Attachment in the Making: Mother and Father Sensitivity and Infants’ Responses during the Still-Face Paradigm

PubMed Central

Braungart-Rieker, Julia M.; Zentall, Shannon; Lickenbrock, Diane M.; Ekas, Naomi V.; Oshio, Toko; Planalp, Elizabeth

2014-01-01

This study examined the extent to which infant and parent response trajectories during the Still-Face-Paradigm (SFP) in early infancy predicted later infant-mother and infant-father attachment. Families (n = 135) participated in the SFP when infants were 3, 5, and 7 months and the Strange Situation when infants were 12 (mothers) and 14 months (fathers). Multilevel models showed that parent sensitivity assessed during the SFP was related to infants’ affective and behavioral response trajectories during the SFP, and that sensitivity and infant response trajectories predicted attachment. Results from the present study support the notion that parent and infant responses in the SFP with mothers and fathers during Bowlby’s Attachment in the Making phase provide insight into the developing parent-child attachment relationship. PMID:24833270

Bayesian inference based on stationary Fokker-Planck sampling.

PubMed

Berrones, Arturo

2010-06-01

A novel formalism for bayesian learning in the context of complex inference models is proposed. The method is based on the use of the stationary Fokker-Planck (SFP) approach to sample from the posterior density. Stationary Fokker-Planck sampling generalizes the Gibbs sampler algorithm for arbitrary and unknown conditional densities. By the SFP procedure, approximate analytical expressions for the conditionals and marginals of the posterior can be constructed. At each stage of SFP, the approximate conditionals are used to define a Gibbs sampling process, which is convergent to the full joint posterior. By the analytical marginals efficient learning methods in the context of artificial neural networks are outlined. Offline and incremental bayesian inference and maximum likelihood estimation from the posterior are performed in classification and regression examples. A comparison of SFP with other Monte Carlo strategies in the general problem of sampling from arbitrary densities is also presented. It is shown that SFP is able to jump large low-probability regions without the need of a careful tuning of any step-size parameter. In fact, the SFP method requires only a small set of meaningful parameters that can be selected following clear, problem-independent guidelines. The computation cost of SFP, measured in terms of loss function evaluations, grows linearly with the given model's dimension.

Environmental and nutrition impact of achieving new School Food Plan recommendations in the primary school meals sector in England

PubMed Central

Wickramasinghe, Kremlin; Rayner, Mike; Goldacre, Michael; Townsend, Nick; Scarborough, Peter

2017-01-01

Objectives The aim of this modelling study was to estimate the expected changes in the nutritional quality and greenhouse gas emissions (GHGEs) of primary school meals due to the adoption of new mandatory food-based standards for school meals. Setting Nationally representative random sample of 136 primary schools in England was selected for the Primary School Food Survey (PSFS) with 50% response rate. Participants A sample of 6690 primary students from PSFS who consumed school meals. Outcome measures Primary School Food Plan (SFP) nutritional impact was assessed using both macronutrient and micronutrient quality. The environmental impact was measured by GHGEs. Methods The scenario tested was one in which every meal served in schools met more than half of the food-based standards mentioned in the SFP (SFP scenario). We used findings from a systematic review to assign GHGE values for each food item in the data set. The GHGE value and nutritional quality of SFP scenario meals was compared with the average primary school meal in the total PSFS data set (pre-SFP scenario). Prior to introduction of the SFP (pre-SFP scenario), the primary school meals had mandatory nutrient-based guidelines. Results The percentage of meals that met the protein standard increased in the SFP scenario and the proportion of meals that met the standards for important micronutrients (eg, iron, calcium, vitamin A and C) also increased. However, the SFP scenario did not improve the salt, saturated fat and free sugar levels. The mean GHGE value of meals which met the SFP standards was 0.79 (95% CI 0.77 to 0.81) kgCO2e compared with a mean value of 0.72 (0.71 to 0.74) kgCO2e for all meals. Adopting the SFP would increase the total emissions associated with primary school meals by 22 000 000 kgCO2e per year. Conclusions The universal adoption of the new food-based standards, without reformulation would result in an increase in the GHGEs of school meals and improve some aspects of the nutritional quality, but it would not improve the average salt, sugar and saturated fat content levels. PMID:28381419

Environmental and nutrition impact of achieving new School Food Plan recommendations in the primary school meals sector in England.

PubMed

Wickramasinghe, Kremlin; Rayner, Mike; Goldacre, Michael; Townsend, Nick; Scarborough, Peter

2017-04-05

The aim of this modelling study was to estimate the expected changes in the nutritional quality and greenhouse gas emissions (GHGEs) of primary school meals due to the adoption of new mandatory food-based standards for school meals. Nationally representative random sample of 136 primary schools in England was selected for the Primary School Food Survey (PSFS) with 50% response rate. A sample of 6690 primary students from PSFS who consumed school meals. Primary School Food Plan (SFP) nutritional impact was assessed using both macronutrient and micronutrient quality. The environmental impact was measured by GHGEs. The scenario tested was one in which every meal served in schools met more than half of the food-based standards mentioned in the SFP (SFP scenario). We used findings from a systematic review to assign GHGE values for each food item in the data set. The GHGE value and nutritional quality of SFP scenario meals was compared with the average primary school meal in the total PSFS data set (pre-SFP scenario). Prior to introduction of the SFP (pre-SFP scenario), the primary school meals had mandatory nutrient-based guidelines. The percentage of meals that met the protein standard increased in the SFP scenario and the proportion of meals that met the standards for important micronutrients (eg, iron, calcium, vitamin A and C) also increased. However, the SFP scenario did not improve the salt, saturated fat and free sugar levels. The mean GHGE value of meals which met the SFP standards was 0.79 (95% CI 0.77 to 0.81) kgCO 2 e compared with a mean value of 0.72 (0.71 to 0.74) kgCO 2 e for all meals. Adopting the SFP would increase the total emissions associated with primary school meals by 22 000 000 kgCO 2 e per year. The universal adoption of the new food-based standards, without reformulation would result in an increase in the GHGEs of school meals and improve some aspects of the nutritional quality, but it would not improve the average salt, sugar and saturated fat content levels. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Fungal Peritonitis: Underestimated Disease in Critically Ill Patients with Liver Cirrhosis and Spontaneous Peritonitis.

PubMed

Lahmer, Tobias; Brandl, Andreas; Rasch, Sebastian; Schmid, Roland M; Huber, Wolfgang

2016-01-01

Spontaneous peritonitis, especially spontaneous fungal peritonitis (SFP), is an important and potentially fatal complication in patients with endstage liver disaese. We evaluated potential risk factors, microbiological findings, and outcome of patients with SFP compared to spontaneous bacterial peritonitis (SBP) in critically ill patients. Retrospective analyses of critically ill patients with suspected spontaneous peritonitis. Out of 205 patients, 20 (10%) had SFP, 28 (14%) had SBP, 48 (24%) had peritonitis without microbiological findings (SP) and 109 (52%) had no-peritonitis (NP). APACHE II and SOFA score were significantly higher in patients with SFP (26; 22-28; p<0.004 and 16; 14-18; p<0.002), SBP (26; 22-28; p<0.004 and 16; 14-18; p<0.002) and SP (24; 18-30; p<0.045 and 14; 10-18; p<0.044) as compared to NP (22; 16-24 and 12; 10-14). CHILD Pugh classification was mainly CHILD C and MELD Score was in patients with SFP (34; 18-40; p<0.001), SBP (32;12-40 p<0.002) and SP (29; 14-40 p<0.003) significantly higher as compared to NP (25;8-40). Nosocomial peritonitis could be significantly more often found in patients with SFP (65%; p<0.023) and SBP (62%, p<0.030) as compared to SP (51 p = 0.243) and NP (45%). Antibiotic pretreatment last 3 month prior peritonitis was significantly more often in patients with SFP (85%; p<0.002), SBP (71%, p<0.033), and SP (56; p<0.040) as compared to NP (33%). Candida albicans (60%; 12/20) was the most common isolated fungus, followed by Candida glabrata (13%) and Candida krusei (13%). Mortality rate was significantly higher in patients with SFP (90%, p<0.001), followed by SBP (75%; p<0.001) and SP (69%; p<0.001) as compared to NP (45%). SFP is not a rare complication in end stage liver disease which is associated with increased mortality. Physicians should be aware of SFP in patients with CHILD C liver cirrhosis, elevated MELD score, antibiotic pretreatment and nosocomial peritonitis.

Evaluation of Saccharomyces cerevisiae fermentation product as an alternative to monensin on growth performance, cost of gain, and carcass characteristics of heavy-weight yearling beef steers.

PubMed

Swyers, K L; Wagner, J J; Dorton, K L; Archibeque, S L

2014-06-01

Two hundred fifty-two cross-bred yearling steers (406 ± 24 kg BW) were used in a completely randomized block design with a 2 × 2 factorial arrangement of treatments (7 pens/treatment) to evaluate the effects of dietary Saccharomyces cerevisiae fermentation product (SFP) and monensin (MON) on growth performance and carcass characteristics. Dietary treatments arranged as a 2 × 2 factorial were 1) with or without SFP and 2) with or without MON. Finishing diets contained 19.7% of DM as dried distiller's grains with solubles. Both SFP and MON were added in the total mixed ration in place of an equal amount of cornmeal (DM basis; target intake = 2.8 g of SFP and 33 mg of MON/kg of dietary DM). Each treatment group was offered ad libitum access to a transition ration from d 1 to 8 and then to the finishing ration from d 9 to 125. Body weights were collected on d 0, 28, 56, 84, 110, and 125. Initial and final BW was an average of 2-d weights (d -1 and 0 and d 124 and 125, respectively). Steers were shipped for harvest on d 125. Overall ADG was decreased (P = 0.03) in steers supplemented with SFP, but final BW was similar among treatments. Feeding SFP was associated with lighter (P < 0.01) HCW and a greater (P = 0.01) number of carcasses grading USDA Choice. Twelfth rib fat thickness was not affected by SFP (P = 0.82) or MON (P = 0.35), but numerical decreases in 12th rib fat thickness among cattle receiving SFP or MON alone contributed to a tendency (P = 0.07) for greater 12 rib fat thickness when SFP and MON were provided. There was no effect of treatment on cost of gain (P ≥ 0.21). The effects of SFP in the current study may have been limited in heavy yearling steers due to consumption of a finishing diet containing 19.7% dried distiller's grains with solubles.

Remedial self-fulfilling prophecy: two field experiments to prevent Golem effects among disadvantaged women.

PubMed

Davidson, O B; Eden, D

2000-06-01

The Pygmalion effect is a self-fulfilling prophecy (SFP) in which raising leader expectations boosts subordinate performance. Although attempts to produce Pygmalion effects have been successful repeatedly among men, attempts to produce Pygmalion effects with female leaders have yielded null results. Also, only 1 experiment has demonstrated the Golem effect (i.e., negative SFP in which low leader expectations impair subordinate performance). In 2 field experiments testing the SFP hypothesis among women leading disadvantaged women, experimental leaders were led to believe that their trainees had higher than usual potential. In reality, the trainees had been assigned randomly. Manipulation checks confirmed that the treatment raised leader expectations toward experimental trainees. Analysis of variance of performance detected the predicted SFP effects in both experiments. These were the first-ever experimental confirmations of SFP among women as leaders.

Structure-based mutational analysis of the 4'-phosphopantetheinyl transferases Sfp from Bacillus subtilis: carrier protein recognition and reaction mechanism.

PubMed

Mofid, Mohammad Reza; Finking, Robert; Essen, Lars Oliver; Marahiel, Mohamed A

2004-04-13

The activation of apo-peptidyl carrier proteins (PCPs) of nonribosomal peptide synthetases (NRPSs), apo-acyl carrier proteins (ACPs) of polyketide synthases (PKSs), and fatty acid synthases (FASs) to their active holo form is accomplished with dedicated 4'-phosphopantetheinyl transferases (PPTases). They catalyze the transfer of the essential prosthetic group 4'-phosphopantetheine (4'-Ppant) from coenzyme A (CoA) to a highly conserved serine residue in all PCPs and ACPs. PPTases, based on sequence and substrate specifity, have been classified into three types: bacterial holo-acyl carrier protein synthase (AcpS), fatty acid synthase of eukaryotes (FAS2) and Sfp, a PPTase of secondary metabolism. The recently solved crystal structures of AcpS and Sfp-type PPTases with CoA revealed a common alpha + beta-fold with a beta(1)alpha(3)beta(2) motif and similarities in CoA binding and polymerization mode. However, it was not possible to discern neither the PCP binding region of Sfp nor the priming reaction mechanism from the Sfp-CoA cocrystal. In this work, we provide a model for the reaction mechanism based on mutational analysis of Sfp that suggests a reaction mechanism in which the highly conserved E151 deprotonates the hydroxyl group of the invariant serine of PCP. That, in turn, acts as a nucleophile to attack the beta-phosphate of CoA. The Sfp mutants K112, E117, and K120 further revealed that the loop region between beta4 and alpha5 (residues T111-S124) in Sfp is the PCP binding region. Also, residues T44, K75, S89, H90, D107, E109, E151, and K155 that have been shown in the Sfp-CoA cocrystal structure to coordinate CoA are now all confirmed by mutational and biochemical analysis.

Evaluation to Improve a High School Summer Science Outreach Program †

PubMed Central

Chiappinelli, Katherine B.; Moss, Britney L.; Lenz, Devjanee Swain; Tonge, Natasha A.; Joyce, Adam; Holt, Glen E.; Holt, Leslie Edmonds; Woolsey, Thomas A.

2016-01-01

The goal of the Young Scientist Program (YSP) at Washington University School of Medicine in St. Louis (WUSM) is to broaden science literacy and recruit talent for the scientific future. In particular, YSP seeks to expose underrepresented minority high school students from St. Louis public schools (SLPS) to a wide variety of careers in the sciences. The centerpiece of YSP, the Summer Focus Program (SFP), is a nine-week, intensive research experience for competitively chosen rising high school seniors (Scholars). Scholars are paired with volunteer graduate student, medical student, or postdoctoral fellow mentors who are active members of the practicing scientific community and serve as guides and exemplars of scientific careers. The SFP seeks to increase the number of underrepresented minority students pursuing STEM undergraduate degrees by making the Scholars more comfortable with science and science literacy. The data presented here provide results of the objective, quick, and simple methods developed by YSP to assess the efficacy of the SFP from 2006 to 2013. We demonstrate that the SFP successfully used formative evaluation to continuously improve the various activities within the SFP over the course of several years and in turn enhance student experiences within the SFP. Additionally we show that the SFP effectively broadened confidence in science literacy among participating high school students and successfully graduated a high percentage of students who went on to pursue science, technology, engineering, and mathematics (STEM) majors at the undergraduate level. PMID:27158303

Evaluation to Improve a High School Summer Science Outreach Program.

PubMed

Chiappinelli, Katherine B; Moss, Britney L; Lenz, Devjanee Swain; Tonge, Natasha A; Joyce, Adam; Holt, Glen E; Holt, Leslie Edmonds; Woolsey, Thomas A

2016-05-01

The goal of the Young Scientist Program (YSP) at Washington University School of Medicine in St. Louis (WUSM) is to broaden science literacy and recruit talent for the scientific future. In particular, YSP seeks to expose underrepresented minority high school students from St. Louis public schools (SLPS) to a wide variety of careers in the sciences. The centerpiece of YSP, the Summer Focus Program (SFP), is a nine-week, intensive research experience for competitively chosen rising high school seniors (Scholars). Scholars are paired with volunteer graduate student, medical student, or postdoctoral fellow mentors who are active members of the practicing scientific community and serve as guides and exemplars of scientific careers. The SFP seeks to increase the number of underrepresented minority students pursuing STEM undergraduate degrees by making the Scholars more comfortable with science and science literacy. The data presented here provide results of the objective, quick, and simple methods developed by YSP to assess the efficacy of the SFP from 2006 to 2013. We demonstrate that the SFP successfully used formative evaluation to continuously improve the various activities within the SFP over the course of several years and in turn enhance student experiences within the SFP. Additionally we show that the SFP effectively broadened confidence in science literacy among participating high school students and successfully graduated a high percentage of students who went on to pursue science, technology, engineering, and mathematics (STEM) majors at the undergraduate level.

Comparison of virulence and antibiotic resistance genes of food poisoning outbreak isolates of Staphylococcus aureus with isolates obtained from bovine mastitis milk and pig carcasses.

PubMed

Johler, Sophia; Layer, Franziska; Stephan, Roger

2011-11-01

Staphylococcus aureus is the etiological agent in a variety of infections in humans and livestock and produces enterotoxins leading to staphylococcal food poisoning (SFP), one of the most prevalent foodborne intoxication diseases worldwide. Pork and bovine milk are considered possible sources of SFP because pig skin is often colonized by S. aureus and bovine mastitis caused by S. aureus is common, but conclusive data are limited. The objective of the present study was to compare S. aureus isolates associated with cases of SFP with isolates obtained from bovine mastitis milk and pig carcasses. DNA microarray analysis and spa gene typing were performed with 100 S. aureus isolates: 20 isolates related to outbreaks of SFP in humans, 39 isolates obtained from pig carcasses, and 41 isolates collected from bovine mastitis milk. No overlap in spa types was observed for SFP isolates (t008, t015, t018, t024, t056, t084, t279, t377, t383, t648, t733, t912, t1239, t1270, t4802, and t6969) and isolates gathered from milk or pork. The porcine isolates were assigned to t034, t208, t337, t524, t899, t1939, t2922, t2971, t4475, and t7006, and the bovine isolates belonged to t267, t524, t529, t1403, t2953, t7007, t7008, and t7013. Comparison of microarray profiles revealed similar virulence gene patterns for isolates collected from the same host (pigs or cattle) but few similarities between SFP isolate profiles and the profiles of isolates obtained from bovine mastitis milk and pig carcasses. Although only some bovine and porcine isolates possessed the β-lactamase gene blaZ (milk, 24%; pork, 28%), significantly higher numbers of SFP isolates contained blaZ (90%). Investigations of these isolates provided no evidence that pork or bovine mastitis milk represent common sources of SFP.

Plasma pharmacokinetics and synovial concentrations of S-flurbiprofen plaster in humans.

PubMed

Yataba, Ikuko; Otsuka, Noboru; Matsushita, Isao; Kamezawa, Miho; Yamada, Ichimaro; Sasaki, Sigeru; Uebaba, Kazuo; Matsumoto, Hideo; Hoshino, Yuichi

2016-01-01

The purpose of this study is to investigate the pharmacokinetics and deep tissue penetration capability of the newly developed S-flurbiprofen plaster (SFPP) in humans. Study 1: SFPP tape-type patch (2-60 mg) was applied to the lower back for 24 h in healthy adult volunteers. S-flurbiprofen (SFP) plasma concentration was measured over time to examine SFP pharmacokinetics. Study 2: SFPP (20 mg) was applied for 12 h to the affected knee of osteoarthritis (OA) patients who were scheduled for total knee arthroplasty. Deep tissues (synovial tissue and synovial fluid) were collected during surgery to compare SFP concentrations after application of SFPP or a commercially available flurbiprofen (FP) gel-type patch. Study 1: The plasma concentration of SFP was sustained during 24-h topical application of the SFPP, showing a high percutaneous absorption ratio of 51.4-72.2 %. Cmax and AUC0-∞ were dose-proportional. Study 2: After application of the SFPP for 12 h, SFP concentrations in the synovial tissue and synovial fluid were 14.8-fold (p = 0.002) and 32.7-fold (p < 0.001) higher, respectively, than those achieved by the FP patch. Sustained plasma concentration of SFP and high percutaneous absorption ratio was observed after 24-h topical application of the SFPP. Compared to the FP patch, the SFPP showed superior percutaneous absorption and greater tissue penetration of SFP into the synovial tissue. Greater tissue penetration of the SFPP seemed to be primarily due to its formulation. Thus, SFPP is expected to show higher efficacy for the treatment of knee OA.

Folic acid-capped PEGylated magnetic nanoparticles enter cancer cells mostly via clathrin-dependent endocytosis.

PubMed

Allard-Vannier, Emilie; Hervé-Aubert, Katel; Kaaki, Karine; Blondy, Thibaut; Shebanova, Anastasia; Shaitan, Konstantin V; Ignatova, Anastasia A; Saboungi, Marie-Louise; Feofanov, Alexey V; Chourpa, Igor

2017-06-01

This work is focused on mechanisms of uptake in cancer cells of rationally designed, covalently assembled nanoparticles, made of superparamagnetic iron oxide nanoparticles (SPIONs), fluorophores (doxorubicin or Nile Blue), polyethylene glycol (PEG) and folic acid (FA), referred hereinafter as SFP-FA. SFP-FA were characterized by DLS, zetametry and fluorescence spectroscopy. The SFP-FA uptake in cancer cells was monitored using fluorescence-based methods like fluorescence-assisted cell sorting, CLSM with single-photon and two-photon excitation. The SFP-FA endocytosis was also analyzed with electron microscopy approaches: TEM, HAADF-STEM and EELS. The SFP-FA have zeta potential below -6mW and stable hydrodynamic diameter close to 100nm in aqueous suspensions of pH range from 5 to 8. They contain ca. 109 PEG-FA, 480 PEG-OCH 3 and 22-27 fluorophore molecules per SPION. The fluorophores protected under the PEG shell allows a reliable detection of intracellular NPs. SFP-FA readily enter into all the cancer cell lines studied and accumulate in lysosomes, mostly via clathrin-dependent endocytosis, whatever the FR status on the cells. The present study highlights the advantages of rational design of nanosystems as well as the possible involvement of direct molecular interactions of PEG and FA with cellular membranes, not limited to FA-FR recognition, in the mechanisms of their endocytosis. Composition, magnetic and optical properties of the SFP-FA as well their ability to enter cancer cells are promising for their applications in cancer theranosis. Combination of complementary analytical approaches is relevant to understand the nanoparticles behavior in suspension and in contact with cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Induction of surfactin production in Bacillus subtilis by gsp, a gene located upstream of the gramicidin S operon in Bacillus brevis.

PubMed Central

Borchert, S; Stachelhaus, T; Marahiel, M A

1994-01-01

The deduced amino acid sequence of the gsp gene, located upstream of the 5' end of the gramicidin S operon (grs operon) in Bacillus brevis, showed a high degree of similarity to the sfp gene product, which is located downstream of the srfA operon in B. subtilis. The gsp gene complemented in trans a defect in the sfp gene (sfpO) and promoted production of the lipopeptide antibiotic surfactin. The functional homology of Gsp and Sfp and the sequence similarity of these two proteins to EntD suggest that the three proteins represent a new class of proteins involved in peptide secretion, in support of a hypothesis published previously (T. H. Grossman, M. Tuckman, S. Ellestad, and M. S. Osburne, J. Bacteriol. 175:6203-6211, 1993). Images PMID:7512553

Can pelvic tilt be predicated by the sacrofemoral-pubic angel in patients with thoracolumbar kyphosis secondary to ankylosing spondylitis?

PubMed

Hu, Jun; Ji, Ming-liang; Qian, Bang-ping; Qiu, Yong; Wang, Bin; Yu, Yang; Zhu, Ze-Zhang; Jiang, Jun

2014-11-01

A retrospective radiographical study. To construct a predictive model for pelvic tilt (PT) based on the sacrofemoral-pubic (SFP) angle in patients with thoracolumbar kyphosis secondary to ankylosing spondylitis (or AS). PT is a key pelvic parameter in the regulation of spine sagittal alignment that can be used to plan the appropriate osteotomy angle in patients with AS with thoracolumbar kyphosis. However, it could be difficult to measure PT in patients with femoral heads poorly visualized on lateral radiographs. Previous studies showed that the SFP angle could be used to evaluate PT in adult patients with scoliosis. However, this method has not been validated in patients with AS. A total of 115 patients with AS with thoracolumbar kyphosis were included. Full-length anteroposterior and lateral spine radiographs were all available, with spinal and pelvic anatomical landmarks clearly identified. PT, SFP angle, and global kyphosis were measured. The patients were randomly divided into group A (n=65) and group B (n=50). In group A, the predictive model for PT was constructed by the results of the linear regression analysis. In group B, the predictive ability and accuracy of the predictive model were investigated. In group A, the Pearson correlation analysis revealed a strong correlation between the SFP angle and PT (r=0.852; P<0.001). The predictive model for PT was constructed as PT=72.3-0.82×(SFP angle). In group B, PT was predicted by the model with a mean error of 4.6° (SD=4.5°) with a predictive value of 78%. PT can be accurately predicted by the SFP angle using the current model: PT=72.3-0.82×(SFP angle), when the femur heads are poorly visualized on lateral radiographs in patients with AS with thoracolumbar kyphosis. 4.

Digital disruption? Maternal mobile device use is related to infant social-emotional functioning.

PubMed

Myruski, Sarah; Gulyayeva, Olga; Birk, Samantha; Pérez-Edgar, Koraly; Buss, Kristin A; Dennis-Tiwary, Tracy A

2017-09-24

Mobile device use has become increasingly prevalent, yet its impact on infant development remains largely unknown. When parents use mobile devices in front of infants, the parent is physically present but most likely distracted and unresponsive. Research using the classic Still Face Paradigm (SFP) suggests that parental withdrawal and unresponsiveness may have negative consequences for children's social-emotional development. In the present study, 50 infants aged 7.20 to 23.60 months (M = 15.40, SD = 4.74) and their mothers completed a modified SFP. The SFP consisted of three phases: free play (FP; parent and infant play and interact), still face (SF; parent withdraws attention and becomes unresponsive), and reunion (RU; parent resumes normal interaction). The modified SFP incorporated mobile device use in the SF phase. Parents reported on their typical mobile device use and infant temperament. Consistent with the standard SFP, infants showed more negative affect and less positive affect during SF versus FP. Infants also showed more toy engagement and more engagement with mother during FP versus SF and RU. Infants showed the most social bids during SF and more room exploration in SF than RU. More frequent reported mobile device use was associated with less room exploration and positive affect during SF, and less recovery (i.e., engagement with mother, room exploration positive affect) during RU, even when controlling for individual differences in temperament. Findings suggest that the SFP represents a promising theoretical framework for understanding the impact of parent's mobile device use on infant social-emotional functioning and parent-infant interactions. © 2017 John Wiley & Sons Ltd.

Analgesic Effect of the Newly Developed S(+)-Flurbiprofen Plaster on Inflammatory Pain in a Rat Adjuvant-Induced Arthritis Model.

PubMed

Sugimoto, Masanori; Toda, Yoshihisa; Hori, Miyuki; Mitani, Akiko; Ichihara, Takahiro; Sekine, Shingo; Hirose, Takuya; Endo, Hiromi; Futaki, Nobuko; Kaku, Shinsuke; Otsuka, Noboru; Matsumoto, Hideo

2016-02-01

Preclinical Research This article describes the properties of a novel topical NSAID (Nonsteroidal anti-inflammatory drug) patch, SFPP (S(+)-flurbiprofen plaster), containing the potent cyclooxygenase (COX) inhibitor, S(+)-flurbiprofen (SFP). The present studies were conducted to confirm human COX inhibition and absorption of SFP and to evaluate the analgesic efficacy of SFPP in a rat adjuvant-induced arthritis (AIA) model. COX inhibition by SFP, ketoprofen and loxoprofen was evaluated using human recombinant COX proteins. Absorption of SFPP, ketoprofen and loxoprofen from patches through rat skin was assessed 24 h after application. The AIA model was induced by injecting Mycobacterium tuberculosis followed 20 days later by the evaluation of the prostaglandin PGE2 content of the inflamed paw and the pain threshold. SFP exhibited more potent inhibitory activity against COX-1 (IC50  = 8.97 nM) and COX-2 (IC50  = 2.94 nM) than the other NSAIDs evaluated. Absorption of SFP was 92.9%, greater than that of ketoprofen and loxoprofen from their respective patches. Application of SFPP decreased PGE2 content from 15 min to 6 h and reduced paw hyperalgesia compared with the control, ketoprofen and loxoprofen patches. SFPP showed analgesic efficacy, and was superior to the ketoprofen and loxoprofen patches, which could be through the potent COX inhibitory activity of SFP and greater skin absorption. The results suggested SFPP can be expected to exert analgesic effect clinically. © 2016 The Authors Drug Development Research Published by Wiley Periodicals, Inc.

Analgesic Effect of the Newly Developed S(+)‐Flurbiprofen Plaster on Inflammatory Pain in a Rat Adjuvant‐Induced Arthritis Model

PubMed Central

Toda, Yoshihisa; Hori, Miyuki; Mitani, Akiko; Ichihara, Takahiro; Sekine, Shingo; Hirose, Takuya; Endo, Hiromi; Futaki, Nobuko; Kaku, Shinsuke; Otsuka, Noboru; Matsumoto, Hideo

2016-01-01

ABSTRACT Preclinical Research This article describes the properties of a novel topical NSAID (Nonsteroidal anti‐inflammatory drug) patch, SFPP (S(+)‐flurbiprofen plaster), containing the potent cyclooxygenase (COX) inhibitor, S(+)‐flurbiprofen (SFP). The present studies were conducted to confirm human COX inhibition and absorption of SFP and to evaluate the analgesic efficacy of SFPP in a rat adjuvant‐induced arthritis (AIA) model. COX inhibition by SFP, ketoprofen and loxoprofen was evaluated using human recombinant COX proteins. Absorption of SFPP, ketoprofen and loxoprofen from patches through rat skin was assessed 24 h after application. The AIA model was induced by injecting Mycobacterium tuberculosis followed 20 days later by the evaluation of the prostaglandin PGE2 content of the inflamed paw and the pain threshold. SFP exhibited more potent inhibitory activity against COX‐1 (IC50 = 8.97 nM) and COX‐2 (IC50 = 2.94 nM) than the other NSAIDs evaluated. Absorption of SFP was 92.9%, greater than that of ketoprofen and loxoprofen from their respective patches. Application of SFPP decreased PGE2 content from 15 min to 6 h and reduced paw hyperalgesia compared with the control, ketoprofen and loxoprofen patches. SFPP showed analgesic efficacy, and was superior to the ketoprofen and loxoprofen patches, which could be through the potent COX inhibitory activity of SFP and greater skin absorption. The results suggested SFPP can be expected to exert analgesic effect clinically. Drug Dev Res 76 : 20–28, 2016. © 2016 Wiley Periodicals, Inc. PMID:26763139

Quantifying immediate radiative forcing by black carbon and organic matter with the Specific Forcing Pulse

NASA Astrophysics Data System (ADS)

Bond, T. C.; Zarzycki, C.; Flanner, M. G.; Koch, D. M.

2010-06-01

We propose a measure to quantify climate warming or cooling by pollutants with atmospheric lifetimes of less than one year: the Specific Forcing Pulse (SFP). SFP is the amount of energy added to the Earth system per mass of pollutant emitted. Global average SFP for black carbon, including atmosphere and cryosphere, is 1.12 GJ g-1 and that for organic matter is -0.061 GJ g-1. We provide regional values for black carbon (BC) and organic matter (OM) emitted from 23 source-region combinations, divided between atmosphere and cryosphere impacts and identifying forcing by latitude. Regional SFP varies by about 40% for black carbon. This variation is relatively small because of compensating effects; particles from regions that affect ice albedo typically have shorter atmospheric lifetimes because of lower convection. The ratio between BC and OM SFP implies that, for direct forcing, an OM:BC mass ratio of 15 has a neutral effect on top-of-atmosphere direct forcing for any region, and any lower ratio induces direct warming. However, important processes, particularly cloud changes that tend toward cooling, have not been included here. We demonstrate ensemble adjustment, in which we produce a "best estimate" by combining a suite of diverse but simple models and enhanced models of greater complexity. Adjustments for black carbon internal mixing and for regional variability are discussed; regions with convection are implicated in greater model diversity. SFP expresses scientific uncertainty and separates it from policy uncertainty; the latter is caused by disagreements about the relevant time horizon, impact, or spatial scale of interest. However, metrics used in policy discussions, such as global warming potentials, are easily derived from SFP. Global-average SFP for biofuel and fossil fuel emissions translates to a 100-year GWP of about 760 for black carbon and -40 for organic matter when snow forcing is included. Ensemble-adjusted estimates of atmospheric radiative impact by black and organic matter using year 2000 emissions are +0.46 W m-2 and -0.17 W m-2, respectively; anthropogenic forcing is +0.38 W m-2 and -0.12 W m-2. The black carbon value is only 11% higher than that of the Intergovernmental Panel on Climate Change (IPCC), although this value includes enhanced absorption due to internal mixing.

Quantifying immediate radiative forcing by black carbon and organic matter with the Specific Forcing Pulse

NASA Astrophysics Data System (ADS)

Bond, T. C.; Zarzycki, C.; Flanner, M. G.; Koch, D. M.

2011-02-01

Climatic effects of short-lived climate forcers (SLCFs) differ from those of long-lived greenhouse gases, because they occur rapidly after emission and because they depend upon the region of emission. The distinctive temporal and spatial nature of these impacts is not captured by measures that rely on global averages or long time integrations. Here, we propose a simple measure, the Specific Forcing Pulse (SFP), to quantify climate warming or cooling by these pollutants, where we define "immediate" as occurring primarily within the first year after emission. SFP is the amount of energy added to or removed from a receptor region in the Earth-atmosphere system by a chemical species, per mass of emission in a source region. We limit the application of SFP to species that remain in the atmosphere for less than one year. Metrics used in policy discussions, such as total forcing or global warming potential, are easily derived from SFP. However, SFP conveys purely physical information without incurring the policy implications of choosing a time horizon for the global warming potential. Using one model (Community Atmosphere Model, or CAM), we calculate values of SFP for black carbon (BC) and organic matter (OM) emitted from 23 source-region combinations. Global SFP for both atmosphere and cryosphere impacts is divided among receptor latitudes. SFP is usually greater for open-burning emissions than for energy-related (fossil-fuel and biofuel) emissions because of the timing of emission. Global SFP for BC varies by about 45% for energy-related emissions from different regions. This variation would be larger except for compensating effects. When emitted aerosol has larger cryosphere forcing, it often has lower atmosphere forcing because of less deep convection and a shorter atmospheric lifetime. A single model result is insufficient to capture uncertainty. We develop a best estimate and uncertainties for SFP by combining forcing results from 12 additional models. We outline a framework for combining a large number of simple models with a smaller number of enhanced models that have greater complexity. Adjustments for black carbon internal mixing and for regional variability are discussed. Emitting regions with more deep convection have greater model diversity. Our best estimate of global-mean SFP is +1.03 ± 0.52 GJ g-1 for direct atmosphere forcing of black carbon, +1.15 ± 0.53 GJ g-1 for black carbon including direct and cryosphere forcing, and -0.064 (-0.02, -0.13) GJ g-1 for organic matter. These values depend on the region and timing of emission. The lowest OM:BC mass ratio required to produce a neutral effect on top-of-atmosphere direct forcing is 15:1 for any region. Any lower ratio results in positive direct forcing. However, important processes, particularly cloud changes that tend toward cooling, have not been included here. Global-average SFP for energy-related emissions can be converted to a 100-year GWP of about 740 ± 370 for BC without snow forcing, and 830 ± 440 with snow forcing. 100-year GWP for OM is -46 (-18, -92). Best estimates of atmospheric radiative impact (without snow forcing) by black and organic matter are +0.47 ± 0.26 W m-2 and -0.17 (-0.07, -0.35) W m-2 for BC and OM, respectively, assuming total emission rates of 7.4 and 45 Tg yr-1. Anthropogenic forcing is +0.40 ± 0.18 W m-2 and -0.13 (-0.05, -0.25) W m-2 for BC and OM, respectively, assuming anthropogenic emission rates of 6.3 and 32.6 Tg yr-1. Black carbon forcing is only 18% higher than that given by the Intergovernmental Panel on Climate Change (IPCC), although the value presented here includes enhanced absorption due to internal mixing.

[Collective scombroid fish poisoning following tuna consumption in Castellon].

PubMed

Arnedo Pena, A; Bellido Blasco, J B; Pac Sa, M R; González Morán, F; Criado Juárez, J; Mesanza del Notario, I; Rodríguez Merquero, N; Balagué López, A

1996-11-16

To investigate and control of a collective scombroid-fish poisoning (SFP) outbreak, that took place in Castellón, Spain. Description of the outbreak and case-control study in order to identify risk factors. Active surveillance of SFP cases, and inspection of implicated markets. Histamine determination in urine of cases and foods. During June 1994, 15 cases of SFP were found out, with 12 cases occurred on June, 28 and 29. Five families were affected (attack rate 68.2%). The median incubation period was 45 minutes. Disease symptoms included facial or general flushing, headache, diarrhea, nausea, abdominal pain, and peppery taste. Implicated food was fresh tuna, bought in a hypermarket of Castellón (odds ratio = 26.4, 95% confidence intervals: 1.05-666.8), adjusted by age and sex using logistic regression analysis. Four samples of urine from cases presented histamine concentration above 35 micrograms/l. Three samples of tuna consumed by cases and one sample of tuna from the hypermarket had histamine concentration above a 200 ppm. Considering the situation of risk, remaining suspected tuna was confiscated from the hypermarket. Rest unknown if the descompositions of tuna occurred in the hypermarket or during capture and distribution. SFP was caused by fresh tuna ingestion with epidemiologic and analytic confirmation. Determination of histamine in urine of patients could permit to confirm SFP.

Children with Elevated Psychosocial Risk Load Benefit Most from a Family-Based Preventive Intervention: Exploratory Differential Analyses from the German "Strengthening Families Program 10-14" Adaptation Trial.

PubMed

Bröning, Sonja; Baldus, Christiane; Thomsen, Monika; Sack, Peter-Michael; Arnaud, Nicolas; Thomasius, Rainer

2017-11-01

While the effectiveness of substance use prevention programs such as the Strengthening Families Program 10-14 (SFP) has been demonstrated in the USA, European SFP adaptations have not replicated these sizable effects. Following the rationale of the risk moderation hypothesis positing that elevated risk groups may benefit more from a preventive intervention than lower-risk groups, we reanalyzed evaluation data from a randomized controlled trial testing the adapted German version of SFP (SFP-D). We hypothesized a differential impact of risk status on intervention results. The study employed a minimal control condition. Of the N = 292 participating children, 73.5% qualified as at-risk because they lived in a deprived urban district, and 26.5% qualified as high risk because they additionally scored as "difficult" in the German Strengths and Difficulty Questionnaire (parents' reports using gender- and age-specific German norms). Outcomes were children's self-reports on substance use, mental health, family functioning, and quality of life. Data were analyzed with repeated measures linear mixed models and relative risk analyses. The high-risk group in the SFP-D condition achieved the best results compared with all other groups, especially in mental health and quality of life. Relative risk analyses on tobacco [alcohol] abstinence showed that an additional percentage of 29.8% [16.0%] of high-risk children in nonabstinent controls would have remained abstinent if they had participated in SFP-D. We conclude that risk load influences the impact of substance use prevention programs and discuss to what extent differential analyses can add value to prevention research.

Cultural adaptation process for international dissemination of the strengthening families program.

PubMed

Kumpfer, Karol L; Pinyuchon, Methinin; Teixeira de Melo, Ana; Whiteside, Henry O

2008-06-01

The Strengthening Families Program (SFP) is an evidence-based family skills training intervention developed and found efficacious for substance abuse prevention by U.S researchers in the 1980s. In the 1990s, a cultural adaptation process was developed to transport SFP for effectiveness trials with diverse populations (African, Hispanic, Asian, Pacific Islander, and Native American). Since 2003, SFP has been culturally adapted for use in 17 countries. This article reviews the SFP theory and research and a recommended cultural adaptation process. Challenges in international dissemination of evidence-based programs (EBPs) are discussed based on the results of U.N. and U.S. governmental initiatives to transport EBP family interventions to developing countries. The technology transfer and quality assurance system are described, including the language translation and cultural adaptation process for materials development, staff training, and on-site and online Web-based supervision and technical assistance and evaluation services to assure quality implementation and process evaluation feedback for improvements.

Sfp1 and Rtg3 reciprocally modulate carbon source‐conditional stress adaptation in the pathogenic yeast Candida albicans

PubMed Central

Kastora, Stavroula L.; Herrero‐de‐Dios, Carmen; Avelar, Gabriela M.; Munro, Carol A.

2017-01-01

Summary The pathogenicity of the clinically important yeast, Candida albicans, is dependent on robust responses to host‐imposed stresses. These stress responses have generally been dissected in vitro at 30°C on artificial growth media that do not mimic host niches. Yet host inputs, such as changes in carbon source or temperature, are known to affect C. albicans stress adaptation. Therefore, we performed screens to identify novel regulators that promote stress resistance during growth on a physiologically relevant carboxylic acid and at elevated temperatures. These screens revealed that, under these ‘non‐standard’ growth conditions, numerous uncharacterised regulators are required for stress resistance in addition to the classical Hog1, Cap1 and Cta4 stress pathways. In particular, two transcription factors (Sfp1 and Rtg3) promote stress resistance in a reciprocal, carbon source‐conditional manner. SFP1 is induced in stressed glucose‐grown cells, whereas RTG3 is upregulated in stressed lactate‐grown cells. Rtg3 and Sfp1 regulate the expression of key stress genes such as CTA4, CAP1 and HOG1 in a carbon source‐dependent manner. These mechanisms underlie the stress sensitivity of C. albicans sfp1 cells during growth on glucose, and rtg3 cells on lactate. The data suggest that C. albicans exploits environmentally contingent regulatory mechanisms to retain stress resistance during host colonisation. PMID:28574606

Transport and uptake effects of marine complex lipid liposomes in small intestinal epithelial cell models.

PubMed

Du, Lei; Yang, Yu-Hong; Xu, Jie; Wang, Yu-Ming; Xue, Chang-Hu; Kurihara, Hideyuki; Takahashi, Koretaro

2016-04-01

Nowadays, marine complex lipids, including starfish phospholipids (SFP) and cerebrosides (SFC) separated from Asterias amurensis as well as sea cucumber phospholipids (SCP) and cerebrosides (SCC) isolated from Cucumaria frondosa, have received much attention because of their potent biological activities. However, little information is known on the transport and uptake of these lipids in liposome forms in small intestinal cells. Therefore, this study was undertaken to investigate the effects of these complex lipid liposomes on transport and uptake in Caco-2 and M cell monolayer models. The results revealed that SFP and SCP contained 42% and 47.9% eicosapentaenoic acid (EPA), respectively. The average particle sizes of liposomes prepared in this study were from 169 to 189 nm. We found that the transport of the liposomes across the M cell monolayer model was much higher than the Caco-2 cell monolayer model. The liposomes consisting of SFP or SCP showed significantly higher transport and uptake than soy phospholipid (soy-PL) liposomes in both Caco-2 and M cell monolayer models. Our results also exhibited that treatment with 1 mM liposomes composed of SFP or SCP for 3 h tended to increase the EPA content in phospholipid fractions of both differentiated Caco-2 and M cells. Moreover, it was also found that the hybrid liposomes consisting of SFP/SFC/cholesterol (Chol) revealed higher transport and uptake across the M cell monolayer in comparison with other liposomes. Furthermore, treatment with SFP/SFC/Chol liposomes could notably decrease the trans-epithelial electrical resistance (TEER) values of Caco-2 and M cell monolayers. The present data also showed that the cell viability of differentiated Caco-2 and M cells was not affected after the treatment with marine complex lipids or soy-PL liposomes. Based on the data in this study, it was suggested that marine complex lipid liposomes exhibit prominent transport and uptake in small intestinal epithelial cell models.

Family Skills Training for Parents and Children. Juvenile Justice Bulletin.

ERIC Educational Resources Information Center

Kumpfer, Karol L.; Tait, Connie M.

Originally designed as a drug abuse prevention program for drug-abusing parents and their children, the Strengthening Families Program (SFP) has developed into a family-change program. Presented in 14 2-hour-long, consecutive weekly sessions, SFP has two versions: for elementary school children and their parents and for parents and youth 10-14…

Parental Participation and Retention in an Alcohol Preventive Family-Focused Programme

ERIC Educational Resources Information Center

Skarstrand, Eva; Branstrom, Richard; Sundell, Knut; Kallmen, Hakan; Andreassen, Sven

2009-01-01

Purpose: The purpose of this paper is to examine factors predicting parental participation and retention in a Swedish version of the Strengthening Families Programme (SFP). Design/methodology/approach: This study is based on data from a randomised controlled trial to evaluate the effects of the Swedish version of the SFP. The sample involves 441…

Seminal fluid protein depletion and replenishment in the fruit fly, Drosophila melanogaster: an ELISA-based method for tracking individual ejaculates

PubMed Central

Sirot, Laura K.; Wolfner, Mariana F.

2014-01-01

In many species, seminal fluid proteins (SFPs) affect female post-mating behavioral patterns, including sperm storage, egg laying, feeding, and remating. Yet, few studies have investigated the patterns of allocation, depletion, and replenishment of SFPs in male animals, despite the importance of these proteins to male and female reproductive success. To investigate such SFP dynamics, it is necessary to have a sensitive method for quantifying SFP levels in males and mated females. We developed such a method by adapting the enzyme-linked immunosorbent assay (ELISA) using anti-SFP antibodies. Here, we first use two Drosophila melanogaster SFPs (ovulin and sex peptide) to demonstrate that ELISAs provide accurate measures of SFP levels. We find that, consistent with previous data from Western blotting or immunofluorescence studies, levels of both ovulin and sex peptide decline in the mated female with time since mating, but they do so at different rates. We then use ELISAs to show that males become depleted of SFPs with repeated matings, but that previously mated males are able to transfer “virgin” levels of SFPs after 3 days of sexual inactivity. Finally, we demonstrate that ELISAs can detect SFPs from wild-caught D. melanogaster males and, thus, potentially can be used to track mating patterns in the wild. This method of measuring SFP dynamics can be used in a wide range of species to address questions related to male reproductive investment, female mating history, and variation in female post-mating behavioral changes. PMID:24733957

Maternal sensitivity and infant autonomic and endocrine stress responses.

PubMed

Bosquet Enlow, Michelle; King, Lucy; Schreier, Hannah Mc; Howard, Jamie M; Rosenfield, David; Ritz, Thomas; Wright, Rosalind J

2014-07-01

Early environmental exposures may help shape the development of the autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis, influencing vulnerability for health problems across the lifespan. Little is known about the role of maternal sensitivity in influencing the development of the ANS in early life. To examine associations among maternal sensitivity and infant behavioral distress and ANS and HPA axis reactivity to the Repeated Still-Face Paradigm (SFP-R), a dyadic stress task. Observational repeated measures study. Thirty-five urban, sociodemographically diverse mothers and their 6-month-old infants. Changes in infant affective distress, heart rate, respiratory sinus arrhythmia (RSA), and T-wave amplitude (TWA) across episodes of the SFP-R were assessed. A measure of cortisol output (area under the curve) in the hour following cessation of the SFP-R was also obtained. Greater maternal insensitivity was associated with greater infant sympathetic activation (TWA) during periods of stress and tended to be associated with greater cortisol output following the SFP-R. There was also evidence for greater affective distress and less parasympathetic activation (RSA) during the SFP-R among infants of predominantly insensitive mothers. Caregiving quality in early life may influence the responsiveness of the sympathetic and parasympathetic branches of the ANS as well as the HPA axis. Consideration of the ANS and HPA axis systems together provides a fuller representation of adaptive versus maladaptive stress responses. The findings highlight the importance of supporting high quality caregiving in the early years of life, which is likely to promote later health. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sulforaphane Inhibits Mitochondrial Permeability Transition and Oxidative Stress

PubMed Central

Greco, Tiffany; Shafer, Jonathan; Fiskum, Gary

2012-01-01

Exposure of mitochondria to oxidative stress and elevated Ca2+ promotes opening of the mitochondrial permeability transition pore (PTP), resulting in membrane depolarization, uncoupling of oxidative phosphorylation, and potentially cell death. This study tested the hypothesis that treatment of rats with sulforaphane (SFP), an activator of the Nrf2 pathway of antioxidant gene expression, increases the resistance of liver mitochondria to redox-regulated PTP opening and elevates mitochondrial levels of antioxidants. Rats were injected with SFP or drug vehicle and liver mitochondria were isolated 40 hr later. Respiring mitochondria actively accumulated added Ca2+, which was then released through PTP opening induced by agents that either cause an oxidized shift in the mitochondrial redox state or that directly oxidize protein thiol groups. SFP treatment of rats inhibited the rate of pro-oxidant-induced mitochondrial Ca2+ release and increased expression of the glutathione peroxidase/reductase system, thioredoxin, and malic enzyme. These results are the first to demonstrate that SFP treatment of animals increases liver mitochondrial antioxidant defenses and inhibits redox-sensitive PTP opening. This novel form of preconditioning could protect against a variety of pathologies that include oxidative stress and mitochondrial dysfunction in their etiologies. PMID:21986339

Object oriented classification of high resolution data for inventory of horticultural crops

NASA Astrophysics Data System (ADS)

Hebbar, R.; Ravishankar, H. M.; Trivedi, S.; Subramoniam, S. R.; Uday, R.; Dadhwal, V. K.

2014-11-01

High resolution satellite images are associated with large variance and thus, per pixel classifiers often result in poor accuracy especially in delineation of horticultural crops. In this context, object oriented techniques are powerful and promising methods for classification. In the present study, a semi-automatic object oriented feature extraction model has been used for delineation of horticultural fruit and plantation crops using Erdas Objective Imagine. Multi-resolution data from Resourcesat LISS-IV and Cartosat-1 have been used as source data in the feature extraction model. Spectral and textural information along with NDVI were used as inputs for generation of Spectral Feature Probability (SFP) layers using sample training pixels. The SFP layers were then converted into raster objects using threshold and clump function resulting in pixel probability layer. A set of raster and vector operators was employed in the subsequent steps for generating thematic layer in the vector format. This semi-automatic feature extraction model was employed for classification of major fruit and plantations crops viz., mango, banana, citrus, coffee and coconut grown under different agro-climatic conditions. In general, the classification accuracy of about 75-80 per cent was achieved for these crops using object based classification alone and the same was further improved using minimal visual editing of misclassified areas. A comparison of on-screen visual interpretation with object oriented approach showed good agreement. It was observed that old and mature plantations were classified more accurately while young and recently planted ones (3 years or less) showed poor classification accuracy due to mixed spectral signature, wider spacing and poor stands of plantations. The results indicated the potential use of object oriented approach for classification of high resolution data for delineation of horticultural fruit and plantation crops. The present methodology is applicable at local levels and future development is focused on up-scaling the methodology for generation of fruit and plantation crop maps at regional and national level which is important for creation of database for overall horticultural crop development.

Integrating mindfulness with parent training: effects of the Mindfulness-Enhanced Strengthening Families Program.

PubMed

Coatsworth, J Douglas; Duncan, Larissa G; Nix, Robert L; Greenberg, Mark T; Gayles, Jochebed G; Bamberger, Katharine T; Berrena, Elaine; Demi, Mary Ann

2015-01-01

There is growing support for the efficacy of mindfulness training with parents as an intervention technique to improve parenting skills and reduce risk for youth problem behaviors. The evidence, however, has been limited to small scale studies, many with methodological shortcomings. This study sought to integrate mindfulness training with parents into the Strengthening Families Program: For Parents and Youth 10-14 (SFP 10-14), an empirically-validated family-based preventive intervention. It used a randomized-controlled comparative effectiveness study design (N = 432 families, 31% racial/ethnic minority) to test the efficacy of the Mindfulness-Enhanced Strengthening Families Program (MSFP), compared to standard SFP 10-14 and a minimal-treatment home study control condition. Results indicated that, in general, MSFP was as effective as SFP 10-14 in improving multiple dimensions of parenting, including interpersonal mindfulness in parenting, parent-youth relationship quality, youth behavior management, and parent well-being, according to both parent and youth reports at both postintervention and 1-year follow-up. This study also found that in some areas MSFP boosted and better sustained the effects of SFP 10-14, especially for fathers. Although the pattern of effects was not as uniform as hypothesized, this study provides intriguing evidence for the unique contribution of mindfulness activities to standard parent training.

Integrating Mindfulness with Parent Training: Effects of the Mindfulness-Enhanced Strengthening Families Program

PubMed Central

Coatsworth, J. Douglas; Duncan, Larissa G.; Nix, Robert L.; Greenberg, Mark T.; Gayles, Jochebed G.; Bamberger, Katharine T.; Berrena, Elaine; Demi, Mary Ann

2015-01-01

There is growing support for the efficacy of mindfulness training with parents as an intervention technique to improve parenting skills and reduce risk for youth problem behaviors. The evidence, however, has been limited to small scale studies, many with methodological shortcomings. This study sought to integrate mindfulness training with parents into the Strengthening Families Program: For Parents and Youth 10-14 (SFP 10-14), an empirically-validated family-based preventive intervention. It used a randomized-controlled comparative effectiveness study design (N = 432 families, 31% racial/ethnic minority) to test the efficacy of the Mindfulness-Enhanced Strengthening Families Program (MSFP), compared to standard SFP 10-14 and a minimal-treatment home study control condition. Results indicated that, in general, MSFP was as effective as SFP 10-14 in improving multiple dimensions of parenting, including interpersonal mindfulness in parenting, parent-youth relationship quality, youth behavior management, and parent well-being, according to both parent and youth reports at both post-intervention and one-year follow-up. This study also found that in some areas MSFP boosted and better sustained the effects of SFP 10-14, especially for fathers. Although the pattern of effects was not as uniform as hypothesized, this study provides intriguing evidence for the unique contribution of mindfulness activities to standard parent training. PMID:25365122

Modulation of Frontoparietal Neurovascular Dynamics in Working Memory

PubMed Central

Ardestani, Allen; Shen, Wei; Darvas, Felix; Toga, Arthur W.; Fuster, Joaquin M.

2016-01-01

Our perception of the world is represented in widespread, overlapping, and interactive neuronal networks of the cerebral cortex. A majority of physiological studies on the subject have focused on oscillatory synchrony as the binding mechanism for representation and transmission of neural information. Little is known, however, about the stability of that synchrony during prolonged cognitive operations that span more than just a few seconds. The present research, in primates, investigated the dynamic patterns of oscillatory synchrony by two complementary recording methods, surface field potentials (SFPs) and near-infrared spectroscopy (NIRS). The signals were first recorded during the resting state to examine intrinsic functional connectivity. The temporal modulation of coactivation was then examined on both signals during performance of working memory ( WM) tasks with long delays (memory retention epochs). In both signals, the peristimulus period exhibited characteristic features in frontal and parietal regions. Examination of SFP signals over delays lasting tens of seconds, however, revealed alternations of synchronization and desynchronization. These alternations occurred within the same frequency bands observed in the peristimulus epoch, without a specific correspondence between any definite cognitive process (e.g., WM) and synchrony within a given frequency band. What emerged instead was a correlation between the degree of SFP signal fragmentation (in time, frequency, and brain space) and the complexity and efficiency of the task being performed. In other words, the incidence and extent of SFP transitions between synchronization and desynchronization—rather than the absolute degree of synchrony—augmented in correct task performance compared with incorrect performance or in a control task without WM demand. An opposite relationship was found in NIRS: increasing task complexity induced more uniform, rather than fragmented, NIRS coactivations. These findings indicate that the particular features of neural oscillations cannot be linearly mapped to cognitive functions. Rather, information and the cognitive operations performed on it are primarily reflected in their modulations over time. The increased complexity and fragmentation of electrical frequencies in WM may reflect the activation of hierarchically diverse cognits (cognitive networks) in that condition. Conversely, the homogeneity in coherence of NIRS responses may reflect the cumulative vascular reactions that accompany that neuroelectrical proliferation of frequencies and the longer time constant of the NIRS signal. These findings are directly relevant to the mechanisms mediating cognitive processes and to physiologically based interpretations of functional brain imaging. PMID:26679214

Investigation of Zircaloy-2 oxidation model for SFP accident analysis

NASA Astrophysics Data System (ADS)

Nemoto, Yoshiyuki; Kaji, Yoshiyuki; Ogawa, Chihiro; Kondo, Keietsu; Nakashima, Kazuo; Kanazawa, Toru; Tojo, Masayuki

2017-05-01

The authors previously conducted thermogravimetric analyses on Zircaloy-2 in air. By using the thermogravimetric data, an oxidation model was constructed in this study so that it can be applied for the modeling of cladding degradation in spent fuel pool (SFP) severe accident condition. For its validation, oxidation tests of long cladding tube were conducted, and computational fluid dynamics analyses using the constructed oxidation model were proceeded to simulate the experiments. In the oxidation tests, high temperature thermal gradient along the cladding axis was applied and air flow rates in testing chamber were controlled to simulate hypothetical SFP accidents. The analytical outputs successfully reproduced the growth of oxide film and porous oxide layer on the claddings in oxidation tests, and validity of the oxidation model was proved. Influence of air flow rate for the oxidation behavior was thought negligible in the conditions investigated in this study.

MELCOR model for an experimental 17x17 spent fuel PWR assembly.

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

Cardoni, Jeffrey

2010-11-01

A MELCOR model has been developed to simulate a pressurized water reactor (PWR) 17 x 17 assembly in a spent fuel pool rack cell undergoing severe accident conditions. To the extent possible, the MELCOR model reflects the actual geometry, materials, and masses present in the experimental arrangement for the Sandia Fuel Project (SFP). The report presents an overview of the SFP experimental arrangement, the MELCOR model specifications, demonstration calculation results, and the input model listing.

The Strengthening Families Program 10-14: influence on parent and youth problem-solving skill.

PubMed

Semeniuk, Y; Brown, R L; Riesch, S K; Zywicki, M; Hopper, J; Henriques, J B

2010-06-01

The aim of this paper is to report the results of a preliminary examination of the efficacy of the Strengthening Families Program (SFP) 10-14 in improving parent and youth problem-solving skill. The Hypotheses in this paper include: (1) youth and parents who participated in SFP would have lower mean scores immediately (T2) and 6 months (T3) post intervention on indicators of hostile and negative problem-solving strategies; (2) higher mean scores on positive problem-solving strategies; and (3) youth who participated in SFP would have higher mean scores at T2 and at T3 on indicators of individual problem solving and problem-solving efficacy than youth in the comparison group. The dyads were recruited from elementary schools that had been stratified for race and assigned randomly to intervention or comparison conditions. Mean age of youth was 11 years (SD = 1.04). Fifty-seven dyads (34-intervention&23-control) were videotaped discussing a frequently occurring problem. The videotapes were analysed using the Iowa Family Interaction Rating Scale (IFIRS) and data were analysed using Dyadic Assessment Intervention Model. Most mean scores on the IFIRS did not change. One score changed as predicted: youth hostility decreased at T3. Two scores changed contrary to prediction: parent hostility increased T3 and parent positive problem solving decreased at T2. SFP demonstrated questionable efficacy for problem-solving skill in this study.

[Children with Multiple Risk Factor Exposition Benefit from the German "Strengthening Families Program"].

PubMed

Bröning, Sonja; Sack, Peter-Michael; Thomsen, Monika; Thomasius, Rainer

2016-09-01

Children with Multiple Risk Factor Exposition Benefit from the German "Strengthening Families Program" The German adaptation of the substance use-preventive family-based Strengthening Families Program 10-14 (SFP, Iowa version) was evaluated in a longitudinal two-year follow-up trial. Participants were N = 292 children with a mean age of twelve years at baseline, and N = 292 parents. We employed a multi-centric, randomized-controlled, two-armed (SFP vs. minimal control condition) study design. Following a "risk moderation hypothesis", we assumed that children with an elevated risk-exposition R(+) would benefit more than children with a low risk-exposition R(-) irrespective of the preventive intervention, and that R(+) under SFP would benefit more than R(+) under the minimal control condition. "Risk-exposition" was measured in correspondence with the Communities That Care Youth Survey-questionnaire. A total of 28 % of children were classified with an elevated risk level. Children's reports confirmed our hypothesis: R(+) report a total of eleven improvements, four of these being significantly more distinct than in the other groups (Anxiety-Depressivity, Punitive Parenting of mother, Punitive Parenting of father, Unbalanced family functioning). In three measures an improvement appears solely in R(+) under SFP (Satisfaction with family functioning, School Attachment and Peer Relationship Quality, Quality of Life). Parents' reports showed a similar tendency, but were less pronounced.

Three forms of assessment of prior knowledge, and improved performance following an enrichment programme, of English second language biology students within the context of a marine theme

NASA Astrophysics Data System (ADS)

Feltham, Nicola F.; Downs, Colleen T.

2002-02-01

The Science Foundation Programme (SFP) was launched in 1991 at the University of Natal, Pietermaritzburg, South Africa in an attempt to equip a selected number of matriculants from historically disadvantaged schools with the skills, resources and self-confidence needed to embark on their tertiary studies. Previous research within the SFP biology component suggests that a major contributor to poor achievement and low retention rates among English second language (ESL) students in the Life Sciences is the inadequate background knowledge in natural history. In this study, SFP student background knowledge was assessed along a continuum of language dependency using a set of three probes. Improved student performance in each of the respective assessments examined the extent to which a sound natural history background facilitated meaningful learning relative to ESL proficiency. Student profiles and attitudes to biology were also examined. Results indicated that students did not perceive language to be a problem in biology. However, analysis of the student performance in the assessment probes indicated that, although the marine course provided the students with the background knowledge that they were initially lacking, they continued to perform better in the drawing and MCQ tools in the post-tests, suggesting that it is their inability to express themselves in the written form that hampers their development. These results have implications for curriculum development within the constructivist framework of the SFP.

Analysis of the structural organization and thermal stability of two spermadhesins. Calorimetric, circular dichroic and Fourier-transform infrared spectroscopic studies.

PubMed

Menéndez, M; Gasset, M; Laynez, J; López-Zumel, C; Usobiaga, P; Töpfer-Petersen, E; Calvete, J J

1995-12-15

The CUB domain is a widespread 110-amino-acid module found in functionally diverse, often developmentally regulated proteins, for which an antiparallel beta-barrel topology similar to that in immunoglobulin V domains has been predicted. Spermadhesins have been proposed as a subgroup of this protein family built up by a single CUB domain architecture. To test the proposed structural model, we have analyzed the structural organization of two members of the spermadhesin protein family, porcine seminal plasma proteins I/II (PSP-I/PSP-II) heterodimer and bovine acidic seminal fluid protein (aSFP) homodimer, using differential scanning calorimetry, far-ultraviolet circular dichroism and Fourier-transform infrared spectroscopy. Thermal unfolding of PSP-I/PSP-II and aSFP were irreversible and followed a one-step process with transition temperatures (Tm) of 60.5 degrees C and 78.6 degrees C, respectively. The calorimetric enthalpy changes (delta Hcat) of thermal denaturation were 439 kJ/mol for PSP-I/PSP-II and 660 kJ/mol for aSFP dimer. Analysis of the calorimetric curves of PSP-I/PSP-II showed that the entire dimer constituted the cooperative unfolding unit. Fourier-transform infrared spectroscopy and deconvolution of circular dichroic spectra using a convex constraint analysis indicated that beta-structure and turns are the major structural element of both PSP-I/PSP-II (53% of beta-sheet, 21% of turns) and aSFP (44% of beta-sheet, 36% of turns), and that the porcine and the bovine proteins contain little, if any, alpha-helical structure. Taken together, our results indicate that the porcine and the bovine spermadhesin molecules are probably all-beta-structure proteins, and would support a beta-barrel topology like that predicted for the CUB domain. Other beta-structure folds, such as the Greek-key pattern characteristic of many carbohydrate-binding protein domains cannot be eliminated. Finally, the same combination of biophysical techniques was used to characterize the residual secondary structure of thermally denatured forms of PSP-I/PSP-II and aSFP, and to emphasize the aggregation tendency of these forms.

Effect of filter designs on hydraulic properties and well efficiency.

PubMed

Kim, Byung-Woo

2014-09-01

To analyze the effect of filter pack arrangement on the hydraulic properties and the well efficiency of a well design, a step drawdown was conducted in a sand-filled tank model. Prior to the test, a single filter pack (SFP), granule only, and two dual filter packs (DFPs), type A (granule-pebble) and type B (pebble-granule), were designed to surround the well screen. The hydraulic properties and well efficiencies related to the filter packs were evaluated using the Hazen's, Eden-Hazel's, Jacob's, and Labadie-Helweg's methods. The results showed that the hydraulic properties and well efficiency of the DFPs were higher than those of a SFP, and the clogging effect and wellhead loss related to the aquifer material were the lowest owing to the grain size and the arrangement of the filter pack. The hydraulic conductivity of the DFPs types A and B was about 1.41 and 6.43 times that of a SFP, respectively. In addition, the well efficiency of the DFPs types A and B was about 1.38 and 1.60 times that of the SFP, respectively. In this study, hydraulic property and well efficiency changes were observed according to the variety of the filter pack used. The results differed from the predictions of previous studies on the grain-size ratio. Proper pack-aquifer ratios and filter pack arrangements are primary factors in the construction of efficient water wells, as is the grain ratio, intrinsic permeability (k), and hydraulic conductivity (K) between the grains of the filter packs and the grains of the aquifer. © 2014, National Ground Water Association.

The Codacs™ direct acoustic cochlear implant actuator: exploring alternative stimulation sites and their stimulation efficiency.

PubMed

Grossöhmichen, Martin; Salcher, Rolf; Kreipe, Hans-Heinrich; Lenarz, Thomas; Maier, Hannes

2015-01-01

This work assesses the efficiency of the Codacs system actuator (Cochlear Ltd., Sydney Australia) in different inner ear stimulation modalities. Originally the actuator was intended for direct perilymph stimulation after stapedotomy using a piston prosthesis. A possible alternative application is the stimulation of middle ear structures or the round window (RW). Here the perilymph stimulation with a K-piston through a stapes footplate (SFP) fenestration (N = 10) as well as stimulation of the stapes head (SH) with a Bell prosthesis (N = 9), SFP stimulation with an Omega/Aerial prosthesis (N = 8) and reverse RW stimulation (N = 10) were performed in cadaveric human temporal bones (TBs). Codacs actuator output is expressed as equivalent sound pressure level (eq. SPL) using RW and SFP displacement responses, measured by Laser Doppler velocimetry as reference. The axial actuator coupling force in stimulation of stapes and RW was adjusted to ~5 mN. The Bell prosthesis and Omega/Aerial prosthesis stimulation generated similar mean eq. SPLs (Bell: 127.5-141.8 eq. dB SPL; Omega/Aerial: 123.6-143.9 eq. dB SPL), being significantly more efficient than K-piston perilymph stimulation (108.6-131.6 eq. dB SPL) and RW stimulation (108.3-128.2 eq. dB SPL). Our results demonstrate that SH, SFP and RW are adequate alternative stimulation sites for the Codacs actuator using coupling prostheses and an axial coupling force of ~5 mN. Based on the eq. SPLs, all investigated methods were adequate for in vivo hearing aid applications, provided that experimental conditions including constant coupling force will be implemented.

Characterization of thermal-hydraulic and ignition phenomena in prototypic, full-length boiling water reactor spent fuel pool assemblies after a complete loss-of-coolant accident.

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

Lindgren, Eric Richard; Durbin, Samuel G

2007-04-01

The objective of this project was to provide basic thermal-hydraulic data associated with a SFP complete loss-of-coolant accident. The accident conditions of interest for the SFP were simulated in a full-scale prototypic fashion (electrically-heated, prototypic assemblies in a prototypic SFP rack) so that the experimental results closely represent actual fuel assembly responses. A major impetus for this work was to facilitate code validation (primarily MELCOR) and reduce questions associated with interpretation of the experimental results. It was necessary to simulate a cluster of assemblies to represent a higher decay (younger) assembly surrounded by older, lower-power assemblies. Specifically, this program providedmore » data and analysis confirming: (1) MELCOR modeling of inter-assembly radiant heat transfer, (2) flow resistance modeling and the natural convective flow induced in a fuel assembly as it heats up in air, (3) the potential for and nature of thermal transient (i.e., Zircaloy fire) propagation, and (4) mitigation strategies concerning fuel assembly management.« less

[Sardine purified proteins improve blood pressure, glycemic control, anti-atherogenic metabolic pathways and antioxidant capacity in obese rats].

PubMed

Affane, F; Bensalah, F; Harrat, N I; Chekkal, H; Louala, S; Lamri-Senhadji, M Y

2018-05-09

The effects of sardine by-products (SBy-P) and fillet proteins (SF-P) were compared to casein (Cas) ; these effects were assessed on blood pressure, glycemic control, reverse cholesterol transport, lipid peroxidation and total antioxidant capacity in obese rats. Eighteen male Wistar rats were subjected for three months, to a high-fat diet. The obese rats were divided into three groups and consumed the same high-fat diet for 28 days after addition of either, 20% SBy-P, SF-P or Cas. The sardine proteins (SBy-P and SF-P) compared respectively to Cas, reduced diastolic (-14%, -11% P<0.05) and systolic pressures (-12%, -8% P<0.05), blood glucose (-24%, -21% P<0.05), glycated hemoglobin (-28%, -21% P<0.05), insulinemia (-29%, -18% P<0.05) and HOMA-IR index (-29%, -18% P<0.05). They improve the reverse cholesterol transport by increasing the lecithin: cholesterol acyltransferase (LCAT) activity (+43%, +30% P<0.05) and high-density lipoproteins in cholesterol esters (+108%, +88% P<0.05), and decreasing the atherogenicity ratios and membrane fluidity (P<0.05). Furthermore, SBy-P and SF-P induced a reduction of reactive thiobarbituric acid substances concentrations in heart (-45%, -25% P<0.05), aorta (-62%, -41% P<0.05), liver (-40%, -21% P<0.05) and adipose tissue (-50%, -37% P<0.05) with an improvement in antioxidant capacity. Sardine proteins, in particular those extracted from by-products, because of their hypotensive, hypoglycemic, anti-atherogenic and antioxidant properties, may have protective effects against the cardiovascular risk associated with obesity. Copyright © 2018. Published by Elsevier SAS.

Evaluation of a Swedish version of the Strengthening Families Programme.

PubMed

Skärstrand, Eva; Sundell, Knut; Andréasson, Sven

2014-08-01

Adolescents' alcohol consumption is a public health concern in Sweden as well as in many other countries. Underage drinking is associated with increased risks of alcohol-related injuries, risky sexual behaviours and dependence later in life. Different strategies have been used in the effort to prevent this behaviour, and to postpone the onset of alcohol. The Strengthening Families Programme 10-14 (SFP 10-14) from the USA has been highlighted as one of the more effective prevention programmes. The aim of the present article was to evaluate the effectiveness of a culturally adapted Swedish version of the SFP 10-14. This was a cluster randomized controlled trial including 587 sixth-grade students (age 12) and their parents in 19 elementary schools in Stockholm. Schools were randomly assigned to either control (9 schools, 216 students) or to the family skills training intervention (10 schools, 371 students). The SFP Swedish version consisted of two parts with seven and five sessions, respectively, held separately for youths and parents except two joint family sessions. Measures of students' self-reported episodes of drunkenness, smoking, illicit drug use and other norm-breaking behaviours were collected at baseline (March 2003) and at three subsequent yearly surveys. Data were analysed using multilevel models with an intention-to-treat approach. No preventive effects were found for smoking, alcohol and illicit drug use and other norm-breaking behaviours, nor did moderators affect the outcome. The Swedish version of the SFP 10-14 was not effective in preventing youths' substance use in a Swedish context. © The Author 2013. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Malnourished children and supplementary feeding during the war emergency in Guinea-Bissau in 1998-1999.

PubMed

Nielsen, Jens; Valentiner-Branth, Palle; Martins, Cesario; Cabral, Fernando; Aaby, Peter

2004-10-01

Supplementary feeding programs (SFPs) are intended to mitigate the deterioration of nutritional status and the increase in mortality among malnourished children. We investigated the effect of an SFP on malnourished children in Guinea-Bissau who were returning to their homes after having been displaced within the country because of war in 1998-1999. The effect of the war on the nutritional status of children aged 6-59 mo who were present in Bissau sometime from September 1998 to June 1999 was evaluated by comparing the mortality and the prevalence of malnutrition with the values expected had the war not occurred and by comparing the severity of malnutrition in malnourished children before and during the war. The quality of the SFP was also evaluated. Children with midupper arm circumference < 130 mm were provided weekly medical consultations and supplementary feeding until recovery. The degree of malnutrition did not increase during the war. The prevalence of malnutrition increased with the start of the war but then decreased. The mortality of malnourished children did not increase during the war. Seventy-four percent of the referred children received treatment; of those, 1% died, 67% recovered, and 32% abandoned treatment. Compliance was 89%. The recovery rate was 13.1. 1000(-1). d(-1), and the median time to recovery was 48 d. Better compliance was associated with shorter time to recovery. Our findings may be biased by changes in the cultural and socioeconomic background of the malnourished children. However, 3 different analyses indicated a beneficial effect of the SFP. Thus, the home-based SFP probably prevented nutritional deterioration during the war in Guinea-Bissau.

The Codacs™ Direct Acoustic Cochlear Implant Actuator: Exploring Alternative Stimulation Sites and Their Stimulation Efficiency

PubMed Central

Grossöhmichen, Martin; Salcher, Rolf; Kreipe, Hans-Heinrich; Lenarz, Thomas; Maier, Hannes

2015-01-01

This work assesses the efficiency of the Codacs system actuator (Cochlear Ltd., Sydney Australia) in different inner ear stimulation modalities. Originally the actuator was intended for direct perilymph stimulation after stapedotomy using a piston prosthesis. A possible alternative application is the stimulation of middle ear structures or the round window (RW). Here the perilymph stimulation with a K-piston through a stapes footplate (SFP) fenestration (N = 10) as well as stimulation of the stapes head (SH) with a Bell prosthesis (N = 9), SFP stimulation with an Omega/Aerial prosthesis (N = 8) and reverse RW stimulation (N = 10) were performed in cadaveric human temporal bones (TBs). Codacs actuator output is expressed as equivalent sound pressure level (eq. SPL) using RW and SFP displacement responses, measured by Laser Doppler velocimetry as reference. The axial actuator coupling force in stimulation of stapes and RW was adjusted to ~ 5 mN. The Bell prosthesis and Omega/Aerial prosthesis stimulation generated similar mean eq. SPLs (Bell: 127.5–141.8 eq. dB SPL; Omega/Aerial: 123.6–143.9 eq. dB SPL), being significantly more efficient than K-piston perilymph stimulation (108.6–131.6 eq. dB SPL) and RW stimulation (108.3–128.2 eq. dB SPL). Our results demonstrate that SH, SFP and RW are adequate alternative stimulation sites for the Codacs actuator using coupling prostheses and an axial coupling force of ~ 5 mN. Based on the eq. SPLs, all investigated methods were adequate for in vivo hearing aid applications, provided that experimental conditions including constant coupling force will be implemented. PMID:25785860

School feeding program has resulted in improved dietary diversity, nutritional status and class attendance of school children.

PubMed

Zenebe, Mastewal; Gebremedhin, Samson; Henry, Carol J; Regassa, Nigatu

2018-01-23

School Feeding Program (SFP) is a targeted safety net program designed to provide educational and health benefits to vulnerable children. However, limited evidence exists regarding the effect of the intervention on the nutritional status and school attendance of children. The study is aimed at examining the effects of SFP on dietary diversity, nutritional status and class attendance of school children in Boricha district, Southern Ethiopia. The study was conducted based on a representative data collected from 290 students drawn from the district. A school-based comparative cross-sectional study was conducted on school children aged 10-14 years. Data were collected using structured pretested questionnaire. The effects of SFP on dietary diversity score (DDS), class attendance rate, body-mass-index for age (BAZ) and height-for-age (HAZ) Z-scores were assessed using multivariable linear regression model. The finding showed significantly higher mean (±SD) of DDS in SFP beneficiaries (5.8 ± 1.1) than the non-beneficiaries (3.5 ± 0.7) (P < 0.001). BAZ and HAZ of the beneficiaries were also higher than their counterparts, which were (0.07 ± 0.93), (- 0.50 ± 0.86) and (- 1.45 ± 1.38), (- 2.17 ± 1.15) respectively (P < 0.001). The mean (±SD) days of absence from school for non-beneficiaries (2.6 ± 1.6) was significantly higher than that of the beneficiaries (1.3 ± 1.7) (P < 0.05). Given the positive effects of the program in improving the DDS, nutritional status, and class attendance of school children, we strongly recommend scaling up the program to other food insecure areas.

Strengthening Family Practices for Latino Families.

PubMed

Chartier, Karen G; Negroni, Lirio K; Hesselbrock, Michie N

2010-01-01

The study examined the effectiveness of a culturally-adapted Strengthening Families Program (SFP) for Latinos to reduce risks for alcohol and drug use in children. Latino families, predominantly Puerto Rican, with a 9-12 year old child and a parent(s) with a substance abuse problem participated in the study. Pre- and post-tests were conducted with each family. Parental stress, parent-child dysfunctional relations, and child behavior problems were reduced in the families receiving the intervention; family hardiness and family attachment were improved. Findings contribute to the validation of the SFP with Latinos, and can be used to inform social work practice with Puerto Rican families.

Spontaneous fungal peritonitis: Epidemiology, current evidence and future prospective.

PubMed

Fiore, Marco; Leone, Sebastiano

2016-09-14

Spontaneous bacterial peritonitis is a complication of ascitic patients with end-stage liver disease (ESLD); spontaneous fungal peritonitis (SFP) is a complication of ESLD less known and described. ESLD is associated to immunodepression and the resulting increased susceptibility to infections. Recent perspectives of the management of the critically ill patient with ESLD do not specify the rate of isolation of fungi in critically ill patients, not even the antifungals used for the prophylaxis, neither optimal treatment. We reviewed, in order to focus the epidemiology, characteristics, and, considering the high mortality rate of SFP, the use of optimal empirical antifungal therapy the current literature.

Gene expression changes in male accessory glands during ageing are accompanied by reproductive decline in Drosophila melanogaster.

PubMed

Koppik, Mareike; Fricke, Claudia

2017-12-01

Senescence is accompanied by loss of reproductive functions. Here, we studied reproductive ageing in Drosophila melanogaster males and asked whether the expected decline in male reproductive success is due to diminished functionality of the male accessory gland (AG). The male AG produces the majority of seminal fluid proteins (SFPs) transferred to the female at mating. SFPs induce female postmating changes and are key to male reproductive success. We measured age-dependent gene expression changes for five representative SFP genes in males from four different age groups ranging from 1 to 6 weeks after eclosion. Simultaneously, we also measured male reproductive success in postmating traits mediated by transfer of these five SFPs. We found a decreased in male SFP gene expression with advancing age and an accompanying decline in male postmating success. Hence, male reproductive senescence is associated with a decline in functionality of the male AG. While overall individual SFP genes decreased in expression, our results point towards the idea that the composition of an ejaculate might change with male age as the rate of change was variable for those five genes. © 2017 John Wiley & Sons Ltd.

Preparation of low molecular weight Sargassum fusiforme polysaccharide and its anticoagulant activity

NASA Astrophysics Data System (ADS)

Sun, Yuhao; Chen, Xiaolin; Liu, Song; Yu, Huahua; Li, Rongfeng; Wang, Xueqin; Qin, Yukun; Li, Pengcheng

2017-10-01

Heparin has been used as an anticoagulant drug for many years, but it has significant side effects. In the search for good substitutes, low molecular weight (MW) polysaccharides from Sargassum fusiforme have been examined and confirmed to possess biological activities. Here, S. fusiforme polysaccharides (SFP) were extracted and subjected to a hydrogen peroxide (H2O2) oxidation method for the preparation of low-MW SFP (LSFP). The effects of temperature, pH, and H2O2 concentration on the degradation process were also examined. Several LSFP of 36, 9, 5.7, and 2.7 kDa were obtained under different conditions, and their anticoagulant activities studied in vitro. The results showed that SFP and LSFP prolonged activated partial thromboplastin (APTT), prothrombin (PT) and thrombin times (TT) significantly, indicating that these low MW polysaccharides possessed anticoagulant activity in the intrinsic, extrinsic, and common coagulation pathways. As these effects were related to the MW of the polysaccharides in APTT and TT but not in PT, the contents of the monosaccharide fucose and sulfate and the polysaccharide MW could have exerted combined effects. The details of this mechanism require further verification.

The C-C motif chemokine ligands CCL5, CCL11, and CCL24 induce the migration of circulating fibrocytes from patients with severe asthma.

PubMed

Isgrò, M; Bianchetti, L; Marini, M A; Bellini, A; Schmidt, M; Mattoli, S

2013-07-01

The C-C motif chemokine ligand 5 (CCL5), CCL11, and CCL24 are involved in the pathogenesis of asthma, and their function is mainly associated with the airway recruitment of eosinophils. This study tested their ability to induce the migration of circulating fibrocytes, which may contribute to the development of irreversible airflow obstruction in severe asthma. The sputum fluid phase (SFP) from patients with severe/treatment-refractory asthma (PwSA) contained elevated concentrations of CCL5, CCL11, and CCL24 in comparison with the SFP from patients with non-severe/treatment-responsive asthma (PwNSA). The circulating fibrocytes from PwSA expressed the receptors for these chemokines at increased levels and migrated in response to recombinant CCL5, CCL11, and CCL24. The SFP from PwSA induced the migration of autologous fibrocytes, and its activity was significantly attenuated by neutralization of endogenous CCL5, CCL11, and CCL24. These findings suggest that CCL5, CCL11, and CCL24 may contribute to the airway recruitment of fibrocytes in severe asthma.

Multiple streams approach to tobacco control policymaking in a tobacco-growing state.

PubMed

Mamudu, Hadii M; Dadkar, Sumati; Veeranki, Sreenivas P; He, Yi; Barnes, Richard; Glantz, Stanton A

2014-08-01

Smokefree policies (SFPs) have diffused throughout the US and worldwide. However, the development of SFPs in the difficult policy environment of tobacco-producing states and economies worldwide has not been well-explored. In 2007, Tennessee, the third largest tobacco producer in the US, enacted the Non-Smoker Protection Act (NSPA). This study utilizes the multiple streams model to provide understanding of why and how this policy was developed by triangulating interviews with key stakeholders and legislative debates with archival documents. In June 2006, the Governor unexpectedly announced support for SFP, which created a window of opportunity for policy change. The Campaign for Healthy and Responsible Tennessee, a health coalition, seized this opportunity and worked with the administration and the Tennessee Restaurant Association to negotiate a comprehensive SFP, however, a weaker bill was used by the legislative leadership to develop the NSPA. Although the Governor and the Tennessee Restaurant Association's support generated an environment for 100% SFP, health groups did not fully capitalize on this environmental change and settled for a weak policy with several exemptions. This study suggests the importance for proponents of policy change to understand changes in their environment and be willing and able to capitalize on these changes.

A microarray-based genotyping and genetic mapping approach for highly heterozygous outcrossing species enables localization of a large fraction of the unassembled Populus trichocarpa genome sequence.

PubMed

Drost, Derek R; Novaes, Evandro; Boaventura-Novaes, Carolina; Benedict, Catherine I; Brown, Ryan S; Yin, Tongming; Tuskan, Gerald A; Kirst, Matias

2009-06-01

Microarrays have demonstrated significant power for genome-wide analyses of gene expression, and recently have also revolutionized the genetic analysis of segregating populations by genotyping thousands of loci in a single assay. Although microarray-based genotyping approaches have been successfully applied in yeast and several inbred plant species, their power has not been proven in an outcrossing species with extensive genetic diversity. Here we have developed methods for high-throughput microarray-based genotyping in such species using a pseudo-backcross progeny of 154 individuals of Populus trichocarpa and P. deltoides analyzed with long-oligonucleotide in situ-synthesized microarray probes. Our analysis resulted in high-confidence genotypes for 719 single-feature polymorphism (SFP) and 1014 gene expression marker (GEM) candidates. Using these genotypes and an established microsatellite (SSR) framework map, we produced a high-density genetic map comprising over 600 SFPs, GEMs and SSRs. The abundance of gene-based markers allowed us to localize over 35 million base pairs of previously unplaced whole-genome shotgun (WGS) scaffold sequence to putative locations in the genome of P. trichocarpa. A high proportion of sampled scaffolds could be verified for their placement with independently mapped SSRs, demonstrating the previously un-utilized power that high-density genotyping can provide in the context of map-based WGS sequence reassembly. Our results provide a substantial contribution to the continued improvement of the Populus genome assembly, while demonstrating the feasibility of microarray-based genotyping in a highly heterozygous population. The strategies presented are applicable to genetic mapping efforts in all plant species with similarly high levels of genetic diversity.

Multiple Streams Approach to Tobacco Control Policymaking in a Tobacco-Growing State

PubMed Central

Mamudu, Hadii M.; Dadkar, Sumati; Veeranki, Sreenivas P.; He, Yi; Barnes, Richard; Glantz, Stanton A.

2014-01-01

Smokefree policies (SFPs) have diffused throughout the US and worldwide. However, the development of SFPs in the difficult policy environment of tobacco-producing states and economies worldwide has not been well-explored. In 2007, Tennessee, the third largest tobacco producer in the US, enacted the Non-Smoker Protection Act (NSPA). This study utilizes the multiple streams model to provide understanding of why and how this policy was developed by triangulating interviews with key stakeholders and legislative debates with archival documents. In June 2006, the Governor unexpectedly announced support for SFP, which created a window of opportunity for policy change. The Campaign for Healthy and Responsible Tennessee, a health coalition, seized this opportunity and worked with the administration and the Tennessee Restaurant Association to negotiate a comprehensive SFP, however, a weaker bill was used by the legislative leadership to develop the NSPA. Although the Governor and the Tennessee Restaurant Association’s support generated an environment for 100 % SFP, health groups did not fully capitalize on this environmental change and settled for a weak policy with several exemptions. This study suggests the importance for proponents of policy change to understand changes in their environment and be willing and able to capitalize on these changes. PMID:24370600

Gas emission from the UO2 samples, containing fission products and burnable absorber

NASA Astrophysics Data System (ADS)

Kopytin, V. P.; Baranov, V. G.; Burlakova, M. A.; Tenishev, A. V.; Kuzmin, R. S.; Pokrovskiy, S. A.; Mikhalchik, V. V.

2016-04-01

The process gas released from the fuel pellets of uranium fuel during fuel burn-up reduces the thermal conductivity of the rod-shell gap, enhances hydrogen embrittlement of the cladding material, causes it's carbonization, as well as transport processes in the fuel. In this study a technique of investigating the thermal desorption of gases from the UO2 fuel material were perfected in the temperature range 300-2000 K for uniform sample heating rate of 15 K/min in vacuum. The characteristic kinetic dependences are acquired for the gas emission from UO2 samples, containing simulators of fission products (SFP) and the burnable neutron absorber (BNA). Depending on the amount of SFP and BNA contained in the sample thermal desorption gas spectra (TDGS) vary. The composition of emitted gas varies, as well as the number of peaks in the TDGS and the peaks shift to higher temperatures. This indicates that introduction of SFPs and BNA alters the sample material structure and cause the creation of so- called traps which have different bonding energies to the gases. The traps can be a grid of dislocations, voids, and contained in the UO2 matrix SFP and BNA. Similar processes will occur in the fuel pellets in the real conditions of the Nuclear Power Plant as well.

Novel Solvent-free Perovskite Deposition in Fabrication of Normal and Inverted Architectures of Perovskite Solar Cells

PubMed Central

Nejand, Bahram Abdollahi; Gharibzadeh, Saba; Ahmadi, Vahid; Shahverdi, H. Reza

2016-01-01

We introduced a new approach to deposit perovskite layer with no need for dissolving perovskite precursors. Deposition of Solution-free perovskite (SFP) layer is a key method for deposition of perovskite layer on the hole or electron transport layers that are strongly sensitive to perovskite precursors. Using deposition of SFP layer in the perovskite solar cells would extend possibility of using many electron and hole transport materials in both normal and invert architectures of perovskite solar cells. In the present work, we synthesized crystalline perovskite powder followed by successful deposition on TiO2 and cuprous iodide as the non-sensitve and sensitive charge transport layers to PbI2 and CH3NH3I solution in DMF. The post compressing step enhanced the efficiency of the devices by increasing the interface area between perovskite and charge transport layers. The 9.07% and 7.71% cell efficiencies of the device prepared by SFP layer was achieved in respective normal (using TiO2 as a deposition substrate) and inverted structure (using CuI as deposition substrate) of perovskite solar cell. This method can be efficient in large-scale and low cost fabrication of new generation perovskite solar cells. PMID:27640991

The rate of metabolism as a factor determining longevity of the Saccharomyces cerevisiae yeast.

PubMed

Molon, Mateusz; Szajwaj, Monika; Tchorzewski, Marek; Skoczowski, Andrzej; Niewiadomska, Ewa; Zadrag-Tecza, Renata

2016-02-01

Despite many controversies, the yeast Saccharomyces cerevisiae continues to be used as a model organism for the study of aging. Numerous theories and hypotheses have been created for several decades, yet basic mechanisms of aging have remained unclear. Therefore, the principal aim of this work is to propose a possible mechanism leading to increased longevity in yeast. In this paper, we suggest for the first time that there is a link between decreased metabolic activity, fertility and longevity expressed as time of life in yeast. Determination of reproductive potential and total lifespan with the use of fob1Δ and sfp1Δ mutants allows us to compare the "longevity" presented as the number of produced daughters with the longevity expressed as the time of life. The results of analyses presented in this paper suggest the need for a change in the definition of longevity of yeast by taking into consideration the time parameter. The mutants that have been described as "long-lived" in the literature, such as the fob1Δ mutant, have an increased reproductive potential but live no longer than their standard counterparts. On the other hand, the sfp1Δ mutant and the wild-type strain produce a similar number of daughter cells, but the former lives much longer. Our results demonstrate a correlation between the decreased efficiency of the translational apparatus and the longevity of the sfp1Δ mutant. We suggest that a possible factor regulating the lifespan is the rate of cell metabolism. To measure the basic metabolism of the yeast cells, we used the isothermal microcalorimetry method. In the case of sfp1Δ, the flow of energy, ATP concentration, polysome profile and translational fitness are significantly lower in comparison with the wild-type strain and the fob1Δ mutant.

Molecular and biochemical characterization of Iranian surfactin-producing Bacillus subtilis isolates and evaluation of their biocontrol potential against Aspergillus flavus and Colletotrichum gloeosporioides.

PubMed

Mohammadipour, Matin; Mousivand, Maryam; Salehi Jouzani, Gholamreza; Abbasalizadeh, Saeed

2009-04-01

The characterization of surfactin-producing Bacillus subtilis isolates collected from different ecological zones of Iran is presented. Characterization was performed using blood agar, PCR, drop-collapse, and reverse-phase high-performance liquid chromatography (HPLC) analyses, and the isolates' biocontrol effects against the aflatoxin-producing agent Aspergillus flavus and the citrus antracnosis agent Colletotrichum gloeosporioides were studied. In total, 290 B. subtilis isolates were isolated from phylosphere and rhizosphere samples collected from fields and gardens of 5 provinces of Iran. Blood agar assays showed that 185 isolates produced different biosurfactants. Isolates containing the sfp gene, coding for surfactin, were detected using the PCR method. It was found that 14 different isolates contained the sfp gene. Drop-collapse assays, which detect isolates with high production of surfactin, showed that 7 isolates produced high levels of surfactin. It was found from HPLC analysis that the isolates containin the sfp gene produced between 55 and 1610 mg of surfactin per litre of broth medium. Four isolates, named BS119m, BS116l, N3dn, and BS113c, produced more than 1000 mg of surfactin per litre of broth. The highest surfactin production level was observed for isolate BS119m (1610 mg/L). The antagonistic potential of the sfp gene-containing isolates was determined using dual culture and chloroform vapour methods. Our bioassay results indicated that isolate BS119m showed high inhibitory effects against A. flavus (100%) and C. gloeosporioides (88%). Furthermore, the effect of purified surfactin on the growth of A. flavus was evaluated. Mycelia growth was considerably reduced with increasing concentration of surfactin, and 36%, 54%, 84%, and 100% inhibitions of mycelia growth were, respectively, observed at 20, 40, 80, and 160 mg/L after 7 days of incubation.

On-chip optical phase locking of single growth monolithically integrated Slotted Fabry Perot lasers.

PubMed

Morrissey, P E; Cotter, W; Goulding, D; Kelleher, B; Osborne, S; Yang, H; O'Callaghan, J; Roycroft, B; Corbett, B; Peters, F H

2013-07-15

This work investigates the optical phase locking performance of Slotted Fabry Perot (SFP) lasers and develops an integrated variable phase locked system on chip for the first time to our knowledge using these lasers. Stable phase locking is demonstrated between two SFP lasers coupled on chip via a variable gain waveguide section. The two lasers are biased differently, one just above the threshold current of the device with the other at three times this value. The coupling between the lasers can be controlled using the variable gain section which can act as a variable optical attenuator or amplifier depending on bias. Using this, the width of the stable phase locking region on chip is shown to be variable.

Proposals for Solutions to Problems Related to the Use of F-34 (SFP) and High Sulphur Diesel on Ground Equipment Using Advanced Reduction Emission Technologies (Propositions de solutions aux problemes lies a l’utilisation de F-34 (SFP) et de diesel a haute teneur en soufre pour le materiel terrestre disposant de technologies avancees de reduction des emissions)

DTIC Science & Technology

2008-09-01

In a two - stage process the urea decomposes to ammonia (NH3) which then reacts with the nitrogen oxides (NOx) and leads to formation of nitrogen and...Sulphur Fuel (HSF) is a potential problem to NATO forces when vehicles and equipment are fitted with advanced emission reduction devices that require Low...worldwide available, standard fuel (F-34) and equipment capable of using such high sulphur fuels (HSF). Recommendations • Future equipment fitted with

MELCOR Model of the Spent Fuel Pool of Fukushima Dai-ichi Unit 4

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

Carbajo, Juan J

2012-01-01

Unit 4 of the Fukushima Dai-ichi Nuclear Power Plant suffered a hydrogen explosion at 6:00 am on March 15, 2011, exactly 3.64 days after the earthquake hit the plant and the off-site power was lost. The earthquake occurred on March 11 at 2:47 pm. Since the reactor of this Unit 4 was defueled on November 29, 2010, and all its fuel was stored in the spent fuel pool (SFP4), it was first believed that the explosion was caused by hydrogen generated by the spent fuel, in particular, by the recently discharged core. The hypothetical scenario was: power was lost, coolingmore » to the SFP4 water was lost, pool water heated/boiled, water level decreased, fuel was uncovered, hot Zircaloy reacted with steam, hydrogen was generated and accumulated above the pool, and the explosion occurred. Recent analyses of the radioisotopes present in the water of the SFP4 and underwater video indicated that this scenario did not occur - the fuel in this pool was not damaged and was never uncovered the hydrogen of the explosion was apparently generated in Unit 3 and transported through exhaust ducts that shared the same chimney with Unit 4. This paper will try to answer the following questions: Could that hypothetical scenario in the SFP4 had occurred? Could the spent fuel in the SPF4 generate enough hydrogen to produce the explosion that occurred 3.64 days after the earthquake? Given the magnitude of the explosion, it was estimated that at least 150 kg of hydrogen had to be generated. As part of the investigations of this accident, MELCOR models of the SFP4 were prepared and a series of calculations were completed. The latest version of MELCOR, version 2.1 (Ref. 1), was employed in these calculations. The spent fuel pool option for BWR fuel was selected in MELCOR. The MELCOR model of the SFP4 consists of a total of 1535 fuel assemblies out of which 548 assemblies are from the core defueled on Nov. 29, 2010, 783 assemblies are older assemblies, and 204 are new/fresh assemblies. The total decay heat of the fuel in the pool was, at the time of the accident, 2.284 MWt, of which 1.872 MWt were from the 548 assemblies of the last core discharged and 0.412 MWt were from the older 783 assemblies. These decay heat values were calculated at Oak Ridge National Laboratory using the ORIGEN2.2 code (Ref. 2) - they agree with values reported elsewhere (Ref. 3). The pool dimensions are 9.9 m x 12.2 m x 11.8 m (height), and with the water level at 11.5 m, the pool volume is 1389 m3, of which only 1240 m3 is water, as some volume is taken by the fuel and by the fuel racks. The initial water temperature of the SFP4 was assumed to be 301 K. The fuel racks are made of an aluminum alloy but are modeled in MELCOR with stainless steel and B4C. MELCOR calculations were completed for different initial water levels: 11.5 m (pool almost full, water is only 0.3 m below the top rim), 4.4577 m (top of the racks), 4.2 m, and 4.026 m (top of the active fuel). A calculation was also completed for a rapid loss of water due to a leak at the bottom of the pool, with the fuel rapidly uncovered and oxidized in air. Results of these calculations are shown in the enclosed Table I. The calculation with the initial water level at 11.5 m (full pool) takes 11 days for the water to boil down to the top of the fuel racks, 11.5 days for the fuel to be uncovered, 14.65 days to generate 150 kg of hydrogen and 19 days for the pool to be completely dry. The calculation with the initial water level at 4.4577 m, takes 1.1 days to uncover the fuel and 4.17 days to generate 150 kg of hydrogen. The calculation with the initial water level at 4.02 m takes 3.63 days to generate 150 kg of hydrogen this is exactly the time when the actual explosion occurred in Unit 4. Finally, fuel oxidation in air after the pool drained the water in 20 minutes, generates only 10 kg of hydrogen this is because very little steam is available and Zircaloy (Zr) oxidation with the oxygen of the air does not generate hydrogen. MELCOR calculated water levels and hydrogen generated in the SFP4 as a function of time for initial water levels of 4.457 m, 4.2 m and 4.02 m are shown in Figs. 1 and 2. Water levels increase at the beginning due to the expansion of the water during the heat-up from 301 K to 373 K. Boiling occurs after the water temperature reaches 373 K. The total amount of hydrogen generated is ~2000 kg, this amount includes hydrogen generated from Zr, which is the largest amount (~1580 kg), from stainless steel (~360 kg), and from B4C (~60 kg). In theory, it is possible to generate up to 3.4 kg of hydrogen per assembly (from oxidation of Zr in the fuel cladding and box), or a total of 4,525 kg from the hot 1331 assemblies stored in the SFP4. The hydrogen generated from oxidation of steel and B4C will be additional. So the answers to the questions are YES according to these MELCOR calculations, enough hydrogen (150 kg) could be generated in the SFP4 3.64 days after the earthquake to produce ...« less

Staphylococcal food poisoning caused by Staphylococcus argenteus harboring staphylococcal enterotoxin genes.

PubMed

Wakabayashi, Yuki; Umeda, Kaoru; Yonogi, Shinya; Nakamura, Hiromi; Yamamoto, Kaori; Kumeda, Yuko; Kawatsu, Kentaro

2018-01-16

Staphylococcal food poisoning (SFP) is caused by staphylococcal enterotoxins (SEs) preformed in food materials. SE genes are encoded on mobile genetic elements and are widely found across Staphylococcus species including S. argenteus, although most SFP cases are caused by S. aureus. S. argenteus, recently discriminated from S. aureus as a novel species, are non-pigmented staphylococci phenotypically related to S. aureus. In 2014 and 2015, two independent food poisoning cases occurred in Osaka, Japan, in which non-pigmented staphylococci were predominantly isolated. Several enterotoxin genes (seb, seg, sei, sem, sen, seo, and selu2) were found in their genome and the production of SEB was confirmed by reverse passive agglutination tests. The non-pigmented isolates from patients, food handlers, food, and cooking utensils all produced the same pulsed-field gel electrophoresis pattern. These non-pigmented isolates were coagulase-positive and biochemically identical to S. aureus. We performed further genetic analysis using nucA sequencing and multi-locus sequence typing, and identified these isolates as S. argenteus. We also found that seb was encoded on the Staphylococcus aureus pathogenicity island, while seg, sei, sem, sen, seo, and selu2 were encoded on the enterotoxin gene cluster. From these results, we concluded that the two food poisoning outbreaks were SFP cases caused by S. argenteus harboring SE genes. Copyright © 2017 Elsevier B.V. All rights reserved.

Performance of Single Friction Pendulum bearing for isolated buildings subjected to seismic actions in Vietnam

NASA Astrophysics Data System (ADS)

Nguyen, N. V.; Nguyen, C. H.; Hoang, H. P.; Huong, K. T.

2018-04-01

Using structural control technology in earthquake resistant design of buildings in Vietnam is very limited. In this paper, a performance evaluation of using Single Friction Pendulum (SFP) bearing for seismically isolated buildings with earthquake conditions in Vietnam is presented. A two-dimensional (2-D) model of the 5-storey building subjected to earthquakes is analyzed in time domain. Accordingly, the model is analyzed for 2 cases: with and without SFP bearing. The ground acceleration data is selected and scaled to suit the design acceleration in Hanoi followed by the Standard TCVN 9386:2012. It is shown that the seismically isolated buildings gets the performance objectives while achieving an 91% reduction in the base shear, a significant decrease in the inter-story drift and absolute acceleration of each story.

[Social marketing and public policies for health: campaign to promote smoke-free spaces in Mexico].

PubMed

Villalobos, Víctor; Ramírez, Olivia Ortiz; Thrasher, James F; Santillán, Edna Arillo; Hernández, Rosaura Pérez; Cedillo, Claudia; González, Wendy

2010-01-01

"Porque todos respiramos lo mismo" is a mass media campaign to promote smoke-free places (SFP). The development stages were: strategic planning; formative research; message development; media plan; and impact evaluation. Development involved formation of a coalition of key actors in various sectors. The target population was smokers and nonsmokers, with the aim of changing social norms around SFP. Nonsmokers were targeted because they comprised the majority and were most likely to appreciate the benefits of SFPs. Campaign materials were aired on television, radio, print and on billboards. One key limitation was the lack of evidence for previous campaigns, which increased the importance of formative research and of including a rigorous evaluation for this one. The campaign evaluation indicates a significant impact, which suggests that future campaigns use similar strategies in their development.

Maternal Posttraumatic Stress Symptoms and Infant Emotional Reactivity and Emotion Regulation

PubMed Central

Enlow, Michelle Bosquet; Kitts, Robert L.; Blood, Emily; Bizarro, Andrea; Hofmeister, Michelle; Wright, Rosalind J.

2011-01-01

The current study examined associations between maternal posttraumatic stress disorder (PTSD) symptoms and infant emotional reactivity and emotion regulation during the first year of life in a primarily low-income, urban, ethnic/racial minority sample of 52 mother-infant dyads. Mothers completed questionnaires assessing their own trauma exposure history and current PTSD and depressive symptoms and their infants’ temperament when the infants were 6 months old. Dyads participated in the repeated Still-Face Paradigm (SFP-R) when the infants were 6 months old, and infant affective states were coded for each SFP-R episode. Mothers completed questionnaires assessing infant trauma exposure history and infant current emotional and behavioral symptoms when the infants were 13 months old. Maternal PTSD symptoms predicted infants’ emotion regulation at 6 months as assessed by (a) infant ability to recover from distress during the SFP-R and (b) maternal report of infant rate of recovery from distress/arousal in daily life. Maternal PTSD symptoms also predicted maternal report of infant externalizing, internalizing, and dysregulation symptoms at 13 months. Maternal PTSD was not associated with measures of infant emotional reactivity. Neither maternal depressive symptoms nor infant direct exposure to trauma accounted for the associations between maternal PTSD symptoms and infant outcomes. These findings suggest that maternal PTSD is associated with offspring emotion regulation difficulties as early as infancy. Such difficulties may contribute to increased risk of mental health problems among children of mothers with PTSD. PMID:21862136

Separated fringe packet observations with the Chara Array. II. ω Andromeda, HD 178911, and ξ Cephei

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

Farrington, C. D.; Ten Brummelaar, T. A.; Turner, N. H.

When observed with optical long-baseline interferometers, components of a binary star that are sufficiently separated produce their own interferometric fringe packets; these are referred to as separated fringe packet (SFP) binaries. These SFP binaries can overlap in angular separation with the regime of systems resolvable by speckle interferometry at single, large-aperture telescopes and can provide additional measurements for preliminary orbits lacking good phase coverage, help constrain elements of already established orbits, and locate new binaries in the undersampled regime between the bounds of spectroscopic surveys and speckle interferometry. In this process, a visibility calibration star is not needed, and themore » SFPs can provide an accurate vector separation. In this paper, we apply the SFP approach to ω Andromeda, HD 178911, and ξ Cephei with the CLIMB three-beam combiner at the CHARA Array. For these systems we determine component masses and parallax of 0.963 ± 0.049 M {sub ☉} and 0.860 ± 0.051 M {sub ☉} and 39.54 ± 1.85 mas for ω Andromeda, for HD 178911 of 0.802 ± 0.055 M {sub ☉} and 0.622 ± 0.053 M {sub ☉} with 28.26 ± 1.70 mas, and masses of 1.045 ± 0.031 M {sub ☉} and 0.408 ± 0.066 M {sub ☉} and 38.10 ± 2.81 mas for ξ Cephei.« less

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.

Hypolipidemic, antioxidant and antiatherogenic property of sardine by-products proteins in high-fat diet induced obese rats.

PubMed

Affane, Fouad; Louala, Sabrine; El Imane Harrat, Nour; Bensalah, Fatima; Chekkal, Hadjera; Allaoui, Amine; Lamri-Senhadji, Myriem

2018-04-15

Fish by-products valorization on account of their richness in bioactive compounds may represent a better alternative to marine products with a view to economic profitability and sustainable development. In this study, we compared the effect of sardine by-product proteins (SBy-P), with those of the fillets (SF-P) or casein (Cas), on growth parameters, serum leptin level, lipids disorders, lipid peroxidation and reverse cholesterol transport, in diet-induced obese rats. Obesity was induced by feeding rats a high-fat diet (20% sheep fat), during 12 weeks. At body weight (BW) of 400 ± 20 g, eighteen obese rats were divided into three homogenous groups and continue to consume the high-fat diet for 4 weeks containing either, 20% SBy-P, SF-P or Cas. The results showed that SBy-P, compared to SF-P and Cas, efficiently reduced food intake (FI), BW gain and serum leptin level, and improved blood lipids levels and reverse cholesterol transport by reducing total cholesterol (TC), triacylglycerols (TG) and low-density lipoprotein cholesterol (LDL-HDL 1 -C) serum levels, increasing the level of high-density lipoprotein cholesterol (HDL 2 -C and HDL 3 -C), and enhancing lecithin: cholesterol acyltransferase (LCAT) activity. Furthermore, they attenuated lipid peroxidation by increasing atheroprotective activity of the paraoxonase-1 (PON-1). Sardine by-product proteins due to their richness in certain essential amino acids, highlight weight-loss, lipid-lowering, antioxidant and anti-atherogenic potentials, contributing to the improvement of the complications associated with obesity. Copyright © 2018 Elsevier Inc. All rights reserved.

Performance of UNHCR nutrition programs in post-emergency refugee camps

PubMed Central

2011-01-01

Background The United Nations High Commissioner for Refugees (UNHCR) launched a health information system (HIS) in 2005 to enhance quality and consistency of routine health information available in post-emergency refugee camps. This paper reviews nutrition indicators and examines their application for monitoring and evaluating the performance of UNHCR nutrition programs in more than 90 refugee camps in 18 countries. Methods The HIS is a primary source of feeding program data which is collected using standardized case definitions and reporting formats across refugee camps in multiple settings. Data was aggregated across time periods and within and across countries for analysis. Basic descriptive statistics were then compared to UNHCR program performance standards. Results Camp populations covered by the HIS ranged from 192,000 to 219,000 between 2007 and mid-2009; 87% of under five children covered by the HIS were in Africa and 13% in Asia. Average moderate acute malnutrition (MAM) and severe acute malnutrition (SAM) rates reported in 74 of 81 camps for the 2007-2009 time periods were 7.0% and 1.6%, respectively. The supplementary feeding program (SFP) admission rate was 151/1000/yr with 93% of SFP admissions occurring in Africa. SFP performance consistently exceeded all UNHCR standards with the exception of length of enrollment. Average length of SFP enrollment was 12 weeks in Africa and 22 weeks in Asia as compared to the UNHCR standard of < 8 weeks. The therapeutic feeding program (TFP) admission was 22/1000/yr with 95% of TFP admissions in Africa. TFP performance met UNHCR standards with the exception of daily weight gain. Conclusions Inclusion of children identified as moderately and severely wasted in the HIS would allow UNHCR to better track and respond to changes in nutrition status. Improved growth monitoring coverage or active malnutrition surveillance would increase UNHCR's ability to identify and treat cases of acute malnutrition. Expansion of nutrition reporting to address the transition to community-based therapeutic care is essential for adequate performance monitoring in the future. In terms of program priorities, a focus on camps and countries with large refugee populations and high feeding program enrollment rates would have the greatest impact in terms of absolute reductions in the incidence and prevalence of malnutrition. PMID:22029657

An Sfp-type PPTase and associated polyketide and nonribosomal peptide synthases in Agrobacterium vitis are essential for induction of tobacco hypersensitive response and grape necrosis.

PubMed

Zheng, Desen; Burr, Thomas J

2013-07-01

An Sfp-type phosphopantetheinyl transferase (PPTase) encoding gene F-avi5813 in Agrobacterium vitis F2/5 was found to be required for the induction of a tobacco hypersensitive response (HR) and grape necrosis. Sfp-type PPTases are post-translation modification enzymes that activate acyl-carry protein (ACP) domains in polyketide synthases (PKS) and peptidyl-carrier protein (PCP) domains of nonribosomal peptide synthases (NRPS). Mutagenesis of PKS and NRPS genes in A. vitis led to the identification of a PKS gene (F-avi4330) and NRPS gene (F-avi3342) that are both required for HR and necrosis. The gene immediately downstream of F-avi4330 (F-avi4329) encoding a predicted aminotransferase was also found to be required for HR and necrosis. Regulation of F-avi4330 and F-avi3342 by quorum-sensing genes avhR, aviR, and avsR and by a lysR-type regulator, lhnR, was investigated. It was determined that F-avi4330 expression is positively regulated by avhR, aviR, and lhnR and negatively regulated by avsR. F-avi3342 was found to be positively regulated by avhR, aviR, and avsR and negatively regulated by lhnR. Our results suggest that a putative hybrid peptide-polyketide metabolite synthesized by F-avi4330 and F-avi3342 is associated with induction of tobacco HR and grape necrosis. This is the first report that demonstrates that NRPS and PKS play essential roles in conferring the unique ability of A. vitis to elicit a non-host-specific HR and host-specific necrosis.

Preventing substance misuse: study protocol for a randomised controlled trial of the Strengthening Families Programme 10–14 UK (SFP 10–14 UK)

PubMed Central

2014-01-01

Background Prevention of alcohol, drug and tobacco misuse by young people is a key public health priority. There is a need to develop the evidence base through rigorous evaluations of innovative approaches to substance misuse prevention. The Strengthening Families Programme 10–14 is a universal family-based alcohol, drugs and tobacco prevention programme, which has achieved promising results in US trials, and which now requires cross-cultural assessment. This paper therefore describes the protocol for a randomised controlled trial of the UK version of the Strengthening Families Programme 10–14 (SFP 10–14 UK). Methods/Design The trial comprises a pragmatic cluster randomised controlled effectiveness trial with families as the unit of randomisation, with embedded process and economic evaluations. Participating families will be randomised to one of two treatment groups - usual care with full access to existing services (control group), or usual care plus SFP 10–14 UK (intervention group). The trial has two primary outcomes - the number of occasions that young people report having drunk alcohol in the last 30 days, and drunkenness during the last 30 days, both dichotomised as ‘never’ and ‘1-2 times or more’. The main follow-up is at 2 years past baseline, and short-term and intermediate outcomes are also measured at 9 and 15 months. Discussion The results from this trial will provide evidence on the effectiveness and cost-effectiveness of an innovative universal family-based substance misuse prevention programme in a UK context. Trial registration Current Controlled Trials ISRCTN63550893. PMID:24438460

Predictive performance of four frailty measures in an older Australian population

PubMed Central

Widagdo, Imaina S.; Pratt, Nicole; Russell, Mary; Roughead, Elizabeth E.

2015-01-01

Background: there are several different frailty measures available for identifying the frail elderly. However, their predictive performance in an Australian population has not been examined. Objective: to examine the predictive performance of four internationally validated frailty measures in an older Australian population. Methods: a retrospective study in the Australian Longitudinal Study of Ageing (ALSA) with 2,087 participants. Frailty was measured at baseline using frailty phenotype (FP), simplified frailty phenotype (SFP), frailty index (FI) and prognostic frailty score (PFS). Odds ratios (OR) were calculated to measure the association between frailty and outcomes at Wave 3 including mortality, hospitalisation, nursing home admission, fall and a combination of all outcomes. Predictive performance was measured by assessing sensitivity, specificity, positive and negative predictive values (PPV and NPV) and likelihood ratio (LR). Area under the curve (AUC) of dichotomised and the multilevel or continuous model of the measures was examined. Results: prevalence of frailty varied from 2% up to 49% between the measures. Frailty was significantly associated with an increased risk of any outcome, OR (95% confidence interval) for FP: 1.9 (1.4–2.8), SFP: 3.6 (1.5–8.8), FI: 3.4 (2.7–4.3) and PFS: 2.3 (1.8–2.8). PFS had high sensitivity across all outcomes (sensitivity: 55.2–77.1%). The PPV for any outcome was highest for SFP and FI (70.8 and 69.7%, respectively). Only FI had acceptable accuracy in predicting outcomes, AUC: 0.59–0.70. Conclusions: being identified as frail by any of the four measures was associated with an increased risk of outcomes; however, their predictive accuracy varied. PMID:26504118

Storage Time and Temperature Effects on Histamine Production in Tuna Salad Preparations.

PubMed

McCarthy, Susan; Bjornsdottir-Butler, Kristin; Benner, Ronald

2015-07-01

Scombrotoxin fish poisoning (SFP), also known as histamine (Hst) poisoning, has been associated with consumption of scombroid-type fish, including tuna and tuna fish products. Preparation of commercial tuna salad contaminated with Hstproducing bacteria (HPB), combined with time-temperature abuse, can present a food safety hazard. A potential source of HPB is raw ingredients, such as celery and onions. The objectives of this study were to determine whether raw ingredients can be a source of HPB and to ascertain the effects of storage time (up to 4 days or 4 weeks) and temperature (4, 10, 18, 25, 30°C) on growth and Hst production by high-HPB (>1,000 ppm of Hst) in tuna salad preparations. Pantoea-Erwinia, Erwinia persicinus, Erwinia spp., and Enterobacter pyrinus isolated from celery in this study were used to inoculate tuna salad and tuna salad with celery or onion. HPB numbers were 0.7 to 4.3 log most probable number per g higher in the presence of celery or onion versus plain tuna salad (3:1 tuna:mayonnaise). E. pyrinus-inoculated plain tuna salad and tuna salad with celery and onion had >500 ppm of Hst after 2 days at 30°C and 4 days at 25°C. E. pyrinus-inoculated salad with celery and onion had >500 ppm of Hst after 4 days at 18°C and 2 weeks at 10°C. Raw celery can introduce HPB into tuna salad, which can cause SFP if the product is time-temperature abused. Tuna salad products must be refrigerated at ≤4°C to prevent growth and Hst production by the HPB used in this study, to protect consumers from potential SFP.

Adherence to the Spanish dietary guidelines and its association with obesity in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Granada study.

PubMed

Molina-Montes, Esther; Uzhova, Irina; Molina-Portillo, Elena; Huerta, José-María; Buckland, Genevieve; Amiano, Pilar; Menéndez, Virginia; Barricarte, Aurelio; González, Carlos A; Sánchez, María-José

2014-11-01

Dietary guidelines are intended to prevent chronic diseases and obesity. The aim of the present study was to develop a diet quality index based on the Spanish Food Pyramid (SFP) and to further explore its association with obesity in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Granada study. Cross-sectional study. The SFP score considered recommendations given for twelve food groups, and for physical activity and alcohol consumption. Obesity was defined as BMI over 30 kg/m2 and abdominal obesity as waist circumference larger than 102 cm (men) and 88 cm (women). Logistic regression was conducted to estimate odds ratios of obesity by quintiles and by 10-point increment in adherence to the score, controlling for potential confounders. EPIC-Granada study. Participants (n 6717) aged 35-69 years (77 % women). A 10-point increase in adherence to the SFP score was associated with a 14 % (OR=0·86; 95 % CI 0·79, 0·94) lower odds of obesity in men (P interaction by sex=0·02). The odds of abdominal obesity decreased globally by 12 % (OR=0·88; 95 % CI 0·84, 0·93) per 10-point increase in adherence to this score. The effect of higher adherence to the score on abdominal obesity was stronger in physically inactive men and women (ORper 10-point increase=0·79; 95 % CI 0·68, 0·92 and ORper 10-point increase=0·89; 95 % CI 0·84, 0·95, respectively). These findings support that the Spanish dietary guidelines might be an effective tool for obesity prevention. However, prospective studies investigating this association are warranted.

Assessment of toxic impact of metals on proline, antioxidant enzymes, and biological characteristics of Pseudomonas aeruginosa inoculated Cicer arietinum grown in chromium and nickel-stressed sandy clay loam soils.

PubMed

Saif, Saima; Khan, Mohammad Saghir

2018-04-17

Considering the heavy metal risk to soil microbiota and agro-ecosystems, the study was designed to determine metal toxicity to bacteria and to find metal tolerant bacteria carrying multifarious plant growth promoting activities and to assess their impact on chickpea cultivated in stressed soils. Metal tolerant strain SFP1 recognized as Pseudomonas aeruginosa employing 16S rRNA gene sequence determination showed maximum tolerance to Cr (400 μg/ml) and Ni (800 μg/ml) and produced variable amounts of indole acetic acid, HCN, NH 3 , and ACC deaminase and could solubilize insoluble phosphates even under Cr (VI) and Ni stress. Metal tolerant P. aeruginosa reduced toxicity of Cr (VI) and Ni and concomitantly enhanced the performance of chickpea grown under stressed and conventional soils. At 144 mg Cr kg -1 , the measured parameters of a bacterial strain was significantly enhanced, but it was lower compared to those recorded at 660 mg Ni kg -1 . The strain SFP1 demonstrated maximum increase in seed yield (81%) and grain protein (16%) at 660 mg Ni kg -1 over uninoculated and untreated control. Stressed plants had more proline, antioxidant enzymes, and metal concentrations in plant tissues. P. aeruginosa, however, remarkably declined the level of stress markers (proline and APX, SOD, CAT, and GR), as well as with Cr (VI) and Ni uptake by chickpea. Conclusively, P. aeruginosa strain SFP1 due to its dual metal tolerant ability, capacity to secrete plant growth promoting regulators even under metal stress and potential to mitigate metal toxicity, could be developed as microbial inoculant for enhancing chickpea production in Cr and Ni contaminated soils.

Alfalfa Biomass Germplasms: SFP Detection and Transcriptome Analysis

USDA-ARS?s Scientific Manuscript database

Advances in alfalfa [Medicago sativa (L.) subsp. sativa] breeding, molecular genetics, and genomics have been slow because this crop is an allogamous autotetraploid (2n = 4x = 32) with complex polysomic inheritance. Increasing cellulose and decreasing lignin in alfalfa stem cell walls would improve ...

Averrhoa carambola L. peel extract suppresses adipocyte differentiation in 3T3-L1 cells.

PubMed

Rashid, Asyifah Mohamed; Lu, Kaihui; Yip, Yew Mun; Zhang, Dawei

2016-02-01

Obesity is associated with an increased risk of many chronic diseases. Recently, a growing body of evidence has shown that phytochemicals may inhibit adipogenesis and obesity. In this study, we report for the first time, the ability of Averrhoa carambola L. peel extract commonly known as star fruit (SFP) to effectively suppress adipocyte differentiation in 3T3-L1 preadipocytes and therefore, address it as a potential candidate to treat obesity and its related diseases. (-)-Epicatechin was identified as a bioactive compound likely responsible for this suppression. As the genetic expression studies revealed that the adipogenic activity of SFP extract was due to the simultaneous downregulation of the C/EBPα and PPARγ as well as the upregulation of PPARα receptor genes, a detailed computational docking study was also elucidated to reveal the likely binding mode of (-)-epicatechin to the receptor of interest, accounting for the likely mechanism that results in the overall suppression of adipocyte differentiation.

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.

Effectiveness of a Culturally Adapted Strengthening Families Program 12-16-Years for High-Risk Irish Families

ERIC Educational Resources Information Center

Kumpfer, Karol L.; Xie, Jing; O'Driscoll, Robert

2012-01-01

Background: Evidence-based programs (EBPs) targeting effective family skills are the most cost effective for improving adolescent behavioural health. Cochrane Reviews have found the "Strengthening Families Program" (SFP) to be the most effective substance abuse prevention intervention. Standardized cultural adaptation processes resulted…

Differentiation of animal fats from different origins: use of polymorphic features detected by Raman spectroscopy.

PubMed

Motoyama, Michiyo; Ando, Masahiro; Sasaki, Keisuke; Hamaguchi, Hiro-O

2010-11-01

Food safety requires the development of reliable techniques that ensure the origin of animal fats. In the present work, we try to verify the efficacy of using the polymorphic features of fats for discriminating animal-fat origins. We use Raman spectroscopy to collect the structural information of fat crystals. It is shown that a single Raman band at 1417 cm(-1) successfully differentiates pork fats from beef fats. This band is known to be characteristic of the β'-polymorph of fats. Pork fats show this band because they contain the β'-polymorph after rapid cooling to 0 °C. In beef-pork-fat mixtures, this band is not detected even in the presence of 50% pork fat; an addition of beef fat to pork fat is likely to produce a mixed fat with a completely different polymorphic behavior. This method seems to have the potential to detect beef products contaminated with pork-adipose tissue.

Templated sequence insertion polymorphisms in the human genome

NASA Astrophysics Data System (ADS)

Onozawa, Masahiro; Aplan, Peter

2016-11-01

Templated Sequence Insertion Polymorphism (TSIP) is a recently described form of polymorphism recognized in the human genome, in which a sequence that is templated from a distant genomic region is inserted into the genome, seemingly at random. TSIPs can be grouped into two classes based on nucleotide sequence features at the insertion junctions; Class 1 TSIPs show features of insertions that are mediated via the LINE-1 ORF2 protein, including 1) target-site duplication (TSD), 2) polyadenylation 10-30 nucleotides downstream of a “cryptic” polyadenylation signal, and 3) preference for insertion at a 5’-TTTT/A-3’ sequence. In contrast, class 2 TSIPs show features consistent with repair of a DNA double-strand break via insertion of a DNA “patch” that is derived from a distant genomic region. Survey of a large number of normal human volunteers demonstrates that most individuals have 25-30 TSIPs, and that these TSIPs track with specific geographic regions. Similar to other forms of human polymorphism, we suspect that these TSIPs may be important for the generation of human diversity and genetic diseases.

Twinning of cubic diamond explains reported nanodiamond polymorphs

NASA Astrophysics Data System (ADS)

Németh, Péter; Garvie, Laurence A. J.; Buseck, Peter R.

2015-12-01

The unusual physical properties and formation conditions attributed to h-, i-, m-, and n-nanodiamond polymorphs has resulted in their receiving much attention in the materials and planetary science literature. Their identification is based on diffraction features that are absent in ordinary cubic (c-) diamond (space group: Fd-3m). We show, using ultra-high-resolution transmission electron microscope (HRTEM) images of natural and synthetic nanodiamonds, that the diffraction features attributed to the reported polymorphs are consistent with c-diamond containing abundant defects. Combinations of {113} reflection and <011> rotation twins produce HRTEM images and d-spacings that match those attributed to h-, i-, and m-diamond. The diagnostic features of n-diamond in TEM images can arise from thickness effects of c-diamonds. Our data and interpretations strongly suggest that the reported nanodiamond polymorphs are in fact twinned c-diamond. We also report a new type of twin (<11> rotational), which can give rise to grains with dodecagonal symmetry. Our results show that twins are widespread in diamond nanocrystals. A high density of twins could strongly influence their applications.

Clinical features of Bim deletion polymorphism and its relation with crizotinib primary resistance in Chinese patients with ALK/ROS1 fusion-positive non-small cell lung cancer.

PubMed

Zhang, Limin; Jiang, Tao; Li, Xuefei; Wang, Yan; Zhao, Chao; Zhao, Sha; Xi, Lei; Zhang, Shijia; Liu, Xiaozhen; Jia, Yijun; Yang, Hui; Shi, Jinpeng; Su, Chunxia; Ren, Shengxiang; Zhou, Caicun

2017-08-01

The authors' previous study demonstrated that the B-cell chronic lymphocytic leukemia/lymphoma (Bcl-2)-like 11 (BCL2L11) (Bim) deletion polymorphism was associated with poor clinical response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC) with EGFR mutations. The objective of the current study was to investigate the impact of the Bim deletion polymorphism among patients with anaplastic lymphoma kinase (ALK)-positive or ROS proto-oncogene 1, receptor tyrosine kinase (ROS1)-positive NSCLC who were treated with crizotinib. A total of 55 patients with ALK-positive NSCLC and 14 patients with ROS1-positive NSCLC who were treated with crizotinib were enrolled into the current study. The Bim deletion polymorphism was analyzed by polymerase chain reaction. The clinical features of the Bim deletion polymorphism and its impact on the effect of crizotinib were investigated. The Bim deletion polymorphism was present in 9 of 69 patients with ALK-positive or ROS1-positive NSCLC (13.0%). There were no differences noted with regard to clinicopathological features between patients with and without the Bim deletion polymorphism. Patients with the Bim deletion polymorphism had a significantly shorter progression-free survival (PFS) and lower objective response rate compared with those without (median PFS, 182 days vs 377 days [P = .008]) (objective response rate, 44.4% vs 81.7% [P =.041]) in all populations. The significant difference in PFS was observed in patients with ALK-positive NSCLC (83 days vs 305 days [P =.0304]) compared with those with ROS1-positive NSCLC (218 days vs not reached [P =.082]). Multivariate analysis indicated that the Bim deletion polymorphism was an independent predictive factor for patients with ALK-positive NSCLC who were treated with crizotinib (hazard ratio, 4.786 [P =.006]). The Bim deletion polymorphism was found to be associated with poor clinical response to crizotinib in patients with ALK fusion-positive NSCLC. Cancer 2017;123:2927-35. © 2017 American Cancer Society. © 2017 American Cancer Society.

77 FR 59186 - Clean Air Act Operating Permit Program; Petition for Objection to State Operating Permit for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-26

... ENVIRONMENTAL PROTECTION AGENCY [Petition IV-2011-1; FRL-9734-2] Clean Air Act Operating Permit Program; Petition for Objection to State Operating Permit for Tennessee Valley Authority's Shawnee Fossil... Valley Authority for its Shawnee Fossil Plant (SFP) facility located in West Paducah, Kentucky. This...

Social values of specialty forest products to rural communities

Treesearch

Marla R. Emery

1999-01-01

Rural communities have long been known for their cultural distinctiveness, independent spirits, and, unfortunately, comparatively high poverty rates. A look at the promotion of Specialty Forest Products (SFP) as a rural development strategy against the backdrop of larger social trends such as welfare reform and economic restructuring suggests the need to ask hard...

Malnutrition, School Feeding and Educational Performance. Notes, Comments...No. 186 = Malnutrition, alimentation scolaire et resultats educatifs.

ERIC Educational Resources Information Center

Levinger, Beryl

Studies reviewed in this paper analyze the relationship between School Feeding Programme (SFP) participation and cognitive development in both developing and industralized countries. Contents concern: (1) the relationship betweeen diet and cognitive development; (2) limitations of intelligence quotient tests and the need for more adequate…

78 FR 38078 - Biweekly Notice; Applications and Amendments to Facility Operating Licenses and Combined Licenses...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-25

... SFP Purification Loop and recirculation and purification of the RWST water using the BARS is not... revise the minimum volume and low level setpoint on the Refueling Water Storage Tank. Because the... proposed change would revise Technical Specification 3.5.4, ``Refueling Water Storage Tank (RWST)'' such...

Strengthening Family Practices for Latino Families

ERIC Educational Resources Information Center

Chartier, Karen G.; Negroni, Lirio K.; Hesselbrock, Michie N.

2010-01-01

This study examined the effectiveness of a culturally adapted Strengthening Families Program (SFP) for Latinos to reduce risks for alcohol and drug use in children. Latino families, predominantly Puerto Rican, with a 9- to 12-year-old child and a parent(s) with a substance abuse problem participated in the study. Pre- and post-tests were conducted…

77 FR 48556 - Applications and Amendments to Facility Operating Licenses and Combined Licenses Involving...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-14

... would use a combination of partial credit for soluble boron, Boral\\TM\\ for Region 1, burnup, rod cluster... storage racks or the new fuel handling processes. Operation of the SFP utilizes soluble boron; crediting this boron for criticality control does not change the probability of any accident. The proposed...

Analysis of gamma ray dose for dried up pond storing low enriched UO2 fuel

NASA Astrophysics Data System (ADS)

Nauchi, Yasushi; Suzuki, Motomu

2017-09-01

Gamma ray dose is calculated for loss of coolant accident in spent fuel pond (SFP) storing irradiated fuels used in light water reactors. Influence of modelling of fuel assemblies, source distributions, and loading fraction of fuel assemblies in the fuel rack on the dose are investigated.

Barriers and Opportunities Related to Whole Grain Foods in Minnesota School Foodservice

ERIC Educational Resources Information Center

Hesse, David; Braun, Curtis; Dostal, Allison; Jeffery, Robert; Marquart, Len

2009-01-01

Purpose/Objectives: The purpose of this research was to identify barriers and opportunities associated with the introduction of whole grain foods into school cafeterias. The primary objective was to elicit input from school foodservice personnel (SFP) regarding their experiences in ordering, purchasing, preparing, and serving whole grain foods in…

The dynamic still-face effect: do infants decrease bidding over time when parents are not responsive?

PubMed

Ekas, Naomi V; Haltigan, John D; Messinger, Daniel S

2013-06-01

The still-face paradigm (SFP) was designed to assess infant expectations that parents will respond to infant communicative signals. During the still-face (SF) episode, the parent ceases interaction and maintains a neutral expression. Original, qualitative descriptions of infant behavior suggested changes within the SF episode: infants decrease bidding and disengage from their impassive parent. Research has documented changes in mean levels of infant behavior between episodes of the SFP. The hypothesis that infant behavior changes within the SF episode has not been empirically tested. In this study, hierarchical linear modeling indicated that infant gazing at the parent, smiling, and social bidding (smiling while gazing at the parent) decreased with time in the SF episode, while infant cry-face expressions increased. Changes in infant behaviors within the SF episode were associated with infant attachment and infant internalizing problems. The dynamic still-face effect quantifies infant initiation of interaction in the face of parental unresponsiveness and is a potential predictor of individual differences in development. PsycINFO Database Record (c) 2013 APA, all rights reserved

Expression of Staphylococcal Enterotoxins under Stress Encountered during Food Production and Preservation.

PubMed

Schelin, Jenny; Susilo, Yusak Budi; Johler, Sophia

2017-12-15

Staphylococcal food poisoning (SFP) is the most prevalent cause of food-borne intoxications worldwide. Consumption of enterotoxins preformed in food causes violent vomiting and can be fatal in children and the elderly. While being repressed by competing bacteria in most matrices, Staphylococcus aureus benefits from crucial competitive advantages in foods with high osmolarity or low pH. During recent years, the long-standing belief in the feasibility of assessing SFP risk based on colony-forming units of S. aureus present in food products has been disproven. Instead, researchers and food business operators are acutely aware of the imminent threat arising from unforeseeable enterotoxin production under stress conditions. This paradigm shift led to a variety of new publications enabling an improved understanding of enterotoxin expression under stress conditions encountered in food. The wealth of data provided by these studies is extremely diverse, as it is based on different methodological approaches, staphylococcal strains, stressors, and enterotoxins. Therefore, in this review, we aggregated and critically evaluated the complex findings of these studies, to provide readers with a current overview of the state of research in the field.

Gas chromatographic quantitation of underivatized amines in the determination of their octanol-0.1 M sodium hydroxide partition coefficients by the shake-flask method.

PubMed

Grunewald, G L; Pleiss, M A; Gatchell, C L; Pazhenchevsky, R; Rafferty, M F

1984-06-01

The use of gas chromatography (GC) for the determination of 0.1 M sodium hydroxide-octanol partition coefficients (log P) for a wide variety of ethylamines is demonstrated. The conventional shake-flask procedure (SFP) is utilized, with the addition of an internal reference, which is cleanly separated from the desired solute and solvents on a 10% Apiezon L, 2% potassium hydroxide on 80-100 mesh Chromosorb W AW column. The partitioned solute is extracted from the aqueous phase with chloroform and analyzed by GC. The method provides an accurate and highly reproducible means of determining log P values, as demonstrated by the low relative standard errors. The technique is both rapid and extremely versatile. The use of the internal standard method of analysis introduces consistency, since variables like the exact weight of solute are not necessary (unlike the traditional SFP) and the volume of sample injected is not critical. The technique is readily accessible to microgram quantities of solutes, making it ideal for a wide range of volatile, amine-bearing compounds.

Are physicians aware of their role in tobacco control? A conference-based survey in Portugal.

PubMed

Ravara, Sofia B; Castelo-Branco, Miguel; Aguiar, Pedro; Calheiros, Jose M

2014-09-20

The crucial role of physicians in tobacco control (TC) is widely recognized. In 2008, Portugal implemented a non-comprehensive smoke-free policy (SFP). In 2009, a conference-survey was carried out to explore Portuguese physicians' engagement in tobacco control, by evaluating the following: 1) attendance at TC training and awareness of training needs; 2) participation in TC activities; 3) attitudes and beliefs regarding SFPs. Questionnaire-based cross-sectional study conducted during two major national medical conferences targeting GPs, hospitalists, and students/recent graduates. Descriptive analysis and logistic regression were performed. Response rate was 63.7% (605/950). Of the 605 participants, 58.3% were GPs, 32.4% hospitalists, 9.3% others; 62.6% were female; mean age was 39.0 ± 12.9 years. Smoking prevalence was 29.2% (95% CI: 23.3-35.1) in males; 15.8% (95% CI: 12.1-19.5) in females, p < 0.001. While the overwhelming majority of physicians strongly agreed that second-hand smoke (SHS) endangers health, awareness of SFP benefits and TC law was limited, p < 0.001. A significant minority (35.5%) believed that SHS can be eliminated by ventilation systems. Most physicians lacked training; only a minority (9.0%) participated regularly in TC. Training was the most consistent predictor of participation in TC. General agreement with SFP was high; but significantly lower for indoor leisure settings, outdoors bans in healthcare/schools settings and smoking restrictions in the home/car, p < 0.001. Smoking behaviour strongly predicted support for smoking restrictions in restaurants and bars/discos, healthcare outdoors and private settings. The findings suggest that Portuguese physicians are not aware of their role in tobacco control. Poor engagement of physicians in TC may contribute to the current lack of comprehensive policies in Portugal and Europe and undermine social norm change. Medical and professional continuing education on tobacco control should be made top priorities.

Positive Regulation of Staphylococcal Enterotoxin H by Rot (Repressor of Toxin) Protein and Its Importance in Clonal Complex 81 Subtype 1 Lineage-Related Food Poisoning

PubMed Central

Sato'o, Yusuke; Hisatsune, Junzo; Nagasako, Yuria; Ono, Hisaya K.; Omoe, Katsuhiko

2015-01-01

We previously demonstrated the clonal complex 81 (CC81) subtype 1 lineage is the major staphylococcal food poisoning (SFP)-associated lineage in Japan (Y. Sato'o et al., J Clin Microbiol 52:2637–2640, 2014, http://dx.doi.org/10.1128/JCM.00661-14). Strains of this lineage produce staphylococcal enterotoxin H (SEH) in addition to SEA. However, an evaluation of the risk for the recently reported SEH has not been sufficiently conducted. We first searched for staphylococcal enterotoxin (SE) genes and SE proteins in milk samples that caused a large SFP outbreak in Japan. Only SEA and SEH were detected, while there were several SE genes detected in the samples. We next designed an experimental model using a meat product to assess the productivity of SEs and found that only SEA and SEH were detectably produced in situ. Therefore, we investigated the regulation of SEH production using a CC81 subtype 1 isolate. Through mutant analysis of global regulators, we found the repressor of toxin (Rot) functioned oppositely as a stimulator of SEH production. SEA production was not affected by Rot. seh mRNA expression correlated with rot both in media and on the meat product, and the Rot protein was shown to directly bind to the seh promoter. The seh promoter sequence was predicted to form a loop structure and to hide the RNA polymerase binding sequences. We propose Rot binds to the promoter sequence of seh and unfolds the secondary structure that may lead the RNA polymerase to bind the promoter, and then seh mRNA transcription begins. This alternative Rot regulation for SEH may contribute to sufficient toxin production by the CC81 subtype 1 lineage in foods to induce SFP. PMID:26341202

Positive Regulation of Staphylococcal Enterotoxin H by Rot (Repressor of Toxin) Protein and Its Importance in Clonal Complex 81 Subtype 1 Lineage-Related Food Poisoning.

PubMed

Sato'o, Yusuke; Hisatsune, Junzo; Nagasako, Yuria; Ono, Hisaya K; Omoe, Katsuhiko; Sugai, Motoyuki

2015-11-01

We previously demonstrated the clonal complex 81 (CC81) subtype 1 lineage is the major staphylococcal food poisoning (SFP)-associated lineage in Japan (Y. Sato'o et al., J Clin Microbiol 52:2637-2640, 2014, http://dx.doi.org/10.1128/JCM.00661-14). Strains of this lineage produce staphylococcal enterotoxin H (SEH) in addition to SEA. However, an evaluation of the risk for the recently reported SEH has not been sufficiently conducted. We first searched for staphylococcal enterotoxin (SE) genes and SE proteins in milk samples that caused a large SFP outbreak in Japan. Only SEA and SEH were detected, while there were several SE genes detected in the samples. We next designed an experimental model using a meat product to assess the productivity of SEs and found that only SEA and SEH were detectably produced in situ. Therefore, we investigated the regulation of SEH production using a CC81 subtype 1 isolate. Through mutant analysis of global regulators, we found the repressor of toxin (Rot) functioned oppositely as a stimulator of SEH production. SEA production was not affected by Rot. seh mRNA expression correlated with rot both in media and on the meat product, and the Rot protein was shown to directly bind to the seh promoter. The seh promoter sequence was predicted to form a loop structure and to hide the RNA polymerase binding sequences. We propose Rot binds to the promoter sequence of seh and unfolds the secondary structure that may lead the RNA polymerase to bind the promoter, and then seh mRNA transcription begins. This alternative Rot regulation for SEH may contribute to sufficient toxin production by the CC81 subtype 1 lineage in foods to induce SFP. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Individual Consistency of Feather Pecking Behavior in Laying Hens: Once a Feather Pecker Always a Feather Pecker?

PubMed Central

Daigle, Courtney L.; Rodenburg, T. Bas; Bolhuis, J. Elizabeth; Swanson, Janice C.; Siegford, Janice M.

2015-01-01

The pecking behavior [severe feather, gentle feather, and aggressive pecks (AP)] of individual White Shaver non-cage laying hens (n = 300) was examined at 21, 24, 27, 32, and 37 weeks. Hens were housed in 30 groups of 10 hens each and on 3 cm litter with access to a feeder, perch, and two nest boxes. The number of severe feather pecks given (SFPG) and received (SFPR) was used to categorize hens as feather peckers (P), victims (V), neutrals (N), or feather pecker-victims (PV) at each age. Hens categorized as PV exhibited pecking behaviors similar to P and received pecks similar to V. SFP given were correlated with APs given, but not with gentle feather pecks (GFP) given throughout the study. State-transition plot maps illustrated that 22.5% of P remained P, while 44% of PV remained PV throughout the duration of the study. Lifetime behavioral categories identified hens as a consistent feather pecker (5%), consistent neutral (3.9%), consistent victim (7.9%), consistent feather pecker-victim (29.4%), or inconsistent (53.8%) in their behavioral patterns throughout their life. Consistent feather peckers performed more SFP than hens of other categories, and consistent neutral hens received fewer GFP than consistent feather PV. No differences in corticosterone or whole blood serotonin levels were observed among the categories. Approximately, half of the population was classified as a feather pecker at least once during the study, while the remainder was never categorized as a feather pecker. Therefore, even if the development and cause of feather pecking may be multifactorial, once the behavior has been developed, some hens may persist in feather pecking. However, as some hens were observed to never receive or perform SFP, emphasis should be made to select for these hens in future breeding practices. PMID:26664935

An application of Extended Normalisation Process Theory in a randomised controlled trial of a complex social intervention: Process evaluation of the Strengthening Families Programme (10-14) in Wales, UK.

PubMed

Segrott, Jeremy; Murphy, Simon; Rothwell, Heather; Scourfield, Jonathan; Foxcroft, David; Gillespie, David; Holliday, Jo; Hood, Kerenza; Hurlow, Claire; Morgan-Trimmer, Sarah; Phillips, Ceri; Reed, Hayley; Roberts, Zoe; Moore, Laurence

2017-12-01

Process evaluations generate important data on the extent to which interventions are delivered as intended. However, the tendency to focus only on assessment of pre-specified structural aspects of fidelity has been criticised for paying insufficient attention to implementation processes and how intervention-context interactions influence programme delivery. This paper reports findings from a process evaluation nested within a randomised controlled trial of the Strengthening Families Programme 10-14 (SFP 10-14) in Wales, UK. It uses Extended Normalisation Process Theory to theorise how interaction between SFP 10-14 and local delivery systems - particularly practitioner commitment/capability and organisational capacity - influenced delivery of intended programme activities: fidelity (adherence to SFP 10-14 content and implementation requirements); dose delivered; dose received (participant engagement); participant recruitment and reach (intervention attendance). A mixed methods design was utilised. Fidelity assessment sheets (completed by practitioners), structured observation by researchers, and routine data were used to assess: adherence to programme content; staffing numbers and consistency; recruitment/retention; and group size and composition. Interviews with practitioners explored implementation processes and context. Adherence to programme content was high - with some variation, linked to practitioner commitment to, and understanding of, the intervention's content and mechanisms. Variation in adherence rates was associated with the extent to which multi-agency delivery team planning meetings were held. Recruitment challenges meant that targets for group size/composition were not always met, but did not affect adherence levels or family engagement. Targets for staffing numbers and consistency were achieved, though capacity within multi-agency networks reduced over time. Extended Normalisation Process Theory provided a useful framework for assessing implementation and explaining variation by examining intervention-context interactions. Findings highlight the need for process evaluations to consider both the structural and process components of implementation to explain whether programme activities are delivered as intended and why.

Methicillin-resistant Staphylococcus aureus: a controversial food-borne pathogen.

PubMed

Sergelidis, D; Angelidis, A S

2017-06-01

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of severe healthcare-associated (HA) infections. Although during the last decade the incidence of HA invasive infections has dropped, the incidence of community-associated MRSA (CA-MRSA) infections has risen among the general population. Moreover, CA-MRSA, livestock-associated MRSA (LA-MRSA) and HA-MRSA (HA-MRSA) can be found in foods intended for human consumption. Several studies from different geographical areas have reported the presence of enterotoxin genes in several MRSA food isolates. Molecular typing studies have revealed genetic relatedness of these enterotoxigenic isolates with isolates incriminated in human infections. The contamination sources for foods, especially animal-origin foods, may be livestock as well as humans involved in animal husbandry and food-processing. Under favourable environmental conditions for growth and enterotoxin production, enterotoxigenic S. aureus isolates present in foods can cause staphylococcal food poisoning (SFP), irrespective of the contamination origin. Owing to the typically moderate clinical manifestations of SFP, the S. aureus strains responsible for SFP (cases or outbreaks) are frequently either not identified or not further characterized. Antimicrobial susceptibility testing is rarely performed, because administration of antimicrobial therapy is not required in the vast majority of cases. Staphylococcal food poisoning is the result of consumption of foods with preformed enterotoxins. Hence, similar to methicillin-sensitive enterotoxigenic S. aureus, enterotoxigenic MRSA can also act as food-borne pathogens upon favourable conditions for growth and enterotoxin production. The severity of the intoxication is not related to the antimicrobial resistance profile of the causative S. aureus strain and therefore MRSA food-borne outbreaks are not expected to be more severe. This review evaluates the potential of methicillin-resistant Staphylococcus aureus (MRSA) as food-borne pathogens based on the current knowledge about the epidemiology of MRSA, their prevalence in livestock, foods of animal origin and humans, and their ability to produce enterotoxins. © 2017 The Society for Applied Microbiology.

[Features of allele polymorphism of genes involved in homocysteine and folate metabolism in patients with atherosclerosis of the lower extremity arteries].

PubMed

Klenkova, N A; Kapustin, S I; Saltykova, N B; Shmeleva, V M; Blinov, M N

2009-01-01

Under study were features of allele polymorphism of genes of methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MS A 2756G), methionine synthase reductase (MTRR A66G) and methylenetetrahydrofolate dehydrogenase (MTHFD G1958A) in patients with atherosclerosis of the lower extremity arteries (ALEA). Patients with hyperhomocysteinemia (HHcy) had statistically significant increase of allele MTHFR 677T and MTRR 66GG as compared both with the control group and with the group of patients without HHcy. It suggests that polymorphism of genes involved in homocystein and folate metabolism might affect the risk of HHcy in patients with ALEA.

78 FR 70589 - Biweekly Notice; Applications and Amendments to Facility Operating Licenses and Combined Licenses...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-26

... the NRC's E-Filing system does not support unlisted software, and the NRC Meta System Help Desk will... Osmosis (RO) system borated water storage tank suction connections. Basis for proposed no significant... requirement. For the SFP, the suction to the RO system is above the required TS water level, therefore, the...

75 FR 77906 - Biweekly Notice; Applications and Amendments to Facility Operating Licenses Involving No...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-14

... level be raised to support SSF RC Makeup System operability. Thus, the SFP water level will not be..., but should note that the NRC's E-Filing system does not support unlisted software, and the NRC Meta... a reverse osmosis system during normal plant operation to remove silica from borated water storage...

Alternative Fuels Data Center: Maps and Data

Science.gov Websites

fleet type from 1992-2014 Last update August 2016 View Graph Graph Download Data Generated_thumb20160830 Trend of S&FP AFV acquisitions by fuel type from 1992-2015 Last update August 2016 View Graph Graph transactions from 1997-2014 Last update August 2016 View Graph Graph Download Data Biofuelsatlas BioFuels Atlas

Alternative Fuels Data Center: Maps and Data

Science.gov Websites

-1paywcu Last update August 2014 View Graph Graph Download Data State & Alt Fuel Providers -kgi9ks Trend of S&FP AFV acquisitions by fleet type from 1992-2014 Last update August 2016 View Graph -2015 Last update August 2016 View Graph Graph Download Data Generated_thumb20160907-12999-119sgvk

76 FR 40628 - Groundfish Fisheries of the EEZ Off Alaska; Pacific Halibut Fisheries; CDQ Program; Bering Sea...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-11

..., business telephone number, e-mail address, port of landing, operation type (for catcher/processors.../processor, the at-sea operation type is pre-filled automatically. (3) If an SFP and crab delivery is... Registered Crab Receiver record in eLandings the region in which the stationary floating processor is located...

Pilot Study to Gauge Acceptability of a Mindfulness-Based, Family-Focused Preventive Intervention

ERIC Educational Resources Information Center

Duncan, Larissa G.; Coatsworth, J. Douglas; Greenberg, Mark T.

2009-01-01

The purpose of the present study was to conduct a test of acceptability of a new model for family-focused drug prevention programs for families of early adolescents. An existing evidence-based behavioral intervention, the Strengthening Families Program: For Parents and Youth 10-14 (SFP), was adapted to include concepts and activities related to…

75 FR 9445 - Notice; Applications and Amendments to Facility Operating Licenses Involving Proposed No...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-02

... evaluated the effects of these ITAs on post- irradiation conditions. The additional heat from the Co-60 decay is insignificant when compared to the total heat from a normal refueling discharge. The small amount of extra heat added by the cobalt isotope rods poses no additional risk of spent fuel pool (SFP...

The Dynamic Still-Face Effect: Do Infants Decrease Bidding over Time when Parents Are Not Responsive?

ERIC Educational Resources Information Center

Ekas, Naomi V.; Haltigan, John D.; Messinger, Daniel S.

2013-01-01

The still-face paradigm (SFP) was designed to assess infant expectations that parents will respond to infant communicative signals. During the still-face (SF) episode, the parent ceases interaction and maintains a neutral expression. Original, qualitative descriptions of infant behavior suggested changes within the SF episode: infants decrease…

Development and application of a 6.5 million feature Affymetrix Genechip® for massively parallel discovery of single position polymorphisms in lettuce (Lactuca spp.)

PubMed Central

2012-01-01

Background High-resolution genetic maps are needed in many crops to help characterize the genetic diversity that determines agriculturally important traits. Hybridization to microarrays to detect single feature polymorphisms is a powerful technique for marker discovery and genotyping because of its highly parallel nature. However, microarrays designed for gene expression analysis rarely provide sufficient gene coverage for optimal detection of nucleotide polymorphisms, which limits utility in species with low rates of polymorphism such as lettuce (Lactuca sativa). Results We developed a 6.5 million feature Affymetrix GeneChip® for efficient polymorphism discovery and genotyping, as well as for analysis of gene expression in lettuce. Probes on the microarray were designed from 26,809 unigenes from cultivated lettuce and an additional 8,819 unigenes from four related species (L. serriola, L. saligna, L. virosa and L. perennis). Where possible, probes were tiled with a 2 bp stagger, alternating on each DNA strand; providing an average of 187 probes covering approximately 600 bp for each of over 35,000 unigenes; resulting in up to 13 fold redundancy in coverage per nucleotide. We developed protocols for hybridization of genomic DNA to the GeneChip® and refined custom algorithms that utilized coverage from multiple, high quality probes to detect single position polymorphisms in 2 bp sliding windows across each unigene. This allowed us to detect greater than 18,000 polymorphisms between the parental lines of our core mapping population, as well as numerous polymorphisms between cultivated lettuce and wild species in the lettuce genepool. Using marker data from our diversity panel comprised of 52 accessions from the five species listed above, we were able to separate accessions by species using both phylogenetic and principal component analyses. Additionally, we estimated the diversity between different types of cultivated lettuce and distinguished morphological types. Conclusion By hybridizing genomic DNA to a custom oligonucleotide array designed for maximum gene coverage, we were able to identify polymorphisms using two approaches for pair-wise comparisons, as well as a highly parallel method that compared all 52 genotypes simultaneously. PMID:22583801

Development and application of a 6.5 million feature Affymetrix Genechip® for massively parallel discovery of single position polymorphisms in lettuce (Lactuca spp.).

PubMed

Stoffel, Kevin; van Leeuwen, Hans; Kozik, Alexander; Caldwell, David; Ashrafi, Hamid; Cui, Xinping; Tan, Xiaoping; Hill, Theresa; Reyes-Chin-Wo, Sebastian; Truco, Maria-Jose; Michelmore, Richard W; Van Deynze, Allen

2012-05-14

High-resolution genetic maps are needed in many crops to help characterize the genetic diversity that determines agriculturally important traits. Hybridization to microarrays to detect single feature polymorphisms is a powerful technique for marker discovery and genotyping because of its highly parallel nature. However, microarrays designed for gene expression analysis rarely provide sufficient gene coverage for optimal detection of nucleotide polymorphisms, which limits utility in species with low rates of polymorphism such as lettuce (Lactuca sativa). We developed a 6.5 million feature Affymetrix GeneChip® for efficient polymorphism discovery and genotyping, as well as for analysis of gene expression in lettuce. Probes on the microarray were designed from 26,809 unigenes from cultivated lettuce and an additional 8,819 unigenes from four related species (L. serriola, L. saligna, L. virosa and L. perennis). Where possible, probes were tiled with a 2 bp stagger, alternating on each DNA strand; providing an average of 187 probes covering approximately 600 bp for each of over 35,000 unigenes; resulting in up to 13 fold redundancy in coverage per nucleotide. We developed protocols for hybridization of genomic DNA to the GeneChip® and refined custom algorithms that utilized coverage from multiple, high quality probes to detect single position polymorphisms in 2 bp sliding windows across each unigene. This allowed us to detect greater than 18,000 polymorphisms between the parental lines of our core mapping population, as well as numerous polymorphisms between cultivated lettuce and wild species in the lettuce genepool. Using marker data from our diversity panel comprised of 52 accessions from the five species listed above, we were able to separate accessions by species using both phylogenetic and principal component analyses. Additionally, we estimated the diversity between different types of cultivated lettuce and distinguished morphological types. By hybridizing genomic DNA to a custom oligonucleotide array designed for maximum gene coverage, we were able to identify polymorphisms using two approaches for pair-wise comparisons, as well as a highly parallel method that compared all 52 genotypes simultaneously.

[Genetic polymorphism of Gentiana lutea L. (Gentianaceae) populations from Chornohora Ridge of Ukrainian Carpathians].

PubMed

Mosula, M Z; Konvaliuk, I I; Mel'nyk, V M; Drobyk, N M; Tsaryk, I V; Nesteruk, Iu I; Kunakh, V A

2014-01-01

The features of genetic structure and level of diversity were investigated for G. lutea populations from Chornohora Ridge of Ukrainian Carpathians using RAPD- and ISSR-PCR. We have shown a high level of genetic diversity for investigated populations. The differences between populations account for 59-72% of the total genetic variation, whereas intrapopulation polymorphism makes up 28-41%. The relationships among genetic variability level and ecological-geographical conditions as well as biological features of the species were assumed to be possible. The obtained results indicate the genetic isolation of G. lutea Chornohora populations from Ukrainian Carpathians. Pozhyzhevska agropopulation was characterized by a high level of polymorphism that means the possibility to use artificial plantings of the investigated species for its conservation.

Overcoming Malnutrition: Putting Federal Programs to Work. A Report on the First National WIC Symposium.

ERIC Educational Resources Information Center

Fleming, Virginia; And Others

This report describes the proceedings of a symposium on the Special Supplemental Food Program for Women, Infants and Children (WIC) and the Commodity Supplemental Food Program (SFP), held in January, 1977. The symposium was intended to bring together a variety of individuals concerned with providing adequate nutrition and health care to low-income…

Alternative Fuels Data Center: Maps and Data

Science.gov Websites

acquisitions by fleet type from 1992-2014 Last update August 2016 View Graph Graph Download Data -m8i0e0 Trend of S&FP AFV acquisitions by fuel type from 1992-2015 Last update August 2016 View Graph transactions from 1997-2014 Last update August 2016 View Graph Graph Download Data Generated_thumb20160907

Sexual imprinting on continuous variation: do female zebra finches prefer or avoid unfamiliar sons of their foster parents?

PubMed

Schielzeth, H; Burger, C; Bolund, E; Forstmeier, W

2008-09-01

Sexual imprinting on discrete variation that serves the identification of species, morphs or sexes is well documented. By contrast, sexual imprinting on continuous variation leading to individual differences in mating preferences within a single species, morph and sex has been studied only once (in humans). We measured female preferences in a captive population of wild-type zebra finches. Individual cross-fostering ensured that all subjects grew up with unrelated foster parents and nest mates. Females from two cohorts (N = 113) were given a simultaneous choice between (two or four) unfamiliar males, one of which was a genetic son of their foster parents (SFP). We found no significant overall preference for the SFP (combined effect size d = 0.14 +/- 0.15). Additionally, we tested if foster parent traits could potentially explain between-female variation in preferences. However, neither the effectiveness of cooperation between the parents nor male contribution to parental care affected female preferences for the son of the foster father. We conclude that at least in zebra finches sexual imprinting is not a major source of between-individual variation in mating preferences.

Legionella shows a diverse secondary metabolism dependent on a broad spectrum Sfp-type phosphopantetheinyl transferase.

PubMed

Tobias, Nicholas J; Ahrendt, Tilman; Schell, Ursula; Miltenberger, Melissa; Hilbi, Hubert; Bode, Helge B

2016-01-01

Several members of the genus Legionella cause Legionnaires' disease, a potentially debilitating form of pneumonia. Studies frequently focus on the abundant number of virulence factors present in this genus. However, what is often overlooked is the role of secondary metabolites from Legionella . Following whole genome sequencing, we assembled and annotated the Legionella parisiensis DSM 19216 genome. Together with 14 other members of the Legionella , we performed comparative genomics and analysed the secondary metabolite potential of each strain. We found that Legionella contains a huge variety of biosynthetic gene clusters (BGCs) that are potentially making a significant number of novel natural products with undefined function. Surprisingly, only a single Sfp-like phosphopantetheinyl transferase is found in all Legionella strains analyzed that might be responsible for the activation of all carrier proteins in primary (fatty acid biosynthesis) and secondary metabolism (polyketide and non-ribosomal peptide synthesis). Using conserved active site motifs, we predict some novel compounds that are probably involved in cell-cell communication, differing to known communication systems. We identify several gene clusters, which may represent novel signaling mechanisms and demonstrate the natural product potential of Legionella .

H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism: clinical and pathologic features in wild-type and E211K cattle following intracranial inoculation

USDA-ARS?s Scientific Manuscript database

In 2006 an H-type bovine spongiform encephalopathy (BSE) case was reported in an animal with an unusual polymorphism (E211K) in the prion protein gene. Although the prevalence of this polymorphism is low, cattle carrying the K211 allele are predisposed to rapid onset of H-type BSE when exposed. The ...

Correlations Between COL2A and Aggrecan Genetic Polymorphisms and the Risk and Clinicopathological Features of Intervertebral Disc Degeneration in a Chinese Han Population: A Case-Control Study.

PubMed

Deng, Yu; Tan, Xin-Ti; Wu, Qiang; Wang, Xin

2017-02-01

This case-control study was designed to evaluate the association of three COL2A1 single nucleotide polymorphism (SNPs) (rs1793953, rs2276454, and rs1793937) and Aggrecan variable number of tandem repeat (VNTR) polymorphisms with the risk and clinicopathological features of intervertebral disc degeneration (IVDD) in a Chinese Han population. Data from 295 IVDD patients (case group) and 324 healthy volunteers (control group) were collected between January 2012 and December 2014. Magnetic resonance examinations were conducted on all included subjects. The frequency distributions of the COL2A1 and Aggrecan polymorphisms were detected using direct sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, respectively. The genotype and allele frequencies of the COL2A1 genetic polymorphisms (rs1793953 and rs2276454) and the Aggrecan VNTR polymorphisms differed significantly between the case group and the control group (all p < 0.05). The haplotype analysis indicated that the frequencies of ACGL (L, long) and GTCL haplotypes were lower in the case group than in the control group (both p < 0.05). In the case group, the genotype and allele frequencies of the COL2A1 genes, rs1793953 and rs2276454, and Aggrecan VNTR significantly differed in terms of Pfirrmann grades III, IV, and V (all p < 0.05). Personal history of spine sprain or crush injury, history of IVDD in a first-degree relative, and COL2A1 rs2276454 and Aggrecan VNTR presence may be independent risk factors of IVDD (all p < 0.05, odds ratio [OR] >1), whereas tea drinking habit, part-time sports participation, and COL2A1 rs1793953 presence may be protective factors of IVDD (all p < 0.05, OR <1). Our study provides evidence that COL2A1 and Aggrecan genetic polymorphisms may be correlated with the risk and clinicopathological features of IVDD in a Chinese Han population, and ACGL and GTCL haplotypes may be protective factors of IVDD.

Different frequencies and effects of ABCB1 T3435C polymorphism on clinical and laboratory features of B cell chronic lymphocytic leukemia in Kurdish patients.

PubMed

Maroofi, Farzad; Amini, Sabrieh; Roshani, Daem; Ghaderi, Bayazid; Abdi, Mohammad

2015-04-01

Finding the effects of gene polymorphism on cancer pathogenesis is very desirable. The ATP-binding cassette is involved in drug metabolism, and the polymorphism of this gene may be an important risk factor in B cell chronic lymphocytic leukemia (B-CLL) or progression and/or response to chemotherapy agents. For the first time, the present study was aimed to evaluate the probable effects of ABCB1 T3435C polymorphism on clinical and laboratory features of Kurdish patients with B-CLL. This descriptive analytical case-control study was performed on 50 B-CLL patients and 100 healthy subjects. Serum levels of beta-2-microglobulin (B2M) and lactate dehydrogenase (LDH) and blood WBC, RBC, Plt and ESR were measured. The T3435C polymorphism of the ABCB1 gene was determined by PCR-RFLP. Concentration of serum and blood markers was significantly higher in the malignant group than in the benign subjects. The CC genotype had the highest frequency (66%) in the patient groups. There are no significant differences between the genotypes and type of treatment. Our results demonstrate the high frequency of C allele of ABCB1 T3435C in B-CLL patients with Kurdish ethnicity. We also show that this polymorphism has a significant risk factor in B-CLL. However, the effect of this polymorphism on clinical and laboratory characteristics of B-CLL patients was not significant.

Intra-procedural Path-insensitve Grams (I-GRAMS) and Disassembly Based Features for Packer Tool Classification and Detection

DTIC Science & Technology

2012-06-14

executable file is packed is a critical step in software security. This research uses machine learning methods to build the Polymorphic and Non-Polymorphic...Packer Detection (PNPD) system that detects whether an executable is packed by either ASPack, UPX, Metasploit’s polymorphic msfencode, or is packed in...detect packed executables used in experiments. Overall, it is discovered i-grams provide the best results with accuracies above 99.5%, average true

Two new phoretomorphic Siteroptes from galleries of the southern pine beetle

Treesearch

Robert L. Smiley; John C. Moser

1976-01-01

This paper provides taxonomic descriptions of two pyemotid mite species displaying polymorphic features discovered by Moser & Cross(1975). Polymorphism in the Acarina was first noted by Canestrini in 1888 for Rhizoglyphus echinopus (Fumouze & Robin). He associated the heteromorphic male with the normal homeomorphicm ale of this species....

Community-level physiological profiles of bacteria and fungi: Plate type and incubation temperature influences on contrasting soils

Treesearch

Aimee T. Classen; Sarah I. Boyle; Kristin E. Haskins; Steven T. Overby; Stephen C. Hart

2003-01-01

Temperature sensitivity of community-level physiological profiles (CLPPs) was examined for two semiarid soils from the southwestern United States using five different C-substrate profile microtiter plates (Biolog GN2, GP2, ECO, SFN2, and SFP2) incubated at five different temperature regimes.The CLPPs produced from all plate types were relatively unaffected by these...

Lessons Learnt from Applying Action Research to Support Strategy Formation Processes in Long-Term Care Networks

ERIC Educational Resources Information Center

Cramer, Hendrik; Dewulf, Geert; Voordijk, Hans

2015-01-01

This study demonstrates how action research (AR) that is aimed at scaling-up experiments can be applied to support a strategy formation process (SFP) in a subsidized long-term care network. Previous research has developed numerous AR frameworks to support experiments in various domains, but has failed to explain how to apply AR and action learning…

A U.S. Forest Service special forest products appraisal system: background, methods, and assessment.

Treesearch

Jerry Smith; Lisa K. Crone; Susan J. Alexander

2010-01-01

Increasing concern over the management and harvest of special forest products (SFP) from national forest lands has led to the development of new Forest Service policy directives. In this paper, we present a brief history of SFPs in the Western United States, highlighting the issues that necessitated new management direction. The new policy directives that led to the...

The (Re)Construction of a Philosophical and Pedagogical Position for the Foundation Programme at UKZN with Particular Reference to the Biology Module

ERIC Educational Resources Information Center

Kirby, N. F.; Dempster, E. R.

2011-01-01

The Centre for Science Access Foundation Programme at the University of KwaZulu-Natal provides alternative access to tertiary science studies to educationally disadvantaged students. The philosophical basis for this Programme is that of constructivism, as adopted by the original Science Foundation Programme (SFP) which was initiated in 1991 on the…

Farm Diversification, Tenancy and CAP Reform: Results from a Survey of Tenant Farmers in England

ERIC Educational Resources Information Center

Maye, Damian; Ilbery, Brian; Watts, David

2009-01-01

Little work has considered explicitly the role of farm tenancy in influencing the uptake (or not) of diversification activities. The need to examine this link has been heightened because of the 2003 CAP reforms and the decision to tie Single Farm Payment (SFP) entitlement to the land rather than what is produced on that land. The main objective of…

Effect of a package of health and nutrition services on sustained recovery in children after moderate acute malnutrition and factors related to sustaining recovery: a cluster-randomized trial.

PubMed

Stobaugh, Heather C; Bollinger, Lucy B; Adams, Sara E; Crocker, Audrey H; Grise, Jennifer B; Kennedy, Julie A; Thakwalakwa, Chrissie; Maleta, Kenneth M; Dietzen, Dennis J; Manary, Mark J; Trehan, Indi

2017-08-01

Background: Children who recover from moderate acute malnutrition (MAM) have high rates of relapse in the year after nutritional recovery. Interventions to decrease these adverse outcomes are needed to maximize the overall effectiveness of supplemental feeding programs (SFPs). Objective: We evaluated the effectiveness of a package of health and nutrition interventions on improving the proportion of children who sustained recovery for 1 y after MAM treatment. We further explored factors related to sustained recovery. Design: We conducted a cluster-randomized clinical effectiveness trial involving rural Malawian children aged 6-62 mo who were enrolled on discharge from an SFP for MAM. We enrolled 718 children at 10 control sites and 769 children at 11 intervention sites. In addition to routine health and nutrition counseling, the intervention group received a package of health and nutrition interventions that consisted of a lipid nutrient supplement, deworming medication, zinc supplementation, a bed net, and malaria chemoprophylaxis. A survival analysis was used to determine the effectiveness of the intervention as well as to identify factors associated with sustained recovery. Results: Of 1383 children who returned for the full 12-mo follow-up period, 407 children (56%) and 347 children (53%) sustained recovery in the intervention and control groups, respectively. There was no significant difference in relapse-free survival curves between the treatment and control groups ( P = 0.380; log-rank test). The risk factors for relapse or death after initial recovery were a smaller midupper arm circumference on SFP admission ( P = 0.01) and discharge ( P < 0.001), a lower weight-for-height z score on discharge ( P < 0.01), and the receipt of ready-to-use supplementary food as opposed to ready-to-use therapeutic food during treatment ( P < 0.05). Conclusion: The provision of a package of health and nutrition services in addition to traditional SFP treatment has no significant effect on improving sustained recovery in children after treatment of MAM. This trial was registered at clinicaltrials.gov as NCT02351687. © 2017 American Society for Nutrition.

Pathological Roles of Interleukin-22 in the Development of Recurrent Hepatitis C after Liver Transplantation

PubMed Central

Li, Jin; Cheung, Eddie; Li, Hanwei; Zhao, Jingmin; Liu, Hongling; Liu, Zhenwen; Zhang, Min

2016-01-01

Objective The aim of this study was to longitudinally evaluate and analyze the role of interleukin-22-producing CD4 positive cells (IL-22) in the pathogenesis of Hepatitis C Virus recurrence after Orthotopic Liver Transplantation (HCV-OLT). Methods 15 HCV-OLT, 15 age- and gender- matched non-HCV post-OLT (OLT) and 15 hepatitis C virus infected (HCV) patients were enrolled into our study from the liver transplantation and research center at Beijing 302 Hospital. We determined the frequencies of IL-22 using flow cytometry and expression of IL-22 mRNA using PCR in peripheral blood and liver tissue. We also divided HCV-OLT patients into rapid fibrosis progression (RFP) and slow fibrosis progression (SFP), examined IL-22 cells and analyzed the correlations between IL-22 frequencies and liver injury, fibrosis and clinical parameters. Moreover, we investigated the role of IL-22 in Human Hepatic Stellate Cells (HSCs). Results The levels of serum IL-22, frequencies of IL-22 producing cells in peripheral blood mononuclear cells, and expression of IL-22 mRNA and protein in the liver in the HCV-OLT group were significantly higher than that in the HCV and OLT groups. Furthermore, eight (53.3%) patients developed RFP after two years; another three patients were diagnosed liver cirrhosis. The frequencies of IL-22 were much higher in RFP compared with SFP, while no significant difference existed between OLT and SFP. Intrahepatic IL-22 positive cells were located in fibrotic areas and significantly correlated with α-smooth muscle actin (α-SMA) and fibrosis staging scores, not with grading scores and HCRVNA. In vitro, IL-22 administration prevented HSCs apoptosis, promoted HSCs proliferation and activation, up-regulated the expression of HSC-sourced growth factors including α-SMA, TGF-β and TIMP-1, and increased the production of liver fibrosis markers including laminin, hyaluronic acid and collagen type IV. Conclusion Peripheral and intrahepatic IL-22 is up-regulated and plays a pathological role in exacerbating liver fibrosis by activating HSCs in HCV-OLT patients, which may predict RFP and serve as an attractive target for anti-fibrotic therapy. PMID:27123854

The AP1000{sup R} nuclear power plant innovative features for extended station blackout mitigation

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

Vereb, F.; Winters, J.; Schulz, T.

2012-07-01

Station Blackout (SBO) is defined as 'a condition wherein a nuclear power plant sustains a loss of all offsite electric power system concurrent with turbine trip and unavailability of all onsite emergency alternating current (AC) power system. Station blackout does not include the loss of available AC power to buses fed by station batteries through inverters or by alternate AC sources as defined in this section, nor does it assume a concurrent single failure or design basis accident...' in accordance with Reference 1. In this paper, the innovative features of the AP1000 plant design are described with their operation inmore » the scenario of an extended station blackout event. General operation of the passive safety systems are described as well as the unique features which allow the AP1000 plant to cope for at least 7 days during station blackout. Points of emphasis will include: - Passive safety system operation during SBO - 'Fail-safe' nature of key passive safety system valves; automatically places the valve in a conservatively safe alignment even in case of multiple failures in all power supply systems, including normal AC and battery backup - Passive Spent Fuel Pool cooling and makeup water supply during SBO - Robustness of AP1000 plant due to the location of key systems, structures and components required for Safe Shutdown - Diverse means of supplying makeup water to the Passive Containment Cooling System (PCS) and the Spent Fuel Pool (SFP) through use of an engineered, safety-related piping interface and portable equipment, as well as with permanently installed onsite ancillary equipment. (authors)« less

[Polymorphism and structure of the population of Proteocephalus longicollis Zeder, 1800 (Cestoda: Proteocephalidae) in the vendace Coregonus albula L].

PubMed

Anikieva, L V; Kharin, V N; Spektor, E N

2004-01-01

Polymorphism and phenotypic diversity of a hostal ecoform of Proteocephalus longicollis from its typical host, the vendace, Coregonus albula L., were studied. A complex phenotypic structure of the parasite population and presence of morphologically different groupings were revealed. We distinguished four groupings based on the external characters and three groupings based on the feed and reproduction features; among latter groupings one has very specific variations of features. We conclude that P. longicollis has high intraspecific and intrapopulation heterogeneity, and the host plays a stabilising role in the parasite species formation.

Fluctuation Induced Almost Invariant Sets

DTIC Science & Technology

2006-12-28

Planck) for the probability density function [15], discrete dynamical systems benefit from using the Frobenius - Perron operator (FP) formalism [12] to...from epidemiology. Conclusions are summarized in Section 4. II. GENERAL THEORY A. Stochastic Frobenius - Perron operator We define the Frobenius - Perron ...function ν(x). The stochastic Frobenius - 3 Perron (SFP) operator is defined to be PF [ρ(x)] = ∫ M ν(x− F (y))ρ(y)dy. (4) For our applications, we will

Optical Sensing Device Containing Fiber Bragg Gratings

DTIC Science & Technology

2000-08-01

Fabry - Perot (SFP) filter-based interrogation (Kersey et al. Opt. Lett.. 18, 1370-2. 1993), tunable acousto-optic filter inteiTOgation (Geiger et al...a tunable Fabry - Perot filter, and a tunable acousto-optical filter. Alternatively, scanning filter 28 can be omitted in device 10 of the present...invention when broadband light source 20 is a tunable broadband light source. More preferably, scanning filter 28 is a tunable Fabry - Perot filter

Special Forest Products on the Green Mountain and Finger Lakes National Forests: a research-based approach to management

Treesearch

Marla R. Emery; Clare Ginger

2014-01-01

Special forest products (SFPs) are gathered from more than 200 vascular and fungal species on the Green Mountain National Forest (GMNF) and Finger Lakes National Forest (FLNF). This report documents those SFPs and proposes an approach to managing them in the context of legislation directing the U.S. Forest Service to institute a program of active SFP management. Based...

The Seminal fluid proteome of the polyandrous Red junglefowl offers insights into the molecular basis of fertility, reproductive ageing and domestication

PubMed Central

Borziak, Kirill; Álvarez-Fernández, Aitor; L. Karr, Timothy; Pizzari, Tommaso; Dorus, Steve

2016-01-01

Seminal fluid proteins (SFPs) are emerging as fundamental contributors to sexual selection given their role in post-mating reproductive events, particularly in polyandrous species where the ejaculates of different males compete for fertilisation. SFP identification however remains taxonomically limited and little is known about avian SFPs, despite extensive work on sexual selection in birds. We characterize the SF proteome of the polyandrous Red junglefowl, Gallus gallus, the wild species that gave rise to the domestic chicken. We identify 1,141 SFPs, including proteins involved in immunity and antimicrobial defences, sperm maturation, and fertilisation, revealing a functionally complex SF proteome. This includes a predominant contribution of blood plasma proteins that is conserved with human SF. By comparing the proteome of young and old males with fast or slow sperm velocity in a balanced design, we identify proteins associated with ageing and sperm velocity, and show that old males that retain high sperm velocity have distinct proteome characteristics. SFP comparisons with domestic chickens revealed both qualitative and quantitative differences likely associated with domestication and artificial selection. Collectively, these results shed light onto the functional complexity of avian SF, and provide a platform for molecular studies of fertility, reproductive ageing, and domestication. PMID:27804984

More than anticipated - production of antibiotics and other secondary metabolites by Bacillus amyloliquefaciens FZB42.

PubMed

Chen, Xiao-Hua; Koumoutsi, Alexandra; Scholz, Romy; Borriss, Rainer

2009-01-01

The genome of environmental Bacillus amyloliquefaciens FZB42 harbors numerous gene clusters involved in synthesis of antifungal and antibacterial acting secondary metabolites. Five gene clusters, srf, bmy, fen, nrs, dhb, covering altogether 137 kb, direct non-ribosomal synthesis of the cyclic lipopeptides surfactin, bacillomycin, fengycin, an unknown peptide, and the iron siderophore bacillibactin. Bacillomycin and fengycin were shown to act against phytopathogenic fungi in a synergistic manner. Three gene clusters, mln, bae, and dif, with a total length of 199 kb were shown to direct synthesis of the antibacterial acting polyketides macrolactin, bacillaene, and difficidin. Both, non-ribosomal synthesis of cyclic lipopeptides and synthesis of polyketides are dependent on the presence of a functional sfp gene product, 4'-phosphopantetheinyl transferase, as evidenced by knockout mutation of the sfp gene resulting in complete absence of all those eight compounds. In addition, here we present evidence that a gene cluster encoding enzymes involved in synthesis and export of the antibacterial acting dipeptide bacilysin is also functional in FZB42. In summary, environmental FZB42 devoted about 340 kb, corresponding to 8.5% of its total genetic capacity, to synthesis of secondary metabolites useful to cope with other competing microorganisms present in the plant rhizosphere. Copyright (c) 2008 S. Karger AG, Basel.

Early maladaptive schemas and aggressive sexual behavior: a preliminary study with male college students.

PubMed

Sigre-Leirós, Vera Lúcia; Carvalho, Joana; Nobre, Pedro

2013-07-01

The influence of adverse early attachment experiences on the development of aggressive sexual behavior has been demonstrated. Nonetheless, there is a gap in the literature regarding the conceptualization of this behavior according to developmental psychopathology models. The purpose of the present study was to investigate a potential association between Early Maladaptive Schemas (EMSs) and aggressive sexual behavior. A total of 166 male college students participated in the study. Participants were divided into two comparative groups according to data from the Sexual Experiences Survey-Short Form Perpetration (SES-SFP): Group of individuals with history of aggressive sexual behavior (N = 37) and Group of individuals without history of aggressive sexual behavior (N = 129). Aggressive sexual behavior was measured by the SES-SFP, and EMSs were measured by the Young Schema Questionnaire (YSQ-S3). Results showed that students who have committed any form of sexually aggressive behavior exhibited significantly higher levels of EMSs from the Disconnection and Rejection domain (namely, Mistrust/Abuse schema), from the Impaired Autonomy and Performance domain (namely, Dependence/Incompetence schema), and from the Overvigilance and Inhibition domain (namely, Negativity/Pessimism schema). These preliminary findings suggest that the EMSs were associated with aggressive sexual behavior, but further investigation is warranted. © 2012 International Society for Sexual Medicine.

The Seminal fluid proteome of the polyandrous Red junglefowl offers insights into the molecular basis of fertility, reproductive ageing and domestication.

PubMed

Borziak, Kirill; Álvarez-Fernández, Aitor; L Karr, Timothy; Pizzari, Tommaso; Dorus, Steve

2016-11-02

Seminal fluid proteins (SFPs) are emerging as fundamental contributors to sexual selection given their role in post-mating reproductive events, particularly in polyandrous species where the ejaculates of different males compete for fertilisation. SFP identification however remains taxonomically limited and little is known about avian SFPs, despite extensive work on sexual selection in birds. We characterize the SF proteome of the polyandrous Red junglefowl, Gallus gallus, the wild species that gave rise to the domestic chicken. We identify 1,141 SFPs, including proteins involved in immunity and antimicrobial defences, sperm maturation, and fertilisation, revealing a functionally complex SF proteome. This includes a predominant contribution of blood plasma proteins that is conserved with human SF. By comparing the proteome of young and old males with fast or slow sperm velocity in a balanced design, we identify proteins associated with ageing and sperm velocity, and show that old males that retain high sperm velocity have distinct proteome characteristics. SFP comparisons with domestic chickens revealed both qualitative and quantitative differences likely associated with domestication and artificial selection. Collectively, these results shed light onto the functional complexity of avian SF, and provide a platform for molecular studies of fertility, reproductive ageing, and domestication.

The TNF-α -308 polymorphism may affect the severity of Crohn's disease

PubMed Central

Santana, Genoile; Bendicho, Maria Teresita; Santana, Tamara Celi; dos Reis, Lidiane Bianca; Lemaire, Denise; Lyra, André Castro

2011-01-01

OBJECTIVE: The goal of this project was to analyze the association between Crohn's disease, its clinical features, and the tumor necrosis factor alpha (TNF-α) -308 polymorphism. METHODS: This is a case-control and cross-sectional study that enrolled 91 patients with Crohn's disease and 91 controls. Patients with Crohn's disease were characterized according to the Montreal Classification, along with their clinical and surgical treatment history. Analysis of the TNF-α -308 polymorphism was performed using a commercial kit. A stratified analysis was applied using an OR (odds ratio) with a 95% confidence interval. The chi-square and Fisher's exact tests were utilized for analysis of the association between the polymorphism and the clinical features of Crohn's disease. RESULTS: The low producer predicted phenotype was present in 76.9% of Crohn's disease cases and 75.8% of controls (OR 0.94 [0.45-1.97]). The TNF2 allele and the high producer predicted phenotype were more frequent among patients with Crohn's disease penetrating behavior (p = 0.004). The TNF2 allele and the high producer predicted phenotype were also associated with a history of colectomy (p = 0.02), and the TNF2 allele was associated with small bowel resection (p = 0.03). CONCLUSIONS: The TNF-α -308 polymorphism appears to affect the severity of the disease. However, TNF-α -308 polymorphism does not appear to be important for the susceptibility in the development of Crohn's disease. PMID:21915486

Polymorphism of SMAD7 gene (rs2337104) and risk of colorectal cancer in an Iranian population: a case-control study

PubMed Central

Akbari, Zahra; Safari-Alighiarloo, Nahid; Taleghani, Mohammad Yaghoob; Mirfakhar, Farzaneh Sadat; Asadzadeh Aghdaei, Hamid; Vahedi, Mohsen; Irani Shemirani, Atena; Nazemalhosseini-Mojarad, Ehsan; Zali, Mohammad Reza

2014-01-01

Aim: The purpose of this study was to evaluate the influence of intronic polymorphism of the SMAD7 (Mothers Against Decantaplegic Homolog 7) gene (rs2337104) on the risk of colorectal cancer (CRC) and clinicopathological features in an Iranian population. Background: SMAD7 has been identified as an antagonist of transforming growth factor beta (TGF-b)-mediating fibrosis, carcinogenesis, and inflammation. Regarding to the recent genome-wide scan, a risk locus for colorectal cancer at 18q21 has been found, which maps to the SMAD7 gene. Patients and methods: This case-control study was performed on 109 CRC patients and 109 healthy controls recruited in Taleghani Hospital. The genotyping of all samples were done by TaqMan assay via an ABI 7500 Real Time PCR System (Applied Biosystems) with DNA from peripheral blood. The association of this polymorphism with the risk of CRC and clinicopathological features was investigated. Results: Our results indicated that there were no significant association between genotypic and allelic frequencies of SMAD7 polymorphism (rs2337104) and CRC risk in our population. Although the T allele is the most frequent one in this population and its frequency was 86.7% in patients compared with 91.7% in controls (OR=1.705, 95% CI= 0.916–3.172). Also, the SMAD7 genotypes were not associated with any clinicopathological characteristics in CRC patients (P>0.05). Conclusion: For the first time, this study results revealed that this SMAD7 polymorphism couldn’t be a potential risk factor for CRC or a prognostic biomarker for prediction of clinicopathological features in an Iranian population. A large-scale case-control study is needed to validate our results. PMID:25289133

Classical phenotype of Laron syndrome in a girl with a heterozygous mutation and heterozygous polymorphism of the growth hormone receptor gene.

PubMed

Shevah, Orit; Galli-Tsinopoulou, Assimina; Rubinstein, Menachem; Nousia-Arvanitakis, Sanda; Laron, Zvi

2004-03-01

We describe here a 19 month-old girl with classical Laron syndrome (LS). Molecular analysis of the GH receptor gene in the patient and her parents was performed. The patient was found to be heterozygous for a mutation in exon 4 (R43X) and heterozygous for a polymorphism in exon 6 (Gly168Gly). Her mother was also heterozygous for R43X but homozygous for the polymorphism. In the father, a heterozygous polymorphism was found. Contrary to previous assumptions that only homozygous patients express the typical phenotype, this patient shows all the classical features of LS, despite being a heterozygote for a pathological defect.

A comparative study of two polymorphs of L-aspartic acid hydrochloride.

PubMed

Benali-Cherif, Rim; Takouachet, Radhwane; Bendeif, El-Eulmi; Benali-Cherif, Nourredine

2014-07-01

Two polymorphs of L-aspartic acid hydrochloride, C4H8NO4(+)·Cl(-), were obtained from the same aqueous solution. Their crystal structures have been determined from single-crystal data collected at 100 K. The crystal structures revealed three- and two-dimensional hydrogen-bonding networks for the triclinic and orthorhombic polymorphs, respectively. The cations and anions are connected to one another via N-H···Cl and O-H···Cl interactions and form alternating cation-anion layer-like structures. The two polymorphs share common structural features; however, the conformations of the L-aspartate cations and the crystal packings are different. Furthermore, the molecular packing of the orthorhombic polymorph contains more interesting interactions which seems to be a favourable factor for more efficient charge transfer within the crystal.

Electron petrography of silica polymorphs associated with pseudotachylite, Vredefort structure, South Africa

NASA Technical Reports Server (NTRS)

White, J. C.

1992-01-01

High-pressure silica polymorphs (coesite and stishovite) were described from the Vredefort structure in association with pseudotachylite veinlets. In addition to the fundamental significance of the polymorphs to genetic interpretations of the structure, it was additionally argued that the type of pseudotachylite with which they occur forms during the compressional phase of the shock process, while the larger, classic pseudotachylite occurrences are barren of polymorphs and formed during passage of the rarefaction wave. This identification of temporal relationships among transient shock features at a regional scale is similar to observations from the Manicouagan structure, Quebec, where texturally distinct diaplectic plagioclase glasses formed during both compressional and decompressional phases of the shock process. The clarification of such relationships impinges directly on interpretations of natural shock processes and the identification of high probability targets for polymorph searches. Detailed analytical scanning (SEM) and transmission electron microscopy (TEM) were utilized to further establish the nature of both the pseudotachylite and the silica polymorph occurrences in the Vredefort rocks. The results of this investigation are discussed.

Comparisons of stemflow and its bio-/abiotic influential factors between two xerophytic shrub species

NASA Astrophysics Data System (ADS)

Yuan, Chuan; Gao, Guangyao; Fu, Bojie

2017-03-01

Stemflow transports nutrient-enriched precipitation to the rhizosphere and functions as an efficient terrestrial flux in water-stressed ecosystems. However, its ecological significance has generally been underestimated because it is relatively limited in amount, and the biotic mechanisms that affect it have not been thoroughly studied at the leaf scale. This study was conducted during the 2014 and 2015 rainy seasons at the northern Loess Plateau of China. We measured the branch stemflow volume (SFb), shrub stemflow equivalent water depth (SFd), stemflow percentage of incident precipitation (SF %), stemflow productivity (SFP), funnelling ratio (FR), the meteorological characteristics and the plant traits of branches and leaves of C. korshinskii and S. psammophila. This study evaluated stemflow efficiency for the first time with the combined results of SFP and FR, and sought to determine the inter- and intra-specific differences of stemflow yield and efficiency between the two species, as well as the specific bio-/abiotic mechanisms that affected stemflow. The results indicated that C. korshinskii had a greater stemflow yield and efficiency at all precipitation levels than that of S. psammophila. The largest inter-specific difference generally occurred at the 5-10 mm branches during rains of ≤ 2 mm. Precipitation amount was the most influential meteorological characteristic that affected stemflow yield and efficiency in these two endemic shrub species. Branch angle was the most influential plant trait on FR. For SFb, stem biomass and leaf biomass were the most influential plant traits for C. korshinskii and S. psammophila, respectively. For SFP of these two shrub species, leaf traits (the individual leaf area) and branch traits (branch size and biomass allocation pattern) had a great influence during lighter rains ≤ 10 mm and heavier rains > 15 mm, respectively. The lower precipitation threshold to start stemflow allowed C. korshinskii (0.9 mm vs. 2.1 mm for S. psammophila) to employ more rains to harvest water via stemflow. The beneficial leaf traits (e.g., leaf shape, arrangement, area, amount) might partly explain the greater stemflow production of C. korshinskii. Comparison of SFb between the foliated and manually defoliated shrubs during the 2015 rainy season indicated that the newly exposed branch surface at the defoliated period and the resulting rainfall intercepting effects might be an important mechanism affecting stemflow in the dormant season.

Further exploration of the conformational space of α-synuclein fibrils: solid-state NMR assignment of a high-pH polymorph.

PubMed

Verasdonck, Joeri; Bousset, Luc; Gath, Julia; Melki, Ronald; Böckmann, Anja; Meier, Beat H

2016-04-01

Polymorphism is a common and important phenomenon for protein fibrils which has been linked to the appearance of strains in prion and other neurodegenerative diseases. Parkinson disease is a frequently occurring neurodegenerative pathology, tightly associated with the formation of Lewy bodies. These deposits mainly consist of α-synuclein in fibrillar, β-sheet-rich form. α-synuclein is known to form numerous different polymorphs, which show distinct structural features. Here, we describe the chemical shift assignments, and derive the secondary structure, of a polymorph that was fibrillized at higher-than-physiological pH conditions. The fibrillar core contains residues 40-95, with both the C- and N-terminus not showing any ordered, rigid parts. The chemical shifts are similar to those recorded previously for an assigned polymorph that was fibrillized at neutral pH.

Molecular mechanisms for protein-encoded inheritance

PubMed Central

Wiltzius, Jed J. W.; Landau, Meytal; Nelson, Rebecca; Sawaya, Michael R.; Apostol, Marcin I.; Goldschmidt, Lukasz; Soriaga, Angela B.; Cascio, Duilio; Rajashankar, Kanagalaghatta; Eisenberg, David

2013-01-01

Strains are phenotypic variants, encoded by nucleic acid sequences in chromosomal inheritance and by protein “conformations” in prion inheritance and transmission. But how is a protein “conformation” stable enough to endure transmission between cells or organisms? Here new polymorphic crystal structures of segments of prion and other amyloid proteins offer structural mechanisms for prion strains. In packing polymorphism, prion strains are encoded by alternative packings (polymorphs) of β-sheets formed by the same segment of a protein; in a second mechanism, segmental polymorphism, prion strains are encoded by distinct β-sheets built from different segments of a protein. Both forms of polymorphism can produce enduring “conformations,” capable of encoding strains. These molecular mechanisms for transfer of information into prion strains share features with the familiar mechanism for transfer of information by nucleic acid inheritance, including sequence specificity and recognition by non-covalent bonds. PMID:19684598

Molecular mechanisms of ribosomal protein gene coregulation

PubMed Central

Reja, Rohit; Vinayachandran, Vinesh; Ghosh, Sujana; Pugh, B. Franklin

2015-01-01

The 137 ribosomal protein genes (RPGs) of Saccharomyces provide a model for gene coregulation. We examined the positional and functional organization of their regulators (Rap1 [repressor activator protein 1], Fhl1, Ifh1, Sfp1, and Hmo1), the transcription machinery (TFIIB, TFIID, and RNA polymerase II), and chromatin at near-base-pair resolution using ChIP-exo, as RPGs are coordinately reprogrammed. Where Hmo1 is enriched, Fhl1, Ifh1, Sfp1, and Hmo1 cross-linked broadly to promoter DNA in an RPG-specific manner and demarcated by general minor groove widening. Importantly, Hmo1 extended 20–50 base pairs (bp) downstream from Fhl1. Upon RPG repression, Fhl1 remained in place. Hmo1 dissociated, which was coupled to an upstream shift of the +1 nucleosome, as reflected by the Hmo1 extension and core promoter region. Fhl1 and Hmo1 may create two regulatable and positionally distinct barriers, against which chromatin remodelers position the +1 nucleosome into either an activating or a repressive state. Consistent with in vitro studies, we found that specific TFIID subunits, in addition to cross-linking at the core promoter, made precise cross-links at Rap1 sites, which we interpret to reflect native Rap1–TFIID interactions. Our findings suggest how sequence-specific DNA binding regulates nucleosome positioning and transcription complex assembly >300 bp away and how coregulation coevolved with coding sequences. PMID:26385964

Bacilysin from Bacillus amyloliquefaciens FZB42 Has Specific Bactericidal Activity against Harmful Algal Bloom Species

PubMed Central

Wu, Liming; Wu, Huijun; Chen, Lina; Xie, Shanshan; Zang, Haoyu; Borriss, Rainer

2014-01-01

Harmful algal blooms, caused by massive and exceptional overgrowth of microalgae and cyanobacteria, are a serious environmental problem worldwide. In the present study, we looked for Bacillus strains with sufficiently strong anticyanobacterial activity to be used as biocontrol agents. Among 24 strains, Bacillus amyloliquefaciens FZB42 showed the strongest bactericidal activity against Microcystis aeruginosa, with a kill rate of 98.78%. The synthesis of the anticyanobacterial substance did not depend on Sfp, an enzyme that catalyzes a necessary processing step in the nonribosomal synthesis of lipopeptides and polyketides, but was associated with the aro gene cluster that is involved in the synthesis of the sfp-independent antibiotic bacilysin. Disruption of bacB, the gene in the cluster responsible for synthesizing bacilysin, or supplementation with the antagonist N-acetylglucosamine abolished the inhibitory effect, but this was restored when bacilysin synthesis was complemented. Bacilysin caused apparent changes in the algal cell wall and cell organelle membranes, and this resulted in cell lysis. Meanwhile, there was downregulated expression of glmS, psbA1, mcyB, and ftsZ—genes involved in peptidoglycan synthesis, photosynthesis, microcystin synthesis, and cell division, respectively. In addition, bacilysin suppressed the growth of other harmful algal species. In summary, bacilysin produced by B. amyloliquefaciens FZB42 has anticyanobacterial activity and thus could be developed as a biocontrol agent to mitigate the effects of harmful algal blooms. PMID:25261512

Study of Lateral Misalignment Tolerance of a Symmetric Free-Space Optical Link for Intra International Space Station Communication

NASA Technical Reports Server (NTRS)

Tedder, Sarah A.; Schoenholz, Bryan; Suddath, Shannon N.

2016-01-01

This paper describes the study of lateral misalignment tolerance of a symmetric high-rate free-space optical link (FSOL) for use between International Space Station (ISS) payload sites and the main cabin. The link will enable gigabit per second (Gbps) transmission of data, which is up to three orders of magnitude greater than the current capabilities. This application includes 10-20 meter links and requires minimum size, weight, and power (SWaP). The optical power must not present an eye hazard and must be easily integrated into the existing ISS infrastructure. On the ISS, rapid thermal changes and astronaut movement will cause flexure of the structure which will potentially misalign the free space transmit and receive optics 9 cm laterally and 0.2 degrees angularly. If this misalignment is not accounted for, a loss of the link or degradation of link performance will occur. Power measurements were collected to better understand the effect of various system design parameters on lateral misalignment. Parameters that were varied include: the type of small form pluggable (SFP) transceivers, type of fiber, and transmitted power level. A potential solution was identified that can reach the lateral misalignment tolerance (decenter span) required to create an FSOL on the ISS by using 105 m core fibers, a duplex SFP, two channels of light, and two fiber amplifiers.

Potential of Visible and Near Infrared Spectroscopy and Pattern Recognition for Rapid Quantification of Notoginseng Powder with Adulterants

PubMed Central

Nie, Pengcheng; Wu, Di; Sun, Da-Wen; Cao, Fang; Bao, Yidan; He, Yong

2013-01-01

Notoginseng is a classical traditional Chinese medical herb, which is of high economic and medical value. Notoginseng powder (NP) could be easily adulterated with Sophora flavescens powder (SFP) or corn flour (CF), because of their similar tastes and appearances and much lower cost for these adulterants. The objective of this study is to quantify the NP content in adulterated NP by using a rapid and non-destructive visible and near infrared (Vis-NIR) spectroscopy method. Three wavelength ranges of visible spectra, short-wave near infrared spectra (SNIR) and long-wave near infrared spectra (LNIR) were separately used to establish the model based on two calibration methods of partial least square regression (PLSR) and least-squares support vector machines (LS-SVM), respectively. Competitive adaptive reweighted sampling (CARS) was conducted to identify the most important wavelengths/variables that had the greatest influence on the adulterant quantification throughout the whole wavelength range. The CARS-PLSR models based on LNIR were determined as the best models for the quantification of NP adulterated with SFP, CF, and their mixtures, in which the rP values were 0.940, 0.939, and 0.867 for the three models respectively. The research demonstrated the potential of the Vis-NIR spectroscopy technique for the rapid and non-destructive quantification of NP containing adulterants. PMID:24129019

Genomic Prediction for Quantitative Traits Is Improved by Mapping Variants to Gene Ontology Categories in Drosophila melanogaster

PubMed Central

Edwards, Stefan M.; Sørensen, Izel F.; Sarup, Pernille; Mackay, Trudy F. C.; Sørensen, Peter

2016-01-01

Predicting individual quantitative trait phenotypes from high-resolution genomic polymorphism data is important for personalized medicine in humans, plant and animal breeding, and adaptive evolution. However, this is difficult for populations of unrelated individuals when the number of causal variants is low relative to the total number of polymorphisms and causal variants individually have small effects on the traits. We hypothesized that mapping molecular polymorphisms to genomic features such as genes and their gene ontology categories could increase the accuracy of genomic prediction models. We developed a genomic feature best linear unbiased prediction (GFBLUP) model that implements this strategy and applied it to three quantitative traits (startle response, starvation resistance, and chill coma recovery) in the unrelated, sequenced inbred lines of the Drosophila melanogaster Genetic Reference Panel. Our results indicate that subsetting markers based on genomic features increases the predictive ability relative to the standard genomic best linear unbiased prediction (GBLUP) model. Both models use all markers, but GFBLUP allows differential weighting of the individual genetic marker relationships, whereas GBLUP weighs the genetic marker relationships equally. Simulation studies show that it is possible to further increase the accuracy of genomic prediction for complex traits using this model, provided the genomic features are enriched for causal variants. Our GFBLUP model using prior information on genomic features enriched for causal variants can increase the accuracy of genomic predictions in populations of unrelated individuals and provides a formal statistical framework for leveraging and evaluating information across multiple experimental studies to provide novel insights into the genetic architecture of complex traits. PMID:27235308

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

PubMed

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

2005-06-01

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

Soil cover patterns and SOC dynamics impacts on the soil processes, land management and ecosystem services in Central Region of Russia

NASA Astrophysics Data System (ADS)

Vasenev, Ivan; Chernikov, Vladimir; Yashin, Ivan; Geraskin, Mikhail; Morev, Dmitriy

2014-05-01

In the Central Region of Russia (CRR) the soil cover patterns usually play the very important role in the soil forming and degradation processes (SFP & SDP) potential and current rates, soil organic carbon (SOC) dynamics and pools, greenhouse gases (GHG) emissions and soluble SOC fluxes that we need take into attention for better assessment of the natural and especially man-changed ecosystems' services and for best land-use practices development. Central Region of Russia is the biggest one in RF according to its population and role in the economy. CRR is characterized by high spatial variability of soil cover due to as original landscape heterogeneity as complicated history of land-use practices during last 700 years. Our long-term researches include the wide zonal-provincial set of representative ecosystems and soil cover patterns with different types and history of land-use (forest, meadow-steppe and agricultural ones) from middle-taiga to steppe zones with different level of continentality. The carried out more than 30-years region- and local-scale researches of representative natural and rural landscapes in Tver', Yaroslavl', Kaluga, Moscow, Vladimir, Saransk (Mordovia), Kursk, Orel, Tambov, Voronezh and Saratov oblasts give us the interregional multi-factorial matrix of elementary soil cover patterns (ESCP) with different soil forming and degradation processes rates and soil organic carbon dynamics due to regionally specific soil-geomorphologic features, environmental and dominated microclimate conditions, land-use current practices and history. The validation and ranging of the limiting factors of SFP and SDP develop¬ment, soil carbon dynamics and sequestration potential, ecosystem (agroecosystem) principal services, land functional qualities and agroecological state have been done for dominating and most dynamical components of ESCP regional-typological forms - with application of SOC structure analysis, regional and local GIS, soil spatial patterns detail mapping, traditional regression kriging, correlation tree models and DSS adapted to concrete region and agrolandscape conditions. The outcomes of statistical process modeling show the essential amplification of erosion, dehumification, CO2, CH4 and N2O emission, soluble SOC fluxes, acidification or alkalization, disaggregation and overcompaction processes due to violation of environmentally sound land-use systems and traditional balances of organic matter, nutrients, Ca and Na in agrolandscapes. Due to long-term intensive and out-of-balance land-use practices the most zonal soils and soil cover pattern essentially lost not only their unique natural features (humus horizons depth till 1 m and more in case of Chernozems, 2-6 % of SOC and favorable agrophysical features), but ecosystem services and ecological functions including terrestrial ecosystem carbon balance and the GHG fluxes control. Key-site monitoring results and regional generalized data showed 1-1.5% SOC lost during last 50 years period and active processes of CO2 emission and humus profile eluvial-illuvial redistribution too. A drop of Corg content below threshold "humus limiting content" values (for different soils they vary from 1 to 3-4% of SOC) considerably reduces effectiveness of used fertilizers and possibility of sustai¬nable agronomy here. Forest-steppe Chernozems are usually characterized by higher stability than steppe ones. The ratio between erosive and biological losses in humus supplies can be ten-tatively estimated as fifty-fifty with strong spatial variability due to slope and land-use parameters. These processes have essentially different sets of environmental consequences and ecosystem services that we need to understand in frame of environmental and agroecological problems development prediction.

Hypothesis: SLC12A3 Polymorphism modifies thiazide hypersensitivity of antenatal Bartter syndrome to thiazide resistance.

PubMed

Mammen, Cherry; Rupps, Rosemarie; Trnka, Peter; Boerkoel, Cornelius F

2012-02-01

We report a 5-year-old boy with thiazide-resistant Bartter syndrome. This is highly unusual since thiazide hypersensitivity is a common diagnostic finding in Bartter syndrome patients. Subsequent molecular testing identified compound heterozygosity for two novel mutations in KCNJ1, (c.556A > G and c.683G > A) which is associated with Bartter syndrome, and a paternally inherited polymorphism in SLC12A3 (c.791G > C). Mutations in SLC12A3 cause the thiazide-resistant tubulopathy Gitelman syndrome. Based on published studies of this polymorphism in SLC12A3 and the features of the proband's father, we postulate that this polymorphism modifies the phenotype of Bartter syndrome in the proband to thiazide resistance. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Association of insertion-deletions polymorphisms with colorectal cancer risk and clinical features.

PubMed

Marques, Diego; Ferreira-Costa, Layse Raynara; Ferreira-Costa, Lorenna Larissa; Correa, Romualdo da Silva; Borges, Aline Maciel Pinheiro; Ito, Fernanda Ribeiro; Ramos, Carlos Cesar de Oliveira; Bortolin, Raul Hernandes; Luchessi, André Ducati; Ribeiro-Dos-Santos, Ândrea; Santos, Sidney; Silbiger, Vivian Nogueira

2017-10-07

To investigate the association between 16 insertion-deletions (INDEL) polymorphisms, colorectal cancer (CRC) risk and clinical features in an admixed population. One hundred and forty patients with CRC and 140 cancer-free subjects were examined. Genomic DNA was extracted from peripheral blood samples. Polymorphisms and genomic ancestry distribution were assayed by Multiplex-PCR reaction, separated by capillary electrophoresis on the ABI 3130 Genetic Analyzer instrument and analyzed on GeneMapper ID v3.2. Clinicopathological data were obtained by consulting the patients' clinical charts, intra-operative documentation, and pathology scoring. Logistic regression analysis showed that polymorphism variations in IL4 gene was associated with increased CRC risk, while TYMS and UCP2 genes were associated with decreased risk. Reference to anatomical localization of tumor Del allele of NFKB1 and CASP8 were associated with more colon related incidents than rectosigmoid. In relation to the INDEL association with tumor node metastasis (TNM) stage risk, the Ins alleles of ACE , HLAG and TP53 (6 bp INDEL) were associated with higher TNM stage. Furthermore, regarding INDEL association with relapse risk, the Ins alleles of ACE , HLAG , and UGT1A1 were associated with early relapse risk, as well as the Del allele of TYMS . Regarding INDEL association with death risk before 10 years, the Ins allele of SGSM3 and UGT1A1 were associated with death risk. The INDEL variations in ACE , UCP2 , TYMS , IL4 , NFKB1 , CASP8 , TP53 , HLAG , UGT1A1 , and SGSM3 were associated with CRC risk and clinical features in an admixed population. These data suggest that this cancer panel might be useful as a complementary tool for better clinical management, and more studies need to be conducted to confirm these findings.

A characteristic of polymorphic membrane protein F of Chlamydia trachomatis isolated from male urogenital tracts in Japan.

PubMed

Yamazaki, Tomohiro; Matsuo, Junji; Takahashi, Satoshi; Kumagai, Shouta; Shimoda, Tomoko; Abe, Kiyotaka; Minami, Kunihiro; Yamaguchi, Hiroyuki

2015-12-01

Although sexually transmitted disease due to Chlamydia trachomatis occurs similarly in both men and women, the female urogenital tract differs from that of males anatomically and physiologically, possibly leading to specific polymorphisms of the bacterial surface molecules. In the present study, we therefore characterized polymorphic features in a high-definition phylogenetic marker, polymorphic outer membrane protein (Pmp) F of C. trachomatis strains isolated from male urogenital tracts in Japan (Category: Japan-males, n = 12), when compared with those isolated from female cervical ducts in Japan (Category: Japan-females, n = 11), female cervical ducts in the other country (Category: Ref-females, n = 12) or homosexual male rectums in the other country (Category: Ref-males, n = 7), by general bioinformatics analysis tool with MAFFT software. As a result, phylogenetic reconstruction of the PmpF amino acid sequences showing three distinct clusters revealed that the Japan-males were limited into cluster 1 and 2, although there were only four clusters even though including an outgroup. Meanwhile, the phylogenetic distance values of PmpF passenger domain without hinge region, but not its full-length sequence, showed that the Japan-males were more stable and displayed less diversity when compared with the other categories, supported by the sequence conservation features. Thus, PmpF passenger domain is a useful phylogenetic maker, and the phylogenic features indicate that C. trachomatis strains isolated from male urogenital tracts in Japan may be unique, suggesting an adaptation depending on selective pressure, such as the presence or absence of microbial flora, furthermore possibly connecting to sexual differentiation. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

TP53 PIN3 and PEX4 polymorphisms and infertility associated with endometriosis or with post-in vitro fertilization implantation failure

PubMed Central

Paskulin, D D; Cunha-Filho, J S L; Souza, C A B; Bortolini, M C; Hainaut, P; Ashton-Prolla, P

2012-01-01

p53 has a crucial role in human fertility by regulating the expression of leukemia inhibitory factor (LIF), a secreted cytokine critical for blastocyst implantation. To examine whether TP53 polymorphisms may be involved with in vitro fertilization (IVF) failure and endometriosis (END), we have assessed the associations between TP53 polymorphism in intron 2 (PIN2; G/C, intron 2), PIN3 (one (N, non-duplicated) or two (D, duplicated) repeats of a 16-bp motif, intron 3) and polymorphism in exon 4 (PEX4; C/G, p.P72R, exon 4) in 98 women with END and 115 women with post-IVF failure. In addition, 134 fertile women and 300 women unselected with respect to fertility-related features were assessed. TP53 polymorphisms and haplotypes were identified by amplification refractory mutation system polymerase chain reaction. TP53 PIN3 and PEX4 were associated with both END (P=0.042 and P=0.007, respectively) and IVF (P=0.004 and P=0.009, respectively) when compared with women both selected and unselected for fertility-related features. Haplotypes D-C and N-C were related to higher risk for END (P=0.002, P=0.001, respectively) and failure of IVF (P=0.018 and P=0.002, respectively) when compared with the Fertile group. These results support that specific TP53 haplotypes are associated with an increased risk of END-associated infertility and with post-IVF failure. PMID:23013791

Epidermal growth factor receptor gene polymorphisms are associated with prognostic features of breast cancer

PubMed Central

2014-01-01

Background The epidermal growth factor receptor (EGFR) is differently expressed in breast cancer, and its presence may favor cancer progression. We hypothesized that two EGFR functional polymorphisms, a (CA)n repeat in intron 1, and a single nucleotide polymorphism, R497K, may affect EGFR expression and breast cancer clinical profile. Methods The study population consisted of 508 Brazilian women with unilateral breast cancer, and no distant metastases. Patients were genotyped for the (CA)n and R497K polymorphisms, and the associations between (CA)n polymorphism and EGFR transcript levels (n = 129), or between either polymorphism and histopathological features (n = 505) were evaluated. The REMARK criteria of tumor marker evaluation were followed. Results (CA)n lengths ranged from 14 to 24 repeats, comprehending 11 alleles and 37 genotypes. The most frequent allele was (CA)16 (0.43; 95% CI = 0.40–0.46), which was set as the cut-off length to define the Short allele. Variant (CA)n genotypes had no significant effect in tumoral EGFR mRNA levels, but patients with two (CA)n Long alleles showed lower chances of being negative for progesterone receptor (ORadjusted = 0.42; 95% CI = 0.19–0.91). The evaluation of R497K polymorphism indicated a frequency of 0.21 (95% CI = 0.19 – 0.24) for the variant (Lys) allele. Patients with variant R497K genotypes presented lower proportion of worse lymph node status (pN2 or pN3) when compared to the reference genotype Arg/Arg (ORadjusted = 0.32; 95% CI = 0.17–0.59), which resulted in lower tumor staging (ORadjusted = 0.34; 95% CI = 0.19-0.63), and lower estimated recurrence risk (OR = 0.50; 95% CI = 0.30-0.81). The combined presence of both EGFR polymorphisms (Lys allele of R497K and Long/Long (CA)n) resulted in lower TNM status (ORadjusted = 0.22; 95% CI = 0.07-0.75) and lower ERR (OR = 0.25; 95% CI = 0.09-0.71). When tumors were stratified according to biological classification, the favorable effects of variant EGFR polymorphisms were preserved for luminal A tumors, but not for other subtypes. Conclusions The data suggest that the presence of the variant forms of EGFR polymorphisms may lead to better prognosis in breast cancer, especially in patients with luminal A tumors. PMID:24629097

Molecular mechanisms of ribosomal protein gene coregulation.

PubMed

Reja, Rohit; Vinayachandran, Vinesh; Ghosh, Sujana; Pugh, B Franklin

2015-09-15

The 137 ribosomal protein genes (RPGs) of Saccharomyces provide a model for gene coregulation. We examined the positional and functional organization of their regulators (Rap1 [repressor activator protein 1], Fhl1, Ifh1, Sfp1, and Hmo1), the transcription machinery (TFIIB, TFIID, and RNA polymerase II), and chromatin at near-base-pair resolution using ChIP-exo, as RPGs are coordinately reprogrammed. Where Hmo1 is enriched, Fhl1, Ifh1, Sfp1, and Hmo1 cross-linked broadly to promoter DNA in an RPG-specific manner and demarcated by general minor groove widening. Importantly, Hmo1 extended 20-50 base pairs (bp) downstream from Fhl1. Upon RPG repression, Fhl1 remained in place. Hmo1 dissociated, which was coupled to an upstream shift of the +1 nucleosome, as reflected by the Hmo1 extension and core promoter region. Fhl1 and Hmo1 may create two regulatable and positionally distinct barriers, against which chromatin remodelers position the +1 nucleosome into either an activating or a repressive state. Consistent with in vitro studies, we found that specific TFIID subunits, in addition to cross-linking at the core promoter, made precise cross-links at Rap1 sites, which we interpret to reflect native Rap1-TFIID interactions. Our findings suggest how sequence-specific DNA binding regulates nucleosome positioning and transcription complex assembly >300 bp away and how coregulation coevolved with coding sequences. © 2015 Reja et al.; Published by Cold Spring Harbor Laboratory Press.

Development and Assessment of CFD Models Including a Supplemental Program Code for Analyzing Buoyancy-Driven Flows Through BWR Fuel Assemblies in SFP Complete LOCA Scenarios

NASA Astrophysics Data System (ADS)

Artnak, Edward Joseph, III

This work seeks to illustrate the potential benefits afforded by implementing aspects of fluid dynamics, especially the latest computational fluid dynamics (CFD) modeling approach, through numerical experimentation and the traditional discipline of physical experimentation to improve the calibration of the severe reactor accident analysis code, MELCOR, in one of several spent fuel pool (SFP) complete loss-ofcoolant accident (LOCA) scenarios. While the scope of experimental work performed by Sandia National Laboratories (SNL) extends well beyond that which is reasonably addressed by our allotted resources and computational time in accordance with initial project allocations to complete the report, these simulated case trials produced a significant array of supplementary high-fidelity solutions and hydraulic flow-field data in support of SNL research objectives. Results contained herein show FLUENT CFD model representations of a 9x9 BWR fuel assembly in conditions corresponding to a complete loss-of-coolant accident scenario. In addition to the CFD model developments, a MATLAB based controlvolume model was constructed to independently assess the 9x9 BWR fuel assembly under similar accident scenarios. The data produced from this work show that FLUENT CFD models are capable of resolving complex flow fields within a BWR fuel assembly in the realm of buoyancy-induced mass flow rates and that characteristic hydraulic parameters from such CFD simulations (or physical experiments) are reasonably employed in corresponding constitutive correlations for developing simplified numerical models of comparable solution accuracy.

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.

FSR: feature set reduction for scalable and accurate multi-class cancer subtype classification based on copy number.

PubMed

Wong, Gerard; Leckie, Christopher; Kowalczyk, Adam

2012-01-15

Feature selection is a key concept in machine learning for microarray datasets, where features represented by probesets are typically several orders of magnitude larger than the available sample size. Computational tractability is a key challenge for feature selection algorithms in handling very high-dimensional datasets beyond a hundred thousand features, such as in datasets produced on single nucleotide polymorphism microarrays. In this article, we present a novel feature set reduction approach that enables scalable feature selection on datasets with hundreds of thousands of features and beyond. Our approach enables more efficient handling of higher resolution datasets to achieve better disease subtype classification of samples for potentially more accurate diagnosis and prognosis, which allows clinicians to make more informed decisions in regards to patient treatment options. We applied our feature set reduction approach to several publicly available cancer single nucleotide polymorphism (SNP) array datasets and evaluated its performance in terms of its multiclass predictive classification accuracy over different cancer subtypes, its speedup in execution as well as its scalability with respect to sample size and array resolution. Feature Set Reduction (FSR) was able to reduce the dimensions of an SNP array dataset by more than two orders of magnitude while achieving at least equal, and in most cases superior predictive classification performance over that achieved on features selected by existing feature selection methods alone. An examination of the biological relevance of frequently selected features from FSR-reduced feature sets revealed strong enrichment in association with cancer. FSR was implemented in MATLAB R2010b and is available at http://ww2.cs.mu.oz.au/~gwong/FSR.

Structural analysis of oligomeric and protofibrillar Aβ amyloid pair structures considering F20L mutation effects using molecular dynamics simulations.

PubMed

Lee, Myeongsang; Chang, Hyun Joon; Baek, Inchul; Na, Sungsoo

2017-04-01

Aβ amyloid proteins are involved in neuro-degenerative diseases such as Alzheimer's, Parkinson's, and so forth. Because of its structurally stable feature under physiological conditions, Aβ amyloid protein disrupts the normal cell function. Because of these concerns, understanding the structural feature of Aβ amyloid protein in detail is crucial. There have been some efforts on lowering the structural stabilities of Aβ amyloid fibrils by decreasing the aromatic residues characteristic and hydrophobic effect. Yet, there is a lack of understanding of Aβ amyloid pair structures considering those effects. In this study, we provide the structural characteristics of wildtype (WT) and phenylalanine residue mutation to leucine (F20L) Aβ amyloid pair structures using molecular dynamics simulation in detail. We also considered the polymorphic feature of F20L and WT Aβ pair amyloids based on the facing β-strand directions between the amyloid pairs. As a result, we were able to observe the varying effects of mutation, polymorphism, and protofibril lengths on the structural stability of pair amyloids. Furthermore, we have also found that opposite structural stability exists on a certain polymorphic Aβ pair amyloids depending on its oligomeric or protofibrillar state, which can be helpful for understanding the amyloid growth mechanism via repetitive fragmentation and elongation mechanism. Proteins 2017; 85:580-592. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

New Insights into the Diverse Electronic Phases of a Novel Vanadium Dioxide Polymorph: A Terahertz Spectroscopy Study

PubMed Central

Lourembam, James; Srivastava, Amar; La-o-vorakiat, Chan; Rotella, H.; Venkatesan, T.; Chia, Elbert E. M.

2015-01-01

A remarkable feature of vanadium dioxide is that it can be synthesized in a number of polymorphs. The conductivity mechanism in the metastable layered polymorph VO2(B) thin films has been investigated by terahertz time-domain spectroscopy (THz-TDS). In VO2(B), a critical temperature of 240 K marks the appearance of a non-zero Drude term in the observed complex conductivity, indicating the evolution from a pure insulating state towards a metallic state. In contrast, the THz conductivity of the well-known VO2(M1) is well fitted only by a modification of the Drude model to include backscattering. We also identified two different THz conductivity regimes separated by temperature in these two polymorphs. The electronic phase diagram is constructed, revealing that the width and onset of the metal-insulator transition in the B phase develop differently from the M1 phase. PMID:25777320

Polymorphism at the ref(2)P locus in Drosophila melanogaster: preliminary experiments concerning the selection mechanisms involved in its maintenance.

PubMed

Fleuriet, A

1981-02-01

It has been shown previously that a polymorphism for two alleles of the ref(2)P locus is a regular feature of French natural populations of Drosophila melanogaster and that this is maintained in laboratory populations raised in cages. In this paper, an experimental population and egg-collection experiments are reported. Differential survival of the three genotypes would be the main factor leading to the equilibrium frequencies, working only in drastic conditions of larval competition.

Identification of hallucinogenic fungi from the genera Psilocybe and Panaeolus by amplified fragment length polymorphism.

PubMed

Lee, J C; Cole, M; Linacre, A

2000-05-01

Unambiguous identification of the hallucinogenic fungi of the genera Psilocybe and Panaeolus is required by national and international drug control legislation. We report on a DNA-based test using the technique of amplified fragment length polymorphism (AFLP). AFLP can differentiate species of the two genera Psilocybe and Panaeolus by using different primer sets. The identification of hallucinogenic fungi using a DNA-based test, which can be used in conjunction with morphological features, will assist in forensic investigations.

Heterogeneous Amyloid β-Sheet Polymorphs Identified on Hydrogen Bond Promoting Surfaces Using 2D SFG Spectroscopy.

PubMed

Ho, Jia-Jung; Ghosh, Ayanjeet; Zhang, Tianqi O; Zanni, Martin T

2018-02-08

Two-dimensional sum-frequency generation spectroscopy (2D SFG) is used to study the structures of the pentapeptide FGAIL on hydrogen bond promoting surfaces. FGAIL is the most amyloidogenic portion of the human islet amyloid polypeptide (hIAPP or amylin). In the presence of a pure gold surface, FGAIL does not form ordered structures. When the gold is coated with a self-assembled monolayer of mercaptobenzoic acid (MBA), 2D SFG spectra reveal features associated with β-sheets. Also observed are cross peaks between the FGAIL peptides and the carboxylic acid groups of the MBA monolayer, indicating that the peptides are in close contact with the surface headgroups. In the second set of samples, FGAIL peptides chemically ligated to the MBA monolayer also exhibited β-sheet features but with a much simpler spectrum. From simulations of the experiments, we conclude that the hydrogen bond promoting surface catalyzes the formation of both parallel and antiparallel β-sheet structures with several different orientations. When ligated, parallel sheets with only a single orientation are the primary structure. Thus, this hydrogen bond promoting surface creates a heterogeneous distribution of polymorph structures, consistent with a concentration effect that allows nucleation of many different amyloid seeding structures. A single well-defined seed favors one polymorph over the others, showing that the concentrating influence of a membrane can be counterbalanced by factors that favor directed fiber growth. These experiments lay the foundation for the measurement and interpretation of β-sheet structures with heterodyne-detected 2D SFG spectroscopy. The results of this model system suggest that a heterogeneous distribution of polymorphs found in nature are an indication of nonselective amyloid aggregation whereas a narrow distribution of polymorph structures is consistent with a specific protein or lipid interaction that directs fiber growth.

TNFalpha and IL-10 gene polymorphisms in inflammatory bowel disease. Association of -1082 AA low producer IL-10 genotype with steroid dependency.

PubMed

Castro-Santos, Patricia; Suarez, Ana; López-Rivas, Laureano; Mozo, Lourdes; Gutierrez, Carmen

2006-05-01

An altered production of cytokines underlies inflammatory bowel disease (IBD) susceptibility. Various polymorphisms at the IL-10 and TNFalpha gene promoters control cytokine production levels. The influence of these polymorphisms on susceptibility to ulcerative colitis (UC) and Crohn's disease (CD) and their association with clinical features were analyzed. Genetic polymorphisms of TNFalpha (-308 G/A) and IL-10 (-1082 G/A, -812 C/T, and -592 C/A) were determined using the LightCycler system with hybridization probes matched with one sequence variant. The study population included 99 UC patients, 146 CD patients, and 343 matched controls. We did not find association between TNFalpha or IL-10 gene polymorphisms and UC or CD susceptibility, though a slight influence of -1082*G allele in UC appearance was observed. In a stratified analysis, a highly significant association between the -1082 AA IL-10 genotype and the steroid dependency was observed in IBD (p < 0.0001), contributing both UC (p = 0.004) and CD (p = 0.003) to this association. In contrast, TNFalpha genotypes did not influence steroid dependency in IBD. Further, the contribution of cytokine genotypes and of clinical features to the appearance of steroid-dependent status (dependent variable) was studied by multivariate analysis. The steroid-dependent phenotype correlated in UC with extensive disease (p = 0.010) and with the low producer -1082 AA IL-10 genotype (p = 0.002) and in CD with penetrating disease (p = 0.010), arthritis (p = 0.011), and the -1082 AA IL-10 genotype (p = 0.006). The main conclusion is that carriage of the -1082 AA IL-10 genotype (low producer) is a relevant risk factor for developing steroid-dependent IBD.

Association of PDCD1 polymorphism to systemic lupus erythematosus and rheumatoid arthritis susceptibility.

PubMed

do Canto, Luisa Matos; Farias, Ticiana Della Justina; Medeiros, Mayara Delagnelo; Coêlho, Cíntia Callegari; Sereia, Aline Fernanda Rodrigues; de Carlos Back, Lia Kubelka Fernandes; de Mello, Filipe Martins; Zimmermann, Adriana Fontes; Pereira, Ivânio Alves; de Souza, Ilíada Rainha

This study aims to analyze the relationship of programmed cell death 1 (PDCD1) gene polymorphism (PD1.3G/A - rs11568821) with features of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in a Southern Brazilian population. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed in 95 SLE and 87 RA patients and 128 control group individuals from Santa Catarina, Southern Brazil. The Hardy-Weinberg equilibrium (HWE) test, and odds ratio (OR) were analyzed, considering CI 95% and p≤0.05. The PD1.3A allele frequencies were 0.095 (SLE), 0.115 (RA) and 0.078 (controls). The genotypes of the control group were in HWE, while those of SLE and RA patients were not. However, we found no association between PD1.3 polymorphism and the SLE or RA susceptibility, nor clinical or epidemiological data. There was no significant association between PD1.3 polymorphism and SLE or RA susceptibility in this Southern Brazilian population. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

Association of PDCD1 polymorphism to Systemic Lupus Erythematosus and Rheumatoid Arthritis susceptibility.

PubMed

Canto, Luisa Matos do; Farias, Ticiana Della Justina; Medeiros, Mayara Delagnelo; Coêlho, Cíntia Callegari; Sereia, Aline Fernanda Rodrigues; Back, Lia Kubelka Fernandes de Carlos; Mello, Filipe Martins de; Zimmermann, Adriana Fontes; Pereira, Ivânio Alves; Souza, Ilíada Rainha de

2015-07-17

This study aims to analyze the relationship of programmed cell death 1 (PDCD1) gene polymorphism (PD1.3G/A - rs11568821) with features of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in a Southern Brazilian population. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was performed in 95 SLE and 87 RA patients and 128 control group individuals from Santa Catarina, Southern Brazil. The Hardy-Weinberg Equilibrium (HWE) test, and odds ratio (OR) were analyzed, considering CI 95% and p≤0.05. The PD1.3A allele frequencies were 0.095 (SLE), 0.115 (RA) and 0.078 (controls). The genotypes of the control group were in HWE, while those of SLE and RA patients were not. However, we found no association between PD1.3 polymorphism and the SLE or RA susceptibility, nor clinical or epidemiological data. There was no significant association between PD1.3 polymorphism and SLE or RA susceptibility in this Southern Brazilian population. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

Functional Interaction of the Ankylosing Spondylitis-associated Endoplasmic Reticulum Aminopeptidase 1 Polymorphism and HLA-B27 in Vivo*

PubMed Central

García-Medel, Noel; Sanz-Bravo, Alejandro; Van Nguyen, Dung; Galocha, Begoña; Gómez-Molina, Patricia; Martín-Esteban, Adrián; Alvarez-Navarro, Carlos; de Castro, José A. López

2012-01-01

The association of ERAP1 with ankylosing spondylitis (AS)1 among HLA-B27-positive individuals suggests that ERAP1 polymorphism may affect pathogenesis by altering peptide-dependent features of the HLA-B27 molecule. Comparisons of HLA-B*27:04-bound peptidomes from cells expressing different natural variants of ERAP1 revealed significant differences in the size, length, and amount of many ligands, as well as in HLA-B27 stability. Peptide analyses suggested that the mechanism of ERAP1/HLA-B27 interaction is a variant-dependent alteration in the balance between epitope generation and destruction determined by the susceptibility of N-terminal flanking and P1 residues to trimming. ERAP1 polymorphism associated with AS susceptibility ensured efficient peptide trimming and high HLA-B27 stability. Protective polymorphism resulted in diminished ERAP1 activity, less efficient trimming, suboptimal HLA-B27 peptidomes, and decreased molecular stability. This study demonstrates that natural ERAP1 polymorphism affects HLA-B27 antigen presentation and stability in vivo and proposes a mechanism for the interaction between these molecules in AS. PMID:22918227

A triclinic polymorph of tri­cyclo­hexyl­phosphane sulfide: crystal structure and Hirshfeld surface analysis

PubMed Central

Tan, Yi Jiun; Yeo, Chien Ing; Halcovitch, Nathan R.; Jotani, Mukesh M.

2017-01-01

The title compound, (C6H11)3PS (systematic name: tri­cyclo­hexyl-λ5-phosphane­thione), is a triclinic (P-1, Z′ = 1) polymorph of the previously reported ortho­rhom­bic form (Pnma, Z′ = 1/2) [Kerr et al. (1977 ▸). Can. J. Chem. 55, 3081–3085; Reibenspies et al. (1996 ▸). Z. Kristallogr. 211, 400]. While conformational differences exist between the non-symmetric mol­ecule in the triclinic polymorph, cf. the mirror-symmetric mol­ecule in the ortho­rhom­bic form, these differences are not chemically significant. The major feature of the mol­ecular packing in the triclinic polymorph is the formation of linear chains along the a axis sustained by methine-C—H⋯S(thione) inter­actions. The chains pack with no directional inter­actions between them. The analysis of the Hirshfeld surface for both polymorphs indicates a high degree of similarity, being dominated by H⋯H (ca 90%) and S⋯H/H⋯S contacts. PMID:28435705

Comparison of macro and micro Raman measurement for reliable quantitative analysis of pharmaceutical polymorphs.

PubMed

Paiva, Eduardo M; da Silva, Vitor H; Poppi, Ronei J; Pereira, Claudete F; Rohwedder, Jarbas J R

2018-05-12

This work reports on the use of micro- and macro-Raman measurements for quantification of mebendazole (MBZ) polymorphs A, B, and C in mixtures. Three Raman spectrophotometers were studied with a laser spot size of 3, 80 and 100 μm and spectral resolutions of 3.9, 9 and 4 cm -1 , respectively. The samples studied were ternary mixtures varying the MBZ polymorphs A and C from 0 to 100% and polymorph B from 0 to 30%. Partial Least Squares (PLS) regression models were developed using the pre-processing spectra (2nd derivative) of the ternary mixtures. The best performance was obtained when the macro-Raman configuration was applied, obtaining RMSEP values of 1.68%, 1.24% and 2.03% w/w for polymorphs A, B, and C, respectively. In general, micro-Raman presented worst results for MBZ polymorphs prediction because the spectra obtained with this configuration does not represent the bulk proportion of mixtures, which have different particle morphologies and sizes. In addition, the influence of these particle features on micro-Raman measurements was also studied. Finally, the results demonstrated that reliable analytical quantifying of MBZ polymorphs can be reached using a laser with wider area illuminated, thus enabling acquisition of more reproductive and representative spectra of the mixtures. Copyright © 2018 Elsevier B.V. All rights reserved.

Inherited Variation in Cytokine, Acute Phase Response, and Calcium Metabolism Genes Affects Susceptibility to Infective Endocarditis

PubMed Central

Rutkovskaya, Natalia V.; Kondyukova, Natalia V.; Odarenko, Yuri N.; Kazachek, Yana V.; Tsepokina, Anna V.; Barbarash, Leonid S.

2017-01-01

Infective endocarditis (IE) is a septic inflammation of the endocardium. Recognition of microbial patterns, cytokine and acute phase responses, hemostasis features, and alterations in plasma lipid and calcium profile all have been reported to affect pathogenesis and clinical course of IE. Having recruited 123 patients with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in the abovementioned pathways, with the further genetic association analysis. We found that the G/A genotype of the rs1143634 polymorphism within the IL1B gene, the G/T genotype of the rs3212227 polymorphism within the IL12B gene, the A/G genotype of the rs1130864 polymorphism within the CRP gene, and the G allele of the rs1801197 polymorphism within the CALCR gene were associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene was associated with a higher risk of IE. Furthermore, heterozygous genotypes of the rs1143634 and rs3212227 polymorphisms were associated with the higher plasma levels of IL-1β and IL-12, respectively. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE. PMID:28659664

Recipient But Not Donor Adiponectin Polymorphisms Are Associated With Early Posttransplant Hepatic Steatosis in Patients Transplanted for Non-Nonalcoholic Fatty Liver Disease Indications.

PubMed

John, Binu V; Aiken, Taylor; Garber, Ari; Thomas, Dawn; Lopez, Rocio; Patil, Deepa; Konjeti, Venkata Rajesh; Fung, John J; McCollough, Arthur J; Askar, Medhat

2018-06-01

De novo steatosis after liver transplant is common and can occur in up to one-third of patients who are transplanted for liver disease other than for nonalcoholic fatty liver disease. Genetic factors may influence posttransplant steatosis; in a posttransplant setting, donor or recipient genetic factors could also play roles. Genetic polymorphisms in the adiponectin gene have been associated with metabolic syndrome in the pretransplant setting. We aimed to assess the association between donor and recipient adiponectin polymorphisms and early posttransplant hepatic steatosis identified on liver biopsies. Clinical data were collected for 302 liver transplant patients who underwent protocol biopsies for hepatitis C. Of these, 111 patients had available biopsies and donor/recipient DNA. Patients with grade 1 steatosis or greater (35% of patients) were compared with patients without posttransplant steatosis with respect to clinical features and donor/recipient adiponectin polymorphism genotypes. Patients who developed posttransplant steatosis and those without steatosis were similar with respect to individual components of metabolic syndrome. The adiponectin polymorphisms rs1501299 G/G and rs17300539 G/G genotypes in recipients were associated with early posttransplant graft steatosis. We found no associations between graft steatosis and donor adiponectin polymorphisms. Genetic polymorphisms in the adiponectin gene of recipients (but not donors) are associated with early de novo posttransplant hepatic steatosis, independent of components of metabolic syndrome.

Correlation between facial morphology and gene polymorphisms in the Uygur youth population.

PubMed

He, Huiyu; Mi, Xue; Zhang, Jiayu; Zhang, Qin; Yao, Yuan; Zhang, Xu; Xiao, Feng; Zhao, Chunping; Zheng, Shutao

2017-04-25

Human facial morphology varies considerably among individuals and can be influenced by gene polymorphisms. We explored the effects of single nucleotide polymorphisms (SNPs) on facial features in the Uygur youth population of the Kashi area in Xinjiang, China. Saliva samples were collected from 578 volunteers, and 10 SNPs previously associated with variations in facial physiognomy were genotyped. In parallel, 3D images of the subjects' faces were obtained using grating facial scanning technology. After delimitation of 15 salient landmarks, the correlation between SNPs and the distances between facial landmark pairs was assessed. Analysis of variance revealed that ENPP1 rs7754561 polymorphism was significantly associated with RAla-RLipCn and RLipCn-Sbn linear distances (p = 0.044 and p = 0.012, respectively) as well as RLipCn-Stm curve distance (p = 0.042). The GHR rs6180 polymorphism correlated with RLipCn-Stm linear distance (p = 0.04), while the GHR rs6184 polymorphism correlated with RLipCn-ULipP curve distance (p = 0.047). The FGFR1 rs4647905 polymorphism was associated with LLipCn-Nsn linear distance (p = 0.042). These results reveal that ENPP1 and FGFR1 influence lower anterior face height, the distance from the upper lip to the nasal floor, and lip shape. FGFR1 also influences the lower anterior face height, while GHR is associated with the length and width of the lip.

Integrated Cox's model for predicting survival time of glioblastoma multiforme.

PubMed

Ai, Zhibing; Li, Longti; Fu, Rui; Lu, Jing-Min; He, Jing-Dong; Li, Sen

2017-04-01

Glioblastoma multiforme is the most common primary brain tumor and is highly lethal. This study aims to figure out signatures for predicting the survival time of patients with glioblastoma multiforme. Clinical information, messenger RNA expression, microRNA expression, and single-nucleotide polymorphism array data of patients with glioblastoma multiforme were retrieved from The Cancer Genome Atlas. Patients were separated into two groups by using 1 year as a cutoff, and a logistic regression model was used to figure out any variables that can predict whether the patient was able to live longer than 1 year. Furthermore, Cox's model was used to find out features that were correlated with the survival time. Finally, a Cox model integrated the significant clinical variables, messenger RNA expression, microRNA expression, and single-nucleotide polymorphism was built. Although the classification method failed, signatures of clinical features, messenger RNA expression levels, and microRNA expression levels were figured out by using Cox's model. However, no single-nucleotide polymorphisms related to prognosis were found. The selected clinical features were age at initial diagnosis, Karnofsky score, and race, all of which had been suggested to correlate with survival time. Both of the two significant microRNAs, microRNA-221 and microRNA-222, were targeted to p27 Kip1 protein, which implied the important role of p27 Kip1 on the prognosis of glioblastoma multiforme patients. Our results suggested that survival modeling was more suitable than classification to figure out prognostic biomarkers for patients with glioblastoma multiforme. An integrated model containing clinical features, messenger RNA levels, and microRNA expression levels was built, which has the potential to be used in clinics and thus to improve the survival status of glioblastoma multiforme patients.

Effect of cyclin [corrected] D1 (CCND1) gene polymorphism on tumor formation and behavior in patients with prolactinoma.

PubMed

Cander, Soner; Ertürk, Erdinç; Karkucak, Mutlu; Oz Gül, Ozen; Görükmez, Orhan; Yakut, Tahsin; Unal, Oğuz Kaan; Ersoy, Canan; Tuncel, Ercan; Imamoğlu, Sazi

2012-11-01

The objective of this study was to investigate the effect of G870A gene polymorphism of CCND1 on the formation and behavioral features of prolactinomas. One hundred and thirteen patients with prolactinoma and 108 age and gender matched control were included in the study. The patients were divided into two groups as noninvasive and invasive tumors. CCND1 G870A gene polymorphism was compared in patients/control and invasive/noninvasive groups. A and G allele frequencies were found as 41.7% and 58.3% in the controls, and 61.1% and 38.9% in the patients (p<0.01). Rates of G/G, G/A and A/A genotypes were found as 11.8%, 55.9% and 32.4% in the noninvasive group, and 15.6%, 44.4% and 40.0% in the invasive group, respectively. Differences between patient and control groups were significant but were not between invasive and noninvasive groups in terms of the allele frequencies and genotype distribution. Mean tumor size and serum levels of prolactin at the time of diagnosis and change in these values after the treatment were not found statistically significant in genotype subgroups. CCND1 G870A gene polymorphism may be an important factor in the early stages of the tumor formation. However, it did not affect the features of the tumor. Copyright © 2012 Elsevier B.V. All rights reserved.

Analysis of the VIDAS® Staph Enterotoxin III (SET3) for Detection of Staphylococcal Enterotoxins G, H, and I in Foods.

PubMed

Hait, Jennifer M; Nguyen, Angela T; Tallent, Sandra M

2018-04-20

Background : Staphylococcal food poisoning (SFP) frequently causes illnesses worldwide. SFP occurs from the ingestion of staphylococcal enterotoxins (SEs) preformed in foods by enterotoxigenic strains of Staphylococcus species, primarily S. aureus . SEG, SEH, and SEI induce emesis and have been implicated in outbreaks. Immunological-based methods are deemed the most practical methods for the routine analysis of SEs in foods given their ease of use, sensitivity, specificity, and commercial availability. These kits are routinely used to test for SEA-SEE. However, only recently has a kit been developed to detect SEG, SEH, and SEI. Objective: Our research examined the performance of the novel VIDAS ® Staph Enterotoxin III (SET3) for the detection of staphylococcal enterotoxins SEG, SEH, and SEI in foods. Methods : Here we assess the sensitivity and specificity of SET3 using duplicate test portions of six foods at varying concentrations of inclusivity and exclusivity inocula: pure SEG, SEH, SEI, S. aureus strain extracts positive for seg, seh , and sei , as well as SEA, SEB, SEC, SED, and SEE. Results : The overall detection limit was less than 2.09 ng/mL for foods inoculated with SEG, SEH, and SEI, with no cross reactivity observed. Highlights : Integrating concurrent testing to detect the presence of SEA-SEE and SEG-SEI utilizing the SET3 along with the VIDAS SET2, Ridascreen ® SET total, or other comparable kits will be instrumental for the future food assessments in our laboratory and may become the new standard for SE analysis of foods.

Sequence-Independent Cloning and Post-Translational Modification of Repetitive Protein Polymers through Sortase and Sfp-Mediated Enzymatic Ligation.

PubMed

Ott, Wolfgang; Nicolaus, Thomas; Gaub, Hermann E; Nash, Michael A

2016-04-11

Repetitive protein-based polymers are important for many applications in biotechnology and biomaterials development. Here we describe the sequential additive ligation of highly repetitive DNA sequences, their assembly into genes encoding protein-polymers with precisely tunable lengths and compositions, and their end-specific post-translational modification with organic dyes and fluorescent protein domains. Our new Golden Gate-based cloning approach relies on incorporation of only type IIS BsaI restriction enzyme recognition sites using PCR, which allowed us to install ybbR-peptide tags, Sortase c-tags, and cysteine residues onto either end of the repetitive gene polymers without leaving residual cloning scars. The assembled genes were expressed in Escherichia coli and purified using inverse transition cycling (ITC). Characterization by cloud point spectrophotometry, and denaturing polyacrylamide gel electrophoresis with fluorescence detection confirmed successful phosphopantetheinyl transferase (Sfp)-mediated post-translational N-terminal labeling of the protein-polymers with a coenzyme A-647 dye (CoA-647) and simultaneous sortase-mediated C-terminal labeling with a GFP domain containing an N-terminal GG-motif in a one-pot reaction. In a further demonstration, we installed an N-terminal cysteine residue into an elastin-like polypeptide (ELP) that was subsequently conjugated to a single chain poly(ethylene glycol)-maleimide (PEG-maleimide) synthetic polymer, noticeably shifting the ELP cloud point. The ability to straightforwardly assemble repetitive DNA sequences encoding ELPs of precisely tunable length and to post-translationally modify them specifically at the N- and C- termini provides a versatile platform for the design and production of multifunctional smart protein-polymeric materials.

[Screening for the risk of allergy and prevention in French maternity units: A survey].

PubMed

Chouraqui, J-P; Simeoni, U; Tohier, C; Nguyen, F; Kempf, C; Beck, L; Lachambre, E

2015-09-01

Allergy has been on the rise for half a century and concerns nearly 30% of children; it has now become a real public health problem. The guidelines on prevention of allergy set up by the French Society of Paediatrics (SFP) and the European Society of Paediatric Allergology and Clinical Immunology (ESPACI) are based on screening children at risk through a systematic search of the family history and recommend, for children at risk, exclusive breastfeeding whenever possible or otherwise utilization of hypoallergenic infant formula, which has demonstrated efficacy. The AllerNaiss practice survey assessed the modes of screening and prevention of allergy in French maternity units in 2012. The SFP guidelines are known by 82% of the maternity units that took part in the survey, and the ESPACI guidelines by 55% of them. A screening strategy is in place in 59% of the participating maternity wards, based on local consensus for 36% of them, 13% of the units having a written screening procedure. Screening is based on the search for a history of allergy in first-degree relatives (99%) during pregnancy (51%), in the delivery room (50%), and after delivery (89%). A mode of prevention of the risk of allergy exists in 62% of the maternity units, most often in writing (49%). A hypoallergenic infant formula is prescribed for non-breastfed children in 90% of the units. The survey shows that there is a real need for formalization of allergy risk screening and prevention of allergy in newborns in French maternity units. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Brain monoamine levels and behaviour of young and adult chickens genetically selected on feather pecking.

PubMed

Kops, M S; Kjaer, J B; Güntürkün, O; Westphal, K G C; Korte-Bouws, G A H; Olivier, B; Korte, S M; Bolhuis, J E

2017-06-01

Severe feather pecking (SFP) in chickens is a detrimental behaviour with possibly neurochemical deficits at its base. Recent neurological studies depicted conflicting results on the role of serotonin (5-hydroxytryptamine, 5-HT) and dopamine (DA) in the development and display of feather pecking. We studied brain monoamine levels and behaviour in domestic chickens divergently genetically selected on feather pecking behaviour, the Low Feather Pecking (LFP) and High Feather Pecking (HFP) lines, both at a young age and when adult, to elucidate the role of 5-HT and DA in feather pecking. Also pecking behaviour and the behavioural response to challenging test situations was determined. At 8 weeks of age, HFP had lower 5-HT and DA turnover in several brain areas than LFP, whereas these differences had disappeared or were even reversed at 25 weeks of age. Line differences in central monoamine activity were found both in emotion-regulating and motor-regulating areas. As expected from previous generations, HFP exceeded LFP in most types of pecking at other birds, including severe feather pecking. Furthermore, HFP responded more actively in most behavioural tests conducted, and seem more impulsive or (hyper)active in their way of coping with challenges. This paper shows different developmental trajectories of the neurochemical systems (5-HT and DA) for chickens divergently selected on feather pecking behaviour, and a remarkable reversion of differences in monoamine activity at a later stage of life. Whether this is a cause or consequence of SFP needs further investigation. Copyright © 2017 Elsevier B.V. All rights reserved.

Facing the rain after the phase out: Performance evaluation of alternative fluorinated and non-fluorinated durable water repellents for outdoor fabrics.

PubMed

Schellenberger, S; Gillgard, P; Stare, A; Hanning, A; Levenstam, O; Roos, S; Cousins, I T

2018-02-01

Fluorinated durable water repellent (DWR) agents are used to obtain water and stain repellent textiles. Due to the on-going phase-out of DWRs based on side-chain fluorinated polymers (SFP) with "long" perfluoroalkyl chains, the textile industry lacks suitable alternatives with comparable material characteristics. The constant development and optimization of SFPs for textile applications initiated more than half a century ago has resulted in a robust and very efficient DWR-technology and textiles with exceptional hydro- and oleo-phobic properties. The industry is now in the predicament that the long-chain SFPs with the best technical performance have undesirable toxicological and environmental behaviour. This study provides a comprehensive overview of the technical performance of presently available fluorinated and non-fluorinated DWRs as part of a chemical alternatives assessment (CAA). The results are based on a study with synthetic outdoor fabrics treated with alternative DWRs and tested for repellency using industrial standard and complementary methods. Using this approach, the complex structure-property relationships of DWR-polymers could be explained on a molecular level. Both short-chain SFPs and non-fluorinated DWRs showed excellent water repellency and durability in some cases while short-chain SFPs were the more robust of the alternatives to long-chain SFPs. A strong decline in oil repellency and durability with perfluoroalkyl chain length was shown for SFP DWRs. Non-fluorinated alternatives were unable to repel oil, which might limit their potential for substitution in textile application that require repellency towards non-polar liquids. Copyright © 2017. Published by Elsevier Ltd.

[Association of I/D and -786 Polymorphisms of ACE and NOS3 Genes With Features of the Course of Ischemic Heart Disease and Diabetes Mellitus Type 2].

PubMed

Afanasiev, S A; Muslimova, E F; Rebrov, T Y; Sergienko, T N; Repin, A N

2016-09-01

to study relationship of ACE insertion-deletion (I/D) polymorphism and NOS3 T-786C polymorphism with characteristics of the course of ischemic heart disease (IHD) at the background of diabetes mellitus. Were examined 114 patients with IHD, 29.8% of patients had type 2 diabetes mellitus. ACE and NOS3 polymorphisms were determined by allele-specific polymerase chain reaction with primers by "Lytech". Patients with combined pathology belonged to older age group, had increased frequency of obesity and predominance of functional class II chronic heart failure. In this group we detected association of D allele of the ACE gene with higher frequency of dyslipidemia and obesity. Among patients with IHD without diabetes we observed associations of ACE I/D and NOS3 T-786C polymorphisms (close and moderate, respectively) with severity of effort angina. We also found that frequency of dyslipidemia among carriers of II and TT genotypes was lower than among carriers of other genotypes. Presence of type 2 diabetes as background pathology leads to a change of character of association of ACE I/D and NOS3 T-786C polymorphisms with clinical characteristics of patients with IHD.

Association of insertion-deletions polymorphisms with colorectal cancer risk and clinical features

PubMed Central

Marques, Diego; Ferreira-Costa, Layse Raynara; Ferreira-Costa, Lorenna Larissa; Correa, Romualdo da Silva; Borges, Aline Maciel Pinheiro; Ito, Fernanda Ribeiro; Ramos, Carlos Cesar de Oliveira; Bortolin, Raul Hernandes; Luchessi, André Ducati; Ribeiro-dos-Santos, Ândrea; Santos, Sidney; Silbiger, Vivian Nogueira

2017-01-01

AIM To investigate the association between 16 insertion-deletions (INDEL) polymorphisms, colorectal cancer (CRC) risk and clinical features in an admixed population. METHODS One hundred and forty patients with CRC and 140 cancer-free subjects were examined. Genomic DNA was extracted from peripheral blood samples. Polymorphisms and genomic ancestry distribution were assayed by Multiplex-PCR reaction, separated by capillary electrophoresis on the ABI 3130 Genetic Analyzer instrument and analyzed on GeneMapper ID v3.2. Clinicopathological data were obtained by consulting the patients’ clinical charts, intra-operative documentation, and pathology scoring. RESULTS Logistic regression analysis showed that polymorphism variations in IL4 gene was associated with increased CRC risk, while TYMS and UCP2 genes were associated with decreased risk. Reference to anatomical localization of tumor Del allele of NFKB1 and CASP8 were associated with more colon related incidents than rectosigmoid. In relation to the INDEL association with tumor node metastasis (TNM) stage risk, the Ins alleles of ACE, HLAG and TP53 (6 bp INDEL) were associated with higher TNM stage. Furthermore, regarding INDEL association with relapse risk, the Ins alleles of ACE, HLAG, and UGT1A1 were associated with early relapse risk, as well as the Del allele of TYMS. Regarding INDEL association with death risk before 10 years, the Ins allele of SGSM3 and UGT1A1 were associated with death risk. CONCLUSION The INDEL variations in ACE, UCP2, TYMS, IL4, NFKB1, CASP8, TP53, HLAG, UGT1A1, and SGSM3 were associated with CRC risk and clinical features in an admixed population. These data suggest that this cancer panel might be useful as a complementary tool for better clinical management, and more studies need to be conducted to confirm these findings. PMID:29085228

Conformational dimorphism in o-nitrobenzoic acid: alternative ways to avoid the O...O clash.

PubMed

Ibragimov, Aziz; Ashurov, Jamshid; Ibragimov, Bakhtiyar; Wang, Ai; Mouhib, Halima; Englert, Ulli

2016-07-01

Polymorphism is a challenging phenomenon and the competitive packing alternatives which are characteristic for polymorphs may be encountered for essentially rigid molecules. A second crystal form of the well known compound o-nitrobenzoic acid, C7H5NO4, an important intermediate in the production of dyes, pharmaceuticals and agrochemicals, is described. Although obtained serendipitously, its intra- and intermolecular features match expectations from database searches and theoretical calculations. O-H...O hydrogen-bonded carboxylic acid dimers represent the building blocks in both polymorphs. For steric reasons and in agreement with a calculated potential energy surface, the carboxylic acid and nitro groups cannot simultaneously be coplanar with the benzene ring but have to tilt. In the well established crystal form, this out-of-plane torsion is more pronounced for the nitro substituent. In contrast, the new polymorph is characterized by a major tilt of the carboxylic acid group. The molecules in both alternative crystal forms achieve a similar compromise with respect to acceptable intramolecular O...O contacts.

DNApod: DNA polymorphism annotation database from next-generation sequence read archives.

PubMed

Mochizuki, Takako; Tanizawa, Yasuhiro; Fujisawa, Takatomo; Ohta, Tazro; Nikoh, Naruo; Shimizu, Tokurou; Toyoda, Atsushi; Fujiyama, Asao; Kurata, Nori; Nagasaki, Hideki; Kaminuma, Eli; Nakamura, Yasukazu

2017-01-01

With the rapid advances in next-generation sequencing (NGS), datasets for DNA polymorphisms among various species and strains have been produced, stored, and distributed. However, reliability varies among these datasets because the experimental and analytical conditions used differ among assays. Furthermore, such datasets have been frequently distributed from the websites of individual sequencing projects. It is desirable to integrate DNA polymorphism data into one database featuring uniform quality control that is distributed from a single platform at a single place. DNA polymorphism annotation database (DNApod; http://tga.nig.ac.jp/dnapod/) is an integrated database that stores genome-wide DNA polymorphism datasets acquired under uniform analytical conditions, and this includes uniformity in the quality of the raw data, the reference genome version, and evaluation algorithms. DNApod genotypic data are re-analyzed whole-genome shotgun datasets extracted from sequence read archives, and DNApod distributes genome-wide DNA polymorphism datasets and known-gene annotations for each DNA polymorphism. This new database was developed for storing genome-wide DNA polymorphism datasets of plants, with crops being the first priority. Here, we describe our analyzed data for 679, 404, and 66 strains of rice, maize, and sorghum, respectively. The analytical methods are available as a DNApod workflow in an NGS annotation system of the DNA Data Bank of Japan and a virtual machine image. Furthermore, DNApod provides tables of links of identifiers between DNApod genotypic data and public phenotypic data. To advance the sharing of organism knowledge, DNApod offers basic and ubiquitous functions for multiple alignment and phylogenetic tree construction by using orthologous gene information.

DNApod: DNA polymorphism annotation database from next-generation sequence read archives

PubMed Central

Mochizuki, Takako; Tanizawa, Yasuhiro; Fujisawa, Takatomo; Ohta, Tazro; Nikoh, Naruo; Shimizu, Tokurou; Toyoda, Atsushi; Fujiyama, Asao; Kurata, Nori; Nagasaki, Hideki; Kaminuma, Eli; Nakamura, Yasukazu

2017-01-01

With the rapid advances in next-generation sequencing (NGS), datasets for DNA polymorphisms among various species and strains have been produced, stored, and distributed. However, reliability varies among these datasets because the experimental and analytical conditions used differ among assays. Furthermore, such datasets have been frequently distributed from the websites of individual sequencing projects. It is desirable to integrate DNA polymorphism data into one database featuring uniform quality control that is distributed from a single platform at a single place. DNA polymorphism annotation database (DNApod; http://tga.nig.ac.jp/dnapod/) is an integrated database that stores genome-wide DNA polymorphism datasets acquired under uniform analytical conditions, and this includes uniformity in the quality of the raw data, the reference genome version, and evaluation algorithms. DNApod genotypic data are re-analyzed whole-genome shotgun datasets extracted from sequence read archives, and DNApod distributes genome-wide DNA polymorphism datasets and known-gene annotations for each DNA polymorphism. This new database was developed for storing genome-wide DNA polymorphism datasets of plants, with crops being the first priority. Here, we describe our analyzed data for 679, 404, and 66 strains of rice, maize, and sorghum, respectively. The analytical methods are available as a DNApod workflow in an NGS annotation system of the DNA Data Bank of Japan and a virtual machine image. Furthermore, DNApod provides tables of links of identifiers between DNApod genotypic data and public phenotypic data. To advance the sharing of organism knowledge, DNApod offers basic and ubiquitous functions for multiple alignment and phylogenetic tree construction by using orthologous gene information. PMID:28234924

Mass and charge distributions of amyloid fibers involved in neurodegenerative diseases: mapping heterogeneity and polymorphism† †Electronic supplementary information (ESI) available: Experimental section and supplementary figures. See DOI: 10.1039/c7sc04542e

PubMed Central

Pansieri, Jonathan; Halim, Mohammad A.; Vendrely, Charlotte; Dumoulin, Mireille; Legrand, François; Sallanon, Marcelle Moulin; Chierici, Sabine; Denti, Simona; Dagany, Xavier; Dugourd, Philippe; Marquette, Christel

2018-01-01

Heterogeneity and polymorphism are generic features of amyloid fibers with some important effects on the related disease development. We report here the characterization, by charge detection mass spectrometry, of amyloid fibers made of three polypeptides involved in neurodegenerative diseases: Aβ1–42 peptide, tau and α-synuclein. Beside the mass of individual fibers, this technique enables to characterize the heterogeneity and the polymorphism of the population. In the case of Aβ1–42 peptide and tau protein, several coexisting species could be distinguished and characterized. In the case of α-synuclein, we show how the polymorphism affects the mass and charge distributions. PMID:29732065

Polymorphism at the REF(2)P Locus in DROSOPHILA MELANOGASTER: Preliminary Experiments concerning the Selection Mechanisms Involved in Its Maintenance

PubMed Central

Fleuriet, Annie

1981-01-01

It has been shown previously that a polymorphism for two alleles of the ref(2)P locus is a regular feature of French natural populations of Drosophila melanogaster and that this is maintained in laboratory populations raised in cages. In this paper, an experimental population and egg-collection experiments are reported. Differential survival of the three genotypes would be the main factor leading to the equilibrium frequencies, working only in drastic conditions of larval competition. PMID:6791986

On the importance of balancing selection in plants

PubMed Central

Delph, Lynda F.; Kelly, John K.

2013-01-01

Summary Balancing selection refers to a variety of selective regimes that maintain advantageous genetic diversity within populations. We review the history of the ideas regarding the types of selection that maintain such polymorphism in flowering plants, notably heterozygote advantage, negative frequency-dependent selection, and spatial heterogeneity. One shared feature of these mechanisms is that whether an allele is beneficial or detrimental is conditional on its frequency in the population. We highlight examples of balancing selection on a variety of discrete traits. These include the well-referenced case of self-incompatibility and recent evidence from species with nuclear-cytoplasmic gynodioecy, both of which exhibit trans-specific polymorphism, a hallmark of balancing selection. We also discuss and give examples of how spatial heterogeneity in particular, which is often thought unlikely to allow protected polymorphism, can maintain genetic variation in plants (which are rooted in place) as a result of microhabitat selection. Lastly, we discuss limitations of the protected polymorphism concept for quantitative traits, where selection can inflate the genetic variance without maintaining specific alleles indefinitely. We conclude that while discrete-morph variation provides the most unambiguous cases of protected polymorphism, they represent only a fraction of the balancing selection at work in plants. PMID:23952298

How social learning adds up to a culture: from birdsong to human public opinion

PubMed Central

Feher, Olga; Fimiarz, Daniel; Conley, Dalton

2017-01-01

ABSTRACT Distributed social learning may occur at many temporal and spatial scales, but it rarely adds up to a stable culture. Cultures vary in stability and diversity (polymorphism), ranging from chaotic or drifting cultures, through cumulative polymorphic cultures, to stable monolithic cultures with high conformity levels. What features can sustain polymorphism, preventing cultures from collapsing into either chaotic or highly conforming states? We investigate this question by integrating studies across two quite separate disciplines: the emergence of song cultures in birds, and the spread of public opinion and social conventions in humans. In songbirds, the learning process has been studied in great detail, while in human studies the structure of social networks has been experimentally manipulated on large scales. In both cases, the manner in which communication signals are compressed and filtered – either during learning or while traveling through the social network – can affect culture polymorphism and stability. We suggest a simple mechanism of a shifting balance between converging and diverging social forces to explain these effects. Understanding social forces that shape cultural evolution might be useful for designing agile communication systems, which are stable and polymorphic enough to promote gradual changes in institutional behavior. PMID:28057835

Development of GaInNAs-based 1.3-μm VCSEL

NASA Astrophysics Data System (ADS)

Ramakrishnan, Arun; Ebbinghaus, G.; Lima, A.; Supper, D.; Kristen, Guenter; Popp, M.; Degen, C.; Althaus, H.-L.; Killer, T.; Scholz, R.; Melinde, M.; Sauter, M.; Weigert, M.; Riechert, Henning; Steinle, Gunther

2003-12-01

In this paper the realization, development and production of 1.3μm vertical cavity surface emitting lasers (VCSEL) with datacom suitable performance are presented. These low cost laser diodes are well suited for optical interconnect applications for LAN and MAN with transmission distances up to 15 km. The possibilities as well as the advantages and limits of shifting the wavelength from commercially available VCSEL emitting at 850nm to 1300nm are discussed. 1300nm VCSELs in a low cost SMD plastic package assembled into an intelligent SFP-module developed by Infineon Technologies are demonstrated.

On-line fission products measurements during a PWR severe accident: the French DECA-PF project

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

Ducros, G.; Allinei, P.G.; Roure, C.

Following the Fukushima accident, a lot of recommendations was drawn by international organizations (IAEA, OECD, NUGENIA network...) in order to improve the safety in such accidental conditions and mitigate their consequences. One of these recommendations was to improve the robustness of the instrumentation, which was dramatically lacking at Fukushima, as well as to better determine the Source Term involved in nuclear accident. The DECA-PF project (Diagnosis of a degraded reactor core through Fission Product measurements) was elaborated in this context and selected as one of 21 collaborative R and D projects in the field of nuclear safety and radioprotection, fundedmore » in May 2013 by the French National Research Agency. Over the months following the Fukushima accident, a CEA crisis team was held in order to analyze on-line the situation taking into account the data delivered by TEPCO and other organizations. Despite the difficulties encountered concerning the reliability of these data, the work performed showed the high capacity of Fission Products (FP) measurements to get a diagnosis relative to the status of the reactors and the spent fuel pools (SFP). Based on these FP measurements, it was possible to conclude that the main origin of the releases was coming from the cores and not from the SFP, in particular for SFP-4 which was of high concern, and that the degradation level of the reactors was very large, including probably an extensive core melting. To improve the reliability of this kind of diagnosis, the necessity to get such measurements as soon as possible after the accident and as near as possible from the reactor was stressed. In this way the present DECA-PF project intends to develop a new and innovative instrumentation taking into account the design of the French nuclear power plants on which sand bed filters have been implemented for severe accident management. Three complementary techniques, devoted to measure the FP release on-line, are being studied: - Gamma spectrometry, with an industrial objective to build a prototype aimed at improving the capacity of the present radiation monitoring system, - Gas chromatography, for the quantification of the fission gases (Xe, Kr) as well as potential carbon oxides produced in case of Molten Corium Concrete Interaction, - Optical absorption spectroscopy, the objective of this most innovative technique being to quantify the tetra-oxide of ruthenium, which could be produced in case of lower head failure, and the gaseous forms of iodine (molecular and organic) released in the environment. A global description and the present status of this project is presented, focusing on the Source Term establishment at the outlet stack of the sand bed filters and on the perspectives of implementation of the on-line gamma spectrometry equipment. (authors)« less

Landscape of Insertion Polymorphisms in the Human Genome

PubMed Central

Onozawa, Masahiro; Goldberg, Liat; Aplan, Peter D.

2015-01-01

Nucleotide substitutions, small (<50 bp) insertions or deletions (indels), and large (>50 bp) deletions are well-known causes of genetic variation within the human genome. We recently reported a previously unrecognized form of polymorphic insertions, termed templated sequence insertion polymorphism (TSIP), in which the inserted sequence was templated from a distant genomic region, and was inserted in the genome through reverse transcription of an RNA intermediate. TSIPs can be grouped into two classes based on nucleotide sequence features at the insertion junctions; class 1 TSIPs show target site duplication, polyadenylation, and preference for insertion at a 5′-TTTT/A-3′ sequence, suggesting a LINE-1 based insertion mechanism, whereas class 2 TSIPs show features consistent with repair of a DNA double strand break by nonhomologous end joining. To gain a more complete picture of TSIPs throughout the human population, we evaluated whole-genome sequence from 52 individuals, and identified 171 TSIPs. Most individuals had 25–30 TSIPs, and common (present in >20% of individuals) TSIPs were found in individuals throughout the world, whereas rare TSIPs tended to cluster in specific geographic regions. The number of rare TSIPs was greater than the number of common TSIPs, suggesting that TSIP generation is an ongoing process. Intriguingly, mitochondrial sequences were a frequent template for class 2 insertions, used more commonly than any nuclear chromosome. Similar to single nucleotide polymorphisms and indels, we suspect that these TSIPs may be important for the generation of human diversity and genetic diseases, and can be useful in tracking historical migration of populations. PMID:25745018

Identification of copper phthalocyanine blue polymorphs in unaged and aged paint systems by means of micro-Raman spectroscopy and Random Forest.

PubMed

Anghelone, Marta; Jembrih-Simbürger, Dubravka; Schreiner, Manfred

2015-10-05

Copper phthalocyanine (CuPc) blues (PB15) are largely used in art and industry as pigments. In these fields mainly three different polymorphic modifications of PB15 are employed: alpha, beta and epsilon. Differentiating among these CuPc forms can give important information for developing conservation strategy and can help in relative dating, since each form was introduced in the market in different time periods. This study focuses on the classification of Raman spectra measured using 532 nm excitation wavelength on: (i) dry pigment powders, (ii) unaged mock-ups of self-made paints, (iii) unaged commercial paints, and (iv) paints subjected to accelerated UV ageing. The ratios among integrated Raman bands are taken in consideration as features to perform Random Forest (RF). Features selection based on Gini Contrast score was carried out on the measured dataset to determine the Raman bands ratios with higher predictive power. These were used as polymorphic markers, in order to establish an easy and accessible method for the identification. Three different ratios and the presence of a characteristic vibrational band allowed the identification of the crystal modification in pigments powder as well as in unaged and aged paint films. Copyright © 2015 Elsevier B.V. All rights reserved.

A Single-Stranded DNA Aptamer That Selectively Binds to Staphylococcus aureus Enterotoxin B

PubMed Central

DeGrasse, Jeffrey A.

2012-01-01

The bacterium Staphylococcus aureus is a common foodborne pathogen capable of secreting a cocktail of small, stable, and strain-specific, staphylococcal enterotoxins (SEs). Staphylococcal food poisoning (SFP) results when improperly handled food contaminated with SEs is consumed. Gastrointestinal symptoms of SFP include emesis, diarrhea and severe abdominal pain, which manifest within hours of ingesting contaminated food. Immuno-affinity based methods directly detect, identify, and quantify several SEs within a food or clinical sample. However, the success of these assays depends upon the availability of a monoclonal antibody, the development of which is non-trivial and costly. The current scope of the available immuno-affinity based methods is limited to the classical SEs and does not encompass all of the known or emergent SEs. In contrast to antibodies, aptamers are short nucleic acids that exhibit high affinity and specificity for their targets without the high-costs and ethical concerns of animal husbandry. Further, researchers may choose to freely distribute aptamers and develop assays without the proprietary issues that increase the per-sample cost of immuno-affinity assays. This study describes a novel aptamer, selected in vitro, with affinity to staphylococcal enterotoxin B (SEB) that may be used in lieu of antibodies in SE detection assays. The aptamer, designated APTSEB1, successfully isolates SEB from a complex mixture of SEs with extremely high discrimination. This work sets the foundation for future aptamer and assay development towards the entire family of SEs. The rapid, robust, and low-cost identification and quantification of all of the SEs in S. aureus contaminated food is essential for food safety and epidemiological efforts. An in vitro generated library of SE aptamers could potentially allow for the comprehensive and cost-effective analysis of food samples that immuno-affinity assays currently cannot provide. PMID:22438927

A single-stranded DNA aptamer that selectively binds to Staphylococcus aureus enterotoxin B.

PubMed

DeGrasse, Jeffrey A

2012-01-01

The bacterium Staphylococcus aureus is a common foodborne pathogen capable of secreting a cocktail of small, stable, and strain-specific, staphylococcal enterotoxins (SEs). Staphylococcal food poisoning (SFP) results when improperly handled food contaminated with SEs is consumed. Gastrointestinal symptoms of SFP include emesis, diarrhea and severe abdominal pain, which manifest within hours of ingesting contaminated food. Immuno-affinity based methods directly detect, identify, and quantify several SEs within a food or clinical sample. However, the success of these assays depends upon the availability of a monoclonal antibody, the development of which is non-trivial and costly. The current scope of the available immuno-affinity based methods is limited to the classical SEs and does not encompass all of the known or emergent SEs. In contrast to antibodies, aptamers are short nucleic acids that exhibit high affinity and specificity for their targets without the high-costs and ethical concerns of animal husbandry. Further, researchers may choose to freely distribute aptamers and develop assays without the proprietary issues that increase the per-sample cost of immuno-affinity assays. This study describes a novel aptamer, selected in vitro, with affinity to staphylococcal enterotoxin B (SEB) that may be used in lieu of antibodies in SE detection assays. The aptamer, designated APT(SEB1), successfully isolates SEB from a complex mixture of SEs with extremely high discrimination. This work sets the foundation for future aptamer and assay development towards the entire family of SEs. The rapid, robust, and low-cost identification and quantification of all of the SEs in S. aureus contaminated food is essential for food safety and epidemiological efforts. An in vitro generated library of SE aptamers could potentially allow for the comprehensive and cost-effective analysis of food samples that immuno-affinity assays currently cannot provide.

Enhancing the Thermotolerance of Entomopathogenic Isaria fumosorosea SFP-198 Conidial Powder by Controlling the Moisture Content Using Drying and Adjuvants

PubMed Central

Lee, Se Jin; Lee, Hyang Burm

2014-01-01

Entomopathogenic fungi are promising pest-control agents but their industrial applicability is limited by their thermosusceptibility. With an aim to increase the thermotolerance of Isaria fumosorosea SFP-198, moisture absorbents were added to dried conidial powder, and the relationship between its water potential and thermotolerance was investigated. Mycotized rice grains were dried at 10℃, 20℃, 30℃, and 40℃ and the drying effect of each temperature for 24, 48, 96, and 140 hr was determined. Drying for 48 hr at 10℃ and 20℃ reduced the moisture content to < 5% without any significant loss of conidial thermotolerance, but drying at 30℃ and 40℃ reduced both moisture content and conidial thermotolerance. To maintain thermotolerance during storage, moisture absorbents, such as calcium chloride, silica gel, magnesium sulfate, white carbon, and sodium sulfate were individually added to previously dried-conidial powder at 10% (w/w). These mixtures was then stored at room temperature for 30 days and subjected to 50℃ for 2 hr. The white carbon mixture had the highest conidial thermotolerance, followed by silica gel, magnesium sulfate, and then the other absorbents. A significant correlation between the water potential and conidial thermotolerance was observed in all conidia-absorbent mixtures tested in this study (r = -0.945). Conidial thermotolerance in wet conditions was evaluated by adding moisturized white carbon (0~20% H2O) to conidia to mimic wet conditions. Notably, the conidia still maintained their thermotolerance under these conditions. Thus, it is evident that conidial thermotolerance can be maintained by drying mycotized rice grains at low temperatures and adding a moisture absorbent, such as white carbon. PMID:24808736

Correlation of interactions between NOS3 polymorphisms and oxygen therapy with retinopathy of prematurity susceptibility

PubMed Central

Yu, Chunhong; Yi, Jinglin; Yin, Xiaolong; Deng, Yan; Liao, Yujun; Li, Xiaobing

2015-01-01

Aim: This study was aimed to detect the correlation of nitric oxide synthase 3 (NOS3) gene polymorphisms (T-786C and G894T) and retinopathy of prematurity (ROP) susceptibility. Interaction between NOS3 gene polymorphisms and the duration of oxygen therapy was also explored in ROP babies. Methods: Genotypes of NOS3 gene polymorphisms were genotyped by MassArray method. Hardy-Weinberg equilibrium (HWE) was used to calculate the representativeness of the cases and controls. Crossover analysis was utilized to explore the gene environment interactions. Relative risk of ROP was presented by odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs). Results: Among the subject features, oxygen therapy had obvious difference between case and control groups (P<0.05). There existed significant association between-786C allele and ROP susceptibility (P=0.049, OR=0.669, 95% CI=0.447-0.999). Genotypes of T-786C polymorphism and genotypes and alleles of G894T polymorphism did not related to the susceptibility of ROP. Interactions were existed between NOS3 gene polymorphisms and oxygen therapy duration. When the duration of oxygen therapy was less than 17 days, both -786CC genotype and 894GT genotype were correlated with ROP susceptibility (P=0.020, OR=0.115, 95% CI=0.014-0.960; P=0.011, OR=0.294, 95% CI=0.100-0.784). Conclusion: -786C allele might have a protective effect for ROP. Interactions of -786CC and 894GT genotype with oxygen therapy duration (less than 17 days) were both protection factors of ROP. PMID:26823875

DNA repair polymorphisms in B-cell chronic lymphocytic leukemia in sufferers of Chernobyl Nuclear Power Plant accident.

PubMed

Abramenko, Iryna; Bilous, Nadiia; Chumak, Anatolyi; Kostin, Alexey; Martina, Zoya; Dyagil, Iryna

2012-01-01

An association between DNA repair gene polymorphisms, environmental factors, and development of some types of cancer has been suggested by several studies. Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the clean-up workers of the Chernobyl Nuclear Power Plant (NPP) accident and it has some specific features. Therefore, we have studied the possible differences in DNA repair gene polymorphisms in CLL patients depending on ionizing radiation (IR) exposure history and their clinical characterictics. Arg399Gln XRCC1, Thr241Met XRCC3, and Lys751Gln XPD polymorphisms were studied in 64 CLL patients, exposed to IR due to the Chernobyl NPP accident, 114 IR-non-exposed CLL patients, and 103 sex- and age-matched IR-exposed controls using polymerase chain reaction-restriction fragment-length polymorphism analysis. All investigated polymorphisms were equally distributed between two groups of CLL patients and IR-exposed controls, except that that there was a significant reduction of the common homozygous Lys/Lys XPD genotype among IR-exposed CLL patients (23.7%) compared with IR-exposed controls (45.6%), OR = 0.37; 95% CI = 0.18-0.75; (P = 0.005). The number of IR-non-exposed CLL patients (37.4%) with the Lys/Lys XPD genotype was also decreased compared to IR-exposed controls, although this difference was not significant (P = 0.223). These preliminary data suggest a possible modifying role of Lys751Gln XPD polymorphism for the development of CLL, expecially in radiation-exposed persons.

Analysis of vitamin D receptor gene polymorphisms in patients with chronic periodontitis.

PubMed

Gunes, Sezgin; Sumer, A Pinar; Keles, Gonca Cayir; Kara, Nurten; Koprulu, Hulya; Bagci, Hasan; Bek, Yuksel

2008-01-01

Genetic polymorphisms in the vitamin D receptor (VDR) gene are related to bone mineral density, bone turnover, and diseases with bone loss. Alveolar bone loss is a key feature in periodontitis. The aim of this study was to determine whether severe generalized chronic periodontitis (CP) in a Turkish population was associated with polymorphisms in the VDR gene. Samples of venous blood and DNA were obtained from 72 patients with severe generalized chronic periodontitis and 102 healthy controls. The polymorphic regions were amplified using PCR followed by digestion with restriction enzymes BsmI A/G(rs1544410), ApaI G/T(rs11168271), TaqI T/C(rs731236), and analyzed electrophoretically. Genotype and allele frequencies were calculated. There were no statistically significant differences in the frequencies of VDR BsmI, ApaI, TaqI genotypes between the CP patients and healthy controls. The GTT haplotype, constructed from the three adjacent restriction fragment length polymorphisms was found to be over-represented among CP cases. This corresponded an OR of 2.4 (95% confidence interval, 1.12-5.18) for heterozygous carriers and 2.27 (95% confidence interval, 0.95-5.4) for homozygous carrier of the risk haplotype. The present findings indicated that BsmI, ApaI, TaqI polymorphisms of the VDR gene were not associated with the severe generalized CP in the studied Turkish patients. Moreover, the VDR genotypes based on haplotype analysis may be associated with chronic periodontitis. In the future, diagnostic periodontal risk assessments like polymorphisms may be useful in detection of individuals susceptible for periodontitis.

Report of Freshwater Mollusks Workshop 19-20 May 1981.

DTIC Science & Technology

1982-05-01

biomes . If discrete groups of individuals may be recognized on the basis of ERM features , and no intergrades occur even in areas of sympatry, it is...the Canadian Interior Basis," Malacologia, Vol 13, pp 1-509. 1979. "Polymorphism in Marine Mollusks and Biome Develop- ment," Smithsonian Contributions...includes data on range, life history, ecological requirements, and identifying features . c. Analyze techniques used to relocate or create habitat for

Genetic association analysis of inositol polyphosphate phosphatase‐like 1 (INPPL1, SHIP2) variants with essential hypertension

PubMed Central

Marçano, Ana Carolina Braga; Burke, Beverley; Gungadoo, Johannie; Wallace, Chris; Kaisaki, Pamela J; Woon, Peng Y; Farrall, Martin; Clayton, David; Brown, Morris; Dominiczak, Anna; Connell, John M; Webster, John; Lathrop, Mark; Caulfield, Mark; Samani, Nilesh; Gauguier, Dominique; Munroe, Patricia B

2007-01-01

Background Inositol polyphosphate phosphatase‐like 1 (INPPL1, SHIP2) is a negative regulator of insulin signalling and has previously been found to be associated with hypertension, obesity and type 2 diabetes in a cohort of families with diabetes in the UK presenting features of metabolic syndrome. In particular, a haplotype of three genetic polymorphisms (rs2276047, rs9886 and an insertion/deletion polymorphism in intron 1) was found to be strongly associated with increased susceptibility to hypertension. Objective and methods To assess if INPPL1 variants play a direct role in the development of essential hypertension, we genotyped the three previously associated INPPL1 polymorphisms in a cohort of 712 families with severe hypertension from the BRIGHT study transmission disequilibrium test cohort. Results We found no evidence of significant association between hypertension and any of the three INPPL1 polymorphisms or haplotypes (p>0.1). Conclusion These results suggest that INPPL1 variants may be involved in mechanisms causing hypertension in metabolic syndrome patients specifically. PMID:17557929

Genetic Polymorphism in Wine Yeasts: Mechanisms and Methods for Its Detection

PubMed Central

Guillamón, José M.; Barrio, Eladio

2017-01-01

The processes of yeast selection for using as wine fermentation starters have revealed a great phenotypic diversity both at interspecific and intraspecific level, which is explained by a corresponding genetic variation among different yeast isolates. Thus, the mechanisms involved in promoting these genetic changes are the main engine generating yeast biodiversity. Currently, an important task to understand biodiversity, population structure and evolutionary history of wine yeasts is the study of the molecular mechanisms involved in yeast adaptation to wine fermentation, and on remodeling the genomic features of wine yeast, unconsciously selected since the advent of winemaking. Moreover, the availability of rapid and simple molecular techniques that show genetic polymorphisms at species and strain levels have enabled the study of yeast diversity during wine fermentation. This review will summarize the mechanisms involved in generating genetic polymorphisms in yeasts, the molecular methods used to unveil genetic variation, and the utility of these polymorphisms to differentiate strains, populations, and species in order to infer the evolutionary history and the adaptive evolution of wine yeasts, and to identify their influence on their biotechnological and sensorial properties. PMID:28522998

The BIM Deletion Polymorphism and its Clinical Implication in Patients with EGFR-Mutant Non-Small-Cell Lung Cancer Treated with EGFR Tyrosine Kinase Inhibitors.

PubMed

Lee, Ji Yun; Ku, Bo Mi; Lim, Sung Hee; Lee, Min-Young; Kim, Haesu; Kim, Moonjin; Kim, Sungmin; Jung, Hyun Ae; Sun, Jong-Mu; Ahn, Jin Seok; Park, Keunchil; Ahn, Myung-Ju

2015-06-01

A germline BIM deletion polymorphism has been proposed to predict poor treatment response to certain kinase inhibitors. The purpose of this study was to explore whether the BIM deletion polymorphism predicts treatment efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in Korean patients with EGFR-mutant non-small-cell lung cancer (NSCLC). Peripheral blood samples from a total of 205 patients with EGFR-mutant NSCLC who were treated with EGFR TKIs between July 2008 and April 2013 were included. The incidence of BIM deletions in these samples was detected by polymerase chain reaction. We compared the clinical outcomes in patients with and without the polymorphism after treatment with EGFR TKIs (gefitinib or erlotinib). The BIM deletion polymorphism was present in 15.6% (32 of 205) of patients. One patient was homozygous for the deletion, and the remaining 31 had heterozygous deletions. The majority of patients were younger than 65 years (74%), female (68%), never smokers (76%), and had stage IV NSCLC (67%). There were no associations between the BIM deletion polymorphism and clinicopathological features including gender, age, smoking status, histology, stage, and number of metastasis sites. Patients with and without the BIM deletion polymorphism had similar objective response rates (91 vs. 84%, p = 0.585). Progression-free survival and overall survival did not differ significantly between patients with and without the BIM deletion polymorphism (median progression-free survival 12 vs. 11 months, p = 0.160; median overall survival 31 vs. 30 months, p = 0.452). Multivariate analysis identified significantly predictive markers for clinical outcomes of EGFR TKIs including Eastern Cooperative Oncology Group performance status 0-1, adenocarcinoma histology, recurrent disease, and EGFR mutation type. The results were validated in an independent cohort of 69 NSCLC patients. It remains to be determined whether the BIM deletion polymorphism provides intrinsic resistance or decreased sensitivity to EGFR TKIs in EGFR-mutant NSCLC patients.

A second ortho-rhom-bic polymorph of (Z)-3-(9-anthr-yl)-1-(2-thien-yl)prop-2-en-1-one.

PubMed

Chantrapromma, Suchada; Suwunwong, Thitipone; Boonnak, Nawong; Fun, Hoong-Kun

2010-01-09

The title heteroaryl chalcone, C(21)H(14)OS, is a second ortho-rhom-bic polymorph which crystallizes in the space group P2(1)2(1)2(1). The structure was previously reported [Fun et al. (2009 ▶). Acta Cryst. E65, o2168-o2169] in the space group Pna2(1). The bond distances and angles are similar in both structures. In contrast, the overall crystal packing is different from that in the first ortho-rhom-bic Pna2(1) polymorph in which mol-ecules were stacked into columns along the b axis and the thio-phene units of two adjacent columns were stacked in a head to tail fashion. In the present polymorph, mol-ecules are found to dimerize through a weak S⋯S inter-action [3.6513 (7) Å] and these dimers are arranged into sheets parallel to the bc plane. There are no classical hydrogen bonds in the packing which features short C⋯O [3.2832 (2)-3.6251 (9) Å], C⋯S [3.4879 (17)-3.6251 (19) Å] and S⋯O [2.9948 (16) Å] contacts, together with C-H⋯π inter-actions. Similar contacts were found in the other polymorph.

Association of XRCC1 Trp194 allele with risk of breast cancer, and Ki67 protein status in breast tumor tissues

PubMed Central

Jalali, Chiya; Ghaderi, Bayazid; Amini, Sabrieh; Abdi, Mohammad; Roshani, Daem

2016-01-01

Objectives: To evaluate the role of this polymorphism as a risk factor for breast cancer in Kurdish patients and to investigate the possible association between Arg194Trp x-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms with clinical and histopathological outcomes of patients with breast cancer. Methods: A total of 100 breast cancer patients and 200 cancer-free controls in Kurdish population of Kurdistan state admitted to Tohid Hospital, Sanandaj, Kurdistan, Iran between January 2012 and May 2015 were enrolled in this cross-sectional study. Tissue expression of estrogen receptor (ER), progesteron receptor (PR), human epidermal growth factor receptor 2 (Her2/neu), and Ki67 were evaluated by immunohistochemistry (IHC). The Arg194Trp genotypes were determined by polymerase chain reaction- restriction fragment length polymorphism method. Results: Our data showed that the risk for breast cancer increased significantly among the Trp variant of XRCC1. Statistically significant association was found between codon 194 polymorphisms and tissue expression of Ki67. Conclusion: The Trp allele of codon 194 XRCC1 is a potential risk factor for breast cancer in Kurdish ethnicity. Furthermore, effect of this polymorphism on clinical and histological features of breast cancer was significant. PMID:27279507

Association between ghrelin gene variations, body mass index, and waist-to-hip ratio in patients with polycystic ovary syndrome.

PubMed

Xu, L; Shi, Y; Gu, J; Wang, Y; Wang, L; You, L; Qi, X; Ye, Y; Chen, Z

2014-03-01

To investigate the association between 2 single nucleotide polymorphisms (SNP501A/C and 604 G/A) in the promoter of the ghrelin gene and the hormonal and metabolic phenotypes of polycystic ovary syndrome (PCOS) in a Chinese population. 285 patients with PCOS and 260 healthy controls were selected for a prospective, case-control study at Shandong Provincial Hospital, Jinan, China. All subjects underwent genotype analysis of the 2 single nucleotide polymorphisms of the ghrelin gene. Measurements were also taken of blood lipids, glucose, and hormone levels, and calculations of body mass index (BMI) and waist-to-hip ratio (WHR) were performed to detect hormonal and metabolic phenotypes. No significant diff erences in polymorphism genotypes were found between PCOS patients and healthy controls. However, the frequency of the -501 A/C A allele was significantly higher in the PCOS group than in the control group. PCOS -501 A/C A carriers had significantly higher BMI and WHR than PCOS women with the CC genotype. -604 G/A polymorphisms were not associated with clinical or biochemical characteristics of PCOS. The -501 A/C polymorphism of the ghrelin gene is associated with metabolic features of PCOS in a Chinese population. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

How social learning adds up to a culture: from birdsong to human public opinion.

PubMed

Tchernichovski, Ofer; Feher, Olga; Fimiarz, Daniel; Conley, Dalton

2017-01-01

Distributed social learning may occur at many temporal and spatial scales, but it rarely adds up to a stable culture. Cultures vary in stability and diversity (polymorphism), ranging from chaotic or drifting cultures, through cumulative polymorphic cultures, to stable monolithic cultures with high conformity levels. What features can sustain polymorphism, preventing cultures from collapsing into either chaotic or highly conforming states? We investigate this question by integrating studies across two quite separate disciplines: the emergence of song cultures in birds, and the spread of public opinion and social conventions in humans. In songbirds, the learning process has been studied in great detail, while in human studies the structure of social networks has been experimentally manipulated on large scales. In both cases, the manner in which communication signals are compressed and filtered - either during learning or while traveling through the social network - can affect culture polymorphism and stability. We suggest a simple mechanism of a shifting balance between converging and diverging social forces to explain these effects. Understanding social forces that shape cultural evolution might be useful for designing agile communication systems, which are stable and polymorphic enough to promote gradual changes in institutional behavior. © 2017. Published by The Company of Biologists Ltd.

Polymorphisms in the oxytocin receptor gene are associated with the development of psychopathy.

PubMed

Dadds, Mark R; Moul, Caroline; Cauchi, Avril; Dobson-Stone, Carol; Hawes, David J; Brennan, John; Urwin, Ruth; Ebstein, Richard E

2014-02-01

The co-occurrence of child conduct problems (CPs) and callous-unemotional (CU) traits confers risk for psychopathy. The oxytocin (OXT) system is a likely candidate for involvement in the development of psychopathy. We tested variations in the OXT receptor gene (OXTR) in CP children and adolescents with varying levels of CU traits. Two samples of Caucasian children, aged 4-16 years, who met DSM criteria for disruptive behavior problems and had no features of autism spectrum disorder, were stratified into low versus high CU traits. Measures were the frequencies of nine candidate OXTR polymorphisms (single nucleotide polymorphisms). In Sample 1, high CU traits were associated with single nucleotide polymorphism rs1042778 in the 3' untranslated region of OXTR and the CGCT haplotype of rs2268490, rs2254298, rs237889, and rs13316193. The association of rs1042778 was replicated in the second rural sample and held across gender and child versus adolescent age groups. We conclude that polymorphic variation of the OXTR characterizes children with high levels of CU traits and CPs. The results are consistent with a hypothesized role of OXT in the developmental antecedents of psychopathy, particularly the differential amygdala activation model of psychopathic traits, and add genetic evidence that high CU traits specify a distinct subgroup within CP children.

Recent developments in the study of opioid receptors.

PubMed

Cox, Brian M

2013-04-01

It is now about 40 years since Avram Goldstein proposed the use of the stereoselectivity of opioid receptors to identify these receptors in neural membranes. In 2012, the crystal structures of the four members of the opioid receptor family were reported, providing a structural basis for understanding of critical features affecting the actions of opiate drugs. This minireview summarizes these recent developments in our understanding of opiate receptors. Receptor function is also influenced by amino acid substitutions in the protein sequence. Among opioid receptor genes, one polymorphism is much more frequent in human populations than the many others that have been found, but the functional significance of this single nucleotide polymorphism (SNP) has been unclear. Recent studies have shed new light on how this SNP might influence opioid receptor function. In this minireview, the functional significance of the most prevalent genetic polymorphism among the opioid receptor genes is also considered.

Micro-evolution in grasshoppers mediated by polymorphic Robertsonian translocations.

PubMed

Colombo, Pablo C

2013-01-01

This review focuses on grasshoppers that are polymorphic for Robertsonian translocations because in these organisms the clarity of meiotic figures allows the study of both chiasma distribution and the orientation of trivalents and multivalents in metaphase I. Only five species of such grasshoppers were found in the literature, and all of them were from the New World: Oedaleonotus enigma (Scudder) (Orthoptera: Acrididae), Leptysma argentina Bruner, Dichroplus pratensis Bruner, Sinipta dalmani Stål, and Cornops aquaticum Bruner. A general feature of these species (except O. enigma) is that fusion carriers suffer a marked reduction of proximal and interstitial (with respect to the centromere) chiasma frequency; this fact, along with the reduction in the number of linkage groups with the consequent loss of independent segregation, produces a marked decrease of recombination in fusion carriers. This reduction in recombination has led to the conclusion that Robertsonian polymorphic grasshopper species share some properties with inversion polymorphic species of Drosophila, such as the central-marginal pattern (marginal populations are monomorphic, central populations are highly polymorphic). This pattern might be present in D. pratensis, which is certainly the most complex Robertsonian polymorphism system in the present study. However, L. argentina and C. aquaticum do not display this pattern. This issue is open to further research. Since C. aquaticum is soon to be released in South Africa as a biological control, the latitudinal pattern found in South America may repeat there. This experiment's outcome is open and deserves to be followed.

No association of the Arg51Gln and Leu72Met polymorphisms of the ghrelin gene and polycystic ovary syndrome.

PubMed

Wang, Kehua; Wang, Leiguang; Zhao, Yueran; Shi, Yuhua; Wang, Laicheng; Chen, Zi-Jiang

2009-02-01

Ghrelin plays a role in regulating glucose metabolism and energy balance. Polymorphisms in preproghrelin and ghrelin gene could be responsible for obesity, insulin resistance and low ghrelin levels observed in some individuals. The objective of this study was to evaluate the influence of two single-nucleotide polymorphisms (SNPs) of ghrelin gene on the clinical, the hormonal and metabolic features in women with polycystic ovary syndrome (PCOS) in a Chinese population. A large sample of Chinese PCOS (n = 271) women and a control group (n = 296) of healthy women matched for age were studied. Hormone and metabolic profiles were measured and blood samples were collected for genotype and allelic frequency analysis. Non-synonymous SNPs in the coding region (exon 2) of the preproghrelin gene (Arg51Gln (346 G>A) and Leu72Met (408 C>A) were studied using PCR and restriction fragment length polymorphism analysis. The polymorphism Arg51Gln was not found in the cohorts studied. The distribution of Leu72Met was similar in PCOS group and in healthy controls. There was no significant difference in age, BMI, waist-hip-ratio and levels of FSH, LH, estradiol, testosterone and prolactin between PCOS patients with different genotypes, and the level of plasma glucose and insulin was also similar. No association was found between Leu72Met and Arg51Gln polymorphisms in the ghrelin gene and PCOS in Chinese population.

Genetic variation in exon 17 of INSR is associated with insulin resistance and hyperandrogenemia among lean Indian women with polycystic ovary syndrome.

PubMed

Mukherjee, Srabani; Shaikh, Nuzhat; Khavale, Sushma; Shinde, Gayatri; Meherji, Pervin; Shah, Nalini; Maitra, Anurupa

2009-05-01

Polycystic ovary syndrome (PCOS) is a multigenic disorder, and insulin resistance is one of its hallmark features. Polymorphisms in exon 17 of insulin receptor (INSR) gene are reported to be associated with PCOS. We investigated this association in Indian women and its putative relationship with PCOS associated traits, which has not been explored so far. In this case control study, the polymorphisms were investigated by direct sequencing in 180 women with PCOS and 144 age matched controls. Clinical, anthropometric, biochemical, and hormonal parameters were also estimated. The silent C/T polymorphism at His1058 in exon 17 of INSR was found to be present in our study population. The polymorphic genotype (CT+TT) was significantly associated with PCOS in lean women (chi(2)=8.493, df=1, P=0.004). It showed association with higher fasting insulin levels (P=0.02), homeostasis model assessment of insulin resistance (P=0.005), free androgen index (P=0.03), and lower quantitative insulin sensitivity check index (P=0.004) in lean PCOS women. No other novel or known polymorphism was identified in exon 17 in this cohort. The study shows significant association of C/T polymorphism at His1058 of INSR with PCOS in the lean rather than obese Indian women. Its association with indices of insulin resistance and hyperandrogenemia is also seen in the same group. The findings strengthen the concept that pathogenesis of PCOS is different in lean and obese women.

Station Climatic Summaries, Latin America

DTIC Science & Technology

1990-06-01

GERONA, CUBA STATION 4: 782210 ICAO ID: MUNG LOCATION: 21 50’N, 82 47’W ELEVATION (FEET): 75 LST - GMT: -5 PREPARED BY: USAFETAC/ECR, MAR 1987 PERIOD...AUG SFP ocr Nt;V DEC ANN 00=02 [, sTr "• -€ -• : € : . : ’ " ’ 06-08 LST # # # 1 0 2 1 #i 1 1 1 2 1 09-1 [IST # 0 i 2 1 3 2 ! 1 # I 13 12-14 LST I # # 2...A N S STATIO .NAME ASU-N-CIU.N./.P.R.ES.- STR SSIR PARAG STATION MSC: 862180 LATITUDE/LOITITE: S 25 14 I 057 31 FIELD ELEVATION: 292 FEET CALL

Separated Fringe Packet Observations with the CHARA Array. II. Omega Andromeda, HD 178911, and Xi Cephei

DTIC Science & Technology

2014-07-31

Printed in the U.S.A. SEPARATED FRINGE PACKET OBSERVATIONS WITH THE CHARA ARRAY. II. ω ANDROMEDA , HD 178911, AND ξ CEPHEI C. D. Farrington1, T. A...calibration star is not needed, and the SFPs can provide an accurate vector separation. In this paper, we apply the SFP approach to ω Andromeda , HD 178911...and 0.860 ± 0.051M and 39.54 ± 1.85 mas for ω Andromeda , for HD 178911 of 0.802 ± 0.055M and 0.622 ± 0.053M with 28.26 ± 1.70 mas, and masses of

CRAWview: for viewing splicing variation, gene families, and polymorphism in clusters of ESTs and full-length sequences.

PubMed

Chou, A; Burke, J

1999-05-01

DNA sequence clustering has become a valuable method in support of gene discovery and gene expression analysis. Our interest lies in leveraging the sequence diversity within clusters of expressed sequence tags (ESTs) to model gene structure for the study of gene variants that arise from, among other things, alternative mRNA splicing, polymorphism, and divergence after gene duplication, fusion, and translocation events. In previous work, CRAW was developed to discover gene variants from assembled clusters of ESTs. Most importantly, novel gene features (the differing units between gene variants, for example alternative exons, polymorphisms, transposable elements, etc.) that are specialized to tissue, disease, population, or developmental states can be identified when these tools collate DNA source information with gene variant discrimination. While the goal is complete automation of novel feature and gene variant detection, current methods are far from perfect and hence the development of effective tools for visualization and exploratory data analysis are of paramount importance in the process of sifting through candidate genes and validating targets. We present CRAWview, a Java based visualization extension to CRAW. Features that vary between gene forms are displayed using an automatically generated color coded index. The reporting format of CRAWview gives a brief, high level summary report to display overlap and divergence within clusters of sequences as well as the ability to 'drill down' and see detailed information concerning regions of interest. Additionally, the alignment viewing and editing capabilities of CRAWview make it possible to interactively correct frame-shifts and otherwise edit cluster assemblies. We have implemented CRAWview as a Java application across windows NT/95 and UNIX platforms. A beta version of CRAWview will be freely available to academic users from Pangea Systems (http://www.pangeasystems.com). Contact :

QTL mapping of potato chip color and tuber traits within an autotetraploid family

USDA-ARS?s Scientific Manuscript database

Cultivated potato (Solanum tuberosum L.) is a highly heterozygous autotetraploid crop species, and this presents challenges for traditional line development and molecular breeding. Recent availability of a single nucleotide polymorphism (SNP) array with 8303 features and software packages for linkag...

Structure-dependent vibrational dynamics of Mg(BH 4 ) 2 polymorphs probed with neutron vibrational spectroscopy and first-principles calculations

DOE PAGES

Dimitrievska, Mirjana; White, James L.; Zhou, Wei; ...

2016-08-19

We investigated the structure-dependent vibrational properties of different Mg(BH 4) 2 polymorphs (α, β, γ, and δ phases) with a combination of neutron vibrational spectroscopy (NVS) measurements and density functional theory (DFT) calculations, with emphasis placed on the effects of the local structure and orientation of the BH 4 - anions. DFT simulations closely match the neutron vibrational spectra. The main bands in the low-energy region (20–80 meV) are associated with the BH4 - librational modes. The features in the intermediate energy region (80–120 meV) are attributed to overtones and combination bands arising from the lower-energy modes. The features inmore » the high-energy region (120–200 meV) correspond to the BH 4 - symmetric and asymmetric bending vibrations, of which four peaks located at 140, 142, 160, and 172 meV are especially intense. There are noticeable intensity distribution variations in the vibrational bands for different polymorphs. We can explain these differences using the spatial distribution of BH 4 - anions within various structures. An example of the possible identification of products after the hydrogenation of MgB 2, using NVS measurements, is presented. Our results provide fundamental insights of benefit to researchers currently studying these promising hydrogen-storage materials.« less

Association of Genetic Polymorphisms in TNF and MIF Gene with the Risk of Primary Dysmenorrhea.

PubMed

Dogru, Hatice Yilmaz; Ozsoy, Asker Zeki; Karakus, Nevin; Delibas, Ilhan Bahri; Isguder, Cigdem Kunt; Yigit, Serbulent

2016-08-01

Primary dysmenorrhea, which affects 90 % of adolescent girls and more than 50 % of menstruating women worldwide, is characterized by recurrent pain during menses in the absence of a detectable organic disease. The aim of this study is to assess the association between MIF -173 and TNF -308 genetic polymorphisms and the clinical features of primary dysmenorrhea. The study population comprised 154 unrelated female patients with clinical diagnosis of dysmenorrhea, and a total of 144 control subjects were recruited consecutively. The MIF -173G > C promoter polymorphism (rs755622) and TNF gene -308G > A (rs1800629) polymorphism were analyzed by polymerase chain reaction-based restriction fragment length polymorphism assay. Two fragments (268 and 97 bp) were seen when the G allele was present at position -173, and three fragments (206, 97, and 62 bp) were observed when the C allele was present. Two fragments (87 and 20 bp) were seen when G allele was present at position -308. There were statistically significant associations between age at menarche and history of back pain among dysmenorrhea patients and MIF gene -173G > C polymorphism (p = 0.003 and p = 0.042, respectively). The genotype and allele frequencies of -308G > A polymorphism showed statistically significant differences between dysmenorrhea patients and controls (p = 0.023 and p = 0.009, respectively). A high association was also observed when the patients were compared with the controls according to the GG genotype versus GA+AA genotypes (p = 0.009). The present study showed that the TNF-α -308 GG genotype may be a useful tool to predict the susceptibility of dysmenorrhea.

Genomic signatures of selection at linked sites: unifying the disparity among species

PubMed Central

Cutter, Asher D.; Payseur, Bret A.

2014-01-01

Population genetics theory supplies powerful predictions about how natural selection interacts with genetic linkage to sculpt the genomic landscape of nucleotide polymorphism. Both the spread of beneficial mutations and removal of deleterious mutations act to depress polymorphism levels, especially in low-recombination regions. However, empiricists have documented extreme disparities among species. Here we characterize the dominant features that could drive variation in linked selection among species, including roles for selective sweeps being ‘hard’ or ‘soft’, and concealing by demography and genomic confounds. We advocate targeted studies of close relatives to unify our understanding of how selection and linkage interact to shape genome evolution. PMID:23478346

Sorbitol-Fermenting Enterohemorrhagic Escherichia coli O157:H− Isolates from Czech Patients with Novel Plasmid Composition Not Previously Seen in German Isolates

PubMed Central

Bauwens, Andreas; Marejková, Monika; Middendorf-Bauchart, Barbara; Prager, Rita; Kossow, Annelene; Zhang, Wenlan; Karch, Helge

2017-01-01

ABSTRACT Sorbitol-fermenting (SF) enterohemorrhagic Escherichia coli (EHEC) O157:H− strains, first identified in Germany, have emerged as important pathogens throughout Europe. Besides chromosomally encoded Shiga toxin 2a (the major virulence factor), several putative virulence loci, including the hly, etp, and sfp operons, encoding EHEC hemolysin, type II secretion system proteins, and Sfp fimbriae, respectively, are located on the 121-kb plasmid pSFO157 in German strains. Here we report novel SF EHEC O157:H− strains isolated from patients in the Czech Republic. These strains share the core genomes and chromosomal virulence loci encoding toxins (stx2a and the cdtV-ABC operon) and adhesins (eae-γ, efa1, lpfAO157OI-141, and lpfAO157OI-154) with German strains but differ essentially in their plasmids. In contrast to all previously detected SF EHEC O157:H− strains, the Czech strains carry two plasmids, of 79 kb and 86 kb. The 79-kb plasmid harbors the sfp operon, but neither of the plasmids contains the hly and etp operons. Sequence analyses demonstrated that the 79-kb plasmid (pSFO157 258/98-1) evolved from pSFO157 of German strains by deletion of a 41,534-bp region via homologous recombination, resulting in loss of the hly and etp operons. The 86-kb plasmid (pSFO157 258/98-2) displays 98% sequence similarity to a 92.7-kb plasmid of an extraintestinal pathogenic E. coli bloodstream isolate. Our finding of this novel plasmid composition in SF EHEC O157:H− strains extends the evolutionary history of EHEC O157 plasmids. Moreover, the unique molecular plasmid characteristics permit the identification of such strains, thereby facilitating further investigations of their geographic distribution, clinical significance, and epidemiology. IMPORTANCE Since their first identification in Germany in 1989, sorbitol-fermenting enterohemorrhagic Escherichia coli O157:H− (nonmotile) strains have emerged as important causes of the life-threatening disease hemolytic-uremic syndrome in Europe. They account for 10 to 20% of sporadic cases of this disease and have caused several large outbreaks. The strains isolated throughout Europe share conserved chromosomal and plasmid characteristics. Here we identified novel sorbitol-fermenting enterohemorrhagic E. coli O157:H− patient isolates in the Czech Republic which differ from all such strains reported previously by their unique plasmid characteristics, including plasmid number, composition of plasmid-carried virulence genes, and plasmid origins. Our findings contribute substantially to understanding the evolution of E. coli O157 strains and their plasmids. In practical terms, they enable the identification of strains with these novel plasmid characteristics in patient stool samples and thus the investigation of their roles as human pathogens in other geographic areas. PMID:28970221

Sorbitol-Fermenting Enterohemorrhagic Escherichia coli O157:H- Isolates from Czech Patients with Novel Plasmid Composition Not Previously Seen in German Isolates.

PubMed

Bauwens, Andreas; Marejková, Monika; Middendorf-Bauchart, Barbara; Prager, Rita; Kossow, Annelene; Zhang, Wenlan; Karch, Helge; Mellmann, Alexander; Bielaszewska, Martina

2017-12-01

Sorbitol-fermenting (SF) enterohemorrhagic Escherichia coli (EHEC) O157:H - strains, first identified in Germany, have emerged as important pathogens throughout Europe. Besides chromosomally encoded Shiga toxin 2a (the major virulence factor), several putative virulence loci, including the hly , etp , and sfp operons, encoding EHEC hemolysin, type II secretion system proteins, and Sfp fimbriae, respectively, are located on the 121-kb plasmid pSFO157 in German strains. Here we report novel SF EHEC O157:H - strains isolated from patients in the Czech Republic. These strains share the core genomes and chromosomal virulence loci encoding toxins ( stx 2a and the cdtV -ABC operon) and adhesins ( eae -γ, efa1 , lpfA O157OI-141 , and lpfA O157OI-154 ) with German strains but differ essentially in their plasmids. In contrast to all previously detected SF EHEC O157:H - strains, the Czech strains carry two plasmids, of 79 kb and 86 kb. The 79-kb plasmid harbors the sfp operon, but neither of the plasmids contains the hly and etp operons. Sequence analyses demonstrated that the 79-kb plasmid (pSFO157 258/98-1) evolved from pSFO157 of German strains by deletion of a 41,534-bp region via homologous recombination, resulting in loss of the hly and etp operons. The 86-kb plasmid (pSFO157 258/98-2) displays 98% sequence similarity to a 92.7-kb plasmid of an extraintestinal pathogenic E. coli bloodstream isolate. Our finding of this novel plasmid composition in SF EHEC O157:H - strains extends the evolutionary history of EHEC O157 plasmids. Moreover, the unique molecular plasmid characteristics permit the identification of such strains, thereby facilitating further investigations of their geographic distribution, clinical significance, and epidemiology. IMPORTANCE Since their first identification in Germany in 1989, sorbitol-fermenting enterohemorrhagic Escherichia coli O157:H - (nonmotile) strains have emerged as important causes of the life-threatening disease hemolytic-uremic syndrome in Europe. They account for 10 to 20% of sporadic cases of this disease and have caused several large outbreaks. The strains isolated throughout Europe share conserved chromosomal and plasmid characteristics. Here we identified novel sorbitol-fermenting enterohemorrhagic E. coli O157:H - patient isolates in the Czech Republic which differ from all such strains reported previously by their unique plasmid characteristics, including plasmid number, composition of plasmid-carried virulence genes, and plasmid origins. Our findings contribute substantially to understanding the evolution of E. coli O157 strains and their plasmids. In practical terms, they enable the identification of strains with these novel plasmid characteristics in patient stool samples and thus the investigation of their roles as human pathogens in other geographic areas. Copyright © 2017 American Society for Microbiology.

FcγRIIa and FcγRIIIb polymorphisms and associations with clinical manifestations in systemic lupus erythematosus patients.

PubMed

Vigato-Ferreira, Isabel Cristina Costa; Toller-Kawahisa, Juliana Escher; Pancoto, João Alexandre Trés; Mendes-Junior, Celso Teixeira; Martinez, Edson Zangiacomi; Donadi, Eduardo Antônio; Louzada-Júnior, Paulo; Del Lama, José Eduardo Cavalcanti; Marzocchi-Machado, Cleni Mara

2014-11-01

In this study, we aimed to investigate whether the distribution of the FcγRIIa and FcγRIIIb polymorphisms determines susceptibility to systemic lupus erythematosus (SLE) and acts as predictors of SLE clinical manifestations in the Brazilian patients. A total of 157 patients that fulfilled the American College of Rheumatology classification criteria for SLE and 160 healthy volunteers were included in this study. FCGR2A and FCGR3B genotypes were determined by polymerase chain reaction-based allotyping methods with allele-specific primers; the clinical features were obtained from the patients' official medical records. In the case of FcγRIIa polymorphism, it was observed association of the allele FCGR2A-R-131 (p = 0.02, odds ratio (OR)=1.44) and genotype RR-131 (p = 0.03, OR = 2.09) with SLE. These associations were higher with allele (p < 0.01, OR = 1.67) as well genotype (p = 0.01, OR = 2.85) when lupus nephritis was considered. In contrast, the allele FCGR2A-H-131 was associated with susceptibility to arthritis and anti-DNA antibodies (p = 0.05 for both). As for FcγRIIIb polymorphism, skewing did not differ significantly between patients and controls, however the genotype FCGR3B*02*02 was associated with susceptibility to arthritis (p = 0.02) and malar rash (p = 0.03), but no association with nephritis was found. The results demonstrate that FcγRIIa polymorphism is associated with susceptibility to SLE in Brazilian patients, whereas for FcγRIIIb polymorphism no association was found. However, notably, both polymorphisms present allelic variants that influence the clinical manifestations and may contribute to the pathogenesis of the disease. In addition, to our knowledge, this is the first study considering the frequency of FcγRIIIb polymorphism in Brazilian SLE patients.

1513A>C polymorphism in the P2X7 receptor gene in patients with papillary thyroid cancer: correlation with histological variants and clinical parameters.

PubMed

Dardano, Angela; Falzoni, Simonetta; Caraccio, Nadia; Polini, Antonio; Tognini, Sara; Solini, Anna; Berti, Piero; Di Virgilio, Francesco; Monzani, Fabio

2009-02-01

The modulation of the purinergic receptor P2X7 may be implicated in human carcinogenesis. The 1513A>C and 489C>T polymorphisms of P2X7R gene induce loss of function and gain of function, respectively. The aim of the study was to assess the frequency of both 1513A>C and 489C>T polymorphisms in patients with papillary thyroid carcinoma (PTC) and to evaluate the possible association with clinical and histological features. P2X7R analysis was performed in lymphocytes from 121 PTC patients (100 women, 21 men; aged 43.4 +/- 13.6 yr), 100 matched healthy subjects, and 80 patients with nodular goiter. The minor allele frequency for 1513A>C polymorphism in PTC patients with the classical variant was similar to controls (0.21 and 0.20, respectively), whereas it resulted in a significant increase in patients with the follicular variant (0.36; P = 0.01 vs. classical variant, and P = 0.005 vs. controls). In detail, 13.6% of patients with PTC follicular variant were homozygous for the 1513C allele, compared to 2.6% of patients with the classical variant and 2% of controls. Moreover, a positive relationship between 1513A>C polymorphism and either cancer diameter (Rho = 0.22; P = 0.02) or TNM stage (Rho = 0.38; P < 0.001) was found. No significant difference in the genotype frequency of 489C>T polymorphism between PTC patients and healthy controls was observed (0.42 and 0.47, respectively). Our data show, for the first time, a strong association between 1513A>C polymorphism of P2X7R gene and the follicular variant of PTC. Further studies are needed to confirm the possible role of this polymorphism as a novel clinical marker of PTC follicular variant and its usefulness in selecting patients with different clinical outcome.

A second ortho­rhom­bic polymorph of (Z)-3-(9-anthr­yl)-1-(2-thien­yl)prop-2-en-1-one1

PubMed Central

Chantrapromma, Suchada; Suwunwong, Thitipone; Boonnak, Nawong; Fun, Hoong-Kun

2010-01-01

The title heteroaryl chalcone, C21H14OS, is a second ortho­rhom­bic polymorph which crystallizes in the space group P212121. The structure was previously reported [Fun et al. (2009 ▶). Acta Cryst. E65, o2168-o2169] in the space group Pna21. The bond distances and angles are similar in both structures. In contrast, the overall crystal packing is different from that in the first ortho­rhom­bic Pna21 polymorph in which mol­ecules were stacked into columns along the b axis and the thio­phene units of two adjacent columns were stacked in a head to tail fashion. In the present polymorph, mol­ecules are found to dimerize through a weak S⋯S inter­action [3.6513 (7) Å] and these dimers are arranged into sheets parallel to the bc plane. There are no classical hydrogen bonds in the packing which features short C⋯O [3.2832 (2)–3.6251 (9) Å], C⋯S [3.4879 (17)–3.6251 (19) Å] and S⋯O [2.9948 (16) Å] contacts, together with C—H⋯π inter­actions. Similar contacts were found in the other polymorph. PMID:21579743

Maximal oxygen uptake is associated with allele -202 A of insulin-like growth factor binding protein-3 (IGFBP3) promoter polymorphism and (CA)n tandem repeats of insulin-like growth factor IGF1 in Caucasians from Poland.

PubMed

Gronek, Piotr; Holdys, Joanna; Kryściak, Jakub; Wieliński, Dariusz; Słomski, Ryszard

2014-01-01

Physical fitness is a trait determined by multiple genes, and its genetic basis is modified by numerous environmental factors. The present study examines the effects of the (CA)n tandem repeats polymorphism in IGFI gene and SNP Alw21I restriction site -202 A>C polymorphism in IGF1BP3 on VO2max--a physiological index of aerobic capacity of high heritability. The study sample consisted of 239 (154 male and 85 female) students of the University School of Physical Education in Poznań and athletes practicing various sports, including members of the Polish national team. An association was found between -202 A/C polymorphism of IGFBP3 gene with VO2max in men. Higher VO2max values were attained by men with CC genotype, especially male athletes practicing endurance sports and sports featuring energy metabolism of aerobic/anaerobic character. A statistically significant influence of allele 188 and genotype 188/188 of tandem repeats (CA)n polymorphism of IGF1 gene on VO2max was found in women. Also, lower values of maximal oxygen uptake were noted in individuals with allele 186 or genotype 186/186, and higher VO2max values in athletes with allele 194.

Association between Mitofusin 2 Gene Polymorphisms and Late-Onset Alzheimer's Disease in the Korean Population

PubMed Central

Kim, Young Jong; Park, Jin Kyung; Kang, Won Sub; Kim, Su Kang; Han, Changsu; Na, Hae Ri; Park, Hae Jeong; Kim, Jong Woo; Kim, Young Youl; Park, Moon Ho

2017-01-01

Objective Mitochondrial dysfunction is a prominent and early feature of Alzheimer's disease (AD). The morphologic changes observed in the AD brain could be caused by a failure of mitochondrial fusion mechanisms. The aim of this study was to investigate whether genetic polymorphisms of two genes involved in mitochondrial fusion mechanisms, optic atrophy 1 (OPA1) and mitofusin 2 (MFN2), were associated with AD in the Korean population by analyzing genotypes and allele frequencies. Methods One coding single nucleotide polymorphism (SNP) in the MFN2, rs1042837, and two coding SNPs in the OPA1, rs7624750 and rs9851685, were compared between 165 patients with AD (83 men and 82 women, mean age 72.3±4.41) and 186 healthy control subjects (82 men and 104 women, mean age 76.5±5.98). Results Among these three SNPs, rs1042837 showed statistically significant differences in allele frequency, and genotype frequency in the co-dominant 1 model and in the dominant model. Conclusion These results suggest that the rs1042837 polymorphism in MFN2 may be involved in the pathogenesis of AD. PMID:28096879

Angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism is not a risk factor for hypertension in SLE nephritis.

PubMed

Negi, Vir S; Devaraju, Panneer; Gulati, Reena

2015-09-01

SLE is a systemic autoimmune disease with high prevalence of hypertension. Around 40-75 % of SLE patients develop nephritis, a major cause of hypertension and mortality. Angiotensin-converting enzyme (ACE) maintains the blood pressure and blood volume homeostasis. An insertion/deletion (I/D) polymorphism in intron 16 of ACE gene was reported to influence the development of hypertension, nephritis, and cardiovascular diseases in different ethnic populations. Despite compelling evidence for the high prevalence of hypertension in individuals with SLE, underlying factors for its development are not well studied. With this background, we analyzed the influence of ACE insertion/deletion polymorphism on susceptibility to SLE, development of nephritis and hypertension, other clinical features and autoantibody phenotype in South Indian SLE patients. Three hundred patients with SLE and 460 age and sex similar ethnicity matched individuals were included as patients and healthy controls, respectively. The ACE gene insertion/deletion polymorphism was analyzed by PCR. Insertion (I) and deletion (D) alleles were observed to be equally distributed among patients (57 and 43 %) and controls (59 and 41 %), respectively. The mutant (D) allele did not confer significant risk for SLE (II vs. ID: p = 0.4, OR 1.15, 95 % CI 0.8-1.6; II vs. DD: p = 0.34, OR 1.22, 95 % CI 0.8-1.85). There was no association of the ACE genotype or the allele with development of lupus nephritis (II vs. ID: p = 0.19, OR 1.41, 95 % CI 0.84-2.36; II vs. DD: p = 0.41, OR 0.74, 95 % CI 0.38-1.41) or hypertension (II vs. ID: p = 0.85, OR 0.9, 95 % CI 0.43-1.8; II vs. DD: p = 0.66, OR 1.217, 95 % CI 0.5-2.8). The presence of mutant allele (D) was not found to influence any clinical features or autoantibody phenotype. The insertion/deletion polymorphism of the ACE gene is not a genetic risk factor for SLE and does not influence development of hypertension or lupus nephritis in South Indian Tamils.

Genetic variants of apolipoprotein A5 T-1131C and apolipoprotein E common polymorphisms and their relationship to features of metabolic syndrome in adult dyslipidemic patients.

PubMed

Novotny, Dalibor; Vaverkova, Helena; Karasek, David; Malina, Pavel

2014-08-01

The aim was to evaluate the relationships of the T-1131C (rs662799) polymorphism variants of apolipoprotein A5 (Apo A5) gene and variants of apolipoprotein E (Apo E) gene common polymorphism (rs429358, rs7412) to signs of metabolic syndrome (MetS). We examined 590 asymptomatic dyslipidemic patients divided into MetS+ (n=146) and MetS- (n=444) groups according to criteria of NCEP ATPIII Panel. We evaluated genotype frequencies and differences in MetS features between individual groups. Logistic regression analysis was used for the evaluation of Apo A5/Apo E variants as possible risk factors for MetS. We found no statistical differences between genotype and allele frequencies for both Apo A5 and Apo E polymorphisms between MetS+ and MetS- groups. In all subjects and MetS- group, we confirmed well-known association of the -1131C Apo A5 minor allele with elevated triglycerides (TG, p<0.001). The Apo E gene E2 and E4 variants were associated with higher levels of TG (p<0.01) in comparison to E33 common variant. However, no statistical differences were observed in MetS+ subjects, regardless of significantly higher TG levels in this group. Apo A5/Apo E variant analysis in all dyslipidemic patients revealed significant increase of TG levels in all subgroups in comparison to common -1131T/E3 variant carriers, the most in -1131C/E4 variant subgroup. Logistic regression analysis models showed no association of Apo A5, Apo E and all Apo A5/Apo E variants with metabolic syndrome, even after adjustment for age and sex. Our study refined the role of Apo A5 and Apo E genetic variants in the group of adult dyslipidemic patients. We demonstrate that except of TG, Apo A5 T-1131C (rs662799) and Apo E (rs429358, rs7412) polymorphisms have no remarkable effect on MetS characteristics. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Association between ADH1C and ALDH2 polymorphisms and alcoholism in a Turkish sample.

PubMed

Ayhan, Yavuz; Gürel, Şeref Can; Karaca, Özgür; Zoto, Teuta; Hayran, Mutlu; Babaoğlu, Melih; Yaşar, Ümit; Bozkurt, Atilla; Dilbaz, Nesrin; Uluğ, Berna Diclenur; Demir, Başaran

2015-04-01

Polymorphisms in the genes encoding alcohol metabolizing enzymes are associated with alcohol dependence. To evaluate the association between the alcohol dehydrogenase 1C (ADH1C) Ile350Val and aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphisms and alcohol dependence in a Turkish sample. 235 individuals (115 alcohol-dependent patients and 120 controls) were genotyped for ADH1C and ALDH2 with PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism). Association between the polymorphisms and family history, daily and maximum amount of alcohol consumed was investigated. The associations between alcohol dependence, severity of consumption and family history and the polymorphisms were analyzed by chi-square or Fisher's exact test where necessary. Relationship between genotypes and dependence related features was evaluated using analysis of variance (ANOVA). The -350Val allele for ADH1C (ADH1C*2) was increased in alcohol-dependent patients (P = 0.05). In individuals with a positive family history, the genotype distribution differed significantly (P = 0.031) and more patients carried the Val allele compared with controls (P = 0.025). Genotyping of 162 participants did not reveal the -504Lys allele in ALDH2. These findings suggest that ADH1C*2 is associated with alcohol dependence in the Turkish population displaying a dominant inheritance model. ADH1C*2 allele may contribute to the variance in heritability of alcohol dependence. The ALDH2 -504Lys/Lys or Glu/Lys genotypes were not present in alcohol-dependent patients, similar to that seen in European populations and in contrast to the findings in the Asian populations.

Mutation covariation of HIV-1 CRF07_BC reverse transcriptase during antiretroviral therapy.

PubMed

Li, Zhenpeng; Huang, Yang; Ouyang, Yabo; Xing, Hui; Liao, Lingjie; Jiang, Shibo; Shao, Yiming; Ma, Liying

2013-11-01

To understand the effect of HIV-1 drug resistance mutations in the context of antiretroviral therapy (ART), we compared the prevalence of protease (PR) and reverse transcriptase (RT) mutations in HIV-1 CRF07_BC sequences from blood samples of treatment-naive and ART-treated patients. Mutation covariation in the RT and PR of HIV-1 CRF07_BC viruses from 542 treatment-naive patients and 261 patients treated with lamivudine/zidovudine/nevirapine or lamivudine/zidovudine/efavirenz was analysed. Stratified networks were used to display the mutation covariation. Based on the comparison between treatment-naive and ART-treated patients, three types of featured mutations for RT and PR were initially identified: treatment-associated mutations, treatment-agonistic mutations and overlapping polymorphisms. Twelve significant covariation pairs were found between five treatment-associated mutations (K103N, M184V, Q197K, G190A and Y181C) and nine overlapping polymorphisms (A36E, D39N, Y121H, D123E, R135I, T200A, R277K, L283I and D291E). Meanwhile, three covariation pairs between three treatment-associated mutations (I132L and M184V for RT and I15V for PR) and three overlapping polymorphisms (L10I, L36M and A71V) for PR were also detected. Finally, the overlapping polymorphisms for RT and PR were both found to have significant correlations with treatment-associated mutations, indicating a possible association between polymorphisms and drug resistance. When compared with HIV-1 subtype B under the same regimens as CRF07_BC, the mutation covariations of CRF07_BC showed a distinct pattern of RT and PR mutation covariation. The role of polymorphisms in the development of drug resistance has been widely reported. Here, we found a significant correlation between overlapping polymorphisms for RT and PR and treatment-associated mutations, indicating that polymorphisms exert a global influence on treatment-associated mutations. Polymorphism mutations might therefore be considered before initiating ART to improve the efficacy of drug combinations.

Spectral characteristics of the iron oxides with application to the Martian bright region mineralogy

NASA Technical Reports Server (NTRS)

Sherman, D. M.; Burns, R. G.; Mee Burns, V.

1982-01-01

Reflectance spectra of eight polymorphs of FeOOH and Fe2O3 are determined in order to clarify the nature and significance of the iron oxide mineralogy on Mars. The effect of other components that might interfere with iron oxide absorption features is qualitatively constrained through the use of the Kebulka-Munk theory. It is found that the effect of temperature complicates the identification of a given Fe(3+) phase based on the position of the 6A1-4T1 absorption feature. While the Fe(3+) crystal field transitions are spin forbidden, most of the iron oxide polymorphs exhibit anomalously intense crystal field absorption features due to magnetic coupling between adjacent FeO6 octahedra. It is suggested that the resulting deviations from observed remotely sensed reflectance spectra of Mars may provide a basis for the exclusion of many iron oxide phases as significant components of the Martian Fe(3+) mineralogy. A comparison of these results with the visible region spectra of Martian bright regions indicates that the predominant Fe(3+)-bearing phase may be a magnetically disordered material, such as amorphous gels, some ferric sulphates, and other minerals in which Fe(3+) ions in the crystal structure are not magnetically coupled.

A laboratory comparison of individual Targis/Vectris posts with standard fiberglass posts.

PubMed

Corsalini, Massimo; Genovese, Katia; Lamberti, Luciano; Pappalettere, Carmine; Carella, Mauro; Carossa, Stefano

2007-01-01

This article presents an in vitro analysis of a specific occlusal loading test on endodontically treated teeth restored with 2 different composite post materials. Individual, customized posts (IFPs) were compared to standard fiberglass posts (SFPs). The selected IFPs (standard cylindric Targis/Vectris posts) were compared to SFPs (Conic 6% Post, Ghimas). The posts were first subjected to a 3-point bending test to compare their flexural elastic properties. They were then used to restore 22 endodontically treated artificial maxillary central incisors and subjected to a specific occlusal loading simulation test. The loading test showed that IFP restorations performed better than SFP restorations. A clinical evaluation of this laboratory observation is suggested.

Navigating at Will on the Water Phase Diagram

NASA Astrophysics Data System (ADS)

Pipolo, S.; Salanne, M.; Ferlat, G.; Klotz, S.; Saitta, A. M.; Pietrucci, F.

2017-12-01

Despite the simplicity of its molecular unit, water is a challenging system because of its uniquely rich polymorphism and predicted but yet unconfirmed features. Introducing a novel space of generalized coordinates that capture changes in the topology of the interatomic network, we are able to systematically track transitions among liquid, amorphous, and crystalline forms throughout the whole phase diagram of water, including the nucleation of crystals above and below the melting point. Our approach, based on molecular dynamics and enhanced sampling or free energy calculation techniques, is not specific to water and could be applied to very different structural phase transitions, paving the way towards the prediction of kinetic routes connecting polymorphic structures in a range of materials.

The Genealogical Consequences of Fecundity Variance Polymorphism

PubMed Central

Taylor, Jesse E.

2009-01-01

The genealogical consequences of within-generation fecundity variance polymorphism are studied using coalescent processes structured by genetic backgrounds. I show that these processes have three distinctive features. The first is that the coalescent rates within backgrounds are not jointly proportional to the infinitesimal variance, but instead depend only on the frequencies and traits of genotypes containing each allele. Second, the coalescent processes at unlinked loci are correlated with the genealogy at the selected locus; i.e., fecundity variance polymorphism has a genomewide impact on genealogies. Third, in diploid models, there are infinitely many combinations of fecundity distributions that have the same diffusion approximation but distinct coalescent processes; i.e., in this class of models, ancestral processes and allele frequency dynamics are not in one-to-one correspondence. Similar properties are expected to hold in models that allow for heritable variation in other traits that affect the coalescent effective population size, such as sex ratio or fecundity and survival schedules. PMID:19433628

Ab initio random structure searching of organic molecular solids: assessment and validation against experimental data.

PubMed

Zilka, Miri; Dudenko, Dmytro V; Hughes, Colan E; Williams, P Andrew; Sturniolo, Simone; Franks, W Trent; Pickard, Chris J; Yates, Jonathan R; Harris, Kenneth D M; Brown, Steven P

2017-10-04

This paper explores the capability of using the DFT-D ab initio random structure searching (AIRSS) method to generate crystal structures of organic molecular materials, focusing on a system (m-aminobenzoic acid; m-ABA) that is known from experimental studies to exhibit abundant polymorphism. Within the structural constraints selected for the AIRSS calculations (specifically, centrosymmetric structures with Z = 4 for zwitterionic m-ABA molecules), the method is shown to successfully generate the two known polymorphs of m-ABA (form III and form IV) that have these structural features. We highlight various issues that are encountered in comparing crystal structures generated by AIRSS to experimental powder X-ray diffraction (XRD) data and solid-state magic-angle spinning (MAS) NMR data, demonstrating successful fitting for some of the lowest energy structures from the AIRSS calculations against experimental low-temperature powder XRD data for known polymorphs of m-ABA, and showing that comparison of computed and experimental solid-state NMR parameters allows different hydrogen-bonding motifs to be discriminated.

Ethnicity and lipoprotein(a) polymorphism in Native Mexican populations.

PubMed

Cardoso-Saldaña, G; De La Peña-Díaz, A; Zamora-González, J; Gomez-Ortega, R; Posadas-Romero, C; Izaguirre-Avila, R; Malvido-Miranda, E; Morales-Anduaga, M E; Anglés-Cano, E

2006-01-01

Lp(a) is a lipoparticle of unknown function mainly present in primates and humans. It consists of a low-density lipoprotein and apo(a), a polymorphic glycoprotein. Apo(a) shares sequence homology and fibrin binding with plasminogen, inhibiting its fibrinolytic properties. Lp(a) is considered a link between atherosclerosis and thrombosis. Marked inter-ethnic differences in Lp(a) concentration related to the genetic polymorphism of apo(a) have been reported in several populations. The study examined the structural and functional features of Lp(a) in three Native Mexican populations (Mayos, Mazahuas and Mayas) and in Mestizo subjects. We determined the plasma concentration of Lp(a) by immunonephelometry, apo(a) isoforms by Western blot, Lp(a) fibrin binding by immuno-enzymatic assay and short tandem repeat (STR) polymorphic marker genetic analysis by capillary electrophoresis. Mestizos presented the less skewed distribution and the highest median Lp(a) concentration (13.25 mg dL(-1)) relative to Mazahuas (8.2 mg dL(-1)), Mayas (8.25 mg dL(-1)) and Mayos (6.5 mg dL(-1)). Phenotype distribution was different in Mayas and Mazahuas as compared with the Mestizo group. The higher Lp(a) fibrin-binding capacity was found in the Maya population. There was an inverse relationship between the size of apo(a) polymorphs and both Lp(a) levels and Lp(a) fibrin binding. There is evidence of significative differences in Lp(a) plasma concentration and phenotype distribution in the Native Mexican and the Mestizo group.

Ethnicity and lipoprotein(a) polymorphism in Native Mexican populations

PubMed Central

Cardoso-Saldaña, Guillermo; De La Peña-Díaz, Aurora; Zamora-González, José; Gomez-Ortega, Rocio; Posadas-Romero, Carlos; Izaguirre-Avila, Raul; Malvido-Miranda, Elsa; Morales-Anduaga, Maria Elena; Angles-Cano, Eduardo

2006-01-01

Background Lp(a) is a lipoparticle of unknown function mainly present in primates and humans. It consists of a low-density lipoprotein and apo(a), a polymorphic glycoprotein. Apo(a) shares sequence homology and fibrin-binding with plasminogen inhibiting its fibrinolytic properties. Lp(a) is considered a link between atherosclerosis and thrombosis. Marked inter-ethnic differences in Lp(a) concentration related to the genetic polymorphism of apo(a), have been reported in several populations. Aim To study the structural and functional features of Lp(a) in three Native Mexican populations (Mayos, Mazahuas and Mayas) and in Mestizo subjects. Methods We determined the plasma concentration of Lp(a) by immunonephelometry, apo(a) isoforms by Western blot, Lp(a) fibrin-binding by immuno-enzymatic assay and STR polymorphic markers genetic analysis by capillary electrophoresis. Results Mestizos presented the less skewed distribution and the highest median Lp(a) concentration (13.25 mg/dL) relative to Mazahuas (8.2 mg/dL), Mayas (8.25 mg/dL) and Mayos (6.5 mg/dL). Phenotype distribution was different in Mayas and Mazahuas as compared to the Mestizo group. The higher Lp(a) fibrin-binding capacity was found in the Maya population. There was an inverse relationship between the size of apo(a) polymorphs and both Lp(a) levels and Lp(a) fibrin binding. Conclusion There is evidence of significative differences in Lp(a) plasma concentration and phenotype distribution in Native Mexican and the Mestizo group. PMID:16684693

Homocysteine and the C677T Gene Polymorphism of Its Key Metabolic Enzyme MTHFR Are Risk Factors of Early Renal Damage in Hypertension in a Chinese Han Population.

PubMed

Yun, Lin; Xu, Rui; Li, Guohua; Yao, Yucai; Li, Jiamin; Cong, Dehong; Xu, Xingshun; Zhang, Lihua

2015-12-01

The combined hyperhomocysteinemia condition is a feature of the Chinese hypertensive population. This study used the case-control method to investigate the association between plasma homocysteine and the C677T gene polymorphism of its key metabolic enzyme, 5, 10-methylenetetrahydrofolate reductase (MTHFR), and early renal damage in a hypertensive Chinese Han population.A total of 379 adult essential hypertensive patients were selected as the study subjects. The personal information, clinical indicators, and the C677T gene polymorphism of MTHFR were texted. This study used the urine microalbumin/urine creatinine ratio (UACR) as a grouping basis: the hypertension without renal damage group (NRD group) and the hypertension combined with early renal damage group (ERD group).Early renal damage in the Chinese hypertensive population was associated with body weight, systolic pressure, diastolic pressure, urea nitrogen, serum creatinine, cystatin C, uric acid, aldosterone, and glomerular filtration rate. The homocysteine level and the UACR in the TT genotype group were higher than those in the CC genotype group. The binary logistic regression analysis results showed that after sex and age were adjusted, the MTHFR C677T gene polymorphism was correlated with early renal damage in hypertension in both the recessive model and in the additive model.Plasma homocysteine and the C677T gene polymorphism of its key metabolic enzyme MTHFR might be independent risk factors of early renal damage in the hypertensive Chinese Han population.

New frontiers in sport training: genetics and artistic gymnastics.

PubMed

Morucci, Gabriele; Punzi, Tiziana; Innocenti, Giovanni; Gulisano, Massimo; Ceroti, Marco; Pacini, Stefania

2014-02-01

The increasing understanding of the genetic influences in sport has prompted an association study between the athletic performances and the polymorphisms of the angiotensin-converting enzyme (ACE), the α-actinin-3 (ACTN3), and the vitamin D receptor genes. The details of these gene polymorphisms can provide useful information to improve and plan new modern training programs for elite athletes. Eighty Italian male high level gymnasts were trained and tested for gymnastic-specific exercises and tested in all the men's artistic gymnastic apparatus (floor, pommel horse, rings, vault, parallel bars, and horizontal bar), and then genotyped. The training parameters of volume, intensity, and density of each gymnast were periodically measured during the season in each apparatus from the tests performed, and the seasonal average values were calculated. Gene polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism assay and studied in association with the performance results. The performances of ACE II gymnasts were significantly lower than that of the ACE ID/DD gymnasts in the apparatus expressing power features, confirming the predisposition of these athletes toward power-oriented sport. Gymnasts with ACTN3 RR/RX genotypes did not show a predisposition to the power-oriented apparatus, having worse performances compared with that of the ACTN3 XX gymnasts. Similarly, gymnasts with ACE II + ACTN3 RR/RX combined genotypes showed lower performances in comparison with that of the other gymnasts. Vitamin D receptor polymorphisms showed no significant association with the athletic performances. Because ACE insertion/deletion (I/D) and ACTN3 R577X polymorphisms heavily affect the physical performance of elite male gymnasts, the Italian Gymnastic Federation trainers have started to customize the current high-level training programs.

Sequence-Based Prioritization of Nonsynonymous Single-Nucleotide Polymorphisms for the Study of Disease Mutations

PubMed Central

Jiang, Rui ; Yang, Hua ; Zhou, Linqi ; Kuo, C.-C. Jay ; Sun, Fengzhu ; Chen, Ting 

2007-01-01

The increasing demand for the identification of genetic variation responsible for common diseases has translated into a need for sophisticated methods for effectively prioritizing mutations occurring in disease-associated genetic regions. In this article, we prioritize candidate nonsynonymous single-nucleotide polymorphisms (nsSNPs) through a bioinformatics approach that takes advantages of a set of improved numeric features derived from protein-sequence information and a new statistical learning model called “multiple selection rule voting” (MSRV). The sequence-based features can maximize the scope of applications of our approach, and the MSRV model can capture subtle characteristics of individual mutations. Systematic validation of the approach demonstrates that this approach is capable of prioritizing causal mutations for both simple monogenic diseases and complex polygenic diseases. Further studies of familial Alzheimer diseases and diabetes show that the approach can enrich mutations underlying these polygenic diseases among the top of candidate mutations. Application of this approach to unclassified mutations suggests that there are 10 suspicious mutations likely to cause diseases, and there is strong support for this in the literature. PMID:17668383

Impact of the 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene on primary nephrotic syndrome.

PubMed

Luo, Yuezhong; Wang, Chao; Tu, Haitao

2014-03-01

The aim of the present study was to investigate whether the four guanosines (4G)/five guanosines (5G) polymorphism in the gene coding for plasminogen activator inhibitor-1 (PAI-1) affects the clinical features of primary nephrotic syndrome (PNS). A cohort of 200 biopsy-diagnosed PNS patients was studied, with 40 healthy subjects as controls. The PAI-1 gene polymorphism was detected by polymerase chain reaction and DNA sequencing. Associations between the PAI-1 4G/5G polymorphism and clinical features and pathological types of PNS were analyzed. The results indicated that the PAI-1 genotype distribution is significantly different between patients with PNS and healthy controls, with significantly higher numbers of the 4G/4G genotype and lower numbers of the 5G5G genotype detected in PNS patients compared to controls (both P<0.05). The frequency of the 4G allele was also significantly higher in PNS patients compared to healthy controls (P<0.01). Among the different pathological types of PNS, IgA nephropathy (IgAN) and membranous nephropathy (MN) were associated with significantly increased frequencies of the 4G/4G and 4G/5G genotypes, as well as of the 4G allele. The increased 4G frequency was also detected in patients with minimal change disease (MCD). Significantly increased international normalized ratio (INR) and prolonged activated partial thromboplastin time (APTT) were observed in 4G/4G compared to 5G/5G PNS subjects. The response to steroids was not significantly different among the three genotypes. In conclusion, the 4G allele of the PAI-1 gene appears to be associated with PNS, especially in MN and IgAN patients. These findings suggest that specific targeting may be required for the treatment of PNS patients with the 4G/4G genotype.

Multilocus Sequence Typing and Virulence-Associated Gene Profile Analysis of Staphylococcus aureus Isolates From Retail Ready-to-Eat Food in China.

PubMed

Yang, Xiaojuan; Yu, Shubo; Wu, Qingping; Zhang, Jumei; Wu, Shi; Rong, Dongli

2018-01-01

The aim of this study was to characterize the subtypes and virulence profiles of 69 Staphylococcus aureus isolates obtained from retail ready-to-eat food in China. The isolates were analyzed using multilocus sequence typing (MLST) and polymerase chain reaction (PCR) analysis of important virulence factor genes, including the staphylococcal enterotoxin (SE) genes ( sea , seb , sec , sed , see , seg , seh , sei , sej ), the exfoliative toxin genes ( eta and etb ), the toxic shock syndrome toxin-1 gene ( tst ), and the Panton-Valentine leucocidin-encoding gene ( pvl ). The isolates encompassed 26 different sequence types (STs), including four new STs (ST3482, ST3484, ST3485, ST3504), clustered in three clonal complexes and 17 singletons. The most prevalent STs were ST1, ST6, and ST15, constituting 34.8% of all isolates. Most STs (15/26, 57.7%) detected have previously been associated with human infections. All 13 toxin genes examined were detected in the S. aureus isolates, with 84.1% of isolates containing toxin genes. The three most prevalent toxin genes were seb (36.2%), sea (33.3%), and seg (33.3%). The classical SE genes ( sea - see ), which contribute significantly to staphylococcal food poisoning (SFP), were detected in 72.5% of the S. aureus isolates. In addition, pvl , eta , etb , and tst were found in 11.6, 10.1, 10.1, and 7.2% of the S. aureus isolates, respectively. Strains ST6 carrying sea and ST1 harboring sec-seh enterotoxin profile, which are the two most common clones associated with SFP, were also frequently detected in the food samples in this study. This study indicates that these S. aureus isolates present in Chinese ready-to-eat food represents a potential public health risk. These data are valuable for epidemiological studies, risk management, and public health strategies.

Multilocus Sequence Typing and Virulence-Associated Gene Profile Analysis of Staphylococcus aureus Isolates From Retail Ready-to-Eat Food in China

PubMed Central

Yang, Xiaojuan; Yu, Shubo; Wu, Qingping; Zhang, Jumei; Wu, Shi; Rong, Dongli

2018-01-01

The aim of this study was to characterize the subtypes and virulence profiles of 69 Staphylococcus aureus isolates obtained from retail ready-to-eat food in China. The isolates were analyzed using multilocus sequence typing (MLST) and polymerase chain reaction (PCR) analysis of important virulence factor genes, including the staphylococcal enterotoxin (SE) genes (sea, seb, sec, sed, see, seg, seh, sei, sej), the exfoliative toxin genes (eta and etb), the toxic shock syndrome toxin-1 gene (tst), and the Panton-Valentine leucocidin-encoding gene (pvl). The isolates encompassed 26 different sequence types (STs), including four new STs (ST3482, ST3484, ST3485, ST3504), clustered in three clonal complexes and 17 singletons. The most prevalent STs were ST1, ST6, and ST15, constituting 34.8% of all isolates. Most STs (15/26, 57.7%) detected have previously been associated with human infections. All 13 toxin genes examined were detected in the S. aureus isolates, with 84.1% of isolates containing toxin genes. The three most prevalent toxin genes were seb (36.2%), sea (33.3%), and seg (33.3%). The classical SE genes (sea–see), which contribute significantly to staphylococcal food poisoning (SFP), were detected in 72.5% of the S. aureus isolates. In addition, pvl, eta, etb, and tst were found in 11.6, 10.1, 10.1, and 7.2% of the S. aureus isolates, respectively. Strains ST6 carrying sea and ST1 harboring sec-seh enterotoxin profile, which are the two most common clones associated with SFP, were also frequently detected in the food samples in this study. This study indicates that these S. aureus isolates present in Chinese ready-to-eat food represents a potential public health risk. These data are valuable for epidemiological studies, risk management, and public health strategies. PMID:29662467

Behavioral and facial thermal variations in 3-to 4-month-old infants during the Still-Face Paradigm

PubMed Central

Aureli, Tiziana; Grazia, Annalisa; Cardone, Daniela; Merla, Arcangelo

2015-01-01

Behavioral and facial thermal responses were recorded in twelve 3- to 4-month-old infants during the Still-Face Paradigm (SFP). As in the usual procedure, infants were observed in a three-step, face-to-face interaction: a normal interaction episode (3 min); the “still-face” episode in which the mother became unresponsive and assumed a neutral expression (1 min); a reunion episode in which the mother resumed the interaction (3 min). A fourth step that consisted of a toy play episode (5 min) was added for our own research interest. We coded the behavioral responses through the Infant and Caregiver Engagement Phases system, and recorded facial skin temperature via thermal infrared (IR) imaging. Comparing still-face episode to play episode, the infants’ communicative engagement decreased, their engagement with the environment increased, and no differences emerged in self-regulatory and protest behaviors. We also found that facial skin temperature increased. For the behavioral results, infants recognized the interruption of the interactional reciprocity caused by the still-face presentation, without showing upset behaviors. According to autonomic results, the parasympathetic system was more active than the sympathetic, as usually happens in aroused but not distressed situations. With respect to the debate about the causal factor of the still-face effect, thermal data were consistent with behavioral data in showing this effect as related to the infants’ expectations of the nature of the social interactions being violated. Moreover, as these are associated to the infants’ subsequent interest in the environment, they indicate the thermal IR imaging as a reliable technique for the detection of physiological variations not only in the emotional system, as indicated by research to date, but also in the attention system. Using this technique for the first time during the SFP allowed us to record autonomic data in a more ecological manner than in previous studies. PMID:26528229

Enhancing the biophysical properties of mRFP1 through incorporation of fluoroproline

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

Deepankumar, Kanagavel; Nadarajan, Saravanan Prabhu; Ayyadurai, Niraikulam

2013-11-01

Graphical abstract: Enhancing the biophysical properties of mRFP1 through incorporation of (2S, 4R)-4-fluoroproline at proline residues after mutating non-permissive site Pro63 into Ala. -- Highlights: •We incorporate (4S)-FP into mRFP1 led to insoluble protein. •Whereas, incorporation of (4R)-FP resulted in soluble but lost its fluorescence. •mRFP1-P63A mutant accommodate (4R)-FP and gave soluble protein with fluorescence. •Moreover mRFP1-P63A[(4R)-FP] showed enhanced biophysical properties of protein. -- Abstract: Here we enhanced the stability and biophysical properties of mRFP1 through a combination of canonical and non-canonical amino acid mutagenesis. The global replacement of proline residue with (2S, 4R)-4-fluoroproline [(4R)-FP] into mRFP1 led to solublemore » protein but lost its fluorescence, whereas (2S, 4S)-4-fluoroproline [(4S)-FP] incorporation resulted in insoluble protein. The bioinformatics analysis revealed that (4R)-FP incorporation at Pro63 caused fluorescence loss due to the steric hindrance of fluorine atom of (4R)-FP with the chromophore. Therefore, Pro63 residue was mutated with the smallest amino acid Ala to maintain non coplanar conformation of the chromophore and helps to retain its fluorescence with (4R)-FP incorporation. The incorporation of (4R)-FP into mRFP1-P63A showed about 2–3-fold enhancement in thermal and chemical stability. The rate of maturation is also greatly accelerated over the presence of (4R)-FP into mRFP1-P63A. Our study showed that a successful enhancement in the biophysical property of mRFP1-P63A[(4R)-FP] using non-canonical amino acid mutagenesis after mutating non-permissive site Pro63 into Ala.« less

Relationships between range access as monitored by radio frequency identification technology, fearfulness, and plumage damage in free-range laying hens.

PubMed

Hartcher, K M; Hickey, K A; Hemsworth, P H; Cronin, G M; Wilkinson, S J; Singh, M

2016-05-01

Severe feather-pecking (SFP), a particularly injurious behaviour in laying hens (Gallus gallus domesticus), is thought to be negatively correlated with range use in free-range systems. In turn, range use is thought to be inversely associated with fearfulness, where fearful birds may be less likely to venture outside. However, very few experiments have investigated the proposed association between range use and fearfulness. This experiment investigated associations between range use (time spent outside), fearfulness, plumage damage, and BW. Two pens of 50 ISA Brown laying hens (n=100) were fitted with radio frequency identification (RFID) transponders (contained within silicone leg rings) at 26 weeks of age. Data were then collected over 13 days. A total of 95% of birds accessed the outdoor run more than once per day. Birds spent an average duration of 6.1 h outside each day over 11 visits per bird per day (51.5 min per visit). The top 15 and bottom 15 range users (n=30), as determined by the total time spent on the range over 13 days, were selected for study. These birds were tonic immobility (TI) tested at the end of the trial and were feather-scored and weighed after TI testing. Birds with longer TI durations spent less time outside (P=0.01). Plumage damage was not associated with range use (P=0.68). The small group sizes used in this experiment may have been conducive to the high numbers of birds utilising the outdoor range area. The RFID technology collected a large amount of data on range access in the tagged birds, and provides a potential means for quantitatively assessing range access in laying hens. The present findings indicate a negative association between fearfulness and range use. However, the proposed negative association between plumage damage and range use was not supported. The relationships between range use, fearfulness, and SFP warrant further research.

Temporal Feeding Pattern May Influence Reproduction Efficiency, the Example of Breeding Mares

PubMed Central

Benhajali, Haifa; Ezzaouia, Mohammed; Lunel, Christophe; Charfi, Faouzia; Hausberger, Martine

2013-01-01

Discomfort in farm animals may be induced by inappropriate types or timing of food supplies. Thus, time restriction of meals and lack of roughage have been shown to be one source of emergence of oral stereotypies and abnormal behaviour in horses which have evolved to eat high-fibre diets in small amounts over long periods of time. This feeding pattern is often altered in domestic environment where horses are often fed low fibre meals that can be rapidly consumed. This study aimed at determining the effect of the temporal pattern of feeding on reproductive efficiency of breeding mares, One hundred Arab breeding mares were divided into two groups that differed only in the temporal pattern of roughage availability: only at night for the standard feeding pattern group (SFP mares), night and day for the “continuous feeding” group (CF mares). The total amount of roughage provided was the same as the CF mares received half of the hay during the day while in paddock (haynets). Mares were tested for oestrus detection by teasing with one stallion and were then examined clinically by rectal palpations and ultrasound before being mated naturally or inseminated by fresh or frozen semen. Multivariate logistic regression was used to analyse data. The treatment affected significantly the reproductive efficiency of the mares with fewer oestrus abnormalities (p = 0.0002) and more fertility (p = 0.024) in CF mares (conception rate = 81% versus 55% in SFP mares). Ensuring semi-continous feeding by providing roughage may be a way of fulfilling the basic physiological needs of the horses' digestive system, reducing stress and associated inhibitors of reproduction. To our knowledge, this study provides the first evidence of an impact of temporal feeding patterns on reproductive success in a Mammal. Temporal patterns of feeding may be a major and underestimated factor in breeding. PMID:24098636

[The morphology, typical combinations of polymorphic genes of hemostasis, and specific features of the pathogenesis of retrochorial hematoma in missed abortion].

PubMed

Milovanov, A P; Kuznetsova, N B; Bushtyreva, I O

to identify mutations and hemostatic gene polymorphisms typical for retrochorial hematoma (RCH) and to study its pathogenesis in missed abortion. A PCR assay was used to detect the genetic forms of thrombophilia in 270 patients with ultrasonographically verified RCH. Logistic regression analysis revealed that with the F7 (proconvertin, coagulation factor (CF) VII G10976A polymorphism or with the F13 (fibrinase, CF XIII) G>T, or FGB (fibrinogen β-chain) G455A polymorphism, the risk of RCH was 2.72, 2.16, and 1.92 times higher, respectively. First trimester missed abortion was found in 42 (15.5%) cases; among them there were 24 (8.8%) women with different polymorphism combinations: F7 (G10976A), F13 (fibrinase, G>T), FGB (G455A). A total of 18 cases of missed abortion due to morphologically verified endometritis, endocrinopathies, and antiphospholipid syndrome were excluded from the sample. Compared to the morphology of medical abortions of the same period (16 women), patients with polymorphic genes of hemostasis were found to have statistically significant incomplete endometrial decidualization, thinning or absence of a Rohr's fibrinoid layer, a smaller number and shortening of syncytiotrophoblast microvilli, and the maximum amount of dissecting hemorrhage and RCH in the utero-chorionic region. The stages of RCH pathogenesis were determined; these included penetration of maternal erythrocytes deep into the decidua ~ dissociation of a layer of decidual cells with impairment of a «hemostatic envelope» ~ formation of RCH with a dense network of fibrin threads ~ final necrosis of surrounding cells and tissues. The investigators identified for the first time the typical combinations of polymorphic genes of predisposition to a high risk for RCH; its complete formation requires additional changes in maternal and placental components that provide local hemostasis.

The role of brain-derived neurotrophic factor (BDNF) Val66Met genetic polymorphism in bipolar disorder: a case-control study, comorbidities, and meta-analysis of 16,786 subjects.

PubMed

González-Castro, Thelma Beatriz; Nicolini, Humberto; Lanzagorta, Nuria; López-Narváez, Lilia; Genis, Alma; Pool García, Sherezada; Tovilla-Zárate, Carlos Alfonso

2015-02-01

The aim of this study was to evaluate the association of Val66Met brain-derived neurotrophic factor (BDNF) polymorphism with bipolar disorder in (i) a meta-analysis and (ii) a case-control study in a Mexican population. We also investigated the possible association of this polymorphism with clinical features. We performed a keyword search of the PubMed and Web of Science databases. A total of 22 studies that have investigated the association of Val66Met (rs6265) with bipolar disorder were selected for inclusion and combined with random effects meta-analysis, using allelic, additive, dominant, and recessive models. Finally, the single nucleotide polymorphism (rs6265) Val66Met in the BDNF gene was genotyped and compared between 139 patients with bipolar disorder and 141 healthy volunteers in a Mexican population. The pooled results from the meta-analysis (9,349 cases and 7,437 controls) did not show a significant association in any of the models. The same results were obtained in our case-control study when analyzing the distribution of the genotypic frequencies of the Val66Met polymorphism in patients with bipolar disorder. However, when we analyzed the association between rs6265 and lifetime history of suicidal behavior, we found an association between genotype Val-Val and suicide attempt (p = 0.02). Although the present study has some limitations, the results indicate a lack of association between the Val66Met polymorphism and bipolar disorder. However, in our case-control study in a Mexican population, the Val66Met polymorphism was associated with suicidal behavior in patients with bipolar disorder. Nevertheless, it is important to consider potential interactions of the BDNF gene, the environment, and different inheritance patterns, when carrying out future genetic studies with larger samples. © 2014 The Authors. Bipolar Disorders Published by John Wiley & Sons Ltd.

HLA-G Haplotypes Are Differentially Associated with Asthmatic Features.

PubMed

Ribeyre, Camille; Carlini, Federico; René, Céline; Jordier, François; Picard, Christophe; Chiaroni, Jacques; Abi-Rached, Laurent; Gouret, Philippe; Marin, Grégory; Molinari, Nicolas; Chanez, Pascal; Paganini, Julien; Gras, Delphine; Di Cristofaro, Julie

2018-01-01

Human leukocyte antigen (HLA)-G, a HLA class Ib molecule, interacts with receptors on lymphocytes such as T cells, B cells, and natural killer cells to influence immune responses. Unlike classical HLA molecules, HLA-G expression is not found on all somatic cells, but restricted to tissue sites, including human bronchial epithelium cells (HBEC). Individual variation in HLA-G expression is linked to its genetic polymorphism and has been associated with many pathological situations such as asthma, which is characterized by epithelium abnormalities and inflammatory cell activation. Studies reported both higher and equivalent soluble HLA-G (sHLA-G) expression in different cohorts of asthmatic patients. In particular, we recently described impaired local expression of HLA-G and abnormal profiles for alternatively spliced isoforms in HBEC from asthmatic patients. sHLA-G dosage is challenging because of its many levels of polymorphism (dimerization, association with β2-microglobulin, and alternative splicing), thus many clinical studies focused on HLA-G single-nucleotide polymorphisms as predictive biomarkers, but few analyzed HLA-G haplotypes. Here, we aimed to characterize HLA-G haplotypes and describe their association with asthmatic clinical features and sHLA-G peripheral expression and to describe variations in transcription factor (TF) binding sites and alternative splicing sites. HLA - G haplotypes were differentially distributed in 330 healthy and 580 asthmatic individuals. Furthermore, HLA-G haplotypes were associated with asthmatic clinical features showed. However, we did not confirm an association between sHLA-G and genetic, biological, or clinical parameters. HLA-G haplotypes were phylogenetically split into distinct groups, with each group displaying particular variations in TF binding or RNA splicing sites that could reflect differential HLA-G qualitative or quantitative expression, with tissue-dependent specificities. Our results, based on a multicenter cohort, thus support the pertinence of HLA-G haplotypes as predictive genetic markers for asthma.

HLA-G Haplotypes Are Differentially Associated with Asthmatic Features

PubMed Central

Ribeyre, Camille; Carlini, Federico; René, Céline; Jordier, François; Picard, Christophe; Chiaroni, Jacques; Abi-Rached, Laurent; Gouret, Philippe; Marin, Grégory; Molinari, Nicolas; Chanez, Pascal; Paganini, Julien; Gras, Delphine; Di Cristofaro, Julie

2018-01-01

Human leukocyte antigen (HLA)-G, a HLA class Ib molecule, interacts with receptors on lymphocytes such as T cells, B cells, and natural killer cells to influence immune responses. Unlike classical HLA molecules, HLA-G expression is not found on all somatic cells, but restricted to tissue sites, including human bronchial epithelium cells (HBEC). Individual variation in HLA-G expression is linked to its genetic polymorphism and has been associated with many pathological situations such as asthma, which is characterized by epithelium abnormalities and inflammatory cell activation. Studies reported both higher and equivalent soluble HLA-G (sHLA-G) expression in different cohorts of asthmatic patients. In particular, we recently described impaired local expression of HLA-G and abnormal profiles for alternatively spliced isoforms in HBEC from asthmatic patients. sHLA-G dosage is challenging because of its many levels of polymorphism (dimerization, association with β2-microglobulin, and alternative splicing), thus many clinical studies focused on HLA-G single-nucleotide polymorphisms as predictive biomarkers, but few analyzed HLA-G haplotypes. Here, we aimed to characterize HLA-G haplotypes and describe their association with asthmatic clinical features and sHLA-G peripheral expression and to describe variations in transcription factor (TF) binding sites and alternative splicing sites. HLA-G haplotypes were differentially distributed in 330 healthy and 580 asthmatic individuals. Furthermore, HLA-G haplotypes were associated with asthmatic clinical features showed. However, we did not confirm an association between sHLA-G and genetic, biological, or clinical parameters. HLA-G haplotypes were phylogenetically split into distinct groups, with each group displaying particular variations in TF binding or RNA splicing sites that could reflect differential HLA-G qualitative or quantitative expression, with tissue-dependent specificities. Our results, based on a multicenter cohort, thus support the pertinence of HLA-G haplotypes as predictive genetic markers for asthma. PMID:29527207

[Interleukin-10-1082 promoter polymorphism and the risk of gastric cancer].

PubMed

Yin, Yi-qiong; Liu, Chun-juan; Zhang, Ming-ming; Zhou, Yong

2012-05-01

To investigate the association between Interleukin-10 (IL-10) promoter polymorphism and the gastric cancer risk in Chinese Han patients. DNA was extracted from blood samples of gastric cancer patients (n = 75) and controls (n = 75). IL-10 -1082 promoter polymorphism in both patient and control group (three genotypes distribution: AA, AG and GG) was identified by PCR-RFLP and its relationship with gastric cancer risk, clinic and pathologic features was also analyzed. Patients with gastric cancer had a significantly lower frequency of AA (OR = 0.43, 95% CI = 0.20, 0.92; P = 0.03) than controls. Patients with proximal gastric cancer had a significantly higher frequency of GG (OR = 3.06, 95% CI = 1.12, 8.36; P = 0.03) than those with distant gastric cancer. Patients with advanced (stage II/IV) gastric cancer had a significantly higher frequency of AA (OR = 5.09, 95% CI = 1.05, 24.70; P = 0.04) than those with early (stage I /IV) gastric cancer. When stratified by the Lauren's classification, histological differentiation of gastric cancer, no statistically significant results was observed. This study suggests that the IL-1 1082 promoter polymorphism may be associated with gastric cancer in Chinese Han patients, and the difference in genotype distribution may be associated with the location and stage of gastric cancer.

In situ 3D topographic and shape analysis by synchrotron radiation X-ray microtomography for crystal form identification in polymorphic mixtures

PubMed Central

Yin, Xian-Zhen; Xiao, Ti-Qiao; Nangia, Ashwini; Yang, Shuo; Lu, Xiao-Long; Li, Hai-Yan; Shao, Qun; He, You; York, Peter; Zhang, Ji-Wen

2016-01-01

Polymorphism denotes the existence of more than one crystal structure of a substance, and great practical and theoretical interest for the chemical and pharmaceutical industries. In many cases, it is challenging to produce a pure crystal form and establish a sensitive detection method for the identification of crystal form in a mixture of polymorphs. In this study, an accurate and sensitive method based on synchrotron radiation X-ray computed microtomography (SR-μCT) was devised to identify the polymorphs of clopidogrel bisulphate (CLP). After 3D reconstruction, crystal particles were extracted and dozens of structural parameters were calculated. Whilst, the particle shapes of the two crystal forms were all irregular, the surface of CLP II was found to be rougher than CLP I. In order to classify the crystal form based on the quantitative morphological property of particles, Volume Bias Percentage based on Surface Smoothing (VBP) was defined and a new method based on VBP was successfully developed, with a total matching rate of 99.91% for 4544 particles and a lowest detectable limit of 1%. More important for the mixtures in solid pharmaceutical formulations, the interference of excipients can be avoided, a feature cannot achieved by other available analytical methods. PMID:27097672

Collapsed state of polyglutamic acid results in amyloid spherulite formation

PubMed Central

Stehli, Daniel; Mulaj, Mentor; Miti, Tatiana; Traina, Joshua; Foley, Joseph; Muschol, Martin

2015-01-01

Self-assembly of proteins and peptides into amyloid fibrils involves multiple distinct intermediates and late-stage fibrillar polymorphs. Understanding the conditions and mechanisms that promote the formation of one type of intermediate and polymorph over the other represents a fundamental challenge. Answers to this question are also of immediate biomedical relevance since different amyloid aggregate species have been shown to have distinct pathogenic potencies. One amyloid polymorph that has received comparatively little attention are amyloid spherulites. Here we report that self-assembly of the intrinsically disordered polymer poly(L-glutamic) acid (PLE) can generate amyloid spherulites. We characterize spherulite growth kinetics, as well as the morphological, optical and tinctorial features of this amyloid polymorph previously unreported for PLE. We find that PLE spherulites share both tinctorial and structural characteristics with their amyloid fibril counterparts. Differences in PLE's molecular weight, polydispersity or chemistry could not explain the selective propensity toward either fibril or spherulite formation. Instead, we provide evidence that PLE polymers can exist in either a collapsed globule or an extended random coil conformation. The collapsed globule consistently produces spherulites while the extended coil assembles into disordered fibril bundles. This results suggests that these 2 PLE conformers directly affect the morphology of the resulting macroscopic amyloid assembly. PMID:28232889

Collapsed state of polyglutamic acid results in amyloid spherulite formation.

PubMed

Stehli, Daniel; Mulaj, Mentor; Miti, Tatiana; Traina, Joshua; Foley, Joseph; Muschol, Martin

2015-01-01

Self-assembly of proteins and peptides into amyloid fibrils involves multiple distinct intermediates and late-stage fibrillar polymorphs. Understanding the conditions and mechanisms that promote the formation of one type of intermediate and polymorph over the other represents a fundamental challenge. Answers to this question are also of immediate biomedical relevance since different amyloid aggregate species have been shown to have distinct pathogenic potencies. One amyloid polymorph that has received comparatively little attention are amyloid spherulites. Here we report that self-assembly of the intrinsically disordered polymer poly(L-glutamic) acid (PLE) can generate amyloid spherulites. We characterize spherulite growth kinetics, as well as the morphological, optical and tinctorial features of this amyloid polymorph previously unreported for PLE. We find that PLE spherulites share both tinctorial and structural characteristics with their amyloid fibril counterparts. Differences in PLE's molecular weight, polydispersity or chemistry could not explain the selective propensity toward either fibril or spherulite formation. Instead, we provide evidence that PLE polymers can exist in either a collapsed globule or an extended random coil conformation. The collapsed globule consistently produces spherulites while the extended coil assembles into disordered fibril bundles. This results suggests that these 2 PLE conformers directly affect the morphology of the resulting macroscopic amyloid assembly.

Gene and Stress History Interplay in Emergence of PTSD-like Features

DTIC Science & Technology

2015-05-27

35–50. [9] Hetherington MM, Cecil JE. Gene–environment interactions in obesity . Forum Nutr 2010;63:195–203. [10] Lau JY, Eley TC. Gene–environment...Psychiatry 2010;34(3):459–62. [56] Binder EB, et al. Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder

Correlation of PD-1/PD-L1 polymorphisms and expressions with clinicopathologic features and prognosis of ovarian cancer.

PubMed

Tan, Dan; Sheng, Li; Yi, Qing-Hua

2018-02-06

To explore the correlation of PD-1/PD-L1 polymorphisms and their expressions with clinicopathologic features and prognosis of ovarian cancer. A total of 164 patients with ovarian cancer were enrolled as case group and 170 healthy women as control group. We conducted quantitative reverse transcription-PCR (qRT-PCR) to determine PD-1/PD-L1 expressions in peripheral blood mononuclear cells (PBMCs). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific amplification were used to detect PD-1 rs2227982 C>T and PD-L1 rs4143815 C>G. PD-1 rs2227982 C>T and PD-L1 rs4143815 C>G polymorphisms increased the risk for ovarian cancer. PD-1 rs2227982 C>T was associated with FIGO stage and differentiation grade, while PD-L1 rs4143815 C>G was correlated with histological type and differentiation grade. Besides, PD-1/PD-L1 expressions were positively correlated in PBMCs of patients with ovarian cancer to be associated with differentiation grade. Compared with wild homozygous patients, PD-1/PD-L1 expressions were significantly decreased in PBMCs of ovarian cancer patients carried with the mutant genotypes of rs2227982 C>T and rs4143815 C>G. The PFS and OS in ovarian cancer patients with wild homozygous genotype of rs2227982 C>T and rs4143815 C>G were significantly higher than those with mutant genotypes, which were significantly lower in patients with low expressions of PD-1/PD-L1 than those with high expressions. Univariate COX regression analysis identified FIGO staging, differentiation grade, rs2227982 C>T, rs4143815 C>G and expressions of PD-1/PD-L1 as the prognostic factors, and multivariate COX regression analysis demonstrated that high FIGO stage and low expressions of PD-1/PD-L1 were independent risk factors for the prognosis of ovarian cancer. PD-1 rs2227982 C>T and PD-L1 rs4143815 C>G polymorphisms increased the risk of ovarian cancer, leading to a poor prognosis, associated with low expressions of PD-1 and PD-L1. While high PD-1 and PD-L1 expressions are indicators of a favorable prognosis in ovarian cancer.

Fas and Fas ligand gene polymorphisms in Turkish patients with Familial Mediterranean Fever.

PubMed

Ozel, Emine Gulce; Duran, Gulay Gulbol; Celik, Muhammet Murat; Duran, Nizami; Gunesacar, Ramazan

2017-08-05

Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disorder characterized by recurrent fever, serositis, abdominal pain, arthritis, arthralgia and erysipelas like erythema. Fas and Fas ligand molecules play a central role in the apoptosis signaling of various cell types including neutrophils. Neutrophils are the major cell population involved in acute inflammation in patients with FMF and the role of Fas and Fas ligand molecules in this cells of FMF patients may be crucial. Therefore, in the present study, we aimed to investigate whether the Fas cell surface receptor gene (FAS); NM_000043.5: c.-671A>G (rs1800682, MvaI) and Fas ligand gene (FASLG), NM_000639.2: c.-844C>T (rs763110, BsrD1) functional polymorphisms in patients with FMF and their relation to the main clinical features of the disease. The polymorphisms in the promoter regions of FAS c.-671A>G and FASLG c.-844C>T were investigated in 97 non-related FMF patients and 70 non-related healthy controls by using PCR-RFLP technique. The frequencies of FAS c-671AG genotype and G allele were not significantly different between FMF patients and healthy subjects. The frequency of FASLG -844TC genotype was found significantly different between the patients with FMF and healthy controls whereas T or C allele frequency was not significantly different between the groups. Haplotype frequencies of the studied polymorphisms were also not significantly different between FMF patients and controls. There were no correlations between the studied FAS c.-671A>G and FASLG c.-844C>T polymorphisms and the main clinical features of FMF such as fever, arthritis, abdominal and chest pain, arthralgia and erysipelas-like erythema. Our findings suggest that FAS c.-671AG genotype or G allele and FASLG c.-844 allele are not to be a risk factor, whereas FASLG c.-844TC genotype may be protective in the studied Turkish population. According to our results we may suggest that although not statistically significant, higher frequencies of FASLG c.-844CC genotype in FMF patients may be related to delayed apoptosis of neutrophils and ultimately cause neutrophilic inflammation by increasing FASLG expression. Copyright © 2017 Elsevier B.V. All rights reserved.

Homocysteine and the C677T Gene Polymorphism of Its Key Metabolic Enzyme MTHFR Are Risk Factors of Early Renal Damage in Hypertension in a Chinese Han Population

PubMed Central

Yun, Lin; Xu, Rui; Li, Guohua; Yao, Yucai; Li, Jiamin; Cong, Dehong; Xu, Xingshun; Zhang, Lihua

2015-01-01

Abstract The combined hyperhomocysteinemia condition is a feature of the Chinese hypertensive population. This study used the case-control method to investigate the association between plasma homocysteine and the C677T gene polymorphism of its key metabolic enzyme, 5, 10-methylenetetrahydrofolate reductase (MTHFR), and early renal damage in a hypertensive Chinese Han population. A total of 379 adult essential hypertensive patients were selected as the study subjects. The personal information, clinical indicators, and the C677T gene polymorphism of MTHFR were texted. This study used the urine microalbumin/urine creatinine ratio (UACR) as a grouping basis: the hypertension without renal damage group (NRD group) and the hypertension combined with early renal damage group (ERD group). Early renal damage in the Chinese hypertensive population was associated with body weight, systolic pressure, diastolic pressure, urea nitrogen, serum creatinine, cystatin C, uric acid, aldosterone, and glomerular filtration rate. The homocysteine level and the UACR in the TT genotype group were higher than those in the CC genotype group. The binary logistic regression analysis results showed that after sex and age were adjusted, the MTHFR C677T gene polymorphism was correlated with early renal damage in hypertension in both the recessive model and in the additive model. Plasma homocysteine and the C677T gene polymorphism of its key metabolic enzyme MTHFR might be independent risk factors of early renal damage in the hypertensive Chinese Han population. PMID:26717388

TSHR intronic polymorphisms (rs179247 and rs12885526) and their role in the susceptibility of the Brazilian population to Graves' disease and Graves' ophthalmopathy.

PubMed

Bufalo, N E; Dos Santos, R B; Marcello, M A; Piai, R P; Secolin, R; Romaldini, J H; Ward, L S

2015-05-01

Intronic thyroid-stimulating hormone receptor polymorphisms have been associated with the risk for both Graves' disease and Graves' ophthalmopathy, but results have been inconsistent among different populations. We aimed to investigate the influence of thyroid-stimulating hormone receptor intronic polymorphisms in a large well-characterized population of GD patients. We studied 279 Graves' disease patients (231 females and 48 males, 39.80 ± 11.69 years old), including 144 with Graves' ophthalmopathy, matched to 296 healthy control individuals. Thyroid-stimulating hormone receptor genotypes of rs179247 and rs12885526 were determined by Real Time PCR TaqMan(®) SNP Genotyping. A multivariate analysis showed that the inheritance of the thyroid-stimulating hormone receptor AA genotype for rs179247 increased the risk for Graves' disease (OR = 2.821; 95 % CI 1.595-4.990; p = 0.0004), whereas the thyroid-stimulating hormone receptor GG genotype for rs12885526 increased the risk for Graves' ophthalmopathy (OR = 2.940; 95 % CI 1.320-6.548; p = 0.0083). Individuals with Graves' ophthalmopathy also presented lower mean thyrotropin receptor antibodies levels (96.3 ± 143.9 U/L) than individuals without Graves' ophthalmopathy (98.3 ± 201.9 U/L). We did not find any association between the investigated polymorphisms and patients clinical features or outcome. We demonstrate that thyroid-stimulating hormone receptor intronic polymorphisms are associated with the susceptibility to Graves' disease and Graves' ophthalmopathy in the Brazilian population, but do not appear to influence the disease course.

Extensive 5.8S nrDNA polymorphism in Mammillaria (Cactaceae) with special reference to the identification of pseudogenic internal transcribed spacer regions.

PubMed

Harpke, Doerte; Peterson, Angela

2008-05-01

The internal transcribed spacer (ITS) region (ITS1, 5.8S rDNA, ITS2) represents the most widely applied nuclear marker in eukaryotic phylogenetics. Although this region has been assumed to evolve in concert, the number of investigations revealing high degrees of intra-individual polymorphism connected with the presence of pseudogenes has risen. The 5.8S rDNA is the most important diagnostic marker for functionality of the ITS region. In Mammillaria, intra-individual 5.8S rDNA polymorphisms of up to 36% and up to nine different types have been found. Twenty-eight of 30 cloned genomic Mammillaria sequences were identified as putative pseudogenes. For the identification of pseudogenic ITS regions, in addition to formal tests based on substitution rates, we attempted to focus on functional features of the 5.8S rDNA (5.8S motif, secondary structure). The importance of functional data for the identification of pseudogenes is outlined and discussed. The identification of pseudogenes is essential, because they may cause erroneous phylogenies and taxonomic problems.

Size-dependent pressure-induced amorphization: a thermodynamic panorama.

PubMed

Machon, Denis; Mélinon, Patrice

2015-01-14

Below a critical particle size, some pressurized compounds (e.g. TiO2, Y2O3, PbTe) undergo a crystal-to-amorphous transformation instead of a polymorphic transition. This effect reflects the greater propensity of nanomaterials for amorphization. In this work, a panorama of thermodynamic interpretations is given: first, a descriptive analysis based on the energy landscape concept gives a general comprehension of the balance between thermodynamics and kinetics to obtain an amorphous state. Then, a formal approach based on Gibbs energy to describe the thermodynamics and phase transitions in nanoparticles gives a basic explanation of size-dependent pressure-induced amorphization. The features of this transformation (amorphization occurs at pressures lower than the polymorphic transition pressure!) and the nanostructuration can be explained in an elaborated model based on the Ginzburg-Landau theory of phase transition and on percolation theory. It is shown that the crossover between polymorphic transition and amorphization is highly dependent on the defect density and interfacial energy, i.e., on the synthesis process. Their behavior at high pressure is a quality control test for the nanoparticles.

The Role of −786T/C Polymorphism in the Endothelial Nitric Oxide Synthase Gene in Males with Clinical and Biochemical Features of the Metabolic Syndrome

PubMed Central

Misiak, Blazej; Krolik, Marta; Kukowka, Anna; Lewera, Anna; Leszczynski, Przemyslaw; Stankiewicz-Olczyk, Joanna; Slezak, Ryszard

2011-01-01

Background. Extensive evidence, arising from models of endothelial nitric oxide synthase gene (NOS3)-knockout mice supports the role of endothelial malfunction in the pathogenesis of the metabolic syndrome (MS). Aims. The aim of this study was to evaluate the role of −786T/C polymorphism in the etiology of MS and assess previously reported interaction with cigarette smoking. Methods. Based on International Diabetes Federation 2005 criteria, we recruited randomly 152 subjects with MS and 75 subjects without MS. Results. Allelic and genotype frequencies did not differ significantly between both groups. Total cholesterol level (CHOLT) and intima-media thickness of carotid arteries were significantly higher in −786CC homozygotes, in comparison with −786TC and −786TT patients. Regarding current smoking status, −786C allele was associated with higher CHOLT than −786T allele. Conclusion. Our study indicates the putative role of −786T/C polymorphism in the development of hypercholesterolemia, in patients with MS, which might be enhanced by cigarette smoking. PMID:22164159

The Role of -786T/C Polymorphism in the Endothelial Nitric Oxide Synthase Gene in Males with Clinical and Biochemical Features of the Metabolic Syndrome.

PubMed

Misiak, Blazej; Krolik, Marta; Kukowka, Anna; Lewera, Anna; Leszczynski, Przemyslaw; Stankiewicz-Olczyk, Joanna; Slezak, Ryszard

2011-01-01

Background. Extensive evidence, arising from models of endothelial nitric oxide synthase gene (NOS3)-knockout mice supports the role of endothelial malfunction in the pathogenesis of the metabolic syndrome (MS). Aims. The aim of this study was to evaluate the role of -786T/C polymorphism in the etiology of MS and assess previously reported interaction with cigarette smoking. Methods. Based on International Diabetes Federation 2005 criteria, we recruited randomly 152 subjects with MS and 75 subjects without MS. Results. Allelic and genotype frequencies did not differ significantly between both groups. Total cholesterol level (CHOLT) and intima-media thickness of carotid arteries were significantly higher in -786CC homozygotes, in comparison with -786TC and -786TT patients. Regarding current smoking status, -786C allele was associated with higher CHOLT than -786T allele. Conclusion. Our study indicates the putative role of -786T/C polymorphism in the development of hypercholesterolemia, in patients with MS, which might be enhanced by cigarette smoking.

Human Alu insertion polymorphisms in North African populations.

PubMed

Cherni, Loth; Frigi, Sabeh; Ennafaa, Hajer; Mtiraoui, Nabil; Mahjoub, Touhami; Benammar-Elgaaied, Amel

2011-10-01

Several features make Alu insertions a powerful tool used in population genetic studies: the polymorphic nature of many Alu insertions, the stability of an Alu insertion event and, furthermore, the ancestral state of an Alu insertion is known to be the absence of the Alu element at a particular locus and the presence of an Alu insertion at the site that forward mutational change. This study analyses seven Alu insertion polymorphisms in a sample of 297 individuals from the autochthonous population of Tunisia (Thala, Smar, Zarzis, and Bou Salem) and Libya with the aim of studying their genetic structure with respect to the populations of North Africa, Western, Eastern and Central Europe. The comparative analyses carried out using the MDS and AMOVA methods reveal the existence of spatial heterogeneity, and identify four population groups. Study populations (Libya, Smar, Zarzis, and Bou Salem) are closest to North African populations whereas Thala is isolated and is closest to Western European populations. In conclusion, Results of the present study support the important role that migratory movements have played in the North African gene pool, at least since the Neolithic period.

Analysis of the association between CD40 and CD40 ligand polymorphisms and systemic sclerosis.

PubMed

Teruel, María; Simeon, Carmen P; Broen, Jasper; Vonk, Madelon C; Carreira, Patricia; Camps, Maria Teresa; García-Portales, Rosa; Delgado-Frías, Esmeralda; Gallego, Maria; Espinosa, Gerard; Beretta, Lorenzo; Airó, Paolo; Lunardi, Claudio; Riemekasten, Gabriela; Witte, Torsten; Krieg, Thomas; Kreuter, Alexander; Distler, Jörg H W; Hunzelmann, Nicolas; Koeleman, Bobby P; Voskuyl, Alexandre E; Schuerwegh, Annemie J; González-Gay, Miguel Angel; Radstake, Timothy R D J; Martin, Javier

2012-06-25

The aim of the present study was to investigate the possible role of CD40 and CD40 ligand (CD40LG) genes in the susceptibility and phenotype expression of systemic sclerosis (SSc). In total, 2,670 SSc patients and 3,245 healthy individuals from four European populations (Spain, Germany, The Netherlands, and Italy) were included in the study. Five single-nucleotide polymorphisms (SNPs) of CD40 (rs1883832, rs4810485, rs1535045) and CD40LG (rs3092952, rs3092920) were genotyped by using a predesigned TaqMan allele-discrimination assay technology. Meta-analysis was assessed to determine whether an association exists between the genetic variants and SSc or its main clinical subtypes. No evidence of association between CD40 and CD40LG genes variants and susceptibility to SSc was observed. Similarly, no significant statistical differences were observed when SSc patients were stratified by the clinical subtypes, the serologic features, and pulmonary fibrosis. Our results do not suggest an important role of CD40 and CD40LG gene polymorphisms in the susceptibility to or clinical expression of SSc.

The role of androgen receptor activity mediated by the CAG repeat polymorphism in the pathogenesis of PCOS.

PubMed

Baculescu, N

2013-03-15

Polycystic ovary syndrome (PCOS), one of the most common and complex endocrine disorders affecting up to 15 % of reproductive age women, is considered a predominantly hyperandrogenic syndrome according to the Androgen Excess Society. It is generally accepted that androgens determine the characteristic features of PCOS; in this context, a hyperactive androgen receptor (AR) at the levels of the GnRH pulse generator in the hypothalamus and at the granulosa cells in the ovary, skeletal muscle or adipocytes senses initially normal testosterone and dihydrotestosterone as biochemical hyperandrogenism and might be a crucial connection between the vicious circles of the PCOS pathogenesis. Polymorphism of the AR gene has been associated with different androgen pattern diseases. Several studies have demonstrated an association between AR with increased activity encoded by shorter CAG repeat polymorphism in the exon 1 of the AR gene and PCOS, although there are conflicting results in this field. The phenomenon is more complex because the AR activity is determined by the epigenetic effect of X chromosome inactivation (XCI). Moreover, we must evaluate the AR as a dynamic heterocomplex, with a large number of coactivators and corepressors that are essential to its function, thus mediating tissue-specific effects. In theory, any of these factors could modify the activity of AR, which likely explains the inconsistent results obtained when this activity was quantified by only the CAG polymorphism in PCOS.

Rapid genetic and epigenetic alterations under intergeneric genomic shock in newly synthesized Chrysanthemum morifolium x Leucanthemum paludosum hybrids (Asteraceae).

PubMed

Wang, Haibin; Jiang, Jiafu; Chen, Sumei; Qi, Xiangyu; Fang, Weimin; Guan, Zhiyong; Teng, Nianjun; Liao, Yuan; Chen, Fadi

2014-01-01

The Asteraceae family is at the forefront of the evolution due to frequent hybridization. Hybridization is associated with the induction of widespread genetic and epigenetic changes and has played an important role in the evolution of many plant taxa. We attempted the intergeneric cross Chrysanthemum morifolium × Leucanthemum paludosum. To obtain the success in cross, we have to turn to ovule rescue. DNA profiling of the amphihaploid and amphidiploid was investigated using amplified fragment length polymorphism, sequence-related amplified polymorphism, start codon targeted polymorphism, and methylation-sensitive amplification polymorphism (MSAP). Hybridization induced rapid changes at the genetic and the epigenetic levels. The genetic changes mainly involved loss of parental fragments and gaining of novel fragments, and some eliminated sequences possibly from the noncoding region of L. paludosum. The MSAP analysis indicated that the level of DNA methylation was lower in the amphiploid (∼45%) than in the parental lines (51.5-50.6%), whereas it increased after amphidiploid formation. Events associated with intergeneric genomic shock were a feature of C. morifolium × L. paludosum hybrid, given that the genetic relationship between the parental species is relatively distant. Our results provide genetic and epigenetic evidence for understanding genomic shock in wide crosses between species in Asteraceae and suggest a need to expand our current evolutionary framework to encompass a genetic/epigenetic dimension when seeking to understand wide crosses.

Chromosome-wide linkage disequilibrium caused by an inversion polymorphism in the white-throated sparrow (Zonotrichia albicollis).

PubMed

Huynh, L Y; Maney, D L; Thomas, J W

2011-04-01

Chromosomal inversions have been of long-standing interest to geneticists because they are capable of suppressing recombination and facilitating the formation of adaptive gene complexes. An exceptional inversion polymorphism (ZAL2(m)) in the white-throated sparrow (Zonotrichia albicollis) is linked to variation in plumage, social behavior and mate choice, and is maintained in the population by negative assortative mating. The ZAL2(m) polymorphism is a complex inversion spanning > 100 Mb and has been proposed to be a strong suppressor of recombination, as well as a potential model for studying neo-sex chromosome evolution. To quantify and evaluate these features of the ZAL2(m) polymorphism, we generated sequence from 8 ZAL2(m) and 16 ZAL2 chromosomes at 58 loci inside and 4 loci outside the inversion. Inside the inversion we found that recombination was completely suppressed between ZAL2 and ZAL2(m), resulting in uniformly high levels of genetic differentiation (F(ST)=0.94), the formation of two distinct haplotype groups representing the alternate chromosome arrangements and extensive linkage disequilibrium spanning ~104 Mb within the inversion, whereas gene flow was not suppressed outside the inversion. Finally, although ZAL2(m) homozygotes are exceedingly rare in the population, occurring at a frequency of < 1%, we detected evidence of historical recombination between ZAL2(m) chromosomes inside the inversion, refuting its potential status as a non-recombining autosome.

Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology

PubMed Central

2018-01-01

Polycystic ovary syndrome is a multifactorial endocrine disorder whose pathophysiology baffles many researchers till today. This syndrome is typically characterized by anovulatory cycles and infertility, altered gonadotropin levels, obesity, and bulky multifollicular ovaries on ultrasound. Hyperandrogenism and insulin resistance are hallmark features of its complex pathophysiology. Hyperandrogenemia is a salient feature of PCOS and a major contributor to cosmetic anomalies including hirsutism, acne, and male pattern alopecia in affected women. Increased androgen levels may be intrinsic or aggravated by preexisting insulin resistance in women with PCOS. Studies have reported augmented ovarian steroidogenesis patterns attributed mainly to theca cell hypertrophy and altered expression of key enzymes in the steroidogenic pathway. Candidate gene studies have been performed in order to delineate the association of polymorphisms in genes, which encode enzymes in the intricate cascade of steroidogenesis or modulate the levels and action of circulating androgens, with risk of PCOS development and its related traits. However, inconsistent findings have impacted the emergence of a unanimously accepted genetic marker for PCOS susceptibility. In the current review, we have summarized the influence of polymorphisms in important androgen related genes in governing genetic predisposition to PCOS and its related metabolic and reproductive traits. PMID:29670770

Self-assembly of hard helices: a rich and unconventional polymorphism.

PubMed

Kolli, Hima Bindu; Frezza, Elisa; Cinacchi, Giorgio; Ferrarini, Alberta; Giacometti, Achille; Hudson, Toby S; De Michele, Cristiano; Sciortino, Francesco

2014-11-07

Hard helices can be regarded as a paradigmatic elementary model for a number of natural and synthetic soft matter systems, all featuring the helix as their basic structural unit, from natural polynucleotides and polypeptides to synthetic helical polymers, and from bacterial flagella to colloidal helices. Here we present an extensive investigation of the phase diagram of hard helices using a variety of methods. Isobaric Monte Carlo numerical simulations are used to trace the phase diagram; on going from the low-density isotropic to the high-density compact phases a rich polymorphism is observed, exhibiting a special chiral screw-like nematic phase and a number of chiral and/or polar smectic phases. We present full characterization of the latter, showing that they have unconventional features, ascribable to the helical shape of the constituent particles. Equal area construction is used to locate the isotropic-to-nematic phase transition, and the results are compared with those stemming from an Onsager-like theory. Density functional theory is also used to study the nematic-to-screw-nematic phase transition; within the simplifying assumption of perfectly parallel helices, we compare different levels of approximation, that is second- and third-virial expansions and a Parsons-Lee correction.

Non-Canonical G-quadruplexes cause the hCEB1 minisatellite instability in Saccharomyces cerevisiae

PubMed Central

Piazza, Aurèle; Cui, Xiaojie; Adrian, Michael; Samazan, Frédéric; Heddi, Brahim; Phan, Anh-Tuan; Nicolas, Alain G

2017-01-01

G-quadruplexes (G4) are polymorphic four-stranded structures formed by certain G-rich nucleic acids in vitro, but the sequence and structural features dictating their formation and function in vivo remains uncertain. Here we report a structure-function analysis of the complex hCEB1 G4-forming sequence. We isolated four G4 conformations in vitro, all of which bear unusual structural features: Form 1 bears a V-shaped loop and a snapback guanine; Form 2 contains a terminal G-triad; Form 3 bears a zero-nucleotide loop; and Form 4 is a zero-nucleotide loop monomer or an interlocked dimer. In vivo, Form 1 and Form 2 differently account for 2/3rd of the genomic instability of hCEB1 in two G4-stabilizing conditions. Form 3 and an unidentified form contribute to the remaining instability, while Form 4 has no detectable effect. This work underscores the structural polymorphisms originated from a single highly G-rich sequence and demonstrates the existence of non-canonical G4s in cells, thus broadening the definition of G4-forming sequences. DOI: http://dx.doi.org/10.7554/eLife.26884.001 PMID:28661396

[Polymorphism of alcohol dehydrogenase gene ADH1B in eastern Slavic and Iranian-speaking populations].

PubMed

2005-11-01

Frequencies of alleles and genotypes for alcohol dehydrogenase gene ADH1B (arg47his polymorphism), associated with alcohol tolerance/sensitivity, were determined. It was demonstrated that the frequency of allele ADH1B*47his, corresponding to atypical alcohol dehydrogenase variant in Russians, Ukrainians, Iranians, and mountain-dwellers of the Pamirs constituted 3, 7, 24, and 22%, respectively. The frequencies established were consistent with the allele frequency distribution pattern among the populations of Eurasia. Russians and Ukrainians were indistinguishable from other European populations relative to the frequency of allele ADH1B*47his, and consequently, relative to specific features of ethanol metabolic pathways. The data obtained provide refinement of the geographic pattern of ADH1B*47his frequency distribution in Eurasia.

Juvenile Spring Eruption: A Variant of Perniosis?

PubMed

Nabatian, Adam S; Rosman, Ilana S; Sturza, Jeffrey; Jacobson, Mark

2015-09-01

Juvenile spring eruption (JSE) is a unique condition that typically affects the helices of the ears of boys and young men. The classical clinical picture of JSE includes the abrupt onset of lesions after spending time outdoors in the early spring. Because of the papulovesicular nature of the rash and the history of sun exposure, JSE is considered a variant of polymorphous light eruption. In addition to the term "juvenile spring eruption," this entity has also been described under other less common terms such as "perniosis juvenilis vernalis aurium" or "spring perniosis," which emphasizes the onset in the spring and the possible pathogenic role of cold weather. We present a case of likely JSE with histopathologic features more consistent with perniosis than polymorphous light eruption and present a review the literature.

Binding of Thioflavin T and Related Probes to Polymorphic Models of Amyloid-β Fibrils.

PubMed

Peccati, Francesca; Pantaleone, Stefano; Riffet, Vanessa; Solans-Monfort, Xavier; Contreras-García, Julia; Guallar, Victor; Sodupe, Mariona

2017-09-28

Alzheimer's disease is a challenge of the utmost importance for contemporary society. An early diagnosis is essential for the development of treatments and for establishing a network of support for the patient. In this light, the deposition in the brain of amyloid-β fibrillar aggregates, which is a distinctive feature of Alzheimer, is key for an early detection of this disease. In this work we propose an atomistic study of the interaction of amyloid tracers with recently published polymorphic models of amyloid-β 1-40 and 1-42 fibrils, highlighting the relationship between marker architectures and binding affinity. This work uncovers the importance of quaternary structure, and in particular of junctions between amyloid-β protofilaments, as the key areas for marker binding.

A Hierarchical Feature and Sample Selection Framework and Its Application for Alzheimer’s Disease Diagnosis

NASA Astrophysics Data System (ADS)

An, Le; Adeli, Ehsan; Liu, Mingxia; Zhang, Jun; Lee, Seong-Whan; Shen, Dinggang

2017-03-01

Classification is one of the most important tasks in machine learning. Due to feature redundancy or outliers in samples, using all available data for training a classifier may be suboptimal. For example, the Alzheimer’s disease (AD) is correlated with certain brain regions or single nucleotide polymorphisms (SNPs), and identification of relevant features is critical for computer-aided diagnosis. Many existing methods first select features from structural magnetic resonance imaging (MRI) or SNPs and then use those features to build the classifier. However, with the presence of many redundant features, the most discriminative features are difficult to be identified in a single step. Thus, we formulate a hierarchical feature and sample selection framework to gradually select informative features and discard ambiguous samples in multiple steps for improved classifier learning. To positively guide the data manifold preservation process, we utilize both labeled and unlabeled data during training, making our method semi-supervised. For validation, we conduct experiments on AD diagnosis by selecting mutually informative features from both MRI and SNP, and using the most discriminative samples for training. The superior classification results demonstrate the effectiveness of our approach, as compared with the rivals.

New data from basal Australian songbird lineages show that complex structure of MHC class II β genes has early evolutionary origins within passerines.

PubMed

Balasubramaniam, Shandiya; Bray, Rebecca D; Mulder, Raoul A; Sunnucks, Paul; Pavlova, Alexandra; Melville, Jane

2016-05-21

The major histocompatibility complex (MHC) plays a crucial role in the adaptive immune system and has been extensively studied across vertebrate taxa. Although the function of MHC genes appears to be conserved across taxa, there is great variation in the number and organisation of these genes. Among avian species, for instance, there are notable differences in MHC structure between passerine and non-passerine lineages: passerines typically have a high number of highly polymorphic MHC paralogs whereas non-passerines have fewer loci and lower levels of polymorphism. Although the occurrence of highly polymorphic MHC paralogs in passerines is well documented, their evolutionary origins are relatively unexplored. The majority of studies have focussed on the more derived passerine lineages and there is very little empirical information on the diversity of the MHC in basal passerine lineages. We undertook a study of MHC diversity and evolutionary relationships across seven species from four families (Climacteridae, Maluridae, Pardalotidae, Meliphagidae) that comprise a prominent component of the basal passerine lineages. We aimed to determine if highly polymorphic MHC paralogs have an early evolutionary origin within passerines or are a more derived feature of the infraorder Passerida. We identified 177 alleles of the MHC class II β exon 2 in seven basal passerine species, with variation in numbers of alleles across individuals and species. Overall, we found evidence of multiple gene loci, pseudoalleles, trans-species polymorphism and high allelic diversity in these basal lineages. Phylogenetic reconstruction of avian lineages based on MHC class II β exon 2 sequences strongly supported the monophyletic grouping of basal and derived passerine species. Our study provides evidence of a large number of highly polymorphic MHC paralogs in seven basal passerine species, with strong similarities to the MHC described in more derived passerine lineages rather than the simpler MHC in non-passerine lineages. These findings indicate an early evolutionary origin of highly polymorphic MHC paralogs in passerines and shed light on the evolutionary forces shaping the avian MHC.

IL23R +2199A/C polymorphism is associated with decreased risk of certain subtypes of gastric cancer in Chinese: a case-control study.

PubMed

Chen, Bin; Zeng, Zhirong; Xu, Lixia; Wu, Xiaoqin; Yu, Jun; Xue, Ling; Hao, Yuantao; Wang, Yiming; Sung, Joseph J Y; Chen, Minhu; Hu, Pinjin

2011-04-01

Today, the causal relationship between inflammation and gastric cancer is more widely accepted. Genetic variations in inflammation-related genes especially cytokines and their receptors, were thought to partly determine the outcome of Helicobacter pylori (H. pylori) infection and progression of gastric lesions. Interleukin 23 receptor (IL23R), as a key cytokine receptor gene in the important inflammatory IL-17/IL-23 axis, may contribute to gastric cancer predisposition. Up till now, the associations of IL23R gene polymorphisms with subtypes of gastric cancer are largely unknown. We investigated whether the association between IL23R +2199 rs10889677 and gastric cancer risk varies by clinical characteristics and the prognostic value of the polymorphism in a case-control study. A population-based case-control study was conducted in Guangdong. 1010 gastric cancer patients and 800 healthy controls were enrolled. Polymorphism in IL23R was analyzed by PCR-RFLP. Compared with AA, CC carriers of IL23R +2199 polymorphism were associated with protection against gastric cancer (OR=0.47, 95% CI=0.31-0.71). In stratified analyses, CC genotype was significantly associated with decreased risk of intestinal type (OR=0.44, 95% CI=0.27-0.70), but not with diffuse or mix type of gastric cancer. CC genotype was found to be associated with poorly differentiated (OR=0.43, 95% CI=0.26-0.70), but not with moderately or well differentiated gastric cancer. Multivariate analysis showed IL23R +2199A/C variant was not an independent prognostic factor for gastric cancer patients. IL23R polymorphism influences certain subtypes of gastric cancer according to clinical and pathological features. Understanding the etiologic heterogeneity of gastric cancer may result in improvements in controlling this disorder. Copyright © 2010 Elsevier Ltd. All rights reserved.

4G/5G plasminogen activator inhibitor-1 and -308 A/G tumor necrosis factor-α promoter gene polymorphisms in Argentinean lupus patients: focus on lupus nephritis.

PubMed

Muñoz, Sebastián Andrés; Aranda, Federico; Allievi, Alberto; Orden, Alberto Omar; Perés Wingeyer, Silvia; Trobo, Rosana; Alvarez, Analía; Eimon, Alicia; Barreira, Juan Carlos; Schneeberger, Emilce; Dal Pra, Fernando; Sarano, Judith; Hofman, Julio; Chamorro, Julián; de Larrañaga, Gabriela

2014-02-01

We investigated the relationship between the 4G/5G plasminogen activator inhibitor (PAI-1) and -308 A/G tumor necrosis factor-α (TNF-α) polymorphisms and the clinical and biochemical features of systemic lupus erythematosus (SLE) in an Argentinean patient cohort. A total of 402 patients were studied, including 179 SLE patients and 223 healthy individuals. PCR-RLFP was used to determine the genotypes of the 4G/5G PAI-1 and -308 A/G TNF-α polymorphisms. SLE patients with lupus nephritis (LN) (n = 86) were compared with patients without LN (n = 93). Additionally, LN patients were divided into proliferative LN and non-proliferative LN groups according to the results of the renal biopsies. No significant differences were noted in the genotype distributions or allele frequencies of these TNF-α and PAI-1 polymorphisms between SLE patients and controls. There were higher numbers of criteria for SLE, more lupus flares and higher damage scores in LN patients, but there were similar frequencies of anti-phospholipid antibody (APA) positivity and anti-phospholipid syndrome. No significant difference was noted for any studied variable between the proliferative LN and non-proliferative LN groups except for the presence of APA. We found no significant differences in the TNF-α and PAI-1 genotype distributions or allele frequencies between groups. We found that the -308 A/G TNF-α and 4G/5G PAI-1 polymorphisms are not associated with susceptibility to SLE in an Argentinean population. We also did not find any association between the presence of any specific allele or genotype and the development of LN in SLE patients. Finally, no association was noted between either of the two polymorphisms and the severity of renal disease.

X-ray structural studies and physicochemical characterization of (E)-6-(3,4-dimethoxyphenyl)-1-ethyl-4-mesitylimino-3-methyl- 3,4-dihydro-2(1H)-pyrimidinone polymorphs.

PubMed

Miyamae, A; Kitamura, S; Tada, T; Koda, S; Yasuda, T

1991-10-01

The polymorphism of (E)-6-(3,4-dimethoxyphenyl)-1-ethyl-4-mesitylimino-3-methyl-3,4-di hydro- 2(1 H)-pyrimidinone (FK664; 1) was characterized by using X-ray powder diffractometry, differential scanning calorimetry (DSC), and IR spectroscopy. Structures of two polymorphs (Forms A and B) were determined by X-ray crystallographic analysis. Form A crystallized in the monoclinic space group P2(1)/c, with a = 13.504(2), b = 6.733(1), c = 24.910(8) A, beta = 96.55(4) degrees, z = 4, and dcal = 1.203 g/cm3, while Form B crystallized in the same space group, with a = 8.067(2), b = 15.128(4), c = 18.657(4) A, beta = 102.34(3) degrees, z = 4, and dcal = 1.216 g/cm3. The conformational features of 1 were very similar between the two polymorphs. Compound 1, in both crystal forms, took an energetically reasonable conformation in three rigid planes, such as 2-pyrimidone, trimethylphenyl, and dimethoxyphenyl rings, but the molecules were packed in different ways between the two polymorphs. In the Form B crystal, a short contact was possible, to form pi-pi interactions between two dimethoxyphenyl groups related with the inversion center in the crystal lattice; this interaction seems to contribute to stabilizing the crystal structure of Form B. Both Forms A and B showed only one endothermic peak due to fusion at 115 and 140 degrees C, respectively, on the DSC thermograms; therefore, it is suggested that there are no transition points between the two polymorphs. The heats of fusion obtained from the DSC thermograms were 33.2(2) kJ/mol for Form A and 36.8(1) kJ/mol for Form B.(ABSTRACT TRUNCATED AT 250 WORDS)

Genotypic and phenotypic predictors of inflammation in patients with chronic kidney disease.

PubMed

Luttropp, Karin; Debowska, Malgorzata; Lukaszuk, Tomasz; Bobrowski, Leon; Carrero, Juan Jesus; Qureshi, Abdul Rashid; Stenvinkel, Peter; Lindholm, Bengt; Waniewski, Jacek; Nordfors, Louise

2016-12-01

In complex diseases such as chronic kidney disease (CKD), the risk of clinical complications is determined by interactions between phenotypic and genotypic factors. However, clinical epidemiological studies rarely attempt to analyse the combined effect of large numbers of phenotype and genotype features. We have recently shown that the relaxed linear separability (RLS) model of feature selection can address such complex issues. Here, it is applied to identify risk factors for inflammation in CKD. The RLS model was applied in 225 CKD stage 5 patients sampled in conjunction with dialysis initiation. Fifty-seven anthropometric or biochemical measurements and 79 genetic polymorphisms were entered into the model. The model was asked to identify phenotypes and genotypes that, when combined, could separate inflamed from non-inflamed patients. Inflammation was defined as a high-sensitivity C-reactive protein concentration above the median (5 mg/L). Among the 60 genotypic and phenotypic features predicting inflammation, 31 were genetic. Among the 10 strongest predictors of inflammation, 8 were single nucleotide polymorphisms located in the NAMPT, CIITA, BMP2 and PIK3CB genes, whereas fibrinogen and bone mineral density were the only phenotypic biomarkers. These results indicate a larger involvement of hereditary factors in inflammation than might have been expected and suggest that inclusion of genotype features in risk assessment studies is critical. The RLS model demonstrates that inflammation in CKD is determined by an extensive panel of factors and may prove to be a suitable tool that could enable a much-needed multifactorial approach as opposed to the commonly utilized single-factor analysis. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Insights into the phase diagram of bismuth ferrite from quasiharmonic free-energy calculations

NASA Astrophysics Data System (ADS)

Cazorla, Claudio; Iñiguez, Jorge

2013-12-01

We have used first-principles methods to investigate the phase diagram of multiferroic bismuth ferrite (BiFeO3 or BFO), revealing the energetic and vibrational features that control the occurrence of various relevant structures. More precisely, we have studied the relative stability of four low-energy BFO polymorphs by computing their free energies within the quasiharmonic approximation, introducing a practical scheme that allows us to account for the main effects of spin disorder. As expected, we find that the ferroelectric ground state of the material (with R3c space group) transforms into an orthorhombic paraelectric phase (Pnma) upon heating. We show that this transition is not significantly affected by magnetic disorder, and that the occurrence of the Pnma structure relies on its being vibrationally (although not elastically) softer than the R3c phase. We also investigate a representative member of the family of nanotwinned polymorphs recently predicted for BFO [S. Prosandeev et al., Adv. Funct. Mater. 23, 234 (2013), 10.1002/adfm.201201467] and discuss their possible stabilization at the boundaries separating the R3c and Pnma regions in the corresponding pressure-temperature phase diagram. Finally, we elucidate the intriguing case of the so-called supertetragonal phases of BFO: Our results explain why such structures have never been observed in the bulk material, despite their being stable polymorphs of very low energy. Quantitative comparison with experiment is provided whenever possible, and the relative importance of various physical effects (zero-point motion, spin fluctuations, thermal expansion) and technical features (employed exchange-correlation energy density functional) is discussed. Our work attests the validity and usefulness of the quasiharmonic scheme to investigate the phase diagram of this complex oxide, and prospective applications are discussed.

Strengthening Incarcerated Families: Evaluating a Pilot Program for Children of Incarcerated Parents and Their Caregivers

PubMed Central

Miller, Alison L.; Perryman, Jamie; Markovitz, Lara; Franzen, Susan; Cochran, Shirley; Brown, Shavonnea

2013-01-01

Parental incarceration can be devastating for families. Children may experience difficulties, and the stress on caregivers who take on unexpected childrearing is high. We implemented and evaluated a family-level intervention with caregivers and children experiencing parental (typically maternal) incarceration, in a community setting. We partnered with a community-based organization serving families with an incarcerated parent to conduct a pilot trial of the Strengthening Families Program (SFP). Process evaluation indicated high implementation fidelity, satisfaction, engagement, and attendance. Outcome evaluation results indicated positive changes in family-level functioning, caregivers’ positive parenting, and caregiver depression symptoms from pre- to post-intervention, with some changes retained at follow-up 4 months later. Implications for preventive interventions with children of incarcerated parents, and their caregivers, are discussed. PMID:24353363

Strengthening Incarcerated Families: Evaluating a Pilot Program for Children of Incarcerated Parents and Their Caregivers.

PubMed

Miller, Alison L; Perryman, Jamie; Markovitz, Lara; Franzen, Susan; Cochran, Shirley; Brown, Shavonnea

2013-10-01

Parental incarceration can be devastating for families. Children may experience difficulties, and the stress on caregivers who take on unexpected childrearing is high. We implemented and evaluated a family-level intervention with caregivers and children experiencing parental (typically maternal) incarceration, in a community setting. We partnered with a community-based organization serving families with an incarcerated parent to conduct a pilot trial of the Strengthening Families Program (SFP). Process evaluation indicated high implementation fidelity, satisfaction, engagement, and attendance. Outcome evaluation results indicated positive changes in family-level functioning, caregivers' positive parenting, and caregiver depression symptoms from pre- to post-intervention, with some changes retained at follow-up 4 months later. Implications for preventive interventions with children of incarcerated parents, and their caregivers, are discussed.

MicroRNA-196a2 Biomarker and Targetome Network Analysis in Solid Tumors.

PubMed

Toraih, Eman A; Fawzy, Manal S; Mohammed, Eman A; Hussein, Mohammad H; El-Labban, Mohamad M

2016-12-01

MicroRNAs (miRNAs) have been linked to cancer development and progression. The molecular mechanisms underlying the genetic associations of the miRNA single nucleotide polymorphism with cancer vary by cancer site. As there are no previous studies on the miR-196a2 variant or expression in any type of cancer among our population, we aimed to determine the expression profile of mature miR-196a2 in various types of solid tumors and to analyze the impact of its polymorphism (rs11614913; C/T) on the expression levels. The study included 230 cancer patients (including 17 types of cancer), 26 patients with pre-cancer lesions, and 100 unrelated controls. Archived formalin-fixed, paraffin-embedded specimens (n = 197) were available for both miRNA expression analysis and single nucleotide polymorphism identification. Venous blood was collected from 59 histologically confirmed sporadic cancer patients and the study controls for single nucleotide polymorphism identification. Real-time polymerase chain reaction analysis was performed for allelic discrimination and relative quantification of miR-196a2 in the study samples. In silico target gene prediction and network analysis was performed. We found that individuals with the T variant were associated with cancer risk under all genetic association models, especially in colorectal, esophageal, skin, lung, thyroid, and renal cancer. Overall and stratified analysis showed miR-196a2 over-expression in most of the current malignant tumor samples relative to their corresponding cancer-free tissues. Carriers of the C allele had significantly higher expression levels of miR-196a2. Correlation with the clinicopathological features of cancer showed organ-specific effects. Gene enrichment analysis of predicted and validated targets speculated the putative role of miR-196a2 in cancer-associated biology. We highlighted cancer-type specific expression profiles of miR-196a2, which was correlated with the clinicopathological features in various types of cancer. Taken together, our results suggest that the miRNA signature could have promising diagnostic and prognostic significance.

Molecular analysis of MLH1 variants in Chinese sporadic colorectal cancer patients.

PubMed

Peng, H X; Xu, X; Yang, R; Chu, Y M; Yang, D M; Xu, Y; Zhou, F L; Ma, W Z; Zhang, X J; Guan, M; Yang, Z H; Jin, Z D

2016-04-26

Single nucleotide polymorphisms (SNPs) in mismatch repair genes, especially in the MLH1 gene, are closely associated with susceptibility to hereditary nonpolyposis colorectal cancer. However, few relevant findings are available regarding the association between sporadic colorectal cancer (SCRC) and SNPs of MLH1 in Chinese patients. Therefore, the present study aimed to describe the pathogenic association between three important MLH1 polymorphisms and SCRC in the Chinese population. Peripheral blood samples from 156 SCRC patients and 311 healthy controls were collected. DNA was purified from peripheral blood, and the V384D, R217C, and I219V polymorphisms were evaluated using high-resolution melting analysis and direct sequencing. The association between the three important MLH1 polymorphisms and clinical pathological features of the SCRC patients was analyzed. In addition, PMS2-MLH1 protein interactions were determined by co-immunoprecipitation (Co-IP) to determine the protein functional alteration induced by these SNPs. Among the three polymorphisms, V384D was significantly associated with the risk of SCRC (OR = 31.36, P < 0.0001). The allele frequencies were 4.81 and 0.16% in the SCRC group. No association was found between SCRC and R217C, or between SCRC and I219V. Moreover, the allele frequency of R217C was significantly higher in the SCRC patients younger than 60 years than in those older than 60 years. Co-IP showed that the MLH1 R217C, V384D, and I219V variants had relative binding abilities with PMS2 of 0.59, 0.70, and 0.80, respectively, compared with the wild-type. These findings suggest that MLH1 V384D could be a promising genetic marker for susceptibility to SCRC.

Interferon regulatory factor 5 (IRF5) gene variants are associated with multiple sclerosis in three distinct populations

PubMed Central

Kristjansdottir, G; Sandling, J K; Bonetti, A; Roos, I M; Milani, L; Wang, C; Gustafsdottir, S M; Sigurdsson, S; Lundmark, A; Tienari, P J; Koivisto, K; Elovaara, I; Pirttilä, T; Reunanen, M; Peltonen, L; Saarela, J; Hillert, J; Olsson, T; Landegren, U; Alcina, A; Fernández, O; Leyva, L; Guerrero, M; Lucas, M; Izquierdo, G; Matesanz, F; Syvänen, A-C

2008-01-01

Background: IRF5 is a transcription factor involved both in the type I interferon and the toll-like receptor signalling pathways. Previously, IRF5 has been found to be associated with systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel diseases. Here we investigated whether polymorphisms in the IRF5 gene would be associated with yet another disease with features of autoimmunity, multiple sclerosis (MS). Methods: We genotyped nine single nucleotide polymorphisms and one insertion-deletion polymorphism in the IRF5 gene in a collection of 2337 patients with MS and 2813 controls from three populations: two case–control cohorts from Spain and Sweden, and a set of MS trio families from Finland. Results: Two single nucleotide polymorphism (SNPs) (rs4728142, rs3807306), and a 5 bp insertion-deletion polymorphism located in the promoter and first intron of the IRF5 gene, showed association signals with values of p<0.001 when the data from all cohorts were combined. The predisposing alleles were present on the same common haplotype in all populations. Using electrophoretic mobility shift assays we observed allele specific differences in protein binding for the SNP rs4728142 and the 5 bp indel, and by a proximity ligation assay we demonstrated increased binding of the transcription factor SP1 to the risk allele of the 5 bp indel. Conclusion: These findings add IRF5 to the short list of genes shown to be associated with MS in more than one population. Our study adds to the evidence that there might be genes or pathways that are common in multiple autoimmune diseases, and that the type I interferon system is likely to be involved in the development of these diseases. PMID:18285424

Methylation-sensitive amplification polymorphism in date palms (Phoenix dactylifera L.) and their off-shoots.

PubMed

Fang, J-G; Chao, C T

2007-07-01

DNA methylation plays an important role in the regulation of gene expression in eukaryotes. In this study, the extent and patterns of DNA methylation were assessed in date palm mother-plants and their off-shoots using the methylation-sensitive amplified polymorphism (MSAP) technique. Three types of bands were generated using 12 pairs of primers. Type I were present in both ECOR I + HPA II and ECOR I + MSP I lanes; type II were present in ECOR I + HPA II lanes, but not in ECOR I + MSP I lanes; and type III bands were present in ECOR I + MSP I lanes, but not in ECOR I + HPA II lanes. The total numbers of these three types of bands were 782, 55, and 34, respectively. Among these three types of bands, the polymorphic bands were, respectively, 37, 10, and 0. The distribution of polymorphic bands among mother-plants and off-shoots suggests the methylation variation was present in both the mother-plants and off-shoots. Forty- four out of these 47 polymorphic bands show clear difference between mother-plant and off-shoots: 38 were present only in off-shoots and 6 in both mother-plants and off-shoots. Compared to methylation status in mother-plants, the methylation variation during off-shoot growth of date palm can be characterized as a process involving primarily de-methylation. Hypomethylation of DNA in off-shoots, compared with mother-plants, reflects the marked expression of this molecular feature, which may be related to gene expression during off-shoot development. The methylation or de-methylation status of specific loci in the mother-plants and their off-shoots were probably random events.

Increased risk of incident stroke associated with the cyclooxygenase 2 (COX-2) G-765C polymorphism in African-Americans: the Atherosclerosis Risk in Communities Study.

PubMed

Kohsaka, Shun; Volcik, Kelly A; Folsom, Aaron R; Wu, Kenneth K; Ballantyne, Christie M; Willerson, James T; Boerwinkle, Eric

2008-02-01

A hallmark feature of atherosclerosis is inflammation mediated by prostaglandins (PGs) catalyzed by the enzyme cyclooxygenase (COX). The present study explored whether the COX-2 G-765C polymorphism contributes to increased incidence of coronary heart disease (CHD) or stroke in the large prospective Atherosclerosis Risk in Communities (ARIC) Study. Incidences of CHD and stroke were identified through annual follow-up and hospital and death certificate surveillance. The study included 1488 incident CHD and 527 stroke events after an average of 14 years of follow-up. The frequency of the -765C variant allele was markedly different between African-Americans and whites, therefore all analyses were performed separately by race. Due to the small number of persons with the -765CC genotype, heterozygous and homozygous variant genotypes were combined for this analysis. The COX-2 G-765C polymorphism was not a significant predictor of CHD in either racial group, but it was a significant predictor of incident stroke in African-Americans. After adjustment for age and gender, the hazard rate ratio for developing stroke for the CG+CC genotypes relative to the GG genotype was 1.34 (95% confidence interval [CI] 1.03-1.74, P=0.03) in African-Americans. This result was essentially unchanged when established predictors such as smoking, diabetes and hypertension were added to the model (HRR 1.34, 95%CI 1.03-1.76, P=0.03). We have found the COX-2 G-765C polymorphism to be a risk factor for incident stroke in African-Americans. This study provides additional evidence for utilizing inflammation-related genetic polymorphisms for identifying individuals at increased risk for stroke.

THE GSTP1 c.313A>G POLYMORPHISM MODULATES THE CARDIORESPIRATORY RESPONSE TO AEROBIC TRAINING.

PubMed

Zarebska, A; Jastrzebski, Z; Kaczmarczyk, M; Ficek, K; Maciejewska-Karlowska, A; Sawczuk, M; Leońska-Duniec, A; Krol, P; Cieszczyk, P; Zmijewski, P; Eynon, N

2014-12-01

The GSTP1 c.313A>G polymorphism is a candidate to explain some of the individual differences in cardiorespiratory fitness phenotypes' responses to aerobic exercise training. We aim to explore the association between the GSTP1 c.313A>G polymorphism and the response to low-high impact aerobic exercise training. Sixty-six Polish Caucasian women were genotyped for the GSTP1 c.313A>G polymorphism; 62 of them completed 12-week aerobic (50-75% HRmax) exercise training and were measured for selected somatic features (body mass and BMI) and cardiorespiratory fitness indices - maximal oxygen uptake (VO2max, maximum heart rate (HRmax), maximum ventilation (VEmax) and anaerobic threshold (AT) - before and after the training period. Two-factor analysis of variance revealed a main training effect for body mass reduction (p=0.007) and BMI reduction (p=0.013), improvements of absolute and relative VO2max (both p<0.001), and increased VEmax (p=0.005), but not for changes in fat-free mass (FFM) (p=0.162). However, a significant training x GSTP1 c.313A>G interaction was found only for FFM (p=0.042), absolute and relative VO2max (p=0.029 and p=0.026), and VEmax (p=0.005). As the result of training, significantly greater improvements in VO2max, VEmax and FFM were gained by the GG+GA group compared to the AA genotype group. The results support the hypothesis that heterogeneity in individual response to training stimuli is at least in part determined by genetics, and GSTP1 c.313A>G may be considered as one (of what appear to be many) target polymorphisms to influence these changes.

THE GSTP1 c.313A>G POLYMORPHISM MODULATES THE CARDIORESPIRATORY RESPONSE TO AEROBIC TRAINING

PubMed Central

Zarebska, A; Jastrzebski, Z; Kaczmarczyk, M; Ficek, K; Maciejewska-Karlowska, A; Sawczuk, M; Leońska-Duniec, A; Krol, P; Cieszczyk, P; Zmijewski, P

2014-01-01

The GSTP1 c.313A>G polymorphism is a candidate to explain some of the individual differences in cardiorespiratory fitness phenotypes’ responses to aerobic exercise training. We aim to explore the association between the GSTP1 c.313A>G polymorphism and the response to low-high impact aerobic exercise training. Sixty-six Polish Caucasian women were genotyped for the GSTP1 c.313A>G polymorphism; 62 of them completed 12-week aerobic (50-75% HRmax) exercise training and were measured for selected somatic features (body mass and BMI) and cardiorespiratory fitness indices – maximal oxygen uptake (VO2max, maximum heart rate (HRmax), maximum ventilation (VEmax) and anaerobic threshold (AT) – before and after the training period. Two-factor analysis of variance revealed a main training effect for body mass reduction (p=0.007) and BMI reduction (p=0.013), improvements of absolute and relative VO2max (both p<0.001), and increased VEmax (p=0.005), but not for changes in fat-free mass (FFM) (p=0.162). However, a significant training x GSTP1 c.313A>G interaction was found only for FFM (p=0.042), absolute and relative VO2max (p=0.029 and p=0.026), and VEmax (p=0.005). As the result of training, significantly greater improvements in VO2max, VEmax and FFM were gained by the GG+GA group compared to the AA genotype group. The results support the hypothesis that heterogeneity in individual response to training stimuli is at least in part determined by genetics, and GSTP1 c.313A>G may be considered as one (of what appear to be many) target polymorphisms to influence these changes. PMID:25435667

Association of the brain-derived neurotrophic factor Val66Met polymorphism with negative symptoms severity, but not cognitive function, in first-episode schizophrenia spectrum disorders.

PubMed

Mezquida, G; Penadés, R; Cabrera, B; Savulich, G; Lobo, A; González-Pinto, A; Penzol, M J; Corripio, I; Fernandez-Egea, E; Gassó, P; Cuesta, M J; Bernardo, M

2016-10-01

A functional polymorphism of the brain-derived neurotrophic factor gene (BDNF) Val66Met has been associated with cognitive function and symptom severity in patients with schizophrenia. It has been suggested that the Val66Met polymorphism has a role as a modulator in a range of clinical features of the illness, including symptoms severity, therapeutic responsiveness, age of onset, brain morphology and cognitive function. However, little work has been done in first-episode schizophrenia (FES) spectrum disorders. The objective of this study is to investigate the association of the BDNF Val66Met polymorphism on cognitive function and clinical symptomatology in FES patients. Using a cross-sectional design in a cohort of 204 patients with FES or a schizophrenia spectrum disorder and 204 healthy matched controls, we performed BDNF Val66Met genotyping and tested its relationship with cognitive testing (attention, working memory, learning/verbal memory and reasoning/problem-solving) and assessment of clinical symptom severity. There was no significant influence of the BDNF allele frequency on cognitive factor scores in either patients or controls. An augmented severity of negative symptoms was found in FES patients that carried the Met allele. The results of this study suggest that in patients with a first-episode of schizophrenia or a schizophrenia spectrum disorder, the BDNF Val66Met polymorphism does not exert an influence on cognitive functioning, but is associated with negative symptoms severity. BDNF may serve as suitable marker of negative symptomatology severity in FES patients within the schizophrenia spectrum. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Analysis of Sequence Diversity at the Highly Polymorphic Cpgp40/15 Locus among Cryptosporidium Isolates from Human Immunodeficiency Virus-Infected Children in South Africa

PubMed Central

Leav, Brett A.; Mackay, Malanie R.; Anyanwu, Akudo; O' Connor, Roberta M.; Cevallos, Ana Maria; Kindra, Gurpreet; Rollins, Nigel C.; Bennish, Michael L.; Nelson, Richard G.; Ward, Honorine D.

2002-01-01

Cryptosporidium sp. is a significant cause of diarrheal disease, particularly in human immunodeficiency virus (HIV)-infected patients in developing countries. We recently cloned and sequenced several alleles of the highly polymorphic single-copy Cryptosporidium parvum gene Cpgp40/15. This gene encodes a precursor protein that is proteolytically cleaved to yield mature cell surface glycoproteins gp40 and gp15, which are implicated in zoite attachment to and invasion of enterocytes. The most-striking feature of the Cpgp40/15 alleles and proteins is their unprecedented degree of sequence polymorphism, which is far greater than that observed for any other gene or protein studied in C. parvum to date. In this study we analyzed nucleic acid and amino acid sequence polymorphism at the Cpgp40/15 locus of 20 C. parvum isolates from HIV-infected South African children. Fifteen isolates exhibited one of four previously identified genotype I alleles at the Cpgp40/15 locus (Ia, Ib, Ic, and Id), while five displayed a novel set of polymorphisms that defined a new Cpgp40/15 genotype I allele, designated genotype Ie. Surprisingly, only 15 of these isolates exhibited concordant type I alleles at the thrombospondin-related adhesive protein of Cryptosporidium and Cryptosporidium oocyst wall protein loci, while five isolates (all of which displayed Cpgp40/15 genotype Ic alleles) displayed genotype II alleles at these loci. Furthermore, the last five isolates also manifested chimeric genotype Ic/Ib or Ic/II alleles at the Cpgp40/15 locus, raising the possibility of sexual recombination within and between prototypal parasite genotypes. Lastly, children infected with isolates having genotype Ic alleles were significantly older than those infected with isolates displaying other genotype I alleles. PMID:12065532

Interferon regulatory factor 5 gene polymorphism in Egyptian children with systemic lupus erythematosus.

PubMed

Hammad, A; Mossad, Y M; Nasef, N; Eid, R

2017-07-01

Background Increased expression of interferon-inducible genes is implicated in the pathogenesis of systemic lupus erythematosus (SLE). Interferon regulatory factor 5 (IRF5) is one of the transcription factors regulating interferon and was proved to be implicated in the pathogenesis of SLE in different populations. Objectives The objective of this study was to investigate the correlation between polymorphisms of the IRF5 gene and SLE susceptibility in a cohort of Egyptian children and to investigate their association with clinico-pathological features, especially lupus nephritis. Subjects and methods Typing of interferon regulatory factor 5 rs10954213, rs2004640 and rs2280714 polymorphisms were done using polymerase chain reaction-restriction fragment length polymorphism for 100 children with SLE and 100 matched healthy controls. Results Children with SLE had more frequent T allele and TT genotype of rs2004640 ( P c  = 0.003 and 0.024, respectively) compared to controls. Patients with nephritis had more frequent T allele of rs2004640 compared to controls ( P c  = 0.003). However the allele and genotype frequencies of the three studied polymorphisms did not show any difference in patients with nephritis in comparison to those without nephritis. Haplotype GTA of rs10954213, rs2004640 and rs2280714, respectively, was more frequent in lupus patients in comparison to controls ( p = 0.01) while the haplotype GGG was more frequent in controls than lupus patients ( p = 0.011). Conclusion The rs2004640 T allele and TT genotype and GTA haplotype of rs rs10954213, rs2004640, and rs2280714, respectively, can be considered as risk factors for the development of SLE. The presence of the rs2004640 T allele increases the risk of nephritis development in Egyptian children with SLE.

EnsembleGASVR: a novel ensemble method for classifying missense single nucleotide polymorphisms.

PubMed

Rapakoulia, Trisevgeni; Theofilatos, Konstantinos; Kleftogiannis, Dimitrios; Likothanasis, Spiros; Tsakalidis, Athanasios; Mavroudi, Seferina

2014-08-15

Single nucleotide polymorphisms (SNPs) are considered the most frequently occurring DNA sequence variations. Several computational methods have been proposed for the classification of missense SNPs to neutral and disease associated. However, existing computational approaches fail to select relevant features by choosing them arbitrarily without sufficient documentation. Moreover, they are limited to the problem of missing values, imbalance between the learning datasets and most of them do not support their predictions with confidence scores. To overcome these limitations, a novel ensemble computational methodology is proposed. EnsembleGASVR facilitates a two-step algorithm, which in its first step applies a novel evolutionary embedded algorithm to locate close to optimal Support Vector Regression models. In its second step, these models are combined to extract a universal predictor, which is less prone to overfitting issues, systematizes the rebalancing of the learning sets and uses an internal approach for solving the missing values problem without loss of information. Confidence scores support all the predictions and the model becomes tunable by modifying the classification thresholds. An extensive study was performed for collecting the most relevant features for the problem of classifying SNPs, and a superset of 88 features was constructed. Experimental results show that the proposed framework outperforms well-known algorithms in terms of classification performance in the examined datasets. Finally, the proposed algorithmic framework was able to uncover the significant role of certain features such as the solvent accessibility feature, and the top-scored predictions were further validated by linking them with disease phenotypes. Datasets and codes are freely available on the Web at http://prlab.ceid.upatras.gr/EnsembleGASVR/dataset-codes.zip. All the required information about the article is available through http://prlab.ceid.upatras.gr/EnsembleGASVR/site.html. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Breccia dikes from the Beaverhead Impact structure, southwest Montana

NASA Technical Reports Server (NTRS)

Fiske, P. S.; Hougen, S. B.; Hargraves, R. B.

1992-01-01

While shatter cones are generally accepted as indicators of meteorite impact, older petrologic features are not widely recognized in the geologic community. Breccia dikes are one such feature. They are found in many large impact structures occurring over an area at least as extensively as shatter cones. Breccia dikes will survive moderate degrees of metamorphism and tectonism, unlike many other microscopic features (shocked quartz grains, high-pressure polymorphs, etc.) and even large-scale features such as annular or bowl-shaped topographic features. Thus, they are important diagnostic criteria, especially for large, poorly preserved impact structures. The Beaverhead Impact structure is a recently discovered, deeply eroded impact structure in southwestern Montana. The remains of the structure are delineated by the occurrence of shatter cones, found in an area greater than 200 sq km, occurring within the Cabin thrust plate, part of the Cretaceous Sevier fold and thrust system. The distribution of shatter cones is further truncated by Tertiary normal faults. The present remains represent an allochthonous fragment of a larger structure.

Shape-designed frustration by local polymorphism in a near-equilibrium colloidal glass.

PubMed

Zhao, Kun; Mason, Thomas G

2015-09-29

We show that hard, convex, lithographic, prismatic kite platelets, each having three 72° vertices and one 144° vertex, preferentially form a disordered and arrested 2D glass when concentrated quasi-statically in a monolayer while experiencing thermal Brownian fluctuations. By contrast with 2D systems of other hard convex shapes, such as squares, rhombs, and pentagons, which readily form crystals at high densities, 72° kites retain a liquid-like disordered structure that becomes frozen-in as their long-time translational and rotational diffusion become highly bounded, yielding a 2D colloidal glass. This robust glass-forming propensity arises from competition between highly diverse few-particle local polymorphic configurations (LPCs) that have incommensurate features and symmetries. Thus, entropy maximization is consistent with the preservation of highly diverse LPCs en route to the arrested glass.

Inherent structures of crystalline pentacene

NASA Astrophysics Data System (ADS)

Della Valle, Raffaele Guido; Venuti, Elisabetta; Brillante, Aldo; Girlando, Alberto

2003-01-01

Using a quasi-Monte Carlo scheme, we search the potential energy surface of crystalline pentacene to sample its local minima, which represent the "inherent" structures, i.e., the possible configurations of mechanical equilibrium. The system is described in terms of rigid molecules interacting through a standard atom-atom potential model. Several hundreds of distinct minima are encountered, with a surprising variety of structural arrangements. We find that deep minima are easily accessible because they exhibit a favorable energy distribution and their attraction basins tend to be wide. Thanks to these features of the potential surface, the localization the global minimum becomes entirely feasible, allowing reliable a priori predictions of the crystallographic structures. The results for pentacene are very satisfactory. In fact, the two deepest minima correspond to the structures of the two known experimental polymorphs, which are described correctly. Further polymorphs are also likely to exist.

Dynamically Alterable Arrays of Polymorphic Data Types

NASA Technical Reports Server (NTRS)

James, Mark

2006-01-01

An application library package was developed that represents data packets for Deep Space Network (DSN) message packets as dynamically alterable arrays composed of arbitrary polymorphic data types. The software was to address a limitation of the present state of the practice for having an array directly composed of a single monomorphic data type. This is a severe limitation when one is dealing with science data in that the types of objects one is dealing with are typically not known in advance and, therefore, are dynamic in nature. The unique feature of this approach is that it enables one to define at run-time the dynamic shape of the matrix with the ability to store polymorphic data types in each of its indices. Existing languages such as C and C++ have the restriction that the shape of the array must be known in advance and each of its elements be a monomorphic data type that is strictly defined at compile-time. This program can be executed on a variety of platforms. It can be distributed in either source code or binary code form. It must be run in conjunction with any one of a number of Lisp compilers that are available commercially or as shareware.

Mutations and new polymorphic changes in the TCOF1 gene of patients with oculo-auriculo-vertebral spectrum and Treacher-Collins syndrome.

PubMed

Su, Pen-Hua; Yu, Ju-Shan; Chen, Jia-Yuh; Chen, Suh-Jen; Li, Shuan-Yow; Chen, Hsiao-Neng

2007-10-01

Oculo-auriculo-vertebral spectrum, the exact genetic predisposition of which has not yet been resolved, is characterized by varying degrees of the prevalently unilateral underdevelopment of craniofacial structures and spinal anomalies. Here, we analyzed four cases exhibiting multiple features of oculo-auriculo-vertebral spectrum and one case with Treacher-Collins syndrome. The cranium was analyzed using three-dimensional computed tomography, which reliably identifies craniofacial malformations. We detected one typical oculo-auriculo-vertebral spectrum patient who had a missense mutation in exon 9 of the TCOF1 gene complex and two silent mutations in exons 10 and 23, three partial oculo-auriculo-vertebral spectrum patients who had no detectable mutations in the TCOF1 gene complex, and one Treacher-Collins syndrome patient who had a nonsense mutation in exon 14. All five patients had eight previously reported polymorphic changes in the TCOF1 exons 10, 11, 12, 16, 21, 22, and 23, and four unreported polymorphisms in exons 9, 17, and 22 that were also detected in 51 Taiwanese control patients. These observations strongly suggest that the TCOF1 genetic changes observed in these five patients might be related to oculo-auriculo-vertebral spectrum symptoms.

MHC class I chain-related A: Polymorphism, regulation and therapeutic value in cancer.

PubMed

Yang, Xi; Kuang, Shuzhen; Wang, Liangjiang; Wei, Yanzhang

2018-07-01

MICA and MICB are stress-induced molecules recognized by NKG2D, one of major activation receptors of natural killer (NK) cells. Upon binding to NKG2D, NKG2D-mediated cytolytic immune response of immune effector cells will be activated against virally infected and tumor cells expressing MICA. In the early oncogenic development, membrane-bound MICA serves as a key signal to recruit anti-tumor immune effectors. Nevertheless, both MICA polymorphic features and its dysregulated expression in evolving tumors have resulted in tumor evasion in various cancer types. Therefore, in order to reconstitute tumor immunosurveilance, it is of great significance that we understand MICA genetics, polymorphisms, mechanisms of MICA-associated tumor escape and molecular/cellular modulation of MICA. In this review, the MICA-associated co-expression networks involving microRNAs (miRNAs) and novel candidate long non-coding RNAs (lncRNAs) were also discussed. Given the current importance in the study of MICA gene, this review paper focuses on the role of MICA in different cancer types, and strategies that we manipulate MICA regulation against tumor proliferation. Copyright © 2018. Published by Elsevier Masson SAS.

[Molecular techniques applied in species identification of Toxocara].

PubMed

Fogt, Renata

2006-01-01

Toxocarosis is still an important and actual problem in human medicine. It can manifest as visceral (VLM), ocular (OLM) or covert (CT) larva migrans syndroms. Complicated life cycle of Toxocara, lack of easy and practical methods of species differentiation of the adult nematode and embarrassing in recognition of the infection in definitive hosts create difficulties in fighting with the infection. Although studies on human toxocarosis have been continued for over 50 years there is no conclusive answer, which of species--T. canis or T. cati constitutes a greater risk of transmission of the nematode to man. Neither blood serological examinations nor microscopic observations of the morphological features of the nematode give the satisfied answer on the question. Since the 90-ths molecular methods were developed for species identification and became useful tools being widely applied in parasitological diagnosis. This paper cover the survey of methods of DNA analyses used for identification of Toxocara species. The review may be helpful for researchers focused on Toxocara and toxocarosis as well as on detection of new species. The following techniques are described: PCR (Polymerase Chain Reaction), RFLP (Restriction Fragment Length Polymorphism), RAPD (Random Amplified Polymorphic DNA) and SSCP (Single Strand Conformation Polymorphism).

Genetic Polymorphism and Expression of CXCR4 in Breast Cancer

PubMed Central

Ariza, Carolina Batista; de Oliveira, Carlos Eduardo Coral; Losi Guembarovski, Roberta; Banin Hirata, Bruna Karina; Vitiello, Glauco Akelinghton Freire; Campos, Clodoaldo Zago; Watanabe, Maria Angelica Ehara

2015-01-01

CXCR4 genetic polymorphisms, as well as their expression level, have been associated with cancer development and prognosis. The present study aimed to investigate the influence of CXCR4 rs2228014 polymorphism on its mRNA and protein expression in breast cancer samples. It was observed that patients presented higher CXCR4 mRNA relative expression (5.7-fold) than normal mammary gland, but this expression was not correlated with patients clinicopathological features (nuclear grade, nodal status, ER status, PR status, p53 staining, Ki67 index, and HER-2 status). Moreover, CXCR4 mRNA relative expression also did not differ regarding the presence or absence of T allele (p = 0.301). In the immunohistochemical assay, no difference was observed for CXCR4 cytoplasmic protein staining in relation to different genotypes (p = 0.757); however, high cytoplasmic CXCR4 staining was verified in invasive breast carcinoma (p < 0.01). All in all, the results from present study indicated that rs2228014 genetic variant does not alter CXCR4 mRNA or protein expression. However, this receptor was more expressed in tumor compared to normal tissue, in both RNA and protein levels, suggesting its promising applicability in the general context of mammary carcinogenesis. PMID:26576337

Correlative Raman spectroscopy and focused ion beam for targeted phase boundary analysis of titania polymorphs

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

Mangum, John S.; Chan, Lisa H.; Schmidt, Ute

Site-specific preparation of specimens using focused ion beam instruments for transmission electron microscopy is at the forefront of targeting regions of interest for nanoscale characterization. Typical methods of pinpointing desired features include electron backscatter diffraction for differentiating crystal structures and energy-dispersive X-Ray spectroscopy for probing compositional variations. Yet there are situations, notably in the titanium dioxide system, where these techniques can fail. Differentiating between the brookite and anatase polymorphs of titania is either excessively laborious or impossible with the aforementioned techniques. However, due to differences in bonding structure, Raman spectroscopy serves as an ideal candidate for polymorph differentiation. In thismore » work, a correlative approach utilizing Raman spectroscopy for targeted focused ion beam specimen preparation was employed. Dark field imaging and diffraction in the transmission electron microscope confirmed the region of interest located via Raman spectroscopy and demonstrated the validity of this new method. Correlative Raman spectroscopy, scanning electron microscopy, and focused ion beam is shown to be a promising new technique for identifying site-specific preparation of nanoscale specimens in cases where conventional approaches do not suffice.« less

Correlative Raman spectroscopy and focused ion beam for targeted phase boundary analysis of titania polymorphs.

PubMed

Mangum, John S; Chan, Lisa H; Schmidt, Ute; Garten, Lauren M; Ginley, David S; Gorman, Brian P

2018-05-01

Site-specific preparation of specimens using focused ion beam instruments for transmission electron microscopy is at the forefront of targeting regions of interest for nanoscale characterization. Typical methods of pinpointing desired features include electron backscatter diffraction for differentiating crystal structures and energy-dispersive X-Ray spectroscopy for probing compositional variations. Yet there are situations, notably in the titanium dioxide system, where these techniques can fail. Differentiating between the brookite and anatase polymorphs of titania is either excessively laborious or impossible with the aforementioned techniques. However, due to differences in bonding structure, Raman spectroscopy serves as an ideal candidate for polymorph differentiation. In this work, a correlative approach utilizing Raman spectroscopy for targeted focused ion beam specimen preparation was employed. Dark field imaging and diffraction in the transmission electron microscope confirmed the region of interest located via Raman spectroscopy and demonstrated the validity of this new method. Correlative Raman spectroscopy, scanning electron microscopy, and focused ion beam is shown to be a promising new technique for identifying site-specific preparation of nanoscale specimens in cases where conventional approaches do not suffice. Copyright © 2018 Elsevier B.V. All rights reserved.

Correlative Raman spectroscopy and focused ion beam for targeted phase boundary analysis of titania polymorphs

DOE PAGES

Mangum, John S.; Chan, Lisa H.; Schmidt, Ute; ...

2018-02-23

Site-specific preparation of specimens using focused ion beam instruments for transmission electron microscopy is at the forefront of targeting regions of interest for nanoscale characterization. Typical methods of pinpointing desired features include electron backscatter diffraction for differentiating crystal structures and energy-dispersive X-Ray spectroscopy for probing compositional variations. Yet there are situations, notably in the titanium dioxide system, where these techniques can fail. Differentiating between the brookite and anatase polymorphs of titania is either excessively laborious or impossible with the aforementioned techniques. However, due to differences in bonding structure, Raman spectroscopy serves as an ideal candidate for polymorph differentiation. In thismore » work, a correlative approach utilizing Raman spectroscopy for targeted focused ion beam specimen preparation was employed. Dark field imaging and diffraction in the transmission electron microscope confirmed the region of interest located via Raman spectroscopy and demonstrated the validity of this new method. Correlative Raman spectroscopy, scanning electron microscopy, and focused ion beam is shown to be a promising new technique for identifying site-specific preparation of nanoscale specimens in cases where conventional approaches do not suffice.« less

Incidence of Clostridium perfringens in commercially produced cured raw meat product mixtures and behavior in cooked products during chilling and refrigerated storage.

PubMed

Taormina, Peter J; Bartholomew, Gene W; Dorsa, Warren J

2003-01-01

A total of 445 whole-muscle and ground or emulsified raw pork, beef, and chicken product mixtures acquired from industry sources were monitored over a 10-month period for vegetative and spore forms of Clostridium perfringens. Black colonies that formed on Shahidi-Ferguson perfringens (SFP) agar after 24 h at 37 degrees C were considered presumptive positive. Samples that were positive after a 15-min heat shock at 75 degrees C were considered presumptive positive for spores. Of 194 cured whole-muscle samples, 1.6% were positive; spores were not detected from those samples. Populations of vegetative cells did not exceed 1.70 log10 CFU/g and averaged 1.56 log10 CFU/g. Of 152 cured ground or emulsified samples, 48.7% were positive, and 5.3% were positive for spores. Populations of vegetative cells did not exceed 2.72 log10 CFU/g and averaged 1.98 log10 CFU/g; spores did not exceed 2.00 log10 CFU/g and averaged 1.56 log10 CFU/g. Raw bologna (70% chicken), chunked ham with emulsion, and whole-muscle ham product mixtures were inoculated with C. perfringens spores (ATCC 12916, ATCC 3624, FD1041, and two product isolates) to ca. 3.0 log10 CFU/g before being subjected either to thermal processes mimicking cooking and chilling regimes determined by in-plant temperature probing or to cooking and extended chilling regimes. Populations of C. perfringens were recovered on SFP from each product at the peak cook temperatures, at 54.4, 26.7, and 7.2 degrees C, and after up to 14 days of storage under vacuum at 4.4 degrees C. In each product, populations remained relatively unchanged during chilling from 54.4 to 7.2 degrees C and declined slightly during refrigerated storage. These findings indicate processed meat products cured with sodium nitrite are not at risk for the growth of C. perfringens during extended chilling and cold storage.

Distribution of putative adhesins in different seropathotypes of Shiga toxin-producing Escherichia coli.

PubMed

Toma, Claudia; Martínez Espinosa, Estela; Song, Tianyan; Miliwebsky, Elizabeth; Chinen, Isabel; Iyoda, Sunao; Iwanaga, Masaaki; Rivas, Marta

2004-11-01

The distribution of eight putative adhesins that are not encoded in the locus for enterocyte effacement (LEE) in 139 Shiga toxin-producing Escherichia coli (STEC) of different serotypes was investigated by PCR. Five of the adhesins (Iha, Efa1, LPF(O157/OI-141), LPF(O157/OI-154), and LPF(O113)) are encoded in regions corresponding to genomic O islands of E. coli EDL933, while the other three adhesins have been reported to be encoded in the STEC megaplasmid of various serotypes (ToxB [O157:H7], Saa [O113:H21], and Sfp [O157:NM]). STEC strains were isolated from humans (n = 54), animals (n = 52), and food (n = 33). They were classified into five seropathotypes (A through E) based on the reported occurrence of STEC serotypes in human disease, in outbreaks, and in the hemolytic-uremic syndrome (M. A. Karmali, M. Mascarenhas, S. Shen, K. Ziebell, S. Johnson, R. Reid-Smith, J. Isaac-Renton, C. Clark, K. Rahn, and J. B. Kaper, J. Clin. Microbiol. 41:4930-4940, 2003). The most prevalent adhesin was that encoded by the iha gene (91%; 127 of 139 strains), which was distributed in all seropathotypes. toxB and efa1 were present mainly in strains of seropathotypes A and B, which were LEE positive. saa was present only in strains of seropathotypes C, D, and E, which were LEE negative. Two fimbrial genes, lpfA(O157/OI-141) and lpfA(O157/OI-154), were strongly associated with seropathotype A. The fimbrial gene lpfA(O113) was present in all seropathotypes except for seropathotype A, while sfpA was not present in any of the strains studied. The distribution of STEC adhesins depends mainly on serotypes and not on the source of isolation. Seropathotype A, which is associated with severe disease and frequently is involved in outbreaks, possesses a unique adhesin profile which is not present in the other seropathotypes. The wide distribution of iha in STEC strains suggested that it could be a candidate for vaccine development.

Rapid Genetic and Epigenetic Alterations under Intergeneric Genomic Shock in Newly Synthesized Chrysanthemum morifolium × Leucanthemum paludosum Hybrids (Asteraceae)

PubMed Central

Wang, Haibin; Jiang, Jiafu; Chen, Sumei; Qi, Xiangyu; Fang, Weimin; Guan, Zhiyong; Teng, Nianjun; Liao, Yuan; Chen, Fadi

2014-01-01

The Asteraceae family is at the forefront of the evolution due to frequent hybridization. Hybridization is associated with the induction of widespread genetic and epigenetic changes and has played an important role in the evolution of many plant taxa. We attempted the intergeneric cross Chrysanthemum morifolium × Leucanthemum paludosum. To obtain the success in cross, we have to turn to ovule rescue. DNA profiling of the amphihaploid and amphidiploid was investigated using amplified fragment length polymorphism, sequence-related amplified polymorphism, start codon targeted polymorphism, and methylation-sensitive amplification polymorphism (MSAP). Hybridization induced rapid changes at the genetic and the epigenetic levels. The genetic changes mainly involved loss of parental fragments and gaining of novel fragments, and some eliminated sequences possibly from the noncoding region of L. paludosum. The MSAP analysis indicated that the level of DNA methylation was lower in the amphiploid (∼45%) than in the parental lines (51.5–50.6%), whereas it increased after amphidiploid formation. Events associated with intergeneric genomic shock were a feature of C. morifolium × L. paludosum hybrid, given that the genetic relationship between the parental species is relatively distant. Our results provide genetic and epigenetic evidence for understanding genomic shock in wide crosses between species in Asteraceae and suggest a need to expand our current evolutionary framework to encompass a genetic/epigenetic dimension when seeking to understand wide crosses. PMID:24407856

Does the MTHFR A1298C Polymorphism Modulate the Cardiorespiratory Response to Training?

PubMed

Cięszczyk, Paweł; Zarębska, Aleksandra; Jastrzębski, Zbigniew; Sawczyn, Michał; Kozakiewicz-Drobnik, Izabela; Leońska-Duniec, Agata; Kaczmarczyk, Mariusz; Maciejewska-Skrendo, Agnieszka; Żmijewski, Piotr; Trybek, Grzegorz; Smółka, Wojciech; Pilch, Jan; Leźnicka, Katarzyna; Lulińska-Kuklik, Ewelina; Sawczuk, Marek; Massidda, Myosotis

2016-12-01

The 5,10-methylenetetrahydrofolate reductase gene (MTHFR) A1298C polymorphic variant is a candidate to explain the individual differences in trainability and response to exercise training. Therefore, the aim of the study was to verify whether the A1298C polymorphism influenced the aerobic and anaerobic performance as well as body and mass composition in young Polish women following low-high impact aerobic exercise training. Two hundred and one women aged 21 ± 1 years (range 19-24) were included in the study. All of them completed a 12-week exercise training program and were measured for selected somatic features, aerobic capacity and cardiorespiratory fitness indices as well as peak anaerobic power and anaerobic capacity, before and after the intervention. A mixed 2 x 2 ANOVA for 20 dependent variables grouped in three categories was conducted. No significant interaction of the genotype with training for body mass and body composition variables was observed. Although, there were three significant genotype x training interactions for maximal oxygen uptake variables, regardless of body mass i.e.: for VO2max (p < 0.05), HRmax (p < 0.0001) and HRAT/HRmax (p < 0.0001). Significantly greater improvement in VO2max was gained by the CC+AC group compared to the AA genotype group. The present results support the hypothesis that individual differences in trainability are at least in part determined by the genetic component and MTHFR A1298C seems to be one of the many polymorphisms involved.

Lessons from the canine Oxtr gene: populations, variants and functional aspects.

PubMed

Bence, M; Marx, P; Szantai, E; Kubinyi, E; Ronai, Z; Banlaki, Z

2017-04-01

Oxytocin receptor (OXTR) acts as a key behavioral modulator of the central nervous system, affecting social behavior, stress, affiliation and cognitive functions. Variants of the Oxtr gene are known to influence behavior both in animals and humans; however, canine Oxtr polymorphisms are less characterized in terms of possible relevance to function, selection criteria in breeding and domestication. In this report, we provide a detailed characterization of common variants of the canine Oxtr gene. In particular (1) novel polymorphisms were identified by direct sequencing of wolf and dog samples, (2) allelic distributions and pairwise linkage disequilibrium patterns of several canine populations were compared, (3) neighbor joining (NJ) tree based on common single nucleotide polymorphisms (SNPs) was constructed, (4) mRNA expression features were assessed, (5) a novel splice variant was detected and (6) in vitro functional assays were performed. Results indicate marked differences regarding Oxtr variations between purebred dogs of different breeds, free-ranging dog populations, wolf subspecies and golden jackals. This, together with existence of explicitly dog-specific alleles and data obtained from the NJ tree implies that Oxtr could indeed have been a target gene during domestication and selection for human preferred aspects of temperament and social behavior. This assumption is further supported by the present observations on gene expression patterns within the brain and luciferase reporter experiments, providing a molecular level link between certain canine Oxtr polymorphisms and differences in nervous system function and behavior. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Association of TNF polymorphisms with JAK2 (V617F) myeloproliferative neoplasms in Brazilian patients.

PubMed

Macedo, Luciana Conci; de Cesare Quintero, Fernanda; Pagliari-E-Silva, Sara; Pagnano, Katia Borgia Barbosa; Rodrigues, Camila; de Alencar, Josiane Bazzo; Sell, Ana Maria; Visentainer, Jeane Eliete Laguila

2016-03-01

The classical chromosome Philadelphia-negative myeloproliferative neoplasms (MPNs) are a group of disorders that share clinical, hematological, and histological features. Proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) are elevated in patients with MPN. The aim of this study was to verify the association between the polymorphisms of TNF gene (-308G/A and -238 G/A) in BCR-ABL-negative MPN in our population. Blood samples obtained from MPN patients were genotyped for the JAK2V617F mutation and both TNF polymorphisms using PCR-RFLP. Thirty three (26.8%) patients with polycythemia vera (PV), 35 (28.7%) essential thrombocythemia (ET), 22 (17.7%) primary myelofibrosis (PMF), and 33 (26.8%) with unclassifiable MPN (MPNu) were included in the study. The JAK2 V617F mutation was detected in 94 (76.42%) patients. Were observed a significant increase on the frequency of the TNF-238 GA genotype in MPN patients compared to controls (OR=2.21, 95% CI=1.02-4.80, P<0.04). The distribution of the genotypes and allelic frequencies of TNF-308 was significantly different among the MPNs, JAK2V617F positive, PV and PMF, and controls. Our data has demonstrated that the polymorphisms on TNF-238 GA, TNF-308 GA were associated to MPN development in this population, triggered by JAK2 V617F mutation. Copyright © 2015. Published by Elsevier Inc.

Molecular population genetics of the insulin/TOR signal transduction pathway: a network-level analysis in Drosophila melanogaster.

PubMed

Alvarez-Ponce, David; Guirao-Rico, Sara; Orengo, Dorcas J; Segarra, Carmen; Rozas, Julio; Aguadé, Montserrat

2012-01-01

The IT-insulin/target of rapamycin (TOR)-signal transduction pathway is a relatively well-characterized pathway that plays a central role in fundamental biological processes. Network-level analyses of DNA divergence in Drosophila and vertebrates have revealed a clear gradient in the levels of purifying selection along this pathway, with the downstream genes being the most constrained. Remarkably, this feature does not result from factors known to affect selective constraint such as gene expression, codon bias, protein length, and connectivity. The present work aims to establish whether the selective constraint gradient detected along the IT pathway at the between-species level can also be observed at a shorter time scale. With this purpose, we have surveyed DNA polymorphism in Drosophila melanogaster and divergence from D. simulans along the IT pathway. Our network-level analysis shows that DNA polymorphism exhibits the same polarity in the strength of purifying selection as previously detected at the divergence level. This equivalent feature detected both within species and between closely and distantly related species points to the action of a general mechanism, whose action is neither organism specific nor evolutionary time dependent. The detected polarity would be, therefore, intrinsic to the IT pathway architecture and function.

Top single nucleotide polymorphisms affecting carbohydrate metabolism in metabolic syndrome: from the LIPGENE study.

PubMed

Delgado-Lista, Javier; Perez-Martinez, Pablo; Solivera, Juan; Garcia-Rios, Antonio; Perez-Caballero, A I; Lovegrove, Julie A; Drevon, Christian A; Defoort, Catherine; Blaak, Ellen E; Dembinska-Kieć, Aldona; Risérus, Ulf; Herruzo-Gomez, Ezequiel; Camargo, Antonio; Ordovas, Jose M; Roche, Helen; Lopez-Miranda, José

2014-02-01

Metabolic syndrome (MetS) is a high-prevalence condition characterized by altered energy metabolism, insulin resistance, and elevated cardiovascular risk. Although many individual single nucleotide polymorphisms (SNPs) have been linked to certain MetS features, there are few studies analyzing the influence of SNPs on carbohydrate metabolism in MetS. A total of 904 SNPs (tag SNPs and functional SNPs) were tested for influence on 8 fasting and dynamic markers of carbohydrate metabolism, by performance of an intravenous glucose tolerance test in 450 participants in the LIPGENE study. From 382 initial gene-phenotype associations between SNPs and any phenotypic variables, 61 (16% of the preselected variables) remained significant after bootstrapping. Top SNPs affecting glucose metabolism variables were as follows: fasting glucose, rs26125 (PPARGC1B); fasting insulin, rs4759277 (LRP1); C-peptide, rs4759277 (LRP1); homeostasis assessment of insulin resistance, rs4759277 (LRP1); quantitative insulin sensitivity check index, rs184003 (AGER); sensitivity index, rs7301876 (ABCC9), acute insulin response to glucose, rs290481 (TCF7L2); and disposition index, rs12691 (CEBPA). We describe here the top SNPs linked to phenotypic features in carbohydrate metabolism among approximately 1000 candidate gene variations in fasting and postprandial samples of 450 patients with MetS from the LIPGENE study.

htsint: a Python library for sequencing pipelines that combines data through gene set generation.

PubMed

Richards, Adam J; Herrel, Anthony; Bonneaud, Camille

2015-09-24

Sequencing technologies provide a wealth of details in terms of genes, expression, splice variants, polymorphisms, and other features. A standard for sequencing analysis pipelines is to put genomic or transcriptomic features into a context of known functional information, but the relationships between ontology terms are often ignored. For RNA-Seq, considering genes and their genetic variants at the group level enables a convenient way to both integrate annotation data and detect small coordinated changes between experimental conditions, a known caveat of gene level analyses. We introduce the high throughput data integration tool, htsint, as an extension to the commonly used gene set enrichment frameworks. The central aim of htsint is to compile annotation information from one or more taxa in order to calculate functional distances among all genes in a specified gene space. Spectral clustering is then used to partition the genes, thereby generating functional modules. The gene space can range from a targeted list of genes, like a specific pathway, all the way to an ensemble of genomes. Given a collection of gene sets and a count matrix of transcriptomic features (e.g. expression, polymorphisms), the gene sets produced by htsint can be tested for 'enrichment' or conditional differences using one of a number of commonly available packages. The database and bundled tools to generate functional modules were designed with sequencing pipelines in mind, but the toolkit nature of htsint allows it to also be used in other areas of genomics. The software is freely available as a Python library through GitHub at https://github.com/ajrichards/htsint.

Total Health Organization.

PubMed

1993-01-01

Total Health Organization is a holistic care an humanitarian relief agency with special emphasis on Africa and Third World countries. It was founded in 1987 with a focus on hunger relief, health assistance, handicap, habitat and human rights of destitutes, socially disadvantaged persons and communities which it has adopted as the socially forgotten people (SFP). Total Health Organization is a non-political, non-profit, and international non-governmental organization, having official relations with several national, regional and world bodies. Some of the project activities include: free mobile clinics to rural destitutes, AIDS and related health education, an information and research library, and an NGO Development Center. For more information, please contact: Dr. Obi Osisiogu, Founder and President, Total Health International Center, 147 Ikot-Ekpene Road, P.O. Box 1726, Aba, Abia State Nigeria, Tel: 082-222279, Telex: 63311 ANYA NG, Fax: 234-82-227512. full text

Bird Ingestion into Large Turbofan Engines

DTIC Science & Technology

1992-05-01

11 FU1( FUKUOKA, JAPAN 3 1 4 HIJ HIROSHIMA,JAPAN 1. 1 HND TOKYO-HND,JAPAN 1 3 4 JKT JAKARTA, INDONESIA 1I KCZ KocHI,JAPAN44 KIJ NIGATA,JAPAN2 MYJ...8217RlPPRI:RCH soý 1 R N C, 10.-L II1$ I Hi N V 2’ -q HPIC 53 7 DEIS U100U.PREFLITE DI’:.P. 6? 1 H N I I FIT L. CURL 14’ 2IG61.11 1U -1i I 𔃺 M N V: V 2...INLET COWL. LI P 6~t 114SFP 192? (AN WARTRIDE. 11.05 2 1.;4 N N 14 V’ I’ !] FSP RPL.IE.LII C:i~f. It?’ CURL .. 11:1 IŔ(CHAP.ii ;�$ 2 37 5 yy: V V v 2

Global image analysis to determine suitability for text-based image personalization

NASA Astrophysics Data System (ADS)

Ding, Hengzhou; Bala, Raja; Fan, Zhigang; Bouman, Charles A.; Allebach, Jan P.

2012-03-01

Lately, image personalization is becoming an interesting topic. Images with variable elements such as text usually appear much more appealing to the recipients. In this paper, we describe a method to pre-analyze the image and automatically suggest to the user the most suitable regions within an image for text-based personalization. The method is based on input gathered from experiments conducted with professional designers. It has been observed that regions that are spatially smooth and regions with existing text (e.g. signage, banners, etc.) are the best candidates for personalization. This gives rise to two sets of corresponding algorithms: one for identifying smooth areas, and one for locating text regions. Furthermore, based on the smooth and text regions found in the image, we derive an overall metric to rate the image in terms of its suitability for personalization (SFP).

Two Polymorphic Forms of a Six-Coordinate Mononuclear Cobalt(II) Complex with Easy-Plane Anisotropy: Structural Features, Theoretical Calculations, and Field-Induced Slow Relaxation of the Magnetization.

PubMed

Roy, Subhadip; Oyarzabal, Itziar; Vallejo, Julia; Cano, Joan; Colacio, Enrique; Bauza, Antonio; Frontera, Antonio; Kirillov, Alexander M; Drew, Michael G B; Das, Subrata

2016-09-06

A mononuclear cobalt(II) complex [Co(3,5-dnb)2(py)2(H2O)2] {3,5-Hdnb = 3,5-dinitrobenzoic acid; py = pyridine} was isolated in two polymorphs, in space groups C2/c (1) and P21/c (2). Single-crystal X-ray diffraction analyses reveal that 1 and 2 are not isostructural in spite of having equal formulas and ligand connectivity. In both structures, the Co(II) centers adopt octahedral {CoN2O4} geometries filled by pairs of mutually trans terminal 3,5-dnb, py, and water ligands. However, the structures of 1 and 2 disclose distinct packing patterns driven by strong intermolecular O-H···O hydrogen bonds, leading to their 0D→2D (1) or 0D→1D (2) extension. The resulting two-dimensional layers and one-dimensional chains were topologically classified as the sql and 2C1 underlying nets, respectively. By means of DFT theoretical calculations, the energy variations between the polymorphs were estimated, and the binding energies associated with the noncovalent interactions observed in the crystal structures were also evaluated. The study of the direct-current magnetic properties, as well as ab initio calculations, reveal that both 1 and 2 present a strong easy-plane magnetic anisotropy (D > 0), which is larger for the latter polymorph (D is found to exhibit values between +58 and 117 cm(-1) depending on the method). Alternating current dynamic susceptibility measurements show that these polymorphs exhibit field-induced slow relaxation of the magnetization with Ueff values of 19.5 and 21.1 cm(-1) for 1 and 2, respectively. The analysis of the whole magnetic data allows the conclusion that the magnetization relaxation in these polymorphs mainly takes place through a virtual excited state (Raman process). It is worth noting that despite the notable difference between the supramolecular networks of 1 and 2, they exhibit almost identical magnetization dynamics. This fact suggests that the relaxation process is intramolecular in nature and that the virtual state involved in the two-phonon Raman process lies at a similar energy in polymorphs 1 and 2 (∼20 cm(-1)). Interestingly, this value is recurrent in Co(II) single-ion magnets, even for those displaying different coordination number and geometry.

A variety of gene polymorphisms associated with idiopathic granulomatous mastitis

PubMed Central

Destek, Sebahattin; Gul, Vahit Onur; Ahioglu, Serkan

2016-01-01

Idiopathic granulomatous mastitis (IGM) is a rare and chronic inflammatory disorder. IGM mimics breast cancer regarding its clinical and radiological features. Etiology of IGM remains unclarified. Our patient was 37-year-old and 14 weeks pregnant. There was pain, redness and swelling in the right breast. The mass suggestive of malignancy was detected in sonography. Serum CA 125 and CA 15-3 levels were high. Genetic analysis was performed for the etiology. methylenetetrahydrofolate reductase (MTHFR) C 677 TT, β-fibrinogen-455 G>A, plasminogen activator inhibitor (PAI)-1 5 G/5 G, angiotensin-converting enzyme (ACE) I/D mutation was found. IGM was diagnosed by cor biopsy. An association was also reported between breast cancer and mutations in MTHFR-C 677 T, PAI-1, ACE genes. Genetic polymorphisms may involve in the development of IGM as it was seen in our case. Further studies should be conducted to better clarify this plausible association. PMID:27619324

Molecular mapping of powdery mildew resistance gene Eg-3 in cultivated oat (Avena sativa L. cv. Rollo).

PubMed

Mohler, Volker; Zeller, Friedrich J; Hsam, Sai L K

2012-05-01

Powdery mildew is a prevalent fungal disease affecting oat (Avena sativa L.) production in Europe. Common oat cultivar Rollo was previously shown to carry the powdery mildew resistance gene Eg-3 in common with cultivar Mostyn. The resistance gene was mapped with restriction fragment length polymorphism (RFLP) markers from Triticeae group-1 chromosomes using a population of F(3) lines from a cross between A. byzantina cv. Kanota and A. sativa cv. Rollo. This comparative mapping approach positioned Eg-3 between cDNA-RFLP marker loci cmwg706 and cmwg733. Since both marker loci were derived from the long arm of barley chromosome 1H, the subchromosomal location of Eg-3 was assumed to be on the long arm of oat chromosome 17. Amplified fragment length polymorphism (AFLP) marker technology featured as an efficient means for obtaining markers closely linked to Eg-3.

Modeling antigen-antibody nanoparticle bioconjugates and their polymorphs

NASA Astrophysics Data System (ADS)

Desgranges, Caroline; Delhommelle, Jerome

2018-03-01

The integration of nanomaterials with biomolecules has recently led to the development of new ways of designing biosensors, and through their assembly, to new hybrid structures for novel and exciting applications. In this work, we develop a coarse-grained model for nanoparticles grafted with antibody molecules and their binding with antigens. In particular, we isolate two possible states for antigen-antibody pairs during the binding process, termed as recognition and anchoring states. Using molecular simulation, we calculate the thermodynamic and structural features of three possible crystal structures or polymorphs, the body-centered cubic, simple cubic, and face-centered cubic phases, and of the melt. This leads us to determine the domain of stability of the three solid phases. In particular, the role played by the switching process between anchoring and recognition states during melting is identified, shedding light on the complex microscopic mechanisms in these systems.

Association between C3435T polymorphism of MDR1 gene and the incidence of drug-resistant epilepsy in the population of Polish children.

PubMed

Stasiołek, Mariusz; Romanowicz, Hanna; Połatyńska, Katarzyna; Chamielec, Maciej; Skalski, Dominik; Makowska, Marianna; Smolarz, Beata

2016-07-08

Epilepsy is a disease of neurological character. Approximately one third of epileptic patients demonstrate a drug-resistant phenotype, which is associated with the development of drug-resistant epilepsy. The multidrug resistance protein 1 and glycoprotein P, encoded by MDR1, play a significant role in the transmembrane transport of anti-epileptic agents. Single nucleotide polymorphism C3435T (rs1045642) within MDR1 gene may be associated with an increased expression of P-gp which affects the levels of antiepileptic drugs in plasma. The presented studies analysed the association between C3435T polymorphism of MDR1 gene and the incidence of drug-resistant epilepsy in the population of Polish children. C3435T polymorphism of MDR1 gene was analysed by the high resolution melting technique in a group of patients with drug-resistant (n = 106) and drug-responsive epilepsy (n = 67), as well as in non-epileptic children (n = 98) hospitalised at the Department of Neurology, Polish Mother's Memorial Hospital in Lodz. Genotype and allele distributions were evaluated and their compatibility with the Hardy-Weinberg distribution was assessed by means of the χ(2) test. Genotype and allele evaluation, regarding their relationship with a given feature, was supported by an analysis of odds ratio and 95 % confidence interval, calculated according to the logistic regression model. An association was observed between the incidence rate of DRE and the presence of C allele in C3435T polymorphism of MDR1 gene, which may enhance the risk of the disease. The T allele may then play a protective role. No differences were found in the studied groups, regarding either genotype or allele distribution in reference to patient's gender or concomitant diseases. Following the obtained results, C3435T polymorphism of MDR1 gene may be connected with the incidence of drug-resistant epilepsy in the population of Polish children. ISRCTN ISRCTN73824458. Registered 28th September 2014.

Discrimination of artificial categories structured by family resemblances: a comparative study in people (Homo sapiens) and pigeons (Columba livia).

PubMed

Makino, Hiroshi; Jitsumori, Masako

2007-02-01

Adult humans (Homo sapiens) and pigeons (Columba livia) were trained to discriminate artificial categories that the authors created by mimicking 2 properties of natural categories. One was a family resemblance relationship: The highly variable exemplars, including those that did not have features in common, were structured by a similarity network with the features correlating to one another in each category. The other was a polymorphous rule: No single feature was essential for distinguishing the categories, and all the features overlapped between the categories. Pigeons learned the categories with ease and then showed a prototype effect in accord with the degrees of family resemblance for novel stimuli. Some evidence was also observed for interactive effects of learning of individual exemplars and feature frequencies. Humans had difficulty in learning the categories. The participants who learned the categories generally responded to novel stimuli in an all-or-none fashion on the basis of their acquired classification decision rules. The processes that underlie the classification performances of the 2 species are discussed.

Characterization of polymorphic states in energetic samples of 1,3,5-trinitro-1,3,5-triazine (RDX) fabricated using drop-on-demand inkjet technology.

PubMed

Emmons, Erik D; Farrell, Mikella E; Holthoff, Ellen L; Tripathi, Ashish; Green, Norman; Moon, Raphael P; Guicheteau, Jason A; Christesen, Steven D; Pellegrino, Paul M; Fountain, Augustus W

2012-06-01

The United States Army and the first responder community are evaluating optical detection systems for the trace detection of hazardous energetic materials. Fielded detection systems must be evaluated with the appropriate material concentrations to accurately identify the residue in theater. Trace levels of energetic materials have been observed in mutable polymorphic phases and, therefore, the systems being evaluated must be able to detect and accurately identify variant sample phases observed in spectral data. In this work, we report on the novel application of drop-on-demand technology for the fabrication of standardized trace 1,3,5-trinitro-1,3,5-triazine (RDX) samples. The drop-on-demand sample fabrication technique is compared both visually and spectrally to the more commonly used drop-and-dry technique. As the drop-on-demand technique allows for the fabrication of trace level hazard materials, concerted efforts focused on characterization of the polymorphic phase changes observed with low concentrations of RDX commonly used in drop-on-demand processing. This information is important when evaluating optical detection technologies using samples prepared with a drop-on-demand inkjet system, as the technology may be "trained" to detect the common bulk α phase of the explosive based on its spectral features but fall short in positively detecting a trace quantity of RDX (β-phase). We report the polymorphic shifts observed between α- and β-phases of this energetic material and discuss the conditions leading to the favoring of one phase over the other.

The impact of ACE gene polymorphism on the incidence and phenotype of sarcoidosis in rural and urban settings.

PubMed

Kieszko, Robert; Krawczyk, Paweł; Powrózek, Tomasz; Szudy-Szczyrek, Aneta; Szczyrek, Michał; Homa, Iwona; Daniluk, Jadwiga; Milanowski, Janusz

2016-12-01

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Current theory on the etiology of this disease involves participation of genetic factors and unknown antigens present in the patients' environment. The aim of the study was to evaluate the prevalence of different polymorphic forms of the ACE gene in healthy individuals and sarcoidosis patients, and to estimate the risk of sarcoidosis in carriers of different ACE genotypes living in rural and urban settings. The study group included 180 patients with pulmonary sarcoidosis. Assessment of the disease was based on clinical features, laboratory and imaging examinations, as well as bronchoscopy with bronchoalveolar lavage (BAL). ACE gene polymorphism was examined in DNA isolated from peripheral blood or BAL fluid (BALF) leukocytes. Incidence of sarcoidosis was not influenced by gender, age or place of residence of the patients. There were no differences in the frequency of particular genotypes in patients with sarcoidosis and in healthy individuals. The risk of disease did not depend on the ACE gene polymorphism. There were no differences in the frequencies of the different genotypes and alleles of the ACE gene in patients with sarcoidosis divided by gender, age and place of residence or by clinical manifestation of sarcoidosis. Our results do not support the previous concept which suggested a higher incidence of sarcoidosis in individuals living in rural areas and in carriers of selected ACE genotypes. It is possible that this is related to the changing environment of rural areas, increasing urbanization and pollution.

A polymorphism in the 5'-flanking region of the serotonin transporter (5-HTT) gene affects fear-related behaviors of adult domestic chickens.

PubMed

Krause, E Tobias; Kjaer, Joergen B; Lüders, Carolin; van, Loc Phi

2017-07-14

The neural serotonin (5-HT)/serotonin transporter (5-HTT) system is involved in the regulation of physiological processes and emotional states. In humans, the short (S) allele in the 5-HTT gene-linked polymorphic region, which decreases 5-HTT expression, has been shown to be associated with behavioral changes including an increased level of anxiety. Also in birds a polymorphism in the 5-HTT gene is described, a deletion (D) has been found to have functional consequences on growth and locomotion. Furthermore, the D-allele leads to an increased 5-HTT expression compared to the wild type (W), a feature which is linked to lower levels of fear in mammalian species. Thus, we aimed here to test whether the polymorphism in the chicken 5-HTT gene also leads to respective alternations of fear-related behaviors. We tested 268 hens of three genotypes (W/W, W/D, D/D) in two behavioral paradigms (open field, light-dark test) to assess fear-related behavior. Both tests revealed that hens possessing the D-allele showed lower levels of fear than those having the W-allele. These similar outcomes in fear-related behaviors in an avian and a mammalian species are associated with an increased 5-HTT expression. In the human 5-HTT gene, the long (L) allele is linked to such increased expression, whereas in chickens it is the D-allele. Thus, increased 5-HTT expression causing decreased fear may be a general mechanism in vertebrates. Copyright © 2017 Elsevier B.V. All rights reserved.

The influence of COMT Val158Met genotype on the character dimension cooperativeness in healthy females

PubMed Central

Baeken, Chris; Claes, Stephan; De Raedt, Rudi

2014-01-01

Objectives Although the Val158Met catechol-O-methyltransferase (COMT) gene has been linked with the temperament dimension Novelty Seeking (NS), new insights in this polymorphism might point to a major role for character features as well. Given that individual life experiences may influence Val158 and Met158 allele carriers differently it has been suggested that the character trait cooperativeness could be implicated. Case report A homogeneous group of eighty right-handed Caucasian healthy female university students were assessed with the TCI and genotyped for the COMT Val158Met polymorphism (rs4680). Gene determination showed that eighteen were Val158 homozygotes, forty-four Val/Met158 heterozygotes, and eighteen were Met158 homozygotes. All were within the same age range and never documented to have suffered from any neuropsychiatric illness. Bonferroni corrected non-parametric analyses showed that only for the character scale cooperativeness Val158 homozygotes displayed significant higher scores when compared to Met158 homozygotes. No significant differences on cooperativeness scores were found between Val158 and Val/Met158 carriers or between Met158 and Val/Met158 carriers. No differences were observed for the COMT Val158Met polymorphism and the other temperament and character scales. Conclusions Our findings support the assumption that the Val158Met single nucleotide polymorphism (SNP) influences character traits and not only temperament. Our results add to the notion that Val158 homozygotes are considered to be helpful and empathic and it suggest that these cooperativeness character traits are related to the dopaminergic system. PMID:25161818

The influence of COMT Val¹⁵⁸Met genotype on the character dimension cooperativeness in healthy females.

PubMed

Baeken, Chris; Claes, Stephan; De Raedt, Rudi

2014-07-01

Although the Val(158)Met catechol-O-methyltransferase (COMT) gene has been linked with the temperament dimension Novelty Seeking (NS), new insights in this polymorphism might point to a major role for character features as well. Given that individual life experiences may influence Val(158) and Met(158) allele carriers differently it has been suggested that the character trait cooperativeness could be implicated. A homogeneous group of eighty right-handed Caucasian healthy female university students were assessed with the TCI and genotyped for the COMT Val(158)Met polymorphism (rs4680). Gene determination showed that eighteen were Val(158) homozygotes, forty-four Val/Met(158) heterozygotes, and eighteen were Met(158) homozygotes. All were within the same age range and never documented to have suffered from any neuropsychiatric illness. Bonferroni corrected non-parametric analyses showed that only for the character scale cooperativeness Val(158) homozygotes displayed significant higher scores when compared to Met(158) homozygotes. No significant differences on cooperativeness scores were found between Val(158) and Val/Met(158) carriers or between Met(158) and Val/Met(158) carriers. No differences were observed for the COMT Val(158)Met polymorphism and the other temperament and character scales. Our findings support the assumption that the Val(158)Met single nucleotide polymorphism (SNP) influences character traits and not only temperament. Our results add to the notion that Val(158) homozygotes are considered to be helpful and empathic and it suggest that these cooperativeness character traits are related to the dopaminergic system.

Prognostic Significance of ESR1 Amplification and ESR1 PvuII, CYP2C19*2, UGT2B15*2 Polymorphisms in Breast Cancer Patients

PubMed Central

Markiewicz, Aleksandra; Wełnicka-Jaśkiewicz, Marzena; Skokowski, Jarosław; Jaśkiewicz, Janusz; Szade, Jolanta; Jassem, Jacek; Żaczek, Anna J.

2013-01-01

Introduction Amplification of the ESR1 gene, coding for estrogen receptor alpha, was shown to predict responsiveness to tamoxifen, however its prognostic impact in breast cancer patients has not been thoroughly investigated. Other factors that could contribute to responsiveness to tamoxifen treatment are polymorphisms in ESR1 gene and genes involved in tamoxifen metabolism. The aim of this study was to assess the prognostic role of ESR1 gene dosage in a consecutive group of breast cancer patients and to correlate this feature with clinico-pathological factors. Additionally, ESR1 PvuII, CYP2C19*2 and UGT2B15*2 polymorphisms were analyzed in the tamoxifen-treated subgroup of patients. Materials and Methods Primary tumor samples from 281 stage I-III consecutive breast cancer patients were analyzed for ESR1 gene dosage using real-time PCR with locked nucleic acids hydrolysis probes. In the tamoxifen-treated subgroup of patients, ESR1 PvuII, CYP2C19*2 and UGT2B15*2 polymorphism in leukocytes genomic DNA were analyzed. Results were correlated with clinico-pathological factors and with disease-free survival (DFS) and overall survival (OS). Results ESR1 amplification (with a cut-off level of 2.0) was found in 12% of the entire group of breast cancer patients, and in 18% of the ER-negative subgroup. This feature was associated with decreased DFS both in the entire group (P=0.007) and in the ER-negative subgroup (P=0.03), but not in the tamoxifen-treated patients. Patients with ESR1 PvuII wt/wt genotype and at least one UGT2B15 wt allele had a worse DFS (P=0.03) and showed a trend towards decreased Os (P=0.08) in comparison to patients with ESR1 PvuII wt/vt or vt/vt genotype and UGT2B15 *2/*2 genotype. Conclusions ESR1 amplification can occur in ER-negative tumors and may carry poor prognosis. In the tamoxifen-treated subgroup, poor prognosis was related to the combined presence of ESR1 PvuII wt/wt and UGT2B15wt/wt or wt/*2 genotype. PMID:23951298

Prognostic significance of ESR1 amplification and ESR1 PvuII, CYP2C19*2, UGT2B15*2 polymorphisms in breast cancer patients.

PubMed

Markiewicz, Aleksandra; Wełnicka-Jaśkiewicz, Marzena; Skokowski, Jarosław; Jaśkiewicz, Janusz; Szade, Jolanta; Jassem, Jacek; Zaczek, Anna J

2013-01-01

Amplification of the ESR1 gene, coding for estrogen receptor alpha, was shown to predict responsiveness to tamoxifen, however its prognostic impact in breast cancer patients has not been thoroughly investigated. Other factors that could contribute to responsiveness to tamoxifen treatment are polymorphisms in ESR1 gene and genes involved in tamoxifen metabolism. The aim of this study was to assess the prognostic role of ESR1 gene dosage in a consecutive group of breast cancer patients and to correlate this feature with clinico-pathological factors. Additionally, ESR1 PvuII, CYP2C19*2 and UGT2B15*2 polymorphisms were analyzed in the tamoxifen-treated subgroup of patients. Primary tumor samples from 281 stage I-III consecutive breast cancer patients were analyzed for ESR1 gene dosage using real-time PCR with locked nucleic acids hydrolysis probes. In the tamoxifen-treated subgroup of patients, ESR1 PvuII, CYP2C19*2 and UGT2B15*2 polymorphism in leukocytes genomic DNA were analyzed. Results were correlated with clinico-pathological factors and with disease-free survival (DFS) and overall survival (OS). ESR1 amplification (with a cut-off level of 2.0) was found in 12% of the entire group of breast cancer patients, and in 18% of the ER-negative subgroup. This feature was associated with decreased DFS both in the entire group (P=0.007) and in the ER-negative subgroup (P=0.03), but not in the tamoxifen-treated patients. Patients with ESR1 PvuII wt/wt genotype and at least one UGT2B15 wt allele had a worse DFS (P=0.03) and showed a trend towards decreased Os (P=0.08) in comparison to patients with ESR1 PvuII wt/vt or vt/vt genotype and UGT2B15 *2/*2 genotype. ESR1 amplification can occur in ER-negative tumors and may carry poor prognosis. In the tamoxifen-treated subgroup, poor prognosis was related to the combined presence of ESR1 PvuII wt/wt and UGT2B15wt/wt or wt/*2 genotype.

The nature, distribution and genesis of the coesite and stishovite associated with the pseudotachylite of the Vredefort Dome, South Africa

NASA Astrophysics Data System (ADS)

Martini, J. E. J.

1991-04-01

The Vredefort Dome represents the uplift centre of a well known 2.00 Ga old impact structure of unusually large magnitude. Shock features like shatter cones, planar features and high-pressure silica polymorphs are common. The present study deals with the description, mode of occurrence, field distribution and post-shock metamorphic alteration of coesite and stishovite which were poorly documented up to now. These minerals occur as unusually large crystals in the quartzite of the wall rock in contact with very thin pseudotachylite veins. In the pseudotachylite itself, which can be interpreted as a friction and/or a shock recovery melt, fine needles of kyanite are ubiquitous. It is proposed that these thin pseudotachylites (A-type) formed during the transit of the shock wave. They preceded the development of thick pseudotachylite and microbreccia veins (B-type) which formed during the tensional period which immediately followed. From comparison with the model of formation of high-pressure polymorphs in porous sandstone, it is suggested that higher pressure and stress was concentrated along the A-type veins at the arrival of the shock front. At this time the quartz was transformed into a "high-pressure phase" which was probably poorly crystalline. Behind the shock front, that is during the rarefaction, the pressure was progressively released and the polymorphs crystallized from this initial "high-pressure phase". Stishovite crystallized first, followed by coesite. The high-pressure conditions may have lasted an unusually long time due to the magnitude of the Vredefort impact. This long time, probably about one second, may account for the large size of the coesite and stishovite crystals. Most of the high-pressure silica polymorphs are corroded to a variable degree by secondary quartz and preserved only in a restricted area of the impact structure. This alteration is attributed to post-shock metamorphism due to the temperature of the rock before impact plus the heat left after shock recovery. Some of the evidence put forward by authors against the impact model is discussed according to the facts arising from this investigation. It is concluded that an origin by impact remains the simplest and most realistic model to explain the origin of the Vredefort Dome.

A novel MALDI–TOF based methodology for genotyping single nucleotide polymorphisms

PubMed Central

Blondal, Thorarinn; Waage, Benedikt G.; Smarason, Sigurdur V.; Jonsson, Frosti; Fjalldal, Sigridur B.; Stefansson, Kari; Gulcher, Jeffery; Smith, Albert V.

2003-01-01

A new MALDI–TOF based detection assay was developed for analysis of single nucleotide polymorphisms (SNPs). It is a significant modification on the classic three-step minisequencing method, which includes a polymerase chain reaction (PCR), removal of excess nucleotides and primers, followed by primer extension in the presence of dideoxynucleotides using modified thermostable DNA polymerase. The key feature of this novel assay is reliance upon deoxynucleotide mixes, lacking one of the nucleotides at the polymorphic position. During primer extension in the presence of depleted nucleotide mixes, standard thermostable DNA polymerases dissociate from the template at positions requiring a depleted nucleotide; this principal was harnessed to create a genotyping assay. The assay design requires a primer- extension primer having its 3′-end one nucleotide upstream from the interrogated site. The assay further utilizes the same DNA polymerase in both PCR and the primer extension step. This not only simplifies the assay but also greatly reduces the cost per genotype compared to minisequencing methodology. We demonstrate accurate genotyping using this methodology for two SNPs run in both singleplex and duplex reactions. We term this assay nucleotide depletion genotyping (NUDGE). Nucleotide depletion genotyping could be extended to other genotyping assays based on primer extension such as detection by gel or capillary electrophoresis. PMID:14654708

Elevated Levels of LDL-C are Associated With ApoE4 but Not With the rs688 Polymorphism in the LDLR Gene.

PubMed

Cahua-Pablo, Gabriel; Cruz, Miguel; Moral-Hernández, Oscar Del; Leyva-Vázquez, Marco A; Antúnez-Ortiz, Diana L; Cahua-Pablo, José A; Alarcón-Romero, Luz Del Carmen; Ortuño-Pineda, Carlos; Moreno-Godínez, Ma Elena; Hernández-Sotelo, Daniel; Flores-Alfaro, Eugenia

2016-07-01

Apolipoprotein E (ApoE) 4 isoform has been associated with elevated levels of cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides (TGs), meanwhile several polymorphisms in the LDL receptor (LDLR) gene have been associated with increased levels of total cholesterol and LDL-C. We studied 400 women from Southwest Mexico. Anthropometric features and biochemical profile were evaluated, and genotyping of single nucleotide polymorphisms rs429358 and rs7412 in the APOE gene and rs688 in the LDLR gene was determined by TaqMan assays. We found significant association between LDL-C (odds ratio [OR] = 3.3, 95% confidence interval [CI]: 1.9-5.7) and marginal association with TG (OR = 1.7, 95% CI: 1.0-2.9) of atherogenic risk in women carriers of the ApoE4 isoform compared to ApoE3. The TT genotype of rs688 in the LDLR gene was not found to be associated with elevated levels of total cholesterol or LDL-C. Our results show that carrier women of the ApoE4 isoform are more likely to have elevated levels of LDL-C and therefore increased risk of developing atherosclerosis. © The Author(s) 2015.

Identification of a New Single-nucleotide Polymorphism within the Apolipoprotein A5 Gene, Which is Associated with Metabolic Syndrome.

PubMed

Salehi, Samaneh; Emadi-Baygi, Modjtaba; Rezaei, Majdaddin; Kelishadi, Roya; Nikpour, Parvaneh

2017-01-01

Metabolic syndrome (MetS) is a common disorder which is a constellation of clinical features including abdominal obesity, increased level of serum triglycerides (TGs) and decrease of serum high-density lipoprotein-cholesterol (HDL-C), elevated blood pressure, and glucose intolerance. The apolipoprotein A5 (APOA5) is involved in lipid metabolism, influencing the level of plasma TG and HDL-C. In the present study, we aimed to investigate the associations between four INDEL variants of APOA5 gene and the MetS risk. In this case-control study, we genotyped 116 Iranian children and adolescents with/without MetS by using Sanger sequencing method for these INDELs. Then, we explored the association of INDELs with MetS risk and their clinical components by logistic regression and one-way analysis of variance analyses. We identified a novel insertion polymorphism, c. *282-283 insAG/c. *282-283 insG variant, which appears among case and control groups. rs72525532 showed a significant difference for TG levels between various genotype groups. In addition, there were significant associations between newly identified single-nucleotide polymorphism (SNP) and rs72525532 with MetS risk. These results show that rs72525532 and the newly identified SNP may influence the susceptibility of the individuals to MetS.

Analysis of polymorphic patterns in candidate genes in Israeli patients with prostate cancer.

PubMed

Figer, Arie; Friedman, Tal; Manguoglu, Ayse Esra; Flex, Dov; Vazina, Amnon; Novikov, Ilia; Shtrieker, Avi; Sidi, A Ami; Tichler, Thomas; Sapir, Einat Even; Baniel, Jack; Friedman, Eitan

2003-10-01

The precise genes involved in conferring prostate cancer risk in sporadic and familial cases are not fully known. To evaluate the genetic profile within several candidate genes of unselected prostate cancer cases and to correlate this profile with disease parameters. Jewish Israeli prostate cancer patients (n = 224) were genotyped for polymorphisms within candidate genes: p53, ER, VDR, GSTT1, CYP1A1, GSTP1, GSTM1, EPHX and HPC2/ELAC2, followed by analysis of the genotype with relevant clinical and pathologic parameters. The EPHX gene His113 allele was detected in 21.4% (33/154) of patients in whom disease was diagnosed above 61 years, compared with 5.7% (4/70) in earlier onset disease (P < 0.001). Within the group of late-onset disease, the same allele was noted in 5.5% (2/36) with grade I tumors compared with 18% (34/188) with grade II and up (P = 0.004). All other tested polymorphisms were not associated with a distinct clinical or pathologic feature in a statistically significant manner. In Israeli prostate cancer patients, the EPHX His113 allele is seemingly associated with a more advanced, late-onset disease. These preliminary data need to be confirmed by a larger and more ethnically diverse study.

Structural polymorphism exhibited by a quasipalindrome present in the locus control region (LCR) of the human beta-globin gene cluster.

PubMed

Kaushik, Mahima; Kukreti, Shrikant

2006-01-01

Structural polymorphism of DNA is a widely accepted property. A simple addition to this perception has been our recent finding, where a single nucleotide polymorphism (SNP) site present in a quasipalindromic sequence of beta-globin LCR exhibited a hairpin-duplex equilibrium. Our current studies explore that secondary structures adopted by individual complementary strands compete with formation of a perfect duplex. Using gel-electrophoresis, ultraviolet (UV)-thermal denaturation, circular dichroism (CD) techniques, we have demonstrated the structural transitions within a perfect duplex containing 11 bp quasipalindromic stretch (TGGGG(G/C)CCCCA), to hairpins and bulge duplex forms. The extended version of the 11 bp duplex, flanked by 5 bp on both sides also demonstrated conformational equilibrium between duplex and hairpin species. Gel-electrophoresis confirms that the duplex coexists with hairpin and bulge duplex/cruciform species. Further, in CD spectra of duplexes, presence of two overlapping positive peaks at 265 and 285 nm suggest the features of A- as well as B-type DNA conformation and show oligomer concentration dependence, manifested in A --> B transition. This indicates the possibility of an architectural switching at quasipalindromic region between linear duplex to a cruciform structure. Such DNA structural variations are likely to be found in the mechanics of molecular recognition and manipulation by proteins.

Diversity Arrays Technology (DArT) for whole-genome profiling of barley

PubMed Central

Wenzl, Peter; Carling, Jason; Kudrna, David; Jaccoud, Damian; Huttner, Eric; Kleinhofs, Andris; Kilian, Andrzej

2004-01-01

Diversity Arrays Technology (DArT) can detect and type DNA variation at several hundred genomic loci in parallel without relying on sequence information. Here we show that it can be effectively applied to genetic mapping and diversity analyses of barley, a species with a 5,000-Mbp genome. We tested several complexity reduction methods and selected two that generated the most polymorphic genomic representations. Arrays containing individual fragments from these representations generated DArT fingerprints with a genotype call rate of 98.0% and a scoring reproducibility of at least 99.8%. The fingerprints grouped barley lines according to known genetic relationships. To validate the Mendelian behavior of DArT markers, we constructed a genetic map for a cross between cultivars Steptoe and Morex. Nearly all polymorphic array features could be incorporated into one of seven linkage groups (98.8%). The resulting map comprised ≈385 unique DArT markers and spanned 1,137 centimorgans. A comparison with the restriction fragment length polymorphism-based framework map indicated that the quality of the DArT map was equivalent, if not superior, to that of the framework map. These results highlight the potential of DArT as a generic technique for genome profiling in the context of molecular breeding and genomics. PMID:15192146

Characterization of the COL2A1 VNTR polymorphism

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

Berg, E.S.; Olaisen, B.

1993-05-01

The variable number of tandem repeat (VNTR) region 3{prime} to the collagen type II gene (COL2A1) was amplified in vitro by the polymerase chain reaction. Subsequent high-resolution gel electrophoresis showed that the five earlier reported alleles could be further subtyped. A total of 17 allelic variants with a heterozygosity of 73.0% were found in 202 unrelated Norwegians. DNA sequencing of 19 COL2A1 alleles has been performed. The internal organization of the VNTR was common for all alleles, as previously shown for a few alleles. Moreover, the polymorphism in the COL2A1 locus is mainly due to variation in the numbers ofmore » copies of two repeat units, containing 34 and 31 bp, respectively, and/or to small deletions in either of the two units. DNA sequencing of alleles with the same electrophoretic size revealed no heterogeneity such as an alternating order of the different units, a feature that might have been expected to be the result of unequal crossing-over events. The observed ordered structure of the VNTR and the possibility of single-stranded DNA from the cores in the VNTR forming hairpins and loops suggest that the COL2A1 polymorphism may have evolved mainly by replication slippage mechanisms. 23 refs., 2 figs., 3 tabs.« less

Polymorphic Imprinting of SLC38A4 Gene in Bovine Placenta.

PubMed

Xu, Da; Zhang, Cui; Li, Junliang; Wang, Guannan; Chen, Weina; Li, Dongjie; Li, Shijie

2018-05-21

Imprinted genes are characterized by monoallelic expression that is dependent on parental origin. Comparative analysis of imprinted genes between species is a powerful tool for understanding the biological significance of genomic imprinting. The slc38a4 gene encodes a neutral amino acid transporter and is identified as imprinted in mice. In this study, the imprinting status of SLC38A4 was assessed in bovine adult tissues and placenta using a polymorphism-based approach. Results indicate that SLC38A4 is not imprinted in eight adult bovine tissues including heart, liver, spleen, lung, kidney, muscle, fat, and brain. It was interesting to note that SLC38A4 showed polymorphic status in five heterogeneous placentas, with three exhibiting paternal monoallelic expression and two exhibiting biallelic expression. Monoallelic expression of imprinted genes is generally associated with allele-specific differentially methylation regions (DMRs) of CpG islands (CGIs)-encompassed promoter; therefore, the DNA methylation statuses of three CGIs in the SLC38A4 promoter and exon 1 region were tested in three placentas (two exhibiting paternal monoallelic and one showing biallelic expression of SLC38A4) and their corresponding paternal sperms. Unexpectedly, extreme hypomethylation (< 3%) of the DNA was observed in all the three detected placentas and their corresponding paternal sperms. The absence of DMR in bovine SLC38A4 promoter region implied that DNA methylation of these three CGIs does not directly or indirectly affect the polymorphic imprinting of SLC38A4 in bovine placenta. This suggested other epigenetic features other than DNA methylation are needed in regulating the imprinting of bovine SLC38A4, which is different from that of mouse with respect to a DMR existence at the mouse's slc38a4 promoter region. Although further work is needed, this first characterization of polymorphic imprinting status of SLC38A4 in cattle placenta provides valuable information on investigating the genomic imprinting phenomenon itself.

Gender differences in association between serotonin transporter gene polymorphism and resting-state EEG activity.

PubMed

Volf, N V; Belousova, L V; Knyazev, G G; Kulikov, A V

2015-01-22

Human brain oscillations represent important features of information processing and are highly heritable. Gender has been observed to affect association between the 5-HTTLPR (serotonin-transporter-linked polymorphic region) polymorphism and various endophenotypes. This study aimed to investigate the effects of 5-HTTLPR on the spontaneous electroencephalography (EEG) activity in healthy male and female subjects. DNA samples extracted from buccal swabs and resting EEG recorded at 60 standard leads were collected from 210 (101 men and 109 women) volunteers. Spectral EEG power estimates and cortical sources of EEG activity were investigated. It was shown that effects of 5-HTTLPR polymorphism on electrical activity of the brain vary as a function of gender. Women with the S/L genotype had greater global EEG power compared to men with the same genotype. In men, current source density was markedly different among genotype groups in only alpha 2 and alpha 3 frequency ranges: S/S allele carriers had higher current source density estimates in the left inferior parietal lobule in comparison with the L/L group. In women, genotype difference in global power asymmetry was found in the central-temporal region. Contrasting L/L and S/L genotype carriers also yielded significant effects in the right hemisphere inferior parietal lobule and the right postcentral gyrus with L/L genotype carriers showing lower current source density estimates than S/L genotype carriers in all but gamma bands. So, in women, the effects of 5-HTTLPR polymorphism were associated with modulation of the EEG activity in a wide range of EEG frequencies. The significance of the results lies in the demonstration of gene by sex interaction with resting EEG that has implications for understanding sex-related differences in affective states, emotion and cognition. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

PON1Q192R genetic polymorphism modifies organophosphorous pesticide effects on semen quality and DNA integrity in agricultural workers from southern Mexico

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

Perez-Herrera, N.; Polanco-Minaya, H.; Salazar-Arredondo, E.

Pesticide exposure, including organophosphorous (OP) insecticides, has been associated with poor semen quality, and paraoxonase (PON1), an enzyme involved in OP deactivation, may have a role on their susceptibility, due to PON1 polymorphisms. Our objective was to evaluate the role of PON1Q192R polymorphism on the susceptibility to OP toxicity on semen quality and DNA integrity in agricultural workers. A cross-sectional study was conducted in farmers with Mayan ascendancy from southeastern Mexico chronically exposed to pesticides; mostly OP. Fifty four agricultural workers (18-55 years old) were included, who provided semen and blood samples. Semen quality was evaluated according to WHO, spermmore » DNA damage by in situ-nick translation (NT-positive cells), PON1Q192R polymorphism by real-time PCR and serum PON1 activity by using phenylacetate and paraoxon. Two OP exposure indexes were created: at the month of sampling and during 3 months before sampling, representing the exposure to spermatids-spermatozoa and to cells at one spermatogenic cycle, respectively. PON1 192R and 192Q allele frequencies were 0.54 and 0.46, respectively. Significant associations were found between OP exposure at the month of sampling and NT-positive cells and sperm viability in homozygote 192RR subjects, and dose-effect relationships were observed between OP exposure during 3 months before sampling and sperm quality parameters and NT-positive cells in homozygote 192RR farmers. This suggests that cells at all stages of spermatogenesis are target of OP, and that there exists an interaction between OP exposure and PON1Q192R polymorphism on these effects; farmers featuring the 192RR genotype were more susceptible to develop reproductive toxic effects by OP exposure.« less

Association of GSK3beta polymorphisms with brain structural changes in major depressive disorder.

PubMed

Inkster, Becky; Nichols, Thomas E; Saemann, Philipp G; Auer, Dorothee P; Holsboer, Florian; Muglia, Pierandrea; Matthews, Paul M

2009-07-01

Indirect evidence suggests that the glycogen synthase kinase-3beta (GSK3beta) gene might be implicated in major depressive disorder (MDD). We evaluated 15 GSK3beta single-nucleotide polymorphisms (SNPs) to test for associations with regional gray matter (GM) volume differences in patients with recurrent MDD. We then used the defined regions of interest based on significant associations to test for MDD x genotype interactions by including a matched control group without any psychiatric disorder, including MDD. General linear model with nonstationary cluster-based inference. Munich, Germany. Patients with recurrent MDD (n = 134) and age-, sex-, and ethnicity-matched healthy controls (n = 143). Associations between GSK3beta polymorphisms and regional GM volume differences. Variation in GM volume was associated with GSK3beta polymorphisms; the most significant associations were found for rs6438552, a putative functional intronic SNP that showed 3 significant GM clusters in the right and left superior temporal gyri and the right hippocampus (P < .001, P = .02, and P = .02, respectively, corrected for multiple comparisons across the whole brain). Similar results were obtained with rs12630592, an SNP in high linkage disequilibrium. A significant SNP x MDD status interaction was observed for the effect on GM volumes in the right hippocampus and superior temporal gyri (P < .001 and P = .01, corrected, respectively). The GSK3beta gene may have a role in determining regional GM volume differences of the right hippocampus and bilateral superior temporal gyri. The association between genotype and brain structure was specific to the patients with MDD, suggesting that GSK3beta genotypes might interact with MDD status. We speculate that this is a consequence of regional neocortical, glial, or neuronal growth or survival. In considering core cognitive features of MDD, the association of GSK3beta polymorphisms with structural variation in the temporal lobe and hippocampus is of particular interest in the context of other evidence for structural and functional abnormalities in the hippocampi of patients with MDD.

Association of Ring Finger Protein 213 Gene P.R4810k Polymorphism with Intracranial Major Artery Stenosis/Occlusion.

PubMed

Zhang, Qian; Yu, Lebao; Ge, Peicong; Ma, Yonggang; Zhang, Dong; Zhang, Yan; Wang, Rong; Wang, Shuo; Zhao, Yuanli; Cao, Yong; Liu, Xingju; Deng, Xiaofeng; Zhao, Jizong

2018-06-01

Intracranial major artery stenosis/occlusion (ICASO) is a common cause of ischemic stroke worldwide. A number of studies have assessed the association of the p.R4810K polymorphism in the ring finger protein 213 (RNF213) gene with ICASO, but the results have not been entirely consistent. We conducted a case-control study to estimate the association between the p.R4810K polymorphism and the risk of ICASO in a Chinese population. A total of 124 patients and 230 controls were enrolled. Moreover, a meta-analysis was performed to evaluate this association in the East Asian populations. In our case-control study, the frequencies of the G/A genotype of p.R4810K were significantly higher in the ICASO patients than in the control group (4.03% versus .43%, P = .021, respectively). Moreover, in the meta-analysis, we assessed 7 case-control studies that included 1239 patients and 1377 controls. The pooled odds ratios (ORs) indicated significant association between the p.R4810K polymorphism and the ICASO risk in the dominant model (OR = 9.37, 95% confidence interval: 4.61-19.02, P = .000), the heterozygote comparison (OR = 8.97, 95% CI: 4.41-18.25, P = .000), and the allele comparison (OR = 9.50, 95% confidence interval: 4.71-19.19, P = .000) in the East Asian populations. Subgroup analysis based on ethnicity revealed that the risks in the Japanese and the Korean populations were higher than that in the Chinese population. The p.R4810K polymorphism was associated with an increased risk of ICASO in the East Asian populations. Further studies on the function of the RNF213 protein and the clinical features of this subtype of ICASO are needed. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Association between MTHFR C677T polymorphism and abdominal aortic aneurysm risk

PubMed Central

Liu, Jie; Jia, Xin; Li, Haifeng; Jia, Senhao; Zhang, Minhong; Xu, Yongle; Du, Xin; Zhang, Nianrong; Lu, Weihang; Guo, Wei

2016-01-01

Abstract Background: Abdominal aortic aneurysm (AAA) is a life-threatening condition. A number of studies reported the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and AAA risk, but substantial controversial findings were observed and the strength of the association remains unclear. Objective: The aim of this study was to investigate the aforementioned association in the overall population and different subgroups. Methods: PUBMED and EMBASE databases were searched until March 2016 to identify eligible studies, restricted to humans and articles published in English. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the susceptibility to AAA. Subgroup meta-analyses were conducted on features of the population, such as ethnicity, sex of the participants, and study design (source of control). Results: Twelve case–control studies on MTHFR C677T polymorphism and AAA risk, including 3555 cases and 6568 case-free controls were identified. The results revealed no significant association between the MTHFR C677T polymorphism and AAA risk in the overall population and within Caucasian or Asian subpopulations in all 5 genetic models. Further subgroup meta-analysis indicated that significantly increased risks were observed among cases with a mean age <70 years (OR = 1.73, 95% CI = 1.10–2.12, P = 0.02), cases with prevalence of smoking <60% (OR = 1.39, 95% CI = 1.02–1.90, P = 0.04), and cases with aneurysm diameter ≥55 mm (OR = 1.55, 95% CI = 1.07–2.24, P = 0.02) in the dominant genetic model. No publication bias was detected in the present study. Conclusion: In conclusion, our comprehensive meta-analysis suggests that the MTHFR C677T polymorphism may play an important role in AAA susceptibility, especially in younger, non-smoking, larger AAA-diameter subgroups of patients PMID:27603386

Significant association between ERCC2 and MTHR polymorphisms and breast cancer susceptibility in Moroccan population: genotype and haplotype analysis in a case-control study.

PubMed

Hardi, Hanaa; Melki, Rahma; Boughaleb, Zouhour; El Harroudi, Tijani; Aissaoui, Souria; Boukhatem, Noureddine

2018-03-15

Genetic determinants of breast cancer (BC) remained largely unknown in the majority of Moroccan patients. The purpose of this study was to explore the association of ERCC2 and MTHFR polymorphisms with genetic susceptibility to breast cancer in Moroccan population. We genotyped ERCC2 polymorphisms (rs1799793 (G934A) and rs13181 (A2251C)) and MTHFR polymorphisms (rs1801133 (C677T) and rs1801131 (A1298C)) using TaqMan SNP Genotyping Assays. Genotypes were compared in 151 BC cases and 156 population-matched controls. Allelic, genotypic and haplotype associations with the risk and clinicopathological features of BC were assessed using logistic regression analyses. ERCC2-rs1799793-AA genotype was associated with high risk of BC compared to wild type genotype (recessive model: OR: 2.90, 95% CI: 1.34-6.26, p = 0.0069) even after Bonferroni correction (p < 0,0125). MTHFR rs1801133-TT genotype was associated with increased risk of BC (recessive model, OR: 2.49, 95% CI: 1.17-5.29, p = 0.017) but the association turned insignificant after Bonferroni correction. For the rest of SNPs, no statistical associations to BC risk were detected. Significant association with clinical features was detected for MTHFR-rs1801133-TC genotype with early age at diagnosis and familial BC. Following Bonferroni correction, only association with familial BC remained significant. MTHFR-rs1801131-CC genotype was associated with sporadic BC. ERCC2-rs1799793-AA genotype correlated with ER+ and PR+ breast cancer. ERCC2-rs13181-CA genotype was significantly associated large tumors (T ≥ 3) in BC patients. None of these associations passed Bonferroni correction. Haplotype analysis showed that ERCC2 A-C haplotype was significantly associated with increased BC risk (OR: 3.71, 95% CI: 1.7-8.12, p = 0.0002 and p = 0.0008 before and after Bonferroni correction, respectively) and positive expression of ER and PR in BC patients. ERCC2 G-C haplotype was correlated with PR negative and larger tumor (T4). We did not find any MTHFR haplotypes associated with BC susceptibility. However, the less common haplotype MTHFR T-C was more frequent in young patients and in familial breast cancer, while MTHFR C-C haplotype was associated with sporadic BC form. Our findings are a first observation of association between ERCC2 SNPs and breast cancer in Moroccan population. The results suggested that ERCC2 and MTHFR polymorphisms may be reliable for assessing risk and prognosis of BC in Moroccan population.

Autoimmunity-Associated PTPN22 Polymorphisms in Latent Autoimmune Diabetes of the Adult Differ from Those of Type 1 Diabetes Patients.

PubMed

Heneberg, Petr; Kocková, Lucie; Čecháková, Marie; Daňková, Pavlína; Černá, Marie

2018-06-12

A portion of adults with humoral immune changes have clinical diabetes that is initially not insulin-requiring (latent autoimmune diabetes of the adult, LADA). One of the genes strongly associated with autoimmune diabetes is PTPN22. We hypothesized that the manifestation and clinical features of LADA are linked to functional variants of PTPN22. We genotyped allelic frequencies of 1 protective and 3 risk-associated PTPN22 variants in 156 Czech LADA patients, 194 type 2 diabetes mellitus patients with LADA-like progression to insulinotherapy and 324 type 1 diabetes mellitus patients, and subsequently examined the associations of PTPN22 variants with the expression of autoantibodies and other clinical features of LADA. We challenged the paradigm that stated that the PTPN22 c.1858T allele serves as a risk allele for LADA, although we confirmed its risk status in the geographically matched T1DM cohort. In contrast, the frequencies of other PTPN22 alleles (c.-1123C, c.788A and c.1970-852C) differed significantly from the healthy controls. We confirmed gender-related differences in the frequency of some PTPN22 polymorphisms (but not c.1858C>T) in LADA. The particular PTPN22 alleles and genotypes were associated with specific clinical features of the examined patients (autoantibodies, HbA1c and age at diagnosis of diabetes). The variability in PTPN22 haplotypes suggests that the genetic signature of LADA is independent and should not be considered a hybrid form of T1DM and T2DM. Further studies should elucidate the associations with clinical characteristics of the LADA patients and focus on the newly emerging types of diabetes with the disease onset in early to mid-adulthood. © 2018 S. Karger AG, Basel.

Mucin (MUC1) Expression and Function in Prostate Cancer Cells

DTIC Science & Technology

2004-03-01

Biophysical Research Communications 293 (2002) 1183-1190 1189 site, and is a feature of MUC4 metabolism [36]. [12] S. Zotter, P.C. Hageman, A. Lossnitzer...W.J. Mooi, J. Hilgers, Although the cleavage site sequence in MUC4 differs Tissue and tumor distribution of human polymorphic epithelial from that of...family of putative secreted (2001) 715-720. and membrane-associated MUC4 mucins, Eur. J. Biochem. 267 [261 M. Boshell, E-N. Lalani, L. Pemberton, J

Integrating Genetic, Neuropsychological and Neuroimaging Data to Model Early-Onset Obsessive Compulsive Disorder Severity

PubMed Central

Mas, Sergi; Gassó, Patricia; Morer, Astrid; Calvo, Anna; Bargalló, Nuria; Lafuente, Amalia; Lázaro, Luisa

2016-01-01

We propose an integrative approach that combines structural magnetic resonance imaging data (MRI), diffusion tensor imaging data (DTI), neuropsychological data, and genetic data to predict early-onset obsessive compulsive disorder (OCD) severity. From a cohort of 87 patients, 56 with complete information were used in the present analysis. First, we performed a multivariate genetic association analysis of OCD severity with 266 genetic polymorphisms. This association analysis was used to select and prioritize the SNPs that would be included in the model. Second, we split the sample into a training set (N = 38) and a validation set (N = 18). Third, entropy-based measures of information gain were used for feature selection with the training subset. Fourth, the selected features were fed into two supervised methods of class prediction based on machine learning, using the leave-one-out procedure with the training set. Finally, the resulting model was validated with the validation set. Nine variables were used for the creation of the OCD severity predictor, including six genetic polymorphisms and three variables from the neuropsychological data. The developed model classified child and adolescent patients with OCD by disease severity with an accuracy of 0.90 in the testing set and 0.70 in the validation sample. Above its clinical applicability, the combination of particular neuropsychological, neuroimaging, and genetic characteristics could enhance our understanding of the neurobiological basis of the disorder. PMID:27093171

Thick keratoconic cornea associated with posterior polymorphous corneal dystrophy.

PubMed

Zaarour, K; Slim, E; Antoun, J; Waked, N

2017-03-01

We herein report a case of bilateral unusually thick non-edematous keratoconic corneas with associated endothelial features of posterior polymorphous corneal dystrophy (PPCD). We report the case of a 27-year-old myopic woman who presented for refractive surgery. Slit lamp exam showed bilateral corneal protrusion with diffuse deep stromal and endothelial vesicular opacities and small paracentral bands. Topography showed generalized advanced corneal steepening in both eyes with increased anterior and posterior central corneal elevations in comparison to the best fit sphere. Ultrasound pachymetry showed central corneal thickness of 605μm (RE) and 612μm (LE). On specular biomicroscopy, cell density of 2503 cells/mm 2 RE and 1526 cells/mm 2 LE with significant cellular pleomorphism and polymegathism were noted. Clinical and paraclinical findings together suggest the presence of simultaneous keratoconus and PPCD. The literature has suggested an association between PPCD and steep cornea. Moreover, many reports have also described cases of associated PPCD and keratoconus with characteristic thinning and ectasia, in comparison to the unusual thick corneas noted in our patient, despite the absence of edema. Identification of genetics factors is further needed to clarify this association. This case describes a patient whose corneas present features of both keratoconus and PPCD and is unique due to the presence of increased corneal thickness despite the absence of edema. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Mechanism and Substrate Recognition of Human Holo ACP Synthase

PubMed Central

Bunkoczi, Gabor; Pasta, Saloni; Joshi, Anil; Wu, Xiaoqiu; Kavanagh, Kathryn L.; Smith, Stuart; Oppermann, Udo

2007-01-01

Summary Mammals utilize a single phosphopantetheinyl transferase for the posttranslational modification of at least three different apoproteins: the carrier protein components of cytosolic and mitochondrial fatty acid synthases and the aminoadipate semialdehyde reductase involved in lysine degradation. We determined the crystal structure of the human phosphopantetheinyl transferase, a eukaryotic phosphopantetheinyl transferase characterized, complexed with CoA and Mg2+, and in ternary complex with CoA and ACP. The involvement of key residues in ligand binding and catalysis was confirmed by mutagenesis and kinetic analysis. Human phosphopantetheinyl transferase exhibits an α/β fold and 2-fold pseudosymmetry similar to the Sfp phosphopantetheinyl transferase from Bacillus subtilis. Although the bound ACP exhibits a typical four-helix structure, its binding is unusual in that it is facilitated predominantly by hydrophobic interactions. A detailed mechanism is proposed describing the substrate binding and catalytic process. PMID:18022563

Selected gene polymorphisms effect on skin and hair pigmentation in Polish children at the prepubertal age.

PubMed

Sitek, Aneta; Rosset, Iwona; Żądzińska, Elżbieta; Siewierska-Górska, Anna; Pietrowska, Edyta; Strapagiel, Dominik

2016-11-01

Background : Human pigmentation, similarly as many other biological features, changes in the course of post-natal ontogenesis, while in case of hair, pigmentation changes are more distinctive than in the skin or the iris. It is therefore extremely important to identify the genes, involved in the constitution of human pigmentation features at various stages of ontogenesis. Results of this type of analyses are of high practical significance in forensic study because they enable to create mathematical tools, allowing for prediction of the pigmentation phenotype, based on DNA studies. Aim : The objective of the investigation was finding out whether the genes, associated with pigmentation of adult subjects, differentiated in any way the newly forming pigmentation phenotype in Polish prepubertal children. Material and methods : The study encompassed Polish children, aged 7 to 10 years, without any abnormalities in skin or hair pigmentation. A total of 245 children were examined. Constitutive skin pigmentation according to skin melanin index (SMI) was evaluated, using a dermaspectrometer, and classified into three groups based on the reference values of 25 and 75 percentile for Polish children. Hair colors were evaluated by means of the descriptive Fischer-Saller scale and classified by a division of color variants (as accepted in that scale) (light blonde, blonde, dark blonde, brown and dark brown). In saliva samples, collected from the children, five (5) single nucleotide polymorphisms were identified: SNPs : rs1800401 ( OCA2 -15q11.2-q12), rs35264875 ( TPCN2 -11q13.3), rs16891982 ( SLC45A2 -5p13.2), rs12913832 ( HERC2 -15q13) and rs1805007 ( MC1R -16q24.3). An association between each allele of verified genotype and skin and hair color phenotypes was assessed, using the z-statistic and associated p -value. The quality of classifiers was evaluated by 10-fold stratified cross-validation and was characterized by the area under the receiver operating characteristic curve (AUC). Results : Light skin pigmentation phenotype (SMI<25 percentile) was associated with rs1805007 ( MC1R ) (allelic OR=3.95; 95% Cl:1.20-12.99; p =0.0235), while the dark shade of the skin (SMI>75 percentile) with rs16891982 ( SLC45A2 ) (allelic OR =14.37; 95% Cl: 1.78-115.88; p =0.0123). The probability of dark hair (brown and dark brown) in childhood was increased by T rs12913832 allele ( HERC2 ) (OR=3.63); 95% Cl: 2.25-5.85; p < 0.0001) and dependent on it - rs1800401 ( OCA2 ) (OR=6.31; 95% Cl: 1.74-22.91; p =0.0051). Other SNPs were not significantly associated with skin and hair color but improved prediction of these features. Conclusions : From the five gene polymorphisms analysed in Polish children the strongest correlation with hair color has the rs12913832 ( HERC2 ) and with skin color - rs16891982 ( SLC45A2 ). Therefore, the above-mentioned polymorphisms may be used as components of potential models, used to predict pigmentation features in European origin children in prepubertal age. To improve predictive value of the potential scoring model for hair color, the following should be additionally included: rs1800401 ( OCA2 ), rs35264875 ( TPCN2 ) and rs1805007 ( MC1R ), while for skin color: rs12913832 ( HERC2 ) and rs1805007 ( MC1R ).

Discovery of human inversion polymorphisms by comparative analysis of human and chimpanzee DNA sequence assemblies.

PubMed

Feuk, Lars; MacDonald, Jeffrey R; Tang, Terence; Carson, Andrew R; Li, Martin; Rao, Girish; Khaja, Razi; Scherer, Stephen W

2005-10-01

With a draft genome-sequence assembly for the chimpanzee available, it is now possible to perform genome-wide analyses to identify, at a submicroscopic level, structural rearrangements that have occurred between chimpanzees and humans. The goal of this study was to investigate chromosomal regions that are inverted between the chimpanzee and human genomes. Using the net alignments for the builds of the human and chimpanzee genome assemblies, we identified a total of 1,576 putative regions of inverted orientation, covering more than 154 mega-bases of DNA. The DNA segments are distributed throughout the genome and range from 23 base pairs to 62 mega-bases in length. For the 66 inversions more than 25 kilobases (kb) in length, 75% were flanked on one or both sides by (often unrelated) segmental duplications. Using PCR and fluorescence in situ hybridization we experimentally validated 23 of 27 (85%) semi-randomly chosen regions; the largest novel inversion confirmed was 4.3 mega-bases at human Chromosome 7p14. Gorilla was used as an out-group to assign ancestral status to the variants. All experimentally validated inversion regions were then assayed against a panel of human samples and three of the 23 (13%) regions were found to be polymorphic in the human genome. These polymorphic inversions include 730 kb (at 7p22), 13 kb (at 7q11), and 1 kb (at 16q24) fragments with a 5%, 30%, and 48% minor allele frequency, respectively. Our results suggest that inversions are an important source of variation in primate genome evolution. The finding of at least three novel inversion polymorphisms in humans indicates this type of structural variation may be a more common feature of our genome than previously realized.

SLC24A5 and ASIP as phenotypic predictors in Brazilian population for forensic purposes.

PubMed

Lima, F A; de Araújo Lima, Felícia; Gonçalves, F T; de Toledo Gonçalves, Fernanda; Fridman, C; Fridman, Cintia

2015-07-01

Pigmentation is a variable and complex trait in humans and it is determined by the interaction of environmental factors, age, disease, hormones, exposure to ultraviolet radiation and genetic factors, including pigmentation genes. Many polymorphisms of these genes have been associated with phenotypic diversity of skin, eyes and hair color in homogeneous populations. Phenotype prediction from biological samples using genetic information has benefited forensic area in some countries, leading some criminal investigations. Herein, we evaluated the association between polymorphisms in the genes SLC24A5 (rs1426654) and ASIP (rs6058017) with skin, eyes and hair colors, in 483 healthy individuals from Brazilian population for attainable use in forensic practice. The volunteers answered a questionnaire where they self-reported their skin, eye and hair colors. The polymorphic homozygous genotype of rs1426654∗A and rs6058017∗A in SLC24A5 and ASIP respectively, showed strongest association with fairer skin (OR 47.8; CI 14.1-161.6 and OR 8.6; CI 2.5-29.8); SLC24A5 alone showed associations with blue eyes (OR 20.7; CI 1.2-346.3) and blond hair (OR 26.6; CI 1.5-460.9). Our data showed that polymorphic genotypes (AA), in both genes, are correlated with characteristics of light pigmentation, while the ancestral genotype (GG) is related to darker traits, corroborating with previous studies in European and African populations. These associations show that specific molecular information of an individual may be useful to access some phenotypic features in an attempt to help forensic investigations, not only on crime scene samples but also in cases of face reconstructions in unknown bodies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Intraspecific Polymorphism, Interspecific Divergence, and the Origins of Function-Altering Mutations in Deer Mouse Hemoglobin

PubMed Central

Natarajan, Chandrasekhar; Hoffmann, Federico G.; Lanier, Hayley C.; Wolf, Cole J.; Cheviron, Zachary A.; Spangler, Matthew L.; Weber, Roy E.; Fago, Angela; Storz, Jay F.

2015-01-01

Major challenges for illuminating the genetic basis of phenotypic evolution are to identify causative mutations, to quantify their functional effects, to trace their origins as new or preexisting variants, and to assess the manner in which segregating variation is transduced into species differences. Here, we report an experimental analysis of genetic variation in hemoglobin (Hb) function within and among species of Peromyscus mice that are native to different elevations. A multilocus survey of sequence variation in the duplicated HBA and HBB genes in Peromyscus maniculatus revealed that function-altering amino acid variants are widely shared among geographically disparate populations from different elevations, and numerous amino acid polymorphisms are also shared with closely related species. Variation in Hb-O2 affinity within and among populations of P. maniculatus is attributable to numerous amino acid mutations that have individually small effects. One especially surprising feature of the Hb polymorphism in P. maniculatus is that an appreciable fraction of functional standing variation in the two transcriptionally active HBA paralogs is attributable to recurrent gene conversion from a tandemly linked HBA pseudogene. Moreover, transpecific polymorphism in the duplicated HBA genes is not solely attributable to incomplete lineage sorting or introgressive hybridization; instead, it is mainly attributable to recurrent interparalog gene conversion that has occurred independently in different species. Partly as a result of concerted evolution between tandemly duplicated globin genes, the same amino acid changes that contribute to variation in Hb function within P. maniculatus also contribute to divergence in Hb function among different species of Peromyscus. In the case of function-altering Hb mutations in Peromyscus, there is no qualitative or quantitative distinction between segregating variants within species and fixed differences between species. PMID:25556236

Preeclampsia is associated with ACE I/D polymorphism, obesity and oxidative damage in Mexican women.

PubMed

González-Garrido, José A; García-Sánchez, José R; Tovar-Rodríguez, José M; Olivares-Corichi, Ivonne M

2017-10-01

This study sought to determine whether the angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphism, obesity and oxidative damage are risk factors for the development of preeclampsia in Mexican women. A total of 66 women with preeclampsia (PE) and 37 women with normal pregnancies (NP) were included in the study. DNA was extracted from whole blood, and the ACE I/D polymorphism was evaluated by polymerase chain reaction. ACE activity and oxidative damage were assessed in plasma. The intergroup comparisons were analyzed by an analysis of variance (ANOVA) with post hoc tests. Hardy-Weinberg equilibrium (HWE) was tested by x 2 analysis, odds ratios (OR) were calculated as a measure of the degree of relative risk of preeclampsia, and for correlations, we used Spearman's correlation coefficient. The frequency of the DD genotype was higher in PE (34.84%) than NP (10.82%). The OR of the DD genotype and D allele were associated with a 4.4-fold (CI=95% 2.24-14) and 3-fold (CI=95% 1.69-5.62) increased risk of developing PE, respectively. Major ACE activity in the DD genotype and obesity were features of the PE group; oxidative damage to proteins and a reduction in the activity of the antioxidant system showed a correlation with BMI (p<0.01). Our results suggest that ACE I/D polymorphism, high ACE activity, body mass index and oxidative damage may play key roles in the pathogenesis of PE in the Mexican population. Furthermore, these findings could be used as predictive factors of PE. Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

The associations of genetic polymorphisms in CYP1A2 and CYP3A4 with clinical outcomes of breast cancer patients in northern China

PubMed Central

Bai, Xianan; Xie, Jingjing; Sun, Shanshan; Zhang, Xianyu; Jiang, Yongdong; Pang, Da

2017-01-01

Background Cytochrome P450 (CYP) 1A2 and CYP3A4 may play a role in the differentiation of clinical outcomes among breast cancer women. This study aimed to analyze the association of genetic polymorphisms in the CYP1A2 and CYP3A4 genes with clinicopathological features, protein expression and prognosis of breast cancer in the northern Chinese population. Results Firstly, SNP rs11636419, rs17861162 and rs2470890 in the CYP1A2 were significantly associated with age and menstruation status. And SNP rs11636419 and rs17861162 were associated with the P53 status. Secondly, SNP rs2470890 was correlated with CYP1A2 protein expression under the co-dominant and dominant model (P = 0.017, P = 0.006, respectively). Thirdly, for SNP rs2470890, the Kaplan–Meier 5 year survival curves showed that patients carrying genotypes CT or TT had a worse OS compared with the genotype CC carriers under both codominant and dominant model (P < 0.001, P < 0.001, respectively). Materials and Methods Four single nucleotide polymorphisms (SNPs) were successfully genotyped in 459 breast cancer patients using the SNaPshot method. The associations of four polymorphisms with protein expression and clinicopathological characteristics were evaluated by Pearson's chi-square test. The Cox hazard regression analysis and Kaplan–Meier survival analysis were performed to evaluate the relationship between the SNPs and overall survival (OS) of breast cancer. Conclusions CYP1A2 rs2470890 was significantly associated with the prognosis of patients with breast cancer and could serve as an independent impact factor of prognosis of breast carcinoma. PMID:28418906

Widespread Impact of HLA Restriction on Immune Control and Escape Pathways of HIV-1

PubMed Central

Listgarten, Jennifer; Pfeifer, Nico; Tan, Vincent; Kadie, Carl; Walker, Bruce D.; Ndung'u, Thumbi; Shapiro, Roger; Frater, John; Brumme, Zabrina L.; Goulder, Philip J. R.; Heckerman, David

2012-01-01

The promiscuous presentation of epitopes by similar HLA class I alleles holds promise for a universal T-cell-based HIV-1 vaccine. However, in some instances, cytotoxic T lymphocytes (CTL) restricted by HLA alleles with similar or identical binding motifs are known to target epitopes at different frequencies, with different functional avidities and with different apparent clinical outcomes. Such differences may be illuminated by the association of similar HLA alleles with distinctive escape pathways. Using a novel computational method featuring phylogenetically corrected odds ratios, we systematically analyzed differential patterns of immune escape across all optimally defined epitopes in Gag, Pol, and Nef in 2,126 HIV-1 clade C-infected adults. Overall, we identified 301 polymorphisms in 90 epitopes associated with HLA alleles belonging to shared supertypes. We detected differential escape in 37 of 38 epitopes restricted by more than one allele, which included 278 instances of differential escape at the polymorphism level. The majority (66 to 97%) of these resulted from the selection of unique HLA-specific polymorphisms rather than differential epitope targeting rates, as confirmed by gamma interferon (IFN-γ) enzyme-linked immunosorbent spot assay (ELISPOT) data. Discordant associations between HLA alleles and viral load were frequently observed between allele pairs that selected for differential escape. Furthermore, the total number of associated polymorphisms strongly correlated with average viral load. These studies confirm that differential escape is a widespread phenomenon and may be the norm when two alleles present the same epitope. Given the clinical correlates of immune escape, such heterogeneity suggests that certain epitopes will lead to discordant outcomes if applied universally in a vaccine. PMID:22379086

Sustainability of renewable fuel infrastructure: a screening LCA case study of anticorrosive graphene oxide epoxy liners in steel tanks for the storage of biodiesel and its blends.

PubMed

Chilkoor, Govinda; Upadhyayula, Venkata K K; Gadhamshetty, Venkataramana; Koratkar, Nikhil; Tysklind, Mats

2017-02-22

Biodiesel is a widely used fuel that meets the renewable fuel standards developed under the Energy Policy Act of 2005. However, biodiesel is known to pose a series of abiotic and biotic corrosion risks to storage tanks. A typical practice (incumbent system) used to protect the tanks from these risks include (i) coating the interior surface of the tank with a solvent-free epoxy (SFE) liner, and (ii) adding a biocide to the tank. Herein, we present a screening-level life-cycle assessment study to compare the environmental performance of a graphene oxide (GO)-epoxy (GOE) liner with the incumbent system. TRACI was used as an impact assessment tool to model the midpoint environmental impacts in ten categories: global warming potential (GWP, kg CO 2 eq.); acidification potential (AP, kg SO 2 eq.); potential human health damage impacts due to carcinogens (HH-CP, CTU h ) and non-carcinogens (HH-NCP, CTU h ); potential respiratory effects (REP, kg PM 2.5 eq.); eutrophication potential (EP, kg N eq.); ozone depletion potential (ODP kg CFC-11 eq.); ecotoxicity potential (ETXP, CTU e ); smog formation potential (SFP kg O 3 eq.) and fossil fuel depletion potential (FFDP MJ surplus). The equivalent functional unit of the LCA study was designed to protect 30 m 2 of the interior surface (unalloyed steel sheet) of a 10 000 liter biodiesel tank against abiotic and biotic corrosion during its service life of 20 years. Overall, this LCA study highlights the improved environmental performance for the GOE liner compared to the incumbent system, whereby the GOE liner showed 91% lower impacts in ODP impact category, 59% smaller in REP, 62% smaller in AP, 67-69% smaller in GWP and HH-CP, 72-76% smaller in EP, SFP, and FFDP, and 81-83% smaller ETXP and HH-NCP category results. The scenario analysis study revealed that these potential impacts change by less than 15% when the GOE liners are functionalized with silanized-GO nanosheets or GO-reinforced polyvinyl carbazole to improve the antimicrobial properties. The results from an uncertainty analysis indicated that the impacts for the incumbent system were more sensitive to changes in the key modeling parameters compared to that for the GOE liner system.

Association of Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Thyroglobulin (TG) Genetic Variants with Autoimmune Hypothyroidism

PubMed Central

Patel, Hinal; Mansuri, Mohmmad Shoab; Singh, Mala; Begum, Rasheedunnisa; Shastri, Minal; Misra, Ambikanandan

2016-01-01

Autoimmune hypothyroidism is known to be caused by immune responses related to the thyroid gland and its immunological feature includes presence of autoimmune antibodies. Therefore the aim was to analyze presence of anti-TPO antibodies in hypothyroidism patients in Gujarat. Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) is one of the susceptibility genes for various autoimmune diseases. Hence, exon1 +49A/G and 3’UTR CT60A/G single nucleotide polymorphisms (SNPs) in CTLA4 and its mRNA expression levels were investigated in autoimmune hypothyroidism patients. Thyroglobulin (TG) is known to be associated with autoimmune thyroid disorders and thus exon 33 (E33) SNP in TG was investigated. We analyzed the presence of anti-TPO antibodies in the plasma samples of 84 hypothyroidism patients and 62 controls by ELISA. PCR-RFLP technique was used for genotyping of polymorphisms. sCTLA4 and flCTLA4 mRNA expression levels were assessed by real time PCR. 59.52% of hypothyroid patients had anti-TPO antibodies in their circulation. The genotype and allele frequencies differed significantly for +49A/G (p = 0.0004 for +49AG, p = 0.0019 for +49GG & p = 0.0004 for allele), CT60 (p = 0.0110 for CT60AG, p = 0.0005 for CT60GG & p<0.0001 for allele) and TG E33 (p = 0.0003 for E33TC p<0.0001 for E33CC& p<0.0001 for allele) SNPs between patients and controls. Patients had significantly decreased mRNA levels of both sCTLA4 (p = 0.0017) and flCTLA4 (p<0.0001) compared to controls. +49A/G and CT60 polymorphisms of CTLA4 were in moderate linkage disequilibrium. Logistic regression analysis indicated significant association of CT49A/G, CT60A/G and TG exon 33 polymorphisms with susceptibility to autoimmune hypothyroidism when adjusted for age and gender. Our results suggest +49A/G and CT60 polymorphism of CTLA4 and E33 polymorphism of TG may be genetic risk factors for autoimmune hypothyroidism susceptibility and down regulation of both forms of CTLA4 advocates the crucial role of CTLA4 in pathogenesis of autoimmune hypothyroidism. PMID:26963610

The Arg72 variant of the p53 functional polymorphism (rs1042522) is associated with coronary artery disease in young South Africans of Indian ancestry.

PubMed

Khan, Sajidah; Phulukdaree, Alisa; Ramkaran, Prithiksha; Moodley, Devapregasan; Chuturgoon, Anil A

2016-11-30

Tumor protein p53 (p53), classically referred to as a tumor suppressor gene, is involved in cell cycle regulation and may be related to atherosclerosis by affecting smooth muscle cell proliferation, a feature of atherogenesis. A polymorphism at codon 72 (rs1042522) results in functional variability and hence plays a role in the pathophysiology of coronary artery disease (CAD). This polymorphism has been well established for its role in cancer and has only recently been investigated in CAD. Limited data is available on South Africans (SA) of Indian ancestry. We examined associations of this polymorphism and clinical markers in a cohort of young SA Indian CAD patients. A total of 284 subjects were recruited into this study which included 100 CAD patients (diagnosed on angiography, mean age 37.5, range 24-45years), 100 age- and sex-matched Indian controls and 84 age- and sex-matched Black controls. Polymorphic variants were assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Data for clinical markers were obtained from pathology reports. Genotype distribution differed significantly between CAD patients and Indian controls (Pro/Pro, Pro/Arg, Arg/Arg: 24%, 48%, 28% vs. 30%, 61%, 9% respectively, p=0.0025). There was a significant genotype distribution between Indian and Black controls (Pro/Pro, Pro/Arg, Arg/Arg: 30%, 61%, 9% vs. 45.2% 40.5%, 14.3% respectively, p=0.0212). A significantly higher frequency of the p53 Arg72 allele was found in CAD patients compared to controls (52% vs. 39.5% respectively, p=0.0159). The variant allele was slightly higher in Indian controls (39.5%) compared to Black controls (34.5%), but this did not reach statistical significance (p=0.3324). The levels of total cholesterol, LDL, HDL, triglycerides, fasting glucose, fasting insulin and %HbA1c were not significantly influenced by the p53 genotypic variants. Although the p53 codon 72 SNP is not associated with clinical markers of disease in CAD, the higher frequency of the variant allele in SA Indians may be a contributing factor for this population having an increased risk of developing premature CAD. Copyright © 2016. Published by Elsevier B.V.

Evidence for the Influence of the Iron Regulatory MHC Class I Molecule HFE on Tumor Progression in Experimental Models and Clinical Populations

PubMed Central

Weston, Cody; Connor, James

2014-01-01

Proteins involved in iron regulation are modifiers of cancer risk and progression. Of these, the HFE protein (high iron gene and its protein product) is of particular interest because of its interaction with both iron handling and immune function and the high rate of genetic polymorphisms resulting in a mutant protein. Clinical studies suggest that HFE polymorphisms increase the risk of certain cancers, but the inconsistent outcomes suggest a more nuanced effect, possibly interacting with other genetic or environmental factors. Some basic science research has been conducted to begin to understand the implications of variant HFE genotype on cancer, but the story is far from complete. In particular, putative mechanisms exist for HFE to affect tumor progression through its role in iron handling and its major histocompatibility complex class I structural features. In this review, the current understanding of the role of HFE in cancer is described and models for future directions are identified. PMID:25520556

Characterization of titanyl phthalocyanine (TiOPc) thin films by microscopic and spectroscopic method

NASA Astrophysics Data System (ADS)

Skonieczny, R.; Makowiecki, J.; Bursa, B.; Krzykowski, A.; Szybowicz, M.

2018-02-01

The titanyl phthalocyanine (TiOPc) thin film deposited on glass, silicon and gold substrate have been studied using Raman spectroscopy, atomic force microscopy (AFM), absorption and profilometry measurements. The TiOPc thin layers have been deposited at room temperature by the quasi-molecular beam evaporation technique. The Raman spectra have been recorded using micro Raman system equipped with a confocal microscope. Using surface Raman mapping techni que with polarized Raman spectra the polymorphic forms of the TiOPc thin films distribution have been obtained. The AFM height and phase image were examined in order to find surface features and morphology of the thin films. Additionally to compare experimental results, structure optimization and vibrational spectra calculation of single TiOPc molecule were performed using DFT calculations. The received results showed that the parameters like polymorphic form, grain size, roughness of the surface in TiOPc thin films can well characterize the obtained organic thin films structures in terms of their use in optoelectronics and photovoltaics devices.

Structural study of polymorphism in methylprednisolone aceponate

NASA Astrophysics Data System (ADS)

Knyazev, A. V.; Somov, N. V.; Shipilova, A. S.; Gusarova, E. V.; Knyazeva, S. S.; Stepanova, O. V.; Chuprunov, E. V.

2017-08-01

The crystal structures of methylprednisolone aceponate were determined by X-ray diffraction analysis at temperatures 90 K and 150 K: space group P212121, a = 14.8592(2), b = 19.6844(5), c = 26.1626(4) Å, Z = 12; R = 0.0598 (T = 90 K); space group P212121, a = 6.57348(14), b = 14.8295(3), c = 26.2214(5) Å, Z = 4; R = 0.0518 (T = 150 K). Features of structural changes in the phase transition were revealed. The abrupt change in the unit cell parameters in the phase transition was shown by low-temperature X-ray powder. The methods of degree of invariance of crystal electron density and molecular Voronoi-Dirichlet polyhedra were used for the analysis of polymorphism in methylprednisolone aceponate. The atomic structure at 90 K have a translational pseudosymmetry of electron density η = 0.329(1). The decrease of number of intermolecular contacts in the high-temperature modification due to rupture of intermolecular non-valence contacts C/O was observed.

Conserved hypothetical protein Rv1977 in Mycobacterium tuberculosis strains contains sequence polymorphisms and might be involved in ongoing immune evasion.

PubMed

Jiang, Yi; Liu, Haican; Wang, Xuezhi; Li, Guilian; Qiu, Yan; Dou, Xiangfeng; Wan, Kanglin

2015-01-01

Host immune pressure and associated parasite immune evasion are key features of host-pathogen co-evolution. A previous study showed that human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved and thus it was deduced that M. tuberculosis lacks antigenic variation and immune evasion. Here, we selected 151 clinical Mycobacterium tuberculosis isolates from China, amplified gene encoding Rv1977 and compared the sequences. The results showed that Rv1977, a conserved hypothetical protein, is not conserved in M. tuberculosis strains and there are polymorphisms existed in the protein. Some mutations, especially one frameshift mutation, occurred in the antigen Rv1977, which is uncommon in M.tb strains and may lead to the protein function altering. Mutations and deletion in the gene all affect one of three T cell epitopes and the changed T cell epitope contained more than one variable position, which may suggest ongoing immune evasion.

The rDNA ITS region in the lessepsian marine angiosperm Halophila stipulacea (Forssk.) Aschers. (Hydrocharitaceae): intragenomic variability and putative pseudogenic sequences.

PubMed

Ruggiero, Maria Valeria; Procaccini, Gabriele

2004-01-01

Halophila stipulacea is a dioecious marine angiosperm, widely distributed along the western coasts of the Indian Ocean and the Red Sea. This species is thought to be a Lessepsian immigrant that entered the Mediterranean Sea from the Red Sea after the opening of the Suez Canal (1869). Previous studies have revealed both high phenotypic and genetic variability in Halophila stipulacea populations from the western Mediterranean basin. In order to test the hypothesis of a Lessepsian introduction, we compare genetic polymorphism between putative native (Red Sea) and introduced (Mediterranean) populations through rDNA ITS region (ITS1-5.8S-ITS2) sequence analysis. A high degree of intraindividual variability of ITS sequences was found. Most of the intragenomic polymorphism was due to pseudogenic sequences, present in almost all individuals. Features of ITS functional sequences and pseudogenes are described. Possible causes for the lack of homogenization of ITS paralogues within individuals are discussed.

Feature-based classification of amino acid substitutions outside conserved functional protein domains.

PubMed

Gemovic, Branislava; Perovic, Vladimir; Glisic, Sanja; Veljkovic, Nevena

2013-01-01

There are more than 500 amino acid substitutions in each human genome, and bioinformatics tools irreplaceably contribute to determination of their functional effects. We have developed feature-based algorithm for the detection of mutations outside conserved functional domains (CFDs) and compared its classification efficacy with the most commonly used phylogeny-based tools, PolyPhen-2 and SIFT. The new algorithm is based on the informational spectrum method (ISM), a feature-based technique, and statistical analysis. Our dataset contained neutral polymorphisms and mutations associated with myeloid malignancies from epigenetic regulators ASXL1, DNMT3A, EZH2, and TET2. PolyPhen-2 and SIFT had significantly lower accuracies in predicting the effects of amino acid substitutions outside CFDs than expected, with especially low sensitivity. On the other hand, only ISM algorithm showed statistically significant classification of these sequences. It outperformed PolyPhen-2 and SIFT by 15% and 13%, respectively. These results suggest that feature-based methods, like ISM, are more suitable for the classification of amino acid substitutions outside CFDs than phylogeny-based tools.

Association of angiotensin-converting-enzyme gene polymorphism with the depressor response to mild exercise therapy in patients with mild to moderate essential hypertension.

PubMed

Zhang, B; Sakai, T; Miura, S; Kiyonaga, A; Tanaka, H; Shindo, M; Saku, K

2002-10-01

We studied the association of angiotensin I-converting enzyme (ACE) gene polymorphism with the depressor response to exercise therapy in 64 Japanese subjects with mild to moderate essential hypertension. Each subject performed 10 weeks of mild (lactate threshold intensity: approximately 50% maximum oxygen consumption) exercise therapy on a bicycle ergometer. Systolic blood pressure (SPB), diastolic blood pressure (DPB), and mean arterial pressure (MAP) were significantly decreased by exercise therapy in subjects with the ACE-II and ID genotypes but not in DD subjects. The time-by-genotype interaction effects were significant for DBP and MAP. According to a multiple logistic regression analysis, the age- and baseline plasma renin activity-adjusted relative risk (odds ratio) for the lack of a depressor response conferred by the D allele (assuming an additive effect) was 2.72 [95% confidence interval (CI), 1.07-6.91; p = 0.034]; for DD genotypes, as compared with the DI and II genotypes (assuming that the D allele is recessive), it was 11.7 (95% CI, 2.25-60.6; p = 0.003). ACE gene I/D polymorphism is associated with the depressor response of essential hypertensives to mild exercise therapy, which suggests that genetic features may underlie, at least in part, the heterogeneity of the depressor response in essential hypertensives to mild exercise therapy.

Tumour Necrosis Factor-α Gene Polymorphism Is Associated with Metastasis in Patients with Triple Negative Breast Cancer.

PubMed

Li, Hui-Hui; Zhu, Hui; Liu, Li-Sheng; Huang, Yong; Guo, Jun; Li, Jie; Sun, Xin-Ping; Chang, Chun-Xiao; Wang, Zhe-Hai; Zhai, Kan

2015-07-13

Tumour necrosis factor-α (TNF-α) is critical in the regulation of inflammation and tumour progression. TNF-α-308G > A is associated with constitutively elevated TNF-α expression. The purpose of this study was to assess the association between TNF-α-308G > A and breast cancer (BC) risk by subtype and the connection between genotypes and clinical features of BC. A total of 768 patients and 565 controls were enrolled in this study, and genotypes were detected using the TaqMan assay. No effect on susceptibility for any BC subtype was found for the TNF-α-308 polymorphism in our study or in the pooled meta-analysis. This polymorphism was shown to be associated with age at menarche in all BC and in progesterone receptor-negative BC. Interestingly, triple negative breast cancer (TNBC) patients with TNF-α-308A had an increased risk of distant tumour metastasis (OR = 3.80, 95% CI: 1.31-11.02, P = 0.009). Multi-regression analysis showed that TNF-α-308A was also a risk factor for distant tumour metastasis after adjustment for tumour size and lymph node metastasis status (OR = 6.26, 95% CI: 1.88-20.87, P = 0.003). These findings indicate that TNF-α might play a distinct role in the progression of TNBC, especially in distant tumour metastasis of TNBC.

Rapid evolution of avirulence genes in rice blast fungus Magnaporthe oryzae

PubMed Central

2014-01-01

Background Rice blast fungus Magnaporthe oryzae is one of the most devastating pathogens in rice. Avirulence genes in this fungus share a gene-for-gene relationship with the resistance genes in its host rice. Although numerous studies have shown that rice blast R-genes are extremely diverse and evolve rapidly in their host populations, little is known about the evolutionary patterns of the Avr-genes in the pathogens. Results Here, six well-characterized Avr-genes and seven randomly selected non-Avr control genes were used to investigate the genetic variations in 62 rice blast strains from different parts of China. Frequent presence/absence polymorphisms, high levels of nucleotide variation (~10-fold higher than non-Avr genes), high non-synonymous to synonymous substitution ratios, and frequent shared non-synonymous substitution were observed in the Avr-genes of these diversified blast strains. In addition, most Avr-genes are closely associated with diverse repeated sequences, which may partially explain the frequent presence/absence polymorphisms in Avr-genes. Conclusion The frequent deletion and gain of Avr-genes and rapid non-synonymous variations might be the primary mechanisms underlying rapid adaptive evolution of pathogens toward virulence to their host plants, and these features can be used as the indicators for identifying additional Avr-genes. The high number of nucleotide polymorphisms among Avr-gene alleles could also be used to distinguish genetic groups among different strains. PMID:24725999

Catechol-O-methyltransferase (COMT) polymorphisms modulate working memory in individuals with schizophrenia and healthy controls.

PubMed

Matsuzaka, Camila T; Christofolini, Denise; Ota, Vanessa K; Gadelha, Ary; Berberian, Arthur A; Noto, Cristiano; Mazzotti, Diego R; Spindola, Leticia M; Moretti, Patricia N; Smith, Marilia A C; Melaragno, Maria I; Belangero, Sintia I; Bressan, Rodrigo A

2017-01-01

Cognitive impairment is a core feature of schizophrenia, related to dopaminergic dysfunction in the prefrontal cortex (PFC). It is hypothesized that functional single nucleotide polymorphism (SNP) rs4680 of the catechol-O-methyltransferase (COMT) gene could mediate the relationship between cognition and dopamine activity in the PFC. Other COMT SNPs could also play a role. We evaluated the role of three COMT SNPs (rs737865, rs165599, and rs4680) in schizophrenia and their impact on three working memory tasks. For genetic association analyses, 212 individuals with schizophrenia and 257 healthy controls (HCs) were selected. The Visual Working Memory (VWM) Task, Keep Track Task, and Letter Memory Task were administered to 133 schizophrenics and 93 HCs. We found a significant association of rs737865, with the GG genotype exerting a protective effect and the GA haplotype (rs4680/rs165599) exerting a risk effect for schizophrenia. COMT rs4680 AA carriers and rs737865 AA carriers scored lowest on the Keep Track Task. When the genotype*group interaction effect was evaluated, rs165599 exerted opposite effects for VWM and Keep Track task performance in patients and controls, with AA carriers scoring lowest on both tests among controls, but highest among patients. These data support the hypothesis that COMT polymorphisms may be associated with schizophrenia and modulate cognition in patients and controls.

Normal and reversed supramolecular chirality of insulin fibrils probed by vibrational circular dichroism at the protofilament level of fibril structure.

PubMed

Kurouski, Dmitry; Dukor, Rina K; Lu, Xuefang; Nafie, Laurence A; Lednev, Igor K

2012-08-08

Fibrils are β-sheet-rich aggregates that are generally composed of several protofibrils and may adopt variable morphologies, such as twisted ribbons or flat-like sheets. This polymorphism is observed for many different amyloid associated proteins and polypeptides. In a previous study we proposed the existence of another level of amyloid polymorphism, namely, that associated with fibril supramolecular chirality. Two chiral polymorphs of insulin, which can be controllably grown by means of small pH variations, exhibit opposite signs of vibrational circular dichroism (VCD) spectra. Herein, using atomic force microscopy (AFM) and scanning electron microscopy (SEM), we demonstrate that indeed VCD supramolecular chirality is correlated not only by the apparent fibril handedness but also by the sense of supramolecular chirality from a deeper level of chiral organization at the protofilament level of fibril structure. Our microscopic examination indicates that normal VCD fibrils have a left-handed twist, whereas reversed VCD fibrils are flat-like aggregates with no obvious helical twist as imaged by atomic force microscopy or scanning electron microscopy. A scheme is proposed consistent with observed data that features a dynamic equilibrium controlled by pH at the protofilament level between left- and right-twist fibril structures with distinctly different aggregation pathways for left- and right-twisted protofilaments. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Polymorphisms in the LPL and CETP Genes and Haplotype in the ESR1 Gene Are Associated with Metabolic Syndrome in Women from Southwestern Mexico.

PubMed

Cahua-Pablo, José Ángel; Cruz, Miguel; Méndez-Palacios, Abigail; Antúnez-Ortiz, Diana Lizzete; Vences-Velázquez, Amalia; del Carmen Alarcón-Romero, Luz; Parra, Esteban Juan; Tello-Flores, Vianet Argelia; Leyva-Vázquez, Marco Antonio; Valladares-Salgado, Adán; Pérez-Macedonio, Claudia Paola; Flores-Alfaro, Eugenia

2015-09-08

Metabolic syndrome (MetS) is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD). Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants in ESR1, LPL and CETP genes with MetS and its components. Four hundred and eighty women were analyzed, anthropometric features and biochemical profiles were evaluated, and genotyping was performed by real-time PCR. We found an association with elevated glucose levels (odds ratio (OR) = 2.9; p = 0.013) in carrying the AA genotype of rs1884051 in the ESR1 gene compared with the GG genotype, and the CC genotype of rs328 in the LPL gene was associated with MetS compared to the CG or GG genotype (OR = 2.8; p = 0.04). Moreover, the GA genotype of rs708272 in the CETP gene is associated with MetS compared to the GG or AA genotype (OR = 1.8; p = 0.006). In addition the ACTCCG haplotype in the ESR1 gene is associated with a decrease in the risk of MetS (OR = 0.02; p < 0.001). In conclusion, our results show the involvement of the variants of ESR1, LPL and CETP genes in metabolic events related to MetS or some of its features.

Polymorphisms in the LPL and CETP Genes and Haplotype in the ESR1 Gene Are Associated with Metabolic Syndrome in Women from Southwestern Mexico

PubMed Central

Cahua-Pablo, José Ángel; Cruz, Miguel; Méndez-Palacios, Abigail; Antúnez-Ortiz, Diana Lizzete; Vences-Velázquez, Amalia; del Carmen Alarcón-Romero, Luz; Parra, Esteban Juan; Tello-Flores, Vianet Argelia; Leyva-Vázquez, Marco Antonio; Valladares-Salgado, Adán; Pérez-Macedonio, Claudia Paola; Flores-Alfaro, Eugenia

2015-01-01

Metabolic syndrome (MetS) is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD). Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants in ESR1, LPL and CETP genes with MetS and its components. Four hundred and eighty women were analyzed, anthropometric features and biochemical profiles were evaluated, and genotyping was performed by real-time PCR. We found an association with elevated glucose levels (odds ratio (OR) = 2.9; p = 0.013) in carrying the AA genotype of rs1884051 in the ESR1 gene compared with the GG genotype, and the CC genotype of rs328 in the LPL gene was associated with MetS compared to the CG or GG genotype (OR = 2.8; p = 0.04). Moreover, the GA genotype of rs708272 in the CETP gene is associated with MetS compared to the GG or AA genotype (OR = 1.8; p = 0.006). In addition the ACTCCG haplotype in the ESR1 gene is associated with a decrease in the risk of MetS (OR = 0.02; p < 0.001). In conclusion, our results show the involvement of the variants of ESR1, LPL and CETP genes in metabolic events related to MetS or some of its features. PMID:26370976

Genetic polymorphisms of Echinococcus tapeworms in China as determined by mitochondrial and nuclear DNA sequences ✩

PubMed Central

Nakao, Minoru; Li, Tiaoying; Han, Xiumin; Ma, Xiumin; Xiao, Ning; Qiu, Jiamin; Wang, Hu; Yanagida, Tetsuya; Mamuti, Wulamu; Wen, Hao; Moro, Pedro L.; Giraudoux, Patrick; Craig, Philip S.; Ito, Akira

2009-01-01

The genetic polymorphisms of Echinococcus spp. in the eastern Tibetan Plateau and the Xinjiang Uyghur Autonomous Region were evaluated by DNA sequencing analyses of genes for mitochondrial cytochrome c oxidase subunit 1 (cox1) and nuclear elongation factor-1 alpha (ef1a). We collected 68 isolates of Echinococcus granulosus sensu stricto (s.s.) from Xinjiang and 113 isolates of E. granulosus s. s., 49 isolates of Echinococcus multilocularis and 34 isolates of Echinococcus shiquicus from the Tibetan Plateau. The results of molecular identification by mitochondrial and nuclear markers were identical, suggesting the infrequency of introgressive hybridization. A considerable intraspecific variation was detected in mitochondrial cox1 sequences. The parsimonious network of cox1 haplotypes showed star-like features in E. granulosus s. s. and E. multilocularis, but a divergent feature in E. shiquicus. The cox1 neutrality indexes computed by Tajima's D and Fu's Fs tests showed high negative values in E. granulosus s. s. and E. multilocularis, indicating significant deviations from neutrality. In contrast, the low positive values of both tests were obtained in E. shiquicus. These results suggest the following hypotheses: (i) recent founder effects arose in E. granulosus and E. multilocularis after introducing particular individuals into the endemic areas by anthropogenic movement or natural migration of host mammals, and (ii) the ancestor of E. shiquicus was segregated into the Tibetan Plateau by colonizing alpine mammals and its mitochondrial locus has evolved without bottleneck effects. PMID:19800346

Serum Anti-TPO and TPO Gene Polymorphism as a Predictive Factor for Hidden Autoimmune Thyroiditis in Patient with Bronchial Asthma and Allergic Rhinitis.

PubMed

El Shabrawy, Reham M; Atta, Amal H; Rashad, Nearmeen M

2016-01-01

Thyroid peroxidase (TPO) is the key enzyme in the biosynthesis of thyroid hormones T3 and T4. Autoimmune thyroiditis is a common disorder affecting 10% of population worldwide. A key feature of autoimmune thyroiditis is the presence of anti TPO antibodies, and some mutation of the TPO gene. Association between autoimmune thyroiditis and other autoimmune disorders has been reported but little is known about association with allergic diseases. In this study, we aimed to evaluate frequency of hidden autoimmune thyroiditis among allergic patient and examine possible relationship between anti-TPO levels and polymorphism at the TPO gene A2173/C exon 12 and different types of allergens. The study included 50 adult Egyptian patients with allergic rhinitis and /or bronchial asthma and 50 controls. For each subject, thyroid stimulating hormone (TSH), thyroxin 4 (T4) and Triiodothyronine (T3) hormones were measured. Anti-thyroid peroxidase (anti-TPO) level was detected by ELISA; and TPO gene polymorphism 2173A>C exon 12 was analyzed using restriction fragment length polymorphism (RFLP). Skin prick test was done to assess allergic response in patients. Serum levels of T3, T4 and TSH did not show any statistical significant difference between patients and groups. However, mean serum anti-TPO level was statistically higher in patients than controls, and correlated positively with body mass index, age, diastolic blood pressure, suggesting higher prevalence of hidden autoimmune thyroiditis in allergic patients than in control group. 2173A>C Genotyping revealed that the frequency of C allele is increased in the patient group. C allele represents a risk factor with odds ratio of 2.37 (1.035-5.44) and a significant P value <0.05. It is concluded that TPO 2173A>C polymorphism may be considered as a risk factor for developing autoimmune thyroiditis in patients with allergic rhinitis and asthma and that these patients should regularly be checked for hidden thyroiditis. Copyright© by the Egyptian Association of Immunologists.

Trans-species polymorphism at antimicrobial innate immunity cathelicidin genes of Atlantic cod and related species

PubMed Central

Árnason, Einar

2015-01-01

Natural selection, the most important force in evolution, comes in three forms. Negative purifying selection removes deleterious variation and maintains adaptations. Positive directional selection fixes beneficial variants, producing new adaptations. Balancing selection maintains variation in a population. Important mechanisms of balancing selection include heterozygote advantage, frequency-dependent advantage of rarity, and local and fluctuating episodic selection. A rare pathogen gains an advantage because host defenses are predominantly effective against prevalent types. Similarly, a rare immune variant gives its host an advantage because the prevalent pathogens cannot escape the host’s apostatic defense. Due to the stochastic nature of evolution, neutral variation may accumulate on genealogical branches, but trans-species polymorphisms are rare under neutrality and are strong evidence for balancing selection. Balanced polymorphism maintains diversity at the major histocompatibility complex (MHC) in vertebrates. The Atlantic cod is missing genes for both MHC-II and CD4, vital parts of the adaptive immune system. Nevertheless, cod are healthy in their ecological niche, maintaining large populations that support major commercial fisheries. Innate immunity is of interest from an evolutionary perspective, particularly in taxa lacking adaptive immunity. Here, we analyze extensive amino acid and nucleotide polymorphisms of the cathelicidin gene family in Atlantic cod and closely related taxa. There are three major clusters, Cath1, Cath2, and Cath3, that we consider to be paralogous genes. There is extensive nucleotide and amino acid allelic variation between and within clusters. The major feature of the results is that the variation clusters by alleles and not by species in phylogenetic trees and discriminant analysis of principal components. Variation within the three groups shows trans-species polymorphism that is older than speciation and that is suggestive of balancing selection maintaining the variation. Using Bayesian and likelihood methods positive and negative selection is evident at sites in the conserved part of the genes and, to a larger extent, in the active part which also shows episodic diversifying selection, further supporting the argument for balancing selection. PMID:26038731

Polymorphisms of alcohol metabolizing enzymes in indigenous Mexican population: unusual high frequency of CYP2E1*c2 allele.

PubMed

Gordillo-Bastidas, Elizabeth; Panduro, Arturo; Gordillo-Bastidas, Daniela; Zepeda-Carrillo, Eloy A; García-Bañuelos, Jesús J; Muñoz-Valle, José F; Bastidas-Ramírez, Blanca E

2010-01-01

Alcohol abuse represents the major identified etiological factor of cirrhosis in México. ADH1B, ALDH2, and CYP2E1 have been considered candidate genes in alcohol-related diseases. Controversial results probably due to ethnic differences, among other factors, have been reported. Mexican Mestizos (MES) derive from the combination of indigenous, Spaniard, and African genes. Huichols (HUI) constitute an indigenous group from western Mexico with no racial admixture. We determined ADH1B*2, ALDH2*2, and CYP2E1*c2 allele frequencies in healthy HUI and MES from western Mexico. Lipid and hepatic profile were also carried out. One hundred and one HUI and 331 MES subjects were studied. Genotype and allele frequency were assessed through polymerase chain reaction-restriction fragment length polymorphism after DNA isolation from peripheral leukocytes. Commercial kits for lipid and hepatic determinations were used. Polymorphic allele distribution in HUI was: 0%ADH1B*2, 0.5%ALDH2*2, 51.5%CYP2E1*c2; in MES: 3.4%ADH1B*2, 0%ALDH2*2, 16.1%CYP2E1*c2. Frequency of ADH1B*2 was statistically (p < 0.001) lower in HUI than MES. CYP2E1*c2 polymorphic allele was significantly higher (p < 0.0001) in HUI than MES. Hepatic profile was normal in both groups. HUI showed a better lipid profile than MES independently of genotype. Huichols exhibited the highest CYP2E1*c2 allele frequency of the world documented up to this date; meanwhile, ADH1B*2 and ALDH2*2 were practically absent. This feature could be useful in the understanding of Mexican population gene composition, alcohol metabolism, and alcoholic liver disease development. However, further association studies are necessary. The heterogeneity of Mexican population was evidenced by the significantly different distribution of CYP2E1*c2 allele observed among different regions of the country. Lipid and hepatic values were not associated to genotype. This report constitutes the first study dealing with gene polymorphisms of alcohol metabolizing enzymes conducted in HUI.

Individual differences in the processing of smoking-cessation video messages: An imaging genetics study.

PubMed

Shi, Zhenhao; Wang, An-Li; Aronowitz, Catherine A; Romer, Daniel; Langleben, Daniel D

2017-09-01

Studies testing the benefits of enriching smoking-cessation video ads with attention-grabbing sensory features have yielded variable results. Dopamine transporter gene (DAT1) has been implicated in attention deficits. We hypothesized that DAT1 polymorphism is partially responsible for this variability. Using functional magnetic resonance imaging, we examined brain responses to videos high or low in attention-grabbing features, indexed by "message sensation value" (MSV), in 53 smokers genotyped for DAT1. Compared to other smokers, 10/10 homozygotes showed greater neural response to High- vs. Low-MSV smoking-cessation videos in two a priori regions of interest: the right temporoparietal junction and the right ventrolateral prefrontal cortex. These regions are known to underlie stimulus-driven attentional processing. Exploratory analysis showed that the right temporoparietal response positively predicted follow-up smoking behavior indexed by urine cotinine. Our findings suggest that responses to attention-grabbing features in smoking-cessation messages is affected by the DAT1 genotype. Copyright © 2017. Published by Elsevier B.V.

[Phenotypic and genetic analysis of a patient presented with Tietz/Waardenburg type II a syndrome].

PubMed

Wang, Huanhuan; Tang, Lifang; Zhang, Jingmin; Hu, Qin; Chen, Yingwei; Xiao, Bing

2015-08-01

To determine the genetic cause for a patient featuring decreased pigmentation of the skin and iris, hearing loss and multiple congenital anomalies. Routine chromosomal banding was performed to analyze the karyotype of the patient and his parents. Single nucleotide polymorphism array (SNP array) was employed to identify cryptic chromosome aberrations, and quantitative real-time PCR was used to confirm the results. Karyotype analysis has revealed no obvious anomaly for the patient and his parents. SNP array analysis of the patient has demonstrated a 3.9 Mb deletion encompassing 3p13p14.1, which caused loss of entire MITF gene. The deletion was confirmed by quantitative real-time PCR. Clinical features of the patient have included severe bilateral hearing loss, decreased pigmentation of the skin and iris and multiple congenital anomalies. The patient, carrying a 3p13p14.1 deletion, has features of Tietz syndrome/Waardenburg syndrome type IIa. This case may provide additional data for the study of genotype-phenotype correlation of this disease.

Combining heterogenous features for 3D hand-held object recognition

NASA Astrophysics Data System (ADS)

Lv, Xiong; Wang, Shuang; Li, Xiangyang; Jiang, Shuqiang

2014-10-01

Object recognition has wide applications in the area of human-machine interaction and multimedia retrieval. However, due to the problem of visual polysemous and concept polymorphism, it is still a great challenge to obtain reliable recognition result for the 2D images. Recently, with the emergence and easy availability of RGB-D equipment such as Kinect, this challenge could be relieved because the depth channel could bring more information. A very special and important case of object recognition is hand-held object recognition, as hand is a straight and natural way for both human-human interaction and human-machine interaction. In this paper, we study the problem of 3D object recognition by combining heterogenous features with different modalities and extraction techniques. For hand-craft feature, although it reserves the low-level information such as shape and color, it has shown weakness in representing hiconvolutionalgh-level semantic information compared with the automatic learned feature, especially deep feature. Deep feature has shown its great advantages in large scale dataset recognition but is not always robust to rotation or scale variance compared with hand-craft feature. In this paper, we propose a method to combine hand-craft point cloud features and deep learned features in RGB and depth channle. First, hand-held object segmentation is implemented by using depth cues and human skeleton information. Second, we combine the extracted hetegerogenous 3D features in different stages using linear concatenation and multiple kernel learning (MKL). Then a training model is used to recognize 3D handheld objects. Experimental results validate the effectiveness and gerneralization ability of the proposed method.

First principles and experimental study of the electronic structure and phase stability of bulk thallium bromide

NASA Astrophysics Data System (ADS)

Smith, Holland M.; Zhou, Yuzhi; Ciampi, Guido; Kim, Hadong; Cirignano, Leonard J.; Shah, Kanai S.; Haller, E. E.; Chrzan, D. C.

2013-08-01

We apply state-of-art first principle calculations to study the polymorphism and electronic structure of three previously reported phases of TlBr. The calculated band structures of NaCl-structure phase and orthorhombic-structure phase have different features than that of commonly observed CsCl-structure phase. We further interpret photoluminescence spectra based on our calculations. Several peaks close to calculated band gap values of the NaCl-structure phase and the orthorhombic-structure phase are found in unpolished TlBr samples.

[Peripheral neuropathy in systemic lupus erythematosus with epineural vasculitis and antiphospholipid antibodies].

PubMed

Rafai, M A; Fadel, H; Boulaajaj, F Z; Gam, I; El Moutawakkil, B; Karkouri, M; Hakim, K; Slassi, I

2007-01-01

Neurological manifestations of systemic lupus erythematosus are frequent and polymorphic. Their frequency varies according to authors (24-75p.cent). Central nervous system complications predominate; peripheral features are rare, classically symmetrical polyneuropathy, multiple mononeuropathies or cranial nerve involvement. We report a case of a 48-year-old woman presenting a histologically documented sensitivo-motor polyneuropathy with severe motor involvement complicating lupus associated with antiphospholipides antibodies. Outcome was good after cyclophosphamid pulse. We discuss the frequency of peripheral involvement in systemic lupus erythematosus, pathogenic mechanisms, therapeutic possibilities and outcome of this complication.

Red cell glucose-6-phosphate dehydrogenase phenotypes in Iraq.

PubMed

Hilmi, F A; Al-Allawi, N A; Rassam, M; Al-Shamma, G; Al-Hashimi, A

2002-01-01

We attempted to characterize biochemically glucose-6-phosphate dehydrogenase (G6PD) variants in Iraqi individuals. Thus 758 healthy Iraqi males aged 18-60 years were randomly selected and 46 (6.1%) were G6PD deficient. Although the predominant non-deficient G6PD phenotype was G6PD B (92.6%), G6PD A+ was found in polymorphic frequency (1.3%). In the deficient group, 31 cases were fully characterized, including 17 cases with features consistent with G6PD Mediterranean variant, while 12 had other biochemical features and were labelled as non-Mediterranean variant. The remaining two deficient cases were characterized as G6PD A- variant. The presence of a significant number of non-Mediterranean variant was unexpected and may be related to the more heterogeneous background of the Iraqi people.

Cone pigment polymorphism in New World monkeys: are all pigments created equal?

PubMed

Rowe, Mickey P; Jacobs, Gerald H

2004-01-01

Most platyrrhine monkeys have a triallelic M/L opsin gene polymorphism that underlies significant individual variations in color vision. A survey of the frequencies of these polymorphic genes suggests that the three alleles occur with equal frequency among squirrel monkeys (subfamily Cebinae), but are not equally frequent in a number of species from the subfamily Callitrichinae. This departure from equal frequency in the Callitrichids should slightly increase the ratio of dichromats to trichromats in the population and significantly alter the relative representation of the three possible dichromatic and trichromatic phenotypes. A particular feature of the inequality is that it leads to a relative increase in the number of trichromats whose M/L pigments have the largest possible spectral separation. To assess whether these trichromatic phenotypes are equally well equipped to make relevant visual discriminations, psychophysical experiments were run on human observers. A technique involving the functional substitution of photopigments was used to simulate the discrimination between fruits among a background of leaves. The goal of the simulation was to reproduce in the cones of human observers excitations equivalent to those produced in monkey cones as the animals view fruit. Three different viewing conditions were examined involving variations in the relative luminances of fruit and leaves and the spectrum of the illuminant. In all cases, performance was best for simulated trichromacies including M/L pigments with the largest spectral separation. Thus, the inequality of opsin gene frequency in Callitrichid monkeys may reflect adaptive pressures.

Molecular genetics analysis of hereditary breast and ovarian cancer patients in India

PubMed Central

Soumittra, Nagasamy; Meenakumari, Balaiah; Parija, Tithi; Sridevi, Veluswami; Nancy, Karunakaran N; Swaminathan, Rajaraman; Rajalekshmy, Kamalalayam R; Majhi, Urmila; Rajkumar, Thangarajan

2009-01-01

Background Hereditary cancers account for 5–10% of cancers. In this study BRCA1, BRCA2 and CHEK2*(1100delC) were analyzed for mutations in 91 HBOC/HBC/HOC families and early onset breast and early onset ovarian cancer cases. Methods PCR-DHPLC was used for mutation screening followed by DNA sequencing for identification and confirmation of mutations. Kaplan-Meier survival probabilities were computed for five-year survival data on Breast and Ovarian cancer cases separately, and differences were tested using the Log-rank test. Results Fifteen (16%) pathogenic mutations (12 in BRCA1 and 3 in BRCA2), of which six were novel BRCA1 mutations were identified. None of the cases showed CHEK2*1100delC mutation. Many reported polymorphisms in the exonic and intronic regions of BRCA1 and BRCA2 were also seen. The mutation status and the polymorphisms were analyzed for association with the clinico-pathological features like age, stage, grade, histology, disease status, survival (overall and disease free) and with prognostic molecular markers (ER, PR, c-erbB2 and p53). Conclusion The stage of the disease at diagnosis was the only statistically significant (p < 0.0035) prognostic parameter. The mutation frequency and the polymorphisms were similar to reports on other ethnic populations. The lack of association between the clinico-pathological variables, mutation status and the disease status is likely to be due to the small numbers. PMID:19656415

Impact of EZH2 polymorphisms on urothelial cell carcinoma susceptibility and clinicopathologic features.

PubMed

Yu, Yung-Luen; Su, Kuo-Jung; Hsieh, Ming-Ju; Wang, Shian-Shiang; Wang, Po-Hui; Weng, Wei-Chun; Yang, Shun-Fa

2014-01-01

The gene EZH2, the polycomb group protein enhancer of zeste 2, encodes a transcriptional repressor that also serves as a histone methyltransferase that is associated with progression to more advanced disease in a variety of malignancies. EZH2 expression level in urothelial cell carcinoma (UCC) is highly correlated with tumor aggressiveness, but it has not been determined if specific EZH2 genetic variants are associated with UCC risk. This study investigated the potential associations of EZH2 single-nucleotide polymorphisms with UCC susceptibility and its clinicopathologic characteristics. A total of 233 UCC patients and 552 cancer-free controls, all of whom were from Taiwan, were analyzed for four EZH2 single-nucleotide polymorphisms (rs6950683, rs2302427, rs3757441, and rs41277434) using real-time PCR genotyping. After adjusting for other co-variants, we found that individuals carrying at least one C allele at EZH2 rs6950683 had a lower risk of developing UCC than did major allele carriers. The CCCA or TGTA haplotype among the four EZH2 sites was also associated with a reduced risk of UCC. Furthermore, UCC patients who carried at least one G allele at rs2302427 had a lower invasive tumor stage than did patients carrying the major allele. The rs6950683 SNPs of EZH2 might contribute to the prediction of UCC susceptibility. This is the first study to provide insight into risk factors associated with EZH2 variants in carcinogenesis of UCC in Taiwan.

Molecular-genetic correlates of infant attachment: A cautionary tale

PubMed Central

Booth-Laforce, Cathryn; Belsky, Jay; Burt, Keith B.; Groh, Ashley M.

2014-01-01

This paper advises caution in relation to the increasing interest in molecular-genetic association studies in developmental psychology based on a set of empirical examples from the NICHD Study of Early Child Care and Youth Development (SECCYD) that highlight the fragility of effects reported in the literature on the molecular-genetic correlates of infant attachment. Specifically, this paper updates and provides three extensions to results reported in Luijk et al. (2011), which recently failed to replicate evidence from smaller-sample studies that a set of dopaminergic, serotonergic, and oxytonergic markers are significantly associated with infant attachment security or disorganization. First, we report here that the average effect of “usual suspect” polymorphisms on infant attachment security and disorganization in the SECCYD is approximately zero. Second, because Luijk et al. (2011) reported data based exclusively on the White infants in the SECCYD, this paper reveals that the average effect of polymorphisms featured in this literature is also of trivial magnitude in the non-White sub-sample (cf. Chen, Barth, Johnson, Gotlib, & Johnson, 2011). Third, this paper attempts, but fails, to replicate a recent finding by Raby et al. (2012) suggesting that, although molecular-genetic polymorphisms might not be implicated in security versus insecurity, the serotonin transporter gene contributes to variation in emotional distress during the Strange Situation Procedure. Implications for future research on the genetics of developmental phenotypes in general and attachment in particular are discussed, with a focus on statistical power and model-based theory testing. PMID:23421800

MutSβ abundance and Msh3 ATP hydrolysis activity are important drivers of CTG•CAG repeat expansions

PubMed Central

Keogh, Norma; Chan, Kara Y.; Li, Guo-Min

2017-01-01

Abstract CTG•CAG repeat expansions cause at least twelve inherited neurological diseases. Expansions require the presence, not the absence, of the mismatch repair protein MutSβ (Msh2-Msh3 heterodimer). To evaluate properties of MutSβ that drive expansions, previous studies have tested under-expression, ATPase function or polymorphic variants of Msh2 and Msh3, but in disparate experimental systems. Additionally, some variants destabilize MutSβ, potentially masking the effects of biochemical alterations of the variations. Here, human Msh3 was mutated to selectively inactivate MutSβ. Msh3−/− cells are severely defective for CTG•CAG repeat expansions but show full activity on contractions. Msh3−/− cells provide a single, isogenic system to add back Msh3 and test key biochemical features of MutSβ on expansions. Msh3 overexpression led to high expansion activity and elevated levels of MutSβ complex, indicating that MutSβ abundance drives expansions. An ATPase-defective Msh3 expressed at normal levels was as defective in expansions as Msh3−/− cells, indicating that Msh3 ATPase function is critical for expansions. Expression of two Msh3 polymorphic variants at normal levels showed no detectable change in expansions, suggesting these polymorphisms primarily affect Msh3 protein stability, not activity. In summary, CTG•CAG expansions are limited by the abundance of MutSβ and rely heavily on Msh3 ATPase function. PMID:28973443

MutSβ abundance and Msh3 ATP hydrolysis activity are important drivers of CTG•CAG repeat expansions.

PubMed

Keogh, Norma; Chan, Kara Y; Li, Guo-Min; Lahue, Robert S

2017-09-29

CTG•CAG repeat expansions cause at least twelve inherited neurological diseases. Expansions require the presence, not the absence, of the mismatch repair protein MutSβ (Msh2-Msh3 heterodimer). To evaluate properties of MutSβ that drive expansions, previous studies have tested under-expression, ATPase function or polymorphic variants of Msh2 and Msh3, but in disparate experimental systems. Additionally, some variants destabilize MutSβ, potentially masking the effects of biochemical alterations of the variations. Here, human Msh3 was mutated to selectively inactivate MutSβ. Msh3-/- cells are severely defective for CTG•CAG repeat expansions but show full activity on contractions. Msh3-/- cells provide a single, isogenic system to add back Msh3 and test key biochemical features of MutSβ on expansions. Msh3 overexpression led to high expansion activity and elevated levels of MutSβ complex, indicating that MutSβ abundance drives expansions. An ATPase-defective Msh3 expressed at normal levels was as defective in expansions as Msh3-/- cells, indicating that Msh3 ATPase function is critical for expansions. Expression of two Msh3 polymorphic variants at normal levels showed no detectable change in expansions, suggesting these polymorphisms primarily affect Msh3 protein stability, not activity. In summary, CTG•CAG expansions are limited by the abundance of MutSβ and rely heavily on Msh3 ATPase function. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Sperm count and motility are quantitatively affected by functional polymorphisms of HTR2A, MAOA and SLC18A.

PubMed

Cortés-Rodriguez, Miriam; Royo, Jose-Luis; Reyes-Palomares, Arturo; Lendínez, Ana M; Ruiz-Galdón, Maximiliano; Reyes-Engel, Armando

2018-05-01

Spermatozoa and neurones share similar membrane characteristics and features. Associations of multiple polymorphisms traditionally related to neurotransmission were investigated. Infertile men were grouped into controls with normospermia (n = 182) and idiopathic infertile men with asthenozoospermia (n = 103), and analysed as a case-control study and as a quantitative association of each genotype. Ten neurotransmission-associated genetic variants were mapped by SNP analysis using quantitative polymerase chain reaction with TaqMan probes. Men with HTR2A rs6313 had a higher risk of asthenozoospermia (OR = 2.14; P = 0.04). MAOA rs3788862 G carriers displayed an increased risk of asthenozoospermia (OR = 2.29; P = 0.02). The SLC18A1 rs1390938 G allele was more frequent among such cases (0.75 versus 0.87; P < 0.01 and P < 0.01 for Armitage trend test); for SLC18A1 rs2270641 P = 0.02 (case-control frequency) and P = 0.01 (Armitage trend test). MAOA rs3788862 was correlated with sperm motility (Spearman ρ = 0.14; P = 0.02); SLC18A1 rs1390938 was correlated with sperm count and motility (Spearman ρ = 0.20; P < 0.01). Gene polymorphisms of HTR2A, MAOA and SLC18A1, related to neurotransmission, are individually associated with asthenozoospermia through variation in sperm count and motility, without detectable allelic or genotype interaction. Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Epigenetic and epistatic interactions between serotonin transporter and brain-derived neurotrophic factor genetic polymorphism: insights in depression.

PubMed

Ignácio, Z M; Réus, G Z; Abelaira, H M; Quevedo, J

2014-09-05

Epidemiological studies have shown significant results in the interaction between the functions of brain-derived neurotrophic factor (BDNF) and 5-HT in mood disorders, such as major depressive disorder (MDD). The latest research has provided convincing evidence that gene transcription of these molecules is a target for epigenetic changes, triggered by stressful stimuli that starts in early childhood and continues throughout life, which are subsequently translated into structural and functional phenotypes culminating in depressive disorders. The short variants of 5-HTTLPR and BDNF-Met are seen as forms which are predisposed to epigenetic aberrations, which leads individuals to a susceptibility to environmental adversities, especially when subjected to stress in early life. Moreover, the polymorphic variants also feature epistatic interactions in directing the functional mechanisms elicited by stress and underlying the onset of depressive disorders. Also emphasized are works which show some mediators between stress and epigenetic changes of the 5-HTT and BDNF genes, such as the hypothalamic-pituitary-adrenal (HPA) axis and the cAMP response element-binding protein (CREB), which is a cellular transcription factor. Both the HPA axis and CREB are also involved in epistatic interactions between polymorphic variants of 5-HTTLPR and Val66Met. This review highlights some research studying changes in the epigenetic patterns intrinsic to genes of 5-HTT and BDNF, which are related to lifelong environmental adversities, which in turn increases the risks of developing MDD. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Sulcal Polymorphisms of the IFC and ACC Contribute to Inhibitory Control Variability in Children and Adults

PubMed Central

Linzarini, Adriano; Dollfus, Sonia; Etard, Olivier; Orliac, François; Houdé, Olivier

2018-01-01

Abstract Inhibitory control (IC) is a core executive function that enables humans to resist habits, temptations, or distractions. IC efficiency in childhood is a strong predictor of academic and professional success later in life. Based on analysis of the sulcal pattern, a qualitative feature of cortex anatomy determined during fetal life and stable during development, we searched for evidence that interindividual differences in IC partly trace back to prenatal processes. Using anatomical magnetic resonance imaging (MRI), we analyzed the sulcal pattern of two key regions of the IC neural network, the dorsal anterior cingulate cortex (ACC) and the inferior frontal cortex (IFC), which limits the inferior frontal gyrus. We found that the sulcal pattern asymmetry of both the ACC and IFC contributes to IC (Stroop score) in children and adults: participants with asymmetrical ACC or IFC sulcal patterns had better IC efficiency than participants with symmetrical ACC or IFC sulcal patterns. Such additive effects of IFC and ACC sulcal patterns on IC efficiency suggest that distinct early neurodevelopmental mechanisms targeting different brain regions likely contribute to IC efficiency. This view shares some analogies with the “common variant–small effect” model in genetics, which states that frequent genetic polymorphisms have small effects but collectively account for a large portion of the variance. Similarly, each sulcal polymorphism has a small but additive effect: IFC and ACC sulcal patterns, respectively, explained 3% and 14% of the variance of the Stroop interference scores. PMID:29527565

Sulcal Polymorphisms of the IFC and ACC Contribute to Inhibitory Control Variability in Children and Adults.

PubMed

Tissier, Cloélia; Linzarini, Adriano; Allaire-Duquette, Geneviève; Mevel, Katell; Poirel, Nicolas; Dollfus, Sonia; Etard, Olivier; Orliac, François; Peyrin, Carole; Charron, Sylvain; Raznahan, Armin; Houdé, Olivier; Borst, Grégoire; Cachia, Arnaud

2018-01-01

Inhibitory control (IC) is a core executive function that enables humans to resist habits, temptations, or distractions. IC efficiency in childhood is a strong predictor of academic and professional success later in life. Based on analysis of the sulcal pattern, a qualitative feature of cortex anatomy determined during fetal life and stable during development, we searched for evidence that interindividual differences in IC partly trace back to prenatal processes. Using anatomical magnetic resonance imaging (MRI), we analyzed the sulcal pattern of two key regions of the IC neural network, the dorsal anterior cingulate cortex (ACC) and the inferior frontal cortex (IFC), which limits the inferior frontal gyrus. We found that the sulcal pattern asymmetry of both the ACC and IFC contributes to IC (Stroop score) in children and adults: participants with asymmetrical ACC or IFC sulcal patterns had better IC efficiency than participants with symmetrical ACC or IFC sulcal patterns. Such additive effects of IFC and ACC sulcal patterns on IC efficiency suggest that distinct early neurodevelopmental mechanisms targeting different brain regions likely contribute to IC efficiency. This view shares some analogies with the "common variant-small effect" model in genetics, which states that frequent genetic polymorphisms have small effects but collectively account for a large portion of the variance. Similarly, each sulcal polymorphism has a small but additive effect: IFC and ACC sulcal patterns, respectively, explained 3% and 14% of the variance of the Stroop interference scores.

Feature co-localization landscape of the human genome

PubMed Central

Ng, Siu-Kin; Hu, Taobo; Long, Xi; Chan, Cheuk-Hin; Tsang, Shui-Ying; Xue, Hong

2016-01-01

Although feature co-localizations could serve as useful guide-posts to genome architecture, a comprehensive and quantitative feature co-localization map of the human genome has been lacking. Herein we show that, in contrast to the conventional bipartite division of genomic sequences into genic and inter-genic regions, pairwise co-localizations of forty-two genomic features in the twenty-two autosomes based on 50-kb to 2,000-kb sequence windows indicate a tripartite zonal architecture comprising Genic zones enriched with gene-related features and Alu-elements; Proximal zones enriched with MIR- and L2-elements, transcription-factor-binding-sites (TFBSs), and conserved-indels (CIDs); and Distal zones enriched with L1-elements. Co-localizations between single-nucleotide-polymorphisms (SNPs) and copy-number-variations (CNVs) reveal a fraction of sequence windows displaying steeply enhanced levels of SNPs, CNVs and recombination rates that point to active adaptive evolution in such pathways as immune response, sensory perceptions, and cognition. The strongest positive co-localization observed between TFBSs and CIDs suggests a regulatory role of CIDs in cooperation with TFBSs. The positive co-localizations of cancer somatic CNVs (CNVT) with all Proximal zone and most Genic zone features, in contrast to the distinctly more restricted co-localizations exhibited by germline CNVs (CNVG), reveal disparate distributions of CNVTs and CNVGs indicative of dissimilarity in their underlying mechanisms. PMID:26854351

Biomarker selection and classification of "-omics" data using a two-step bayes classification framework.

PubMed

Assawamakin, Anunchai; Prueksaaroon, Supakit; Kulawonganunchai, Supasak; Shaw, Philip James; Varavithya, Vara; Ruangrajitpakorn, Taneth; Tongsima, Sissades

2013-01-01

Identification of suitable biomarkers for accurate prediction of phenotypic outcomes is a goal for personalized medicine. However, current machine learning approaches are either too complex or perform poorly. Here, a novel two-step machine-learning framework is presented to address this need. First, a Naïve Bayes estimator is used to rank features from which the top-ranked will most likely contain the most informative features for prediction of the underlying biological classes. The top-ranked features are then used in a Hidden Naïve Bayes classifier to construct a classification prediction model from these filtered attributes. In order to obtain the minimum set of the most informative biomarkers, the bottom-ranked features are successively removed from the Naïve Bayes-filtered feature list one at a time, and the classification accuracy of the Hidden Naïve Bayes classifier is checked for each pruned feature set. The performance of the proposed two-step Bayes classification framework was tested on different types of -omics datasets including gene expression microarray, single nucleotide polymorphism microarray (SNParray), and surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) proteomic data. The proposed two-step Bayes classification framework was equal to and, in some cases, outperformed other classification methods in terms of prediction accuracy, minimum number of classification markers, and computational time.

Anhydrous 1:1 proton-transfer compounds of isonipecotamide with picric acid and 3,5-dinitrosalicylic acid: 4-carbamoylpiperidinium 2,4,6-trinitrophenolate and two polymorphs of 4-carbamoylpiperidinium 2-carboxy-4,6-dinitrophenolate.

PubMed

Smith, Graham; Wermuth, Urs D

2010-12-01

The structures of the anhydrous 1:1 proton-transfer compounds of isonipecotamide (piperidine-4-carboxamide) with picric acid and 3,5-dinitrosalicylic acid, namely 4-carbamoylpiperidinium 2,4,6-trinitrophenolate, C(6)H(13)N(2)O(+)·C(6)H(2)N(3)O(7)(-), (I), and 4-carbamoylpiperidinium 2-carboxy-4,6-dinitrophenolate [two forms of which were found, the monoclinic α-polymorph, (II), and the triclinic β-polymorph, (III)], C(6)H(13)N(2)O(+)·C(7)H(3)N(2)O(7)(-), have been determined at 200 K. All three compounds form hydrogen-bonded structures, viz. one-dimensional in (II), two-dimensional in (I) and three-dimensional in (III). In (I), the cations form centrosymmetric cyclic head-to-tail hydrogen-bonded homodimers [graph set R(2)(2)(14)] through lateral duplex piperidinium-amide N-H...O interactions. These dimers are extended into a two-dimensional network structure through further interactions with phenolate and nitro O-atom acceptors, including a direct symmetric piperidinium-phenol/nitro N-H...O,O cation-anion association [graph set R(1)(2)(6)]. The monoclinic polymorph, (II), has a similar R(1)(2)(6) cation-anion hydrogen-bonding interaction to (I) but with an additional conjoint symmetrical R(1)(2)(4) interaction as well as head-to-tail piperidinium-amide N-H...O,O hydrogen bonds and amide-carboxyl N-H...O hydrogen bonds, giving a network structure which includes large R(4)(3)(20) rings. The hydrogen bonding in the triclinic polymorph, (III), is markedly different from that of monoclinic (II). The asymmetric unit contains two independent cation-anion pairs which associate through cyclic piperidinium-carboxyl N-H...O,O' interactions [graph set R(1)(2)(4)]. The cations also show the zigzag head-to-tail piperidinium-amide N-H...O hydrogen-bonded chain substructures found in (II), but in addition feature amide-nitro and amide-phenolate N-H...O associations. As well, there is a centrosymmetric double-amide N-H...O(carboxyl) bridged bis(cation-anion) ring system [graph set R(4)(2)(8)] in the three-dimensional framework. The structures reported here demonstrate the utility of the isonipecotamide cation as a synthon with previously unrecognized potential for structure assembly applications. Furthermore, the structures of the two polymorphic 3,5-dinitrosalicylic acid salts show an unusual dissimilarity in hydrogen-bonding characteristics, considering that both were obtained from identical solvent systems.

Modeling evaporation from spent nuclear fuel storage pools: A diffusion approach

NASA Astrophysics Data System (ADS)

Hugo, Bruce Robert

Accurate prediction of evaporative losses from light water reactor nuclear power plant (NPP) spent fuel storage pools (SFPs) is important for activities ranging from sizing of water makeup systems during NPP design to predicting the time available to supply emergency makeup water following severe accidents. Existing correlations for predicting evaporation from water surfaces are only optimized for conditions typical of swimming pools. This new approach modeling evaporation as a diffusion process has yielded an evaporation rate model that provided a better fit of published high temperature evaporation data and measurements from two SFPs than other published evaporation correlations. Insights from treating evaporation as a diffusion process include correcting for the effects of air flow and solutes on evaporation rate. An accurate modeling of the effects of air flow on evaporation rate is required to explain the observed temperature data from the Fukushima Daiichi Unit 4 SFP during the 2011 loss of cooling event; the diffusion model of evaporation provides a significantly better fit to this data than existing evaporation models.

Separated Fringe Packet Observations with the CHARA Array. I. Methods and New Orbits for χ Draconis, HD 184467, and HD 198084

NASA Astrophysics Data System (ADS)

Farrington, C. D.; ten Brummelaar, T. A.; Mason, B. D.; Hartkopf, W. I.; McAlister, H. A.; Raghavan, D.; Turner, N. H.; Sturmann, L.; Sturmann, J.; Ridgway, S. T.

2010-06-01

We present the modification of the orbits of χ Draconis and HD 184467, and a completely new orbit for HD 198084, including data taken at the Center for High Angular Resolution Astronomy (CHARA) Array. These data were obtained using a modification of the technique of separated fringe packets (SFPs). The accuracy of the SFP data surpasses that of data taken by speckle, but the technique is much more time and labor intensive. Additionally, using SFPs with the CHARA Array, it is possible to obtain separations below the detection range of speckle interferometry (>=30 mas) above the range in "classic" long-baseline interferometry where fringes from a binary overlap are no longer separated (<=10 mas). Using spectroscopic binary systems with published speckle orbits, we are able to test our new measurements against their ephemerides to calibrate the method as well as produce entirely new orbits for systems with no current astrometric observations.

Fluorescent techniques for discovery and characterization of phosphopantetheinyl transferase inhibitors

PubMed Central

Kosa, Nicolas M.; Foley, Timothy L.; Burkart, Michael D.

2016-01-01

Phosphopantetheinyl transferase (E.C. 2.7.8.-) activates biosynthetic pathways that synthesize both primary and secondary metabolites in bacteria. Inhibitors of these enzymes have the potential to serve as antibiotic compounds that function through a unique mode of action and possess clinical utility. Here we report a direct and continuous assay for this enzyme class based upon monitoring polarization of a fluorescent phosphopantetheine analog as it is transferred from a low molecular weight coenzyme A substrate to higher molecular weight protein acceptor. We demonstrate the utility of this method for the biochemical characterization of phosphopantetheinyl transferase Sfp, a canonical representative from this class. We also establish the portability of this technique to other homologs by adapting the assay to function with the human phosphopantetheinyl transferase, a target for which a microplate detection method does not currently exist. Comparison of these targets provides a basis to predict therapeutic index of inhibitor candidates and offers a valuable characterization of enzyme activity. PMID:24192555

Selective aggregation of the splicing factor Hsh155 suppresses splicing upon genotoxic stress.

PubMed

Mathew, Veena; Tam, Annie S; Milbury, Karissa L; Hofmann, Analise K; Hughes, Christopher S; Morin, Gregg B; Loewen, Christopher J R; Stirling, Peter C

2017-12-04

Upon genotoxic stress, dynamic relocalization events control DNA repair as well as alterations of the transcriptome and proteome, enabling stress recovery. How these events may influence one another is only partly known. Beginning with a cytological screen of genome stability proteins, we find that the splicing factor Hsh155 disassembles from its partners and localizes to both intranuclear and cytoplasmic protein quality control (PQC) aggregates under alkylation stress. Aggregate sequestration of Hsh155 occurs at nuclear and then cytoplasmic sites in a manner that is regulated by molecular chaperones and requires TORC1 activity signaling through the Sfp1 transcription factor. This dynamic behavior is associated with intron retention in ribosomal protein gene transcripts, a decrease in splicing efficiency, and more rapid recovery from stress. Collectively, our analyses suggest a model in which some proteins evicted from chromatin and undergoing transcriptional remodeling during stress are targeted to PQC sites to influence gene expression changes and facilitate stress recovery. © 2017 Mathew et al.

Development of ROACH firmware for microwave multiplexed X-ray TES microcalorimeters

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

Madden, T. J.; Cecil, T. W.; Gades, L. M.

We are developing room temperature electronics based upon the ROACH platform for reading out microwave multiplexed X-ray TES. ROACH is an open-source hardware and software platform featuring a large Xilinx Field Programmable Gate Array (FPGA), Power PC processor, several 10GB Ethernet SFP+ interfaces, and a collection of daughter boards for analog signal generation and acquisition. The combination of a ROACH board, ADC/DAC conversion daughter boards, and hardware for RF mixing allows for the generation and capture of multiple RF tones for reading out microwave multiplexed x-ray TES microcalorimeters. The FPGA is used to generate multiple tones in base band, frommore » 10MHz to 250MHz, which are subsequently mixed to RF in the multiple GHz range and sent through the microwave multiplexer. The tones are generated in the FPGA by storing a large lookup table in Quad Data Rate (QDR) SRAM modules and playing out the waveform to a DAC board. Once the signal has been modulated to RF, passed through the microwave multiplexer, and has been modulated back to base band, the signal is digitized by an ADC board. The tones are modulated to 0Hz by using a FPGA circuit consisting of a polyphase filter bank, several Xilinx FFT blocks, Xilinx CORDIC blocks (for converting to magnitude and phase), and special phase accumulator circuit for mixing to exactly 0Hz. Upwards of 256 channels can be simultaneously captured and written into a bank of 256 First-In-First-Out (FIFO) memories, with each FIFO corresponding to a channel. Individual channel data can be further processed in the FPGA before being streamed through a 10GB Ethernet fiber-optic interface to a Linux system. The Linux system runs software written in Python and QT C++ for controlling the ROACH system, capturing data, and processing data.« less

Disordered amorphous calcium carbonate from direct precipitation

DOE PAGES

Farhadi Khouzani, Masoud; Chevrier, Daniel M.; Güttlein, Patricia; ...

2015-06-01

Amorphous calcium carbonate (ACC) is known to play a prominent role in biomineralization. Different studies on the structure of biogenic ACCs have illustrated that they can have distinct short-range orders. However, the origin of so-called proto-structures in synthetic and additive-free ACCs is not well understood. In the current work, ACC has been synthesised in iso-propanolic media by direct precipitation from ionic precursors, and analysed utilising a range of different techniques. The data suggest that this additive-free type of ACC does not resemble clear proto-structural motifs relating to any crystalline polymorph. This can be explained by the undefined pH value inmore » iso-propanolic media, and the virtually instantaneous precipitation. Altogether, this work suggests that aqueous systems and pathways involving pre-nucleation clusters are required for the generation of clear proto-structural features in ACC. Experiments on the ACC-to-crystalline transformation in solution with and without ethanol highlight that polymorph selection is under kinetic control, while the presence of ethanol can control dissolution re-crystallisation pathways.« less

Distinct Genetic Architectures for Male and Female Inflorescence Traits of Maize

PubMed Central

Brown, Patrick J.; Upadyayula, Narasimham; Mahone, Gregory S.; Tian, Feng; Bradbury, Peter J.; Myles, Sean; Holland, James B.; Flint-Garcia, Sherry; McMullen, Michael D.; Buckler, Edward S.; Rocheford, Torbert R.

2011-01-01

We compared the genetic architecture of thirteen maize morphological traits in a large population of recombinant inbred lines. Four traits from the male inflorescence (tassel) and three traits from the female inflorescence (ear) were measured and studied using linkage and genome-wide association analyses and compared to three flowering and three leaf traits previously studied in the same population. Inflorescence loci have larger effects than flowering and leaf loci, and ear effects are larger than tassel effects. Ear trait models also have lower predictive ability than tassel, flowering, or leaf trait models. Pleiotropic loci were identified that control elongation of ear and tassel, consistent with their common developmental origin. For these pleiotropic loci, the ear effects are larger than tassel effects even though the same causal polymorphisms are likely involved. This implies that the observed differences in genetic architecture are not due to distinct features of the underlying polymorphisms. Our results support the hypothesis that genetic architecture is a function of trait stability over evolutionary time, since the traits that changed most during the relatively recent domestication of maize have the largest effects. PMID:22125498

Cumulative Risk on the Oxytocin Receptor Gene (OXTR) Predicts Empathic Communication by Physician Assistant Students.

PubMed

Floyd, Kory; Generous, Mark Alan; Clark, Lou; McLeod, Ian; Simon, Albert

2017-10-01

In the relationship between patients and health care providers, few communicative features are as significant as the providers' ability to express empathy. A robust empirical literature describes the importance of physician communication skills-particularly those that convey empathy-yet few studies have examined empathic communication by physician assistants, who provide primary care for an increasing number of Americans. The present study examines the empathic communication of physician assistant students in interactions with standardized patients. Over a 6-month period, each student conducted three clinical interviews, each of which was evaluated for empathic communication by the patients, the students' clinical instructors, and third-party observers. Students also provided saliva samples for genotyping six single-nucleotide polymorphisms on the oxytocin receptor gene (OXTR) that are linked empirically to empathic behavior. Consistent with recent research, this study adopted a cumulative risk approach wherein students were scored for their number of risky alleles on the single-nucleotide polymorphisms. Results indicated that cumulative risk on OXTR receptor gene predicted lower patient empathy scores as rated by instructors and observers, but not by standardized patients.

Optical phonon characteristics of an orthorhombic-transformed polymorph of CaTa2O6 single crystal fibre

NASA Astrophysics Data System (ADS)

Almeida, R. M.; Andreeta, M. R. B.; Hernandes, A. C.; Dias, A.; Moreira, R. L.

2014-03-01

Infrared-reflectivity spectroscopy and micro-Raman scattering were used to determine the optical phonon features of orthorhombic calcium tantalite (CaTa2O6) single crystal fibres. The fibres, obtained by the Laser-Heated Pedestal Growth method, grew into an ordered cubic structure \\left( Pm\\bar{3} \\right). Long-time annealing was used to induce a polymorphic transformation to an aeschynite orthorhombic structure (Pnma space group). The phase transformation led to the appearance of structural domains and micro-cracks, responsible for diffuse scattering and depolarization of the scattered light in the visible range, but not in the infrared region. Thus, polarized infrared spectroscopy could be performed within oriented single domains, with an appropriate microscope, allowing us to determine all relevant polar phonons of the orthorhombic CaTa2O6. The obtained phononic dielectric response, {{\\epsilon }_{r}} = 22.4 and = 86 × 103 GHz, shows the appropriateness of the material for microwave applications. Totally symmetric Raman modes could be resolved by polarization, after re-polishing the cracked sample surface.

An Ultra-High-Density, Transcript-Based, Genetic Map of Lettuce

PubMed Central

Truco, Maria José; Ashrafi, Hamid; Kozik, Alexander; van Leeuwen, Hans; Bowers, John; Wo, Sebastian Reyes Chin; Stoffel, Kevin; Xu, Huaqin; Hill, Theresa; Van Deynze, Allen; Michelmore, Richard W.

2013-01-01

We have generated an ultra-high-density genetic map for lettuce, an economically important member of the Compositae, consisting of 12,842 unigenes (13,943 markers) mapped in 3696 genetic bins distributed over nine chromosomal linkage groups. Genomic DNA was hybridized to a custom Affymetrix oligonucleotide array containing 6.4 million features representing 35,628 unigenes of Lactuca spp. Segregation of single-position polymorphisms was analyzed using 213 F7:8 recombinant inbred lines that had been generated by crossing cultivated Lactuca sativa cv. Salinas and L. serriola acc. US96UC23, the wild progenitor species of L. sativa. The high level of replication of each allele in the recombinant inbred lines was exploited to identify single-position polymorphisms that were assigned to parental haplotypes. Marker information has been made available using GBrowse to facilitate access to the map. This map has been anchored to the previously published integrated map of lettuce providing candidate genes for multiple phenotypes. The high density of markers achieved in this ultradense map allowed syntenic studies between lettuce and Vitis vinifera as well as other plant species. PMID:23550116

An Ultra-High-Density, Transcript-Based, Genetic Map of Lettuce.

PubMed

Truco, Maria José; Ashrafi, Hamid; Kozik, Alexander; van Leeuwen, Hans; Bowers, John; Wo, Sebastian Reyes Chin; Stoffel, Kevin; Xu, Huaqin; Hill, Theresa; Van Deynze, Allen; Michelmore, Richard W

2013-04-09

We have generated an ultra-high-density genetic map for lettuce, an economically important member of the Compositae, consisting of 12,842 unigenes (13,943 markers) mapped in 3696 genetic bins distributed over nine chromosomal linkage groups. Genomic DNA was hybridized to a custom Affymetrix oligonucleotide array containing 6.4 million features representing 35,628 unigenes of Lactuca spp. Segregation of single-position polymorphisms was analyzed using 213 F 7:8 recombinant inbred lines that had been generated by crossing cultivated Lactuca sativa cv. Salinas and L. serriola acc. US96UC23, the wild progenitor species of L. sativa The high level of replication of each allele in the recombinant inbred lines was exploited to identify single-position polymorphisms that were assigned to parental haplotypes. Marker information has been made available using GBrowse to facilitate access to the map. This map has been anchored to the previously published integrated map of lettuce providing candidate genes for multiple phenotypes. The high density of markers achieved in this ultradense map allowed syntenic studies between lettuce and Vitis vinifera as well as other plant species. Copyright © 2013 Truco et al.

VNTR alleles associated with the {alpha}-globin locus are haplotype and population related

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

Martinson, J.J.; Clegg, J.B.; Boyce, A.J.

1994-09-01

The human {alpha}-globin complex contains several polymorphic restriction-enzyme sites (i.e., RFLPs) linked to form haplotypes and is flanked by two hypervariable VNTR loci, the 5{prime} hypervariable region (HVR) and the more highly polymorphic 3{prime}HVR. Using a combination of RFLP analysis and PCR, the authors have characterized the 5{prime}HVR and 3{prime}HVR alleles associated with the {alpha}-globin haplotypes of 133 chromosomes, and they here show that specific {alpha}-globin haplotypes are each associated with discrete subsets of the alleles observed at these two VNTR loci. This statistically highly significant association is observed over a region spanning {approximately} 100 kb. With the exception ofmore » closely related haplotypes, different haplotypes do not share identically sized 3{prime}HVR alleles. Earlier studies have shown that {alpha}-globin haplotype distributions differ between populations; the current findings also reveal extensive population substructure in the repertoire of {alpha}-globin VNTRs. If similar features are characteristic of other VNTR loci, this will have important implications for forensic and anthropological studies. 42 refs., 5 figs., 5 tabs.« less

Erythrocyte selenium concentration predicts intensive care unit and hospital mortality in patients with septic shock: a prospective observational study

PubMed Central

2014-01-01

Introduction Selenoenzymes can modulate the extent of oxidative stress, which is recognized as a key feature of septic shock. The pathophysiologic role of erythrocyte selenium concentration in patients with septic shock remains unknown. Therefore, the objective of this study was to evaluate the association of erythrocyte selenium concentration with glutathione peroxidase (GPx1) activity, GPx1 polymorphisms and with ICU and hospital mortality in septic shock patients. Methods This prospective study included all patients older than 18 years with septic shock on admission or during their ICU stay, admitted to one of the three ICUs of our institution, from January to August 2012. At the time of the patients’ enrollment, demographic information was recorded. Blood samples were taken within the first 72 hours of the patients’ admission or within 72 hours of the septic shock diagnosis for determination of selenium status, protein carbonyl concentration, GPx1 activity and GPx1 Pro198Leu polymorphism (rs 1050450) genotyping. Results A total of 110 consecutive patients were evaluated. The mean age was 57.6 ± 15.9 years, 63.6% were male. Regarding selenium status, only erythrocyte selenium concentration was lower in patients who died in the ICU. The frequencies for GPx1 Pro198Leu polymorphism were 55%, 38% and 7% for Pro/Pro, Pro/Leu and Leu/Leu, respectively. In the logistic regression models, erythrocyte selenium concentration was associated with ICU and hospital mortality in patients with septic shock even after adjustment for protein carbonyl concentration and acute physiology and chronic health evaluation II score (APACHE II) or sequential organ failure assessment (SOFA). Conclusions Erythrocyte selenium concentration was a predictor of ICU and hospital mortality in patients with septic shock. However, this effect was not due to GPx1 activity or Pro198Leu polymorphism. PMID:24887198

Monoclinic structures of niobium trisulfide

NASA Astrophysics Data System (ADS)

Bloodgood, Matthew A.; Wei, Pingrong; Aytan, Ece; Bozhilov, Krassimir N.; Balandin, Alexander A.; Salguero, Tina T.

2018-02-01

Two new polymorphs of niobium trisulfide are established by single crystal x-ray diffraction. NbS3-iv crystallizes in the monoclinic space group P21/c with lattice parameters a = 6.7515(5) Å, b = 4.9736(4) Å, c = 18.1315(13) Å, and β = 90.116(2)°. Its structure is based on chains of [NbS6] trigonal prisms containing Nb-Nb pairs with a bond length of 3.0448(8) Å; this pairing causes the chains to corrugate slightly along their axis, a feature also present in triclinic NbS3-i that leads to semiconductor properties. The stacking arrangement of chains is different in these polymorphs, however, with NbS3-i having an ABCDE repeating sequence of chain bilayers and NbS3-iv having an AB repeating sequence. HRTEM studies show the presence of topotactically-oriented intergrown zones and numerous dislocations, which result in mosaic structuring. A second new polymorph, NbS3-v, crystallizes in the monoclinic space group P21/m with lattice parameters a = 4.950(5) Å, b = 3.358(4) Å, c = 9.079(10) Å, β = 97.35(2)°. In contrast to NbS3-iv, NbS3-v maintains fixed a Nb-Nb bond distance of 3.358(4) Å along the chains, and it has an ABCDE repeating sequence of chain bilayers similar to NbS3-i. High resolution scanning transmission electron microscopy (HR-STEM) imaging of an exfoliated NbS3-v nanoribbon shows the continuous [NbS6] chains oriented along the b-axis. These results provide the first firmly established structural data for monoclinic NbS3. In addition, SEM images show the formation of NbS3 rings and cylinders, and a combination of powder x-ray diffraction and Raman spectroscopy provides a way to distinguish between NbS3 polymorphs.

Characterization of Capsicum annuum Genetic Diversity and Population Structure Based on Parallel Polymorphism Discovery with a 30K Unigene Pepper GeneChip

PubMed Central

Hill, Theresa A.; Ashrafi, Hamid; Reyes-Chin-Wo, Sebastian; Yao, JiQiang; Stoffel, Kevin; Truco, Maria-Jose; Kozik, Alexander; Michelmore, Richard W.; Van Deynze, Allen

2013-01-01

The widely cultivated pepper, Capsicum spp., important as a vegetable and spice crop world-wide, is one of the most diverse crops. To enhance breeding programs, a detailed characterization of Capsicum diversity including morphological, geographical and molecular data is required. Currently, molecular data characterizing Capsicum genetic diversity is limited. The development and application of high-throughput genome-wide markers in Capsicum will facilitate more detailed molecular characterization of germplasm collections, genetic relationships, and the generation of ultra-high density maps. We have developed the Pepper GeneChip® array from Affymetrix for polymorphism detection and expression analysis in Capsicum. Probes on the array were designed from 30,815 unigenes assembled from expressed sequence tags (ESTs). Our array design provides a maximum redundancy of 13 probes per base pair position allowing integration of multiple hybridization values per position to detect single position polymorphism (SPP). Hybridization of genomic DNA from 40 diverse C. annuum lines, used in breeding and research programs, and a representative from three additional cultivated species (C. frutescens, C. chinense and C. pubescens) detected 33,401 SPP markers within 13,323 unigenes. Among the C. annuum lines, 6,426 SPPs covering 3,818 unigenes were identified. An estimated three-fold reduction in diversity was detected in non-pungent compared with pungent lines, however, we were able to detect 251 highly informative markers across these C. annuum lines. In addition, an 8.7 cM region without polymorphism was detected around Pun1 in non-pungent C. annuum. An analysis of genetic relatedness and diversity using the software Structure revealed clustering of the germplasm which was confirmed with statistical support by principle components analysis (PCA) and phylogenetic analysis. This research demonstrates the effectiveness of parallel high-throughput discovery and application of genome-wide transcript-based markers to assess genetic and genomic features among Capsicum annuum. PMID:23409153

Characterization of Capsicum annuum genetic diversity and population structure based on parallel polymorphism discovery with a 30K unigene Pepper GeneChip.

PubMed

Hill, Theresa A; Ashrafi, Hamid; Reyes-Chin-Wo, Sebastian; Yao, JiQiang; Stoffel, Kevin; Truco, Maria-Jose; Kozik, Alexander; Michelmore, Richard W; Van Deynze, Allen

2013-01-01

The widely cultivated pepper, Capsicum spp., important as a vegetable and spice crop world-wide, is one of the most diverse crops. To enhance breeding programs, a detailed characterization of Capsicum diversity including morphological, geographical and molecular data is required. Currently, molecular data characterizing Capsicum genetic diversity is limited. The development and application of high-throughput genome-wide markers in Capsicum will facilitate more detailed molecular characterization of germplasm collections, genetic relationships, and the generation of ultra-high density maps. We have developed the Pepper GeneChip® array from Affymetrix for polymorphism detection and expression analysis in Capsicum. Probes on the array were designed from 30,815 unigenes assembled from expressed sequence tags (ESTs). Our array design provides a maximum redundancy of 13 probes per base pair position allowing integration of multiple hybridization values per position to detect single position polymorphism (SPP). Hybridization of genomic DNA from 40 diverse C. annuum lines, used in breeding and research programs, and a representative from three additional cultivated species (C. frutescens, C. chinense and C. pubescens) detected 33,401 SPP markers within 13,323 unigenes. Among the C. annuum lines, 6,426 SPPs covering 3,818 unigenes were identified. An estimated three-fold reduction in diversity was detected in non-pungent compared with pungent lines, however, we were able to detect 251 highly informative markers across these C. annuum lines. In addition, an 8.7 cM region without polymorphism was detected around Pun1 in non-pungent C. annuum. An analysis of genetic relatedness and diversity using the software Structure revealed clustering of the germplasm which was confirmed with statistical support by principle components analysis (PCA) and phylogenetic analysis. This research demonstrates the effectiveness of parallel high-throughput discovery and application of genome-wide transcript-based markers to assess genetic and genomic features among Capsicum annuum.

Controlling the Immunological Crosstalk during Conception and Pregnancy: HLA-G in Reproduction

PubMed Central

Lynge Nilsson, Line; Djurisic, Snezana; Hviid, Thomas Vauvert F.

2014-01-01

In several years after its discovery in the placenta, the human leukocyte antigen (HLA) class Ib protein, HLA-G, was not given much attention, nor was it assigned great importance. As time has unraveled, HLA-G has proven to have distinctive functions and an unforeseen and possibly important role in reproduction. HLA-G is characterized mainly by its low polymorphism and restricted tissue distribution in non-pathological conditions. In fact, its expression pattern is primarily limited to extravillous cytotrophoblast cells at the maternal-fetal interface during pregnancy. Due to low polymorphism, almost the same protein is expressed by virtually all individuals. It is these unique features that make HLA-G differ from its highly polymorphic HLA class Ia counterparts, the HLA-A, -B, and -C molecules. Its function, seemingly diverse, is typically receptor-mediated, and involves interactions with a wide range of immune cells. As the expression of HLA-G primarily is limited to gestation, this has given rise to the hypothesis that HLA-G plays an important role in the immunological tolerance of the fetus by the mother. In keeping with this, it might not be surprising that polymorphisms in the HLA-G gene, and levels of HLA-G expression, have been linked to reproductive failure and pre-eclampsia. Based on recent studies, we speculate that HLA-G might be involved in mechanisms in reproductive immunology even before conception because HLA-G can be detected in the genital tract and in the blood of non-pregnant women, and is present in seminal fluid from men. In addition, HLA-G expression has been found in the pre-implanted embryo. Therefore, we propose that a combined contribution from the mother, the father, and the embryo/fetus is likely to be important. Furthermore, this review presents important aspects of HLA-G in relation to reproduction: from genetics to physiological effects, from pregnancy and pregnancy complications to a short discussion on future possible means of preventative measures and therapy. PMID:24860568

Combined effects of ankylosing spondylitis-associated ERAP1 polymorphisms outside the catalytic and peptide-binding sites on the processing of natural HLA-B27 ligands.

PubMed

Martín-Esteban, Adrian; Gómez-Molina, Patricia; Sanz-Bravo, Alejandro; López de Castro, José A

2014-02-14

ERAP1 polymorphism involving residues 528 and 575/725 is associated with ankylosing spondylitis among HLA-B27-positive individuals. We used four recombinant variants to address the combined effects of the K528R and D575N polymorphism on the processing of HLA-B27 ligands. The hydrolysis of a fluorogenic substrate, Arg-528/Asp-575 < Lys-528/Asp-575 < Arg-528/Asn-575 < Lys-528/Asn-575, indicated that the relative activity of variants carrying Arg-528 or Lys-528 depends on residue 575. Asp-575 conferred lower activity than Asn-575, but the difference depended on residue 528. The same hierarchy was observed with synthetic precursors of HLA-B27 ligands, but the effects were peptide-dependent. Sometimes the epitope yields were variant-specific at all times. For other peptides, concomitant generation and destruction led to similar epitope amounts with all the variants at long, but not at short, digestion times. The generation/destruction balance of two related HLA-B27 ligands was analyzed in vitro and in live cells. Their relative yields at long digestion times were comparable with those from HLA-B27-positive cells, suggesting that ERAP1 was a major determinant of the abundance of these peptides in vivo. The hydrolysis of fluorogenic and peptide substrates by an HLA-B27 ligand or a shorter peptide, respectively, was increasingly inhibited as a function of ERAP1 activity, indicating that residues 528 and 575 affect substrate inhibition of ERAP1 trimming. The significant and complex effects of co-occurring ERAP1 polymorphisms on multiple HLA-B27 ligands, and their potential to alter the immunological and pathogenetic features of HLA-B27 as a function of the ERAP1 context, explain the epistatic association of both molecules in ankylosing spondylitis.

Combined Effects of Ankylosing Spondylitis-associated ERAP1 Polymorphisms Outside the Catalytic and Peptide-binding Sites on the Processing of Natural HLA-B27 Ligands*

PubMed Central

Martín-Esteban, Adrian; Gómez-Molina, Patricia; Sanz-Bravo, Alejandro; López de Castro, José A.

2014-01-01

ERAP1 polymorphism involving residues 528 and 575/725 is associated with ankylosing spondylitis among HLA-B27-positive individuals. We used four recombinant variants to address the combined effects of the K528R and D575N polymorphism on the processing of HLA-B27 ligands. The hydrolysis of a fluorogenic substrate, Arg-528/Asp-575 < Lys-528/Asp-575 < Arg-528/Asn-575 < Lys-528/Asn-575, indicated that the relative activity of variants carrying Arg-528 or Lys-528 depends on residue 575. Asp-575 conferred lower activity than Asn-575, but the difference depended on residue 528. The same hierarchy was observed with synthetic precursors of HLA-B27 ligands, but the effects were peptide-dependent. Sometimes the epitope yields were variant-specific at all times. For other peptides, concomitant generation and destruction led to similar epitope amounts with all the variants at long, but not at short, digestion times. The generation/destruction balance of two related HLA-B27 ligands was analyzed in vitro and in live cells. Their relative yields at long digestion times were comparable with those from HLA-B27-positive cells, suggesting that ERAP1 was a major determinant of the abundance of these peptides in vivo. The hydrolysis of fluorogenic and peptide substrates by an HLA-B27 ligand or a shorter peptide, respectively, was increasingly inhibited as a function of ERAP1 activity, indicating that residues 528 and 575 affect substrate inhibition of ERAP1 trimming. The significant and complex effects of co-occurring ERAP1 polymorphisms on multiple HLA-B27 ligands, and their potential to alter the immunological and pathogenetic features of HLA-B27 as a function of the ERAP1 context, explain the epistatic association of both molecules in ankylosing spondylitis. PMID:24352655

Interleukin 1 β (IL-1B) and IL-1 antagonist receptor (IL-1RN) gene polymorphisms are associated with the genetic susceptibility and steroid dependence in patients with ulcerative colitis.

PubMed

Yamamoto-Furusho, Jesús K; Santiago-Hernández, Jean J; Pérez-Hernández, Nonanzit; Ramírez-Fuentes, Silvestre; Fragoso, José Manuel; Vargas-Alarcón, Gilberto

2011-07-01

Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology. Among cytokines induced in UC, interleukin 1 antagonist (IL-1ra) and interleukin 1 β (IL-1β) seems to have a central role because of its immunoregulatory and proinflammatory activities. To determine the association between IL-1RA and IL-1B gene polymorphisms and the clinical features of UC in the Mexican Mestizo population. Five polymorphisms in the IL-1 gene cluster members IL-1B (rs16944), IL1F10 (rs3811058), and IL-1RN (rs419598, rs315952, and rs315951) were genotyped by 5' exonuclease TaqMan genotyping assays in a group of 200 Mexican patients with UC and 248 ethnically matched unrelated healthy controls. We found a significant increased frequencies of IL-1RN6/1 TC (rs315952) and RN6/2 CC (rs315951) and decreased frequency of IL-1B-511 TC (rs16944) genotypes in UC patients as compared with healthy controls. In the subgroup analysis, we found a significant association between the RN6/2 GG (rs315951) and IL-1B-511 CC (rs16944) genotypes and the presence of steroid-dependence in UC patients (pC=00001, OR=15.6 and pC=0.008, OR=4.09, respectively). Patients with UC showed increased frequencies of IL-1RN "CTC" and "TCG" haplotypes when compared with healthy controls (P=0.019, OR=1.43 and P<10(-7), OR=2.63, respectively). Two haplotypes (TTG and CTG) showed decreased frequency in patients when compared with healthy controls (P=9×10(-7), OR=0.11 and P=8×10(-6), OR=0.11, respectively). IL-1 RN and IL-1B polymorphisms were associated with the genetic susceptibility to develop UC and might be associated with the presence of steroid-dependence in UC patients.

Identification and Characterization of Microsatellite Markers Derived from the Whole Genome Analysis of Taenia solium.

PubMed

Pajuelo, Mónica J; Eguiluz, María; Dahlstrom, Eric; Requena, David; Guzmán, Frank; Ramirez, Manuel; Sheen, Patricia; Frace, Michael; Sammons, Scott; Cama, Vitaliano; Anzick, Sarah; Bruno, Dan; Mahanty, Siddhartha; Wilkins, Patricia; Nash, Theodore; Gonzalez, Armando; García, Héctor H; Gilman, Robert H; Porcella, Steve; Zimic, Mirko

2015-12-01

Infections with Taenia solium are the most common cause of adult acquired seizures worldwide, and are the leading cause of epilepsy in developing countries. A better understanding of the genetic diversity of T. solium will improve parasite diagnostics and transmission pathways in endemic areas thereby facilitating the design of future control measures and interventions. Microsatellite markers are useful genome features, which enable strain typing and identification in complex pathogen genomes. Here we describe microsatellite identification and characterization in T. solium, providing information that will assist in global efforts to control this important pathogen. For genome sequencing, T. solium cysts and proglottids were collected from Huancayo and Puno in Peru, respectively. Using next generation sequencing (NGS) and de novo assembly, we assembled two draft genomes and one hybrid genome. Microsatellite sequences were identified and 36 of them were selected for further analysis. Twenty T. solium isolates were collected from Tumbes in the northern region, and twenty from Puno in the southern region of Peru. The size-polymorphism of the selected microsatellites was determined with multi-capillary electrophoresis. We analyzed the association between microsatellite polymorphism and the geographic origin of the samples. The predicted size of the hybrid (proglottid genome combined with cyst genome) T. solium genome was 111 MB with a GC content of 42.54%. A total of 7,979 contigs (>1,000 nt) were obtained. We identified 9,129 microsatellites in the Puno-proglottid genome and 9,936 in the Huancayo-cyst genome, with 5 or more repeats, ranging from mono- to hexa-nucleotide. Seven microsatellites were polymorphic and 29 were monomorphic within the analyzed isolates. T. solium tapeworms were classified into two genetic groups that correlated with the North/South geographic origin of the parasites. The availability of draft genomes for T. solium represents a significant step towards the understanding the biology of the parasite. We report here a set of T. solium polymorphic microsatellite markers that appear promising for genetic epidemiology studies.

GLUTATHIONE PEROXIDASE-1 PRO200LEU POLYMORPHISM (RS1050450) IS ASSOCIATED WITH MORBID OBESITY INDEPENDENTLY OF THE PRESENCE OF PREDIABETES OR DIABETES IN WOMEN FROM CENTRAL MEXICO.

PubMed

Hernández Guerrero, César; Hernández Chávez, Paulina; Martínez Castro, Noemí; Parra Carriedo, Alicia; García Del Rio, Sandra; Pérez Lizaur, Ana

2015-10-01

obesity affects more than a third of Mexican population. Oxidative stress participates actively in the etiology of this phenomenon. Glutathione peroxidase-1 (GPX-1) plays a protective role against oxidative stress. The SNP Pro200Leu (rs10504050) has been reported to affect the activity of the enzyme. to determine the frequency of rs10504050 polymorphism in women with obesity and normal weight control, asses the concentration of peripheral TBARS and evaluate the consumption of pro and antioxidants. 104 women with obesity and 70 healthy controls (CG) were included in the study. Anthropometric, biochemical, clinical and dietary features were evaluated. GPx-1 rs10504050 was determined by PCR/RFLP method. TBARS was assayed spectrophotometrically in plasma. The subjects were stratified and compared by obesity grades and by subgroups of prediabetes and diabetes condition. Statistical analysis included ANOVA of Kruskal Wallis, Xi squared and Pearson correlation. for rs10504050 polymorphism there were differences (Xi2 = 6; p = 0.01) between frequency (0.61) of obese carriers (Pro/Leu plus Leu/Leu) and CG carriers (0.42), and between (Xi2 = 8; p = 0.004) morbid (IMC > 40) obesity (0.74) and CG carriers. The obese group (OB) showed a prevalence of 66% of prediabetes plus diabetes. There were no differences in frequencies of rs10504050 in OB with pre or diabetes versus CG, or versus obese participants without diabetes. TBARS concentration was greater in all the degrees of OB versus CG. GPx-1 Pro200Leu polymorphism was associated with obesity especially with morbid obesity, but not with obese participants with prediabetes or diabetes. Oxidative stress is present in all grades of obesity significantly. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

TERT Polymorphism rs2736100-C Is Associated with EGFR Mutation-Positive Non-Small Cell Lung Cancer

PubMed Central

Zheng, Yonglan; Niu, Xiaomin; Weng, Xiaoling; Zhang, Hong; Favus, Murray; Zhang, Lanjun; Jia, Weihua; Zeng, Yixin; Amos, Christopher I; Lu, Shun; Wang, Hui-Yun; Liu, Yun; Liu, Wanqing

2015-01-01

Purpose Epidermal growth factor receptor (EGFR) mutation-positive (EGFRmut+) non-small cell lung cancer (NSCLC) may be a unique orphan disease. Previous studies suggested that the telomerase reverse transcriptase (TERT) gene polymorphism is associated with demographic and clinical features strongly associated with EGFR mutations, e.g. adenocarcinoma histology, never-smoking history and female gender. We aim to test the association between TERT polymorphism and EGFRmut+ NSCLC. Experimental Design We conducted a genetic association study in Chinese NSCLC patients (n=714) and healthy controls (n=2,520), between the rs2736100 polymorphism and EGFRmut+ NSCLC. We further tested the association between the EGFR mutation status and mean leukocyte telomere length (LTL). The potential function of rs2736100 in lung epithelial cells was also explored. Results The rs2736100-C allele was significantly associated with EGFRmut+ NSCLC (OR=1.52, 95%CI=1.28–1.80, p=1.6×10−6) but not EGFRmut− NSCLC (OR=1.07, 95%CI=0.92–1.24, p=0.4). While NSCLC patients as a whole have significantly longer LTL compared to healthy controls (p≤10−13), the EGFRmut+ patients have even longer LTL compared to EGFRmut-patients (p=0.008). Meanwhile, rs2736100 was significantly associated with TERT mRNA expression in both normal and tumor lung tissues. All results remained significant after controlling for age, gender, smoking status and histology (p<0.05 for all tests). Moreover, the rs2736100 DNA sequence has an allele-specific affinity to nuclear proteins extracted from lung epithelial cells, which led to an altered enhancer activity of the sequence in vitro. Conclusion Our study suggests that telomerase and telomere function may be essential for carcinogenesis of EGFRmut+ NSCLC. Further investigation for the underlying mechanism is warranted. PMID:26149460

The CHRNA3 rs578776 Variant is Associated with an Intrinsic Reward Sensitivity Deficit in Smokers.

PubMed

Robinson, Jason D; Versace, Francesco; Lam, Cho Y; Minnix, Jennifer A; Engelmann, Jeffrey M; Cui, Yong; Karam-Hage, Maher; Shete, Sanjay S; Tomlinson, Gail E; Chen, Tina T-L; Wetter, David W; Green, Charles E; Cinciripini, Paul M

2013-01-01

A compromised brain reward system has been postulated as a key feature of drug dependence. We examined whether several polymorphisms of genes found to regulate nicotinic acetylcholine receptor (nAChR) and dopamine expression were related to an intrinsic reward sensitivity (IRS) deficit we previously identified among a subgroup of smokers using event-related potentials (ERPs). We examined genetic polymorphisms within the CHRNA5-A3-B4 gene cluster (CHRNA3 rs578776, CHRNA5 rs16969968, LOC123688 rs8034191, and CHRNA3 rs1051730), the ANKK1 gene (rs1800497), and the D2 dopamine receptor gene (DRD2 rs1079597, DRD2 rs1799732) from 104 smokers of European ancestry in a smoking cessation trial. Prior to treatment, we recorded ERPs evoked by emotional (both pleasant and unpleasant), neutral, and cigarette-related pictures. Smokers were assigned to two groups (IRS+/IRS-) based on the amplitude of the late positive potential (LPP) component to the pictures, a neural marker of motivational salience. Smokers (n = 42) with blunted brain responses to intrinsically rewarding (pleasant) pictures and enhanced responses to cigarette pictures were assigned to the IRS- group, while smokers (n = 62) with the opposite pattern of LPP responding were assigned to the IRS+ group. Carriers of the protective minor T allele (T/T, C/T) of the CHRNA3 rs578776 were less likely to be members of the IRS- group than those homozygous for the at-risk C allele (C/C). The CHRNA3 rs578776 polymorphism did not differ on questionnaires of nicotine dependence, depressed mood, or trait affective disposition and did not predict abstinence at 6 months after the quit date. These results suggest that polymorphisms of genes influencing nAChR expression are related to an endophenotype of reward sensitivity in smokers.

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.

GESPA: classifying nsSNPs to predict disease association.

PubMed

Khurana, Jay K; Reeder, Jay E; Shrimpton, Antony E; Thakar, Juilee

2015-07-25

Non-synonymous single nucleotide polymorphisms (nsSNPs) are the most common DNA sequence variation associated with disease in humans. Thus determining the clinical significance of each nsSNP is of great importance. Potential detrimental nsSNPs may be identified by genetic association studies or by functional analysis in the laboratory, both of which are expensive and time consuming. Existing computational methods lack accuracy and features to facilitate nsSNP classification for clinical use. We developed the GESPA (GEnomic Single nucleotide Polymorphism Analyzer) program to predict the pathogenicity and disease phenotype of nsSNPs. GESPA is a user-friendly software package for classifying disease association of nsSNPs. It allows flexibility in acceptable input formats and predicts the pathogenicity of a given nsSNP by assessing the conservation of amino acids in orthologs and paralogs and supplementing this information with data from medical literature. The development and testing of GESPA was performed using the humsavar, ClinVar and humvar datasets. Additionally, GESPA also predicts the disease phenotype associated with a nsSNP with high accuracy, a feature unavailable in existing software. GESPA's overall accuracy exceeds existing computational methods for predicting nsSNP pathogenicity. The usability of GESPA is enhanced by fast SQL-based cloud storage and retrieval of data. GESPA is a novel bioinformatics tool to determine the pathogenicity and phenotypes of nsSNPs. We anticipate that GESPA will become a useful clinical framework for predicting the disease association of nsSNPs. The program, executable jar file, source code, GPL 3.0 license, user guide, and test data with instructions are available at http://sourceforge.net/projects/gespa.

Genetic architecture and balancing selection: the life and death of differentiated variants.

PubMed

Llaurens, Violaine; Whibley, Annabel; Joron, Mathieu

2017-05-01

Balancing selection describes any form of natural selection, which results in the persistence of multiple variants of a trait at intermediate frequencies within populations. By offering up a snapshot of multiple co-occurring functional variants and their interactions, systems under balancing selection can reveal the evolutionary mechanisms favouring the emergence and persistence of adaptive variation in natural populations. We here focus on the mechanisms by which several functional variants for a given trait can arise, a process typically requiring multiple epistatic mutations. We highlight how balancing selection can favour specific features in the genetic architecture and review the evolutionary and molecular mechanisms shaping this architecture. First, balancing selection affects the number of loci underlying differentiated traits and their respective effects. Control by one or few loci favours the persistence of differentiated functional variants by limiting intergenic recombination, or its impact, and may sometimes lead to the evolution of supergenes. Chromosomal rearrangements, particularly inversions, preventing adaptive combinations from being dissociated are increasingly being noted as features of such systems. Similarly, due to the frequency of heterozygotes maintained by balancing selection, dominance may be a key property of adaptive variants. High heterozygosity and limited recombination also influence associated genetic load, as linked recessive deleterious mutations may be sheltered. The capture of deleterious elements in a locus under balancing selection may reinforce polymorphism by further promoting heterozygotes. Finally, according to recent genomewide scans, balanced polymorphism might be more pervasive than generally thought. We stress the need for both functional and ecological studies to characterize the evolutionary mechanisms operating in these systems. © 2017 John Wiley & Sons Ltd.

The signature of positive selection at randomly chosen loci.

PubMed

Przeworski, Molly

2002-03-01

In Drosophila and humans, there are accumulating examples of loci with a significant excess of high-frequency-derived alleles or high levels of linkage disequilibrium, relative to a neutral model of a random-mating population of constant size. These are features expected after a recent selective sweep. Their prevalence suggests that positive directional selection may be widespread in both species. However, as I show here, these features do not persist long after the sweep ends: The high-frequency alleles drift to fixation and no longer contribute to polymorphism, while linkage disequilibrium is broken down by recombination. As a result, loci chosen without independent evidence of recent selection are not expected to exhibit either of these features, even if they have been affected by numerous sweeps in their genealogical history. How then can we explain the patterns in the data? One possibility is population structure, with unequal sampling from different subpopulations. Alternatively, positive selection may not operate as is commonly modeled. In particular, the rate of fixation of advantageous mutations may have increased in the recent past.

Transforming AdaPT to Ada9x

NASA Technical Reports Server (NTRS)

Goldsack, Stephen J.; Holzbach-Valero, A. A.; Volz, Richard A.; Waldrop, Raymond S.

1993-01-01

How the concepts of AdaPT can be transformed into programs using the object oriented features proposed in the preliminary mapping for Ada9x are described. Emphasizing, as they do, the importance of data types as units of program, these features match well with the development of partitions as translations into Abstract Data Types which was exploited in the Ada83 translation covered in report R3. By providing a form of polymorphic type, the Ada83 version also gives support for the conformant partition idea which could be achieved in Ada83 only by using UNCHECKED CONVERSIONS. It is assumed that the reader understands AdaPT itself, but the translation into Ada83 is briefly reviewed, by applying it to a small example. This is then used to show how the same translation would be achieved in the 9x version. It is important to appreciate that the distribution features which are proposed in current mapping are not used or discussed in any detail, as those are not well matched to the AdaPT approach. Critical evaluation and comparison of these approaches is given in a separate report.

Recurrent intraoral HSV-1 infection: A retrospective study of 58 immunocompetent patients from Eastern Europe.

PubMed

Tovaru, Serban; Parlatescu, Ioanina; Tovaru, Mihaela; Cionca, Lucia; Arduino, Paolo-Giacomo

2011-03-01

To revise the clinical features of the recurrent intraoral herpetic infection (RIOH) with respect to precipitating factors, demographic, clinical features and outcome. Fifty-eight, unrelated Caucasian, immunocompetent patients with positive laboratory test for intraoral Herpes simplex virus infection were studied. The mean age in the women's group (n=42) was 41.23 years (± 21.73) and in the men's group was 32.25 years (±15.68). Possible trigger factors were identified in 9 cases (15.5%). General symptoms were noted in 20 cases (34.48%). Most of patients in this study presented multiple lesions. 14 patients had vermillion lesions associated with intraoral lesions. In most of the cases both fixed and mobile mucosa was concomitantly involved. Treatment was prescribed in order to control the symptoms and to shorten the evolution with minimal side effects. Intraoral secondary herpetic infection could be polymorphous and sometimes associated with general symptoms. The recognition of its atypical features may prevent unnecessary and costly investigations and treatments for unrelated though clinically similar-appearing disorders.

2q24 deletion in a 9-month old girl with anal atresia, hearing impairment, and hypotonia.

PubMed

Zhao, Peiwei; Mao, Bing; Cai, Xiaonan; Jiang, Jun; Liu, Zhisheng; Lin, Jun; He, Xuelian

2018-06-01

Deletion of 2q24.2 is a rare cytogenetic aberration in patients, exhibiting heterogeneous clinical features, and common phenotypes included developmental delay, intellectual disability, hypotonia, and mild dysmorphic features. Hearing impairment and anal atresia are rarely described. Here we described a 9-month-old female patient with hypotonia in all four limbs, developmental delay, and intellectual disability. In addition, congenital anal atresia was diagnosed and treated after birth, and hearing impairment was found in right ear. Single nucleotide polymorphisms (SNP) array detected a 5.2 Mb deletion on 2q24.2q24.3, including 19 genes (ITGB6; TBR1; SLC4A10; KCNH7 SCN3A; SCN2A et al.). Among these genes, it is affirmative that TBR1 is a causative gene for intellectual disability; however, the pathogenic genes of other phenotypes remain unclear. We briefly review the knowledge of genes likely involved in these clinical features, including hearing impairment, anal atresia, and developmental delay. Copyright © 2018 Elsevier B.V. All rights reserved.

What chickens would tell you about the evolution of antigen processing and presentation.

PubMed

Kaufman, Jim

2015-06-01

Outside of mammals, antigen processing and presentation have only been investigated in chickens. The chicken MHC is organized differently than mammals, allowing the co-evolution of polymorphic genes, with each MHC haplotype having a set of TAP1, TAP2 and tapasin alleles directed to high expression of a single classical class I molecule. However, the class I alleles vary in the size of peptide-binding repertoire, along with a suite of other properties. The salient features of the chicken MHC are found in many non-mammalian vertebrates, and are likely to have been set at the origin of the adaptive immune system of jawed vertebrates, with unrelated genes co-evolving to set up the original pathways. Half a billion years later, various features of presentation and resistance to disease still reflect this ancestral arrangement. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Molecular Taxonomy of the Trichophyton rubrum Complex

PubMed Central

Gräser, Y.; Kuijpers, A. F. A.; Presber, W.; de Hoog, G. S.

2000-01-01

The validity of taxa around Trichophyton rubrum was evaluated by a combination of phenetic and molecular methods. Morphological and physiological features were compared to results of sequencing of the internal transcribed spacer region of the ribosomal operon, PCR fingerprinting, and amplified fragment length polymorphism analysis. The 15 species and varieties investigated (Trichophyton circonvolutum, Trichophyton fischeri, Trichophyton fluviomuniense, Trichophyton glabrum, Trichophyton gourvilii, Trichophyton kanei, Trichophyton kuryangei, Trichophyton megninii, Trichophyton pedis, Trichophyton raubitschekii, Trichophyton rodhaini, Trichophyton rubrum var. nigricans, Trichophyton soudanense, Trichophyton violaceum var. indicum, and Trichophyton yaoundei) were reclassified or synonymized as T. rubrum or T. violaceum. PMID:10970379

C++ Programming Language

NASA Technical Reports Server (NTRS)

Shaykhian, Gholam Ali

2007-01-01

C++ Programming Language: The C++ seminar covers the fundamentals of C++ programming language. The C++ fundamentals are grouped into three parts where each part includes both concept and programming examples aimed at for hands-on practice. The first part covers the functional aspect of C++ programming language with emphasis on function parameters and efficient memory utilization. The second part covers the essential framework of C++ programming language, the object-oriented aspects. Information necessary to evaluate various features of object-oriented programming; including encapsulation, polymorphism and inheritance will be discussed. The last part of the seminar covers template and generic programming. Examples include both user defined and standard templates.

Memcomputing with membrane memcapacitive systems

NASA Astrophysics Data System (ADS)

Pershin, Y. V.; Traversa, F. L.; Di Ventra, M.

2015-06-01

We show theoretically that networks of membrane memcapacitive systems—capacitors with memory made out of membrane materials—can be used to perform a complete set of logic gates in a massively parallel way by simply changing the external input amplitudes, but not the topology of the network. This polymorphism is an important characteristic of memcomputing (computing with memories) that closely reproduces one of the main features of the brain. A practical realization of these membrane memcapacitive systems, using, e.g., graphene or other 2D materials, would be a step forward towards a solid-state realization of memcomputing with passive devices.

Prion protein gene analysis in three kindreds with fatal familial insomnia (FFI): Codon 178 mutation and codon 129 polymorphism

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

Medori, R.; Tritschler, H.J.

1993-10-01

Fatal familial insomnia (FFI) is a disease linked to a GAC(Asp) [yields] AAC(Asn) mutation in codon 178 of the prion protein (PrP) gene. FFI is characterized clinically by untreatable progressive insomnia, dysautonomia, and motor dysfunctions and is characterized pathologically by selective thalamic atrophy. The authors confirmed the 178[sup Asn] mutation in the PrP gene of a third FFI family of French ancestry. Three family members who are under 40 years of age and who inherited the mutation showed only reduced perfusion in the basal ganglia on single photon emission computerized tomography. Some FFI features differ from the clinical and neuropathologicmore » findings associated with 178[sup Asn] reported elsewhere. However, additional intragenic mutations accounting for the phenotypic differences were not observed in two affected individuals. In other sporadic and familial forms of Creutzfeldt-Jakob disease and Gerstmann-Straeussler syndrome, Met or Val homozygosity at polymorphic codon 129 is associated with a more severe phenotype, younger age at onset, and faster progression. In FFI, young and old individuals at disease onset had 129[sup Met/Val]. Moreover, of five 178[sup Asn] individuals who are above age-at-onset range and who are well, two have 129[sup Met] and three have 129[sup Met/Val], suggesting that polymorphic site 129 does not modulate FFI phenotypic expression. Genetic heterogeneity and environment may play an important role in inter- and intrafamilial variability of the 178[sup Asn] mutation. 32 refs., 5 figs., 1 tab.« less

FAS/FASL gene polymorphisms in Turkish patients with chronic myeloproliferative disorders.

PubMed

Ozdemirkiran, Fusun Gediz; Nalbantoglu, Sinem; Gokgoz, Zafer; Payzin, Bahriye Kadriye; Vural, Filiz; Cagirgan, Seckin; Berdeli, Afig

2017-03-01

Chronic myeloproliferative disorders (CMPD) are chronic myeloid hematological disorders, characterized by increased myeloid cell proliferation and fibrosis. Impaired apoptotic mechanisms, increased cell proliferation, uncontrolled hematopoietic cell proliferation and myeloaccumulation may contribute to the pathogenesis of CMPD. The aim of our study was to show the possible role of FAS/FASL gene polymorphisms in CMPD pathogenesis and investigate the association with clinical parameters and susceptibility to disease. We included 101 (34 polycythemia vera (PV), 23 primary myelofibrosis (PMF), 44 essential thrombocythemia (ET)) CMPD patients diagnosed according to the WHO classification criteria and 95 healthy controls in this study. All the patients and the controls were investigated for FAS/FASL gene expression, allele frequencies and phenotype features, and also FAS mRNA levels were analyzed. Chronic myeloproliferative disorders patients showed increased FAS-670AG + GG genotype distribution compared with the control group ( p < 0.05). While the A allele was more frequent in both groups, AG genotype was more frequent in CMPD patients. There was no association between FAS-670A>G gene polymorphism and some clinical parameters such as splenomegaly and thrombosis ( p > 0.05). No statistically significant difference in FASL+843C>T genotype or allele frequency was found between groups ( p > 0.05). Moreover, no statistically significant difference was detected in FASL and JAK2V617F mutations ( p > 0.05). FAS mRNA expression was 1.5-fold reduced in patients compared to healthy subjects. According to our findings, FAS/FASL gene expression may contribute to the molecular and immunological pathogenesis of CMPD. More investigations are needed to support these data.

Polymorphisms within the tumor necrosis factor and lymphotoxin-alpha genes and endemic pemphigus foliaceus--are there any associations?

PubMed

Roxo, V M M S; Pereira, N F; Pavoni, D P; Lin, M-T; Hansen, J A; de O Poersch, C; Filho, A Marquart; Petzl-Erler, M L

2003-11-01

The purpose of this study was to analyze the possible influence of the TNF and LTA loci polymorphisms on the susceptibility/resistance to endemic pemphigus foliaceus, also named fogo selvagem (FS), an autoimmune disease characterized by blisters due to acantholysis of the superficial-most epidermal cells. Autoantibodies, mainly of the IgG4 subclass, are directed against a desmosomal glycoprotein known as desmoglein 1. FS shares clinical, histological and immunological features with nonendemic pemphigus foliaceus. Most residents of the endemic regions do not develop the disease, and familial clustering has been documented, suggesting that host factors play a role in susceptibility. In fact, strong positive and negative associations with HLA class II genes have been reported. The TNF and LTA genes are located in the class III region of the Human Major Histocompatibility Complex. Their location, the function of their products, which are cytokines and pluripotent immunomodulators, as well as their genetic variability make them candidate genes for complex diseases with an altered immune response. A total of 162 patients and 191 controls were enrolled in this study. No significant associations were found with any one of the three LTA single nucleotide polymorphisms (SNP) analyzed (at nucleotides 249, 365, 720), nor with the TNF SNP located at positions -863 and -308. The frequency of allele TNF*238A was slightly decreased in patients (OR = 0.45). In conclusion, the results of this study indicate that genetic variability of the TNF and LTA genes does not play a major role in susceptibility/resistance to pemphigus foliaceus.

Polymorphism at the 3'-UTR of the thymidylate synthase gene: A potential predictor for outcomes in Caucasian patients with esophageal adenocarcinoma treated with preoperative chemoradiation

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

Liao Zhongxing; Liu Hongji; Swisher, Stephen G.

2006-03-01

Purpose: To test the hypothesis that TS3'UTR polymorphisms predict outcomes in 146 Caucasian patients with esophageal adenocarcinoma treated with preoperative 5-fluorouracil-based chemoradiation. Methods and Materials: DNA was extracted from hematoxylin-and-eosin stained histologic slides of normal esophageal or gastric mucosa sections from paraffin blocks of esophagectomy specimens. Genotypes of the TS3'UTR polymorphism were determined by polymerase chain reaction for a 6-bp insertion. The genotype groups (0bp/0bp, 6bp/0bp, and 6bp/6bp) were compared for clinical features and overall survival, recurrence-free-survival, locoregional control (LRC), and distant metastasis control. Multivariable Cox regression analyses were performed to find independent predictors for the stated outcomes. Results: Theremore » was a trend of association between 6bp/6bp genotype and a decreased risk of local regional recurrence (hazards ratio = 0.211, 95% confidence interval = 0.041-1.095, p = 0.06) compared with other genotypes. There was a trend that patients with 6bp/6bp genotype had a higher 3-year probability of LRC compared with patients with the other two genotypes combined (p = 0.07); however, the difference was not statistically significant. Conclusions: The null hypotheses were not rejected in this study, probably owing to small sample size or the single gene examined. Prospective studies with adequate statistical power analyzing a family of genes involved in the 5-fluorouracil metabolism are needed to assess genetic determinants of treatment-related outcomes in esophageal adenocarcinoma.« less

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.

Examining the Impact of Maternal Individual Features on Children's Behavioral Problems in Adoptive Families: The Role of Maternal Temperament and Neurobiological Markers.

PubMed

Ozturk, Yagmur; Barone, Virginia; Barone, Lavinia

2018-01-24

The first year after adoption constitutes a sensitive period for both strengthening the new emotional bond in the family and checking its appropriate development by adoption services. A key variable for children's catch-up are adoptive parents' socioemotional and individual features. The aim of this study is to investigate links between adoptive mothers' individual features and behavioral problems in their children in the first year after adoption placement, by testing the moderating role of both age at adoption and maternal genetic polymorphisms. Seventy-eight adoptive mothers completed temperament and genetic measures. Mothers showed a specific pattern of interaction between basic temperament traits and genetic markers in their assessment of children's behavioral problems; dopamine D4 receptor gene and children's age at adoption are two moderators in the association in which mothers' temperament was affecting the evaluation of their children's behavioral problems. Findings highlight a still undervalued area of parenting resources in the process of post-institutionalized children's catch-up after adoption placement, by showing how individual features count in the commonly measured variable of children's behavioral and emotional problems. This could help in orienting identification and choice of key variables for family assessment after adoption placement, thus contributing in fostering children's healthy development.

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

Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms.

PubMed

Nelson, J E; Handa, P; Aouizerat, B; Wilson, L; Vemulakonda, L A; Yeh, M M; Kowdley, K V

2016-12-01

Non-alcoholic fatty liver disease (NAFLD) is a complex, multifactorial disease affected by diet, lifestyle and genetics. Proinflammatory cytokines like IL-1β and IL-6 have been shown to be elevated in non-alcoholic steatohepatitis (NASH). To investigate the relationship between IL1B and IL6 gene polymorphisms and histological features of NAFLD in the NASH CRN cohort. A total of 604 adult (≥18 years) non-Hispanic Caucasians with biopsy-proven NAFLD were genotyped for the following SNPs: IL1B, rs16944, rs1143634; IL6, rs1800795, rs10499563. Logistic regression was used to examine the relationship between genotype and a definitive diagnosis and advanced histological features of NASH after controlling for the following variables selected a priori: age, sex, diabetes, obesity and HOMA-IR level. The IL6 rs10499563 C allele was independently associated with the presence of definitive NASH, and increased ballooning and Mallory bodies. The IL1B rs1143634 TT genotype was associated with advanced fibrosis and increased Mallory bodies. The IL6 rs1800795 C allele was associated with not only increased risk for severe steatosis, >66% but also decreased risk for advanced fibrosis and lobular inflammation and Mallory body formation. These results suggest that common variants in the IL6 and IL1B genes may increase susceptibility for NASH and confer a higher risk of hepatic parenchymal damage including increased ballooning, increased Mallory bodies, and bridging fibrosis or cirrhosis. In contrast, the IL6 rs1800795 C allele may confer a higher risk for steatosis, but less parenchymal damage. Our findings support the development of therapeutics aimed at IL-1β and IL-6 suppression. © 2016 John Wiley & Sons Ltd.

An Induced Pluripotent Stem Cell Patient Specific Model of Complement Factor H (Y402H) Polymorphism Displays Characteristic Features of Age-Related Macular Degeneration and Indicates a Beneficial Role for UV Light Exposure.

PubMed

Hallam, Dean; Collin, Joseph; Bojic, Sanja; Chichagova, Valeria; Buskin, Adriana; Xu, Yaobo; Lafage, Lucia; Otten, Elsje G; Anyfantis, George; Mellough, Carla; Przyborski, Stefan; Alharthi, Sameer; Korolchuk, Viktor; Lotery, Andrew; Saretzki, Gabriele; McKibbin, Martin; Armstrong, Lyle; Steel, David; Kavanagh, David; Lako, Majlinda

2017-11-01

Age-related macular degeneration (AMD) is the most common cause of blindness, accounting for 8.7% of all blindness globally. Vision loss is caused ultimately by apoptosis of the retinal pigment epithelium (RPE) and overlying photoreceptors. Treatments are evolving for the wet form of the disease; however, these do not exist for the dry form. Complement factor H polymorphism in exon 9 (Y402H) has shown a strong association with susceptibility to AMD resulting in complement activation, recruitment of phagocytes, RPE damage, and visual decline. We have derived and characterized induced pluripotent stem cell (iPSC) lines from two subjects without AMD and low-risk genotype and two patients with advanced AMD and high-risk genotype and generated RPE cells that show local secretion of several proteins involved in the complement pathway including factor H, factor I, and factor H-like protein 1. The iPSC RPE cells derived from high-risk patients mimic several key features of AMD including increased inflammation and cellular stress, accumulation of lipid droplets, impaired autophagy, and deposition of "drüsen"-like deposits. The low- and high-risk RPE cells respond differently to intermittent exposure to UV light, which leads to an improvement in cellular and functional phenotype only in the high-risk AMD-RPE cells. Taken together, our data indicate that the patient specific iPSC model provides a robust platform for understanding the role of complement activation in AMD, evaluating new therapies based on complement modulation and drug testing. Stem Cells 2017;35:2305-2320. © 2017 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Increased Parenchymal Damage and Steatohepatitis in Caucasian Nonalcoholic Fatty Liver Disease Patients with Common IL1B and IL6 Polymorphisms

PubMed Central

Nelson, James E.; Handa, Priya; Aouizerat, Bradley; Wilson, Laura; Vemulakonda, L Akhila; Yeh, Matthew M.; Kowdley, Kris V.

2016-01-01

Background Nonalcoholic fatty liver disease (NAFLD) is a complex, multifactorial disease affected by diet, lifestyle and genetics. Proinflammatory cytokines like IL-1β and IL-6 have been shown to be elevated in nonalcoholic steatohepatitis (NASH). The goal of this study was to investigate the relationship between IL1B and IL6 gene polymorphisms and histologic features of NAFLD in the NASH CRN cohort. Methods 604 adult (≥18 yrs) non-Hispanic Caucasians with biopsy-proven NAFLD were genotyped for the following SNPs: IL1B, rs16944, rs1143634; IL6, rs1800795, rs10499563. Logistic regression was used to examine the relationship between genotype and a definitive diagnosis and advanced histological features of NASH after controlling for the following variables selected a priori: age, sex, diabetes, obesity and HOMA-IR level. Results The IL6 rs10499563 C allele was independently associated with the presence of definitive NASH, and increased ballooning and Mallory bodies. The IL1B rs1143634 TT genotype was associated with advanced fibrosis and increased Mallory bodies. The IL6 rs1800795 C allele was associated with increased risk for severe steatosis, >66% but also decreased risk for advanced fibrosis and lobular inflammation and Mallory body formation. Conclusions These results suggest that common variants in the IL6 and IL1B genes may increase susceptibility for NASH and confer a higher risk of hepatic parenchymal damage including increased ballooning, increased Mallory bodies, and bridging fibrosis or cirrhosis. In contrast, the IL6 rs1800795 C allele may confer a higher risk for steatosis, but less parenchymal damage. Our findings support the development of therapeutics aimed at IL-1β and IL-6 suppression. PMID:27730688

Calculation of Electronic and Optical Properties of AgGaO2 Polymorphs Using Many-Body Approaches

NASA Astrophysics Data System (ADS)

Dadsetani, Mehrdad; Nejatipour, Reihan

2018-02-01

Ab initio calculations based on many-body perturbation theory have been used to study the electronic and optical properties of AgGaO2 in rhombohedral, hexagonal, and orthorhombic phases. GW calculations showed that AgGaO2 is an indirect-bandgap semiconductor in all three phases with energy bandgap of 2.35 eV, 2.23 eV, and 2.07 eV, in good agreement with available experimental values. By solving the Bethe-Salpeter equation (BSE) using the full potential linearized augmented plane wave basis, optical properties of the AgGaO2 polymorphs were calculated and compared with those obtained using the GW-corrected random phase approximation (RPA) and with existing experimental data. Strong anisotropy in the optical absorption spectra was observed, and the excitonic structures which were absent in the RPA calculations were reproduced in GWBSE calculations, in good agreement with the optical absorption spectrum of the rhombohedral phase. While modifying peak positions and intensities of the absorption spectra, the GWBSE gave rise to the redistribution of oscillator strengths. In comparison with the z-polarized response, excitonic effects in the x-polarized response were dominant. In the x- (and y-) polarized responses of r- and h-AgGaO2, spectral features and excitonic effects occur at the lower energies, but in the case of o-AgGaO2, the spectral structures of the z-polarized response occur at lower energies. In addition, the low-energy loss functions of AgGaO2 were calculated and compared using the GWBSE approach. Spectral features in the energy loss function components near the bandgap region were attributed to corresponding excitonic structures in the imaginary part of the dielectric function.

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.

Isolation and characterization of major histocompatibility complex class IIB genes from the nurse shark.

PubMed

Bartl, S; Weissman, I L

1994-01-04

The major histocompatibility complex (MHC) contains a set of linked genes which encode cell surface proteins involved in the binding of small peptide antigens for their subsequent recognition by T lymphocytes. MHC proteins share structural features and the presence and location of polymorphic residues which play a role in the binding of antigens. In order to compare the structure of these molecules and gain insights into their evolution, we have isolated two MHC class IIB genes from the nurse shark, Ginglymostoma cirratum. Two clones, most probably alleles, encode proteins which differ by 13 amino acids located in the putative antigen-binding cleft. The protein structure and the location of polymorphic residues are similar to their mammalian counterparts. Although these genes appear to encode a typical MHC protein, no T-cell-mediated responses have been demonstrated in cartilaginous fish. The nurse shark represents the most phylogenetically primitive organism in which both class IIA [Kasahara, M., Vazquez, M., Sato, K., McKinney, E.C. & Flajnik, M.F. (1992) Proc. Natl. Acad. Sci USA 89, 6688-6692] and class IIB genes, presumably encoding the alpha/beta heterodimer, have been isolated.

Complete 13C NMR chemical shifts assignment for cholesterol crystals by combined CP-MAS spectral editing and ab initio GIPAW calculations with dispersion forces.

PubMed

Küçükbenli, Emine; Sonkar, Kanchan; Sinha, Neeraj; de Gironcoli, Stefano

2012-04-12

We report here the first fully ab initio determination of (13)C NMR spectra for several crystal structures of cholesterol, observed in various biomaterials. We combine Gauge-Including Projector Augmented Waves (GIPAW) calculations at relaxed structures, fully including dispersion forces, with Magic Angle Spinning Solid State NMR experiments and spectral editing to achieve a detailed interpretation of the complex NMR spectra of cholesterol crystals. By introducing an environment-dependent secondary referencing scheme in our calculations, not only do we reproduce the characteristic spectral features of the different crystalline polymorphs, thus clearly discriminating among them, but also closely represent the spectrum in the region of several highly overlapping peaks. This, in combination with spectral editing, allows us to provide a complete peak assignment for monohydrate (ChM) and low-temperature anhydrous (ChAl) crystal polymorphs. Our results show that the synergy between ab initio calculations and refined experimental techniques can be exploited for an accurate and efficient NMR crystallography of complex systems of great interest for biomaterial studies. The method is general in nature and can be applied for studies of various complex biomaterials.

Initial sequence and comparative analysis of the cat genome

PubMed Central

Pontius, Joan U.; Mullikin, James C.; Smith, Douglas R.; Lindblad-Toh, Kerstin; Gnerre, Sante; Clamp, Michele; Chang, Jean; Stephens, Robert; Neelam, Beena; Volfovsky, Natalia; Schäffer, Alejandro A.; Agarwala, Richa; Narfström, Kristina; Murphy, William J.; Giger, Urs; Roca, Alfred L.; Antunes, Agostinho; Menotti-Raymond, Marilyn; Yuhki, Naoya; Pecon-Slattery, Jill; Johnson, Warren E.; Bourque, Guillaume; Tesler, Glenn; O’Brien, Stephen J.

2007-01-01

The genome sequence (1.9-fold coverage) of an inbred Abyssinian domestic cat was assembled, mapped, and annotated with a comparative approach that involved cross-reference to annotated genome assemblies of six mammals (human, chimpanzee, mouse, rat, dog, and cow). The results resolved chromosomal positions for 663,480 contigs, 20,285 putative feline gene orthologs, and 133,499 conserved sequence blocks (CSBs). Additional annotated features include repetitive elements, endogenous retroviral sequences, nuclear mitochondrial (numt) sequences, micro-RNAs, and evolutionary breakpoints that suggest historic balancing of translocation and inversion incidences in distinct mammalian lineages. Large numbers of single nucleotide polymorphisms (SNPs), deletion insertion polymorphisms (DIPs), and short tandem repeats (STRs), suitable for linkage or association studies were characterized in the context of long stretches of chromosome homozygosity. In spite of the light coverage capturing ∼65% of euchromatin sequence from the cat genome, these comparative insights shed new light on the tempo and mode of gene/genome evolution in mammals, promise several research applications for the cat, and also illustrate that a comparative approach using more deeply covered mammals provides an informative, preliminary annotation of a light (1.9-fold) coverage mammal genome sequence. PMID:17975172

Liver peroxisomal alanine:glyoxylate aminotransferase and the effects of mutations associated with Primary Hyperoxaluria Type I: An overview.

PubMed

Oppici, Elisa; Montioli, Riccardo; Cellini, Barbara

2015-09-01

Liver peroxisomal alanine:glyoxylate aminotransferase (AGT) (EC 2.6.1.44) catalyses the conversion of l-alanine and glyoxylate to pyruvate and glycine, a reaction that allows glyoxylate detoxification. Inherited mutations on the AGXT gene encoding AGT lead to Primary Hyperoxaluria Type I (PH1), a rare disorder characterized by the deposition of calcium oxalate crystals primarily in the urinary tract. Here we describe the results obtained on the biochemical features of AGT as well as on the molecular and cellular effects of polymorphic and pathogenic mutations. A complex scenario on the molecular pathogenesis of PH1 emerges in which the co-inheritance of polymorphic changes and the condition of homozygosis or compound heterozygosis are two important factors that determine the enzymatic phenotype of PH1 patients. All the reported data represent relevant steps toward the understanding of genotype/phenotype correlations, the prediction of the response of the patients to the available therapies, and the development of new therapeutic approaches. This article is part of a Special Issue entitled: Cofactor-dependent proteins: evolution, chemical diversity and bio-applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Applications of NIR spectroscopy to monitoring and analyzing the solid state during industrial crystallization processes.

PubMed

Févotte, G; Calas, J; Puel, F; Hoff, C

2004-04-01

Fiber-optic near infrared (NIR) spectroscopy was used to investigate several key features of the polymorphic transitions observed during the crystallization and the filtration of SaC, an Active Pharmaceutical Ingredient (API) produced by Sanofi-Synthelabo. Using few samples, the spectroscopic data were calibrated to provide measurements of the polymorphic composition of the solid product which is likely to appear in two crystalline forms or in the amorphous state. Both qualitative and quantitative methods were successfully evaluated to characterize the API. The NIR spectroscopy measurement was then applied to investigate the kinetic behavior of the phase transition phenomena against various operating conditions. From the viewpoint of industrial process development several applications are presented. The effects of temperature and seed crystal habits on the rate of transition of filtration cakes are briefly investigated; and a study of the effect of residual water in the solvent on the transition occurring during filtration is more deeply analyzed. The experimental results demonstrate that highly valuable information can be provided by the NIR spectroscopy measurements, when one aims at understanding more deeply and optimizing the consequences of various and complex phenomena involved during the solid processing chain.

High-speed atomic force microscopy reveals structural dynamics of amyloid β1–42 aggregates

PubMed Central

Watanabe-Nakayama, Takahiro; Ono, Kenjiro; Itami, Masahiro; Takahashi, Ryoichi; Teplow, David B.; Yamada, Masahito

2016-01-01

Aggregation of amyloidogenic proteins into insoluble amyloid fibrils is implicated in various neurodegenerative diseases. This process involves protein assembly into oligomeric intermediates and fibrils with highly polymorphic molecular structures. These structural differences may be responsible for different disease presentations. For this reason, elucidation of the structural features and assembly kinetics of amyloidogenic proteins has been an area of intense study. We report here the results of high-speed atomic force microscopy (HS-AFM) studies of fibril formation and elongation by the 42-residue form of the amyloid β-protein (Aβ1–42), a key pathogenetic agent of Alzheimer's disease. Our data demonstrate two different growth modes of Aβ1–42, one producing straight fibrils and the other producing spiral fibrils. Each mode depends on initial fibril nucleus structure, but switching from one growth mode to another was occasionally observed, suggesting that fibril end structure fluctuated between the two growth modes. This switching phenomenon was affected by buffer salt composition. Our findings indicate that polymorphism in fibril structure can occur after fibril nucleation and is affected by relatively modest changes in environmental conditions. PMID:27162352

Association analysis identifies 65 new breast cancer risk loci.

PubMed

Michailidou, Kyriaki; Lindström, Sara; Dennis, Joe; Beesley, Jonathan; Hui, Shirley; Kar, Siddhartha; Lemaçon, Audrey; Soucy, Penny; Glubb, Dylan; Rostamianfar, Asha; Bolla, Manjeet K; Wang, Qin; Tyrer, Jonathan; Dicks, Ed; Lee, Andrew; Wang, Zhaoming; Allen, Jamie; Keeman, Renske; Eilber, Ursula; French, Juliet D; Qing Chen, Xiao; Fachal, Laura; McCue, Karen; McCart Reed, Amy E; Ghoussaini, Maya; Carroll, Jason S; Jiang, Xia; Finucane, Hilary; Adams, Marcia; Adank, Muriel A; Ahsan, Habibul; Aittomäki, Kristiina; Anton-Culver, Hoda; Antonenkova, Natalia N; Arndt, Volker; Aronson, Kristan J; Arun, Banu; Auer, Paul L; Bacot, François; Barrdahl, Myrto; Baynes, Caroline; Beckmann, Matthias W; Behrens, Sabine; Benitez, Javier; Bermisheva, Marina; Bernstein, Leslie; Blomqvist, Carl; Bogdanova, Natalia V; Bojesen, Stig E; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brand, Judith S; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Brinton, Louise; Broberg, Per; Brock, Ian W; Broeks, Annegien; Brooks-Wilson, Angela; Brucker, Sara Y; Brüning, Thomas; Burwinkel, Barbara; Butterbach, Katja; Cai, Qiuyin; Cai, Hui; Caldés, Trinidad; Canzian, Federico; Carracedo, Angel; Carter, Brian D; Castelao, Jose E; Chan, Tsun L; David Cheng, Ting-Yuan; Seng Chia, Kee; Choi, Ji-Yeob; Christiansen, Hans; Clarke, Christine L; Collée, Margriet; Conroy, Don M; Cordina-Duverger, Emilie; Cornelissen, Sten; Cox, David G; Cox, Angela; Cross, Simon S; Cunningham, Julie M; Czene, Kamila; Daly, Mary B; Devilee, Peter; Doheny, Kimberly F; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dumont, Martine; Durcan, Lorraine; Dwek, Miriam; Eccles, Diana M; Ekici, Arif B; Eliassen, A Heather; Ellberg, Carolina; Elvira, Mingajeva; Engel, Christoph; Eriksson, Mikael; Fasching, Peter A; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Fritschi, Lin; Gaborieau, Valerie; Gabrielson, Marike; Gago-Dominguez, Manuela; Gao, Yu-Tang; Gapstur, Susan M; García-Sáenz, José A; Gaudet, Mia M; Georgoulias, Vassilios; Giles, Graham G; Glendon, Gord; Goldberg, Mark S; Goldgar, David E; González-Neira, Anna; Grenaker Alnæs, Grethe I; Grip, Mervi; Gronwald, Jacek; Grundy, Anne; Guénel, Pascal; Haeberle, Lothar; Hahnen, Eric; Haiman, Christopher A; Håkansson, Niclas; Hamann, Ute; Hamel, Nathalie; Hankinson, Susan; Harrington, Patricia; Hart, Steven N; Hartikainen, Jaana M; Hartman, Mikael; Hein, Alexander; Heyworth, Jane; Hicks, Belynda; Hillemanns, Peter; Ho, Dona N; Hollestelle, Antoinette; Hooning, Maartje J; Hoover, Robert N; Hopper, John L; Hou, Ming-Feng; Hsiung, Chia-Ni; Huang, Guanmengqian; Humphreys, Keith; Ishiguro, Junko; Ito, Hidemi; Iwasaki, Motoki; Iwata, Hiroji; Jakubowska, Anna; Janni, Wolfgang; John, Esther M; Johnson, Nichola; Jones, Kristine; Jones, Michael; Jukkola-Vuorinen, Arja; Kaaks, Rudolf; Kabisch, Maria; Kaczmarek, Katarzyna; Kang, Daehee; Kasuga, Yoshio; Kerin, Michael J; Khan, Sofia; Khusnutdinova, Elza; Kiiski, Johanna I; Kim, Sung-Won; Knight, Julia A; Kosma, Veli-Matti; Kristensen, Vessela N; Krüger, Ute; Kwong, Ava; Lambrechts, Diether; Le Marchand, Loic; Lee, Eunjung; Lee, Min Hyuk; Lee, Jong Won; Neng Lee, Chuen; Lejbkowicz, Flavio; Li, Jingmei; Lilyquist, Jenna; Lindblom, Annika; Lissowska, Jolanta; Lo, Wing-Yee; Loibl, Sibylle; Long, Jirong; Lophatananon, Artitaya; Lubinski, Jan; Luccarini, Craig; Lux, Michael P; Ma, Edmond S K; MacInnis, Robert J; Maishman, Tom; Makalic, Enes; Malone, Kathleen E; Kostovska, Ivana Maleva; Mannermaa, Arto; Manoukian, Siranoush; Manson, JoAnn E; Margolin, Sara; Mariapun, Shivaani; Martinez, Maria Elena; Matsuo, Keitaro; Mavroudis, Dimitrios; McKay, James; McLean, Catriona; Meijers-Heijboer, Hanne; Meindl, Alfons; Menéndez, Primitiva; Menon, Usha; Meyer, Jeffery; Miao, Hui; Miller, Nicola; Taib, Nur Aishah Mohd; Muir, Kenneth; Mulligan, Anna Marie; Mulot, Claire; Neuhausen, Susan L; Nevanlinna, Heli; Neven, Patrick; Nielsen, Sune F; Noh, Dong-Young; Nordestgaard, Børge G; Norman, Aaron; Olopade, Olufunmilayo I; Olson, Janet E; Olsson, Håkan; Olswold, Curtis; Orr, Nick; Pankratz, V Shane; Park, Sue K; Park-Simon, Tjoung-Won; Lloyd, Rachel; Perez, Jose I A; Peterlongo, Paolo; Peto, Julian; Phillips, Kelly-Anne; Pinchev, Mila; Plaseska-Karanfilska, Dijana; Prentice, Ross; Presneau, Nadege; Prokofyeva, Darya; Pugh, Elizabeth; Pylkäs, Katri; Rack, Brigitte; Radice, Paolo; Rahman, Nazneen; Rennert, Gadi; Rennert, Hedy S; Rhenius, Valerie; Romero, Atocha; Romm, Jane; Ruddy, Kathryn J; Rüdiger, Thomas; Rudolph, Anja; Ruebner, Matthias; Rutgers, Emiel J T; Saloustros, Emmanouil; Sandler, Dale P; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schmidt, Daniel F; Schmutzler, Rita K; Schneeweiss, Andreas; Schoemaker, Minouk J; Schumacher, Fredrick; Schürmann, Peter; Scott, Rodney J; Scott, Christopher; Seal, Sheila; Seynaeve, Caroline; Shah, Mitul; Sharma, Priyanka; Shen, Chen-Yang; Sheng, Grace; Sherman, Mark E; Shrubsole, Martha J; Shu, Xiao-Ou; Smeets, Ann; Sohn, Christof; Southey, Melissa C; Spinelli, John J; Stegmaier, Christa; Stewart-Brown, Sarah; Stone, Jennifer; Stram, Daniel O; Surowy, Harald; Swerdlow, Anthony; Tamimi, Rulla; Taylor, Jack A; Tengström, Maria; Teo, Soo H; Beth Terry, Mary; Tessier, Daniel C; Thanasitthichai, Somchai; Thöne, Kathrin; Tollenaar, Rob A E M; Tomlinson, Ian; Tong, Ling; Torres, Diana; Truong, Thérèse; Tseng, Chiu-Chen; Tsugane, Shoichiro; Ulmer, Hans-Ulrich; Ursin, Giske; Untch, Michael; Vachon, Celine; van Asperen, Christi J; Van Den Berg, David; van den Ouweland, Ans M W; van der Kolk, Lizet; van der Luijt, Rob B; Vincent, Daniel; Vollenweider, Jason; Waisfisz, Quinten; Wang-Gohrke, Shan; Weinberg, Clarice R; Wendt, Camilla; Whittemore, Alice S; Wildiers, Hans; Willett, Walter; Winqvist, Robert; Wolk, Alicja; Wu, Anna H; Xia, Lucy; Yamaji, Taiki; Yang, Xiaohong R; Har Yip, Cheng; Yoo, Keun-Young; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Zhu, Bin; Ziogas, Argyrios; Ziv, Elad; Lakhani, Sunil R; Antoniou, Antonis C; Droit, Arnaud; Andrulis, Irene L; Amos, Christopher I; Couch, Fergus J; Pharoah, Paul D P; Chang-Claude, Jenny; Hall, Per; Hunter, David J; Milne, Roger L; García-Closas, Montserrat; Schmidt, Marjanka K; Chanock, Stephen J; Dunning, Alison M; Edwards, Stacey L; Bader, Gary D; Chenevix-Trench, Georgia; Simard, Jacques; Kraft, Peter; Easton, Douglas F

2017-11-02

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10 -8 . The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

Mutational analysis of the PTPN11 gene in Egyptian patients with Noonan syndrome.

PubMed

Essawi, Mona L; Ismail, Manal F; Afifi, Hanan H; Kobesiy, Maha M; El Kotoury, Ahmed; Barakat, Maged M

2013-11-01

Noonan syndrome (NS) is inherited as an autosomal dominant disorder with dysmorphic facies, short stature, and cardiac defects, which can be caused by missense mutations in the protein tyrosine phosphatase nonreceptor type 11 (PTPN11) gene, which encodes src homology region 2 domain containing tyrosine phosphatase-2 (SHP-2), a protein tyrosine phosphatase that acts in signal transduction downstream to growth factors and cytokines. The current study aimed to study the molecular characterization of the PTPN11 gene among Egyptian patients with Noonan syndrome. Eleven exons of the PTPN11 gene were amplified and screened by single stranded conformational polymorphism (SSCP). DNA samples showing band shift in SSCP were subjected to sequencing. Mutational analysis of the PTPN11 gene revealed T→C transition at position 854 in exon 8, predicting Phe285Ser substitution within PTP domain of SHP-2 protein, in one NS patient and -21C→T polymorphism in intron 7 in four other cases. Knowing that NS is phenotypically heterogeneous, molecular characterization of the PTPN11 gene should serve to establish NS diagnosis in patients with atypical features, although lack of a mutation does not exclude the possibility of NS. Copyright © 2012. Published by Elsevier B.V.

FABP4: a novel candidate gene for polycystic ovary syndrome.

PubMed

Wang, Jing; Tang, Jingwen; Wang, Binbin; Song, Junjie; Liu, Jingjing; Wei, Zhaolian; Zhang, Feng; Ma, Xu; Cao, Yunxia

2009-12-01

Polycystic ovary syndrome (PCOS) is a complex multifactorial disorder involving a number of genetic and environmental factors. Adipocyte-fatty acid-binding protein (FABP4) is an adipokine regulating systemic insulin sensitivity, lipid and glucose metabolism. In humans serum FABP4 levels correlate significantly with features of PCOS. Previous researches showed strong evidences that FABP4 impacted the developing of PCOS possibly through its protein alteration or transcription regulation. Thus, the present study is the first attempt to identify the possible genetic role of FABP4 gene in the development of PCOS. About 1000 bp of the promoter region and four exons of FABP4 gene of 178 PCOS patients and 171 healthy controls were directly sequenced. Three polymorphisms, rs16909225, rs3834363, and rs16909220, were identified, of which rs16909225 and rs16909220 were completely linked (r² = 1) and not associated with the development of PCOS, while the -2-bp/-2-bp genotype of rs3834363 was significantly higher in PCOS than in the controls (χ² = 7.39, df = 1, P = 0.007, OR = 1.80 95% CI: 1.18-2.75). The present study is the first to establish an association between FABP4 gene polymorphisms and the development of PCOS.

ReadXplorer—visualization and analysis of mapped sequences

PubMed Central

Hilker, Rolf; Stadermann, Kai Bernd; Doppmeier, Daniel; Kalinowski, Jörn; Stoye, Jens; Straube, Jasmin; Winnebald, Jörn; Goesmann, Alexander

2014-01-01

Motivation: Fast algorithms and well-arranged visualizations are required for the comprehensive analysis of the ever-growing size of genomic and transcriptomic next-generation sequencing data. Results: ReadXplorer is a software offering straightforward visualization and extensive analysis functions for genomic and transcriptomic DNA sequences mapped on a reference. A unique specialty of ReadXplorer is the quality classification of the read mappings. It is incorporated in all analysis functions and displayed in ReadXplorer's various synchronized data viewers for (i) the reference sequence, its base coverage as (ii) normalizable plot and (iii) histogram, (iv) read alignments and (v) read pairs. ReadXplorer's analysis capability covers RNA secondary structure prediction, single nucleotide polymorphism and deletion–insertion polymorphism detection, genomic feature and general coverage analysis. Especially for RNA-Seq data, it offers differential gene expression analysis, transcription start site and operon detection as well as RPKM value and read count calculations. Furthermore, ReadXplorer can combine or superimpose coverage of different datasets. Availability and implementation: ReadXplorer is available as open-source software at http://www.readxplorer.org along with a detailed manual. Contact: rhilker@mikrobio.med.uni-giessen.de Supplementary information: Supplementary data are available at Bioinformatics online. PMID:24790157

Characterizing polymorphic inversions in human genomes by single-cell sequencing

PubMed Central

Sanders, Ashley D.; Hills, Mark; Porubský, David; Guryev, Victor; Falconer, Ester; Lansdorp, Peter M.

2016-01-01

Identifying genomic features that differ between individuals and cells can help uncover the functional variants that drive phenotypes and disease susceptibilities. For this, single-cell studies are paramount, as it becomes increasingly clear that the contribution of rare but functional cellular subpopulations is important for disease prognosis, management, and progression. Until now, studying these associations has been challenged by our inability to map structural rearrangements accurately and comprehensively. To overcome this, we coupled single-cell sequencing of DNA template strands (Strand-seq) with custom analysis software to rapidly discover, map, and genotype genomic rearrangements at high resolution. This allowed us to explore the distribution and frequency of inversions in a heterogeneous cell population, identify several polymorphic domains in complex regions of the genome, and locate rare alleles in the reference assembly. We then mapped the entire genomic complement of inversions within two unrelated individuals to characterize their distinct inversion profiles and built a nonredundant global reference of structural rearrangements in the human genome. The work described here provides a powerful new framework to study structural variation and genomic heterogeneity in single-cell samples, whether from individuals for population studies or tissue types for biomarker discovery. PMID:27472961

The modulator driven polymorphism of Zr(IV) based metal-organic frameworks

NASA Astrophysics Data System (ADS)

Drache, Franziska; Bon, Volodymyr; Senkovska, Irena; Getzschmann, Jürgen; Kaskel, Stefan

2017-01-01

The reaction of ZrCl4 and 2,5-thiophenedicarboxylic acid (H2tdc) in the presence of trifluoroacetic acid (Htfa) as modulator results in the formation of the new metal-organic framework (MOF) named DUT-126 (DUT = Dresden University of Technology). The nature and concentration of modulators are found to be decisive synthetic parameters affecting the topology of the formed product. DUT-126 (hbr) extends the series of polymorphs differing in topology, namely DUT-67 (reo), DUT-68 (bon) and DUT-69 (bct) to four, where DUT-67 and DUT-68 show the same eight-connected secondary building units as in DUT-126. In DUT-126, linker molecules have a peculiar orientation, resulting in hbr topology, which is described for the first time in this work for MOFs. DUT-126 contains three pore types, including two micropores surrounding mesoporous channels. DUT-126 is stable against hydrolysis and features permanent porosity with a specific surface area of 1297 m2 g-1 and a total pore volume of 0.48 cm3 g-1, calculated from the nitrogen physisorption isotherm measured at 77 K. This article is part of the themed issue 'Coordination polymers and metal-organic frameworks: materials by design'.

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

FIFS: A data mining method for informative marker selection in high dimensional population genomic data.

PubMed

Kavakiotis, Ioannis; Samaras, Patroklos; Triantafyllidis, Alexandros; Vlahavas, Ioannis

2017-11-01

Single Nucleotide Polymorphism (SNPs) are, nowadays, becoming the marker of choice for biological analyses involving a wide range of applications with great medical, biological, economic and environmental interest. Classification tasks i.e. the assignment of individuals to groups of origin based on their (multi-locus) genotypes, are performed in many fields such as forensic investigations, discrimination between wild and/or farmed populations and others. Τhese tasks, should be performed with a small number of loci, for computational as well as biological reasons. Thus, feature selection should precede classification tasks, especially for Single Nucleotide Polymorphism (SNP) datasets, where the number of features can amount to hundreds of thousands or millions. In this paper, we present a novel data mining approach, called FIFS - Frequent Item Feature Selection, based on the use of frequent items for selection of the most informative markers from population genomic data. It is a modular method, consisting of two main components. The first one identifies the most frequent and unique genotypes for each sampled population. The second one selects the most appropriate among them, in order to create the informative SNP subsets to be returned. The proposed method (FIFS) was tested on a real dataset, which comprised of a comprehensive coverage of pig breed types present in Britain. This dataset consisted of 446 individuals divided in 14 sub-populations, genotyped at 59,436 SNPs. Our method outperforms the state-of-the-art and baseline methods in every case. More specifically, our method surpassed the assignment accuracy threshold of 95% needing only half the number of SNPs selected by other methods (FIFS: 28 SNPs, Delta: 70 SNPs Pairwise FST: 70 SNPs, In: 100 SNPs.) CONCLUSION: Our approach successfully deals with the problem of informative marker selection in high dimensional genomic datasets. It offers better results compared to existing approaches and can aid biologists in selecting the most informative markers with maximum discrimination power for optimization of cost-effective panels with applications related to e.g. species identification, wildlife management, and forensics. Copyright © 2017 Elsevier Ltd. All rights reserved.

An enhanced chemoenzymatic method for loading substrates onto carrier protein domains.

PubMed

Kittilä, Tiia; Cryle, Max J

2018-06-01

Non-ribosomal peptide synthetase (NRPS) machineries produce many medically relevant peptides that cannot be easily accessed by chemical synthesis. Thus, understanding NRPS mechanism is of crucial importance to allow efficient redesign of these machineries to produce new compounds. During NRPS-mediated synthesis, substrates are covalently attached to peptidyl carrier proteins (PCPs), and studies of NRPSs are impeded by difficulties in producing PCPs loaded with substrates. Different approaches to load substrates onto PCP domains have been described, but all suffer from difficulties in either the complexity of chemical synthesis or low enzymatic efficiency. Here, we describe an enhanced chemoenzymatic loading method that combines 2 approaches into a single, highly efficient one-pot loading reaction. First, d-pantetheine and ATP are converted into dephospho-coenzyme A via the actions of 2 enzymes from coenzyme A (CoA) biosynthesis. Next, phosphoadenylates are dephosphorylated using alkaline phosphatase to allow linker attachment to PCP domain by Sfp mutant R4-4, which is inhibited by phosphoadenylates. This route does not depend on activity of the commonly problematic dephospho-CoA kinase and, therefore, offers an improved method for substrate loading onto PCP domains.

Evaluation of the Illumigene Malaria LAMP: A Robust Molecular Diagnostic Tool for Malaria Parasites

PubMed Central

Lucchi, Naomi W.; Gaye, Marie; Diallo, Mammadou Alpha; Goldman, Ira F.; Ljolje, Dragan; Deme, Awa Bineta; Badiane, Aida; Ndiaye, Yaye Die; Barnwell, John W.; Udhayakumar, Venkatachalam; Ndiaye, Daouda

2016-01-01

Isothermal nucleic acid amplification assays such as the loop mediated isothermal amplification (LAMP), are well suited for field use as they do not require thermal cyclers to amplify the DNA. To further facilitate the use of LAMP assays in remote settings, simpler sample preparation methods and lyophilized reagents are required. The performance of a commercial malaria LAMP assay (Illumigene Malaria LAMP) was evaluated using two sample preparation workflows (simple filtration prep (SFP)) and gravity-driven filtration prep (GFP)) and pre-dispensed lyophilized reagents. Laboratory and clinical samples were tested in a field laboratory in Senegal and the results independently confirmed in a reference laboratory in the U.S.A. The Illumigene Malaria LAMP assay was easily implemented in the clinical laboratory and gave similar results to a real-time PCR reference test with limits of detection of ≤2.0 parasites/μl depending on the sample preparation method used. This assay reliably detected Plasmodium sp. parasites in a simple low-tech format, providing a much needed alternative to the more complex molecular tests for malaria diagnosis. PMID:27827432

Lime enhanced chromium removal in advanced integrated wastewater pond system.

PubMed

Tadesse, I; Isoaho, S A; Green, F B; Puhakka, J A

2006-03-01

The removal of trivalent chromium from a combined tannery effluent in horizontal settling tanks and subsequent Advanced Integrated Wastewater Pond System (AIWPS) reactors was investigated. The raw combined effluent from Modjo tannery had pH in the range of 11.2-12. At this pH, a trivalent chromium removal of 46-72% was obtained in the horizontal settling tanks after a one-day detention time. Trivalent chromium precipitated as chromium hydroxide, Cr(OH)3. 58-95% Cr(III) was removed in the advanced facultative pond (AFP) where the water column pH of 7.2-8.4 was close to pH 8, which is the optimum precipitation pH for trivalent chromium. Chromium removals in the secondary facultative pond (SFP) and maturation pond (MP) were 30-50% and 6-16%, respectively. With Cr(III) concentration of 0.2-0.8 mg/l in the final treated effluent, the AIWPS preceded by horizontal settling tanks produced effluent that could easily meet most of the current Cr(III) discharge limits to receive water bodies.

Biomarker sensing using nanostructured metal oxide sensors

NASA Astrophysics Data System (ADS)

Kalyanasundaram, Krithika

Resistive Chemical sensors are those gas sensitive materials, typically semiconducting metal oxides, that change their electrical properties in response to a change in the ambient. The key features of a chemosensor are sensitivity, selectivity, response time and sensor stability. The hypothesis of this work is that, since metal oxides are polymorphic compounds, the crystal structure of the specific polymorph determines the relative gas selectivity of the material; also that the morphology of the sensing element determines the gas sensitivity limit. This work focuses on the synthesis of nanostructured metal oxides for chemosensors used in selective 'biomarker' detection. Biomarkers are chemical compounds, products of human metabolism which act as specific disease markers. The biomarkers studied in this work include NO, isoprene, NH3, ethanol and acetone which can all be found in exhaled human breath and which allow the non-invasive detection of a range of diseases. Sensors based on three different metal oxides-MoO3, WO 3, and TiO2 were fabricated using sol-gel, electrospinning and spray pyrolysis techniques and tested both as single elements and in an array configuration (electronic nose). The effects of the processing method used, grain size and shape and crystal phase of the material produced, and temperature effects of postsynthesis processing and sensing have been evaluated. Structural characterization has been carried out using X-Ray Diffraction, Scanning and High Resolution Transmission Electron Microscopy, while spectroscopic measurements using XPS, Raman and In-situ FTIR provide valuable information about the surface-analyte interactions. This work has shown that the use of monoclinic polymorph of WO3 yields a selective response to NO, while the other phase of the same oxide give a non-selective chemical response. The orthorhombic phase of MoO 3 exhibits specificity to NH3. An explanation for the variable sensing properties is given based on the gas interactions with the given polymorph involving adsorption/reaction processes. Another major finding of this work is that there was orders of magnitude increase in gas sensitivity when high aspect ratio nanowires as opposed to nanoparticles of the same diameter were used.

Influence of glutathione S-transferase polymorphisms (GSTT1, GSTM1, GSTP1) on type-2 diabetes mellitus (T2D) risk in an endogamous population from north India.

PubMed

Mastana, Sarabjit S; Kaur, Antarpreet; Hale, Rachel; Lindley, Martin R

2013-12-01

Glutathione S-transferases (GSTs) belong to a group of multigene and multifunctional detoxification enzymes, which defend cells against a wide variety of toxic insults and oxidative stress. Oxidative stress leads to cellular dysfunction which contributes to the pathophysiology of diseases such as cancer, atherosclerosis, and diabetes mellitus. It is important to assess whether the glutathione S-Transferase (GSTT1, GSTM1 and GSTP1) genotypes are associated with type 2 diabetes mellitus as deletion polymorphisms have an impaired capability to counteract the oxidative stress which is a feature of diabetes. GSTT1, GSTM1 and GSTP1 gene polymorphisms were analysed in 321 patients and 309 healthy controls from an endogamous population from north India. An association analysis was carried out at two levels (a) individual genes and (b) their double and triple combinations. The proportion of GSTT1 and GSTM1 null genotypes was higher in diabetics compared to controls (GSTT1 30.8 vs. 21.0 %; GSTM1 49.5 vs. 27.2 %). The frequency of the null genotype at both loci was higher in diabetics (19.6 vs. 7.8 %) leading to an odds ratio of 2.90 (CI 1.76-4.78, P < 0.0001). At GSTP1locus, patients had a higher frequency of the V/V genotype (15.6 vs. 7.5 %) and significant susceptible odds ratio (2.56, CI 1.47-4.48, P < 0.001). A combination of null genotypes at GSTT1 and GSTM1 loci and V/V genotype of GSTP1 locus showed highest odds ratio (9.64, CI 1.53-60.63, P < 0.01). Overall this study highlights that GST genes may play an important role in the pathogenesis of type 2 diabetes. The risk is higher in individuals carrying more than one susceptible genotype at these loci. The potential role of GST polymorphisms as markers of susceptibility to type 2 diabetes needs further investigations in a larger number of patients and populations.

Seasonal influenza A/H3N2 virus infection and IL-1Β, IL-10, IL-17, and IL-28 polymorphisms in Iranian population.

PubMed

Rogo, Lawal Dahiru; Rezaei, Farhad; Marashi, Seyed Mahdi; Yekaninejad, Mir Saeed; Naseri, Maryam; Ghavami, Nastaran; Mokhtari-Azad, Talat

2016-12-01

Increased blood cytokines is the main immunopathological process that were attributed to severe clinical outcomes in cases of influenza A/H3N2 virus infection. The study was aimed to investigate the polymorphisms of IL-1β, IL-10, IL-17, and IL-28 genes to find the possibility of their association with the clinical outcome of influenza A/H3N2 virus infection among the infected patients in Iran. This is a Case-Control study in which influenza A/H3N2 virus positive confirmed with real-time PCR were the cases. DNA samples from groups were genotyped for polymorphisms in rs16944 (IL-1β), rs1800872 (IL-10), rs2275913 (IL-17), and rs8099917 (IL-28). Confidence interval (95%CI) and Odds ratio (OR) were calculated. IL-17 rs2275913 (GG and AG) were associated with risk of infection with that were statistically significant (P < 0.05, OR = 2.08-2.94). IL-1β (rs16944) (GG) was associated with reduced risk of infection (P < 0.01, OR = 0.46). Genotype GG and GT of IL-10 (rs1800872) were associated with increased risk of infection with influenza A/H3N2 virus (P < 0.05, OR = 2.04-2.58). In addition, IL-28 (rs8099917) genotypes GG (P < 0.05, OR = 0.49) and TG (P < 0.05, OR = 0.59) were associated with reduced risk of ILI symptom while genotype TT (P < 0.01, OR = 4.31) was associated with increased risk of ILI symptom. The results of this study demonstrated that polymorphisms of genes involved in the inflammatory and anti-inflammatory process affect the outcome of disease caused by influenza A/H3N2 virus. Thorough insight on host immune response at the time of influenza A virus infection is required to ensure adequate patient care in the case of feature outbreaks. J. Med. Virol. 88:2078-2084, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Identification and Characterization of Microsatellite Markers Derived from the Whole Genome Analysis of Taenia solium

PubMed Central

Pajuelo, Mónica J.; Eguiluz, María; Dahlstrom, Eric; Requena, David; Guzmán, Frank; Ramirez, Manuel; Sheen, Patricia; Frace, Michael; Sammons, Scott; Cama, Vitaliano; Anzick, Sarah; Bruno, Dan; Mahanty, Siddhartha; Wilkins, Patricia; Nash, Theodore; Gonzalez, Armando; García, Héctor H.; Gilman, Robert H.; Porcella, Steve; Zimic, Mirko

2015-01-01

Background Infections with Taenia solium are the most common cause of adult acquired seizures worldwide, and are the leading cause of epilepsy in developing countries. A better understanding of the genetic diversity of T. solium will improve parasite diagnostics and transmission pathways in endemic areas thereby facilitating the design of future control measures and interventions. Microsatellite markers are useful genome features, which enable strain typing and identification in complex pathogen genomes. Here we describe microsatellite identification and characterization in T. solium, providing information that will assist in global efforts to control this important pathogen. Methods For genome sequencing, T. solium cysts and proglottids were collected from Huancayo and Puno in Peru, respectively. Using next generation sequencing (NGS) and de novo assembly, we assembled two draft genomes and one hybrid genome. Microsatellite sequences were identified and 36 of them were selected for further analysis. Twenty T. solium isolates were collected from Tumbes in the northern region, and twenty from Puno in the southern region of Peru. The size-polymorphism of the selected microsatellites was determined with multi-capillary electrophoresis. We analyzed the association between microsatellite polymorphism and the geographic origin of the samples. Results The predicted size of the hybrid (proglottid genome combined with cyst genome) T. solium genome was 111 MB with a GC content of 42.54%. A total of 7,979 contigs (>1,000 nt) were obtained. We identified 9,129 microsatellites in the Puno-proglottid genome and 9,936 in the Huancayo-cyst genome, with 5 or more repeats, ranging from mono- to hexa-nucleotide. Seven microsatellites were polymorphic and 29 were monomorphic within the analyzed isolates. T. solium tapeworms were classified into two genetic groups that correlated with the North/South geographic origin of the parasites. Conclusions/Significance The availability of draft genomes for T. solium represents a significant step towards the understanding the biology of the parasite. We report here a set of T. solium polymorphic microsatellite markers that appear promising for genetic epidemiology studies. PMID:26697878

Genetic variation of clock genes and cancer risk: a field synopsis and meta-analysis

PubMed Central

Benna, Clara; Helfrich-Förster, Charlotte; Rajendran, Senthilkumar; Monticelli, Halenya; Pilati, Pierluigi; Nitti, Donato; Mocellin, Simone

2017-01-01

BACKGROUND The number of studies on the association between clock genes’ polymorphisms and cancer susceptibility has increased over the last years but the results are often conflicting and no comprehensive overview and quantitative summary of the evidence in this field is available. RESULTS Literature search identified 27 eligible studies comprising 96756 subjects (cases: 38231) and investigating 687 polymorphisms involving 14 clock genes. Overall, 1025 primary and subgroup meta-analyses on 366 gene variants were performed. Study distribution by tumor was as follows: breast cancer (n=15), prostate cancer (n=3), pancreatic cancer (n=2), non-Hodgkin's lymphoma (n=2), glioma (n=1), chronic lymphocytic leukemia (n=1), colorectal cancer (n=1), non-small cell lung cancer (n=1) and ovarian cancer (n=1). We identified 10 single nucleotide polymorphisms (SNPs) significantly associated with cancer risk: NPAS2 rs10165970 (mixed and breast cancer shiftworkers), rs895520 (mixed), rs17024869 (breast) and rs7581886 (breast); CLOCK rs3749474 (breast) and rs11943456 (breast); RORA rs7164773 (breast and breast cancer postmenopausal), rs10519097 (breast); RORB rs7867494 (breast cancer postmenopausal), PER3 rs1012477 (breast cancer subgroups) and assessed the level of quality evidence to be intermediate. We also identified polymorphisms with lower quality statistically significant associations (n=30). CONCLUSIONS Our work supports the hypothesis that genetic variation of clock genes might affect cancer risk. These findings also highlight the need for more efforts in this research field in order to fully establish the contribution of clock gene variants to the risk of developing cancer. METHODS We conducted a systematic review and meta-analysis of the evidence on the association between clock genes’ germline variants and the risk of developing cancer. To assess result credibility, summary evidence was graded according to the Venice criteria and false positive report probability (FPRP) was calculated to further validate result noteworthiness. Subgroup meta-analysis was also performed based on participant features and tumor type. The breast cancer subgroup was further stratified by work conditions, estrogen receptor/progesterone receptor status and menopausal status, conditions associated with the risk of breast cancer in different studies. PMID:28177907

Genetic variation of clock genes and cancer risk: a field synopsis and meta-analysis.

PubMed

Benna, Clara; Helfrich-Förster, Charlotte; Rajendran, Senthilkumar; Monticelli, Halenya; Pilati, Pierluigi; Nitti, Donato; Mocellin, Simone

2017-04-04

The number of studies on the association between clock genes' polymorphisms and cancer susceptibility has increased over the last years but the results are often conflicting and no comprehensive overview and quantitative summary of the evidence in this field is available. Literature search identified 27 eligible studies comprising 96756 subjects (cases: 38231) and investigating 687 polymorphisms involving 14 clock genes. Overall, 1025 primary and subgroup meta-analyses on 366 gene variants were performed. Study distribution by tumor was as follows: breast cancer (n=15), prostate cancer (n=3), pancreatic cancer (n=2), non-Hodgkin's lymphoma (n=2), glioma (n=1), chronic lymphocytic leukemia (n=1), colorectal cancer (n=1), non-small cell lung cancer (n=1) and ovarian cancer (n=1).We identified 10 single nucleotide polymorphisms (SNPs) significantly associated with cancer risk: NPAS2 rs10165970 (mixed and breast cancer shiftworkers), rs895520 (mixed), rs17024869 (breast) and rs7581886 (breast); CLOCK rs3749474 (breast) and rs11943456 (breast); RORA rs7164773 (breast and breast cancer postmenopausal), rs10519097 (breast); RORB rs7867494 (breast cancer postmenopausal), PER3 rs1012477 (breast cancer subgroups) and assessed the level of quality evidence to be intermediate. We also identified polymorphisms with lower quality statistically significant associations (n=30). Our work supports the hypothesis that genetic variation of clock genes might affect cancer risk. These findings also highlight the need for more efforts in this research field in order to fully establish the contribution of clock gene variants to the risk of developing cancer. We conducted a systematic review and meta-analysis of the evidence on the association between clock genes' germline variants and the risk of developing cancer. To assess result credibility, summary evidence was graded according to the Venice criteria and false positive report probability (FPRP) was calculated to further validate result noteworthiness. Subgroup meta-analysis was also performed based on participant features and tumor type. The breast cancer subgroup was further stratified by work conditions, estrogen receptor/progesterone receptor status and menopausal status, conditions associated with the risk of breast cancer in different studies.