoma (PEXG) were genotyped for single nucleotide polymorphisms (SNPs) rs11720822 in PDIA5 and 471 POAG, 184 PACG and 218 PEXG patients were genotyped for rs2754511 in BIRC6. Genotyping was done by allelic discrimination PCR, and genotype and allele frequencies were calculated. Logistic regression analyses were performed using R software to determine the association of these SNPs with glaucoma. The allele and genotype frequencies of rs11720822 in PDIA5 were not associated with POAG, PACG or PEXG. The TT genotype of rs2754511 in BIRC6 was found to be protective for PEXG (p = 0.05, OR 0.42 [0.22–0.81]) in the Pakistani population, but not for POAG or PACG. This study did not confirm a previously reported association of risk alleles in PDIA5 and BIRC6 with POAG, but did demonstrate a protective role of the T allele of rs2754511 in the BIRC6 gene in PEXG. This supports a role for the unfolded protein response pathway and regulation of apoptotic cell death in the pathogenesis of PEXG. PMID:25118708

Ribonuclease A Homologues of the Zebrafish: Polymorphism, Crystal Structures of Two Representatives and their Evolutionary Implications

PubMed Central

Kazakou, Konstantina; Holloway, Daniel E.; Prior, Stephen H.; Subramanian, Vasanta; Acharya, K. Ravi

2008-01-01

The widespread and functionally varied members of the ribonuclease A (RNase A) superfamily provide an excellent opportunity to study evolutionary forces at work on a conserved protein scaffold. Representatives from the zebrafish are of particular interest as the evolutionary distance from non-ichthyic homologues is large. We conducted an exhaustive survey of available zebrafish DNA sequences and found significant polymorphism among its four known homologues. In an extension of previous nomenclature, the variants have been named RNases ZF-1a–c,-2a–d,-3a–e and-4. We present the first X-ray crystal structures of zebrafish ribonucleases, RNases ZF-1a and-3e at 1.35-and 1.85 Å resolution, respectively. Structure-based clustering with ten other ribonuclease structures indicates greatest similarity to mammalian angiogenins and amphibian ribonucleases, and supports the view that all present-day ribonucleases evolved from a progenitor with three disulphide bonds. In their details, the two structures are intriguing melting-pots of features present in ribonucleases from other vertebrate classes. Whereas in RNase ZF-1a the active site is obstructed by the C-terminal segment (as observed in angiogenin), in RNase ZF-3e the same region is open (as observed in more catalytically efficient homologues). The progenitor of present-day ribonucleases is more likely to have had an obstructive C terminus, and the relatively high similarity (late divergence) of RNases ZF-1 and-3 infers that the active site unblocking event has happened independently in different vertebrate lineages. PMID:18508078

Temperature-dependent mechanical properties of single-layer molybdenum disulphide: Molecular dynamics nanoindentation simulations

NASA Astrophysics Data System (ADS)

Zhao, Junhua; Jiang, Jin-Wu; Rabczuk, Timon

2013-12-01

The temperature-dependent mechanical properties of single-layer molybdenum disulphide (MoS2) are obtained using molecular dynamics (MD) nanoindentation simulations. The Young's moduli, maximum load stress, and maximum loading strain decrease with increasing temperature from 4.2 K to 500 K. The obtained Young's moduli are in good agreement with those using our MD uniaxial tension simulations and the available experimental results. The tendency of maximum loading strain with different temperature is opposite with that of metal materials due to the short range Stillinger-Weber potentials in MoS2. Furthermore, the indenter tip radius and fitting strain effect on the mechanical properties are also discussed.

Geometrical analysis of Cys-Cys bridges in proteins and their prediction from incomplete structural information

NASA Technical Reports Server (NTRS)

Goldblum, A.; Rein, R.

1987-01-01

Analysis of C-alpha atom positions from cysteines involved in disulphide bridges in protein crystals shows that their geometric characteristics are unique with respect to other Cys-Cys, non-bridging pairs. They may be used for predicting disulphide connections in incompletely determined protein structures, such as low resolution crystallography or theoretical folding experiments. The basic unit for analysis and prediction is the 3 x 3 distance matrix for Cx positions of residues (i - 1), Cys(i), (i +1) with (j - 1), Cys(j), (j + 1). In each of its columns, row and diagonal vector--outer distances are larger than the central distance. This analysis is compared with some analytical models.

Tungsten disulphide based all fiber Q-switching cylindrical-vector beam generation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, J.; Yan, K.; Zhou, Y.

2015-11-09

We proposed and demonstrated an all fiber passively Q-switching laser to generate cylindrical-vector beam, a two dimensional material, tungsten disulphide (WS{sub 2}), was adopted as a saturable absorber inside the laser cavity, while a few-mode fiber Bragg grating was used as a transverse mode-selective output coupler. The repetition rate of the Q-switching output pulses can be varied from 80 kHz to 120 kHz with a shortest duration of 958 ns. Attributed to the high damage threshold and polarization insensitivity of the WS{sub 2} based saturable absorber, the radially polarized beam and azimuthally polarized beam can be easily generated in the Q-switching fiber laser.

Hydrophobic interactions in donor-disulphide-acceptor (DSSA) probes looking beyond fluorescence resonance energy transfer theory.

PubMed

Sanjeeva, Shilpa Kammaradi; Korrapati, Swathi; Nair, Chandrasekhar B; Rao, P V Subba; Pullela, Phani Kumar; Vijayalakshmi, U; Siva, Ramamoorthy

2014-07-01

Donor-linker-acceptor (DSSA) is a concept in fluorescence chemistry with acceptor being a fluorescent compound (FRET) or quencher. The DSSA probes used to measure thiol levels in vitro and in vivo. The reduction potential of these dyes are in the range of -0.60 V, much lower than the best thiol reductant reported in literature, the DTT (-0.33 V). DSSA disulphide having an unusually low reduction potential compared to the typical thiol reductants is a puzzle. Secondly, DSSA probes have a cyclized rhodamine ring as acceptor which does not have any spectral overlap with fluorescein, but quenches its absorbance and fluorescence. To understand the structural features of DSSA probes, we have synthesized DSSANa and DSSAOr. The calculated reduction potential of these dyes suggest that DSSA probes have an alternate mechanism from the FRET based quenching, namely hydrophobic interaction or dye to dye quenching. The standard reduction potential change with increasing complexity and steric hindrance of the molecule is small, suggesting that ultra- low Eo' has no contribution from the disulphide linker and is based on structural interactions between fluorescein and cyclized rhodamine. Our results help to understand the DSSA probe quenching mechanism and provide ways to design fluorescent probes.

UV-Light Exposure of Insulin: Pharmaceutical Implications upon Covalent Insulin Dityrosine Dimerization and Disulphide Bond Photolysis

PubMed Central

Correia, Manuel; Neves-Petersen, Maria Teresa; Jeppesen, Per Bendix; Gregersen, Søren; Petersen, Steffen B.

2012-01-01

In this work we report the effects of continuous UV-light (276 nm, ∼2.20 W.m−2) excitation of human insulin on its absorption and fluorescence properties, structure and functionality. Continuous UV-excitation of the peptide hormone in solution leads to the progressive formation of tyrosine photo-product dityrosine, formed upon tyrosine radical cross-linkage. Absorbance, fluorescence emission and excitation data confirm dityrosine formation, leading to covalent insulin dimerization. Furthermore, UV-excitation of insulin induces disulphide bridge breakage. Near- and far-UV-CD spectroscopy shows that UV-excitation of insulin induces secondary and tertiary structure losses. In native insulin, the A and B chains are held together by two disulphide bridges. Disruption of either of these bonds is likely to affect insulin’s structure. The UV-light induced structural changes impair its antibody binding capability and in vitro hormonal function. After 1.5 and 3.5 h of 276 nm excitation there is a 33.7% and 62.1% decrease in concentration of insulin recognized by guinea pig anti-insulin antibodies, respectively. Glucose uptake by human skeletal muscle cells decreases 61.7% when the cells are incubated with pre UV-illuminated insulin during 1.5 h. The observations presented in this work highlight the importance of protecting insulin and other drugs from UV-light exposure, which is of outmost relevance to the pharmaceutical industry. Several drug formulations containing insulin in hexameric, dimeric and monomeric forms can be exposed to natural and artificial UV-light during their production, packaging, storage or administration phases. We can estimate that direct long-term exposure of insulin to sunlight and common light sources for indoors lighting and UV-sterilization in industries can be sufficient to induce irreversible changes to human insulin structure. Routine fluorescence and absorption measurements in laboratory experiments may also induce changes in protein structure. Structural damage includes insulin dimerization via dityrosine cross-linking or disulphide bond disruption, which affects the hormone’s structure and bioactivity. PMID:23227203

UV-light exposure of insulin: pharmaceutical implications upon covalent insulin dityrosine dimerization and disulphide bond photolysis.

PubMed

Correia, Manuel; Neves-Petersen, Maria Teresa; Jeppesen, Per Bendix; Gregersen, Søren; Petersen, Steffen B

2012-01-01

In this work we report the effects of continuous UV-light (276 nm, ~2.20 W.m(-2)) excitation of human insulin on its absorption and fluorescence properties, structure and functionality. Continuous UV-excitation of the peptide hormone in solution leads to the progressive formation of tyrosine photo-product dityrosine, formed upon tyrosine radical cross-linkage. Absorbance, fluorescence emission and excitation data confirm dityrosine formation, leading to covalent insulin dimerization. Furthermore, UV-excitation of insulin induces disulphide bridge breakage. Near- and far-UV-CD spectroscopy shows that UV-excitation of insulin induces secondary and tertiary structure losses. In native insulin, the A and B chains are held together by two disulphide bridges. Disruption of either of these bonds is likely to affect insulin's structure. The UV-light induced structural changes impair its antibody binding capability and in vitro hormonal function. After 1.5 and 3.5 h of 276 nm excitation there is a 33.7% and 62.1% decrease in concentration of insulin recognized by guinea pig anti-insulin antibodies, respectively. Glucose uptake by human skeletal muscle cells decreases 61.7% when the cells are incubated with pre UV-illuminated insulin during 1.5 h. The observations presented in this work highlight the importance of protecting insulin and other drugs from UV-light exposure, which is of outmost relevance to the pharmaceutical industry. Several drug formulations containing insulin in hexameric, dimeric and monomeric forms can be exposed to natural and artificial UV-light during their production, packaging, storage or administration phases. We can estimate that direct long-term exposure of insulin to sunlight and common light sources for indoors lighting and UV-sterilization in industries can be sufficient to induce irreversible changes to human insulin structure. Routine fluorescence and absorption measurements in laboratory experiments may also induce changes in protein structure. Structural damage includes insulin dimerization via dityrosine cross-linking or disulphide bond disruption, which affects the hormone's structure and bioactivity.

Mutational analysis of the extracellular disulphide bridges of the atypical chemokine receptor ACKR3/CXCR7 uncovers multiple binding and activation modes for its chemokine and endogenous non-chemokine agonists.

PubMed

Szpakowska, Martyna; Meyrath, Max; Reynders, Nathan; Counson, Manuel; Hanson, Julien; Steyaert, Jan; Chevigné, Andy

2018-07-01

The atypical chemokine receptor ACKR3/CXCR7 plays crucial roles in numerous physiological processes but also in viral infection and cancer. ACKR3 shows strong propensity for activation and, unlike classical chemokine receptors, can respond to chemokines from both the CXC and CC families as well as to the endogenous peptides BAM22 and adrenomedullin. Moreover, despite belonging to the G protein coupled receptor family, its function appears to be mainly dependent on β-arrestin. ACKR3 has also been shown to continuously cycle between the plasma membrane and the endosomal compartments, suggesting a possible role as a scavenging receptor. So far, the molecular basis accounting for these atypical binding and signalling properties remains elusive. Noteworthy, ACKR3 extracellular domains bear three disulphide bridges. Two of them lie on top of the two main binding subpockets and are conserved among chemokine receptors, and one, specific to ACKR3, forms an intra-N terminus four-residue-loop of so far unknown function. Here, by mutational and functional studies, we examined the impact of the different disulphide bridges for ACKR3 folding, ligand binding and activation. We showed that, in contrast to most classical chemokine receptors, none of the extracellular disulphide bridges was essential for ACKR3 function. However, the disruption of the unique ACKR3 N-terminal loop drastically reduced the binding of CC chemokines whereas it only had a mild impact on CXC chemokine binding. Mutagenesis also uncovered that chemokine and endogenous non-chemokine ligands interact and activate ACKR3 according to distinct binding modes characterized by different transmembrane domain subpocket occupancy and N-terminal loop contribution, with BAM22 mimicking the binding mode of CC chemokine N terminus. Copyright © 2018 Elsevier Inc. All rights reserved.

Comparison of occupational exposure to carbon disulphide in a viscose rayon factory before and after technical adjustments.

PubMed

Bulat, Petar; Daemen, Edgard; Van Risseghem, Marleen; De Bacquer, Dirk; Tan, Xiaodong; Braeckman, Lutgart; Vanhoorne, Michel

2002-01-01

The objective of this follow-up study was to verify the efficacy of the technical adjustments gradually introduced in departments of a viscose rayon factory from 1989 onward. Personal exposure to carbon disulphide was assessed by means of personal monitoring through active sampling. Six job titles in three departments of the factory were sampled. Geometric means were calculated and used as estimates of time-weighted average (TWA) concentrations. The results from the present study were compared with similar measurements from a previous study in the same factory. Due to organizational changes, only three job titles (spinner, first spinner, and viscose preparator) could be compared directly. Two new job titles were identified, although tasks performed in these two job titles already existed. The measurements from one job title could not be compared, due to a substantial reorganization and automation of the tasks carried out in the department. The comparison before and after technical improvements shows that personal exposure of spinner and first spinner has been substantially reduced. Even the geometric means of measurements outside the fresh air mask are below the TWA-TLV (Threshold Limit Value). Despite the difficulties in comparing the results from the two studies, it is concluded that the technical measures reduced up to tenfold personal exposure to carbon disulphide and personal protection reduced it further by a factor two.

Entropy generation in a mixed convection Poiseulle flow of molybdenum disulphide Jeffrey nanofluid

NASA Astrophysics Data System (ADS)

Gul, Aaiza; Khan, Ilyas; Makhanov, Stanislav S.

2018-06-01

Entropy analysis in a mixed convection Poiseulle flow of a Molybdenum Disulphide Jeffrey Nanofluid (MDJN) is presented. Mixed convection is caused due to buoyancy force and external pressure gradient. The problem is formulated in terms of a boundary value problem for a system of partial differential equations. An analytical solution for the velocity and the temperature is obtained using the perturbation technique. Entropy generation has been derived as a function of the velocity and temperature gradients. The solutions are displayed graphically and the relevant importance of the input parameters is discussed. A Jeffrey nanofluid (JN) has been compared with a second grade nanofluid (SGN) and Newtonian nanofluid (NN). It is found that the entropy generation decreases when the temperature increases whereas increasing the Brickman number increases entropy generation.

A coarse-grained simulation for the folding of molybdenum disulphide

NASA Astrophysics Data System (ADS)

Wang, Cui-Xia; Zhang, Chao; Jiang, Jin-Wu; Rabczuk, Timon

2016-01-01

We investigate the folding of molybdenum disulphide (MoS2) using coarse-grained (CG) simulations, in which all the parameters are determined analytically from the Stillinger-Weber atomic potential. Owing to its simplicity, the CG model can be used to derive analytic predictions for the relaxed configuration of the folded MoS2 and the resonant frequency for the breathing-like oscillation. We disclose two interesting phenomena for the breathing-like oscillation in the folded MoS2. First, the breathing-like oscillation is self-actuated, since this oscillation can be actuated by intrinsic thermal vibrations without any external actuation force. Second, the resonant frequency of the breathing-like oscillation is insensitive to the adsorption effect. These two features enable practical applications of the folded MoS2 based nanoresonators, where stable resonant oscillations are desirable.

Increasing operational life of brush-contact device in the turbine generator due to using lubricating molybdenum disulphide brushes

NASA Astrophysics Data System (ADS)

Izotov, A. I.; Fominykh, A. A.; Nikulin, S. V.; Prokoshev, D. K.; Legoti, A. B.; Timina, N. V.

2018-01-01

A way of reducing irregular current distribution in multi-brush systems of sliding current transfer with its wear reduction due to installing lubricating molybdenum disulphide brushes on slip rings to ensure a greasing nano-sized cover on the slip ring surface is proposed. The authors give the results of industrial tests estimated on the performance effectiveness of lubricating brushes on slip rings of the TBB-320-2UZ-type turbine generator. The results showed that the lubricating brushes reduce a) the wear of 6110 OM+M and EG2AF+M brushes by 1.2 and 2.1 times respectively, b) current distribution irregularity in parallel operating brushes due to stabilizing the contact arc, and c) the temperature of the electrical brush-contact device due to the friction reduction in brushes.

Chemistry of gluten proteins.

PubMed

Wieser, Herbert

2007-04-01

Gluten proteins play a key role in determining the unique baking quality of wheat by conferring water absorption capacity, cohesivity, viscosity and elasticity on dough. Gluten proteins can be divided into two main fractions according to their solubility in aqueous alcohols: the soluble gliadins and the insoluble glutenins. Both fractions consist of numerous, partially closely related protein components characterized by high glutamine and proline contents. Gliadins are mainly monomeric proteins with molecular weights (MWs) around 28,000-55,000 and can be classified according to their different primary structures into the alpha/beta-, gamma- and omega-type. Disulphide bonds are either absent or present as intrachain crosslinks. The glutenin fraction comprises aggregated proteins linked by interchain disulphide bonds; they have a varying size ranging from about 500,000 to more than 10 million. After reduction of disulphide bonds, the resulting glutenin subunits show a solubility in aqueous alcohols similar to gliadins. Based on primary structure, glutenin subunits have been divided into the high-molecular-weight (HMW) subunits (MW=67,000-88,000) and low-molecular-weight (LMW) subunits (MW=32,000-35,000). Each gluten protein type consists or two or three different structural domains; one of them contains unique repetitive sequences rich in glutamine and proline. Native glutenins are composed of a backbone formed by HMW subunit polymers and of LMW subunit polymers branched off from HMW subunits. Non-covalent bonds such as hydrogen bonds, ionic bonds and hydrophobic bonds are important for the aggregation of gliadins and glutenins and implicate structure and physical properties of dough.

Chaperone-like properties of tobacco plastid thioredoxins f and m

PubMed Central

Sanz-Barrio, Ruth; Fernández-San Millán, Alicia; Carballeda, Jon; Corral-Martínez, Patricia; Seguí-Simarro, José M.; Farran, Inmaculada

2012-01-01

Thioredoxins (Trxs) are ubiquitous disulphide reductases that play important roles in the redox regulation of many cellular processes. However, some redox-independent functions, such as chaperone activity, have also been attributed to Trxs in recent years. The focus of our study is on the putative chaperone function of the well-described plastid Trxs f and m. To that end, the cDNA of both Trxs, designated as NtTrxf and NtTrxm, was isolated from Nicotiana tabacum plants. It was found that bacterially expressed tobacco Trx f and Trx m, in addition to their disulphide reductase activity, possessed chaperone-like properties. In vitro, Trx f and Trx m could both facilitate the reactivation of the cysteine-free form of chemically denatured glucose-6 phosphate dehydrogenase (foldase chaperone activity) and prevent heat-induced malate dehydrogenase aggregation (holdase chaperone activity). Our results led us to infer that the disulphide reductase and foldase chaperone functions prevail when the proteins occur as monomers and the well-conserved non-active cysteine present in Trx f is critical for both functions. By contrast, the holdase chaperone activity of both Trxs depended on their oligomeric status: the proteins were functional only when they were associated with high molecular mass protein complexes. Because the oligomeric status of both Trxs was induced by salt and temperature, our data suggest that plastid Trxs could operate as molecular holdase chaperones upon oxidative stress, acting as a type of small stress protein. PMID:21948853

A study of electron and thermal transport in layered titanium disulphide single crystals

NASA Astrophysics Data System (ADS)

Suri, Dhavala; Siva, Vantari; Joshi, Shalikram; Senapati, Kartik; Sahoo, P. K.; Varma, Shikha; Patel, R. S.

2017-12-01

We present a detailed study of thermal and electrical transport behavior of single crystal titanium disulphide flakes, which belong to the two dimensional, transition metal dichalcogenide class of materials. In-plane Seebeck effect measurements revealed a typical metal-like linear temperature dependence in the range of 85-285 K. Electrical transport measurements with in-plane current geometry exhibited a nearly T 2 dependence of resistivity in the range of 42-300 K. However, transport measurements along the out-of-plane current geometry showed a transition in temperature dependence of resistivity from T 2 to T 5 beyond 200 K. Interestingly, Au ion-irradiated TiS2 samples showed a similar T 5 dependence of resistivity beyond 200 K, even in the current-in-plane geometry. Micro-Raman measurements were performed to study the phonon modes in both pristine and ion-irradiated TiS2 crystals.

Purification and Characterization of 2S Albumin from Seeds of Wrightia tinctoria Exhibiting Antibacterial and DNase Activity.

PubMed

Sharma, Anchal; Kumar, Pramod; Kesari, Pooja; Neetu; Katiki, Madhusudhanarao; Mishra, Manisha; Singh, Pradhyumna K; Gurjar, Bhola R; Sharma, Ashwani K; Tomar, Shailly; Kumar, Pravindra

2017-01-01

2S albumin is a low-molecular-weight seed storage protein belonging to the prolamin superfamily. In the present work a small 2S albumin (WTA) protein of ~16 kDa has been purified from the seeds of Wrightia tinctoria. The WTA is a heterodimer protein with a small subunit of ~5 kDa and a larger subunit of ~11 kDa bridged together through disulphide bonds. The protein exhibits deoxyribonucleases activity against closed circular pBR322 plasmid DNA and linear BL21 genomic DNA. The protein also showed antibacterial activity against Morexalla catarrhalis. CD studies indicate a high α-helical content in the protein. The conserved disulphide bonds in the protein suggest that the WTA is highly stable under high pH and temperature like other 2S albumin. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Electron driven processes in sulphur containing compounds CH3SCH3 and CH3SSCH3

NASA Astrophysics Data System (ADS)

Kopyra, Janina; Władziński, Jakub

2015-06-01

Dissociative electron attachment to gas phase dimethyl sulphide (CH3SCH3) and dimethyl disulphide (CH3SSCH3) has been studied by means of a crossed beams apparatus. Cleavage of the C-S bond within CH3SCH3 and the S-S bond within CH3SSCH3 is observed within a resonance in the energy range below 2 eV and visible preferentially via the appearance of the fragment CH2S-. The striking finding is that the intensity of CH2S- generated from CH3SSCH3 is more than two orders of magnitude higher than the intensity of the respective anionic fragment generated from CH3SCH3. Our results clearly demonstrate that the CH3SSCH3 molecule, which contains disulphide bridge is substantially more sensitive towards electron attachment resulting mainly in dissociation along the S-S bridge.

Efficiency Improvement Using Molybdenum Disulphide Interlayers in Single-Wall Carbon Nanotube/Silicon Solar Cells.

PubMed

Alzahly, Shaykha; Yu, LePing; Shearer, Cameron J; Gibson, Christopher T; Shapter, Joseph G

2018-04-21

Molybdenum disulphide (MoS₂) is one of the most studied and widely applied nanomaterials from the layered transition-metal dichalcogenides (TMDs) semiconductor family. MoS₂ has a large carrier diffusion length and a high carrier mobility. Combining a layered structure of single-wall carbon nanotube (SWCNT) and MoS₂ with n-type silicon (n-Si) provided novel SWCNT/n-Si photovoltaic devices. The solar cell has a layered structure with Si covered first by a thin layer of MoS₂ flakes and then a SWCNT film. The films were examined using scanning electron microscopy, atomic force microscopy and Raman spectroscopy. The MoS₂ flake thickness ranged from 5 to 90 nm while the nanosheet’s lateral dimensions size ranged up to 1 μm². This insertion of MoS₂ improved the photoconversion efficiency (PCE) of the SWCNT/n-Si solar cells by approximately a factor of 2.

Spin-orbit proximity effect in graphene

NASA Astrophysics Data System (ADS)

Avsar, A.; Tan, J. Y.; Taychatanapat, T.; Balakrishnan, J.; Koon, G. K. W.; Yeo, Y.; Lahiri, J.; Carvalho, A.; Rodin, A. S.; O'Farrell, E. C. T.; Eda, G.; Castro Neto, A. H.; Özyilmaz, B.

2014-09-01

The development of spintronics devices relies on efficient generation of spin-polarized currents and their electric-field-controlled manipulation. While observation of exceptionally long spin relaxation lengths makes graphene an intriguing material for spintronics studies, electric field modulation of spin currents is almost impossible due to negligible intrinsic spin-orbit coupling of graphene. In this work, we create an artificial interface between monolayer graphene and few-layer semiconducting tungsten disulphide. In these devices, we observe that graphene acquires spin-orbit coupling up to 17 meV, three orders of magnitude higher than its intrinsic value, without modifying the structure of the graphene. The proximity spin-orbit coupling leads to the spin Hall effect even at room temperature, and opens the door to spin field effect transistors. We show that intrinsic defects in tungsten disulphide play an important role in this proximity effect and that graphene can act as a probe to detect defects in semiconducting surfaces.

Molecular cloning and biochemical characterization of rabbit factor XI.

PubMed Central

Sinha, Dipali; Marcinkiewicz, Mariola; Gailani, David; Walsh, Peter N

2002-01-01

Human factor XI, a plasma glycoprotein required for normal haemostasis, is a homodimer (160 kDa) formed by a single interchain disulphide bond linking the Cys-321 of each Apple 4 domain. Bovine, porcine and murine factor XI are also disulphide-linked homodimers. Rabbit factor XI, however, is an 80 kDa polypeptide on non-reducing SDS/PAGE, suggesting that rabbit factor XI exists and functions physiologically either as a monomer, as does prekallikrein, a structural homologue to factor XI, or as a non-covalent homodimer. We have investigated the structure and function of rabbit factor XI to gain insight into the relation between homodimeric structure and factor XI function. Characterization of the cDNA sequence of rabbit factor XI and its amino acid translation revealed that in the rabbit protein a His residue replaces the Cys-321 that forms the interchain disulphide linkage in human factor XI, explaining why rabbit factor XI is a monomer in non-reducing SDS/PAGE. On size-exclusion chromatography, however, purified plasma rabbit factor XI, like the human protein and unlike prekallikrein, eluted as a dimer, demonstrating that rabbit factor XI circulates as a non-covalent dimer. In functional assays rabbit factor XI and human factor XI behaved similarly. Both monomeric and dimeric factor XI were detected in extracts of cells expressing rabbit factor XI. We conclude that the failure of rabbit factor XI to form a covalent homodimer due to the replacement of Cys-321 with His does not impair its functional activity because it exists in plasma as a non-covalent homodimer and homodimerization is an intracellular process. PMID:12084014

Reptilian transferrins: evolution of disulphide bridges and conservation of iron-binding center.

PubMed

Ciuraszkiewicz, Justyna; Biczycki, Marian; Maluta, Aleksandra; Martin, Samuel; Watorek, Wiesław; Olczak, Mariusz

2007-07-01

Transferrins, found in invertebrates and vertebrates, form a physiologically important family of proteins playing a major role in iron acquisition and transport, defense against microbial pathogens, growth and differentiation. These proteins are bilobal in structure and each lobe is composed of two domains divided by a cleft harboring an iron atom. Vertebrate transferrins comprise of serotransferrins, lactoferrins and ovotransferrins. In mammals serotransferrins transport iron in physiological fluids and deliver it to cells, while lactoferrins scavenge iron, limiting its availability to invading microbes. In oviparous vertebrates there is only one transferrin gene, expressed either in the liver to be delivered to physiological fluids as serotransferrin, or in the oviduct with a final localization in egg white as ovotransferrin. Being products of one gene sero- and ovotransferrin are identical at the amino-acid sequence level but with different, cell specific glycosylation patterns. Our knowledge of the mechanisms of transferrin iron binding and release is based on sequence and structural data obtained for human serotransferrin and hen and duck ovotransferrins. No sequence information about other ovotransferrins was available until our recent publication of turkey, ostrich, and red-eared turtle (TtrF) ovotransferrin mRNA sequences [Ciuraszkiewicz, J., Olczak, M., Watorek, W., 2006. Isolation, cloning and sequencing of transferrins from red-eared turtle, African ostrich and turkey. Comp. Biochem. Physiol. 143 B, 301-310]. In the present paper, ten new reptilian mRNA transferrin sequences obtained from the Nile crocodile (NtrF), bearded dragon (BtrF), Cuban brown anole (AtrF), veiled and Mediterranean chameleons (VtrF and KtrF), sand lizard (StrF), leopard gecko (LtrF), Burmese python (PtrF), African house snake (HtrF), and grass snake (GtrF) are presented and analyzed. Nile crocodile and red-eared turtle transferrins have a disulphide bridge pattern identical to known bird homologues. A partially different disulphide bridge pattern was found in the Squamata (snakes and lizards). The possibility of a unique interdomain disulphide bridge was predicted for LtrF. Differences were found in iron-binding centers from those of previously known transferrins. Substitutions were found in the iron-chelating residues of StrF and TtrF and in the synergistic anion-binding residues of NtrF. In snakes, the transferrin (PtrF, HtrF and GtrF) N-lobe "dilysine trigger" occurring in all other known transferrins was not found, which indicates a different mechanism of iron release.

Structure of chymopapain M the late-eluted chymopapain deduced by comparative modelling techniques and active-centre characteristics determined by pH-dependent kinetics of catalysis and reactions with time-dependent inhibitors: the Cys-25/His-159 ion-pair is insufficient for catalytic competence in both chymopapain M and papain.

PubMed Central

Thomas, M P; Topham, C M; Kowlessur, D; Mellor, G W; Thomas, E W; Whitford, D; Brocklehurst, K

1994-01-01

Chymopapain M, the monothiol cysteine proteinase component of the chymopapain band eluted after chymopapains A and B in cation-exchange chromatography, was isolated from the dried latex of Carica papaya and characterized by kinetic and chromatographic analysis. This late-eluted chymopapain is probably a component of the cysteine proteinase fraction of papaya latex discovered by Schack [(1967) Compt. Rend. Trav. Lab. Carlsberg 36, 67-83], named papaya peptidase B by Lynn [(1979) Biochim. Biophys. Acta 569, 193-201] and partially characterized by Polgár [(1981) Biochim. Biophys. Acta 658, 262-269] and is the enzyme with unusual specificity characteristics (papaya proteinase IV) that Buttle, Kembhavi, Sharp, Shute, Rich and Barrett [Biochem. J. (1989) 261, 469-476] claimed to be a previously undetected cysteine proteinase eluted from a cation-exchange column near to the early-eluted chymopapains. A study of the time-dependent chromatographic consequences of thiol-dependent proteolysis of the components of papaya latex is reported. Chymopapain M was isolated by (i) affinity chromatography followed by separation from papain using cation-exchange f.p.l.c. on a Mono S HR5/5 column and (ii) cation-exchange chromatography followed by an unusual variant of covalent chromatography by thiol-disulphide interchange. The existence in chymopapain M of a nucleophilic interactive Cys/His catalytic-site system analogous to those in papain (EC 3.4.22.2) and other cysteine proteinases was deduced from the characteristics shape of the pH-second-order rate constant (k) profiles for its reactions with 2,2'-dipyridyl disulphide and ethyl 2-pyridyl disulphide. Analysis of the pH-k data for the reactions of chymopapain M with the 2-pyridyl disulphides and with 4,4'-dipyridyl disulphide permits the assignment of molecular pKa values of 3.4 and 8.7 to the formation and subsequent dehydronation of the Cys-S-/His-Im+H state of the catalytic site and reveals three other kinetically influential ionizations with pKa values 3.4, 4.3 and 5.6. The pH-dependences of kcat./Km for the hydrolysis of N-acetyl-L-Phe-Gly-4-nitroanilide at 25.0 degrees C and I0.1 M catalysed by chymopapain M and papain were determined. For both enzymes, little catalytic activity (5-7% of the maximal) develops consequent on formation of the catalytic site Cys-S-/His-Im+H ion-pair state (across pKa 3.4 for both enzymes). For papain, full expression of Kcat./Km for the uncharged substrate requires only the additional hydronic dissociation with pKa 4.2. By contrast, full expression of kcat./Km for chymopapain M requires additional hydronic dissociation with pKa values of 4.3 and 5.6.(ABSTRACT TRUNCATED AT 400 WORDS) Images Figure 6 Figure 7 PMID:8010964

Effect of Initial Headspace O2 Level on the Growth and Volatile Metabolite Production of Leuconostoc Mesenteriodes and the Microbial and Sensorial Quality of Modified Atmosphere Packaged Par-Fried French Fries.

PubMed

Samapundo, Simbarashe; Mujuru, Felix Mugove; de Baenst, Ilse; Denon, Quenten; Devlieghere, Frank

2016-02-01

This study evaluated the effect of residual O2 level (0% to 5%) on microbial growth and volatile metabolite production on par-fried French fries packaged in a modified atmosphere with 60% CO2 (rest N2 ) at 4 °C. The results obtained showed that the initial headspace (IH) O2 level had an effect on growth of Leuconostoc mesenteroides on French fry simulation agar, whereby growth was slightly faster under 5% O2 . In terms of quantity, ethanol, 2-methyl-1-propanol, and dimethyl disulphide were the most significant volatile metabolites produced by L. mesenteroides. The production of ethanol by L. mesenteroides was highest on simulation agar packaged under low IH O2 levels (0% to 1%), indicating that the fermentative metabolism was induced under these conditions. In agreement with the results observed on the simulation medium, growth of native lactic acid bacteria was faster under an IH O2 level of 5%. In addition, ethanol, 2-methyl-1-propanol, and dimethyl disulphide were also quantitatively the most important volatile metabolites. However, in contrast, greater quantities of ethanol and dimethyl disulphide were produced on par-fried French fries packaged under 5% O2 . This was attributed to the limited growth of the native flora on the par-fried French fries under residual O2 levels of 0% and 1%. Although some significant differences (P < 0.05) occurred between the French fries packaged in 0%, 1%, and 5 % residual O2 during storage, all products were considered to be acceptable for consumption. The results of this study can be used to optimize the shelf-life of packaged chill stored potato products. © 2016 Institute of Food Technologists®

The PDI genes of wheat and their syntenic relationship to the esp2 locus of rice.

PubMed

Johnson, Joshua C; Appels, Rudi; Bhave, Mrinal

2006-04-01

The storage protein polymers in the endosperm, stabilised by disulphide bonds, determine a number of processing qualities of wheat dough. The enzyme protein disulphide isomerase (PDI), involved in the formation of disulphide bonds, is strongly suggested to play a role in the formation of wheat storage protein bodies. Reports of the rice mutant esp2 exhibiting aberrant storage protein deposition in conjunction with a lack of PDI expression provided strong indications of a direct role for PDI in storage protein deposition. The potential significance of wheat PDI prompted the present studies into exploring any orthology between wheat PDI genes and rice PDI and esp2 loci. By designing allele-specific (AS)-polymerase chain reaction (PCR) markers, two of the three wheat PDI genes could be genetically mapped to group 4 chromosomes and showed close association with GERMIN genes. Physical mapping led to localisation of wheat PDI genes to chromosomal "bins" on the proximal section of chromosome 4AL and distal sections of 4BS and 4DS. Identification of the putative PDI gene of rice and its comparison to the esp2 locus revealed that they were present at similar positions on the short arm of chromosome 11. Analysis of a large section of the PDI-containing section of rice chromosome 11S revealed a number of putative orthologues from The Institute for Genomic Research Triticum aestivum Gene Index database, of which five had been mapped, each localising to group 4 chromosomes, many in good agreement with our mapping results. The results strongly suggest a close linkage between the esp2 marker and the PDI gene of rice and an orthology between the PDI loci of rice and wheat and predict quantitative-trait loci involved in storage protein deposition at the PDI loci.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Hui; Zou Kang; Guo Shaohuan

A nanostructural drug-inorganic clay composite involving a pharmaceutically active compound captopril (Cpl) intercalated Mg-Al-layered double hydroxides (Cpl-LDHs) with Mg/Al molar ratio of 2.06 has been assembled by coprecipitation method. Powder X-ray diffraction (XRD), Fourier transform infrared spectra (FT-IR) and Raman spectra analysis indicate a successful intercalation of Cpl between the layers with a vertical orientation of Cpl disulphide-containing S-S linkage. SEM photo indicates that as-synthesized Cpl-LDHs possess compact and non-porous structure with approximately and linked elliptical shape particles of ca. 50 nm. TG-DTA analyses suggest that the thermal stability of intercalated organic species is largely enhanced due to host-guest interactionmore » involving the hydrogen bond compared to pure form before intercalation. The in vitro release studies show that both the release rate and release percentages markedly decrease with increasing pH from 4.60 to 7.45 due to possible change of release mechanism during the release process. The kinetic simulation for the release data, and XRD and FT-IR analyses for samples recovered from release media indicate that the dissolution mechanism is mainly responsible for the release behaviour of Cpl-LDHs at pH 4.60, while the ion-exchange one is responsible for that at pH 7.45. - Graphical abstract: Based on XRD, FT-IR and Raman spectra analyses, it is suggested that captopril (Cpl) exists as its disulphide metabolites in the interlayer of Mg-Al-LDHs via hydrogen bonding between guest carboxylate function and hydroxyl group of the host layers. A schematic supramolecular structure of Cpl intercalates involving a vertical orientation of Cpl disulphide-containing S-S bond between the layers with carboxylate anions pointing to both hydroxide layers is presented.« less

The EGFR family of receptors sensitizes cancer cells towards UV light

NASA Astrophysics Data System (ADS)

Petersen, Steffen; Neves-Petersen, Maria Teresa; Olsen, Birgitte

2008-02-01

A combination of bioinformatics, biophysical, advanced laser studies and cell biology lead to the realization that laser-pulsed UV light stops cancer growth and induces apoptosis. We have previously shown that laser-pulsed UV (LP-UV) illumination of two different skin-derived cancer cell lines both over expressing the EGF receptor, lead to arrest of the EGFR signaling pathway. We have investigated the available sequence and experimental 3D structures available in the Protein Data Bank. The EGF receptor contains a Furin like cystein rich extracellular domain. The cystein content is highly unusual, 25 disulphide bridges supports the 621 amino acid extracellular protein domain scaffold (1mb6.pdb). In two cases a tryptophan is neighboring a cystein in the primary sequence, which in itself is a rare observation. Aromatic residues is observed to be spatially close to all observed 25 disulphide bridges. The EGF receptor is often overexpressed in cancers and other proliferative skin disorders, it might be possible to significantly reduce the proliferative potential of these cells making them good targets for laser-pulsed UV-light treatment. The discovery that UV light can be used to open disulphide bridges in proteins upon illumination of nearby aromatic amino acids was the first step that lead to the hypothesis that UV light could modulate the structure and therefore the function of these key receptor proteins. The observation that membrane receptors (EGFR) contained exactly the motifs that are sensitive to UV light lead to the prediction that UV light could modify these receptors permanently and stop cancer proliferation. We hereby show that the EGFR family of receptors has the necessary structural motifs that make this family of proteins highly sensitive to UV light.

In vitro pepsin resistance of proteins: Effect of non-reduced SDS-PAGE analysis on fragment observation.

PubMed

Pickles, Juliette; Rafiq, Samera; Cochrane, Stella A; Lalljie, Anja

2014-01-01

The introduction of novel proteins to food products carries with it the need to assess the potential allergenicity of such materials. Resistance to in vitro pepsin digestion is one parameter considered in such a risk assessment using a weight of evidence approach; however, the methodology used to investigate this has not been fully standardised. In vitro pepsin resistance assays typically involve SDS-PAGE performed under reducing conditions, with limited published data available on the assay using non-reducing conditions despite the need to consider non-reducing analysis techniques having been highlighted by regulatory bodies such as the European Food Safety Authority (EFSA). The purpose of the work reported here was to investigate the applicability of (and additional insight provided by) non-reducing analyses, by digesting a set of proteins using a ring-trial validated method, with analysis by SDS-PAGE under both reducing and non-reducing conditions. In silico prediction of digest fragments was also investigated. Significant differences were observed between results under reduced and non-reduced conditions for proteins in which disulphide bonds have a major role in protein structure, such as ribulose 1,5-diphosphate carboxylase (RUBISCO) and bovine serum albumin. For proteins with no or few disulphide bonds, no significant differences were seen in the results. Structural information such as disulphide bond numbers and positions should be considered during experimental design, as a non-reduced approach may be appropriate for some proteins. The in silico approach was a useful tool to suggest potential digest fragments, however the predictions were not always confirmed in vitro and should be considered a guide only.

Violaxanthin de-epoxidase disulphides and their role in activity and thermal stability.

PubMed

Hallin, Erik Ingmar; Guo, Kuo; Åkerlund, Hans-Erik

2015-05-01

Violaxanthin de-epoxidase (VDE) catalyses the conversion of violaxanthin to zeaxanthin at the lumen side of the thylakoids during exposure to intense light. VDE consists of a cysteine-rich N-terminal domain, a lipocalin-like domain and a negatively charged C-terminal domain. That the cysteines are important for the activity of VDE is well known, but in what way is less understood. In this study, wild-type spinach VDE was expressed in E. coli as inclusion bodies, refolded and purified to give a highly active and homogenous preparation. The metal content (Fe, Cu, Ni, Mn, Co and Zn) was lower than 1 mol% excluding a metal-binding function of the cysteines. To investigate which of the 13 cysteines that could be important for the function of VDE, we constructed mutants where the cysteines were replaced by serines, one by one. For 12 out of 13 mutants the activity dropped by more than 99.9%. A quantification of free cysteines showed that only the most N-terminal of these cysteines was in reduced form in the native VDE. A disulphide pattern in VDE of C9-C27, C14-C21, C33-C50, C37-C46, C65-C72 and C118-C284 was obtained after digestion of VDE with thermolysin followed by mass spectroscopy analysis of reduced versus non-reduced samples. The residual activity found for the mutants showed a variation that was consistent with the results obtained from mass spectroscopy. Reduction of the disulphides resulted in loss of a rigid structure and a decrease in thermal stability of 15 °C.

Expression, Purification and Characterization of GMZ2'.10C, a Complex Disulphide-Bonded Fusion Protein Vaccine Candidate against the Asexual and Sexual Life-Stages of the Malaria-Causing Plasmodium falciparum Parasite.

PubMed

Mistarz, Ulrik H; Singh, Susheel K; Nguyen, Tam T T N; Roeffen, Will; Yang, Fen; Lissau, Casper; Madsen, Søren M; Vrang, Astrid; Tiendrebeogo, Régis W; Kana, Ikhlaq H; Sauerwein, Robert W; Theisen, Michael; Rand, Kasper D

2017-09-01

Production and characterization of a chimeric fusion protein (GMZ2'.10C) which combines epitopes of key malaria parasite antigens: glutamate-rich protein (GLURP), merozoite surface protein 3 (MSP3), and the highly disulphide bonded Pfs48/45 (10C). GMZ2'.10C is a potential candidate for a multi-stage malaria vaccine that targets both transmission and asexual life-cycle stages of the parasite. GMZ2'.10C was produced in Lactococcus lactis and purified using either an immunoaffinity purification (IP) or a conventional purification (CP) method. Protein purity and stability was analysed by RP-HPLC, SEC-HPLC, 2-site ELISA, gel-electrophoresis and Western blotting. Structural characterization (mass analysis, peptide mapping and cysteine connectivity mapping) was performed by LC-MS/MS. CP-GMZ2'.10C resulted in similar purity, yield, structure and stability as compared to IP-GMZ2'.10C. CP-GMZ2'.10C and IP-GMZ2'.10C both elicited a high titer of transmission blocking (TB) antibodies in rodents. The intricate disulphide-bond connectivity of C-terminus Pfs48/45 was analysed by tandem mass spectrometry and was established for GMZ2'.10C and two reference fusion proteins encompassing similar parts of Pfs48/45. GMZ2'.10C, combining GMZ2' and correctly-folded Pfs48/45 can be produced by the Lactoccus lactis P170 based expression system in purity and quality for pharmaceutical development and elicit high level of TB antibodies. The cysteine connectivity for the 10C region of Pfs48/45 was revealed experimentally, providing an important guideline for employing the Pfs48/45 antigen in vaccine design.

Serum ischemia modified albumin level and its relationship with the thiol/disulfide balance in placenta percreta patients.

PubMed

Uyanikoglu, Hacer; Sak, Muhammet Erdal; Tatli, Faik; Hilali, Nese Gul; Sak, Sibel; Incebiyik, Adnan; Barut, Mert Ulas; Erel, Ozcan; Gonel, Ataman

2018-06-08

The pathogenesis of placenta percreta (PP) is not very well known. This study was designed to analyse the oxidative stress (OS), the thiol/disulphide balance, and ischaemia-modified albumin (IMA) the women with PP. The study included 38 pregnant women with PP and 40 similarly aged healthy pregnant women in their third trimester of gestation. We measured the IMA, native and total thiols, and disulphide concentrations in the maternal sera of all of the participating women. The IMA levels were higher and the native and total thiols were lower in the PP group than in the control group. However, there was no statistical significance with respect to the thiol/disulphide balance between the two groups. The results of this study suggest that an increase in the ischaemia and OS and a decrease in the antioxidant status may contribute to the pathogenesis of PP. Impact statement What is already known on this subject? Placenta percreta (PP) is a serious complication of pregnancy. Although there are several studies investigating the pathophysiological mechanism of PP, whether the pathology results from a lack of decidua or from the over-invasiveness of trophoblasts remains controversial. The pathology of PP is poorly understood. What do the results of this study add? This prospective study has shown an increased ischaemia modified albumin (IMA) and a decreased antioxidant capacity in the patients with placenta percreta. The results from 38 women with PP suggest that the serum concentrations of IMA and the oxidative stress parameters may be able to predict PP in cases of uncertainty. What are the implications of these findings for clinical practice and/or further research? The implication of these findings shed light on understanding the pathogenesis of PP for further research.

Purification and biochemical characterization of native ERp29 from rat liver

PubMed Central

2004-01-01

ERp29 is a recently characterized resident of the ER (endoplasmic reticulum) lumen that has broad biological significance, being expressed ubiquitously and abundantly in animal cells. As an apparent housekeeper, ERp29 is thought to be a general folding assistant for secretory proteins and to probably function as a PDI (protein disulphide isomerase)-like molecular chaperone. In the present paper, we report the first purification to homogeneity and direct functional analysis of native ERp29, which has led to the unexpected finding that ERp29 lacks PDI-like folding activities. ERp29 was purified 4800-fold in non-denaturing conditions exploiting an unusual affinity for heparin. Two additional biochemical hallmarks that will assist the classification of ERp29 homologues were identified, namely the idiosyncratic behaviours of ERp29 on size-exclusion chromatography (Mrmonomeric mass). In contrast with PDI and parallel-purified co-residents (calreticulin, ERp60), native ERp29 lacked classical chaperone, disulphide reductase and isomerase, and calcium-binding activities. In the chaperone assays, ERp29 neither protected substrate proteins against thermal aggregation nor interacted stably with chemically denatured proteins as detected by cross-linking. ERp29 also did not exhibit helper activity toward calreticulin (chaperone) or PDI and ERp60 (disulphide reductase). By refuting long-standing predictions about chaperone activity, these results expose ERp29 as a functionally distinct member of the ER machinery and prompt a revised hypothesis that ERp29 acts as a non-classical folding assistant. The native preparation and biochemical hallmarks established here provide a useful foundation for ongoing efforts to resolve the functional orphan status of ERp29. PMID:15500441

Electron Microscopy of Tungsten Disulphide Inorganic Nanomaterials

DTIC Science & Technology

2009-09-01

cylindrical molecule similar to a carbon nanotube. Inorganic nanotubes have been observed in some mineral deposits. Linus Pauling suggested the...diffraction pattern was due to the carbon coating. Figure 6 SAED taken from the single nanotube shown in figure 5 REFERENCES 1. Pauling , L; "The

Gene networks in the synthesis and deposition of protein polymers during grain development of wheat.

PubMed

She, Maoyun; Ye, Xingguo; Yan, Yueming; Howit, C; Belgard, M; Ma, Wujun

2011-03-01

As the amino acid storing organelle, the protein bodies provide nutrients for embryo development, seed germination and early seedling growth through storage proteolysis in cereal plants, such as wheat and rice. In protein bodies, the monomeric and polymeric prolamins, i.e. gliadins and glutenins, form gluten and play a key role in determining dough functionality and end-product quality of wheat. The formation of intra- and intermolecular bonds, including disulphide and tyrosine bonds, in and between prolamins confers cohesivity, viscosity, elasticity and extensibility to wheat dough during mixing and processing. In this review, we summarize recent progress in wheat gluten research with a focus on the fundamental molecular biological aspects, including transcriptional regulation on genes coding for prolamin components, biosynthesis, deposition and secretion of protein polymers, formation of protein bodies, genetic control of seed storage proteins, the transportation of the protein bodies and key enzymes for determining the formation of disulphide bonds of prolamin polymers.

Mixed convection flow of sodium alginate (SA-NaAlg) based molybdenum disulphide (MoS2) nanofluids: Maxwell Garnetts and Brinkman models

NASA Astrophysics Data System (ADS)

Ahmed, Tarek Nabil; Khan, Ilyas

2018-03-01

This article aims to study the mixed convection heat transfer in non-Newtonian nanofluids over an infinite vertical plate. Mixed convection is caused due to buoyancy force and sudden plate motion. Sodium alginate (SA-NaAlg) is considered as non-Newtonian base fluid and molybdenum disulphide (MoS2) as nanoparticles are suspended in it. The effective thermal conductivity and viscosity of nanofluid are calculated using the Maxwell-Garnetts (MG) and Brinkman models, respectively. The flow is modeled in the form of partial differential equations with imposed physical conditions. Exact solutions for velocity and temperature fields are developed by means of the Laplace transform technique. Numerical computations are performed for different governing parameters such as non-Newtonian parameter, Grashof number and nanoparticle volume fraction and the results are plotted in various graphs. Results for skin friction and Nusselt number are presented in tabular form which show that increasing nanoparticle volume fraction leads to heat transfer enhancement and increasing skin friction.

Preferential cross-linking of the small subunit of the electron-transfer flavoprotein to general acyl-CoA dehydrogenase.

PubMed Central

Steenkamp, D J

1987-01-01

The interaction between pig liver mitochondrial electron-transfer flavoprotein (ETF) and general acyl-CoA dehydrogenase (GAD) was investigated by means of the heterobifunctional reagent N-succinimidyl 3-(2-pyridyldithio)propionate. Neither ETF or GAD contained reactive thiol groups. The substitution of 9.4 lysine residues/FAD group in GAD with pyridyl disulphide structures did not affect the catalytic activity of the enzyme. Thiol groups were introduced into ETF by thiolation with methyl 4-mercaptobutyrimidate. ETF containing 10.5 reactive thiol groups/FAD group showed undiminished electron-acceptor activity with respect to GAD. The reaction of thiolated ETF and GAD containing pyridyl disulphide structures resulted in a decreased staining intensity of the small subunit of ETF on SDS/polyacrylamide-gel electrophoresis. Preferential cross-linking of the smaller subunit of ETF to GAD did not take place when ETF was first treated with SDS, but was unaffected by reduction of GAD by octanoyl-CoA. Images Fig. 2. Fig. 3. Fig. 5. PMID:3115254

From Allergen Back to Antigen:. a Rational Approach to New Forms of Immunotherapy

NASA Astrophysics Data System (ADS)

Colombo, Paolo; Trapani, Antonino; Geraci, Domenico; Golino, Massimiliano; Gianguzza, Fabrizio; Bonura, Angela

2007-12-01

Mapping an epitope on a protein by gene fragmentation and/or point mutations is often expensive and time consuming. Analysis of a 3D model can be utilized to detect the amino acids residues which are exposed to the solvent surface and thus represent potential epitope residues. Parj1 and Parj2 are the two major allergens of the Parietaria judaica pollen belonging to the Lipid Transfer Protein family. Using their three-dimensional structures as a guide, a head to tail dimer expressing disulphide bond variants of the major allergens was generated by means of DNA recombinant technology. The hybrid was expressed in E.coli and its immunological activity studied in vivo and in vitro. Our results demonstrate that a hybrid polypeptide expressing disulphide bond variants of the major allergens of the Parietaria pollen displayed reduced allergenicity and enhanced T cell reactivity for induction of protective antibodies able to block human IgE induced during the natural course of sensitization against the Parietaria pollen.

Redox Regulation in Amyotrophic Lateral Sclerosis

PubMed Central

Parakh, Sonam; Spencer, Damian M.; Halloran, Mark A.; Soo, Kai Y.; Atkin, Julie D.

2013-01-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results from the death of upper and lower motor neurons. Due to a lack of effective treatment, it is imperative to understand the underlying mechanisms and processes involved in disease progression. Regulations in cellular reduction/oxidation (redox) processes are being increasingly implicated in disease. Here we discuss the possible involvement of redox dysregulation in the pathophysiology of ALS, either as a cause of cellular abnormalities or a consequence. We focus on its possible role in oxidative stress, protein misfolding, glutamate excitotoxicity, lipid peroxidation and cholesterol esterification, mitochondrial dysfunction, impaired axonal transport and neurofilament aggregation, autophagic stress, and endoplasmic reticulum (ER) stress. We also speculate that an ER chaperone protein disulphide isomerase (PDI) could play a key role in this dysregulation. PDI is essential for normal protein folding by oxidation and reduction of disulphide bonds, and hence any disruption to this process may have consequences for motor neurons. Addressing the mechanism underlying redox regulation and dysregulation may therefore help to unravel the molecular mechanism involved in ALS. PMID:23533690

Efficiency Improvement Using Molybdenum Disulphide Interlayers in Single-Wall Carbon Nanotube/Silicon Solar Cells

PubMed Central

Alzahly, Shaykha; Yu, LePing; Gibson, Christopher T.

2018-01-01

Molybdenum disulphide (MoS2) is one of the most studied and widely applied nanomaterials from the layered transition-metal dichalcogenides (TMDs) semiconductor family. MoS2 has a large carrier diffusion length and a high carrier mobility. Combining a layered structure of single-wall carbon nanotube (SWCNT) and MoS2 with n-type silicon (n-Si) provided novel SWCNT/n-Si photovoltaic devices. The solar cell has a layered structure with Si covered first by a thin layer of MoS2 flakes and then a SWCNT film. The films were examined using scanning electron microscopy, atomic force microscopy and Raman spectroscopy. The MoS2 flake thickness ranged from 5 to 90 nm while the nanosheet’s lateral dimensions size ranged up to 1 μm2. This insertion of MoS2 improved the photoconversion efficiency (PCE) of the SWCNT/n-Si solar cells by approximately a factor of 2. PMID:29690503

Molybdenum disulphide and graphene quantum dots as electrode modifiers for laccase biosensor.

PubMed

Vasilescu, Ioana; Eremia, Sandra A V; Kusko, Mihaela; Radoi, Antonio; Vasile, Eugeniu; Radu, Gabriel-Lucian

2016-01-15

A nanocomposite formed from molybdenum disulphide (MoS2) and graphene quantum dots (GQDs) was proposed as a novel and suitable support for enzyme immobilisation displaying interesting electrochemical properties. The conductivity of the carbon based screen-printed electrodes was highly improved after modification with MoS2 nanoflakes and GQDs, the nanocomposite also providing compatible matrix for laccase immobilisation. The influence of different modification steps on the final electroanalytical performances of the modified electrode were evaluated by UV-vis absorption and fluorescence spectroscopy, scanning electron microscopy, transmission electron microscopy, X ray diffraction, electrochemical impedance spectroscopy and cyclic voltammetry. The developed laccase biosensor has responded efficiently to caffeic acid over a concentration range of 0.38-100µM, had a detection limit of 0.32µM and a sensitivity of 17.92nAµM(-1). The proposed analytical tool was successfully applied for the determination of total polyphenolic content from red wine samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Recent trends in the formulation of permanent waving products for hair.

PubMed

Puri, A K

1979-02-01

Synopsis Current trends in the formulation of permanent waving products for hair are discussed in light of recently reported findings on the reactivity of disulphide bond in the hair keratin and theories on the mechanism of permanent waving. Effectiveness of protein and other additives is discussed in detail.

Liquid chromatographic determination of total homocysteine in blood plasma with photometric detection.

PubMed

Zhloba, Alexander A; Blashko, Eduard L

2004-02-05

A rapid and sensitive method for quantification of homocysteine total forms and glutathione levels in blood plasma via HPLC was developed. Dithiotreitol as a water soluble agent has been used as a reductant for both protein and nonprotein disulphides. Dithiotreitol reacts with the mixed disulphides under 60 degrees C treatment within 10 min. Reduced aminothiols and homocystein were easily derivated with 5,5'-dithiobis-(2-nitrobenzoic acid) and the resultant ultraviolet absorbance within 330 nm was detected by the HPLC method. The concentration of total plasma homocysteine was significantly higher in groups of patients: with the end stage of renal disease: 45.5+/-40.9 micromol/l (n=79), with cerebral vascular disorders 12.3+/-7.0 micromol/l (n=65), and with coronary atherosclerosis 15.4+/-10.9 micromol/l (n=15) than that in healthy subjects (6.2+/-1.74 micromol/l, n=20). Some major advantages of the method include: simultaneous measurement of both total homocysteine and total glutathione, no loss of oxidized form during processing of blood plasma for aminothiols measurement, use of protein-bound aminothiols solution as a calibrator.

N-terminal domains of fibrillin 1 and fibrillin 2 direct the formation of homodimers: a possible first step in microfibril assembly.

PubMed Central

Trask, T M; Ritty, T M; Broekelmann, T; Tisdale, C; Mecham, R P

1999-01-01

Aggregation of fibrillin molecules via disulphide bonds is postulated to be an early step in microfibril assembly. By expressing fragments of fibrillin 1 and fibrillin 2 in a mammalian expression system, we found that the N-terminal region of each protein directs the formation of homodimers and that disulphide bonds stabilize this interaction. A large fragment of fibrillin 1 containing much of the region downstream from the N-terminus remained as a monomer when expressed in the same cell system, indicating that this region of the protein lacks dimerization domains. This finding also confirms that the overexpression of fibrillin fragments does not in itself lead to spurious dimer formation. Pulse-chase analysis demonstrated that dimer formation occurred intracellularly, suggesting that the process of fibrillin aggregation is initiated early after biosynthesis of the molecules. These findings also implicate the N-terminal region of fibrillin 1 and fibrillin 2 in directing the formation of a dimer intermediate that aggregates to form the functional microfibril. PMID:10359653

The use of D-penicillamine in patients with rheumatoid arthritis undergoing hemodialysis.

PubMed

Matthey, F; Perrett, D; Greenwood, R N; Baker, L R

1986-05-01

D-penicillamine and its major metabolites cysteine-penicillamine disulphide (CP) and penicillamine disulphide (P2) concentrations were measured in plasma from a hemodialysis patient with rheumatoid arthritis. CP and P2 alone were measured in plasma and a plasma ultrafiltrate from a second patient. On penicillamine 250 mg thrice weekly taken after dialysis pre-dialysis penicillamine concentrations were in the range 5.9-9.9 mumol/l. CP and P2 concentrations remained stable (range 139-197 mumol/l and 10-20 mumol/l) over 5 weeks and were of the same order as previously found in patients with normal renal function on higher doses of the drug. On penicillamine 250 mg daily concentrations of metabolites CP and P2 reach 193 mumol/l and 59.2 mumol/l after 2 and 3 weeks respectively. Concentration of metabolites fell by about half and of penicillamine by about a third after dialysis. Concentration of metabolites in ultrafiltrate were on average 75% lower than in plasma. Penicillamine 250 mg thrice weekly given after dialysis appears to be an appropriate dose for hemodialysis patients with rheumatoid arthritis.

An effective approach to synthesize monolayer tungsten disulphide crystals using tungsten halide precursor

NASA Astrophysics Data System (ADS)

Thangaraja, Amutha; Shinde, Sachin M.; Kalita, Golap; Tanemura, Masaki

2016-02-01

The synthesis of large-area monolayer tungsten disulphide (WS2) single crystal is critical for realistic application in electronic and optical devices. Here, we demonstrate an effective approach to synthesize monolayer WS2 crystals using tungsten hexachloride (WCl6) as a solid precursor in atmospheric chemical vapor deposition process. In this technique, 0.05M solution of WCl6 in ethanol was drop-casted on SiO2/Si substrate to create an even distribution of the precursor, which was reduced and sulfurized at 750 °C in Ar atmosphere. We observed growth of triangular, star-shaped, as well as dendritic WS2 crystals on the substrate. The crystal geometry evolves with the shape and size of the nuclei as observed from the dendritic structures. These results show that controlling the initial nucleation and growth process, large WS2 single crystalline monolayer can be grown using the WCl6 precursor. Our finding shows an easier and effective approach to grow WS2 monolayer using tungsten halide solution-casting, rather than evaporating the precursor for gas phase reaction.

Protein disulphide isomerase is required for signal peptide peptidase-mediated protein degradation

PubMed Central

Lee, Seong-Ok; Cho, Kwangmin; Cho, Sunglim; Kim, Ilkwon; Oh, Changhoon; Ahn, Kwangseog

2010-01-01

The human cytomegalovirus glycoprotein US2 induces dislocation of MHC class I heavy chains from the endoplasmic reticulum (ER) into the cytosol and targets them for proteasomal degradation. Signal peptide peptidase (SPP) has been shown to be integral for US2-induced dislocation of MHC class I heavy chains although its mechanism of action remains poorly understood. Here, we show that knockdown of protein disulphide isomerase (PDI) by RNA-mediated interference inhibited the degradation of MHC class I molecules catalysed by US2 but not by its functional homolog US11. Overexpression of the substrate-binding mutant of PDI, but not the catalytically inactive mutant, dominant-negatively inhibited US2-mediated dislocation of MHC class I molecules by preventing their release from US2. Furthermore, PDI associated with SPP independently of US2 and knockdown of PDI inhibited SPP-mediated degradation of CD3δ but not Derlin-1-dependent degradation of CFTR DeltaF508. Together, our data suggest that PDI is a component of the SPP-mediated ER-associated degradation machinery. PMID:19942855

All-optical tunable dual Fano resonance in nonlinear metamaterials in optical communication range

NASA Astrophysics Data System (ADS)

Zhou, Yi; Hu, Xiaoyong; Li, Chong; Yang, Hong; Gong, Qihuang

2018-01-01

Low-power, ultra-fast all-optical tunable dual Fano resonance was realized in a metamaterial coated with a non-linear nanocomposite layer composed of gold nanoparticle-doped polycrystalline barium strontium titanate and multilayer tungsten disulphide microsheets. A high non-linear refractive index of -2.148 × 10-11 m2/W was achieved in the nanocomposite material that originated in the non-linearity enhancement associated with the quantum confinement effect, the local-field enhancement effect, and reinforced interactions between photons and the multilayer tungsten disulphide microsheets. An ultra-low threshold pump intensity of 600 kW/cm2 was obtained. An ultra-fast response time of 25.4 ps was maintained because of the fast relaxation dynamics of the bound electrons in the nanoscale polycrystalline barium strontium titanate grains. The large third-order non-linear responses of the metamaterial were confirmed with a high third harmonic generation conversion efficiency of 5.4 × 10-5. This work may help to pave the way towards realization of ultra-high-speed information processing chips and multifunctional integrated photonic devices based on metamaterials.

Protein disulphide isomerase is required for signal peptide peptidase-mediated protein degradation.

PubMed

Lee, Seong-Ok; Cho, Kwangmin; Cho, Sunglim; Kim, Ilkwon; Oh, Changhoon; Ahn, Kwangseog

2010-01-20

The human cytomegalovirus glycoprotein US2 induces dislocation of MHC class I heavy chains from the endoplasmic reticulum (ER) into the cytosol and targets them for proteasomal degradation. Signal peptide peptidase (SPP) has been shown to be integral for US2-induced dislocation of MHC class I heavy chains although its mechanism of action remains poorly understood. Here, we show that knockdown of protein disulphide isomerase (PDI) by RNA-mediated interference inhibited the degradation of MHC class I molecules catalysed by US2 but not by its functional homolog US11. Overexpression of the substrate-binding mutant of PDI, but not the catalytically inactive mutant, dominant-negatively inhibited US2-mediated dislocation of MHC class I molecules by preventing their release from US2. Furthermore, PDI associated with SPP independently of US2 and knockdown of PDI inhibited SPP-mediated degradation of CD3delta but not Derlin-1-dependent degradation of CFTR DeltaF508. Together, our data suggest that PDI is a component of the SPP-mediated ER-associated degradation machinery.

Room temperature rubbing for few-layer two-dimensional thin flakes directly on flexible polymer substrates

PubMed Central

Yu, Yan; Jiang, Shenglin; Zhou, Wenli; Miao, Xiangshui; Zeng, Yike; Zhang, Guangzu; Liu, Sisi

2013-01-01

The functional layers of few-layer two-dimensional (2-D) thin flakes on flexible polymers for stretchable applications have attracted much interest. However, most fabrication methods are “indirect” processes that require transfer steps. Moreover, previously reported “transfer-free” methods are only suitable for graphene and not for other few-layer 2-D thin flakes. Here, a friction based room temperature rubbing method is proposed for fabricating different types of few-layer 2-D thin flakes (graphene, hexagonal boron nitride (h-BN), molybdenum disulphide (MoS2), and tungsten disulphide (WS2)) on flexible polymer substrates. Commercial 2-D raw materials (graphite, h-BN, MoS2, and WS2) that contain thousands of atom layers were used. After several minutes, different types of few-layer 2-D thin flakes were fabricated directly on the flexible polymer substrates by rubbing procedures at room temperature and without any transfer step. These few-layer 2-D thin flakes strongly adhere to the flexible polymer substrates. This strong adhesion is beneficial for future applications. PMID:24045289

The failure to express a protein disulphide isomerase-like protein results in a floury endosperm and an endoplasmic reticulum stress response in rice.

PubMed

Han, Xiaohua; Wang, Yihua; Liu, Xi; Jiang, Ling; Ren, Yulong; Liu, Feng; Peng, Cheng; Li, Jingjing; Jin, Ximing; Wu, Fuqing; Wang, Jiulin; Guo, Xiuping; Zhang, Xin; Cheng, Zhijun; Wan, Jianmin

2012-01-01

The rice somaclonal mutant T3612 produces small grains with a floury endosperm, caused by the loose packing of starch granules. The positional cloning of the mutation revealed a deletion in a gene encoding a protein disulphide isomerase-like enzyme (PDIL1-1). In the wild type, PDIL1-1 was expressed throughout the plant, but most intensely in the developing grain. In T3612, its expression was abolished, resulting in a decrease in the activity of plastidial phosphorylase and pullulanase, and an increase in that of soluble starch synthase I and ADP-glucose pyrophosphorylase. The amylopectin in the T3612 endosperm showed an increase in chains with a degree of polymerization 8-13 compared with the wild type. The expression in the mutant's endosperm of certain endoplasmic reticulum stress-responsive genes was noticeably elevated. PDIL1-1 appears to play an important role in starch synthesis. Its absence is associated with endoplasmic reticulum stress in the endosperm, which is likely to underlie the formation of the floury endosperm in the T3612 mutant.

Physicochemical properties of natural actomyosin from threadfin bream (Nemipterus spp.) induced by high hydrostatic pressure.

PubMed

Zhou, Aimei; Lin, Liying; Liang, Yan; Benjakul, Soottawat; Shi, Xiaoling; Liu, Xin

2014-08-01

Changes of physicochemical properties in natural actomyosin (NAM) from threadfin bream (Nemipterus spp.) induced by high hydrostatic pressure (200, 400, 600MPa for 10, 30, 50min) were studied. The increase in turbidity of NAM was coincidental with the decrease in protein solubility with increasing pressure and time, suggesting the formation of protein aggregates. SDS-PAGE showed that polymerisation and degradation of myosin heavy chain were induced by high pressure. Ca(2+)-ATPase activity of NAM treated by high pressure was lost, suggesting the denaturation of myosin and the dissociation of actomyosin complex. Surface hydrophobicity of NAM increased when the pressure and pressurization time increased, indicating that the exposed hydrophobic residues increased upon application of high pressure. Decrease in total sulfhydryl content and increase in surface-reactive sulfhydryl content of NAM samples were observed with the extension of pressurizing time, indicating the formation of disulphide bonds through oxidation of SH groups or disulphide interchanges. The above changes of physicochemical properties suggested conformational changes of NAM from muscle of threadfin bream induced by high hydrostatic pressure. Copyright © 2014 Elsevier Ltd. All rights reserved.

Stability of encapsulated beef-like flavourings prepared from enzymatically hydrolysed mushroom proteins with other precursors under conventional and microwave heating.

PubMed

Lotfy, Shereen N; Fadel, Hoda H M; El-Ghorab, Ahmed H; Shaheen, Mohamed S

2015-11-15

A comparative study was carried out between two beef-like flavourings prepared by conventional and microwave heating (CBF and MBF) of enzymatic hydrolysate of mushroom protein with other flavour precursors. GC-MS analysis of the isolated volatiles revealed that the thiol containing compounds were the predominate in both samples. However, MBF comprised higher concentration of these compounds (13.84 ± 0.06%) than CBF (10.74 ± 0.06%). The effect of microencapsulation with gum Arabic by using spray drying on the odour profile and volatile compounds of the two encapsulated samples (E-CBF and E-MBF) was investigated. The results revealed significant qualitative and quantitative variations in the volatiles of both samples. The highly volatile compounds decreased remarkably in concentration with encapsulation, while the pyrazines, thiazoles and disulphides showed opposite trend. The significant decrease in the thiol containing compounds in E-CBF and E-MBF were attributed to their oxidation to other compounds such as disulphide compounds which showed significant increase in the encapsulated samples. Copyright © 2015 Elsevier Ltd. All rights reserved.

Noise-like pulse generation in an ytterbium-doped fiber laser using tungsten disulphide

NASA Astrophysics Data System (ADS)

Zhang, Wenping; Song, Yanrong; Guoyu, Heyang; Xu, Runqin; Dong, Zikai; Li, Kexuan; Tian, Jinrong; Gong, Shuang

2017-12-01

We demonstrated the noise-like pulse (NLP) generation in an ytterbium-doped fiber (YDF) laser with tungsten disulphide (WS2). Stable fundamental mode locking and second-order harmonic mode locking were observed. The saturable absorber (SA) was a WS2-polyvinyl alcohol film. The modulation depth of the WS2 film was 2.4%, and the saturable optical intensity was 155 MW cm-2. Based on this SA, the fundamental NLP with a pulse width of 20 ns and repetition rate of 7 MHz were observed. The autocorrelation trace of output pulses had a coherent spike, which came from NLP. The average pulse width of the spike was 550 fs on the top of a broad pedestal. The second-order harmonic NLP had a spectral bandwidth of 1.3 nm and pulse width of 10 ns. With the pump power of 400 mW, the maximum output power was 22.2 mW. To the best of our knowledge, this is the first time a noise-like mode locking in an YDF laser based on WS2-SA in an all normal dispersion regime was obtained.

Volatile sulphur compounds in UHT milk.

PubMed

Al-Attabi, Z; D'Arcy, B R; Deeth, H C

2009-01-01

Several volatile sulphur compounds have been detected in raw and processed milk. These are hydrogen sulphide, methanethiol, carbonyl sulphide, dimethyl sulphide, carbon disulphide, dimethyl disulphide, dimethyl trisulphide, dimethyl sulphoxide, and dimethyl sulphone. Many of these increase in milk during heat processing and are associated with the cooked flavor of heat-treated milks, particularly UHT and sterilized milk. Several researchers have attempted to explain the origin of these volatiles in both raw and processed milk, and how to reduce the associated cooked flavor that has a negative impact on consumer acceptability of processed milk. These compounds are difficult to detect and analyze due to their high volatility, sensitivity to oxidation and heat, and in some cases, their very low concentrations. However, methods of detection and quantification have improved in recent years. Pre-concentration methods such as solid phase microextraction (SPME) together with gas chromatography equipped with sulphur-selective detectors now enable low concentrations of these compounds to be analyzed. In this review, methods of extraction and analyzes of these volatile sulphur compounds are compared, and their occurrence in milk is reviewed.

Use of variations in unit cell length, reflectance and hardness for determining the origin of Fe disulphides in sedimentary rocks

NASA Astrophysics Data System (ADS)

Dill, H. G.; Eberhard, E.; Hartmann, B.

1997-01-01

Fe disulphides are common opaque accessories in sedimentary rocks. Both marcasite and pyrite may shed some light on the depositional environment and help determine the diagenesis of their host rocks. Quantitative ore microscopy (reflectance measurements, Vickers hardness numbers) and X-ray diffraction methods, supplemented with scanning electron microscopy and chemical analyses, were applied to pyrite (and some marcasite) hosted by sedimentary rocks spanning the interval from the Devonian to the Pliocene, and formed in various marine and continental environments. Quantitative ore microscopy of pyrites of sedimentary origin does not seem to be an efficient tool for analyzing the environment owing to the inhomogeneous nature of sulphide aggregates when viewed under the ore microscope, and the variable amounts of minor elements (e.g., As, Ni, and Co) that control the reflectance values (RV) and Vickers hardness numbers (VHN) of the host sulphides. However, such parameters as crystal habit and unit cell length of pyrite, which correlate with FeS x, are useful for environmental analysis. The redox conditions and the presence of organic remains during formation are the main factors determining these crystallographic parameters. Differences in these parameters from those of pure, ideal FeS 2 can be related to substitution of, e.g., wustite in the pyrite lattice, reflecting moderate oxidation (i.e. in the microenvironment). As far as crystal habit and length of the cell edge are concerned, late stage diagenesis is obviously less important than the microenvironment attending initial formation. The environment of deposition (i.e. the macroenvironment) of pyrite-bearing rocks has no influence on the crystal morphology or the length of the unit cell of Fe disulphide. X-ray diffraction measurements demonstrate that this method provides useful evidence on the microenvironment of sulphide precipitation around a single, equant pyrite, as well as around pyritized fossils.

Characterisation of DEFB107 by mass spectrometry

NASA Astrophysics Data System (ADS)

McCullough, Bryan J.; Eastwood, Hayden; Clark, Dave J.; Polfer, Nick C.; Campopiano, Dominic J.; Dorin, Julia A.; Maxwell, Alison; Langley, Ross J.; Govan, John R. W.; Bernstein, Summer L.; Bowers, Michael T.; Barran, Perdita E.

2006-05-01

Mammalian defensins are small endogenous cationic proteins which form a class of antimicrobial peptides that is part of the innate immune response of all mammalian species [R. Lehrer, Nat. Rev. Microbiol. 2 (9) (2004) 727; T. Ganz, R.I. Lehrer, Curr. Opin. Immunol. 6 (4) (1994) 584] [1] and [2]. We have developed mass spectrometry based strategies for characterising the structure-activity relationship of defensins [D.J. Campopiano, D.J. Clarke, N.C. Polfer, P.E. Barran, R.J. Langley, J.R.W. Govan, A. Maxwell, J.R. Dorin, J. Biol. Chem. 279 (47) (2004) 48671; P.E. Barran, N.C. Polfer, D.J. Campopiano, D.J. Clarke, P.R.R. Langridge-Smith, R.J. Langley, J.R.W. Govan, A. Maxwell, J.R. Dorin, R.P. Millar, M.T. Bowers, Int. J. Mass Spectrom. 240 (2005) 273] [3] and [4], and here we present data obtained from a five cysteine containing [beta]-defensin, DEFB107. The synthetic product of this human defensin exists with a glutathione capping group, its oxidation state and disulphide connectivity have been determined via accurate mass measurements and peptide mass mapping respectively, and despite possessing three disulphide bridges, it does not fit the [beta]-defensin canonical motif. With the use of molecular modelling, we have generated candidate geometries to discern the influence of disulphide bridging on the overall tertiary structure of DEFB107. These are compared with experimental results from ion mobility measurements. Defensins display activity against a wide variety of pathogens including both gram-negative and gram-positive bacteria. Their mechanism of mode of action is unknown, but is believed to involve defensin aggregation at cell surfaces, followed by cell permeabilisation and hence deathE To probe this mechanism, the localisation of DEFB107 in synthetic vesicles was studied using H/D exchange and mass spectrometry. The results obtained are used to analyse the antimicrobial activity of DEFB107.

An interleukin 13 receptor α 2–specific peptide homes to human Glioblastoma multiforme xenografts

PubMed Central

Pandya, Hetal; Gibo, Denise M.; Garg, Shivank; Kridel, Steven; Debinski, Waldemar

2012-01-01

Interleukin 13 receptor α 2 (IL-13Rα2) is a glioblastoma multiforme (GBM)–associated plasma membrane receptor, a brain tumor of dismal prognosis. Here, we isolated peptide ligands for IL-13Rα2 with use of a cyclic disulphide-constrained heptapeptide phages display library and 2 in vitro biopanning schemes with GBM cells that do (G26-H2 and SnB19-pcDNA cells) or do not (G26-V2 and SnB19-asIL-13Rα2 cells) over-express IL-13Rα2. We identified 3 peptide phages that bind to IL-13Rα2 in cellular and protein assays. One of the 3 peptide phages, termed Pep-1, bound to IL-13Rα2 with the highest specificity, surprisingly, also in a reducing environment. Pep-1 was thus synthesized and further analyzed in both linear and disulphide-constrained forms. The linear peptide bound to IL-13Rα2 more avidly than did the disulphide-constrained form and was efficiently internalized by IL-13Rα2–expressing GBM cells. The native ligand, IL-13, did not compete for the Pep-1 binding to the receptor and vice versa in any of the assays, indicating that the peptide might be binding to a site on the receptor different from the native ligand. Furthermore, we demonstrated by noninvasive near infrared fluorescence imaging in nude mice that Pep-1 binds and homes to both subcutaneous and orthotopic human GBM xenografts expressing IL-13Rα2 when injected by an intravenous route. Thus, we identified a linear heptapeptide specific for the IL-13Rα2 that is capable of crossing the blood-brain tumor barrier and homing to tumors. Pep-1 can be further developed for various applications in cancer and/or inflammatory diseases. PMID:21946118

Pierced Lasso Proteins

NASA Astrophysics Data System (ADS)

Jennings, Patricia

Entanglement and knots are naturally occurring, where, in the microscopic world, knots in DNA and homopolymers are well characterized. The most complex knots are observed in proteins which are harder to investigate, as proteins are heteropolymers composed of a combination of 20 different amino acids with different individual biophysical properties. As new-knotted topologies and new proteins containing knots continue to be discovered and characterized, the investigation of knots in proteins has gained intense interest. Thus far, the principle focus has been on the evolutionary origin of tying a knot, with questions of how a protein chain `self-ties' into a knot, what the mechanism(s) are that contribute to threading, and the biological relevance and functional implication of a knotted topology in vivo gaining the most insight. Efforts to study the fully untied and unfolded chain indicate that the knot is highly stable, remaining intact in the unfolded state orders of magnitude longer than first anticipated. The persistence of ``stable'' knots in the unfolded state, together with the challenge of defining an unfolded and untied chain from an unfolded and knotted chain, complicates the study of fully untied protein in vitro. Our discovery of a new class of knotted proteins, the Pierced Lassos (PL) loop topology, simplifies the knotting approach. While PLs are not easily recognizable by the naked eye, they have now been identified in many proteins in the PDB through the use of computation tools. PL topologies are diverse proteins found in all kingdoms of life, performing a large variety of biological responses such as cell signaling, immune responses, transporters and inhibitors (http://lassoprot.cent.uw.edu.pl/). Many of these PL topologies are secreted proteins, extracellular proteins, as well as, redox sensors, enzymes and metal and co-factor binding proteins; all of which provide a favorable environment for the formation of the disulphide bridge. In the PL topologies, the threaded topology is formed by a covalent loop where part of the polypeptide chain is threaded through, forming what we term a PL. The advantage of a PL topology for fundamental studies, compared to other knotted proteins, is that the threaded topology can easily be manipulated to yield an unknotted state. Exploiting the oxidative state of the cysteines, the building blocks that form the disulphide bridge generating the covalent loop, through altering the chemical environment, and thereby controlling the formation of the covalent loop, easily generates unknotted protein. The biological advantage, we have found, is that the PL can exert allosteric control through this on/off mechanism in a target protein. Most significantly, as the disulphide bridge acts as an on/off switch in knotting, the biophysical investigation of PL topologies can provide a new tool to steer folding and function in proteins, as disulphide bridges are commonly used in protein engineering and therapeutics.

Wear resistance and friction reduction in acrylo nitrile butadiene rubber through hybrid combination of graphite flakes and nano tungsten disulphide

NASA Astrophysics Data System (ADS)

Agrawal, Neha; Pandey, Akanksha; Parihar, A. S.; Mishra, A. K.; Gandhi, M. N.; Bhattacharyya, A. R.; Mukhopadhyay, K.; Prasad, N. E.

2016-05-01

Friction and wear have considerable role in the life span of two interacting parts. Incorporation of nanofillers in polymers/elastomers matrix causes commendable changes in its tribologicalproperties. The main purpose of this work is to reduce the coefficient of friction and wear rate of Acrylo Nitrile Butadiene rubber (NBR). To achieve such objective traditionally well knownlubricants graphite(G), tungsten disulphide (WS2) and there hybrid combination was incorporated in NBR matrix. Effect of applied load (force) and concentration of fillers on tribological properties of NBR had been studied. The filler incorporation enhanced the hardnessby 8%, showed resistance to hydraulic oil and aging effect also got improved significantly. A particular optimized concentration of NBR with hybrid combination of 2% WS2 and 4% Graphite showed minimum coefficient of friction as well as wear rate. A hypothesis could be attributed that similar lamellar structure of WS2 and Graphite along with formation of a stable nanoscale disulfide tribofilmcould result in lowering of friction. These substantially improved properties of nanoreinforced rubber materials would definitely pave promising path for plethora of potential technological applications.

Wear resistance and friction reduction in acrylo nitrile butadiene rubber through hybrid combination of graphite flakes and nano tungsten disulphide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agrawal, Neha, E-mail: neha87bhu@gmail.com; Indian Institute of Technology Bombay, Powai, Mumbai 400076, Maharashtra; Pandey, Akanksha

Friction and wear have considerable role in the life span of two interacting parts. Incorporation of nanofillers in polymers/elastomers matrix causes commendable changes in its tribologicalproperties. The main purpose of this work is to reduce the coefficient of friction and wear rate of Acrylo Nitrile Butadiene rubber (NBR). To achieve such objective traditionally well knownlubricants graphite(G), tungsten disulphide (WS{sub 2}) and there hybrid combination was incorporated in NBR matrix. Effect of applied load (force) and concentration of fillers on tribological properties of NBR had been studied. The filler incorporation enhanced the hardnessby 8%, showed resistance to hydraulic oil and agingmore » effect also got improved significantly. A particular optimized concentration of NBR with hybrid combination of 2% WS{sub 2} and 4% Graphite showed minimum coefficient of friction as well as wear rate. A hypothesis could be attributed that similar lamellar structure of WS{sub 2} and Graphite along with formation of a stable nanoscale disulfide tribofilmcould result in lowering of friction. These substantially improved properties of nanoreinforced rubber materials would definitely pave promising path for plethora of potential technological applications.« less

Pressure-induced structural and electronic transitions, metallization, and enhanced visible-light responsiveness in layered rhenium disulphide

NASA Astrophysics Data System (ADS)

Wang, Pei; Wang, Yonggang; Qu, Jingyu; Zhu, Qiang; Yang, Wenge; Zhu, Jinlong; Wang, Liping; Zhang, Weiwei; He, Duanwei; Zhao, Yusheng

2018-06-01

Triclinic rhenium disulphide (Re S2 ) is a promising candidate for postsilicon electronics because of its unique optic-electronic properties. The electrical and optical properties of Re S2 under high pressure, however, remain unclear. Here we present a joint experimental and theoretical study on the structure, electronic, and vibrational properties, and visible-light responses of Re S2 up to 50 GPa. There is a direct-to-indirect band-gap transition in 1 T -Re S2 under low-pressure regime up to 5 GPa. Upon further compression, 1 T -Re S2 undergoes a structural transition to distorted-1 T' phase at 7.7 GPa, followed by the isostructural metallization at 38.5 GPa. Both in situ Raman spectrum and electronic structure analysis reveal that interlayer sulfur-sulfur interaction is greatly enhanced during compression, leading to the remarkable modifications on the electronic properties observed in our subsequent experimental measurements, such as band-gap closure and enhanced photoresponsiveness. This study demonstrates the critical role of pressure in tuning materials properties and the potential usage of layered Re S2 for pressure-responsive optoelectronic applications.

An effective approach to synthesize monolayer tungsten disulphide crystals using tungsten halide precursor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thangaraja, Amutha; Shinde, Sachin M.; Kalita, Golap, E-mail: kalita.golap@nitech.ac.jp

2016-02-01

The synthesis of large-area monolayer tungsten disulphide (WS{sub 2}) single crystal is critical for realistic application in electronic and optical devices. Here, we demonstrate an effective approach to synthesize monolayer WS{sub 2} crystals using tungsten hexachloride (WCl{sub 6}) as a solid precursor in atmospheric chemical vapor deposition process. In this technique, 0.05M solution of WCl{sub 6} in ethanol was drop-casted on SiO{sub 2}/Si substrate to create an even distribution of the precursor, which was reduced and sulfurized at 750 °C in Ar atmosphere. We observed growth of triangular, star-shaped, as well as dendritic WS{sub 2} crystals on the substrate. The crystalmore » geometry evolves with the shape and size of the nuclei as observed from the dendritic structures. These results show that controlling the initial nucleation and growth process, large WS{sub 2} single crystalline monolayer can be grown using the WCl{sub 6} precursor. Our finding shows an easier and effective approach to grow WS{sub 2} monolayer using tungsten halide solution-casting, rather than evaporating the precursor for gas phase reaction.« less

On the reasons for low sulphur utilization in the lithium-sulphur batteries

NASA Astrophysics Data System (ADS)

Kolosnitsyn, V. S.; Kuzmina, E. V.; Karaseva, E. V.

2015-01-01

This work is to study the reasons for the relatively low efficiency of sulphur reduction (about 75%) in lithium-sulphur batteries. The two main reasons for that are suggested to be: the relatively low electrochemical activity of low order lithium polysulphides and blocking of the carbon framework of the sulphur electrode by insoluble products of electrochemical reactions - sulphur and lithium sulphide. The electrochemical activity of lithium polysulphides with different composition (Li2Sn, n = 2-6) has been studied in 1 M solutions of CF3SO3Li in sulfolane. It is shown that lithium polysulphides including lithium disulphide are able to electrochemically reduce with efficiency close to 100%. The electrochemical activity of lithium polysulphides decreases with the order. The order of lithium polysulphides affects the value of voltage of discharge plateaus but not the efficiency of sulphur reducing in the lithium polysulphides species. The relatively low efficiency of sulphur reduction in the lithium-sulphur batteries is more likely caused by blocking of carbon particles in the sulphur electrode by insoluble products of electrochemical reactions (sulphur and lithium sulphide). This prevents the electrochemical reduction of low order lithium polysulphides and especially lithium disulphide.

Defensin-related peptide 1 (Defr1) is allelic to Defb8 and chemoattracts immature DC and CD4+ T cells independently of CCR6

PubMed Central

Taylor, Karen; Rolfe, Mark; Reynolds, Natalie; Kilanowski, Fiona; Pathania, Uday; Clarke, Dave; Yang, De; Oppenheim, Joost; Samuel, Kay; Howie, Sarah; Barran, Perdita; Macmillan, Derek; Campopiano, Dominic; Dorin, Julia

2009-01-01

β-Defensins comprise a family of cationic, antimicrobial and chemoattractant peptides. The six cysteine canonical motif is retained throughout evolution and the disulphide connectivities stabilise the conserved monomer structure. A murine β-defensin gene (Defr1) present in the main defensin cluster of C57B1/6 mice, encodes a peptide with only five of the canonical six cysteine residues. In other inbred strains of mice, the allele encodes Defb8, which has the six cysteine motif. We show here that in common with six cysteine β-defensins, defensin-related peptide 1 (Defr1) displays chemoattractant activity for CD4+ T cells and immature DC (iDC), but not mature DC cells or neutrophils. Murine Defb2 replicates this pattern of attraction. Defb8 is also able to attract iDC but not mature DC. Synthetic analogues of Defr1 with the six cysteines restored (Defr1 Y5C) or with only a single cysteine (Defr1-1cV) chemoattract CD4+ T cells with reduced activity, but do not chemoattract DC. β-Defensins have previously been shown to attract iDC through CC receptor 6 (CCR6) but neither Defr1 or its related peptides nor Defb8, chemoattract cells overexpressing CCR6. Thus, we demonstrate that the canonical six cysteines of β-defensins are not required for the chemoattractant activity of Defr1 and that neither Defr1 nor the six cysteine polymorphic variant allele Defb8, act through CCR6. PMID:19404978

Defensin-related peptide 1 (Defr1) is allelic to Defb8 and chemoattracts immature DC and CD4+ T cells independently of CCR6.

PubMed

Taylor, Karen; Rolfe, Mark; Reynolds, Natalie; Kilanowski, Fiona; Pathania, Uday; Clarke, Dave; Yang, De; Oppenheim, Joost; Samuel, Kay; Howie, Sarah; Barran, Perdita; Macmillan, Derek; Campopiano, Dominic; Dorin, Julia

2009-05-01

Beta-defensins comprise a family of cationic, antimicrobial and chemoattractant peptides. The six cysteine canonical motif is retained throughout evolution and the disulphide connectivities stabilise the conserved monomer structure. A murine beta-defensin gene (Defr1) present in the main defensin cluster of C57B1/6 mice, encodes a peptide with only five of the canonical six cysteine residues. In other inbred strains of mice, the allele encodes Defb8, which has the six cysteine motif. We show here that in common with six cysteine beta-defensins, defensin-related peptide 1 (Defr1) displays chemoattractant activity for CD4(+) T cells and immature DC (iDC), but not mature DC cells or neutrophils. Murine Defb2 replicates this pattern of attraction. Defb8 is also able to attract iDC but not mature DC. Synthetic analogues of Defr1 with the six cysteines restored (Defr1 Y5C) or with only a single cysteine (Defr1-1c(V)) chemoattract CD4(+) T cells with reduced activity, but do not chemoattract DC. Beta-defensins have previously been shown to attract iDC through CC receptor 6 (CCR6) but neither Defr1 or its related peptides nor Defb8, chemoattract cells overexpressing CCR6. Thus, we demonstrate that the canonical six cysteines of beta-defensins are not required for the chemoattractant activity of Defr1 and that neither Defr1 nor the six cysteine polymorphic variant allele Defb8, act through CCR6.

The NADH:flavin oxidoreductase Nox from Rhodococcus erythropolis MI2 is the key enzyme of 4,4'-dithiodibutyric acid degradation.

PubMed

Khairy, H; Wübbeler, J H; Steinbüchel, A

2016-12-01

The reduction of the disulphide bond is the initial catabolic step of the microbial degradation of the organic disulphide 4,4'-dithiodibutyric acid (DTDB). Previously, an NADH:flavin oxidoreductase from Rhodococcus erythropolis MI2 designated as Nox MI2 , which belongs to the old yellow enzyme (OYE) family, was identified. In the present study, it was proven that Nox MI2 has the ability to cleave the sulphur-sulphur bond in DTDB. In silico analysis revealed high sequence similarities to proteins of the flavin mononucleotide (FMN) reductase family identified in many strains of R. erythropolis. Therefore, nox was heterologously expressed in the pET23a(+) expression system using Escherichia coli strain BL21(DE3) pLysS, which effectively produces soluble active Nox MI2 . Nox MI2 showed a maximum specific activity (V max ) of 3·36 μmol min -1  mg -1 corresponding to a k cat of 2·5 s -1 and an apparent substrate K m of 0·6 mmol l -1 , when different DTDB concentrations were applied. No metal cofactors were required. Moreover, Nox MI2 had very low activity with other sulphur-containing compounds like 3,3'-dithiodipropionic acid (8·0%), 3,3'-thiodipropionic acid (7·6%) and 5,5'-dithiobis(2-nitrobenzoic acid) (8·0%). The UV/VIS spectrum of Nox MI2 revealed the presence of the cofactor FMN. Based on results obtained, Nox MI2 adds a new physiological substrate and mode of action to OYE members. It was unequivocally demonstrated in this study that an NADH:flavin oxidoreductase from Rhodococcus erythropolis MI2 (Nox MI2 ) is able to cleave the xenobiotic disulphide 4,4'-dithiodibutyric acid (DTDB) into two molecules of 4-mercaptobutyric acid (4MB) with concomitant consumption of NADH. Nox MI2 showed a high substrate specificity as well as high heat stability. This study provides the first detailed characterization of the initial cleavage of DTDB, which is considered as a promising polythioester precursor. © 2016 The Society for Applied Microbiology.

Structural requirements for fibromodulin binding to collagen and the control of type I collagen fibrillogenesis--critical roles for disulphide bonding and the C-terminal region.

PubMed

Font, B; Eichenberger, D; Goldschmidt, D; Boutillon, M M; Hulmes, D J

1998-06-15

Fibromodulin belongs to the family of small, leucine-rich proteoglycans which have been reported to interact with collagens and to inhibit type I collagen fibrillogenesis. Decorin and fibromodulin exhibit a noticeable degree of sequence similarity. However, as previously reported [Font, B., Eichenberger, D., Rosenberg, L. M. & van der Rest, M. (1996) Matrix Biol. 15, 341-348] the domains of these molecules implicated in the interactions with type XII and type XIV collagens are different, these being the dermatan sulphate/chondroitin sulphate chain for decorin and the core protein for fibromodulin. At the present time the fibromodulin domains implicated in the interactions with fibrillar collagens remain unknown. In experiments reported here, we have sought to identify the structural requirements for fibromodulin interaction with collagen and for the control of type I collagen fibrillogenesis. Circular dichroism spectra and fibrillogenesis inhibition studies show that fibromodulin structure and its collagen fibrillogenesis control function are strictly dependent on the presence of intact disulphide bridge(s). In addition, we show that the binding of fibromodulin (or fibromodulin-derived fragments) to type I collagen is not necessarily correlated with fibrillogenesis inhibition. To isolate fibromodulin domains, the native proteoglycan was submitted to mild proteolysis. We have isolated an alpha-chymotrypsin-resistant fragment which contains the bulk of the N-terminal and central region of the molecule including the leucine-rich repeats 4 and 6 reported for decorin to be involved in type I collagen binding. This fragment does not bind to type I collagen. Using enzymes with different specificities, a number of large fragments of fibromodulin were obtained, suggesting a compact structure for this molecule which is relatively resistant to proteolysis. None of these N-glycosylated fragments were able to bind to type I collagen in co-sedimentation experiments. Taken together these results suggest that fibromodulin-type I collagen interactions leading to fibrillogenesis inhibition require more than one binding domain. One of these domains could be the C-terminal end of the molecule containing the disulphide loop which is absent in the chymotrypsin-resistant fragment.

Sirtuin 1 protects the aging heart from contractile dysfunction mediated through the inhibition of endoplasmic reticulum stress-mediated apoptosis in cardiac-specific Sirtuin 1 knockout mouse model.

PubMed

Hsu, Yu-Juei; Hsu, Shih-Che; Hsu, Chiao-Po; Chen, Yen-Hui; Chang, Yung-Lung; Sadoshima, Junichi; Huang, Shih-Ming; Tsai, Chien-Sung; Lin, Chih-Yuan

2017-02-01

The longevity regulator Sirtuin 1 is an NAD + -dependent histone deacetylase that regulates endoplasmic reticulum stress and influences cardiomyocyte apoptosis during cardiac contractile dysfunction induced by aging. The mechanism underlying Sirtuin 1 function in cardiac contractile dysfunction related to aging has not been completely elucidated. We evaluated cardiac contractile function, endoplasmic reticulum stress, apoptosis, and oxidative stress in 6- and 12month-old cardiac-specific Sirtuin 1 knockout (Sirt1 -/- ) and control (Sirt1 f/f ) mice using western blotting and immunohistochemistry. Mice were injected with a protein disulphide isomerase inhibitor. For in vitro analysis, cultured H9c2 cardiomyocytes were exposed to either a Sirtuin 1 inhibitor or activator, with or without a mitochondrial inhibitor, to evaluate the effects of Sirtuin 1 on endoplasmic reticulum stress, nitric oxide synthase expression, and apoptosis. The effects of protein disulphide isomerase inhibition on oxidative stress and ER stress-related apoptosis were also investigated. Compared with 6-month-old Sirt1 f/f mice, marked impaired contractility was observed in 12-month-old Sirt1 -/- mice. These findings were consistent with increased endoplasmic reticulum stress and apoptosis in the myocardium. Measures of oxidative stress and nitric oxide synthase expression were significantly higher in Sirt1 -/- mice compared with those in Sirt1 f/f mice at 6months. In vitro experiments revealed increased endoplasmic reticulum stress-mediated apoptosis in H9c2 cardiomyocytes treated with a Sirtuin 1 inhibitor; the effects were ameliorated by a Sirtuin 1 activator. Moreover, consistent with the in vitro findings, impaired cardiac contractility was demonstrated in Sirt1 -/- mice injected with a protein disulphide isomerase inhibitor. The present study demonstrates that the aging heart is characterized by contractile dysfunction associated with increased oxidative stress and endoplasmic reticulum stress and Sirtuin 1 might have the ability to protect the aging hearts from the inhibition of endoplasmic reticulum-mediated apoptosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Role of Oxidoreductases in Determining the Function of the Neisserial Lipid A Phosphoethanolamine Transferase Required for Resistance to Polymyxin

PubMed Central

Piek, Susannah; Wang, Zhirui; Ganguly, Jhuma; Lakey, Adam M.; Bartley, Stephanie N.; Mowlaboccus, Shakeel; Anandan, Anandhi; Stubbs, Keith A.; Scanlon, Martin J.; Vrielink, Alice; Azadi, Parastoo; Carlson, Russell W.; Kahler, Charlene M.

2014-01-01

The decoration of the lipid A headgroups of the lipooligosaccharide (LOS) by the LOS phosphoethanolamine (PEA) transferase (LptA) in Neisseria spp. is central for resistance to polymyxin. The structure of the globular domain of LptA shows that the protein has five disulphide bonds, indicating that it is a potential substrate of the protein oxidation pathway in the bacterial periplasm. When neisserial LptA was expressed in Escherichia coli in the presence of the oxidoreductase, EcDsbA, polymyxin resistance increased 30-fold. LptA decorated one position of the E. coli lipid A headgroups with PEA. In the absence of the EcDsbA, LptA was degraded in E. coli. Neisseria spp. express three oxidoreductases, DsbA1, DsbA2 and DsbA3, each of which appear to donate disulphide bonds to different targets. Inactivation of each oxidoreductase in N. meningitidis enhanced sensitivity to polymyxin with combinatorial mutants displaying an additive increase in sensitivity to polymyxin, indicating that the oxidoreductases were required for multiple pathways leading to polymyxin resistance. Correlates were sought between polymyxin sensitivity, LptA stability or activity and the presence of each of the neisserial oxidoreductases. Only meningococcal mutants lacking DsbA3 had a measurable decrease in the amount of PEA decoration on lipid A headgroups implying that LptA stability was supported by the presence of DsbA3 but did not require DsbA1/2 even though these oxidoreductases could oxidise the protein. This is the first indication that DsbA3 acts as an oxidoreductase in vivo and that multiple oxidoreductases may be involved in oxidising the one target in N. meningitidis. In conclusion, LptA is stabilised by disulphide bonds within the protein. This effect was more pronounced when neisserial LptA was expressed in E. coli than in N. meningitidis and may reflect that other factors in the neisserial periplasm have a role in LptA stability. PMID:25215579

The Respiratory Arsenite Oxidase: Structure and the Role of Residues Surrounding the Rieske Cluster

PubMed Central

Warelow, Thomas P.; Oke, Muse; Schoepp-Cothenet, Barbara; Dahl, Jan U.; Bruselat, Nicole; Sivalingam, Ganesh N.; Leimkühler, Silke; Thalassinos, Konstantinos; Kappler, Ulrike; Naismith, James H.; Santini, Joanne M.

2013-01-01

The arsenite oxidase (Aio) from the facultative autotrophic Alphaproteobacterium Rhizobium sp. NT-26 is a bioenergetic enzyme involved in the oxidation of arsenite to arsenate. The enzyme from the distantly related heterotroph, Alcaligenes faecalis, which is thought to oxidise arsenite for detoxification, consists of a large α subunit (AioA) with bis-molybdopterin guanine dinucleotide at its active site and a 3Fe-4S cluster, and a small β subunit (AioB) which contains a Rieske 2Fe-2S cluster. The successful heterologous expression of the NT-26 Aio in Escherichia coli has resulted in the solution of its crystal structure. The NT-26 Aio, a heterotetramer, shares high overall similarity to the heterodimeric arsenite oxidase from A. faecalis but there are striking differences in the structure surrounding the Rieske 2Fe-2S cluster which we demonstrate explains the difference in the observed redox potentials (+225 mV vs. +130/160 mV, respectively). A combination of site-directed mutagenesis and electron paramagnetic resonance was used to explore the differences observed in the structure and redox properties of the Rieske cluster. In the NT-26 AioB the substitution of a serine (S126 in NT-26) for a threonine as in the A. faecalis AioB explains a −20 mV decrease in redox potential. The disulphide bridge in the A. faecalis AioB which is conserved in other betaproteobacterial AioB subunits and the Rieske subunit of the cytochrome bc 1 complex is absent in the NT-26 AioB subunit. The introduction of a disulphide bridge had no effect on Aio activity or protein stability but resulted in a decrease in the redox potential of the cluster. These results are in conflict with previous data on the betaproteobacterial AioB subunit and the Rieske of the bc 1 complex where removal of the disulphide bridge had no effect on the redox potential of the former but a decrease in cluster stability was observed in the latter. PMID:24023621

Identification of Disulphide Stress-responsive Extracytoplasmic Function Sigma Factors in Rothia mucilaginosa

DTIC Science & Technology

2013-01-01

GC) content of deoxyribonucleic acid (DNA).1 This organism belongs to the actinobacteria , which includes the genera Actinomyces, Corynebacterium...however, it still remains unclear how Rothia species respond to environmental stress. The responsiveness and adaptation of a few actinobacteria to various... actinobacteria , the number of sigma factors in R. mucilaginosa is relatively small (microbial signal transduction (MiST2) database, http://mistdb.com/); however

Odour-causing compounds in air samples: gas-liquid partition coefficients and determination using solid-phase microextraction and GC with mass spectrometric detection.

PubMed

Godayol, Anna; Alonso, Mònica; Sanchez, Juan M; Anticó, Enriqueta

2013-03-01

A quantification method based on solid-phase microextraction followed by GC coupled to MS was developed for the determination of gas-liquid partition coefficients and for the air monitoring of a group of odour-causing compounds that had previously been found in wastewater samples including dimethyl disulphide, phenol, indole, skatole, octanal, nonanal, benzothiazole and some terpenes. Using a divinylbenzene/carboxen/polydimethylsiloxane fibre, adsorption kinetics have been studied to define an extraction time that would avoid coating saturation. It was found that for an extraction time of 10 min, external calibration could be performed in the range of 0.4-100 μg/m(3), with detection limits between 0.1 and 20 μg/m(3). Inter-day precision of the developed method was evaluated (n = 5) and RSD values between 12 and 24% were obtained for all compounds. The proposed method has been applied to the analysis of air samples surrounding a wastewater treatment plant in Catalonia (Spain). In all air samples evaluated, dimethyl disulphide, limonene and phenol were detected, and the first two were the compounds that showed the highest partition coefficients. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Behavioural effects of prenatal exposure to carbon disulphide and to aromatol in rats.

PubMed

Lehotzky, K; Szeberényi, J M; Ungváry, G; Kiss, A

1985-01-01

The neurotoxic effects of prenatal organosolvent inhalation were studied in rats, because of the expectation that a developing organism may be more sensitive than the adult to the induction of functional deficits. The aim was to determine whether prenatal exposure to the new organosolvent mixture, Aromatol, and the well known neurotoxic carbon disulphide, would impair reflex ontogeny or produce neurobehavioural dysfunctions in the offspring. Development of gait, motor coordination, and activity, avoidance learning and swimming were tested in the offspring of CFY rat mothers, exposed to CS2 inhalation (0, less than 10, 700 and 2000 mg/m3) and to Aromatol (0, 600, 1000 and 2000 mg/m3) on days 7-15 gestation. Prenatal CS2 inhalation induced dose related perinatal mortality of pups. Eye opening and the auditory startle were retarded. There were immature gait, motor incoordination, diminished open field activity and altered behavioural patterns on day 21 and 36 but they were nearly age-appropriate on day 90. As signs of disturbed learning ability, there were diminished performance and lengthened latency of the conditioned avoidance response, related to the concentrations administered. Contrary to expectations, prenatal Aromatol inhalation had no effect on maturation of gait, behaviour patterns, or learning ability.

Structural and optical properties of tin disulphide thin films grown by flash evaporation

NASA Astrophysics Data System (ADS)

Banotra, Arun; Padha, Naresh

2018-04-01

Tin Disulphide thin films were deposited by Flash Evaporation method on corning Glass Substrate at different substrate temperatures. The deposited films were undertaken for Structural, Optical and compositional characterizations. Compositional analysis of the films exhibited decrease in the sulphur content enabling S/Sn ratio to vary from 2.05 to 1.32 with increasing substrate temperature. X-ray diffraction reveals amorphous nature of the as-deposited films with varying substrate temperatures. Optical measurements estimated from absorbance spectra suggest higher absorbance at λ≤500nm and higher transmission at λ≥500nm with bandgap changes from 2.45eV to 2.09eV. The 323K as-deposited films were undertaken for annealing which transforms the films into crystalline form corresponding to hexagonal SnS2 phase at 423K and above. However, the optical response for the annealed samples shows a higher transmission of 70% in the visible region which increases further in the Infrared region of the spectrum achieving maximum transmission upto 98%. This higher transmission in the Visible to Infrared region of the solar spectrum in amorphous as well as crystalline form makes the film suitable for their use as a window layer in the Solar Cell Design.

Membrane proteins from the cyanobacterium Synechocystis sp. PCC 6803 interacting with thioredoxin.

PubMed

Mata-Cabana, Alejandro; Florencio, Francisco J; Lindahl, Marika

2007-11-01

Cysteine dithiol/disulphide exchange forms the molecular basis for regulation of a wide variety of enzymatic activities and for transduction of cellular signals. Thus, the search for proteins with reactive, accessible cysteines is expected to contribute to the unravelling of new molecular mechanisms for enzyme regulation and signal transduction. Several methods have been designed for this purpose taking advantage of the interactions between thioredoxins and their protein substrates. Thioredoxins comprise a family of redox-active enzymes, which catalyse reduction of protein disulphides and sulphenic acids. Due to the inherent practical difficulties associated with studies of membrane proteins these have been largely overlooked in the many proteomic studies of thioredoxin-interacting proteins. In the present work, we have developed a procedure to isolate membrane proteins interacting with thioredoxin by binding in situ to a monocysteinic His-tagged thioredoxin added directly to the intact membranes. Following fractionation and solubilisation of the membranes, thioredoxin target proteins were isolated by Ni-affinity chromatography and 2-DE SDS-PAGE under nonreducing/reducing conditions. Applying this method to total membranes, including thylakoid and plasma membranes, from the cyanobacterium Synechocystis sp. PCC 6803 we have identified 50 thioredoxin-interacting proteins. Among the 38 newly identified thioredoxin targets are the ATP-binding subunits of several transporters and members of the AAA-family of ATPases.

Regulation of microRNA using promising dietary phytochemicals: Possible preventive and treatment option of malignant mesothelioma.

PubMed

Sayeed, Md Abu; Bracci, Massimo; Lucarini, Guendalina; Lazzarini, Raffaella; Di Primio, Roberto; Santarelli, Lory

2017-10-01

Malignant mesothelioma (MM) is a very aggressive, lethal cancer, and its incidence is increasing worldwide. Development of multi-drug resistance, therapy related side-effects, and disease recurrence after therapy are the major problems for the successful treatment of MM. Emerging evidence indicates that dietary phytochemicals can exert anti-cancer activities by regulating microRNA expression. Until now, only one dietary phytochemical (ursolic acid) has been reported to have MM microRNA regulatory ability. A large number of dietary phytochemicals still remain to be tested. In this paper, we have introduced some dietary phytochemicals (curcumin, epigallocatechin gallate, quercetin, genistein, pterostilbene, resveratrol, capsaicin, ellagic acid, benzyl isothiocyanate, phenethyl isothiocyanate, sulforaphane, indole-3-carbinol, 3,3'-diindolylmethane, diallyl disulphide, betulinic acid, and oleanolic acid) which have shown microRNA regulatory activities in various cancers and could regulate MM microRNAs. In addition to microRNA regulatory activities, curcumin, epigallocatechin gallate, quercetin, genistein, resveratrol, phenethyl isothiocyanate, and sulforaphane have anti-mesothelioma potentials, and pterostilbene, capsaicin, ellagic acid, benzyl isothiocyanate, indole-3-carbinol, 3,3'-diindolylmethane, diallyl disulphide, betulinic acid, and oleanolic acid have potentials to inhibit cancer by regulating the expression of various genes which are also known to be aberrant in MM. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

A general approach to the synthesis of 5-S-functionalized pyrimidine nucleosides and their analogues.

PubMed

Kananovich, Dzmitry G; Reino, Alli; Ilmarinen, Kaja; Rõõmusoks, Marko; Karelson, Mati; Lopp, Margus

2014-08-14

A general and efficient approach was developed for the introduction of S-functionality at the C-5 position of cytosine and uracil nucleosides and their analogues. The key step is a palladium-catalyzed C-S coupling of the corresponding 5-bromo nucleoside derivative and alkyl thiol. The butyl 3-mercaptopropionate coupling products were further converted to the corresponding disulphides, the stable precursors of 5-mercaptopyrimidine nucleosides.

Studies of the Electrochemical Detection of Thiols. Part 2. An Investigation of the Reactions Occurring in NAIAD, and the Effect of HCN, Guaiacol and GB on these Reactions

DTIC Science & Technology

1977-01-01

OF THE REDUCTION OF CHOLINE T DISULPHIDE (5 x 10-4 M) AT A PLATINUM ELECTRODE UNDER STATIONARY, DEOXYGENATED CONDITIONS Sweep rate Cathodic current... voltametry (10 - 100 s) which reoxidises at E = -0.7V. This product is not thiocholine, which is oxidised at E = +0.8V, and was not 3; identified. Thus, in

[New-generation proton pump inhibitors: progress in the treatment of peptic acid diseases?].

PubMed

de Korwin, Jean-Dominique; Ducrotté, Philippe; Vallot, Thierry

2004-06-19

EFFECTS AND INCONVENIENCIES OF THE OLDER PRODUCTS: The proton pump inhibitors (PPIs) are now universally considered the treatment of choice for management of gastric-acid-related diseases, mainly gastro-oesophageal reflux disease (GERD). These drugs share similar properties: general structure, acid-activation step, covalent binding to the proton pump of the gastric parietal cell via the production of covalent disulphide bonds, relatively stable inhibition of H+,K+-ATPase. However, the older PPIs (omeprazole, lansoprazole et pantoprazole) have notable limitations. These drugs exhibit substantial interpatient variability and may have significant interactions with other drugs. These first-generation PPIs also do not achieve a rapid and sustained suppression of gastric acid, leading to the development of new acid-pump antagonists. The new-generation PPIs, esomeprazole and rabeprazole, offer several pharmacokinetic advantages: lower oxidative hepatic metabolism rate via the CYP 2C19 reducing the activity variations due to genetic polymorphisms and decreasing the risk of significant drug-drug interactions (advantages mainly for rabeprazole), lower metabolic clearance of esomeprazole (S-enantiomer of omeprazole) increasing plasma concentrations and acid suppression of this new PPI, higher accumulation of rabeprazole in the parietal cell due to its higher pKa. Gastric pH studies and therapeutic trials have demonstrated significant advantages of esomeprazole and rabeprazole compared with the older PPIs, which omeprazole is the prototype: a greater inhibition of acid secretion, a more rapid onset of action to provide reflux symptoms relief over 24 hours with lower GERD-related cost for rabeprazole, a sustained acid suppression, cost-effectiveness advantages for esomeprazole in the healing and maintenance of erosive esophagitis compared with lansoprazole, reduced potential for clinically significant drug-drug interactions with rabeprazole compared with omeprazole and esomeprazole. Due to their properties, esomeprazole and rabeprazole are the best candidates for "on demand" treatment of GERD.

Central role of the flowering repressor ZCCT2 in the redox control of freezing tolerance and the initial development of flower primordia in wheat

PubMed Central

2014-01-01

Background As both abiotic stress response and development are under redox control, it was hypothesised that the pharmacological modification of the redox environment would affect the initial development of flower primordia and freezing tolerance in wheat (Triticum aestivum L.). Results Pharmacologically induced redox changes were monitored in winter (T. ae. ssp. aestivum cv. Cheyenne, Ch) and spring (T. ae. ssp. spelta; Tsp) wheat genotypes grown after germination at 20/17°C for 9 d (chemical treatment: last 3 d), then at 5°C for 21 d (chemical treatment: first 4 d) and subsequently at 20/17°C for 21 d (recovery period). Thiols and their disulphide forms were measured and based on these data reduction potentials were calculated. In the freezing-tolerant Ch the chemical treatments generally increased both the amount of thiol disulphides and the reduction potential after 3 days at 20/17°C. In the freezing-sensitive Tsp a similar effect of the chemicals on these parameters was only observed after the continuation of the treatments for 4 days at 5°C. The applied chemicals slightly decreased root fresh weight and increased freezing tolerance in Ch, whereas they increased shoot fresh weight in Tsp after 4 days at 5°C. As shown after the 3-week recovery at 20/17°C, the initial development of flower primordia was accelerated in Tsp, whereas it was not affected by the treatments in Ch. The chemicals differently affected the expression of ZCCT2 and that of several other genes related to freezing tolerance and initial development of flower primordia in Ch and Tsp after 4 d at 5°C. Conclusions Various redox-altering compounds and osmotica had differential effects on glutathione disulphide content and reduction potential, and consequently on the expression of the flowering repressor ZCCT2 in the winter wheat Ch and the spring wheat Tsp. We propose that the higher expression of ZCCT2 in Ch may be associated with activation of genes of cold acclimation and its lower expression in Tsp with the induction of genes accelerating initial development of flower primordia. In addition, ZCCT2 may be involved in the coordinated control of the two processes. PMID:24708599

Central role of the flowering repressor ZCCT2 in the redox control of freezing tolerance and the initial development of flower primordia in wheat.

PubMed

Gulyás, Zsolt; Boldizsár, Akos; Novák, Aliz; Szalai, Gabriella; Pál, Magda; Galiba, Gábor; Kocsy, Gábor

2014-04-07

As both abiotic stress response and development are under redox control, it was hypothesised that the pharmacological modification of the redox environment would affect the initial development of flower primordia and freezing tolerance in wheat (Triticum aestivum L.). Pharmacologically induced redox changes were monitored in winter (T. ae. ssp. aestivum cv. Cheyenne, Ch) and spring (T. ae. ssp. spelta; Tsp) wheat genotypes grown after germination at 20/17°C for 9 d (chemical treatment: last 3 d), then at 5°C for 21 d (chemical treatment: first 4 d) and subsequently at 20/17°C for 21 d (recovery period). Thiols and their disulphide forms were measured and based on these data reduction potentials were calculated. In the freezing-tolerant Ch the chemical treatments generally increased both the amount of thiol disulphides and the reduction potential after 3 days at 20/17°C. In the freezing-sensitive Tsp a similar effect of the chemicals on these parameters was only observed after the continuation of the treatments for 4 days at 5°C. The applied chemicals slightly decreased root fresh weight and increased freezing tolerance in Ch, whereas they increased shoot fresh weight in Tsp after 4 days at 5°C. As shown after the 3-week recovery at 20/17°C, the initial development of flower primordia was accelerated in Tsp, whereas it was not affected by the treatments in Ch. The chemicals differently affected the expression of ZCCT2 and that of several other genes related to freezing tolerance and initial development of flower primordia in Ch and Tsp after 4 d at 5°C. Various redox-altering compounds and osmotica had differential effects on glutathione disulphide content and reduction potential, and consequently on the expression of the flowering repressor ZCCT2 in the winter wheat Ch and the spring wheat Tsp. We propose that the higher expression of ZCCT2 in Ch may be associated with activation of genes of cold acclimation and its lower expression in Tsp with the induction of genes accelerating initial development of flower primordia. In addition, ZCCT2 may be involved in the coordinated control of the two processes.

Evaluation and application of static headspace-multicapillary column-gas chromatography-ion mobility spectrometry for complex sample analysis.

PubMed

Denawaka, Chamila J; Fowlis, Ian A; Dean, John R

2014-04-18

An evaluation of static headspace-multicapillary column-gas chromatography-ion mobility spectrometry (SHS-MCC-GC-IMS) has been undertaken to assess its applicability for the determination of 32 volatile compounds (VCs). The key experimental variables of sample incubation time and temperature have been evaluated alongside the MCC-GC variables of column polarity, syringe temperature, injection temperature, injection volume, column temperature and carrier gas flow rate coupled with the IMS variables of temperature and drift gas flow rate. This evaluation resulted in six sets of experimental variables being required to separate the 32 VCs. The optimum experimental variables for SHS-MCC-GC-IMS, the retention time and drift time operating parameters were determined; to normalise the operating parameters, the relative drift time and normalised reduced ion mobility for each VC were determined. In addition, a full theoretical explanation is provided on the formation of the monomer, dimer and trimer of a VC. The optimum operating condition for each VC calibration data was obtained alongside limit of detection (LOD) and limit of quantitation (LOQ) values. Typical detection limits ranged from 0.1ng bis(methylthio)methane, ethylbutanoate and (E)-2-nonenal to 472ng isovaleric acid with correlation coefficient (R(2)) data ranging from 0.9793 (for the dimer of octanal) through to 0.9990 (for isobutyric acid). Finally, the developed protocols were applied to the analysis of malodour in sock samples. Initial work involved spiking an inert matrix and sock samples with appropriate concentrations of eight VCs. The average recovery from the inert matrix was 101±18% (n=8), while recoveries from the sock samples were lower, that is, 54±30% (n=8) for sock type 1 and 78±24% (n=6) for sock type 2. Finally, SHS-MCC-GC-IMS was applied to sock malodour in a field trial based on 11 volunteers (mixed gender) over a 3-week period. By applying the SHS-MCC-GC-IMS database, four VCs were identified and quantified: ammonia, dimethyl disulphide, dimethyl trisulphide and butyric acid. A link was identified between the presence of high ammonia and dimethyl disulphide concentrations and a high malodour odour grading, that is, ≥ 6. Statistical analysis did not find any correlation between the occurrence of dimethyl disulphide and participant gender. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sumant, Anirudha

The integration of 2D materials such as molybdenum disulphide (MoS2) with diamond (3D) was achieved by forming an heterojunction between these two materials and its electrical performance was studied experimentally. The device charactertics did show good rectifying nature when p-type single crystal diamond was integrated with n-type MoS2. These results are very encouraging indicating possible applications in semiconductor electronics, however further studies are required for a detailed understanding of the transport phenomena at the MoS2/diamond interface.

Disruption of host-seeking behaviour by the salmon louse, Lepeophtheirus salmonis, using botanically derived repellents.

PubMed

O'Shea, B; Wadsworth, S; Pino Marambio, J; Birkett, M A; Pickett, J A; Mordue Luntz, A J

2017-04-01

The potential for developing botanically derived natural products as novel feed-through repellents for disrupting settlement of the salmon louse, Lepeophtheirus salmonis (Caligidae) upon farmed Atlantic salmon, Salmo salar, was investigated using an established laboratory vertical Y-tube behavioural bioassay for assessing copepodid behaviour. Responses to artificial sea water conditioned with the odour of salmon, or to the known salmon-derived kairomone component, α-isophorone, in admixture with selected botanical materials previously known to interfere with invertebrate arthropod host location were recorded. Materials included oils extracted from garlic, Allium sativum (Amaryllidaceae), rosemary, Rosmarinus officinalis (Lamiaceae), lavender, Lavandula angustifolia (Lamiaceae), and bog myrtle, Myrica gale (Myricaceae), and individual components (diallyl sulphide and diallyl disulphide from garlic; allyl, propyl, butyl, 4-pentenyl and 2-phenylethyl isothiocyanate from plants in the Brassica genus). Removal of attraction to salmon-conditioned water (SCW) or α-isophorone was observed when listed materials were presented at extremely low parts per trillion (ppt), that is picograms per litre or 10 -12 level. Significant masking of attraction to SCW was observed at a level of 10 ppt for diallyl disulphide and diallyl sulphide, and allyl isothiocyanate and butyl isothiocyanate. The potential of very low concentrations of masking compounds to disrupt Le. salmonis copepodid settlement on a host fish has been demonstrated in vitro. © 2016 John Wiley & Sons Ltd.

Degradation of dimethyl disulphide in soil with or without biochar amendment.

PubMed

Han, Dawei; Yan, Dongdong; Cao, Aocheng; Fang, Wensheng; Liu, Pengfei; Li, Yuan; Ouyang, Canbin; Wang, Qiuxia

2017-09-01

Dimethyl disulphide (DMDS) is a new and effective alternative to methyl bromide for soil fumigation. The effect of biochar on the fate of DMDS in soil is not fully understood. The objective of this study was to determine the degradation kinetics of DMDS in different soils and evaluate the effect of biochar amendment on DMDS degradation using incubation experiments. The degradation half-life of DMDS was between 1.05 and 6.66 days under non-sterile conditions, and 12.63 to 22.67 days under sterile conditions in five types of soil. Seven out of the eight tested biochar amendments (BC-2 to BC-8) delayed the degradation of DMDS in soil, increasing the half-life of DMDS in Fangshan soil from 1.05 to 1.16-5.87 days following amendment with 1% (w/w) biochar. The degradation rate of DMDS in Fangshan soil accelerated as the amendment rate of BC-1 increased, and decreased as the amendment rate of BC-7 increased. Biodegradation is an important degradation route for DMDS in soil, and DMDS degraded faster in alkaline soil. The effects of biochar amendments on DMDS degradation in soil are determined by complex multiple factors (such as surface area, pH and physicochemical composition), rather than by any single property of biochar. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

The possibility of modifying the elements of the bearing assembly with nanoparticles in order to reduce the friction coefficient

NASA Astrophysics Data System (ADS)

Stankevich, P.; Mironovs, V.; Vasilyeva, E.; Breki, A.; Tolochko, O.

2017-10-01

Recent study considers the tribological characteristics of the sintered bushings used in the connecting nodes brake lever system of railway cars. Particular attention is paid sleeves low content of alloying elements. Bushings had been prepared by powder metallurgy route by using low alloyed powders of Fe-Cu-C system. Porosity after sintering was about 20%. Generally, before using material was impregnated by industrial mineral oil in order to improve friction condition. In the recent study we use new lubricating compositions for impregnating in sintered bodies. Such compositions consist of basic mineral oil with addition of 4 wt.% of layered tungsten dichalcogenides (WS2 and WSe2) nanoparticles, which were ultrasonically dispersed. Tungsten disulphide nanoparticles have spherical shape with the diameter of 30-50 nm, and diselenide nanoparticles have a flat shape with the mean dimensions of 5x70 nm. Tribological testing of the product was provided. Sintered bushings impregnated with commercial oil and suspension of nanoparticles were tested in the spinning friction conditions in the couple with bearing steel at the load of 210 N and spinning rate of 200 rpm. The friction test in couple with steel exhibited the value of friction moment to be about 2 times less as compared with commercial oil. The additions of tungsten disulphide nanoparticles also significantly decrease oscillations the friction torque.

Catalytic hydrolysis of carbonyl sulphide and carbon disulphide over Fe2O3 cluster: Competitive adsorption and reaction mechanism.

PubMed

Ning, Ping; Song, Xin; Li, Kai; Wang, Chi; Tang, Lihong; Sun, Xin

2017-10-31

The competitive adsorption and reaction mechanism for the catalytic hydrolysis of carbonyl sulphide (COS) and carbon disulphide (CS 2 ) over Fe 2 O 3 cluster was investigated. Compared with experimental results, the theoretical study was used to further investigate the competitive adsorption and effect of H 2 S in the hydrolysis reaction of COS and CS 2 . Experimental results showed that Fe 2 O 3 cluster enhanced the catalytic hydrolysis effect. Meanwhile, H 2 S was not conducive to the hydrolysis of COS and CS 2 . Theoretical calculations indicated that the order of competitive adsorption on Fe 2 O 3 is as follows: H 2 O (strong) >CS 2 (medium) >COS (weak). In the hydrolysis process, the C=S bond cleavage occurs easier than C=O bond cleavage. The hydrolysis reaction is initiated via the migration of an H-atom, which triggers C=S bond cleavage and S-H bond formation. Additionally, we find the first step of CS 2 hydrolysis to be rate limiting. The presence of H 2 S increases the reaction energy barrier, which is not favourable for COS hydrolysis. Fe 2 O 3 can greatly decrease the maximum energy barrier, which decreases the minimum energy required for hydrolysis, making it relatively facile to occur. In general, the theoretical results were consistent with experimental results, which proved that the theoretical study was reliable.

Targeted σ factor turnover inserts negative control into a positive feedback loop

PubMed Central

Donohue, Timothy J.

2009-01-01

Summary Since their classification as members of the σ70 super-family, Group IV alternative σ factors have been found to control gene expression in response to diverse environmental or stress signals. Activity of the Streptomyces coelicolor Group IV family member, σR (SigR), is increased by changes in the oxidation-reduction state of cytoplasmic disulphide bonds. Once released by its cognate anti-σ factor RsrA, σR activates expression of gene products that help cells reduce cytoplasmic disulphide bonds. In this issue of Molecular Microbiology, Kim and co-workers provide new insights into positive and negative control of σR activity. The authors show that a transcript derived from the inducible σR-dependent sigRrsrA p2 promoter operon encodes a σR protein of a higher molecular weight (termed σR′) than is found in uninduced cells. One major difference between σR′ and the smaller σR protein found in uninduced cells is the rapid proteolysis of σR′ by the ClpP1/P2 protease system. The genes for the ClpP1/ClpP2 protease subunits are themselves members of the σR regulon. The newly identified positive (σR′ synthesis) and negative control (selective σR′ turnover) aspects of this circuit are either found or predicted to exist in other related Group IV σ factor family members. PMID:19682265

The thioredoxin reductase--Thioredoxin redox system cleaves the interchain disulphide bond of botulinum neurotoxins on the cytosolic surface of synaptic vesicles.

PubMed

Pirazzini, Marco; Azarnia Tehran, Domenico; Zanetti, Giulia; Lista, Florigio; Binz, Thomas; Shone, Clifford C; Rossetto, Ornella; Montecucco, Cesare

2015-12-01

Botulinum neurotoxins (BoNTs) are Janus toxins, as they are at the same time the most deadly substances known and one of the safest drugs used in human therapy. They specifically block neurotransmission at peripheral nerves through the proteolysis of SNARE proteins, i.e. the essential proteins which are the core of the neuroexocytosis machinery. Even if BoNTs are traditionally known as seven main serotypes, their actual number is much higher as each serotype exists in many different subtypes, with individual biological properties and little antigenic relations. Since BoNTs can be used as biological weapons, and the only currently available therapy is based on immunological approaches, the existence of so many different subtypes is a major safety problem. Nevertheless, all BoNT isoforms are structurally similar and intoxicate peripheral nerve endings via a conserved mechanism. They consist of two chains linked by a unique disulphide bond which must be reduced to enable their toxicity. We found that thioredoxin 1 and its reductase compose the cell redox system responsible for this reduction, and its inhibition via specific chemicals significantly reduces BoNTs activity, in vitro as well as in vivo. Such molecules can be considered as lead compounds for the development of pan-inhibitors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthesis of controlled polymeric cross-linked coatings via iniferter polymerisation in the presence of tetraethyl thiuram disulphide chain terminator.

PubMed

Bossi, A; Whitcombe, M J; Uludag, Y; Fowler, S; Chianella, I; Subrahmanyam, S; Sanchez, I; Piletsky, S A

2010-05-15

A "grafting from" approach has been used for controlled deposition of cross-linked polymers by living radical polymerisation. Borosilicate glass was modified with N,N-diethylaminodithiocarbamoylpropyl(trimethoxy)silane, in order to confine the iniferter reactive groups solely at its surface, then placed in solution with monomers and cross-linker. The polymerisation was initiated by UV irradiation. Formation of the cross-linked polymers was studied in terms of time course of the reaction, type of monomers incorporated and influence of oxygen. Grafted surfaces were characterised by AFM, FT-IR, ellipsometry and contact angle measurements. The ability to control the grafted layer improved dramatically when the chain terminator agent, N,N-N',N'-tetraethyl thiuram disulphide (TED) was added. Upon irradiation TED increases the concentration of passive capping radicals and decreases the possibility of recombination of active macro-radicals, thus prolonging their lifetime. In the absence of TED the thickness of produced coatings was below 10 nm. TED added at different concentrations assisted in the formation of grafted layers of 10-130 nm thickness. Iniferter chemistry in the presence of TED can be used for growing nanometre-scale polymer layers on solid supports. It constitutes a robust general platform for controlled grafting and offer a general solution to address the needs of surface derivatisation in sensors technology. 2010 Elsevier B.V. All rights reserved.

Disulphide linkage: To get cleaved or not? Bulk and nano copper based SERS of cystine

NASA Astrophysics Data System (ADS)

P. J., Arathi; Seemesh, Bhaskar; Rajendra Kumar Reddy, G.; Suresh Kumar, P.; Ramanathan, V.

2018-05-01

Different nano-structures of noble metals have been the conventional substrates for carrying out Surface Enhanced Raman Spectroscopy (SERS). In this paper we examine electrodeposited copper (Cu) nano-structures on pencil graphite as novel substrate to carry out SERS measurements by considering L-cystine (Cys-Cys) (dimer of the amino acid cysteine) as the probe. The formation of monolayer of the probe molecule on the substrates was confirmed using cyclic voltammetric measurements. Mode of adsorption of Cys-Cys was observed to be different on bulk Cu (taken in the wire form) and nano-structured Cu on pencil graphite. Whereas in the former the disulphide bond of Cys-Cys remained intact, it got cleaved when Cys-Cys was adsorbed on electrodeposited copper indicating the activated nature of the nano-structure compared to bulk copper. Csbnd S stretching mode of vibration underwent blue shift in Cys-Cys adsorbed on Cu on pencil graphite vis-à-vis Cys-Cys adsorbed on Cu wire. Further evidence on the cleavage of the Csbnd S bond on an activated substrate was obtained by considering a bimetallic substrate comprising of silver on copper which was electrodeposited on pencil graphite. Our studies have demonstrated that nano-copper surface is an excellent substrate for SERS giving 200 μM as lower detection limit for Cys-Cys.

Calcium-binding protein from mouse Ehrlich ascites-tumour cells is homologous to human calcyclin.

PubMed Central

Kuźnicki, J; Filipek, A; Hunziker, P E; Huber, S; Heizmann, C W

1989-01-01

A Ca2+-binding protein was purified from mouse Ehrlich ascites-tumour cells. The protein forms monomers and disulphide-linked dimers, which can be separated by reverse-phase h.p.l.c. A partial amino acid sequence analysis demonstrated that the protein has an EF-hand structure. A striking homology was found to rat and human calcyclin (a member of the S-100 protein family), which is possibly involved in cell-cycle regulation. Images Fig. 1. Fig. 2. PMID:2597136

Recent advances in self-assembled monolayers based biomolecular electronic devices.

PubMed

Arya, Sunil K; Solanki, Pratima R; Datta, Monika; Malhotra, Bansi D

2009-05-15

Self-assembled monolayers (SAMs) have aroused much interest due to their potential applications in biosensors, biomolecular electronics and nanotechnology. This has been largely attributed to their inherent ordered arrangement and controllable properties. SAMs can be formed by chemisorption of organic molecules containing groups like thiols, disulphides, amines, acids or silanes, on desired surfaces and can be used to fabricate biomolecular electronic devices. We focus on recent applications of organosulphur compounds (thiols) based SAMs to biomolecular electronic devices in the last about 3 years.

Characterization of Methanogen Membrane Function: A Genetic Approach

DTIC Science & Technology

1989-06-22

strain Marburg) which has recently been found to catalyze the reduction of CH3-S-CoH with H-S- HTP (mercaptoheptanoyl-O-phospho-L-threonine) to form CH4...and CoH-S-S- HTP . The mixed disulphide is subsequently reduced to yield H-S-CoM (2-mercaptoetljanesulfonic acid) and HS- HTP (7). While all examined...membrane and lipoprotein samples: manual and automated procedures. Meth. Enzy.ZZ:296-301. 16. Mopper, K. and B.F. Taylor. 1986. Biogeochemical cycling

Spectroscopic Constants for Selected Homonuclear Diatomic Molecules. Volume 2. K through Z

DTIC Science & Technology

1976-02-16

in Active Nitrogen, Part 1. - Mercury Hg(63P1)," J. Chem. Soc. Faraday Trans, II 68, 2023-30 R. S. Hickman and L. Liang, "Comment...and G. M. Skardis, "Quenching of Mercury -Sensitized Fluorescence in Sodium induced in Collisions With N2 Molecules, " Can. J. Phys. 51...34 Nature 210, 1034-5 (67. 87) N. Basco and A. E. Pearson, "Reactions of Sulphur Atoms in Presence of Carbon Disulphide, Carbonyl Sulphide and

Laser Induced Damage in Optical Materials: 1979.

DTIC Science & Technology

1980-07-01

as pre- T -1-1viously reported by Hellwarth. Values n2 ranged from 10 13 esu for acetic acid to 10 esu for carbon disulphide. For these nine liquids a...vibrational frequencies of various surface carbonate complexes [13]. It is interesting to note that our data reveal in general a peak in absorption...this valley. The absorption between 5.5 to 8 pm seems to be due to surface carbonates . However, the absence of absorption at 1070 cmŕ signals that the

Synthesis, structure and bonding of actinide disulphide dications in the gas phase

DOE PAGES

Lucena, Ana F.; Bandeira, Nuno A. G.; Pereira, Claudia C. L.; ...

2017-01-01

Actinide disulphide dications, AnS 2 2+, were produced in the gas phase for An = Th and Np by reaction of An 2+ cations with the sulfur-atom donor COS, in a sequential abstraction process of two sulfur atoms, as examined by FTICR mass spectrometry. For An = Pu and Am, An 2+ ions were unreactive with COS and did not yield any sulphide species. High level multiconfigurational (CASPT2) calculations were performed to assess the structures and bonding of the new AnS 2 2+ species obtained for An = Th, Np, as well as for An = Pu to examine trendsmore » along the An series, and for An = U to compare with a previous experimental study and DFT computational scrutiny of US 2 2+. The CASPT2 results showed that, like in the case of uranium, the new AnS 2 2+ ions have ground states with triangular geometries, corresponding to the presence of a persulphide in the case of thorium that formally leads to a stable Th IV S 2 2+ species, while a supersulphide appears to be present in the case of U, Np and Pu, formally leading to a An IIIS 2 2+ species. Finally, the computations also revealed that linear thioactinyl structures are higher in energy, with a difference that increases fourfold upon moving from U to Pu, apparently indicating that it will be even more pronounced for Am.« less

Hierarchical assembly of urchin-like alpha-iron oxide hollow microspheres and molybdenum disulphide nanosheets for ethanol gas sensing.

PubMed

Zhang, Dongzhi; Fan, Xin; Yang, Aijun; Zong, Xiaoqi

2018-08-01

In this paper, we fabricated a high-performance ethanol sensor using layer-by-layer self-assembled urchin-like alpha-iron oxide (α-Fe 2 O 3 ) hollow microspheres/molybdenum disulphide (MoS 2 ) nanosheets heterostructure as sensitive materials. The nanostructural, morphological, and compositional properties of the as-prepared α-Fe 2 O 3 /MoS 2 heterostructure were characterized by X-ray diffraction (XRD), energy dispersive spectrometer (EDS), scanning electron microscopy (SEM), transmission electron microscope (TEM) and X-ray photoelectron spectroscopy (XPS), which confirmed its successful preparation and rationality. The α-Fe 2 O 3 /MoS 2 nanocomposite sensor shows good selectivity, excellent reproducibility, fast response/recovery time and low detection limit towards ethanol gas at room temperature, which is superior to the single component of α-Fe 2 O 3 hollow microspheres and MoS 2 nanosheets. Furthermore, the response of the α-Fe 2 O 3 /MoS 2 nanocomposite sensor as a function of ethanol gas concentration was also demonstrated. The enhanced ethanol sensing properties of the α-Fe 2 O 3 /MoS 2 nanocomposite sensor were ascribed to the synergistic effect and heterojunction between the urchin-Like α-Fe 2 O 3 hollow microspheres and MoS 2 nanosheets. This work verifies that the hierarchical α-Fe 2 O 3 /MoS 2 nanoheterostructure is a potential candidate for fabricating room-temperature ethanol gas sensor. Copyright © 2018 Elsevier Inc. All rights reserved.

Two-dimensional molybdenum disulphide nanoflakes synthesized by liquid-solid phase reaction method: regenerative photocatalytic performance under UV-visible light irradiation by advance oxidation process

NASA Astrophysics Data System (ADS)

Afsar, M. F.; Rafiq, M. A.; Siddique, Fizza; Saira, F.; Chaudhary, M. M.; Hasan, M. M.; Tok, A. I. Y.

2018-05-01

Molybdenum disulphide (MoS2) nanoflakes were prepared through liquid-solid phase reaction technique. X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and transmission electron microscopy (TEM) analysis revealed the formation of pure, polycrystalline, hexagonal phase of MoS2 nanoflakes. The texture coefficient (T{c}hkl) analysis showed that (100) plane was preferentially oriented. The specific surface area of the nanoflakes was 21 m2 g‑1 as determined using Brunaure-Emmett-Teller (BET) technique. A band gap of ∼2.05 eV for MoS2 nanoflakes was estimated from UV-visible spectrum. Regenerative photocatalytic activity of MoS2 nanoflakes was assessed by degrading methylene blue (MB) and safranin-o (SO) dyes under UV-visible light irradiation. Under light irradiation, degradation efficiency for MB was ∼99.58% in 100 min while for SO it was ∼99.89% in 70 min. The MoS2 nanoflakes exhibited excellent photocatalytic performance and good stability in a wide pH range (3–11). MoS2 nanoflakes showed a high reaction rate constant (k app ) for SO ∼ 0.104 49 min‑1 and MB ∼ 0.092 18 min‑1 as compared to other MoS2 nanostructures. The obtained exceptional photocatalytic performance of MoS2 nanoflakes offers potential applications for the treatment of polluted water as well as in other correlated fields.

Structural changes in slenderized yak hair induced by heat-humidity conditions using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Liu, H. L.; Zhao, B. Y.; Yu, W. D.

2013-04-01

In this study, estimation of structure was accomplished with the use of deconvolution, secondary derivation and curve-fitting. The structural changes of slenderized yak hair treated by heat-humidity conditions were quantified by analyzing the disulfide bond (S-S), amide I and amide III regions. The results showed that the amount of the disulphide bond in the yak hair decreases with the increase of treating time. The secondary structure of yak hair transforms from the α-helix and β pleated to the disordered conformation during the heat humidity processing.

Structural and functional properties of kunitz proteinase inhibitors from leguminosae: a mini review.

PubMed

Oliva, Maria Luiza Vilela; Ferreira, Rodrigo da Silva; Ferreira, Joana Gasperazzo; de Paula, Cláudia Alessandra Andrade; Salas, Carlos E; Sampaio, Misako Uemura

2011-08-01

Seed proteins that inhibit proteinases are classified in families based on amino acid sequence similarity, nature of reactive site and mechanism of action, and are used as tools for investigating proteinases in physiological and pathological events. More recently, the plant Kunitz family of inhibitors with two disulphide bridges was enlarged with members containing variable number of cysteine residues, ranging from no cysteine at all to more than four residues. The characteristic of these proteins, as well the interactions with their target proteinases, are briefly discussed.

Dietary garlic and hip osteoarthritis: evidence of a protective effect and putative mechanism of action

PubMed Central

2010-01-01

Background Patterns of food intake and prevalent osteoarthritis of the hand, hip, and knee were studied using the twin design to limit the effect of confounding factors. Compounds found in associated food groups were further studied in vitro. Methods Cross-sectional study conducted in a large population-based volunteer cohort of twins. Food intake was evaluated using the Food Frequency Questionnaire; OA was determined using plain radiographs. Analyses were adjusted for age, BMI and physical activity. Subsequent in vitro studies examined the effects of allium-derived compounds on the expression of matrix-degrading proteases in SW1353 chondrosarcoma cells. Results Data were available, depending on phenotype, for 654-1082 of 1086 female twins (median age 58.9 years; range 46-77). Trends in dietary analysis revealed a specific pattern of dietary intake, that high in fruit and vegetables, showed an inverse association with hip OA (p = 0.022). Consumption of 'non-citrus fruit' (p = 0.015) and 'alliums' (p = 0.029) had the strongest protective effect. Alliums contain diallyl disulphide which was shown to abrogate cytokine-induced matrix metalloproteinase expression. Conclusions Studies of diet are notorious for their confounding by lifestyle effects. While taking account of BMI, the data show an independent effect of a diet high in fruit and vegetables, suggesting it to be protective against radiographic hip OA. Furthermore, diallyl disulphide, a compound found in garlic and other alliums, represses the expression of matrix-degrading proteases in chondrocyte-like cells, providing a potential mechanism of action. PMID:21143861

Tyrosine aminotransferase: biochemical and structural properties and molecular dynamics simulations.

PubMed

Mehere, Prajwalini; Han, Qian; Lemkul, Justin A; Vavricka, Christopher J; Robinson, Howard; Bevan, David R; Li, Jianyong

2010-11-01

Tyrosine aminotransferase (TAT) catalyzes the transamination of tyrosine and other aromatic amino acids. The enzyme is thought to play a role in tyrosinemia type II, hepatitis and hepatic carcinoma recovery. The objective of this study is to investigate its biochemical and structural characteristics and substrate specificity in order to provide insight regarding its involvement in these diseases. Mouse TAT (mTAT) was cloned from a mouse cDNA library, and its recombinant protein was produced using Escherichia coli cells and purified using various chromatographic techniques. The recombinant mTAT is able to catalyze the transamination of tyrosine using α-ketoglutaric acid as an amino group acceptor at neutral pH. The enzyme also can use glutamate and phenylalanine as amino group donors and p-hydroxy-phenylpyruvate, phenylpyruvate and alpha-ketocaproic acid as amino group acceptors. Through macromolecular crystallography we have determined the mTAT crystal structure at 2.9 Å resolution. The crystal structure revealed the interaction between the pyridoxal-5'-phosphate cofactor and the enzyme, as well as the formation of a disulphide bond. The detection of disulphide bond provides some rational explanation regarding previously observed TAT inactivation under oxidative conditions and reactivation of the inactive TAT in the presence of a reducing agent. Molecular dynamics simulations using the crystal structures of Trypanosoma cruzi TAT and human TAT provided further insight regarding the substrate-enzyme interactions and substrate specificity. The biochemical and structural properties of TAT and the binding of its cofactor and the substrate may help in elucidation of the mechanism of TAT inhibition and activation.

Rational design of hypoallergens applied to the major cat allergen Fel d 1.

PubMed

Saarne, T; Kaiser, L; Grönlund, H; Rasool, O; Gafvelin, G; van Hage-Hamsten, M

2005-05-01

Allergen-specific immunotherapy is the only treatment for allergic disease providing long-lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy. The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen. The three-dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition-ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay. Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400-900 times lower IgE-binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1. By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE-binding capacities and retained T cell reactivities. This strategy may be applied to any well-characterized allergen to improve immunotherapy for allergic patients.

X-linked juvenile retinoschisis: Clinical diagnosis, genetic analysis, and molecular mechanisms

PubMed Central

Molday, Robert S.; Kellner, Ulrich; Weber, Bernhard H.F.

2012-01-01

X-linked juvenile retinoschisis (XLRS, MIM 312700) is a common early onset macular degeneration in males characterized by mild to severe loss in visual acuity, splitting of retinal layers, and a reduction in the b-wave of the electroretinogram (ERG). The RS1 gene (MIM 300839) associated with the disease encodes retinoschisin, a 224 amino acid protein containing a discoidin domain as the major structural unit, an N-terminal cleavable signal sequence, and regions responsible for subunit oligomerization. Retinoschisin is secreted from retinal cells as a disulphide-linked homo-octameric complex which binds to the surface of photoreceptors and bipolar cells to help maintain the integrity of the retina. Over 190 disease-causing mutations in the RS1 gene are known with most mutations occurring as non-synonymous changes in the discoidin domain. Cell expression studies have shown that disease-associated missense mutations in the discoidin domain cause severe protein misfolding and retention in the endoplasmic reticulum, mutations in the signal sequence result in aberrant protein synthesis, and mutations in regions flanking the discoidin domain cause defective disulphide-linked subunit assembly, all of which produce a non-functional protein. Knockout mice deficient in retinoschisin have been generated and shown to display most of the characteristic features found in XLRS patients. Recombinant adeno-associated virus (rAAV) mediated delivery of the normal RS1 gene to the retina of young knockout mice result in long term retinoschisin expression and rescue of retinal structure and function providing a ‘proof of concept’ that gene therapy may be an effective treatment for XLRS. PMID:22245536

X-linked juvenile retinoschisis: clinical diagnosis, genetic analysis, and molecular mechanisms.

PubMed

Molday, Robert S; Kellner, Ulrich; Weber, Bernhard H F

2012-05-01

X-linked juvenile retinoschisis (XLRS, MIM 312700) is a common early onset macular degeneration in males characterized by mild to severe loss in visual acuity, splitting of retinal layers, and a reduction in the b-wave of the electroretinogram (ERG). The RS1 gene (MIM 300839) associated with the disease encodes retinoschisin, a 224 amino acid protein containing a discoidin domain as the major structural unit, an N-terminal cleavable signal sequence, and regions responsible for subunit oligomerization. Retinoschisin is secreted from retinal cells as a disulphide-linked homo-octameric complex which binds to the surface of photoreceptors and bipolar cells to help maintain the integrity of the retina. Over 190 disease-causing mutations in the RS1 gene are known with most mutations occurring as non-synonymous changes in the discoidin domain. Cell expression studies have shown that disease-associated missense mutations in the discoidin domain cause severe protein misfolding and retention in the endoplasmic reticulum, mutations in the signal sequence result in aberrant protein synthesis, and mutations in regions flanking the discoidin domain cause defective disulphide-linked subunit assembly, all of which produce a non-functional protein. Knockout mice deficient in retinoschisin have been generated and shown to display most of the characteristic features found in XLRS patients. Recombinant adeno-associated virus (rAAV) mediated delivery of the normal RS1 gene to the retina of young knockout mice result in long-term retinoschisin expression and rescue of retinal structure and function providing a 'proof of concept' that gene therapy may be an effective treatment for XLRS. Copyright © 2012 Elsevier Ltd. All rights reserved.

Production, Quality Control, Stability and Pharmacotoxicity of a Malaria Vaccine Comprising Three Highly Similar PfAMA1 Protein Molecules to Overcome Antigenic Variation

PubMed Central

Houard, Sophie; Havelange, Nicolas; Drossard, Jürgen; Mertens, Hubert; Croon, Alexander; Kastilan, Robin; Byrne, Richard; van der Werff, Nicole; van der Eijk, Marjolein; Thomas, Alan W.; Kocken, Clemens H. M.; Remarque, Edmond J.

2016-01-01

Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a leading asexual blood stage vaccine candidate for malaria. In preparation for clinical trials, three Diversity Covering (DiCo) PfAMA1 ectodomain proteins, designed to overcome the intrinsic polymorphism that is present in PfAMA1, were produced under Good Manufacturing Practice (GMP) in Pichia pastoris. Using identical methodology, the 3 strains were cultivated in 70-L scale fed-batch fermentations and PfAMA1-DiCos were purified by two chromatography steps, an ultrafiltration/diafiltration procedure and size exclusion chromatography, resulting in highly pure (>95%) PfAMA1-DiCo1, PfAMA1 DiCo2 and PfAMA1 DiCo3, with final yields of 1.8, 1.9 and 1.3 gram, respectively. N-terminal determinations showed that approximately 50% of each of the proteins lost 12 residues from their N-terminus, in accordance with SDS-PAGE (2 main bands) and MS-data. Under reducing conditions a site of limited proteolytic cleavage within a disulphide bonded region became evident. The three proteins quantitatively bound to the mAb 4G2 that recognizes a conformational epitope, suggesting proper folding of the proteins. The lyophilized Drug Product (1:1:1 mixture of PfAMA1-DiCo1, DiCo2, DiCo3) fulfilled all pre-set release criteria (appearance, dissolution rate, identity, purity, protein content, moisture content, sub-visible particles, immuno-potency (after reconstitution with adjuvant), abnormal toxicity, sterility and endotoxin), was stable in accelerated and real-time stability studies at -20°C for over 24 months. When formulated with adjuvants selected for clinical phase I evaluation, the Drug Product did not show adverse effect in a repeated-dose toxicity study in rabbits. The Drug Product has entered a phase Ia/Ib clinical trial. PMID:27695087

The location of the thioglycolic acid molecules in intrafibrillar unordered areas of the human hair keratin structure.

PubMed

Zabashta, Y F; Kasprova, A V; Senchurov, S P; Grabovskii, Y E

2012-06-01

It has been established after conducting an X-ray diffraction study of the structure of hair treated with the thioglycolic acid solution that the preferable location of thioglycolic acid molecules should be the intrafibrillar unordered areas. Based on this fact it has been concluded that the redistribution of disulphide bonds of hair occurs mainly in the mentioned above areas when treated with thioglycolic acid solution. © 2012 The Authors. ICS © 2012 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Rational mutagenesis by engineering disulphide bonds improves Kluyveromyces lactis beta-galactosidase for high-temperature industrial applications

PubMed Central

Rico-Díaz, Agustín; Álvarez-Cao, María-Efigenia; Escuder-Rodríguez, Juan-José; González-Siso, María-Isabel; Cerdán, M. Esperanza; Becerra, Manuel

2017-01-01

Kluyveromyces lactis β-galactosidase (Kl-β-Gal) is one of the most important enzymes in the dairy industry. The poor stability of this enzyme limits its use in the synthesis of galactooligosaccharides (GOS) and other applications requiring high operational temperature. To obtain thermoresistant variants, a rational mutagenesis strategy by introducing disulphide bonds in the interface between the enzyme subunits was used. Two improved mutants, R116C/T270C and R116C/T270C/G818C, had increased half-lives at 45 °C compared to Kl-β-Gal (2.2 and 6.8 fold increases, respectively). Likewise, Tm values of R116C/T270C and R116C/T270C/G818C were 2.4 and 8.5 °C, respectively, higher than Kl-β-Gal Tm. Enrichment in enzymatically active oligomeric forms in these mutant variants also increased their catalytic efficiency, due to the reinforcement of the interface contacts. In this way, using an artificial substrate (p-nitrophenyl-β-D-galactopyranoside), the Vmax values of the mutants were ~1.4 (R116C/T270C) and 2 (R116C/T270C/G818C) fold higher than that of native Kl-β-Gal. Using the natural substrate (lactose) the Vmax for R116C/T270C/G818C almost doubled the Vmax for Kl-β-Gal. Validation of these mutant variants of the enzyme for their use in applications that depend on prolonged incubations at high temperatures was achieved at the laboratory scale by monitoring their catalytic activity in GOS synthesis. PMID:28361909

Identification and In Silico Analysis of Major Redox Modulated Proteins from Brassica juncea Seedlings Using 2D Redox SDS PAGE (2-Dimensional Diagonal Redox Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis).

PubMed

Chaurasia, Satya Prakash; Deswal, Renu

2017-02-01

The thiol-disulphide exchange regulates the activity of proteins by redox modulation. Many studies to analyze reactive oxygen species (ROS), particularly, hydrogen peroxide (H 2 O 2 ) induced changes in the gene expression have been reported, but efforts to detect H 2 O 2 modified proteins are comparatively few. Two-dimensional diagonal redox sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) was used to detect polypeptides which undergo thiol-disulphide exchange in Brassica juncea seedlings following H 2 O 2 (10 mM) treatment for 30 min. Eleven redox responsive polypeptides were identified which included cruciferin, NLI [Nuclear LIM (Lin11, Isl-1 & Mec-3 domains)] interacting protein phosphatase, RuBisCO (ribulose-1,5-bisphosphate carboxylase/oxygenase) large subunit, and myrosinase. Redox modulation of RuBisCO large subunit was further confirmed by western blotting. However, the small subunit of RuBisCO was not affected by these redox changes. All redox modulated targets except NLI interacting protein (although it contains two cysteines) showed oxidation sensitive cysteines by in silico analysis. Interestingly, interactome of cruciferin and myrosinase indicated that they may have additional function(s) beside their well-known roles in the seedling development and abiotic stress respectively. Cruciferin showed interactions with stress associated proteins like defensing-like protein 192 and 2-cys peroxiredoxin. Similarly, myrosinase showed interactions with nitrilase and cytochrome p450 which are involved in nitrogen metabolism and/or hormone biosynthesis. This simple procedure can be used to detect major stress mediated redox changes in other plants.

Bufo arenarum egg jelly coat: purification and characterization of two highly glycosylated proteins.

PubMed Central

Arranz, S E; Albertali, I E; Cabada, M O

1997-01-01

Egg jelly coats from Bufo arenarum are formed by components secreted along the oviduct. These secretion products overlay the oocytes as they transit along the different oviductal portions. In this study, we have isolated two highly glycosylated proteins of the jelly coat, which are secreted almost all the way along the oviduct. Both glycoproteins [designated as highly glycosylated protein (HGP) and low-molecular-mass highly glycosylated protein (L-HGP)] were purified to homogeneity, from the secretion of the caudal oviduct portion, by CsCl density gradient ultracentrifugation. HGP is a high-molecular-mass protein with mucin-like characteristics: high viscosity, a high content of serine and threonine, about 70% carbohydrate by weight, and a protease-resistant domain. Cleavage of disulphide bridges with reducing agents resulted in the release of a single subunit (300000 Da). L-HGP is also a disulphide-cross-linked protein with lower apparent monomeric molecular mass, in the range 100-120 kDa and containing 50% carbohydrate by weight. HGP contains galactose, fucose, N-acetylgalactosamine and sialic acid, but no mannose, suggesting the presence of O-linked oligosaccharides exclusively. The secretion ratio of HGP increases from cephalic (16% of total protein in pars preconvoluta) to caudal (40% of total protein in pars convoluta) oviductal portions. It appears to be the major structural component of the jelly coat. Our purification data suggest that HGP is non-covalently linked to the other egg jelly proteins. Polyclonal antiserum to each purified glycoprotein from secretion was raised in rabbits and used to localize both glycoproteins in the different oviductal portions, total egg jelly and the aqueous medium where oocyte strings were incubated. HGP forms a stable fibre matrix around the oocyte. L-HGP is present in the jelly coat and is released into the incubation medium. PMID:9173897

Ligand specificities and structural requirements of two Tachypleus plasma lectins for bacterial trapping

PubMed Central

2005-01-01

TPL (Tachypleus plasma lectin)-1 was purified by using a Sepharose column and TPL-2 was purified from an LPS–Sepharose (LPS coupled to Sepharose matrix) affinity column, as described previously [Chiou, Chen, Y.-W., Chen, S.-C., Chao and Liu (2000) J. Biol. Chem. 275, 1630–1634] and the corresponding genes were cloned [Chen, Yen, Yeh, Huang and Liu (2001) J. Biol. Chem. 276, 9631–9639]. In the present study, TPL-1 and -2 were produced in yeast, and the recombinant proteins secreted into the media were purified and characterized. The proteins show specific PGN (peptidoglycan)- and LPS-binding activity, suggesting a role in trapping Gram-positive and Gram-negative bacteria respectively in innate immunity. Using BIAcore® assays, the dissociation constant for the TPL-1–PGN complex was measured as 8×10−8 M. Replacement of Asn74, the N-glycosylation site of TPL-1, with Asp abolishes the PGN-binding affinity, whereas the unglycosylated TPL-2 N3D mutant retains LPS-binding activity. DTT (dithiothreitol) treatment to break disulphide linkages abrogates TPL-2 activity but does not interfere with TPL-1 function. Cys4 in TPL-2 may form an intermolecular disulphide bond, which is essential for activity. As a result, the TPL-2 C4S mutant is inactive and is eluted as a monomer on a non-reducing gel. TPL-2 C6S is active and forms a non-covalently linked dimer. A model describing TPL-2 binding with LPS is proposed. These two plasma lectins that have different ligand specificities can be used for the detection and discrimination of bacteria and removal of endotoxins. PMID:16229681

Novel Antimicrobial Peptides EeCentrocins 1, 2 and EeStrongylocin 2 from the Edible Sea Urchin Echinus esculentus Have 6-Br-Trp Post-Translational Modifications

PubMed Central

Solstad, Runar Gjerp; Li, Chun; Isaksson, Johan; Johansen, Jostein; Svenson, Johan; Stensvåg, Klara; Haug, Tor

2016-01-01

The global problem of microbial resistance to antibiotics has resulted in an urgent need to develop new antimicrobial agents. Natural antimicrobial peptides are considered promising candidates for drug development. Echinoderms, which rely on innate immunity factors in the defence against harmful microorganisms, are sources of novel antimicrobial peptides. This study aimed to isolate and characterise antimicrobial peptides from the Edible sea urchin Echinus esculentus. Using bioassay-guided purification and cDNA cloning, three antimicrobial peptides were characterised from the haemocytes of the sea urchin; two heterodimeric peptides and a cysteine-rich peptide. The peptides were named EeCentrocin 1 and 2 and EeStrongylocin 2, respectively, due to their apparent homology to the published centrocins and strongylocins isolated from the green sea urchin Strongylocentrotus droebachiensis. The two centrocin-like peptides EeCentrocin 1 and 2 are intramolecularly connected via a disulphide bond to form a heterodimeric structure, containing a cationic heavy chain of 30 and 32 amino acids and a light chain of 13 amino acids. Additionally, the light chain of EeCentrocin 2 seems to be N-terminally blocked by a pyroglutamic acid residue. The heavy chains of EeCentrocins 1 and 2 were synthesised and shown to be responsible for the antimicrobial activity of the natural peptides. EeStrongylocin 2 contains 6 cysteines engaged in 3 disulphide bonds. A fourth peptide (Ee4635) was also discovered but not fully characterised. Using mass spectrometric and NMR analyses, EeCentrocins 1 and 2, EeStrongylocin 2 and Ee4635 were all shown to contain post-translationally brominated Trp residues in the 6 position of the indole ring. PMID:27007817

Enhanced Sampling Methods for the Computation of Conformational Kinetics in Macromolecules

NASA Astrophysics Data System (ADS)

Grazioli, Gianmarc

Calculating the kinetics of conformational changes in macromolecules, such as proteins and nucleic acids, is still very much an open problem in theoretical chemistry and computational biophysics. If it were feasible to run large sets of molecular dynamics trajectories that begin in one configuration and terminate when reaching another configuration of interest, calculating kinetics from molecular dynamics simulations would be simple, but in practice, configuration spaces encompassing all possible configurations for even the simplest of macromolecules are far too vast for such a brute force approach. In fact, many problems related to searches of configuration spaces, such as protein structure prediction, are considered to be NP-hard. Two approaches to addressing this problem are to either develop methods for enhanced sampling of trajectories that confine the search to productive trajectories without loss of temporal information, or coarse-grained methodologies that recast the problem in reduced spaces that can be exhaustively searched. This thesis will begin with a description of work carried out in the vein of the second approach, where a Smoluchowski diffusion equation model was developed that accurately reproduces the rate vs. force relationship observed in the mechano-catalytic disulphide bond cleavage observed in thioredoxin-catalyzed reduction of disulphide bonds. Next, three different novel enhanced sampling methods developed in the vein of the first approach will be described, which can be employed either separately or in conjunction with each other to autonomously define a set of energetically relevant subspaces in configuration space, accelerate trajectories between the interfaces dividing the subspaces while preserving the distribution of unassisted transition times between subspaces, and approximate time correlation functions from the kinetic data collected from the transitions between interfaces.

Rational mutagenesis by engineering disulphide bonds improves Kluyveromyces lactis beta-galactosidase for high-temperature industrial applications.

PubMed

Rico-Díaz, Agustín; Álvarez-Cao, María-Efigenia; Escuder-Rodríguez, Juan-José; González-Siso, María-Isabel; Cerdán, M Esperanza; Becerra, Manuel

2017-03-31

Kluyveromyces lactis β-galactosidase (Kl-β-Gal) is one of the most important enzymes in the dairy industry. The poor stability of this enzyme limits its use in the synthesis of galactooligosaccharides (GOS) and other applications requiring high operational temperature. To obtain thermoresistant variants, a rational mutagenesis strategy by introducing disulphide bonds in the interface between the enzyme subunits was used. Two improved mutants, R116C/T270C and R116C/T270C/G818C, had increased half-lives at 45 °C compared to Kl-β-Gal (2.2 and 6.8 fold increases, respectively). Likewise, Tm values of R116C/T270C and R116C/T270C/G818C were 2.4 and 8.5 °C, respectively, higher than Kl-β-Gal Tm. Enrichment in enzymatically active oligomeric forms in these mutant variants also increased their catalytic efficiency, due to the reinforcement of the interface contacts. In this way, using an artificial substrate (p-nitrophenyl-β-D-galactopyranoside), the Vmax values of the mutants were ~1.4 (R116C/T270C) and 2 (R116C/T270C/G818C) fold higher than that of native Kl-β-Gal. Using the natural substrate (lactose) the Vmax for R116C/T270C/G818C almost doubled the Vmax for Kl-β-Gal. Validation of these mutant variants of the enzyme for their use in applications that depend on prolonged incubations at high temperatures was achieved at the laboratory scale by monitoring their catalytic activity in GOS synthesis.

Structure of the detoxification catalyst mercuric ion reductase from Bacillus sp. strain RC607

NASA Astrophysics Data System (ADS)

Schiering, N.; Kabsch, W.; Moore, M. J.; Distefano, M. D.; Walsh, C. T.; Pai, E. F.

1991-07-01

SEVERAL hundred million tons of toxic mercurials are dispersed in the biosphere1. Microbes can detoxify organo-mercurials and mercury salts through sequential action of two enzymes, organomercury lyase2 and mercuric ion reductase (MerA) 3-5. The latter, a homodimer with homology to the FAD-dependent disulphide oxidoreductases6, catalyses the reaction NADPH + Hg(II) --> NADP+ + H+Hg(0), one of the very rare enzymic reactions with metal substrates. Human glutathione reductase7,8 serves as a reference molecule for FAD-dependent disulphide reductases and between its primary structure9 and that of MerA from Tn501 (Pseudomonas), Tn21 (Shigella), pI258 (Staphylococcus) and Bacillus, 25-30% of the residues have been conserved10,11. All MerAs have a C-terminal extension about 15 residues long but have very varied N termini. Although the enzyme from Streptomyces lividans has no addition, from Pseudomonas aeruginosa Tn5Ol and Bacillus sp. strain RC607 it has one and two copies respectively of a domain of 80-85 residues, highly homologous to MerP, the periplasmic component of proteins encoded by the mer operon11. These domains can be proteolytically cleaved off without changing the catalytic efficiency3. We report here the crystal structure of MerA from the Gram-positive bacterium Bacillus sp. strain RC607. Analysis of its complexes with nicotinamide dinucleotide substrates and the inhibitor Cd(II) reveals how limited structural changes enable an enzyme to accept as substrate what used to be a dangerous inhibitor. Knowledge of the mode of mercury ligation is a prerequisite for understanding this unique detoxification mechanism.

Natural structural variation in enzymes as a tool in the study of mechanism exemplified by a comparison of the catalytic-site structure and characteristics of cathepsin B and papain. pH-dependent kinetics of the reactions of cathepsin B from bovine spleen and from rat liver with a thiol-specific two-protonic-state probe (2,2'-dipyridyl disulphide) and with a specific synthetic substrate (N-alpha-benzyloxycarbonyl-L-arginyl-L-arginine 2-naphthylamide).

PubMed Central

Willenbrock, F; Brocklehurst, K

1984-01-01

Cathepsin B (EC 3.4.22.1) from bovine spleen and the analogous enzyme from rat liver were investigated at 25 degrees C at I0.1 in acidic media by kinetic study of (a) the reactions of their catalytic-site thiol groups towards the two-protonic-state reactivity probe 2,2'-dipyridyl disulphide and (b) their catalysis of the hydrolysis of N-alpha-benzyloxycarbonyl-L-arginyl-L-arginine 2-naphthylamide. Reactivity-probe kinetics showed that nucleophilic character is generated in the sulphur atom of cathepsin B by protonic dissociation with pKa 3.4, presumably to form an S-/ImH+ ion-pair. Substrate-catalysis kinetics showed that ion-pair formation is not sufficient to generate catalytic competence in cathepsin B, because catalytic activity is not generated as the pH is raised across pKa 3.4 but rather as it is raised across pKa 5-6 (5.1 for kcat; 5.6 for kcat./Km for the bovine spleen enzyme and 5.8 for kcat./Km for the rat liver enzyme). The implications of these results and of known structural differences between the catalytic sites of the rat liver enzyme and papain (EC 3.4.22.2) for the mechanism of cysteine-proteinase-catalysed hydrolysis are discussed. PMID:6534384

Molecular basis for potentiation of Cx36 gap junction channel conductance by n-alcohols and general anesthetics.

PubMed

Raškevičius, Vytautas; Jotautis, Vaidas; Rimkutė, Lina; Marandykina, Alina; Kazokaitė, Mintautė; Kairys, Visvaldas; Skeberdis, Vytenis Arvydas

2018-02-28

In our recent study, we have demonstrated that short carbon chain n -alcohols (up to octanol) stimulated while long carbon chain n -alcohols inhibited the conductance of connexin (Cx) 36 (Cx36) gap junction (GJ) channels. In contrast, GJ channels composed of other types of Cxs all were inhibited by n -alcohols independent of their carbon chain length. To identify the putative structural domains of Cx36, responsible for the dual effect of n -alcohols, we performed structural modeling of Cx36 protein docking with hexanol and isoflurane that stimulated as well as nonanol and carbenoxolone that inhibited the conductance of Cx36 GJs and revealed their multiple common docking sites and a single pocket accessible only to hexanol and isoflurane. The pocket is located in the vicinity of three unique cysteine residues, namely C264 in the fourth, and C92 and C87 in the second transmembrane domain of the neighboring Cx36 subunits. To examine the hypothesis that disulphide bonding might be involved in the stimulatory effect of hexanol and isoflurane, we generated cysteine substitutions in Cx36 and demonstrated by a dual whole-cell patch-clamp technique that in HeLa (human cervix carcinoma cell line) and N2A (mouse neuroblastoma cell line) cells these mutations reversed the stimulatory effect of hexanol and isoflurane to inhibitory one, typical of other Cxs that lack respective cysteines and a specific docking pocket for these compounds. Our findings suggest that the stimulatory effect of hexanol and isoflurane on Cx36 GJ conductance could be achieved by re-shuffling of the inter-subunit disulphide bond between C264 and C92 to the intra-subunit one between C264 and C87. © 2018 The Author(s).

Isolation and characterization of an IgNAR variable domain specific for the human mitochondrial translocase receptor Tom70.

PubMed

Nuttall, Stewart D; Krishnan, Usha V; Doughty, Larissa; Pearson, Kylie; Ryan, Michael T; Hoogenraad, Nicholas J; Hattarki, Meghan; Carmichael, Jennifer A; Irving, Robert A; Hudson, Peter J

2003-09-01

The new antigen receptor (IgNAR) from sharks is a disulphide bonded dimer of two protein chains, each containing one variable and five constant domains, and functions as an antibody. In order to assess the antigen-binding capabilities of isolated IgNAR variable domains (VNAR), we have constructed an in vitro library incorporating synthetic CDR3 regions of 15-18 residues in length. Screening of this library against the 60 kDa cytosolic domain of the 70 kDa outer membrane translocase receptor from human mitochondria (Tom70) resulted in one dominant antigen-specific clone (VNAR 12F-11) after four rounds of in vitro selection. VNAR 12F-11 was expressed into the Escherichia coli periplasm and purified by anti-FLAG affinity chromatography at yields of 3 mg x L(-1). Purified protein eluted from gel filtration columns as a single monomeric protein and CD spectrum analysis indicated correct folding into the expected beta-sheet conformation. Specific binding to Tom70 was demonstrated by ELISA and BIAcore (Kd = 2.2 +/- 0.31 x 10(-9) m-1) indicating that these VNAR domains can be efficiently displayed as bacteriophage libraries, and selected against target antigens with an affinity and stability equivalent to that obtained for other single domain antibodies. As an initial step in producing 'intrabody' variants of 12F-11, the impact of modifying or removing the conserved immunoglobulin intradomain disulphide bond was assessed. High affinity binding was only retained in the wild-type protein, which combined with our inability to affinity mature 12F-11, suggests that this particular VNAR is critically dependent upon precise CDR loop conformations for its binding affinity.

Alignment and Imaging of the CS2 Dimer Inside Helium Nanodroplets

NASA Astrophysics Data System (ADS)

Pickering, James D.; Shepperson, Benjamin; Hübschmann, Bjarke A. K.; Thorning, Frederik; Stapelfeldt, Henrik

2018-03-01

The carbon disulphide (CS2) dimer is formed inside He nanodroplets and identified using fs laser-induced Coulomb explosion, by observing the CS2+ ion recoil velocity. It is then shown that a 160 ps moderately intense laser pulse can align the dimer in advantageous spatial orientations which allow us to determine the cross-shaped structure of the dimer by analysis of the correlations between the emission angles of the nascent CS2+ and S+ ions, following the explosion process. Our method will enable fs time-resolved structural imaging of weakly bound molecular complexes during conformational isomerization, including formation of exciplexes.

Onset of superconductivity in sodium and potassium intercalated molybdenum disulphide

NASA Technical Reports Server (NTRS)

Somoano, R. B.; Rembaum, A.

1971-01-01

Molybdenum disulfide in the form of natural crystals or powder has been intercalated at -65 to -70 C with sodium and potassium using the liquid ammonia technique. All intercalated samples were found to show a superconducting transition. A plot of the percent of diamagnetic throw versus temperature indicates the possible existence of two phases in the potassium intercalated molybdenum disulfide. The onset of superconductivity in potassium and sodium intercalated molybdenite powder was found to be approximately 6.2 and approximately 4.5 K, respectively. The observed superconductivity is believed to be due to an increase in electron density as a result of intercalation.

A new detector for mass spectrometry: direct detection of low energy ions using a multi-pixel photon counter.

PubMed

Wilman, Edward S; Gardiner, Sara H; Nomerotski, Andrei; Turchetta, Renato; Brouard, Mark; Vallance, Claire

2012-01-01

A new type of ion detector for mass spectrometry and general detection of low energy ions is presented. The detector consists of a scintillator optically coupled to a single-photon avalanche photodiode (SPAD) array. A prototype sensor has been constructed from a LYSO (Lu(1.8)Y(0.2)SiO(5)(Ce)) scintillator crystal coupled to a commercial SPAD array detector. As proof of concept, the detector is used to record the time-of-flight mass spectra of butanone and carbon disulphide, and the dependence of detection sensitivity on the ion kinetic energy is characterised.

Analysis of disulphide bonds found in human hair by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Pina-Ruiz, A. L.; Cordova-Fraga, T.; Plascencia-Castro, A. S.; Hernandez-Rayas, A.; Ruvalcaba, J. M.

2017-04-01

Raman spectroscopy offers information-rich spectra, making it a technique easy to use in areas such as biology, chemistry, and in the field. Human hair spectra has been recorded obtaining interesting information about its composition. Correlating information obtained from these spectra to bone health and determining if Raman spectroscopy could be used as a diagnostic tool of bone health is proposed. Spectra from healthy women were compared to the spectra of women who have suffered a bone fracture, all which were aged 39-60. This technique has potential to become a regular diagnostic tool and further investigation to improve and validate this method are needed.

Functionalization of lamellar molybdenum disulphide nanocomposite with gold nanoparticles

NASA Astrophysics Data System (ADS)

Lavayen, V.; O'Dwyer, C.; Ana, M. A. Santa; Mirabal, N.; Benavente, E.; Cárdenas, G.; González, G.; Torres, C. M. Sotomayor

2007-01-01

This work explores the functionalization of an organic-inorganic MoS2 lamellar compound, prepared by a chemical liquid deposition method (CLD), that has an interlamellar distance of ∼5.2 nm, using clusters of gold nanoparticles. The gold nanoparticles have a mean diameter of 1.2 nm, a stability of ∼85 days, and a zeta potential measured to be ζ = -6.8 mV (solid). The nanoparticles are localized in the hydrophilic zones, defined by the presence of amine groups of the surfactant between the lamella of MoS2. SEM, TEM, EDAX and electron diffraction provide conclusive evidence of the interlamellar insertion of the gold nanoparticles in the MoS2.

A convenient spectrophotometric assay for the determination of l-ergothioneine in blood

PubMed Central

Carlsson, Jan; Kierstan, Marek P. J.; Brocklehurst, Keith

1974-01-01

1. A convenient spectrophotometric assay for the determination of l-ergothioneine in solution including deproteinized blood haemolysate was developed. 2. The method consists of deproteinization by heat precipitation and Cu2+-catalysed oxidation of thiols such as glutathione and of l-ascorbic acid, both in alkaline media, and titration of l-ergothioneine (which is not oxidized under these conditions) by its virtually instantaneous reaction with 2,2′-dipyridyl disulphide at pH1. 3. This method and the results obtained with it for the analysis of human, horse, sheep and pig blood are compared with existing methods of l-ergothioneine analysis and the results obtained thereby. PMID:4463946

Photonic Activation of Plasminogen Induced by Low Dose UVB

PubMed Central

Correia, Manuel; Snabe, Torben; Thiagarajan, Viruthachalam; Petersen, Steffen Bjørn; Campos, Sara R. R.; Baptista, António M.; Neves-Petersen, Maria Teresa

2015-01-01

Activation of plasminogen to its active form plasmin is essential for several key mechanisms, including the dissolution of blood clots. Activation occurs naturally via enzymatic proteolysis. We report that activation can be achieved with 280 nm light. A 2.6 fold increase in proteolytic activity was observed after 10 min illumination of human plasminogen. Irradiance levels used are in the same order of magnitude of the UVB solar irradiance. Activation is correlated with light induced disruption of disulphide bridges upon UVB excitation of the aromatic residues and with the formation of photochemical products, e.g. dityrosine and N-formylkynurenine. Most of the protein fold is maintained after 10 min illumination since no major changes are observed in the near-UV CD spectrum. Far-UV CD shows loss of secondary structure after illumination (33.4% signal loss at 206 nm). Thermal unfolding CD studies show that plasminogen retains a native like cooperative transition at ~70 ºC after UV-illumination. We propose that UVB activation of plasminogen occurs upon photo-cleavage of a functional allosteric disulphide bond, Cys737-Cys765, located in the catalytic domain and in van der Waals contact with Trp761 (4.3 Å). Such proximity makes its disruption very likely, which may occur upon electron transfer from excited Trp761. Reduction of Cys737-Cys765 will result in likely conformational changes in the catalytic site. Molecular dynamics simulations reveal that reduction of Cys737-Cys765 in plasminogen leads to an increase of the fluctuations of loop 760–765, the S1-entrance frame located close to the active site. These fluctuations affect the range of solvent exposure of the catalytic triad, particularly of Asp646 and Ser74, which acquire an exposure profile similar to the values in plasmin. The presented photonic mechanism of plasminogen activation has the potential to be used in clinical applications, possibly together with other enzymatic treatments for the elimination of blood clots. PMID:25635856

The nairovirus nairobi sheep disease virus/ganjam virus induces the translocation of protein disulphide isomerase-like oxidoreductases from the endoplasmic reticulum to the cell surface and the extracellular space.

PubMed

Lasecka, Lidia; Baron, Michael D

2014-01-01

Nairobi sheep disease virus (NSDV) of the genus Nairovirus causes a haemorrhagic gastroenteritis in sheep and goats with mortality up to 90%; the virus is found in East and Central Africa, and in India, where the virus is called Ganjam virus. NSDV is closely related to the human pathogen Crimean-Congo haemorrhagic fever virus, which also causes a haemorrhagic disease. As with other nairoviruses, replication of NSDV takes place in the cytoplasm and the new virus particles bud into the Golgi apparatus; however, the effect of viral replication on cellular compartments has not been studied extensively. We have found that the overall structure of the endoplasmic reticulum (ER), the ER-Golgi intermediate compartment and the Golgi were unaffected by infection with NSDV. However, we observed that NSDV infection led to the loss of protein disulphide isomerase (PDI), an oxidoreductase present in the lumen of the endoplasmic reticulum (ER) and which assists during protein folding, from the ER. Further investigation showed that NSDV-infected cells have high levels of PDI at their surface, and PDI is also secreted into the culture medium of infected cells. Another chaperone from the PDI family, ERp57, was found to be similarly affected. Analysis of infected cells and expression of individual viral glycoproteins indicated that the NSDV PreGn glycoprotein is involved in redistribution of these soluble ER oxidoreductases. It has been suggested that extracellular PDI can activate integrins and tissue factor, which are involved respectively in pro-inflammatory responses and disseminated intravascular coagulation, both of which manifest in many viral haemorrhagic fevers. The discovery of enhanced PDI secretion from NSDV-infected cells may be an important finding for understanding the mechanisms underlying the pathogenicity of haemorrhagic nairoviruses.

The Nairovirus Nairobi Sheep Disease Virus/Ganjam Virus Induces the Translocation of Protein Disulphide Isomerase-Like Oxidoreductases from the Endoplasmic Reticulum to the Cell Surface and the Extracellular Space

PubMed Central

Lasecka, Lidia; Baron, Michael D.

2014-01-01

Nairobi sheep disease virus (NSDV) of the genus Nairovirus causes a haemorrhagic gastroenteritis in sheep and goats with mortality up to 90%; the virus is found in East and Central Africa, and in India, where the virus is called Ganjam virus. NSDV is closely related to the human pathogen Crimean-Congo haemorrhagic fever virus, which also causes a haemorrhagic disease. As with other nairoviruses, replication of NSDV takes place in the cytoplasm and the new virus particles bud into the Golgi apparatus; however, the effect of viral replication on cellular compartments has not been studied extensively. We have found that the overall structure of the endoplasmic reticulum (ER), the ER-Golgi intermediate compartment and the Golgi were unaffected by infection with NSDV. However, we observed that NSDV infection led to the loss of protein disulphide isomerase (PDI), an oxidoreductase present in the lumen of the endoplasmic reticulum (ER) and which assists during protein folding, from the ER. Further investigation showed that NSDV-infected cells have high levels of PDI at their surface, and PDI is also secreted into the culture medium of infected cells. Another chaperone from the PDI family, ERp57, was found to be similarly affected. Analysis of infected cells and expression of individual viral glycoproteins indicated that the NSDV PreGn glycoprotein is involved in redistribution of these soluble ER oxidoreductases. It has been suggested that extracellular PDI can activate integrins and tissue factor, which are involved respectively in pro-inflammatory responses and disseminated intravascular coagulation, both of which manifest in many viral haemorrhagic fevers. The discovery of enhanced PDI secretion from NSDV-infected cells may be an important finding for understanding the mechanisms underlying the pathogenicity of haemorrhagic nairoviruses. PMID:24714576

Redox regulation of carbon storage and partitioning in response to light and sugars.

PubMed

Geigenberger, Peter; Kolbe, Anna; Tiessen, Axel

2005-06-01

Redox signals generated by the photosynthetic electron transport chain are known to be involved in regulating the Calvin cycle, ATP synthesis, and NADPH export from chloroplasts in response to light. The signal cascade involves transfer of electrons from photosystem I via the ferredoxin-thioredoxin system to target enzymes that are activated by reduction of regulatory disulphide bonds. The purpose of this review is to discuss recent findings showing that this concept can be extended to the regulation of carbon storage and partitioning in plants. Starch is the major carbon store in plants, and ADP-glucose pyrophosphorylase (AGPase) is the key regulatory enzyme of starch synthesis in the plastid. It has been shown that AGPase from potato tubers is subject to post-translational redox modification, and here experimental data will be provided showing that the isozyme from pea leaf chloroplasts is activated by reduced thioredoxin f or m in a similar way. Recent reports will be summarized providing in planta evidence that this mechanism regulates storage starch synthesis in response to light and sugars. Post-translational redox activation of AGPase in response to sugars is part of a signalling mechanism linking the rate of starch synthesis to the availability of carbon in diverse plant tissues. Some of the components of the signalling pathway reporting changes in the cytosolic sugar status to the plastid have been postulated, but detailed work is in progress to confirm the exact mode of action. Recent evidence will be discussed showing that key enzymes of de novo fatty acid synthesis (acetyl-CoA carboxylase) and ammonium assimilation (glutamine synthetase and glutamine:oxoglutarate amino transferase) are regulated by reversible disulphide-bond formation similar to AGPase. Redox regulation is proposed to be the preferred strategy of plastidial enzymes to regulate various metabolic processes such as carbon fixation, starch metabolism, lipid synthesis, and amino acid synthesis in response to physiological and environmental inputs.

Effect of common pesticides used in the Niger Delta basin of southern Nigeria on soil microbial populations.

PubMed

Ekundayo, E O

2003-11-01

The effects of eleven pesticides on the populations of bacteria, actinomycetes, fungi and protozoa was investigated by treating a garden soil with their recommended rates. The microbial populations were estimated using the standard plate-count technique. Of the 11 pesticides investigated, phenylmercuric acetate (agrosan) at 50 microg g(-1) inhibited bacterial density the most, i.e. from 4,600,000 to 220 cells g(-1). The pesticides were Pentachloronitrobenzene (PCNB), tetramethylmethylthiuram disulphide (thiram), 1-naphthylmethylcarbamate (Vetox 85), 1,2,3,4,5,6-hexachlorocyclohexane (Gammalin 20), phenylmercuric acetate (Agrosan), tetrachloroterephthalic acid (Dacthal), 4-nitrophenyl-2-nitro-4-trifluoromethylphenyl ether (Preforan), 2-ethyl-6-methyl-N-2-methoxy-1-methyl ethyl-chloroacetanide (Dual), Benlate, Brestan and Gramoxone. Pentachloronitrobenzene (PCNB) at 240,000 microg g(-1) reduced bacterial population from 4,600,000 to 2,100 cells g(-1), whereas tetramethylthiuram disulphide (thiram) at 100 microg g(-1) suppressed it by 2 log orders of magnitude. Soil application of 1-naphthylmethylcarbamate (Vetox 85) at 100 microg g(-1) and 1,2,3,4,5,6,-hexachlorocyclohexane (Gamalin 20) at 1,300 microg g(-1) repressed the bacterial numbers by 2 log orders of magnitude each. Pentachloronitrobenzene reduced the actinomycetes density from 340,000 to 320 cells g(-1) and completely eliminated all fungal and protozoan propagules from the soil. The Gammalin 20 completely wiped out all the fungi, whereas phenylmercuric acetate totally eliminated all the protozoa and reduced the fungal population from 34,000 to 60 cells g(-1). In general, protozoa and fungi were more susceptible to fungicides than bacteria and actinomycetes. Pentachloronitrobenzene, 1,2,3,4,5,6,-hexachlorocyclohexane and phenylmercuric acetate were toxic particularly to soil microorganisms, whereas the herbicides dacthal, Preforan and Dual were quite harmless in soil at application rates of 0.1, 0.06 and 0.02 microg g(-1) respectively.

Evolution stings: the origin and diversification of scorpion toxin peptide scaffolds.

PubMed

Sunagar, Kartik; Undheim, Eivind A B; Chan, Angelo H C; Koludarov, Ivan; Muñoz-Gómez, Sergio A; Antunes, Agostinho; Fry, Bryan G

2013-12-13

The episodic nature of natural selection and the accumulation of extreme sequence divergence in venom-encoding genes over long periods of evolutionary time can obscure the signature of positive Darwinian selection. Recognition of the true biocomplexity is further hampered by the limited taxon selection, with easy to obtain or medically important species typically being the subject of intense venom research, relative to the actual taxonomical diversity in nature. This holds true for scorpions, which are one of the most ancient terrestrial venomous animal lineages. The family Buthidae that includes all the medically significant species has been intensely investigated around the globe, while almost completely ignoring the remaining non-buthid families. Australian scorpion lineages, for instance, have been completely neglected, with only a single scorpion species (Urodacus yaschenkoi) having its venom transcriptome sequenced. Hence, the lack of venom composition and toxin sequence information from an entire continent's worth of scorpions has impeded our understanding of the molecular evolution of scorpion venom. The molecular origin, phylogenetic relationships and evolutionary histories of most scorpion toxin scaffolds remain enigmatic. In this study, we have sequenced venom gland transcriptomes of a wide taxonomical diversity of scorpions from Australia, including buthid and non-buthid representatives. Using state-of-art molecular evolutionary analyses, we show that a majority of CSα/β toxin scaffolds have experienced episodic influence of positive selection, while most non-CSα/β linear toxins evolve under the extreme influence of negative selection. For the first time, we have unraveled the molecular origin of the major scorpion toxin scaffolds, such as scorpion venom single von Willebrand factor C-domain peptides (SV-SVC), inhibitor cystine knot (ICK), disulphide-directed beta-hairpin (DDH), bradykinin potentiating peptides (BPP), linear non-disulphide bridged peptides and antimicrobial peptides (AMP). We have thus demonstrated that even neglected lineages of scorpions are a rich pool of novel biochemical components, which have evolved over millions of years to target specific ion channels in prey animals, and as a result, possess tremendous implications in therapeutics.

Cross-linking of the electron-transfer flavoprotein to electron-transfer flavoprotein-ubiquinone oxidoreductase with heterobifunctional reagents.

PubMed Central

Steenkamp, D J

1988-01-01

The mitochondrial electron-transfer flavoprotein (ETF) is a heterodimer containing only one FAD. In previous work on the structure-function relationships of ETF, its interaction with the general acyl-CoA dehydrogenase (GAD) was studied by chemical cross-linking with heterobifunctional reagents [D. J. Steenkamp (1987) Biochem. J. 243, 519-524]. GAD whose lysine residues were substituted with 3-(2-pyridyldithio)propionyl groups was preferentially cross-linked to the small subunit of ETF, the lysine residues of which had been substituted with 4-mercaptobutyramidine (MBA) groups. This work was extended to the interaction of ETF with ETF-ubiquinone oxidoreductase (ETF-Q ox). ETF-Q ox was partially inactivated by modification with N-succinimidyl 3-(2-pyridyldithio)propionate to introduce pyridyl disulphide structures. A similar modification of ETF caused a large increase in the apparent Michaelis constant of ETF-Q ox for modified ETF owing to the loss of positive charge on some critical lysines of ETF. When ETF-Q ox was modified with 2-iminothiolane to introduce 4-mercaptobutyramidine groups, only a minor effect on the activity of the enzyme was observed. To retain the positive charges on the lysine residues of ETF, pyridyl disulphide structures were introduced by treating ETF with 2-iminothiolane in the presence of 2,2'-dithiodipyridyl. The electron-transfer activity of the resultant ETF preparation containing 4-(2-pyridyldithio)butyramidine (PDBA) groups was only slightly affected. When ETF-Q ox substituted with MBA groups was mixed with ETF bearing PDBA groups, at least 70% of the cross-links formed between the two proteins were between the small subunit of ETF and ETF-Q ox. ETF-Q ox, therefore, interacts predominantly with the same subunit of ETF as GAD. Variables which affect the selectivity of ETF-Q ox cross-linking to the subunits of ETF are considered. Images Fig. 4. Fig. 5. Fig. 6. PMID:3145738

Lysozyme Photochemistry as a Function of Temperature. The Protective Effect of Nanoparticles on Lysozyme Photostability

PubMed Central

Oliveira Silva, Catarina; Petersen, Steffen B.; Pinto Reis, Catarina; Rijo, Patrícia; Molpeceres, Jesús; Vorum, Henrik; Neves-Petersen, Maria Teresa

2015-01-01

The presence of aromatic residues and their close spatial proximity to disulphide bridges makes hen egg white lysozyme labile to UV excitation. UVB induced photo-oxidation of tryptophan and tyrosine residues leads to photochemical products, such as, kynurenine, N–formylkynurenine and dityrosine and to the disruption of disulphide bridges in proteins. We here report that lysozyme UV induced photochemistry is modulated by temperature, excitation power, illumination time, excitation wavelength and by the presence of plasmonic quencher surfaces, such as gold, and by the presence of natural fluorescence quenchers, such as hyaluronic acid and oleic acid. We show evidence that the photo-oxidation effects triggered by 295 nm at 20°C are reversible and non-reversible at 10°C, 25°C and 30°C. This paper provides evidence that the 295 nm damage threshold of lysozyme lies between 0.1 μW and 0.3 μW. Protein conformational changes induced by temperature and UV light have been detected upon monitoring changes in the fluorescence emission spectra of lysozyme tryptophan residues and SYPRO® Orange. Lysozyme has been conjugated onto gold nanoparticles, coated with hyaluronic acid and oleic acid (HAOA). Steady state and time resolved fluorescence studies of free and conjugated lysozyme onto HAOA gold nanoparticles reveals that the presence of the polymer decreased the rate of the observed photochemical reactions and induced a preference for short fluorescence decay lifetimes. Size and surface charge of the HAOA gold nanoparticles have been determined by dynamic light scattering and zeta potential measurements. TEM analysis of the particles confirms the presence of a gold core surrounded by a HAOA matrix. We conclude that HAOA gold nanoparticles may efficiently protect lysozyme from the photochemical effects of UVB light and this nanocarrier could be potentially applied to other proteins with clinical relevance. In addition, this study confirms that the temperature plays a critical role in the photochemical pathways a protein enters upon UV excitation. PMID:26656259

Lysozyme Photochemistry as a Function of Temperature. The Protective Effect of Nanoparticles on Lysozyme Photostability.

PubMed

Oliveira Silva, Catarina; Petersen, Steffen B; Pinto Reis, Catarina; Rijo, Patrícia; Molpeceres, Jesús; Vorum, Henrik; Neves-Petersen, Maria Teresa

2015-01-01

The presence of aromatic residues and their close spatial proximity to disulphide bridges makes hen egg white lysozyme labile to UV excitation. UVB induced photo-oxidation of tryptophan and tyrosine residues leads to photochemical products, such as, kynurenine, N-formylkynurenine and dityrosine and to the disruption of disulphide bridges in proteins. We here report that lysozyme UV induced photochemistry is modulated by temperature, excitation power, illumination time, excitation wavelength and by the presence of plasmonic quencher surfaces, such as gold, and by the presence of natural fluorescence quenchers, such as hyaluronic acid and oleic acid. We show evidence that the photo-oxidation effects triggered by 295 nm at 20°C are reversible and non-reversible at 10°C, 25°C and 30°C. This paper provides evidence that the 295 nm damage threshold of lysozyme lies between 0.1 μW and 0.3 μW. Protein conformational changes induced by temperature and UV light have been detected upon monitoring changes in the fluorescence emission spectra of lysozyme tryptophan residues and SYPRO® Orange. Lysozyme has been conjugated onto gold nanoparticles, coated with hyaluronic acid and oleic acid (HAOA). Steady state and time resolved fluorescence studies of free and conjugated lysozyme onto HAOA gold nanoparticles reveals that the presence of the polymer decreased the rate of the observed photochemical reactions and induced a preference for short fluorescence decay lifetimes. Size and surface charge of the HAOA gold nanoparticles have been determined by dynamic light scattering and zeta potential measurements. TEM analysis of the particles confirms the presence of a gold core surrounded by a HAOA matrix. We conclude that HAOA gold nanoparticles may efficiently protect lysozyme from the photochemical effects of UVB light and this nanocarrier could be potentially applied to other proteins with clinical relevance. In addition, this study confirms that the temperature plays a critical role in the photochemical pathways a protein enters upon UV excitation.

Coupled cluster investigation on the thermochemistry of dimethyl sulphide, dimethyl disulphide and their dissociation products: the problem of the enthalpy of formation of atomic sulphur

NASA Astrophysics Data System (ADS)

Denis, Pablo A.

2014-04-01

By means of coupled cluster theory and correlation consistent basis sets we investigated the thermochemistry of dimethyl sulphide (DMS), dimethyl disulphide (DMDS) and four closely related sulphur-containing molecules: CH3SS, CH3S, CH3SH and CH3CH2SH. For the four closed-shell molecules studied, their enthalpies of formation (EOFs) were derived using bomb calorimetry. We found that the deviation of the EOF with respect to experiment was 0.96, 0.65, 1.24 and 1.29 kcal/mol, for CH3SH, CH3CH2SH, DMS and DMDS, respectively, when ΔHf,0 = 65.6 kcal/mol was utilised (JANAF value). However, if the recently proposed ΔHf,0 = 66.2 kcal/mol was used to estimate EOF, the errors dropped to 0.36, 0.05, 0.64 and 0.09 kcal/mol, respectively. In contrast, for the CH3SS radical, a better agreement with experiment was obtained if the 65.6 kcal/mol value was used. To compare with experiment avoiding the problem of the ΔHf,0 (S), we determined the CH3-S and CH3-SS bond dissociation energies (BDEs) in CH3S and CH3SS. At the coupled cluster with singles doubles and perturbative triples correction level of theory, these values are 48.0 and 71.4 kcal/mol, respectively. The latter BDEs are 1.5 and 1.2 kcal/mol larger than the experimental values. The agreement can be considered to be acceptable if we take into consideration that these two radicals present important challenges when determining their EOFs. It is our hope that this work stimulates new studies which help elucidate the problem of the EOF of atomic sulphur.

The electrophoretically 'slow' and 'fast' forms of the alpha 2-macroglobulin molecule.

PubMed Central

Barrett, A J; Brown, M A; Sayers, C A

1979-01-01

alpha 2-Macroglobulin (alpha 2M) was isolated from human plasma by a four-step procedure: poly(ethylene glyco) fractionation, gel chromatography, euglobulin precipitation and immunoadsorption. No contaminants were detected in the final preparations by electrophoresis or immunoprecipitation. The protein ran as a single slow band in gel electrophoresis, and was designated 'S-alpha 2M'. S-alpha 2M bound about 2 mol of trypsin/mol. Treatment of S-alpha 2M with a proteinase or ammonium salts produced a form of the molecule more mobile in electrophoresis, and lacking proteinase-binding activity (F-alpha 2M). The electrophoretic mobility of the F-alpha 2M resulting from reaction with NH4+ salts was identical with that of proteinase complexes. We attribute the change in electrophoretic mobility of the alpha 2M to a conformation change, but there was no evidence of a change in pI or Strokes radius. Electrophoresis of S-alpha 2M in the presence of sodium dodecylsulphate gave results consistent with the view that the alpha 2M molecule is a tetramer of identical subunits, assembled as a non-covalent pair of disulphide-linked dimers. Some of the subunits seemed to be 'nicked' into two-thires-length and one-third-length chains, however. This was not apparent with F-alpha 2M produced by ammonium salts. F-alpha 2M produced by trypsin showed two new bands attributable to cleavage of the subunit polypeptide chain near the middle. Immunoassays of F-alpha 2M gave 'rockets' 12-29% lower than those with S-alpha 2M. The nature of the interactions between subunits in S-alpha 2M and F-alpha 2M was investigated by treating each form with glutaraldehyde before electrophoresis in the presence of sodium dodecyl sulphate. A much greater degree of cross-linking was observed with the F-alpha 2M, indicating that the subunits interact most closely in this form of the molecule. Exposure of S-alpha 2M to 3 M-urea or pH3 resulted in dissociation to the disulphide-bonded half-molecules; these did not show the proteinase-binding activity characteristic of the intact alpha 2M. F-alpha 2M was less easily dissociated than was S-alpha 2M. S-alpha 2M was readily dissociated to the quarter-subunits by mild reduction, with the formation of 3-4 new thiol groups per subunit. Inact reactive alpha 2M could then be regenerated in high yield by reoxidation of the subunits. F-alpha 2M formed by reaction with a proteinase or ammonium salts was not dissociated under the same conditions, although the interchain disulphide bonds were reduced. If the thiol groups of the quarter-subunits of S-alpha 2M were blocked by carboxymethylation, oxidative reassociation did not occur. Nevertheless treatment of these subunits with methylammonium salts or a proteinase caused the reassembly of half-molecules and intact (F-) tetramers. It is emphasized that F-alpha 2M does not have the properties of a denatured form of the protein... Images Fig. 3. Fig. 4. Fig. 5. Fig. 6. PMID:91367

Two-dimensional molybdenum disulphide nanosheet-covered metal nanoparticle array as a floating gate in multi-functional flash memories

NASA Astrophysics Data System (ADS)

Han, Su-Ting; Zhou, Ye; Chen, Bo; Zhou, Li; Yan, Yan; Zhang, Hua; Roy, V. A. L.

2015-10-01

Semiconducting two-dimensional materials appear to be excellent candidates for non-volatile memory applications. However, the limited controllability of charge trapping behaviors and the lack of multi-bit storage studies in two-dimensional based memory devices require further improvement for realistic applications. Here, we report a flash memory consisting of metal NPs-molybdenum disulphide (MoS2) as a floating gate by introducing a metal nanoparticle (NP) (Ag, Au, Pt) monolayer underneath the MoS2 nanosheets. Controlled charge trapping and long data retention have been achieved in a metal (Ag, Au, Pt) NPs-MoS2 floating gate flash memory. This controlled charge trapping is hypothesized to be attributed to band bending and a built-in electric field ξbi between the interface of the metal NPs and MoS2. The metal NPs-MoS2 floating gate flash memories were further proven to be multi-bit memory storage devices possessing a 3-bit storage capability and a good retention capability up to 104 s. We anticipate that these findings would provide scientific insight for the development of novel memory devices utilizing an atomically thin two-dimensional lattice structure.Semiconducting two-dimensional materials appear to be excellent candidates for non-volatile memory applications. However, the limited controllability of charge trapping behaviors and the lack of multi-bit storage studies in two-dimensional based memory devices require further improvement for realistic applications. Here, we report a flash memory consisting of metal NPs-molybdenum disulphide (MoS2) as a floating gate by introducing a metal nanoparticle (NP) (Ag, Au, Pt) monolayer underneath the MoS2 nanosheets. Controlled charge trapping and long data retention have been achieved in a metal (Ag, Au, Pt) NPs-MoS2 floating gate flash memory. This controlled charge trapping is hypothesized to be attributed to band bending and a built-in electric field ξbi between the interface of the metal NPs and MoS2. The metal NPs-MoS2 floating gate flash memories were further proven to be multi-bit memory storage devices possessing a 3-bit storage capability and a good retention capability up to 104 s. We anticipate that these findings would provide scientific insight for the development of novel memory devices utilizing an atomically thin two-dimensional lattice structure. Electronic supplementary information (ESI) available: Energy-dispersive X-ray spectroscopy (EDS) spectra of the metal NPs, SEM image of MoS2 on Au NPs, erasing operations of the metal NPs-MoS2 memory device, transfer characteristics of the standard FET devices and Ag NP devices under programming operation, tapping-mode AFM height image of the fabricated MoS2 film for pristine MoS2 flash memory, gate signals used for programming the Au NPs-MoS2 and Pt NPs-MoS2 flash memories, and data levels recorded for 100 sequential cycles. See DOI: 10.1039/c5nr05054e

Effect of added thiamine on the key odorant compounds and aroma of cooked ham.

PubMed

Thomas, Caroline; Mercier, Frédéric; Tournayre, Pascal; Martin, Jean-Luc; Berdagué, Jean-Louis

2015-04-15

This study shows that thiamine plays a major role in the formation of three key odorants of cooked ham: 2-methyl-3-furanthiol, 2-methyl-3-methyldithiofuran, and bis(2-methyl-3-furyl)disulphide. Analyses revealed that under identical cooking conditions, the productions of these three aroma compounds increase in a closely intercorrelated way when the dose of thiamine increases. Using a specific 2-methyl-3-furanthiol extraction-quantification method, it was possible to relate the amounts of thiamine added in model cooked hams to the amounts of 2-methyl-3-furanthiol produced in the cooking process. Sensory analyses highlighted the role of thiamine as a precursor of cooked ham aroma. Copyright © 2014 Elsevier Ltd. All rights reserved.

Identification of a new mutation in platelet glycoprotein IX (GPIX) in a patient with Bernard-Soulier syndrome.

PubMed

Rivera, C E; Villagra, J; Riordan, M; Williams, S; Lindstrom, K J; Rick, M E

2001-01-01

We describe a new mutation in glycoprotein IX (GPIX) in a patient with Bernard-Soulier syndrome (BSS). Sequencing of GPIX revealed a homozygous (T-->C) transition at nucleotide 1717 (GenBank/HUMGPIX/M80478), resulting in a Cys(8) (TGT)-->Arg (CGT) replacement in the mature peptide. DNA restriction enzyme analysis using BsaAI revealed that the patient was homozygous and that his parents were heterozygous for the defect. This mutation disrupts a putative disulphide bond between the Cys(8) and Cys(12) that would alter the secondary structure of GPIX and which probably accounts for the absence of the GPIb/IX/V complex from the platelet surface in this patient.

What Happens during Natural Protein Fibre Dissolution in Ionic Liquids.

PubMed

Chen, Jingyu; Vongsanga, Kylie; Wang, Xungai; Byrne, Nolene

2014-08-28

Here, we monitor the dissolution of several natural protein fibres such as wool, human hair and silk, in various ionic liquids (ILs). The dissolution of protein-based materials using ILs is an emerging area exploring the production of new materials from waste products. Wool is a keratin fibre, which is extensively used in the textiles industry and as a result has considerable amounts of waste produced each year. Wool, along with human hair, has a unique morphology whereby the outer layer, the cuticle, is heavily cross linked with disulphide bonds, whereas silk does not have this outer layer. Here we show how ILs dissolve natural protein fibres and how the mechanism of dissolution is directly related to the structure and morphology of the wool fibre.

Development of the MOOSY4 eNose IoT for Sulphur-Based VOC Water Pollution Detection

PubMed Central

Climent, Enric; Pelegri-Sebastia, Jose; Sogorb, Tomas; Talens, J. B.; Chilo, Jose

2017-01-01

In this paper, we describe a new low-cost and portable electronic nose instrument, the Multisensory Odor Olfactory System MOOSY4. This prototype is based on only four metal oxide semiconductor (MOS) gas sensors suitable for IoT technology. The system architecture consists of four stages: data acquisition, data storage, data processing, and user interfacing. The designed eNose was tested with experiment for detection of volatile components in water pollution, as a dimethyl disulphide or dimethyl diselenide or sulphur. Therefore, the results provide evidence that odor information can be recognized with around 86% efficiency, detecting smells unwanted in the water and improving the quality control in bottled water factories. PMID:28825645

Geraniol as a novel antivirulence agent against bacillary dysentery-causing Shigella sonnei.

PubMed

Mirza, Zainulabedeen R M H; Hasan, Thaer; Seidel, Veronique; Yu, Jun

2018-01-01

Antimicrobial resistance has emerged as a major challenge to modern medicine and it has become urgent to seek alternative approaches to treat infections caused by fast-evolving multi-resistant clones of bacillary dysentery-causing Shigella sonnei. Here, we show that geraniol, a natural substance present in the essential oils of plants such as rose and lemongrass, can reduce S. sonnei proliferation inside host cells and protect Galleria mellonella larvae from killing by S. sonnei infection. We present evidence that geraniol competitively inhibits the catalytic activity of the master virulence regulator, DsbA, a periplasmic disulphide bond oxidoreductase required for Shigella survival in the host cell cytosol. Our observations suggest that geraniol holds a great therapeutic potential that should be further exploited.

Nanocomposite TiN films with embedded MoS2 inorganic fullerenes produced by combining supersonic cluster beam deposition with cathodic arc reactive evaporation

NASA Astrophysics Data System (ADS)

Piazzoni, C.; Blomqvist, M.; Podestà, A.; Bardizza, G.; Bonati, M.; Piseri, P.; Milani, P.; Davies, C.; Hatto, P.; Ducati, C.; Sedláčková, K.; Radnóczi, G.

2008-01-01

We report the production and characterization of nanocomposite thin films consisting of a titanium nitride matrix with embedded molybdenum disulphide fullerene-like nanoparticles. This was achieved by combining a cluster source generating a pulsed supersonic beam of MoS2 clusters with an industrial cathodic arc reactive evaporation apparatus used for TiN deposition. Cluster-assembled films show the presence of MoS2 nanocages and nanostructures and the survival of such structures dispersed in the TiN matrix in the co-deposited samples. Nanotribological characterization by atomic force microscopy shows that the presence of MoS2 nanoparticles even in very low concentration modifies the behaviour of the TiN matrix.

Magnetoreflection spectroscopy of monolayer transition-metal dichalcogenide semiconductors in pulsed magnetic fields

DOE PAGES

Stier, Andreas V.; McCreary, Kathleen M.; Jonker, Berend T.; ...

2016-05-13

The authors describe recent experimental efforts to perform polarization-resolved optical spectroscopy of monolayer transition-metal dichalcogenide semiconductors in very large pulsed magnetic fields to 65 T. The experimental setup and technical challenges are discussed in detail, and temperature-dependent magnetoreflection spectra from atomically thin tungsten disulphide are presented. The data clearly reveal not only the valley Zeeman effect in these two-dimensional semiconductors but also the small quadratic exciton diamagnetic shift from which the very small exciton size can be directly inferred. Lastly, the authors present model calculations that demonstrate how the measured diamagnetic shifts can be used to constrain estimates of themore » exciton binding energy in this new family of monolayer semiconductors.« less

Antibacterial peptides from plants: what they are and how they probably work.

PubMed

Barbosa Pelegrini, Patrícia; Del Sarto, Rafael Perseghini; Silva, Osmar Nascimento; Franco, Octávio Luiz; Grossi-de-Sa, Maria Fátima

2011-01-01

Plant antibacterial peptides have been isolated from a wide variety of species. They consist of several protein groups with different features, such as the overall charge of the molecule, the content of disulphide bonds, and structural stability under environmental stress. Although the three-dimensional structures of several classes of plant peptides are well determined, the mechanism of action of some of these molecules is still not well defined. However, further studies may provide new evidences for their function on bacterial cell wall. Therefore, this paper focuses on plant peptides that show activity against plant-pathogenic and human-pathogenic bacteria. Furthermore, we describe the folding of several peptides and similarities among their three-dimensional structures. Some hypotheses for their mechanisms of action and attack on the bacterial membrane surface are also proposed.

Microscopic origin of low frequency noise in MoS{sub 2} field-effect transistors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghatak, Subhamoy; Jain, Manish; Ghosh, Arindam

2014-09-01

We report measurement of low frequency 1/f noise in molybdenum di-sulphide (MoS{sub 2}) field-effect transistors in multiple device configurations including MoS{sub 2} on silicon dioxide as well as MoS{sub 2}-hexagonal boron nitride (hBN) heterostructures. All as-fabricated devices show similar magnitude of noise with number fluctuation as the dominant mechanism at high temperatures and density, although the calculated density of traps is two orders of magnitude higher than that at the SiO{sub 2} interface. Measurements on the heterostructure devices with vacuum annealing and dual gated configuration reveals that along with the channel, metal-MoS{sub 2} contacts also play a significant role inmore » determining noise magnitude in these devices.« less

Solid-Lubricant, Polymer - Polymeric and Functionalized Fiber- and Powder Reinforced Composites of Ultra-High Molecular Weight Polyethylene

NASA Astrophysics Data System (ADS)

Panin, S. V.; Alexenko, V. O.; Buslovich, D. G.; Anh, Nguyen Duc; Qitao, Huang

2018-01-01

Mechanical and tribotechnical characteristics of solid-lubricant and polymer-polymeric composites of UHMWPE were studied for the sake of design extrudable, wear-resistant, self-lubricant polymer mixtures for Additive Manufacturing (AM). Tribotechnical properties of UHMWPE blends with the optimized content of solid lubricant fillers (polytetrafluoroethylene, calcium stearate, molybdenum disulphide, colloidal graphite, boron nitride) were studied under dry sliding friction at different velocities (V = 0.3 and 0.5 m/s) and loads (P = 60 and 140 N). Also, in order to increase strength and wear-resistance of UHMWPE composites they were reinforced with wollastonite microfibers and aluminum metahydroxide AlO (OH) microparticles preliminary treated (functionalized) in polyorganosiloxane. The comparison on measured mechanical and tribotechnical properties are given with interpretation of the mechanisms of observed phenomenon.

Essential oil composition and antiradical activity of the oil of Iraq plants.

PubMed

Kiralan, Mustafa; Bayrak, Ali; Abdulaziz, Omar Fawzi; Ozbucak, Tuğba

2012-01-01

This study examined the antiradical activity and chemical composition of essential oils of some plants grown in Mosul, Iraq. The essential oils of myrtle and parsley seed contained α-pinene (36.08% and 22.89%, respectively) as main constituents. Trans-Anethole was the major compound found in fennel and aniseed oils (66.98% and 93.51%, respectively). The dominant constituent of celery seed oil was limonene (76.63%). Diallyl disulphide was identified as the major component in garlic oil (36.51%). Antiradical activity was higher in garlic oil (76.63%) and lower in myrtle oil (39.23%). The results may suggest that some essential oils from Iraq possess compounds with antiradical activity, and these oils can be used as natural antioxidants in food applications.

What Happens during Natural Protein Fibre Dissolution in Ionic Liquids

PubMed Central

Chen, Jingyu; Vongsanga, Kylie; Wang, Xungai; Byrne, Nolene

2014-01-01

Here, we monitor the dissolution of several natural protein fibres such as wool, human hair and silk, in various ionic liquids (ILs). The dissolution of protein-based materials using ILs is an emerging area exploring the production of new materials from waste products. Wool is a keratin fibre, which is extensively used in the textiles industry and as a result has considerable amounts of waste produced each year. Wool, along with human hair, has a unique morphology whereby the outer layer, the cuticle, is heavily cross linked with disulphide bonds, whereas silk does not have this outer layer. Here we show how ILs dissolve natural protein fibres and how the mechanism of dissolution is directly related to the structure and morphology of the wool fibre. PMID:28788183

The friction coefficient evolution of a MoS2/WC multi-layer coating system during sliding wear

NASA Astrophysics Data System (ADS)

Chan, T. Y.; Hu, Y.; Gharbi, Mohammad M.; Politis, D. J.; Wang, L.

2016-08-01

This paper discusses the evolution of friction coefficient for the multi-layered Molybdenum Disulphide (MoS2) and WC coated substrate during sliding against Aluminium AA 6082 material. A soft MoS2 coating was prepared over a hard WC coated G3500 cast iron tool substrate and underwent friction test using a pin-on-disc tribometer. The lifetime of the coating was reduced with increasing load while the Aluminium debris accumulated on the WC hard coating surfaces, accelerated the breakdown of the coatings. The lifetime of the coating was represented by the friction coefficient and the sliding distance before MoS2 coating breakdown and was found to be affected by the load applied and the wear mechanism.

Untying a nanoscale knotted polymer structure to linear chains for efficient gene delivery in vitro and to the brain

NASA Astrophysics Data System (ADS)

Newland, B.; Aied, A.; Pinoncely, A. V.; Zheng, Y.; Zhao, T.; Zhang, H.; Niemeier, R.; Dowd, E.; Pandit, A.; Wang, W.

2014-06-01

The purpose of this study was to develop a platform transfection technology, for applications in the brain, which could transfect astrocytes without requiring cell specific functionalization and without the common cause of toxicity through high charge density. Here we show that a simple and scalable preparation technique can be used to produce a ``knot'' structured cationic polymer, where single growing chains can crosslink together via disulphide intramolecular crosslinks (internal cyclizations). This well-defined knot structure can thus ``untie'' under reducing conditions, showing a more favorable transfection profile for astrocytes compared to 25 kDa-PEI (48-fold), SuperFect® (39-fold) and Lipofectamine®2000 (18-fold) whilst maintaining neural cell viability at over 80% after four days of culture. The high transfection/lack of toxicity of this knot structured polymer in vitro, combined with its ability to mediate luciferase transgene expression in the adult rat brain, demonstrates its use as a platform transfection technology which should be investigated further for neurodegenerative disease therapies.The purpose of this study was to develop a platform transfection technology, for applications in the brain, which could transfect astrocytes without requiring cell specific functionalization and without the common cause of toxicity through high charge density. Here we show that a simple and scalable preparation technique can be used to produce a ``knot'' structured cationic polymer, where single growing chains can crosslink together via disulphide intramolecular crosslinks (internal cyclizations). This well-defined knot structure can thus ``untie'' under reducing conditions, showing a more favorable transfection profile for astrocytes compared to 25 kDa-PEI (48-fold), SuperFect® (39-fold) and Lipofectamine®2000 (18-fold) whilst maintaining neural cell viability at over 80% after four days of culture. The high transfection/lack of toxicity of this knot structured polymer in vitro, combined with its ability to mediate luciferase transgene expression in the adult rat brain, demonstrates its use as a platform transfection technology which should be investigated further for neurodegenerative disease therapies. Electronic supplementary information (ESI) available: 1H NMR spectroscopy data and gel permeation chromatography data. See DOI: 10.1039/c3nr06737h

Odorous gaseous emissions as influence by process condition for the forced aeration composting of pig slaughterhouse sludge.

PubMed

Blazy, V; de Guardia, A; Benoist, J C; Daumoin, M; Lemasle, M; Wolbert, D; Barrington, S

2014-07-01

Compost sustainability requires a better control of its gaseous emissions responsible for several impacts including odours. Indeed, composting odours have stopped the operation of many platforms and prevented the installation of others. Accordingly, present technologies collecting and treating gases emitted from composting are not satisfactory and alternative solutions must be found. Thus, the aim of this paper was to study the influence of composting process conditions on gaseous emissions. Pig slaughterhouse sludge mixed with wood chips was composted under forced aerationin 300 L laboratory reactors. The process conditions studied were: aeration rate of 1.68, 4.03, 6.22, 9.80 and 13.44 L/h/kg of wet sludge; incorporation ratio of 0.55, 0.83 and 1.1 (kg of wet wood chips/kg of wet sludge), and; bulking agent particles size of <10, 10<20 and 20<30 mm. Out-going gases were sampled every 2 days and their composition was analysed using gas chromatography coupled with mass spectrometry (GC-MS). Fifty-nine compounds were identified and quantified. Dividing the cumulated mass production over 30 days of composting, by odour threshold, 9 compounds were identified as main potential odour contributors: hydrogen sulphide, trimethylamine, ammonia, 2-pentanone, 1-propanol-2-methyl, dimethyl sulphide, dimethyl disulphide, dimethyl trisulphide and acetophenone. Five gaseous compounds were correlated with both aeration rate and bulking agent to waste ratio: hydrogen sulphide, trimethylamine, ammonia, 2-pentanone and 1-propanol-2-methyl. However, dropping the aeration rate and increasing the bulking agent to waste ratio reduced gaseous odour emissions by a factor of 5-10, when the required threshold dilution factor ranged from 10(5) to 10(6), to avoid nuisance at peak emission rates. Process influence on emissions of dimethyl sulphide, dimethyl disulphide, dimethyl trisulphide were poorly correlated with both aeration rate and bulking agent to waste ratio as a reaction with hydrogen sulphide was suspected. Acetophenone emissions originated from the wood chips. Olfactory measurements need to be correlated to gaseous emissions for a more accurate odour emission evaluation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Role of individual cysteine residues in the processing and antigenicity of the measles virus haemagglutinin protein.

PubMed

Hu, A; Norrby, E

1994-09-01

The haemagglutinin (H) protein is the dominant envelope glycoprotein of measles virus. The protein contains 13 cysteine residues among its 617 amino acids and all are located in its ectodomain. In previous studies, the capacity of a panel of monoclonal antibodies (MAbs) to react with continuous and discontinuous epitopes was defined. It was shown that the absence of disulphide bonds impaired the capacity of the protein to react with MAbs specific for the discontinuous epitopes. In the present study, our objective was to determine the contribution of individual cysteine residues to the folding of H protein into its native conformation. Site-directed oligonucleotide mutagenesis was used to create 13 mutants, each with a serine replacing a cysteine. The mutated genes were directly expressed in the BHK-21 cells by use of a vaccinia virus-driven T7 polymerase system. Investigations of the antigenic structure and intracellular processing properties of the mutant proteins reveal the following outcome. (i) Replacements of cysteine residues 139, 154, 188, 386, 570 or 606 had no detectable effect on the antigenic structure and intracellular processing of the H protein. However, a mutant with a replaced cysteine residue 154 displayed modified migration properties. (ii) Alterations of cysteine residues 381 or 494 displayed a moderate effect on H protein properties. The two mutants expressed discontinuous epitopes, indicating that they were partially folded, but they did not oligomerize, did not reach the medial Golgi complex and failed to be transported to the cell surface. (iii) Substitutions of cysteine residues 287, 300, 394, 579 or 583 resulted in a complete loss of binding of the MAbs that recognize the discontinuous epitopes, with no effect on the binding of a MAb reacting with a continuous epitope. No dimeric form of the proteins was observed and only high mannose oligosaccharides were demonstrated in these mutants, suggesting that the modified proteins did not oligomerize and were retained in the endoplasmic reticulum. In conclusion, cysteine residues 287, 300, 381, 394, 494, 579 and 583 appear to play a particularly critical role in the antigenic structure and processing of the H molecules and they probably participate in the inter- or intramolecular disulphide bonding.

Industrial grade 2D molybdenum disulphide (MoS2): an in vitro exploration of the impact on cellular uptake, cytotoxicity, and inflammation

NASA Astrophysics Data System (ADS)

Moore, Caroline; Movia, Dania; Smith, Ronan J.; Hanlon, Damien; Lebre, Filipa; Lavelle, Ed C.; Byrne, Hugh J.; Coleman, Jonathan N.; Volkov, Yuri; McIntyre, Jennifer

2017-06-01

The recent surge in graphene research, since its liquid phase monolayer isolation and characterization in 2004, has led to advancements which are accelerating the exploration of alternative 2D materials such as molybdenum disulphide (MoS2), whose unique physico-chemical properties can be exploited in applications ranging from cutting edge electronic devices to nanomedicine. However, to assess any potential impact on human health and the environment, the need to understand the bio-interaction of MoS2 at a cellular and sub-cellular level is critical. Notably, it is important to assess such potential impacts of materials which are produced by large scale production techniques, rather than research grade materials. The aim of this study was to explore cytotoxicity, cellular uptake and inflammatory responses in established cell-lines that mimic different potential exposure routes (inhalation, A549; ingestion, AGS; monocyte, THP-1) following incubation with MoS2 flakes of varying sizes (50 nm, 117 nm and 177 nm), produced by liquid phase exfoliation. Using high content screening (HCS) and Live/Dead assays, it was established that 1 µg ml-1 (for the three different MoS2 sizes) did not induce toxic effects on any of the cell-lines. Confocal microscopy images revealed a normal cellular morphology in all cases. Transmission electron microscopy (TEM) confirmed the uptake of all MoS2 nanomaterials in all the cell-lines, the MoS2 ultimately locating in single membrane vesicles. At such sub-lethal doses, inflammatory responses are observed, however, associated, at least partially, with the presence of lipopolysaccharide endotoxin in nanomaterial suspensions and surfactant samples. Therefore, the inflammatory response of the cells to the MoS2 or endotoxin contamination was interrogated using a 10-plex ELISA which illustrates cytokine production. The experiments carried out using wild-type and endotoxin hyporesponsive bone marrow derived dendritic cells confirmed that the inflammatory responses result from a combination of endotoxin contamination, the MoS2 nanomaterials themselves, and the stabilizing surfactant.

Evolution Stings: The Origin and Diversification of Scorpion Toxin Peptide Scaffolds

PubMed Central

Sunagar, Kartik; Undheim, Eivind A. B.; Chan, Angelo H. C.; Koludarov, Ivan; Muñoz-Gómez, Sergio A.; Antunes, Agostinho; Fry, Bryan G.

2013-01-01

The episodic nature of natural selection and the accumulation of extreme sequence divergence in venom-encoding genes over long periods of evolutionary time can obscure the signature of positive Darwinian selection. Recognition of the true biocomplexity is further hampered by the limited taxon selection, with easy to obtain or medically important species typically being the subject of intense venom research, relative to the actual taxonomical diversity in nature. This holds true for scorpions, which are one of the most ancient terrestrial venomous animal lineages. The family Buthidae that includes all the medically significant species has been intensely investigated around the globe, while almost completely ignoring the remaining non-buthid families. Australian scorpion lineages, for instance, have been completely neglected, with only a single scorpion species (Urodacus yaschenkoi) having its venom transcriptome sequenced. Hence, the lack of venom composition and toxin sequence information from an entire continent’s worth of scorpions has impeded our understanding of the molecular evolution of scorpion venom. The molecular origin, phylogenetic relationships and evolutionary histories of most scorpion toxin scaffolds remain enigmatic. In this study, we have sequenced venom gland transcriptomes of a wide taxonomical diversity of scorpions from Australia, including buthid and non-buthid representatives. Using state-of-art molecular evolutionary analyses, we show that a majority of CSα/β toxin scaffolds have experienced episodic influence of positive selection, while most non-CSα/β linear toxins evolve under the extreme influence of negative selection. For the first time, we have unraveled the molecular origin of the major scorpion toxin scaffolds, such as scorpion venom single von Willebrand factor C-domain peptides (SV-SVC), inhibitor cystine knot (ICK), disulphide-directed beta-hairpin (DDH), bradykinin potentiating peptides (BPP), linear non-disulphide bridged peptides and antimicrobial peptides (AMP). We have thus demonstrated that even neglected lineages of scorpions are a rich pool of novel biochemical components, which have evolved over millions of years to target specific ion channels in prey animals, and as a result, possess tremendous implications in therapeutics. PMID:24351712

Interaction between synthetic analogues of quinoxaline antibiotics and nucleic acids: role of the disulphide cross-bridge and D-amino acid centres in des-N-tetramethyl-triostin A.

PubMed Central

Fox, K. R.; Olsen, R. K.; Waring, M. J.

1980-01-01

1 [Ala3, Ala7] TANDEM is an analogue of des-N-tetramethyl-triostin A (TANDEM) in which both L-Cys residues of the octapeptide ring are replaced by L-Ala; accordingly it lacks the disulphide cross-bridge which limits the conformational flexibility of TANDEM. 2 In [L-Ser1] TANDEM the configuration of one of the serine residues is inverted, altering the disposition of one of the quinoxaline chromophores with respect to the peptide ring. 3 Both compounds interact weakly but detectably with natural DNAs as judged by spectral shifts and increases in the thermal denaturation ('melting') temperature Tm. They also raise the Tm of poly rA . poly rU. 4 Binding isotherms determined by solvent partition analysis with [Ala3, Ala7] TANDEM yield association constants of about 10(3) M-1 for its interaction with natural DNAs. A Scatchard plot for binding to poly(dA-dT) determined by solvent partition and spectrophotometric methods shows marked evidence of cooperativity with an intrinsic association constant 1.9 x 10(4) M-1, 8.7 nucleotides per binding site, and cooperativity parameter 15. 5 Binding of [Ala3, Ala7] TANDEM to short rod-like fragments of poly(dA-dT) increases their contour length by almost the theoretical amount expected for an ideal process of bifunctional intercalation. 6 No effect of either compound on the winding of the DNA helix could be detected in sedimentation experiments with closed circular duplex PM2 DNA. 7 It is concluded that the cross-bridge of TANDEM greatly stabilizes its binding to DNA, most probably via entropic factors, but is not the only structural feature that influences its AT sequence-selectivity. The consequences of epimerising one of the D-Ser residues appear as disastrous as epimerising both. 8 The experimental details for the synthesis of [Ala3, Ala7] TANDEM and [L-Ser1] TANDEM are given in an appendix to this paper. PMID:7426829

Tryptic digestion of human GPIIIa. Isolation and biochemical characterization of the 23 kDa N-terminal glycopeptide carrying the antigenic determinant for a monoclonal antibody (P37) which inhibits platelet aggregation.

PubMed Central

Calvete, J J; Rivas, G; Maruri, M; Alvarez, M V; McGregor, J L; Hew, C L; Gonzalez-Rodriguez, J

1988-01-01

Early digestion of pure human platelet glycoprotein IIIa (GPIIIa) leads to a single cleavage of the molecule at 23 kDa far from one of the terminal amino acids. Automated Edman degradation demonstrates that GPIIIa and the smaller (23 kDa) tryptic fragment share the same N-terminal amino acid sequence. A further cleavage occurs in the larger fragment (80 kDa), reducing its apparent molecular mass by 10 kDa. The 23 kDa fragment remains attached to the larger ones in unreduced samples. Stepwise reduction of early digested GPIIIa with dithioerythritol selectively reduces the single disulphide bond joining the smaller (23 kDa) to the larger (80/70 kDa) fragments. Two fractions were obtained by size-exclusion chromatography of early digested GPIIIa after partial or full reduction and alkylation. The larger-size fraction contains the 80/70 kDa fragments, while the 23 kDa fragment is isolated in the smaller. The amino acid compositions of these fractions do not differ very significantly from the composition of GPIIIa; however the 23 kDa fragment contains only 10.2% by weight of sugars and is richer in neuraminic acid. Disulphide bonds are distributed four in the 23 kDa glycopeptide and 20-21 in the 80/70 kDa glycopeptide. The epitope for P37, a monoclonal antibody which inhibits platelet aggregation [Melero & González-Rodríguez (1984) Eur. J. Biochem. 141, 421-427] is situated within the first 17 kDa of the N-terminal region of GPIIIa, which gives a special functional interest to this extracellular region of GPIIIa. On the other hand, the epitopes for GPIIIa-specific monoclonal antibodies, P6, P35, P40 and P97, which do not interfere with platelet aggregation, are located within the larger tryptic fragment (80/70 kDa). Thus, the antigenic areas available in the extracellular surface of GPIIIa for these five monoclonal antibodies are now more precisely delineated. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:2455507

2D molybdenum disulphide (2D-MoS2) modified electrodes explored towards the oxygen reduction reaction.

PubMed

Rowley-Neale, Samuel J; Fearn, Jamie M; Brownson, Dale A C; Smith, Graham C; Ji, Xiaobo; Banks, Craig E

2016-08-21

Two-dimensional molybdenum disulphide nanosheets (2D-MoS2) have proven to be an effective electrocatalyst, with particular attention being focused on their use towards increasing the efficiency of the reactions associated with hydrogen fuel cells. Whilst the majority of research has focused on the Hydrogen Evolution Reaction (HER), herein we explore the use of 2D-MoS2 as a potential electrocatalyst for the much less researched Oxygen Reduction Reaction (ORR). We stray from literature conventions and perform experiments in 0.1 M H2SO4 acidic electrolyte for the first time, evaluating the electrochemical performance of the ORR with 2D-MoS2 electrically wired/immobilised upon several carbon based electrodes (namely; Boron Doped Diamond (BDD), Edge Plane Pyrolytic Graphite (EPPG), Glassy Carbon (GC) and Screen-Printed Electrodes (SPE)) whilst exploring a range of 2D-MoS2 coverages/masses. Consequently, the findings of this study are highly applicable to real world fuel cell applications. We show that significant improvements in ORR activity can be achieved through the careful selection of the underlying/supporting carbon materials that electrically wire the 2D-MoS2 and utilisation of an optimal mass of 2D-MoS2. The ORR onset is observed to be reduced to ca. +0.10 V for EPPG, GC and SPEs at 2D-MoS2 (1524 ng cm(-2) modification), which is far closer to Pt at +0.46 V compared to bare/unmodified EPPG, GC and SPE counterparts. This report is the first to demonstrate such beneficial electrochemical responses in acidic conditions using a 2D-MoS2 based electrocatalyst material on a carbon-based substrate (SPEs in this case). Investigation of the beneficial reaction mechanism reveals the ORR to occur via a 4 electron process in specific conditions; elsewhere a 2 electron process is observed. This work offers valuable insights for those wishing to design, fabricate and/or electrochemically test 2D-nanosheet materials towards the ORR.

Evolutionary Determinants of Morphological Polymorphism in Colonial Animals.

PubMed

Simpson, Carl; Jackson, Jeremy B C; Herrera-Cubilla, Amalia

2017-07-01

Colonial animals commonly exhibit morphologically polymorphic modular units that are phenotypically distinct and specialize in specific functional tasks. But how and why these polymorphic modules have evolved is poorly understood. Across colonial invertebrates, there is wide variation in the degree of polymorphism, from none in colonial ascidians to extreme polymorphism in siphonophores, such as the Portuguese man-of-war. Bryozoa are a phylum of exclusively colonial invertebrates that uniquely exhibit almost the entire range of polymorphism, from monomorphic species to others that rival siphonophores in their polymorphic complexity. Previous approaches to understanding the evolution of polymorphism have been based on analyses of (1) the functional role of polymorphs or (2) presumed evolutionary costs and benefits based on evolutionary theory that postulates polymorphism should be evolutionarily sustainable only in more stable environments because polymorphism commonly leads to the loss of feeding and sexual competence. Here we use bryozoans from opposite shores of the Isthmus of Panama to revisit the environmental hypothesis by comparison of faunas from distinct oceanographic provinces that differ greatly in environmental variability, and we then examine the correlations between the extent of polymorphism in relation to patterns of ecological succession and variation in life histories. We find no support for the environmental hypothesis. Distributions of the incidence of polymorphism in the oceanographically unstable Eastern Pacific are indistinguishable from those in the more stable Caribbean. In contrast, the temporal position of species in a successional sequence is collinear with the degree of polymorphism because species with fewer types of polymorphs are competitively replaced by species with higher numbers of polymorphs on the same substrata. Competitively dominant species also exhibit patterns of growth that increase their competitive ability. The association between degrees of polymorphism and variations in life histories is fundamental to understanding of the macroevolution of polymorphism.

Characterization of a novel glycine-rich protein from the cell wall of maize silk tissues.

PubMed

Tao, T Y; Ouellet, T; Dadej, K; Miller, S S; Johnson, D A; Singh, J

2006-08-01

The isolation, characterization and regulation of expression of a maize silk-specific gene is described. zmgrp5 (Zea mays glycine-rich protein 5) encodes a 187 amino acid glycine-rich protein that displays developmentally regulated silk-specific expression. Northern, Western, in situ mRNA hybridization and transient gene expression analyses indicate that zmgrp5 is expressed in silk hair and in cells of the vascular bundle and pollen tube transmitting tissue elements. The protein is secreted into the extracellular matrix and is localized in the cell wall fraction mainly through interactions mediated by covalent disulphide bridges. Taken together, these results suggest that the protein may play a role in maintaining silk structure during development. This is the first documented isolation of a stigma-specific gene from maize, an important agronomic member of the Poaceae family.

The MillSOT-A Spiral Orbit Tribometer on a Milling Machine

NASA Technical Reports Server (NTRS)

Pepper, Stephen V.

2014-01-01

A spiral orbit tribometer (SOT) intended to characterize friction and wear phenomena has been constructed on a milling machine. The instrument, essentially a retainerless thrust bearing with one ball and flat races, is exceedingly simple and inexpensive to construct. The capabilities of the tribometer to measure both the coefficient of friction and contact electrical resistance are demonstrated with clean specimens as well as with well known lubricants such as molybdenum disulphide and Krytox oil. Operation in a purged environment of inert gas is also demonstrated. The results with these lubricants are quite close to what is obtained by other methods. Suggestions for extending the capabilities of the tribometer are given. This arrangement may find use in university mechanical engineering laboratories to introduce and study rolling contact motion as well as for research in contact mechanics and tribology.

Protein characterization of protein bodies from cotyledons of Mucuna pruriens (L.) DC.

PubMed

Bellani, Lorenza; Giglioni, Stefania; Muccifora, Simonetta

2013-03-01

Seeds of Mucuna pruriens (L.) DC. (Fabaceae) were analyzed for protein composition of protein bodies isolated from cotyledons. Protein bodies were successfully separated by Lympholyte and those of dry seeds, observed by scanning electron microscope, were elliptical or spherical in shape with a diameter of 5-12 μm. Protein content in dry seed protein bodies was 10.6 mg/g dry weight. Globulin was the largest protein fraction isolated (62.5 %), followed by albumin (18.3 %), glutelin (15.8 %) and prolamin (3.4 %). The prolamin fraction and high glutelin content are uncommon in legumes. SDS-PAGE of albumins, globulins, prolamins and glutelins provided different band numbers and molecular weights under reducing and non reducing conditions and suggested that the albumin fraction is rich in disulphide bonds.

The application of UV LEDs for differential optical absorption spectroscopy

NASA Astrophysics Data System (ADS)

Geiko, Pavel P.; Smirnov, Sergey S.; Samokhvalov, Ignatii V.

2018-04-01

Modern UV LEDs represent a potentially very advantageous alternative to thermal light sources, in particular xenon arc lamps, which are the most common light sources in trace gas-analyzers. So, the light-emitting diodes are very attractive for use of as light sources for Long Path Differential Optical Absorption Spectroscopy (DOAS) measurements of trace gases in the open atmosphere. Recent developments in fibre-coupling telescope technology and the availability of ultraviolet light emitting diodes have now allowed us to construct a portable, long path DOAS instrument for use at remote locations and specifically for measuring degassing from active volcanic systems. First of all, we are talking about the measurement of sulphur dioxide, carbon disulphide and, oxides of chlorine and bromine. The parallel measurements of sulfur dioxide using a certified gas analyzer, were conducted and showed good correlation.

Identifying disease polymorphisms from case-control genetic association data.

PubMed

Park, L

2010-12-01

In case-control association studies, it is typical to observe several associated polymorphisms in a gene region. Often the most significantly associated polymorphism is considered to be the disease polymorphism; however, it is not clear whether it is the disease polymorphism or there is more than one disease polymorphism in the gene region. Currently, there is no method that can handle these problems based on the linkage disequilibrium (LD) relationship between polymorphisms. To distinguish real disease polymorphisms from markers in LD, a method that can detect disease polymorphisms in a gene region has been developed. Relying on the LD between polymorphisms in controls, the proposed method utilizes model-based likelihood ratio tests to find disease polymorphisms. This method shows reliable Type I and Type II error rates when sample sizes are large enough, and works better with re-sequenced data. Applying this method to fine mapping using re-sequencing or dense genotyping data would provide important information regarding the genetic architecture of complex traits.

Polymorphism in molecular solids: an extraordinary system of red, orange, and yellow crystals.

PubMed

Yu, Lian

2010-09-21

Diamond and graphite are polymorphs of each other: they have the same composition but different structures and properties. Many other substances exhibit polymorphism: inorganic and organic, natural and manmade. Polymorphs are encountered in studies of crystallization, phase transition, materials synthesis, and biomineralization and in the manufacture of specialty chemicals. Polymorphs can provide valuable insights into crystal packing and structure-property relationships. 5-Methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile, known as ROY for its red, orange, and yellow crystals, has seven polymorphs with solved structures, the largest number in the Cambridge Structural Database. First synthesized by medicinal chemists, ROY has attracted attention from solid-state chemists because it demonstrates the remarkable diversity possible in organic solids. Many structures of ROY polymorphs and their thermodynamic properties are known, making ROY an important model system for testing computational models. Though not the most polymorphic substance on record, ROY is extraordinary in that many of its polymorphs can crystallize simultaneously from the same liquid and are kinetically stable under the same conditions. Studies of ROY polymorphs have revealed a new crystallization mechanism that invalidates the common view that nucleation defines the polymorph of crystallization. A slow-nucleating polymorph can still dominate the product if it grows rapidly and nucleates on another polymorph. Studies of ROY have also helped understand a new, surprisingly fast mode of crystal growth in organic liquids cooled to the glass transition temperature. This growth mode exists only for those polymorphs that have more isotropic, and perhaps more liquid-like, packing. The rich polymorphism of ROY results from a combination of favorable thermodynamics and kinetics. Not only must there be many polymorphs of comparable energies or free energies, many polymorphs must be kinetically stable and crystallize at comparable rates to be observed. This system demonstrates the unique insights that polymorphism provides into solid-state structures and properties, as well as the inadequacy of our current understanding of the phenomenon. Despite many studies of ROY, it is still impossible to predict the next molecule that is equally or more polymorphic. ROY is a lucky gift from medicinal chemists.

Rivastigmine hydrogen tartrate polymorphs: Solid-state characterisation of transition and polymorphic conversion via milling

NASA Astrophysics Data System (ADS)

Amaro, Maria Inês; Simon, Alice; Cabral, Lúcio Mendes; de Sousa, Valéria Pereira; Healy, Anne Marie

2015-11-01

Rivastigmine (RHT) is an active pharmaceutical ingredient that is used for the treatment of mild to moderately severe dementia in Alzheimer's disease, and is known to present two polymorphic forms and to amorphise upon granulation. To date there is no information in the scientific or patent literature on polymorphic transition and stability. Hence, the aim of the current study was to gain a fundamental understanding of the polymorphic forms by (1) evaluating RHT thermodynamic stability (monotropy or enantiotropy) and (2) investigating the potential for polymorphic transformation upon milling. The two polymorphic and amorphous forms were characterised using X-ray powder diffractometry, thermal analyses, infra-red spectroscopy and water sorption analysis. The polymorphic transition was found to be spontaneous (ΔG0 < 0) and exothermic (ΔH0 < 0), indicative of a monotropic polymorph pair. The kinetic studies showed a fast initial polymorphic transition characterised by a heterogeneous nucleation, followed by a slow crystal growth. Ball milling can be used to promote the polymorphic transition and for the production of RHT amorphous form.

Thermal, spectroscopic and structural characterization of isostructural phase transition in 4-hydroxybenzaldehyde

NASA Astrophysics Data System (ADS)

Panicker, Lata

2018-05-01

Polycrystalline samples of 4-hydroxybenzaldehyde (4-HOBAL) were investigated using differential scanning calorimeter (DSC), Raman spectroscopy and X-ray powder diffraction. The DSC data indicated that 4-HOBAL on heating undergoes a polymorphic transformation from polymorph I to polymorph II. The polymorph II formed remains metastable at ambient condition and transforms to polymorph I when annealed at ambient temperature for more than seven days. The structural information of polymorphs I and II obtained using its X-ray powder diffraction patterns indicated that 4-HOBAL undergoes an isostructural phase transition from polymorph I (monoclinic, P21/c) to polymorph II (monoclinic, P21/c). Raman data suggest that this structural change is associated with some change in its molecular interactions. Thus, in 4-HOBAL the polymorphic phase transformation (II to I) even though energetically favoured is kinetically hindered.

Thermal, spectroscopic, and ab initio structural characterization of carprofen polymorphs.

PubMed

Bruni, Giovanna; Gozzo, Fabia; Capsoni, Doretta; Bini, Marcella; Macchi, Piero; Simoncic, Petra; Berbenni, Vittorio; Milanese, Chiara; Girella, Alessandro; Ferrari, Stefania; Marini, Amedeo

2011-06-01

Commercial and recrystallized polycrystalline samples of carprofen, a nonsteroidal anti-inflammatory drug, were studied by thermal, spectroscopic, and structural techniques. Our investigations demonstrated that recrystallized sample, stable at room temperature (RT), is a single polymorphic form of carprofen (polymorph I) that undergoes an isostructural polymorphic transformation by heating (polymorph II). Polymorph II remains then metastable at ambient conditions. Commercial sample is instead a mixture of polymorphs I and II. The thermodynamic relationships between the two polymorphs were determined through the construction of an energy/temperature diagram. The ab initio structural determination performed on synchrotron X-Ray powder diffraction patterns recorded at RT on both polymorphs allowed us to elucidate, for the first time, their crystal structure. Both crystallize in the monoclinic space group type P2(1) /c, and the unit cell similarity index and the volumetric isostructurality index indicate that the temperature-induced polymorphic transformation I → II is isostructural. Polymorphs I and II are conformational polymorphs, sharing a very similar hydrogen bond network, but with different conformation of the propanoic skeleton, which produces two different packing. The small conformational change agrees with the low value of transition enthalpy obtained by differential scanning calorimetry measurements and the small internal energy computed with density functional methods. Copyright © 2011 Wiley-Liss, Inc.

Altering the Polymorphic Accessibility of Polycyclic Aromatic Hydrocarbons with Fluorination

DOE PAGES

Hiszpanski, Anna M.; Woll, Arthur R.; Kim, Bumjung; ...

2017-04-25

Here, substituting hydrogen with fluorine is an extensively employed strategy to improve the macroscopic properties of compounds for use in fields as diverse as pharmaceutics and optoelectronics. The role fluorine substitution plays on polymorphism—the ability of a compound to adopt more than one crystal structure—has not been previously studied. Yet, this understanding is important as different polymorphs of the same compound can result in drastically different bulk properties (e.g., solubility, absorptivity, and conductivity). Strategies to either promote or suppress the crystallization of particular polymorphs are thus desired. Here, we show that substituting hydrogen with fluorine affects the polymorphic behavior ofmore » contorted hexabenzocoronene (cHBC). A polycyclic aromatic hydrocarbon and molecular semiconductor, cHBC exhibits two polymorphs (i.e., P2 1/c crystal structure which we refer to as polymorph I and a triclinic crystal structure which we refer to as polymorph II) that are accessible through postdeposition processing of amorphous films. While the same two polymorphs remain accessible in fluorinated derivatives of cHBC, fluorination appears to favor the formation of polymorph I, with progressively smaller energy barrier for transformation from polymorph II to polymorph I with fluorination.« less

Altering the Polymorphic Accessibility of Polycyclic Aromatic Hydrocarbons with Fluorination

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hiszpanski, Anna M.; Woll, Arthur R.; Kim, Bumjung

Here, substituting hydrogen with fluorine is an extensively employed strategy to improve the macroscopic properties of compounds for use in fields as diverse as pharmaceutics and optoelectronics. The role fluorine substitution plays on polymorphism—the ability of a compound to adopt more than one crystal structure—has not been previously studied. Yet, this understanding is important as different polymorphs of the same compound can result in drastically different bulk properties (e.g., solubility, absorptivity, and conductivity). Strategies to either promote or suppress the crystallization of particular polymorphs are thus desired. Here, we show that substituting hydrogen with fluorine affects the polymorphic behavior ofmore » contorted hexabenzocoronene (cHBC). A polycyclic aromatic hydrocarbon and molecular semiconductor, cHBC exhibits two polymorphs (i.e., P2 1/c crystal structure which we refer to as polymorph I and a triclinic crystal structure which we refer to as polymorph II) that are accessible through postdeposition processing of amorphous films. While the same two polymorphs remain accessible in fluorinated derivatives of cHBC, fluorination appears to favor the formation of polymorph I, with progressively smaller energy barrier for transformation from polymorph II to polymorph I with fluorination.« less

Lack of association between the BIM deletion polymorphism and the risk of lung cancer with and without EGFR mutations.

PubMed

Ebi, Hiromichi; Oze, Isao; Nakagawa, Takayuki; Ito, Hidemi; Hosono, Satoyo; Matsuda, Fumihiko; Takahashi, Meiko; Takeuchi, Shinji; Sakao, Yukinori; Hida, Toyoaki; Faber, Anthony C; Tanaka, Hideo; Yatabe, Yasushi; Mitsudomi, Tetsuya; Yano, Seiji; Matsuo, Keitaro

2015-01-01

The BIM deletion polymorphism in intron 2 was found in a significant percent of the Asian population. Patients with epidermal growth factor receptor (EGFR) mutant lung cancers harboring this BIM polymorphism have shorter progression free survival and overall response rates to EGFR tyrosine kinase inhibitors. However, the association between the BIM deletion polymorphism and lung cancer risk is unknown. The BIM deletion polymorphism was screened by polymerase chain reaction in 765 lung cancer cases and 942 healthy individuals. Carriers possessing one allele of the BIM polymorphism were observed in 13.0% of control cases and 12.8% of lung cancer cases, similar to incidence rates reported earlier in healthy individuals. Homozygote for the BIM polymorphism was observed in four of 942 healthy controls and three of 765 lung cancer cases. The frequency of the BIM deletion polymorphism in lung cancer patients was not related to age, sex, smoking history, or family history of lung cancer. The BIM deletion polymorphism was found in 30 of 212 patients with EGFR wild type lung cancers and 16 of 120 patients with EGFR mutant lung cancers. The frequency of the BIM polymorphism is similar between cancers with wild type EGFR and mutated EGFR (p = 0.78). The BIM deletion polymorphism was not associated with lung cancer susceptibility. Furthermore, the BIM polymorphism is not associated with EGFR mutant lung cancer.

[Use of a novel polymer, the in-situ gelling mucoadhesive thiolated poly(aspartic acid) in ophthalmic drug delivery].

PubMed

Horvát, Gabriella; Budai-Szűcs, Mária; Berkó, Szilvia; Szabóné-Révész, Piroska; Gyarmati, Benjámin; Szilágyi, Barnabas Áron; Szilágyi, András; Csányi Erzsébet

2015-01-01

The bioavailability of drugs used on mucosal surfaces can be increased by the use of mucoadhesive polymers. A new type of mucoadhesive polymers is the group of thiolated polymers with thiol group containing side chains. These polymers are able to form covalent bonds (disulphide linkages) with the mucin glycoproteins. For the formulation of an ocular drug delivery system (DDS) thiolated poly(aspartic acid) polymer (ThioPASP) was used. Our aim was to determine their biocompatibility, mucoadhesion and drug release property. According to the results it can be established that the thiolated poly(aspartic acid) polymers can be a potential vehicle of an ocular drug delivery system due to their biocompatibility, good mucoadhesive property and drug release profile. Thanks to their properties controlled drug delivery can be achieved and bioavailability of the ophthalmic formulation can be increased, while the usage frequency can be decreased.

Site-directed mutagenesis reveals a novel catalytic mechanism of Mycobacterium tuberculosis alkylhydroperoxidase C.

PubMed Central

Chauhan, Radha; Mande, Shekhar C

2002-01-01

Mycobacterium tuberculosis alkylhydroperoxidase C (AhpC) belongs to the peroxiredoxin family, but unusually contains three cysteine residues in its active site. It is overexpressed in isoniazid-resistant strains of M. tuberculosis. We demonstrate that AhpC is capable of acting as a general antioxidant by protecting a range of substrates including supercoiled DNA. Active-site Cys to Ala mutants show that all three cysteine residues are important for activity. Cys-61 plays a central role in activity and Cys-174 also appears to be crucial. Interestingly, the C174A mutant is inactive, but double mutant C174/176A shows significant revertant activity. Kinetic parameters indicate that the C176A mutant is active, although much less efficient. We suggest that M. tuberculosis AhpC therefore belongs to a novel peroxiredoxin family and might follow a unique disulphide-relay reaction mechanism. PMID:12084012

Extendible-retractable electric field measurement antenna for IMP J

NASA Technical Reports Server (NTRS)

Larrick, W.

1973-01-01

An antenna dispenser mechanism for the IMP J spacecraft was designed, fabricated, and tested. Upon command the mechanism deploys or retracts a conductor for use as a receiving antenna for an electric field measurement experiment. Five identical units were fabricated and tested to the IMP H & J environmental test specification. Of these, four are designated for flight on the IMP J spacecraft and one as a prototype flight spare. The testing program was successfully completed although certain design modifications were required as problems were uncovered by the testing; particularly thermal vacuum operation. The antenna mechanism functions well under the expected environmental and loading conditions. The wear life and load capability of the dry molybdenum disulphide lubricant originally used on the heavily loaded worm and gear pair were disappointing and a substitute material was applied. The lubricant finally applied performed well; although other problems were generated.

Strongly anisotropic spin relaxation in graphene-transition metal dichalcogenide heterostructures at room temperature

NASA Astrophysics Data System (ADS)

Benítez, L. Antonio; Sierra, Juan F.; Savero Torres, Williams; Arrighi, Aloïs; Bonell, Frédéric; Costache, Marius V.; Valenzuela, Sergio O.

2018-03-01

A large enhancement in the spin-orbit coupling of graphene has been predicted when interfacing it with semiconducting transition metal dichalcogenides. Signatures of such an enhancement have been reported, but the nature of the spin relaxation in these systems remains unknown. Here, we unambiguously demonstrate anisotropic spin dynamics in bilayer heterostructures comprising graphene and tungsten or molybdenum disulphide (WS2, MoS2). We observe that the spin lifetime varies over one order of magnitude depending on the spin orientation, being largest when the spins point out of the graphene plane. This indicates that the strong spin-valley coupling in the transition metal dichalcogenide is imprinted in the bilayer and felt by the propagating spins. These findings provide a rich platform to explore coupled spin-valley phenomena and offer novel spin manipulation strategies based on spin relaxation anisotropy in two-dimensional materials.

Considerations for spectroscopy of liquid-exfoliated 2D materials: emerging photoluminescence of N-methyl-2-pyrrolidone.

PubMed

Ogilvie, Sean P; Large, Matthew J; Fratta, Giuseppe; Meloni, Manuela; Canton-Vitoria, Ruben; Tagmatarchis, Nikos; Massuyeau, Florian; Ewels, Christopher P; King, Alice A K; Dalton, Alan B

2017-12-01

N-methyl-2-pyrrolidone (NMP) has been shown to be the most effective solvent for liquid phase exfoliation and dispersion of a range of 2D materials including graphene, molybdenum disulphide (MoS 2 ) and black phosphorus. However, NMP is also known to be susceptible to sonochemical degradation during exfoliation. We report that this degradation gives rise to strong visible photoluminescence of NMP. Sonochemical modification is shown to influence exfoliation of layered materials in NMP and the optical absorbance of the solvent in the dispersion. The emerging optical properties of the degraded solvent present challenges for spectroscopy of nanomaterial dispersions; most notably the possibility of observing solvent photoluminescence in the spectra of 2D materials such as MoS 2 , highlighting the need for stable solvents and exfoliation processes to minimise the influence of solvent degradation on the properties of liquid-exfoliated 2D materials.

Trap-mediated electronic transport properties of gate-tunable pentacene/MoS2 p-n heterojunction diodes

PubMed Central

Kim, Jae-Keun; Cho, Kyungjune; Kim, Tae-Young; Pak, Jinsu; Jang, Jingon; Song, Younggul; Kim, Youngrok; Choi, Barbara Yuri; Chung, Seungjun; Hong, Woong-Ki; Lee, Takhee

2016-01-01

We investigated the trap-mediated electronic transport properties of pentacene/molybdenum disulphide (MoS2) p-n heterojunction devices. We observed that the hybrid p-n heterojunctions were gate-tunable and were strongly affected by trap-assisted tunnelling through the van der Waals gap at the heterojunction interfaces between MoS2 and pentacene. The pentacene/MoS2 p-n heterojunction diodes had gate-tunable high ideality factor, which resulted from trap-mediated conduction nature of devices. From the temperature-variable current-voltage measurement, a space-charge-limited conduction and a variable range hopping conduction at a low temperature were suggested as the gate-tunable charge transport characteristics of these hybrid p-n heterojunctions. Our study provides a better understanding of the trap-mediated electronic transport properties in organic/2-dimensional material hybrid heterojunction devices. PMID:27829663

Two-band induced superconductivity in single-layer graphene and topological insulator bismuth selenide

NASA Astrophysics Data System (ADS)

Talantsev, E. F.; Crump, W. P.; Tallon, J. L.

2018-01-01

Proximity-induced superconductivity in single-layer graphene (SLG) and in topological insulators represent almost ideal examples of superconductivity in two dimensions. Fundamental mechanisms governing superconductivity in the 2D limit are of central interest for modern condensed-matter physics. To deduce fundamental parameters of superconductor/graphene/superconductor and superconductor/bismuth selenide/superconductor junctions we investigate the self-field critical currents in these devices using the formalism of the Ambegaokar-Baratoff model. Our central finding is that the induced superconducting state in SLG and bismuth selenide each exhibits gapping on two superconducting bands. Based on recent results obtained on ultra-thin films of natural superconductors, including single-atomic layer of iron selenide, double and triple atomic layers of gallium, and several atomic layer tantalum disulphide, we conclude that a two-band induced superconducting state in SLG and bismuth selenide is part of a wider, more general multiple-band phenomenology of currently unknown origin.

A theoretical modeling of photocurrent generation and decay in layered MoS2 thin-film transistor photosensors

NASA Astrophysics Data System (ADS)

Hur, Ji-Hyun; Park, Junghak; Jeon, Sanghun

2017-02-01

A model that universally describes the characteristics of photocurrent in molybdenum disulphide (MoS2) thin-film transistor (TFT) photosensors in both ‘light on’ and ‘light off’ conditions is presented for the first time. We considered possible material-property dependent carrier generation and recombination mechanisms in layered MoS2 channels with different numbers of layers. We propose that the recombination rates that are mainly composed of direct band-to-band recombination and interface trap-involved recombination change on changing the light condition and the number of layers. By comparing the experimental results, it is shown that the model performs well in describing the photocurrent behaviors of MoS2 TFT photosensors, including the photocurrent generation under illumination and a hugely long time persistent trend of the photocurrent decay in the dark condition, for a range of MoS2 layer numbers.

New deposition technique for metal films containing inorganic fullerene-like (IF) nanoparticles.

PubMed

Goldbart, Ohad; Yoffe, Alexander; Cohen, Sidney R; Rosentsveig, Rita; Feldman, Yishay; Rapoport, Lev; Tenne, Reshef

2013-07-22

This study describes a new method for fabrication of thin composite films using physical vapor deposition (PVD). Titanium (Ti) and hybrid films of titanium containing tungsten disulphide nanoparticles with inorganic fullerene-like structure (Ti/IF-WS2) were fabricated with a modified PVD machine. The evaporation process includes the pulsed deposition of IF-WS2 by a sprayer head. This process results in IF-WS2 nanoparticles embedded in a Ti matrix. The layers were characterized by various techniques, which confirm the composition and structure of the hybrid film. The Ti/IF-WS2 shows better wear resistance and a lower friction coefficient when compared to the Ti layer or Ti substrate. The Ti/IF films show very good antireflective properties in the visible and near-IR region. Such films may find numerous applications, for example, in the aerospace and medical technology. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structure of a bacterial homologue of vitamin K epoxide reductase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Weikai; Schulman, Sol; Dutton, Rachel J.

Vitamin K epoxide reductase (VKOR) generates vitamin K hydroquinone to sustain {gamma}-carboxylation of many blood coagulation factors. Here, we report the 3.6 {angstrom} crystal structure of a bacterial homologue of VKOR from Synechococcus sp. The structure shows VKOR in complex with its naturally fused redox partner, a thioredoxin-like domain, and corresponds to an arrested state of electron transfer. The catalytic core of VKOR is a four transmembrane helix bundle that surrounds a quinone, connected through an additional transmembrane segment with the periplasmic thioredoxin-like domain. We propose a pathway for how VKOR uses electrons from cysteines of newly synthesized proteins tomore » reduce a quinone, a mechanism confirmed by in vitro reconstitution of vitamin K-dependent disulphide bridge formation. Our results have implications for the mechanism of the mammalian VKOR and explain how mutations can cause resistance to the VKOR inhibitor warfarin, the most commonly used oral anticoagulant.« less

Improved Fab presentation on phage surface with the use of molecular chaperone coplasmid system.

PubMed

Loh, Qiuting; Leong, Siew Wen; Tye, Gee Jun; Choong, Yee Siew; Lim, Theam Soon

2015-05-15

The low presentation efficiency of Fab (fragment antigen binding) fragments during phage display is largely due to the complexity of disulphide bond formation. This can result in the presentation of Fab fragments devoid of a light chain during phage display. Here we propose the use of a coplasmid system encoding several molecular chaperones (DsbA, DsbC, FkpA, and SurA) to improve Fab packaging. A comparison was done using the Fab fragment from IgG and IgD. We found that the use of the coplasmid during phage packaging was able to improve the presentation efficiency of the Fab fragment on phage surfaces. A modified version of panning using the coplasmid system was evaluated and was successful at enriching Fab binders. Therefore, the coplasmid system would be an attractive alternative for improved Fab presentation for phage display. Copyright © 2015 Elsevier Inc. All rights reserved.

Trap-mediated electronic transport properties of gate-tunable pentacene/MoS2 p-n heterojunction diodes

NASA Astrophysics Data System (ADS)

Kim, Jae-Keun; Cho, Kyungjune; Kim, Tae-Young; Pak, Jinsu; Jang, Jingon; Song, Younggul; Kim, Youngrok; Choi, Barbara Yuri; Chung, Seungjun; Hong, Woong-Ki; Lee, Takhee

2016-11-01

We investigated the trap-mediated electronic transport properties of pentacene/molybdenum disulphide (MoS2) p-n heterojunction devices. We observed that the hybrid p-n heterojunctions were gate-tunable and were strongly affected by trap-assisted tunnelling through the van der Waals gap at the heterojunction interfaces between MoS2 and pentacene. The pentacene/MoS2 p-n heterojunction diodes had gate-tunable high ideality factor, which resulted from trap-mediated conduction nature of devices. From the temperature-variable current-voltage measurement, a space-charge-limited conduction and a variable range hopping conduction at a low temperature were suggested as the gate-tunable charge transport characteristics of these hybrid p-n heterojunctions. Our study provides a better understanding of the trap-mediated electronic transport properties in organic/2-dimensional material hybrid heterojunction devices.

Trap-mediated electronic transport properties of gate-tunable pentacene/MoS2 p-n heterojunction diodes.

PubMed

Kim, Jae-Keun; Cho, Kyungjune; Kim, Tae-Young; Pak, Jinsu; Jang, Jingon; Song, Younggul; Kim, Youngrok; Choi, Barbara Yuri; Chung, Seungjun; Hong, Woong-Ki; Lee, Takhee

2016-11-10

We investigated the trap-mediated electronic transport properties of pentacene/molybdenum disulphide (MoS 2 ) p-n heterojunction devices. We observed that the hybrid p-n heterojunctions were gate-tunable and were strongly affected by trap-assisted tunnelling through the van der Waals gap at the heterojunction interfaces between MoS 2 and pentacene. The pentacene/MoS 2 p-n heterojunction diodes had gate-tunable high ideality factor, which resulted from trap-mediated conduction nature of devices. From the temperature-variable current-voltage measurement, a space-charge-limited conduction and a variable range hopping conduction at a low temperature were suggested as the gate-tunable charge transport characteristics of these hybrid p-n heterojunctions. Our study provides a better understanding of the trap-mediated electronic transport properties in organic/2-dimensional material hybrid heterojunction devices.

Zero-valent sulphur is a key intermediate in marine methane oxidation.

PubMed

Milucka, Jana; Ferdelman, Timothy G; Polerecky, Lubos; Franzke, Daniela; Wegener, Gunter; Schmid, Markus; Lieberwirth, Ingo; Wagner, Michael; Widdel, Friedrich; Kuypers, Marcel M M

2012-11-22

Emissions of methane, a potent greenhouse gas, from marine sediments are controlled by anaerobic oxidation of methane coupled primarily to sulphate reduction (AOM). Sulphate-coupled AOM is believed to be mediated by a consortium of methanotrophic archaea (ANME) and sulphate-reducing Deltaproteobacteria but the underlying mechanism has not yet been resolved. Here we show that zero-valent sulphur compounds (S(0)) are formed during AOM through a new pathway for dissimilatory sulphate reduction performed by the methanotrophic archaea. Hence, AOM might not be an obligate syntrophic process but may be carried out by the ANME alone. Furthermore, we show that the produced S(0)--in the form of disulphide--is disproportionated by the Deltaproteobacteria associated with the ANME. Our observations expand the diversity of known microbially mediated sulphur transformations and have significant implications for our understanding of the biogeochemical carbon and sulphur cycles.

Synthesis and Characterization of Novel Anchorlipids for Tethered Bilayer Lipid Membranes.

PubMed

Andersson, Jakob; Knobloch, Jacqueline J; Perkins, Michael V; Holt, Stephen A; Köper, Ingo

2017-05-09

Tethered bilayer lipid membranes are versatile solid-supported model membrane systems. Core to these systems is an anchorlipid that covalently links a lipid bilayer to a support. The molecular structure of these lipids can have a significant impact on the properties of the resulting bilayer. Here, the synthesis of anchorlipids containing ester groups in the tethering part is described. The lipids are used to form bilayer membranes, and the resulting structures are compared with membranes formed using conventional anchorlipids or sparsely tethered membranes. All membranes showed good electrical sealing properties; the disulphide-terminated anchorlipids could be used in a sparsely tethered system without significantly reducing the sealing properties of the lipid bilayers. The sparsely tethered systems also allowed for higher ion transport across the membrane, which is in good correlation with higher hydration of the spacer region as seen by neutron scattering.

Cysteine reacts to form blue-green pigments with thiosulfinates obtained from garlic (Allium sativum L.).

PubMed

Shin, Young Keum; Kyung, Kyu Hang

2014-01-01

Cysteine was found to form pigments with garlic thiosulfinates in this investigation, in contrast to previous reports. Pigments were formed only when the molar concentration ratios of cysteine to total thiosulfinates were smaller than 2:1. Cysteine does not form pigments with thiosulfinates in the same manner as other pigment-forming amino compounds because it has a sulfhydryl (SH) group. A colour reaction of cysteine with thiosulfinates is proposed where colourless disulphide-type S-alk(en)yl mercaptocysteines (SAMCs) are formed first by the SH-involved reaction between cysteine and thiosulfinates, and then SAMCs react with residual thiosulfinates to form pigments. When the cysteine to total thiosulfinate molar concentration ratio was 2:1 or greater, total thiosulfinates were consumed to form SAMCs without leaving any thiosulfinates remaining available for the following colour reactions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Polymorphism at codon 36 of the p53 gene.

PubMed

Felix, C A; Brown, D L; Mitsudomi, T; Ikagaki, N; Wong, A; Wasserman, R; Womer, R B; Biegel, J A

1994-01-01

A polymorphism at codon 36 in exon 4 of the p53 gene was identified by single strand conformation polymorphism (SSCP) analysis and direct sequencing of genomic DNA PCR products. The polymorphic allele, present in the heterozygous state in genomic DNAs of four of 100 individuals (4%), changes the codon 36 CCG to CCA, eliminates a FinI restriction site and creates a BccI site. Including this polymorphism there are four known polymorphisms in the p53 coding sequence.

Plasminogen activator inhibitor-1 4G/5G promoter polymorphism and coagulation factor VII Arg353-->Gln polymorphism in Korean patients with coronary artery disease.

PubMed Central

Song, J.; Yoon, Y. M.; Jung, H. J.; Hong, S. H.; Park, H.; Kim, J. Q.

2000-01-01

An increased risk for arterial thrombosis is associated with high plasma levels of coagulation and fibrinolytic factors such as PAI-1 and FVII. In this study, the 4G/5G polymorphism in the promoter of PAI-1 gene and Arg353-->Gln polymorphism in the FVII gene were analysed in 139 normal adults and 158 patients with coronary artery disease (CAD), and their association with plasma lipid traits was investigated. There were no significant differences in the allele frequencies of PAI-1 and FVII polymorphisms between control and patient groups. The allelic distributions of both polymorphisms in Koreans were similar to those in Japanese but significantly different from those in Caucasians. In the CAD group, the 4G homozygotes of PAI-1 polymorphism showed significantly higher levels of total (p=0.0250) and LDL cholesterol (p=0.0335) with individuals having other genotypes. However, FVII polymorphism showed no association with lipid levels. In conclusion, the 4G/5G PAI-1 promoter polymorphism and Arg353-->Gln FVII polymorphism are not major genetic risk factors for CAD in Koreans. However, 4G allele of PAI-1 polymorphism revealed to be associated with the levels of cholesterol, especially LDL cholesterol levels in CAD patients. PMID:10803689

MAOA and TNF-β gene polymorphisms are associated with photophobia but not osmophobia in patients with migraine.

PubMed

Ishii, Masakazu; Usami, Shino; Hara, Hajime; Imagawa, Atsuko; Masuda, Yutaka; Shimizu, Shuniichi

2014-06-01

Photophobia and osmophobia are typical symptoms associated with migraine, but the contributions of gene polymorphisms to these symptoms are not fully elucidated. We investigated whether the gene polymorphisms are involved in photophobia and osmophobia in patients with migraine. Ninety-one migraine patients and 119 non-headache healthy volunteers were enrolled. The 12 gene polymorphisms were determined by polymerase-chain-reaction (PCR) and PCR restriction-fragment-length polymorphism analysis. Photophobia and osmophobia were observed in 49 (54%) and 31 patients (34%), respectively. Distributions of monoamine oxidase A (MAOA) T941G and tumour necrosis factor-β (TNF-β) G252A polymorphisms were significantly different between patients with photophobia and controls. However, no gene polymorphism differences were observed between patients with osmophobia and controls. The MAOA T941G and TNF-β G252A gene polymorphisms appear to contribute to photophobia but not to osmophobia. We propose that different gene polymorphisms are responsible for photophobia and osmophobia symptoms during migraine.

Combined crystal structure prediction and high-pressure crystallization in rational pharmaceutical polymorph screening

PubMed Central

Neumann, M. A.; van de Streek, J.; Fabbiani, F. P. A.; Hidber, P.; Grassmann, O.

2015-01-01

Organic molecules, such as pharmaceuticals, agro-chemicals and pigments, frequently form several crystal polymorphs with different physicochemical properties. Finding polymorphs has long been a purely experimental game of trial-and-error. Here we utilize in silico polymorph screening in combination with rationally planned crystallization experiments to study the polymorphism of the pharmaceutical compound Dalcetrapib, with 10 torsional degrees of freedom one of the most flexible molecules ever studied computationally. The experimental crystal polymorphs are found at the bottom of the calculated lattice energy landscape, and two predicted structures are identified as candidates for a missing, thermodynamically more stable polymorph. Pressure-dependent stability calculations suggested high pressure as a means to bring these polymorphs into existence. Subsequently, one of them could indeed be crystallized in the 0.02 to 0.50 GPa pressure range and was found to be metastable at ambient pressure, effectively derisking the appearance of a more stable polymorph during late-stage development of Dalcetrapib. PMID:26198974

Asymmetric Dispersal Can Maintain Larval Polymorphism: A Model Motivated by Streblospio benedicti

PubMed Central

Zakas, Christina; Hall, David W.

2012-01-01

Polymorphism in traits affecting dispersal occurs in a diverse variety of taxa. Typically, the maintenance of a dispersal polymorphism is attributed to environmental heterogeneity where parental bet-hedging can be favored. There are, however, examples of dispersal polymorphisms that occur across similar environments. For example, the estuarine polychaete Streblospio benedicti has a highly heritable offspring dimorphism that affects larval dispersal potential. We use analytical models of dispersal to determine the conditions necessary for a stable dispersal polymorphism to exist. We show that in asexual haploids, sexual haploids, and in sexual diploids in the absence of overdominance, asymmetric dispersal is required in order to maintain a dispersal polymorphism when patches do not vary in intrinsic quality. Our study adds an additional factor, dispersal asymmetry, to the short list of mechanisms that can maintain polymorphism in nature. The region of the parameter space in which polymorphism is possible is limited, suggesting why dispersal polymorphisms within species are rare. PMID:22576818

Structural and abinitio studies on the polymorphism of iminophosphorane (CH3C6H4)3Pdbnd NP[(dbnd O)(OPh)2

NASA Astrophysics Data System (ADS)

Petric, Mihaela F.; Crisan, Manuela E.; Chumakov, Yurii M.; Varga, Richard A.; Micle, Andreea; Neda, Ion; Ilia, Gheorghe

2015-03-01

Two polymorphic forms of a new iminophosphorane have been investigated by infrared, nuclear magnetic resonance and mass spectroscopy, X-ray crystallography and studied through ab initio quantum chemical calculations. The monoclinic polymorph α contains two independent molecules (αI and αII) in the asymmetric unit, while the orthorhombic polymorph ß has one molecule in the asymmetric unit. The molecules in polymorphs α and β adopt different conformations. Hirshfeld surfaces and fingerprint plots were generated in order to compare the two independent molecules αI and αII in the asymmetric unit and also for a comparison of ß molecule, in the orthorhombic crystal system, with the previously reported monoclinic polymorph. The results show that the packing motifs in polymorphs α and β differ mainly due to the redistribution of Csbnd H⋯O and Csbnd H⋯π hydrogen-bond interactions rather than their percentage Hirshfeld surface area contributions. The dipole-dipole interactions significantly influence the intermolecular interactions in polymorphs α and β. The calculated lattice energies indicate that polymorph α is slightly more stable than polymorph α.

Genetic polymorphisms in lung disease: bandwagon or breakthrough?

PubMed Central

Iannuzzi, Michael C; Maliarik, Mary; Rybicki, Benjamin

2002-01-01

The study of genetic polymorphisms has touched every aspect of pulmonary and critical care medicine. We review recent progress made using genetic polymorphisms to define pathophysiology, to identify persons at risk for pulmonary disease and to predict treatment response. Several pitfalls are commonly encountered in studying genetic polymorphisms, and this article points out criteria that should be applied to design high-quality genetic polymorphism studies. PMID:11980584

Telomerase reverse transcriptase locus polymorphisms and cancer risk: a field synopsis and meta-analysis.

PubMed

Mocellin, Simone; Verdi, Daunia; Pooley, Karen A; Landi, Maria T; Egan, Kathleen M; Baird, Duncan M; Prescott, Jennifer; De Vivo, Immaculata; Nitti, Donato

2012-06-06

Several recent studies have provided evidence that polymorphisms in the telomerase reverse transcriptase (TERT) gene sequence are associated with cancer development, but a comprehensive synopsis is not available. We conducted a systematic review and meta-analysis of the available molecular epidemiology data regarding the association between TERT locus polymorphisms and predisposition to cancer. A systematic review of the English literature was conducted by searching PubMed, Embase, Cancerlit, Google Scholar, and ISI Web of Knowledge databases for studies on associations between TERT locus polymorphisms and cancer risk. Random-effects meta-analysis was performed to pool per-allele odds ratios for TERT locus polymorphisms and risk of cancer, and between-study heterogeneity and potential bias sources (eg, publication and chasing bias) were assessed. Because the TERT locus includes the cleft lip and palate transmembrane 1-like (CLPTM1L) gene, which is in linkage disequilibrium with TERT, CLPTM1L polymorphisms were also analyzed. Cumulative evidence for polymorphisms with statistically significant associations was graded as "strong," "moderate," and "weak" according to the Venice criteria. The joint population attributable risk was calculated for polymorphisms with strong evidence of association. Eighty-five studies enrolling 490 901 subjects and reporting on 494 allelic contrasts were retrieved. Data were available on 67 TERT locus polymorphisms and 24 tumor types, for a total of 221 unique combinations of polymorphisms and cancer types. Upon meta-analysis, a statistically significant association with the risk of any cancer type was found for 22 polymorphisms. Strong, moderate, and weak cumulative evidence for association with at least one tumor type was demonstrated for 11, 9, and 14 polymorphisms, respectively. For lung cancer, which was the most studied tumor type, the estimated joint population attributable risk for three polymorphisms (TERT rs2736100, intergenic rs4635969, and CLPTM1L rs402710) was 41%. Strong evidence for lack of association was identified for five polymorphisms in three tumor types. To our knowledge, this is the largest collection of data for associations between TERT locus polymorphisms and cancer risk. Our findings support the hypothesis that genetic variability in this genomic region can modulate cancer susceptibility in humans.

Prevalence of combinatorial CYP2C9 and VKORC1 genotypes in Puerto Ricans: implications for warfarin management in Hispanics.

PubMed

Duconge, Jorge; Cadilla, Carmen L; Windemuth, Andreas; Kocherla, Mohan; Gorowski, Krystyna; Seip, Richard L; Bogaard, Kali; Renta, Jessica Y; Piovanetti, Paola; D'Agostino, Darrin; Santiago-Borrero, Pedro J; Ruaño, Gualberto

2009-01-01

Polymorphisms in the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) genes significantly alter the effective warfarin dose. We determined the frequencies of alleles, single carriers, and double carriers of single nucleotide polymorphisms (SNPs) in the CYP2C9 and VKORC1 genes in a Puerto Rican cohort and gauged the impact of these polymorphisms on warfarin dosage using a published algorithm. A total of 92 DNA samples were genotyped using Luminex x-MAP technology. The polymorphism frequencies were 6.52%, 5.43% and 28.8% for CYP2C9 *2, *3 and VKORC1-1639 C>A polymorphisms, respectively. The prevalence of combinatorial genotypes was 16% for carriers of both the CYP2C9 and VKORC1 polymorphisms, 9% for carriers of CYP2C9 polymorphisms, 35% for carriers of the VKORC1 polymorphism, and the remaining 40% were non-carriers for either gene. Based on a published warfarin dosing algorithm, single, double and triple carriers of functionally deficient polymorphisms predict reductions of 1.0-1.6, 2.0-2.9, and 2.9-3.7 mg/day, respectively, in warfarin dose. Overall, 60% of the population carried at least a single polymorphism predicting deficient warfarin metabolism or responsiveness and 13% were double carriers with polymorphisms in both genes studied. Combinatorial genotyping of CYP2C9 and VKORC1 can allow for individualized dosing of warfarin among patients with gene polymorphisms, potentially reducing the risk of stroke or bleeding.

Selection with Gene-Cytoplasm Interactions. I. Maintenance of Cytoplasm Polymorphisms

PubMed Central

Gregorius, H. R.; Ross, M. D.

1984-01-01

General conditions for the protectedness of gene-cytoplasm polymorphisms are considered for a biallelic model with two cytoplasm types and under the assumption that nuclear polymorphisms cannot be maintained in the presence of only one cytoplasm type. Analytical results involving male fertilities, female fertilities, viabilities and selfing rates are obtained, and numerical results show spiral and cyclic behavior of population trajectories. It is shown that a maternally inherited cytoplasmic polymorphism cannot be maintained in the absence of a nuclear polymorphism, and that a gene-cytoplasm polymorphism can only be maintained if the population shows sexual asymmetry, i.e. , if the ratio of male to female fertility varies among genotypes. Thus, the classical viability selection model does not allow gene-cytoplasm polymorphisms. PMID:17246213

Cloning of polymorphisms (COP): enrichment of polymorphic sequences from complex genomes

PubMed Central

Li, Jingfeng; Wang, Fuli; Zabarovska, Veronika; Wahlestedt, Claes; Zabarovsky, Eugene R.

2000-01-01

Here we describe a new procedure (cloning of polymorphisms, COP) for enrichment of single nucleotide polymorphisms (SNPs) that represent restriction fragment length polymorphisms (RFLPs). COP would be applicable to the isolation of SNPs from particular regions of the genome, e.g. CpG islands, chromosomal bands, YACs or PAC contigs. A combination of digestion with restriction enzymes, treatment with uracil-DNA glycosylase and mung bean nuclease, PCR amplification and purification with streptavidin magnetic beads was used to isolate polymorphic sequences from the genomes of two human samples. After only two cycles of enrichment, 80% of the isolated clones were found to contain RFLPs. A simple method for the PCR detection of these polymorphisms was also developed. PMID:10606669

Associations of polymorphisms in the Pit-1 gene with growth and carcass traits in Angus beef cattle.

PubMed

Zhao, Q; Davis, M E; Hines, H C

2004-08-01

The Pit-1 gene was studied as a candidate for genetic markers of growth and carcass traits. Angus beef cattle that were divergently selected for high- or low-blood serum IGF-I concentration were used in this study. The single-strand conformation polymorphism method was used to identify polymorphism in the Pit-1 gene including regions from intron 2 to exon 6. Two polymorphisms, Pit1I3H (HinfI) and Pit1I3NL (NlaIII), were detected in intron 3 of the Pit-1 gene. One polymorphism, Pit1I4N (BstNI), was found in intron 4, and a single nucleotide polymorphism, Pit1I5, was found in intron 5. The previously reported polymorphism in exon 6, Pit1E6H (HinfI), was also studied in 416 Angus beef cattle. Associations of the polymorphisms with growth traits, carcass traits, and IGF-I concentration were analyzed using a general linear model procedure. No significant associations were observed between these polymorphisms and growth and carcass traits.

Inverse Correlation of Population Similarity and Introduction Date for Invasive Ascidians

PubMed Central

Silva, Nathan; Smith, William C.

2008-01-01

The genomes of many marine invertebrates, including the purple sea urchin and the solitary ascidians Ciona intestinalis and Ciona savignyi, show exceptionally high levels of heterozygosity, implying that these populations are highly polymorphic. Analysis of the C. savignyi genome found little evidence to support an elevated mutation rate, but rather points to a large population size contributing to the polymorphism level. In the present study, the relative genetic polymorphism levels in sampled populations of ten different ascidian species were determined using a similarity index generated by AFLP analysis. The goal was to determine the range of polymorphism within the populations of different species, and to uncover factors that may contribute to the high level of polymorphism. We observe that, surprisingly, the levels of polymorphism within these species show a negative correlation with the reported age of invasive populations, and that closely related species show substantially different levels of genetic polymorphism. These findings show exceptions to the assumptions that invasive species start with a low level of genetic polymorphism that increases over time and that closely related species have similar levels of genetic polymorphism. PMID:18575620

Selective loss of polymorphic mating types is associated with rapid phenotypic evolution during morphic speciation.

PubMed

Corl, Ammon; Davis, Alison R; Kuchta, Shawn R; Sinervo, Barry

2010-03-02

Polymorphism may play an important role in speciation because new species could originate from the distinctive morphs observed in polymorphic populations. However, much remains to be understood about the process by which morphs found new species. To detail the steps of this mode of speciation, we studied the geographic variation and evolutionary history of a throat color polymorphism that distinguishes the "rock-paper-scissors" mating strategies of the side-blotched lizard, Uta stansburiana. We found that the polymorphism is geographically widespread and has been maintained for millions of years. However, there are many populations with reduced numbers of throat color morphs. Phylogenetic reconstruction showed that the polymorphism is ancestral, but it has been independently lost eight times, often giving rise to morphologically distinct subspecies/species. Changes to the polymorphism likely involved selection because the allele for one particular male strategy, the "sneaker" morph, has been lost in all cases. Polymorphism loss was associated with accelerated evolution of male size, female size, and sexual dimorphism, which suggests that polymorphism loss can promote rapid divergence among populations and aid species formation.

Nucleation control and separation of paracetamol polymorphs through swift cooling crystallization process

NASA Astrophysics Data System (ADS)

Sudha, C.; Srinivasan, K.

2014-09-01

Polymorphic nucleation behavior of pharmaceutical solid paracetamol has been investigated by performing swift cooling crystallization process. Saturated aqueous solution prepared at 318 K was swiftly cooled to 274 K in steps of every 1 K in the temperature range from 274 K to 313 K with uniform stirring of 100 rpm. The resultant supersaturation generated in the mother solution favours the nucleation of three different polymorphs of paracetamol. Lower supersaturation region σ=0.10-0.83 favours stable mono form I; the intermediate supersaturation region σ=0.92-1.28 favours metastable ortho form II and the higher supersaturation region σ=1.33-1.58 favours unstable form III polymorphic nucleation. Depending upon the level of supersaturation generated during swift cooling process and the corresponding solubility limit and metastable zone width (MSZW) of each polymorph, the nucleation of a particular polymorph occurs in the system. The type of polymorphs was identified by in-situ optical microscopy and the internal structure was confirmed by Powder X-ray diffraction (PXRD) study. By this novel approach, the preferred nucleation regions of all the three polymorphs of paracetamol are optimized in terms of different cooling ranges employed during the swift cooling process. Also solution mediated polymorphic transformations from unstable to mono and ortho to mono polymorphs have been studied by in-situ.

New polymorphisms of Xeroderma Pigmentosum DNA repair genes in myelodysplastic syndrome.

PubMed

Santiago, Sabrina Pinheiro; Junior, Howard Lopes Ribeiro; de Sousa, Juliana Cordeiro; de Paula Borges, Daniela; de Oliveira, Roberta Taiane Germano; Farias, Izabelle Rocha; Costa, Marília Braga; Maia, Allan Rodrigo Soares; da Nóbrega Ito, Mayumi; Magalhães, Silvia Maria Meira; Pinheiro, Ronald Feitosa

2017-07-01

The association between Xeroderma Pigmentosum DNA repair genes (XPA rs1800975, XPC rs2228000, XPD rs1799793 and XPF rs1800067) polymorphisms and myelodysplastic syndrome (MDS) have not been reported. To assess the functional role between these polymorphisms and MDS, we evaluated 189 samples stratified in two groups: 95 bone marrow samples from MDS patients and 94 from healthy elderly volunteers used as controls. Genotypes for all polymorphisms were identified in DNA samples in an allelic discrimination experiment by real-time polymerase chain reaction (qPCR). We also studied the mRNA expression of XPA and XPC genes to evaluate if its polymorphisms were functional in 53 RNAm MDS patients by qPCR methodologies. To the rs2228000 polymorphism, the CT and TT polymorphic genotype were associated with increased odds ratio (OR) of more profound cytopenia (hemoglobin and neutrophils count). To the rs1799793 polymorphism, we found that the GG homozygous wild-type genotype was associated with a decreased chance of developing MDS. We observed low expression of XPA in younger patients, in hypoplastic MDS and patients with abnormal karyotype when presented AG or AA polymorphic genotypes. We also found that there was a statistically significant interaction between the presence of micromegakaryocyte on down regulation of XPC regarding the CT heterozygous genotype of the rs1800975 polymorphism. Our results suggest that new functional polymorphisms of Xeroderma Pigmentosum DNA repair genes in MDS are related to its pathogenesis and prognosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Is colour polymorphism advantageous to populations and species?

PubMed

Forsman, Anders

2016-06-01

I am writing in response to an article by Bolton, Rollins and Griffith (2015) entitled 'The danger within: the role of genetic, behavioural and ecological factors in population persistence of colour polymorphic species' that was recently published as an Opinion under the NEWS AND VIEWS section in Molecular Ecology. Bolton et al. (Molecular Ecology, 2015, 24, 2907) argue that colour polymorphism may reduce population fitness and increase extinction risk and emphasize that this is contrary to predictions put forward by Forsman et al. (Ecology, 89, 2008, 34) and Wennersten & Forsman (Biological Reviews 87, 2012, 756) that the existence of multiple colour morphs with co-adapted gene complexes and associated trait values may increase the ecological and evolutionary success of polymorphic populations and species. Bolton et al. (Molecular Ecology, 2015, 24, 2907) further state that there is no clear evidence from studies of 'true polymorphic species' that polymorphism promotes population persistence. In response, I (i) challenge their classifications of polymorphisms and revisit the traditional definitions recognizing the dynamic nature of polymorphisms, (ii) review empirical studies that have examined whether and how polymorphism is associated with extinction risk, (iii) discuss the roles of trait correlations between colour pattern and other phenotypic dimensions for population fitness and (iv) highlight that the causes and mechanisms that influence the composition and maintenance of polymorphisms are different from the consequences of the polymorphic condition and how it may impact on aspects of ecological success and long-term persistence of populations and species. © 2016 John Wiley & Sons Ltd.

Colour Polymorphism Protects Prey Individuals and Populations Against Predation.

PubMed

Karpestam, Einat; Merilaita, Sami; Forsman, Anders

2016-02-23

Colour pattern polymorphism in animals can influence and be influenced by interactions between predators and prey. However, few studies have examined whether polymorphism is adaptive, and there is no evidence that the co-occurrence of two or more natural prey colour variants can increase survival of populations. Here we show that visual predators that exploit polymorphic prey suffer from reduced performance, and further provide rare evidence in support of the hypothesis that prey colour polymorphism may afford protection against predators for both individuals and populations. This protective effect provides a probable explanation for the longstanding, evolutionary puzzle of the existence of colour polymorphisms. We also propose that this protective effect can provide an adaptive explanation for search image formation in predators rather than search image formation explaining polymorphism.

Colour Polymorphism Protects Prey Individuals and Populations Against Predation

PubMed Central

Karpestam, Einat; Merilaita, Sami; Forsman, Anders

2016-01-01

Colour pattern polymorphism in animals can influence and be influenced by interactions between predators and prey. However, few studies have examined whether polymorphism is adaptive, and there is no evidence that the co-occurrence of two or more natural prey colour variants can increase survival of populations. Here we show that visual predators that exploit polymorphic prey suffer from reduced performance, and further provide rare evidence in support of the hypothesis that prey colour polymorphism may afford protection against predators for both individuals and populations. This protective effect provides a probable explanation for the longstanding, evolutionary puzzle of the existence of colour polymorphisms. We also propose that this protective effect can provide an adaptive explanation for search image formation in predators rather than search image formation explaining polymorphism. PMID:26902799

AS3MT, GSTO, and PNP polymorphisms: impact on arsenic methylation and implications for disease susceptibility.

PubMed

Antonelli, Ray; Shao, Kan; Thomas, David J; Sams, Reeder; Cowden, John

2014-07-01

Oral exposure to inorganic arsenic (iAs) is associated with adverse health effects. Epidemiological studies suggest differences in susceptibility to these health effects, possibly due to genotypic variation. Genetic polymorphisms in iAs metabolism could lead to increased susceptibility by altering urinary iAs metabolite concentrations. To examine the impact of genotypic polymorphisms on iAs metabolism. We screened 360 publications from PubMed and Web of Science for data on urinary mono- and dimethylated arsenic (MMA and DMA) percentages and polymorphic genes encoding proteins that are hypothesized to play roles in arsenic metabolism. The genes we examined were arsenic (+3) methyltransferase (AS3MT), glutathione-s-transferase omega (GSTO), and purine nucleoside phosphorylase (PNP). Relevant data were pooled to determine which polymorphisms are associated across studies with changes in urinary metabolite concentration. In our review, AS3MT polymorphisms rs3740390, rs11191439, and rs11191453 were associated with statistically significant changes in percent urinary MMA. Studies of GSTO polymorphisms did not indicate statistically significant associations with methylation, and there are insufficient data on PNP polymorphisms to evaluate their impact on metabolism. Collectively, these data support the hypothesis that AS3MT polymorphisms alter in vivo metabolite concentrations. Preliminary evidence suggests that AS3MT genetic polymorphisms may impact disease susceptibility. GSTO polymorphisms were not associated with iAs-associated health outcomes. Additional data are needed to evaluate the association between PNP polymorphisms and iAs-associated health outcomes. Delineation of these relationships may inform iAs mode(s) of action and the approach for evaluating low-dose health effects for iAs. Genotype impacts urinary iAs metabolite concentrations and may be a potential mechanism for iAs-related disease susceptibility. Published by Elsevier Inc.

PREVALENCE OF COMBINATORIAL CYP2C9 AND VKORC1 GENOTYPES IN PUERTO RICANS: IMPLICATIONS FOR WARFARIN MANAGEMENT IN HISPANICS

PubMed Central

Duconge, Jorge; Cadilla, Carmen L.; Windemuth, Andreas; Kocherla, Mohan; Gorowski, Krystyna; Seip, Richard L.; Bogaard, Kali; Renta, Jessica Y.; Piovanetti, Paola; D’Agostino, Darrin; Santiago-Borrero, Pedro J.; Ruaño, Gualberto

2010-01-01

Polymorphisms in the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) genes significantly alter the effective warfarin dose. We determined the frequencies of alleles, single carriers, and double carriers of single nucleotide polymorphisms (SNPs) in the CYP2C9 and VKORC1 genes in a Puerto Rican cohort and gauged the impact of these polymorphisms on warfarin dosage using a published algorithm. A total of 92 DNA samples were genotyped using Luminex® x-MAP technology. The polymorphism frequencies were 6.52%, 5.43% and 28.8% for CYP2C9 *2, *3 and VKORC1-1639 G>A polymorphisms, respectively. The prevalence of combinatorial genotypes was 16% for carriers of both the CYP2C9 and VKORC1 polymorphisms, 9% for carriers of CYP2C9 polymorphisms, 35% for carriers of the VKORC1 polymorphism, and the remaining 40% were non-carriers for either gene. Based on a published warfarin dosing algorithm, single, double and triple carriers of functionally deficient polymorphisms predict reductions of 1.0–1.6, 2.0–2.9, and 2.9–3.7 mg/day, respectively, in warfarin dose. Overall, 60% of the population carried at least a single polymorphism predicting deficient warfarin metabolism or responsiveness and 13% were double carriers with polymorphisms in both genes studied. Combinatorial genotyping of CYP2C9 and VKORC1 can allow for individualized dosing of warfarin among patients with gene polymorphisms, potentially reducing the risk of stroke or bleeding. PMID:20073138

The effect of a promoter polymorphism on the transcription of nitric oxide synthase 1 and its relevance to Parkinson's disease.

PubMed

Rife, Terrie; Rasoul, Bareza; Pullen, Nicholas; Mitchell, David; Grathwol, Kristen; Kurth, Janice

2009-08-01

Transcriptional changes of the enzyme nitric oxide synthase I (NOS1) are believed to play a role in the development of many diseases. The gene for NOS1 has 12 alternative first exons (1A-1L). The 1F exon is one of the most highly utilized first exons in the brain and has a polymorphism ((TG)(m)TA(TG)(n)) located in its promoter region. The polymorphism's length has been suggested to affect NOS1 transcription and play a role in Parkinson's disease (PD); however, the actual influence of the polymorphism on NOS1 transcription has not been studied. To better characterize the links of the polymorphism with PD, a genotyping study was done comparing polymorphism length among 170 PD patients and 150 age-matched controls. The pattern of changes between the two group's allele frequencies shows statistical significance (P = 0.0359). The smallest polymorphism sizes are more predominant among PD patients than controls. To study the effects of this polymorphism on NOS1 gene transcription, reporter gene constructs were made by cloning the NOS1 1F promoter with polymorphism lengths of either 42, 54, or 62 bp in front of the luciferase gene and transfecting them into HeLa or Sk-N-MC cells. NOS1-directed reporter gene constructs with the 62-bp polymorphism increased transcription of luciferase 2.2-fold in HeLa and 1.8-fold in Sk-N-MC cells compared with reporter gene constructs with the 42-bp polymorphism. These data suggest that if smaller polymorphism size contributes to the higher NOS1 levels in PD patients, an as yet unknown transcriptional mechanism is required. Copyright 2009 Wiley-Liss, Inc.

Phase stabilisation of hexagonal barium titanate doped with transition metals: A computational study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dawson, J.A., E-mail: mtp09jd@sheffield.ac.uk; Freeman, C.L.; Harding, J.H.

Interatomic potentials recently developed for the modelling of BaTiO{sub 3} have been used to explore the stabilisation of the hexagonal polymorph of BaTiO{sub 3} by doping with transition metals (namely Mn, Co, Fe and Ni) at the Ti-site. Classical simulations have been completed on both the cubic and hexagonal polymorphs to investigate the energetic consequences of transition metal doping on each polymorph. Ti-site charge compensation mechanisms have been used for the multi-valent transition metal ions and cluster binding energies have been considered. Simulations show a significant energetic gain when doping occurs at Ti sites in the face sharing dimers (Ti{submore » 2} sites) of the hexagonal polymorph compared with the doping of the cubic polymorph. This energetic difference between the two polymorphs is true for all transition metals tested and all charge states and in the case of tri- and tetra-valent dopants negative solution energies are found for the hexagonal polymorph suggesting actual polymorph stabilisation occurs with the incorporation of these ions as observed experimentally. Oxidation during incorporation of Ni{sup 2+} and Fe{sup 3+} ions has also been considered. - Graphical abstract: The representation of the strongest binding energy clusters for tri-valent dopants—(a) Ti{sub 2}/O{sub 1} cluster and (b) Ti{sub 2}/O{sub 2} cluster. Highlights: ► Classical simulations show a significant energetic gain when doping occurs at Ti sites in the face sharing dimers (Ti2 sites) of the hexagonal polymorph compared with the doping of the cubic polymorph. ► This energetic difference between the two polymorphs is true for all transition metals tested and all charge states. ► In the case of tri- and tetra- valent dopants negative solution energies are found for the hexagonal polymorph suggesting actual polymorph stabilisation occurs with the incorporation of these ions.« less

LPA gene: interaction between the apolipoprotein(a) size ('kringle IV' repeat) polymorphism and a pentanucleotide repeat polymorphism influences Lp(a) lipoprotein level.

PubMed

Røsby, O; Berg, K

2000-01-01

In order to search for factors influencing the Lp(a) lipoprotein level, we have examined the apolipoprotein(a) (apo(a)) size polymorphism as well as a pentanucleotide (TTTTA) repeat polymorphism in the 5' control region of the LPA gene. Lp(a) lipoprotein levels were compared between individuals with different genotypes as defined by pulsed field gel electrophoresis of DNA plugs, and PCR of DNA samples followed by polyacrylamide gel electrophoresis. DNA plugs and DNA were prepared from blood samples collected from blood donors. Twenty-seven different K IV repeat alleles were observed in the 71 women and 92 men from which apo(a) size polymorphism results were obtained. Alleles encoding 26-32 Kringle IV repeats were the most frequent. Alleles encoding seven to 11 TTTTA repeats were detected in the 84 women and 122 men included in the pentanucleotide polymorphism study, and homozygosity for eight TTTTA repeats was the most common genotype. The eight TTTTA repeat allele occurred with almost any apo(a) allele. An inverse relationship between number of K IV repeats and Lp(a) concentration was confirmed. The contributions of the apo(a) size polymorphism and the pentanucleotide repeat polymorphism to the interindividual variance of Lp(a) lipoprotein concentrations were 9.7 and 3.5%, respectively (type IV sum of squares). Nineteen per cent of the variance in Lp(a) lipoprotein level appeared to be the result of the multiplication product (interaction) between the apo(a) size polymorphism and the pentanucleotide repeat polymorphism. The contribution of the apo(a) size polymorphism alone to the variation in Lp(a) lipoprotein level was lower than previously reported. However, the multiplicative interaction effect between the K IV repeat polymorphism and the pentanucleotide repeat polymorphism may be an important factor explaining the variation in Lp(a) lipoprotein levels among the populations.

Lack of association between alpha2-macroglobulin polymorphisms and Alzheimer's disease.

PubMed

Wang, X; Luedecking, E K; Minster, R L; Ganguli, M; DeKosky, S T; Kamboh, M I

2001-02-01

This study was undertaken to investigate the role of two alpha2-macroglobulin (A2M) polymorphisms, an intronic 5-bp deletion and Ile1000Val, in the development of Alzheimer's disease (AD) and to evaluate the interaction between the apolipoprotein E (APOE) and A2M polymorphisms. The A2M polymorphisms were screened by using polymerase-chain-reaction-based assays in 555 white late-onset AD cases and 446 controls. The gentoype distributions of the 5-bp deletion and Ile1000Val polymorphisms were comparable between cases and controls (P = 0.158 and P = 0.148, respectively). Likewise, there was no significant difference in allele frequencies of each polymorphism among cases and controls (P = 0.361 and P = 0.062, respectively). The stratification of data by APOE*4 status also did not yield any significant association. In conclusion, we observed no association between either the intronic deletion polymorphism or the Ile1000Val polymorphism of A2M and AD in our case-control cohort.

HFE p.H63D polymorphism does not influence ALS phenotype and survival.

PubMed

Chiò, Adriano; Mora, Gabriele; Sabatelli, Mario; Caponnetto, Claudia; Lunetta, Christian; Traynor, Bryan J; Johnson, Janel O; Nalls, Mike A; Calvo, Andrea; Moglia, Cristina; Borghero, Giuseppe; Monsurrò, Maria Rosaria; La Bella, Vincenzo; Volanti, Paolo; Simone, Isabella; Salvi, Fabrizio; Logullo, Francesco O; Nilo, Riva; Giannini, Fabio; Mandrioli, Jessica; Tanel, Raffaella; Murru, Maria Rita; Mandich, Paola; Zollino, Marcella; Conforti, Francesca L; Penco, Silvana; Brunetti, Maura; Barberis, Marco; Restagno, Gabriella

2015-10-01

It has been recently reported that the p.His63Asp polymorphism of the HFE gene accelerates disease progression both in the SOD1 transgenic mouse and in amyotrophic lateral sclerosis (ALS) patients. We have evaluated the effect of HFE p.His63Asp polymorphism on the phenotype in 1351 Italian ALS patients (232 of Sardinian ancestry). Patients were genotyped for the HFE p.His63Asp polymorphism (CC, GC, and GG). All patients were also assessed for C9ORF72, TARDBP, SOD1, and FUS mutations. Of the 1351 ALS patients, 363 (29.2%) were heterozygous (GC) for the p.His63Asp polymorphism and 30 (2.2%) were homozygous for the minor allele (GG). Patients with CC, GC, and GG polymorphisms did not significantly differ by age at onset, site of onset of symptoms, and survival; however, in SOD1 patients with CG or GG polymorphism had a significantly longer survival than those with a CC polymorphism. Differently from what observed in the mouse model of ALS, the HFE p.His63Asp polymorphism has no effect on ALS phenotype in this large series of Italian ALS patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Study of polymorphic control in an ethanol-water binary solvent

NASA Astrophysics Data System (ADS)

Kitano, Hiroshi; Tanaka, Takayuki; Hirasawa, Izumi

2017-07-01

Three polymorphs of L-Citrulline crystals, anhydrate (Form α, γ and δ) and pseudo polymorph (dihydrate), were confirmed. In this study, polymorphic control of L-Citrulline was attempted by changing the ethanol concentration in ethanol-water binary solvents. First, each polymorph of L-Citrulline crystals was added to the prepared ethanol-water binary solvents and samples which were obtained chronologically were measured by XRD. Also, the crystal sizes and shapes in transformation were observed by microscope. Then, polymorphs of the crystals after transformation were determined by XRD pattern. As a result, the transformation from dihydrate to anhydrate was observed by adding dihydrate crystals to the ethanol-water binary solvent. Similarly, the transformation from anhydrate to another anhydrate was observed. Especially in the case of adding dihydrate, the existences of all polymorphs were confirmed by adjusting ethanol-water binary solvent. According to the results, it was revealed that polymorphic transformation was affected by the trace amount of water contained in ethanol-water binary solvent. Moreover, transformation from dihydrate to anhydrate was constructed with three phases, dissolution of dihydrate, nucleation and growth of anhydrate. Therefore, the solution-mediated polymorphic transformation was supposed to be a key mechanism for this transformation.

Infraspecific DNA methylation polymorphism in cotton (Gossypium hirsutum L.).

PubMed

Keyte, Anna L; Percifield, Ryan; Liu, Bao; Wendel, Jonathan F

2006-01-01

Cytosine methylation is important in the epigenetic regulation of gene expression and development in plants and has been implicated in silencing duplicate genes after polyploid formation in several plant groups. Relatively little information exists, however, on levels and patterns of methylation polymorphism (MP) at homologous loci within species. Here we explored the levels and patterns of methylation-polymorphism diversity at CCGG sites within allotetraploid cotton, Gossypium hirsutum, using a methylation-sensitive amplified fragment length polymorphism screen and a selected set of 20 G. hirsutum accessions for which we have information on genetic polymorphism levels and relationships. Methylation and MP exist at high levels within G. hirsutum: of 150 HpaII/MspI sites surveyed, 48 were methylated at the inner cytosine (32%) and 32 of these were polymorphic (67%). Both these values are higher than comparable measures of genetic diversity using restriction fragment length polymorphisms. The high percentage of methylation-polymorphic sites and potential relationship to gene expression underscore the potential significance of MP within and among populations. We speculate that biased correlation of methylation-polymorphic sites and genes in cotton may be a consequence of polyploidy and the attendant doubling of all genes.

Association between MTHFR polymorphisms and acute myeloid leukemia risk: a meta-analysis.

PubMed

Qin, Yu-Tao; Zhang, Yong; Wu, Fang; Su, Yan; Lu, Ge-Ning; Wang, Ren-Sheng

2014-01-01

Previous observational studies investigating the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and acute myeloid leukemia risk (AML) have yielded inconsistent results. The aim of this study is to derive a more precise estimation of the association between MTHFR (C677T and A1298C) polymorphisms and acute myeloid leukemia risk. PubMed and Embase databases were systematically searched to identify relevant studies from their inception to August 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were the metric of choice. Thirteen studies were selected for C677T polymorphism (1838 cases and 5318 controls) and 9 studies (1335 patients and 4295 controls) for A1298C polymorphism. Overall, pooled results showed that C677T polymorphism was not significant associated with AML risk(OR, 0.98-1.04; 95% CI, 0.86-0.92 to 1.09-1.25). Similar results were observed for the A1298C polymorphism and in subgroup analysis. All comparisons revealed no substantial heterogeneity nor did we detect evidence of publication bias. In summary, this meta-analysis provides evidence that MTHFR polymorphisms were not associated with AML risk. Further investigations are needed to offer better insight into the role of these polymorphisms in AML carcinogenesis.

Telomerase Reverse Transcriptase Locus Polymorphisms and Cancer Risk: A Field Synopsis and Meta-Analysis

PubMed Central

Verdi, Daunia; Pooley, Karen A.; Landi, Maria T.; Egan, Kathleen M.; Baird, Duncan M.; Prescott, Jennifer; De Vivo, Immaculata; Nitti, Donato

2012-01-01

Background Several recent studies have provided evidence that polymorphisms in the telomerase reverse transcriptase (TERT) gene sequence are associated with cancer development, but a comprehensive synopsis is not available. We conducted a systematic review and meta-analysis of the available molecular epidemiology data regarding the association between TERT locus polymorphisms and predisposition to cancer. Methods A systematic review of the English literature was conducted by searching PubMed, Embase, Cancerlit, Google Scholar, and ISI Web of Knowledge databases for studies on associations between TERT locus polymorphisms and cancer risk. Random-effects meta-analysis was performed to pool per-allele odds ratios for TERT locus polymorphisms and risk of cancer, and between-study heterogeneity and potential bias sources (eg, publication and chasing bias) were assessed. Because the TERT locus includes the cleft lip and palate transmembrane 1-like (CLPTM1L) gene, which is in linkage disequilibrium with TERT, CLPTM1L polymorphisms were also analyzed. Cumulative evidence for polymorphisms with statistically significant associations was graded as “strong,” “moderate,” and “weak” according to the Venice criteria. The joint population attributable risk was calculated for polymorphisms with strong evidence of association. Results Eighty-five studies enrolling 490 901 subjects and reporting on 494 allelic contrasts were retrieved. Data were available on 67 TERT locus polymorphisms and 24 tumor types, for a total of 221 unique combinations of polymorphisms and cancer types. Upon meta-analysis, a statistically significant association with the risk of any cancer type was found for 22 polymorphisms. Strong, moderate, and weak cumulative evidence for association with at least one tumor type was demonstrated for 11, 9, and 14 polymorphisms, respectively. For lung cancer, which was the most studied tumor type, the estimated joint population attributable risk for three polymorphisms (TERT rs2736100, intergenic rs4635969, and CLPTM1L rs402710) was 41%. Strong evidence for lack of association was identified for five polymorphisms in three tumor types. Conclusions To our knowledge, this is the largest collection of data for associations between TERT locus polymorphisms and cancer risk. Our findings support the hypothesis that genetic variability in this genomic region can modulate cancer susceptibility in humans. PMID:22523397

Conformational flexibility and packing plausibility of repaglinide polymorphs

NASA Astrophysics Data System (ADS)

Rani, Dimpy; Goyal, Parnika; Chadha, Renu

2018-04-01

The present manuscript highlights the structural insight into the repaglinide polymorphs. The experimental screening for the possible crystal forms were carried out using various solvents, which generated three forms. The crystal structure of Form II and III was determined using PXRD pattern whereas structural analysis of Form I has already been reported. Form I, II and II was found to exist in P212121, PNA21 and P21/c space groups respectively. Conformational analysis was performed to account the conformational flexibility of RPG. The obtained conformers were further utilized to obtain the information about the crystal packing pattern of RPG polymorphs by polymorph prediction module. The lattice energy landscape, depicting the relationship between lattice energy and density of the polymorphs has been obtained for various possible polymorphs. The experimentally isolated polymorphs were successfully fitted into lattice energy landscape.

Coplanar semiconductor-metal circuitry defined on few-layer MoTe2 via polymorphic heteroepitaxy

NASA Astrophysics Data System (ADS)

Sung, Ji Ho; Heo, Hoseok; Si, Saerom; Kim, Yong Hyeon; Noh, Hyeong Rae; Song, Kyung; Kim, Juho; Lee, Chang-Soo; Seo, Seung-Young; Kim, Dong-Hwi; Kim, Hyoung Kug; Yeom, Han Woong; Kim, Tae-Hwan; Choi, Si-Young; Kim, Jun Sung; Jo, Moon-Ho

2017-11-01

Crystal polymorphism selectively stabilizes the electronic phase of atomically thin transition-metal dichalcogenides (TMDCs) as metallic or semiconducting, suggesting the potential to integrate these polymorphs as circuit components in two-dimensional electronic circuitry. Developing a selective and sequential growth strategy for such two-dimensional polymorphs in the vapour phase is a critical step in this endeavour. Here, we report on the polymorphic integration of distinct metallic (1T‧) and semiconducting (2H) MoTe2 crystals within the same atomic planes by heteroepitaxy. The realized polymorphic coplanar contact is atomically coherent, and its barrier potential is spatially tight-confined over a length of only a few nanometres, with a lowest contact barrier height of ∼25 meV. We also demonstrate the generality of our synthetic integration approach for other TMDC polymorph films with large areas.

Association of TNFα-308, IFNγ+874, and IL10-1082 gene polymorphisms and the risk of non-small cell lung cancer in the population of the South Indian state of Telangana.

PubMed

Peddireddy, Vidyullatha; Badabagni, Siva Prasad; Sulthana, Shehnaz; Kolla, Venkata Karunakar; Gundimeda, Sandhya Devi; Mundluru, Hemaprasad

2016-10-01

Cytokine-mediated inflammation is important in the pathogenesis of non-small cell lung cancer (NSCLC). Genetic polymorphisms in cytokine genes and their association with lung cancer in the Indian population have not been reported. For the first time, we analyzed genetic polymorphisms of TNFα -308 , IFNγ +874 , and IL10 -1082 genes in 246 NSCLC patients and 250 healthy controls in the South Indian population from Telangana using ARMS PCR. IFNγ +874 A/T and IL10 -1082 G/G gene polymorphisms were found to be significantly associated with NSCLC with 1.56- and 1.68-fold disease risk, respectively. There was no association between the risk of NSCLC and TNFα -308 polymorphism. Gene polymorphisms stratified according to smoking revealed that IFNγ +874 A/T polymorphisms in smokers increased the disease risk by 2.91 fold. IL10 -1082 G/G polymorphisms showed 2-fold increased risk among patients who were smokers when compared to the controls. However, there was no association between TNFα -308 , IFNγ +874 , and IL10 -1082 gene polymorphism and the stage of the NSCLC patients. The overall risk associated with the combination of these polymorphisms indicated that the TNFα -308 G/A + IFNγ +874 A/T + IL10 -1082 G/G genotype increased the risk by 1.5 fold. The results of our study indicate an association between cytokine gene polymorphisms and the risk of NSCLC in an Indian population.

The Role of Lattice Matching Techniques in the Characterization of Polymorphic Forms.

PubMed

Mighell, Alan D

2011-01-01

An inspection of the recent literature reveals that polymorphism is a frequently encountered phenomenon. The recognition of polymorphic forms plays a vital role in the materials sciences because such structures are characterized by different crystal packing and accordingly have different physical properties. In the pharmaceutical industry, recognition of polymorphic forms can be critical for, in certain cases, a polymorphic form of a drug may be an ineffective therapeutic agent due to its unfavorable physical properties. A check of the recent literature has revealed that in some cases new polymorphic forms are not recognized. In other instances, a supposedly new polymeric form is actually the result of an incorrect structure determination. Fortunately, lattice-matching techniques, which have proved invaluable in the identification and characterization of crystal structures, represent a powerful tool for analyzing polymorphic forms. These lattice-matching methods are based on either of two strategies: (a) the reduced cell strategy-the matching of reduced cells of the respective lattices or (b) the matrix strategy-the determination of a matrix or matrices relating the two lattices coupled with an analysis of the matrix elements. Herein, these techniques are applied to three typical cases-(a) the identification of a new polymorphic form, (b) the demonstration that a substance may not be a new polymorphic form due to missed symmetry, and (c) the evaluation of pseudo polymorphism because of a missed lattice. To identify new polymorphic forms and to prevent errors, it is recommended that these lattice matching techniques become an integral part of the editorial review process of crystallography journals.

Are "functionally related polymorphisms" of renin-angiotensin-aldosterone system gene polymorphisms associated with hypertension?

PubMed

Hahntow, Ines N; Mairuhu, Gideon; van Valkengoed, Irene Gm; Koopmans, Richard P; Michel, Martin C

2010-06-02

Genotype-phenotype association studies are typically based upon polymorphisms or haplotypes comprised of multiple polymorphisms within a single gene. It has been proposed that combinations of polymorphisms in distinct genes, which functionally impact the same phenotype, may have stronger phenotype associations than those within a single gene. We have tested this hypothesis using genes encoding components of the renin-angiotensin-aldosterone system and the high blood pressure phenotype. Our analysis is based on 1379 participants of the cross-sectional SUNSET study randomly selected from the population register of Amsterdam. Each subject was genotyped for the angiotensinogen M235T, the angiotensin-converting enzyme insertion/deletion and the angiotensin II type 1 receptor A1166C polymorphism. The phenotype high blood pressure was defined either as a categorical variable comparing hypertension versus normotension as in most previous studies or as a continuous variable using systolic, diastolic and mean blood pressure in a multiple regression analysis with gender, ethnicity, age, body-mass-index and antihypertensive medication as covariates. Genotype-phenotype relationships were explored for each polymorphism in isolation and for double and triple polymorphism combinations. At the single polymorphism level, only the A allele of the angiotensin II type 1 receptor was associated with a high blood pressure phenotype. Using combinations of polymorphisms of two or all three genes did not yield stronger/more consistent associations. We conclude that combinations of physiologically related polymorphisms of multiple genes, at least with regard to the renin-angiotensin-aldosterone system and the hypertensive phenotype, do not necessarily offer additional benefit in analyzing genotype/phenotype associations.

Two polymorphs of safinamide, a selective and reversible inhibitor of monoamine oxidase B.

PubMed

Ravikumar, Krishnan; Sridhar, Balasubramanian

2010-06-01

Two polymorphs of safinamide {systematic name: (2S)-2-[4-(3-fluorobenzyloxy)benzylamino]propionamide}, C(17)H(19)FN(2)O(2), a potent selective and reversible monoamine oxidase B (MAO-B) inhibitor, are described. Both forms are orthorhombic and regarded as conformational polymorphs due to the differences in the orientation of the 3-fluorobenzyloxy and propanamide groups. Both structures pack with layers in the ac plane. In polymorph (I), the layers have discrete wide and narrow regions which are complementary when located next to adjacent layers. In polymorph (II), the layer has long flanges protruding from each side, which interdigitate when packed with the adjacent layers. N-H...O hydrogen bonds are present in both structures, whereas N-H...F hydrogen bonding is seen in polymorph (I), while N-H...N hydrogen bonding is seen in polymorph (II).

Detection of DNA methylation changes in micropropagated banana plants using methylation-sensitive amplification polymorphism (MSAP).

PubMed

Peraza-Echeverria, S; Herrera-Valencia, V A.; Kay, A -J.

2001-07-01

The extent of DNA methylation polymorphisms was evaluated in micropropagated banana (Musa AAA cv. 'Grand Naine') derived from either the vegetative apex of the sucker or the floral apex of the male inflorescence using the methylation-sensitive amplification polymorphism (MSAP) technique. In all, 465 fragments, each representing a recognition site cleaved by either or both of the isoschizomers were amplified using eight combinations of primers. A total of 107 sites (23%) were found to be methylated at cytosine in the genome of micropropagated banana plants. In plants micropropagated from the male inflorescence explant 14 (3%) DNA methylation events were polymorphic, while plants micropropagated from the sucker explant produced 8 (1.7%) polymorphisms. No DNA methylation polymorphisms were detected in conventionally propagated banana plants. These results demonstrated the usefulness of MSAP to detect DNA methylation events in micropropagated banana plants and indicate that DNA methylation polymorphisms are associated with micropropagation.

Survey and analysis of crystal polymorphism in organic structures

PubMed Central

Kaur, Ramanpreet

2018-01-01

With the intention of producing the most comprehensive treatment of the prevalence of crystal polymorphism among structurally characterized materials, all polymorphic compounds flagged as such within the Cambridge Structural Database (CSD) are analysed and a list of crystallographically characterized organic polymorphic compounds is assembled. Classifying these structures into subclasses of anhydrates, salts, hydrates, non-hydrated solvates and cocrystals reveals that there are significant variations in polymorphism prevalence as a function of crystal type, a fact which has not previously been recognized in the literature. It is also shown that, as a percentage, polymorphic entries are decreasing temporally within the CSD, with the notable exception of cocrystals, which continue to rise at a rate that is a constant fraction of the overall entries. Some phenomena identified that require additional scrutiny include the relative prevalence of temperature-induced phase transitions among organic salts and the paucity of polymorphism in crystals with three or more chemical components. PMID:29765601

Anagostic interactions in chiral separation. Polymorphism in a [Co(II)(L)] complex: Crystallographic and theoretical studies

NASA Astrophysics Data System (ADS)

Awwadi, Firas F.; Hodali, Hamdallah A.

2018-02-01

Syntheses and crystal structures of two polymorphs of the complex [Co(II)(L)], where H2L = 2,2'-[cis-1,2-diaminocyclohexanediylbis (nitrilo-methylidyne)]bis (5-dimethyl-amino]phenol, have been studied. The two polymorphs concomitantly crystallized by vapour diffusion of solvent. The first polymorph (I) crystallized as a racemate in the centrosymmetric tetragonal I41/a space group. The second polymorph (II) crystallized in the chiral orthorhombic space group P212121. The chiral conformers of symmetrical cis-1,2-disubstituted cyclohexane molecules cannot be resolved in the liquid or gas phases, due to the rapid ring inversion. In the present study, the two chiral conformers are present in crystals of polymorph I, whereas, only one chiral conformer is present in crystals of polymorph II. Crystal structure analysis indicated that the formation of two different polymorphs of [Co(II)(L)] complex can be rationalized based on Csbnd H⋯Co anagostic interactions. Density Functional Theory (DFT) calculations indicated that Csbnd H⋯Co interactions are due to HOMO-LUMO interactions.

Association of BIM Deletion Polymorphism and BIM-γ RNA Expression in NSCLC with EGFR Mutation.

PubMed

Isobe, Kazutoshi; Kakimoto, Atsushi; Mikami, Tetsuo; Kaburaki, Kyohei; Kobayashi, Hiroshi; Yoshizawa, Takahiro; Makino, Takashi; Otsuka, Hajime; Sano, G O; Sugino, Keishi; Sakamoto, Susumu; Takai, Yujiro; Tochigi, Naobumi; Iyoda, Akira; Homma, Sakae

This pilot study assessed the association of BIM deletion polymorphism and BIM RNA isoform in patients with EGFR-positive non-small cell lung cancer (NSCLC). The study included 33 patients with EGFR-positive NSCLC treated with gefitinib. BIM deletion polymorphism and BIM RNA isoform (EL/L/S/γ) were determined by polymerase chain reaction (PCR). BIM-γ expression was significantly higher in patients with BIM deletion polymorphism than among those without BIM deletion polymorphism inside tumors (p=0.038) and around tumors (p=0.0024). Relative BIM-γ expression was significantly higher in patients with BIM deletion polymorphism than among those without BIM deletion polymorphism (p=0.0017). Patients with BIM-γ had significantly shorter progression-free survival than those without BIM-γ (median: 304 vs. 732 days; p=0.023). Expression of BIM-γ mRNA and BIM deletion polymorphism were strongly associated. BIM-γ overexpression may have a role in apoptosis related to EGFR-tyrosine kinase inhibitor. Copyright© 2016, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

[Prevalence of dyslipidemia in middle-aged adults with NOS3 gene polymorphism and low cardiorespiratory fitness].

PubMed

Malagrino, Pamella A; Sponton, Carlos H G; Esposti, Rodrigo D; Franco-Penteado, Carla F; Fernandes, Romulo A; Bezerra, Marcos André C; Albuquerque, Dulcinéia M; Rodovalho, Cynara M; Bacci, Maurício; Zanesco, Angelina

2013-02-01

To evaluate the influence of the interaction between endothelial nitric oxide synthase gene (NOS3) polymorphisms at positions -786T>C, Glu298Asp and intron 4b/a, and cardiorespiratory fitness on plasma nitrite/nitrate levels, blood pressure, lipid profile, and prevalence of cardiometabolic disorders. Ninety-two volunteers were genotyped for NOS3 polymorphisms at positions (-786T>C and Glu298Asp) and (intron 4b/a) and divided according to the genotype: non-polymorphic (NP) and polymorphic (P). After that, they were subdivided according to the cardiorespiratory fitness associated with genotype: high (HNP and HP) and low (LNP and LP). The subjects with polymorphism for the interactions at positions Glu298Asp + intron 4b/a, and Glu298Asp+-786T>C showed the highest values in total cholesterol, as well as dyslipidemia. Our findings show that NOS3 gene polymorphisms at positions -786T>C, Glu298Asp, and intron 4b/a exert negative effects on the lipid profile compared with those who do not carry polymorphisms.

The evaluation of angiotensin-converting enzyme (ACE) gene I/D and IL-4 gene intron 3 VNTR polymorphisms in coronary artery disease.

PubMed

Basol, Nursah; Celik, Atac; Karakus, Nevin; Ozturk, Sibel Demir; Ozsoy, Sibel Demir; Yigit, Serbulent

2014-01-01

Genetic polymorphism is a strong risk factor for coronary artery disease (CAD). In the present study, our aim was to evaluate angiotensin-converting enzyme (ACE) gene I/D polymorphism and interleukin-4 (IL-4) gene Intron 3 variable number of tandem repeat (VNTR) polymorphism in CAD. One hundred and twenty-four CAD patients and one hundred and twenty-three controls were enrolled. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) analyses. The risk associated with inheriting the combined genotypes for the two polymorphisms were evaluated and it was found that the individuals who were P2P2-homozygous at IL-4 gene intron 3 VNTR and DD-homozygous at ACE gene I/D have a higher risk of developing CAD. Although, there is no correlation between IL4 VNTR polymorphism and ACE gene polymorphism and CAD, there is a strong association between CAD and co-existence of IL-4 VNTR and ACE gene polymorphisms in the Turkish population. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Role of ACE and AGT gene polymorphisms in genetic susceptibility to diabetes mellitus type 2 in a Brazilian sample.

PubMed

Wollinger, L M; Dal Bosco, S M; Rempe, C; Almeida, S E M; Berlese, D B; Castoldi, R P; Arndt, M E; Contini, V; Genro, J P

2015-12-29

The aim of the current study was to investigate the association between the InDel polymorphism in the angiotensin I-converting enzyme gene (ACE) and the rs699 polymorphism in the angiotensinogen gene (AGT) and diabetes mellitus type 2 (DM2) in a sample population from Southern Brazil. A case-control study was conducted with 228 patients with DM2 and 183 controls without DM2. The ACE InDel polymorphism was genotyped by polymerase chain reaction (PCR) with specific primers, followed by electrophoresis on 1.5% agarose gel. The AGT rs699 polymorphism was genotyped using a real-time PCR assay. No significant association between the ACE InDel polymorphism and DM2 was detected (P = 0.97). However, regarding the AGT rs699 polymorphism, DM2 patients had a significantly higher frequency of the AG genotype and lower frequency of the GG genotype when compared to the controls (P = 0.03). Our results suggest that there is an association between the AGT rs699 polymorphism and DM2 in a Brazilian sample.

DRD2/ANKK1 gene polymorphisms in forensic autopsies of methamphetamine intoxication fatalities.

PubMed

Matsusue, Aya; Ishikawa, Takaki; Ikeda, Tomoya; Tani, Naoto; Arima, Hisatomi; Waters, Brian; Hara, Kenji; Kashiwagi, Masayuki; Takayama, Mio; Ikematsu, Natsuki; Kubo, Shin-Ichi

2018-04-22

Dopamine D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1) gene polymorphisms have been associated with responses to psychotropic drugs and addiction. We analyzed two DRD2/ANKK1 polymorphisms, Taq1A and -141C Ins/Del, in 37 fatal methamphetamine (MA) intoxication cases and 235 control cases in which MA and psychotropic drugs were not detected. The association among polymorphism, cause of death, and cerebrospinal fluid (CSF) dopamine concentration was evaluated. The Taq1A polymorphism distribution in the fatal MA intoxication cases differed from in the controls (P = 0.030) with a significantly high A1/A1 + A1/A2 genotype frequency. No significant associations were observed between -141C Ins/Del polymorphisms and MA intoxication cases or between DRD2/ANKK1 polymorphisms and CSF dopamine concentrations. Our findings suggest that the DRD2/ANKK1 Taq1A polymorphism is associated with susceptibility to fatal MA intoxication. Copyright © 2018 Elsevier B.V. All rights reserved.

No evidence of association between NOD2/CARD15 gene polymorphism and atherosclerotic events after renal transplantation

PubMed Central

Courivaud, Cécile; Ferrand, Christophe; Deschamps, Marina; Tiberghien, Pierre; Chalopin, Jean-Marc; Duperrier, Anne; Saas, Philippe; Ducloux, Didier

2006-01-01

Stable renal transplant recipients (RTR) display high rates of atherosclerotic events (AE). Innate immunity and especially vascular inflammation play a role in the pathogenesis of atherosclerosis. It is illustrated both by an increased occurrence of post-renal transplant cardiovascular events in patients with elevated levels of C-reactive protein and by a correlation between post-transplant AE and Toll-like receptor-4 Asp299Gly polymorphism. Here, we analyze the influence NOD2/CARD15 gene polymorphism since NOD2 can modulate macrophage pro-inflammatory activity and macrophage is present in early atherosclerotic lesions. The incidence of single nucleotide polymorphism (SNP) in the three major polymorphic region of NOD2 gene (SNP8, SNP12 and SNP13) was assessed in 182 RTR and the correlation between such polymorphism and the development of AE was analyzed. No correlation was observed between NOD2 gene polymorphism and the occurrence of AE after renal transplantation. NOD2 gene polymorphism thus does not appear to influence cardiovascular complications in RTR. PMID:16641610

Uterine leiomyoma is associated with a polymorphism in the interleukin 1-beta gene.

PubMed

Pietrowski, Detlef; Thewes, Roberta; Sator, Michael; Denschlag, Dominik; Keck, Christoph; Tempfer, Clemens

2009-08-01

To investigate whether polymorphisms in the interleukin-1beta (IL-1beta) gene are associated with uterine leiomyoma. Case-control study in a collective of 131 patients and 280 controls. Genotyping of the IL-1beta-511 and IL-1beta-3954 polymorphism was performed by PCR amplification and subsequent RFLP analysis. A significant difference in the allele frequencies of the IL-1beta-511 C

The germline BIM deletion polymorphism is not associated with the treatment efficacy of sorafenib in patients with advanced hepatocellular carcinoma.

PubMed

Shao, Yu-Yun; Chang, Yung-Lin; Huang, Chung-Yi; Hsu, Chih-Hung; Cheng, Ann-Lii

2013-01-01

A germline BIM deletion polymorphism has been proposed to predict a poor treatment efficacy of certain kinase inhibitors. The current study aimed to explore whether the BIM deletion polymorphism predicts the treatment efficacy of sorafenib for advanced hepatocellular carcinoma (HCC). All patients who were enrolled in clinical trials to receive sorafenib-containing regimens as first-line therapy for advanced HCC and consented to providing peripheral blood samples were included. Polymerase chain reaction followed by gel electrophoresis was used to detect the germline BIM deletion polymorphism. A total of 89 patients were enrolled; 69 (77%) patients had chronic hepatitis B infection, and 18 (20%) had chronic hepatitis C infection. The heterozygous BIM deletion polymorphism was identified in 9 (10%) patients. Patients with and without the BIM deletion polymorphism had similar response rates (11 vs. 6%) and disease control rates (56 vs. 61%). The time to progression, progression-free survival, and overall survival were similar between patients with and without the BIM deletion polymorphism. After adjusting for basic clinicopathologic variables and treatment regimens, the BIM polymorphism still could not predict treatment outcomes. The BIM deletion polymorphism was not associated with the treatment efficacy of sorafenib for advanced HCC. © 2013 S. Karger AG, Basel.

Environmental Adaptation Contributes to Gene Polymorphism across the Arabidopsis thaliana Genome

PubMed Central

Lee, Cheng-Ruei

2012-01-01

The level of within-species polymorphism differs greatly among genes in a genome. Many genomic studies have investigated the relationship between gene polymorphism and factors such as recombination rate or expression pattern. However, the polymorphism of a gene is affected not only by its physical properties or functional constraints but also by natural selection on organisms in their environments. Specifically, if functionally divergent alleles enable adaptation to different environments, locus-specific polymorphism may be maintained by spatially heterogeneous natural selection. To test this hypothesis and estimate the extent to which environmental selection shapes the pattern of genome-wide polymorphism, we define the "environmental relevance" of a gene as the proportion of genetic variation explained by environmental factors, after controlling for population structure. We found substantial effects of environmental relevance on patterns of polymorphism among genes. In addition, the correlation between environmental relevance and gene polymorphism is positive, consistent with the expectation that balancing selection among heterogeneous environments maintains genetic variation at ecologically important genes. Comparison of the gene ontology annotations shows that genes with high environmental relevance are enriched in unknown function categories. These results suggest an important role for environmental factors in shaping genome-wide patterns of polymorphism and indicate another direction of genomic study. PMID:22798389

Association between MTHFR Polymorphisms and Acute Myeloid Leukemia Risk: A Meta-Analysis

PubMed Central

Su, Yan; Lu, Ge-Ning; Wang, Ren-Sheng

2014-01-01

Previous observational studies investigating the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and acute myeloid leukemia risk (AML) have yielded inconsistent results. The aim of this study is to derive a more precise estimation of the association between MTHFR (C677T and A1298C) polymorphisms and acute myeloid leukemia risk. PubMed and Embase databases were systematically searched to identify relevant studies from their inception to August 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were the metric of choice. Thirteen studies were selected for C677T polymorphism (1838 cases and 5318 controls) and 9 studies (1335 patients and 4295 controls) for A1298C polymorphism. Overall, pooled results showed that C677T polymorphism was not significant associated with AML risk(OR, 0.98–1.04; 95% CI, 0.86–0.92 to 1.09–1.25). Similar results were observed for the A1298C polymorphism and in subgroup analysis. All comparisons revealed no substantial heterogeneity nor did we detect evidence of publication bias. In summary, this meta-analysis provides evidence that MTHFR polymorphisms were not associated with AML risk. Further investigations are needed to offer better insight into the role of these polymorphisms in AML carcinogenesis. PMID:24586405

Controlling the crystal polymorph by exploiting the time dependence of nucleation rates.

PubMed

Little, Laurie J; King, Alice A K; Sear, Richard P; Keddie, Joseph L

2017-10-14

Most substances can crystallise into two or more different crystal lattices called polymorphs. Despite this, there are no systems in which we can quantitatively predict the probability of one competing polymorph forming instead of the other. We address this problem using large scale (hundreds of events) studies of the competing nucleation of the alpha and gamma polymorphs of glycine. In situ Raman spectroscopy is used to identify the polymorph of each crystal. We find that the nucleation kinetics of the two polymorphs is very different. Nucleation of the alpha polymorph starts off slowly but accelerates, while nucleation of the gamma polymorph starts off fast but then slows. We exploit this difference to increase the purity with which we obtain the gamma polymorph by a factor of ten. The statistics of the nucleation of crystals is analogous to that of human mortality, and using a result from medical statistics, we show that conventional nucleation data can say nothing about what, if any, are the correlations between competing nucleation processes. Thus we can show that with data of our form it is impossible to disentangle the competing nucleation processes. We also find that the growth rate and the shape of a crystal depend on it when nucleated. This is new evidence that nucleation and growth are linked.

IL-1 polymorphism and periimplantitis. A literature review.

PubMed

Bormann, Kai-Hendrik; Stühmer, Constantin; Z'Graggen, Marcel; Kokemöller, Horst; Rücker, Martin; Gellrich, Nils-Claudius

2010-01-01

The most important factor leading to periimplantitis with bone loss appears to be an inflammatory process due to plaque accumulation. The object of this article was to present a review of the literature on a possible correlation between IL-1 polymorphism and periimplantitis. Research was carried out in the PUBMED and WEB OF KNOWLEDGE literature databases and 27 relevant articles were found. Of these articles, 4 groups of authors came to the conclusion that no correlation exists between IL-1 polymorphism and periimplantitis. In 5 articles by 4 groups of authors, the influence of IL-1 polymorphism on periimplantitis is unclear. 9 studies prove a correlation between IL-1 polymorphism and periimplantitis, and 6 studies also document a direct linkage between gene polymorphism and periimplantitis, if certain cofactors are present. IL-1 polymorphism is frequently connected with "noninfectious periimplant bone loss". Other studies prove that the inflammatory mediators and IL-1beta were significantly elevated in the gingival crevicular fluid (GCF) of infected implants. Many studies document that IL-1 polymorphism alone cannot be considered a risk factor for bone loss, but in combination with smoking, it is closely associated with periimplant bone loss. More studies are needed to discover possible correlations between IL-1 polymorphism and periimplantitis.

Characterization and compilation of polymorphic simple sequence repeat (SSR) markers of peanut from public database

PubMed Central

2012-01-01

Background There are several reports describing thousands of SSR markers in the peanut (Arachis hypogaea L.) genome. There is a need to integrate various research reports of peanut DNA polymorphism into a single platform. Further, because of lack of uniformity in the labeling of these markers across the publications, there is some confusion on the identities of many markers. We describe below an effort to develop a central comprehensive database of polymorphic SSR markers in peanut. Findings We compiled 1,343 SSR markers as detecting polymorphism (14.5%) within a total of 9,274 markers. Amongst all polymorphic SSRs examined, we found that AG motif (36.5%) was the most abundant followed by AAG (12.1%), AAT (10.9%), and AT (10.3%).The mean length of SSR repeats in dinucleotide SSRs was significantly longer than that in trinucleotide SSRs. Dinucleotide SSRs showed higher polymorphism frequency for genomic SSRs when compared to trinucleotide SSRs, while for EST-SSRs, the frequency of polymorphic SSRs was higher in trinucleotide SSRs than in dinucleotide SSRs. The correlation of the length of SSR and the frequency of polymorphism revealed that the frequency of polymorphism was decreased as motif repeat number increased. Conclusions The assembled polymorphic SSRs would enhance the density of the existing genetic maps of peanut, which could also be a useful source of DNA markers suitable for high-throughput QTL mapping and marker-assisted selection in peanut improvement and thus would be of value to breeders. PMID:22818284

Evaluation of a Panel of Single-Nucleotide Polymorphisms in miR-146a and miR-196a2 Genomic Regions in Patients with Chronic Periodontitis.

PubMed

Venugopal, Priyanka; Lavu, Vamsi; RangaRao, Suresh; Venkatesan, Vettriselvi

2017-04-01

Periodontitis is an inflammatory disease caused by bacterial triggering of the host immune-inflammatory response, which in turn is regulated by microRNAs (miRNA). Polymorphisms in the miRNA pathways affect the expression of several target genes such as tumor necrosis factor-α and interleukins, which are associated with progression of disease. The objective of this study was to identify the association between the MiR-146a single nucleotide polymorphisms (SNPs) (rs2910164, rs57095329, and rs73318382), the MiR-196a2 (rs11614913) SNP and chronic periodontitis. Genotyping was performed for the MiR-146a (rs2910164, rs57095329, and rs73318382) and the MiR-196a2 (rs11614913) polymorphisms in 180 healthy controls and 190 cases of chronic periodontitis by the direct Sanger sequencing technique. The strength of the association between the polymorphisms and chronic periodontitis was evaluated using logistic regression analysis. Haplotype and linkage analyses among the polymorphisms was performed. Multifactorial dimensionality reduction was performed to determine epistatic interaction among the polymorphisms. The MiR-196a2 polymorphism revealed a significant inverse association with chronic periodontitis. Haplotype analysis of MiR-146a and MiR-196a2 polymorphisms revealed 13 different combinations, of which 5 were found to have an inverse association with chronic periodontitis. The present study has demonstrated a significant inverse association of MiR-196a2 polymorphism with chronic periodontitis.

Genetic polymorphisms, hormone levels, and hot flashes in midlife women.

PubMed

Schilling, Chrissy; Gallicchio, Lisa; Miller, Susan R; Langenberg, Patricia; Zacur, Howard; Flaws, Jodi A

2007-06-20

Hot flashes disrupt the lives of millions of women each year. Although hot flashes are a public health concern, little is known about risk factors that predispose women to hot flashes. Thus, the objective of this study was to examine whether sex steroid hormone levels and genetic polymorphisms in hormone biosynthesis and degradation enzymes are associated with the risk of hot flashes. In a cross-sectional study design, midlife women aged 45-54 years (n=639) were recruited from Baltimore and its surrounding counties. Participants completed a questionnaire and donated a blood sample for steroid hormone analysis and genotyping. The associations between genetic polymorphisms and hormone levels, as well as the associations between genetic polymorphisms, hormone levels, and hot flashes were examined using statistical models. A polymorphism in CYP1B1 was associated with lower dehydroepiandrosterone-sulfate (DHEA-S) and progesterone levels, while a polymorphism in CYP19 (aromatase) was associated with higher testosterone and DHEA-S levels. Lower progesterone and sex hormone binding globulin levels, lower free estradiol index, and a higher ratio of total androgens to total estrogens were associated with the experiencing of hot flashes. A polymorphism in CYP1B1 and a polymorphism in 3betaHSD were both associated with hot flashes. Some genetic polymorphisms may be associated with altered levels of hormones in midlife women. Further, selected genetic polymorphisms and altered hormone levels may be associated with the risk of hot flashes in midlife women.

Intragenomic polymorphisms among high-copy loci: a genus-wide study of nuclear ribosomal DNA in Asclepias (Apocynaceae).

PubMed

Weitemier, Kevin; Straub, Shannon C K; Fishbein, Mark; Liston, Aaron

2015-01-01

Despite knowledge that concerted evolution of high-copy loci is often imperfect, studies that investigate the extent of intragenomic polymorphisms and comparisons across a large number of species are rarely made. We present a bioinformatic pipeline for characterizing polymorphisms within an individual among copies of a high-copy locus. Results are presented for nuclear ribosomal DNA (nrDNA) across the milkweed genus, Asclepias. The 18S-26S portion of the nrDNA cistron of Asclepias syriaca served as a reference for assembly of the region from 124 samples representing 90 species of Asclepias. Reads were mapped back to each individual's consensus and at each position reads differing from the consensus were tallied using a custom perl script. Low frequency polymorphisms existed in all individuals (mean = 5.8%). Most nrDNA positions (91%) were polymorphic in at least one individual, with polymorphic sites being less frequent in subunit regions and loops. Highly polymorphic sites existed in each individual, with highest abundance in the "noncoding" ITS regions. Phylogenetic signal was present in the distribution of intragenomic polymorphisms across the genus. Intragenomic polymorphisms in nrDNA are common in Asclepias, being found at higher frequency than any other study to date. The high and variable frequency of polymorphisms across species highlights concerns that phylogenetic applications of nrDNA may be error-prone. The new analytical approach provided here is applicable to other taxa and other high-copy regions characterized by low coverage genome sequencing (genome skimming).

Association of estrogen receptor gene polymorphisms with human precocious puberty: a systematic review and meta-analysis.

PubMed

Luo, Yan; Liu, Qin; Lei, Xun; Wen, Yi; Yang, Ya-Lan; Zhang, Rui; Hu, Meng-Yao

2015-07-01

This study aims to estimate the association between ESR1 polymorphisms (PvuII and XbaI) and ESR2 polymorphisms (RsaI and AluI) with precocious puberty. Relevant studies published before March 2014 were retrieved by a electronic search among nine databases. Meta-analysis of the pooled odds ratios (ORs) with 95% confidence intervals (CIs) was calculated. Four eligible case-control studies including 491 precocious puberty patients and 370 healthy controls were identified. Three studies reported ESR1 PvuII and XbaI polymorphism and one study reported ESR2 RsaI and AluI polymorphism. Increment of precocious puberty risk was associated with PvuII polymorphism in the heterosis model ((CT) versus TT: OR 1.42, 95% CI: 1.05-1.91, p = 0.02). Risk of precocious puberty was associated with XbaI polymorphism in the dominant model (GG + GA versus AA: OR 1.48, 95% CI: 1.11-1.97, p = 0.007) and the heterosis model (GA versus AA: OR 1.68, 95% CI: 1.23-2.29, p = 0.001). This meta-analysis suggests that ESR1 XbaI and PvuII polymorphisms are associated with precocious puberty susceptibility, and the relationship between ESR2 RsaI and AluI polymorphism with precocious puberty remains to be further investigated. Well-designed studies with large sample size among different polymorphisms and ethnicities are in urgent need to provide and update reliable data for comprehensive and definite conclusion.

Association of COL1A1 polymorphisms with osteoporosis: a meta-analysis of clinical studies

PubMed Central

Xie, Peigen; Liu, Bin; Zhang, Liangming; Chen, Ruiqiang; Yang, Bu; Dong, Jianwen; Rong, Limin

2015-01-01

Objective: To conduct a meta-analysis of all association studies on two of the collagen 1 alpha 1 (COL1A1) gene polymorphisms, the -1997G/T (rs1107946) and the -1663indelT (rs2412298) polymorphisms and osteoporosis/BMD and fracture. Methods: PubMed/Medline and Web of Knowledge were searched for relevant association studies published in English. Pooled OR and its corresponding 95% CI or pooled MD and its corresponding 95% CI was calculated with the Cochrane Review Manager (Revman, version 5.2) using a random-effect or a fixed effect model. Results: No significant association between the -1997G/T polymorphism and Lumbar Spine (LS) and Femoral Neck (FN) BMD except for the Caucasian subpopulation wherein subjects with the T allele of the -1997G/T polymorphism was associated with significantly higher LS BMD. Our analysis did reveal that women, especially postmenopausal or perimenopausal women with the GG genotype, had significantly higher Total Hip (TH) BMD than those with the GT. Additionally, our meta-analysis did not show significant association between the -1997G/T polymorphism and risk of fracture, between the -1663indelT polymorphism and LS BMD in postmenopausal or perimenopausal women, or between the -1663indelT polymorphism and the risk of fracture. Conclusions: Our results suggested the possibility of the COL1A1 -1997G/T and the -1663indelT polymorphisms individually playing very little role in osteoporosis and fracture, although more studies are needed especially for the analysis of association between these two polymorphisms and fracture. Haplotype studies may become one important future direction of study to further elucidate whether and how various COL1A1 polymorphisms affect bone health, osteoporosis and fracture. PMID:26628959

Association of -604G/A and -501A/C Ghrelin and Obestatin Prepropeptide Gene Polymorphisms with Polycystic Ovary Syndrome.

PubMed

Ghaleh, Talaat Dabbaghi; Skandari, Somayeh Saadat; Najafipour, Reza; Rashvand, Zahra; Darabi, Masoud; Sahmani, Mehdi

2018-04-01

Ghrelin hormone has an important role in a wide range of metabolic and non-metabolic processes. Polymorphisms of ghrelin gene could be associated with a large number of diseases. The aim of this study was to evaluate the association of -604G/A and -501A/C polymorphisms in ghrelin and obestatin prepropeptide gene (GHRL) with polycystic ovary syndrome (PCOS) in a sample of Iranian women. One hundred and fifty-two women with PCOS and 162 age-matched apparently healthy women as control group were enrolled in this study. The study subjects were genotyped for polymorphisms in the ghrelin gene using polymerase chain reaction-restriction fragment length polymorphism-based methods. Biochemical parameters, serum prolactin, luteinizing hormone, follicle stimulating hormone, estradiol, and testosterone were estimated by chemiluminescence assay. Serum lipids and lipoproteins were determined by standard enzymatic methods. The association between the risk of PCOS and ghrelin gene polymorphisms was examined using Multivariate analysis. The frequency of the -604G/A and -501A/C polymorphisms was not statistically different between patients and the control group of women (p = 0.12 and p = 0.21, respectively). A significantly higher level of LDL-C was found in the wild-type AA genotype compared with CC genotype of -501A/C polymorphism (p = 0.02). Our findings indicate that neither -604G/A and nor -501A/C polymorphisms of ghrelin gene are associated with PCOS, but suggest a relation between the presence of polymorphic allele of -501A/C polymorphism and LDL-C level in a sample of Iranian women.

Clinical relevance of IL-6 gene polymorphism in severely injured patients

PubMed Central

Jeremić, Vasilije; Alempijević, Tamara; Mijatović, Srđan; Šijački, Ana; Dragašević, Sanja; Pavlović, Sonja; Miličić, Biljana; Krstić, Slobodan

2014-01-01

In polytrauma, injuries that may be surgically treated under regular circumstances due to a systemic inflammatory response become life-threatening. The inflammatory response involves a complex pattern of humoral and cellular responses and the expression of related factors is thought to be governed by genetic variations. This aim of this paper is to examine the influence of interleukin (IL) 6 single nucleotide polymorphism (SNP) -174C/G and -596G/A on the treatment outcome in severely injured patients. Forty-seven severely injured patients were included in this study. Patients were assigned an Injury Severity Score. Blood samples were drawn within 24 h after admission (designated day 1) and on subsequent days (24, 48, 72 hours and 7days) of hospitalization. The IL-6 levels were determined through ELISA technique. Polymorphisms were analyzed by a method of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR). Among subjects with different outcomes, no statistically relevant difference was found with regards to the gene IL-6 SNP-174G/C polymorphism. More than a half of subjects who died had the SNP-174G/C polymorphism, while this polymorphism was represented in a slightly lower number in survivors. The incidence of subjects without polymorphism and those with heterozygous and homozygous gene IL-6 SNP-596G/A polymorphism did not present statistically significant variations between survivors and those who died. The levels of IL-6 over the observation period did not present any statistically relevant difference among subjects without the IL-6 SNP-174 or IL-6 SNP -596 gene polymorphism and those who had either a heterozygous or a homozygous polymorphism. PMID:24856384

The 894G>T endothelial nitric oxide synthase genetic polymorphism affects hemodynamic responses to mental stress performed before and after exercise.

PubMed

Rocha, Natália Galito; Neves, Fabricia Junqueira; Silva, Bruno Moreira; Sales, Allan Robson Kluser; Nóbrega, Antonio Claudio

2012-03-01

Nitric oxide is the primary mediator of vasodilation during mental stress. Since genetic polymorphisms in the nitric oxide synthase (eNOS) gene seem to impair the production of NO, this study aimed to evaluate the effect of an exercise bout on hemodynamic responses to mental stress in subjects with the 894G>T polymorphism of eNOS. Subjects without (wild-type group; n = 16) or with (polymorphic-type group; n = 19) the 894G>T polymorphism underwent a mental stress challenge before and after a maximal cardiopulmonary exercise test. Blood pressure was measured by auscultation and forearm blood flow by venous occlusion plethysmography. The groups were similar regarding anthropometric, metabolic, resting blood pressure and exercise variables. Before exercise, systolic blood pressure response during mental stress was higher in the polymorphic-type group (∆wild-type: 8.0 ± 2.0% vs. ∆polymorphic-type: 12.5 ± 1.8%, P = 0.01), while the increase in forearm vascular conductance was similar between the groups (∆wild-type 90.8 ± 26.4% vs. ∆polymorphic-type: 86.3 ± 24.1%, P = 0.44). After exercise, the systolic blood pressure at baseline and during mental stress was lower than before exercise in the whole group (P < 0.05), but the pressure response during mental stress was still higher in the polymorphic-type group (∆wild-type: 5.8 ± 1.5% vs. ∆polymorphic-type: 10.2 ± 1.4%, P = 0.01). The increase in forearm vascular conductance was inhibited only in the polymorphic-type group (∆before exercise 86.3 ± 24.1% vs. ∆after exercise: 41.5 ± 12.6%, P = 0.04). In conclusion, these results suggest the 894G>T eNOS polymorphism is associated with altered hemodynamic responses to mental stress both before and after a single bout of dynamic exercise with potential clinical implications.

Genetic polymorphism of antioxidant enzymes in eosinophilic and non-eosinophilic nasal polyposis.

PubMed

Akyigit, Abdulvahap; Keles, Erol; Etem, Ebru Onalan; Ozercan, Ibrahim; Akyol, Hatice; Sakallioglu, Oner; Karlidag, Turgut; Polat, Cahit; Kaygusuz, Irfan; Yalcin, Sinasi

2017-01-01

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the paranasal sinuses, and its pathophysiology is not yet precisely known. It is suggested that oxygen free radicals play an important role in the pathogenesis of nasal polyposis. This study aimed to identify genetic polymorphisms of superoxide dismutase (SOD 2), catalase (CAT), and inducible nitric oxide synthase (iNOS) enzymes in eosinophilic CRSwNP and non-eosinophilic CRSwNP patients; the study also aimed to evaluate the effect of genetic polymorphism of antioxidant enzymes on CRSwNP etiopathogenesis. One hundred thirty patients, who received endoscopic sinus surgery due to CRSwNP, and 188 control individuals were included in this study. Nasal polyp tissues were divided into two groups histopathologically as eosinophilic CRSwNP and non-eosinophilic CRSwNP. Venous blood samples were taken from the patient and control groups. Polymorphisms in the Ala16Va1 gene, which is the most common variation of SOD-2 gene, and 21 A/T polymorphisms in catalase gene were evaluated with the restriction fragment length polymorphism method and -277 C/T polymorphism in the iNOS gene was evaluated with the DNA sequencing method. The GG genotype distribution for the (-277) A/G polymorphism in the iNOS gene was a statistically significant difference between eosinophilic CRSwNP and control groups (p < 0.05). The CC genotype distribution for the SOD2 A16V (C/T) polymorphism was not statistically significant in all groups (p > 0.05). The TT genotype distribution for the A/T polymorphism in catalase gene at position -21 was statistically significant differences in eosinophilic CRSwNP and control groups (p < 0.05). Increased free oxygen radical levels, which are considered effective factors in the pathogenesis of CRSwNP, can occur due to genetic polymorphism of enzymes in the antioxidant system and genetic polymorphism of antioxidant enzymes in eosinophilic CRSwNP patients might contribute to the pathophysiology.

Interleukin-10 promoter 1082/-819/-592 polymorphisms are associated with asthma susceptibility in Asians and atopic asthma: a meta-analysis.

PubMed

Zheng, Xue-yan; Guan, Wei-jie; Mao, Chen; Chen, Hui-fang; Ding, Hong; Zheng, Jin-ping; Hu, Ting-ting; Luo, Min-hong; Huang, Yan-hui; Chen, Qing

2014-02-01

Although interleukin-10 (IL-10) is a potent inhibitor of allergic diseases, the association between promoter -1082/-819/-592 polymorphisms and asthma susceptibility remains inconclusive. We sought to determine if IL-10 promoter -1082/-819/-592 polymorphisms contribute to asthma susceptibility and are associated with phenotypes of atopic asthma. Systematic computerized searches were performed. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated by using random-effect and fixed-effect models, based on between-study heterogeneity. Subgroup analyses were performed according to age, ethnicity, and atopy. Publication bias was detected by funnel plot using Egger's test. A total of 4,716 asthmatic patients and 5,093 controls were included. The asthma susceptibility correlated significantly with IL-10 promoter gene -1082 polymorphism [OR (95 % CI) 1.26 (1.02, 1.55) for AA vs. AG + GG] and -592 polymorphism [OR (95 % CI) 1.12 (1.07, 1.34) for AC + AA vs. CC] (both P < 0.05), but not with -819 polymorphism (P > 0.05). Subgroup analyzes suggested that the AA versus AG + GG genotype of -1082A/G polymorphism and AC + AA versus CC genotype of -592A/C polymorphism contributed significantly to increased asthma susceptibility in adults [OR (95 % CI) 1.39 (1.03, 1.87) for -1082A/G and 1.53 (1.25, 1.87) for -592A/C polymorphism]. The Asian population [OR (95 % CI) 1.35 (1.1, 1.7) for -1082A/G and 1.4 (1.12, 1.64) for -592A/C polymorphism] and subjects with atopic asthma [OR (95 % CI) 1.49 (1.18, 1.88) for -1082A/G and 1.23 (1.01, 1.48) for -592A/C polymorphism] also had an increased susceptibility of asthma. No publication bias was detected. IL-10 promoter -1028A/G, -592A/C polymorphisms and their haplotypes, but not -819T/C polymorphism, correlate with asthma susceptibility.

Identification of new polymorphisms of the angiotensin I-converting enzyme (ACE) gene, and study of their relationship to plasma ACE levels by two-QTL segregation-linkage analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Villard, E.; Soubrier, F.; Tiret, L.

1996-06-01

Plasma angiotensin I-converting enzyme (ACE) levels are highly genetically determined. A previous segregation-linkage analysis suggested the existence of a functional mutation located within or close to the ACE locus, in almost complete linkage disequilibrium (LD) with the ACE insertion/deletion (I/D) polymorphism and accounting for half the ACE variance. In order to identify the functional variant at the molecular level, we compared ACE gene sequences between four subjects selected for having contrasted ACE levels and I/D genotypes. We identified 10 new polymorphisms, among which 8 were genotyped in 95 healthy nuclear families, in addition to the I/D polymorphism. These polymorphisms couldmore » be divided into two groups: five polymorphisms in the 5{prime} region and three in the coding sequence and the 3{prime} UTR. Within each group, polymorphisms were in nearly complete association, whereas polymorphisms from the two groups were in strong negative LD. After adjustment for the I/D polymorphism, all polymorphisms of the 5{prime} group remained significantly associated with ACE levels, which suggests the existence of two quantitative trait loci (QTL) acting additively on ACE levels. Segregation-linkage analyses including one or two ACE-linked QTLs in LD with two ACE markers were performed to test this hypothesis. The two QTLs and the two markers were assumed to be in complete LD. Results supported the existence of two ACE-linked QTLs, which would explain 38% and 49% of the ACE variance in parents and offspring, respectively. One of these QTLs might be the I/D polymorphism itself or the newly characterized 4656(CT){sub 2/3} polymorphism. The second QTL would have a frequency of {approximately}.20, which is incompatible with any of the yet-identified polymorphisms. More extensive sequencing and extended analyses in larger samples and in other populations will be necessary to characterize definitely the functional variants. 30 refs., 1 fig., 6 tabs.« less

Comparison of CYP2C9, CYP2C19, CYP2D6, ABCB1, and SLCO1B1 gene-polymorphism frequency in Russian and Nanai populations

PubMed Central

Sychev, Dmitrij Alekseevitch; Shuev, Grigorij Nikolaevich; Suleymanov, Salavat Shejhovich; Ryzhikova, Kristina Anatol’evna; Mirzaev, Karin Badavievich; Grishina, Elena Anatol’evna; Snalina, Natalia Evgenievna; Sozaeva, Zhannet Alimovna; Grabuzdov, Anton Mikhailovich; Matsneva, Irina Andreevna

2017-01-01

Background The efficiency and safety of drug therapy depends on the peculiarities of functioning of the P450 cytochrome group and transporting proteins. There are significant differences for single-nucleotide polymorphism (SNP) frequency. Materials and methods We studied the peculiarities of P450 cytochrome polymorphisms, SLCO1B1 transporting protein, and P-glycoprotein carriage in healthy volunteers in the Nanai ethnic group living in Russia, and compared them to the carriage of SNPs in the Russian population according to literature data. Results After performing the real-time polymerase chain reactions on the samples from 70 healthy volunteers from the Nanai group, for the CYP2C9*2C430T polymorphism we determined 70 CC-genotype carriers. As for the CYP2C9*3A1075C polymorphism, we found 62 AA-genotype carriers and eight AC-genotype carriers. For the CYP2C19*2G681A polymorphism, we determined 39 GG-genotype carriers and 28 GA-genotype carriers, for the CYP2C19*3G636A polymorphism 58 GG-genotype carriers and 12 GA-genotype carriers, and for the CYP2C19*17C806T polymorphism 67 CC-genotype carriers and three CT-genotype carriers. For the CYP2D6*4G1846A polymorphism, the GG genotype had 68 carriers, and the GA genotype two carriers. For the ABCB1*6C3435T polymorphism, there were 19 CC-genotype carriers and 39 CT-genotype carriers. For the SLCO1B1*5T521C polymorphism, the TT genotype had 41 carriers and the CT genotype 25 carriers. The distribution of genotypes fitted the Hardy–Weinberg equilibrium for all the polymorphisms, except those of CYP2C9*2. There were also significant differences in allele frequencies for some polymorphisms between the Nanais and the Russians. Conclusion In the Nanai population, there are polymorphisms connected with the decrease in safety and efficiency of drug therapy. Studying the ethnic differences might influence the determination of priority in the introduction of pharmacogenetic tests in clinical practice in different regions of Russia. PMID:28435307

Insertion and deletion polymorphisms of the ancient AluS family in the human genome.

PubMed

Kryatova, Maria S; Steranka, Jared P; Burns, Kathleen H; Payer, Lindsay M

2017-01-01

Polymorphic Alu elements account for 17% of structural variants in the human genome. The majority of these belong to the youngest AluY subfamilies, and most structural variant discovery efforts have focused on identifying Alu polymorphisms from these currently retrotranspositionally active subfamilies. In this report we analyze polymorphisms from the evolutionarily older AluS subfamily, whose peak activity was tens of millions of years ago. We annotate the AluS polymorphisms, assess their likely mechanism of origin, and evaluate their contribution to structural variation in the human genome. Of 52 previously reported polymorphic AluS elements ascertained for this study, 48 were confirmed to belong to the AluS subfamily using high stringency subfamily classification criteria. Of these, the majority (77%, 37/48) appear to be deletion polymorphisms. Two polymorphic AluS elements (4%) have features of non-classical Alu insertions and one polymorphic AluS element (2%) likely inserted by a mechanism involving internal priming. Seven AluS polymorphisms (15%) appear to have arisen by the classical target-primed reverse transcription (TPRT) retrotransposition mechanism. These seven TPRT products are 3' intact with 3' poly-A tails, and are flanked by target site duplications; L1 ORF2p endonuclease cleavage sites were also observed, providing additional evidence that these are L1 ORF2p endonuclease-mediated TPRT insertions. Further sequence analysis showed strong conservation of both the RNA polymerase III promoter and SRP9/14 binding sites, important for mediating transcription and interaction with retrotransposition machinery, respectively. This conservation of functional features implies that some of these are fairly recent insertions since they have not diverged significantly from their respective retrotranspositionally competent source elements. Of the polymorphic AluS elements evaluated in this report, 15% (7/48) have features consistent with TPRT-mediated insertion, thus suggesting that some AluS elements have been more active recently than previously thought, or that fixation of AluS insertion alleles remains incomplete. These data expand the potential significance of polymorphic AluS elements in contributing to structural variation in the human genome. Future discovery efforts focusing on polymorphic AluS elements are likely to identify more such polymorphisms, and approaches tailored to identify deletion alleles may be warranted.

Inheritance of restriction fragment length polymorphisms, random amplified polymorphic DNAs and isozymes in coastal Douglas-fir

Treesearch

K.D. Jermstad; A.M. Reem; J.R. Henifin; N.C. Wheeler; D.B Neale

1994-01-01

A total of 225 new genetic loci [151 restriction fragment length polymorphisms (RFLP) and 74 random amplified polymorphic DNAs (RAPD)] in coastal Douglas- fir [Pseudotsuga menziesii (Mirb.) Franco var. menziesii] have been identified using a three-generation outbred pedigree. The Mendelian inheritance of 16 RFLP loci and 29...

Polymorphous computing fabric

DOEpatents

Wolinski, Christophe Czeslaw [Los Alamos, NM; Gokhale, Maya B [Los Alamos, NM; McCabe, Kevin Peter [Los Alamos, NM

2011-01-18

Fabric-based computing systems and methods are disclosed. A fabric-based computing system can include a polymorphous computing fabric that can be customized on a per application basis and a host processor in communication with said polymorphous computing fabric. The polymorphous computing fabric includes a cellular architecture that can be highly parameterized to enable a customized synthesis of fabric instances for a variety of enhanced application performances thereof. A global memory concept can also be included that provides the host processor random access to all variables and instructions associated with the polymorphous computing fabric.

The rs4846049 polymorphism in the 3'UTR region of the MTHFR gene increases the migraine susceptibility in an Iranian population.

PubMed

Salehi, Mohaddeseh; Amin-Beidokhti, Mona; Safarpour Lima, Behnam; Gholami, Milad; Javadi, Gholam-Reza; Mirfakhraie, Reza

2018-01-01

Migraine is a painful complex neurovascular disease characterized by recurrent moderate-to-severe headaches. Increased level of homocysteine is related to dilation of cerebral vessels and endothelial injury that could trigger migraine attacks. Functional polymorphisms in the MTHFR gene affect homocysteine metabolism and, therefore, play an important role in the etiology of the disease. We aimed to investigate the possible association between MTHFR gene rs4846049, C677T, and A1298C polymorphisms and the risk of migraine in Iranian population. In this genetic association study, 498 individuals were enrolled, including 223 migraine patients and 275 healthy controls. Genotyping was performed using tetra-primer ARMS-PCR for rs4846049 and PCR-restriction fragment length polymorphism for C677T and A1298C polymorphisms. The association between rs4846049 and C677T polymorphisms and migraine was observed. For the rs4846049 polymorphism, the association was detected under a dominant model ( P =0.007; odds ratio [OR] =0.60; 95% confidence interval [CI], 0.41-0.87), and for the C677T polymorphism, the TT genotype frequency was significantly different in the studied groups ( P =0.009; OR =2.48; 95% CI, 1.25-4.92). No significant differences in the genotype or allele frequencies were found for the A1298C polymorphism between the migraineurs and controls. Present data provide evidence for the association of rs4846049 and C677T polymorphisms in the MTHFR gene and migraine. Further studies are required to validate the significance of the studied genetic variations in diverse ethnic populations.

Association of Calpain (CAPN) 10 (UCSNP-43, rs3792267) gene polymorphism with elevated serum androgens in young women with the most severe phenotype of polycystic ovary syndrome (PCOS).

PubMed

Anastasia, Karela; Koika, Vasiliki; Roupas, Nikolaos D; Armeni, Anastasia; Marioli, Dimitra; Panidis, Dimitrios; George, Adonakis; Georgopoulos, Neoklis A

2015-01-01

To highlight a possible association of Calpain (CAPN 10) gene UCSNP-43 polymorphism with hormonal and metabolic traits of young women with different phenotypes of polycystic ovary syndrome (PCOS). PCOS women were genotyped for the CAPN 10 gene UCSNP-43 polymorphism. A comparison of clinical and biochemical features of women with PCOS stratified on the basis of the CAPN 10 gene UCSNP-43 variants was assessed. Anthropometric, hormonal and biochemical measurements were carried out in 668 PCOS women and 200 healthy controls. Subjects were also genotyped for the CAPN 10 gene UCSNP-43 polymorphism. The genotype frequency distributions between groups and controls were compared using the chi-square test. The association of the polymorphism with the clinical and biochemical features of the study cohort was estimated as well. No association of the frequency of CAPN 10 gene UCSNP-43 polymorphism with PCOS was detected. No association of the polymorphism with the anthropometric, biochemical and hormonal features was detected both in PCOS and control women. The polymorphism was associated with serum Δ4 androstenedione (p = 0.018), as well as with 17-OH progesterone (17-hydroxyprogesterone) among women with PCOS phenotype A (p = 0.012). CAPN 10 gene polymorphism UCSNP-43 is deprived of a metabolic contribution to cardiovascular disease (CVD). However, due to its association with androgen excess in phenotype A, CAPN 10 gene polymorphism UCSNP-43 could be used as a genetic marker for CVD in young PCOS women.

Impact of the Bim Deletion Polymorphism on Survival Among Patients With Completely Resected Non-Small-Cell Lung Carcinoma.

PubMed

Atsumi, Jun; Shimizu, Kimihiro; Ohtaki, Yoichi; Kaira, Kyoichi; Kakegawa, Seiichi; Nagashima, Toshiteru; Enokida, Yasuaki; Nakazawa, Seshiru; Obayashi, Kai; Takase, Yoshiaki; Kawashima, Osamu; Kamiyoshihara, Mitsuhiro; Sugano, Masayuki; Ibe, Takashi; Igai, Hitoshi; Takeyoshi, Izumi

2016-02-01

A deletion polymorphism of the Bim gene has been reported to be a prognostic factor for patients with non-small-cell lung cancer (NSCLC) treated with epidermal growth factor receptor-tyrosine kinase inhibitors in the Asian population. We investigated the impact of the Bim deletion polymorphism on survival among patients with completely resected NSCLC. The Bim polymorphism was detected by polymerase chain reaction analysis. We measured overall survival (OS) and recurrence-free survival rates in 411 patients and postrecurrence survival (PRS) in 94 patients who experienced recurrence and received additional anticancer therapy. The Bim deletion polymorphism was detected in 61 patients (14.8%). OS rates were significantly lower for patients with the Bim deletion polymorphism than for those with the wild-type sequence. On multivariable analysis, the Bim deletion polymorphism was identified as an independent prognostic factor for OS (hazard ratio, 1.98; 95% CI, 1.17 to 3.36; P = .011). Among the 94 patients who experienced recurrence and were treated with anticancer therapy, patients with the Bim deletion polymorphism showed significantly poorer PRS than those with the wild-type sequence (median, 9.8 months v 26.9 months, respectively; P < .001). Multivariable analysis revealed that the Bim deletion polymorphism was an independent predictor of PRS (hazard ratio, 3.36; 95% CI, 1.75 to 6.47; P < .001). This trend remained apparent in subgroup analyses stratified by EGFR status, histology, and therapeutic modality. The Bim deletion polymorphism is a novel indicator of shortened PRS among patients with recurrent NSCLC treated with anticancer therapy in the Asian population.

Effects of fentanyl administration on locomotor response in horses with the G57C μ-opioid receptor polymorphism.

PubMed

Wetmore, Lois A; Pascoe, Peter J; Shilo-Benjamini, Yael; Lindsey, Jane C

2016-08-01

OBJECTIVE To determine the locomotor response to the administration of fentanyl in horses with and without the G57C polymorphism of the μ-opioid receptor. ANIMALS 20 horses of various breeds and ages (10 horses heterozygous for the G57C polymorphism and 10 age-, breed-, and sex-matched horses that did not have the G57C polymorphism). PROCEDURES The number of steps each horse took was counted over consecutive 2-minute periods for 20 minutes to determine a baseline value. The horse then received a bolus of fentanyl (20 μg/kg, IV), and the number of steps was again counted during consecutive 2-minute periods for 60 minutes. The mean baseline value was subtracted from each 2-minute period after fentanyl administration; step counts with negative values were assigned a value of 0. Data were analyzed by use of a repeated-measures ANOVA. RESULTS Data for 19 of 20 horses (10 horses with the G57C polymorphism and 9 control horses without the G57C polymorphism) were included in the analysis. Horses with the G57C polymorphism had a significant increase in locomotor activity, compared with results for horses without the polymorphism. There was a significant group-by-time interaction. CONCLUSIONS AND CLINICAL RELEVANCE Horses heterozygous for the G57C polymorphism of the μ-opioid receptor had an increased locomotor response to fentanyl administration, compared with the response for horses without this polymorphism. The clinical impact of this finding should be investigated.

An innovative way to highlight the power of each polymorphism on elite athletes phenotype expression.

PubMed

Contrò, Valentina; Schiera, Gabriella; Abbruzzo, Antonino; Bianco, Antonino; Amato, Alessandra; Sacco, Alessia; Macchiarella, Alessandra; Palma, Antonio; Proia, Patrizia

2018-01-12

The purpose of this study was to determine the probability of soccer players having the best genetic background that could increase performance, evaluating the polymorphism that are considered Performance Enhancing Polymorphism (PEPs) distributed on five genes: PPARα, PPARGC1A, NRF2, ACE e CKMM. Particularly, we investigated how each polymorphism works directly or through another polymorphism to distinguish elite athletes from non-athletic population. Sixty professional soccer players (age 22.5 ± 2.2) and sixty healthy volunteers (age 21.2± 2.3) were enrolled. Samples of venous blood was used to prepare genomic DNA. The polymorphic sites were scanned using PCR-RFLP protocols with different enzyme. We used a multivariate logistic regression analysis to demonstrate an association between the five PEPs and elite phenotype. We found statistical significance in NRF2 (AG/GG genotype) polymorphism/soccer players association (p < 0.05) as well as a stronger association in ACE polymorphism (p =0.02). Particularly, we noticed that the ACE ID genotype and even more the II genotype are associated with soccer player phenotype. Although the other PEPs had no statistical significance, we proved that some of these may work indirectly, amplifying the effect of another polymorphism; for example, seems that PPARα could acts on NRF2 (GG) enhancing the effect of the latter, notwithstanding it had not shown a statistical significance. In conclusion, to establish if a polymorphism can influence the performance, it is necessary to understand how they act and interact, directly and indirectly, on each other.

Intragenomic polymorphisms among high-copy loci: a genus-wide study of nuclear ribosomal DNA in Asclepias (Apocynaceae)

PubMed Central

Straub, Shannon C.K.; Fishbein, Mark; Liston, Aaron

2015-01-01

Despite knowledge that concerted evolution of high-copy loci is often imperfect, studies that investigate the extent of intragenomic polymorphisms and comparisons across a large number of species are rarely made. We present a bioinformatic pipeline for characterizing polymorphisms within an individual among copies of a high-copy locus. Results are presented for nuclear ribosomal DNA (nrDNA) across the milkweed genus, Asclepias. The 18S-26S portion of the nrDNA cistron of Asclepias syriaca served as a reference for assembly of the region from 124 samples representing 90 species of Asclepias. Reads were mapped back to each individual’s consensus and at each position reads differing from the consensus were tallied using a custom perl script. Low frequency polymorphisms existed in all individuals (mean = 5.8%). Most nrDNA positions (91%) were polymorphic in at least one individual, with polymorphic sites being less frequent in subunit regions and loops. Highly polymorphic sites existed in each individual, with highest abundance in the “noncoding” ITS regions. Phylogenetic signal was present in the distribution of intragenomic polymorphisms across the genus. Intragenomic polymorphisms in nrDNA are common in Asclepias, being found at higher frequency than any other study to date. The high and variable frequency of polymorphisms across species highlights concerns that phylogenetic applications of nrDNA may be error-prone. The new analytical approach provided here is applicable to other taxa and other high-copy regions characterized by low coverage genome sequencing (genome skimming). PMID:25653903

Study of the HFE gene common polymorphisms in French patients with sporadic amyotrophic lateral sclerosis.

PubMed

Praline, Julien; Blasco, Hélène; Vourc'h, Patrick; Rat, Valérian; Gendrot, Chantal; Camu, William; Andres, Christian R

2012-06-15

Our objective was to investigate whether the C282Y (p.Cys 282 Tyr) and H63D (p. His 63 Asp) HFE polymorphisms were associated with sporadic amyotrophic lateral sclerosis (SALS) in the French population. We searched for a relation of HFE polymorphisms with the clinical characteristics of the disease. The HFE polymorphisms were studied in 824 patients with SALS and 583 controls. We compared the frequency of the polymorphisms between SALS and controls groups by univariate and multivariate statistics, taking into account gender, site, age-at-onset and survival. We did not observe significant difference in the frequency of H63D polymorphism between SALS and control group. We observed a significant difference for C282Y between patients and controls with a low frequency of the Y allele in patients (3.2%) compared to our control group (5.9%). Disease duration, distribution of gender, site-of-onset, age-at-onset did not differ between groups taking into account genotypes of each polymorphism. Our results in this large cohort of ALS patients indicate that H63D polymorphism is not associated with SALS in the French population. This conclusion does not exclude a weak effect of the HFE gene polymorphisms in certain ALS populations, or an effect of other rare HFE gene variants. Copyright © 2012 Elsevier B.V. All rights reserved.

Genetic association of cyclooxygenase-2 gene polymorphisms with Parkinson's disease susceptibility in Chinese Han population.

PubMed

Dai, Yi; Wu, Yuquan; Li, Yansheng

2015-01-01

The aim of this study was to explore the genetic association of cyclooxygenase-2 (COX2) gene promoter region polymorphisms with Parkinson's disease (PD) susceptibility in Chinese Han population. The genotyping of COX2 gene polymorphisms was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 122 patients with PD and 120 healthy persons. The association strength of gene polymorphism with disease was measured by odds ratio (OR) and 95% confidence interval (95% CI) calculated using χ(2) test which also evaluated the Hardy-Weinberg equilibrium (HWE) of gene polymorphism in controls. The linkage disequilibrium and haplotype were also analyzed as evidence in the analysis of association. On condition that the genotypes distributions of COX2 -1290A>G, -1195G>A, -765G>C in the control group all conformed to HWE, however, only the homozygous genotype AA of -1195G>A polymorphism showed an association with PD (OR=0.432, 95% CI=0.196-0.950). In addition, in haplotype analysis, G-A-C haplotype frequency in cases was significantly lower than the controls, compared with the common haplotype A-G-G (P=0.031, OR=0.375, 95% CI=0.149-0.940). COX2 -1195G>A polymorphism might play a protective role in the onset of PD and G-A-C haplotype in this three promoter region polymorphisms also showed a negative association.

Clinical relevance of the interleukin 10 promoter polymorphisms in Chinese Han patients with major trauma: genetic association studies.

PubMed

Zeng, Ling; Gu, Wei; Chen, Kehong; Jiang, Dongpo; Zhang, Lianyang; Du, Dingyuan; Hu, Ping; Liu, Qing; Huang, Suna; Jiang, Jianxin

2009-01-01

An excessive inflammatory response is thought to account for the pathogenesis of sepsis and multiple organ dysfunction syndrome (MODS) after severe trauma. The interleukin-10 (IL-10) is a potent anti-inflammatory cytokine. The objectives of this prospective study were to investigate the distribution of IL-10 promoter polymorphisms in a cohort of 308 Chinese Han patients with major trauma, and to identify associations of IL-10 promoter polymorphisms with IL-10 production and incidence of sepsis and MODS. A total of 308 patients with major trauma were included in this study. The genotypes of polymorphisms -1082, -819 and -592 were determined by polymerase chain reaction-restriction fragment length polymorphism. The IL-10 levels in the supernatants were determined with enzyme-linked immunoabsorbent assay. The -1082A and -592A alleles were significantly associated with lower lipopolysaccharide-induced IL-10 production in an allele-dose dependent fashion. There was no significant difference for the -819 polymorphism. Except for the -1082 polymorphism, the -819 and -592 polymorphisms were not significantly associated with sepsis morbidity rate and MOD scores. Our results further confirm the functionality of the IL-10 promoter single nucleotide polymorphisms in relation to IL-10 production. They also suggest that individual difference in IL-10 production in trauma patients might be at least in part related to genetic variations in the IL-10 promoter region.

Obesity-related gene ADRB2, ADRB3 and GHRL polymorphisms and the response to a weight loss diet intervention in adult women.

PubMed

Saliba, Louise F; Reis, Rodrigo S; Brownson, Ross C; Hino, Adriano A; Tureck, Luciane V; Valko, Cheryl; de Souza, Ricardo L R; Furtado-Alle, Lupe

2014-03-01

The individual response to diet may be influenced by gene polymorphisms. This study hypothesized that ADRB2 (Gln27Glu, rs1042714 and Arg16Gly, rs1042713), ADRB3 (Trp64Arg, rs4994) and GHRL (Leu72Met, rs696217) polymorphisms moderate weight loss. The study was a seven weeks dietary weight loss intervention with Brazilian adult obese women (n = 109). The body mass index (BMI) was calculated and polymorphisms in these genes were assessed by real-time PCR assays. Two-way repeated-measures ANOVA (2 × 2) were used to analyze the intervention effect between polymorphisms and BMI over the period and after stratification for age and socioeconomic status (SES). The weight loss intervention resulted in decreased BMI over the seven-week period (p < 0.001), for high and low SES (p < 0.05) and mainly for participants with 30-49 y. The intervention did not result in a statistically significant difference in weight loss between polymorphism carriers and non-carriers, and although, the ADRB2, ADRB3 and GHRL polymorphisms did not moderate weight loss, the Gln27Glu polymorphism carriers showed a lower BMI compared to non-carriers in the low SES (p = 0.018) and the 30-39 y (p = 0.036) groups, suggesting a role for this polymorphism related to BMI control.

Obesity-related gene ADRB2, ADRB3 and GHRL polymorphisms and the response to a weight loss diet intervention in adult women

PubMed Central

Saliba, Louise F.; Reis, Rodrigo S.; Brownson, Ross C.; Hino, Adriano A.; Tureck, Luciane V.; Valko, Cheryl; de Souza, Ricardo L.R.; Furtado-Alle, Lupe

2014-01-01

The individual response to diet may be influenced by gene polymorphisms. This study hypothesized that ADRB2 (Gln27Glu, rs1042714 and Arg16Gly, rs1042713), ADRB3 (Trp64Arg, rs4994) and GHRL (Leu72Met, rs696217) polymorphisms moderate weight loss. The study was a seven weeks dietary weight loss intervention with Brazilian adult obese women (n = 109). The body mass index (BMI) was calculated and polymorphisms in these genes were assessed by real-time PCR assays. Two-way repeated-measures ANOVA (2 × 2) were used to analyze the intervention effect between polymorphisms and BMI over the period and after stratification for age and socioeconomic status (SES). The weight loss intervention resulted in decreased BMI over the seven-week period (p < 0.001), for high and low SES (p < 0.05) and mainly for participants with 30–49 y. The intervention did not result in a statistically significant difference in weight loss between polymorphism carriers and non-carriers, and although, the ADRB2, ADRB3 and GHRL polymorphisms did not moderate weight loss, the Gln27Glu polymorphism carriers showed a lower BMI compared to non-carriers in the low SES (p = 0.018) and the 30–39 y (p = 0.036) groups, suggesting a role for this polymorphism related to BMI control. PMID:24688286

Roles of beta2-adrenergic receptor gene polymorphisms in a Turkish population with obstructive sleep apnea syndrome or obesity.

PubMed

Gök, I; Celebi, I; Hüseyinoğlu, N; Ozic, C

2014-10-20

We determined the distribution of the Arg16Gly and Gln27Glu polymorphisms of the beta-2 adrenergic receptor gene (ADRB2) in patients with obstructive sleep apnea syndrome as well as a control group in Northeastern Turkey. A total of 52 patients diagnosed with obstructive sleep apnea in a sleep laboratory and 78 control subjects were examined. Peripheral blood samples were taken from patients diagnosed with obstructive sleep apnea by polysomnography. DNA was extracted from blood samples and amplified using polymerase chain reaction. Amplification products were digested with restriction enzymes to investigate gene polymorphisms. Restriction products were extracted from agarose gel electrophoresis and polymorphisms were analyzed using gel images. The Arg16Gly polymorphism was observed in 18 of 52 patients and in 23 of 78 controls. The Gln27Glu polymorphism was observed in 21 of 52 patients and in 28 of 78 controls. In conclusion, there was no correlation among polymorphic frequencies between patient and control groups. Based on the results, these polymorphisms do not contribute to the clinical diagnosis of this syndrome. However, the distribution of Arg16Gly vs Gln27Glu polymorphisms may contribute to obesity in patients with a body mass index greater than 30 (P < 0.05). Different results may be obtained if the parameters of obstructive sleep apnea disease are changed.

Conformational polymorphs of a novel TCNQ derivative carrying an acetylene group

NASA Astrophysics Data System (ADS)

Iida, Yuki; Kataoka, Makoto; Okuno, Tsunehisa

2018-01-01

TCNQ is one of the most important organic acceptors and lots of its derivatives have been prepared. However the reports on their crystal polymorphs are limited to their complexes, and simple polymorphs of TCNQ derivatives are uncommon. We succeeded in preparation of a novel TCNQ derivative, 2,2'-(2-(prop-2-yn-1-yloxy)cyclohexa-2,5-diene-1,4-diylidene)dimalononitrile, having a propynyloxy group on a substituent. This compound was found to have two crystal polymorphs depending on a solvent for recrystallization. In polymorph I, dimeric hydrogen bonds are formed between acetylenic hydrogens and cyano nitrogens with the molecule in an inversion symmetry. While, in polymorph II, the molecules make intermolecular hydrogen bonds between acetylenic hydrogens and cyano nitrogens with the molecule in 21 symmetry, forming a hydrogen bonded molecular helix along the b axis. Besides patterns of the intermolecular hydrogen bonds, difference was recognized in conformation of propynyloxy group. The molecule has an anti conformation in polymorph I and a gauche conformation in polymorph II. DFT calculation indicates that the anti conformer is less stable than the gauche one. But a solvation model suggests the anti conformer is estimated to be more stable in a toluene solution.

Selecting the spin crossover profile with controlled crystallization of mononuclear Fe(iii) polymorphs.

PubMed

Vicente, Ana I; Ferreira, Liliana P; Carvalho, Maria de Deus; Rodrigues, Vítor H N; Dîrtu, Marinela M; Garcia, Yann; Calhorda, Maria José; Martinho, Paulo N

2018-05-08

Two polymorphic species of the [Fe(5-Br-salEen)2]ClO4 compound were obtained, each of them being selectively recovered after evaporation of the solvent at a controlled rate. While polymorph 1a is formed during slow evaporation, fast evaporation favors polymorph 1b. The importance of the evaporation rate was recognized after detailed studies of the reaction temperature, solvent evaporation rate and crystallization temperature effects. The complex in the new polymorphic form 1a showed an abrupt spin crossover at 172 K with a small 1 K hysteresis window and over a narrow 10 K range. 57Fe Mössbauer spectroscopy and differential scanning calorimetry, complemented by X-ray studies for both the high-spin and low-spin forms, were used to further characterize the new polymorphic phase 1a. Both polymorphs are based on the same Fe(iii) complex cation hydrogen bonded to the perchlorate anion. These units are loosely bound in the crystals via weak interactions. In the new polymorph 1a, the hydrogen bonds are stronger, while the weak hydrogen and halogen bonds, as well as π-π stacking, create a cooperative network, not present in 1b, responsible for the spin transition profile.

Common polymorphisms in interleukin genes (IL4, IL6, IL8 and IL12) are not associated with alcoholic liver disease or alcoholism in Spanish men.

PubMed

Marcos, Miguel; Pastor, Isabel; González-Sarmiento, Rogelio; Laso, Francisco-Javier

2009-03-01

Preliminary data suggest that polymorphisms in cytokine genes may be involved in the genetic predisposition to alcoholic liver cirrhosis or alcohol use disorders. We thus analyze the association between these diseases and the following polymorphisms: -33T>C IL4, -174 G>C IL6, -251 T>A IL8 and 1188 A>C IL12B. 258 male alcoholics (161 without liver disease and 97 with liver cirrhosis) and 101 healthy controls were genotyped for the above mentioned polymorphisms. We examined the relationship between genotype and allele frequencies and the presence of disease, as well as the correlation with combinations of putative pro-inflammatory genotypes. Haplotypes were inferred using the expectation-maximization algorithm and haplotype frequencies were compared. We found no statistically significant association between any of these polymorphisms or the combinations of pro-inflammatory polymorphisms and the risk of alcoholic liver cirrhosis or alcohol abuse or dependence. Haplotype analysis of the IL4 and IL12B polymorphisms did not show any statistical relationship either. Our results do not support the hypothesis that the analyzed polymorphisms confer differences in alcoholic liver cirrhosis or alcohol use disorders susceptibility.

Transcobalamin II (TCN2 67A>G and TCN2 776C>G) and transcobalamin II receptor (TCblR 1104C>T) polymorphisms in Korean patients with idiopathic recurrent spontaneous abortion.

PubMed

Kim, Hyun Seok; Lee, Bo Eun; Jeon, Young Joo; Rah, HyungChul; Lee, Woo Sik; Shin, Ji Eun; Choi, Dong Hee; Kim, Nam Keun

2014-09-01

The transcobalamin II (TCN2) 776C>G polymorphism has been reported to be a genetic risk factor for idiopathic recurrent spontaneous abortion (RSA). However, the sample size in previous studies was small, and other TCN2 polymorphisms have not been studied. Moreover, the TCN2 67A>G and 776C>G polymorphisms, and the transcobalamin II receptor (TCblR/CD320) 1104C>T polymorphism, have demonstrated associations with immune responses. Three hundred and seventy-eight RSA patients who had at least two consecutive spontaneous abortions were enrolled. Two hundred and seven control subjects were collected from a convenience sample. Polymerase chain reaction and restriction fragment length polymorphism analysis were performed to identify the TCN2 67A>G and 776C>G polymorphisms, and the TCblR 1104C>T polymorphism. RSA patients showed significantly different frequencies of the TCN2 67AG+GG genotypes compared with control subjects. The TCN2 67G allele is a possible risk factor for idiopathic RSA. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Association of ACE Gene I/D polymorphism with migraine in Kashmiri population.

PubMed

Wani, Irfan Yousuf; Sheikh, Saleem; Shah, Zafar Amin; Pandith, Arshid A; Wani, Mushtaq; Asimi, Ravouf; Wani, Maqbool; Sheikh, Shahnawaz; Mehraj, Iqra

2016-01-01

Migraine is a complex, recurrent headache disorder that is one of the most common complaints in neurology practice. The role of various genes in its pathogenesis is being studied. We did this study to see whether an association exists between ACE gene I/D polymorphism and migraine in our region. The study included 100 patients diagnosed with migraine and 121 healthy controls. The study subject were age and gender matched. The analysis was based on Polymerase Chain Reaction (PCR) and included following steps: DNA extraction from blood, PCR and Restriction Fragment Length Polymorphism (RFLP). Out of 100 cases, 69 were females and 31 were males. Fifty-seven were having migraine without aura and 43 had migraine with aura. 45 of the cases had II polymorphism, 40 had ID polymorphism and 15 had DD polymorphism in ACE gene. We were not able to find a statistically significant association between ACE gene I/D polymorphism with migraine. The reason for difference in results between our study and other studies could be because of different ethnicity in study populations. So a continuous research is needed in this regard in order to find the genes and different polymorphism that increase the susceptibility of Kashmiri population to migraine.

Synchrotron X-ray diffuse scattering from a stable polymorphic material: terephthalic acid, C 8 H 6 O 4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goossens, D. J.; Chan, E. J.

Terephthalic acid (TPA, C 8H 6O 4) is an industrially important chemical, one that shows polymorphism and disorder. Three polymorphs are known, two triclinic [(I) and (II)] and one monoclinic (III). Of the two triclinic polymorphs, (II) has been shown to be more stable in ambient conditions. This paper presents models of the local order of polymorphs (I) and (II), and compares the single-crystal diffuse scattering (SCDS) computed from the models with that observed from real crystals. TPA shows relatively weak and less-structured diffuse scattering than some other polymorphic materials, but it does appear that the SCDS is less wellmore » modelled by a purely harmonic model in polymorph (I) than in polymorph (II), according to the idea that the diffuse scattering is sensitive to anharmonicity that presages a structural phase transition. The work here verifies that displacive correlations are strong along the molecular chains and weak laterally, and that it is not necessary to allow the —COOH groups to librate to successfully model the diffuse scattering – keeping in mind that the data are from X-ray diffraction and not directly sensitive to H atoms.« less

A model of ecological and evolutionary consequences of color polymorphism.

PubMed

Forsman, Anders; Ahnesjö, Jonas; Caesar, Sofia; Karlsson, Magnus

2008-01-01

We summarize direct and indirect effects on fitness components of animal color pattern and present a synthesis of theories concerning the ecological and evolutionary dynamics of chromatic multiple niche polymorphisms. Previous endeavors have aimed primarily at identifying conditions that promote the evolution and maintenance of polymorphisms. We consider in a conceptual model also the reciprocal influence of color polymorphism on population processes and propose that polymorphism entails selective advantages that may promote the ecological success of polymorphic species. The model begins with an evolutionary branching event from mono- to polymorphic condition that, under the influence of correlational selection, is predicted to promote the evolution of physical integration of coloration and other traits (cf. multi-trait coevolution and complex phenotypes). We propose that the coexistence within a population of alternative ecomorphs with coadapted gene complexes promotes utilization of diverse environmental resources, population stability and persistence, colonization success, and range expansions, and enhances the evolutionary potential and speciation. Conversely, we predict polymorphic populations to be less vulnerable to environmental change and at lower risk of range contractions and extinctions compared with monomorphic populations. We offer brief suggestions as to how these falsifiable predictions may be tested.

A meta-analysis evaluating the relationship between IL-18 gene promoter polymorphisms and an individual's susceptibility to HCV infection.

PubMed

Chen, W; Jing, M; Zhang, Q; Yuan, R; Jing, S

2018-01-01

Several observational studies have investigated interleukin-18 (IL-18) gene polymorphisms with regard to susceptibility to hepatitis C virus (HCV) infection, but the results have been inconsistent. To evaluate the relationships between functional polymorphisms in the IL-18 gene and an individual's susceptibility to HCV infection, a meta-analysis was performed. Methods: A literature search was conducted using the PubMed, EMBASE, Web of Science and China BioMedicine databases to investigate the correlation between IL-18 gene polymorphisms and susceptibility to HCV infection. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The polymorphisms IL-18-607 C>A and -137 G>C were correlated with susceptibility to HCV infection in Asian populations. However, there was no evidence indicating a correlation between either of these polymorphisms and susceptibility to HCV infection in Caucasian populations. Our current meta-analysis suggests that the -607 C>A and -137 G>C polymorphisms in the IL-18 gene promoter play important roles in determining the response to HCV in Asian populations. More studies with larger sample sizes are needed to evaluate the associations between IL-18 genetic polymorphisms and HCV infection risk. © Acta Gastro-Enterologica Belgica.

Genetic polymorphism of estrogen receptor alpha gene in Egyptian women with type II diabetes mellitus

PubMed Central

Motawi, Tarek M.K.; El-Rehany, Mahmoud A.; Rizk, Sherine M.; Ramzy, Maggie M.; el-Roby, Doaa M.

2015-01-01

Estrogen might play an important role in type 2 diabetes mellitus pathogenesis. A number of polymorphisms have been reported in the estrogen receptor alpha gene including the XbaI and PvuII restriction enzyme polymorphisms. The aim of this study was to determine if ESRα gene polymorphisms are associated with type 2 diabetes mellitus and correlated with lipid profile. Ninety diabetic Egyptian patients were compared with forty healthy controls. ESRα genotyping of PvuII and XbaI was performed using restriction fragment length polymorphism analysis. Our study showed that there is more significant difference in the frequency of C and G polymorphic allele between patients and control groups in PvuII and XbaI respectively. Also carriers of minor C and G alleles of PvuII and XbaI gene polymorphisms were associated with increased fasting blood glucose and disturbance in lipid profile as there is an increase in total cholesterol, triglycerides and Low density lipoprotein. So findings of present study suggest the possibility that PvuII and XbaI polymorphisms in ERα are related to T2DM and with increased serum lipids among Egyptian population. PMID:26401488

Residue-Specific Side-Chain Polymorphisms via Particle Belief Propagation.

PubMed

Ghoraie, Laleh Soltan; Burkowski, Forbes; Li, Shuai Cheng; Zhu, Mu

2014-01-01

Protein side chains populate diverse conformational ensembles in crystals. Despite much evidence that there is widespread conformational polymorphism in protein side chains, most of the X-ray crystallography data are modeled by single conformations in the Protein Data Bank. The ability to extract or to predict these conformational polymorphisms is of crucial importance, as it facilitates deeper understanding of protein dynamics and functionality. In this paper, we describe a computational strategy capable of predicting side-chain polymorphisms. Our approach extends a particular class of algorithms for side-chain prediction by modeling the side-chain dihedral angles more appropriately as continuous rather than discrete variables. Employing a new inferential technique known as particle belief propagation, we predict residue-specific distributions that encode information about side-chain polymorphisms. Our predicted polymorphisms are in relatively close agreement with results from a state-of-the-art approach based on X-ray crystallography data, which characterizes the conformational polymorphisms of side chains using electron density information, and has successfully discovered previously unmodeled conformations.

Chromosomal polymorphism in mammals: an evolutionary perspective.

PubMed

Dobigny, Gauthier; Britton-Davidian, Janice; Robinson, Terence J

2017-02-01

Although chromosome rearrangements (CRs) are central to studies of genome evolution, our understanding of the evolutionary consequences of the early stages of karyotypic differentiation (i.e. polymorphism), especially the non-meiotic impacts, is surprisingly limited. We review the available data on chromosomal polymorphisms in mammals so as to identify taxa that hold promise for developing a more comprehensive understanding of chromosomal change. In doing so, we address several key questions: (i) to what extent are mammalian karyotypes polymorphic, and what types of rearrangements are principally involved? (ii) Are some mammalian lineages more prone to chromosomal polymorphism than others? More specifically, do (karyotypically) polymorphic mammalian species belong to lineages that are also characterized by past, extensive karyotype repatterning? (iii) How long can chromosomal polymorphisms persist in mammals? We discuss the evolutionary implications of these questions and propose several research avenues that may shed light on the role of chromosome change in the diversification of mammalian populations and species. © 2015 Cambridge Philosophical Society.

Polymorphisms in exons 1B and 1C of the type I interleukin-1 receptor gene in patients with endometriosis.

PubMed

D'Amora, Paulo; Sato, Hélio; Girão, Manoel J B C; Silva, Ismael D C G; Schor, Eduardo

2006-09-01

To study possible correlation between the prevalence of polymorphisms in the type I interleukin-1 receptor gene and pelvic endometriosis. Genotypes of 223 women were analyzed: 109 women with surgically and histologically confirmed endometriosis and 114 healthy women. Distributions of two single-base polymorphisms of the human interleukin-1 receptor type I (IL-1RI) gene were evaluated: PstI, due to a C-->T transition in exon 1B and BsrBI a C-->A transition at position 52 in exon 1C. Polymorphisms were detected by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism analysis (RFLP) resolved on 3% agarose gels stained with ethidium bromide. Genotypes for PstI polymorphisms did not differ significantly among control and endometriosis (P = 0.058). However, in relation to BsrBI polymorphism, protective risk was observed for the development of endometriosis [OR 0.39-IC 95% (0.2-0.9)]. BsrBI heterozygote genotype (C/A) showed protective effect against endometriosis development.

Association between ADAM metallopeptidase domain 33 gene polymorphism and risk of childhood asthma: a meta-analysis.

PubMed

Sun, F J; Zou, L Y; Tong, D M; Lu, X Y; Li, J; Deng, C B

2017-08-31

This study aimed to investigate the association between ADAM metallopeptidase domain 33 (ADAM33) gene polymorphisms and the risk of childhood asthma. The relevant studies about the relationship between ADAM33 gene polymorphisms and childhood asthma were searched from electronic databases and the deadline of retrieval was May 2016. The single nucleotide polymorphisms (SNPs) of ADAM33 (rs511898, rs2280092, rs3918396, rs528557, rs2853209, rs44707, rs2280091 and rs2280089) were analyzed based on several models including the allele, codominant, recessive and dominant models. The results showed that the ADAM33 rs2280091 polymorphism in all four genetic models was associated with an increased risk of childhood asthma. Positive associations were also found between the polymorphisms rs2280090, rs2787094, rs44707 and rs528557 and childhood asthma in some genetic models. This meta-analysis suggested that ADAM33 polymorphisms rs2280091, rs2280090, rs2787094, rs44707 and rs528557 were significantly associated with a high risk of childhood asthma.

Assessment of the rs4340 ACE gene polymorphism in acute coronary syndrome in a Western Mexican population.

PubMed

Valdez-Haro, A; Valle, Y; Valdes-Alvarado, E; Casillas-Muñoz, F; Muñoz-Valle, J F; Reynoso-Villalpando, G L; Flores-Salinas, H E; Padilla-Gutiérrez, J R

2017-09-27

Acute coronary syndrome (ACS) is considered one of the main causes of death worldwide. Contradictory findings concerning the impact of the angiotensin-converting enzyme (ACE) gene on cardiovascular diseases have been reported. Previous conclusions point out that the variability in results depends on ethnicity and genetic polymorphisms to determine the association of rs4340 polymorphisms of the ACE gene and ACE circulating levels in ACS. Genotyping of rs4340 polymorphisms was performed in a total of 600 individuals from Western Mexico divided into two groups: the ACS and the control group (CG). The polymorphisms were identified by polymerase chain reaction. Serum ACE concentration was determined by enzyme-linked immunosorbent assay. D/D carriers had higher ACE levels than I/I carriers (3.6 vs 2.8 ng/mL, P < 0.0021) in the CG. The D/D genotype of the rs4340 polymorphism is associated with higher ACE concentration levels; however, the polymorphism was not associated with ACS.

MTHFR 677C-->T and 1298A-->C polymorphisms in children with Down syndrome and acute myeloid leukemia in Brazil.

PubMed

Amorim, Marcia R; Zanrosso, Crisiane Wais; Magalhães, Isis Q; Pereira, Simone C; Figueiredo, Alexandre; Emerenciano, Mariana; Pinheiro, Vitoria Regia; d'Andréa, Maria Lydia; Orioli, Ieda M; Koifman, Sergio; Pombo-de-Oliveira, Maria S

2008-12-01

Down syndrome (DS) is an important risk factor associated with acute leukemia (AL). The presence of polymorphisms that reduce 5,10-methylenetetrahydrofolate reductase (MTHFR) activity has been linked to the multifactorial leukemogenic process. The authors have conducted a study to test whether 677C-->T and/or 1298A-->C polymorphisms of MTHFR would play an additional role in susceptibility of acute myeloid leukemia (AML) in DS children. They also verified whether any polymorphism in the MTHFR gene was associated with the risk of DS. Genetic polymorphisms determination was carried out in 248 samples from healthy individuals as controls and a total of 115 DS children (65 without leukemia and 50 with AML). The present study failed to reveal any association between these polymorphisms and risk of AML in DS children. The data also indicate that MTHFR polymorphisms are not associated with risk of being a DS child.

Polymorphisms at the Ligand Binding Site of the Vitamin D Receptor Gene and Osteomalacia

PubMed Central

Ak, Duygu Gezen; Kahraman, Hakkí; Dursun, Erdinç; Duman, Belgin Süsleyici; Erensoy, Nevin; Alagöl, Faruk; Tanakol, Refik; Yılmazer, Selma

2005-01-01

Vitamin D receptor (VDR) gene polymorphisms have been suggested as possible determinants of bone mineral density (BMD) and calcium metabolism. In this study, our aim was to determine whether there is an association between VDR gene polymorphism and osteomalacia or not. We determined ApaI and TaqI polymorphisms in the vitamin D receptor gene in 24 patients with osteomalacia and 25 age-matched healthy controls. Serum calcium, phosphorus, ALP, PTH, 25OHD levels were also examined. We used PCR and RFLP methods to test for an association between osteomalacia and polymorphisms within, intron 8 and exon 9 of the VDR gene. When the control and patients were compared for their ApaI and TaqI genotypes there was no relationship between VDR gene allelic polymorphisms and osteomalacia. Whereas a nearly significant difference for A allele was found in the allellic distribution of the patients (p = 0.08). Also no association between biochemical data and VDR gene polymorphisms was observed. PMID:16403954

Identification and characterization of microsatellite markers from the tropical sea cucumber, Stichopus horrens (Selenka).

PubMed

Shangguan, J B; Li, Z B; Yuan, Y; Huang, Y S

2015-10-28

Tropical commercial sea cucumber Stichopus horrens is extensively distributed throughout the tropical Indo-Pacific region, and wild stocks have been severely depleted over the past decade. In this study, we used the microsatellite enrichment library of S. horrens to identify and characterize 13 microsatellite loci, including 11 polymorphic loci and 2 monomorphic loci. Among the 11 polymorphic loci, the number of alleles was 3-8. The observed and expected heterozygosity varied from 0.1364 to 0.8966 and from 0.1653 to 0.7551, respectively. Additionally, all 11 polymorphic loci showed moderate and high polymorphism with the polymorphism information content (0.271-0.7311). A total of 9 polymorphic loci were in Hardy-Weinberg equilibrium, except for 2 loci (adjusted P = 0.004545). Linkage disequilibrium was not detected in any pairs of polymorphic loci. The present study will be useful for studying genetic structure, population conservation, and breeding of wild S. horrens; moreover, our results contribute to the phylogeny and evolutionary research of Holothuroidea.

Diffuse Scattering as an Aid to the Understanding of Polymorphism in Pharmaceuticals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Welberry, T.R.; Chan, E.J.; Goossens, D.J.

Polymorphism occurs when the same molecular compound can crystallize in more than one distinct crystal structure. Its study is a field of great interest and activity. This is largely driven by its importance in the pharmaceutical industry, but polymorphism is also an issue in the pigments, dyes, and explosives industries. The polymorph formed by a compound generally exerts a strong influence on its solid-state properties. The polymorphic form of a drug molecule may affect the ease of manufacture and processing, shelf life, and most significantly the rate of uptake of the molecule by the human body. They can even varymore » in toxicity; one polymorph may be safe, while a second may be toxic. In this review of recently published work, we show how diffuse scattering experiments coupled with Monte Carlo (MC) computer modeling can aid in the understanding of polymorphism. Examples of the two common pharmaceuticals, benzocaine and aspirin, both of which are bimorphic, at ambient temperatures, are discussed.« less

Diffuse Scattering as an Aid to the Understanding of Polymorphism in Pharmaceuticals

NASA Astrophysics Data System (ADS)

Welberry, T. R.; Chan, E. J.; Goossens, D. J.; Heerdegen, A. P.

2012-05-01

Polymorphism occurs when the same molecular compound can crystallize in more than one distinct crystal structure. Its study is a field of great interest and activity. This is largely driven by its importance in the pharmaceutical industry, but polymorphism is also an issue in the pigments, dyes, and explosives industries. The polymorph formed by a compound generally exerts a strong influence on its solid-state properties. The polymorphic form of a drug molecule may affect the ease of manufacture and processing, shelf life, and most significantly the rate of uptake of the molecule by the human body. They can even vary in toxicity; one polymorph may be safe, while a second may be toxic. In this review of recently published work, we show how diffuse scattering experiments coupled with Monte Carlo (MC) computer modeling can aid in the understanding of polymorphism. Examples of the two common pharmaceuticals, benzocaine and aspirin, both of which are bimorphic, at ambient temperatures, are discussed.

A polymorphism (rs1042522) in TP53 gene is a risk factor for Down Syndrome in Sicilian mothers.

PubMed

Salemi, Michele; Barone, Concetta; Salluzzo, Maria Grazia; Giambirtone, Mariaconcetta; Scillato, Francesco; Galati Rando, Rosanna; Romano, Carmelo; Morale, Maria Concetta; Ridolfo, Federico; Romano, Corrado

2017-11-01

Trisomy 21 is the most frequent genetic cause of intellectual disability. Tumor Protein 53 (TP53) gene down-regulation triggers chromosomal instability. A TP53 gene polymorphism c.215G > C (rs1042522) is associated with accumulation of aneuploid cells. We analyzed the TP53 c.215G > C (rs1042522) polymorphism in Sicilian mothers of subjects with Down Syndrome (DS) within a case-control study. Nucleotide polymorphism was detected by pyrosequencing technology. The distribution of TP53 c.215G > C polymorphism showed significant difference between mothers of subjects with DS and controls. Our data show that TP53 c.215G > C polymorphism is a risk factor for DS in Sicilian mothers.

The effect of high pressure on the functional properties of pork myofibrillar proteins.

PubMed

Grossi, Alberto; Olsen, Karsten; Bolumar, Tomas; Rinnan, Åsmund; Øgendal, Lars H; Orlien, Vibeke

2016-04-01

Complementary methodologies were used to analyse the pressure-induced modification and functionality of myofibrillar proteins from pork meat pressurised at 200, 400, 600, or 800 MPa (10 min, 5 or 20 °C). Pressure at 400 MPa was found to be the threshold for loss of solubility, and the structural proteins, myosin and actin, lost their native solubility due to aggregation. The results from the extraction of proteins with different reagents targeting the disruption of specific molecular interactions suggested that pressure-induced aggregation was caused mainly by hydrogen bonding during pressurisation and not hydrophobic interactions nor disulphide cross-links. Furthermore, the soluble proteins were exposed to remarkable structural changes already at 200 MPa and lost their native functionality. The modification of the proteins in pressurised meat affected the water binding sites of the myofibrillar proteins and, thereby, the interactions between proteins and water molecules, and distribution between myofibrillar and extra-myofibrillar compartments. Copyright © 2015 Elsevier Ltd. All rights reserved.

Micrometer sized immobilization of protein molecules onto quartz, silicium and gold.

NASA Astrophysics Data System (ADS)

Petersen, Steffen B.; Neves-Petersen, Maria Teresa; Klitgaard, Søren; Duroux, Meg Crookshanks

2006-02-01

We demonstrate that ultraviolet light can be used to make sterically oriented covalent immobilization of a large variety of protein molecules onto either gold or thiolated quartz or silicium. The reaction mechanism behind the reported new technology involves light induced breakage of disulphide bridges in proteins upon UV illumination of nearby aromatic amino acids, resulting in the formation of free, reactive thiol groups that will form covalent bonds with thiol reactive surfaces. The protein molecules in general retain their function. The size of the immobilization spot is determined by the dimension of the UV beam. In principle, the spot size may be as small as 1 micrometer or less. We have developed the necessary technology for preparing large protein arrays of enzymes and fragments of monoclonal antibodies. Dedicated Image Processing Software has been developed for making quality assessment of the protein arrays. A multitude of important application areas such as drug carriers and drug delivery, bioelectronics, carbon nanotubes, nanoparticles as well as protein glue are discussed.

An Alternative Chemical Redox Method for the Production of Bispecific Antibodies: Implication in Rapid Detection of Food Borne Pathogens

PubMed Central

Owais, Mohammad; Kazmi, Shadab; Tufail, Saba; Zubair, Swaleha

2014-01-01

Bi-functional antibodies with the ability to bind two unrelated epitopes have remarkable potential in diagnostic and bio-sensing applications. In the present study, bispecific antibodies that recognize human red blood cell (RBC) and the food borne pathogen Listeria monocytogenes (L. monocytogenes) were engineered. The procedure involves initial reduction of a mixture of anti-RBC and anti-Listeria antibodies followed by gradual re-oxidation of the reduced disulphides. This facilitates association of the separated antibody chains and formation of hybrid immunoglobulins with affinity for the L. monocytogenes and human RBC. The bispecific antibodies caused the agglutination of the RBCs only in the presence of L. monocytogenes cells. The agglutination process necessitated the specific presence of L. monocytogenes and the red colored clumps formed were readily visible with naked eyes. The RBC agglutination assay described here provides a remarkably simple approach for the rapid and highly specific screening of various pathogens in their biological niches. PMID:24637674

S-nitrosylation of the thioredoxin-like domains of protein disulfide isomerase and its role in neurodegenerative conditions.

NASA Astrophysics Data System (ADS)

Conway, Myra; Harris, Matthew

2015-04-01

Correct protein folding and inhibition of protein aggregation is facilitated by a cellular ‘quality control system’ that engages a network of protein interactions including molecular chaperones and the ubiquitin proteasome system. Key chaperones involved in these regulatory mechanisms are the protein disulphide isomerases (PDI) and their homologues, predominantly expressed in the endoplasmic reticulum of most tissues. Redox changes that disrupt ER homeostasis can lead to modification of these enzymes or chaperones with the loss of their proposed neuroprotective role resulting in an increase in protein misfolding. Misfolded protein aggregates have been observed in several disease states and are considered to play a pivotal role in the pathogenesis of neurodegenerative conditions such as Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral sclerosis. This review will focus on the importance of the thioredoxin-like -CGHC- active site of PDI and how our understanding of this structural motif will play a key role in unravelling the pathogenic mechanisms that underpin these neurodegenerative conditions.

Black Phosphorus and its Biomedical Applications

PubMed Central

Choi, Jane Ru; Yong, Kar Wey; Choi, Jean Yu; Nilghaz, Azadeh; Lin, Yang; Xu, Jie; Lu, Xiaonan

2018-01-01

Black phosphorus (BP), also known as phosphorene, has attracted recent scientific attention since its first successful exfoliation in 2014 owing to its unique structure and properties. In particular, its exceptional attributes, such as the excellent optical and mechanical properties, electrical conductivity and electron-transfer capacity, contribute to its increasing demand as an alternative to graphene-based materials in biomedical applications. Although the outlook of this material seems promising, its practical applications are still highly challenging. In this review article, we discuss the unique properties of BP, which make it a potential platform for biomedical applications compared to other 2D materials, including graphene, molybdenum disulphide (MoS2), tungsten diselenide (WSe2) and hexagonal boron nitride (h-BN). We then introduce various synthesis methods of BP and review its latest progress in biomedical applications, such as biosensing, drug delivery, photoacoustic imaging and cancer therapies (i.e., photothermal and photodynamic therapies). Lastly, the existing challenges and future perspective of BP in biomedical applications are briefly discussed. PMID:29463996

Changes in the folding landscape of the WW domain provide a molecular mechanism for an inherited genetic syndrome.

PubMed

Pucheta-Martinez, Encarna; D'Amelio, Nicola; Lelli, Moreno; Martinez-Torrecuadrada, Jorge L; Sudol, Marius; Saladino, Giorgio; Gervasio, Francesco Luigi

2016-07-26

WW domains are small domains present in many human proteins with a wide array of functions and acting through the recognition of proline-rich sequences. The WW domain belonging to polyglutamine tract-binding protein 1 (PQBP1) is of particular interest due to its direct involvement in several X chromosome-linked intellectual disabilities, including Golabi-Ito-Hall (GIH) syndrome, where a single point mutation (Y65C) correlates with the development of the disease. The mutant cannot bind to its natural ligand WBP11, which regulates mRNA processing. In this work we use high-field high-resolution NMR and enhanced sampling molecular dynamics simulations to gain insight into the molecular causes the disease. We find that the wild type protein is partially unfolded exchanging among multiple beta-strand-like conformations in solution. The Y65C mutation further destabilizes the residual fold and primes the protein for the formation of a disulphide bridge, which could be at the origin of the loss of function.

Kinetic gating mechanism of DNA damage recognition by Rad4/XPC

NASA Astrophysics Data System (ADS)

Chen, Xuejing; Velmurugu, Yogambigai; Zheng, Guanqun; Park, Beomseok; Shim, Yoonjung; Kim, Youngchang; Liu, Lili; van Houten, Bennett; He, Chuan; Ansari, Anjum; Min, Jung-Hyun

2015-01-01

The xeroderma pigmentosum C (XPC) complex initiates nucleotide excision repair by recognizing DNA lesions before recruiting downstream factors. How XPC detects structurally diverse lesions embedded within normal DNA is unknown. Here we present a crystal structure that captures the yeast XPC orthologue (Rad4) on a single register of undamaged DNA. The structure shows that a disulphide-tethered Rad4 flips out normal nucleotides and adopts a conformation similar to that seen with damaged DNA. Contrary to many DNA repair enzymes that can directly reject non-target sites as structural misfits, our results suggest that Rad4/XPC uses a kinetic gating mechanism whereby lesion selectivity arises from the kinetic competition between DNA opening and the residence time of Rad4/XPC per site. This mechanism is further supported by measurements of Rad4-induced lesion-opening times using temperature-jump perturbation spectroscopy. Kinetic gating may be a general mechanism used by site-specific DNA-binding proteins to minimize time-consuming interrogations of non-target sites.

Changes in the folding landscape of the WW domain provide a molecular mechanism for an inherited genetic syndrome

NASA Astrophysics Data System (ADS)

Pucheta-Martinez, Encarna; D'Amelio, Nicola; Lelli, Moreno; Martinez-Torrecuadrada, Jorge L.; Sudol, Marius; Saladino, Giorgio; Gervasio, Francesco Luigi

2016-07-01

WW domains are small domains present in many human proteins with a wide array of functions and acting through the recognition of proline-rich sequences. The WW domain belonging to polyglutamine tract-binding protein 1 (PQBP1) is of particular interest due to its direct involvement in several X chromosome-linked intellectual disabilities, including Golabi-Ito-Hall (GIH) syndrome, where a single point mutation (Y65C) correlates with the development of the disease. The mutant cannot bind to its natural ligand WBP11, which regulates mRNA processing. In this work we use high-field high-resolution NMR and enhanced sampling molecular dynamics simulations to gain insight into the molecular causes the disease. We find that the wild type protein is partially unfolded exchanging among multiple beta-strand-like conformations in solution. The Y65C mutation further destabilizes the residual fold and primes the protein for the formation of a disulphide bridge, which could be at the origin of the loss of function.

Effect of the cooking method (grilling, roasting, frying and sous-vide) on the oxidation of thiols, tryptophan, alkaline amino acids and protein cross-linking in jerky chicken.

PubMed

Silva, Fábio A P; Ferreira, Valquíria C S; Madruga, Marta S; Estévez, Mario

2016-08-01

Broiler breast ( pectoralis major ) meat was submitted to salting with NaCl + NaNO 3 followed by a drying process to produce jerky-type chicken. The final product (raw broiler charqui) was desalted and then cooked using grilled, roasted, fried and sous-vide techniques. Sous-vide cooked samples showed lowest results of moisture loss compared to roasted and fried ones. Fatty acid profile suffered minor changes after cooking of broiler charqui. Regarding to protein oxidation, tryptophan fluorescence, protein carbonylation and disulphide bonds formation of chicken charqui were affected by cooking temperature while free thiol groups, Schiff base formation and hardness were mostly impacted by the length of cooking. Instrumental color of broiler charqui was affected by the type of cooking, being closely related with Maillard products formation. In conclusion, sous-vide technique seems to be the most advantageous cooking method to obtain high-quality ready-to-eat chicken charqui.

Adsorbent capability testing using desorption efficiency method on palm oil fiber

NASA Astrophysics Data System (ADS)

Manap, Nor Rahafza Abdul; Shamsudin, Roslinda

2015-09-01

The palm oil fiber had been used as filler in making thermoplastics, biocomposites and also used as adsorbent in treating waste water. In this study, palm oil fiber was used as adsorbent to treat indoor air pollutants that caused by toluene, ethylbenzene, ortho-, meta-, and para- xylene (o-, m-, p-xylene). Known amount of pollutants, ranges between 1.3 to 28 ppm was spiked into palm oil fiber and left in refrigerator for 24 hours. Then, elution of the pollutants was carried out by carbon disulphide as mobile phase or eluent. The ability of palm oil fiber as adsorbent was determine using desorption efficiency technique by gas chromatography with flame ionization detector (GC/FID). The desorption efficiency percentage given by toluene was in the range of 88.9% to 100%, 91% to 100% for ethylbenzene, 65% to 100% for pm-xylene and 92.9% to 100% for o-xylene. This percentage indicates that palm oil fiber can be used as adsorbent to treat indoor air pollutants.

Adsorption enhancement of elemental mercury onto sulphur-functionalized silica gel adsorbents.

PubMed

Johari, Khairiraihanna; Saman, Norasikin; Mat, Hanapi

2014-01-01

In this study, elemental mercury (EM) adsorbents were synthesized using tetraethyl orthosilicate (TEOS) and 3-mercaptopropyl trimethoxysilane as silica precursors. The synthesized silica gel (SG)-TEOS was further functionalized through impregnation with elemental sulphur and carbon disulphide (CS2). The SG adsorbents were then characterized by using scanning electron microscope, Fourier transform infra-red spectrophotometer, nitrogen adsorption/desorption, and energy-dispersive X-ray diffractometer. The EM adsorption of the SG adsorbents was determined using fabricated fixed-bed adsorber. The EM adsorption results showed that the sulphur-functionalized SG adsorbents had a greater Hgo breakthrough adsorption capacity, confirming that the presence of sulphur in silica matrices can improve Hgo adsorption performance due to their high affinity towards mercury. The highest Hgo adsorption capacity was observed for SG-TEOS(CS2) (82.62 microg/g), which was approximately 2.9 times higher than SG-TEOS (28.47 microg/g). The rate of Hgo adsorption was observed higher for sulphur-impregnated adsorbents, and decreased with the increase in the bed temperatures.

Effect of Thiobacillus thioparus 1904 and sulphur addition on odour emission during aerobic composting.

PubMed

Gu, Wenjie; Sun, Wen; Lu, Yusheng; Li, Xia; Xu, Peizhi; Xie, Kaizhi; Sun, Lili; Wu, Hangtao

2018-02-01

The effects of sulphur and Thiobacillus thioparus 1904 on odour emissions during composting were studied. Results indicated that the sulphur addition reduced the pH and decreased cumulative emission of ammonia and the nitrogen loss by 47.80% and 44.23%, respectively, but the amount of volatile sulphur compounds (VSCs) and the sulphur loss increased. The addition of T. thioparus 1904 effectively reduced the cumulative emissions of H 2 S, methyl sulphide, methanethiol, dimethyl disulphide and the sulphur loss by 33.24%, 81.24%, 32.70%, 54.22% and 54.24%, respectively. T. thioparus 1904 also limited the nitrogen loss. The combined application of sulphur and T. thioparus 1904 resulted in the greatest amount of nitrogen retention. The accumulation of ammonia emissions was reduced by 63.33%, and the nitrogen loss was reduced by 71.93%. The combined treatment did not increase the emission of VSCs. The application of sulphur and T. thioparus 1904 may help to control the odour of compost. Copyright © 2017. Published by Elsevier Ltd.

Kinetic gating mechanism of DNA damage recognition by Rad4/XPC

DOE PAGES

Chen, Xuejing; Velmurugu, Yogambigai; Zheng, Guanqun; ...

2015-01-06

The xeroderma pigmentosum C (XPC) complex initiates nucleotide excision repair by recognizing DNA lesions before recruiting downstream factors. How XPC detects structurally diverse lesions embedded within normal DNA is unknown. Here we present a crystal structure that captures the yeast XPC orthologue (Rad4) on a single register of undamaged DNA. The structure shows that a disulphide-tethered Rad4 flips out normal nucleotides and adopts a conformation similar to that seen with damaged DNA. Contrary to many DNA repair enzymes that can directly reject non-target sites as structural misfits, our results suggest that Rad4/XPC uses a kinetic gating mechanism whereby lesion selectivitymore » arises from the kinetic competition between DNA opening and the residence time of Rad4/XPC per site. This mechanism is further supported by measurements of Rad4-induced lesion-opening times using temperature-jump perturbation spectroscopy. Lastly, kinetic gating may be a general mechanism used by site-specific DNA-binding proteins to minimize time-consuming interrogations of non-target sites.« less

The Third Ambient Aspirin Polymorph

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shtukenberg, Alexander G.; Hu, Chunhua T.; Zhu, Qiang

Polymorphism in aspirin (acetylsalicylic acid), one of the most widely consumed medications, was equivocal until the structure of a second polymorph II, similar in structure to the original form I, was reported in 2005. Here, the third ambient polymorph of aspirin is described. Lastly, it was crystallized from the melt and its structure was determined using a combination of X-ray powder diffraction analysis and crystal structure prediction algorithms.

The Third Ambient Aspirin Polymorph

DOE PAGES

Shtukenberg, Alexander G.; Hu, Chunhua T.; Zhu, Qiang; ...

2017-05-17

Polymorphism in aspirin (acetylsalicylic acid), one of the most widely consumed medications, was equivocal until the structure of a second polymorph II, similar in structure to the original form I, was reported in 2005. Here, the third ambient polymorph of aspirin is described. Lastly, it was crystallized from the melt and its structure was determined using a combination of X-ray powder diffraction analysis and crystal structure prediction algorithms.

Endothelial nitric oxide synthase polymorphisms and adaptation of parasympathetic modulation to exercise training.

PubMed

Silva, Bruno M; Neves, Fabricia J; Negrão, Marcelo V; Alves, Cleber R; Dias, Rodrigo G; Alves, Guilherme B; Pereira, Alexandre C; Rondon, Maria U; Krieger, José E; Negrão, Carlos E; DA Nóbrega, Antonio Claudio Lucas

2011-09-01

There is a large interindividual variation in the parasympathetic adaptation induced by aerobic exercise training, which may be partially attributed to genetic polymorphisms. Therefore, we investigated the association among three polymorphisms in the endothelial nitric oxide gene (-786T>C, 4b4a, and 894G>T), analyzed individually and as haplotypes, and the parasympathetic adaptation induced by exercise training. Eighty healthy males, age 20-35 yr, were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis, and haplotypes were inferred using the software PHASE 2.1. Autonomic modulation (i.e., HR variability and spontaneous baroreflex sensitivity) and peak oxygen consumption (VO(2peak)) were measured before and after training (running, moderate to severe intensity, three times per week, 60 min·day(-1), during 18 wk). Training increased VO(2peak) (P < 0.05) and decreased mean arterial pressure (P < 0.05) in the whole sample. Subjects with the -786C polymorphic allele had a significant reduction in baroreflex sensitivity after training (change: wild type (-786TT) = 2% ± 89% vs polymorphic (-786TC/CC) = -28% ± 60%, median ± quartile range, P = 0.03), and parasympathetic modulation was marginally reduced in subjects with the 894T polymorphic allele (change: wild type (894GG) = 8% ± 67% vs polymorphic (894GT/TT) = -18% ± 59%, median ± quartile range, P = 0.06). Furthermore, parasympathetic modulation percent change was different between the haplotypes containing wild-type alleles (-786T/4b/894G) and polymorphic alleles at positions -786 and 894 (-786C/4b/894T) (-6% ± 56% vs -41% ± 50%, median ± quartile range, P = 0.04). The polymorphic allele at position -786 and the haplotype containing polymorphic alleles at positions -786 and 894 in the endothelial nitric oxide gene were associated with decreased parasympathetic modulation after exercise training.

HOTAIR gene polymorphisms contribute to increased neuroblastoma susceptibility in Chinese children.

PubMed

Yang, Xu; He, Jing; Chang, Yitian; Luo, Annie; Luo, Ailing; Zhang, Jiao; Zhang, Ruizhong; Xia, Huimin; Xu, Ling

2018-06-15

Neuroblastoma is the most frequently diagnosed extracranial solid tumor in children. Previous studies have shown that single-nucleotide polymorphisms in some genes are associated with the risk of multiple cancers, including neuroblastoma. Although Hox transcript antisense intergenic RNA (HOTAIR) gene polymorphisms have been investigated in a variety of cancers, to the authors' knowledge the relationships between HOTAIR gene polymorphisms and neuroblastoma susceptibility have not been reported to date. The objective of the current study was to evaluate the correlation between HOTAIR gene polymorphisms and neuroblastoma risk in Chinese children. The authors genotyped 6 polymorphisms (rs920778 A>G, rs12826786 C>T, rs4759314 A>G, rs7958904 G>C, rs874945 C>T, and rs1899663 C>A) of the HOTAIR gene in 2 Chinese populations including 393 neuroblastoma cases and 812 healthy controls. The strength of the associations was evaluated using odds ratios and 95% confidence intervals. Further stratification analyses were conducted to explore the association between the HOTAIR gene polymorphisms rs12826786 C>T, rs874945 C>T, and rs1899663 C>A with neuroblastoma susceptibility in terms of age, sex, clinical stage of disease, and sites of origin. The authors found that the rs12826786 C>T (P =.013), rs874945 C>T (P =.020), and rs1899663 C>A (P =.029) polymorphisms were significantly associated with increased neuroblastoma risk. In stratification analyses, these associations were more predominant in females and among patients with tumor in the retroperitoneal region or mediastinum. The remaining 3 polymorphisms were not found to be related to neuroblastoma susceptibility. The results of the current study verified that HOTAIR gene polymorphisms are associated with increased neuroblastoma risk and suggest that HOTAIR gene polymorphisms might be a potential biomarker for neuroblastoma susceptibility. Cancer 2018;124:2599-606. © 2018 American Cancer Society. © 2018 American Cancer Society.

Associations of Estrogen Receptor Alpha Gene Polymorphisms with Type 2 Diabetes Mellitus and Metabolic Syndrome: A Systematic Review and Meta-Analysis.

PubMed

Yang, Jiajia; Han, Renfang; Chen, Mengya; Yuan, Yaping; Hu, Xingxing; Ma, Yubo; Wu, Meng; Zhang, Xu; Wang, Mengmeng; Jiang, Shanqun; Pan, Faming

2018-06-01

The associations between PvuII (T>C) and XbaI (A>G) polymorphisms of estrogen receptor alpha (ESR1) gene with type 2 diabetes mellitus (T2DM) or metabolic syndrome (MetS) are reported in many studies, but the results are inconsistent. This present work aims to assess the associations by performing a comprehensive meta-analysis. Relevant studies were searched through several databases. The pooled odd ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the associations of PvuII and XbaI polymorphisms with the risk of T2DM and MetS by using the STATA 14.0 software. Eight studies for T2DM and three articles about MetS were included in this meta-analysis. The overall results indicated that PvuII, rather than XbaI polymorphism, was associated with T2DM (regressive model: OR=0.673, 95% CI=0.550 to 0.823, p raw <0.001, p FDR <0.003). The subgroup analysis based on race revealed an association of PvuII polymorphism with the decreased T2DM risk in Chinese population and a relationship between XbaI polymorphism and the reduced T2DM susceptibility in Caucasians. The difference of country may be one source of the heterogeneity for PvuII polymorphism and T2DM. However, neither PvuII nor XbaI polymorphism was related to the risk of MetS. The C allele of PvuII polymorphism presents a protective role in T2DM risk, especially in Chinese people. The G allele of XbaI polymorphism is related to a reduced risk for T2DM in Caucasian population. Nevertheless, neither of PvuII nor XbaI polymorphism is associated with MetS risk. © Georg Thieme Verlag KG Stuttgart · New York.

Paraoxonase 1 polymorphisms and haplotypes and the risk for having offspring affected with spina bifida in Southeast Mexico.

PubMed

Gonzalez-Herrera, Lizbeth; Martín Cerda-Flores, Ricardo; Luna-Rivero, Marianne; Canto-Herrera, Jorge; Pinto-Escalante, Doris; Perez-Herrera, Norma; Quintanilla-Vega, Betzabet

2010-11-01

Spina bifida (SB) is a common congenital malformation in Southeast Mexico. Parents of children with SB reside in areas with frequent pesticide spraying or have agriculture activities, suggesting potential exposure to pesticides. Paraoxonase 1 (PON1) is the responsible enzyme for deactivation of organophosphates (OP) in the central nervous system. Polymorphisms of PON1 genes influence the catalytic activity and plasma protein level of the enzyme, therefore, genotypic characterization of PON1 gene represents a potential predictor for susceptibility to OP-related effects. The frequency of PON1 haplotypes and polymorphisms (-108CT, L55M, and Q192R) were determined in this study. A case-control study was performed to evaluate the risk for having offspring affected by SB in 152 cases and 160 control parents. Polymorphisms were determined by PCR amplification and restriction fragment length polymorphism and Real Time-PCR. Odds ratios and confidence interval 95% were estimated. Genotype frequencies for the three PON1 polymorphisms were distributed according to Hardy-Weinberg expectations (p > 0.05) and were significantly different between cases and controls (p < 0.05). The heterozygous CT genotype of -108CT polymorphism, the RR genotype of Q192R polymorphism, both LM and MM genotypes of L55M polymorphism, and the haplotypes 221 and 222 (for -108CT, L55M, and Q192R) were associated with the risk for having a child affected by SB (p < 0.02). The heterozygous -108CT genotype was associated only maternally, whereas the heterozygous L55M genotype was relevant only in the fathers. The RR homozygous genotype was relevant both in mothers and fathers, suggesting the importance of this substrate-specific polymorphism. Results suggest that PON1 polymorphisms are relevant risk factors for having offspring affected with SB in this population from Southeast Mexico. © 2010 Wiley-Liss, Inc.

Association of interleukins genes polymorphisms with multi-drug resistant tuberculosis in Ukrainian population.

PubMed

Butov, Dmytro O; Kuzhko, Mykhaylo M; Makeeva, Natalia I; Butova, Tetyana S; Stepanenko, Hanna L; Dudnyk, Andrii B

2016-01-01

Multi-drug resistant tuberculosis (MDR TB) is a significant health problem in some parts of the world. Three major cytokines involved in TB immunopathogenesis include IL-2, IL-4 and IL-10. The susceptibility to MDR TB may be genetically determined. The aim of the study was to assess the association of IL-2, IL-4, IL-10 gene polymorphisms with multi-drug resistant tuberculosis (MDR TB) in Ukrainian population. We observed 140 patients suffering from infiltrative pulmonary tuberculosis (PT) and 30 apparently healthy subjects. The patients were assigned to two groups whether they suffer or do not suffer from pulmonary MDR TB. Interleukin gene (IL) polymorphisms, particularly T330G polymorphism in the IL-2 gene, C589T polymorphism in the IL-4 gene and G1082A polymorphism in the IL-10 gene were studied through polymerase chain reaction. Circulating levels of IL-2, IL-4 and IL-10 in venous blood were estimated using ELISA. Prior to treatment, patients with PT showed significant increase of IL-2 levels and decrease of IL-4 and IL-10 levels compared to apparently healthy subjects. Circulating IL-4 and IL-10 levels were significantly decreased whilst serum IL-2 level was significantly increased in patients with MDR TB compared to non-MDR TB. Low IL-4 and IL-10 secretion and considerable IL-2 alterations were shown to be significantly associated with mutations of homozygous and heterozygous genotypes affecting C589T polymorphism in the IL-4 gene, G1082A polymorphism in the IL-10 gene and T330G polymorphism in the IL-2 gene in patients with PT. Heterozygous genotype and mutations homozygous genotypes gene in polymorphisms determining specified cytokines' production is a PT risk factor and may lead to disease progression into chronic phase. Heterozygous genotype of aforementioned cytokine genetic polymorphisms was significantly the most frequent in patients with MDR TB.

Associations between TNFSF15 polymorphisms and susceptibility to ulcerative colitis and Crohn's disease: A meta-analysis.

PubMed

Zhang, Jixiang; Zhang, Jihui; Wu, Dandan; Wang, Jun; Dong, Weiguo

2014-12-01

Several polymorphisms have been identified in TNFSF15, while their roles in the incidence of ulcerative colitis (UC) and Crohn's disease (CD) are conflicting. This meta-analysis was aimed to clarify the impact of these polymorphisms on UC and CD risk. Databases were searched until 31 January 2014 for eligible studies on TNFSF15 polymorphisms. Data were extracted, and pooled odd ratios (ORs) as well as 95% confidence intervals (95% CIs) were calculated. Fifteen studies with 8903 CD patients, 4687 UC patients and 12 606 controls were included. Except for rs4263839 polymorphism, significant associations were found between the rest six TNFSF15 polymorphisms and CD risk (rs3810936: OR = 2.10, 95% CI, 1.47-3.00; rs6478108: OR = 2.19, 95% CI, 1.53-3.13; rs4979462: OR = 1.89, 95% CI, 1.42-2.52; rs6478109: OR = 2.00, 95% CI, 1.39-2.88; rs7848647: OR = 1.54, 95% CI, 1.15-2.06; rs7869487: OR = 1.51, 95% CI, 1.06-2.17). And we found rs3810936, rs6478108 and rs6478109 polymorphism were significantly associated with UC risk (rs3810936: OR = 1.19, 95% CI, 1.06-1.34; rs6478108: OR = 1.16, 95% CI, 1.06-1.26; rs6478109: OR = 1.16, 95% CI, 1.03-1.32). According to the subgroup analysis by ethnicity, except for rs4263839 in Caucasian and rs4979462 in Asian, all the rest investigated TNFSF15 polymorphisms were associated with CD risk and rs3810936 and rs7848647 polymorphism in Asian as well as rs6478108 polymorphism in Caucasian were associated with UC risk. This meta-analysis indicated that most of the seven TNFSF15 polymorphisms (except for rs4263839) were risk factors contributed to CD and UC susceptibility. The differences in ethnicity did not influence the risk obviously.

TLR-4 polymorphisms and leukocyte TLR-4 expression in febrile UTI and renal scarring.

PubMed

Bayram, Meral Torun; Soylu, Alper; Ateş, Halil; Kızıldağ, Sefa; Kavukçu, Salih

2013-09-01

In this study, we aimed to determine the relation of TLR-4 Asp299Gly and Thr399Ile polymorphisms and monocyte/neutrophil TLR-4 expression to febrile urinary tract infection (UTI) and renal scar development in children. The study was performed in children with a history of febrile UTI. Patients with and without renal scarring were classified as group 1 and group 2, respectively, while the control cases in our previous study were used as the control group (group 3). All three groups were compared for the rate of TLR-4 Asp299Gly and Thr399Ile polymorphisms, and for basal and lipopolysaccharide-stimulated monocyte/neutrophil TLR-4 expression levels. There were 168 patients (86 in group 1, 82 in group 2) and 120 control cases. Monocyte/neutrophil TLR-4 expression levels were similar in groups 1 and 2. However, both groups had lower TLR-4 expression than group 3. The rate of TLR-4 Asp299Gly polymorphism was not different in all groups. TLR-4 Thr399Ile polymorphism was higher in groups 1 and 2 than in group 3 (14.0, 12.2, and 2.0 %, respectively), while group 1 and group 2 were not different. Furthermore, monocyte TLR-4 expression level was lower in those having TLR-4 Thr399Ile polymorphism than in those without this polymorphism. Patients with febrile UTI had more frequent TLR-4 Thr399Ile polymorphism and lower monocyte/neutrophil TLR-4 expression. These findings indicate that children carrying TLR-4 Thr399Ile polymorphism and/or having low level of monocyte/neutrophil TLR-4 expression have a tendency to develop febrile UTI. However, we could not show the association of TLR-4 polymorphisms and of TLR-4 expression level to renal scarring.

Arg753gln and Arg677 Trp Polymorphisms of Toll-Like Receptor 2 In Acute Apical Abscess

PubMed Central

Miri-Moghaddam, Ebrahim; Farhad Mollashahi, Narges; Naghibi, Nava; Garme, Yasaman; Bazi, Ali

2018-01-01

Statement of the Problem: Genetic polymorphisms can alter immunity response against pathogens, which in turn influence individuals’ susceptibility to certain infections. Purpose: Our aim was to determine the association of Arg753Gln (rs5743708) and Arg677Trp (rs12191786) polymorphisms of toll like receptor-2 gene with the two clinical forms of apical periodontitis: acute apical abscess (AAA) and asymptomatic apical periodontitis (AAP). Materials and Method: There were 50 patients with AAA as case group and 50 with AAP as control group. Genotyping was done using Tetra-ARMS (amplification refractory mutation system) PCR. Results: Heterozygous genotype of Arg677Trp polymorphism was associated with risk of AAA (OR=1.9, 95% CI: 0.7-5.5, p= 0.05). Although statistically insignificant, Arg677Trp polymorphism promoted the risk of AAA in dominant model (OR=2.1, 95% CI: 0.7-5.9, p> 0.05). The frequency of mutant allele (T) of Arg677Trp polymorphism was higher in AAA (14%) than AAP (7%) subjects (OR=1.7, 95% CI: 0.6-4.7). For Arg753Gln polymorphism, wild homozygous (GG) represented the dominant genotype in both cases (96%) and controls (100%). Variant allele (A) of Arg753Gln polymorphism was identified in 2% of AAA, while no individual represented with this allele in AAP subjects. Individuals with Arg753Gln; Arg677Trp (GG; TC) combination showed an elevated risk of AAA (OR=1.6, 95% CI: 0.5- 4.2, p> 0.05). Conclusion: Arg677Trp polymorphism of TLR-2 rendered a higher risk for the development of abscesses in apical periodontitis. It is recommended to explore role of this polymorphism in other populations. PMID:29854884

9β Polymorphism of the Glucocorticoid Receptor Gene Appears to Have Limited Impact in Patients with Addison’s Disease

PubMed Central

Ross, Ian Louis; Dandara, Collet; Swart, Marelize; Lacerda, Miguel; Schatz, Desmond; Blom, Dirk Jacobus

2014-01-01

Background Addison’s disease (AD) has been associated with an increased risk of cardiovascular disease. Glucocorticoid receptor polymorphisms that alter glucocorticoid sensitivity may influence metabolic and cardiovascular risk factors in patients with AD. The 9β polymorphism of the glucocorticoid receptor gene is associated with relative glucocorticoid resistance and has been reported to increase the risk of myocardial infarction in the elderly. We explored the impact of this polymorphism in patients with AD. Materials and Methods 147 patients with AD and 147 age, gender and ethnicity matched healthy controls were recruited. Blood was taken in a non-fasted state for plasma lipid determination, measurement of cardiovascular risk factors and DNA extraction. Results Genotype data for the 9β polymorphism was available for 139 patients and 146 controls. AD patients had a more atherogenic lipid profile characterized by an increase in the prevalence of small dense LDL (p = 0.003), increased triglycerides (p = 0.002), reduced HDLC (p<0.001) an elevated highly sensitive C-reactive protein (p = 0.01), compared with controls. The 9β polymorphism (at least one G allele) was found in 28% of patients and controls respectively. After adjusting for age, gender, ethnicity, BMI and hydrocortisone dose per metre square of body surface area in patients, there were no significant metabolic associations with this polymorphism and hydrocortisone doses were not higher in patients with the polymorphism. Conclusions This study did not identify any associations between the 9β polymorphism and cardiovascular risk factors or hydrocortisone dose and determination of this polymorphism is therefore unlikely to be of clinical benefit in the management of patients with AD. PMID:24466047

9β Polymorphism of the glucocorticoid receptor gene appears to have limited impact in patients with Addison's disease.

PubMed

Ross, Ian Louis; Dandara, Collet; Swart, Marelize; Lacerda, Miguel; Schatz, Desmond; Blom, Dirk Jacobus

2014-01-01

Addison's disease (AD) has been associated with an increased risk of cardiovascular disease. Glucocorticoid receptor polymorphisms that alter glucocorticoid sensitivity may influence metabolic and cardiovascular risk factors in patients with AD. The 9β polymorphism of the glucocorticoid receptor gene is associated with relative glucocorticoid resistance and has been reported to increase the risk of myocardial infarction in the elderly. We explored the impact of this polymorphism in patients with AD. 147 patients with AD and 147 age, gender and ethnicity matched healthy controls were recruited. Blood was taken in a non-fasted state for plasma lipid determination, measurement of cardiovascular risk factors and DNA extraction. Genotype data for the 9β polymorphism was available for 139 patients and 146 controls. AD patients had a more atherogenic lipid profile characterized by an increase in the prevalence of small dense LDL (p = 0.003), increased triglycerides (p = 0.002), reduced HDLC (p<0.001) an elevated highly sensitive C-reactive protein (p = 0.01), compared with controls. The 9β polymorphism (at least one G allele) was found in 28% of patients and controls respectively. After adjusting for age, gender, ethnicity, BMI and hydrocortisone dose per metre square of body surface area in patients, there were no significant metabolic associations with this polymorphism and hydrocortisone doses were not higher in patients with the polymorphism. This study did not identify any associations between the 9β polymorphism and cardiovascular risk factors or hydrocortisone dose and determination of this polymorphism is therefore unlikely to be of clinical benefit in the management of patients with AD.

Investigation of glucocorticoid receptor polymorphisms in relation to metabolic parameters in Addison's disease.

PubMed

Ross, I L; Levitt, N S; Van der Merwe, L; Schatz, D A; Johannsson, G; Dandara, C; Pillay, T S; Blom, D J

2013-03-01

Uncertainty exists whether glucocorticoid receptor (GCR) polymorphisms play a role in steroid-related side effects in Addison's disease (AD) patients on hydrocortisone. The polymorphisms Bcll and N363S appear to increase sensitivity to cortisol, while the ER22/23EK polymorphism has been associated with resistance to cortisol. One hundred and forty seven AD patients, and gender, and ethnicity-matched controls were recruited in South Africa. Three polymorphisms in the GCR were studied, using PCR followed by restriction fragment length analysis. Associations with BMI, lipids, glucose and inflammatory markers were investigated. In both patients and controls, the Bcll polymorphism occurred more frequently in whites than in other ethnic groups studied but was not associated with any of the metabolic parameters tested. The ER22/23EK polymorphism was associated with an increased BMI in both patients (29.4 vs 24.7  kg/m²) and control subjects (26.3 vs 24.2  kg/m²). The ER22/23EK polymorphism was also associated with lower LDL cholesterol in control subjects (3.46 vs 3.93  mmol/l) and in patients (3.52 vs 4.10  mmol/l). N363S was associated with increased BMI in controls 29.9  kg/m² vs wild type 24.8  kg/m². Median hydrocortisone doses were greater in patients heterozygous for either ER22/23EK 30.0  mg or N363S 25.0  mg polymorphisms than in wild type patients 20.0  mg (both comparisons). Alterations in lipids, BMI and hydrocortisone dose were associated with two polymorphisms. Further larger studies are warranted to corroborate these findings.

[Polymorphism of genes encoding proteins of DNA repair vs. occupational and environmental exposure to lead, arsenic and pesticides].

PubMed

Bukowski, Karol; Woźniak, Katarzyna

2018-03-09

Genetic polymorphism is associated with the occurrence of at least 2 different alleles in the locus with a frequency higher than 1% in the population. Among polymorphisms we can find single nucleotide polymorphism (SNP) and polymorphism of variable number of tandem repeats. The presence of certain polymorphisms in genes encoding DNA repair enzymes is associated with the speed and efficiency of DNA repair and can protect or expose humans to the effects provoked by xenobiotics. Chemicals, such as lead, arsenic pesticides are considered to exhibit strong toxicity. There are many different polymorphisms in genes encoding DNA repair enzymes, which determine the speed and efficiency of DNA damage repair induced by these xenobiotics. In the case of lead, the influence of various polymorphisms, such as APE1 (apurinic/apyrimidinic endonuclease 1) (rs1130409), hOGG1 (human 8-oxoguanine glycosylase) (rs1052133), XRCC1 (X-ray repair cross-complementing protein group 1) (rs25487), XRCC1 (rs1799782) and XRCC3 (X-ray repair cross-complementing protein group 3) (rs861539) were described. For arsenic polymorphisms, such as ERCC2 (excision repair cross-complementing) (rs13181), XRCC3 (rs861539), APE1 (rs1130409) and hOGG1 (rs1052133) were examined. As to pesticides, separate and combined effects of polymorphisms in genes encoding DNA repair enzymes, such as XRCC1 (rs1799782), hOGG1 (rs1052133), XRCC4 (X-ray repair cross-complementing protein group 4) (rs28360135) and the gene encoding the detoxification enzyme PON1 paraoxonase (rs662) were reported. Med Pr 2018;69(2):225-235. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

BIM Gene Polymorphism Lowers the Efficacy of EGFR-TKIs in Advanced Nonsmall Cell Lung Cancer With Sensitive EGFR Mutations: A Systematic Review and Meta-Analysis.

PubMed

Huang, Wu Feng; Liu, Ai Hua; Zhao, Hai Jin; Dong, Hang Ming; Liu, Lai Yu; Cai, Shao Xi

2015-08-01

The strong association between bcl-2-like 11 (BIM) triggered apoptosis and the presence of epidermal growth factor receptor (EGFR) mutations has been proven in nonsmall cell lung cancer (NSCLC). However, the relationship between EGFR-tyrosine kinase inhibitor's (TKI's) efficacy and BIM polymorphism in NSCLC EGFR is still unclear.Electronic databases were searched for eligible literatures. Data on objective response rates (ORRs), disease control rates (DCRs), and progression-free survival (PFS) stratified by BIM polymorphism status were extracted and synthesized based on random-effect model. Subgroup and sensitivity analyses were conducted.A total of 6 studies that involved a total of 773 EGFR mutant advanced NSCLC patients after EGFR-TKI treatment were included. In overall, non-BIM polymorphism patients were associated with significant prolonged PFS (hazard ratio 0.63, 0.47-0.83, P = 0.001) compared to patients with BIM polymorphism. However, only marginal improvements without statistical significance in ORR (odds ratio [OR] 1.71, 0.91-3.24, P = 0.097) and DCR (OR 1.56, 0.85-2.89, P = 0.153) were observed. Subgroup analyses showed that the benefits of PFS in non-BIM polymorphism group were predominantly presented in pooled results of studies involving chemotherapy-naive and the others, and retrospective studies. Additionally, we failed to observe any significant benefit from patients without BIM polymorphism in every subgroup for ORR and DCR.For advanced NSCLC EGFR mutant patients, non-BIM polymorphism ones are associated with longer PFS than those with BIM polymorphism after EGFR-TKIs treatment. BIM polymorphism status should be considered an essential factor in studies regarding EGFR-targeted agents toward EGFR mutant patients.

Epistatic interaction between FCRL3 and NFκB1 genes in Spanish patients with rheumatoid arthritis

PubMed Central

Martínez, A; Sánchez, E; Valdivia, A; Orozco, G; López‐Nevot, M A; Pascual‐Salcedo, D; Balsa, A; Fernández‐Gutiérrez, B; de la Concha, E G; García‐Sánchez, A; Koeleman, B P C; Urcelay, E; Martín, J

2006-01-01

Background A Japanese study has described a strong association between rheumatoid arthritis and several polymorphisms located in the Fc receptor‐like 3 (FCRL3) gene, a member of a family of genes related to Fc receptors located on chromosome 1q21–23. Objectives To evaluate the association between rheumatoid arthritis and FCLR3 polymorphisms in a large cohort of Caucasian patients with rheumatoid arthritis and healthy controls of Spanish origin. Owing to the described functional link between the FCRL3 polymorphisms and the transcription factor nuclear factor κB (NFκB), a functional polymorphism located in the NFκB1 gene was included. Methods 734 patients with rheumatoid arthritis from Madrid and Granada, Spain, were included in the study, along with 736 healthy controls. Polymorphisms in the FCRL3 gene were studied by TaqMan technology. The −94ins/delATTG NFκB1 promoter polymorphism was analysed by fragment analysis after polymerase chain reaction with labelled primers. Genotypes were compared using 3×2 contingency tables and χ2 values. Results No overall differences were found in any of the FCRL3 polymorphisms and in the NFκB1 promoter polymorphism when patients were compared with controls. However, when stratified according to NFκB1 genotypes, a susceptibility effect of FCRL3 polymorphisms was observed in patients who were heterozygotes for NFκB1 (pc = 0.003). Conclusions The FCRL3 polymorphisms associated with rheumatoid arthritis in a Japanese population are not associated per se with rheumatoid arthritis in a Spanish population. A genetic interaction was found between NFκB1 and FCRL3 in Spanish patients with rheumatoid arthritis. These findings may provide a general rationale for divergent genetic association results in different populations. PMID:16476711

Characterization of early follicular cDNA library suggests evidence for genetic polymorphisms in the inbred strain C108 of Bombyx mori.

PubMed

Mills, D R; Goldsmith, M R

2000-04-01

Recent work towards the completion of a saturated molecular genetic linkage map for the lepidopteran silkworm, Bombyx mori (n = 28), has provided evidence for existing polymorphisms in the inbred strain C108. Two inbred parental strains, p50 and C108, were crossed to produce the F1 (P/C) hybrid offspring. The populations used in this project were comprised of a combination of 29 F2 (F1 x F1) and 31 reciprocal backcross (P/C x C/C, P/C x P/P) progeny. All restriction fragment length polymorphisms (RFLPs) for the initial analysis were hybridized with anonymous probes derived from a random early follicular cDNA (Rcf) library from Bombyx. A total of 19 Rcf probes were selected as showing scorable codominant polymorphic patterns when screened against F2 and backcross DNAs digested with the restriction enzymes EcoRI, HindIII, or PstI, and Southern blotted to nylon membranes for hybridization. Of the newly reported Rcf probes, 7 (37%) were characterized as producing 'simple' polymorphic patterns, while 12 (63%) were characterized as producing 'complex' polymorphic patterns. Further characterization of the complex patterns subdivided this group into two general classes: polymorphisms that contained an additional allele, and multiple bands that contained an easily scored two banded polymorphism. Because the extra allele class was limited to the (P/C x C/C) backcross progeny, it is suggested that the inbred parental strain C108 harbors polymorphic loci that are inherited in a simple Mendelian fashion. A genetic analysis discussing plausible origins and maintenance of these polymorphisms is presented.

Association of Helicobacter pylori infection with Toll-like receptor-4 Thr399Ile polymorphism increased the risk of peptic ulcer development in North of Iran.

PubMed

Tourani, Mehdi; Habibzadeh, Maryam; Shokri-Shirvani, Javad; Teymournejad, Omid; Mostafazadeh, Amrollah; Khafri, Soraya; Nouri, Hamid Reza

2018-01-01

Toll-like receptor-4 (TLR4) polymorphisms may influence host immune response against Helicobacter pylori (H. pylori). This study aimed to investigate whether TLR4 polymorphisms are associated with H. pylori susceptibility and risk of peptic ulcer development or not. The TLR4 + 3725 G/C polymorphism was studied using polymerase chain reaction with confronting two-pair primers (PCR-CTPP). In addition, TLR4 Asp299Gly and Thr399Ile polymorphisms were evaluated by PCR-restriction fragment length polymorphism (RFLP). There was no significant difference in TLR4 + 3725 G/C and Asp299Gly genotype frequencies between non-peptic ulcer (NPUD) and peptic ulcer (PUD) individuals in the context of peptic ulcer development and susceptibility to infection with H. pylori. Nevertheless, a significant association with increased risk for PUD development was observed for polymorphism TLR4 Thr399Ile [odds ratio (OR) = 4.2; 95% confidence interval (CI) = 1.35-13.26; p = 0.01]. Correspondingly, TLR4 Thr399Ile polymorphism was associated with H. pylori susceptibility (OR = 0.27; 95% CI = 0.08-0.88; p = 0.04). In addition, TLR4 Thr399Ile polymorphism increased 4.2-fold, the risk of peptic ulcer development in individuals infected by H. pylori carrying CT + TT genotype. Our results showed that TLR4 Thr399Ile polymorphism along with H. pylori infection may play critical roles in peptic ulcer development in North of Iran. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Angiotensin-converting enzyme activity in Cavalier King Charles Spaniels with an ACE gene polymorphism and myxomatous mitral valve disease.

PubMed

Meurs, Kathryn M; Olsen, Lisbeth H; Reimann, Maria J; Keene, Bruce W; Atkins, Clarke E; Adin, Darcy; Aona, Brent; Condit, Julia; DeFrancesco, Teresa; Reina-Doreste, Yamir; Stern, Joshua A; Tou, Sandra; Ward, Jessica; Woodruff, Kathleen

2018-02-01

Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is particularly common in the Cavalier King Charles Spaniel (CKCS) breed and affected dogs are frequently managed with angiotensin-converting enzyme inhibitors (ACE-I). We have previously identified a canine ACE gene polymorphism associated with a decrease in angiotensin-converting enzyme (ACE) activity. The aim of this study was to evaluate for the prevalence of the ACE polymorphism in CKCS with mitral valve disease and to determine whether the presence of the polymorphism is associated with alterations in ACE activity at different stages of cardiac disease. Seventy-three dogs with a diagnosis of mitral valve disease were evaluated and a blood sample was drawn for ACE polymorphism genotyping and ACE activity measurement. Forty-three dogs were homozygous for the ACE polymorphism; five were heterozygous and 25 were homozygous wild type. The mean age and the median severity of disease were not different for dogs with the polymorphism and dogs with the wild-type sequence. The median baseline ACE activity was significantly lower for the ACE polymorphism (27.0 U/l) than the wild-type sequence dogs (31.0 U/l) (P=0.02). Dogs with more severe disease and the ACE polymorphism had significantly lower levels of ACE activity than dogs with the wild-type sequence (P=0.03). The CKCS appears to have a high prevalence of the ACE variant. Dogs with the ACE variant had lower levels of ACE activity even in more advanced mitral valve disease than dogs without the variant. The clinical significance of this finding and its impact on the need for ACE-I in dogs with the polymorphism and heart disease deserves further study.

Estimation of the relationship between the polymorphisms of selected genes: ACE, AGTR1, TGFβ1 and GNB3 with the occurrence of primary vesicoureteral reflux.

PubMed

Życzkowski, Marcin; Żywiec, Joanna; Nowakowski, Krzysztof; Paradysz, Andrzej; Grzeszczak, Władyslaw; Gumprecht, Janusz

2017-03-01

Etiopathogenesis of VUR is composite and not fully understood. Many data indicate the importance of genetic predisposition. The aim of this study was to establish the relationship of selected polymorphisms: 14094 polymorphism of the ACE, polymorphism rs1800469 of TGFβ-1, rs5443 gene polymorphism of the GNB3 and receptor gene polymorphism rs5186 type 1 AGTR1 with the occurrence of the primary vesicoureteral reflux. The study included 190 children: 90 with the primary VUR confirmed with the voiding cystourethrogram and excluded secondary VUR and a control group of 100 children without a history of the diseases of the genitourinary tract. The study was planned in the scheme: "tested case versus control." Genomic DNA was isolated from the leukocytes of peripheral blood samples. The results were statistically analyzed in the Statistica 10 using χ 2 test and analysis of the variance Anova. Any of the four studied polymorphisms showed no difference in the distribution of genotypes between patients with primary vesicoureteral reflux and the control group. In patients with VUR and TT genotype polymorphism rs5443 GNB3 gene, the glomerular filtration rate was significantly higher than in patients with genotype CC or CT. (1) No relationship was found between the studied polymorphisms (14094 ACE gene, rs1800469 gene TGFβ1, GNB3 gene rs5443, rs5186 AGTR1 gene) and the occurrence of primary vesicoureteral reflux. (2) TT genotype polymorphism rs5443 GNB3 gene may be a protective factor for the improved renal function in patients with primary vesicoureteral reflux in patients with genotype CC or CT.

Neuropsychological correlates of transcription factor AP-2Beta, and its interaction with COMT and MAOA in healthy females.

PubMed

Schabram, Ina; Eggermann, Thomas; Siegel, Steven J; Gründer, Gerhard; Zerres, Klaus; Vernaleken, Ingo

2013-01-01

The transcription factor AP-2β has been shown to impact clinical and neuropsychological properties. Apparently, it regulates the transcription of genes that code for molecules which are part of the catecholaminergic transmission system. This investigation focuses on possible effects of the transcription factor AP-2β intron 2 polymorphism on cognitive performance parameters. This hypothesis-driven investigation examined the effects and interactions of the transcription factor AP-2β intron 2 polymorphism, the Val158Met catechol-O-methyltransferase (COMT) polymorphism, and the variable number of tandem repeat polymorphism of monoamine oxidase A (MAOA) on cognitive performance parameters within a group of 200 healthy women (age: mean ± SD, 23.93 ± 3.33 years). The AP-2β polymorphism significantly influenced cognitive performance (in particular, the Trail Making Test part B), whereas the MAOA and COMT polymorphisms did not. However, there was an interaction effect of the AP-2β × MAOA × COMT genotypes on the decision bias β of the degraded-stimulus version of the continuous performance task. Only the Val158Met COMT polymorphism showed an influence on personality questionnaires (openness and self-transcendence; NEO Five-Factor Inventory, Temperament and Character Inventory). The transcription factor AP-2β intron 2 polymorphism had more influence on cognition than the MAOA and COMT polymorphisms. Possibly, the AP-2β genotype might influence cognition through pathways other than those that regulate MAOA and COMT transcription. Interactions of transcription factor AP-2β, COMT, and MAOA polymorphisms suggest higher leverage effects of transcription factor AP-2β in subjects with high dopamine availability. Copyright © 2013 S. Karger AG, Basel.

Associations between oxytocin receptor gene (OXTR) polymorphisms and self-reported aggressive behavior and anger: Interactions with alcohol consumption.

PubMed

Johansson, Ada; Westberg, Lars; Sandnabba, Kenneth; Jern, Patrick; Salo, Benny; Santtila, Pekka

2012-09-01

Oxytocin has been implicated in the regulation of social as well as aggressive behaviors, and in a recent study we found that the effect of alcohol on aggressive behavior was moderated by the individual's genotype on an oxytocin receptor gene (OXTR) polymorphism (Johansson et al., 2012). In this study we wanted to deepen and expand the analysis by exploring associations between three (rs1488467, rs4564970, rs1042778) OXTR polymorphisms and aggressive behavior, trait anger as well as anger control in a population-based sample of Finnish men and women (N=3577) aged between 18 and 49 years (M=26.45 years, SD=5.02). A specific aim was to investigate if the polymorphisms would show interactive effects with alcohol consumption on aggressive behavior and trait anger, as well as to explore whether these polymorphisms affect differences in anger control between self-reported sober and intoxicated states. The results showed no main effects of the polymorphisms, however, three interactions between the polymorphisms and alcohol consumption were found. The effect of alcohol consumption on aggressive behavior was moderated by the genotype of the individual on the rs4564970 polymorphism, in line with previous results (Johansson et al., 2012). For trait anger, both the rs1488467 and the rs4564970 polymorphisms interacted with alcohol consumption. It appears that the region of the OXTR gene including both the rs4564970 and the rs1488467 polymorphisms may be involved in the regulation of the relationship between alcohol and aggressive behavior as well as between alcohol and the propensity to react to situations with elevated levels of anger. Copyright © 2012 Elsevier Ltd. All rights reserved.

Polymorphisms in the ghrelin gene are associated with serum high-density lipoprotein cholesterol level and not with type 2 diabetes mellitus in Koreans.

PubMed

Choi, Hyung Jin; Cho, Young Min; Moon, Min Kyong; Choi, Hye Hun; Shin, Hyoung Doo; Jang, Hak Chul; Kim, Seong Yeon; Lee, Hong Kyu; Park, Kyong Soo

2006-11-01

Ghrelin is known to play a role in glucose metabolism and in beta-cell function. There are controversies regarding the role of ghrelin polymorphisms in diabetes and diabetes-related phenotypes. The objective of this study was to examine polymorphisms of the ghrelin gene in a Korean cohort and investigate associations between them and susceptibility to type 2 diabetes and its related phenotypes. The ghrelin gene was sequenced to identify polymorphisms in 24 DNA samples. Common variants were then genotyped in 760 type 2 diabetic patients and 641 nondiabetic subjects. Genetic associations with diabetes-related phenotypes were also analyzed. Nine polymorphisms were identified, and four common polymorphisms [g.-1500C>G, g.-1062G > C, g.-994C > T, g.+408C > A (Leu72Met)] were genotyped in a larger study. The genotype distributions of these four common polymorphisms in type 2 diabetes patients were similar to those of normal nondiabetic controls. However, these four common polymorphisms were variably associated with several diabetes-related phenotypes, such as high-density lipoprotein (HDL) cholesterol, fasting plasma glucose, and homeostasis model assessment of insulin resistance. In particular, subjects harboring g.-1062C were associated with a lower serum HDL cholesterol level after adjusting for other variables (P = 0.0004 or 0.01 after Bonferroni correction for 24 tests). The aforementioned four common polymorphisms in the ghrelin gene were not found to be significantly associated with susceptibility to type 2 diabetes mellitus in the Korean population. However, the common polymorphism g.-1062G > C in the promoter region of the ghrelin gene was found to be significantly associated with serum HDL cholesterol levels.

Arg753gln and Arg677 Trp Polymorphisms of Toll-Like Receptor 2 In Acute Apical Abscess.

PubMed

Miri-Moghaddam, Ebrahim; Farhad Mollashahi, Narges; Naghibi, Nava; Garme, Yasaman; Bazi, Ali

2018-06-01

Genetic polymorphisms can alter immunity response against pathogens, which in turn influence individuals' susceptibility to certain infections. Our aim was to determine the association of Arg753Gln (rs5743708) and Arg677Trp (rs12191786) polymorphisms of toll like receptor-2 gene with the two clinical forms of apical periodontitis: acute apical abscess (AAA) and asymptomatic apical periodontitis (AAP). There were 50 patients with AAA as case group and 50 with AAP as control group. Genotyping was done using Tetra-ARMS (amplification refractory mutation system) PCR. Heterozygous genotype of Arg677Trp polymorphism was associated with risk of AAA (OR=1.9, 95% CI: 0.7-5.5, p = 0.05). Although statistically insignificant, Arg677Trp polymorphism promoted the risk of AAA in dominant model (OR=2.1, 95% CI: 0.7-5.9, p > 0.05). The frequency of mutant allele (T) of Arg677Trp polymorphism was higher in AAA (14%) than AAP (7%) subjects (OR=1.7, 95% CI: 0.6-4.7). For Arg753Gln polymorphism, wild homozygous (GG) represented the dominant genotype in both cases (96%) and controls (100%). Variant allele (A) of Arg753Gln polymorphism was identified in 2% of AAA, while no individual represented with this allele in AAP subjects. Individuals with Arg753Gln; Arg677Trp (GG; TC) combination showed an elevated risk of AAA (OR=1.6, 95% CI: 0.5- 4.2, p > 0.05). Arg677Trp polymorphism of TLR-2 rendered a higher risk for the development of abscesses in apical periodontitis. It is recommended to explore role of this polymorphism in other populations.

Isolation and cross-familial amplification of 41 microsatellites for the brook charr (Salvelinus fontinalis)

USGS Publications Warehouse

Perry, G.M.L.; King, T.L.; St. -Cyr, J.; Valcourt, M.; Bernatchez, L.

2005-01-01

The brook charr (Salvelinus fontinalis; Osteichthyes: Salmonidae) is a phenotypically diverse fish species inhabiting much of North America. But relatively few genetic diagnostic resources are available for this fish species. We isolated 41 microsatellites from S. fontinalis polymorphic in one or more species of salmonid fish. Thirty-seven were polymorphic in brook charr, 15 in the congener Arctic charr (Salvelinus alpinus) and 14 in the lake charr (Salvelinus namaycush). Polymorphism was also relatively high in Oncorhynchus, where 21 loci were polymorphic in rainbow trout (Oncorhynchus mykiss) and 16 in cutthroat trout (Oncorhynchus clarkii) but only seven and four microsatellite loci were polymorphic in the more distantly related lake whitefish (Coregonus clupeaformis) and Atlantic salmon (Salmo salar), respectively. One duplicated locus (Sfo228Lav) was polymorphic at both duplicates in S. fontinalis. ?? 2005 Blackwell Publishing Ltd.

Investigation of the L-Glutamic acid polymorphism: Comparison between stirred and stagnant conditions

NASA Astrophysics Data System (ADS)

Tahri, Yousra; Gagnière, Emilie; Chabanon, Elodie; Bounahmidi, Tijani; Mangin, Denis

2016-02-01

This work highlights the effect of the stirring, the temperature and the supersaturation on the cooling crystallization of L-Glutamic acid (LGlu) polymorphs. First, solubility measurements of the metastable polymorph α and the stable polymorph β were performed. Then, crystallization experiments were carried out in stirred vessel and in stagnant cell. All these experiments were monitored by in situ devices. The effect of the temperature on the LGlu polymorphs was found to be more relevant than the supersaturation in the stirred crystallizer. In the stagnant cell, only the stable form β crystallized regardless of the operating conditions. Moreover, an unexpected and new habit of the β form was discovered and confirmed. These results suggest that the temperature and the stirring can strongly affect the nucleation and the growth kinetics of polymorphic forms.

Bactericidal/permeability increasing protein gene polymorphism and inflammatory bowel diseases: meta-analysis of five case-control studies.

PubMed

Fan, Lijuan; Fu, Guoning; Ding, Yuanyuan; Lv, Peng; Li, Hongyun

2017-03-01

Bactericidal/permeability increasing protein (BPI) gene polymorphisms have been extensively investigated in terms of their associations with inflammatory bowel disease (IBD), with contradictory results. The aim of this meta-analysis was to evaluate associations between BPI gene polymorphisms and the risk of IBD, Crohn's disease (CD), and ulcerative colitis (UC). Eligible studies from PubMed, Embase, and Cochrane library databases were identified. Ten studies (five CD and five UC) published in five papers were included in this meta-analysis. G645A polymorphism was associated with a decreased risk of UC in allele model, dominant model, and homozygous model. Our data suggested that BPI G645A polymorphism was associated with a decreased risk of UC; the BPI G645A polymorphism was not associated with the risk of CD.

Genetically-determined polymorphism of nonspecific esterases and phosphoglucomutase in eight introduced breeds of the silkworm, Bombyx mori, raised in Bulgaria.

PubMed

Staykova, Teodora

2008-01-01

Isoenzymes are very suitable markers for the study of the inter-breed diversity of the silkworm Bombyx mon L. (Lepidoptera: Bombycidae). More than 250 breeds are raised in Bulgaria, which are not very well studied with regard to their isoenzymic polymorphism. Polymorphism of nonspecific esterases from pupal haemolymph was analyzed, as well as of phosphoglucomutase from different organs of larvae, pupae and imago, from eight introduced breeds. Electrophoresis in polyacrylamide gels was used. A polylocus control of nonspecific esterases, and possible monolocus control of phosphoglucomutase was ascertained. Biallele and triallele polymorphism of phosphoglucomutase locus and in three of the esterase loci was determined. The allelic frequencies of the polymorphic loci in each breed were analyzed. Inter-breed differences were found in different allelic frequencies, different heterozygosity and polymorphism.

Crystallization of D-mannitol in binary mixtures with NaCl: phase diagram and polymorphism.

PubMed

Telang, Chitra; Suryanarayanan, Raj; Yu, Lian

2003-12-01

To study the crystallization, polymorphism, and phase behavior of D-mannitol in binary mixtures with NaCl to better understand their interactions in frozen aqueous solutions. Differential scanning calorimetry, hot-stage microscopy, Raman microscopy, and variable-temperature X-ray diffractometry were used to characterize D-mannitol-NaCl mixtures. NaCl and D-mannitol exhibited significant melt miscibility (up to 7.5% w/w or 0.20 mole fraction of NaCl) and a eutectic phase diagram (eutectic composition 7.5% w/w NaCl; eutectic temperature 150 degrees C for the alpha and beta polymorphs of D-mannitol and 139 degrees C for the delta). The presence of NaCl did not prevent mannitol from crystallizing but, depending on sample size, affected the polymorph crystallized: below 10 mg, delta was obtained; above 100 mg, alpha was obtained. Pure mannitol crystallized under the same conditions first as the delta polymorph and then as the a polymorph, with the latter nucleating on the former. KCl showed similar eutectic points and melt miscibility with D-mannitol as NaCl. LiCl yielded lower eutectic melting points, inhibited the crystallization of D-mannitol during cooling, and enabled the observation of its glass transition. Despite their structural dissimilarity, significant melt miscibility exists between D-mannitol and NaCl. Their phase diagram has been determined and features polymorph-dependent eutectic points. NaCl influences the polymorphic behavior of mannitol, and the effect is linked to the crystallization of mannitol in two polymorphic stages.

A meta-analysis of data associating DRD4 gene polymorphisms with schizophrenia.

PubMed

Xu, Feng-Ling; Wu, Xue; Zhang, Jing-Jing; Wang, Bao-Jie; Yao, Jun

2018-01-01

To explore the association between DRD4 polymorphisms and schizophrenia risk, a meta-analysis was carried out with 41 case-control articles. Specifically, we included 28 articles (5,735 cases and 5,278 controls) that pertained to the 48 bp variable number tandem repeat (VNTR) polymorphism, nine articles (1,517 cases and 1,746 controls) that corresponded to the 12 bp tandem repeat (TR), six articles (1,912 cases and 1,836 controls) that addressed the 120 bp TR, 10 articles (2,927 cases and 2,938 controls) that entailed the -521 C>T polymorphism, six articles (1,735 cases and 1,724 controls) that pertained to the -616 C>G polymorphism, and four articles (1,191 cases and 1,215 controls) that involved the -376 C>T polymorphism. Pooled analysis, subgroup analysis, and sensitivity analysis were performed, and the data were visualized by means of forest and funnel plots. Results of pooled analysis indicated that the -521 CC variant ( P z =0.009, odds ratio [OR] =1.218, 95% confidence interval [CI] =1.050-1.413) and genotype L/L (ie, long allele) of the 120 bp TR were risk factors of schizophrenia ( P z =0.004, OR =1.275, 95% CI =1.081-1.504). The 48 bp VNTR, the 12 bp TR, the -616 C>G polymorphism, and the -376 C>T polymorphism were not associated with schizophrenia. Additional research is warranted to explore the association between polymorphisms of DRD4 and schizophrenia risk.

Association of Gene Polymorphisms in Interleukin 6 in Infantile Bronchial Asthma.

PubMed

Babusikova, Eva; Jurecekova, Jana; Jesenak, Milos; Evinova, Andrea

2017-07-01

The genetic background of bronchial asthma is complex, and it is likely that multiple genes contribute to its development both directly and through gene-gene interactions. Cytokines contribute to different aspects of asthma, as they determine the type, severity and outcomes of asthma pathogenesis. Allergic asthmatics undergoing an asthmatic attack exhibit significantly higher levels of pro-inflammatory cytokines, such as interleukins and chemokines. In recent years, cytokines and their receptors have been shown to be highly polymorphic, and this prompted us to investigate interleukin 6 promoter polymorphisms at position -174G/C (rs1800795) and at -572G/C (rs1800796) in relation to asthma in children. Interleukin 6 promoter polymorphisms were analyzed in bronchial asthma patients and healthy children using polymerase chain reaction-restriction fragment length polymorphism analysis. We observed a significant association between polymorphism at -174G/C and bronchial asthma (OR=3.4, 95% CI: 2.045-5.638, P<.001). Higher associations between polymorphism at IL-6 -174G/C and bronchial asthma were observed in atopic patients (OR=4.1, 95% CI: 2.308-7.280, P<8.10 -7 ). Interleukin 6 polymorphism is associated with bronchial asthma, particularly its atopic phenotype. Expression and secretion of interleukins in asthmatic patients may be affected by genetic polymorphisms, and could have a disease-modifying effect in the asthmatic airway and modify the therapeutic response. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Association study of interleukin-4 polymorphisms with paranoid schizophrenia in the Polish population: a critical approach.

PubMed

Fila-Danilow, Anna; Kucia, Krzysztof; Kowalczyk, Malgorzata; Owczarek, Aleksander; Paul-Samojedny, Monika; Borkowska, Paulina; Suchanek, Renata; Kowalski, Jan

2012-08-01

Changes in immunological system are one of dysfunctions reported in schizophrenia. Some changes based on an imbalance between Th1 and Th2 cytokines results from cytokine gene polymorphisms. Interleukin-4 gene (IL4) is considered as a potential candidate gene in schizophrenia association studies. The aim of the current case-control study was to examine whether the -590C/T (rs2243250) and -33C/T (rs2070874) IL4 gene polymorphisms are implicated in paranoid schizophrenia development in the Polish population. Genotyping of polymorphisms was performed by using PCR-RFLP technique. The genotypes and alleles distribution of both SNPs were analysed in patients (n = 182) and healthy individuals constituted the control group (n = 215). The connection between some clinical variables and studied polymorphisms has been examined as well. We did not revealed any association between the -590C/T and -33C/T polymorphisms and paranoid schizophrenia. In case of both SNPs the homozygous TT genotype was extremely rare. Both polymorphic sites of the IL4 gene were found to be in a very strong linkage disequilibrium. However we did not identify a haplotype predispose to paranoid schizophrenia. No associations were also observed between the clinical course and psychopathology of the disease and the genotypes of both analysed polymorphisms. Our results suggest that the polymorphisms -590C/T in IL4 gene promoter region and -33C/T in the 5'-UTR are not involved in the pathophysiology of paranoid schizophrenia in Polish residents.

Antioxidant-related gene polymorphisms associated with the cardio-ankle vascular index in young Russians.

PubMed

Sorokin, Alexander V; Kotani, Kazuhiko; Bushueva, Olga Y; Polonikov, Alexey V

2016-04-01

The cardio-ankle vascular index is a measure of arterial stiffness, whereas oxidative stress underlies arterial pathology. This study aimed to investigate the association between the cardio-ankle vascular index and antioxidant-related gene polymorphisms in young Russians. A total of 89 patients (mean age, 21.6 years) were examined by the cardio-ankle vascular index and for 15 gene polymorphisms related to antioxidant enzymes including FMO3 (flavin-containing monooxygenase 3), GPX1 (glutathione peroxidase 1), and GPX4 (glutathione peroxidase 4). A higher cardio-ankle vascular index level was detected in carriers with the KK-genotype of FMO3 polymorphism rs2266782 than in those without (mean levels: 6.2 versus 5.6, respectively, p<0.05). Similarly, a higher cardio-ankle vascular index level was seen in carriers with the CC-genotype of GPX4 polymorphism rs713041 than in those without (6.0 versus 5.5, respectively, p<0.05). We did not observe significant associations between the cardio-ankle vascular index levels and the other gene polymorphisms. Although carriers with the LL-genotype of GPX1 polymorphism rs1050450 showed a higher diastolic blood pressure level than those without, the polymorphism did not affect the cardio-ankle vascular index level. This study showed a significant association between rs2266782 and rs713041 polymorphisms and arterial stiffness, as measured by the cardio-ankle vascular index, in young Russians. The pathways utilised by antioxidant enzymes may be responsible for early arterial stiffening in the Russian population.

Association between norepinephrine transporter gene (SLC6A2) polymorphisms and suicide in patients with major depressive disorder.

PubMed

Kim, Yong-Ku; Hwang, Jung-A; Lee, Heon-Jeong; Yoon, Ho-Kyoung; Ko, Young-Hoon; Lee, Bun-Hee; Jung, Han-Yong; Hahn, Sang-Woo; Na, Kyoung-Sae

2014-04-01

Although several studies have investigated possible associations between norepinephrine neurotransmitter transporter gene (SLC6A2) polymorphisms and depression, few studies have examined associations between SLC6A2 polymorphisms and suicide. Three single-nucleotide polymorphisms (rs2242446, rs28386840, and rs5569) were measured in 550 patients: 201 with major depressive disorder (MDD) and suicide attempt/s, 160 with MDD without suicide attempts, and 189 healthy controls. Analysis of single-nucleotide polymorphisms (SNPs) and haplotype was conducted for the three groups. Subsequently, multivariate logistic regression analysis adjusting for age and gender was conducted to identify independent influences of each SNP. A possible association between suicide lethality and SLC6A2 polymorphisms was also investigated. In the genotype and allele frequency analysis, there were significant differences in rs28386840 between suicidal MDD patients and healthy controls. In the haplotype analysis, TAA (rs2242446-rs28386840-rs5569, from left to right) was associated with suicide attempts in MDD, although the significance (p=0.043) disappeared after Bonferroni correction. There were no relationships between lethality scores and SLC6A2 polymorphisms in suicidal MDD. Modest sample size and a single type of neurotransmitter analyzed (norepinephrine) are the primary limitations. Our results suggest that SLC6A2 polymorphisms were associated with suicide risk in patients with MDD. Future studies are warranted to elucidate possible mechanisms by which SLC6A2 polymorphisms influence suicide risk. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility

DOE Office of Scientific and Technical Information (OSTI.GOV)

White, Tommy E.; Brandariz-Nuñez, Alberto; Valle-Casuso, Jose Carlos

SAMHD1 is a human restriction factor that prevents efficient infection of macrophages, dendritic cells and resting CD4+ T cells by HIV-1. Here we explored the antiviral activity and biochemical properties of human SAMHD1 polymorphisms. Our studies focused on human SAMHD1 polymorphisms that were previously identified as evolving under positive selection for rapid amino acid replacement during primate speciation. The different human SAMHD1 polymorphisms were tested for their ability to block HIV-1, HIV-2 and equine infectious anemia virus (EIAV). All studied SAMHD1 variants block HIV-1, HIV-2 and EIAV infection when compared to wild type. We found that these variants did notmore » lose their ability to oligomerize or to bind RNA. Furthermore, all tested variants were susceptible to degradation by Vpx, and localized to the nuclear compartment. We tested the ability of human SAMHD1 polymorphisms to decrease the dNTP cellular levels. In agreement, none of the different SAMHD1 variants lost their ability to reduce cellular levels of dNTPs. Finally, we found that none of the tested human SAMHD1 polymorphisms affected the ability of the protein to block LINE-1 retrotransposition. - Highlights: • Human SAMHD1 single-nucleotide polymorphisms block HIV-1 and HIV-2 infection. • SAMHD1 polymorphisms do not affect its ability to block LINE-1 retrotransposition. • SAMHD1 polymorphisms decrease the cellular levels of dNTPs.« less

Endometriosis and RAS system gene polymorphisms: the association of ACE A2350G polymorphism with endometriosis in Polish individuals.

PubMed

Kowalczyńska, Liliana J; Ferenc, Tomasz; Wojciechowski, Michał; Mordalska, Anna; Pogoda, Krzysztof; Malinowski, Andrzej

2014-05-01

To analyze the polymorphisms of angiotensin I converting enzyme (ACE) gene (insertion/deletion [I/D], A2350G) and angiotensin II type 1 receptor gene (A1166C) in women with endometriosis and to determine the correlation of the identified genotypes with the severity of the disease. Additionally, to estimate the prognostic value of the polymorphisms in patients with endometriosis treated due to infertility. The study group included 241 women, the control group (without endometriosis)-127. The molecular analysis was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism technique. For I/D ACE and A1166C AT1 polymorphisms no significant differences were observed between the study and control groups and between the severity grades of the disease (p>0.05). For A2350G ACE polymorphism the frequency of genotypes for the study and control groups respectively was the following: AA-31.54%, AG-54.36%, GG-14.11% and AA-55.12%, AG-36.22%, GG-8.66% (x(2)=19.36, p<0.0001). Statistically significant differences were found between the frequency of A and G alleles between both groups (x(2)=15.16, p=0.0001), but not when individual grades of the disease severity were compared. There was no association between the investigated polymorphisms and the effect of infertility treatment. A2350G polymorphism (allele G, AG genotype) of ACE gene seems to be associated with the development of endometriosis.

Sexual selection and genetic colour polymorphisms in animals.

PubMed

Wellenreuther, Maren; Svensson, Erik I; Hansson, Bengt

2014-11-01

Genetic colour polymorphisms are widespread across animals and often subjected to complex selection regimes. Traditionally, colour morphs were used as simple visual markers to measure allele frequency changes in nature, selection, population divergence and speciation. With advances in sequencing technology and analysis methods, several model systems are emerging where the molecular targets of selection are being described. Here, we discuss recent studies on the genetics of sexually selected colour polymorphisms, aiming at (i) reviewing the evidence of sexual selection on colour polymorphisms, (ii) highlighting the genetic architecture, molecular and developmental basis underlying phenotypic colour diversification and (iii) discuss how the maintenance of such polymorphisms might be facilitated or constrained by these. Studies of the genetic architecture of colour polymorphism point towards the importance of tight clustering of colour loci with other trait loci, such as in the case of inversions and supergene structures. Other interesting findings include linkage between colour loci and mate preferences or sex determination, and the role of introgression and regulatory variation in fuelling polymorphisms. We highlight that more studies are needed that explicitly integrate fitness consequences of sexual selection on colour with the underlying molecular targets of colour to gain insights into the evolutionary consequences of sexual selection on polymorphism maintenance. © 2014 John Wiley & Sons Ltd.

Regulatory considerations of pharmaceutical solid polymorphism in Abbreviated New Drug Applications (ANDAs).

PubMed

Raw, Andre S; Furness, M Scott; Gill, Devinder S; Adams, Richard C; Holcombe, Frank O; Yu, Lawrence X

2004-02-23

A sponsor of an Abbreviated New Drug Application (ANDA) must have information to show that the proposed generic product and the innovator product are both pharmaceutically equivalent and bioequivalent, and therefore, therapeutically equivalent. Many pharmaceutical solids exist in several crystalline forms and thus exhibit polymorphism. Polymorphism may result in differences in the physico-chemical properties of the active ingredient and variations in these properties may render a generic drug product to be bioinequivalent to the innovator brand. For this reason, in ANDAs, careful attention is paid to the effect of polymorphism in the context of generic drug product equivalency. This review discusses the impact of polymorphism on drug product manufacturability, quality, and performance. Conclusions from this analysis demonstrate that pharmaceutical solid polymorphism has no relevance to the determination of drug substance "sameness" in ANDAs. Three decision trees for solid oral dosage forms or liquid suspensions are provided for evaluating when and how polymorphs of drug substances should be monitored and controlled in ANDA submissions. Case studies from ANDAs are provided which demonstrate the irrelevance of polymorphism to the determination of drug substance "sameness". These case studies also illustrate the conceptual framework from these decision trees and illustrate how their general principles are sufficient to assure both the quality and the therapeutic equivalence of marketed generic drug products.

Intergenic Variable-Number Tandem-Repeat Polymorphism Upstream of rocA Alters Toxin Production and Enhances Virulence in Streptococcus pyogenes.

PubMed

Zhu, Luchang; Olsen, Randall J; Horstmann, Nicola; Shelburne, Samuel A; Fan, Jia; Hu, Ye; Musser, James M

2016-07-01

Variable-number tandem-repeat (VNTR) polymorphisms are ubiquitous in bacteria. However, only a small fraction of them has been functionally studied. Here, we report an intergenic VNTR polymorphism that confers an altered level of toxin production and increased virulence in Streptococcus pyogenes The nature of the polymorphism is a one-unit deletion in a three-tandem-repeat locus upstream of the rocA gene encoding a sensor kinase. S. pyogenes strains with this type of polymorphism cause human infection and produce significantly larger amounts of the secreted cytotoxins S. pyogenes NADase (SPN) and streptolysin O (SLO). Using isogenic mutant strains, we demonstrate that deleting one or more units of the tandem repeats abolished RocA production, reduced CovR phosphorylation, derepressed multiple CovR-regulated virulence factors (such as SPN and SLO), and increased virulence in a mouse model of necrotizing fasciitis. The phenotypic effect of the VNTR polymorphism was nearly the same as that of inactivating the rocA gene. In summary, we identified and characterized an intergenic VNTR polymorphism in S. pyogenes that affects toxin production and virulence. These new findings enhance understanding of rocA biology and the function of VNTR polymorphisms in S. pyogenes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The BIM deletion polymorphism: A paradigm of a permissive interaction between germline and acquired TKI resistance factors in chronic myeloid leukemia.

PubMed

Ko, Tun Kiat; Chin, Hui San; Chuah, Charles T H; Huang, John W J; Ng, King-Pan; Khaw, Seong Lin; Huang, David C S; Ong, S Tiong

2016-01-19

Both germline polymorphisms and tumor-specific genetic alterations can determine the response of a cancer to a given therapy. We previously reported a germline deletion polymorphism in the BIM gene that was sufficient to mediate intrinsic resistance to tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML), as well as other cancers [1]. The deletion polymorphism favored the generation of BIM splice forms lacking the pro-apoptotic BH3 domain, conferring a relative resistance to the TKI imatinib (IM). However, CML patients with the BIM deletion polymorphism developed both partial and complete IM resistance. To understand the mechanisms underlying the latter, we grew CML cells either with or without the BIM deletion polymorphism in increasing IM concentrations. Under these conditions, the BIM deletion polymorphism enhanced the emergence of populations with complete IM resistance, mimicking the situation in patients. Importantly, the combined use of TKIs with the BH3 mimetic ABT-737 overcame the BCR-ABL1-dependent and -independent resistance mechanisms found in these cells. Our results illustrate the interplay between germline and acquired genetic factors in confering TKI resistance, and suggest a therapeutic strategy for patients with complete TKI resistance associated with the BIM deletion polymorphism.

A meta-analysis of eNOS and ACE gene polymorphisms and risk of pre-eclampsia in women.

PubMed

Shaik, A P; Sultana, A; Bammidi, V K; Sampathirao, K; Jamil, K

2011-10-01

A meta-analyses of endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) gene polymorphisms in pre-eclampsia was performed. We shortlisted 33 studies (17 for ACE; 16 for eNOS gene polymorphisms), of which 29 articles (16 for ACE and 15 for eNOS) were analysed. Overall, 1,620 cases with pre-eclampsia and 2,158 controls were analysed for intron 16 insertion-deletion polymorphism in ACE gene. A total of 1,610 subjects with pre-eclampsia and 2,875 controls were analysed for the Glu298Asp in eNOS gene. Overall, the random-effects odds ratio (OR) with Glu298Asp in eNOS gene was 0.958 (95% confidence intervals, CI 0.747-1.228, p > 0.05), and for the insertion-deletion/ACE polymorphism was 0.987 (95% CI 0.698-1.395, p > 0.05). Significant heterogeneity was observed in the studies that evaluated polymorphisms in ACE (Q value = 55.6; I(2) = 73; p value = 0.000); and eNOS (Q value = 37.2; I(2) = 62.4; p value = 0.001) polymorphisms. No significant risk of pre-eclampsia was observed in both eNOS and ACE genes with these polymorphisms.

Do estrogen receptor alpha polymorphisms have any impact on the outcome in an ART program?

PubMed

Anagnostou, Elli; Malamas, Fotodotis; Mavrogianni, Despina; Dinopoulou, Vasiliki; Drakakis, Peter; Kallianidis, Konstantinos; Loutradis, Dimitris

2013-04-01

To investigate two of the most studied estrogen receptor alpha polymorphisms (PvuII and XbaI) in combination, in order to evaluate their impact on an ART program outcome. 203 normally ovulating women who underwent IVF or ICSI treatment were genotyped for PvuII and XbaI polymorphisms in ESR1 intron 1 using Real-Time PCR. The relationship between the presence of polymorphic alleles and the ovulation induction parameters and outcome was examined. Women were grouped according to the number of polymorphic alleles they carried in two groups (0-2 versus 3-4 polymorphic alleles). The presence of 3 or more polymorphic alleles was associated with significantly lower E2 levels on the day of hCG administration and a significantly lower rate of good quality embryos. There is an association between ESR1 polymorphisms and some ART parameters such as the level of E2 on the day of hCG administration and the quality of the embryos. These results underline the importance of ESR1 as a candidate gene for the prediction of ovarian response to IVF/ICSI protocols. Future research work concerning several more genes is necessary for a better evaluation of patients before entering an IVF/ICSI program.

Functional polymorphisms in the sigma1 receptor gene associated with alcoholism.

PubMed

Miyatake, Ryosuke; Furukawa, Aizo; Matsushita, Sachio; Higuchi, Susumu; Suwaki, Hiroshi

2004-01-01

Sigma1 receptors are involved in the pathogenesis of drug abuse. Two polymorphisms (GC-241-240TT and Gln2Pro) in the sigma1 receptor gene (SIGMAR1) have been identified. To investigate the role of SIGMAR1 in conveying susceptibility to alcoholism, we performed a functional analysis of polymorphisms in the SIGMAR1 and a case-control study. We initially screened for polymorphisms in the 5'-upstream region. The effects of the polymorphisms on transcriptional activity were determined using a gene reporter assay. The distribution of SIGMAR1 polymorphisms was analyzed in 307 alcoholic and 302 control subjects. A novel T-485A polymorphism was identified. The transcriptional activity of the A-485 allele and the TT-241-240 allele was significantly reduced compared with that of the T-485 allele and the GC-241-240 allele. The frequencies of the A-485 allele (chi2=5.575, df=1, p=.0205) and the TT-241-240/Pro2 haplotype (chi2=21.464, df=1, p<.0001) were significantly higher in control subjects compared with alcoholic subjects. The T-485A and the GC-241-240TT may be functional polymorphisms, and the A-485 allele and TT-241-240/Pro2 haplotype are possible protective factors for the development of alcoholism.

Polymorphic Protein Crystal Growth: Influence of Hydration and Ions in Glucose Isomerase

PubMed Central

Gillespie, C. M.; Asthagiri, D.; Lenhoff, A. M.

2014-01-01

Crystal polymorphs of glucose isomerase were examined to characterize the properties and to quantify the energetics of protein crystal growth. Transitions of polymorph stability were measured in poly(ethylene glycol)/NaCl solutions, and one transition point was singled out for more detailed quantitative analysis. Single crystal x-ray diffraction was used to confirm space groups and identify complementary crystal structures. Crystal polymorph stability was found to depend on the NaCl concentration, with stability transitions requiring > 1 M NaCl combined with a low concentration of PEG. Both salting-in and salting-out behavior was observed and was found to differ for the two polymorphs. For NaCl concentrations above the observed polymorph transition, the increase in solubility of the less stable polymorph together with an increase in the osmotic second virial coefficient suggests that changes in protein hydration upon addition of salt may explain the experimental trends. A combination of atomistic and continuum models was employed to dissect this behavior. Molecular dynamics simulations of the solvent environment were interpreted using quasi-chemical theory to understand changes in protein hydration as a function of NaCl concentration. The results suggest that protein surface hydration and Na+ binding may introduce steric barriers to contact formation, resulting in polymorph selection. PMID:24955067

Synthesis, characterization, crystal structure and DFT study of two new polymorphs of a Schiff base (E)-2-((2,6-dichlorobenzylidene)amino)benzonitrile

NASA Astrophysics Data System (ADS)

Benarous, N.; Cherouana, A.; Aubert, Emmanuel; Durand, Pierrick; Dahaoui, S.

2016-02-01

Two new polymorphs of Schiff base, (E)-2-((2,6-dichlorobenzylidene)amino)benzonitrile, were prepared from the condensation of 4-amino-benzonitrile and 2,6-dichlorobenzaldehyde. The two polymorphs crystallize in two different space groups: P21/c for polymorph (I) with volume 1264.23(2) Å3 and Pbca for polymorph (II) with volume 2469.3(2) Å3. The two polymorphs have been characterized by FT-IR and UV-VIS spectroscopy. The crystal structures of both compounds were determined by single X-ray analysis. The difference between the two polymorphs was observed at the angle between the two phenyl rings which is 4.81° for the first one and 82.27° for the second one. Both crystal structures are built on the basis of moderate and weak hydrogen bonds. Theoretical calculations on isolated molecules at the MP2 cc-pVDZ level show that the two polymorphs correspond to two molecular conformations that are within less than 1 kJ mol-1 and DFT periodic calculations indicate that (II) is more stable than (I) by 4.1 kJ mol-1 of formula unit. Additionally, we performed TD-DFT calculation for free ligands to support the experimental data.

The Joint Effects of Body Mass Index and MAOA Gene Polymorphism on Depressive Symptoms.

PubMed

Liu, Yangyang

2015-07-01

The objective of the present study was to examine the joint effects of the body mass index and the MAOA gene polymorphism on depressive symptoms. In two independent Chinese samples, we measured adolescents' depressive symptoms and body mass index and collected their DNA. The results indicated that the main effects of the MAOA gene polymorphism on depressive symptoms were significant. However, the main effects of body mass index and the interaction of the MAOA gene polymorphism and body mass index on depressive symptoms were not significant. By using Chinese adolescents, this study confirmed that the MAOA gene polymorphism directly influenced adolescents' depressive symptoms.

Restriction fragment length polymorphism among Israeli Holstein-Friesian dairy bulls.

PubMed

Beckmann, J S; Kashi, Y; Hallerman, E M; Nave, A; Soller, M

1986-01-01

Israeli Holstein-Friesian dairy bulls were screened for restriction fragment length polymorphisms by hybridizing cloned DNA probes for bovine growth hormone, for chymosin, and for rat muscle beta-actin to restriction endonuclease-digested DNA immobilized on nitrocellulose filters. The population proved to be polymorphic at the growth hormone locus, with evidence consistent with the phenotypes being inherited in allelic fashion. A low level of polymorphism was also observed at one of the beta-actin gene family loci. The chymosin locus was monomorphic with the restriction enzymes utilized. The results illustrate the power of restriction fragment length polymorphism methodology in visualizing genetic variability in dairy cattle populations.

[Single nucleotide polymorphism and its application in allogeneic hematopoietic stem cell transplantation--review].

PubMed

Li, Su-Xia

2004-12-01

Single nucleotide polymorphism (SNP) is the third genetic marker after restriction fragment length polymorphism (RFLP) and short tandem repeat. It represents the most density genetic variability in the human genome and has been widely used in gene location, cloning, and research of heredity variation, as well as parenthood identification in forensic medicine. As steady heredity polymorphism, single nucleotide polymorphism is becoming the focus of attention in monitoring chimerism and minimal residual disease in the patients after allogeneic hematopoietic stem cell transplantation. The article reviews SNP heredity characterization, analysis techniques and its applications in allogeneic stem cell transplantation and other fields.

Glutathione S-transferase gene polymorphisms (GSTM1, GSTT1, and GSTP1) in Egyptian pediatric patients with sickle cell disease.

PubMed

Shiba, Hala Fathy; El-Ghamrawy, Mona Kamal; Shaheen, Iman Abd El-Mohsen; Ali, Rasha Abd El-Ghani; Mousa, Somaia Mohammed

2014-01-01

Sickle cell disease (SCD) complications are associated with oxidative stress. Glutathione S-transferases (GSTs) are a group of enzymes that protect against oxidative stress. The aims of this study was to evaluate the prevalence of GSTM1, GSTT1, and GSTP1 gene polymorphisms among homozygous sickle cell anemia patients and to investigate the possible association between the presence of these polymorphisms and SCD severity and complications. Genotyping the polymorphisms in GSTT1 and GSTM1 genes was performed using the multiplex polymerase chain reaction (PCR) method. The GSTP1 ILe105Val polymorphism was determined using PCR-restriction fragment length polymorphism. GSTM1 null genotype was significantly associated with increased risk of severe vaso-occlusive crises (VOC) (odds ratio  =  1.52, 95% confidence interval  =  0.42-5.56, P  =  0.005). We found no significant association between GST genotypes and frequency of sickle cell-related pain, transfusion frequency, disease severity, or hydroxyurea treatment. GSTM1 gene polymorphism may be associated with risk of severe VOC among Egyptian SCD patients.

Theoretical investigation of the breakdown electric field of SiC polymorphs

NASA Astrophysics Data System (ADS)

Yamaguchi, Kikou; Kobayashi, Daisuke; Yamamoto, Tomoyuki; Hirose, Kazuyuki

2018-03-01

The breakdown electric field of several SiC polymorphs has been investigated theoretically using a concept of "recovery rate," which is obtained by first principles calculations. A good relationship between the experimental breakdown electric fields and the calculated recovery rate of 4H-, 6H-, and 3C-SiC was obtained. In order to examine the stability of SiC polymorphs, the total electronic energies of various types of SiC crystal structures were calculated. Here, two candidates of polymorphs-GeS-type- and 2H-SiC-with energies comparable to those of experimentally well-established structures, have been obtained. The breakdown electric fields of these two polymorphs were estimated using a relationship obtained from the results of 4H-, 6H-, and 3C-SiC. This indicates that one of these polymorphs, GeS-type-SiC, has higher breakdown electric field than any other SiC polymorphs. In addition to the investigation with the recovery rate, relationship between experimental breakdown electric field and calculated band gap with recently developed accurate electron-correlation potential has been also discussed.

Gene analysis of steroid 5 alpha-reductase 1 in hyperandrogenic women.

PubMed

Eminović, Izet; Komel, Radovan; Prezelj, Janez; Karamehić, Jasenko; Gavrankapetanović, Faris; Heljić, Becir

2005-08-01

To examine the gene encoding for 5alpha-reductase type 1 in hyperandrogenic women, and assess the association of its eventual mutations or polymorphisms with the development of the hyperandrogenic female pattern. Sixteen hyperandrogenic women were included in the study. Single-stranded conformation polymorphism analysis (SSCP) and DNA sequencing were performed after polymerase chain reaction amplification of each of the 5 exons of the SRD5A1 gene in both hyperandrogenic and control group (16 participants). Sequence analysis identified the existence of many polymorphisms; in codon 24 of exon 1, GGC (Gly) into GAC (Asp); in codon 30 of exon 1, CGG (Arg) into CGC (Arg); in exon 3 codon 169, ACA to ACG (both encoding for threonine); in exon 5, AGA to AGG (both encoding for arginine, codon 260); and T/C polymorphism in intron 2. Polymorphisms were found in both groups. Polymorphisms of SRD5A1 gene were the same in both hyperandrogenic and healthy women, indicating no significant associations of genetic polymorphisms/variations of SRD5A1 gene with clinical manifestations of hyperandrogenic disorders in women.

Contribution of NKX2-3 Polymorphisms to Inflammatory Bowel Diseases: A Meta-Analysis of 35358 subjects

PubMed Central

Lu, XiaoCheng; Tang, Linjun; Li, Kai; Zheng, JinYu; Zhao, Penglai; Tao, Yi; Li, Li-Xin

2014-01-01

Polymorphisms in NKX2-3 gene have been inconsistently associated with Crohn's disease (CD) and ulcerative colitis (UC). To generate large-scale evidence on whether NKX2-3 polymorphisms are associated with CD or UC susceptibility we have conducted a meta-analysis of 17 studies involving 17329 patients and 18029 controls. A significantly increased CD or UC risk was observed in persons carrying a G allele at rs10883365 polymorphism (A/G) compared with those with a A allele. (OR = 1.226, 95%CI: 1.177–1.277 and OR = 1.274, 95%CI: 1.175–1.382 respectively). In the subgroup analysis, a significantly increased CD risk was found in both Europeans and Asians. For rs11190140 polymorphism (C/T) and CD risk, the risk estimate for the allele contrast was OR = 1.201 (1.136–1.269). This meta-analysis provided a robust result that persons with a G or T allele may have a moderately increased risk of CD, and suggested that rs10883365 polymorphism was also a candidate gene polymorphism for UC susceptibility. PMID:24473197

Subunit composition and structure of subcomponent C1q of the first component of human complement.

PubMed

Reid, K B; Porter, R R

1976-04-01

1. Unreduced human subcomponent C1q was shown by electrophoresis on polyacrylamide gels run in the presence of sodium dodecyl sulphate to be composed of two types of non-covalently linked subunits of apparent mol.wts. 69 000 and 54 000. The ratio of the two subunits was markedly affected by the ionic strength of the applied sample. At a low ionic strength of applied sample, which gave the optimum value for the 54 000-apparent mol.wt. subunit, a ratio of 1.99:1.00 was obtained for the ratio of the 69 000-apparent mol.wt. subunit to the 5400-apparent-mol.wt. subunit. The amount of the 54 000-apparent-mol.wt. subunit detected in the expected position on the gel was found to be inversely proportional to increases in the ionic strength of the applled sample. 2. Human subcomponent C1q on reduction and alkylation, or oxidation, yields equimolar amounts of three chains designated A, B and C [Reid et al. (1972) Biochem. J. 130, 749-763]. The results obtained by Yonemasu & Stroud [(1972) Immunochemistry 9, 545-554], which showed that the 69 000-apparent-mol.wt. subunit was a disulphide-linked dimer of the A and B chains and that the 54 000-apparent-mol.wt. subunit was a disulphide-linked dimer of the C chain, were confirmed. 3. Gel filtration on Sephadex G-200 in 6.0M-guanidinium chloride showed that both types of unreduced subunit were eluted together as a single symmetrical peak of apparent mol.wt. 49 000-50 000 when globular proteins were used as markers. The molecular weights of the oxidized or reduced A, B and C chains have been shown previously to be very similar all being in the range 23 000-24 000 [Reid et al. (1972) Biochem. J. 130, 749-763; Reid (1974) Biochem. J. 141, 189-203]. 4. It is proposed that subcomponent C1q (mol.wt. 410000) is composed of nine non-covalently linked subunits, i.e. six A-B dimers and three C-C dimers. 5. A structure for subcomponent C1q is proposed and is based on the assumption that the collagen-like regions of 78 residues in each of the A, B and C chains are combined to form a triple-helical structure of the same type as is found in collagens.

Folate and Breast Cancer: Role of Intake, Blood Levels, and Metabolic Gene Polymorphisms

DTIC Science & Technology

2006-06-01

polymorphisms . The specific aims are 1) methodological training in the analysis of gene - gene and gene -environment interactions by studying folate...evaluation of folate intake, plasma folate, and metabolic gene polymorphisms in relation to breast cancer risk: Months 1-19. b. Prepare blood samples...isolated for the folate and gene polymorphism assays among the 184 cases and matched controls. The folate assays are on-going at this time and over

Inaccurate Color Discrimination by Pollinators Promotes Evolution of Discrete Color Polymorphism in Food-Deceptive Flowers.

PubMed

Kagawa, Kotaro; Takimoto, Gaku

2016-02-01

Many plant species employing a food-deceptive pollination strategy show discrete or continuous floral polymorphism within their populations. Previous studies have suggested that negative frequency-dependent selection (NFDS) caused by the learning behavior of pollinators was responsible for the maintenance of floral polymorphism. However, NFDS alone does not explain why and when discrete or continuous polymorphism evolves. In this study, we use an evolutionary simulation model to propose that inaccurate discrimination of flower colors by pollinators results in evolution of discrete flower color polymorphism. Simulations showed that associative learning based on inaccurate discrimination in pollinators caused disruptive selection of flower colors. The degree of inaccuracy determined the number of discrete flower colors that evolved. Our results suggest that animal behavior based on inaccurate discrimination may be a general cause of disruptive selection that promotes discrete trait polymorphism.

Molecular Identification of Date Palm Cultivars Using Random Amplified Polymorphic DNA (RAPD) Markers.

PubMed

Al-Khalifah, Nasser S; Shanavaskhan, A E

2017-01-01

Ambiguity in the total number of date palm cultivars across the world is pointing toward the necessity for an enumerative study using standard morphological and molecular markers. Among molecular markers, DNA markers are more suitable and ubiquitous to most applications. They are highly polymorphic in nature, frequently occurring in genomes, easy to access, and highly reproducible. Various molecular markers such as restriction fragment length polymorphism (RFLP), amplified fragment length polymorphism (AFLP), simple sequence repeats (SSR), inter-simple sequence repeats (ISSR), and random amplified polymorphic DNA (RAPD) markers have been successfully used as efficient tools for analysis of genetic variation in date palm. This chapter explains a stepwise protocol for extracting total genomic DNA from date palm leaves. A user-friendly protocol for RAPD analysis and a table showing the primers used in different molecular techniques that produce polymorphisms in date palm are also provided.

[CCR5, CCR2, apoe, p53, ITGB3 and HFE gene polymorphism in Western Siberia long-livers].

PubMed

Ivanoshchuk, D E; Mikhaĭlova, S V; Kulikov, I V; Maksimov, V N; Voevoda, M I; Romashchenko, A G

2012-01-01

In order to estimate the distribution of some polymorphisms for the CCR5, CCR2, apoE, p53, ITGB3, and HFE genes in Russian long-livers from Western Siberia, a sample of 271 individuals (range 90-105 years) was examined. It was demonstrated that carriage of the delta32 polymorphism for the CCR5 gene, V64/polymorphism for the CCR2 gene, e2/e3/e4 for the apoE gene, L33P for the ITGB3 gene, as well as H63D and S65C polymorphisms for the HFE gene does not influence on predisposition to the longevity; carriage of the 282 Y allele for the HFE gene negatively influences on the longevity; carriage of the heterozygous genotype for the R72P polymorphism for the p53 gene correlates with the longevity of elderly people.

Binary polymorphic cocrystals: an update on the available literature in the Cambridge Structural Database, including a new polymorph of the pharmaceutical 1:1 cocrystal theophylline-3,4-dihydroxybenzoic acid.

PubMed

Mnguni, Malitsatsi J; Michael, Joseph P; Lemmerer, Andreas

2018-06-01

An analysis and classification of the 2925 neutral binary organic cocrystals in the Cambridge Structural Database is reported, focusing specifically on those both showing polymorphism and containing an active pharmaceutical ingredient (API). The search was confined to molecules having only C, H, N, O, S and halogens atoms. It was found that 400 out of 2925 cocrystals can be classified as pharmaceutical cocrystals, containing at least one API, and that of those, 56 can be classified as being polymorphic cocrystals. In general, the total number of polymorphic cocrystal systems of any type stands at 125. In addition, a new polymorph of the pharmaceutical cocrystal theophylline-3,4-dihydroxybenzoic acid (1/1), C 7 H 8 N 4 O 2 ·C 7 H 6 O 4 , is reported.

The relationship of polymorphisms in ABCC2 and SLCO1B3 with docetaxel pharmacokinetics and neutropenia: CALGB 60805 (Alliance).

PubMed

Lewis, Lionel D; Miller, Antonius A; Owzar, Kouros; Bies, Robert R; Markova, Svetlana; Jiang, Chen; Kroetz, Deanna L; Egorin, Merrill J; McLeod, Howard L; Ratain, Mark J

2013-01-01

Docetaxel-related neutropenia was associated with polymorphisms in the drug transporters ABCC2 and SLCO1B3 in Japanese cancer patients. We hypothesized that this association is because of reduced docetaxel clearance, associated with polymorphisms in those genes. We studied 64 US cancer patients who received a single cycle of 75 mg/m of docetaxel monotherapy. We found that the ABCC2 polymorphism at rs-12762549 trended to show a relationship with reduced docetaxel clearance (P=0.048), but not with neutropenia. There was no significant association of the SLCO1B3 polymorphisms with docetaxel clearance or neutropenia. We conclude that the relationship between docetaxel-associated neutropenia and polymorphisms in drug transporters identified in Japanese patients was not confirmed in this cohort of US cancer patients. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

SdsA polymorph isolation and improvement of their crystal quality using nonconventional crystallization techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

De la Mora, Eugenio; Flores-Hernández, Edith; Jakoncic, Jean

SdsA, a sodium dodecyl sulfate hydrolase, from Pseudomonas aeruginosa was crystallized in three different crystal polymorphs and their three-dimensional structure was determined. The different polymorphs present different crystal packing habits. One of the polymorphs suggests the existence of a tetramer, an oligomeric state not observed previously, while the crystal packing of the remaining two polymorphs obstructs the active site entrance but stabilizes flexible regions of the protein. Nonconventional crystallization methods that minimize convection, such as counterdiffusion in polyvinyl alcohol gel coupled with the influence of a 500 MHz (10.2 T) magnetic field, were necessary to isolate the poorest diffracting polymorphmore » and increase its internal order to determine its structure by X-ray diffraction. In conclusion, the results obtained show the effectiveness of nonconventional crystallographic methods to isolate different crystal polymorphs.« less

Association of ghrelin polymorphisms with metabolic syndrome in Han Nationality Chinese.

PubMed

Xu, Ling-Ling; Xiang, Hong-Ding; Qiu, Chang-Chun; Xu, Qun

2008-06-01

To investigate the association of ghrelin gene polymorphisms with metabolic syndrome in Han Nationality Chinese. A total of 240 patients with metabolic syndrome and 427 adults aged above forty years were recruited. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The allelic frequency of the Leu72Met polymorphism was 17.3% in the patient group and 11.9% in the control group (chi2 = 7.36, P = 0.007). Metabolic syndrome was more prevalent among carriers of the Met72 variant (43.8 vs 33.1%, age- and sex-adjusted odds ratio = 1.57, P = 0.01). No Arg51Gln variants were found in our study subjects. Rather than being associated with its individual components, Leu72Met polymorphism is associated with metabolic syndrome in the Han Nationality Chinese. Arg51Gln polymorphism is rare in the Han Nationality Chinese.

No association of the neuropeptide Y (Leu7Pro) and ghrelin gene (Arg51Gln, Leu72Met, Gln90Leu) single nucleotide polymorphisms with eating disorders.

PubMed

Kindler, Jochen; Bailer, Ursula; de Zwaan, Martina; Fuchs, Karoline; Leisch, Friedrich; Grün, Bettina; Strnad, Alexandra; Stojanovic, Mirjana; Windisch, Julia; Lennkh-Wolfsberg, Claudia; El-Giamal, Nadja; Sieghart, Werner; Kasper, Siegfried; Aschauer, Harald

2011-06-01

Genetic factors likely contribute to the biological vulnerability of eating disorders. Case-control association study on one neuropeptide Y gene (Leu7Pro) polymorphism and three ghrelin gene (Arg51Gln, Leu72Met and Gln90Leu) polymorphisms. 114 eating disorder patients (46 with anorexia nervosa, 30 with bulimia nervosa, 38 with binge eating disorder) and 164 healthy controls were genotyped. No differences were detected between patients and controls for any of the four polymorphisms in allele frequency and genotype distribution (P > 0.05). Allele frequencies and genotypes had no significant influence on body mass index (P > 0.05) in eating disorder patients. Positive findings of former case-control studies of associations between ghrelin gene polymorphisms and eating disorders could not be replicated. Neuropeptide Y gene polymorphisms have not been investigated in eating disorders before.

[Polymorphic loci and polymorphism analysis of short tandem repeats within XNP gene].

PubMed

Liu, Qi-Ji; Gong, Yao-Qin; Guo, Chen-Hong; Chen, Bing-Xi; Li, Jiang-Xia; Guo, Yi-Shou

2002-01-01

To select polymorphic short tandem repeat markers within X-linked nuclear protein (XNP) gene, genomic clones which contain XNP gene were recognized by homologous analysis with XNP cDNA. By comparing the cDNA with genomic DNA, non-exonic sequences were identified, and short tandem repeats were selected from non-exonic sequences by using BCM search Launcher. Polymorphisms of the short tandem repeats in Chinese population were evaluated by PCR amplification and PAGE. Five short tandem repeats were identified from XNP gene, two of which were polymorphic. Four and 11 alleles were observed in Chinese population for XNPSTR1 and XNPSTR4, respectively. Heterozygosities were 47% for XNPSTR1 and 70% for XNPSTR4. XNPSTR1 and XNPSTR4 localized within 3' end and intron 10, respectively. Two polymorphic short tandem repeats have been identified within XNP gene and will be useful for linkage analysis and gene diagnosis of XNP gene.

Lack of association of the two polymorphisms in alpha-2 macroglobulin with Alzheimer disease.

PubMed

Poduslo, S E; Shook, B; Drigalenko, E; Yin, X

2002-06-01

Alzheimer disease is a complex neurodegenerative disorder that is characterized by cognitive decline and distinct neuropathology. The gene for alpha-2 macroglobulin (A2M) on chromosome 12 has two polymorphisms that, in some cases, are associated with Alzheimer disease. We examined these two polymorphisms in our families in the DNA Bank (a collection of DNA samples from families with Alzheimer disease in Texas). Using both association studies and sib transmission/disequilibrium tests, we found no association of the two polymorphisms with the disease in our collection. In addition, we did not find an association of the disease with the two polymorphisms in A2M in a small subset of National Institute of Mental Health (NIMH) families. Thus, our studies do not support the A2M polymorphisms as a risk factor for Alzheimer disease. Copyright 2002 Wiley-Liss, Inc.

Identification of possible genetic polymorphisms involved in cancer cachexia: a systematic review.

PubMed

Tan, Benjamin H L; Ross, James A; Kaasa, Stein; Skorpen, Frank; Fearon, Kenneth C H

2011-04-01

Cancer cachexia is a polygenic and complex syndrome. Genetic variations in regulation of the inflammatory response, muscle and fat metabolic pathways, and pathways in appetite regulation are likely to contribute to the susceptibility or resistance to developing cancer cachexia. A systematic search of Medline and EmBase databases, covering 1986-2008 was performed for potential candidate genes/genetic polymorphisms relating to cancer cachexia. Related genes were then identified using pathway functional analysis software. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Genes with variants which had functional or clinical associations with cachexia and replicated in at least one study were entered into pathway analysis software to reveal possible network associations between genes. A total of 184 polymorphisms with functional or clinical relevance to cancer cachexia were identified in 92 candidate genes. Of these, 42 polymorphisms (in 33 genes) were replicated in more than one study with 13 polymorphisms found to influence two or more hallmarks of cachexia (i.e. inflammation, loss of fat mass and/or lean mass and reduced survival). Thirty-three genes were found to be significantly interconnected in two major networks with four genes (ADIPOQ, IL6, NFKB1 and TLR4) interlinking both networks. Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides an initial framework to select genes/polymorphisms for further study in cancer cachexia, and to develop their potential as susceptibility biomarkers of developing cachexia.

WDR1 and CLNK gene polymorphisms correlate with serum glucose and high-density lipoprotein levels in Tibetan gout patients.

PubMed

Lan, Bing; Chen, Peng; Jiri, Mutu; He, Na; Feng, Tian; Liu, Kai; Jin, Tianbo; Kang, Longli

2016-03-01

Current evidence suggests heredity and metabolic syndrome contributes to gout progression. Specifically, the WDR1 and CLNK genes may play a role in gout progression in European ancestry populations. However, no studies have focused on Chinese populations, especially Tibetan individuals. This study aims to determine whether variations in these two genes correlate with gout-related indices in Chinese-Tibetan gout patients. Eleven single-nucleotide polymorphisms in the WDR1 and CLNK genes were detected in 319 Chinese-Tibetan gout patients and 318 controls. We used one-way analysis of variance to evaluate the polymorphisms' effects on gout based on mean serum levels of metabolism indicators, such as albumin, glucose (GLU), triglycerides, cholesterol, high-density lipoproteins (HDL-C), creatinine, and uric acid, from fasting venous blood samples. All p values were Bonferroni corrected. Polymorphisms of the WDR1 and CLNK genes affected multiple risk factors for gout development. Significant differences in serum GLU levels were detected between different genotypic groups with WDRI polymorphisms rs4604059 (p = 0.005) and rs12498927 (p = 0.005). In addition, significant differences in serum HDL-C levels were detected between different genotypic groups with the CLNK polymorphism rs2041215 (p = 0.001). Polymorphisms of CLNK also affected levels of albumin, triglycerides, and creatinine. This study is the first to investigate and identify positive correlations between WDR1 and CLNK gene polymorphisms in Chinese-Tibetan populations. Our findings provide significant evidence for the effect of genetic polymorphisms on gout-related factors in Chinese-Tibetan populations.

CCL2 Serum Levels and Adiposity Are Associated with the Polymorphic Phenotypes -2518A on CCL2 and 64ILE on CCR2 in a Mexican Population with Insulin Resistance.

PubMed

Guzmán-Ornelas, Milton-Omar; Petri, Marcelo Heron; Vázquez-Del Mercado, Mónica; Chavarría-Ávila, Efraín; Corona-Meraz, Fernanda-Isadora; Ruíz-Quezada, Sandra-Luz; Madrigal-Ruíz, Perla-Monserrat; Castro-Albarrán, Jorge; Sandoval-García, Flavio; Navarro-Hernández, Rosa-Elena

2016-01-01

Genetic susceptibility has been described in insulin resistance (IR). Chemokine (C-C motif) ligand-2 (CCL2) is overexpressed in white adipose tissue and is the ligand of C-C motif receptor-2 (CCR2). The CCL2 G-2518A polymorphism is known to regulate gene expression, whereas the physiological effects of the CCR2Val64Ile polymorphism are unknown. The aim of the study is to investigate the relationship between these polymorphisms with soluble CCL2 levels (sCCL2), metabolic markers, and adiposity. In a cross-sectional study we included 380 Mexican-Mestizo individuals, classified with IR according to Stern criteria. Polymorphism was identified using PCR-RFLP/sequence-specific primers. Anthropometrics and metabolic markers were measured by routine methods and adipokines and sCCL2 by ELISA. The CCL2 polymorphism was associated with IR (polymorphic A+ phenotype frequencies were 70.9%, 82.6%, in individuals with and without IR, resp.). Phenotype carriers CCL2 (A+) displayed lower body mass and fat indexes, insulin and HOMA-IR, and higher adiponectin levels. Individuals with IR presented higher sCCL2 compared to individuals without IR and was associated with CCR2 (Ile+) phenotype. The double-polymorphic phenotype carriers (A+/Ile+) exhibited higher sCCL2 than double-wild-type phenotype carriers (A-/Ile-). The present findings suggest that sCCL2 production possibly will be associated with the adiposity and polymorphic phenotypes of CCL2 and CCR2, in Mexican-Mestizos with IR.

Unsupportive social interactions and affective states: examining associations of two oxytocin-related polymorphisms.

PubMed

McInnis, Opal A; McQuaid, Robyn J; Matheson, Kimberly; Anisman, Hymie

2017-01-01

Two single-nucleotide polymorphisms (SNPs) on oxytocin-related genes, specifically the oxytocin receptor (OXTR) rs53576 and the CD38 rs3796863 variants, have been associated with alterations in prosocial behaviors. A cross-sectional study was conducted among undergraduate students (N = 476) to examine associations between the OXTR and CD38 polymorphisms and unsupportive social interactions and mood states. Results revealed no association between perceived levels of unsupportive social interactions and the OXTR polymorphism. However, A carriers of the CD38 polymorphism, a variant previously associated with elevated oxytocin, reported greater perceived peer unsupportive interactions compared to CC carriers. As expected, perceived unsupportive interactions from peers was associated with greater negative affect, which was moderated by the CD38 polymorphism. Specifically, this relation was stronger among CC carriers of the CD38 polymorphism (a variant thought to be linked to lower oxytocin). When examining whether the OXTR polymorphism moderated the relation between unsupportive social interactions from peers and negative affect there was a trend toward significance, however, this did not withstand multiple testing corrections. These findings are consistent with the perspective that a variant on an oxytocin polymorphism that may be tied to lower oxytocin is related to poor mood outcomes in association with negative social interactions. At the same time, having a genetic constitution presumed to be associated with higher oxytocin was related to increased perceptions of unsupportive social interactions. These seemingly paradoxical findings could be related to previous reports in which variants associated with prosocial behaviors were also tied to relatively more effective coping styles to deal with challenges.

Tumor Necrosis Factor-Alpha Gene Promoter Region Polymorphism and the Risk of Coronary Heart Disease

PubMed Central

Asifa, Gul Zareen; Kazmi, Syed Ali Raza; Javed, Qamar

2013-01-01

Background. Tumor necrosis factor-alpha (TNF-α) gene polymorphisms have been implicated in the manifestation of atherosclerosis. Controversy exists regarding the link between the cytokine's variant genotype and CHD among different ethnic groups. There have been fewer studies on the TNF-α gene −1031T>C and −863C>A polymorphisms in relation to CHD. Therefore, the current study was designed to investigate the association of the TNF-α gene −1031T>C and −863C>A polymorphisms with CHD in a Pakistani population. Methods. Patients with CHD (n = 310) and healthy individuals (n = 310) were enrolled in this study. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results. A significant difference was observed in the −863C>A polymorphism between patients with CHD and control subjects (P < 0.0001). CHD risk was positively associated with the variant allele −863A (P < 0.0001) in the study subjects. There was no significant link between the −1031T>C polymorphism and CHD risk in the study population. Haplotypes A-T and A-C of the TNF-alpha gene loci at −863 and −1031 showed higher frequency in the patient group compared with controls (P < 0.05). Conclusion. The TNF-α  −863C>A gene polymorphism was associated with the pathogenesis of CHD while the −1031T>C polymorphism did not show any link with the disease in a Pakistani population. PMID:24381514

Estrogen receptor alpha polymorphisms and the risk of prostate cancer development.

PubMed

Jurečeková, Jana; Babušíková, Eva; Kmeťová, Monika; Kliment, Ján; Dobrota, Dušan

2015-11-01

The main purpose of the study was to evaluate the effect of two polymorphisms in the estrogen receptor alpha, rs2077647 and rs3798577, on the development of prostate cancer, their correlation with selected clinical characteristics, as well as consideration of potential interactions between four estrogen receptor alpha polymorphisms (rs2077647, rs3798577, PvuII, XbaI). The study was performed using 395 patients with histologically verified prostate cancer and 253 healthy male controls. The CC genotype of rs2077647 was significantly associated with prostate cancer (OR = 1.61). No association was found between rs3798577 polymorphism and prostate cancer. After stratification of patients according to the age at diagnosis and Gleason score, we observed significant correlation between rs2077647 polymorphism and prostate cancer risk in patients diagnosed before the age of 60 as well as patients with Gleason score <7, while rs3798577 was significantly associated with prostate cancer risk development in patients older than 60 and with Gleason score ≥7. Double analysis of each combination of four studied polymorphisms showed that presence of at least three variant alleles was associated with prostate cancer risk in all combinations, while each containing rs3798577 was significantly associated with development of high-grade carcinomas. The present study suggests that rs2077647 polymorphism may be a risk factor for prostate cancer especially in patients diagnosed before the age of 60, while rs3798577 polymorphism could probably serve rather as promoting factor in combination with other polymorphisms in estrogen receptor alpha contributing preferably to development of high-grade carcinomas.

Association of the osteopontin rs1126616 polymorphism and a higher serum osteopontin level with lupus nephritis

PubMed Central

SALIMI, SAEEDEH; NOORA, MEHRANGIZ; NABIZADEH, SIMA; REZAEI, MAHNAZ; SHAHRAKI, HOSSAIN; MILAD, MOHAMMADOO-KHORASSANI; NAGHAVI, ANOOSH; FARAJIAN-MASHHADI, FARZANEH; ZAKERI, ZAHRA; SANDOUGHI, MAHNAZ

2016-01-01

Osteopontin (OPN) is a chemokine-like glycoprotein that has a prominent role in regulating inflammation and immunity. OPN polymorphisms and elevated OPN levels are associated with systemic lupus erythematosus (SLE) in several populations. The aim of present study was to evaluate the association between the OPN rs1126616 polymorphism and OPN level with SLE susceptibility. A total of 163 SLE patients and 180 age-, gender- and ethnically matched controls were genotyped for the rs1126616 polymorphism by the polymerase chain reaction-restriction fragment length polymorphism method. Serum OPN levels were assayed by the enzyme-linked immunosorbent assay. There was no association between the OPN rs1126616 C/T polymorphism and SLE. The frequency of the OPN rs1126616 CT genotype was significantly higher in SLE patients with nephritis compared to SLE patients without nephritis and controls. Additionally, the frequency of TT genotypes was higher in SLE patients with nephritis compared to controls. The serum OPN levels were significantly higher in SLE patients compared to controls (50.6±22 vs. 35.6±15.8 ng/ml, P<0.001). Increased serum OPN levels were observed in SLE patients with lupus nephritis and joint symptoms. There was no correlation between OPN levels and the OPN rs1126616 polymorphism. The present data suggest that the CT and TT genotypes of the OPN rs1126616 polymorphism could be a risk factor for lupus nephritis. The OPN level is associated with SLE and certain SLE manifestations. However, there was no association between the OPN rs1126616 C/T polymorphism and SLE susceptibility. PMID:26998275

The D allele of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is associated with worse functional outcome of ischaemic stroke.

PubMed

Malueka, Rusdy Ghazali; Dwianingsih, Ery Kus; Sutarni, Sri; Bawono, Rheza Gandi; Bayuangga, Halwan Fuad; Gofir, Abdul; Setyopranoto, Ismail

2017-12-29

Insertion/deletion polymorphism in ACE gene (ACE I/D) is known to be associated with the occurrence of ischaemic stroke through its effect on pathogenesis of atherosclerosis and hypertension. This study was aimed to examine the association between this polymorphism with functional outcome of ischaemic stroke. This was a cross-sectional study. The subjects were patients with ischaemic stroke in a reference hospital in Yogyakarta, Indonesia. Data on demographic characteristics, stroke risk factors, comorbidities and stroke severity were assessed on admission. The functional outcome, Barthel index (BI), was assessed when the patients were discharged from the hospital. ACE I/D genotypes of the patients were identified by polymerase chain reaction (PCR). In total, 61 patients were included. Of these, 38 patients (62.3%) had II polymorphism, 22 patients (36.1%) had ID polymorphism and 1 patient (1.6%) had DD polymorphism in the ACE gene. There were significant differences in the functional outcomes between patients without D allele (II polymorphisms) and patients with D allele (ID and DD polymorphism) (mean BI on discharge: 75 ± 23.57 and 60.65 ± 27.15, respectively; p = 0.034). Multiple linear regression model showed that the availability of D allele is an independent variable negatively associated with functional outcome as assessed by BI (β = -0.232, p = 0.024). This study showed that the D allele in ACE I/D polymorphism is associated with worse functional outcomes. This highlights the possibility of further research to improve functional outcomes of ischaemic stroke by inhibiting the ACE system.

Genetic polymorphism in postoperative sepsis after open heart surgery in infants.

PubMed

Fakhri, Dicky; Djauzi, Samsuridjal; Murni, Tri Wahyu; Rachmat, Jusuf; Harahap, Alida Roswita; Rahayuningsih, Sri Endah; Mansyur, Muchtaruddin; Santoso, Anwar

2016-05-01

Sepsis is one of the complications following open heart surgery. Toll-like receptor 2 and toll-interacting protein polymorphism influence the immune response after open heart surgery. This study aimed to assess the genetic distribution of toll-like receptor 2 N199N and toll-interacting protein rs5743867 polymorphism in the development of postoperative sepsis. A prospective cohort study was conducted in 108 children <1-year old who underwent open heart surgery with a Basic Aristotle score ≥6. Patients with an accompanying congenital anomaly, human immunodeficiency virus infection, or history of previous open heart surgery were excluded. The patients' nutritional status and genetic polymorphism were assessed prior to surgery. The results of genetic polymorphism were obtained through genotyping. Patients' ages on the day of surgery and cardiopulmonary bypass times were recorded. The diagnosis of sepsis was established according to Surviving Sepsis Campaign criteria. Postoperative sepsis was observed in 21% of patients. There were 92.6% patients with toll-like receptor 2 N199N polymorphism and 52.8% with toll-interacting protein rs5743867 polymorphism. Toll-like receptor 2 N199N polymorphism tends to increase the risk of sepsis (odds ratio = 1.974; 95% confidence interval: 0.23-16.92; p = 0.504), while toll-interacting protein rs5743867 polymorphism tends to decrease the risk of sepsis (odds ratio = 0.496; 95% confidence interval: 0.19-1.27; p = 0.139) in infants <1-year old undergoing complex open heart surgery. © The Author(s) 2016.

The association of AKNA gene polymorphisms with knee osteoarthritis suggests the relevance of this immune response regulator in the disease genetic susceptibility.

PubMed

Martínez-Nava, Gabriela Angélica; Fernández-Torres, Javier; Martínez-Flores, Karina; Zamudio-Cuevas, Yessica; Clavijo-Cornejo, Denise; Espinosa-Morales, Rolando; Lozada, Carlos A; Gutierrez, Marwin; Granados, Julio; Pineda, Carlos; Madrid-Marina, Vicente; López-Reyes, Alberto

2018-04-01

Recent studies have identified AKNA as a potential susceptibility gene for several inflammatory diseases. Here, we aimed to assess the potential association of AKNA polymorphisms with knee osteoarthritis (KOA) susceptibility in a Mexican population, following STREGA recommendations. From a DNA bank of 181 KOA patients and 140 healthy controls, two AKNA SNPs were genotyped using TaqMan probes. The association between KOA susceptibility and AKNA polymorphisms genotypes was evaluated by multivariated logistic regression analysis. Information regarding patients' inflammatory biomarkers levels was obtained and their association with AKNA polymorphisms genotypes was assessed by lineal regression. We found a positive association with the recessive inheritance model of both AKNA polymorphisms (A/A genotype for both) and KOA susceptibility adjusting by age, body mass index (BMI), gender and place of birth (OR = 2.48, 95% CI 1.09-5.65 for rs10817595 polymorphism; and OR = 4.96; 95% CI 2.421-10.2 for rs3748176 polymorphism). Additionally these associations were also seen after stratifying patients by KOA severity and age. Furthermore the total leukocyte count was positively associated with rs10817595 AKNA polymorphism (β = 1.39; 95% CI 0.44-2.34) adjusting by age, BMI, gender, place of birth and disease severity. We suggest that regulatory and coding polymorphisms of the inflammatory modulator gene AKNA can influence the development of KOA. Further structural and functional studies might reveal the role of AKNA in OA and other rheumatic diseases.

Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1.

PubMed

Cheng, Timothy H T; Thompson, Deborah; Painter, Jodie; O'Mara, Tracy; Gorman, Maggie; Martin, Lynn; Palles, Claire; Jones, Angela; Buchanan, Daniel D; Win, Aung Ko; Hopper, John; Jenkins, Mark; Lindor, Noralane M; Newcomb, Polly A; Gallinger, Steve; Conti, David; Schumacher, Fred; Casey, Graham; Giles, Graham G; Pharoah, Paul; Peto, Julian; Cox, Angela; Swerdlow, Anthony; Couch, Fergus; Cunningham, Julie M; Goode, Ellen L; Winham, Stacey J; Lambrechts, Diether; Fasching, Peter; Burwinkel, Barbara; Brenner, Hermann; Brauch, Hiltrud; Chang-Claude, Jenny; Salvesen, Helga B; Kristensen, Vessela; Darabi, Hatef; Li, Jingmei; Liu, Tao; Lindblom, Annika; Hall, Per; de Polanco, Magdalena Echeverry; Sans, Monica; Carracedo, Angel; Castellvi-Bel, Sergi; Rojas-Martinez, Augusto; Aguiar Jnr, Samuel; Teixeira, Manuel R; Dunning, Alison M; Dennis, Joe; Otton, Geoffrey; Proietto, Tony; Holliday, Elizabeth; Attia, John; Ashton, Katie; Scott, Rodney J; McEvoy, Mark; Dowdy, Sean C; Fridley, Brooke L; Werner, Henrica M J; Trovik, Jone; Njolstad, Tormund S; Tham, Emma; Mints, Miriam; Runnebaum, Ingo; Hillemanns, Peter; Dörk, Thilo; Amant, Frederic; Schrauwen, Stefanie; Hein, Alexander; Beckmann, Matthias W; Ekici, Arif; Czene, Kamila; Meindl, Alfons; Bolla, Manjeet K; Michailidou, Kyriaki; Tyrer, Jonathan P; Wang, Qin; Ahmed, Shahana; Healey, Catherine S; Shah, Mitul; Annibali, Daniela; Depreeuw, Jeroen; Al-Tassan, Nada A; Harris, Rebecca; Meyer, Brian F; Whiffin, Nicola; Hosking, Fay J; Kinnersley, Ben; Farrington, Susan M; Timofeeva, Maria; Tenesa, Albert; Campbell, Harry; Haile, Robert W; Hodgson, Shirley; Carvajal-Carmona, Luis; Cheadle, Jeremy P; Easton, Douglas; Dunlop, Malcolm; Houlston, Richard; Spurdle, Amanda; Tomlinson, Ian

2015-12-01

High-risk mutations in several genes predispose to both colorectal cancer (CRC) and endometrial cancer (EC). We therefore hypothesised that some lower-risk genetic variants might also predispose to both CRC and EC. Using CRC and EC genome-wide association series, totalling 13,265 cancer cases and 40,245 controls, we found that the protective allele [G] at one previously-identified CRC polymorphism, rs2736100 near TERT, was associated with EC risk (odds ratio (OR) = 1.08, P = 0.000167); this polymorphism influences the risk of several other cancers. A further CRC polymorphism near TERC also showed evidence of association with EC (OR = 0.92; P = 0.03). Overall, however, there was no good evidence that the set of CRC polymorphisms was associated with EC risk, and neither of two previously-reported EC polymorphisms was associated with CRC risk. A combined analysis revealed one genome-wide significant polymorphism, rs3184504, on chromosome 12q24 (OR = 1.10, P = 7.23 × 10(-9)) with shared effects on CRC and EC risk. This polymorphism, a missense variant in the gene SH2B3, is also associated with haematological and autoimmune disorders, suggesting that it influences cancer risk through the immune response. Another polymorphism, rs12970291 near gene TSHZ1, was associated with both CRC and EC (OR = 1.26, P = 4.82 × 10(-8)), with the alleles showing opposite effects on the risks of the two cancers.

Pressure-tuning micro-Raman spectra of artists' pigments: α- and β-copper phthalocyanine polymorphs.

PubMed

Beaulieu-Houle, Guillaume; Gilson, Denis F R; Butler, Ian S

2014-01-03

The two polymorphs of copper phthalocyanine, α- and β-CuPc, have been examined by micro-Raman spectroscopy at pressures approaching 5.0 GPa. The metastable α-polymorph does not exhibit any structural changes, while the more thermodynamically stable β-polymorph does exhibit a reversible phase transition at 2.0 GPa. The pressure dependences (dν/dP) for a selected number of vibrational modes are reported. Two regions of the Raman spectra, 800-900 cm(-1) and 1100-1200 cm(-1), are sensitive to pressure such that they can be used as indicators of the polymorphic form. Copyright © 2013 Elsevier B.V. All rights reserved.

Solid-state NMR and IR for the analysis of pharmaceutical solids: polymorphs of fosinopril sodium.

PubMed

Brittain, H G; Morris, K R; Bugay, D E; Thakur, A B; Serajuddin, A T

1993-01-01

The two polymorphic modifications of fosinopril sodium have been characterized as to their differences in melting behaviour, powder X-ray diffraction patterns, Fourier transform infrared spectra (FTIR), and solid-state 31P- and 13C-NMR spectra. The polymorphs were found to be enantiotropically related based upon melting point, heat of fusion, and solution mediated transformation data. Analysis of the solid-state FTIR and 13C-NMR data indicated that the environment of the acetal side chain of fosinopril sodium differed in two polymorphs, and that there might be cis-trans isomerization about the C6-N peptide bond. These conformational differences are postulated as the origin of the observed polymorphism.

The initial (earliest) report of polymorphous ventricular tachycardia.

PubMed

Jani, Sonal; Schweitzer, Paul

2006-07-01

In these short historical notes, we describe the early history of polymorphic ventricular tachycardia. Polymorphous ventricular tachycardia was probably first noted in 1918 by Wilson and Robinson. In a publication describing complete heart block and ventriculophasic arrhythmia, they noted a tachyarrhythmia characterized by multiple extrasystoles of different types at a rapid rate. Also, we briefly discuss the earliest recognized torsades de pointes by Dessertenes in 1966 and the first description of catecholaminergic polymorphic ventricular tachycardia, by Reid in 1977.

Folate and Breast Cancer: Role of Intake, Blood Levels, and Metabolic Gene Polymorphisms

DTIC Science & Technology

2005-07-01

folate, and metabolic gene polymorphisms in relation to breast cancer risk: Months 1-19. b. Prepare blood samples for relevant assays: Months 1-19... gene polymorphism assays among the 184 cases and matched controls. The folate assays are on-going at this time. DNA assays will commence in the... methotrexate . Ann Oncol 13: 1915–1918, 2002 13. Toffoli G, Veronesi A, Boiocchi M, Crivellari D: MTHFR gene polymorphism and severe toxicity during

A novel analytical method for pharmaceutical polymorphs by terahertz spectroscopy and the optimization of crystal form at the discovery stage.

PubMed

Ikeda, Yukihiro; Ishihara, Yoko; Moriwaki, Toshiya; Kato, Eiji; Terada, Katsuhide

2010-01-01

A novel analytical method for the determination of pharmaceutical polymorphs was developed using terahertz spectroscopy. It was found out that each polymorph of a substance showed a specific terahertz absorption spectrum. In particular, analysis of the second derivative spectrum was enormously beneficial in the discrimination of closely related polymorphs that were difficult to discern by powder X-ray diffractometry. Crystal forms that were obtained by crystallization from various solvents and stored under various conditions were specifically characterized by the second derivative of each terahertz spectrum. Fractional polymorphic transformation for substances stored under stressed conditions was also identified by terahertz spectroscopy during solid-state stability test, but could not be detected by powder X-ray diffractometry. Since polymorphs could be characterized clearly by terahertz spectroscopy, further physicochemical studies could be conducted in a timely manner. The development form of compound examined was determined by the results of comprehensive physicochemical studies that included thermodynamic relationships, as well as chemical and physicochemical stability. In conclusion, terahertz spectroscopy, which has unique power in the elucidation of molecular interaction within a crystal lattice, can play more important role in physicochemical research. Terahertz spectroscopy has a great potential as a tool for polymorphic determination, particularly since the second derivative of the terahertz spectrum possesses high sensitivity for pharmaceutical polymorphs.

The association of factor V G1961A (factor V Leiden), prothrombin G20210A, MTHFR C677T and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss in Bosnian women.

PubMed

Jusić, Amela; Balić, Devleta; Avdić, Aldijana; Pođanin, Maja; Balić, Adem

2018-08-01

Aim To investigate association of factor V Leiden, prothrombin G20210A, MTHFR C677T and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss in Bosnian women. Methods A total of 60 women with two or more consecutive miscarriages before 20 weeks of gestation with the same partners and without history of known causes or recurrent pregnancy loss were included. A control group included 80 healthy women who had one or more successful pregnancies without history of any complication which could be associated with miscarriages. Genotyping of factor V Leiden, prothrombin G20210A, MTHFR C677T and PAI-1 4G/5G polymorphisms were performed by polymerase chain reaction/restriction fragments length polymorphism method (PCR/RFLP). Results Both factor V Leiden and MTHFR C677T polymorphisms were significantly associated with recurrent pregnancy loss (RPL) in Bosnian women while prothrombin G20210A and PAI-1 4G/5G polymorphisms did not show strongly significant association. Conclusion The presence of thrombophilic polymorphisms may predispose women to recurrent pregnancy loss. Future investigation should be addressed in order to find when carriers of those mutations, polymorphisms should be treated with anticoagulant therapy. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

Association of a single-nucleotide polymorphism in the promoter region of the VEGF gene with the risk of renal cell carcinoma.

PubMed

Ajaz, Sadia; Khaliq, Shagufta; Abid, Aiysha; Hassan, Asad Shehzad; Hashmi, Altaf; Sultan, Gauhar; Mohsin, Rehan; Mubarrak, Mohammad; Naqvi, Syed Ali Anwar; Rizvi, Syed Adib-ul-Hasan; Mehdi, Syed Qasim

2011-09-01

Vascular endothelial growth factor (VEGF) protein plays an important role in tumor development and progression. Polymorphisms in the VEGF gene may lead to over- or underexpression of the protein and may be associated with either risk or progression of malignancy. The aim of this case-control study is to identify and quantify the correlation between VEGF polymorphisms and renal cell carcinoma (RCC). Restriction fragment length polymorphism methods were used for the analysis of VEGF polymorphisms at -2578 and +936 positions in the promoter and 3'-untranslated regions, respectively. The VEGF -2578 A-allele was associated with an increased risk of RCC (odds ratio: 1.6; 95% CI: 1.2-2.3) and A-carrier genotypes were strongly correlated (odds ratio: 2.7; 95% CI: 1.5-4.7) with higher risk. Comparison of VEGF +936 C/T polymorphism between patient and control groups revealed no association with renal carcinoma. Both VEGF -2578 C/A and VEGF +936 C/T polymorphisms showed no significant association with the histopathological parameters of RCC. This study shows that VEGF -2578 A-allele and A-carrier genotypes are associated with an increased risk of RCC. In groups with higher incidence of RCC, a screening test for this polymorphism may be recommended in conjunction with other established markers.

Association of glutathione S-transferase pi (GSTP1) Ile105Val polymorphism with the risk of skin cancer: a meta-analysis.

PubMed

Zhou, Cheng-Fan; Ma, Tai; Zhou, Deng-Chuan; Shen, Tong; Zhu, Qi-Xing

2015-08-01

Numerous epidemiological studies have evaluated the association of Glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism with the risk of skin cancer. However, the results remain inconclusive. To derive a more precise estimation of the association between the GSTP1 Ile105Val polymorphism and skin cancer risk, a meta-analysis was performed. A comprehensive search was conducted to identify the eligible studies. We used odds ratios (ORs) with 95 % confidence intervals (CIs) to assess the association of GSTP1 Ile105Val polymorphism with skin cancer risk. Thirteen case-control studies in nine articles, which included a total of 1504 cases and 2243 controls. Overall, we found that GSTP1 Ile105Val polymorphism was not associated with skin cancer risk. Furthermore, subgroup analysis by histological types showed that GSTP1 Ile105Val polymorphism was associated with risks of malignant melanoma under the dominant model (Val/Val + Val/Ile vs. Ile/Ile: OR 1.230, 95 % CI 1.017-1.488, P = 0.033). However, lack of association between GSTP1 Ile105Val polymorphism and BCC and SCC risk in all genetic models. Our meta-analysis suggested that the GSTP1 Ile105Val polymorphism might be associated with increased risk of malignant melanoma in Caucasian population.

Development of highly polymorphic EST-SSR markers and segregation in F₁ hybrid population of Vitis vinifera L.

PubMed

Kayesh, E; Zhang, Y Y; Liu, G S; Bilkish, N; Sun, X; Leng, X P; Fang, J G

2013-09-23

The objectives of this investigation were to develop and validate the expressed sequence tag (EST)-simple sequence repeat (SSR) markers from large EST sequences, and to study the segregation and distribution of SSRs within two grapevine parental lines. In total, 94 F₁ lines crossed between "Early Rose" and "Red Globe" were studied. Approximately 2100 EST-SSR sequences of Vitis vinifera L. were searched for SSRs and analyzed for the design of polymerase chain reaction (PCR) primers amplifying the SSR-rich regions. Trinucleotide repeats were found to be the most abundant, followed by other nucleotide repeats. A total of 182 SSR primer pairs were first developed for the study on the parental polymorphism. Among the 182 SSR primers, 142 primer pairs (78%) could amplify the anticipated PCR products, among which only 52 primer pairs (36.62%) showed polymorphism between the two parents. These polymorphic bands were further surveyed among the 94 F₁ lines, and the results showed that a total of 162 bands were amplified, and 98 of them were polymorphic in both parents (60.86% polymorphism), with an average of 1.88 polymorphic DNA bands for each primer pair. After testing with the chi-square test, 33 of the clearly amplified polymorphic bands followed a 3:1 ratio, and 37 followed a 1:1 ratio. The rest showed distorted segregation ratios.

The Pressure-Temperature Phase Diagram of Metacetamol and Its Comparison to the Phase Diagram of Paracetamol.

PubMed

Barrio, Maria; Huguet, Judit; Rietveld, Ivo B; Robert, Benoît; Céolin, René; Tamarit, Josep-Lluis

2017-06-01

Understanding the polymorphic behavior of active pharmaceutical ingredients is important for formulation purposes and regulatory reasons. Metacetamol is an isomer of paracetamol and it similarly exhibits polymorphism. In the present article, it has been found that one of the polymorphs of metacetamol is only stable under increased pressure, which has led to the conclusion that metacetamol like paracetamol is a monotropic system under ordinary (= laboratory) conditions and that it becomes enantiotropic under pressure with the I-II-L triple point coordinates for metacetamol T I-II-L  = 535 ± 10 K and P I-II-L  = 692 ± 70 MPa. However, whereas for paracetamol the enantiotropy under pressure can be foreseen, because the metastable polymorph is denser, in the case of metacetamol this is not possible, as the metastable polymorph is less dense than the stable one. The existence of the stability domain for the less dense polymorph of metacetamol can only be demonstrated by the construction of the topological phase diagram as presented in this article. It is a delicate interplay between the specific volume differences and the enthalpy differences causing the stability domain of the less dense polymorph to be sandwiched between the denser polymorph and the liquid. Metacetamol shares this behavior with bicalutamide and fluoxetine nitrate. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Significant Association of the MDM2 T309G Polymorphism with Breast Cancer Risk in a Turkish Population

PubMed

Yilmaz, Meral; Tas, Ayca; Donmez, Gonca; Kacan, Turgut; Silig, Yavuz

2018-04-27

Background: Breast cancer is a leading cause of death in women worldwide. Genetic polymorphisms have been reported to be important etiological factors. Murine double minute 2 (MDM2) T309G interacts with p53 and mutations in p53 are present in approximately 50% of all cancers. However, it has been reported that effect of the polymorphism on breast cancer risk may vary in different populations. Here, we therefore investigated whether there is an association between MDM2 T309G (rs2279744) polymorphism and breast cancer in a Turkish population. Materials and Methods: We analysed 110 patients with breast cancer and 138 matched? controls. For genotyping, polymerase chain reaction and restriction length fragment polymorphism methods were used. Results: A significant difference was observed between case and control groups with regard to the distribution of the MDM2 T309G polymorphism (p<0.05). There was a significantly higher frequency of the TT genotype in the control group (p=0.028; OR, 2.42; 95% CI, 1.09-5.37). However, we did not find any relationships among tumor grade and metastasis status and this polymorphism. Conclusion: This study indicates that the MDM2 T309G polymorphism GG genotype and the TG+GG combination may be risk factors for breast cancer in our Turkish population. Creative Commons Attribution License

Polymorphisms of three genes (ACE, AGT and CYP11B2) in the renin-angiotensin-aldosterone system are not associated with blood pressure salt sensitivity: A systematic meta-analysis.

PubMed

Sun, Jiahong; Zhao, Min; Miao, Song; Xi, Bo

2016-01-01

Many studies have suggested that polymorphisms of three key genes (ACE, AGT and CYP11B2) in the renin-angiotensin-aldosterone system (RAAS) play important roles in the development of blood pressure (BP) salt sensitivity, but they have revealed inconsistent results. Thus, we performed a meta-analysis to clarify the association. PubMed and Embase databases were searched for eligible published articles. Fixed- or random-effect models were used to pool odds ratios and 95% confidence intervals based on whether there was significant heterogeneity between studies. In total, seven studies [237 salt-sensitive (SS) cases and 251 salt-resistant (SR) controls] for ACE gene I/D polymorphism, three studies (130 SS cases and 221 SR controls) for AGT gene M235T polymorphism and three studies (113 SS cases and 218 SR controls) for CYP11B2 gene C344T polymorphism were included in this meta-analysis. The results showed that there was no significant association between polymorphisms of these three polymorphisms in the RAAS and BP salt sensitivity under three genetic models (all p > 0.05). The meta-analysis suggested that three polymorphisms (ACE gene I/D, AGT gene M235T, CYP11B2 gene C344T) in the RAAS have no significant effect on BP salt sensitivity.

The role of the methylenetetrahydrofolate reductase 677 and 1298 polymorphisms in Cretan children with acute lymphoblastic leukemia.

PubMed

Karathanasis, Nikolaos V; Stiakaki, Eftichia; Goulielmos, George N; Kalmanti, Maria

2011-01-01

Acute lymphoblastic leukemia (ALL) is the most common form of malignancy in children. Recently, many studies have examined factors influencing both the susceptibility to ALL and the metabolism of widely used chemotherapeutic agents. These factors include, among others, single-nucleotide polymorphisms in various genes, such as the gene encoding for methylenetetrahydrofolate reductase (MTHFR), which has been proven polymorphic at the nucleotide positions 677 and 1298. Thirty-five children with ALL and 48 healthy adults of Cretan origin were genotyped for the presence of the MTHFR 677 and 1298 single-nucleotide polymorphisms. The possible correlation of the polymorphisms with the risk for ALL and the presence of methotrexate-induced toxicities were examined. No significant association between the MTHFR genotypes and the susceptibility to ALL was observed. A borderline statistically significant relationship was detected after methotrexate administration, between the C677T genotype (polymorphisms) and leukopenia (p = 0.050) and between the A1298C polymorphism and normal aspartate transaminase and alanine transaminase values (p = 0.065 and p = 0.053, respectively), which was strengthened for aspartate transaminase, after grouping the A1298A and A1298C genotypes together (p = 0.039). In our population the MTHFR C677T and A1298C polymorphisms are related with hematologic toxicity and hepatotoxicity, respectively, and could be suggested as prognostic factors for these adverse events.

Polymorphisms in FTO and TCF7L2 genes of Euro-Brazilian women with gestational diabetes.

PubMed

de Melo, Sandra Fabrico; Frigeri, Henrique Ravanhol; dos Santos-Weiss, Izabella Castilhos Ribeiro; Réa, Rosângela Roginski; de Souza, Emanuel Maltempi; Alberton, Dayane; Gomes de Moraes Rego, Fabiane; Picheth, Geraldo

2015-11-01

To investigate the association between fat mass and obesity-associated (FTO) gene polymorphisms rs8050136C>A and rs9939609T>A, and transcription factor 7-like 2 (TCF7L2) gene polymorphisms rs12255372G>T and rs7903146C>T, in a sample group of pregnant Euro-Brazilian women with or without gestational diabetes mellitus (GDM). Subjects were classified as either healthy pregnant control (n=200) or GDM (n=200) according to the 2010 criteria of the American Diabetes Association. The polymorphisms were genotyped using fluorescent probes (TaqMan®). All groups were in the Hardy-Weinberg equilibrium. The genotype and allele frequencies of the examined polymorphisms did not exhibit significant difference (P>0.05) between the groups. In the healthy and GDM pregnant women groups, the A-allele frequencies (95% CI) of FTO polymorphisms rs8050136 and rs9939609 were 39% (34-44%); 38% (33-43%) and 40% (35-45%); 41% (36-46%), respectively; and the T-allele frequencies of TCF7L2 polymorphisms rs12255372 and rs7903146 were 30% (26-35%), 32% (27-37%) and 29% (25-34%), 36% (31-41%), respectively. The examined polymorphisms were not associated with GDM in the Euro-Brazilian population studied. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Does colour polymorphism enhance survival of prey populations?

PubMed Central

Wennersten, Lena; Forsman, Anders

2009-01-01

That colour polymorphism may protect prey populations from predation is an old but rarely tested hypothesis. We examine whether colour polymorphic populations of prey exposed to avian predators in an ecologically valid visual context were exposed to increased extinction risk compared with monomorphic populations. We made 2976 artificial pastry prey, resembling Lepidoptera larvae, in four different colours and presented them in 124 monomorphic and 124 tetramorphic populations on tree trunks and branches such that they would be exposed to predation by free-living birds, and monitored their ‘survival’. Among monomorphic populations, there was a significant effect of prey coloration on survival, confirming that coloration influenced susceptibility to visually oriented predators. Survival of polymorphic populations was inferior to that of monomorphic green populations, but did not differ significantly from monomorphic brown, yellow or red populations. Differences in survival within polymorphic populations paralleled those seen among monomorphic populations; the red morph most frequently went extinct first and the green morph most frequently survived the longest. Our findings do not support the traditional protective polymorphism hypothesis and are in conflict with those of earlier studies. As a possible explanation to our findings, we offer a competing ‘giveaway cue’ hypothesis: that polymorphic populations may include one morph that attracts the attention of predators and that polymorphic populations therefore may suffer increased predation compared with some monomorphic populations. PMID:19324729

Association of Polymorphisms of Cytochrome P450 2D6 With Blood Hydroxychloroquine Levels in Patients With Systemic Lupus Erythematosus.

PubMed

Lee, Ji Yeon; Vinayagamoorthy, Nadimuthu; Han, Kyungdo; Kwok, Seung Ki; Ju, Ji Hyeon; Park, Kyung Su; Jung, Seung-Hyun; Park, Sung-Won; Chung, Yeun-Jun; Park, Sung-Hwan

2016-01-01

To evaluate associations of genetic polymorphisms in cytochrome P450 (CYP) isoforms 2D6, 3A5, and 3A4 with blood concentrations of hydroxychloroquine (HCQ) and its metabolite, N-desethyl HCQ (DHCQ), in patients with systemic lupus erythematosus (SLE). SLE patients taking HCQ for >3 months were recruited and were genotyped for 4 single-nucleotide polymorphisms in CYP2D6*10, CYP3A5*3, and CYP3A4*18B. Blood HCQ and DHCQ concentrations ([HCQ] and [DHCQ]) were measured and their association with corresponding genotypes was investigated. A total of 194 patients were included in the analysis. CYP2D6*10 polymorphisms (rs1065852 and rs1135840) were significantly associated with the [DHCQ]:[HCQ] ratio after adjustment for age, sex, dose per weight per day, and SLE Disease Activity Index score (P = 0.03 and P < 0.01, respectively). In adjusted models, the [DHCQ]:[HCQ] ratio was highest in patients with the G/G genotype of the CYP2D6*10 (rs1065852) polymorphism and lowest in those with the A/A genotype (P = 0.03). Similarly, the [DHCQ]:[HCQ] ratio was highest in patients with the C/C genotype of the CYP2D6*10 (rs1135840) polymorphism and lowest in those with the G/G genotype (P < 0.01). The CYP2D6*10 (rs1065852) polymorphism was significantly related to the [DHCQ] (P = 0.01). However, the polymorphisms of CYP3A5*3 and CYP3A4*18B did not show any significant association with the [HCQ], [DHCQ], or [DHCQ]:[HCQ] ratio. Our study showed that the [DHCQ]:[HCQ] ratio was related to CYP2D6 polymorphisms in Korean lupus patients taking oral HCQ. CYP polymorphisms may explain why there is wide variation in blood HCQ concentrations. The role of an individual's CYP polymorphisms should be considered when prescribing oral HCQ. © 2016, American College of Rheumatology.

Dopamine D{sub 3} receptor gene: Organization transcript variants, and polymorphism associated with schizophrenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Griffon, N.; Pilon, C.; Martres, M.P.

1996-02-16

DNA fragments from a genomic library were used to establish the partial structure of the human dopamine D{sub 3} receptor gene (DRD3). Its coding sequence contains 6 exons and stretches over 40,000 base pairs. The complete DRD3 transcript and three shorter variants, in which the second and/or third exon are deleted, were detected in similar proportions in brains from four controls and three psychiatric patients. The Msp I polymorphism was localized in the fifth intron of the gene, 40,000 base pairs downstream the Bal I polymorphism and a PCR-based method was developed for genotyping this polymorphism. The distributions of themore » Msp I and Bal I genotypes were not independent in 297 individuals ({chi}{sup 2} = 10.5, df = 4, P = 0.03), but only a weak association was found between allele 1 of the Bal I polymorphism and allele 2 of the Msp I polymorphism ({chi}{sup 2} = 3.99, df = 1, P = 0.04). The previously reported association between homozygosity at both alleles of the Bal I polymorphism and schizophrenia was presently maintained in an extended sample, comprising 119 DSM-III-R chronic schizophrenics and 85 controls ({chi}{sup 2}= 5.3, df = 1, P = 0.02) and found more important in males than in females. The presence of the Bal I allele 2 is associated with an early age at onset, particularly in males (df = 35, t value = 2.6, P = 0.014). In the same sample, allelic frequencies, genotype counts, and proportion of homozygotes for the Msp I polymorphism did not differ between schizophrenics and controls ({chi}{sup 2}= 0.06, df = 1, P = 0.80, {chi}{sup 2} = 0.22, df = 1, P = 0.90 and {chi}{sup 2} = 0.16, df = 1, P = 0.69, respectively). The large distance of the Msp I polymorphism from the Bal I polymorphism and its localization in the 3{prime} part of the gene may explain the discrepant results obtained with the two polymorphisms. 36 refs., 2 figs., 4 tabs.« less

[Amplicon density-weighted algorithms for analyzing dissimilarity and dynamic alterations of RAPD polymorphisms of Cordyceps sinensis].

PubMed

Yao, Yi-sang; Gao, Ling; Li, Yu-ling; Ma, Shao-li; Wu, Zi-mei; Tan, Ning-zhi; Wu, Jian-yong; Ni, Lu-qun; Zhu, Jia-shi

2014-08-18

To examine the dynamic maturational alterations of random amplified polymorphic DNA (RAPD) molecular marker polymorphism resulted from differential expressions of multiple fungi in the caterpillar body, stroma and ascocarp portion of Cordyceps sinensis (Cs). Used the fuzzy, integral RAPD molecular marker polymorphism method with 20 random primers; used density-weighted cluster algorithms and ZUNIX similarity equations; compared RAPD polymorphisms of the caterpillar body, stroma and ascocarp of Cs during maturation; and compared RAPD polymorphisms of Cs and Hirsutella sinensis (Hs). Density-unweighted algorithms neglected the differences in density of the DNA amplicons. Use of the density-weighted ZUNIX similarity equations and the clustering method integrated components of the amplicon density differences in similarity computations and clustering construction and prevented from the loss of the information of fungal genomes. An overall similarity 0.42 (< the overall dissimilarity 0.58) was observed for all compartments of Cs at different maturation stages. The similarities for the stromata or caterpillar bodies of Cs at 3 maturational stages were 0.57 or 0.50, respectively. During Cs maturation, there were dynamic Low→High→Low alterations of the RAPD polymorphisms between stromata and caterpillar bodies dissected from the same pieces of Cs. The polymorphic similarity was the highest (0.87) between the ascocarp and mature stroma, forming a clustering clade, while the premature stroma and caterpillar body formed another clade. These 2 clades merged into one cluster. Another clade containing the maturing stroma and caterpillar body merged with mature caterpillar body, forming another cluster. The RAPD polymorphic similarities between Hs and Cs samples were 0.55-0.69. Hs were separated from Cs clusters by the out-group control Paecilomyces militaris. The wealthy RAPD polymorphisms change dynamically in the Cs compartments with maturation. The different RAPD polymorphism for Hs from those for Cs supports the hypothesis of integrated micro-ecosystem Cs with multiple fungi, but does not support the "single fungal species" hypothesis for Cs and the anamorph-teleomorph connection between Hs and Cs.

In silico screening of the chicken genome for overlaps between genomic regions: microRNA genes, coding and non-coding transcriptional units, QTL, and genetic variations.

PubMed

Zorc, Minja; Kunej, Tanja

2016-05-01

MicroRNAs (miRNAs) are a class of non-coding RNAs involved in posttranscriptional regulation of target genes. Regulation requires complementarity between target mRNA and the mature miRNA seed region, responsible for their recognition and binding. It has been estimated that each miRNA targets approximately 200 genes, and genetic variability of miRNA genes has been reported to affect phenotypic variability and disease susceptibility in humans, livestock species, and model organisms. Polymorphisms in miRNA genes could therefore represent biomarkers for phenotypic traits in livestock animals. In our previous study, we collected polymorphisms within miRNA genes in chicken. In the present study, we identified miRNA-related genomic overlaps to prioritize genomic regions of interest for further functional studies and biomarker discovery. Overlapping genomic regions in chicken were analyzed using the following bioinformatics tools and databases: miRNA SNiPer, Ensembl, miRBase, NCBI Blast, and QTLdb. Out of 740 known pre-miRNA genes, 263 (35.5 %) contain polymorphisms; among them, 35 contain more than three polymorphisms The most polymorphic miRNA genes in chicken are gga-miR-6662, containing 23 single nucleotide polymorphisms (SNPs) within the pre-miRNA region, including five consecutive SNPs, and gga-miR-6688, containing ten polymorphisms including three consecutive polymorphisms. Several miRNA-related genomic hotspots have been revealed in chicken genome; polymorphic miRNA genes are located within protein-coding and/or non-coding transcription units and quantitative trait loci (QTL) associated with production traits. The present study includes the first description of an exonic miRNA in a chicken genome, an overlap between the miRNA gene and the exon of the protein-coding gene (gga-miR-6578/HADHB), and the first report of a missense polymorphism located within a mature miRNA seed region. Identified miRNA-related genomic hotspots in chicken can serve researchers as a starting point for further functional studies and association studies with poultry production and health traits and the basis for systematic screening of exonic miRNAs and missense/miRNA seed polymorphisms in other genomes.

Strong Impact of TGF-β1 Gene Polymorphisms on Breast Cancer Risk in Indian Women: A Case-Control and Population-Based Study

PubMed Central

Rajender, Singh; Tamang, Rakesh; Rajkumar, Raja; Saini, Karan Singh; Megu, Kaling; Goel, Madhu Mati; Surekha, Daminani; Rao, Digumarthi Raghunatha; Rao, Lakshmi; Ramachandra, Lingadakai; Kumar, Sandeep; Kumar, Surender; Vishnupriya, Satti; Satyamoorthy, Kapaettu; Negi, Mahendra Pal Singh; Thangaraj, Kumarasamy; Konwar, Rituraj

2013-01-01

Introduction TGF-β1 is a multi-functional cytokine that plays an important role in breast carcinogenesis. Critical role of TGF-β1 signaling in breast cancer progression is well documented. Some TGF-β1 polymorphisms influence its expression; however, their impact on breast cancer risk is not clear. Methods We analyzed 1222 samples in a candidate gene-based genetic association study on two distantly located and ethnically divergent case-control groups of Indian women, followed by a population-based genetic epidemiology study analyzing these polymorphisms in other Indian populations. The c.29C>T (Pro10Leu, rs1982073 or rs1800470) and c.74G>C (Arg25Pro, rs1800471) polymorphisms in the TGF-β1 gene were analyzed using direct DNA sequencing, and peripheral level of TGF-β1 were measured by ELISA. Results c.29C>T substitution increased breast cancer risk, irrespective of ethnicity and menopausal status. On the other hand, c.74G>C substitution reduced breast cancer risk significantly in the north Indian group (p = 0.0005) and only in the pre-menopausal women. The protective effect of c.74G>C polymorphism may be ethnicity-specific, as no association was seen in south Indian group. The polymorphic status of c.29C>T was comparable among Indo-Europeans, Dravidians, and Tibeto-Burmans. Interestingly, we found that Tibeto-Burmans lack polymorphism at c.74G>C locus as true for the Chinese populations. However, the Brahmins of Nepal (Indo-Europeans) showed polymorphism in 2.08% of alleles. Mean TGF-β1 was significantly elevated in patients in comparison to controls (p<0.001). Conclusion c.29C>T and c.74G>C polymorphisms in the TGF-β1 gene significantly affect breast cancer risk, which correlates with elevated TGF-β1 level in the patients. The c.29C>T locus is polymorphic across ethnically different populations, but c.74G>C locus is monomorphic in Tibeto-Burmans and polymorphic in other Indian populations. PMID:24146803

Patterns of gene variation in central and marginal populations of Drosophila robusta.

PubMed

Prakash, S

1973-10-01

The central and marginal populations of D. robusta differ greatly in the level of inversion polymorphism; the marginal populations are monomorphic or nearly so and the central populations are highly polymorphic. This paper presents the frequencies of alleles at forty gene loci in various populations of D. robusta, studied by electrophoresis of proteins and enzymes. Population samples were obtained from eight widely separated populations of D. robusta which included the central, the extreme marginal and the intervening populations between the center and the margins. We find that the proportion of polymorphic loci and average heterozygosity per individual is slightly higher in the marginal populations than the central populations. In D. robusta on an average, 39% of the loci are polymorphic and the average proportion of loci heterozygous per individual is 11%. A breakdown of loci in three categories, viz, hydrolytic enzymes and some other enzymes, larval proteins and glycolytic and Kreb's cycle enzymes, shows that in all populations the level of polymorphism is highest in the hydrolytic enzymes, intermediate in larval proteins and least in the glycolytic and Kreb's cycle enzymes. On the average, the proportion of loci heterozygous per individual for three groups of loci is: hydrolytic enzymes and others (.164), larval proteins (.115) and glycolytic and Kreb's cycle enzymes (.037). We also observe that in all populations the level of polymorphism on the X chromosome is far less than the expected 38%; in salivary gland cells the euchromatic length of the X chromosome is 38% of the entire genome. Lower levels of polymorphism for the X chromosome loci are explained due to low probability of balanced polymorphisms for the X-linked loci since the conditions for establishment of balanced polymorphism for X-linked loci are more restrictive than for the autosomal loci.-The polymorphic loci can be grouped according to pattern of allele frequencies in different populations as follows: (1) The allele frequencies are similar in all populations at the XDH, Pep-1 and Hex-1 loci. (2) The alleles at the Est-1, Est-2, Amy loci and the AP-4(1.0) and the LAP-1(.90) alleles show north south clinal change in frequency. (3) There is north south and east west differentiation at the Pt-5, Pt-8 and Pt-9 loci and the allele AP-4(.81). (4) Polymorphism at loci such as Fum, B.Ox, Hex-8, Pep-2 and Pep-3 are restricted to only one or two of the populations. (5) Allele frequencies at the MDH and ODH loci fluctuate between populations. (6) Allele frequencies at many polymorphic loci such as Est-1, Est-2, LAP-1, AP-4, Pt-5, Pt-8, Pt-9, Pt-16, MDH, Fum change clinally within a gene arrangement. The pattern of gene variation in D. robusta is very complex and cannot be easily explained due to migration of neutral alleles between once-isolated populations or to semi-isolation of neutral alleles. The observations of the pattern of allele variation in different populations, high levels of polymorphism in the marginal populations which have small population size and low levels of polymorphism of the X chromosome loci all support the argument in favor of balancing selection as the main mechanism for the maintenance of these polymorphisms. Environmental factors must play a role in the maintenance of a great deal of these polymorphisms, since we observe clinal allele frequency changes even within a given inversion type.

Patterns of Gene Variation in Central and Marginal Populations of DROSOPHILA ROBUSTA

PubMed Central

Prakash, Satya

1973-01-01

The central and marginal populations of D. robusta differ greatly in the level of inversion polymorphism; the marginal populations are monomorphic or nearly so and the central populations are highly polymorphic. This paper presents the frequencies of alleles at forty gene loci in various populations of D. robusta, studied by electrophoresis of proteins and enzymes. Population samples were obtained from eight widely separated populations of D. robusta which included the central, the extreme marginal and the intervening populations between the center and the margins. We find that the proportion of polymorphic loci and average heterozygosity per individual is slightly higher in the marginal populations than the central populations. In D. robusta on an average, 39% of the loci are polymorphic and the average proportion of loci heterozygous per individual is 11%. A breakdown of loci in three categories, viz, hydrolytic enzymes and some other enzymes, larval proteins and glycolytic and Kreb's cycle enzymes, shows that in all populations the level of polymorphism is highest in the hydrolytic enzymes, intermediate in larval proteins and least in the glycolytic and Kreb's cycle enzymes. On the average, the proportion of loci heterozygous per individual for three groups of loci is: hydrolytic enzymes and others (.164), larval proteins (.115) and glycolytic and Kreb's cycle enzymes (.037). We also observe that in all populations the level of polymorphism on the X chromosome is far less than the expected 38%; in salivary gland cells the euchromatic length of the X chromosome is 38% of the entire genome. Lower levels of polymorphism for the X chromosome loci are explained due to low probability of balanced polymorphisms for the X-linked loci since the conditions for establishment of balanced polymorphism for X-linked loci are more restrictive than for the autosomal loci.—The polymorphic loci can be grouped according to pattern of allele frequencies in different populations as follows: (1) The allele frequencies are similar in all populations at the XDH, Pep-1 and Hex-1 loci. (2) The alleles at the Est-1, Est-2, Amy loci and the AP-41.0 and the LAP-1.90 alleles show north south clinal change in frequency. (3) There is north south and east west differentiation at the Pt-5, Pt-8 and Pt-9 loci and the allele AP-4.81. (4) Polymorphism at loci such as Fum, B.Ox, Hex-8, Pep-2 and Pep-3 are restricted to only one or two of the populations. (5) Allele frequencies at the MDH and ODH loci fluctuate between populations. (6) Allele frequencies at many polymorphic loci such as Est-1, Est-2, LAP-1, AP-4, Pt-5, Pt-8, Pt-9, Pt-16, MDH, Fum change clinally within a gene arrangement. The pattern of gene variation in D. robusta is very complex and cannot be easily explained due to migration of neutral alleles between once-isolated populations or to semi-isolation of neutral alleles. The observations of the pattern of allele variation in different populations, high levels of polymorphism in the marginal populations which have small population size and low levels of polymorphism of the X chromosome loci all support the argument in favor of balancing selection as the main mechanism for the maintenance of these polymorphisms. Environmental factors must play a role in the maintenance of a great deal of these polymorphisms, since we observe clinal allele frequency changes even within a given inversion type. PMID:4203580

Genetic basis of interindividual susceptibility to cancer cachexia: selection of potential candidate gene polymorphisms for association studies.

PubMed

Johns, N; Tan, B H; MacMillan, M; Solheim, T S; Ross, J A; Baracos, V E; Damaraju, S; Fearon, K C H

2014-12-01

Cancer cachexia is a complex and multifactorial disease. Evolving definitions highlight the fact that a diverse range of biological processes contribute to cancer cachexia. Part of the variation in who will and who will not develop cancer cachexia may be genetically determined. As new definitions, classifications and biological targets continue to evolve, there is a need for reappraisal of the literature for future candidate association studies. This review summarizes genes identified or implicated as well as putative candidate genes contributing to cachexia, identified through diverse technology platforms and model systems to further guide association studies. A systematic search covering 1986-2012 was performed for potential candidate genes / genetic polymorphisms relating to cancer cachexia. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Pathway analysis software was used to reveal possible network associations between genes. Functionality of SNPs/genes was explored based on published literature, algorithms for detecting putative deleterious SNPs and interrogating the database for expression of quantitative trait loci (eQTLs). A total of 154 genes associated with cancer cachexia were identified and explored for functional polymorphisms. Of these 154 genes, 119 had a combined total of 281 polymorphisms with functional and/or clinical significance in terms of cachexia associated with them. Of these, 80 polymorphisms (in 51 genes) were replicated in more than one study with 24 polymorphisms found to influence two or more hallmarks of cachexia (i.e., inflammation, loss of fat mass and/or lean mass and reduced survival). Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides a contemporary basis to select genes and/or polymorphisms for further association studies in cancer cachexia, and to develop their potential as susceptibility biomarkers of cachexia.

Association between maternal, fetal and paternal MTHFR gene C677T and A1298C polymorphisms and risk of recurrent pregnancy loss: a comprehensive evaluation.

PubMed

Yang, Yi; Luo, Yunyao; Yuan, Jing; Tang, Yidan; Xiong, Lang; Xu, MangMang; Rao, XuDong; Liu, Hao

2016-06-01

Numerous studies have investigated the associations between methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms and risk of recurrent pregnancy loss (RPL); however, the results remain controversial. The aim of this study is to drive a more precise estimation of association between MTHFR gene polymorphisms and risk of RPL. We searched PubMed, EMBASE, Cochrane library, Web of Science and China Knowledge Resource Integrated Database for papers on MTHFR gene C677T and A1298C polymorphisms and RPL risk. The pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of association in the homozygous model, heterozygous model, dominant model, recessive model and an additive model. The software STATA (Version 13.0) was used for statistical analysis. Overall, 57 articles were included in the final meta-analysis. In maternal group the MTHFR C677T polymorphism showed pooled odds ratios for the homozygous comparison [OR = 2.285, 95 % CI (1.702, 3.067)] and the MTHFR A1298C polymorphism showed pooled odds ratios for recessive model [OR = 1.594, 95 % CI (1.136, 2.238)]. In fetal group the MTHFR C677T polymorphism showed pooled odds ratios for dominant model [OR = 1.037, 95 % CI (0.567, 1.894)] and the MTHFR A1298C polymorphism showed pooled odds ratios for dominant model [OR = 1.495, 95 % CI (1.102, 2.026)]. In summary, the results of our meta-analysis indicate that maternal and paternal MTHFR gene C677T and A1298C polymorphisms are associated with RPL. We also observed a significant association between fetal MTHFR A1298C polymorphism and RPL but not C677T.

Association of neonatal necrotizing enterocolitis with myeloid differentiation-2 and GM2 activator protein genetic polymorphisms.

PubMed

Zhou, Wei; Yuan, Weiming; Huang, Longguang; Wang, Ping; Rong, Xiao; Tang, Juan

2015-07-01

The aim of the present study was to investigate the association of neonatal necrotizing enterocolitis (NEC) with myeloid differentiation-(MD-2) and GM2 activator protein (GM2A) genetic polymorphisms. Gene resequencing of the MD-2 and GM2A gene exons was performed on 42 neonates, diagnosed with NEC (NEC group), as well as in the rs11465996 locus, located in the MD-2 gene promoter region. The aim was to detect the genetic polymorphisms present in the neonates with NEC and compare the functional polymorphic loci with 83 neonates without NEC (control group), who had been born during the same period. A polymorphic locus with abnormal frequency was detected in the exon region of the MD-2 gene. In the NEC group, the frequency of genotypes carrying the low frequency allele (G) in the rs11465996 locus (MD-2 promoter region) was significantly higher compared with the control group (χ(2)=4.388, P=0.036). Furthermore, the frequencies of genotypes carrying the low frequency A and C alleles in the rs1048719 (GM2A gene exon 1) and rs2075783 loci (GM2A intron), respectively, were significantly higher in the NEC group compared with the control group (χ(2)=4.316, P=0.038; and χ(2)=13.717, P=0.000, respectively). In addition, the rs11465996 polymorphism in the MD-2 gene promoter region was found to be associated with the severity of NEC. Furthermore, the rs2075783 polymorphism in the GM2A gene exon 1 and the rs1048719 polymorphism in the intron region of this gene, were associated with the occurrence of NEC. The present study demonstrated that gene polymorphisms of MD-2 and GM2A were associated with the occurrence or severity of NEC; however, further in-depth exploration is required to clarify the associations between genetic predispositions to polymorphisms, and NEC.

Structural and computational analysis of intermolecular interactions in a new 2-thiouracil polymorph.

PubMed

Fabijanić, Ivana; Matković-Čalogović, Dubravka; Pilepić, Viktor; Sanković, Krešimir

2017-12-01

The crystallization and characterization of a new polymorph of 2-thiouracil by single-crystal X-ray diffraction, Hirshfeld surface analysis and periodic density functional theory (DFT) calculations are described. The previously published polymorph (A) crystallizes in the triclinic space group P\\overline{1}, while that described herein (B) crystallizes in the monoclinic space group P2 1 /c. Periodic DFT calculations showed that the energies of polymorphs A and B, compared to the gas-phase geometry, were -108.8 and -29.4 kJ mol -1 , respectively. The two polymorphs have different intermolecular contacts that were analyzed and are discussed in detail. Significant differences in the molecular structure were found only in the bond lengths and angles involving heteroatoms that are involved in hydrogen bonds. Decomposition of the Hirshfeld fingerprint plots revealed that O...H and S...H contacts cover over 50% of the noncovalent contacts in both of the polymorphs; however, they are quite different in strength. Hydrogen bonds of the N-H...O and N-H...S types were found in polymorph A, whereas in polymorph B, only those of the N-H...O type are present, resulting in a different packing in the unit cell. QTAIM (quantum theory of atoms in molecules) computational analysis showed that the interaction energies for these weak-to-medium strength hydrogen bonds with a noncovalent or mixed interaction character were estimated to fall within the ranges 5.4-10.2 and 4.9-9.2 kJ mol -1 for polymorphs A and B, respectively. Also, the NCI (noncovalent interaction) plots revealed weak stacking interactions. The interaction energies for these interactions were in the ranges 3.5-4.1 and 3.1-5.5 kJ mol -1 for polymorphs A and B, respectively, as shown by QTAIM analysis.

Associations of fractalkine receptor (CX3CR1) and CCR5 gene variants with hypertension, diabetes and atherosclerosis in chronic renal failure patients undergoing hemodialysis.

PubMed

Bagci, Binnur; Bagci, Gokhan; Huzmeli, Can; Sezgin, Ilhan; Ozdemir, Ozturk

2016-07-01

We aimed to investigate the associations of fractalkine receptor (CX3CR1) V249I, T280M and CCR5-59029 A/G gene polymorphisms in chronic renal failure (CRF) subjects undergoing hemodialysis and to evaluate possible associations of these polymorphisms with hypertension (HT), diabetes mellitus (DM) and atherosclerosis (AS). A total of 225 CRF subjects undergoing hemodialysis and 201 healthy controls were enrolled in the study. CRF subjects were divided into three major subgroups according to comorbidities including HT (n = 127), DM (n = 65) and AS (n = 33). Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism method. The II genotype and I allele frequencies of CX3CR1 V249I polymorphism were found significantly more frequent in CRF subjects, CRF subjects with DM and CRF subjects with AS compared with controls (p < 0.05 for all comparisons). G allele frequency of CCR5 polymorphism was found significantly more prevalent in CRF subjects with DM than that of controls. Further, GG genotype and G allele frequencies of CCR5 polymorphism were significantly more prevalent in CRF subjects with AS compared with controls (p < 0.05). We also explored these polymorphisms among CRF subjects with and without following comorbidities: HT, DM, AS. We found significant association between CRF subjects with HT and without HT in terms of genotype and allele frequencies of V249I polymorphism (p < 0.05). CX3CR1 T280M polymorphism was not found significantly different in none of the comparisons. These data demonstrate possible associations between CX3CR1 V249I and CCR5-59029 A/G polymorphisms and/or HT, DM and AS in CRF subjects.

Identification of SNP and SSR Markers in Finger Millet Using Next Generation Sequencing Technologies

PubMed Central

Gimode, Davis; Odeny, Damaris A.; de Villiers, Etienne P.; Wanyonyi, Solomon; Dida, Mathews M.; Mneney, Emmarold E.; Muchugi, Alice; Machuka, Jesse; de Villiers, Santie M.

2016-01-01

Finger millet is an important cereal crop in eastern Africa and southern India with excellent grain storage quality and unique ability to thrive in extreme environmental conditions. Since negligible attention has been paid to improving this crop to date, the current study used Next Generation Sequencing (NGS) technologies to develop both Simple Sequence Repeat (SSR) and Single Nucleotide Polymorphism (SNP) markers. Genomic DNA from cultivated finger millet genotypes KNE755 and KNE796 was sequenced using both Roche 454 and Illumina technologies. Non-organelle sequencing reads were assembled into 207 Mbp representing approximately 13% of the finger millet genome. We identified 10,327 SSRs and 23,285 non-homeologous SNPs and tested 101 of each for polymorphism across a diverse set of wild and cultivated finger millet germplasm. For the 49 polymorphic SSRs, the mean polymorphism information content (PIC) was 0.42, ranging from 0.16 to 0.77. We also validated 92 SNP markers, 80 of which were polymorphic with a mean PIC of 0.29 across 30 wild and 59 cultivated accessions. Seventy-six of the 80 SNPs were polymorphic across 30 wild germplasm with a mean PIC of 0.30 while only 22 of the SNP markers showed polymorphism among the 59 cultivated accessions with an average PIC value of 0.15. Genetic diversity analysis using the polymorphic SNP markers revealed two major clusters; one of wild and another of cultivated accessions. Detailed STRUCTURE analysis confirmed this grouping pattern and further revealed 2 sub-populations within wild E. coracana subsp. africana. Both STRUCTURE and genetic diversity analysis assisted with the correct identification of the new germplasm collections. These polymorphic SSR and SNP markers are a significant addition to the existing 82 published SSRs, especially with regard to the previously reported low polymorphism levels in finger millet. Our results also reveal an unexploited finger millet genetic resource that can be included in the regional breeding programs in order to efficiently optimize productivity. PMID:27454301

Identification of SNP and SSR Markers in Finger Millet Using Next Generation Sequencing Technologies.

PubMed

Gimode, Davis; Odeny, Damaris A; de Villiers, Etienne P; Wanyonyi, Solomon; Dida, Mathews M; Mneney, Emmarold E; Muchugi, Alice; Machuka, Jesse; de Villiers, Santie M

2016-01-01

Finger millet is an important cereal crop in eastern Africa and southern India with excellent grain storage quality and unique ability to thrive in extreme environmental conditions. Since negligible attention has been paid to improving this crop to date, the current study used Next Generation Sequencing (NGS) technologies to develop both Simple Sequence Repeat (SSR) and Single Nucleotide Polymorphism (SNP) markers. Genomic DNA from cultivated finger millet genotypes KNE755 and KNE796 was sequenced using both Roche 454 and Illumina technologies. Non-organelle sequencing reads were assembled into 207 Mbp representing approximately 13% of the finger millet genome. We identified 10,327 SSRs and 23,285 non-homeologous SNPs and tested 101 of each for polymorphism across a diverse set of wild and cultivated finger millet germplasm. For the 49 polymorphic SSRs, the mean polymorphism information content (PIC) was 0.42, ranging from 0.16 to 0.77. We also validated 92 SNP markers, 80 of which were polymorphic with a mean PIC of 0.29 across 30 wild and 59 cultivated accessions. Seventy-six of the 80 SNPs were polymorphic across 30 wild germplasm with a mean PIC of 0.30 while only 22 of the SNP markers showed polymorphism among the 59 cultivated accessions with an average PIC value of 0.15. Genetic diversity analysis using the polymorphic SNP markers revealed two major clusters; one of wild and another of cultivated accessions. Detailed STRUCTURE analysis confirmed this grouping pattern and further revealed 2 sub-populations within wild E. coracana subsp. africana. Both STRUCTURE and genetic diversity analysis assisted with the correct identification of the new germplasm collections. These polymorphic SSR and SNP markers are a significant addition to the existing 82 published SSRs, especially with regard to the previously reported low polymorphism levels in finger millet. Our results also reveal an unexploited finger millet genetic resource that can be included in the regional breeding programs in order to efficiently optimize productivity.

Association of Nitric Oxide Levels and Endothelial Nitric Oxide Synthase G894T Polymorphism with Coronary Artery Disease in the Iranian Population

PubMed Central

Mahmoodi, Khalil; Nasehi, Leila; Karami, Elham; Soltanpour, Mohammad Soleiman

2016-01-01

Purpose: The endothelial nitric oxide synthase (eNOS) G894T polymorphism has been reported to cause endothelial dysfunction and may have a role in the development of coronary artery disease (CAD). The aim of the present study was to investigate the association of eNOS G894T genetic polymorphism and plasma levels of nitric oxide (NO) with CAD risk in an Iranian population. Materials and Methods: We studied 200 patients with angiographically documented CAD and 100 matched controls. Analysis of G894T genetic polymorphism of eNOS was performed by polymerase chain reaction-restriction fragment length polymorphism method. Plasma levels of NO were determined using Griess method. Biochemical analysis was conducted by routine colorimetric methods. Results: Plasma levels of NO were significantly lower in CAD patients than control subjects (41.60±12.70 vs. 55.48±16.57, P=0.001). Also, the mean plasma levels of NO were significantly lower in T allele carriers of eNOS G894T polymorphism than G allele carriers (P<0.001). The genotype distribution and minor T allele frequency of eNOS G894T polymorphism significantly differed between CAD patients and control subjects (P<0.05). However, no significant association was found between the eNOS G894T polymorphism and the severity of CAD (number of diseased vessel) or the lipid profile of CAD patients (P>0.05). Conclusion: Reduced plasma level of NO is associated with increased risk of CAD in our population. Moreover, eNOS G894T polymorphism is a significant risk factor for CAD development via reducing the plasma levels of NO. However, eNOS G894T polymorphism is not a contributing factor for the severity of CAD. PMID:27699157

Association between TYK2 polymorphisms and susceptibility to autoimmune rheumatic diseases: a meta-analysis.

PubMed

Lee, Y H; Bae, S-C

2016-10-01

This study aimed to explore whether TYK2 polymorphisms are associated with susceptibility to autoimmune rheumatic diseases. We conducted a meta-analysis on the association between TYK2 polymorphisms and autoimmune rheumatic diseases. Twelve studies with a total of 16,335 patients and 30,065 controls were included in the meta-analysis. Meta-analysis revealed an association between rheumatic diseases and the 2 allele of the TYK2 rs2304256 (OR = 0.885, 95% CI = 0.802-0.978, p = 0.016). Furthermore, stratification by ethnicity identified a significant association between this polymorphism and rheumatic diseases in Caucasians (OR = 0.822, 95% CI = 0.706-0.889, p = 9.5 × 10(-7)), but not in Asians (OR = 1.127, 95% CI = 0.835-1.522, p = 0.434). Meta-analysis by rheumatic disease type revealed a significant association between the 2 allele of the TYK2 rs2304256 and SLE in Caucasians (OR = 0.737, 95% CI = 0.673-0.808, p < 1.0 × 10(-8)) but not in Asians (OR = 1.211, 95% CI = 0.813-1.804, p = 0.347). Meta-analysis revealed that the rs12720356 polymorphism was associated with susceptibility to rheumatic diseases in Caucasians (OR = 0.812, 95% CI = 0.661-0.997, p = 0.046) but not in Asians. Interestingly, the rs280519 polymorphism was significantly associated with susceptibility to SLE both in Caucasians and Asians. However, no associations were found between the rs12720270, rs280500, rs280523 and rs8108236 polymorphisms and susceptibility to rheumatic diseases. This meta-analysis demonstrates that the TYK2 rs2304256 and rs12720356 polymorphisms are associated with susceptibility to rheumatic diseases, rs2304256 polymorphism is associated with SLE in Caucasians, and rs280519 polymorphism is associated with SLE in Caucasians and Asians. © The Author(s) 2016.

Molecular and functional characterization of polymorphisms in the secreted phospholipase A2 group X gene: relevance to coronary artery disease.

PubMed

Gora, Sarah; Perret, Claire; Jemel, Ikram; Nicaud, Viviane; Lambeau, Gérard; Cambien, François; Ninio, Ewa; Blankenberg, Stefan; Tiret, Laurence; Karabina, Sonia-Athina

2009-07-01

Among secreted phospholipases A2 (sPLA2s), human group X sPLA2 (hGX sPLA2) is emerging as a novel attractive therapeutic target due to its implication in inflammatory diseases. To elucidate whether hGX sPLA2 plays a causative role in coronary artery disease (CAD), we screened the human PLA2G10 gene to identify polymorphisms and possible associations with CAD end-points in a prospective study, AtheroGene. We identified eight polymorphisms, among which, one non-synonymous polymorphism R38C in the propeptide region of the sPLA2. The T-512C polymorphism located in the 5' untranslated region was associated with a decreased risk of recurrent cardiovascular events during follow-up. The functional analysis of the R38C polymorphism showed that it leads to a profound change in expression and activity of hGX sPLA2, although there was no detectable impact on CAD risk. Due to the potential role of hGX sPLA2 in inflammatory processes, these polymorphisms should be investigated in other inflammatory diseases.

MCT1, MCT4 and CD147 gene polymorphisms in healthy horses and horses with myopathy.

PubMed

Mykkänen, A K; Koho, N M; Reeben, M; McGowan, C M; Pösö, A R

2011-12-01

Polymorphisms in human lactate transporter proteins (monocarboxylate transporters; MCTs), especially the MCT1 isoform, can affect lactate transport activity and cause signs of exercise-induced myopathy. Muscles express MCT1, MCT4 and CD147, an ancillary protein, indispensable for the activity of MCT1 and MCT4. We sequenced the coding sequence (cDNA) of horse MCT4 for the first time and examined polymorphisms in the cDNA of MCT1, MCT4 and CD147 of 16 healthy horses. To study whether signs of myopathy are linked to the polymorphisms, biopsy samples were taken from 26 horses with exercise-induced recurrent myopathy. Two polymorphisms that cause a change in amino acid sequence were found in MCT1 (Val(432)Ile and Lys(457)Gln) and one in CD147 (Met(125)Val). All polymorphisms in MCT4 were silent. Mutations in MCT1 or CD147 in equine muscle were not associated with myopathy. In the future, a functional study design is needed to evaluate the physiological role of the polymorphisms found. Copyright © 2010 Elsevier Ltd. All rights reserved.

Polymorph Impact on the Bioavailability and Stability of Poorly Soluble Drugs.

PubMed

Censi, Roberta; Di Martino, Piera

2015-10-15

Drugs with low water solubility are predisposed to poor and variable oral bioavailability and, therefore, to variability in clinical response, that might be overcome through an appropriate formulation of the drug. Polymorphs (anhydrous and solvate/hydrate forms) may resolve these bioavailability problems, but they can be a challenge to ensure physicochemical stability for the entire shelf life of the drug product. Since clinical failures of polymorph drugs have not been uncommon, and some of them have been entirely unexpected, the Food and Drug Administration (FDA) and the International Conference on Harmonization (ICH) has required preliminary and exhaustive screening studies to identify and characterize all the polymorph crystal forms for each drug. In the past, the polymorphism of many drugs was detected fortuitously or through manual time consuming methods; today, drug crystal engineering, in particular, combinatorial chemistry and high-throughput screening, makes it possible to easily and exhaustively identify stable polymorphic and/or hydrate/dehydrate forms of poorly soluble drugs, in order to overcome bioavailability related problems or clinical failures. This review describes the concepts involved, provides examples of drugs characterized by poor solubility for which polymorphism has proven important, outlines the state-of-the-art technologies and discusses the pertinent regulations.

[Association between HRE-2 gene polymorphism at codon 655 and genetic susceptibility of colorectal cancer].

PubMed

Liang, Xia; Zhang, Yong-jing; Liu, Bing; Ni, Qin; Jin, Ming-juan; Ma, Xin-yuan; Yao, Kai-yan; Li, Qi-long; Chen, Kun

2009-06-01

To explore the distribution of HER-2 genetic polymorphism at codon 655 and its association with susceptibility of colorectal cancer in Chinese. A population-based case-control study was carried out. 292 patients with colorectal cancer and 842 healthy controls were interviewed. Meanwhile, the genetic polymorphism of HRE-2 was detected using polymerase chain reaction-restriction fragment length polymorphism. The frequencies of Ile/Val+Val/Val genotypes and Val allele were both higher in cases (25.34% and 13.36%) than those in controls (18.41% and 9.74%) (P<0.05). Compared with Ile/Ile genotype, Ile/Val+Val/Val genotypes were significantly associated with colorectal cancer [ORadjusted=1.54, 95% CI: 1.11-2.14]. The adjusted odds ratio of interactions between this polymorphism and smoking, alcohol drinking were 1.43 (95%CI: 0.88-2.30) and 1.29 (95%CI: 0.73-2.29), respectively. The present findings suggest that HER-2 genetic polymorphism at codon 655 may be associated with the risk of colorectal cancer in Chinese. In addition, there are no interactions between this polymorphism and smoking, alcohol drinking, respectively.

Epitaxial stabilization and phase instability of VO2 polymorphs

NASA Astrophysics Data System (ADS)

Lee, Shinbuhm; Ivanov, Ilia N.; Keum, Jong K.; Lee, Ho Nyung

2016-01-01

The VO2 polymorphs, i.e., VO2(A), VO2(B), VO2(M1) and VO2(R), have a wide spectrum of functionalities useful for many potential applications in information and energy technologies. However, synthesis of phase pure materials, especially in thin film forms, has been a challenging task due to the fact that the VO2 polymorphs are closely related to each other in a thermodynamic framework. Here, we report epitaxial stabilization of the VO2 polymorphs to synthesize high quality single crystalline thin films and study the phase stability of these metastable materials. We selectively deposit all the phases on various perovskite substrates with different crystallographic orientations. By investigating the phase instability, phonon modes and transport behaviours, not only do we find distinctively contrasting physical properties of the VO2 polymorphs, but that the polymorphs can be on the verge of phase transitions when heated as low as ~400 °C. Our successful epitaxy of both VO2(A) and VO2(B) phases, which are rarely studied due to the lack of phase pure materials, will open the door to the fundamental studies of VO2 polymorphs for potential applications in advanced electronic and energy devices.

Epitaxial stabilization and phase instability of VO2 polymorphs.

PubMed

Lee, Shinbuhm; Ivanov, Ilia N; Keum, Jong K; Lee, Ho Nyung

2016-01-20

The VO2 polymorphs, i.e., VO2(A), VO2(B), VO2(M1) and VO2(R), have a wide spectrum of functionalities useful for many potential applications in information and energy technologies. However, synthesis of phase pure materials, especially in thin film forms, has been a challenging task due to the fact that the VO2 polymorphs are closely related to each other in a thermodynamic framework. Here, we report epitaxial stabilization of the VO2 polymorphs to synthesize high quality single crystalline thin films and study the phase stability of these metastable materials. We selectively deposit all the phases on various perovskite substrates with different crystallographic orientations. By investigating the phase instability, phonon modes and transport behaviours, not only do we find distinctively contrasting physical properties of the VO2 polymorphs, but that the polymorphs can be on the verge of phase transitions when heated as low as ~400 °C. Our successful epitaxy of both VO2(A) and VO2(B) phases, which are rarely studied due to the lack of phase pure materials, will open the door to the fundamental studies of VO2 polymorphs for potential applications in advanced electronic and energy devices.

Epitaxial stabilization and phase instability of VO2 polymorphs

PubMed Central

Lee, Shinbuhm; Ivanov, Ilia N.; Keum, Jong K.; Lee, Ho Nyung

2016-01-01

The VO2 polymorphs, i.e., VO2(A), VO2(B), VO2(M1) and VO2(R), have a wide spectrum of functionalities useful for many potential applications in information and energy technologies. However, synthesis of phase pure materials, especially in thin film forms, has been a challenging task due to the fact that the VO2 polymorphs are closely related to each other in a thermodynamic framework. Here, we report epitaxial stabilization of the VO2 polymorphs to synthesize high quality single crystalline thin films and study the phase stability of these metastable materials. We selectively deposit all the phases on various perovskite substrates with different crystallographic orientations. By investigating the phase instability, phonon modes and transport behaviours, not only do we find distinctively contrasting physical properties of the VO2 polymorphs, but that the polymorphs can be on the verge of phase transitions when heated as low as ~400 °C. Our successful epitaxy of both VO2(A) and VO2(B) phases, which are rarely studied due to the lack of phase pure materials, will open the door to the fundamental studies of VO2 polymorphs for potential applications in advanced electronic and energy devices. PMID:26787259

Polymorphism in 'L' shaped lipids: structure of N-, O-diacylethanolamines with mixed acyl chains.

PubMed

Tarafdar, Pradip K; Swamy, Musti J

2009-11-01

Although solid state polymorphism in lipids has been established by spectroscopic and calorimetric studies long ago, only in a few cases crystal structures of different polymorphs of the same compound have been reported, possibly due to difficulties in obtaining high quality single crystals of individual polymorphs. Recent studies show that N-, O-diacylethanolamines (DAEs) can be derived by the O-acylation of the stress-related lipids, the N-acylethanolamines under physiological conditions. In this study, two DAEs with mixed acyl chains, namely N-palmitoyl, O-octanoylethanolamine and N-palmitoyl, O-decanoylethanolamine have been synthesized and their three-dimensional structures were determined. Both the compounds were found to adopt 'L' shaped structures and exist in two polymorphic forms, alpha and beta. In the alpha form a mixed-type chain packing has been observed whereas in the beta form the chain packing is symmetric. Similar polymorphic forms are likely to exist in other 'L' shaped lipids such as 1,3-diacylglycerols and ceramides, where polymorphism has been detected earlier, but three-dimensional structures - which can give precise information about the packing at atomic resolution - have not been reported.

Association of adiponectin gene -11377C>G polymorphism with adiponectin levels and the metabolic syndrome in Thais.

PubMed

Suriyaprom, Kanjana; Phonrat, Benjaluck; Tungtrongchitr, Rungsunn

2014-01-01

The metabolic syndrome is related to increased risk of developing cardiovascular disease and type 2 diabetes. Adiponectin is an adipocyte-secreted protein with insulin-sensitizing and anti-atherogenic properties. The aims of this study were to evaluate adiponectin levels and biochemical parameters in metabolic-syndrome subjects and healthy controls. The study also sought to identify links between two polymorphisms, -11377C>G (rs266729) and +45T>G (rs2241766) of the adiponectin gene, in relation to adiponectin levels and the metabolic syndrome. Three hundres and thirty-two Thai volunteers: 164 metabolic-syndrome subjects and 168 healthy control subjects were investigated. The adiponectin and HDL-C levels of the metabolic-syndrome group were significantly lower than the control group (p<0.001). Decreased concentration of adiponectin was associated with -11377C>G polymorphism (p<0.001); this polymorphism was significantly more frequent in the metabolic syndrome group than in the control group (p<0.001). However, +45T>G polymorphism of the adiponectin gene was found not to be related to adiponectin level or metabolic syndrome. Therefore, -11377C>G polymorphism was related to the metabolic syndrome susceptibility, and this polymorphism impacted on circulating adiponectin concentrations among Thais.

HLA-G+3027 polymorphism is associated with tumor relapse in pediatric Hodgkin's lymphoma.

PubMed

De Re, Valli; Caggiari, Laura; Mussolin, Lara; d'Amore, Emanuele Stefano; Famengo, Barbara; De Zorzi, Mariangela; Martina, Lia; Elia, Caterina; Pillon, Marta; Santoro, Nicola; Muggeo, Paola; Buffardi, Salvatore; Bianchi, Maurizio; Sala, Alessandra; Farruggia, Piero; Vinti, Luciana; Carosella, Edgardo D; Burnelli, Roberta; Mascarin, Maurizio

2017-12-01

In this study, we tested whether polymorphisms in human leukocyte antigen G (HLA-G) were associated with event-free survival (EFS) in pediatric Hodgkin's lymphoma (HL). We evaluated the association of HLA-G 3'-UTR polymorphisms with EFS in 113 pediatric HL patients treated using the AIEOP LH-2004 protocol. Patients with the +3027-C/A genotype (rs17179101, UTR-7 haplotype) showed lower EFS than those with the +3027-C/C genotype (HR= 3.23, 95%CI: 0.99-10.54, P=0.012). Female patients and systemic B symptomatic patients with the HLA-G +3027 polymorphism showed lower EFS. Multivariate analysis showed that the +3027-A polymorphism (HR 3.17, 95%CI 1.16-8.66, P=0.025) was an independent prognostic factor. Immunohistochemical analysis showed that HL cells from patients with the +3027-C/A genotype did not express HLA-G. Moreover, HLA-G +3027 polymorphism improved EFS prediction when added to the algorithm for therapeutic group classification of pediatric HL patients. Our findings suggest HLA-G +3027 polymorphism is a prognostic marker in pediatric HL patients undergoing treatment according to LH-2004 protocol.

[Association between feeding behavior, and genetic polymorphism of leptin and its receptor in obese Chilean children].

PubMed

Valladares, Macarena; Obregón, Ana María; Weisstaub, Gerardo; Burrows, Raquel; Patiño, Ana; Ho-Urriola, Judith; Santos, José Luis

2014-09-12

Leptin (LEP) is mainly produced in adipose tissue and acts in the hypothalamus to regulate energy intake. Mutations in the LEP gene or its receptor (LEPR) that produce monogenic obesity are infrequent. However, LEP and LEPR polymorphisms have been associated with obesity multifactorial, due to the association found with body weight and eating behavior. Measure the association between LEP and LEPR polymorphisms with childhood obesity and eating behavior. 221 Chilean obese children (BMI above the 95th percentile) were recruited. Parents of 134 of these children were also recruited to determine the association between LEP and LEPR polymorphisms with obesity in a case study-parent trio. Eating behavior was measured through the questionnaire of three factors progenitors' version (TFEQ-P19) and eating behavior in children (CEBQ). No significant difference between the studied polymorphisms and childhood obesity, after correction for multiple comparisons, was observed. The dimensions; "Slow eating", "emotional eating", "enjoyment of food" and "uncontrolling eating" were significant associated with certain polymorphisms of LEP and LEPR. There would be an association between polymorphisms of the LEP and LEPR genes with eating behavior in Chilean obese children. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Functional analysis of regulatory single-nucleotide polymorphisms.

PubMed

Pampín, Sandra; Rodríguez-Rey, José C

2007-04-01

The identification of regulatory polymorphisms has become a key problem in human genetics. In the past few years there has been a conceptual change in the way in which regulatory single-nucleotide polymorphisms are studied. We revise the new approaches and discuss how gene expression studies can contribute to a better knowledge of the genetics of common diseases. New techniques for the association of single-nucleotide polymorphisms with changes in gene expression have been recently developed. This, together with a more comprehensive use of the old in-vitro methods, has produced a great amount of genetic information. When added to current databases, it will help to design better tools for the detection of regulatory single-nucleotide polymorphisms. The identification of functional regulatory single-nucleotide polymorphisms cannot be done by the simple inspection of DNA sequence. In-vivo techniques, based on primer-extension, and the more recently developed 'haploChIP' allow the association of gene variants to changes in gene expression. Gene expression analysis by conventional in-vitro techniques is the only way to identify the functional consequences of regulatory single-nucleotide polymorphisms. The amount of information produced in the last few years will help to refine the tools for the future analysis of regulatory gene variants.

Sturgeon and paddlefish (Acipenseridae) saggital otoliths are composed of the calcium carbonate polymorphs vaterite and calcite: acipenseridae otoliths are vaterite and calcite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pracheil, Brenda M.; Chakoumakos, Bryan C.; Feygenson, Mikhail

The otoliths of modern fishes are most commonly comprised of the metastable aragonite polymorph of calcium carbonate (CaCO3); however, sturgeons have otoliths reportedly comprised of the least stable of the three most-common polymorphs, vaterite. In this study, we used neutron diffraction to characterize CaCO3 polymorph composition of lake sturgeon and paddlefish otoliths. Based on previous summaries of CaCO3 composition over fish evolutionary history, we hypothesized that sturgeon and paddlefish otoliths would have similar polymorph composition. We found that despite previous reports of sturgeon otoliths being comprised entirely of vaterite, that all otoliths we examined in this study also had amore » calcite fraction that ranged from 17.9+ 6.0 wt. % to 35.9 + 2.9 wt. %. We also conducted a grinding experiment that demonstrated that calcite fractions were due to biological variation and not an artifact of polymorph transformation during preparation. Our study provides the initial characterization of the polymorph composition of the otoliths of lake sturgeon, and paddlefish and also provides the first-ever report of otoliths of Acipenserids as having a calcite fraction.« less

Preproghrelin Leu72Met polymorphism in patients with type 2 diabetes mellitus.

PubMed

Ukkola, O; Kesäniemi, Y A

2003-10-01

The association between the Leu72Met polymorphism of the preproghrelin gene and diabetic complications was examined in patients with type 2 diabetes mellitus. A total of 258 patients with type 2 diabetes mellitus and 522 control subjects were screened. Genotypes were determined by polymerase chain reaction technique. The diagnosis of coronary heart disease was based on clinical and ECG criteria. Laboratory analyses were carried out in the hospital laboratory. No differences in the genotype distributions and allele frequencies of the preproghrelin Leu72Met polymorphism were found between type 2 diabetes mellitus patients and controls. The polymorphism was not associated with macro- or micro-angiopathy or hypertension. However, Leu72Met polymorphism was associated with serum creatinine (P = 0.006) and lipoprotein(a) [Lp(a)] levels (P = 0.006) with Leu72Leu subjects showing the highest values. This association was observed only amongst diabetic group. The Leu72Met polymorphism of the preproghrelin gene was not related to cardiovascular disease in type 2 diabetes mellitus patients. Leu72Met polymorphism was, however, associated with serum creatinine and Lp(a) levels in diabetic patients. The mechanism might be associated with a possible change in ghrelin product and its somatotropic effect.

Vascular endothelial growth factor (VEGF-634G/C) polymorphism and retinopathy of prematurity: a meta-analysis

PubMed Central

Malik, Manzoor Ahmad; Shukla, Swati; Azad, Shorya Vardhan; Kaur, Jasbir

2014-01-01

Purpose Vascular endothelial growth factor polymorphism (VEGF-634G/C, rs 2010963) has been considered a risk factor for the development of retinopathy of prematurity (ROP). However, the results remain controversial. Therefore, the aim of the present meta-analysis was to determine the association between VEGF-634G/C polymorphism and ROP risk. Methods Published literature from PubMed and other databases were retrieved. All studies evaluating the association between VEGF-634G/C polymorphism and ROP risk were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random or fixed effects model. A total of six case-control studies including 355 cases and 471 controls were included. Results By pooling all the studies, we found that VEGF-634G/C polymorphism was not associated with ROP risk at co-dominant and allele levels and no association was also found in dominant and recessive models. While stratifying on ethnicity level no association was observed in Caucasian and Asian population. Discussion This meta-analysis suggests that VEGF-634G/C polymorphism may not be associated with ROP risk, the association between single VEGF-634G/C polymorphism and ROP risk awaits further investigation. PMID:25473347

Modulation of risk of squamous cell carcinoma head and neck in North Indian population with polymorphisms in xeroderma pigmentosum complementation Group C gene.

PubMed

Yadav, Suresh Kumar; Singh, Sudhir; Gupta, Shalini; Brahma Bhatt, Madan Lal; Mishra, Durga P; Roy, D; Sanyal, Somali

2018-01-01

Genetic variations in nucleotide excision repair genes can alter the risk of squamous cell carcinoma of head and neck (SCCHN). The present study has genotyped 334 subjects from North Indian population for xeroderma pigmentosum complementation Group C (XPC) rs2228001A>C, XPC rs77907221 polyadenylate (PAT) deletion/insertion (D/I), xeroderma pigmentosum complementation Group D - rs13181A>C, and xeroderma pigmentosum complementation Type G rs17655 G>C polymorphisms with polymerase chain reaction (PCR)-restriction-fragment length polymorphism or allele-specific PCR methods. Compared to D allele, I allele for XPC PAT D/I polymorphism was associated with significantly decreased the risk of SCCHN (odds ratios = 0.67, 95% confidence interval [CI] =0.48-0.94, P = 0.03). Haplotype CI constituted from XPC polymorphisms was also associated with decreased risk of SCCHN (P = 0.004). In contrast, haplotype Crohn's disease significantly increased the risk for SCCHN (P < 0.00). A significant early onset of SCCHN was observed in individuals with CC genotype for XPC A>C polymorphism (P = 0.004). Our results suggest a possible risk modulation for SCCHN with XPC polymorphisms in North Indian population.

A functional EGF+61 polymorphism is associated with severity of obstructive sleep apnea.

PubMed

Ding, Qunli; Cao, Chao; Chen, Zhongbo; Tabusi, Mahebali; Chen, Li; Deng, Zaichun

2015-05-01

Involvement of epidermal growth factor (EGF) is reported in diseases caused by hypoxia. Its functional polymorphism may alter its transcription, affecting EGF expression, contributing to obstructive sleep apnea (OSA). The aim of this study was to investigate associations of EGF+61 polymorphism and risk of OSA. Two hundred two participants were enrolled in this case-control study. DNA was extracted from peripheral blood, and EGF 61A/G polymorphism was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. No significant association between EGF 61 A/G polymorphism and risk of OSA was observed in any of the gene models tested (AA vs. GG: OR = 0.97, 95% CI = 0.37-2.55; P = 0.95). However, compared with GG genotype, AG genotype associated with decreased risk of severe OSA (AG vs. GG: OR = 0.32, 95% CI = 0.11-0.94). Our study showed that AG genotype has a protective effect on OSA patients against severe disease, although EGF 61A/G polymorphisms have no role on the risk of the disease. Additional large studies should further validate our findings.

Polymorphs and polymorphic cocrystals of temozolomide.

PubMed

Babu, N Jagadeesh; Reddy, L Sreenivas; Aitipamula, Srinivasulu; Nangia, Ashwini

2008-07-07

Crystal polymorphism in the antitumor drug temozolomide (TMZ), cocrystals of TMZ with 4,4'-bipyridine-N,N'-dioxide (BPNO), and solid-state stability were studied. Apart from a known X-ray crystal structure of TMZ (form 1), two new crystalline modifications, forms 2 and 3, were obtained during attempted cocrystallization with carbamazepine and 3-hydroxypyridine-N-oxide. Conformers A and B of the drug molecule are stabilized by intramolecular amide N--HN(imidazole) and N--HN(tetrazine) interactions. The stable conformer A is present in forms 1 and 2, whereas both conformers crystallized in form 3. Preparation of polymorphic cocrystals I and II (TMZBPNO 1:0.5 and 2:1) were optimized by using solution crystallization and grinding methods. The metastable nature of polymorph 2 and cocrystal II is ascribed to unused hydrogen-bond donors/acceptors in the crystal structure. The intramolecularly bonded amide N-H donor in the less stable structure makes additional intermolecular bonds with the tetrazine C==O group and the imidazole N atom in stable polymorph 1 and cocrystal I, respectively. All available hydrogen-bond donors and acceptors are used to make intermolecular hydrogen bonds in the stable crystalline form. Synthon polymorphism and crystal stability are discussed in terms of hydrogen-bond reorganization.

Sturgeon and paddlefish (Acipenseridae) saggital otoliths are composed of the calcium carbonate polymorphs vaterite and calcite: acipenseridae otoliths are vaterite and calcite

DOE PAGES

Pracheil, Brenda M.; Chakoumakos, Bryan C.; Feygenson, Mikhail; ...

2016-07-27

The otoliths of modern fishes are most commonly comprised of the metastable aragonite polymorph of calcium carbonate (CaCO3); however, sturgeons have otoliths reportedly comprised of the least stable of the three most-common polymorphs, vaterite. In this study, we used neutron diffraction to characterize CaCO3 polymorph composition of lake sturgeon and paddlefish otoliths. Based on previous summaries of CaCO3 composition over fish evolutionary history, we hypothesized that sturgeon and paddlefish otoliths would have similar polymorph composition. We found that despite previous reports of sturgeon otoliths being comprised entirely of vaterite, that all otoliths we examined in this study also had amore » calcite fraction that ranged from 17.9+ 6.0 wt. % to 35.9 + 2.9 wt. %. We also conducted a grinding experiment that demonstrated that calcite fractions were due to biological variation and not an artifact of polymorph transformation during preparation. Our study provides the initial characterization of the polymorph composition of the otoliths of lake sturgeon, and paddlefish and also provides the first-ever report of otoliths of Acipenserids as having a calcite fraction.« less

Genomic and genotyping characterization of haplotype-based polymorphic microsatellites in Prunus

USDA-ARS?s Scientific Manuscript database

Efficient utilization of microsatellites in genetic studies remains impeded largely due to the unknown status of their primer reliability, chromosomal location, and allele polymorphism. Discovery and characterization of microsatellite polymorphisms in a taxon will disclose the unknowns and gain new ...

Frequency of CYP450 enzyme gene polymorphisms in the Greek population: review of the literature, original findings and clinical significance.

PubMed

Ragia, Georgia; Giannakopoulou, Efstathia; Karaglani, Makrina; Karantza, Ioanna-Maria; Tavridou, Anna; Manolopoulos, Vangelis G

2014-01-01

The cytochrome P450 (CYP450) enzyme family is involved in the oxidative metabolism of many therapeutic drugs and various endogenous substrates. These enzymes are highly polymorphic. Prevalence of CYP450 enzyme gene polymorphisms vary among different populations and substantial inter- and intra-ethnic variability in frequency of CYP450 enzyme gene polymorphisms has been reported. This paper provides an overview and investigation of CYP450 genotypic and phenotypic reports published in the Greek population.

Evaluation of human epidermal growth factor receptor 2 (HER2) single nucleotide polymorphisms (SNPs) in normal and breast tumor tissues and their link with breast cancer prognostic factors.

PubMed

Furrer, Daniela; Lemieux, Julie; Côté, Marc-André; Provencher, Louise; Laflamme, Christian; Barabé, Frédéric; Jacob, Simon; Michaud, Annick; Diorio, Caroline

2016-12-01

Amplification of the human epidermal growth factor receptor 2 (HER2) gene is associated with worse prognosis and decreased overall survival in breast cancer patients. The HER2 gene contains several polymorphisms; two of the best-characterized HER2 polymorphisms are Ile655Val and Ala1170Pro. The aim of this study was to evaluate the association between these two HER2 polymorphisms in normal breast and breast cancer tissues and known breast cancer prognostic factors in a retrospective cohort study of 73 women with non-metastatic HER2-positive breast cancer. HER2 polymorphisms were assessed in breast cancer tissue and normal breast tissue using TaqMan assay. Ala1170Pro polymorphism in normal breast tissue was associated with age at diagnosis (p = 0.007), tumor size (p = 0.004) and lymphovascular invasion (p = 0.06). Similar significant associations in cancer tissues were observed. No association between the Ile655Val polymorphism and prognostic factors were observed. However, we found significant differences in the distribution of Ile655Val (p = 0.03) and Ala1170Pro (p = 0.01) genotypes between normal breast and breast tumor tissues. This study demonstrates that only the Ala1170Pro polymorphism is associated with prognostic factors in HER2-positive breast cancer patients. Moreover, our results suggest that both HER2 polymorphisms could play a significant role in carcinogenesis in non-metastatic HER2-positive breast cancer women. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetic polymorphisms in the ESR1 gene and cerebral infarction risk: a meta-analysis.

PubMed

Gao, Hong-Hua; Gao, Lian-Bo; Wen, Jia-Mei

2014-09-01

A number of studies have documented that estrogen receptor α (ESR1) may play an important role in the development and progression of cerebral infarction, but many existing studies have yielded inconclusive results. This meta-analysis was performed to evaluate the relationships between ESR1 genetic polymorphisms and cerebral infarction risk. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before October 1, 2013, without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Seven case-control studies were included with a total of 1471 patients with cerebral infarction and 4688 healthy control subjects. Two common single-nucleotide polymorphisms (SNPs) in the ESR1 gene (rs2234693 T>C and rs9340799 A>G) were assessed. Our meta-analysis results revealed that ESR1 genetic polymorphisms might increase the risk of cerebral infarction. Subgroup analysis by SNP type indicated that both rs2234693 and rs9340799 polymorphisms in the ESR1 gene were strongly associated with an increased risk of cerebral infarction. Further subgroup analysis by ethnicity showed significant associations between ESR1 genetic polymorphisms and increased risk of cerebral infarction among both Asians and Caucasians. In the stratified subgroup analysis by gender, the results suggested that ESR1 genetic polymorphisms were associated with an increased risk of cerebral infarction in the female population. However, there were no statistically significant associations between ESR1 genetic polymorphisms and cerebral infarction risk in the male population. Meta-regression analyses also confirmed that gender might be a main source of heterogeneity. Our findings indicate that ESR1 genetic polymorphisms may contribute to the development of cerebral infarction, especially in the female population.

The Evaluation of IL6 and ESR1 Gene Polymorphisms in Primary Dysmenorrhea.

PubMed

Ozsoy, Asker Zeki; Karakus, Nevin; Yigit, Serbulent; Cakmak, Bulent; Nacar, Mehmet Can; Yılmaz Dogru, Hatice

2016-01-01

Primary dysmenorrhea is the most common gynecological complaint with painful menstrual cramps in pelvis without any pathology. It affects about half of menstruating women, and it causes significant disruption in quality of life. We investigated the association between IL6 gene promoter and ESR1 gene XbaI and PvuII polymorphisms and primary dysmenorrhea. In this case-control study, 152 unrelated young women with primary dysmenorrhea and 150 unrelated healthy age-matched controls participated. Genomic DNA was isolated and IL6 and ESR1 gene polymorphisms were genotyped using PCR-based RFLP assay. The distribution of genotype and allele frequencies of IL6 gene promoter and ESR1 gene XbaI polymorphisms were not statistically different between patients and controls (p > 0.05). However, the genotype and allele frequencies of ESR1 gene PvuII polymorphism showed statistically significant differences between primary dysmenorrhea patients and controls (p = 0.009 and p = 0.021, respectively). Statistically significant associations were also observed between age and married status of primary dysmenorrhea patients and ESR1 gene PvuII polymorphism (p = 0.044 and p = 0.023, respectively). In combined genotype analyses, AG at ESR1 XbaI and TC at ESR1 PvuII loci encoded a p-value of 0.027. Thus, individuals who are heterozygote at both loci have a lower risk of developing primary dysmenorrhea. Our study suggests no strong association between IL6 gene promoter and ESR1 gene XbaI polymorphisms and primary dysmenorrhea in Turkish women. However, ESR1 gene PvuII polymorphism showed statistically significant differences between primary dysmenorrhea patients and controls. The potential association between ESR1 gene PvuII polymorphism and age and married status of dysmenorrhea patients deserves further consideration.

Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes.

PubMed

Albrechtsen, A; Grarup, N; Li, Y; Sparsø, T; Tian, G; Cao, H; Jiang, T; Kim, S Y; Korneliussen, T; Li, Q; Nie, C; Wu, R; Skotte, L; Morris, A P; Ladenvall, C; Cauchi, S; Stančáková, A; Andersen, G; Astrup, A; Banasik, K; Bennett, A J; Bolund, L; Charpentier, G; Chen, Y; Dekker, J M; Doney, A S F; Dorkhan, M; Forsen, T; Frayling, T M; Groves, C J; Gui, Y; Hallmans, G; Hattersley, A T; He, K; Hitman, G A; Holmkvist, J; Huang, S; Jiang, H; Jin, X; Justesen, J M; Kristiansen, K; Kuusisto, J; Lajer, M; Lantieri, O; Li, W; Liang, H; Liao, Q; Liu, X; Ma, T; Ma, X; Manijak, M P; Marre, M; Mokrosiński, J; Morris, A D; Mu, B; Nielsen, A A; Nijpels, G; Nilsson, P; Palmer, C N A; Rayner, N W; Renström, F; Ribel-Madsen, R; Robertson, N; Rolandsson, O; Rossing, P; Schwartz, T W; Slagboom, P E; Sterner, M; Tang, M; Tarnow, L; Tuomi, T; van't Riet, E; van Leeuwen, N; Varga, T V; Vestmar, M A; Walker, M; Wang, B; Wang, Y; Wu, H; Xi, F; Yengo, L; Yu, C; Zhang, X; Zhang, J; Zhang, Q; Zhang, W; Zheng, H; Zhou, Y; Altshuler, D; 't Hart, L M; Franks, P W; Balkau, B; Froguel, P; McCarthy, M I; Laakso, M; Groop, L; Christensen, C; Brandslund, I; Lauritzen, T; Witte, D R; Linneberg, A; Jørgensen, T; Hansen, T; Wang, J; Nielsen, R; Pedersen, O

2013-02-01

Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) >1% with common metabolic phenotypes. The study comprised three stages. We performed medium-depth (8×) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI >27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. Exome sequencing identified 70,182 polymorphisms with MAF >1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 × 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 × 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 × 10(-10)). We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.

Gender-related survival differences associated with EGFR polymorphisms in metastatic colon cancer.

PubMed

Press, Oliver A; Zhang, Wu; Gordon, Michael A; Yang, Dongyun; Lurje, Georg; Iqbal, Syma; El-Khoueiry, Anthony; Lenz, Heinz-Josef

2008-04-15

Evidence is accumulating supporting gender-related differences in the development of colonic carcinomas. Sex steroid hormone receptors are expressed in the colon and interact with epidermal growth factor receptor (EGFR), a gene widely expressed in colonic tissue. Increased EGFR expression is linked with poor prognosis in colon cancer. Within the EGFR gene there are two functional polymorphisms of interest: a polymorphism located at codon 497 (HER-1 R497K) and a dinucleotide (CA)(n) repeat polymorphism located within intron 1. These germ-line polymorphisms of EGFR were analyzed in genomic DNA from 318 metastatic colon cancer patients, 177 males and 141 females, collected from 1992 to 2003. Gender-related survival differences were associated with the HER-1 R497K polymorphism (P(interaction) = 0.003). Females with the HER-1 497 Arg/Arg variant had better overall survival (OS) when compared with the Lys/Lys and/or Lys/Arg variants. In males the opposite was true. The EGFR dinucleotide (CA)(n) repeat also trended with a gender-related OS difference (P(interaction) = 0.11). Females with both short <20 (CA)(n) repeat alleles had better OS than those with any long >or=20 (CA)(n) repeats. In males the opposite was true. Combination analysis of the two polymorphisms taken together also revealed the same gender-related survival difference (P(interaction) = 0.002). These associations were observed using multivariable analysis. The two polymorphisms were not in linkage disequilibrium and are independent of one another. This study supports the role of functional EGFR polymorphisms as independent prognostic markers in metastatic colon cancer. As a prognostic factor, these variants had opposite prognostic implications based on gender.

Polymorphism in endothelin-related genes limits exercise-induced decreases in arterial stiffness in older subjects.

PubMed

Iemitsu, Motoyuki; Maeda, Seiji; Otsuki, Takeshi; Sugawara, Jun; Tanabe, Takumi; Jesmin, Subrina; Kuno, Shinya; Ajisaka, Ryuichi; Miyauchi, Takashi; Matsuda, Mitsuo

2006-05-01

Increase in arterial stiffness is associated with aging, which is improved by regular exercise. Endothelin (ET) system has crucial roles in regulating vascular tone and in the progression of atherosclerosis. We hypothesized that molecular variations (ie, gene polymorphisms) in ET-related gene might affect exercise-induced improvement in arterial stiffness with age in human subjects. The present study provides a cross-sectional investigation of 191 healthy middle-aged and older (65+/-1 years) human subjects to clarify the relationship between the regular exercise-induced improvement of arterial stiffness and the gene polymorphisms of ET converting enzyme (ECE)-1, ECE-2, ET-A receptor (ET-A), and ET-B receptor (ET-B). The study subjects were divided into active and inactive groups based on the median value (186 kcal/d) of energy expenditure. Brachial-ankle arterial pulse wave velocity (baPWV) was used to evaluate arterial stiffness. All individuals were genotyped for 4 different polymorphisms of the ET system: 2013(+289)A/G in intron 17 of ECE-1, 669(+17)T/C in intron 5 of ECE-2, 958A/G in exon 6 of ET-A, and 831A/G in exon 4 of ET-B. The baseline baPWV was significantly lower in the active group without any change in blood pressure. Polymorphisms in ECE-1 influenced basal blood pressure. Polymorphisms in ECE-1 and ECE-2 had no effect on baPWV between active and inactive groups. However, polymorphisms in both ET-A and ET-B affected baPWV in the 2 groups. The present results suggest that differences in ET-A and ET-B polymorphisms may influence the response of the vascular wall to exercise whereas ECE-1 polymorphisms may affect basal blood pressure.

Bitterness of the Non-nutritive Sweetener Acesulfame Potassium Varies With Polymorphisms in TAS2R9 and TAS2R31

PubMed Central

2013-01-01

Demand for nonnutritive sweeteners continues to increase due to their ability to provide desirable sweetness with minimal calories. Acesulfame potassium and saccharin are well-studied nonnutritive sweeteners commonly found in food products. Some individuals report aversive sensations from these sweeteners, such as bitter and metallic side tastes. Recent advances in molecular genetics have provided insight into the cause of perceptual differences across people. For example, common alleles for the genes TAS2R9 and TAS2R38 explain variable response to the bitter drugs ofloxacin in vitro and propylthiouracil in vivo. Here, we wanted to determine whether differences in the bitterness of acesulfame potassium could be predicted by common polymorphisms (genetic variants) in bitter taste receptor genes (TAS2Rs). We genotyped participants (n = 108) for putatively functional single nucleotide polymorphisms in 5 TAS2Rs and asked them to rate the bitterness of 25 mM acesulfame potassium on a general labeled magnitude scale. Consistent with prior reports, we found 2 single nucleotide polymorphisms in TAS2R31 were associated with acesulfame potassium bitterness. However, TAS2R9 alleles also predicted additional variation in acesulfame potassium bitterness. Conversely, single nucleotide polymorphisms in TAS2R4, TAS2R38, and near TAS2R16 were not significant predictors. Using 1 single nucleotide polymorphism each from TAS2R9 and TAS2R31, we modeled the simultaneous influence of these single nucleotide polymorphisms on acesulfame potassium bitterness; together, these 2 single nucleotide polymorphisms explained 13.4% of the variance in perceived bitterness. These data suggest multiple polymorphisms within TAS2Rs contribute to the ability to perceive the bitterness from acesulfame potassium. PMID:23599216

[Retrospective Study of Efficacy in BIM Gene Polymorphism on First-line EGFR-TKIs Treatment for Advanced Lung Adenocarcinoma].

PubMed

Qian, Kun; Zhang, Yi; Zhi, Xiuyi

2017-08-20

The aim of this study is to detect the BIM polymorphism in 85 formalin-fixed and parrffin-embedded (FFPE) and some blood samples of advanced lung adenocarcinoma patients and study the relativity betweenthe BIM polymorphism and tyrosine kinase inhibitor (TKI). The correlation between BIM detection of different types of specimens was discussed. There were 85 patients who were diagnosed as advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) 19 or 21 exon mutation in thoracic surgery of Xuanwu Hospital from February 2013 to November 2014, all of who were received EGFR-TKI as first-line treatment in the study. FFPE and some blood were used to detect the BIM polymorphism. The objective response rate (ORR) and progression-free survival (PFS) of two groups were compared. According to smoking, sex, EGFR mutation and other factors, the single factor analysis was performed, and the correlation between paraffin samples and blood test BIM was compared. The ORR in BIM polymorphism and non-polymorphism groups was no significant differences (P>0.05). The median PFS in BIM polymorphism and non-polymorphism group was 7.1 months and 12.8 months, respectively (P=0.013). Univariate analysis the median PFS, women were longer than men (12.1 months vs 10.7 months, P=0.835); Non-smokers were longer than smokers (12.1 months vs 9.7 months, P=0.974). Group in EGFR exon 21 is longer than group in EGFR exon 19 (12.2 months vs 8.7 months, P=0.303). Detection of BIM gene polymorphism in lung cancer patients with EGFR-TKIs treatment might be helpful for predicting prognosis. But a large sample study is needed.

To evaluate the effect of various magnesium stearate polymorphs using powder rheology and thermal analysis.

PubMed

Okoye, Patrick; Wu, Stephen H; Dave, Rutesh H

2012-12-01

The effects of magnesium stearate (MgSt) polymorphs-anhydrate (MgSt-A), monohydrate (MgSt-M), and dihydrate (MgSt-D)-on rheological properties of powders were evaluated using techniques such as atomic analysis and powder rheometry. Additional evaluation was conducted using thermal analysis, micromeritics, and tableting forces. In this study, binary ratios of neat MgSt polymorphs were employed as lubricants in powder blends containing acetaminophen (APAP), microcrystalline cellulose (MCC), and lactose monohydrate (LAC-M). Powder rheometry was studied using permeability, basic flow energy (BFE), density, and porosity analysis. Thermal conductivity and differential scanning calorimetric analysis of MgSt polymorphs were employed to elucidate MgSt effect on powder blends. The impact of MgSt polymorphs on compaction characteristics were analyzed via tablet compression forces. Finally, the distribution of atomized magnesium (Mg) ions as a function of intensity was evaluated using laser-induced breakdown spectroscopy (LIBS) on tablets. The results from LIBS analysis indicated the dependency of the MgSt polymorphic forms on the atomized Mg ion intensity, with higher Mg ion intensity suggesting higher lubricity index (i.e. greater propensity to over-lubricate). The results from lubricity index suggested the tendency of blends to over-lubricate based on the MgSt polymorphic forms. Finally, tableting forces suggested that MgSt-D and MgSt-A offered processing benefits such as lower ejection and compression forces, and that MgSt-M showed the most stable compression force in single or combined polymorphic ratios. These results suggested that the initial moisture content, crystal arrangement, intra- and inter-molecular packing of the polymorphs defined their effects on the rheology of lubricated powders.

Markers and mapping revisited: finding your gene.

PubMed

Jones, Neil; Ougham, Helen; Thomas, Howard; Pasakinskiene, Izolda

2009-01-01

This paper is an update of our earlier review (Jones et al., 1997, Markers and mapping: we are all geneticists now. New Phytologist 137: 165-177), which dealt with the genetics of mapping, in terms of recombination as the basis of the procedure, and covered some of the first generation of markers, including restriction fragment length polymorphisms (RFLPs), random amplified polymorphic DNA (RAPDs), simple sequence repeats (SSRs) and quantitative trait loci (QTLs). In the intervening decade there have been numerous developments in marker science with many new systems becoming available, which are herein described: cleavage amplification polymorphism (CAP), sequence-specific amplification polymorphism (S-SAP), inter-simple sequence repeat (ISSR), sequence tagged site (STS), sequence characterized amplification region (SCAR), selective amplification of microsatellite polymorphic loci (SAMPL), single nucleotide polymorphism (SNP), expressed sequence tag (EST), sequence-related amplified polymorphism (SRAP), target region amplification polymorphism (TRAP), microarrays, diversity arrays technology (DArT), single-strand conformation polymorphism (SSCP), denaturing gradient gel electrophoresis (DGGE), temperature gradient gel electrophoresis (TGGE) and methylation-sensitive PCR. In addition there has been an explosion of knowledge and databases in the area of genomics and bioinformatics. The number of flowering plant ESTs is c. 19 million and counting, with all the opportunity that this provides for gene-hunting, while the survey of bioinformatics and computer resources points to a rapid growth point for future activities in unravelling and applying the burst of new information on plant genomes. A case study is presented on tracking down a specific gene (stay-green (SGR), a post-transcriptional senescence regulator) using the full suite of mapping tools and comparative mapping resources. We end with a brief speculation on how genome analysis may progress into the future of this highly dynamic arena of plant science.

Investigation of the Sensitivity of Transmission Raman Spectroscopy for Polymorph Detection in Pharmaceutical Tablets.

PubMed

Feng, Hanzhou; Bondi, Robert W; Anderson, Carl A; Drennen, James K; Igne, Benoît

2017-08-01

Polymorph detection is critical for ensuring pharmaceutical product quality in drug substances exhibiting polymorphism. Conventional analytical techniques such as X-ray powder diffraction and solid-state nuclear magnetic resonance are utilized primarily for characterizing the presence and identity of specific polymorphs in a sample. These techniques have encountered challenges in analyzing the constitution of polymorphs in the presence of other components commonly found in pharmaceutical dosage forms. Laborious sample preparation procedures are usually required to achieve satisfactory data interpretability. There is a need for alternative techniques capable of probing pharmaceutical dosage forms rapidly and nondestructively, which is dictated by the practical requirements of applications such as quality monitoring on production lines or when quantifying product shelf lifetime. The sensitivity of transmission Raman spectroscopy for detecting polymorphs in final tablet cores was investigated in this work. Carbamazepine was chosen as a model drug, polymorph form III is the commercial form, whereas form I is an undesired polymorph that requires effective detection. The concentration of form I in a direct compression tablet formulation containing 20% w/w of carbamazepine, 74.00% w/w of fillers (mannitol and microcrystalline cellulose), and 6% w/w of croscarmellose sodium, silicon dioxide, and magnesium stearate was estimated using transmission Raman spectroscopy. Quantitative models were generated and optimized using multivariate regression and data preprocessing. Prediction uncertainty was estimated for each validation sample by accounting for all the main variables contributing to the prediction. Multivariate detection limits were calculated based on statistical hypothesis testing. The transmission Raman spectroscopic model had an absolute prediction error of 0.241% w/w for the independent validation set. The method detection limit was estimated at 1.31% w/w. The results demonstrated that transmission Raman spectroscopy is a sensitive tool for polymorphs detection in pharmaceutical tablets.

G-231A and G+70C Polymorphisms of Endothelin Receptor Type-A Gene could Affect the Psoriasis Area and Severity Index Score and Endothelin 1 Levels.

PubMed

Okan, Gökhan; Yıldız, Zeynep; Gökdemir, Gonca; Yorulmaz, Eda; Vural, Pervin; Doğru-Abbasoğlu, Semra; Uysal, Müjdat

2015-01-01

The etiopathogenesis of psoriasis has not been clearly elucidated although the role of chronic inflammation, imbalance between pro- and anti-inflammatory cytokines, and many immunological events have been established. Endothelin 1 (EDN1) and endothelin receptor type-A (EDNRA) are implicated in the inflammatory process. The relationships between EDN1 and EDNRA polymorphisms with several diseases have been found. This study examined the possible association of EDN1 (G5665T and T-1370G) and EDNRA (G-231A and G + 70C) single nucleotide polymorphisms (SNPs) with the occurence of psoriasis, and evaluated the relationship between genotypes and clinical/laboratory manifestation of psoriasis. We analyzed genotype and allele distributions of the above-mentioned polymorphisms in 151 patients with psoriasis and 152 healthy controls by real-time PCR combined with melting curve analysis. We did not find significant differences in the genotype and allele distributions of EDN1 T-1370G, EDNRA G-231A, and EDNRA G+70C polymorphisms between patients with psoriasis and healthy controls. Psoriasis area and severity index (PASI) score of EDNRA -231 polymorphic A allele carrying subjects (AA and AA + AG) was higher than that of wild homozygotes (P = 0.044 and P = 0.027, respectively). In addition, EDN1 levels in EDNRA+70 polymorphic C allele carriers (CC + CG) were elevated when compared with GG genotype; however, the difference was at borderline significance (P = 0.05). Although there were no associations between studied polymorphisms and psoriasis susceptibility, the PASI score and EDN1 levels seem to be affected by EDNRA G-231A and G + 70C polymorphisms.

Association between ALDH2 rs671 G>A polymorphism and gastric cancer susceptibility in Eastern Asia

PubMed Central

Jiang, You; Zhang, Jun; Wu, Yuee; Wang, Jian; Li, Liang

2017-01-01

To date, the relationship between the aldehyde dehydrogenases-2 (ALDH2) rs671 G>A (Glu504Lys) polymorphism and gastric cancer (GC) risk has not been thoroughly elucidated. To derive a more precise estimation of the effect of the ALDH2 rs671 G>A polymorphism on GC, we conducted this meta-analysis. We searched for qualified studies in the Embase, PubMed, Wang Fan and China National Knowledge Infrastructure databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association. A total of 6,421 GC patients and 8,832 control subjects were included in the present study. The pooled results indicated no significant relationship between the ALDH2 rs671 G>A polymorphism and GC susceptibility in all genetic models. A stratified analysis by country showed that the ALDH2 rs671 G>A polymorphism might be a risk factor for GC in Japan (Allele model: P unadjusted = 0.034; Dominant model: P unadjusted = 0.040); however, the result was nonsignificant when the Bonferroni correction and false discovery rate (FDR) were applied. In subgroup analyses by drinking status in the dominant model, our study revealed that the ALDH2 rs671 G>A polymorphism significantly increased the risk of GC for drinkers (dominant model: P < 0.001). No relationship between the ALDH2 rs671 G>A polymorphism and GC risk was observed in any other subgroup. Our present study indicated no association between the ALDH2 rs671 G>A polymorphism and GC risk in Eastern Asian populations. However, the ALDH2 rs671 G>A polymorphism can significantly increase GC risk for drinkers. PMID:29254255

Prevalence of alpha actinin-3 gene (ACTN3) R577X and angiotensin converting enzyme (ACE) insertion / deletion gene polymorphisms in national and amateur Turkish athletes.

PubMed

Eroğlu, Onur; Zileli, Rayif; Nalbant, M Ali; Ulucan, Korkut

2018-04-30

Studies to date showed the importance of alpha- actinin-3 (ACTN3) R577X and angiotensin converting enzyme (ACE) ID polymorphisms on determining athletic performance. Therefore, in this study, we aimed to examine polymorphisms given to Turkish athletes and compare them with sedentary individuals. Genomic DNAs were extracted from peripheral blood by using commercially available DNA isolation kit (Macherey-Nagel, NucleoSpin®, Germany). For this study, a total of 84 volunteers (23 national athletes, 27 amateur athletes and 34 sedentary controls) was recruited.  ACE ID genotypes were determined by conventional polymerase chain reaction, and ACTN3 R577X polymorphisms by polymerase chain reaction- restriction fragment length polymorphism methodology.   In ACTN3 R577X polymorphism, RX was the dominating genotype, and we detected no RR genotype in national athletes. (no RR genotype was detected in national athletes) X allele is more frequent in national athletes and R allele was more frequent in both amateur athletes and control group. II genotype was more frequent in national athletes and in control group, whereas DD genotype was more frequent in amateur athletes for ACE ID polymorphism. When we consider alleles, D allele was found more frequently in amateur athletes and control group whereas I allele was more frequent in national athletes in ACE ID polymorphism. For ACTN3, X allele was superior to R allele. ACTN3 R577X and ACE ID polymorphisms were important biomarkers in determining athletic performance. However, our results in Turkish athletes suggest that ACE D allele and ACTN3 X alleles may be beneficial to athletes potentially, regardless of the distance they perform.

Presence of the p.L456V polymorphism in Cuban patients clinically diagnosed with Wilson's disease.

PubMed

Clark-Feoktistova, Y; Ruenes-Domech, C; García-Bacallao, E F; Roblejo-Balbuena, H; Feoktistova, L; Clark-Feoktistova, I; Jay-Herrera, O; Collazo-Mesa, T

2018-06-10

Wilson's disease is characterized by the accumulation of copper in different organs, mainly affecting the liver, brain, and cornea, and is caused by mutations in the ATP7B gene. More than 120 polymorphisms in the ATP7B gene have been reported in the medical literature. The aim of the present study was to identify the conformational changes in the exon 3 region of the ATP7B gene and detect the p.L456V polymorphism in Cuban patients clinically diagnosed with Wilson's disease. A descriptive study was conducted at the Centro Nacional de Genética Médica and the Instituto Nacional de Gastroenterología within the time frame of 2007-2012 and included 105 patients with a clinical diagnosis of Wilson's disease. DNA extraction was performed through the salting-out method and the fragment of interest was amplified using the polymerase chain reaction technique. The conformational shift changes in the exon 3 region and the presence of the p.L456V polymorphism were identified through the Single-Strand Conformation Polymorphism analysis. The so-called b and c conformational shift changes, corresponding to the p.L456V polymorphism in the heterozygous and homozygous states, respectively, were identified. The allelic frequency of the p.L456V polymorphism in the 105 Cuban patients that had a clinical diagnosis of Wilson's disease was 41% and liver-related symptoms were the most frequent in the patients with that polymorphism. The p.L456V polymorphism was identified in 64 Cuban patients clinically diagnosed with Wilson's disease, making future molecular study through indirect methods possible. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Genetic polymorphisms in the amino acid transporters LAT1 and LAT2 in relation to the pharmacokinetics and side effects of melphalan.

PubMed

Kühne, Annett; Kaiser, Rolf; Schirmer, Markus; Heider, Ulrike; Muhlke, Sabine; Niere, Wiebke; Overbeck, Tobias; Hohloch, Karin; Trümper, Lorenz; Sezer, Orhan; Brockmöller, Jürgen

2007-07-01

Melphalan is widely used in the treatment of multiple myeloma. Pharmacokinetics of this alkylating drug shows high inter-individual variability. As melphalan is a phenylalanine derivative, the pharmacokinetic variability may be determined by genetic polymorphisms in the L-type amino acid transporters LAT1 (SLC7A5) and LAT2 (SLC7A8). Pharmacokinetics were analysed in 64 patients after first administration of intravenous melphalan. Severity of side effects was documented according to WHO criteria. Genomic DNA was analysed for polymorphisms in LAT1 and LAT2 by sequencing of the entire coding region, intron-exon boundaries and 2 kb upstream promoter region. Selected polymorphisms in the common heavy chain of both transporters, the protein 4F2hc (SLC3A2), were analysed by single nucleotide primer extension. Melphalan pharmacokinetics was highly variable with up to 6.2-fold differences in total clearance. A total of 44 polymorphisms were identified in LAT1 and 21 polymorphisms in LAT2. From all variants, only five were in the coding region and only one heterozygous non-synonymous polymorphism (Ala94Thr) was found in LAT2. Numerous polymorphisms were found in the LAT1 and LAT2 5'-flanking regions but did not correlate with expression of the respective genes. No significant correlations could be observed between the polymorphisms in 4F2hc, LAT1, and LAT2 with melphalan pharmacokinetics or with melphalan side effects. The study confirmed that these transporter genes are highly conserved, particularly in the coding sequences. Genetic variation in 4F2hc, LAT1, and LAT2 does not appear to be a major cause of inter-individual variability in pharmacokinetics and of adverse reactions to melphalan.

Mismatch repair gene MSH3 polymorphism is associated with the risk of sporadic prostate cancer.

PubMed

Hirata, Hiroshi; Hinoda, Yuji; Kawamoto, Ken; Kikuno, Nobuyuki; Suehiro, Yutaka; Okayama, Naoko; Tanaka, Yuichiro; Dahiya, Rajvir

2008-05-01

The mismatch repair system is a DNA repair mechanism that corrects mispaired bases during DNA replication errors. Cancer cells deficient in MMR proteins have a 10(2) to 10(3)-fold increase in the mutation rate. Single nucleotide polymorphisms of mismatch repair genes have been shown to cause a decrease in DNA repair activity. We hypothesized that mismatch repair gene polymorphism could be a risk factor for prostate cancer and p53 Pro/Pro genotype carriers could influence MSH3 and MSH6 polymorphisms. DNA samples from 110 patients with prostate cancer and 110 healthy controls were analyzed by single strand conformational polymorphism and polymerase chain reaction-restriction fragment length polymorphism to determine the genotypic frequency of 5 polymorphic loci on 2 MMR genes (MSH3 and MSH6) and p53 codon72. The chi-square test was applied to compare genotype frequency between patients and controls. A significant increase in the G/A+A/A genotype of MSH3 Pro222Pro was observed in patients compared to controls (OR 1.87, 95% CI 1.0-3.5). The frequency of A/G + G/G genotypes of MSH3 exon23 Thr1036Ala also tended to increase in patients (OR 1.57, 95% CI 0.92-2.72). In p53 codon72 Arg/Pro + Pro/Pro carriers the frequency of the AG + GG genotype of MSH3 exon23 was significantly increased in patients compared to controls (OR 2.1, 95% CI 1.05-4.34). To our knowledge this is the first report of the association of MSH3 gene polymorphisms in prostate cancer. These results suggest that the MSH3 polymorphism may be a risk factor for prostate cancer.

The association of RANK gene C421T and C575T polymorphisms with bone mineral density in postmenopausal Turkish women.

PubMed

Işleten, Banu; Durmaz, Burak; Durmaz, Berrin; Onay, Hüseyin; Ozkınay, Ferda; Durmaz, Asude; Turan, Volkan; Oztekin, Kemal

2013-10-01

To investigate the association between C421T polymorphism within exon 4, C575T polymorphism within exon 6 of the RANK gene and bone mineral density (BMD) variations in postmenopausal Turkish women. One hundred seventy-eight postmenopausal women (patients = 100 and controls = 78) who applied to Ege University Faculty of Medicine, Department of Physical Medicine and Rehabilitation, for osteoporosis examination were analyzed. BMDs of the lumbar spine and femoral sites were measured. Patient and control groups were established based on their T-score values being above and/or below -1. After venous blood sampling, C421T and C575T polymorphisms of the RANK gene were assessed through PCR process following DNA extraction. Genotype frequencies for the C421T and C575T polymorphisms were compared between the control group and the patient group. No significant difference was detected between the two groups for both polymorphisms. There was also no significant difference between the control and patient groups in terms of the combined genotype (p = 0.752) and the combined haplotype analysis of the C421T and C575T polymorphisms (p = 0.723). In the control and patient groups separately, no significant differences in BMD values either at the femoral sites or at the lumbar spine were detected between the combined genotypes of the two polymorphisms. The genotypes, combined genotypes and allele frequencies of C421T and C575T polymorphisms of the RANK gene have not been found to be associated with BMD in Turkish women. Further studies including both sexes and more cases are required.

Association of CRTC1 polymorphisms with obesity markers in subjects from the general population with lifetime depression.

PubMed

Quteineh, Lina; Preisig, Martin; Rivera, Margarita; Milaneschi, Yuri; Castelao, Enrique; Gholam-Rezaee, Mehdi; Vandenberghe, Frederik; Saigi-Morgui, Nuria; Delacrétaz, Aurélie; Cardinaux, Jean-René; Willemsen, Gonneke; Boomsma, Dorret I; Penninx, Brenda W J H; Ching-López, Ana; Conus, Philippe; Eap, Chin B

2016-07-01

Psychiatric disorders have been hypothesized to share common etiological pathways with obesity, suggesting related neurobiological bases. We aimed to examine whether CRTC1 polymorphisms were associated with major depressive disorder (MDD) and to test the association of these polymorphisms with obesity markers in several large case-control samples with MDD. The association between CRTC1 polymorphisms and MDD was investigated in three case-control samples with MDD (PsyCoLaus n1=3,362, Radiant n2=3,148 and NESDA/NTR n3=4,663). The effect of CRTC1 polymorphisms on obesity markers was then explored. CRTC1 polymorphisms were not associated with MDD in the three samples. CRTC1 rs6510997C>T was significantly associated with fat mass in the PsyCoLaus study. In fact, a protective effect of this polymorphism was found in MDD cases (n=1,434, β=-1.32%, 95% CI -2.07 to -0.57, p<0.001), but not in controls. In the Radiant study, CRTC1 polymorphisms were associated with BMI, exclusively in individuals with MDD (n=2,138, β=-0.75kg/m(2), 95% CI -1.30 to -0.21, p=0.007), while no association with BMI was found in the NESDA/NTR study. Estimated fat mass using bioimpedance that capture more accurately adiposity was only present in the PsyCoLaus sample. CRTC1 polymorphisms seem to play a role with obesity markers in individuals with MDD rather than non-depressive individuals. Therefore, the weak association previously reported in the population-based samples was driven by cases diagnosed with lifetime MDD. However, CRTC1 seems not to be implicated directly in the development of psychiatric diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Association of UGT2B7 and UGT1A4 Polymorphisms with Serum Concentration of Antiepileptic Drugs in Children.

PubMed

Du, Zhongliang; Jiao, Yukun; Shi, Lianting

2016-10-31

BACKGROUND This study aimed to analyze the relationship of UGT2B7 and UGT1A4 polymorphisms with metabolism of valproic acid (VPA) and lamotrigine (LTG) in epileptic children. MATERIAL AND METHODS We administered VPA (102) and LTG (102) to 204 children with epilepsy. Blood samples were collected before the morning dose. Serum concentration of LTG was measured by high-performance liquid chromatography (HPLC). Serum VPA concentration was tested by fluorescence polarization immunoassay. UGT2B7 A268G, C802T, and G211T polymorphisms, as well as UGT1A4 L48V polymorphism, were assayed by direct automated DNA sequencing after PCR. Evaluation of efficacy was conducted using the Engel method. RESULTS The adjusted serum concentration of VPA was 4.26 μg/mL per mg/kg and LTG was 1.56 μg/mL per mg/kg. Multiple linear regression analysis revealed that VPA or LTG adjusted concentration showed a good linear relation with sex and age. UGT2B7 A268G and C802T polymorphisms were demonstrated to affect the serum concentration of VPA (F=3.147, P=0.047; F=22.754, P=0.000). UGT1A4 L48V polymorphism was not related with the serum concentration of LTG (F=5.328, P=0.006). In the efficacy analysis, we found that C802T polymorphism exerted strong effects on efficacy of VPA (χ²=9.265, P=0.010). L48V polymorphism also showed effects on efficacy of LTG (χ²=17.397, P=0.001). CONCLUSIONS UGT2B7, UGT1A4 polymorphisms play crucial roles in metabolism of VPA and LTG.

Colour polymorphism is associated with lower extinction risk in birds.

PubMed

Ducatez, Simon; Giraudeau, Mathieu; Thébaud, Christophe; Jacquin, Lisa

2017-08-01

Colour polymorphisms have played a major role in enhancing current understanding of how selection and demography can impact phenotypes. Because different morphs often display alternative strategies and exploit alternative ecological niches, colour polymorphism can be expected to promote adaptability to environmental changes. However, whether and how it could influence populations' and species' response to global changes remains debated. To address this question, we built an up-to-date and complete database on avian colour polymorphism based on the examination of available data from all 10,394 extant bird species. We distinguished between true polymorphism (where different genetically determined morphs co-occur in sympatry within the same population) and geographic variation (parapatric or allopatric colour variation), because these two patterns of variation are expected to have different consequences on populations' persistence. Using the IUCN red list, we then showed that polymorphic bird species are at lesser risk of extinction than nonpolymorphic ones, after controlling for a range of factors such as geographic range size, habitat breadth, life history, and phylogeny. This appears consistent with the idea that high genetic diversity and/or the existence of alternative strategies in polymorphic species promotes the ability to adaptively respond to changing environmental conditions. In contrast, polymorphic species were not less vulnerable than nonpolymorphic ones to specific drivers of extinction such as habitat alteration, direct exploitation, climate change, and invasive species. Thus, our results suggest that colour polymorphism acts as a buffer against environmental changes, although further studies are now needed to understand the underlying mechanisms. Developing accurate quantitative indices of sensitivity to specific threats is likely a key step towards a better understanding of species response to environmental changes. © 2017 John Wiley & Sons Ltd.

Relationship of MTHFR gene polymorphisms with renal and cardiac disease

PubMed Central

Trovato, Francesca M; Catalano, Daniela; Ragusa, Angela; Martines, G Fabio; Pirri, Clara; Buccheri, Maria Antonietta; Di Nora, Concetta; Trovato, Guglielmo M

2015-01-01

AIM: To investigate the effects of different methylenetetrahydrofolate reductase (MTHFR) 677C>T gene polymorphism and hyperhomocysteinemia for the development of renal failure and cardiovascular events, which are controversial. METHODS: We challenged the relationship, if any, of MTHFR 677C>T and MTHFR 1298A>C polymorphisms with renal and heart function. The present article is a reappraisal of these concepts, investigating within a larger population, and including a subgroup of dialysis patients, if the two most common MTHFR polymorphisms, C677T and A1298C, as homozygous, heterozygous or with a compound heterozygous state, show different association with chronic renal failure requiring hemodialysis. MTHFR polymorphism could be a favorable evolutionary factor, i.e., a protective factor for many ominous conditions, like cancer and renal failure. A similar finding was reported in fatty liver disease in which it is suggested that MTHFR polymorphisms could have maintained and maintain their persistence by an heterozygosis advantage mechanism. We studied a total of 630 Italian Caucasian subject aged 54.60 ± 16.35 years, addressing to the increased hazard of hemodialysis, if any, according to the studied MTHFR genetic polymorphisms. RESULTS: A favorable association with normal renal function of MTHFR polymorphisms, and notably of MTHFR C677T is present independently of the negative effects of left ventricular hypertrophy, increased Intra-Renal arterial Resistance and hyperparathyroidism. CONCLUSION: MTHFR gene polymorphisms could have a protective role on renal function as suggested by their lower frequency among our dialysis patients in end-stage renal failure; differently, the association with left ventricular hypertrophy and reduced left ventricular relaxation suggest some type of indirect, or concurrent mechanism. PMID:25664255