Parental Socio-Economic Status as Correlate of Child Labour in Ile-Ife, Nigeria

ERIC Educational Resources Information Center

Elegbeleye, O. S.; Olasupo, M. O.

2012-01-01

This study investigated the relationship between parental socio-economic status and child labour practices in Ile-Ife, Nigeria. The study employed survey method to gather data from 200 parents which constituted the study population. Pearson Product Moment Correlation and t-test statistics were used for the data analyses. The outcome of the study…

The Prevalence and Pattern of Superficial Fungal Infections among School Children in Ile-Ife, South-Western Nigeria

PubMed Central

Oke, Olaide Olutoyin; Onayemi, Olaniyi; Olasode, Olayinka Abimbola; Omisore, Akinlolu Gabriel; Oninla, Olumayowa Abimbola

2014-01-01

Fungal infections of the skin and nails are common global problems with attendant morbidity among affected individuals. Children are mostly affected due to predisposing factors such as overcrowding and low socioeconomic factors. The aim of this study was to determine the prevalence and the clinical patterns of superficial fungal infections among primary school children in Ile-Ife. A multistage sampling was conducted to select eight hundred pupils from ten primary schools in Ile-Ife. Data on epidemiological characteristics and clinical history was collected using a semistructured questionnaire and skin scrapings were done. The prevalence of superficial fungal infections among the 800 respondents was 35.0%. Male pupils constituted 51.0% of respondents while the females were 49.0%. The mean age for all the respondents was 9.42 ± 2.00. Tinea capitis was the commonest infection with a prevalence of 26.9% and tinea unguium, tinea corporis, and tinea faciei had a prevalence of 0.8%, 0.6%, and 0.5%, respectively. Tinea manuum had the least prevalence of 0.1%. Pityriasis versicolor had a prevalence of 4.4%. Microsporum audouinii was the leading organism isolated. The study shows that the prevalence of superficial fungal infection (SFI) among primary school children in Ile-Ife is high with tinea capitis as the commonest SFI. PMID:25574161

Effect of the melanocortin-3 receptor Thr6Lys and Val81Ile genetic variants on body composition and substrate oxidation in Chilean obese children.

PubMed

Obregón, Ana M; Diaz, Erik; Santos, Jose L

2012-03-01

Mice genetically deficient in the melanocortin-3 receptor gene are characterized by normal body weight, increased body fat, mild hypophagia, reduced locomotor activity, and increased respiratory quotient compared with wild-type mice. In humans, the 6Lys-81Ile haplotype of melanocortin-3 receptor (MC3R) gene has been associated with childhood obesity, higher body fat percentage, and reduced fat oxidation compared to non-carriers. The aim of this study was to evaluate the association between MC3R 6Lys-81Ile haplotype with body composition and substrate oxidation in response to moderate exercise in obese children. Eight Chilean obese children (aged 8-12) carriers of MC3R 6Lys-81Ile haplotype were compared with eight age-gender-matched obese non-carriers. Children were identified through a previous cross-sectional study on genetic determinants of childhood obesity (n = 229). Genotypes for MC3R Thr6Lys and Val81Ile were determined by polymerase chain reaction-restriction fragment length polymorphism. Body composition was assessed by the four-compartment model (dual-energy X-ray absorptiometry, total body water by the deuterium dilution technique, and total fat mass by air-displacement plethysmography). Substrate oxidation was assessed by indirect calorimetry in response to moderate exercise (60% VO(2 max)). Wilcoxon matched-pairs test was used to compare quantitative variables. No significant differences among carriers and non-carriers were found in anthropometrical and body composition measurements. The Carriers of the 6Lys-81Ile haplotype showed higher respiratory quotient (p = 0.06) and a significantly higher glucose oxidation (p = 0.01) compared with non-carriers after standardization for fat-free mass. Our results are consistent with a possible participation of MC3R 6Lys-81Ile variants in glucose oxidation in response to moderate exercise.

Home-to-work trips during the transportation strikes in Ile-de-France at the end of 1995

DOT National Transportation Integrated Search

1998-10-01

In November and December 1995, the region of Ile-de- France experienced strikes resulting in a virtually complete interruption of public transport. During this period, a majority of economic activity continued. The Direction Rigionale de Iquipement (...

Identification of a Novel GLA Gene Mutation, p.Ile239Met, in Fabry Disease With a Predominant Cardiac Phenotype.

PubMed

Csányi, Beáta; Hategan, Lidia; Nagy, Viktória; Obál, Izabella; Varga, Edina T; Borbás, János; Tringer, Annamária; Eichler, Sabrina; Forster, Tamás; Rolfs, Arndt; Sepp, Róbert

2017-05-31

Fabry disease (FD) is an X-linked inherited lysosomal storage disorder caused by mutations in the GLA gene, encoding for the enzyme α-galactosidase A. Although hundreds of mutations in the GLA gene have been described, many of them are variants of unknown significance. Here we report a novel GLA mutation, p.Ile239Met, identified in a large Hungarian three-generation family with FD. A 69 year-old female index patient with a clinical history of renal failure, hypertrophic cardiomyopathy, and 2nd degree AV block was screened for mutation in the GLA gene. Genetic screening identified a previously unreported heterozygous mutation in exon 5 of the GLA gene (c.717A>G; p.Ile239Met). Family screening indicated that altogether 6 family members carried the mutation (5 females, 1 male, average age: 55 ± 16 years). Three family members, including the index patient, manifested the cardiac phenotype of hypertrophic cardiomyopathy, while two other family members were diagnosed with left ventricular hypertrophy. Taking affection status as the presence of hypertrophic cardiomyopathy, left ventricular hypertrophy or elevated lyso-Gb3 levels, all affected family members carried the mutation. Linkage analysis of the family gave a two-point LOD score of 2.01 between the affection status and the p.Ile239Met GLA mutation. Lyso-Gb3 levels were elevated in all carrier family members (range: 2.4-13.8 ng/mL; upper limit of normal +2STD: ≤ 1.8 ng/mL). The GLA enzyme level was markedly reduced in the affected male family member (< 0.2 µmol/L/hour; upper limit of normal ± 2STD: ≥ 2.6 µmol/L/hour). We conclude that the p. Ile239Met GLA mutation is a pathogenic mutation for FD associated with predominant cardiac phenotype.

Physical fitness levels of adolescents in the Ile de France region: comparisons with European standards and relevance for future cardiovascular risk.

PubMed

Vanhelst, Jérémy; Fardy, Paul S; Chapelot, Didier; Czaplicki, Grégory; Ulmer, Zekya

2016-11-01

The aim was to assess physical fitness in French schoolchildren in the region of Ile de France and to compare the results with European countries. The relationship between physical fitness and future health profile was of particular interest. Participants were 1851 French youth in the Ile de France region. Cardiorespiratory fitness, muscular endurance, speed, flexibility and speed agility were tested. Independent t-tests were used to compare differences between different variables. Spearman's rho correlation coefficients assessed the relationship between body mass index, socio-economic status and physical fitness. Boys were physically fitter than girls with the most significant difference being in agility. Subjects of normal weight have significantly better results than overweight or obese adolescents (+10·9% to 56·1%) (P<0·05). Subjects with high socio-economic status had better physical fitness than those with low socio-economic status (+0·5% to 9·4%) (P<0·05). Results also showed that the percentage of adolescents at increased future cardiovascular risk was 15·3% and 10·2% for boys and girls, respectively. Physical fitness in French schoolchildren living in the region of Ile de France is relatively low and unfavourable, especially in girls, when compared with existing European test results. In contrast, the adolescent boys are generally fitter and also above the average of the European data. Introducing a health promotion curriculum in the schools of Ile de France is suggested to improve health and physical fitness. © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

No evidence for a role of Ile587Val polymorphism of EIF2B5 gene in multiple sclerosis in Kashmir Valley of India.

PubMed

Zahoor, Insha; Asimi, Ravouf; Haq, Ehtishamul

2015-12-15

Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the nervous system with a profound genetic element. It is already known that alterations in Eukaryotic Translation Initiation Factor 2B (EIF2B) gene encoding the five subunits of eIF2B complex cause Vanishing White Matter (VWM) disease of the brain and emerging evidences have advocated certain resemblances between MS and VWM in terms of clinical and epidemiological characteristics, thus validating the association study between EIF2B and MS. Moreover, a recent study has implicated EIF2B5 Ile587Val (rs843358) polymorphism as a susceptibility factor for MS. In order to investigate the association of EIF2B5 Ile587Val polymorphism with MS susceptibility in Kashmir region in India, we screened EIF2B5 Exon 13 in 30 MS patients and 65 controls (a total of 95 participants). During the present course of study, we could not find statistically significant difference in the frequency of Ile587Val between MS patients and controls, thus indicating that such alteration does not appear to influence MS development in Kashmiri population. Our results provide evidence against a major role for Ile587Val polymorphism in MS susceptibility. Copyright © 2015 Elsevier B.V. All rights reserved.

Glutathione S-transferase P1 Ile105Val Polymorphism and Male Infertility Risk: An Updated Meta-analysis

PubMed Central

Huang, Xue-Kun; Huang, Yong-Han; Huang, Juan-Hua; Liang, Jing-Yao

2017-01-01

Background: Several studies concerning the association between glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism and male infertility risk have reported controversial findings. The present study was aimed to explore this association using a meta-analysis. Methods: The PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the association. Results: A total of 3282 cases and 3268 controls in nine case-control studies were included. There was no significant association between GSTP1 Ile105Val polymorphism and male infertility in the overall population, but significant associations were found under the dominant (OR = 1.23, 95% CI = 1.04–1.46, I2 = 32.2%) and heterozygote (OR = 1.29, 95% CI = 1.08–1.53, I2 = 26.8%) models after excluding studies for which the data did not satisfy Hardy-Weinberg equilibrium (HWE). Similarly, subgroup analyses revealed no significant association in Asians or Chinese population although a significant association was apparent among Chinese population in studies with HWE under the heterozygote model (OR = 1.25, 95% CI = 1.03–1.52, I2 = 44.1%). Significant heterogeneity could be observed in some genetic models, but this heterogeneity was not significant when stratified by HWE. No evidence for publication bias was found. Conclusions: The GSTP1 Ile105Val polymorphism might not be associated with male infertility risk, and thus additional well-designed studies with larger sample size are warranted. PMID:28397729

Association of Helicobacter pylori infection with Toll-like receptor-4 Thr399Ile polymorphism increased the risk of peptic ulcer development in North of Iran.

PubMed

Tourani, Mehdi; Habibzadeh, Maryam; Shokri-Shirvani, Javad; Teymournejad, Omid; Mostafazadeh, Amrollah; Khafri, Soraya; Nouri, Hamid Reza

2018-01-01

Toll-like receptor-4 (TLR4) polymorphisms may influence host immune response against Helicobacter pylori (H. pylori). This study aimed to investigate whether TLR4 polymorphisms are associated with H. pylori susceptibility and risk of peptic ulcer development or not. The TLR4 + 3725 G/C polymorphism was studied using polymerase chain reaction with confronting two-pair primers (PCR-CTPP). In addition, TLR4 Asp299Gly and Thr399Ile polymorphisms were evaluated by PCR-restriction fragment length polymorphism (RFLP). There was no significant difference in TLR4 + 3725 G/C and Asp299Gly genotype frequencies between non-peptic ulcer (NPUD) and peptic ulcer (PUD) individuals in the context of peptic ulcer development and susceptibility to infection with H. pylori. Nevertheless, a significant association with increased risk for PUD development was observed for polymorphism TLR4 Thr399Ile [odds ratio (OR) = 4.2; 95% confidence interval (CI) = 1.35-13.26; p = 0.01]. Correspondingly, TLR4 Thr399Ile polymorphism was associated with H. pylori susceptibility (OR = 0.27; 95% CI = 0.08-0.88; p = 0.04). In addition, TLR4 Thr399Ile polymorphism increased 4.2-fold, the risk of peptic ulcer development in individuals infected by H. pylori carrying CT + TT genotype. Our results showed that TLR4 Thr399Ile polymorphism along with H. pylori infection may play critical roles in peptic ulcer development in North of Iran. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Effect of herbicide resistance endowing Ile-1781-Leu and Asp-2078-Gly ACCase gene mutations on ACCase kinetics and growth traits in Lolium rigidum

PubMed Central

Vila-Aiub, Martin M.; Yu, Qin; Han, Heping; Powles, Stephen B.

2015-01-01

The rate of herbicide resistance evolution in plants depends on fitness traits endowed by alleles in both the presence and absence (resistance cost) of herbicide selection. The effect of two Lolium rigidum spontaneous homozygous target-site resistance-endowing mutations (Ile-1781-Leu, Asp-2078-Gly) on both ACCase activity and various plant growth traits have been investigated here. Relative growth rate (RGR) and components (net assimilation rate, leaf area ratio), resource allocation to different organs, and growth responses in competition with a wheat crop were assessed. Unlike plants carrying the Ile-1781-Leu resistance mutation, plants homozygous for the Asp-2078-Gly mutation exhibited a significantly lower RGR (30%), which translated into lower allocation of biomass to roots, shoots, and leaves, and poor responses to plant competition. Both the negligible and significant growth reductions associated, respectively, with the Ile-1781-Leu and Asp-2078-Gly resistance mutations correlated with their impact on ACCase activity. Whereas the Ile-1781-Leu mutation showed no pleiotropic effects on ACCase kinetics, the Asp-2078-Gly mutation led to a significant reduction in ACCase activity. The impaired growth traits are discussed in the context of resistance costs and the effects of each resistance allele on ACCase activity. Similar effects of these two particular ACCase mutations on the ACCase activity of Alopecurus myosuroides were also confirmed. PMID:26019257

DNA polymerase β variant Ile260Met generates global gene expression changes related to cellular transformation

PubMed Central

Sweasy, Joann B.

2012-01-01

Maintenance of genomic stability is essential for cellular survival. The base excision repair (BER) pathway is critical for resolution of abasic sites and damaged bases, estimated to occur 20,000 times in cells daily. DNA polymerase β (Pol β) participates in BER by filling DNA gaps that result from excision of damaged bases. Approximately 30% of human tumours express Pol β variants, many of which have altered fidelity and activity in vitro and when expressed, induce cellular transformation. The prostate tumour variant Ile260Met transforms cells and is a sequence-context-dependent mutator. To test the hypothesis that mutations induced in vivo by Ile260Met lead to cellular transformation, we characterized the genome-wide expression profile of a clone expressing Ile260Met as compared with its non-induced counterpart. Using a 1.5-fold minimum cut-off with a false discovery rate (FDR) of <0.05, 912 genes exhibit altered expression. Microarray results were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and revealed unique expression profiles in other clones. Gene Ontology (GO) clusters were analyzed using Ingenuity Pathways Analysis to identify altered gene networks and associated nodes. We determined three nodes of interest that exhibited dysfunctional regulation of downstream gene products without themselves having altered expression. One node, peroxisome proliferator-activated protein γ (PPARG), was sequenced and found to contain a coding region mutation in PPARG2 only in transformed cells. Further analysis suggests that this mutation leads to dominant negative activity of PPARG2. PPARG is a transcription factor implicated to have tumour suppressor function. This suggests that the PPARG2 mutant may have played a role in driving cellular transformation. We conclude that PPARG induces cellular transformation by a mutational mechanism. PMID:22914675

Effect of herbicide resistance endowing Ile-1781-Leu and Asp-2078-Gly ACCase gene mutations on ACCase kinetics and growth traits in Lolium rigidum.

PubMed

Vila-Aiub, Martin M; Yu, Qin; Han, Heping; Powles, Stephen B

2015-08-01

The rate of herbicide resistance evolution in plants depends on fitness traits endowed by alleles in both the presence and absence (resistance cost) of herbicide selection. The effect of two Lolium rigidum spontaneous homozygous target-site resistance-endowing mutations (Ile-1781-Leu, Asp-2078-Gly) on both ACCase activity and various plant growth traits have been investigated here. Relative growth rate (RGR) and components (net assimilation rate, leaf area ratio), resource allocation to different organs, and growth responses in competition with a wheat crop were assessed. Unlike plants carrying the Ile-1781-Leu resistance mutation, plants homozygous for the Asp-2078-Gly mutation exhibited a significantly lower RGR (30%), which translated into lower allocation of biomass to roots, shoots, and leaves, and poor responses to plant competition. Both the negligible and significant growth reductions associated, respectively, with the Ile-1781-Leu and Asp-2078-Gly resistance mutations correlated with their impact on ACCase activity. Whereas the Ile-1781-Leu mutation showed no pleiotropic effects on ACCase kinetics, the Asp-2078-Gly mutation led to a significant reduction in ACCase activity. The impaired growth traits are discussed in the context of resistance costs and the effects of each resistance allele on ACCase activity. Similar effects of these two particular ACCase mutations on the ACCase activity of Alopecurus myosuroides were also confirmed. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Hematopoietic prostaglandin D synthase (HPGDS): a high stability, Val187Ile isoenzyme common among African Americans and its relationship to risk for colorectal cancer

PubMed Central

Tippin, Brigette L.; Levine, A. Joan; Materi, Alicia M.; Song, Wen-Liang; Keku, Temitope O.; Goodman, Julie E.; Sansbury, Leah B.; Das, Sudipto; Dai, Aihua; Kwong, Alan M.; Lin, Amy M.; Lin, John M.; Park, Jae Man; Patterson, Ruth E.; Chlebowski, Rowan T.; Garavito, R. Michael; Inoue, Tsuyoshi; Cho, Wonhwa; Lawson, John A.; Kapoor, Shiv; Kolonel, Laurence N.; Marchand, Loïc Le; Haile, Robert W.; Sandler, Robert S.; Lin, Henry J.

2011-01-01

Intestinal tumors in ApcMin/+ mice are suppressed by over-production of HPGDS, which is a glutathione transferase that forms prostaglandin D2 (PGD2). We characterized naturally occurring HPGDS isoenzymes, to see if HPGDS variation is associated with human colorectal cancer risk. We used DNA heteroduplex analysis and sequencing to identify HPGDS variants among healthy individuals. HPGDS isoenzymes were produced in bacteria, and their catalytic activities were tested. To determine in vivo effects, we conducted pooled case-control analyses to assess whether there is an association of the isoenzyme with colorectal cancer. Roughly 8% of African Americans and 2% of Caucasians had a highly stable Val187lle isoenzyme (with isoleucine instead of valine at position 187). At 37 °C, the wild-type enzyme lost 15% of its activity in one hour, whereas the Val187Ile form remained >95% active. At 50 °C, the half life of native HPGDS was 9 minutes, compared to 42 minutes for Val187Ile. The odds ratio for colorectal cancer among African Americans with Val187Ile was 1.10 (95% CI, 0.75–1.62; 533 cases, 795 controls). Thus, the Val187Ile HPGDS isoenzyme common among African Americans is not associated with colorectal cancer risk. Other approaches will be needed to establish a role for HPGDS in occurrence of human intestinal tumors, as indicated by a mouse model. PMID:21821144

Organochlorine pesticide residues in dried cocoa beans obtained from cocoa stores at Ondo and Ile-Ife, Southwestern Nigeria.

PubMed

Oyekunle, J A O; Akindolani, O A; Sosan, M B; Adekunle, A S

2017-01-01

Levels of organochlorine pesticides (OCPs) were determined in dried cocoa beans obtained from cocoa produce stores at Ondo and Ile-Ife, Southwestern Nigeria. Cocoa beans samples were sun dried to a constant weight, pulverized and soxhlet extracted with dichloromethane to obtain the OCPs. Qualitative identification and quantitative evaluation of the extracted OCPs after clean-up on silica gel were accomplished with the aid of a Gas Chromatography coupled with an Electron Capture Detector (GC-ECD). Levels of OCPs in cocoa beans from Ondo had a mean range of ND (p, p'-DDE) to 82.17 ± 54.53 ng/g (p, p'-DDT) were higher than the OCPs levels in cocoa beans from Ile-Ife with a mean range of 0.37 ± 0.63 ng/g (Endrin) to 57.76 ± 81.48 ng/g (p, p'-DDT). The higher levels of OCPs detected in the cocoa beans from Ondo could be an indication of higher volume of OCPs application by cocoa farmers in Ondo and its environs since cocoa plantations were more concentrated than Ile-Ife environs. Levels of OCPs determined in the cocoa beans were within the Maximum Residue Limit (MRLs) for OCPs set by the World Health Organization/Food and Agricultural Organization. The study established the presence of OCPs in an important crop of Nigeria. Hence, there is the need to keep monitoring ecotoxicological chemical substances in agricultural food products of Nigeria so as to take steps that ensure health safety of end users.

Improving Science, Technology and Mathematics Education in Nigeria: A Case Study of Obafemi Awolowo University, Ile-Ife

ERIC Educational Resources Information Center

Alaba, Sofowora Olaniyi; Adekomi, Bimbo

2012-01-01

The study assessed the impact of a World Bank Assisted Project "STEP-B" on teaching and learning of Science, Technology and Mathematics Education (STM) in Nigeria. It also described the contribution of Obafemi Awolowo University, Ile-Ife to the improvement of STM through research development, utilization of ICT, human resources and…

Association between glutathione S-transferase P1 Ile (105) Val gene polymorphism and chronic obstructive pulmonary disease: A meta-analysis based on seventeen case-control studies.

PubMed

Yang, Lingjing; Li, Xixia; Tong, Xiang; Fan, Hong

2015-12-01

Previous studies have shown that glutathione S-transferase P1 (GSTP1) was associated with chronic obstructive pulmonary disease (COPD). However, the association between GSTP1 Ile (105) Val gene polymorphism and COPD remains controversial. To drive a more precise estimation, we performed a meta-analysis based on published case-control studies. An electronic search of PubMed, EMBASE, Cochrane library, Web of Science and China Knowledge Resource Integrated (CNKI) Database for papers on GSTP1 Ile (105) Val gene polymorphism and COPD risk was performed. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the homozygote model, heterozygote model, dominant model, recessive model and an additive mode. Statistical heterogeneity, test of publication bias and sensitivity analysis was performed. The software STATA (Version 13.0) was used data analysis. Overall, seventeen studies with 1892 cases and 2012 controls were included in this meta-analysis. The GSTP1 Ile (105) Val polymorphism showed pooled odds ratios for the homozygote comparison (OR = 1.501, 95%CI [0.862, 2.614]), heterozygote comparison (OR = 0.924, 95%CI [0.733, 1.165]), dominant model (OR = 1.003, 95%CI [0.756, 1.331]), recessive model (OR = 1.510, 95%CI [0.934, 2.439]), and an additive model (OR = 1.072, 95%CI [0.822, 1.398]). In conclusion, the current meta-analysis, based on the most updated information, showed no significant association between GSTP1 Ile (105) Val gene polymorphism and COPD risk in any genetic models. The results of subgroup analysis also showed no significant association between GSTP1 Ile (105) Val gene polymorphism and COPD risk in Asian population and Caucasian population. Further studies involving large populations and careful control with age, sex, ethnicity, and cigarette smoking are greatly needed.

Association between glutathione S-transferase P1 Ile (105) Val gene polymorphism and chronic obstructive pulmonary disease: A meta-analysis based on seventeen case–control studies

PubMed Central

Yang, Lingjing; Li, Xixia; Tong, Xiang; Fan, Hong

2015-01-01

Introduction Previous studies have shown that glutathione S-transferase P1 (GSTP1) was associated with chronic obstructive pulmonary disease (COPD). However, the association between GSTP1 Ile (105) Val gene polymorphism and COPD remains controversial. To drive a more precise estimation, we performed a meta-analysis based on published case–control studies. Methods An electronic search of PubMed, EMBASE, Cochrane library, Web of Science and China Knowledge Resource Integrated (CNKI) Database for papers on GSTP1 Ile (105) Val gene polymorphism and COPD risk was performed. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the homozygote model, heterozygote model, dominant model, recessive model and an additive mode. Statistical heterogeneity, test of publication bias and sensitivity analysis was performed. The software STATA (Version 13.0) was used data analysis. Results Overall, seventeen studies with 1892 cases and 2012 controls were included in this meta-analysis. The GSTP1 Ile (105) Val polymorphism showed pooled odds ratios for the homozygote comparison (OR = 1.501, 95%CI [0.862, 2.614]), heterozygote comparison (OR = 0.924, 95%CI [0.733, 1.165]), dominant model (OR = 1.003, 95%CI [0.756, 1.331]), recessive model (OR = 1.510, 95%CI [0.934, 2.439]), and an additive model (OR = 1.072, 95%CI [0.822, 1.398]). Conclusions In conclusion, the current meta-analysis, based on the most updated information, showed no significant association between GSTP1 Ile (105) Val gene polymorphism and COPD risk in any genetic models. The results of subgroup analysis also showed no significant association between GSTP1 Ile (105) Val gene polymorphism and COPD risk in Asian population and Caucasian population. Further studies involving large populations and careful control with age, sex, ethnicity, and cigarette smoking are greatly needed. PMID:26504746

Mass Spectrometric Assignment of Leu/Ile in Neuropeptides From Single Neurohemal Organ Preparations of Insets

DTIC Science & Technology

2005-01-01

spectrometry has been applied for the first time on an insect/arthropod target, focusing on PVK/CAP2b neuropeptides in the housefly Musca domestica and...critical physiological processes in insects. The unnatural Ile analog is 4.5 times more active than the native Leu sequence in a housefly Malpighian...periviscerokinin/cardioacceleratory peptide 2b) neuropeptides from single neurohemal organ preparations of adults of the housefly Musca domestica and flesh fly

Trophic relationships between metazooplankton communities and their plankton food sources in the Iles Eparses (Western Indian Ocean).

PubMed

Dupuy, Christine; Pagano, Marc; Got, Patrice; Domaizon, Isabelle; Chappuis, Alexis; Marchessaux, Guillaume; Bouvy, Marc

2016-05-01

Coral reef and atoll lagoons are among the most diversified marine ecosystems but also the most affected by the combined effects of climate change and human activities. The Iles Eparses (Scattered Islands) in the Western Indian Ocean have been little affected by human pressure and can be considered to be "pristine" ecosystems. Metazooplankton plays a major role in the functioning and productivity of aquatic ecosystems, and this study was undertaken: (i) to determine the spatial abundance, distribution and species composition of metazooplankton, (ii) to assess the effect of metazooplankton grazing on pico- and nanophytoplankton and (iii) to analyze the trophic positions of metazooplankton by using the stable isotope signatures of a wide variety of taxa and particulate organic matter from the Iles Eparses and Mayotte. Tromelin Island (which is not located in the Mozambique Channel) had the lowest metazooplankton abundance with no cyanobacteria Trichodesmium spp. or mollusks (pteropods) presence, and with δ(15)N signatures of organisms that were higher than for the islands in the Mozambique Channel. Trichodesmium spp. was found in the Mozambique Channel and the plankton food web was probably based preferentially on these cyanobacteria with lower δ(15)N signatures indicating direct or indirect trophic transfer of diazotrophic nitrogen to metazooplankton. Three of the islands were distinct: Europa had the highest proportion of copepods, with oithonids being dominant, which is typical of rich mangrove systems, while Juan de Nova and Mayotte seemed to be the sites most affected by human activity with a high abundance of appendicularians and distinct particulate organic matter ∂(13)C signatures. Grazing experiments showed that food could be a limiting factor for metazooplankton in the Iles Eparses. However, the effect of metazooplankton grazing on phytoplankton appeared to be very low (0.01-2.32% of the total phytoplankton per day). Copyright © 2016 Elsevier Ltd. All

Impact of intimate partner violence on anxiety and depression amongst women in Ile-Ife, Nigeria.

PubMed

Mapayi, Boladale; Makanjuola, R O A; Mosaku, S K; Adewuya, O A; Afolabi, O; Aloba, O O; Akinsulore, A

2013-02-01

Research into intimate partner violence in the Nigerian environment has been limited. The objective of this study was to determine, amongst a sample of women attending the Enuwa Primary Health Care Center, Ile-Ife, the association between intimate partner violence and anxiety/depression. A descriptive cross-sectional study was conducted amongst 373 women who attended the antenatal clinic and welfare units of a primary health centre in Ile-Ife using the Composite Abuse Scale, the Hospital Anxiety and Depression Scale and a socio-demographic scale as instruments. Slightly over a third (36.7 %) reported intimate partner violence within the past year, 5.6 % had anxiety and 15.5 % were depressed. Anxiety and depression in the respondents were significantly associated with intimate partner violence. Women were ten times more likely to report being depressed and 17 times more likely to report anxiety if they were in violent relationships. This research has shown that the magnitude of intimate partner violence within the study population is comparable to those found in the developing countries. There are significant associations between intimate partner violence, anxiety and depression amongst the study population and this fact undoubtedly has implications for the mental health of the Nigerian woman.

Spiritual Content of Yoruba Concept of Sexuality and Sustenance of Family Values through Eko-Ile (Home Training)

ERIC Educational Resources Information Center

Olaniyan, Gabriel O.

2016-01-01

This paper examined the spiritual content of the Yoruba concept of sexuality and the implications it has for the sustenance of family values by use of "eko ile" (home training) which parents are expected to provide for their children as they prepare them for good citizenship. It is observed that most complaints about bad behaviours of…

Molecular dynamics simulations show how the FMRP Ile304Asn mutation destabilizes the KH2 domain structure and affects its function.

PubMed

Di Marino, Daniele; Achsel, Tilmann; Lacoux, Caroline; Falconi, Mattia; Bagni, Claudia

2014-01-01

Mutations or deletions of FMRP, involved in the regulation of mRNA metabolism in brain, lead to the Fragile X syndrome (FXS), the most frequent form of inherited intellectual disability. A severe manifestation of the disease has been associated with the Ile304Asn mutation, located on the KH2 domain of the protein. Several hypotheses have been proposed to explain the possible molecular mechanism responsible for the drastic effect of this mutation in humans. Here, we performed a molecular dynamics simulation and show that the Ile304Asn mutation destabilizes the hydrophobic core producing a partial unfolding of two α-helices and a displacement of a third one. The affected regions show increased residue flexibility and motion. Molecular docking analysis revealed strongly reduced binding to a model single-stranded nucleic acid in agreement with known data that the two partially unfolded helices form the RNA-binding surface. The third helix, which we show here to be also affected, is involved in the PAK1 protein interaction. These two functional binding sites on the KH2 domain do not overlap spatially, and therefore, they can simultaneously bind their targets. Since the Ile304Asn mutation affects both binding sites, this may justify the severe clinical manifestation observed in the patient in which both mRNA metabolism activity and cytoskeleton remodeling would be affected.

A new interpretation of the structure of the Sept Iles Intrusive suite, Canada

NASA Astrophysics Data System (ADS)

Higgins, Michael D.

2005-08-01

The layered mafic intrusion at Sept Iles, Canada, is one of the largest intrusions in the world. A new interpretation of its structure is proposed, based on a review of its geology and a comparison with the Skaergaard intrusion, Greenland. Several different magmatic components are recognized; hence the name Sept Iles Intrusive suite (SIIS) is proposed. Emplacement of the suite may have been preceded by eruption of flood basalts. The first magmas of the suite rose in the crust to accumulate beneath the density filter afforded by the basalts. The largest component is the Sept Iles Mafic intrusion (SIMI). The Lower series of the SIMI is dominated by leucotroctolites and leucogabbros. Above it lie the Layered series, which is largely comprised of gabbro and troctolite. Both these units are unchanged from earlier interpretations. The anorthosites (s.l.), gabbros and monzogabbros, formerly called the Transitional series, are now considered to be the Upper Border series, developed by floatation of plagioclase. Common autoliths in the Layered series are parts of the hydrothermally altered Upper Border series from towards the interior of the intrusion, which have foundered and settled through the magma. The contamination of the magma that accompanied this event oxidised iron in the magma and led to the precipitation of magnetite around the periphery of the intrusion. The subsequent depletion of Fe 3+ and/or increase in SiO 2, CaO and P 2O 5 may have induced apatite saturation and accumulation to form two layers rich in apatite, near the base and at top of the Layered series. Granitic magma was developed by fractional crystallisation and was emplaced along the roof of the chamber, where it acquired large quantities of xenoliths. These were probably derived from the flood basalts, their evolved members and fragments of mafic dykes chilled by the granitic magma. Accumulations of monzonite pillows in this unit testify to another magmatic event and a floor to the granitic magma

The beta-arrestin pathway-selective type 1A angiotensin receptor (AT1A) agonist [Sar1,Ile4,Ile8]angiotensin II regulates a robust G protein-independent signaling network.

PubMed

Kendall, Ryan T; Strungs, Erik G; Rachidi, Saleh M; Lee, Mi-Hye; El-Shewy, Hesham M; Luttrell, Deirdre K; Janech, Michael G; Luttrell, Louis M

2011-06-03

The angiotensin II peptide analog [Sar(1),Ile(4),Ile(8)]AngII (SII) is a biased AT(1A) receptor agonist that stimulates receptor phosphorylation, β-arrestin recruitment, receptor internalization, and β-arrestin-dependent ERK1/2 activation without activating heterotrimeric G-proteins. To determine the scope of G-protein-independent AT(1A) receptor signaling, we performed a gel-based phosphoproteomic analysis of AngII and SII-induced signaling in HEK cells stably expressing AT(1A) receptors. A total of 34 differentially phosphorylated proteins were detected, of which 16 were unique to SII and eight to AngII stimulation. MALDI-TOF/TOF mass fingerprinting was employed to identify 24 SII-sensitive phosphoprotein spots, of which three (two peptide inhibitors of protein phosphatase 2A (I1PP2A and I2PP2A) and prostaglandin E synthase 3 (PGES3)) were selected for validation and further study. We found that phosphorylation of I2PP2A was associated with rapid and transient inhibition of a β-arrestin 2-associated pool of protein phosphatase 2A, leading to activation of Akt and increased phosphorylation of glycogen synthase kinase 3β in an arrestin signalsome complex. SII-stimulated PGES3 phosphorylation coincided with an increase in β-arrestin 1-associated PGES3 and an arrestin-dependent increase in cyclooxygenase 1-dependent prostaglandin E(2) synthesis. These findings suggest that AT(1A) receptors regulate a robust G protein-independent signaling network that affects protein phosphorylation and autocrine/paracrine prostaglandin production and that these pathways can be selectively modulated by biased ligands that antagonize G protein activation.

Association of GSTM1, GSTT1, GSTP1-ILE105VAL and ACE I/D polymorphisms with ankylosing spondylitis.

PubMed

İnal, Esra Erkol; Görükmez, Orhan; Eroğlu, Selma; Görükmez, Özlem; Solak, Özlem; Topak, Ali; Yakut, Tahsin

2016-01-01

Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown origin. The aim of this study is to clarify the relationships between susceptibility and severity of AS and GST-mu1 (GSTM1), GST-theta1 (GSTT1), GST-pi1 (GSTP1)-Ile105Val and angiotensin-converting enzyme (ACE) I/D polymorphisms in AS patients. One hundred thirty-eight AS patients and seventy-one healthy controls were enrolled in this study. Erythrocyte sedimentation rate and C-reactive protein (CRP) levels of the AS patients were recorded. The scores of the numeric rating scale (NRS) pain, the Bath Ankylosing Spondylitis Activity Index, the Bath Ankylosing Spondylitis Metrology Index and the Bath Ankylosing Spondylitis Functional Index were calculated. The genotypes distributions and allele frequencies of GSTM1, GSTT1, GSTP1-Ile105Val and ACE I/D polymorphisms were compared between patients and healthy controls. The Multiplex polymerase chain reaction (PCR) and the PCR-restriction fragment length polymorphism methods were used to detect the polymorphisms of ACE I/D, the GSTT1 and GSTM1 genes and the GSTP1-Ile105Val polymorphism, respectively. There were significantly higher levels of the GSTT1 null and the ACE II genotypes in AS patients compared to those in healthy controls (p = 0.002 and 0.005, respectively). We found significantly higher levels of CRP and the NRS pain scores in the patients with ACE ID or DD genotypes compared to those in the patients with ACE II genotypes (p = 0.005 and 0.035, respectively). The present results showed that genes involved in protection from oxidative stress and ACE gene may influence disease development and course in AS.

Life without tRNAIle-lysidine synthetase: translation of the isoleucine codon AUA in Bacillus subtilis lacking the canonical tRNA2Ile

PubMed Central

Köhrer, Caroline; Mandal, Debabrata; Gaston, Kirk W.; Grosjean, Henri; Limbach, Patrick A.; RajBhandary, Uttam L.

2014-01-01

Translation of the isoleucine codon AUA in most prokaryotes requires a modified C (lysidine or agmatidine) at the wobble position of tRNA2Ile to base pair specifically with the A of the AUA codon but not with the G of AUG. Recently, a Bacillus subtilis strain was isolated in which the essential gene encoding tRNAIle-lysidine synthetase was deleted for the first time. In such a strain, C34 at the wobble position of tRNA2Ile is expected to remain unmodified and cells depend on a mutant suppressor tRNA derived from tRNA1Ile, in which G34 has been changed to U34. An important question, therefore, is how U34 base pairs with A without also base pairing with G. Here, we show (i) that unlike U34 at the wobble position of all B. subtilis tRNAs of known sequence, U34 in the mutant tRNA is not modified, and (ii) that the mutant tRNA binds strongly to the AUA codon on B. subtilis ribosomes but only weakly to AUG. These in vitro data explain why the suppressor strain displays only a low level of misreading AUG codons in vivo and, as shown here, grows at a rate comparable to that of the wild-type strain. PMID:24194599

[Medication administration practices in elderly residential facilities in Ile de France Region in 2014: findings and room for improvement].

PubMed

de Saunière, Anne; Bonneau, Laetitia; Donio, Valérie; Godinot, Valérie; Flouzat, Jean-Philippe; Bensasson, Géraldine; Code, Christelle; Galay, Guillaume; Pige, Dominique

2016-11-25

The institutions expressed great interest in medication administration systems and tools designed to monitor all stages of medication administration. A dozen simple and pragmatic improvement actions were identified and listed in the Ile-de-France Regional Health Agency action plan to improve medication administration management of in EHPAD..

The mitochondrial calcium uniporter is involved in mitochondrial calcium cycle dysfunction: Underlying mechanism of hypertension associated with mitochondrial tRNA(Ile) A4263G mutation.

PubMed

Chen, Xi; Zhang, Yu; Xu, Bin; Cai, Zhongqi; Wang, Lin; Tian, Jinwen; Liu, Yuqi; Li, Yang

2016-09-01

Recent studies have shown that the mitochondrial DNA mutations are involved in the pathogenesis of hypertension. Our previous study identified mitochondrial tRNA(Ile) A4263G mutation in a large Chinese Han family with maternally-inherited hypertension. This mutation may contribute to mitochondrial Ca(2+) cycling dysfuntion, but the mechanism is unclear. Lymphoblastoid cell lines were derived from hypertensive and normotensive individuals, either with or without tRNA(Ile) A4263G mutation. The mitochondrial calcium ([Ca(2+)]m) in cells from hypertensive subjects with the tRNA(Ile) A4263G mutation, was lower than in cells from normotension or hypertension without mutation, or normotension with mutation (P<0.05). Meanwhile, cytosolic calcium ([Ca(2+)]c) in hypertensive with mutation cells was higher than another three groups. After exposure to caffeine, which could increase the [Ca(2+)]c by activating ryanodine receptor on endoplasmic reticulum, [Ca(2+)]c/[Ca(2+)]m increased higher than in hypertensive with mutation cells from another three groups. Moreover, MCU expression was decreased in hypertensive with mutation cells compared with in another three groups (P<0.05). [Ca(2+)]c increased and [Ca(2+)]m decreased after treatment with Ru360 (an inhibitor of MCU) or an siRNA against MCU. In this study we found decreased MCU expression in hypertensive with mutation cells contributed to dysregulated Ca(2+) uptake into the mitochondria, and cytoplasmic Ca(2+) overload. This abnormality might be involved in the underlying mechanisms of maternally inherited hypertension in subjects carrying the mitochondrial tRNA(Ile) A4263G mutation. Copyright © 2016 Elsevier Ltd. All rights reserved.

A novel natural mutation AαPhe98Ile in the fibrinogen coiled-coil affects fibrinogen function.

PubMed

Riedelová-Reicheltová, Zuzana; Kotlín, Roman; Suttnar, Jiří; Geierová, Véra; Riedel, Tomáš; Májek, Pavel; Dyr, Jan Evangelista

2014-01-01

The aim of this study was to investigate the structure and function of fibrinogen obtained from a patient with normal coagulation times and idiopathic thrombophilia. This was done by SDS-PAGE and DNA sequence analyses, scanning electron microscopy, fibrinopeptide release, fibrin polymerisation initiated by thrombin and reptilase, fibrinolysis, and platelet aggregometry. A novel heterozygous point mutation in the fibrinogen Aα chain, Phe98 to Ile, was found and designated as fibrinogen Vizovice. The mutation, which is located in the RGDF sequence (Aα 95-98) of the fibrinogen coiled-coil region, significantly affected fibrin clot morphology. Namely, the clot formed by fibrinogen Vizovice contained thinner and curled fibrin fibers with reduced length. Lysis of the clots prepared from Vizovice plasma and isolated fibrinogen were found to be impaired. The lysis rate of Vizovice clots was almost four times slower than the lysis rate of control clots. In the presence of platelets agonists the mutant fibrinogen caused increased platelet aggregation. The data obtained show that natural mutation of Phe98 to Ile in the fibrinogen Aα chain influences lateral aggregation of fibrin protofibrils, fibrinolysis, and platelet aggregation. They also suggest that delayed fibrinolysis, together with the abnormal fibrin network morphology and increased platelet aggregation, may be the direct cause of thrombotic complications in the patient associated with pregnancy loss.

Predictive value of GSTP1 Ile105Val polymorphism in clinical outcomes of chemotherapy in gastric and colorectal cancers: a systematic review and meta-analysis.

PubMed

Shen, Xiaobing; Wang, Jia; Yan, Xiaoluan; Ren, Xiaofeng; Wang, Fan; Chen, Xiaowei; Xu, Yuchao

2016-06-01

Gastric and colorectal cancers remain the major causes of cancer-related death with a bad prognosis. Up to now, platinum combined with fluoropyrimidines has been most commonly used in chemotherapy regimens of gastric and colorectal cancers. Recently, a series of studies have been conducted to investigate the associations of biomarkers, such as GSTP1 Ile105Val polymorphism, with the chemotherapy efficacy in gastric and colorectal cancers; however, the results were not consistent and inconclusive. Here, we performed a systematic review and meta-analysis to summarize the associations of GSTP1 Ile105Val polymorphism with the chemotherapy efficacy in gastric and colorectal cancers. A systematic review was conducted to search relevant studies in English databases (PubMed, ISI Web of Science, and EMBASE) up to November 30, 2015. The pooling ORs or HRs were used to assess the strength of the associations of GSTP1 Ile105Val polymorphism with clinical outcomes such as tumor response, toxicity, progression-free survival (PFS), and overall survival (OS). Forty-one papers containing 8169 cases were finally included in the present meta-analysis study. Of which, 28 articles were performed in colorectal cancers, one in gastrointestinal carcinoma (gastric and colon cancer), 11 in gastric cancers, and one in colorectal and gastroesophageal cancers. After pooling all the eligible studies, we identified significant associations of GSTP1 Ile105Val polymorphism with chemotherapy-related tumor response (G vs. A: OR 1.697, 95 % CI 1.191-2.418; GG vs. AA: OR 2.804, 95 % CI 1.414-5.560; AG vs. AA: OR 1.540, 95 % CI 1.011-2.347; GG vs. AAAG: OR 2.139, 95 % CI 1.256-3.641), PFS (GG vs. AA, HR 0.640, 95 % CI 0.455-0.900; AGGG vs. AA: HR 0.718, 95 % CI 0.562-0.919), and OS (AG vs. AA: HR 0.857, 95 % CI 0.746-0.986; GG vs. AA: HR 0.679, 95 % CI 0.523-0.882; AGGG vs. AA: HR 0.663, 95 % CI 0.542-0.812) in gastric and colorectal cancers and no significant association was found

Role of Thr399Ile and Asp299Gly polymorphisms of toll-like receptor-4 gene in acute dental abscess.

PubMed

Miri-Moghaddam, Ebrahim; Farhad-Mollashahi, Narges; Baghaee, Elnaz; Bazi, Ali; Garme, Yasaman

2017-02-01

Apical Periodontitis (AP) is an inflammatory disease that affects the tissues surrounding the root end of a tooth. The disease which is caused by endodontic infections presents in different clinical ways including development of an acute abscess. Recent studies have provided information suggesting role of a multitude of factors in pathogenesis of acute apical abscess (AAA). In this case-control study, our goal was to evaluate the frequency and potential role of two common polymorphisms of toll like receptor-4 (TLR-4) gene; Thr399Ile (1196 C>T) and Asp299Gly (+896 A>G), in 50 patients with AAA as cases and 50 patients with asymptomatic apical periodontitis (AAP) as controls. Saliva sample containing mucosal epithelial cells was used for DNA extraction. Polymorphisms were detected by Tetra-ARMS (Amplification Refractory Mutation System) PCR method. Statistical analyses were carried out in SPSS 21 software. Homozygous wild type (CC) and heterozygous (CT) genotypes of Thr399Ile polymorphism were detected in 84% and 16% of AAA patients respectively. In controls, respective ratios were 94% (CC) and 6% (CT). Observed difference was not statistically significant ( P >0.05) for distribution of these genotypes. The mutant homozygous (TT) genotype of this polymorphism was identified in neither of the participants. Overall, T allele frequency was obtained 8% in AAA and 3% in AAP (OR=2.6, 95% CI; 0. 6-10.6, p >0.05). For Asp299Gly polymorphism, no individual was detected with the mutant allele in case or control groups. Our results indicated a possible role for Thr399Ile polymorphism in acute presentations of abscess in AAA. However, the impact of this polymorphism needs to be more assessed in future studies. Key words: Genetic polymorphism, periapical abscess, periapical periodontitis, toll-like receptor 4.

Role of Thr399Ile and Asp299Gly polymorphisms of toll-like receptor-4 gene in acute dental abscess

PubMed Central

Miri-Moghaddam, Ebrahim; Baghaee, Elnaz; Bazi, Ali; Garme, Yasaman

2017-01-01

Background Apical Periodontitis (AP) is an inflammatory disease that affects the tissues surrounding the root end of a tooth. The disease which is caused by endodontic infections presents in different clinical ways including development of an acute abscess. Recent studies have provided information suggesting role of a multitude of factors in pathogenesis of acute apical abscess (AAA). In this case-control study, our goal was to evaluate the frequency and potential role of two common polymorphisms of toll like receptor-4 (TLR-4) gene; Thr399Ile (1196 C>T) and Asp299Gly (+896 A>G), in 50 patients with AAA as cases and 50 patients with asymptomatic apical periodontitis (AAP) as controls. Material and Methods Saliva sample containing mucosal epithelial cells was used for DNA extraction. Polymorphisms were detected by Tetra-ARMS (Amplification Refractory Mutation System) PCR method. Statistical analyses were carried out in SPSS 21 software. Results Homozygous wild type (CC) and heterozygous (CT) genotypes of Thr399Ile polymorphism were detected in 84% and 16% of AAA patients respectively. In controls, respective ratios were 94% (CC) and 6% (CT). Observed difference was not statistically significant (P>0.05) for distribution of these genotypes. The mutant homozygous (TT) genotype of this polymorphism was identified in neither of the participants. Overall, T allele frequency was obtained 8% in AAA and 3% in AAP (OR=2.6, 95% CI; 0. 6-10.6, p>0.05). For Asp299Gly polymorphism, no individual was detected with the mutant allele in case or control groups. Conclusions Our results indicated a possible role for Thr399Ile polymorphism in acute presentations of abscess in AAA. However, the impact of this polymorphism needs to be more assessed in future studies. Key words:Genetic polymorphism, periapical abscess, periapical periodontitis, toll-like receptor 4. PMID:28210435

CCL2 Serum Levels and Adiposity Are Associated with the Polymorphic Phenotypes -2518A on CCL2 and 64ILE on CCR2 in a Mexican Population with Insulin Resistance.

PubMed

Guzmán-Ornelas, Milton-Omar; Petri, Marcelo Heron; Vázquez-Del Mercado, Mónica; Chavarría-Ávila, Efraín; Corona-Meraz, Fernanda-Isadora; Ruíz-Quezada, Sandra-Luz; Madrigal-Ruíz, Perla-Monserrat; Castro-Albarrán, Jorge; Sandoval-García, Flavio; Navarro-Hernández, Rosa-Elena

2016-01-01

Genetic susceptibility has been described in insulin resistance (IR). Chemokine (C-C motif) ligand-2 (CCL2) is overexpressed in white adipose tissue and is the ligand of C-C motif receptor-2 (CCR2). The CCL2 G-2518A polymorphism is known to regulate gene expression, whereas the physiological effects of the CCR2Val64Ile polymorphism are unknown. The aim of the study is to investigate the relationship between these polymorphisms with soluble CCL2 levels (sCCL2), metabolic markers, and adiposity. In a cross-sectional study we included 380 Mexican-Mestizo individuals, classified with IR according to Stern criteria. Polymorphism was identified using PCR-RFLP/sequence-specific primers. Anthropometrics and metabolic markers were measured by routine methods and adipokines and sCCL2 by ELISA. The CCL2 polymorphism was associated with IR (polymorphic A+ phenotype frequencies were 70.9%, 82.6%, in individuals with and without IR, resp.). Phenotype carriers CCL2 (A+) displayed lower body mass and fat indexes, insulin and HOMA-IR, and higher adiponectin levels. Individuals with IR presented higher sCCL2 compared to individuals without IR and was associated with CCR2 (Ile+) phenotype. The double-polymorphic phenotype carriers (A+/Ile+) exhibited higher sCCL2 than double-wild-type phenotype carriers (A-/Ile-). The present findings suggest that sCCL2 production possibly will be associated with the adiposity and polymorphic phenotypes of CCL2 and CCR2, in Mexican-Mestizos with IR.

[Outbreak of carbon monoxide poisoning in the Ile-de-France region during the spring 2016 Seine flooding].

PubMed

Dufayet, Laurène; Médernach, Chantal; Bassi, Clément; Garnier, Robert; Langrand, Jérôme

2017-01-01

Heavy rainfall in May 2016 caused large-scale flooding of the Seine and its tributaries. Analysis of this unusual event showed that it could recur on an even larger scale. The sanitary consequences were less frequently assessed in this analysis, particularly the risk of accidental collective carbon monoxide (CO) poisoning caused by the use of combustion engine drainage pumps. We retrospectively reviewed all cases of acute accidental carbon monoxide exposure observed in the Ile-de-France region, related to the use of drainage pumps in spring and summer 2016 and notified to the Ile-de-France CO poisoning surveillance network. Five events were identified, including 45 people exposed to carbon monoxide. Thirty-four of these people were poisoned, 5 were not poisoned and insufficient data were available for 6 people. Three people showed signs of severity and 2 were treated by hyperbaric oxygen therapy. The other poisoned individuals were managed in hospital and treated by oxygen therapy. All were cured. Collective CO poisonings are common sanitary events during flooding and can be potentially severe. They can occur during the event or over the following days. Preventive measures may help to reduce the risk of CO poisoning, such as increased awareness among professionals, better information of individuals who rent these types of devices or even the use of CO detectors during their use.

Changing Water-Resources on Ile de la Gonave, Haiti

NASA Astrophysics Data System (ADS)

Troester, J. W.

2002-12-01

Ile de la Gonave is a 750-square-kilometer island off the western coast of Haiti. The island is composed of Eocene and Miocene limestones unconformably overlain by Pleistocene limestone. The highest elevation is 778 meters. Annual precipitation varies across the island because of the orographic effect and ranges from 800 to 1,400 millimeters. There is no surface water except immediately after large storms. Droughts, some extending for more than one year, and frequent crop failures due to droughts have been reported. Potential evaporation is estimated to be about 2,000 millimeters at the coast, but less at higher elevations. Consequently most rain is lost through evapotranspiration; recharge to the limestone aquifers apparently occurs only after large storms and is estimated to be about 4 percent of the mean annul precipitation based on a chloride mass balance. Depth to the water table ranges from less than 30 meters in the Eocene and Miocene limestones to over 60 meters in the 300-meter thick Quaternary limestone. Average annual precipitation at Port au-Prince (50 kilometers to the east and on the main island of Hispaniola) has decreased from about 1600 millimeters in 1860's to about 1300 mm in the 1950's. Precipitation data from Port-au-Prince after the 1950's are sporadic, making further comments about climate change difficult. Even without decreasing precipitation, which may be due in part to climate change or the deforestation of Haiti, the increasing population on Ile de la Gonave has and will continue to exacerbate the scarce water supply, particularly because of the small number of sources (springs, cave pools, and wells) where people can obtain water. Women take an average of almost three hours per day to travel an average of 2.5 kilometers (one-way) to obtain water for their families. Because of the difficulties in obtaining freshwater, the 100,000 inhabitants use an average of only 7 to 13 liters per person per day. Reconnaissance field analyses indicate

Chronic Airflow Obstruction in a Black African Population: Results of BOLD Study, Ile-Ife, Nigeria.

PubMed

Obaseki, Daniel O; Erhabor, Gregory E; Gnatiuc, Louisa; Adewole, Olufemi O; Buist, Sonia A; Burney, Peter G

2016-01-01

Global estimates suggest that Chronic Obstructive Pulmonary Disease (COPD) is emerging as a leading cause of death in developing countries but there are few spirometry-based general population data on its prevalence and risk factors in sub-Saharan Africa. We used the Burden of Obstructive Lung Disease (BOLD) protocol to select a representative sample of adults aged 40 years and above in Ile-Ife, Nigeria. All the participants underwent spirometry and provided information on smoking history, biomass and occupational exposures as well as diagnosed respiratory diseases and symptoms. Chronic Airflow Obstruction (CAO) was defined as the ratio of post-bronchodilator (BD) one second Forced Expiratory Volume (FEV1) to Forced Vital Capacity (FVC) below the lower limit of normal (LLN) of the population distribution for FEV1/FVC. The overall prevalence of obstruction (post-BD FEV1/FVC < LLN) was 7.7% (2.7% above LLN) using Global Lung Function Initiative (GLI) equations. It was associated with few respiratory symptoms; 0.3% reported a previous doctor-diagnosed chronic bronchitis, emphysema or COPD. Independent predictors included a lack of education (OR 2.5, 95% CI: 1.0, 6.4) and a diagnosis of either TB (OR 23.4, 95% CI: 2.0, 278.6) or asthma (OR 35.4, 95%CI: 4.9, 255.8). There was no association with the use of firewood or coal for cooking or heating. The vast majority of this population (89%) are never smokers. We conclude that the prevalence of CAO is low in Ile-Ife, Nigeria and unrelated to biomass exposure. The key independent predictors are poor education, and previous diagnosis of tuberculosis or asthma.

Towards the Use of Information and Communication Technology in Undergraduates Learning: Possession, Perception and Problems in Obafemi Awolowo University, Ile-Ife, Nigeria

ERIC Educational Resources Information Center

Egbedokun, A. O.; Oyewusi, L. M.

2014-01-01

This paper focuses the potentials of information and communication technologies (ICT) on three main areas as related to students learning (possession, perception and problems). It investigated students' possession, perception and problems (as envisaged or experienced) by students of Obafemi Awolowo University, Ile-Ife on the use of ICT facilities.…

Inventory of echinoderms in the Iles Eparses (Europa, Glorieuses, Juan de Nova), Mozambique Channel, France

NASA Astrophysics Data System (ADS)

Conand, C.; Mulochau, T.; Stöhr, S.; Eléaume, M.; Chabanet, P.

2016-04-01

The multidisciplinary programme BioReCIE (Biodiversity, Resources and Conservation of coral reefs at Eparses Is.) inventoried multiple marine animal groups in order to provide information on the coral reef health of the Iles Eparses. All five classes of echinoderms were observed by visual census, photographed and later identified. About 100 species are reported, including a few unidentified ones which require further studies. The Holothuroidea and Ophiuroidea are the most diverse. One new species, the asterinid Aquilonastra chantalae O'Loughlin and McKenzie (2013), was discovered in addition to several new records of echinoderms. The illegal fishery targeting holothurians, which are presently highly valuable resources in this zone, is discussed.

Association of GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms with clinical response to imatinib mesylate treatment among Malaysian chronic myeloid leukaemia patients.

PubMed

Makhtar, Siti Maziras; Husin, Azlan; Baba, Abdul Aziz; Ankathil, Ravindran

2017-09-01

The detoxifying activity of glutathione S-transferases (GST) enzymes not only protect cells from the adverse effects of xenobiotics, but also alters the effectiveness of drugs in cancer cells, resulting in toxicity or drug resistance. In this study, we aimed to evaluate the association of GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms with treatment response among Malaysian chronic myeloid leukaemia (CML) patients who everyday undergo 400 mg of imatinib mesylate (IM) therapy. Multiplex polymerase chain reaction (multiplex-PCR) was performed to detect GSTM1 and GSTT1 polymorphisms simultaneously and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was conducted to detect the GSTP1 Ile195Val polymorphism. On evaluating the association of the variant genotype with treatment outcome, heterozygous variant (AG) and homozygous variant (GG) of GSTP1 Ile105Val showed significantly a higher risk for the development of resistance to IM with OR: 1.951 (95% CI: 1.186-3.209, P = 0.009) and OR: 3.540 (95% CI: 1.305-9.606, P = 0.013), respectively. Likewise, GSTT1 null genotype was also associated with a significantly higher risk for the development of resistance to IM with OR = 1.664 (95% CI: 1.011-2.739, P = 0.045). Our results indicate the potential usefulness of GST polymorphism genotyping in predicting the IM treatment response among CML patients.

Conservation and promotion of the geological heritage in the «Ile-de-France» region (France): Establishment of a decision support-tool based on inventory

NASA Astrophysics Data System (ADS)

Auberger, Elise; Gély, Jean-Pierre; De Wever, Patrick; Merle, Didier

2017-04-01

Based on an initiative by the "Regional Commission of Geological Patrimony" (CRPG), the French state and the regional government of Ile-de-France co-financed the setting up of an inventory with the aim of safeguarding geological sites of patrimonial interest. This project forms part of larger scale policies, at the national and European level. Geological studies in the Paris region began as early as the 18th century, in the fields of cartography and paleontology. Later on, prominent scientists like G. Cuvier, A. Brongniart and A. d'Orbigny established the first concepts in sedimentology and stratigraphy through the description of Cenozoic fossil sites that rank amongst the richest in the world and geological formations in the Paris Basin. Eventually, later on, five historical stratotypes were established in the Ile-de-France region. Yet, at present, this geological heritage is constantly threatened by expanding urbanisation. To conserve this diverse geological patrimony, we have set up a protocol composed of 4 main actions: i) The exhaustive and objective referencing of geological sites in Ile-de-France. This information is centralised in a database, which currently comprises 639 sites (mainly of anthropic nature such as quarries) ii) The pre-selection of sites (298 out of the initial 639) based on sufficient accessibility and potential geological interest. iii) The use of a method of description and hierarchisation - following the guidelines of the National Geological Heritage Inventory Program (INPG) - on the pre-selected sites. iv) Establishment of a schedule specifying actions of geo-conservation which will take into account the patrimonial value of the sites, but also their threats, their juridical status and the socio-economic context of the region. The purpose of this program is to conserve a collection of geological sites that reflect the totality of the regional geology in Ile-de-France. The results of this study will be released to the general public and

The Amoco CadizOil Spill: Evolution of Petroleum Hydrocarbons in the Ile Grande Salt Marshes (Brittany) after a 13-year Period

NASA Astrophysics Data System (ADS)

Mille, G.; Munoz, D.; Jacquot, F.; Rivet, L.; Bertrand, J.-C.

1998-11-01

The Ile Grande salt marshes (Brittany coast) were polluted by petroleum hydrocarbons after theAmoco Cadizgrounding in 1978. Thirteen years after the oil spill, sediments were analysed for residual hydrocarbons in order to monitor the aliphatic and aromatic hydrocarbon signatures and to assess both qualitatively and quantitatively the changes in composition of theAmoco Cadizoil. Six stations were selected in the Ile Grande salt marshes and sediments were sampled to a depth of 20 cm. For each sample, the hydrocarbon compositions were determined for alkanes, alkenes, aromatics and biomarkers (terpanes, steranes, diasteranes). Hydrocarbon levels drastically decreased between 1978 and 1991, but to different extents according to the initial degree of contamination. In 1991, hydrocarbon concentrations never exceeded 1·7 g kg-1sediment dry weight, and in most cases were less than 0·1 g kg-1sediment dry weight. Even though petroleum hydrocarbons are still present, natural hydrocarbons were also detected at several stations. Changes in some biomarker distributions were observed 13 years after the oil spill. Nevertheless, most of the biomarkers are very stable in the salt marsh environment and remain unaltered even after a 13-year period.

Influence of family size, household food security status, and child care practices on the nutritional status of under-five children in Ile-Ife, Nigeria.

PubMed

Ajao, K O; Ojofeitimi, E O; Adebayo, A A; Fatusi, A O; Afolabi, O T

2010-12-01

Fertility pattern and reproductive behaviours affect infant death in Nigeria. Household food insecurity and poor care practices also place children at risk of morbidity and mortality. The objectives of this study were to assess the influence of family size, household food security status, and child care practices on the nutritional status of under-five children in Ile-Ife, Nigeria. The study employed a descriptive cross-sectional design. A semi-structured questionnaire was used to collect data from 423 mothers of under-five children and their children in the households selected through multistage sampling methods. Food-insecure households were five times more likely than secure households to have wasted children (crude OR = 5.707, 95 percent CI = 1.31-24.85). Children with less educated mothers were significantly more likely to be stunted. The prevalence of food insecurity among households in Ile-Ife was high. Households with food insecurity and less educated mothers were more likely to have malnourished children.

Self Concept and Motivation Variables as Correlates of Acquisition of ICT Competence among Social Studies Students of Obafemi Awolowo University, Ile-Ife, Nigeria

ERIC Educational Resources Information Center

Adeyemi, B. A.

2014-01-01

The study examined the level of ICT competence among Social Studies undergraduates of Obafemi Awolowo University, Ile-Ife, Nigeria. It also investigated the influence of motivation variables as well as the influence of self concept on the acquisition of ICT competence. This was with a view to improving ICT competence in higher institutions of…

Val-407 and Ile-408 in the β5′-Loop of Pancreatic Lipase Mediate Lipase-Colipase Interactions in the Presence of Bile Salt Micelles*

PubMed Central

Freie, Angela Bourbon; Ferrato, Francine; Carrière, Frédéric; Lowe, Mark E.

2013-01-01

In a previous study, we demonstrated that the β5′-loop in the C-terminal domain of human pancreatic triglyceride lipase (hPTL) makes a major contribution in the function of hPTL (Chahinian et al. (2002) Biochemistry 41, 13725–13735). In the present study, we characterized the contribution of three residues in the β5′-loop, Val-407, Ile-408, and Leu-412, to the function of hPTL. By substituting charged residues, aspartate or lysine, in these positions, we altered the hydrophilic to lipophilic ratio of the β5′-loop. Each of the mutants was expressed, purified, and characterized for activity and binding with both monolayers and emulsions and for binding to colipase. Experiments with monolayers and with emulsions suggested that the interaction of hPTL with a phospholipid monolayer differs from the interaction of the hPTL-colipase complex with a dicaprin monolayer or a triglyceride emulsion (i.e. neutral lipids). Val-407, Ile-408, and Leu-412 make major contributions to interactions with monolayers, whereas only Val-407 and Ile-408 appear essential for activity on triglyceride emulsions in the presence of bile salt micelles. In solutions of taurodeoxycholate at micellar concentrations, a major effect of the β5′-loop mutations is to change the interaction between hPTL and colipase. These observations support a major contribution of residues in the β5′-loop in the function of hPTL and suggest that a third partner, bile salt micelles or the lipid interface or both, influence the binding of colipase and hPTL through interactions with the β5′-loop. PMID:16431912

Environmental assessment of biofuel pathways in Ile de France based on ecosystem modeling.

PubMed

Gabrielle, Benoît; Gagnaire, Nathalie; Massad, Raia Silvia; Dufossé, Karine; Bessou, Cécile

2014-01-01

The objective of the work reported here was to reduce the uncertainty on the greenhouse gas balances of biofuels using agro-ecosystem modeling at a high resolution over the Ile-de-France region in Northern France. The emissions simulated during the feedstock production stage were input to a life-cycle assessment of candidate biofuel pathways: bioethanol from wheat, sugar-beet and miscanthus, and biodiesel from oilseed rape. Compared to the widely-used methodology based on fixed emission factors, ecosystem modeling lead to 55-70% lower estimates for N2O emissions, emphasizing the importance of regional factors. The life-cycle GHG emissions of first-generation biofuels were 50-70% lower than fossil-based equivalents, and 85% lower for cellulosic ethanol. When including indirect land-use change effects, GHG savings became marginal for biodiesel and wheat ethanol, but were positive due to direct effects for cellulosic ethanol. Copyright © 2013 Elsevier Ltd. All rights reserved.

Frequencies of the Arg16Gly, Gln27Glu and Thr164Ile Adrenoceptor β2 Polymorphisms among Omanis

PubMed Central

Al-Balushi, Khalid; Zadjali, Fahad; Al-Sinani, Sawsan; Al-Zadjali, Al-Muatasim; Bayoumi, Riad

2015-01-01

Objectives: This study aimed to assess the distribution of missense mutations in the adrenoceptor β2 (ADRB2) gene in an Omani cohort. Methods: This study was carried out between May 2014 and March 2015 at the Sultan Qaboos University, Muscat, Oman. Blood samples were taken from 316 unrelated Omani subjects. Genotyping for rs1042713 (c.46A>G, p.Arg16Gly), rs1042714 (c.79C>G, p.Gln27Glu) and rs1800888 (c.491C>T, p.Thr164Ile) polymorphisms was performed by real-time polymerase chain reaction using single nucleotide polymorphism (SNP) genotyping assays. The allelic frequencies of these polymorphisms were estimated on the basis of the observed numbers of specific alleles from the genotype data for male and female subjects. The genotype frequencies for each polymorphism were tested for deviation from the Hardy-Weinberg equilibrium. Results: Gly16 and Glu27 were the most frequent variants found among the cohort (63% and 75%, respectively). The Ile164 variant was not detected in the study population. There was a significant linkage disequilibrium between the rs1042713 and rs1042714 SNPs (r2 = 0.209; P ≤0.001). The most observed haplotypes were Gly16-Gln27 and Arg16-Gln27 (0.37 and 0.38, respectively). The frequency of Gly16-Glu27 was 0.25, comprising all Glu27 carriers. Conclusion: The allelic distribution of variants in this Omani cohort was similar to distributions reported among Caucasian populations. PMID:26629374

A novel missense substitution (Val1483Ile) in the fatty acid synthase gene (FAS) is associated with percentage of body fat and substrate oxidation rates in nondiabetic Pima Indians.

PubMed

Kovacs, Peter; Harper, Inge; Hanson, Robert L; Infante, Aniello M; Bogardus, Clifton; Tataranni, P Antonio; Baier, Leslie J

2004-07-01

Inhibition of fatty acid synthase (FAS) induces a rapid decline in fat stores in mice, suggesting a role for this enzyme in energy homeostasis. The human FAS gene (FAS) maps to chromosome 17q25, a region previously shown to have suggestive linkage to adiposity in a genome-wide linkage scan for genetic determinants of obesity in Pima Indians. To investigate the potential role of FAS in the pathophysiology of human obesity, the FAS gene was sequenced and 13 single nucleotide polymorphisms (SNPs) were identified. Five representative SNPs were genotyped in 216 full-blooded, nondiabetic Pima Indians for association analyses. A Val1483Ile polymorphism (GTC to ATC; allele frequency of A = 0.10) was associated with percentage of body fat and 24-h substrate oxidation rates measured in a respiratory chamber. Compared with homozygotes for the Val variant, subjects with Ile/x had a lower mean percentage of body fat (30 +/- 1 vs. 33 +/- 1%, P = 0.002; adjusted for age, sex, and family membership) and a lower mean carbohydrate oxidation rate (983 +/- 41 vs. 1,094 +/- 19 kcal/day, P = 0.03), which resulted in a lower mean 24-h respiratory quotient (0.845 +/- 0.01 vs. 0.850 +/- 0.01 kcal/day, P = 0.04; both adjusted for age, sex, family membership, percentage of body fat, and energy balance). Our findings indicate that the Val1483Ile substitution in FAS is protective against obesity in Pima Indians, an effect possibly explained by the role of this gene in the regulation of substrate oxidation.

Declining prevalence of duodenal ulcer at endoscopy in Ile-Ife, Nigeria.

PubMed

Ijarotimi, O; Soyoye, D O; Adekanle, O; Ndububa, D A; Umoru, B I; Alatise, O I

2017-08-25

Duodenal ulcer is the most common peptic ulcer disease worldwide. In the past, sub-Saharan Africa has been described as an area of mixed prevalence for peptic ulcer disease, but recent reports have disputed this. Changes in the prevalence of duodenal ulcer have been reported, with various reasons given for these. To describe the change in endoscopic prevalence of duodenal ulcer at Obafemi Awolowo University Teaching Hospital (OAUTH), Ile-Ife, Nigeria, between January 2000 and December 2010. This was a retrospective, descriptive study of patients who underwent upper gastrointestinal endoscopy in the endoscopy unit of OAUTH between January 2000 and December 2010. The data were obtained from the endoscopy register, demographic indices, presenting symptoms and post-endoscopic diagnoses being retrieved for each patient. The study period was divided into the years 2000 - 2004 and 2005 - 2010, the frequencies of duodenal ulcer and other post-endoscopic diagnoses being compared between these two time periods to see whether there were changes. Over the study period, 292 patients (15.8%) were diagnosed with duodenal ulcer, second only to 471 patients (26.2%) with acute gastritis. The prevalence of duodenal ulcer for 2000 - 2004 was 22.9% (n=211 patients) compared with 9.2% (n=81) for 2005 - 2010 (p<0.001). There was a significant decline in the endoscopic prevalence of duodenal ulcer over the decade.

Heavy metals in industrially emitted particulate matter in Ile-Ife, Nigeria.

PubMed

Ogundele, Lasun T; Owoade, Oyediran K; Hopke, Philip K; Olise, Felix S

2017-07-01

Iron and steel smelting facilities generate large quantities of airborne particulate matter (PM) through their various activities and production processes. The resulting PM that contains a variety of heavy metals has potentially detrimental impacts on human health and the environment. This study was conducted to assess the potential health effects of the pollution from the heavy metals in the airborne PM sampled in the vicinity of secondary smelting operations in Ile-Ife, Nigeria. X-ray fluorescence (XRF) was used to determine the elemental concentration of Pb, Cr, Cd, Zn, Mn, As, Fe, Cu, and Ni in the size-segregated PM samples. Pollution Indices (PI) consisting of Contamination Factor (CF), Degree of Contamination (DC) and Pollution Index Load (PLI) and Target Hazard Quotient (THQ) were employed to assess the pollution risk associated with the heavy metals in the PM. CF, DC and PLI values were 3< CF <6, >32 and >1, respectively for the three sites, indicating deterioration of the ambient air quality in the vicinity of the smelter. The heavy metals in the airborne PM pose a severe health risk to people living in vicinity of the facility and to its workers. The diminished air quality with the associated health risks directly depends on the industrial emissions from steel production and control measures are recommended to mitigate the likely risks. Copyright © 2017 Elsevier Inc. All rights reserved.

Planned vaginal delivery versus Caesarean section for breech presentation in Ile-Ife, Nigeria.

PubMed

Orji, E O; Ajenifuja, K O

2003-11-01

The optimum mode of breech delivery remains a matter of controversy among obstetricians worldwide. To determine whether term breech babies born by planned vaginal delivery are at higher risk of neonatal mortality and morbidity than those born by planned caesarean delivery. A hospital based non-experimental comparison of outcome of breech delivery. Ife State Hospitals Complex, Ile-Ife. Two hundred and fourty four singleton breech deliveries occurring at term. They include low 5-minute Apgar score, birth trauma, maternal and perinatal morbidity and mortality. The perinatal mortality was not significantly different in both groups: OR 2.7 (95% C.I. 0.3-26.8). The low 5-minute Apgar scores were higher in the planned vaginal delivery OR 9.0 (95% C.I. 1-73.4), but the traumatic morbidity was not (OR 1.8, 95% C.I. 0.2-20.1). Maternal morbidity occurred more in the planned Caesarean delivery group OR 0.4 (95% C.I. 0.2-0.9). Given appropriate selection criteria and management protocol, the outcome from elective caesarean section might not be better than from planned vaginal delivery.

Genetic characterization of type 2a canine parvoviruses from Taiwan reveals the emergence of an Ile324 mutation in VP2

PubMed Central

2014-01-01

Background Canine parvovirus 2 (CPV 2) is a major infectious cause of mortality in puppies. The characteristic symptom of CPV 2 disease is intestinal hemorrhage with severe bloody diarrhea. Soon after CPV was first recognized in the late 1970s, the original virus, CPV 2, was replaced in the canine population by strains carrying minor antigenic variants (termed 2a, 2b, and 2c) of the VP2 gene that could be distinguished using monoclonal antibodies and molecular analyses. Here, we provide an updated molecular characterization of the CPV 2 circulating in Taiwan. Methods In this study, 28 isolates of CPV 2 from 144 dogs with suspected CPV infection were obtained from northern, central, and southern Taiwan from 2008 to 2012 and screened by PCR. The 28 isolates were sequenced, and a phylogenetic analysis of the VP2 gene was performed. Results Of the 28 Taiwanese CPV 2 isolates, 15 were identified as new CPV 2a, and 13 were identified as new CPV 2b. Compared to the reference CPV 2a, all 15 of the CPV 2a sequences collected in this study contain an Ile324 mutation caused by a TAT to ATT mutation at nucleotides 970–972 of the VP2 gene. Conclusion Our VP2 sequence data revealed that both types are currently prevalent CPV 2 field strains circulating in Taiwan, and a unique Ile324 VP2 mutation was found in our Taiwanese CPV 2a isolates and recent Asian isolates. CPV 2c was not observed in this study. PMID:24568207

Backbone and stereospecific (13)C methyl Ile (δ1), Leu and Val side-chain chemical shift assignments of Crc.

PubMed

Sharma, Rakhi; Sahu, Bhubanananda; Ray, Malay K; Deshmukh, Mandar V

2015-04-01

Carbon catabolite repression (CCR) allows bacteria to selectively assimilate a preferred compound among a mixture of several potential carbon sources, thus boosting growth and economizing the cost of adaptability to variable nutrients in the environment. The RNA-binding catabolite repression control (Crc) protein acts as a global post-transcriptional regulator of CCR in Pseudomonas species. Crc triggers repression by inhibiting the expression of genes involved in transport and catabolism of non-preferred substrates, thus indirectly favoring assimilation of preferred one. We report here a nearly complete backbone and stereospecific (13)C methyl side-chain chemical shift assignments of Ile (δ1), Leu and Val of Crc (~ 31 kDa) from Pseudomonas syringae Lz4W.

Antinociceptive effect induced by a combination of opioid and neurotensin moieties vs. their hybrid peptide [Ile(9)]PK20 in an acute pain treatment in rodents.

PubMed

Kleczkowska, Patrycja; Hermans, Emmanuel; Kosson, Piotr; Kowalczyk, Agnieszka; Lesniak, Anna; Pawlik, Karolina; Bojnik, Engin; Benyhe, Sandor; Nowicka, Barbara; Bujalska-Zadrozny, Magdalena; Misicka, Aleksandra; Lipkowski, Andrzej W

2016-10-01

Hybrid compounds are suggested to be a more effective remedy for treatment of various diseases than combination therapy, since the attenuation or total disappearance of side effects, typically induced by a single moiety, can be observed. This is of great importance, especially when we consider problems resulting from the use of opioid analgesics. However, although it seems that such compounds can be valuable therapeutic tools, the lack of conviction among the public as to the appropriateness of their use still remains; therefore patients are commonly treated with polypharmacy. Thus, in the presented paper we show a comparison of the antinociceptive effect between a novel opioid-neurotensin chimera called [Ile(9)]PK20 and a mixture of its structural elements, delivered intrathecally and systemically. Additionally, motor coordination was assessed in the rotarod test. The results clearly indicate that spinal administration of the examined compounds, resulted in a long-lasting, dose- and time-dependent antinociceptive effect. Although the mixture of both pharmacophores was found to be more active than [Ile(9)]PK20, motor impairments surfaced as a side effect. This in turn illustrates the advantageous use of hybrid structures over drug cocktails. Copyright © 2016 Elsevier B.V. All rights reserved.

Design of specific peptide inhibitors of phospholipase A2: structure of a complex formed between Russell's viper phospholipase A2 and a designed peptide Leu-Ala-Ile-Tyr-Ser (LAIYS).

PubMed

Chandra, Vikas; Jasti, Jayasankar; Kaur, Punit; Dey, Sharmistha; Srinivasan, A; Betzel, Ch; Singh, T P

2002-10-01

Phospholipase A(2) (EC 3.1.1.4) is a key enzyme of the cascade mechanism involved in the production of proinflammatory compounds known as eicosanoids. The binding of phospholipase A(2) to membrane surfaces and the hydrolysis of phospholipids are thought to involve the formation of a hydrophobic channel into which a single substrate molecule diffuses before cleavage. In order to regulate the production of proinflammatory compounds, a specific peptide inhibitor of PLA(2), Leu-Ala-Ile-Tyr-Ser, has been designed. Phospholipase A(2) from Daboia russelli pulchella (DPLA(2)) and peptide Leu-Ala-Ile-Tyr-Ser (LAIYS) have been co-crystallized. The structure of the complex has been determined and refined to 2.0 A resolution. The structure contains two crystallographically independent molecules of DPLA(2), with one molecule of peptide specifically bound to one of them. The overall conformations of the two molecules are essentially similar except in three regions; namely, the calcium-binding loop including Trp31 (residues 25-34), the beta-wing consisting of two antiparallel beta-strands (residues 74-85) and the C-terminal region (residues 119-133). Of these, the most striking difference pertains to the orientation of Trp31 in the two molecules. The conformation of Trp31 in molecule A was suitable to allow the binding of peptide LAIYS, while that in molecule B prevented the entry of the ligand into the hydrophobic channel. The structure of the complex clearly showed that the OH group of Tyr of the inhibitor formed hydrogen bonds with both His48 N(delta1) and Asp49 O(delta1), while O(gamma)H of Ser was involved in a hydrogen bond with Trp31. Other peptide backbone atoms interact with protein through water molecules, while Leu, Ala and Ile form strong hydrophobic interactions with the residues of the hydrophobic channel.

Structure-function characterization of the human mitochondrial thiamin pyrophosphate transporter (hMTPPT; SLC25A19): Important roles for Ile(33), Ser(34), Asp(37), His(137) and Lys(291).

PubMed

Sabui, Subrata; Subramanian, Veedamali S; Kapadia, Rubina; Said, Hamid M

2016-08-01

Thiamin plays a critical role in cellular energy metabolism. Mammalian cells obtain the vitamin from their surroundings, converted it to thiamin pyrophosphate (TPP) in the cytoplasm, followed by uptake of TPP by mitochondria via a carrier-mediated process that involves the MTPPT (product of the SLC25A19 gene). Previous studies have characterized different physiological/biological aspects of the human MTPPT (hMTPPT), but less is known about structural features that are important for its function. Here, we used a protein-docking model ("Phyre2" and "DockingServer") to predict residues that may be important for function (substrate recognition) of the hMTPPT; we also examined the role of conserved positively-charged residues predicted ("PRALINE") to be in the trans-membrane domains (TMDs) in uptake of the negatively-charged TPP. Among the six residues predicted by the docking model (i.e., Thr(29), Arg(30), Ile(33), Ser(34), Asp(37) and Phe(298)), only Ile(33), Ser(34) and Asp(37) were found to be critical for function. While no change in translational efficiency/protein stability of the Ser(34) mutant was observed, both the Ile(33) and Asp(37) mutants showed a decrease in this parameter(s); there was also a decrease in the expression of the latter two mutants in mitochondria. A need for a polar residue at position 34 of the hMTPPT was evident. Our findings with the positively-charged residues (i.e., His(82), His(137), Lys(231) and Lys(291)) predicted in the TMD showed that His(137) and Lys(291) are important for function (via a role in proper delivery of the protein to mitochondria). These investigations provide important information about the structure-function relationship of the hMTPPT. Copyright © 2016 Elsevier B.V. All rights reserved.

Substance use Among University Undergraduates: A Study of Pattern and Beliefs in Ile-Ife.

PubMed

Fatoye, F O

2007-03-01

To determine the prevalence of substance use and to investigate the relationship between psychosocial variables and current use of psychoactive substances among university undergraduates. A cross-sectional survey of randomly selected undergraduates of the Obafemi Awolowo University, Ile Ife was carried out using the WHO drug use questionnaire. Alcohol, stimulants, hypnosedatives, tobacco and cannabis with current use prevalence rates of 20.2 %, 17.7%, 9.8%, 9.0% and 8.2 % respectively were the most commonly used substances. Inhalants/organic solvents, cocaine, heroin, hallucinogens and pethidine/morphine with current use rates of 3.2%, 2.6%, 2.2%, 1.0% and 0.5% respectively belonged to the 'low - use' category. However, these rates were marginally higher than most previous findings. Five variables (sex, polygamy, living outside the university campus, poor mental health and study difficulty), were significantly associated with the use of many of the substances. Also, perceived harmfulness was observed to be a possible deterrent to substance use and most users were engaged in the use of cheap and easily available substances. The observations are largely similar to those from other locations in Nigeria and may therefore be useful in preventive programmes.

Backbone and sidechain methyl Ile (δ1), Leu and Val chemical shift assignments of RDE-4 (1-243), an RNA interference initiation protein in C. elegans.

PubMed

Chiliveri, Sai Chaitanya; Kumar, Sonu; Marelli, Udaya Kiran; Deshmukh, Mandar V

2012-10-01

The RNAi pathway of several organisms requires presence of double stranded RNA binding proteins for functioning of Dicer in gene regulation. In C. elegans, a double stranded RNA binding protein, RDE-4 (385 aa, 44 kDa) recognizes long exogenous dsRNA and initiates the RNAi pathway. We have achieved complete backbone and stereospecific methyl sidechain Ile (δ1), Leu and Val chemical shifts of first 243 amino acids of RDE-4, namely RDE-4ΔC.

Technical Note: New ground-based FTIR measurements at Ile de La Réunion: observations, error analysis, and comparisons with independent data

NASA Astrophysics Data System (ADS)

Senten, C.; de Mazière, M.; Dils, B.; Hermans, C.; Kruglanski, M.; Neefs, E.; Scolas, F.; Vandaele, A. C.; Vanhaelewyn, G.; Vigouroux, C.; Carleer, M.; Coheur, P. F.; Fally, S.; Barret, B.; Baray, J. L.; Delmas, R.; Leveau, J.; Metzger, J. M.; Mahieu, E.; Boone, C.; Walker, K. A.; Bernath, P. F.; Strong, K.

2008-01-01

Ground-based high spectral resolution Fourier-transform infrared (FTIR) solar absorption spectroscopy is a powerful remote sensing technique to obtain information on the total column abundances and on the vertical distribution of various constituents in the atmosphere. This work presents results from two short-term FTIR measurement campaigns in 2002 and 2004, held at the (sub)tropical site Ile de La Réunion (21°S, 55°E). These campaigns represent the first FTIR observations carried out at this site. The results include total column amounts from the surface up to 100 km of ozone (O3), methane (CH4), nitrous oxide (N2O), carbon monoxide (CO), ethane (C2H6), hydrogen chloride (HCl), hydrogen fluoride (HF) and nitric acid (HNO3), as well as some vertical profile information for the first four mentioned trace gases. The data are characterised in terms of the vertical information content and associated error budget. In the 2004 time series, the seasonal increase of the CO concentration was observed by the end of October, along with a sudden rise that has been attributed to biomass burning events in southern Africa and Madagascar. This attribution was based on trajectory modeling. In the same period, other biomass burning gases such as C2H6 also show an enhancement in their total column amounts which is highly correlated with the increase of the CO total columns. The observed total column values for CO are consistent with correlative data from MOPITT (Measurements Of Pollution In The Troposphere). Comparisons between our ground-based FTIR observations and space-borne observations from ACE-FTS (Atmospheric Chemistry Experiment - Fourier Transform Spectrometer) and HALOE (Halogen Occultation Experiment) confirm the feasibility of the FTIR measurements at Ile de La Réunion.

AURKA Phe31Ile polymorphism interacted with use of alcohol, betel quid, and cigarettes at multiplicative risk of oral cancer occurrence.

PubMed

Lee, Chi-Pin; Chiang, Shang-Lun; Lee, Chien-Hung; Tsai, Yi-Shan; Wang, Zhi-Hong; Hua, Chun-Hung; Chen, Yuan-Chien; Tsai, Eing-Mei; Ko, Ying-Chin

2015-11-01

The expression levels of two DNA repair genes (CHAF1A and CHAF1B) and a chromosome segregation gene (AURKA) were susceptible to arecoline exposure, a major alkaloid of areca nut. We hypothesize that genetic variants of these genes might also be implicated in the risk of oral cancer and could be modified by substance use of betel quid or alcohol and cigarettes. A case-control study, which included 507 patients with oral cancer and 717 matched controls, was performed in order to evaluate the cancer susceptibility by the tagging single-nucleotide polymorphisms (tagSNPs) in AURKA, CHAF1A, and CHAF1B using a genotyping assay and gene-environment interaction analysis. The Phe31Ile polymorphism (rs2273535, T91A) of AURKA was significantly associated with an increased risk of oral cancer (odds ratio (OR) = 2.1, 95% confidence interval (CI) 1.2-3.5). The gene dosage of the 91A allele also showed a significant trend in risk of oral cancer (P = 0.008). Furthermore, we found the AURKA 91AA homozygote was modifiable by substance use of alcohol, betel quid, and cigarettes (ABC), leading to increased risk of oral cancer in an additive or a multiplicative model (combined effect indexes = 1.2-4.0 and 1.5-2.2, respectively). However, no association was observed between the genetic variants of CHAF1A or CHAF1B and oral cancer risk in the study. These findings reveal the functional Phe31Ile polymorphism tagSNP of AURKA may be a strong susceptibility gene in ABC-related oral cancer occurrence. The results of this betel-related oral cancer study provide the evidence of environment-gene interaction for early prediction and molecular diagnosis.

Ocean bottom characterestics between Iles Rodrigues and Chagos-Maldives Archepelago in western Indian Ocean

NASA Astrophysics Data System (ADS)

Longhinos, Biju; Thanu Iyer, Radhakrishnan; Mohan, Karthika

2014-05-01

The geological and geophysical complexities in Indian ocean basin, pointed out by many earlier workers remained unresolved. Instead, taking aid from stop gap arguments, the data has been construed to follow plate tectonics format. The concept of large igneous complexes emplaced through crustal drifting ( between the India and Mozambique) during later Mesozoic to Recent fail to address geophysical characteristics exhibited here. The geophysical signatures of the sub crustal part of the ocean here resemble to that of continental regions elsewhere. Granites, greenstones and mylonized gabbro, recovered from the western Indian ocean basin, rather give Late Pre- Cambrian and Paleozoic isotopic dates. Under this light, the present paper looks into the ocean bottom characteristics of a region between iles Rodrigues and Chagos- Maldives archipelago. The region has first order curvilienar fractures, with along which the crust has displaced more than 1000m. The sea-bottom topography of the region has been modeled in Geographical Information System environment using Modified ETOPO5 provided by National Institute of Oceanography. The spatial relationship of topography with gravity and magnetic data area are analysed visually and mathematically. The detail bathymetry, gravity and magnetic data give morphology similar to that of half graben formed on a felsic crust, which later has undergone basification / eclogitization through first order fracture zones.

Correlates of Self-Report of Rape Among Male School Adolescents in Ile-Ife, Nigeria.

PubMed

Ogunfowokan, Adesola A; Olagunju, Oluwayemisi E; Olajubu, Aanuoluwapo O; Faremi, Funmilola A; Oloyede, Ajoke S; Sharps, Phyllis W

2016-02-01

This study examined male adolescents' self-report of rape of adolescent girls and the socio-demographic variables that correlated with self-report of rape. Descriptive-correlational design was used and the study was conducted in five public senior secondary schools in Ile-Ife, Nigeria. Three hundred and thirty-eight male adolescents participated in the study. A structured questionnaire was used to collect data. Findings from the study revealed the mean age of the adolescent males to be 16 years, with the majority (73%) of them in the middle adolescent stage. Six percent of the adolescent males reported they had raped an adolescent girl in the past. Among the boys who reported rape, 55% reported they had raped their sexual partners, and 55% reported they had perpetrated gang rape. Smoking (p = .0001), alcohol consumption (p = .001), and birth order (p = .006) predicted self-report of rape. The coefficient of birth order showed that odds of self-report of rape by first-born male increases by 6 times compared with other children. Study findings also provided evidence that adolescent males are moving from lone rape to gang rape in intimate partner relationships. Male adolescents are important group to target in rape prevention programs. © The Author(s) 2014.

Türk Lise Öğrencilerinde Okul Terkinin Yordanması: Aracı ve Etkileşim Değişkenleri ile Bir Model Testi

PubMed Central

Özer, Arif; Gençtanirim, Dilek; Ergene, Tuncay

2011-01-01

Bu araştırmada ilk olarak, dürtüsel davranma ile okulu terk etme riski arasındaki ilişkiye disiplin cezası almanın, antisosyal davranışların ve sigara-alkol kullanımının aracılık edip etmediği incelenmiştir. İkinci olarak, öğretmen desteği ve antisosyal davranış etkileşiminin okulu terk etme riski üzerindeki etkisi test edilmiştir. Araştırma grubunu 2009-2010 yılında Ankara İlinde genel liselere devam eden 478 öğrenci oluşturmuştur. Sonuçlar okulu terk etme riskini aile ve arkadaş desteğinin azalttığını, dürtüsel davranmanın ise artırdığını göstermiştir. Ayrıca disiplin cezası, alkol-sigara kullanma ve antisosyal davranışlar okulu terk etme riskini artıran aracı değişkenlerdir. Antisosyal davranışlarla okulu terk etme arasındaki ilişki öğretmen desteğine bağlı olarak değişmektedir. Öğrencilerin cinsiyet ve başarıları ile okulu terk etme riskleri arasında anlamlı bir ilişki bulunmamaktadır. PMID:22003257

A novel Ile1455Thr variant in the skeletal muscle sodium channel alpha-subunit in a patient with a severe adult-onset proximal myopathy with electrical myotonia and a patient with mild paramyotonia phenotype.

PubMed

Bednarz, Marcin; Stunnenberg, Bas C; Kusters, Benno; Kamsteeg, Erik-Jan; Saris, Christiaan G; Groome, James; Winston, Vern; Meola, Giovanni; Jurkat-Rott, Karin; Voermans, Nicol C

2017-02-01

In sodium channelopathies, a severe fixed myopathy caused by a dominant mutation is rare. We describe two unrelated patients with a novel variant, p.Ile1455Thr, with phenotypes of paramyotonia in one case and fixed proximal myopathy with latent myotonia in another. In-vitro whole cell patch-clamp studies show that the mutation slows inactivation and accelerates recovery, in line with other paramyotonia variants with destabilized fast inactivation as pathomechanism. Additionally, p.IleI1455 causes a loss-of-function by reduced membrane insertion, right-shift of activation, and slowed kinetics. Molecular dynamics simulations comparing wild type and mutant Nav1.4 showed that threonine substitution hindered D4S4 mobility in response to membrane depolarization, consistent with effects of the mutation on channel inactivation. The fixed myopathy is likely to be associated to gain-of-function leading to sodium accumulation, regional edema, T-tubular swelling and mitochondrial stress. A possible contribution of the loss-of-function features towards myotonia and myopathy is discussed. Copyright © 2016. Published by Elsevier B.V.

Technical Note: New ground-based FTIR measurements at Ile de La Réunion: observations, error analysis, and comparisons with independent data

NASA Astrophysics Data System (ADS)

Senten, C.; de Mazière, M.; Dils, B.; Hermans, C.; Kruglanski, M.; Neefs, E.; Scolas, F.; Vandaele, A. C.; Vanhaelewyn, G.; Vigouroux, C.; Carleer, M.; Coheur, P. F.; Fally, S.; Barret, B.; Baray, J. L.; Delmas, R.; Leveau, J.; Metzger, J. M.; Mahieu, E.; Boone, C.; Walker, K. A.; Bernath, P. F.; Strong, K.

2008-07-01

Ground-based high spectral resolution Fourier-transform infrared (FTIR) solar absorption spectroscopy is a powerful remote sensing technique to obtain information on the total column abundances and on the vertical distribution of various constituents in the atmosphere. This work presents results from two FTIR measurement campaigns in 2002 and 2004, held at Ile de La Réunion (21° S, 55° E). These campaigns represent the first FTIR observations carried out at a southern (sub)tropical site. They serve the initiation of regular, long-term FTIR monitoring at this site in the near future. To demonstrate the capabilities of the FTIR measurements at this location for tropospheric and stratospheric monitoring, a detailed report is given on the retrieval strategy, information content and corresponding full error budget evaluation for ozone (O3), methane (CH4), nitrous oxide (N2O), carbon monoxide (CO), ethane (C2H6), hydrogen chloride (HCl), hydrogen fluoride (HF) and nitric acid (HNO3) total and partial column retrievals. Moreover, we have made a thorough comparison of the capabilities at sea level altitude (St.-Denis) and at 2200 m a.s.l. (Maïdo). It is proved that the performances of the technique are such that the atmospheric variability can be observed, at both locations and in distinct altitude layers. Comparisons with literature and with correlative data from ozone sonde and satellite (i.e., ACE-FTS, HALOE and MOPITT) measurements are given to confirm the results. Despite the short time series available at present, we have been able to detect the seasonal variation of CO in the biomass burning season, as well as the impact of particular biomass burning events in Africa and Madagascar on the atmospheric composition above Ile de La Réunion. We also show that differential measurements between St.-Denis and Maïdo provide useful information about the concentrations in the boundary layer.

Occult Hepatitis B virus infection in previously screened, blood donors in Ile-Ife, Nigeria: implications for blood transfusion and stem cell transplantation.

PubMed

Olotu, Amadin A; Oyelese, Adesola O; Salawu, Lateef; Audu, Rosemary A; Okwuraiwe, Azuka P; Aboderin, Aaron O

2016-05-05

Hepatitis B virus (HBV) transmission through blood transfusion is reduced by screening for hepatitis B surface antigen (HBsAg). However this method cannot detect the presence of occult hepatitis B virus infection. This study sought to determine the prevalence of occult hepatitis B virus infection among blood donors in Ile-Ife, Nigeria. For the first time in Nigeria we employed an automated real-time PCR- method to investigate the prevalence of occult HBV in blood donors. Blood donors screened with HBsAg immunochromatographic rapid test kits at the blood transfusion units of two hospitals and found to be negative were recruited into the study. Questionnaires to elicit risk factors for HBV infection were administered and then 10 ml of blood was collected from each donor. Plasma samples obtained from these HBsAg negative blood donors were screened again for HBsAg using an enzyme-linked immunosorbent assay (ELISA) method, and those found negative were screened for the presence of total antibody to the HBV core antigen (anti-HBc) using ELISA method. Those positive to anti-HBc were then tested for HBV DNA, using an automated real-time PCR method. Five hundred and seven blood donors found HBsAg negative by immunochromatographic rapid test kits at both blood transfusion units, were tested for HBsAg using ELISA and 5 (1 %) were HBsAg positive. The 502 found negative were tested for anti-HBc and 354 (70.5 %) were found positive implying previous exposure to HBV and 19 (5.4 %) of the 354 anti-HBc positive had HBV DNA signifying occult HBV infection. No risk factors were found to be associated with the presence of HBV DNA among those who tested positive. Occult HBV infection exists in blood donors in Ile-Ife, Nigeria and the use of HBsAg alone for screening prospective donors will not eliminate the risk of HBV transmission in blood transfusion or stem cell transplantation.

Coral reef monitoring in the Iles Eparses, Mozambique Channel (2011-2013)

NASA Astrophysics Data System (ADS)

Chabanet, P.; Bigot, L.; Nicet, J.-B.; Durville, P.; Massé, L.; Mulochau, T.; Russo, C.; Tessier, E.; Obura, D.

2016-04-01

Monitoring of coral reefs has become a major tool for understanding how they are changing, and for managing them in a context of increasing degradation of coastal ecosystems. The Global Coral Reef Monitoring Network (GCRMN) has near-global coverage, but there are few remote sites free of direct human impact that can serve as reference sites. This study provides baseline data for the French Iles Eparses in the Mozambique Channel, Western Indian Ocean (WIO), whose coral reefs are little known owing to their limited accessibility, and have been free from fishing pressure for over 20 years. Surveys of coral reef health and fish community structure were undertaken at four of the islands (Europa, Bassas da India, Juan de Nova and Glorieuses) in 2011-2013. Monitoring was conducted using standardized GCRMN methods for benthos and fish communities, at the highest taxonomic level. Benthic cover showed a latitudinal gradient, with higher coral cover and conversely lower algae cover (60% and 14% respectively) in the south of the Mozambique Channel. This could be due to the geomorphology of the islands, the latitudinal temperature gradient, and/or the history of chronic stress and bleaching events during the last decades. Fish also showed a latitudinal gradient with higher diversity in the north, in a center of diversity for the western Indian Ocean already recognized for corals. An exceptional biomass fish was recorded (approximately 3500 kg/ha excluding sharks, compared to a maximum of 1400 kg/ha elsewhere in the WIO). The presence of large predators and sharks in all the islands as well as the absence of fleshy benthic algae were indicators of the good health of the reef systems. Nevertheless, these islands are beginning to experience illegal fishing, particularly in the north of the Mozambique Channel, demonstrating their vulnerability to exploitation and the need to protect them as reference sites for coral reef studies, including of climate change impacts, for the region

Plankton communities in the five Iles Eparses (Western Indian Ocean) considered to be pristine ecosystems

NASA Astrophysics Data System (ADS)

Bouvy, M.; Got, P.; Domaizon, I.; Pagano, M.; Leboulanger, C.; Bouvier, C.; Carré, C.; Roques, C.; Dupuy, C.

2016-04-01

Coral reef environments are generally recognized as being the most threatened of marine ecosystems. However, it is extremely difficult to distinguish the effects of climate change from other forcing factors, mainly because it is difficult to study ecosystems that are isolated from human pressure. The five Iles Eparses (Scattered Islands) are located in the Western Indian Ocean (WIO) and can be considered to be "pristine" ecosystems not subject to anthropogenic pressure. This study characterized their plankton assemblages for the first time, by determining the abundances of microbial (virus, bacteria, heterotrophic protists and phytoplankton) and metazooplankton communities in various lagoon and ocean sites around each island. The Europa lagoon has extensive, productive mangrove forests, which have the highest nutrient concentrations (nitrogen forms, dissolved organic carbon) and whose microbial communities present a peculiar structure and functioning. By means of bioassay experiments, we observed that bacterial production and growth rates are higher in Europa than those reported for the other islands. Tromelin, which lies outside the Mozambique Channel, had the lowest biological productivity, nutrient concentrations, and bacterial growth rates. Multivariate analysis indicated that distinct microbial assemblages occur in association to varying nutrient concentrations. Molecular fingerprinting showed clear discrimination of the structure of the archaea, bacteria and eukaryotes community between the sites. Our results suggest that the geographical distance can influence the diversity of dominant microbial taxa in the WIO.

Composition and Source Identification of Chemical Species in Dust from Selected Indoor Environments in Ile-Ife, Nigeria

NASA Astrophysics Data System (ADS)

Ogundele, Lasun T.; Olasinde, Roseline T.; Owoade, Oyediran K.; Olise, Felix S.

2018-05-01

This study presents the elemental compositions and concentrations of indoor dust and identifies the major sources in some selected indoor environments in Ile-Ife, Nigeria. The dust samples were collected from 16 indoor environments comprising offices, churches, residential and staff quarters using a cyclonic high power vacuum cleaner. The dust samples were analyzed for elemental concentrations using x-ray fluorescences. The data sets were analyzed for the possible sources and their contributions using Principal Component Factor Analysis (PCFA). The result showed that dust samples contained several elements: K, Ca, Ti, Mn, Fe, Ni, Cu, Zn, Ga, As, Rb, Sr, Se, Zr, V, and Sc. The PCFA identified three factors with the percentage variance of 92, 77, 71 and 68%, for the office, church, residential, and staff quarters, respectively, for the combined elemental data of each of the site classes. The identified sources were track-in-soil, road and windblown soil dust, paint debris, household dust from personal care materials, cooking, and cleaning activities. The unintentional track-in-soil due to mobility of the occupants, structural materials, and outdoor air was the major sources contributing to the indoor dust.

Autosomal dominant Carvajal plus syndrome due to the novel desmoplakin mutation c.1678A > T (p.Ile560Phe).

PubMed

Finsterer, Josef; Stöllberger, Claudia; Wollmann, Eva; Dertinger, Susanne; Laccone, Franco

2016-09-01

Carvajal syndrome is an autosomal dominant or autosomal recessive disorder, manifesting with dilated cardiomyopathy, woolly hair, and palmoplantar keratoma. Additional manifestations can be occasionally found. Carvajal syndrome may be due to mutations in the desmocollin-2, desmoplakin, or plakophilin-2 gene. We report a family with Carvajal syndrome which additionally presented with hypoacusis, noncompaction, recurrent pharyngeal infections, oligodontia, and recurrent diarrhoea. Father and brother were also affected and had died suddenly, the father despite implantation of a cardioverter defibrillator (ICD). Genetic studies revealed the novel pathogenic mutation c.1678A > T in the desmoplakin gene resulting in the amino acid change Ile to Phe at position 560 in the index case and her brother. The index case underwent ICD implantation recently. Phenotypic manifestations of Carvajal syndrome are even broader than so far anticipated, the number of mutations in the desmoplakin gene responsible for Carvajal syndrome is still increasing, and these patients require implantation of an ICD as soon as their diagnosis is established.

Sex-specific effect of CPB2 Ala147Thr but not Thr325Ile variants on the risk of venous thrombosis: A comprehensive meta-analysis

PubMed Central

Zwingerman, Nora; Medina-Rivera, Alejandra; Kassam, Irfahan; Wilson, Michael D.; Morange, Pierre-Emmanuel; Trégouët, David-Alexandre; Gagnon, France

2017-01-01

Background Thrombin activatable fibrinolysis inhibitor (TAFI), encoded by the Carboxypeptidase B2 gene (CPB2), is an inhibitor of fibrinolysis and plays a role in the pathogenesis of venous thrombosis. Experimental findings support a functional role of genetic variants in CPB2, while epidemiological studies have been unable to confirm associations with risk of venous thrombosis. Sex-specific effects could underlie the observed inconsistent associations between CPB2 genetic variants and venous thrombosis. Methods A comprehensive literature search was conducted for associations between Ala147Thr and Thr325Ile variants with venous thrombosis. Authors were contacted to provide sex-specific genotype counts from their studies. Combined and sex-specific random effects meta-analyses were used to estimate a pooled effect estimate for primary and secondary genetic models. Results A total of 17 studies met the inclusion criteria. A sex-specific meta-analysis applying a dominant model supported a protective effect of Ala147Thr on venous thrombosis in females (OR = 0.81, 95%CI: 0.68,0.97; p = 0.018), but not in males (OR = 1.06, 95%CI:0.96–1.16; p = 0.263). The Thr325Ile did not show a sex-specific effect but showed variation in allele frequencies by geographic region. A subgroup analysis of studies in European countries showed decreased risk, with a recessive model (OR = 0.83, 95%CI:0.71–0.97, p = 0.021) for venous thrombosis. Conclusions A comprehensive literature review, including unpublished data, provided greater statistical power for the analyses and decreased the likelihood of publication bias influencing the results. Sex-specific analyses explained apparent discrepancies across genetic studies of Ala147Thr and venous thrombosis. While, careful selection of genetic models based on population genetics, evolutionary and biological knowledge can increase power by decreasing the need to adjust for testing multiple models. PMID:28552956

Sex-specific effect of CPB2 Ala147Thr but not Thr325Ile variants on the risk of venous thrombosis: A comprehensive meta-analysis.

PubMed

Zwingerman, Nora; Medina-Rivera, Alejandra; Kassam, Irfahan; Wilson, Michael D; Morange, Pierre-Emmanuel; Trégouët, David-Alexandre; Gagnon, France

2017-01-01

Thrombin activatable fibrinolysis inhibitor (TAFI), encoded by the Carboxypeptidase B2 gene (CPB2), is an inhibitor of fibrinolysis and plays a role in the pathogenesis of venous thrombosis. Experimental findings support a functional role of genetic variants in CPB2, while epidemiological studies have been unable to confirm associations with risk of venous thrombosis. Sex-specific effects could underlie the observed inconsistent associations between CPB2 genetic variants and venous thrombosis. A comprehensive literature search was conducted for associations between Ala147Thr and Thr325Ile variants with venous thrombosis. Authors were contacted to provide sex-specific genotype counts from their studies. Combined and sex-specific random effects meta-analyses were used to estimate a pooled effect estimate for primary and secondary genetic models. A total of 17 studies met the inclusion criteria. A sex-specific meta-analysis applying a dominant model supported a protective effect of Ala147Thr on venous thrombosis in females (OR = 0.81, 95%CI: 0.68,0.97; p = 0.018), but not in males (OR = 1.06, 95%CI:0.96-1.16; p = 0.263). The Thr325Ile did not show a sex-specific effect but showed variation in allele frequencies by geographic region. A subgroup analysis of studies in European countries showed decreased risk, with a recessive model (OR = 0.83, 95%CI:0.71-0.97, p = 0.021) for venous thrombosis. A comprehensive literature review, including unpublished data, provided greater statistical power for the analyses and decreased the likelihood of publication bias influencing the results. Sex-specific analyses explained apparent discrepancies across genetic studies of Ala147Thr and venous thrombosis. While, careful selection of genetic models based on population genetics, evolutionary and biological knowledge can increase power by decreasing the need to adjust for testing multiple models.

Characterization of Ile-His-Arg-Phe, a novel rice-derived vasorelaxing peptide with hypotensive and anorexigenic activities.

PubMed

Kontani, Noriyasu; Omae, Ryo; Kagebayashi, Tomomi; Kaneko, Kentaro; Yamada, Yuko; Mizushige, Takafumi; Kanamoto, Ryuhei; Ohinata, Kousaku

2014-02-01

Recently, we found that dipeptide Arg-Phe (RF) had cholecystokinin (CCK)-dependent vasorelaxing activity. The RF sequence is often observed in the primary structure of natural food proteins. In the current study, we investigated enzymatic conditions for the release of RF-related peptides from rice glutelin, a major storage protein, using gastrointestinal proteases. RF-related peptides were then characterized. It was found that RF and Ile-His-Arg-Phe (IHRF) were released in the chymotrypsin digest of the partial structure of rice glutelin. We then focused on previously unidentified IHRF, corresponding to rice glutelin(155-158). IHRF had vasorelaxing activity in the mesenteric artery of spontaneous hypertensive rats (SHRs). Orally administered IHRF lowered systolic blood pressure in SHRs. The antihypertensive activity of IHRF was more potent and long-lasting than that of RF. IHRF-induced vasorelaxing activity was not blocked by inhibitors of nitric oxide synthase and cyclooxygenase, but by an antagonist for CCK₁ receptor. IHRF also had CCK-like suppressive activities in food intake and gastrointestinal transit. IHRF increased intracellular Ca²⁺ flux and CCK release in the enteroendocrine cell STC-1. IHRF, a novel CCK-dependent vasorelaxing peptide, decreases both blood pressure and food intake in rodents. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Monitoring austral and cyclonic swells in the "Iles Eparses" (Mozambique channel) from microseismic noise

NASA Astrophysics Data System (ADS)

Barruol, Guilhem; Davy, Céline; Fontaine, Fabrice R.; Schlindwein, V.; Sigloch, K.

2016-04-01

We deployed five broadband three-components seismic stations in the Iles Eparses in the south-west Indian Ocean and on Mayotte Island, between April 2011 and January 2014. These small and remote oceanic islands suffer the effects of strong ocean swells that affect their coastal environments but most islands are not instrumented by wave gauges to characterize the swells. However, wave action on the coast causes high levels of ground vibrations in the solid earth, so-called microseismic noise. We use this link between the solid earth and ocean wave activity to quantify the swells locally. Spectral analyses of the continuous seismic data show clear peaks in the 0.05-0.10 Hz frequency band (periods between 10 and 20 s), corresponding to the ocean wave periods of the local swells. We analyze an example of austral swell occurring in August 2013 and a cyclonic event (Felleng) that developed in January 2013, and quantify the ground motion at each station induced by these events. In both cases, we find a linear polarization in the horizontal plane with microseismic amplitude directly correlated to the swell height (as predicted by the global swell model WaveWatchIII), and a direction of polarization close to the predicted swell propagation direction. Although this analysis has not been performed in real time, it demonstrates that terrestrial seismic stations can be efficiently used as wave gauges, and are particularly well suited for quantifying extreme swell events. This approach may therefore provide useful and cheaper alternatives to wave buoys for monitoring swells and the related environmental processes such as beach erosion or coral reef damages.

Comparative evaluation of perceptions of dental students to three methods of teaching in Ile-Ife, Nigeria.

PubMed

Esan, T A; Oziegbe, E O

2015-12-01

The World Health Organization in 1994 recommended that dental education should be problem based, socially and culturally relevant, and community oriented. To explore the perceptions of Pre-phase II (pre-clinical II) dental students on three methods of teaching used during two academic sessions. All part IV dental students in two consecutive sessions undergoing pre phase II course in the Faculty of Dentistry, Obafemi Awolowo University, Ile-Ife were recruited into the study. Three different modes of teaching that is, Problem based learning (PBL), hybrid PBL and traditional teaching were used to teach the students. A twenty two itemed anonymous questionnaire on a five point Likert scale was administered to the students at the end of the course. Six perceived factors were extracted from the questionnaire using factor analysis. There was a statistically significant difference (p < 0.01) between the overall mean of PBL method compared to the other methods of teaching. The perceived factor "communication with peers" had the highest mean score for PBL in both sessions (4.57 ± 0.58 and 4.09 ± 0.93 respectively). However, PBL method was very helpful in all the six perceived factors while the students perceived that the traditional method of teaching was not helpful in "interaction with tutors" and "challenge to critical thinking". The findings showed that students preferred the PBL method to other forms of teaching. PBL enhanced the students' communication skill, was very useful as pedagogic tool and improved their critical thinking.

Phenotypic similarities and differences in patients with a p.Met112Ile mutation in SOX10.

PubMed

Pingault, Veronique; Pierre-Louis, Laurence; Chaoui, Asma; Verloes, Alain; Sarrazin, Elisabeth; Brandberg, Goran; Bondurand, Nadege; Uldall, Peter; Manouvrier-Hanu, Sylvie

2014-09-01

Waardenburg syndrome (WS) is characterized by an association of pigmentation abnormalities and sensorineural hearing loss. Four types, defined on clinical grounds, have been delineated, but this phenotypic classification correlates imperfectly with known molecular anomalies. SOX10 mutations have been found in patients with type II and type IV WS (i.e., with Hirschsprung disease), more complex syndromes, and partial forms of the disease. The phenotype induced by SOX10 mutations is highly variable and, except for the neurological forms of the disease, no genotype-phenotype correlation has been characterized to date. There is no mutation hotspot in SOX10 and most cases are sporadic, making it particularly difficult to correlate the phenotypic and genetic variability. This study reports on three independent families with SOX10 mutations predicted to result in the same missense mutation at the protein level (p.Met112Ile), offering a rare opportunity to improve our understanding of the mechanisms underlying phenotypic variability. The pigmentation defects of these patients are very similar, and the neurological symptoms showed a somewhat similar evolution over time, indicating a potential partial genotype-phenotype correlation. However, variability in gastrointestinal symptoms suggests that other genetic factors contribute to the expression of these phenotypes. No correlation between the rs2435357 polymorphism of RET and the expression of Hirschsprung disease was found. In addition, one of the patients has esophageal achalasia, which has rarely been described in WS. © 2014 Wiley Periodicals, Inc.

Phenotypic similarities and differences in patients with a p.Met112Ile mutation in SOX10

PubMed Central

Pingault, Veronique; Pierre-Louis, Laurence; Chaoui, Asma; Verloes, Alain; Sarrazin, Elisabeth; Brandberg, Goran; Bondurand, Nadege; Uldall, Peter; Manouvrier-Hanu, Sylvie

2014-01-01

Waardenburg syndrome (WS) is characterized by an association of pigmentation abnormalities and sensorineural hearing loss. Four types, defined on clinical grounds, have been delineated, but this phenotypic classification correlates imperfectly with known molecular anomalies. SOX10 mutations have been found in patients with type II and type IV WS (i.e., with Hirschsprung disease), more complex syndromes, and partial forms of the disease. The phenotype induced by SOX10 mutations is highly variable and, except for the neurological forms of the disease, no genotype-phenotype correlation has been characterized to date. There is no mutation hotspot in SOX10 and most cases are sporadic, making it particularly difficult to correlate the phenotypic and genetic variability. This study reports on three independent families with SOX10 mutations predicted to result in the same missense mutation at the protein level (p.Met112Ile), offering a rare opportunity to improve our understanding of the mechanisms underlying phenotypic variability. The pigmentation defects of these patients are very similar, and the neurological symptoms showed a somewhat similar evolution over time, indicating a potential partial genotype-phenotype correlation. However, variability in gastrointestinal symptoms suggests that other genetic factors contribute to the expression of these phenotypes. No correlation between the rs2435357 polymorphism of RET and the expression of Hirschsprung disease was found. In addition, one of the patients has esophageal achalasia, which has rarely been described in WS. PMID:24845202

Knowledge Attitude and Practices Toward Lassa Fever Control and Prevention Among Residents of Ile-Ife, Southwest Nigeria.

PubMed

Olowookere, S A; Adegbenro, C A; Idowu, A; Omisore, A G; Shabi, O M; Ikem, U R; Ekwere, G A; Oderinde, I F

2017-01-01

Lassa fever had been reported as a cause of death especially in endemic parts of Nigeria. This study assessed the knowledge, attitude, and practices toward Lassa fever control and prevention among residents of Ile-Ife, southwest Nigeria. Descriptive cross-sectional study was conducted among consenting randomly selected adults using an interviewer administered questionnaire. Data were analyzed using descriptive and inferential statistics. A total of 400 questionnaires with completed data were analyzed (response rate 96%). Majority, 207 (51.8%), were males while 193 (48.2%) were females. Most, 234 (58.5%), had tertiary education while 148 (37%) had secondary education. Fifty-nine percent had heard of Lassa fever with radio as their major source of information. About 76% had inadequate knowledge, 54% had negative attitude while 51% had poor practice toward Lassa fever. Determinants of knowledge of Lassa fever include having higher education (Adjusted Odd Ratio (AOR) = 11.49, 95% CI [3.10, 42.69], p = .0001), being in civil service (AOR = 0.22, 95% CI [0.09, 0.51], p = .01), and earning higher income (AOR = 4.23, 95% CI [2.61, 6.84], p = .0001). In conclusion, the knowledge, attitude, as well as preventive practices to Lassa fever were poor. It is necessary to increase public education and improve hygienic practices.

Co-occurrence of hypertrophic cardiomyopathy and myeloproliferative disorder in a neonate with Noonan syndrome carrying Thr73Ile mutation in PTPN11.

PubMed

Yagasaki, Hideaki; Nakane, Takaya; Hasebe, Youhei; Watanabe, Atsushi; Kise, Hiroaki; Toda, Takako; Koizumi, Keiichi; Hoshiai, Minako; Sugita, Kanji

2015-12-01

Most cases of Noonan syndrome (NS) result from mutations in one of the RAS-MAPK signaling genes, including PTPN11, SOS1, KRAS, NRAS, RAF1, BRAF, SHOC2, MEK1 (MAP2K1), and CBL. Cardiovascular diseases of varying severity, such as pulmonary stenosis and hypertrophic cardiomyopathy (HCM), are common in NS patients. RAF1 mutations are most frequent in NS with HCM, while PTPN11 mutations are also well known. Thr73Ile is a gain-of-function mutation of PTPN11, which has been highly associated with juvenile myelomonocytic leukemia and NS/myeloproliferative disease (MPD), but has not previously been reported in HCM. Here, we report a Japanese female infant with NS carrying the PTPN11 T73I mutation with NS/MPD, complete atrio-ventricular septal defect, and rapidly progressive HCM. No other HCM-related mutations were detected in PTPN11, RAF1, KRAS, BRAF, and SHOC2. This patient provides additional information regarding the genotype-phenotype correlation for PTPN11 T73I mutation in NS. © 2015 Wiley Periodicals, Inc.

Application of a JA-Ile Biosynthesis Inhibitor to Methyl Jasmonate-Treated Strawberry Fruit Induces Upregulation of Specific MBW Complex-Related Genes and Accumulation of Proanthocyanidins.

PubMed

Delgado, Laura D; Zúñiga, Paz E; Figueroa, Nicolás E; Pastene, Edgar; Escobar-Sepúlveda, Hugo F; Figueroa, Pablo M; Garrido-Bigotes, Adrián; Figueroa, Carlos R

2018-06-13

Fleshy fruits are an important source of anthocyanins and proanthocyanidins (PAs), which protect plants against stress, and their consumption provides beneficial effects for human health. In strawberry fruit, the application of exogenous methyl jasmonate (MeJA) upregulates anthocyanin accumulation, although the relationship between the jasmonate pathway and anthocyanin and PA biosynthesis in fruits remains to be understood. Anthocyanin and PA accumulation is mainly regulated at the transcriptional level through R2R3-MYB and bHLH transcription factors in different plant species and organs. Here, the effect of jarin-1, a specific inhibitor of bioactive JA (jasmonoyl-isoleucine, JA-Ile) biosynthesis, on anthocyanin and PA accumulation was evaluated during strawberry ( Fragaria × ananassa ) fruit development using an in vitro ripening system for 48 h. Also, we observed the effects of MeJA and the application of jarin-1 to MeJA-treated fruits (MeJA + jarin-1 treatment). We assessed changes of expression levels for the JA-Ile and MeJA biosynthetic ( FaJAR1.2 and FaJMT ), JA signaling-related ( FaMYC2 and FaJAZ1 ), MYB-bHLH-WD40 (MBW) complex-related ( FabHLH3/33 , FaMYB9/10/11 , and repressor FaMYB1 ), and anthocyanin and PA biosynthetic (FaANS , FaUFGT , FaANR , and FaLAR ) genes. In addition, the promoter region of MBW complex-related MYB genes was isolated and sequenced. We found a higher redness of strawberry fruit skin and anthocyanin content in MeJA-treated fruits with respect to jarin-1-treated ones concomitant with an upregulation of FaANS and FaUFGT genes. Inversely, the PA content was higher in jarin-1- and MeJA + jarin-1-treated than in MeJA-treated fruits. MeJA + jarin-1 treatment resulted in an upregulation of FaANR and associated transcription factors such as FabHLH33 and FaMYB9/11 along with FaJMT and FaJAR1.2 . Finally, we found JA-responsive elements in the promoter regions of FaMYB1/9/10/11 genes. It is proposed that PA biosynthesis-related genes

Identification of sperm subpopulations with defined motility characteristics in ejaculates from Ile de France rams.

PubMed

Bravo, J A; Montanero, J; Calero, R; Roy, T J

2011-11-01

The aims of this study were to identify different motile sperm subpopulations in fresh ejaculates from six Ile de France rams, by using a computer-assisted sperm motility analysis (CASA) system, and to evaluate the effects of individual ram and season on population distribution. Overall sperm motility and individual kinematic parameters of motile spermatozoa were evaluated for 125,312 spermatozoa, defined by curvilinear velocity (VCL), linear velocity (VSL), average path velocity (VAP), linearity coefficient (LIN), straightness coefficient (STR), wobble coefficient (WOB), mean amplitude of lateral head displacement (ALH) and frequency of head displacement (BCF). A multivariate cluster analysis was carried out to classify these spermatozoa into a reduced number of subpopulations according to their movement patterns. The statistical analysis clustered the whole motile sperm population into five separate groups: subpopulation 1, constituted by rapid, progressive and non sinuous spermatozoa (VCL=126.41 μm/s, STR=92.87% and LIN=86.47%); subpopulation 2, characterized by progressive spermatozoa with moderate velocity (VCL=74.74 μm/s and STR=84.03%); subpopulation 3, represented by rapid, progressive and sinuous spermatozoa (VCL=130.45 μm/s, STR=76.02% and LIN=47.68%); subpopulation 4 represents rapid nonprogressive spermatozoa (VCL=128.69 μm/s and STR=44.09%); subpopulation 5 includes poorly motile, nonprogressive spermatozoa with a very irregular trajectory (VCL=36.81 μm/s and STR=47.04%). Our results show the existence of five subpopulations of motile spermatozoa in ram ejaculates. The frequency distribution of spermatozoa within subpopulations was quite similar for the six rams, and the five subpopulations turned out to be very stable along seasons. Copyright © 2011 Elsevier B.V. All rights reserved.

How does Pseudomonas fluorescens avoid suicide from its antibiotic pseudomonic acid?: Evidence for two evolutionarily distinct isoleucyl-tRNA synthetases conferring self-defense.

PubMed

Yanagisawa, Tatsuo; Kawakami, Makoto

2003-07-11

Two isoleucyl-tRNA synthetases (IleRSs) encoded by two distinct genes (ileS1 and ileS2) were identified in pseudomonic acid (mupirocin)-producing Pseudomonas fluorescens. The most striking difference between the two IleRSs (IleRS-R1 and IleRS-R2) is the difference in their abilities to resist pseudomonic acid. Purified IleRS-R2 showed no sensitivity to pseudomonic acid even at a concentration of 5 mm, 105 times higher than the Ki value of IleRS-R1. The amino acid sequence of IleRS-R2 exhibits eukaryotic features that are originally found in eukaryotic proteins. Escherichia coli cells transformed with the ileS2 gene exerted pseudomonic acid resistance more than did those transformed with ileS1. Cells transformed with both genes became almost as resistant as P. fluorescens. These results suggest that the presence of IleRS-R2 could be the major reason why P. fluorescens is intrinsically resistant to the antibiotic. Here we suggest that the evolutionary scenario of the eukaryotic ileS2 gene can be explained by gene acquisition and that the pseudomonic acid producer may have maintained the ileS2 gene to protect itself from pseudomonic acid.

Hepatobiliary Ultrasonographic Abnormalities in Adult Patients with Sickle Cell Anaemia in Steady State in Ile-Ife, Nigeria.

PubMed

Oguntoye, Oluwatosin O; Ndububa, Dennis A; Yusuf, Musah; Bolarinwa, Rahman A; Ayoola, Oluwagbemiga O

2017-01-01

Sickle cell anaemia (SCA) is associated with structural manifestations in the hepatobiliary axis. This study aimed to investigate the hepatobiliary ultrasonographic abnormalities in adult patients with sickle cell anaemia in steady state attending the Haematology clinic of a federal tertiary health institution in Ile-Ife, Nigeria. Basic demographic data as well as right upper abdominal quadrant ultrasonography of 50 consecutive sickle cell anaemia patients were compared with those of 50 age- and sex-matched subjects with HbAA as controls. Each of the study groups (patients and controls) comprised of 21 (42%) males and 29 (58%) females. The age range of the patients was 18-45 years with a mean (±SD) of 27.6±7.607 years, while that of the controls was 21-43 years with a mean (±SD) of 28.0±5.079 years (p=0.746). Amongst the patients, 32 (64%) had hepatomegaly, 15 (30%) cholelithiasis and 3 (6%) biliary sludge. Fourteen (28%) of the patients had normal hepatobiliary ultrasound findings. In the control group, one (2%) person had cholelithiasis, one (2%) biliary sludge, one (2%) fatty liver and none hepatomegaly. Forty-seven (94%) of the controls had normal hepatobiliary ultrasound findings. There was a statistically significant difference in the prevalence of hepatomegaly and cholelithiasis between the patients and controls (p value <0.001 for both comparisons). In this study, hepatomegaly, cholelithiasis and biliary sludge were the most common hepatobiliary ultrasound findings in patients with sickle cell anaemia. Ultrasonography is a useful tool for assessing hepatobiliary abnormalities in patients with sickle cell anaemia.

Respiratory symptoms, lung function and particulate matter pollution in residential indoor environment in Ile-Ife, Nigeria

PubMed Central

Ibhafidon, Lawrence I.; Obaseki, Daniel O.; Erhabor, Gregory E.; Akor, Alexander A.; Irabor, Iziegbe; Obioh, IB

2014-01-01

Introduction: Particulate air pollution is associated with increased incidence of respiratory symptoms and decreased pulmonary, function but the relative impact of pollution from different domestic energy sources is not well-known or studied. Aim: The study was aimed at assessing the association between particulate concentrations, respiratory symptoms and lung function. Materials and Methods: It was a cross-sectional study comprised of randomly selected residents of three communities. These communities were selected according to the predominant type of fuel used for household cooking which were: firewood, kerosene and liquefied petroleum gas (LPG). Assessment of the indoor PM10 levels was done by filtration using the Gent stacked filter unit sampler for collection of atmospheric aerosol in two size fractions (PM2.5 and PM10). The Medical Research Council (MRC) questionnaire was administered followed by spirometry test. Results: The mean PM10 concentration in participants using LPG, kerosene and firewood was 80.8 ± 9.52 μg/m3, 236.9 ± 26.5 μg/m3 and 269 ±93.7 μg/m3, respectively. The mean age and height-adjusted percent predicted forced expiratory volumes in 1 s (FEV1) for men were 127 ± 7, 109 ± 40 and 91 ± 20 and for women were 129 ± 13, 115 ± 14, 100 ± 14 in users of LPG, kerosene and firewood, respectively. A similar trend was found in the forced vital capacity (FVCs). Users of firewood had significantly lower FEV1 and FVC compared with LPG users (P < 0.05). The participants using firewood had the highest prevalence of pulmonary and non-pulmonary symptoms (57.1%), whereas subjects using LPG had the lowest (23.8%). Conclusion: There are high levels of particulate matter pollutions with respiratory effects in residential indoor environments in Ile-Ife, Nigeria PMID:24970970

Respiratory symptoms, lung function and particulate matter pollution in residential indoor environment in Ile-Ife, Nigeria.

PubMed

Ibhafidon, Lawrence I; Obaseki, Daniel O; Erhabor, Gregory E; Akor, Alexander A; Irabor, Iziegbe; Obioh, Ib

2014-01-01

Particulate air pollution is associated with increased incidence of respiratory symptoms and decreased pulmonary, function but the relative impact of pollution from different domestic energy sources is not well-known or studied. The study was aimed at assessing the association between particulate concentrations, respiratory symptoms and lung function. It was a cross-sectional study comprised of randomly selected residents of three communities. These communities were selected according to the predominant type of fuel used for household cooking which were: firewood, kerosene and liquefied petroleum gas (LPG). Assessment of the indoor PM10 levels was done by filtration using the Gent stacked filter unit sampler for collection of atmospheric aerosol in two size fractions (PM2.5 and PM10). The Medical Research Council (MRC) questionnaire was administered followed by spirometry test. The mean PM10 concentration in participants using LPG, kerosene and firewood was 80.8 ± 9.52 μg/m(3), 236.9 ± 26.5 μg/m(3) and 269 ±93.7 μg/m(3), respectively. The mean age and height-adjusted percent predicted forced expiratory volumes in 1 s (FEV1) for men were 127 ± 7, 109 ± 40 and 91 ± 20 and for women were 129 ± 13, 115 ± 14, 100 ± 14 in users of LPG, kerosene and firewood, respectively. A similar trend was found in the forced vital capacity (FVCs). Users of firewood had significantly lower FEV1 and FVC compared with LPG users (P < 0.05). The participants using firewood had the highest prevalence of pulmonary and non-pulmonary symptoms (57.1%), whereas subjects using LPG had the lowest (23.8%). There are high levels of particulate matter pollutions with respiratory effects in residential indoor environments in Ile-Ife, Nigeria.

Hepatobiliary Ultrasonographic Abnormalities in Adult Patients with Sickle Cell Anaemia in Steady State in Ile-Ife, Nigeria

PubMed Central

Oguntoye, Oluwatosin O.; Ndububa, Dennis A.; Yusuf, Musah; Bolarinwa, Rahman A.; Ayoola, Oluwagbemiga O.

2017-01-01

Summary Background Sickle cell anaemia (SCA) is associated with structural manifestations in the hepatobiliary axis. This study aimed to investigate the hepatobiliary ultrasonographic abnormalities in adult patients with sickle cell anaemia in steady state attending the Haematology clinic of a federal tertiary health institution in Ile-Ife, Nigeria. Material/Methods Basic demographic data as well as right upper abdominal quadrant ultrasonography of 50 consecutive sickle cell anaemia patients were compared with those of 50 age- and sex-matched subjects with HbAA as controls. Results Each of the study groups (patients and controls) comprised of 21 (42%) males and 29 (58%) females. The age range of the patients was 18–45 years with a mean (±SD) of 27.6±7.607 years, while that of the controls was 21–43 years with a mean (±SD) of 28.0±5.079 years (p=0.746). Amongst the patients, 32 (64%) had hepatomegaly, 15 (30%) cholelithiasis and 3 (6%) biliary sludge. Fourteen (28%) of the patients had normal hepatobiliary ultrasound findings. In the control group, one (2%) person had cholelithiasis, one (2%) biliary sludge, one (2%) fatty liver and none hepatomegaly. Forty-seven (94%) of the controls had normal hepatobiliary ultrasound findings. There was a statistically significant difference in the prevalence of hepatomegaly and cholelithiasis between the patients and controls (p value <0.001 for both comparisons). Conclusions In this study, hepatomegaly, cholelithiasis and biliary sludge were the most common hepatobiliary ultrasound findings in patients with sickle cell anaemia. Ultrasonography is a useful tool for assessing hepatobiliary abnormalities in patients with sickle cell anaemia. PMID:28105246

Implant failure in lower limb long bone diaphyseal fractures at a tertiary hospital in Ile- Ife. Nigeria.

PubMed

Esan, O; Ikem, I C; Orimolade, E A; Esan, O T

2014-06-01

This included determining aetiology of failure and comparing the failure rate in implant fixations using solid intramedullary nail and DCP. A retrospective study conducted at the Orthopaedic Department, Obafemi Awolowo University Teaching Hospital, Ile-Ife,Nigeria. Records of all operated cases of lower limb long bone diaphyseal fractures including those with failed fixations from August 2006-July 2011 were reviewed. Data retrieved included type of implant used, aetiology and characteristics of Implant failure. Data were analysed using SPSS version 16. Frequency distribution of the variables of interest was done. Difference in failure rate of intramedullary nail versus DCP was tested using chi-square. Statistical significance was inferred at p<0.05. A total of 280 patients were studied out of which two hundred and twenty-one patients had long bone diaphyseal fractures and met inclusion criteria, of which 135 had intramedullary nail fixation and 86 had DCP. The rate of implant failure in intramedullary nail was 1.5% while it was 5.8% in patients with DCP (p=0.113; 0R=4.10; 95% CI=0.65- 43.77). Implant fracture was the commonest type of failure seen (100% versus 60%) and non union was the commonest cause of failure seen (50% versus 40%) in the intramedullary nailing and DCP groups respectively. The likelihood of a failed implant is higher in fixations done with DCP compared with intramedullary nail though the difference was not statistically significant. Commonest reason for failure in both groups was non-union. Findings from this study may guide surgeons in choice of implant in the management of long bone fractures.

Rational improvement of gp41-targeting HIV-1 fusion inhibitors: an innovatively designed Ile-Asp-Leu tail with alternative conformations.

PubMed

Zhu, Yun; Su, Shan; Qin, Lili; Wang, Qian; Shi, Lei; Ma, Zhenxuan; Tang, Jianchao; Jiang, Shibo; Lu, Lu; Ye, Sheng; Zhang, Rongguang

2016-09-26

Peptides derived from the C-terminal heptad repeat (CHR) of HIV gp41 have been developed as effective fusion inhibitors against HIV-1, but facing the challenges of enhancing potency and stability. Here, we report a rationally designed novel HIV-1 fusion inhibitor derived from CHR-derived peptide (Trp628~Gln653, named CP), but with an innovative Ile-Asp-Leu tail (IDL) that dramatically increased the inhibitory activity by up to 100 folds. We also determined the crystal structures of artificial fusion peptides N36- and N43-L6-CP-IDL. Although the overall structures of both fusion peptides share the canonical six-helix bundle (6-HB) configuration, their IDL tails adopt two different conformations: a one-turn helix with the N36, and a hook-like structure with the longer N43. Structural comparison showed that the hook-like IDL tail possesses a larger interaction interface with NHR than the helical one. Further molecular dynamics simulations of the two 6-HBs and isolated CP-IDL peptides suggested that hook-like form of IDL tail can be stabilized by its binding to NHR trimer. Therefore, CP-IDL has potential for further development as a new HIV fusion inhibitor, and this strategy could be widely used in developing artificial fusion inhibitors against HIV and other enveloped viruses.

The causes and outcomes of cancellation of orthopaedic surgeries at the obafemi awolowo university teaching hospital complex ile-ife, Nigeria.

PubMed

Oluwadiya, K S; Olasinde, A A; Olakulehin, O A; Olatoke, S A; Oginni, L M; Ako, F

2007-03-01

Cancellation of cases on the scheduled day of surgery leads to an inefficient utilisation of scarce hospital and patient's resources. Identifying the causes of such cancellations will assist in taking steps to avoid them. This is a retrospective study spanning 10 years. Record was taken of all patients who had orthopaedic surgery at the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife Nigeria. The age, sex, type of operation, whether or not the surgery was ever postponed or cancelled, the duration and reasons for such postponements and the duration of admission were collated and analysed. Five hundred and fifty two (40.8%) of the 1,353 orthopaedic patients scheduled for surgery experienced cancellation. The most common reasons were attributable to the hospital (48.7%) mainly due to infrastructural breakdown (28.7%) and procedural lapses by hospital personnel (20.0%). Self cancellation by patient (37.8%) followed and was mainly due to financial constraints (25.6%). Upper respiratory tract infections were responsible for the cancellation in 8.6%. These delays were responsible for more than 30% of the duration of admission in 93 (16.8%) patients. The incidence of postponement of cases on the scheduled day of surgery is still high. Most of the causes are preventable. Better infrastructural facilities, enhanced interdepartmental communication and improved attitude to work would reduce the rate and thus enhance utilisation of theatre space.

Determining the optimal isoleucine:lysine ratio for ten- to twenty-two-kilogram and twenty-four- to thirty-nine-kilogram pigs fed diets containing nonexcess levels of leucine.

PubMed

Htoo, J K; Zhu, C L; Huber, L; de Lange, C F M; Quant, A D; Kerr, B J; Cromwell, G L; Lindemann, M D

2014-08-01

Three 21-d experiments were conducted to determine the optimum standardized ileal digestible (SID) Ile:Lys ratio in 10- to 22-kg and 24- to 39-kg pigs. In Exp. 1, 144 Yorkshire pigs (initial BW = 10.2 kg) were assigned to 6 diets with 6 pens per treatment. Diets 1 to 5 were formulated to contain 5 graded SID Ile:Lys (44, 51, 57, 63, and 70%), 1.18% SID Leu, and 0.90% SID Lys (second limiting). Diet 6 (diet 5 with added Lys) was formulated (1.06% SID Lys) as a positive control. Pigs fed diet 6 had higher (P < 0.05) ADG and G:F and lower (P < 0.05) plasma urea N (PUN) than pigs fed diet 5 (P < 0.02), indicating that Lys was limiting in diets 1 to 5. Final BW, ADG, and ADFI increased (linear and quadratic, P < 0.05) while G:F and PUN at d 21 were not affected (P > 0.10) by dietary Ile:Lys. Overall, ADG and ADFI were highest for pigs fed diet 2 (51% SID Ile:Lys). In Exp. 2, 216 Yorkshire pigs (initial BW = 9.6 kg) were assigned to 9 diets with 6 pens per treatment. Diets 1 to 4 contained 0.40, 0.47, 0.54, and 0.61% SID Ile, respectively, and 1.21% SID Lys; diets 5 to 8 contained 0.72, 0.84, 0.96, and 1.08% SID Lys, respectively, and 0.68% SID Ile. Diet 9 was high in both Ile and Lys (0.68% SID Ile and 1.21% SID Lys). All diets contained 1.21% SID Leu. The ADG and G:F increased (linear and quadratic, P < 0.05) as SID Ile:Lys increased (diets 1 to 4 and 9). The ADG and G:F increased (linear, P < 0.05) as SID Lys increased (diets 5 to 9). The PUN at d 21 decreased (linear, P < 0.05) by increasing dietary Ile:Lys. The SID Ile:Lys to optimize ADG was 46% by curvilinear plateau or exponential regression. For G:F, the optimal SID Ile:Lys was 47 and 51% by curvilinear plateau and exponential regressions, respectively. In Exp. 3, 80 pigs (PIC 327 × C23; initial BW = 24.0 kg) were allotted to 5 treatments with 4 pigs per pen. Diets 1 to 5 were formulated to contain 5 graded SID Ile:Lys (39, 46, 53, 61, and 68%), 1.17% SID Leu, and 0.91% SID Lys (second limiting). Final BW and

Personality profiles and psychopathology among students exposed to dating violence at theObafemi AwolowoUniversity, Ile-Ife.

PubMed

Boladale, Mapayi; Yetunde, Oladimeji; Adesanmi, Akinsulore; Olutayo, Aloba; Olanrewaju, Ibigbami

2015-01-01

Dating violence is a complex phenomenon, and researchers continue to examine a wide range of precursors and contributing factors. Evidence indicates that violent intimate partners may be more likely to have personality disorders and dependency and attachment problems compared with non-violent ones. The aim of the present study is to evaluate the interaction between the personality profiles, pattern of psychopathology, and dating violence among university students in Obafemi Awolowo University, Ile-Ife. The study utilized a cross-sectional survey design with a total of 400 students selected using a multistage sampling technique. They completed the Sociodemographic Data Schedule, the Conflict Tactic Scale (CTS), Eysenck Personality Questionnaire (EPQ), and the General Health Questionnaire (GHQ). Univariate analysis was used to determine the prevalence of dating violence, psychopathology, and personality traits, and these were expressed in percentages. Association at bivariate level was assessed using chi-square and at multivariate level using logistic regression and correlations as was appropriate depending on the type of variable. The age of the respondents ranged between 18 and 35 years (M = 21.44, SD = 2.99). The prevalence of dating violence in the previous 12 months was 34%, and the prevalence of psychopathology was 15%. In the logistic regression model constructed, it was found that the significant predictors of dating violence were the psychoticism and neuroticism personality traits, which were also found to be positive correlates of psychopathology. The magnitude of dating violence found in this study is comparable with those found in other countries of the world. This study found an association between dating violence and personality in the study population and also between certain personality traits and psychopathology. The personality profiles of students could affect their interpersonal relationships greatly, and this fact must feature in dating violence

The bacteriological quality of different brands of bottled water available to consumers in Ile-Ife, south-western Nigeria.

PubMed

Igbeneghu, Oluwatoyin A; Lamikanra, Adebayo

2014-11-28

The upsurge in the demand for bottled water has prompted the interest of many manufacturers in the production of bottled water and very many water bottling companies are therefore involved in its production. These range from large scale multinational companies to medium scale business enterprises, institutional and government business investment companies as well as small scale entrepreneurs. There is however little information on the comparative quality of bottled water brands produced by different classes of water bottling companies in Nigeria. This study was undertaken to determine the bacteriological quality of brands of bottled water available to consumers in Ile-Ife. Forty-three samples of bottled water comprising of three batches each of thirteen bottled water brands and two batches of two brands were purchased and analyzed for total bacterial count, presence of coliform and the presence of other bacterial indicators of drinking water quality. Only 67.4% of the water samples representing the products of 10 companies or 66.7% of the brands had heterotrophic counts within the acceptable limits. Coliforms present in 100 ml of water were detected in 26.7% of the bottled water brands. Other indicator organisms detected included Staphylococci isolated from 27.9% of the samples (33.3% of the brands) and specifically Staphylococcus aureus found in four brands constituting 14% of the samples. Pseudomonas strains were consistently detected in consecutive batches of three brands of the water samples. Bottled water samples produced by the large scale multinational producers were of acceptable bacteriological quality unlike those produced by most small companies. There is need for a greater control of water bottling processes carried out by commercial bottled water producers in Nigeria.

Endoplasmic reticulum-associated inactivation of the hormone jasmonoyl-L-isoleucine by multiple members of the cytochrome P450 94 family in Arabidopsis.

PubMed

Koo, Abraham J; Thireault, Caitlin; Zemelis, Starla; Poudel, Arati N; Zhang, Tong; Kitaoka, Naoki; Brandizzi, Federica; Matsuura, Hideyuki; Howe, Gregg A

2014-10-24

The plant hormone jasmonate (JA) controls diverse aspects of plant immunity, growth, and development. The amplitude and duration of JA responses are controlled in large part by the intracellular level of jasmonoyl-L-isoleucine (JA-Ile). In contrast to detailed knowledge of the JA-Ile biosynthetic pathway, little is known about enzymes involved in JA-Ile metabolism and turnover. Cytochromes P450 (CYP) 94B3 and 94C1 were recently shown to sequentially oxidize JA-Ile to hydroxy (12OH-JA-Ile) and dicarboxy (12COOH-JA-Ile) derivatives. Here, we report that a third member (CYP94B1) of the CYP94 family also participates in oxidative turnover of JA-Ile in Arabidopsis. In vitro studies showed that recombinant CYP94B1 converts JA-Ile to 12OH-JA-Ile and lesser amounts of 12COOH-JA-Ile. Consistent with this finding, metabolic and physiological characterization of CYP94B1 loss-of-function and overexpressing plants demonstrated that CYP94B1 and CYP94B3 coordinately govern the majority (>95%) of 12-hydroxylation of JA-Ile in wounded leaves. Analysis of CYP94-promoter-GUS reporter lines indicated that CYP94B1 and CYP94B3 serve unique and overlapping spatio-temporal roles in JA-Ile homeostasis. Subcellular localization studies showed that CYP94s involved in conversion of JA-Ile to 12COOH-JA-Ile reside on endoplasmic reticulum (ER). In vitro studies further showed that 12COOH-JA-Ile, unlike JA-Ile, fails to promote assembly of COI1-JAZ co-receptor complexes. The double loss-of-function mutant of CYP94B3 and ILL6, a JA-Ile amidohydrolase, displayed a JA profile consistent with the collaborative action of the oxidative and the hydrolytic pathways in JA-Ile turnover. Collectively, our results provide an integrated view of how multiple ER-localized CYP94 and JA amidohydrolase enzymes attenuate JA signaling during stress responses. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Endoplasmic Reticulum-associated Inactivation of the Hormone Jasmonoyl-l-Isoleucine by Multiple Members of the Cytochrome P450 94 Family in Arabidopsis*

PubMed Central

Koo, Abraham J.; Thireault, Caitlin; Zemelis, Starla; Poudel, Arati N.; Zhang, Tong; Kitaoka, Naoki; Brandizzi, Federica; Matsuura, Hideyuki; Howe, Gregg A.

2014-01-01

The plant hormone jasmonate (JA) controls diverse aspects of plant immunity, growth, and development. The amplitude and duration of JA responses are controlled in large part by the intracellular level of jasmonoyl-l-isoleucine (JA-Ile). In contrast to detailed knowledge of the JA-Ile biosynthetic pathway, little is known about enzymes involved in JA-Ile metabolism and turnover. Cytochromes P450 (CYP) 94B3 and 94C1 were recently shown to sequentially oxidize JA-Ile to hydroxy (12OH-JA-Ile) and dicarboxy (12COOH-JA-Ile) derivatives. Here, we report that a third member (CYP94B1) of the CYP94 family also participates in oxidative turnover of JA-Ile in Arabidopsis. In vitro studies showed that recombinant CYP94B1 converts JA-Ile to 12OH-JA-Ile and lesser amounts of 12COOH-JA-Ile. Consistent with this finding, metabolic and physiological characterization of CYP94B1 loss-of-function and overexpressing plants demonstrated that CYP94B1 and CYP94B3 coordinately govern the majority (>95%) of 12-hydroxylation of JA-Ile in wounded leaves. Analysis of CYP94-promoter-GUS reporter lines indicated that CYP94B1 and CYP94B3 serve unique and overlapping spatio-temporal roles in JA-Ile homeostasis. Subcellular localization studies showed that CYP94s involved in conversion of JA-Ile to 12COOH-JA-Ile reside on endoplasmic reticulum (ER). In vitro studies further showed that 12COOH-JA-Ile, unlike JA-Ile, fails to promote assembly of COI1-JAZ co-receptor complexes. The double loss-of-function mutant of CYP94B3 and ILL6, a JA-Ile amidohydrolase, displayed a JA profile consistent with the collaborative action of the oxidative and the hydrolytic pathways in JA-Ile turnover. Collectively, our results provide an integrated view of how multiple ER-localized CYP94 and JA amidohydrolase enzymes attenuate JA signaling during stress responses. PMID:25210037

A Novel Heme Pocket Hemoglobin Variant Associated with Normal Hematology: Hb Zara or α91(FG3)Leu→Ile (α2) (HBA2: c.274C > A).

PubMed

Trova, Sandro; Mereu, Paolo; Decandia, Luca; Cocco, Elena; Masala, Bruno; Manca, Laura; Pirastru, Monica

2015-08-13

We report a new hemoglobin (Hb) variant on the HBA2 gene, Hb Zara [α91(FG3)Leu→Ile (α2); HBA2: c.274C > A], which was found in a Caucasian man from Croatia. It was observed by routine cation exchange chromatography as an abnormal 21.8% fraction overlapping Hb A 2 , and associated with normal hematology. It was slightly unstable by the standard isopropanol precipitation test. DNA analysis revealed the CTT > ATT mutation at codon 91 on an α2 gene of a normal α-globin gene arrangement. This new variant represents the sixth described mutation at codon α91 and fourth on the α2 locus. As a result of the slight instability due to the significant role of the α91 residue in the α1β2 contact, the level of the Hb Zara variant was lower than levels observed for several stable variants codified by the α2 locus.

A Novel Heme Pocket Hemoglobin Variant Associated with Normal Hematology: Hb Zara or α91(FG3)Leu→Ile (α2) (HBA2: c.274C > A).

PubMed

Trova, Sandro; Mereu, Paolo; Decandia, Luca; Cocco, Elena; Masala, Bruno; Manca, Laura; Pirastru, Monica

2015-01-01

We report a new hemoglobin (Hb) variant on the HBA2 gene, Hb Zara [α91(FG3)Leu→Ile (α2); HBA2: c.274C > A], which was found in a Caucasian man from Croatia. It was observed by routine cation exchange chromatography as an abnormal 21.8% fraction overlapping Hb A2, and associated with normal hematology. It was slightly unstable by the standard isopropanol precipitation test. DNA analysis revealed the CTT > ATT mutation at codon 91 on an α2 gene of a normal α-globin gene arrangement. This new variant represents the sixth described mutation at codon α91 and fourth on the α2 locus. As a result of the slight instability due to the significant role of the α91 residue in the α1β2 contact, the level of the Hb Zara variant was lower than levels observed for several stable variants codified by the α2 locus.

Toll like receptor-4 gene polymorphisms in patients with solitary cysticercus granuloma.

PubMed

Singh, Akhilesh; Garg, Ravindra Kumar; Jain, Amita; Malhotra, Hardeep Singh; Prakash, Shantanu; Verma, Rajesh; Sharma, Praveen Kumar

2015-08-15

Solitary cysticercus granuloma (SCG) of the brain is the most common type of neurocysticercosis in India. In this study, we evaluated TLR4 polymorphisms in patients with SCG. One-hundred-forty-three patients with SCG and 134 controls were enrolled. Assessment for TLR4 Asp299Gly and Thr399Ile polymorphism was done. TLR4 genotype was determined by PCR-sequencing chain termination method. The patients were followed for 6 months. Asp/Gly (P=0.024) and Thr/Ile (P=0.004) genotypes were significantly associated with the SCG. The Gly (Asp/Gly plus Gly/Gly) genotype (P=0.025) and Ile (Thr/Ile plus Ile/Ile) genotype (P=0.008) were significantly associated with the SCG. Gly/Gly and Ile/Ile genotypes were not significantly associated with SCG (P=0.767 for Gly/Gly, P=0.936 for Ile/Ile). At 6 months, TLR4 299Asp/Gly (P=0.02) and 399Ile/Thr (P=0.023) polymorphisms were significantly associated with the calcification or persistence of SCG. TLR4 polymorphisms are associated with the susceptibility to infection with SCG. Copyright © 2015 Elsevier B.V. All rights reserved.

Clinical and Serologic Features in Patients With Incomplete Lupus Classification Versus Systemic Lupus Erythematosus Patients and Controls.

PubMed

Aberle, Teresa; Bourn, Rebecka L; Munroe, Melissa E; Chen, Hua; Roberts, Virginia C; Guthridge, Joel M; Bean, Krista; Robertson, Julie M; Sivils, Kathy L; Rasmussen, Astrid; Liles, Meghan; Merrill, Joan T; Harley, John B; Olsen, Nancy J; Karp, David R; James, Judith A

2017-12-01

Incomplete lupus erythematosus (ILE) involves clinical and/or serologic manifestations consistent with but insufficient for systemic lupus erythematosus (SLE) classification. Because the nature of ILE is poorly understood and no treatment recommendations exist, we examined the clinical manifestations, medication history, and immunologic features in a diverse collection of ILE and SLE patients. Medical records of subjects enrolled in the Lupus Family Registry and Repository were reviewed for medication history and American College of Rheumatology (ACR) classification criteria to identify ILE patients (3 ACR criteria; n = 440) and SLE patients (≥4 ACR criteria; n = 3,397). Participants completed the Connective Tissue Disease Screening Questionnaire. Anticardiolipin and plasma B lymphocyte stimulator (BLyS) were measured by enzyme-linked immunosorbent assay, antinuclear antibodies (ANAs) by indirect immunofluorescence, and 13 autoantibodies by bead-based assays. On average, ILE patients were older than SLE patients (46.2 years versus 42.0 years; P < 0.0001), and fewer ILE patients were African American (23.9% versus 32.2%; P < 0.001). ILE patients exhibited fewer autoantibody specificities than SLE patients (1.3 versus 2.6; P < 0.0001) and were less likely to have ANA titers ≥1:1,080 (10.5% versus 19.5%; P < 0.0001). BLyS levels were intermediate in ILE patients (controls < ILE; P = 0.016; ILE < SLE; P = 0.008). Pericarditis, renal, or neurologic manifestations occurred in 12.5% of ILE patients and were associated with non-European American race/ethnicity (P = 0.012). Hydroxychloroquine use increased over time, but was less frequent in ILE than SLE patients (65.2% versus 83.1%; P < 0.0001). Although usually characterized by milder symptoms, ILE manifestations may require immunomodulatory treatments. Longitudinal studies are necessary to understand how ILE affects organ damage and future SLE risk, and to delineate molecular pathways unique to ILE. © 2017, American

Glutathione S-Transferase Pi-Ile 105 Val Polymorphism and Susceptibility to T2DM in Population from Turabah Region of Saudi Arabia.

PubMed

Mergani, Adil; Mansour, Ahmed Abdelkhalik; Askar, Tamer; Zahran, Rasha Nabeel; Mustafa, Adil Musa; Mohammed, Mukhtar Ahmed; Saleh, Osama Mosailhy

2016-08-01

Type 2 diabetes mellitus is characterized by chronic hyperglycemia and associated with oxidative stress resulting from accumulation of free radicals in body's tissues, which especially affects beta cells in pancreas and is an important factor in the development of diabetes and its complications. Glutathione S-transferases (GSTs) are a family of antioxidant enzymes that play important roles in decreasing ROS species and act as a kind of antioxidant defense. In a case-control study, we investigated the role of GSTP1 Ile105Val polymorphism in predisposition to T2DM in patients from Tarabah province, Saudi Arabia. The polymorphism was screened by PCR-RFLP in 90 T2DM patients and 87 healthy controls. The genotypes and alleles frequencies in cases and controls were assessed using Cochran-Armitage trend test and odds ratios (ORs), and 95 % confidence intervals (CIs) in different genetic models of inheritance were calculated. Our data indicate that G allele (Val) is associated with an increased risk for T2DM in this population in any combination (OR 4.101, 95 % CI 1.986-8.469, P = 0.00008). This indicates that individuals who are carriers for the mutant allele, either in homozygous (GG) or heterozygous (AG) state, are at fourfold higher risk for development of T2DM than other subjects in this population.

Tectonic evolution of part of the Southern Metamorphic Belt of the Armorican Massif including the Ile de Groix

NASA Astrophysics Data System (ADS)

Richards, Lawrence Edward

The Southern Metamorphic Belt (SMB) of the Armorican Massifextends 400km along the south coast of Brittany and into Vendee. It is separated from the Central Armorican Domain by a major, late-Hercynian shear belt, known as the South Armorican Shear Zone. In the area studied, belts of metasedimentary and metavolcanic schist of uncertain age are separated by belts of granitic gneiss; areas of migmatite and Hercynian granite plutons cross-cut these belts. Three distinctive lithologic assemblages have been identified in the schist belts, characteristic of different depositional environments: the Le Pouldu Group, Kerleven and Gouesnach formations probably originated as abyssal black shales deposited on oceanic crust; the St. Laurent Formation and Melgven Schists probably formed as distal greywacke deposits on a deep continental shelf; the Nerly and Beg-Meil formations probably formed in a proximal marine or fluviatile environment. These disparate assemblages were tectonically juxtaposed by overthrusting (obduction) before an amphibolite facies metamorphism and deformation during the Cadomian Orogeny. The Moelan Gneiss, a Lower Ordovician alkali-granite intrusion, postdates M1/D1 and probably formed in a rifting environment at the onset of ocean-floor spreading along an axis south of the present Armorican Massif. The famous blueschists of the Ile de Groix probably formed in a subduction zone on the south side of the ocean and were obducted onto the passive southern margin of the Armorican Massif following closure of the ocean and continental collision. A second phase of regional deformation, producing a cataclastic foliation in the Moelan Gneiss, probably resulted from the collision. Large-scale overthrusting of the southern continent onto the Armorican Massif took place, causing metamorphism with partial melting at depth generating migmatites. A third phase of pervasive deformation may correlate with oroclinal bending of the Ibero-Armorican Arc during the Hercynian

Effect of community level intervention on nutritional status and feeding practices of under five children in Ile Ife, Nigeria.

PubMed

Ogundele, Olorunfemi Akinbode; Ogundele, Tolulope

2015-01-01

Childhood malnutrition remains a widespread problem in developing world like Nigeria. The country ranks second among the ten countries contributing to sixty percent of the world's wasted under-five children. Community Integrated Management of Childhood illness (CIMCI) is a programme that employs the use of community based counsellors to address child health and nutritional challenges of the under-five and has the potential to reduce the morbidity and mortality resulting from poor nutritional and feeding practices. The study assessed the effect of community level intervention on nutritional status and feeding practices of children in Ile-Ife, Nigeria. A cross-sectional comparative study that employed the use of multi stage cluster sampling techniques in selecting 722 mothers of index under five children. The study was done in two Local Government Areas of Osun State, Nigeria. Quantitative techniques were used in data collection. Data analysis was done using SPSS version 20.0. Descriptive and bivariate analyses was performed. The two Local Government Area (LGA) did not differ significantly in their wealth index (p = 0.344). However, more children in the non-implementing LGA (16.1%) had low weight for age compared with 3.6% in the CIMCI implementing LGA (p = 0.000). A statistically significant difference exist in the MUAC measurement of children 12-23 months between the CIMCI implementing and non-implementing communities (p = 0.007). A higher percentage of caregivers (19.3%) introduced complementary feeding earlier than 6 months in the non-implementing area (p < 0.001). Using community level nutritional counseling can greatly improve nutritional status and feeding practices of under five children.

The Recently Identified Isoleucine Conjugate of cis-12-Oxo-Phytodienoic Acid Is Partially Active in cis-12-Oxo-Phytodienoic Acid-Specific Gene Expression of Arabidopsis thaliana

PubMed Central

Floková, Kristýna; Miersch, Otto; Strnad, Miroslav; Novák, Ondřej; Wasternack, Claus; Hause, Bettina

2016-01-01

Oxylipins of the jasmonate family are active as signals in plant responses to biotic and abiotic stresses as well as in development. Jasmonic acid (JA), its precursor cis-12-oxo-phytodienoic acid (OPDA) and the isoleucine conjugate of JA (JA-Ile) are the most prominent members. OPDA and JA-Ile have individual signalling properties in several processes and differ in their pattern of gene expression. JA-Ile, but not OPDA, is perceived by the SCFCOI1-JAZ co-receptor complex. There are, however, numerous processes and genes specifically induced by OPDA. The recently identified OPDA-Ile suggests that OPDA specific responses might be mediated upon formation of OPDA-Ile. Here, we tested OPDA-Ile-induced gene expression in wild type and JA-deficient, JA-insensitive and JA-Ile-deficient mutant background. Tests on putative conversion of OPDA-Ile during treatments revealed only negligible conversion. Expression of two OPDA-inducible genes, GRX480 and ZAT10, by OPDA-Ile could be detected in a JA-independent manner in Arabidopsis seedlings but less in flowering plants. The data suggest a bioactivity in planta of OPDA-Ile. PMID:27611078

The SCN8A encephalopathy mutation p.Ile1327Val displays elevated sensitivity to the anticonvulsant phenytoin.

PubMed

Barker, Bryan S; Ottolini, Matteo; Wagnon, Jacy L; Hollander, Rachel M; Meisler, Miriam H; Patel, Manoj K

2016-09-01

SCN8A encephalopathy (early infantile epileptic encephalopathy; EIEE13) is caused by gain-of-function mutations resulting in hyperactivity of the voltage-gated sodium channel Nav 1.6. The channel is concentrated at the axon initial segment (AIS) and is involved in establishing neuronal excitability. Clinical features of SCN8A encephalopathy include seizure onset between 0 and 18 months of age, intellectual disability, and developmental delay. Seizures are often refractory to treatment with standard antiepileptic drugs, and sudden unexpected death in epilepsy (SUDEP) has been reported in approximately 10% of patients. In a recent study, high doses of phenytoin were effective in four patients with SCN8A encephalopathy. In view of this observation, we have investigated the relationship between the functional effect of the SCN8A mutation p.Ile1327Val and its response to phenytoin. The mutation was introduced into the Scn8a cDNA by site-directed mutagenesis. Channel activity was characterized in transfected ND7/23 cells. The effects of phenytoin (100 μm) on mutant and wild-type (WT) channels were compared. Channel activation parameters were shifted in a hyperpolarizing direction in the mutant channel, whereas inactivation parameters were shifted in a depolarizing direction, increasing Na channel window current. Macroscopic current decay was slowed in I1327V channels, indicating an impairment in the transition from open state to inactivated state. Channel deactivation was also delayed, allowing more channels to remain in the open state. Phenytoin (100 μm) resulted in hyperpolarized activation and inactivation curves as well as greater tonic block and use-dependent block of I1327V mutant channels relative to WT. SCN8A - I1327V is a gain-of-function mutation with altered features that are predicted to increase neuronal excitability and seizure susceptibility. Phenytoin is an effective inhibitor of the mutant channel and may be of use in treating patients with gain

The SCN8A encephalopathy mutation p.Ile1327Val displays elevated sensitivity to the anticonvulsant phenytoin

PubMed Central

Barker, Bryan S.; Ottolini, Matteo; Wagnon, Jacy L.; Hollander, Rachel; Meisler, Miriam H.; Patel, Manoj K.

2016-01-01

Objective SCN8A encephalopathy (EIEE13) is caused by gain-of-function mutations resulting in hyperactivity of the voltage-gated sodium channel Nav1.6. The channel is concentrated at the axon initial segment (AIS) and is involved in establishing neuronal excitability. Clinical features of SCN8A encephalopathy include seizure onset between 0–18 months of age, intellectual disability, and developmental delay. Seizures are often refractory to treatment with standard anti-epileptic drugs, and sudden unexpected death in epilepsy (SUDEP) has been reported in approximately 10% of patients. In a recent study, high doses of phenytoin were effective in four patients with SCN8A encephalopathy. In view of this observation, we have investigated the relationship between the functional effect of the SCN8A mutation p.Ile1327Val and its response to phenytoin. Methods The mutation was introduced into the Scn8a cDNA by site-directed mutagenesis. Channel activity was characterized in transfected ND7/23 cells. The effects of phenytoin (100 μM) on mutant and wild type (WT) channels were compared. Results Channel activation parameters were shifted in a hyperpolarizing direction in the mutant channel, while inactivation parameters were shifted in a depolarizing direction, increasing Na channel window current. Macroscopic current decay was slowed in I1327V channels, indicating an impairment in the transition from open state to inactivated state. Channel deactivation was also delayed, allowing more channels to remain in the open state. Phenytoin (100 μM) resulted in hyperpolarized activation and inactivation curves as well as greater tonic block and use dependent block of I1327V mutant channels relative to WT. Significance SCN8A – I1327V is a gain-of-function mutation with altered features that are predicted to increase neuronal excitability and seizure susceptibility. Phenytoin is an effective inhibitor of the mutant channel and may be of use in treating patients with gain

Groundwater contamination in the basement-complex area of Ile-Ife, southwestern Nigeria: A case study using the electrical-resistivity geophysical method

NASA Astrophysics Data System (ADS)

Adepelumi, A. A.; Ako, B. D.; Ajayi, T. R.

2001-11-01

Hydrogeoenvironmental studies were carried out at the sewage-disposal site of Obafemi Awolowo University campus, Ile-Ife, Nigeria. The objective of the survey was to determine the reliability of the electrical-resistivity method in mapping pollution plumes in a bedrock environment. Fifty stations were occupied with the ABEM SAS 300C Terrameter using the Wenner array. The electrical-resistivity data were interpreted by a computer-iteration technique. Water samples were collected at a depth of 5.0 m in 20 test pits and analyzed for quality. The concentrations of Cr, Cd, Pb, Zn, and Cu are moderately above the World Health Organization recommended guidelines. Plumes of contaminated water issuing from the sewage ponds were delineated. The geoelectric sections reveal four subsurface layers, with increasing depth, lateritic clay, clayey sand/sand, and weathered/fractured bedrock, and fresh bedrock. The deepest layers, 3 and 4, constitute the main aquifer, which has a thickness of 3.1-67.1 m. The distribution of the elements in the sewage effluent confirms a hydrological communication between the disposal ponds and groundwater. The groundwater is contaminated, as shown by sampling and the geophysical results. Thus, the results demonstrate the reliability of the direct-current electrical-resistivity geophysical method in sensing and mapping pollution plumes in a crystalline bedrock environment. Résumé. Des études géo-environnementales ont été réalisées sur le site d'épandages du campus universitaire d'Obafemi Awolowo, à Ile-Ife (Nigeria). L'objectif de ce travail était de déterminer la fiabilité de la méthode des résistivités électriques pour cartographier les panaches de pollution dans un environnement de socle. Cinquante stations ont été soumises à mesures au moyen d'un ABEM SAS 300C Terrameter en utilisant le dispositif de Wenner. Les données de résistivité électrique ont été interprétées au moyen d'une technique de calcul itérative. Des �

Undernutrition and anaemia among HAART-naïve HIV infected children in Ile-Ife, Nigeria: a case-controlled, hospital based study.

PubMed

Anyabolu, Henry Chineme; Adejuyigbe, Ebunoluwa Aderonke; Adeodu, Oluwagbemiga Oyewole

2014-01-01

Case control studies that assess the burden and factors associated with undernutrition and anaemia among HAART naïve HIV infected children in Nigeria is very sparse. This will help to formulate nutritional programs among these children. Seventy HAART naive HIV infected children aged 18 months and above were as well as seventy age and sex matched HIV negative children were recruited from August 2007 to January 2009 at Paediatric Clinic of Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria. Their bio data, WHO clinical stage, anthropometric measurements, haematocrit, serum albumin and CD4 counts were taken with other parameters according to a study proforma. The prevalence of stunting, underweight and wasting among the HIV infected subjects were 48. 6%,58. 6% and 31. 4% respectively which as significantly higher than 28. 1%, 7. 1% and 28. 1% among the HIV negative controls. 20. 1% of the HIV infected children were marasmic compared to 2. 3% of the controls. Triple anthropometric failure was found in 7. 1% of the subjects as compared to none among the controls. Anaemia is significantly more prevalent among the subjects than the controls (70. 0% vs 31. 4%; p<0. 001). The prevalence of anaemia was higher in the HIV infected subjects with undernutrition. Low socioeconomic status, hypoalbuminemia and severe immunosuppression are significantly associated with higher undernutrition prevalence. Several years after availability of HAART, undernutrition and anaemia remain widely prevalent among newly presenting HAART naïve HIV infected Nigerian children. Nutritional supplementation and evaluation for anaemia still need close attention in the management of these children.

Structure-guided modification of Rhizomucor miehei lipase for production of structured lipids.

PubMed

Zhang, Jun-Hui; Jiang, Yu-Yan; Lin, Ying; Sun, Yu-Fei; Zheng, Sui-Ping; Han, Shuang-Yan

2013-01-01

To improve the performance of yeast surface-displayed Rhizomucor miehei lipase (RML) in the production of human milk fat substitute (HMFS), we mutated amino acids in the lipase substrate-binding pocket based on protein hydrophobicity, to improve esterification activity. Five mutants: Asn87Ile, Asn87Ile/Asp91Val, His108Leu/Lys109Ile, Asp256Ile/His257Leu, and His108Leu/Lys109Ile/Asp256Ile/His257Leu were obtained and their hydrolytic and esterification activities were assayed. Using Discovery Studio 3.1 to build models and calculate the binding energy between lipase and substrates, compared to wild-type, the mutant Asp256Ile/His257Leu was found to have significantly lower energy when oleic acid (3.97 KJ/mol decrease) and tripalmitin (7.55 KJ/mol decrease) were substrates. This result was in accordance with the esterification activity of Asp256Ile/His257Leu (2.37-fold of wild-type). The four mutants were also evaluated for the production of HMFS in organic solvent and in a solvent-free system. Asp256Ile/His257Leu had an oleic acid incorporation of 28.27% for catalyzing tripalmitin and oleic acid, and 53.18% for the reaction of palm oil with oleic acid. The efficiency of Asp256Ile/His257Leu was 1.82-fold and 1.65-fold that of the wild-type enzyme for the two reactions. The oleic acid incorporation of Asp256Ile/His257Leu was similar to commercial Lipozyme RM IM for palm oil acidolysis with oleic acid. Yeast surface-displayed RML mutant Asp256Ile/His257Leu is a potential, economically feasible catalyst for the production of structured lipids.

Dysfibrinogen Kagoshima with the amino acid substitution gammaThr-314 to Ile: analyses of molecular abnormalities and thrombophilic nature of this abnormal molecule.

PubMed

Niwa, Kazuki; Mimuro, Jun; Miyata, Masaaki; Sugo, Teruko; Ohmori, Tsukasa; Madoiwa, Seiji; Tei, Chuwa; Sakata, Yoichi

2008-01-01

Emerging lines of evidence have suggested that certain dysfibrinogens present a significant risk of thrombosis. The thrombophilic nature of a new-type of dysfibrinogen Kagoshima identified in a 36-year-old female with deep vein thrombosis during the postpartum period was studied. Based on the analyses of the patient fibrinogen and the fibrinogen genes, fibrinogen Kagoshima was shown to have the amino acid substitution of gammaThr-314 to Ile that resulted in impaired function and hypofibrinogenemia. Polymerization of fibrin monomers derived from patient fibrinogen was severely impaired with a partial correction in the presence of calcium ions, causing very low clottability and delayed cross-linking of patient fibrin catalyzed by activated factor XIII. Because of the low clottability, a large amount of soluble fibrin was formed upon thrombin treatment, resulting in an increase of thrombin in the soluble fraction. Additionally, tPA-mediated plasmin generation on fibrin was impaired and calcium-ion-dependent integrity of the gamma-chain D domain of Kagoshima fibrinogen was perturbed. The presence of many tapered-fiber ends inside the tangled fibrin networks, observed by scanning electron microscopy, suggested early termination of fibrin polymerization and the structural alteration. These data suggest that fibrinogen Kagoshima is dysfunctional, giving rise to formation of fibrinolysis-resistant soluble fibrin polymers and entrance of soluble fibrin associating with thrombin to the circulation, partly accounting for the thrombophilic nature of the affected fibrinogen and fibrin molecules.

Biological and Clinical Aspects of an Olive Oil-Based Lipid Emulsion-A Review.

PubMed

Cai, Wei; Calder, Phillip C; Cury-Boaventura, Maria F; De Waele, Elisabeth; Jakubowski, Julie; Zaloga, Gary

2018-06-15

Intravenous lipid emulsions (ILEs) have been an integral component of parenteral nutrition for more than 50 years. Numerous formulations are available and are based on vegetable (soybean, olive, coconut) and animal (fish) oils. Therefore, each of these formulations has a unique fatty acid composition that offers both benefits and limitations. As clinical experience and our understanding of the effects of fatty acids on various physiological processes has grown, there is evidence to suggest that some ILEs may have benefits compared with others. Current evidence suggests that olive oil-based ILE may preserve immune, hepatobiliary, and endothelial cell function, and may reduce lipid peroxidation and plasma lipid levels. There is good evidence from a large randomized controlled study to support a benefit of olive oil-based ILE over soybean oil-based ILE on reducing infections in critically ill patients. At present there is limited evidence to demonstrate a benefit of olive oil-based ILE over other ILEs on glucose metabolism, and few data exist to demonstrate a benefit on clinical outcomes such as hospital or intensive care unit stay, duration of mechanical ventilation, or mortality. We review the current research and clinical evidence supporting the potential positive biological and clinical aspects of olive oil-based ILE and conclude that olive oil-based ILE is well tolerated and provides effective nutritional support to various PN-requiring patient populations. Olive oil-based ILE appears to support the innate immune system, is associated with fewer infections, induces less lipid peroxidation, and is not associated with increased hepatobiliary or lipid disturbances. These data would suggest that olive oil-based ILE is a valuable option in various PN-requiring patient populations.

The topical penta-peptide Gly-Pro-Ile-Gly-Ser increases the proportion of thick hair in Japanese men with androgenetic alopecia.

PubMed

Iwabuchi, Tokuro; Takeda, Shunsuke; Yamanishi, Haruyo; Ideta, Ritsuro; Ehama, Ritsuko; Tsuruda, Akinori; Shibata, Hideaki; Ito, Tomoko; Komatsu, Nobuyuki; Terai, Keiko; Oka, Syuichi

2016-06-01

A penta-peptide, Gly-Pro-Ile-Gly-Ser (GPIGS), promotes proliferation of mouse hair keratinocytes and accelerates hair growth in mice. This study focused on the ability of the peptide to promote human hair growth. We used a human hair keratinocyte proliferation assay and organ cultures of human hair follicle as in vitro systems. The lotions with and without the penta-peptide were administered to 22 Japanese men with androgenetic alopecia (AGA) for 4 months in a double-blind and randomized clinical study. The penta-peptide significantly stimulated the proliferation of human hair keratinocytes at a concentration of 2.3 μm (P < 0.01), and 5.0 μm of this peptide had a marked effect on hair shaft elongation in the organ culture (P < 0.05). The change in the proportion of thick hair (≥60 μm) compared to baseline in patients that received the peptide was significantly higher than in the placebo (P = 0.006). The change in the proportion of vellus hair (<40 μm) was also significantly lower in the peptide group than in the placebo (P = 0.029). The penta-peptide also significantly improved the appearance of baldness (P = 0.020) when blinded reviewers graded photographs of the participants according to a standardized baldness scale. No adverse dermatological effects due to treatment were noted during this clinical study. This penta-peptide promotes proliferation of human hair keratinocytes and hair shaft elongation of human hair follicles, in vitro. This peptide increases thick hair ratio in vivo, and this compound is useful for the improvement of AGA. © 2016 Wiley Periodicals, Inc.

Utilisation of the isobole methodology to study dietary peptide-drug and peptide-peptide interactive effects on dipeptidyl peptidase IV (DPP-IV) inhibition.

PubMed

Nongonierma, Alice B; FitzGerald, Richard J

2015-01-01

Inhibition of dipeptidyl peptidase-IV (DPP-IV) is used as a means to regulate post-prandial serum glucose in type 2 diabetics. The effect of drug (Sitagliptin®)/peptide and binary peptide mixtures on DPP-IV inhibition was studied using an isobole approach. Five peptides (Ile-Pro-Ile-Gln-Tyr, Trp-Lys, Trp-Pro, Trp-Arg and Trp-Leu), having DPP-IV half maximum inhibitory concentration values (IC₅₀)<60 μM and reported to act through different inhibition mechanisms, were investigated. The dose response relationship of Sitagliptin : peptide (1:0, 0:1, 1:852, 1:426 and 1:1704 on a molar basis) and binary Ile-Pro-Ile-Gln-Tyr : peptide (1:0, 0:1, 1:1, 1:2 and 2:1 on a molar basis) mixtures for DPP-IV inhibition was characterised. Isobolographic analysis showed, in most instances, an additive effect on DPP-IV inhibition. However, a synergistic effect was observed with two Sitagliptin:Ile-Pro-Ile-Gln-Tyr (1:426 and 1:852) mixtures and an antagonistic effect was seen with one Sitagliptin : Trp-Pro (1:852) mixture, and three binary peptide mixtures (Ile-Pro-Ile-Gln-Tyr : Trp-Lys (1:1 and 2:1) and Ile-Pro-Ile-Gln-Tyr:Trp-Leu (1:2)). The results show that Sitagliptin and food protein-derived peptides can interact, thereby enhancing overall DPP-IV inhibition. Combination of Sitagliptin with food protein-derived peptides may help in reducing drug dosage and possible associated side-effects.

Sweet Taste Receptor TAS1R2 Polymorphism (Val191Val) Is Associated with a Higher Carbohydrate Intake and Hypertriglyceridemia among the Population of West Mexico

PubMed Central

Ramos-Lopez, Omar; Panduro, Arturo; Martinez-Lopez, Erika; Roman, Sonia

2016-01-01

Some high-carbohydrate diets may lead to obesity and multiple metabolic disorders, including hypertriglyceridemia (HTG). This lipid abnormality is considered an important risk factor for cardiovascular disease and type 2 diabetes. The sweet taste receptor TAS1R2 polymorphism (Ile191Val) has been reported to be associated with carbohydrate intake. The aim of this study was to analyze the association of the TAS1R2 gene polymorphism with carbohydrate intake and HTG among the population of West Mexico. In a cross-sectional study, 441 unrelated subjects were analyzed for TAS1R2 genotypes (Ile/Ile, Ile/Val and Val/Val) by an allelic discrimination assay. Biochemical tests and a three-day food record were assessed. The Val/Val genotype carriers had a higher intake of total carbohydrates, fiber and servings of cereals and vegetables than the other genotype carriers. The Val/Val genotype conferred a higher risk for HTG than the Ile/Val and Ile/Ile genotypes (OR = 3.26, 95%CI 1.35–7.86, p = 0.006 and OR = 2.61, 95%CI 1.12–6.07, p = 0.02, respectively). Furthermore, the Val/Val genotype was associated with approximately 30% higher triglycerides compared with Ile/Val and Ile/Ile genotypes (β = 44.09, 95%CI 9.94–78.25, p = 0.01 and β = 45.7, 95%CI 10.85–80.54, p = 0.01, respectively). In conclusion, the Val/Val genotype of TAS1R2 was associated with a higher carbohydrate intake and HTG. PMID:26907331

The Role of Intralipid Emulsion in the Rat Model of Digoxin Intoxication.

PubMed

Turan, Cansu Arslan; Ozturk, Tuba Cimilli; Akoglu, Ebru Unal; Ak, Rohat; Aygun, Kemal; Sahiner, Ali; Sumer, Engin; Somay, Adnan; Onur, Ozge Ecmel

2018-02-03

Although the mechanism of action is not well known, intravenous lipid emulsion (ILE) has been shown to be effective in the treatment of lipophilic drug intoxications. It is thought that, ILE probably separates the lipophilic drugs from target tissue by creating a lipid-rich compartment in the plasma. The second theory is that ILE provides energy to myocardium with high-dose free fatty acids activating the voltage-gated calcium channels in the myocytes. In this study, effects of ILE treatment on digoxin overdose were searched in an animal model in terms of cardiac side effects and survival. Forty Sprague-Dawley rats were divided into five groups. As the pre-treatment, the groups were administered saline, ILE, DigiFab and DigiFab and ILE. Following that, digoxin was infused to all groups until death except the control group. First arrhythmia and cardiac arrest observation times were recorded. According to the results, there was no statistically significant difference among the group in terms of first arrhythmia time and cardiac arrest times. However, when the saline group compared with ILE-treated group separately, significant difference was observed. DigiFab, ILE or ILE-DigiFab treatment make no significant difference in terms of the first arrhythmia and cardiac arrest duration in digoxin-intoxicated rats. However, it is not possible to say that at the given doses, ILE treatment might be successful at least as a known antidote. The fact that the statistical significance between the two groups is not observed in the subgroup analysis, the study should be repeated with larger groups.

Application of histogram analysis for the evaluation of vascular permeability in glioma by the K2 parameter obtained with the dynamic susceptibility contrast method: Comparisons with Ktrans obtained with the dynamic contrast enhance method and cerebral blood volume.

PubMed

Taoka, Toshiaki; Kawai, Hisashi; Nakane, Toshiki; Hori, Saeka; Ochi, Tomoko; Miyasaka, Toshiteru; Sakamoto, Masahiko; Kichikawa, Kimihiko; Naganawa, Shinji

2016-09-01

The "K2" value is a factor that represents the vascular permeability of tumors and can be calculated from datasets obtained with the dynamic susceptibility contrast (DSC) method. The purpose of the current study was to correlate K2 with Ktrans, which is a well-established permeability parameter obtained with the dynamic contrast enhance (DCE) method, and determine the usefulness of K2 for glioma grading with histogram analysis. The subjects were 22 glioma patients (Grade II: 5, III: 6, IV: 11) who underwent DSC studies, including eight patients in which both DSC and DCE studies were performed on separate days within 10days. We performed histogram analysis of regions of interest of the tumors and acquired 20th percentile values for leakage-corrected cerebral blood volume (rCBV20%ile), K2 (K220%ile), and for patients who underwent a DCE study, Ktrans (Ktrans20%ile). We evaluated the correlation between K220%ile and Ktrans20%ile and the statistical difference between rCBV20%ile and K220%ile. We found a statistically significant correlation between K220%ile and Ktrans20%ile (r=0.717, p<0.05). rCBV20%ile showed a significant difference between Grades II and III and between Grades II and IV, whereas K220%ile showed a statistically significant (p<0.05) difference between Grades II and IV and between Grades III and IV. The K2 value calculated from the DSC dataset, which can be obtained with a short acquisition time, showed a correlation with Ktrans obtained with the DCE method and may be useful for glioma grading when analyzed with histogram analysis. Copyright © 2016 Elsevier Inc. All rights reserved.

NMR analyses of the conformations of L-isoleucine and L-valine bound to Escherichia coli isoleucyl-tRNA synthetase

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

Kohda, D.; Kawai, G.; Yokoyama, S.

1987-10-06

The 400-MHz /sup 1/H NMR spectra of L-isoleucine and L-valine were measured in the presence of Escherichia coli isoleucyl-tRNA synthetase (IleRS). Because of chemical exchange of L-isoleucine or L-valine between the free state and the IleRS-bound state, a transferred nuclear Overhauser effect (TRNOE) was observed among proton resonances of L-isoleucine or L-valine. However, in the presence of isoleucyl adenylate tightly bound to the amino acid activation site of IleRS, no TRNOE for L-isoleucine or L-valine was observed. This indicates that the observed TRNOE is due to the interaction of L-isoleucine or L-valine with the amino acid activation site of IleRS.more » The conformations of these amino acids in the amino acid activation site of IleRS were determined by the analyses of time dependences of TRNOEs and TRNOE action spectra. The IleRS-bound L-isoleucine takes the gauche/sup +/ form about the C/sub ..cap alpha../-C/sub ..beta../ bond and the trans form about the C/sub ..beta../-C/sub ..gamma../sub 1// bond. The IleRS-bound L-valine takes the guache/sup -/ form about the C/sub ..cap alpha../-C/sub ..beta../ bond. Thus, the conformation of the IleRS-bound L-valine is the same as that of IleRS-bound L-isoleucine except for the delta-methyl group. The side chain of L-isoleucine or L-valine lies in an aliphatic hydrophobic pocket of the active site of IleRS. Such hydrophobic interaction with IleRS is more significant for L-isoleucine than for L-valine. The TRNOE analysis is useful for studying the amino acid discrimination mechanism of aminoacyl-tRNA synthetases.« less

CYP94-mediated jasmonoyl-isoleucine hormone oxidation shapes jasmonate profiles and attenuates defence responses to Botrytis cinerea infection

PubMed Central

Aubert, Yann; Widemann, Emilie; Miesch, Laurence; Pinot, Franck; Heitz, Thierry

2015-01-01

Induced resistance to the necrotrophic pathogen Botrytis cinerea depends on jasmonate metabolism and signalling in Arabidopsis. We have presented here extensive jasmonate profiling in this pathosystem and investigated the impact of the recently reported jasmonoyl-isoleucine (JA-Ile) catabolic pathway mediated by cytochrome P450 (CYP94) enzymes. Using a series of mutant and overexpressing (OE) plant lines, we showed that CYP94B3 and CYP94C1 are integral components of the fungus-induced jasmonate metabolic pathway and control the abundance of oxidized conjugated but also some unconjugated derivatives, such as sulfated 12-HSO4-JA. Despite causing JA-Ile overaccumulation due to impaired oxidation, CYP94 deficiency had negligible impacts on resistance, associated with enhanced JAZ repressor transcript levels. In contrast, plants overexpressing (OE) CYP94B3 or CYP94C1 were enriched in 12-OH-JA-Ile or 12-COOH-JA-Ile respectively. This shift towards oxidized JA-Ile derivatives was concomitant with strongly impaired defence gene induction and reduced disease resistance. CYP94B3-OE, but unexpectedly not CYP94C1-OE, plants displayed reduced JA-Ile levels compared with the wild type, suggesting that increased susceptibility in CYP94C1-OE plants may result from changes in the hormone oxidation ratio rather than absolute changes in JA-Ile levels. Consistently, while feeding JA-Ile to seedlings triggered strong induction of JA pathway genes, induction was largely reduced or abolished after feeding with the CYP94 products 12-OH-JA-Ile and 12-COOH-JA-Ile, respectively. This trend paralleled in vitro pull-down assays where 12-COOH-JA-Ile was unable to promote COI1–JAZ9 co-receptor assembly. Our results highlight the dual function of CYP94B3/C1 in antimicrobial defence: by controlling hormone oxidation status for signal attenuation, these enzymes also define JA-Ile as a metabolic hub directing jasmonate profile complexity. PMID:25903915

[Construction of thr461 --> Asn461 and Ile462 --> Val462 mutation vector of P4501A1 gene].

PubMed

Wei, Qing; Liu, Yi-Min; Wang, Hui; Zhao, Xiao-Lin; Ren, Tie-ling; Xiao, Yong-mei

2006-09-01

To construct Thr461 --> Asn461 and Ile462 --> Val462 mutation vector of P4501A1 gene and to provide scientific base for deeply researching on the function of cytochrome 1A1 gene (CYP1A1) and the mechanism of carcinogenesis. According to cDNA sequence of human CYP1A1 gene, universal primers (Pm3/Pm4) and mutant primers (Pt15/Pt16 and Pt17/Pt18) containing restriction enzyme site and mutation site were designed. The first set of primers involving Pm3/Pt16 and Pm3/Pt18 amplified a forward 1.5kb fragment from pGEM-T-CYP1A1 plasmid. The second set of primers involving Pt15/Pm4 and Pt17/Pm4 amplified a reverse 177-bp fragment from 10ng pGEM-T-CYP1A1 plasmid. The third set of primers involving Pm3/Pm4 amplified a 1.5kb fragment from the fomer PCR amplifications. The third PCR products were separated, purified and recovered from 1% agarose gel, then inserted into pMD-T vector. Subsequently the conjunct products were transformed into E. coil strain DH-5alpha., then the single clone was screened out and plasmids were extracted from such clone finally verified by restriction endonuclease analysis and sequencing. A 1.5kb fragment of tricycle PCR amplifications were digested by restriction endonucleases (BamHI and SailI) and sequenced bidirectionally by universal primers(T7p and SP6). The results verified that the cloned fragment including Asn461 and Val462 mutant site had 99.9% homology with the human cDNA of CYP1A1 gene in Genebank. The objective fragment containing Asn461 and Va462 mutant site with cDNA of the CYP1A1 gene has been successfully constructed in this experiment.

Ile-1781-Leu and Asp-2078-Gly Mutations in ACCase Gene, Endow Cross-resistance to APP, CHD, and PPZ in Phalaris minor from Mexico

PubMed Central

Cruz-Hipolito, Hugo; Fernandez, Pablo; Alcantara, Ricardo; Gherekhloo, Javid; Osuna, Maria Dolores; De Prado, Rafael

2015-01-01

Herbicides that inhibit acetyl coenzyme A carboxylase (ACCase) are commonly used in Mexico to control weedy grasses such as little seed canarygrass (Phalaris minor). These herbicides are classified into three major families (ariloxyphenoxypropionates (APP), cyclohexanodiones (CHD), and, recently, phenylpyrazolines (PPZ)). In this work, the resistance to ACCase (APP, CHD, and PPZ) inhibiting herbicides was studied in a biotype of Phalaris minor (P. minor) from Mexico, by carrying out bioassays at the whole-plant level and investigating the mechanism behind this resistance. Dose-response and ACCase in vitro activity assays showed cross-resistance to all ACCase herbicides used. There was no difference in the absorption, translocation, and metabolism of the 14C-diclofop-methyl between the R and S biotypes. The PCR generated CT domain fragments of ACCase from the R biotype and an S reference were sequenced and compared. The Ile-1781-Leu and Asp-2078-Gly point mutations were identified. These mutations could explain the loss of affinity for ACCase by the ACCase-inhibing herbicides. This is the first report showing that this substitution confers resistance to APP, CHD, and PPZ herbicides in P. minor from Mexico. The mutations have been described previously only in a few cases; however, this is the first study reporting on a pattern of cross-resistance with these mutations in P. minor. The findings could be useful for better management of resistant biotypes carrying similar mutations. PMID:26370967

The influence of monovalent cations on trimeric G protein G(i)1α activity in HEK293 cells stably expressing DOR-G(i)1α (Cys(351)-Ile(351)) fusion protein.

PubMed

Vošahlíková, M; Svoboda, P

2011-01-01

The effect of monovalent cations on trimeric G protein G(i)1α was measured at equimolar concentration of chloride anion in pertussis-toxin (PTX)-treated HEK293 cells stably expressing PTX-insensitive DOR- G(i)1α (Cys(351)-Ile(351)) fusion protein by high-affinity [(35)S]GTPgammaS binding assay. The high basal level of binding was detected in absence of DOR agonist and monovalent ions and this high level was inhibited with the order of: Na(+) > K(+) > Li(+). The first significant inhibition was detected at 1 mM NaCl. The inhibition by monovalent ions was reversed by increasing concentrations of DOR agonist DADLE. The maximum DADLE response was also highest for sodium and decreased in the order of: Na(+) > K(+) ~ Li(+). Our data indicate i) an inherently high activity of trimeric G protein G(i)1α when expressed within DOR- G(i)1α fusion protein and determined in the absence of monovalent cations, ii) preferential sensitivity of DOR- G(i)1alpha to sodium as far as maximum of agonist response is involved.

Recovery of an injured cingulum concurrent with improvement of short-term memory in a patient with mild traumatic brain injury.

PubMed

Jang, Sung Ho; Kim, Seong Ho; Seo, Jeong Pyo

2018-01-01

We reported on a patient with mild traumatic brain injury (TBI) who showed recovery of an injured cingulum concurrent with improvement of short-term memory, which was demonstrated on follow-up diffusion tensor tractography (DTT). A 55-year-old male patient suffered head trauma resulting from falling from approximately 2 m while working at a construction site. The patient showed mild memory impairment (especially short-term memory impairment) at 3 months after onset: Memory Assessment Scale (global memory: 95 (37%ile), short-term memory: 75 (5%ile), verbal memory: 80 (9%ile) and visual memory: 112 (79%ile)). By contrast, at 2 years after onset, his mild memory impairment had improved to a normal state: Memory Assessment Scale (global memory: 104 (61%ile), short-term memory: 95 (37%ile), verbal memory: 101 (53%ile) and visual memory: 106 (66%ile)). On 3-month DTT, discontinuation of the right anterior cingulum was observed over the genu of the corpus callosum, while on 2-year DTT, the discontinued right anterior cingulum was elongated to the right basal forebrain. In conclusion, recovery of an injured cingulum concurrent with improvement of short-term memory was demonstrated in a patient with mild TBI.

Reference percentiles of FEV1 for the Canadian cystic fibrosis population: comparisons across time and countries.

PubMed

Kim, Sang-Ook; Corey, Mary; Stephenson, Anne L; Strug, Lisa J

2018-05-01

Forced expiratory volume in 1 s (FEV1) indicates lung health in cystic fibrosis (CF). FEV1 is commonly communicated as a per cent predicted of a healthy individual sharing the same age, sex, race and height. CF-specific reference equations are complementary and calibrate a patient's FEV1 to that of their CF peers. (1) To derive Canadian CF-specific FEV1 reference percentiles (FEV1%iles), (2) characterize how they have changed over time and (3) compare the Canadian FEV1%iles to those for USA and European CF populations. CF FEV1%iles are calculated using the Canadian CF Registry and quantile regression. The Canadian FEV1%iles demonstrated better lung function in more recent time periods within Canada, especially below the 50% percentile and in males. When compared to USA and European FEV1%iles for the same time period, Canadian FEV1%iles were higher. CF-specific FEV1%iles can provide useful information about changes in lung health. An online calculator (available at cfpercentile. sickkids.ca) makes these FEV1%iles accessible. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Ligand-receptor co-evolution shaped the jasmonate pathway in land plants.

PubMed

Monte, Isabel; Ishida, Sakiko; Zamarreño, Angel M; Hamberg, Mats; Franco-Zorrilla, José M; García-Casado, Gloria; Gouhier-Darimont, Caroline; Reymond, Philippe; Takahashi, Kosaku; García-Mina, José M; Nishihama, Ryuichi; Kohchi, Takayuki; Solano, Roberto

2018-05-01

The phytohormone jasmonoyl-isoleucine (JA-Ile) regulates defense, growth and developmental responses in vascular plants. Bryophytes have conserved sequences for all JA-Ile signaling pathway components but lack JA-Ile. We show that, in spite of 450 million years of independent evolution, the JA-Ile receptor COI1 is functionally conserved between the bryophyte Marchantia polymorpha and the eudicot Arabidopsis thaliana but COI1 responds to different ligands in each species. We identified the ligand of Marchantia MpCOI1 as two isomeric forms of the JA-Ile precursor dinor-OPDA (dinor-cis-OPDA and dinor-iso-OPDA). We demonstrate that AtCOI1 functionally complements Mpcoi1 mutation and confers JA-Ile responsiveness and that a single-residue substitution in MpCOI1 is responsible for the evolutionary switch in ligand specificity. Our results identify the ancestral bioactive jasmonate and clarify its biosynthetic pathway, demonstrate the functional conservation of its signaling pathway, and show that JA-Ile and COI1 emergence in vascular plants required co-evolution of hormone biosynthetic complexity and receptor specificity.

Lipid resuscitation in acute poisoning: after a decade of publications, what have we really learned?

PubMed

Hoegberg, Lotte C G; Gosselin, Sophie

2017-08-01

The decision to provide intravenous lipid emulsion (ILE) therapy as a treatment modality for the reversal of various drug toxicity was discovered in the last decade. Numerous publications, in both humans and animals attest to its clinical use, but current supporting evidence is inconsistent. A recent systematic review reported evidence for benefit of ILE in bupivacaine toxicity. Human randomized trials, large observational studies as well as animal models of orogastric poisoning failed to report a clear benefit of ILE for nonlocal anesthetics poisoning. ILE can be used to resuscitate local anesthetics especially bupivacaine. The impact of ILE on oral overdoses is controversial and clear evidence on benefit is lacking. A thorough risk benefit assessment with consideration of alternative options is warranted to minimize the risk of adverse effects. Evidence supports using bolus doses of ILE, while infusion rates are still debatable.

Impact of the Ile105Val Polymorphism of the Glutathione S-transferase P1 (GSTP1) Gene on Obesity and Markers of Cardiometabolic Risk in Young Adult Population.

PubMed

Chielle, E O; Trott, A; da Silva Rosa, B; Casarin, J N; Fortuna, P C; da Cruz, I B M; Moretto, M B; Moresco, R N

2017-05-01

The aim of the study was to investigate the association between Glutathione S-transferase P1 (GSTP1) gene polymorphism with obesity and markers of cardiometabolic risk. A cross-sectional study was carried out in individuals aged≥18 and ≤30 years. The study included 54 normal weight, 27 overweight and 68 obese volunteers. Anthropometric measurements and biochemical parameters were evaluated, the DNA was extracted from blood samples and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to measure GSTP1 Ile 105 Val gene polymorphism of the study participants. Also, biochemical analysis and hormone assays were carried out. A positive association between GSTP1 polymorphism and obesity was observed on subjects carrying at least one G allele (AG and GG). GG genotype was found only in the obese group. The G allele carriers presented 2.4 times higher chance of obesity when compared to those with the AA genotype. These results were independent of sex and age. We suggest that despite a study in population regional (south of Brazil), the GSTP1 gene polymorphism may play a significant role in the increase of susceptibility of obesity and contribute to identify the cardiovascular risk in young adults. © Georg Thieme Verlag KG Stuttgart · New York.

Exploring the structural basis of the selective inhibition of monoamine oxidase A by dicarbonitrile aminoheterocycles: role of Asn181 and Ile335 validated by spectroscopic and computational studies.

PubMed

Juárez-Jiménez, Jordi; Mendes, Eduarda; Galdeano, Carles; Martins, Carla; Silva, Daniel B; Marco-Contelles, José; do Carmo Carreiras, Maria; Luque, F Javier; Ramsay, Rona R

2014-02-01

Since cyanide potentiates the inhibitory activity of several monoamine oxidase (MAO) inhibitors, a series of carbonitrile-containing aminoheterocycles was examined to explore the role of nitriles in determining the inhibitory activity against MAO. Dicarbonitrile aminofurans were found to be potent, selective inhibitors against MAO A. The origin of the MAO A selectivity was identified by combining spectroscopic and computational methods. Spectroscopic changes induced in MAO A by mono- and dicarbonitrile inhibitors were different, providing experimental evidence for distinct binding modes to the enzyme. Similar differences were also found between the binding of dicarbonitrile compounds to MAO A and to MAO B. Stabilization of the flavin anionic semiquinone by monocarbonitrile compounds, but destabilization by dicarbonitriles, provided further support to the distinct binding modes of these compounds and their interaction with the flavin ring. Molecular modeling studies supported the role played by the nitrile and amino groups in anchoring the inhibitor to the binding cavity. In particular, the results highlight the role of Asn181 and Ile335 in assisting the interaction of the nitrile-containing aminofuran ring. The network of interactions afforded by the specific attachment of these functional groups provides useful guidelines for the design of selective, reversible MAO A inhibitors. Copyright © 2013 Elsevier B.V. All rights reserved.

[Modalities of transition of diabetic adolescents from pediatrics to the adult care in the Paris-Ile-de-France region: an appeal to cooperative work for improving quality of care. Paris-Ile-de-France Section of DESG (Diabetes Education Study Group) in French language].

PubMed

Crosnier, H; Tubiana-Rufi, N

1998-12-01

The purpose of this study was to evaluate the conditions in which diabetic adolescents are transferred from pediatric to adult health care, and to record the opinions of the physicians about this issue. A questionnaire-based study was performed among all the pediatricians in the hospital setting and all the diabetologists from the Paris-Ile-de-France area. Questionnaires from 50 pediatricians and 51 diabetologists were completed (response rate: 68%). 1) Not enough information was transmitted: a quarter of the diabetologists were visiting for the first time without any information on the adolescent, and only half the pediatricians received feedback information from the internists after the first visit. And yet, when considered, it was important to be kept informed after the first visit and the following ones. 2) Medical relationships were poor: more than three out of four pediatricians and diabetologists had none or very few professional meetings, and two thirds of them were not aware of the way the others were working. 3) Eighty percent of pediatricians and diabetologists considered that the transfer of diabetic adolescents had to be organised in order to keep the coherence of medical follow-up, to minimise the psychological effects of the transition, and to avoid a complete break in the patient follow-up. 4) The expectations of the pediatricians were: the validation of their previous follow-up through the feedback information from diabetologists and the continuity of the medical follow-up; those of the diabetologists were: to gain the patient's confidence and to master the patient's previous history, in order to provide a better follow-up. 5) According to the opinion of both pediatricians and diabetologists, the main errors to avoid were, by the paediatricians, to miss the time and the preparation of the transfer and, by the diabetologists, to denigrate the previous pediatric management and to change the insulin regimen immediately. This study demonstrates a lack

Occurrence of the angiotensin-converting enzyme inhibiting tripeptides Val-Pro-Pro and Ile-Pro-Pro in different cheese varieties of Swiss origin.

PubMed

Bütikofer, U; Meyer, J; Sieber, R; Walther, B; Wechsler, D

2008-01-01

The contents of the 2 antihypertensive peptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) were determined in 101 samples from 10 different Swiss cheese varieties using HPLC with subsequent triple mass spectrometry. In the category of extra hard and hard cheeses, the Protected Denomination of Origin cheeses Berner Alpkäse and Berner Hobelkäse, L'Etivaz à rebibes, Le Gruyère, Sbrinz, Emmentaler (organic and conventional) and in the category of semihard cheeses, the varieties Tilsiter, Appenzeller 1/4 fat and full fat, Tête de Moine, and Vacherin fribourgeois were screened in the study. The average concentration of the sum of VPP and IPP in the screened cheese varieties varied to a large extent, and substantial variations were obtained for individual samples within the cheese varieties. The lowest average concentration of the 2 tri-petides was found in L'Etivaz à rebibes (n = 3) at 19.1 mg/kg, whereas Appenzeller 1/4 fat (n = 4) contained the greatest concentration at 182.2 mg/kg. In individual samples, the total concentration of VPP and IPP varied between 1.6 and 424.5 mg/kg. With the exception of a 10-yr-old cheese, VPP was always present at greater concentrations than IPP. Milk pretreatment, cultures, scalding conditions, and ripening time were identified as the key factors influencing the concentration of these 2 naturally occurring bioactive peptides in cheese. The results of the present study show that various traditional cheese varieties contain, on average, similar concentrations of the 2 antihypertensive peptides to the recently developed fermented milk products with blood pressure-lowering property. This may serve as a basis for the development of a functional cheese with blood pressure-lowering property.

Mullinamides A and B, New Cyclopeptides Produced by the Ruth Mullins Coal Mine Fire Isolate Streptomyces sp. RM-27-46

PubMed Central

Wang, Xiachang; Shaaban, Khaled A.; Elshahawi, Sherif I.; Ponomareva, Larissa V.; Sunkara, Manjula; Copley, Gregory C.; Hower, James C.; Morris, Andrew J.; Kharel, Madan K.; Thorson, Jon S.

2014-01-01

Two new cyclopeptides, mullinamides A [cyclo-(-l-Gly-l-Glu-l-Val-l-Ile-l-Pro-)] and B [cyclo-(-l-Glu-l-Met-l-Pro-)] were isolated from the crude extract of terrestrial Streptomyces sp. RM-27-46 along with the three known cyclopeptides surugamide A [cyclo-(-l-Ile-d-Ile-l-Lys-l-Ile-d-Phe-d-Leu-l-Ile-d-Ala-)], cyclo-(-l-Pro-l-Phe-) and cyclo-(-l-Pro-l-Leu-). The structures of the new compounds were elucidated by the cumulative analyses of NMR spectroscopy and high resolution mass spectrometry. While mullinamides A and B displayed no appreciable antimicrobial/fungal activity or cytotoxicity, this study highlights the first reported antibacterial activity of surugamide A. PMID:24713874

Flesh quality loss in response to dietary isoleucine deficiency and excess in fish: a link to impaired Nrf2-dependent antioxidant defense in muscle.

PubMed

Gan, Lu; Jiang, Wei-Dan; Wu, Pei; Liu, Yang; Jiang, Jun; Li, Shu-Hong; Tang, Ling; Kuang, Sheng-Yao; Feng, Lin; Zhou, Xiao-Qiu

2014-01-01

The present study explored the impact of dietary isoleucine (Ile) on fish growth and flesh quality and revealed a possible role of muscle antioxidant defense in flesh quality in relation to dietary Ile. Grass carp (weighing 256.8±3.5 g) were fed diets containing six graded levels of Ile (3.8, 6.6, 9.3, 12.5, 15.2 and 18.5 g/kg) for eight weeks. The results indicated that compared with Ile deficiency (3.8 g/kg diets) and excess (18.5 g/kg diets) groups, 9.3-15.2 g Ile/kg diet supplementations promoted fish growth and muscle fat deposition, whereas 6.6-15.2 g Ile/kg diets supplementation enhanced muscle nutrients (protein and total EAAs) deposition. Furthermore, muscle shear force, pH value, and hydroxyproline concentration were improved by 9.3-12.5, 9.3 and 9.3 g Ile/kg diet supplementations, respectively. However, muscle cooking loss, lactate content, and activities of cathepsin B and L were decreased by 6.6-15.2, 9.3-12.5, 9.3-12.5 and 9.3-15.2 g Ile/kg diet supplementations, respectively. Additionally, 6.6-15.2 and 6.6-12.5 g Ile/kg diet supplementations attenuated malondialdehyde and protein carbonyl contents, respectively. The activities of copper/zinc superoxide dismutase (Cu/Zn-SOD) and glutathione peroxidase (GPx), and glutathione content were enhanced by 6.6-9.3, 6.6-12.5 and 6.6-15.2 g Ile/kg diet supplementations, respectively. Moreover, the relative mRNA expressions of antioxidant enzymes, including Cu/Zn-SOD (6.6-12.5 g/kg diets) and GPx (12.5 g/kg diets), as well as antioxidant-related signaling molecules, including NF-E2-related factor 2 (Nrf2) (6.6-12.5 g/kg diets), target of rapamycin (6.6-12.5 g/kg diets), ribosomal S6 protein kinase 1 (9.3-12.5 g/kg diets) and casein kinase 2 (6.6-12.5 g/kg diets), were up-regulated when Ile diet supplementations were administered at these levels, respectively, whereas the relative mRNA expression of Kelch-like ECH-associated protein 1 was down-regulated with 9.3 g Ile/kg diet supplementations. Collectively, the

United States Navy DL Perspective

DTIC Science & Technology

2010-08-10

United States Navy DL Perspective CAPT Hank Reeves Navy eLearning Project Director 10 August 2010 Report Documentation Page Form ApprovedOMB No...Marine Corps (USMC) Navy eLearning Ongoing Shared with USMC, Coast Guard 9 NeL Help Site https://ile-help.nko.navy.mil/ile/ https://s-ile

Telecommunication Policy in the Caribbean: A Comparison of Telecommunications in the Dominican Republic and Haiti

DTIC Science & Technology

2011-09-01

Mexico and South America. By 1625, French buccaneers had established a settlement on the island of Tortuga and survived by pirating English and Spanish...smaller islands in its territory; these are: Ile de la Gonave, Ile de la Tortue ( Tortuga Island), Grande Cayemite, and Ile de la Vache. The island

Adrenal hormones and the anorectic response and adaptation of rats to amino acid imbalance.

PubMed

Hammer, V A; Gietzen, D W; Sworts, V D; Beverly, J L; Rogers, Q R

1990-12-01

The role of adrenal function in the anorectic response and adaptation of rats to a diet with an isoleucine (Ile) imbalance was investigated. In the first of four experiments, rats were fed a mildly Ile-imbalanced diet after treatment with metyrapone, and inhibitor of glucocorticoid synthesis. In two separate experiments, rats were presented with either a mildly or severely Ile-imbalanced diet (4.93 and 9.86% imbalanced amino acid mixture, respectively) after bilateral adrenalectomy. Finally, the effects of ICS 205-930, a serotonin-3 receptor antagonist, on the intake of mildly Ile-imbalanced diet were tested in adrenalectomized animals. In each experiment a 2 X 2 factorial design was used. Neither metyrapone nor adrenalectomy altered the initial depression in the intake of an imbalanced diet. The adaptation phase in the response of adrenalectomized rats fed a mildly Ile-imbalanced diet was not different from that of controls, but adrenalectomized rats fed severely Ile-imbalanced diets were unable to adapt. Adrenalectomy did not alter the anti-anoretic activity of ICS 205-930 in this model. These results suggest that adrenal hormones are not necessary for the initial anoretic response or adaptation of rats to an Ile-imbalanced diet, nor are they implicated in the anti-anorectic effect of serotonin-3 blockade.

Polymorphisms of glutathione S-transferase Mu 1 (GSTM1), Theta 1 (GSTT1), and Pi 1 (GSTP1) genes and epithelial ovarian cancer risk.

PubMed

Oliveira, Cristiane; Lourenço, Gustavo Jacob; Sagarra, Regina Aparecida Martinho; Derchain, Sophie Françoise Mauricette; Segalla, José Getulio; Lima, Carmen Silvia Passos

2012-01-01

Exposure of ovarian cells to estrogen, which is detoxified by glutathione S-transferases (GSTs), has been associated with epithelial ovarian cancer (EOC) development. We tested in this study whether the GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms alter the risk of EOC. Genomic DNA from 132 EOC patients and 132 controls was analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. The differences between groups were analyzed by χ ^{2} or Fisher's exact test. The frequencies of GSTP1 Ile/Ile (57.6% versus 45.5%, P=0.03), GSTM1 null plus GSTP1 Ile/Ile (43.5% versus 25.8%; P=0.03) and GSTM1 null plus GSTT1 null plus GSTP1 Ile/Ile (30.3% versus 7.7%; P=0.007) genotypes were higher in patients than in controls. Individuals with the respective genotypes had a 1.80 (95% CI: 1.06-3.06), 2.38 (95% CI: 1.08-5.24) and 11.28 (95%CI: 1.95-65.30)-fold increased risks of EOC than those with the remaining genotypes. Our data present preliminary evidence that GSTM1, GSTT1 and GSTP1 polymorphisms, particularly in combination, constitute important inherited EOC determinants in individuals from Southeastern Brazil.

Breast Cancer Risk Associated with Genotype Polymorphisms of the Aurora Kinase a Gene (AURKA): a Case-Control Study in a High Altitude Ecuadorian Mestizo Population.

PubMed

López-Cortés, Andrés; Cabrera-Andrade, Alejandro; Oña-Cisneros, Fabián; Rosales, Felipe; Ortiz, Malena; Tejera, Eduardo; Paz-Y-Miño, César

2018-07-01

Breast cancer (BC) is the leading cause of cancer related death among women in 2014. The AURKA gene that encodes the protein called Aurora kinase A plays an important role in the progression of the cell cycle, by controlling and promoting the entry into the phase of mitosis. The single nucleotide polymorphism AURKA T91A (rs2273535) (Phe21Ile) has been identified as functional alternator of this kinase, the Ile allele is associated with the occurrence of chromosome segregation errors and tumor progression. Therefore, it is essential to know how BC risk is associated with histopathological characteristics, immunohistochemical characteristics, and genotype polymorphism in a high altitude Ecuadorian mestizo population. In this retrospective case-control study 200 individuals were analyzed. DNA was extracted from 100 healthy and 100 affected women. Genotypes were determined by genomic sequencing. We found significant association between the AURKA T91A (rs2273535) (Phe21Ile) genotype and an increased risk of BC development: Phe/Ile (odds ratio [OR] = 2.6; 95% confidence interval [CI] = 1.4-4.9; P = 0.004), Ile/Ile (OR = 3.8; 95% CI = 1.6-9.0; P = 0.002), and Phe/Ile + Ile/Ile (OR = 2.9; 95% CI = 1.6-5.2; P = 0.001). Additionally, the rs2273535 variant was associated with the tumor grade SBR III (OR = 9.6; 95% CI = 1.0-91.9; P = 0.048) and the Ki-67 ≥ 20 (OR = 16.5; 95% CI = 2.7-101.3; P = 0.002). In brief, this study provides the first evidence where the Ile allele of the AURKA gene could act as potentially predictive biomarker of BC in the high altitude Ecuadorian mestizo population that lives at 2800 m above sea level (masl).

Silencing of Essential Genes within a Highly Coordinated Operon in Escherichia coli

PubMed Central

Hohmeier, Angela; Stone, Timothy C.; Offord, Victoria; Sarabia, Francisco; Garcia-Ruiz, Cristina; Good, Liam

2015-01-01

Essential bacterial genes located within operons are particularly challenging to study independently because of coordinated gene expression and the nonviability of knockout mutants. Essentiality scores for many operon genes remain uncertain. Antisense RNA (asRNA) silencing or in-frame gene disruption of genes may help establish essentiality but can lead to polar effects on genes downstream or upstream of the target gene. Here, the Escherichia coli ribF-ileS-lspA-fkpB-ispH operon was used to evaluate the possibility of independently studying an essential gene using expressed asRNA and target gene overexpression to deregulate coupled expression. The gene requirement for growth in conditional silencing strains was determined by the relationship of target mRNA reduction with growth inhibition as the minimum transcript level required for 50% growth (MTL50). Mupirocin and globomycin, the protein inhibitors of IleS and LspA, respectively, were used in sensitization assays of strains containing both asRNA-expressing and open reading frame-expressing plasmids to examine deregulation of the overlapping ileS-lspA genes. We found upstream and downstream polar silencing effects when either ileS or lspA was silenced, indicating coupled expression. Weighted MTL50 values (means and standard deviations) of ribF, ileS, and lspA were 0.65 ± 0.18, 0.64 ± 0.06, and 0.76 ± 0.10, respectively. However, they were not significantly different (P = 0.71 by weighted one-way analysis of variance). The gene requirement for ispH could not be determined due to insufficient growth reduction. Mupirocin and globomycin sensitization experiments indicated that ileS-lspA expression could not be decoupled. The results highlight the inherent challenges associated with genetic analyses of operons; however, coupling of essential genes may provide opportunities to improve RNA-silencing antimicrobials. PMID:26070674

Meat and poultry consumption contribution to the natural radionuclide intake of the inhabitants of the Obafemi Awolowo University, Ile-Ife, Nigeria

NASA Astrophysics Data System (ADS)

Akinloye, M. K.; Olomo, J. B.; Olubunmi, P. A.

1999-02-01

The mean activity concentrations of the naturally occurring radionuclides ( 226Ra, 228Ra and 40K) in three types of meat (goat meat, beef and pork) from stock animals as well as free-range and intensive poultry raised within the OAU environment of the Obafemi Awolowo University (OAU), Ile-Ife, were measured by means of a well-calibrated high-purity germanium detector. The specific activities of 226Ra in the three types of meat ranged from 1.11 to 5.83 Bq kg -1 with a mean of 3.10±1.52 Bq kg -1. 228Ra was not detectable in both beef and pork but had a range of 1.53-1.63 Bq kg -1 with a mean of 1.58±0.30 Bq kg -1 in goat meat while 40K recorded an average specific activity of 360.00±54.20 Bq kg -1 for the various samples of meat. The mean activity values of 226Ra, 228Ra and 40K for the poultry were 2.59±0.48, 0.78±0.13 and 265.01±15.90 Bq kg -1, respectively. The results obtained for the daily radionuclide intake of the various meat types showed that those of 226Ra ranged from 0.4 to 8.1 mBq d -1 with a mean of 4.9±0.4 mBq d -1. Since 228Ra was not detectable in beef and pork its daily intake could not be estimated. However, a mean value of intake of 2.2±0.4 mBq d -1 was obtained for goat meat. The values of 40K intake ranged from 150.0 to 672.7 mBq d -1 with an average of 455.5±19.0 mBq d -1. The mean daily intakes of 226Ra, 228Ra and 40K for the two types of poultry were 6.15±0.70, 1.9±0.3 and 633.4±38.0 mBq d -1, respectively.

Potential intake of vitamins "A" and "D" through branded intravenous lipid emulsions: Liquid Chromatography-Tandem Mass Spectrometry Analysis.

PubMed

Forchielli, Maria Luisa; Conti, Matteo; Patrono, Daniela; Mancini, Rita; Pession, Andrea; Puggioli, Cristina; Bersani, Germana

2017-04-01

No data exist for vitamin A group and vitamin D2/D3 content in branded intravenous lipid emulsions (ILEs). Our goal is to evaluate and quantify their concentrations in different ILEs to assess whether they are clinically relevant. Analyses were carried out in triplicates on six ILEs: 1) 30% soybean oil-based, 2) 20% olive-soybean oil based, 3) 10 + 10% soybean - MCT coconut oil based, 4) 20% soybean-olive-MCT-fish oil based, 5) 20% soybean-MCT-fish oil based and 6) 10% pure fish oil based, respectively. Retinol group (vitamin A) and ergo-chole-calciferol (vitamin D2/D3) were analyzed and quantified by a quali-quantitative Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method after potassium hydroxide alkaline hydrolysis, hexane extraction, reverse phase-liquid chromatography and specific multiple-reaction-monitoring (MRM) detection. On average, measured retinol content was in the range of 200-1000 μg/L in ILEs (1,2, and 3), whereas it was higher (1000-2000 μg/L) in the ILEs containing fish-oil. Vitamin D content was in the range of 1-10 μg/L in the fish-oil based ILEs, but undetectable in those ILEs containing purely vegetable oils. This study shows that vitamin A and D contents are variably present in ILEs based on their different lipid sources. Both contents should be explicitly mentioned in the products. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The use of intravenous lipid emulsion as an antidote in veterinary toxicology.

PubMed

Fernandez, Alberto L; Lee, Justine A; Rahilly, Louisa; Hovda, Lynn; Brutlag, Ahna G; Engebretsen, Kristin

2011-08-01

To review the use of IV lipid emulsion (ILE) for the treatment of toxicities related to fat-soluble agents; evaluate current human and veterinary literature; and to provide proposed guidelines for the use of this emerging therapy in veterinary medicine and toxicology. Human and veterinary medical literature. Human data are composed mostly of case reports describing the response to treatment with ILE as variant from mild improvement to complete resolution of clinical signs, which is suspected to be due to the variability of lipid solubility of the drugs. The use of ILE therapy has been advocated as an antidote in cases of local anesthetic and other lipophilic drug toxicoses, particularly in the face of cardiopulmonary arrest and unsuccessful cardiopulmonary cerebral resuscitation. The use of ILE therapy in veterinary medicine has recently been advocated by animal poison control centers for toxicoses associated with fat-soluble agents, but there are only few clinical reports documenting successful use of this therapy. Evidence for the use of ILE in both human and veterinary medicine is composed primarily from experimental animal data. The use of ILE appears to be a safe therapy for the poisoned animal patient, but is warranted only with certain toxicoses. Adverse events associated with ILE in veterinary medicine are rare and anecdotal. Standard resuscitation protocols should be exhausted before considering this therapy and the potential side effects should be evaluated before administration of ILE as a potential antidote in cases of lipophilic drug toxicoses. Further research is waranted. © Veterinary Emergency and Critical Care Society 2011.

The Phe932Ile mutation in KCNT1 channels associated with severe epilepsy, delayed myelination and leukoencephalopathy produces a loss-of-function channel phenotype.

PubMed

Evely, Katherine M; Pryce, Kerri D; Bhattacharjee, Arin

2017-05-20

Sodium-activated potassium (K Na ) channels contribute to firing frequency adaptation and slow after hyperpolarization. The KCNT1 gene (also known as SLACK) encodes a K Na subunit that is expressed throughout the central and peripheral nervous systems. Missense mutations of the SLACK C-terminus have been reported in several patients with rare forms of early onset epilepsy and in some cases severely delayed myelination. To date, such mutations identified in patients with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), epilepsy of infancy with migrating focal seizures (EIMFS) and Ohtahara syndrome (OS) have been reported to be gain-of-function mutations (Villa and Combi, 2016). An exome sequencing study identified a p.Phe932Ile KCNT1 mutation as the disease-causing change in a child with severe early infantile epileptic encephalopathy and abnormal myelination (Vanderver et al., 2014). We characterized an analogous mutation in the rat Slack channel and unexpectedly found this mutation to produce a loss-of-function phenotype. In an effort to restore current, we tested the known Slack channel opener loxapine. Loxapine exhibited no effect, indicating that this mutation either caused the channel to be insensitive to this established opener or proper translation and trafficking to the membrane was disrupted. Protein analysis confirmed that while total mutant protein did not differ from wild type, membrane expression of the mutant channel was substantially reduced. Although gain-of-function mutations to the Slack channel are linked to epileptic phenotypes, this is the first reported loss-of-function mutation linked to severe epilepsy and delayed myelination. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

The prevalence, pattern and clinical presentation of developmental dental hard-tissue anomalies in children with primary and mix dentition from Ile-Ife, Nigeria.

PubMed

Temilola, Dada Oluwaseyi; Folayan, Morenike Oluwatoyin; Fatusi, Olawunmi; Chukwumah, Nneka Maureen; Onyejaka, Nneka; Oziegbe, Elizabeth; Oyedele, Titus; Kolawole, Kikelomo Adebanke; Agbaje, Hakeem

2014-10-16

The study of dental anomalies is important because it generates information that is important for both the anthropological and clinical management of patients. The objective of this study is to determine the prevalence and pattern of presentation of dental hard-tissue developmental anomalies in the mix dentition of children residing in Ile-Ife, a suburban region of Nigeria. Information on age, sex and socioeconomic status was collected from 1,036 children aged four months to 12 years through a household survey. Clinical examination was conducted to assess the presence of dental anomalies. Associations between age, sex, socioeconomic status, prevalence, and pattern of presentation of the developmental hard-tissue dental anomalies were determined. Two hundred and seventy six (26.6%) children had dental anomalies. Of these, 23.8% had one anomaly, 2.5% had two anomalies, and 0.3% had more than two anomalies. Of the children with anomalies, 49.3%were male, 50.7%were female, and 47.8%, 28.6% and 23.6% were children from low, middle and high socioeconomic classes, respectively. More anomalies were seen in permanent than primary dentition. Anomalies of tooth structure were most prevalent (16.1%); anomalies which affect tooth number were least prevalent (1.3%). Dens evaginatus, peg-shaped lateral, macrodontia, and talon cusp were more prevalent in the permanent dentition, and dens evaginatus peg-shaped lateral and macrodontia were more prevalent in the maxilla. There were significantly more macrodontia anomalies in males and in children of high socioeconomic status. This large survey of dental hard-tissue anomalies found in the primary dentition and mixed dentition of children in Nigeria provides anthropological and clinical data that may aid the detection and management of dental problems of children in Nigeria.

Recent rapid rise of a permethrin knock down resistance allele in Aedes aegypti in México.

PubMed

García, Gustavo Ponce; Flores, Adriana E; Fernández-Salas, Ildefonso; Saavedra-Rodríguez, Karla; Reyes-Solis, Guadalupe; Lozano-Fuentes, Saul; Guillermo Bond, J; Casas-Martínez, Mauricio; Ramsey, Janine M; García-Rejón, Julián; Domínguez-Galera, Marco; Ranson, Hilary; Hemingway, Janet; Eisen, Lars; Black IV, William C

2009-10-13

Aedes aegypti, the 'yellow fever mosquito', is the primary vector to humans of dengue and yellow fever flaviviruses (DENV, YFV), and is a known vector of the chikungunya alphavirus (CV). Because vaccines are not yet available for DENV or CV or are inadequately distributed in developing countries (YFV), management of Ae. aegypti remains the primary option to prevent and control outbreaks of the diseases caused by these arboviruses. Permethrin is one of the most widely used active ingredients in insecticides for suppression of adult Ae. aegypti. In 2007, we documented a replacement mutation in codon 1,016 of the voltage-gated sodium channel gene (para) of Ae. aegypti that encodes an isoleucine rather than a valine and confers resistance to permethrin. Ile1,016 segregates as a recessive allele conferring knockdown resistance to homozygous mosquitoes at 5-10 microg of permethrin in bottle bioassays. A total of 81 field collections containing 3,951 Ae. aegypti were made throughout México from 1996 to 2009. These mosquitoes were analyzed for the frequency of the Ile1,016 mutation using a melting-curve PCR assay. Dramatic increases in frequencies of Ile1,016 were recorded from the late 1990's to 2006-2009 in several states including Nuevo León in the north, Veracruz on the central Atlantic coast, and Yucatán, Quintana Roo and Chiapas in the south. From 1996 to 2000, the overall frequency of Ile1,016 was 0.04% (95% confidence interval (CI95) = 0.12%; n = 1,359 mosquitoes examined). The earliest detection of Ile1,016 was in Nuevo Laredo on the U.S. border in 1997. By 2003-2004 the overall frequency of Ile1,016 had increased approximately 100-fold to 2.7% (+ or - 0.80% CI95; n = 808). When checked again in 2006, the frequency had increased slightly to 3.9% (+ or - 1.15% CI95; n = 473). This was followed in 2007-2009 by a sudden jump in Ile1,016 frequency to 33.2% (+ or - 1.99% CI95; n = 1,074 mosquitoes). There was spatial heterogeneity in Ile1,016 frequencies among 2007

Recent Rapid Rise of a Permethrin Knock Down Resistance Allele in Aedes aegypti in México

PubMed Central

García, Gustavo Ponce; Flores, Adriana E.; Fernández-Salas, Ildefonso; Saavedra-Rodríguez, Karla; Reyes-Solis, Guadalupe; Lozano-Fuentes, Saul; Guillermo Bond, J.; Casas-Martínez, Mauricio; Ramsey, Janine M.; García-Rejón, Julián; Domínguez-Galera, Marco; Ranson, Hilary; Hemingway, Janet; Eisen, Lars; Black, William C.

2009-01-01

Background Aedes aegypti, the ‘yellow fever mosquito’, is the primary vector to humans of dengue and yellow fever flaviviruses (DENV, YFV), and is a known vector of the chikungunya alphavirus (CV). Because vaccines are not yet available for DENV or CV or are inadequately distributed in developing countries (YFV), management of Ae. aegypti remains the primary option to prevent and control outbreaks of the diseases caused by these arboviruses. Permethrin is one of the most widely used active ingredients in insecticides for suppression of adult Ae. aegypti. In 2007, we documented a replacement mutation in codon 1,016 of the voltage-gated sodium channel gene (para) of Ae. aegypti that encodes an isoleucine rather than a valine and confers resistance to permethrin. Ile1,016 segregates as a recessive allele conferring knockdown resistance to homozygous mosquitoes at 5–10 µg of permethrin in bottle bioassays. Methods and Findings A total of 81 field collections containing 3,951 Ae. aegypti were made throughout México from 1996 to 2009. These mosquitoes were analyzed for the frequency of the Ile1,016 mutation using a melting-curve PCR assay. Dramatic increases in frequencies of Ile1,016 were recorded from the late 1990's to 2006–2009 in several states including Nuevo León in the north, Veracruz on the central Atlantic coast, and Yucatán, Quintana Roo and Chiapas in the south. From 1996 to 2000, the overall frequency of Ile1,016 was 0.04% (95% confidence interval (CI95) = 0.12%; n = 1,359 mosquitoes examined). The earliest detection of Ile1,016 was in Nuevo Laredo on the U.S. border in 1997. By 2003–2004 the overall frequency of Ile1,016 had increased ∼100-fold to 2.7% (±0.80% CI95; n = 808). When checked again in 2006, the frequency had increased slightly to 3.9% (±1.15% CI95; n = 473). This was followed in 2007–2009 by a sudden jump in Ile1,016 frequency to 33.2% (±1.99% CI95; n = 1,074 mosquitoes). There was spatial heterogeneity

Specificity of the collagenolytic serine proteinase from the pancreas of the catfish (Parasilurus asotus).

PubMed

Yoshinaka, R; Sato, M; Yamashita, M; Itoko, M; Ikeda, S

1987-01-01

The collagenolytic serine proteinase from the pancreas of the catfish (Parasilus asotus) had a pH optimum of 7.5 for native, reconstituted calf skin collagen fibrils. The enzyme was most stable at pH 6-9. The enzyme hydrolyzed heat-denatured collagen (gelatin), casein, hemoglobin and elastin in addition to native collagen but not virtually Tos-Arg-OEe, Bz-Tyr-OEe and Suc-(Ala)3-NA. The enzyme cleaved Leu-Gly (or Gln-Gly), Gly-Ile and Ile-Ala bonds on DNP-Pro-Leu-Gly-Ile-Ala-Gly-Arg-NH2 and DNP-Pro-Gln-Gly-Ile-Ala-Gly-Gln-D-Arg.

Flesh Quality Loss in Response to Dietary Isoleucine Deficiency and Excess in Fish: A Link to Impaired Nrf2-Dependent Antioxidant Defense in Muscle

PubMed Central

Gan, Lu; Jiang, Wei-Dan; Wu, Pei; Liu, Yang; Jiang, Jun; Li, Shu-Hong; Tang, Ling; Kuang, Sheng-Yao; Feng, Lin; Zhou, Xiao-Qiu

2014-01-01

The present study explored the impact of dietary isoleucine (Ile) on fish growth and flesh quality and revealed a possible role of muscle antioxidant defense in flesh quality in relation to dietary Ile. Grass carp (weighing 256.8±3.5 g) were fed diets containing six graded levels of Ile (3.8, 6.6, 9.3, 12.5, 15.2 and 18.5 g/kg) for eight weeks. The results indicated that compared with Ile deficiency (3.8 g/kg diets) and excess (18.5 g/kg diets) groups, 9.3–15.2 g Ile/kg diet supplementations promoted fish growth and muscle fat deposition, whereas 6.6–15.2 g Ile/kg diets supplementation enhanced muscle nutrients (protein and total EAAs) deposition. Furthermore, muscle shear force, pH value, and hydroxyproline concentration were improved by 9.3–12.5, 9.3 and 9.3 g Ile/kg diet supplementations, respectively. However, muscle cooking loss, lactate content, and activities of cathepsin B and L were decreased by 6.6–15.2, 9.3–12.5, 9.3–12.5 and 9.3–15.2 g Ile/kg diet supplementations, respectively. Additionally, 6.6–15.2 and 6.6–12.5 g Ile/kg diet supplementations attenuated malondialdehyde and protein carbonyl contents, respectively. The activities of copper/zinc superoxide dismutase (Cu/Zn-SOD) and glutathione peroxidase (GPx), and glutathione content were enhanced by 6.6–9.3, 6.6–12.5 and 6.6–15.2 g Ile/kg diet supplementations, respectively. Moreover, the relative mRNA expressions of antioxidant enzymes, including Cu/Zn-SOD (6.6–12.5 g/kg diets) and GPx (12.5 g/kg diets), as well as antioxidant-related signaling molecules, including NF-E2-related factor 2 (Nrf2) (6.6–12.5 g/kg diets), target of rapamycin (6.6–12.5 g/kg diets), ribosomal S6 protein kinase 1 (9.3–12.5 g/kg diets) and casein kinase 2 (6.6–12.5 g/kg diets), were up-regulated when Ile diet supplementations were administered at these levels, respectively, whereas the relative mRNA expression of Kelch-like ECH-associated protein 1 was down-regulated with 9.3 g Ile/kg diet

Plasma protein and supplemental isoleucine in milk replacers for dairy calves.

PubMed

Vasquez, K M; Morrison, S Y; Campbell, J M; Drackley, J K

2017-01-01

We measured the effects of milk replacers containing 0, 33, 66, or 100% of the total replaceable whey protein as bovine plasma protein (PP), without or with Ile supplementation, on the intake, growth, and health of 124 male Holstein calves for 35d. Milk replacers were formulated to contain 18% crude protein and 20% fat, with contents of Lys and Met equalized. When fed to calves at 1.5% of body weight (dry matter basis) under thermoneutral conditions, diets were predicted to allow average daily gains of 0.55kg/d based on metabolizable energy or 0.40kg/d based on apparent digestible protein. Protein supply was more limiting than energy so that differences in protein use could be detected. Dry matter intakes decreased with increased PP, irrespective of Ile supplementation. Final body weights decreased linearly with increasing PP, regardless of Ile supplementation. Average daily gain tended to be affected in a quadratic manner as PP increased, either with or without Ile supplementation; average daily gain and gain-feed ratio were greatest for calves fed diets containing 33% PP and lowest for calves fed 100% PP. The analyzed Lys content in the milk replacers was variable compared with formulated values, and this may have affected growth results. However, the gain-Lys ratio was affected by an interaction of the linear effect of increasing PP with Ile supplementation: it decreased with increasing PP but was improved by supplementation with Ile for calves fed 100% PP. Body measurements decreased with increasing PP inclusion; only decreased heart girth was reversed with Ile supplementation. The lowest and highest inclusion of PP, regardless of Ile supplementation, decreased the occurrence of scours compared with the control diet (all whey protein). Calves fed the lowest and highest PP without Ile supplementation also had fewer total days of scours in the first 21d. In addition, calves fed 100% PP without supplementation of Ile had fewer days of medication compared with the

Regulation of taste-active components of meat by dietary branched-chain amino acids; effects of branched-chain amino acid antagonism.

PubMed

Imanari, M; Kadowaki, M; Fujimura, S

2008-05-01

1. The effects of dietary branched-chain amino acids (BCAAs) including leucine (Leu), isoleucine (Ile) and valine (Val) on taste-active components, especially free glutamate (Glu), in meat were investigated. 2. Broiler chickens (28 d old) were given varied dietary BCAA levels for 10 d before marketing. Dietary BCAA content ratios were either 100:100:100 (Low Leu group), 150:100:100 (Control group) or 150:150:150 (High Ile + Val group) for Leu:Ile:Val (% of each BCAA requirement according to NRC, 1994). Taste-related components of meat (free amino acids and ATP metabolites) and sensory scores of meat soup were estimated. 3. Free Glu content, the main taste-active component of meat, was significantly increased by dietary BCAA. Compared to the Control group, free Glu content increased by 30% in the High Ile + Val group. However, the inosine monophosphate (IMP) content in meat did not change among groups. 4. Sensory evaluation of meat soups showed that Control and High Ile + Val groups had different meat flavours. The sensory score of overall taste intensity was significantly higher in the High Ile + Val group. 5. These results suggest that dietary BCAA concentrations regulate free Glu in meat. Increasing dietary Ile + Val induces an increase in free Glu content of meat, improves meat taste and is more effective for increasing free Glu content in meat than decreasing dietary Leu level.

Interactive effects of dietary leucine and isoleucine on growth, blood parameters, and amino acid profile of Japanese flounder Paralichthys olivaceus.

PubMed

Wang, Liping; Han, Yuzhe; Jiang, Zhiqiang; Sun, Menglei; Si, Bin; Chen, Fei; Bao, Ning

2017-10-01

A 60-day feeding trial was conducted to assess the interactions of dietary leucine (Leu) and isoleucine (Ile) on Japanese flounder. Fish of 2.69 ± 0.04 g were fed experimental diets containing two levels of Leu (2.58 and 5.08% of diet) combined with three levels of Ile (1.44, 2.21, and 4.44% of diet), respectively. After the feeding trial, growth, proximate composition, muscle total amino acid profile, blood parameters, mucus lysozyme activity, and stress tolerance to freshwater were measured. Statistically significant (P < 0.05) interactive effects of Leu and Ile were found on growth parameters (final body weight, body weight gain, and special growth rate) of Japanese flounder. Antagonism was discovered in high dietary Leu groups, while stimulatory effects were obtained for increased dietary Ile in low Leu groups. Interactive effects of these two branched-chain amino acids were also found on hepatosomatic index of test fish. In addition, crude lipid content of fish whole body was significantly altered by various diets, with antagonism observed in low dietary Leu groups. Interactive effects also existed in muscle amino acid profiles for low fish meal diets, but no interactive impacts were observed on blood parameters. Furthermore, lysozyme activities and freshwater stress were significantly affected by different diets. And antagonism was found on lysozyme activities in low Leu groups. Moreover, high Leu and high Ile levels of diet significantly altered freshwater stress tolerance of Japanese flounder. These findings suggested that dietary Leu and Ile can effect interactively, and fish fed with diets containing 2.58% Leu with 4.44% Ile and 5.08% Leu with 1.44% Ile showed better growth performance.

A Potential Yeast Actin Allosteric Conduit Dependent on Hydrophobic Core Residues Val-76 and Trp-79*

PubMed Central

Wen, Kuo-Kuang; McKane, Melissa; Stokasimov, Ema; Fields, Jonathon; Rubenstein, Peter A.

2010-01-01

Intramolecular allosteric interactions responsible for actin conformational regulation are largely unknown. Previous work demonstrated that replacing yeast actin Val-76 with muscle actin Ile caused decreased nucleotide exchange. Residue 76 abuts Trp-79 in a six-residue linear array beginning with Lys-118 on the surface and ending with His-73 in the nucleotide cleft. To test if altering the degree of packing of these two residues would affect actin dynamics, we constructed V76I, W79F, and W79Y single mutants as well as the Ile-76/Phe-79 and Ile-76/Tyr-79 double mutants. Tyr or Phe should decrease crowding and increase protein flexibility. Subsequent introduction of Ile should restore packing and dampen changes. All mutants showed decreased growth in liquid medium. W79Y alone was severely osmosensitive and exhibited vacuole abnormalities. Both properties were rescued by Ile-76. Phe-79 or Tyr decreased the thermostability of actin and increased its nucleotide exchange rate. These effects, generally greater for Tyr than for Phe, were reversed by introduction of Ile-76. HD exchange showed that the mutations caused propagated conformational changes to all four subdomains. Based on results from phosphate release and light-scattering assays, single mutations affected polymerization in the order of Ile, Phe, and Tyr from least to most. Introduction of Ile-76 partially rescued the polymerization defects caused by either Tyr-79 or Phe-79. Thus, alterations in crowding of the 76–79 residue pair can strongly affect actin conformation and behavior, and these results support the theory that the amino acid array in which they are located may play a central role in actin regulation. PMID:20442407

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

Buxbaum, J.; Pastore, R.; Yaghoubian, R.

Point mutations in the protein transthyretin (TTR) cause familial amyloidosis involving mainly the heart and peripheral nerves. To determine the TTR Ile 122 gene frequency in African Americans, the allele encoding TTR Ile 122 was identified by PCR-Primer Introduced Restriction Analysis of TTR exon 4 and FokI digestion on 1659 control DNA samples from 1659 African Americans: 64 were heterozygous and one homozygous (allele frequency .02). To determine the risk to gene carriers of developing cardiac amyloidosis, immunohistochemical and genetic studies were performed on amyloid-containing samples identified among 52,370 autopsy samples examined over 32 years. In autopsy samples from patientsmore » over age 60, isolated cardiac amyloidosis was more common in African Americans (1.6%) than in White Americans (.40%), suggesting a genetic risk factor. All 29 samples from African Americans were immunohistochemically TTR-positive, and 5 were heterozygous for the TTR Ile 122 allele (17%), as compared with 5/108 heterozygotes (4.6%) among age-matched (over age 60) African American controls without amyloidosis from the same autopsy study (one-tailed P value < .03). Among the 29 amyloid-positive samples were 16 with 1+ or 2+ deposition and 13 with 3+ or 4+ deposition. All 5 TTR Ile 122 heterozygotes had 3+ or 4+ deposition. None of 15 samples from White Americans with cardiac amyloidosis was TTR Ile 122-positive. Extrapolating from the 5/29 samples from which we were able to obtain genetic data, we estimate that 9/54 samples containing cardiac amyloid were TTR Ile 122 heterozygotes. We conclude that heterozygosity for TTR Ile 122 is associated with a greater frequency (relative risk 5.8) and greater severity of cardiac amyloid deposition than in non-carriers of the TTR Ile 122 gene. Of over 40 TTR point mutations associated with amyloidosis described to date, TTR Ile 122 appears to be the most common worldwide and to have the lowest penetrance in causing disease.« less

Silencing of Essential Genes within a Highly Coordinated Operon in Escherichia coli.

PubMed

Goh, Shan; Hohmeier, Angela; Stone, Timothy C; Offord, Victoria; Sarabia, Francisco; Garcia-Ruiz, Cristina; Good, Liam

2015-08-15

Essential bacterial genes located within operons are particularly challenging to study independently because of coordinated gene expression and the nonviability of knockout mutants. Essentiality scores for many operon genes remain uncertain. Antisense RNA (asRNA) silencing or in-frame gene disruption of genes may help establish essentiality but can lead to polar effects on genes downstream or upstream of the target gene. Here, the Escherichia coli ribF-ileS-lspA-fkpB-ispH operon was used to evaluate the possibility of independently studying an essential gene using expressed asRNA and target gene overexpression to deregulate coupled expression. The gene requirement for growth in conditional silencing strains was determined by the relationship of target mRNA reduction with growth inhibition as the minimum transcript level required for 50% growth (MTL50). Mupirocin and globomycin, the protein inhibitors of IleS and LspA, respectively, were used in sensitization assays of strains containing both asRNA-expressing and open reading frame-expressing plasmids to examine deregulation of the overlapping ileS-lspA genes. We found upstream and downstream polar silencing effects when either ileS or lspA was silenced, indicating coupled expression. Weighted MTL50 values (means and standard deviations) of ribF, ileS, and lspA were 0.65 ± 0.18, 0.64 ± 0.06, and 0.76 ± 0.10, respectively. However, they were not significantly different (P = 0.71 by weighted one-way analysis of variance). The gene requirement for ispH could not be determined due to insufficient growth reduction. Mupirocin and globomycin sensitization experiments indicated that ileS-lspA expression could not be decoupled. The results highlight the inherent challenges associated with genetic analyses of operons; however, coupling of essential genes may provide opportunities to improve RNA-silencing antimicrobials. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Jasmonoyl-l-Isoleucine Coordinates Metabolic Networks Required for Anthesis and Floral Attractant Emission in Wild Tobacco (Nicotiana attenuata)[C][W][OPEN

PubMed Central

Stitz, Michael; Hartl, Markus; Baldwin, Ian T.; Gaquerel, Emmanuel

2014-01-01

Jasmonic acid and its derivatives (jasmonates [JAs]) play central roles in floral development and maturation. The binding of jasmonoyl-l-isoleucine (JA-Ile) to the F-box of CORONATINE INSENSITIVE1 (COI1) is required for many JA-dependent physiological responses, but its role in anthesis and pollinator attraction traits remains largely unexplored. Here, we used the wild tobacco Nicotiana attenuata, which develops sympetalous flowers with complex pollination biology, to examine the coordinating function of JA homeostasis in the distinct metabolic processes that underlie flower maturation, opening, and advertisement to pollinators. From combined transcriptomic, targeted metabolic, and allometric analyses of transgenic N. attenuata plants for which signaling deficiencies were complemented with methyl jasmonate, JA-Ile, and its functional homolog, coronatine (COR), we demonstrate that (1) JA-Ile/COR-based signaling regulates corolla limb opening and a JA-negative feedback loop; (2) production of floral volatiles (night emissions of benzylacetone) and nectar requires JA-Ile/COR perception through COI1; and (3) limb expansion involves JA-Ile-induced changes in limb fresh mass and carbohydrate metabolism. These findings demonstrate a master regulatory function of the JA-Ile/COI1 duet for the main function of a sympetalous corolla, that of advertising for and rewarding pollinator services. Flower opening, by contrast, requires JA-Ile signaling-dependent changes in primary metabolism, which are not compromised in the COI1-silenced RNA interference line used in this study. PMID:25326292

Intravenous lipid emulsion does not reverse dabigatran-induced anticoagulation in a rat model.

PubMed

Blum, Jared; Carreiro, Stephanie; Hack, Jason B

2013-10-01

The anticoagulant dabigatran has no reversal agent and may cause life-threatening bleeding in patients with trauma or closed-space hemorrhage. Intravenous lipid emulsion (ILE) is thought to create a lipid compartment in serum that sequesters lipophilic drugs. Dabigatran is lipophilic, and its anticoagulant effects are concentration dependent. The study objective was to determine if ILE therapy reverses dabigatran's anticoagulant effects. Twenty rats were selected at random, 10 in the ILE group and 10 in a normal saline (NS) control group. Animals had a baseline tail bleeding time (T0), followed by oral dabigatran administration (15 mg/kg). At 45 minutes (T45), a second tail bleed time measurement was performed, followed by a 7-minute infusion of 15 mL/kg ILE or NS. A final 60-minute (T60) bleed time measurement was obtained. An ILE-only group of five animals had bleeding times assessed prior to (T0) and 15 minutes after (T15) ILE therapy. A mixed-effect repeated-measures analysis of variance modeling the effect of time, group, and the interaction of group and time on bleed times was conducted. There was a significant within-subject change in bleeding time across the assessment points (F(2,36) = 33; p < 0.001), but there were no effect of group (F(1,18) = 1.42, p = 0.25) or an interaction between group and assessment point on mean bleeding time (F(2,36) = 0.59, p = 56). Between T0 and T45, average bleeding times increased from 109.5 seconds (95% confidence interval [CI] = 94 to 125 seconds) to 231.8 seconds (95% CI = 193 to 271 seconds; p < 0.0001) for both the ILE group and the NS control group. Between T45 and T60, bleeding times in the ILE group decreased by 31.5 seconds (95% CI = -77 to 14 seconds) and by 6 seconds (95% CI = -67 to 55 seconds) in the NS group (p = 0.46). In the five ILE-only animals, the average bleeding time at T0 was 114 seconds (95% CI = 62 to 166 seconds), which increased significantly at T15 to 237�

The Relationship Between Glutathione S-Transferase-P1 and Beta-2 Adrenoreceptor Genotypes with Asthmatic Patients in the Turkish Population.

PubMed

Kaymak, Cetin; Aygun Kocabas, Neslihan; Aydın, Nesrin; Oztuna, Derya; Karakaya, Ali Esat

2016-09-01

Individual differences in the activity of enzymes that metabolize xenobiotics can impact health and disease. Beta-2 adrenoreceptor (ADRB2) is a functional G-coupled protein expressed in the vascular endothelium of lungs, alveolar walls, and the ganglions of cholinergic nerves which induces bronchodilation in response to catecholamines. Glutathione S-Transferase-P1 (GSTP1) is a candidate pi class GST gene, which controls pi class glutathione S-transferase activity. In this study we determined the relationship between the ADRB2 Arg16Gly polymorphism and GSTP1 polymorphisms, involved in bronchodilator response and oxidative stress, respectively, with susceptibility to asthma. In this study, 129 asthmatic patients and 127 healthy control cases were recruited to determine ADRB2 and GSTP1 genotypes by allele-specific polymerase chain reaction and restriction fragment length polymorphism assays, respectively. The ADRB2 genotype frequencies of the patients and control cases were found to be 10.9% (Arg16Arg), 48.8% (Arg16Gly), and 40.3% (Gly16Gly) and 24.4% (Arg16Arg), 36.2% (Arg16Gly), and 39.4% (Gly16Gly), respectively. GSTP1 genotype frequencies of patients and control cases were found to be 55% (Ile105Ile), 43.4% (Ile105Val), and 1.6% (Val105Val) and 75.6% (Ile105Ile), 22% (Ile105Val), and 2.4% (Val105Val), respectively. In the case of the GSTP1 gene, we found statistically significant differences in the genotype frequency of Ile105Val and the allele frequency of Val105 in the asthmatic group compared with the controls. Moreover, we observed a relationship between allele frequencies and clinical phenotypes including atopia nocturnal dyspnea, and steroid dependency in the asthmatic patients. Our results suggest that the GSTP1 Ile105Val polymorphism may be linked to the severeness of airway dysfunction.

Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning.

PubMed

Gosselin, Sophie; Hoegberg, Lotte C G; Hoffman, Robert S; Graudins, Andis; Stork, Christine M; Thomas, Simon H L; Stellpflug, Samuel J; Hayes, Bryan D; Levine, Michael; Morris, Martin; Nesbitt-Miller, Andrea; Turgeon, Alexis F; Bailey, Benoit; Calello, Diane P; Chuang, Ryan; Bania, Theodore C; Mégarbane, Bruno; Bhalla, Ashish; Lavergne, Valéry

2016-12-01

Although intravenous lipid emulsion (ILE) was first used to treat life-threatening local anesthetic (LA) toxicity, its use has expanded to include both non-local anesthetic (non-LA) poisoning and less severe manifestations of toxicity. A collaborative workgroup appraised the literature and provides evidence-based recommendations for the use of ILE in poisoning. Following a systematic review of the literature, data were summarized in four publications: LA and non-LA poisoning efficacy, adverse effects, and analytical interferences. Twenty-two toxins or toxin categories and three clinical situations were selected for voting. Voting statements were proposed using a predetermined format. A two-round modified Delphi method was used to reach consensus on the voting statements. Disagreement was quantified using RAND/UCLA Appropriateness Method. For the management of cardiac arrest, we recommend using ILE with bupivacaine toxicity, while our recommendations are neutral regarding its use for all other toxins. For the management of life-threatening toxicity, (1) as first line therapy, we suggest not to use ILE with toxicity from amitriptyline, non-lipid soluble beta receptor antagonists, bupropion, calcium channel blockers, cocaine, diphenhydramine, lamotrigine, malathion but are neutral for other toxins, (2) as part of treatment modalities, we suggest using ILE in bupivacaine toxicity if other therapies fail, but are neutral for other toxins, (3) if other therapies fail, we recommend ILE for bupivacaine toxicity and we suggest using ILE for toxicity due to other LAs, amitriptyline, and bupropion, but our recommendations are neutral for all other toxins. In the treatment of non-life-threatening toxicity, recommendations are variable according to the balance of expected risks and benefits for each toxin. For LA-toxicity we suggest the use of Intralipid ® 20% as it is the formulation the most often reported. There is no evidence to support a recommendation for the best

Recombinant Brucella abortus gene expressing immunogenic protein

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

Mayfield, J.E.; Tabatabai, L.B.

This patent describes a synthetic recombinant DNA molecule containing a DNA sequence. It comprises a gene of Brucella abortus encoding an immunogenic protein having a molecular weight of approximately 31,000 daltons as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis under denaturing conditions, the protein having an isoelectric point around 4.9, and containing a twenty-five amino acid sequence from its amino terminal end consisting of Gln-Ala-Pro-Thr-Phe-Phe-Arg-Ile-Gly-Thr-Gly-Gly-Thr-Ala-Gly-Thr-Tyr-Tyr-Pro-Ile-Gly-Gly-Leu-Ile-Ala, wherein Gln, Ala, Pro, Thr, Phe, Arg, Ile, Gly, Tyr, and Leu, respectively, represent glutamine, alanine, proline, threonine, phenylalanine, arginine, isolecuine, glycine, tyrosine, and leucine.

Miniaturized LEDs for flat-panel displays

NASA Astrophysics Data System (ADS)

Radauscher, Erich J.; Meitl, Matthew; Prevatte, Carl; Bonafede, Salvatore; Rotzoll, Robert; Gomez, David; Moore, Tanya; Raymond, Brook; Cok, Ronald; Fecioru, Alin; Trindade, António Jose; Fisher, Brent; Goodwin, Scott; Hines, Paul; Melnik, George; Barnhill, Sam; Bower, Christopher A.

2017-02-01

Inorganic light emitting diodes (LEDs) serve as bright pixel-level emitters in displays, from indoor/outdoor video walls with pixel sizes ranging from one to thirty millimeters to micro displays with more than one thousand pixels per inch. Pixel sizes that fall between those ranges, roughly 50 to 500 microns, are some of the most commercially significant ones, including flat panel displays used in smart phones, tablets, and televisions. Flat panel displays that use inorganic LEDs as pixel level emitters (μILED displays) can offer levels of brightness, transparency, and functionality that are difficult to achieve with other flat panel technologies. Cost-effective production of μILED displays requires techniques for precisely arranging sparse arrays of extremely miniaturized devices on a panel substrate, such as transfer printing with an elastomer stamp. Here we present lab-scale demonstrations of transfer printed μILED displays and the processes used to make them. Demonstrations include passive matrix μILED displays that use conventional off-the shelf drive ASICs and active matrix μILED displays that use miniaturized pixel-level control circuits from CMOS wafers. We present a discussion of key considerations in the design and fabrication of highly miniaturized emitters for μILED displays.

Evaluation of ionic liquid epoxy carbon fiber composites in a cryogenic environment

NASA Astrophysics Data System (ADS)

Lyne, Christopher T.; Henry, Christopher R.; Kaukler, William F.; Grugel, R. N.

2018-03-01

A novel ionic liquid epoxy (ILE) was used to fabricate carbon fiber composite discs which were then subjected to biaxial strain testing in liquid nitrogen. The ILE composite showed a greater strain-to-failure at cryogenic temperatures when compared to a commercial epoxy. This result is likely an effect, as shown in micrographs, of the strong ILE bonding with the carbon fibers as well as it exhibiting plastic deformation at the fracture surface.

Genotype-phenotype correlation in FMF patients: A "non classic" recessive autosomal or "atypical" dominant autosomal inheritance?

PubMed

Procopio, V; Manti, S; Bianco, G; Conti, G; Romeo, A; Maimone, F; Arrigo, T; Cutrupi, M C; Salpietro, C; Cuppari, C

2018-01-30

Uncertainty remains on the pathogenetic mechanisms, model of inheritance as well as genotype-phenotype correlation of FMF disease. To investigate the impact of genetic factors on the FMF phenotype and the disease inheritance model. A total of 107 FMF patients were enrolled. Patients were diagnosed clinically. All patients underwent genetic analysis of the FMF locus on 16p13.3. 9 distinct mutations were detected. Specifically, the 85.98% of patients showed a heterozygous genotype. The most common genotypes were p.Met680Ile/wt and p.Met694Val/wt. The most frequent clinical findings were fever, abdominal pain, joint pain, thoracic pain, and erysipelas-like erythema. Analysis of clinical data did not detect any significant difference in clinical phenotype among heterozygous, homozygous as well as compound homozygous subjects, further supporting the evidence that, contrary to the recessive autosomal inheritance, heterozygous patients fulfilled the criteria of clinical FMF. Moreover, subjects with p.Met694Val/wt and p.Met680Ile/wt genotype reported the most severe clinical phenotype. p.Ala744Ser/wt, p.Glu148Gln/Met680Ile, p.Met680Ile/Met680Ile, p.Met680Ile/Met694Val, p.Pro369Ser/wt, p.Met694Ile/wt, p.Glu148Gln/Glu148Gln, p.Lys695Arg/wt resulted in 100% pathogenicity. The existence of a "non classic" autosomal recessive inheritance as well as of an "atypical" dominant autosomal inheritance with incomplete penetrance and variable expressivity cannot be excluded in FMF. Copyright © 2017 Elsevier B.V. All rights reserved.

Intravenous lipid emulsion alters the hemodynamic response to epinephrine in a rat model.

PubMed

Carreiro, Stephanie; Blum, Jared; Jay, Gregory; Hack, Jason B

2013-09-01

Intravenous lipid emulsion (ILE) is an adjunctive antidote used in selected critically ill poisoned patients. These patients may also require administration of advanced cardiac life support (ACLS) drugs. Limited data is available to describe interactions of ILE with standard ACLS drugs, specifically epinephrine. Twenty rats with intra-arterial and intravenous access were sedated with isoflurane and split into ILE or normal saline (NS) pretreatment groups. All received epinephrine 15 μm/kg intravenously (IV). Continuous mean arterial pressure (MAP) and heart rate (HR) were monitored until both indices returned to baseline. Standardized t tests were used to compare peak MAP, time to peak MAP, maximum change in HR, time to maximum change in HR, and time to return to baseline MAP/HR. There was a significant difference (p = 0.023) in time to peak MAP in the ILE group (54 s, 95 % CI 44-64) versus the NS group (40 s, 95 % CI 32-48) and a significant difference (p = 0.004) in time to return to baseline MAP in ILE group (171 s, 95 % CI 148-194) versus NS group (130 s, 95 % CI 113-147). There were no significant differences in the peak change in MAP, peak change in HR, time to minimum HR, or time to return to baseline HR between groups. ILE-pretreated rats had a significant difference in MAP response to epinephrine; ILE delayed the peak effect and prolonged the duration of effect of epinephrine on MAP, but did not alter the peak increase in MAP or the HR response.

Comparison of lipid emulsions on antioxidant capacity in preterm infants receiving parenteral nutrition.

PubMed

Köksal, Nilgün; Kavurt, Ahmet V; Cetinkaya, Merih; Ozarda, Yesim; Ozkan, Hilal

2011-08-01

Although a variety of different lipid emulsions with varying fatty acid contents have been developed, there are some concerns about the administration of these lipid emulsions because of potential adverse effects, including oxidative stress-related morbidity. The aim of the present study was to evaluate and compare the effects of the standard soybean oil-based and olive oil-based i.v. lipid emulsions (ILE) on oxidative stress, determined by total antioxidant capacity (TAC), and to investigate the safety of the use of these two emulsions in terms of biochemical indices. In this prospective study, premature infants were randomly assigned to two groups, each group consisting of 32 patients who received parenteral ILE of either 20% olive oil or 20% soybean oil. They were given ILE for 7 days and then were evaluated with regard to TAC. No statistically significant difference was observed between the groups in terms of routine biochemical parameters. TAC for both groups on day 7 was significantly lower compared with that on day 0. Although the decrease in TAC within 7 days of ILE administration was greater in the soybean group compared with that in the olive oil group, it was not statistically significant. Olive oil-based ILE exhibit similar antioxidant activity and can be used as an alternative to soybean oil-based ILE. TAC significantly decreased in infants following administration of either lipid emulsion, and premature infants tolerated either ILE well, both biochemically and clinically. © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.

Substitutions of Thr-103-Ile and Trp-138-Gly in amidase from Pseudomonas aeruginosa are responsible for altered kinetic properties and enzyme instability.

PubMed

Karmali, A; Pacheco, R; Tata, R; Brown, P

2001-03-01

Pseudomonas aeruginosa Ph1 is a mutant strain derived from strain AI3. The strain AI3 is able to use acetanilide as a carbon source through a mutation (T103I) in the amiE gene that encodes an aliphatic amidase (EC 3.5.1.4). The mutations in the amiE gene have been identified (Thr103Ile and Trp138Gly) by direct sequencing of PCR-amplified mutant gene from strain Ph1 and confirmed by sequencing the cloned PCR-amplified gene. Site-directed mutagenesis was used to alter the wild-type amidase gene at position 138 for Gly. The wild-type and mutant amidase genes (W138G, T103I-W138G, and T103I) were cloned into an expression vector and these enzymes were purified by affinity chromatography on epoxy-activated Sepharose 6B-acetamide/phenylacetamide followed by gel filtration chromatography. Altered amidases revealed several differences in kinetic properties, namely, in substrate specificity, sensitivity to urea, optimum pH, and enzyme stability, compared with the wild-type enzyme. The W138G enzyme acted on acetamide, acrylamide, phenylacetamide, and p-nitrophenylacetamide, whereas the double mutant (W138G and T103I) amidase acted only on p-nitrophenylacetamide and phenylacetamide. On the other hand, the T103I enzyme acted on p-nitroacetanilide and acetamide. The heat stability of altered enzymes revealed that they were less thermostable than the wild-type enzyme, as the mutant (W138G and W138G-T103I) enzymes exhibited t1/2 values of 7.0 and 1.5 min at 55 degrees C, respectively. The double substitution T103I and W138G on the amidase molecule was responsible for increased instability due to a conformational change in the enzyme molecule as detected by monoclonal antibodies. This conformational change in altered amidase did not alter its M(r) value and monoclonal antibodies reacted differently with the active and inactive T103I-W138G amidase.

Analytical investigations on the thermal properties of microscale inorganic light-emitting diodes on an orthotropic substrate

NASA Astrophysics Data System (ADS)

Li, Y.; Chen, J.; Xing, Y.; Song, J.

2017-03-01

The microscale inorganic light-emitting diodes (μ-ILEDs) create novel opportunities in biointegrated applications such as wound healing acceleration and optogenetics. Analytical expressions, validated by finite element analysis, are obtained for the temperature increase of a rectangular μ-ILED device on an orthotropic substrate, which could offer an appealing advantage in controlling the heat flow direction to achieve the goal in thermal management. The influences of various parameters (e.g., thermal conductivities of orthotropic substrate, loading parameters) on the temperature increase of the μ-ILED are investigated based on the obtained closed-form solutions. These results provide a novel route to control the temperature distribution in the μ-ILED system and provide easily interpretable guidelines to minimize the adverse thermal effects.

2006 Marine Corps Systems Command Advanced Planning Briefing to Industry

DTIC Science & Technology

2006-04-14

Virginia Beach 34 5 m ile s 34 5 m ile s 2 00 m ile s Philadelphia 9 Video of AAV and EFV 10 Success Story – Amphibious Assault Vehicle Turret...Director Information Systems & InfrastructureProduct Group 10 Overview, Ms. Elizabeth Sedlacek Product Group Director Advanced Planning Briefing to...managers. The slick sheets will contain the names and phone numbers of everyone in the product groups. Corporate – Ms. Gloria Pryor & Ms. Tammy York PG 10

Intravenous lipid emulsion in the resuscitation of cocaine-induced cardiovascular arrest in a rat model.

PubMed

Chai, Peter R; Hack, Jason B

2016-08-01

Intravenous lipid emulsion (ILE) is a potential antidote for severe overdose of certain lipophilic drugs. Cocaine overdose is often fatal and has no antidote. The use of ILE after cocaine-induced cardiac arrest has been suggested but is not well characterized. The objective of the study is to determine if ILE would reverse cocaine-induced cardiac arrest in a rat model. Twelve Sprague-Dawley rats with intra-arterial and intravenous access were sedated with isoflurane and split into 2 cocaine dose groups, then given either ILE or normal saline (NS) intravenously (IV)-group A, 7 animals received cocaine (10 mg/kg IV) with 6 of 7 given ILE (15 mg/kg IV) and 1 of 7 given NS (equal volume); group B, 5 animals received cocaine (5 mg/kg IV) with 3 of 5 given ILE (15 mg/kg IV) and 2 of 5 given NS (equal volume). Closed chest compressions were initiated for asystole and continued for 15 minutes with rhythm checks every minute. All 12 rats experienced cardiac arrest after cocaine bolus. Resuscitation was successful in 1 of 7 rats in group A and 0 of 5 in group B. Intravenous lipid emulsion administration did not affect outcome of cocaine-induced cardiac arrest compared with control in this model. Copyright © 2016 Elsevier Inc. All rights reserved.

Characterization of two peptides isolated from the venom of social wasp Chartergellus communis (Hymenoptera: Vespidae): Influence of multiple alanine residues and C-terminal amidation on biological effects.

PubMed

Lopes, Kamila Soares; Campos, Gabriel Avohay Alves; Camargo, Luana Cristina; de Souza, Adolfo Carlos Barros; Ibituruna, Beatriz Vasconcelos; Magalhães, Ana Carolina Martins; da Rocha, Lucas Ferreira; Garcia, Alessa Bembom; Rodrigues, Mosar Correa; Ribeiro, Dagon Manoel; Costa, Michelle Cruz; López, Manuel Humberto Mera; Nolli, Luciana Marangni; Zamudio-Zuniga, Fernando; Possani, Lourival Domingos; Schwartz, Elisabeth Ferroni; Mortari, Márcia Renata

2017-09-01

Chatergellus communis is a wasp species endemic to the neotropical region and its venom constituents have never been described. In this study, two peptides from C. communis venom, denominated Communis and Communis-AAAA, were chemically and biologically characterized. In respect to the chemical characterization, the following amino acid sequences and molecular masses were identified: Communis: Ile-Asn-Trp-Lys-Ala-Ile-Leu-Gly-Lys-Ile-Gly-Lys-COOH (1340.9Da) Communis-AAAA: Ile-Asn-Trp-Lys-Ala-Ile-Leu-Gly-Lys-Ile-Gly-Lys-Ala-Ala-Ala-Ala-Val-Xle-NH 2 (1836.3Da). Furthermore, their biological effects were compared, accounting for the differences in structural characteristics between the two peptides. To this end, three biological assays were performed in order to evaluate the hyperalgesic, edematogenic and hemolytic effects of these molecules. Communis-AAAA, unlike Communis, showed a potent hemolytic activity with EC 50 =142.6μM. Moreover, the highest dose of Communis-AAAA (2nmol/animal) induced hyperalgesia in mice. On the other hand, Communis (10nmol/animal) was able to induce edema but did not present hemolytic or hyperalgesic activity. Although both peptides have similarities in linear structures, we demonstrated the distinct biological effects of Communis and Communis-AAAA. This is the first study with Chartegellus communis venom, and both Communis and Communis-AAAA are unpublished peptides. Copyright © 2017 Elsevier Inc. All rights reserved.

Interactive Lecture Experiments in Large Introductory Physics Classes

NASA Astrophysics Data System (ADS)

Milner-Bolotin, Marina M.; Kotlicki, A.; Rieger, G.; Bates, F.; Moll, R.; McPhee, K.; Nashon, S.

2006-12-01

We describe Interactive Lecture Experiments (ILE), which build on Interactive Lecture Demonstrations proposed by Sokoloff and Thornton (2004) and extends it by providing students with the opportunity to analyze experiments demonstrated in the lecture outside of the classroom. Real time experimental data is collected, using Logger Pro combined with the digital video technology. This data is uploaded to the Internet and made available to the students for further analysis. Student learning is assessed in the following lecture using conceptual questions (clickers). The goal of this project is to use ILE to make large lectures more interactive and promote student interest in science, critical thinking and data analysis skills. We report on the systematic study conducted using the Colorado Learning Attitudes about Science Survey, Force Concept Inventory, open-ended physics problems and focus group interviews to determine the impact of ILE on student academic achievement, motivation and attitudes towards physics. Three sections of students (750 students) experienced four ILE experiments. The surveys were administered twice and academic results for students who experienced the ILE for a particular topic were compared to the students, from a different section, who did not complete the ILE for that topic. Additional qualitative data on students’ attitudes was collected using open ended survey questions and interviews. We will present preliminary conclusions about the role of ILEs as an effective pedagogy in large introductory physics courses. Sokoloff, D.R. and R.K. Thornton (2004). Interactive Lecture Demonstrations: Active Learning in Introductory Physics, J.Wiley & Sons, INC. Interactive Lecture Experiments: http://www.physics.ubc.ca/ year1lab/p100/LectureLabs/lectureLabs.html

Application of isotope labeling experiments and (13)C flux analysis to enable rational pathway engineering.

PubMed

McAtee, Allison G; Jazmin, Lara J; Young, Jamey D

2015-12-01

Isotope labeling experiments (ILEs) and (13)C flux analysis provide actionable information for metabolic engineers to identify knockout, overexpression, and/or media optimization targets. ILEs have been used in both academic and industrial labs to increase product formation, discover novel metabolic functions in previously uncharacterized organisms, and enhance the metabolic efficiency of host cell factories. This review highlights specific examples of how ILEs have been used in conjunction with enzyme or metabolic engineering to elucidate host cell metabolism and improve product titer, rate, or yield in a directed manner. We discuss recent progress and future opportunities involving the use of ILEs and (13)C flux analysis to characterize non-model host organisms and to identify and subsequently eliminate wasteful byproduct pathways or metabolic bottlenecks. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structural basis of glyphosate resistance resulting from the double mutation Thr97 -> Ile and Pro101 -> Ser in 5-enolpyruvylshikimate-3-phosphate synthase from Escherichia coli.

PubMed

Funke, Todd; Yang, Yan; Han, Huijong; Healy-Fried, Martha; Olesen, Sanne; Becker, Andreas; Schönbrunn, Ernst

2009-04-10

The shikimate pathway enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) is the target of the broad spectrum herbicide glyphosate. The genetic engineering of EPSPS led to the introduction of glyphosate-resistant crops worldwide. The genetically engineered corn lines NK603 and GA21 carry distinct EPSPS enzymes. CP4 EPSPS, expressed in NK603 corn and transgenic soybean, cotton, and canola, belongs to class II EPSPS, glyphosate-insensitive variants of this enzyme isolated from certain Gram-positive bacteria. GA21 corn, on the other hand, was created by point mutations of class I EPSPS, such as the enzymes from Zea mays or Escherichia coli, which are sensitive to low glyphosate concentrations. The structural basis of the glyphosate resistance resulting from these point mutations has remained obscure. We studied the kinetic and structural effects of the T97I/P101S double mutation, the molecular basis for GA21 corn, using EPSPS from E. coli. The T97I/P101S enzyme is essentially insensitive to glyphosate (K(i) = 2.4 mm) but maintains high affinity for the substrate phosphoenolpyruvate (PEP) (K(m) = 0.1 mm). The crystal structure at 1.7-A resolution revealed that the dual mutation causes a shift of residue Gly(96) toward the glyphosate binding site, impairing efficient binding of glyphosate, while the side chain of Ile(97) points away from the substrate binding site, facilitating PEP utilization. The single site T97I mutation renders the enzyme sensitive to glyphosate and causes a substantial decrease in the affinity for PEP. Thus, only the concomitant mutations of Thr(97) and Pro(101) induce the conformational changes necessary to produce catalytically efficient, glyphosate-resistant class I EPSPS.

Isoleucine epimerization in the high-molecular-weight fraction of pleistocene Arctica

NASA Astrophysics Data System (ADS)

Kaufman, Darrell S.; Sejrup, Hans-Petter

The extent of amino acid racemization, as traditionally determined in the entire (total acid hydrolysate) pool of amino acids comprising the organic remains of fossils, is a function of the integrated effects of a complex diagenetic reaction network. We investigated the possibility that some of the complications involved in protein diagenesis might be circumvented by isolating one component of the reaction network and studying the extent of racemization in that fraction alone. We used gel-filtration to extract the high-molecular-weight (HMW) fraction of proteinaceous matter from fossil and modem molluscan shells. This fraction contains the largest (ca. > 15,000 MW), most-pristine macromolecules and has been less affected by diagenesis than the more-degraded, lower molecular-weight fractions. Variations in the extent of racemization (isoleucine epimerization; alle/Ile) measured in the HMW fraction of subsamples taken along cross sections of Arctica shells from two interglacial sites, Bø and Fjøsanger, southwestern Norway, are within the range of analytical uncertainty [coefficient of variation (cv) = 5-8%], despite the strong gradient (cv = 20-24%) in alle/Ile of the total amino acid population. Because there is no age difference across a shell, this finding supports the idea that the HMW fraction contains more geochronologically reliable proteinaceous matter than the total amino acid pool. Weighted mean alle/Ile ratios in the HMW fraction of aliquots of powdered sample from the two shells overlap at ± 1σ, despite significantly different alle/Ile ratios in the total amino acid population of some shells from the two sites. The difference in alle/Ile ratios in the total population is attributed to a greater proportion of low-molecular-weight (ca. 300 MW), and hence, extensively epimerized molecules measured in gel-filtered samples from the Fjøsanger shell. Because the rate of epimerization in the HMW fraction is much lower than in the total population, the

Intralipid™ administration attenuates the hypotensive effects of acute intravenous amiodarone overdose in a swine model.

PubMed

Xanthos, Theodoros; Psichalakis, Nikolaos; Russell, David; Papalois, Apostolos; Koutsovasilis, Anastasios; Athanasopoulos, Dimitrios; Gkiokas, Georgios; Chalkias, Athanasios; Iacovidou, Nicoletta

2016-08-01

To investigate whether a lipid emulsion could counteract the hypotensive effects of amiodarone overdose after an acute intravenous administration and improve 4 h survival in an established model of swine cardiovascular research. Twenty pigs were intubated and instrumented to measure aortic pressures and central venous pressures (CVP). After allowing the animals to stabilize for 60 minutes, amiodarone overdose (1 mg/kg/min) was initiated for a maximum of 20 minutes. Afterwards, the animals were randomized into 2 groups. Group A (n = 10) received 0.9% Normal Saline (NS) and Group B (n = 10) received 20% Intralipid® (ILE). A bolus dose of 2 ml/kg in over 2 min time was initially administered in both groups followed by a 45 min infusion (0.2 ml/kg/min) of either NS or ILE. All animals survived the overdose and all animals survived the monitoring period of 4 hours. Systolic aortic pressure (SpthAorta) (6.90 vs 14.10 mmHg, P = .006) and mean arterial pressure (MAP) (6.10 vs 14.90 mmHg, P = .001) were higher in the ILE group 2 min after the bolus ILE infusion. This difference was maintained for 15 min after ILE infusion for both SpthAorta (7.85 vs 13.15 mmHg, P = .044) and MAP (7.85 vs 13.15 mmHg, P = .042). Animals that received ILE had higher CVP (11.6 vs 15.7 mmHg, P = .046), an effect which was attenuated 2 and 4 hours post administration. Animals receiving ILE were more acidotic (7.21 vs 7.38, P = .048) in the monitoring period compared to animals receiving NS. Intralipid attenuated the hypotensive effects of amiodarone toxicity for a period of 15 minutes compared to animals receiving NS. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthesis and mode of action studies of N-[(-)-jasmonyl]-S-tyrosin and ester seiridin jasmonate.

PubMed

Reveglia, Pierluigi; Chini, Andrea; Mandoli, Alessandro; Masi, Marco; Cimmino, Alessio; Pescitelli, Gennaro; Evidente, Antonio

2018-03-01

Recent analyses on fungal jasmonic acid (JA)-containing metabolites suggest a mode-of-action of these naturally occurring compounds as inactive storage pools of JA. Plants and/or fungi can catabolize JA into the bioactive jasmonyl-isoleucine (JA-Ile) that in turn activates the JA-Ile-pathway in planta. To extend our knowledge on JA-derivates related to natural occurring JA conjugates, N-[(-)-jasmonyl]-S-tyrosin (JA-Tyr) and the ester JA-Sei between JA and seiridin, a fungal disubstituted furanone, were synthesized. The classical procedures for ester synthesis were applied for compound JA-Sei, while N-[(-)-jasmonyl]-S-tyrosin was synthesized with an optimized procedure. JA-Tyr and JA-Sei were characterized by spectroscopic method (essentially 1D and 2D NMR spectroscopy and ESI-MS) and their stereochemical composition was determined by means of HPLC and circular dichroism analysis. Finally, the activity of these JA-derivates was analyzed in planta. JA-Tyr and JA-Sei trigger JA-regulated plant responses, such as protein degradation and growth inhibition. These effects require the conversion of JA into JA-Ile and its recognition by the plant JA-Ile perception complex COI1-JAZ. Overall, these data suggest a mode-of-action of JA-Tyr and JA-Sei as inactive pool of JA that can be transformed into the bioactive JA-Ile to induce the canonical JA-Ile-pathway. Copyright © 2017 Elsevier Ltd. All rights reserved.

Silencing brassinosteroid receptor BRI1 impairs herbivory-elicited accumulation of jasmonic acid-isoleucine and diterpene glycosides, but not jasmonic acid and trypsin proteinase inhibitors in Nicotiana attenuata.

PubMed

Yang, Da-Hai; Baldwin, Ian T; Wu, Jianqiang

2013-06-01

The brassinosteroid (BR) receptor, BR insensitive 1 (BRI1), plays a critical role in plant development, but whether BRI1-mediated BR signaling is involved in plant defense responses to herbivores was largely unknown. Here, we examined the function of BRI1 in the resistance of Nicotiana attenuata (Solanaceae) to its specialist insect herbivore Manduca sexta. Jasmonic acid (JA) and JA-isoleucine conjugate (JA-Ile) are important hormones that mediate resistance to herbivores and we found that after wounding or simulated herbivory NaBRI1 had little effect on JA levels, but was important for the induction of JA-Ile. Further experiments revealed that decreased JAR (the enzyme for JA-Ile production) activity and availability of Ile in NaBRI1-silenced plants were likely responsible for the low JA-Ile levels. Consistently, M. sexta larvae gained more weight on NaBRI1-silenced plants than on the control plants. Quantification of insect feeding-induced secondary metabolites revealed that silencing NaBRI1 resulted in decreased levels of carbon-rich defensive secondary metabolites (hydroxygeranyllinalool diterpene glycosides, chlorogenic acid, and rutin), but had little effect on the nitrogen-rich ones (nicotine and trypsin proteinase inhibitors). Thus, NaBRI1-mediated BR signaling is likely involved in plant defense responses to M. sexta, including maintaining JA-Ile levels and the accumulation of several carbon-rich defensive secondary metabolites. © 2013 Institute of Botany, Chinese Academy of Sciences.

Small Peptides Derived from Penetratin as Antibacterial Agents.

PubMed

Parravicini, Oscar; Somlai, Csaba; Andujar, Sebastián A; Garro, Adriana D; Lima, Beatriz; Tapia, Alejandro; Feresin, Gabriela; Perczel, Andras; Tóth, Gabor; Cascales, Javier López; Rodríguez, Ana M; Enriz, Ricardo D

2016-04-01

The synthesis, in vitro evaluation and conformational study of several small-size peptides acting as antibacterial agents are reported. Among the compounds evaluated, the peptides Arg-Gln-Ile-Lys-Ile-Trp-Arg-Arg-Met-Lys-Trp-Lys-Lys-NH2 , Arg-Gln-Ile-Lys-Ile-Arg-Arg-Met-Lys-Trp-Arg-NH2 , and Arg-Gln-Ile-Trp-Trp-Trp-Trp-Gln-Arg-NH2 exhibited significant antibacterial activity. These were found to be very active antibacterial compounds, considering their small molecular size. In order to better understand the antibacterial activity obtained for these peptides, an exhaustive conformational analysis was performed, using both theoretical calculations and experimental measurements. Molecular dynamics simulations using two different media (water and trifluoroethanol/water) were employed. The results of these theoretical calculations were corroborated by experimental circular dichroism measurements. A brief discussion on the possible mechanism of action of these peptides at molecular level is also presented. Some of the peptides reported here constitute very interesting structures to be used as starting compounds for the design of new small-size peptides possessing antibacterial activity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Intrauterine Linear Echogenicities in the Gravid Uterus: What Radiologists Should Know.

PubMed

Jensen, Kyle K; Oh, Karen Y; Kennedy, Anne M; Sohaey, Roya

2018-01-01

Intrauterine linear echogenicity (ILE) is a common ultrasonographic finding in the gravid uterus and has variable causes and variable maternal and fetal outcomes. Correctly categorizing ILE during pregnancy is crucial for guiding surveillance and advanced imaging strategies. Common causes of ILE include membranes in multiple gestations, uterine synechiae with amniotic sheets, and uterine duplication anomalies. Less common causes include circumvallate placenta, chorioamniotic separation, and hemorrhage between membranes. Amniotic band syndrome is a rare but important diagnosis to consider, as it causes severe fetal defects. Imaging findings enable body stalk anomaly, a lethal defect, to be distinguished from amniotic bands, which although destructive are not necessarily lethal. This review describes the key imaging findings used to differentiate the various types of ILE in pregnancy, thus enabling accurate diagnosis and appropriate patient counseling. Online supplemental material is available for this article. © RSNA, 2018.

Usefulness of a topical combination of dinotefuran and pyriproxyfen for long-term control of clinical signs of allergic dermatitis in privately-owned cats in Ile-de-France region.

PubMed

Crosaz, Odile; Bonati, Silvia; Briand, Amaury; Chapelle, Elodie; Cochet-Faivre, Noëlle; Ka, Diane; Darmon-Hadjaje, Céline; Varloud, Marie; Guillot, Jacques

2017-08-23

The present study assessed the activity of a combination of dinotefuran and pyriproxyfen (Vectra® Felis) for long-term control (3 months) of allergic dermatitis (AD) in privately-owned cats under common household conditions in Ile-de-France region. This was an open pre-treatment vs post-treatment study. Twenty-eight client-owned cats with clinical signs of AD were enrolled in the study. They received topical application of the combination of dinotefuran and pyriproxyfen on days 0, 28, 56 and 84. Two parameters (clinical signs and pruritus severity) were used to assess the animals' condition on days 0, 28 and 84. Fleas were counted if they were observed. Of the 28 cats initially enrolled, 26 were presented on day 28 and 20 for the final evaluation on day 84. A significant improvement in clinical signs and pruritus was observed in cats for which fleas and/or flea feces were detected on day 0. Globally, the post-treatment AD clinical scores on days 28 and 84 were different from that of the pre-treatment on day 0, with a reduction of 30% and 71%, respectively. For cats with fleas and/or flea feces, the reduction on days 28 and 84 was 33% and 85%, respectively. The improvement of clinical signs and pruritus was not significant in cats with no visible fleas and no flea feces at the beginning of the trial (n = 8). The present study indicated that the treatment with a combination of dinotefuran and pyriproxyfen should be considered as useful in controlling fleas on cats without additional environmental treatment and useful for long-term control of clinical signs and pruritus in allergic cats.

Hot topic: Changes in angiotensin-converting enzyme inhibition and concentrations of the tripeptides Val-Pro-Pro and Ile-Pro-Pro during ripening of different Swiss cheese varieties.

PubMed

Meyer, J; Bütikofer, U; Walther, B; Wechsler, D; Sieber, R

2009-03-01

The angiotensin-converting enzyme (ACE) inhibitory activity and the concentration of the 2 ACE-inhibiting tripeptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) were studied during cheese ripening in 7 Swiss cheese varieties. The semi-hard cheeses Tilsiter, Appenzeller 1/4 fat, Tête de Moine, and Vacherin fribourgeois and the extra-hard and hard cheeses Berner Hobelkäse, Le Gruyère, and Emmentaler were investigated. Three loaves of each variety manufactured in different cheese factories were purchased at the beginning of commercial ripeness and investigated at constant intervals until the end of the usual sale period. Good agreement was found between ACE-inhibitory activity and the total concentration of VPP and IPP at advanced ripening stages. In most of the investigated varieties ACE-inhibitory activity and the concentration of the 2 tripeptides initially increased during the study period. A decline in the concentration of VPP and IPP was obtained toward the end of the investigated period for Tilsiter and Gruyère. The ratio of VPP/IPP decreased during ripening in all varieties with the exception of Emmentaler. However, large variations were observed among the cheese varieties as well as the individual loaves of the same variety. Chemical characterization of the investigated cheeses revealed that qualitative differences in the proteolysis pattern, not quantitative differences in the degree of proteolysis, are responsible for the observed variations in the concentrations of VPP and IPP. The presence of Lactobacillus helveticus in the starter culture was associated with elevated concentrations of VPP and IPP. The results of the present study show that concentrations of VPP and IPP above 100 mg/kg are attainable in semi-hard cheese varieties after ripening periods of about 4 to 7 mo and that stable concentrations of the 2 antihypertensive tripeptides can be expected over several weeks of cheese ripening.

Sodium caprate enables the blood pressure-lowering effect of Ile-Pro-Pro and Leu-Lys-Pro in spontaneously hypertensive rats by indirectly overcoming PepT1 inhibition.

PubMed

Gleeson, John P; Frías, Jesús M; Ryan, Sinéad M; Brayden, David J

2018-04-20

The tripeptides, Ile-Pro-Pro (IPP) and Leu-Lys-Pro (LKP), inhibit angiotensin-converting enzyme (ACE) resulting in lowered blood pressure. Our hypothesis was that the medium chain fatty acid permeation enhancer, sodium caprate (C 10 ), may prevent the decrease in permeability of the tripeptides when PepT1 is inhibited by glycyl-sarcosine (Gly-Sar), a situation that may occur in the presence of food hydrolysates. Using Caco-2 monolayers and isolated rat jejunal tissue, the apparent permeability coefficients (P app ) of [ 3 H]-IPP and [ 3 H]-LKP were assessed in the presence of Gly-Sar with and without C 10 . Gly-Sar decreased the P app of both tripeptides across monolayers and isolated jejunal tissue, but C 10 restored it. C 10 likely increased the paracellular permeability of the tripeptides, as indicated by immunofluorescence changes in tight junction proteins in Caco-2 monolayers accompanied by a concentration-dependent decrease in transepithelial electrical resistance (TEER). [ 3 H]-IPP and [ 3 H]-LKP were orally-gavaged to normal rats with Gly-Sar, C 10 , or with a mixture. Plasma levels of both peptides were reduced by Gly-Sar to less than half that of the levels detected in its absence, but were restored when C 10 was co-administered. In spontaneously hypertensive rats (SHRs), unlabelled IPP and LKP lowered blood pressure when delivered either by i.v. or oral routes. Oral gavage of Gly-Sar reduced the hypotensive action of peptides in SHRs, but the effect was restored in the presence of C 10 . In conclusion, there was a reduction in the hypotensive effects of IPP and LKP in SHRs when intestinal PepT1 was inhibited by Gly-Sar, but C 10 may circumvent this by enhancing paracellular permeability. Copyright © 2018 Elsevier B.V. All rights reserved.

Long-term outcomes of minimally invasive Ivor Lewis esophagostomy for esophageal squamous cell carcinoma: Compared with open approach.

PubMed

Zhang, Zhenghua; Xu, Meiqing; Guo, Mingfa; Liu, Xuegang

2017-09-01

To investigate the safety and long-term efficacy of combined thoraco-laparoscopic minimally invasive Ivor Lewis esophagostomy(MI-ILE) in the treatment of esophageal squamous cell carcinoma. The clinical data of patients with esophageal squamous cell carcinoma who underwent Ivor Lewis esophagostomy of esophageal cancer from October 2011 to June 2013 were retrospectively analyzed. Of which 90 patients received MI-ILE, 95 patients underwent open Ivor Lewis esophagostomy (O-ILE). The clinicopathological features, intraoperative records and incidences of postoperative complications of the two groups were compared with t-test and χ2 test. The primary end point of the study was 3-year disease-free survival (DFS) and 3-year overall survival (OS) was a secondary end point. There were no statistically significant differences in gender, age, preoperative comorbidities, American Society of Anesthesiologists score and position of the tumor between the two groups. There was also no significant difference in clinicopathological characteristics, operation time, length of tumor resection margin and number of resected lymph nodes between the two groups (P > 0.05). In MI-ILE group, the blood loss was lower than in the O-ILE group [(159.1 + 97.4) ml vs. (191.7 + 141.9) ml, t = 1.811, P = 1.811]and the postoperative hospital stay was shorter [(11.5 + 4.5) d vs. (13.9 + 6.2) d, t = 2.944, P = 0.004]. There was no significant difference in the incidences of perioperative mortality and major morbidities (P > 0.05). Minor complications including incision infection rate (1.1% vs 8.4%, χ2 = 3.873, P = 0.049) and pulmonary infection incidence (3.3% vs 11.57%, χ2 = 4.492, P = 0.034) is lower in MIILE group. There was no significant difference in 3-year disease-free survival (DFS) and 3-year overall survival (OS) between the two groups. MI-ILE is a technically safe and feasible approach for esophageal squamous cell carcinoma treatment. The oncologic outcomes of MI-ILE

Variants of glutathione s-transferase pi 1 exhibit differential enzymatic activity and inhibition by heavy metals.

PubMed

Goodrich, Jaclyn M; Basu, Niladri

2012-06-01

Nonsynonymous single nucleotide polymorphisms in glutathione s-transferase pi 1 (GSTP1; Ile/Val 105, Ala/Val 114) have been associated with altered toxicant metabolism in epidemiological cohorts. We explored the impact of GSTP1 genotype on enzyme kinetics and heavy metal inhibition in vitro. Four GSTP1 allozymes (105/114: Ile/Ala, Val/Ala, Ile/Val, Val/Val) were expressed in and purified from Escherichia coli. Enzyme activity assays quantifying the rate of glutathione conjugation with 1-chloro-2,4-dinitrobenzene (CDNB) revealed significant differences in kinetic parameters depending on genotype (p<0.01). Allozymes with Ile105 had better catalytic efficiency and greater affinity for CDNB (mean ± SEM: Ile105 Ala114 K(m)=0.33 ± 0.07 mM vs. Val105 Ala114 K(m)=1.15 ± 0.07 mM). Inhibition of GSTP1 activity by heavy metals was assessed following treatment with mercury (inorganic-HgCl(2), methylmercury-MeHg), selenium, cadmium, lead, arsenic, and manganese. All allozymes were inhibited by HgCl(2) (IC(50) range: 24.1-172 μM), MeHg (93.9-480 μM), and selenium (43.7-62.8 μM). Genotype significantly influenced the potency of mercury with GSTP1 Ile105 Val114 the least sensitive and Val105 Ala114 the most sensitive to inhibition by HgCl(2) and MeHg. Overall, genotype of two nonsynonymous polymorphisms in GSTP1 influenced enzyme kinetics pertaining to an electrophilic substrate and inhibition by two mercury species. Published by Elsevier Ltd.

Variants of glutathione s-transferase pi 1 exhibit differential enzymatic activity and inhibition by heavy metals

PubMed Central

Goodrich, Jaclyn M.; Basu, Niladri

2012-01-01

Nonsynonymous single nucleotide polymorphisms in glutathione s-transferase pi 1 (GSTP1; Ile/Val 105, Ala/Val 114) have been associated with altered toxicant metabolism in epidemiological cohorts. We explored the impact of GSTP1 genotype on enzyme kinetics and heavy metal inhibition in vitro. Four GSTP1 allozymes (105/114: Ile/Ala, Val/Ala, Ile/Val, Val/Val) were expressed in and purified from E. coli. Enzyme activity assays quantifying the rate of glutathione conjugation with 1-chloro-2,4-dinitrobenzene (CDNB) revealed significant differences in kinetic parameters depending on genotype (p<0.01). Allozymes with Ile105 had better catalytic efficiency and greater affinity for CDNB (mean ±SEM: Ile105 Ala114 Km= 0.33±0.07 mM vs. Val105 Ala114 Km=1.15±0.07 mM). Inhibition of GSTP1 activity by heavy metals was assessed following treatment with mercury (inorganic- HgCl2, methylmercury- MeHg), selenium, cadmium, lead, arsenic, and manganese. All allozymes were inhibited by HgCl2 (IC50 range: 24.1–172 μM), MeHg (93.9–480 μM), and selenium (43.7–62.8 μM). Genotype significantly influenced the potency of mercury with GSTP1 Ile105 Val114 the least sensitive and Val105 Ala114 the most sensitive to inhibition by HgCl2 and MeHg. Overall, genotype of two nonsynonymous polymorphisms in GSTP1 influenced enzyme kinetics pertaining to an electrophilic substrate and inhibition by two mercury species. PMID:22401947

Structural insights into the N-terminal GIY-YIG endonuclease activity of "Arabidopsis" glutaredoxin AtGRXS16 in chloroplasts

USDA-ARS?s Scientific Manuscript database

Glutaredoxins (Grxs) have been identified across taxa as important mediators in various physiological functions. A chloroplastic monothiol glutaredoxin, AtGRXS16 from "Arabidopsis thaliana", comprises two distinct functional domains, an N-terminal domain (NTD) with GlyIleTyr-TyrIleGly (GIY-YIG) endo...

Characterizing Navigation in Interactive Learning Environments

ERIC Educational Resources Information Center

Liang, Hai-Ning; Sedig, Kamran

2009-01-01

Interactive learning environments (ILEs) are increasingly used to support and enhance instruction and learning experiences. ILEs maintain and display information, allowing learners to interact with this information. One important method of interacting with information is navigation. Often, learners are required to navigate through the information…

Hahn AB, Hunsbruck, Germany. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F

DTIC Science & Technology

1978-09-29

FREQUENCY OF WIND DIRECTION AND SPEED (FROM HOURLY OBSERVATIONS) 34_D5_ 1 hf.H A / -/ rJC< L:: P .,-’l 7 STAMIn SIAT..AS II I""n SSy. __ _L r nl :..T...opposite > 0. Froa the table: Visibility>, 3 Iles -95.-I%. Visibility> 2 Iles - 96.9%. Viaibility > 1 Ile - 96.3%. EM4PLE j3 To Obtain combintions of celling ...VERSUS VISIBILITY A;IR E, T-"F S 7 " " PERCENTAGE FREQUENCY OF OCCURRENCE (FROM HOURLY OBSERVATIONS) CEll , tWINSIB4ITY STATUTE MILES C,00 I/IN- . I

Methodology for AACT evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning.

PubMed

Gosselin, Sophie; Morris, Martin; Miller-Nesbitt, Andrea; Hoffman, Robert S; Hayes, Bryan D; Turgeon, Alexis F; Gilfix, Brian M; Grunbaum, Ami M; Bania, Theodore C; Thomas, Simon H L; Morais, José A; Graudins, Andis; Bailey, Benoit; Mégarbane, Bruno; Calello, Diane P; Levine, Michael; Stellpflug, Samuel J; Hoegberg, Lotte C G; Chuang, Ryan; Stork, Christine; Bhalla, Ashish; Rollins, Carol J; Lavergne, Valéry

2015-07-01

Intravenous lipid emulsion (ILE) therapy is a novel treatment that was discovered in the last decade. Despite unclear understanding of its mechanisms of action, numerous and diverse publications attested to its clinical use. However, current evidence supporting its use is unclear and recommendations are inconsistent. To assist clinicians in decision-making, the American Academy of Clinical Toxicology created a workgroup composed of international experts from various clinical specialties, which includes representatives of major clinical toxicology associations. Rigorous methodology using the Appraisal of Guidelines for Research and Evaluation or AGREE II instrument was developed to provide a framework for the systematic reviews for this project and to formulate evidence-based recommendations on the use of ILE in poisoning. Systematic reviews on the efficacy of ILE in local anesthetic toxicity and non-local anesthetic poisonings as well as adverse effects of ILE are planned. A comprehensive review of lipid analytical interferences and a survey of ILE costs will be developed. The evidence will be appraised using the GRADE system. A thorough and transparent process for consensus statements will be performed to provide recommendations, using a modified Delphi method with two rounds of voting. This process will allow for the production of useful practice recommendations for this therapy.

Aminiphilus circumscriptus gen. nov., sp. nov., an anaerobic amino-acid-degrading bacterium from an upflow anaerobic sludge reactor.

PubMed

Díaz, C; Baena, S; Fardeau, M-L; Patel, B K C

2007-08-01

Strain ILE-2(T) was isolated from an upflow anaerobic sludge bed reactor treating brewery wastewater. The motile, non-sporulating, slightly curved cells (2-4 x 0.1 microm) stained Gram-negative and grew optimally at 42 degrees C and pH 7.1 with 0.5 % NaCl. The strain required yeast extract for growth and fermented Casamino acids, peptone, isoleucine, arginine, lysine, alanine, valine, glutamate, histidine, glutamine, methionine, malate, fumarate, glycerol and pyruvate to acetate, propionate and minor amounts of branched-chain fatty acids. Carbohydrates, formate, acetate, propionate, butyrate, isovalerate, methanol, ethanol, 1-propanol, butanol, lactate, succinate, starch, casein, gelatin, xylan and a number of other amino acids were not utilized. The DNA G+C content of strain ILE-2(T) was 52.7 mol%. 16S rRNA gene sequence analysis revealed that ILE-2(T) was distantly related to members of the genera Aminobacterium (83 % similarity) and Aminomonas (85 % similarity) in the family Syntrophomonadaceae, order Clostridiales, phylum Firmicutes. On the basis of the results of our polyphasic analysis, strain ILE-2(T) represents a novel species and genus within the family Syntrophomonadaceae, for which the name Aminiphilus circumscriptus gen. nov., sp. nov. is proposed. The type strain of Aminiphilus circumscriptus is ILE-2(T) (=DSM 16581(T) =JCM 14039(T)).

Exploring Students' Use of Explanatory Help during Math Problem Solving in Interactive Learning Environments

ERIC Educational Resources Information Center

Huang, Xudong

2016-01-01

Help-seeking is a crucial behavior during learning in interactive learning environments (ILEs). Appropriate help-seeking promotes learning, while inappropriate help-seeking prohibits learning. However, many students are unaware of effective help-seeking behaviors. Therefore, research is needed to examine how students seek help in ILEs. Although…

Protein geranylgeranyltransferase of Saccharomyces cerevisiae is specific for Cys-Xaa-Xaa-Leu motif proteins and requires the CDC43 gene product but not the DPR1 gene product.

PubMed Central

Finegold, A A; Johnson, D I; Farnsworth, C C; Gelb, M H; Judd, S R; Glomset, J A; Tamanoi, F

1991-01-01

Protein prenylation occurs by modification of proteins with one of at least two isoprenoids, the farnesyl group and the geranylgeranyl group. Protein farnesyltransferases have been identified, but no such enzyme has been identified for geranylgeranylation. We report the identification of an activity in crude soluble yeast extracts that catalyzes the transfer of a geranylgeranyl moiety from geranylgeranyl pyrophosphate to proteins having the C-terminal sequence Cys-Ile-Ile-Leu or Cys-Val-Leu-Leu but not to a similar protein ending with Cys-Ile-Ile-Ser. This activity is dependent upon the CDC43/CAL1 gene, which is involved in budding and the control of cell polarity, but does not require the DPR1/RAM1 gene, which is known to be required for the farnesylation of Ras proteins. These results indicate that the protein geranylgeranyltransferase activity is distinct from the protein farnesyltransferase activity and that its specificity depends in part on the extreme C-terminal leucine in the protein to be prenylated. Images PMID:2034682

A terrestrial vertebrate palaeontological review of Aldabra Atoll, Aldabra Group, Seychelles

PubMed Central

2018-01-01

The Pleistocene vertebrate assemblage of Aldabra Atoll has been comparatively well studied. Three Upper Pleistocene fossil localities have been described yielding birds, reptiles and terrestrial molluscs. Those of Bassin Cabri and Bassin Lebine on Ile Picard are undated but must be in excess of 136,000 YBP, whereas Point Hodoul on Malabar Island is circa 100,000 YBP. Aldabra was seemingly completely submerged between deposition of the Ile Picard and Point Hodoul deposits, resulting in local faunal extinctions. Here we present the results of an ongoing study of fossil material collected on Ile Picard in 1987, which reveals a more diverse assemblage than previously realised. Notable discoveries are an Ardeola heron, three Procellariformes, tropic-bird Phaethon, gull Larus, rail Dryolimnas, harrier Circus and owl Tyto, plus evidence of recolonisation of the atoll by some seabirds, rail, harrier, owl, giant tortoises and lizards after the Ile Picard/Point Hodoul submergence event. PMID:29590117

High-Resolution Structure of a Self-Assembly-Competent Form of a Hydrophobic Peptide Captured in a Soluble [beta]-Sheet Scaffold

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

Makabe, Koki; Biancalana, Matthew; Yan, Shude

2010-02-08

{beta}-Rich self-assembly is a major structural class of polypeptides, but still little is known about its atomic structures and biophysical properties. Major impediments for structural and biophysical studies of peptide self-assemblies include their insolubility and heterogeneous composition. We have developed a model system, termed peptide self-assembly mimic (PSAM), based on the single-layer {beta}-sheet of Borrelia outer surface protein A. PSAM allows for the capture of a defined number of self-assembly-like peptide repeats within a water-soluble protein, making structural and energetic studies possible. In this work, we extend our PSAM approach to a highly hydrophobic peptide sequence. We show that amore » penta-Ile peptide (Ile{sub 5}), which is insoluble and forms {beta}-rich self-assemblies in aqueous solution, can be captured within the PSAM scaffold in a form capable of self-assembly. The 1.1-{angstrom} crystal structure revealed that the Ile{sub 5} stretch forms a highly regular {beta}-strand within this flat {beta}-sheet. Self-assembly models built with multiple copies of the crystal structure of the Ile5 peptide segment showed no steric conflict, indicating that this conformation represents an assembly-competent form. The PSAM retained high conformational stability, suggesting that the flat {beta}-strand of the Ile{sub 5} stretch primed for self-assembly is a low-energy conformation of the Ile{sub 5} stretch and rationalizing its high propensity for self-assembly. The ability of the PSAM to 'solubilize' an otherwise insoluble peptide stretch suggests the potential of the PSAM approach to the characterization of self-assembling peptides.« less

Delayed degeneration of the left fornical crus with verbal memory impairment in a patient with mild traumatic brain injury

PubMed Central

Jang, Sung Ho; Seo, Jeong Pyo

2017-01-01

Abstract Rationale: We report on a patient who showed delayed degeneration of the left fornical crus with verbal memory impairment following mild traumatic brain injury (TBI), which was demonstrated by diffusion tensor tractography (DTT). Patient concerns: fter flexion and hyperextension of her head to the opposite side, the patient experienced a dazed feeling for a while at the time of head trauma. The patient's Glasgow Coma Scale score was 15, and mini-mental state examination score was 30. Diagnoses: A 50-year-old right-handed female with 12 years of education suffered from head trauma resulting from a car accident. Interventions: A The patient showed normal memory function at one year after onset: the Memory Assessment Scale (global memory: 124 (95 percentile (%ile)), verbal memory: 111 (77%ile), and visual memory: 132 (98%ile) (A percentile is a measure used in statistics indicating the value below which a given percentage of observations in a group of observations fall). However, the patient began to experience decline of memory function such as forgetfulness at approximately 1.5 years after onset. On the 2-year evaluation, she showed decrement of memory function (global memory: 108 (70%ile), verbal memory: 86 (18%ile), and visual memory: 129 (97%ile). Outcomes: On 1-year DTT, the integrity of the fornix was well preserved between the fornical column and fornical crus. However, on 2-year DTT, a discontinuation was observed in the left fornical crus. Lessons: Delayed degeneration of the left fornical crus was demonstrated in a patient who showed delayed onset of verbal memory impairment following mild TBI. PMID:29390470

Regulation of extrafloral nectar secretion by jasmonates in lima bean is light dependent

PubMed Central

Radhika, Venkatesan; Kost, Christian; Mithöfer, Axel; Boland, Wilhelm

2010-01-01

To maximize fitness, plants need to perceive changes in their light environment and adjust their physiological responses accordingly. Whether and how such changes also affect the regulation of their defense responses against herbivores remains largely unclear. We addressed this issue by studying the secretion of extrafloral nectar (EFN) in lima bean (Phaseolus lunatus), which is known to be activated by the phytohormone jasmonic acid (JA) and functions as an indirect defense mechanism against herbivores. We found that the plant’s EFN secretion in response to JA was light dependent: In the dark, JA reduced EFN secretion, whereas under light conditions, JA induced EFN secretion relative to controls. This modulation was affected by the light’s spectral composition [i.e., ratio of red to far-red (R:FR) radiation], but not light intensity. These findings demonstrate a unique differential effect of JA on EFN secretion depending on the ambient light conditions. Interestingly, treatment with the isoleucine–JA conjugate (JA–Ile) enhanced EFN secretion under light conditions yet did not reduce EFN secretion in the dark. Moreover, inhibition of Ile biosynthesis in light-exposed plants significantly decreased the EFN secretion rate. This reduction could be recovered by additional application of JA–Ile, suggesting that JA–Ile is the active compound required to up-regulate EFN secretion. Finally, experiments with mechanically damaged plants revealed that light was required for the formation of JA–Ile, but not of JA. These results demonstrate that in lima bean, the light environment modulates the plant’s response to jasmonates as well as JA–Ile biosynthesis, which controls the subsequent EFN secretion. PMID:20855624

Toward a Narrative Pedagogy for Interactive Learning Environments

ERIC Educational Resources Information Center

Hazel, Paul

2008-01-01

The use of narrative within interactive learning environments (ILEs) is widespread. Reviewing recent research in the fields of ethnography, cognitive psychology, neurobiology, discourse analysis, and education, this paper proposes a rationale for the use of narrative in ILEs. Starting with a description of the origin of narrative in the brain, the…

Glutathione-S-transferase pi (GSTP1) codon 105 polymorphism is not associated with oxaliplatin efficacy or toxicity in advanced colorectal cancer patients.

PubMed

Kweekel, Dina M; Gelderblom, Hans; Antonini, Ninja F; Van der Straaten, Tahar; Nortier, Johan W R; Punt, Cornelis J A; Guchelaar, Henk-Jan

2009-03-01

Oxaliplatin is detoxified by conjugation to glutathione via the enzyme Glutathione-S-transferase pi (GSTP1). The aim of this study is to investigate the association of GSTP1 Ile105Val genetic polymorphism with oxaliplatin efficacy and toxicity in advanced colorectal cancer (ACC) patients. A total of 91 ACC patients received capecitabine and oxaliplatin (CAPOX) as a part of a multicentre phase-III study of the Dutch Colorectal Cancer Group. Tumour response was evaluated according to RECIST, toxicity was graded using CTC, and GSTP1 Ile105Val was determined by pyrosequencing. Overall survival after CAPOX was similar for patients with the Ile/Ile (11.5 mo), Ile/Val (11.6 mo) and Val/Val (12.6 mo) genotypes (p=0.602). Likewise, there were no statistically significant differences in progression-free survival (p=0.252). Overall grades 3-4 toxicity was not related to genotype (p=0.313). There were no differences in any grade or grades 3-4 neurotoxicity amongst the patients who received > or =500 mg/m(2) of oxaliplatin (p-values of 0.376 and 0.772, respectively). The results of this study indicate that the GSTP1 genotype is not predictive for progression-free survival or overall survival in ACC patients treated with CAPOX. Moreover, overall neurotoxicity and neurotoxicity in patients receiving 500 mg/m(2) of oxaliplatin was not associated with GSTP1 genotype.

The alyteserins: two families of antimicrobial peptides from the skin secretions of the midwife toad Alytes obstetricans (Alytidae).

PubMed

Conlon, J Michael; Demandt, Anni; Nielsen, Per F; Leprince, Jérôme; Vaudry, Hubert; Woodhams, Douglas C

2009-06-01

Two families of structurally related C-terminally alpha-amidated antimicrobial peptides have been identified in norepinephrine-stimulated skin secretions of the midwife toad Alytes obstetricans (Alytidae). The alyteserin-1 peptides (Gly-Leu-Lys-(Asp/Glu)-Ile-Phe-Lys-Ala-Gly-Leu-Gly-Ser-Leu-Val-Lys-(Gly/Asn)-Ile-Ala-Ala-His-Val-Ala-(Asn/Ser).NH(2)) show limited structural similarity to the ascaphins from the skins of frogs of the family Leiopelmatidae. Alyteserin-2a (Ile-Leu-Gly-Lys-Leu-Leu-Ser-Thr-Ala-Ala-Gly-Leu-Leu-Ser-Asn-Leu.NH(2)) and alyteserin-2b and -2c (Ile-Leu-Gly-Ala-Ile-Leu-Pro-Leu-Val-Ser-Gly-Leu-Leu-Ser-(Asn/Ser)-Lys-Leu x NH(2)) show limited sequence identity with bombinin H6, present in the skins of frogs of the family Bombinatoridae. The alyteserin-1 peptides show selective growth inhibitory activity against the Gram-negative bacteria Escherichia coli (MIC=25 microM) whereas alyteserin-2a is more potent against the Gram-positive bacteria Staphylococcus aureus (MIC=50 microM). The hemolytic activity against human erythrocytes of all peptides tested is relatively weak (LC(50)>100 microM). The data demonstrate that the frogs belonging to the family Alytidae are among those producing dermal antimicrobial peptides that may represent a component of the animal's system of innate immunity.

Structural Basis of Glyphosate Resistance Resulting from the Double Mutation Thr97 → Ile and Pro101 → Ser in 5-Enolpyruvylshikimate-3-phosphate Synthase from Escherichia coli*S⃞

PubMed Central

Funke, Todd; Yang, Yan; Han, Huijong; Healy-Fried, Martha; Olesen, Sanne; Becker, Andreas; Schönbrunn, Ernst

2009-01-01

The shikimate pathway enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) is the target of the broad spectrum herbicide glyphosate. The genetic engineering of EPSPS led to the introduction of glyphosate-resistant crops worldwide. The genetically engineered corn lines NK603 and GA21 carry distinct EPSPS enzymes. CP4 EPSPS, expressed in NK603 corn and transgenic soybean, cotton, and canola, belongs to class II EPSPS, glyphosate-insensitive variants of this enzyme isolated from certain Gram-positive bacteria. GA21 corn, on the other hand, was created by point mutations of class I EPSPS, such as the enzymes from Zea mays or Escherichia coli, which are sensitive to low glyphosate concentrations. The structural basis of the glyphosate resistance resulting from these point mutations has remained obscure. We studied the kinetic and structural effects of the T97I/P101S double mutation, the molecular basis for GA21 corn, using EPSPS from E. coli. The T97I/P101S enzyme is essentially insensitive to glyphosate (Ki = 2.4 mm) but maintains high affinity for the substrate phosphoenolpyruvate (PEP) (Km = 0.1 mm). The crystal structure at 1.7-Å resolution revealed that the dual mutation causes a shift of residue Gly96 toward the glyphosate binding site, impairing efficient binding of glyphosate, while the side chain of Ile97 points away from the substrate binding site, facilitating PEP utilization. The single site T97I mutation renders the enzyme sensitive to glyphosate and causes a substantial decrease in the affinity for PEP. Thus, only the concomitant mutations of Thr97 and Pro101 induce the conformational changes necessary to produce catalytically efficient, glyphosate-resistant class I EPSPS. PMID:19211556

TLR-4 polymorphisms and leukocyte TLR-4 expression in febrile UTI and renal scarring.

PubMed

Bayram, Meral Torun; Soylu, Alper; Ateş, Halil; Kızıldağ, Sefa; Kavukçu, Salih

2013-09-01

In this study, we aimed to determine the relation of TLR-4 Asp299Gly and Thr399Ile polymorphisms and monocyte/neutrophil TLR-4 expression to febrile urinary tract infection (UTI) and renal scar development in children. The study was performed in children with a history of febrile UTI. Patients with and without renal scarring were classified as group 1 and group 2, respectively, while the control cases in our previous study were used as the control group (group 3). All three groups were compared for the rate of TLR-4 Asp299Gly and Thr399Ile polymorphisms, and for basal and lipopolysaccharide-stimulated monocyte/neutrophil TLR-4 expression levels. There were 168 patients (86 in group 1, 82 in group 2) and 120 control cases. Monocyte/neutrophil TLR-4 expression levels were similar in groups 1 and 2. However, both groups had lower TLR-4 expression than group 3. The rate of TLR-4 Asp299Gly polymorphism was not different in all groups. TLR-4 Thr399Ile polymorphism was higher in groups 1 and 2 than in group 3 (14.0, 12.2, and 2.0 %, respectively), while group 1 and group 2 were not different. Furthermore, monocyte TLR-4 expression level was lower in those having TLR-4 Thr399Ile polymorphism than in those without this polymorphism. Patients with febrile UTI had more frequent TLR-4 Thr399Ile polymorphism and lower monocyte/neutrophil TLR-4 expression. These findings indicate that children carrying TLR-4 Thr399Ile polymorphism and/or having low level of monocyte/neutrophil TLR-4 expression have a tendency to develop febrile UTI. However, we could not show the association of TLR-4 polymorphisms and of TLR-4 expression level to renal scarring.

A comparison of the left thoracoabdominal and Ivor-Lewis esophagectomy.

PubMed

Davies, A R; Zylstra, J; Baker, C R; Gossage, J A; Dellaportas, D; Lagergren, J; Findlay, J M; Puccetti, F; El Lakis, M; Drummond, R J; Dutta, S; Mera, A; Van Hemelrijck, M; Forshaw, M J; Maynard, N D; Allum, W H; Low, D; Mason, R C

2018-03-01

The purpose of this study was to assess the oncological outcomes of a large multicenter series of left thoracoabdominal esophagectomies, and compare these to the more widely utilized Ivor-Lewis esophagectomy. With ethics approval and an established study protocol, anonymized data from five centers were merged into a structured database. The study exposure was operative approach (ILE or LTE). The primary outcome measure was time to death. Secondary outcome measures included time to tumor recurrence, positive surgical resection margins, lymph node yield, postoperative death, and hospital length of stay. Cox proportional hazards models provided hazard ratios (HR) with 95% confidence intervals (CI) adjusting for age, pathological tumor stage, tumor grade, lymphovascular invasion, and neoadjuvant treatment. Among 1228 patients (598 ILE; 630 LTE), most (86%) had adenocarcinoma (AC) and were male (81%). Comparing ILE and LTE for AC patients, no difference was seen in terms of time to death (HR 0.904 95%CI 0.749-1.1090) or time to recurrence (HR 0.973 95%CI 0.768-1.232). The risk of a positive resection margin was also similar (OR 1.022 95%CI 0.731-1.429). Median lymph node yield did not differ between approaches (LTE 21; ILE 21; P = 0.426). In-hospital mortality was 2.4%, significantly lower in the LTE group (LTE 1.3%; ILE 3.6%; P = 0.004). Median hospital stay was 11 days in the LTE group and 14 days in the ILE group (P < 0.0001). In conclusion, this is the largest series of left thoracoabdominal esophagectomies to be submitted for publication and the only one to compare two different transthoracic esophagectomy strategies. It demonstrates oncological equivalence between operative approaches but possible short- term advantages to the left thoracoabdominal esophagectomy.

Re/assembling "Innovative" Learning Environments: Affective Practice and Its Politics

ERIC Educational Resources Information Center

Mulcahy, Dianne; Morrison, Carol

2017-01-01

In this article, we argue that the interest being taken by governments in establishing innovative learning environments (ILEs) in schools relies on a conception of space as a largely neutral arena. In consequence, relations of space and power inherent in the infrastructural shift to ILEs tend to drop from view. Adopting an assemblage approach to…

Theoretical study of the gas-phase structures of sodiated and cesiated leucine and isoleucine: zwitterionic structure disfavored in kinetic method experiments.

PubMed

Rozman, Marko

2005-10-01

The most stable charge-solvated (CS) and zwitterionic (ZW) structures of sodiated and cesiated leucine and isoleucine were studied by density functional theory methods. According to the Boltzmann distribution in gas phase, both forms of LeuNa+ and IleNa+ exist, but in LeuCs+ and IleCs+, the ZW forms are dominant. Results for the sodiated compounds are consistent with the relationship found between decrease in relative stability of CS versus ZW form and aliphatic amino acid side chain length. The observed degeneracy in energy for IleNa+ conformers is at odds with kinetic method results. Additional calculations showed that kinetic method structural determinations for IleNa+ do not reflect relative order of populations in the lowest energy conformers. Since complexation of cationized amino acids into ion-bound dimers disfavors ZW structure by approximately 8 kJ mol(-1), it is suggested that for energy close conformers of sodium-cationized amino acids, the kinetic method may not be reliable for structural determinations. Copyright (c) 2005 John Wiley & Sons, Ltd.

N-Terminal Ile-Orn- and Trp-Orn-Motif Repeats Enhance Membrane Interaction and Increase the Antimicrobial Activity of Apidaecins against Pseudomonas aeruginosa

PubMed Central

Bluhm, Martina E. C.; Schneider, Viktoria A. F.; Schäfer, Ingo; Piantavigna, Stefania; Goldbach, Tina; Knappe, Daniel; Seibel, Peter; Martin, Lisandra L.; Veldhuizen, Edwin J. A.; Hoffmann, Ralf

2016-01-01

The Gram-negative bacterium Pseudomonas aeruginosa is a life-threatening nosocomial pathogen due to its generally low susceptibility toward antibiotics. Furthermore, many strains have acquired resistance mechanisms requiring new antimicrobials with novel mechanisms to enhance treatment options. Proline-rich antimicrobial peptides, such as the apidaecin analog Api137, are highly efficient against various Enterobacteriaceae infections in mice, but less active against P. aeruginosa in vitro. Here, we extended our recent work by optimizing lead peptides Api755 (gu-OIORPVYOPRPRPPHPRL-OH; gu = N,N,N′,N′-tetramethylguanidino, O = L-ornithine) and Api760 (gu-OWORPVYOPRPRPPHPRL-OH) by incorporation of Ile-Orn- and Trp-Orn-motifs, respectively. Api795 (gu-O(IO)2RPVYOPRPRPPHPRL-OH) and Api794 (gu-O(WO)3RPVYOPRPRPPHPRL-OH) were highly active against P. aeruginosa with minimal inhibitory concentrations of 8–16 and 8–32 μg/mL against Escherichia coli and Klebsiella pneumoniae. Assessed using a quartz crystal microbalance, these peptides inserted into a membrane layer and the surface activity increased gradually from Api137, over Api795, to Api794. This mode of action was confirmed by transmission electron microscopy indicating some membrane damage only at the high peptide concentrations. Api794 and Api795 were highly stable against serum proteases (half-life times >5 h) and non-hemolytic to human erythrocytes at peptide concentrations of 0.6 g/L. At this concentration, Api795 reduced the cell viability of HeLa cells only slightly, whereas the IC50 of Api794 was 0.23 ± 0.09 g/L. Confocal fluorescence microscopy revealed no colocalization of 5(6)-carboxyfluorescein-labeled Api794 or Api795 with the mitochondria, excluding interactions with the mitochondrial membrane. Interestingly, Api795 was localized in endosomes, whereas Api794 was present in endosomes and the cytosol. This was verified using flow cytometry showing a 50% higher uptake of Api794 in HeLa cells compared

Intravenous Lipid Emulsion Therapy Does Not Improve Hypotension Compared to Sodium Bicarbonate for Tricyclic Antidepressant Toxicity: A Randomized, Controlled Pilot Study in a Swine Model

DTIC Science & Technology

2014-11-01

ORIGINAL CONTRIBUTION Intravenous Lipid Emulsion Therapy Does Not Improve Hypotension Compared to Sodium Bicarbonate for Tricyclic Antidepressant...and chronic pain. Intravenous lipid emulsion (ILE) is a recent antidote for lipophilic drug overdose with unclear effectiveness. ILE has been studied in...Intravenous Lipid Emulsion Therapy Does Not Improve Hypotension Compared to Sodium Bicarbonate for Tricyclic Antidepressant Toxicity: A Randomized, Controlled

First observation of N-acetyl leucine and N-acetyl isoleucine in diabetic patient hair and quantitative analysis by UPLC-ESI-MS/MS.

PubMed

Min, Jun Zhe; Tomiyasu, Yuki; Morotomi, Takashi; Jiang, Ying-Zi; Li, Gao; Shi, Qing; Yu, Hai-Fu; Inoue, Koichi; Todoroki, Kenichiro; Toyo'oka, Toshimasa

2015-04-15

Type 2 diabetes patients (DP) have significantly higher plasma levels of valine, leucine, isoleucine and alanine than the controls. Specific amino acids may acutely and chronically regulate insulin secretion from the pancreatic β-cells. We recently identified a metabolic signature of N-acetyl leucine (Ac-Leu) that strongly predicts diabetes development in mice hair. The Ac-Leu appears to be a potential biomarker candidate related to diabetes. However, the determination of Ac-Leu in human hair has not been reported. We measured the Ac-Leu, and its structure is similar to N-acetyl isoleucine (Ac-Ile) in human hair by ultra-performance liquid chromatography (UPLC) with electrospray ionization tandem mass spectrometry (ESI-MS/MS). The developed method was applied to the determination of Ac-Leu and Ac-Ile in the hair of healthy volunteers (HV) and DP. Ac-Leu, Ac-Ile and N-acetyl norleucine (Ac-Nle, IS) were extracted from human hair samples by a micropulverized extraction procedure, then separated on a C18 column by isocratic elution of acetonitrile-0.1% formic acid in water:0.1% formic acid (14:86, vol./vol.). MRM using the fragmentation transitions of m/z 174.1→86.1 in the positive ESI mode was performed to quantify the N-acetyl leucine, N-acetyl isoleucine and IS. Ac-Leu, Ac-Ile and Ac-Nle in the human hair samples were completely separated by isocratic elution of a 5.0 min duration wash program using a reversed-phase column, and sensitively detected by LC-MS/MS in the ESI(+) MRM mode. The amounts of Ac-Leu and Ac-Ile in the hairs of HV and DP were determined. When comparing the concentrations between DP and those from HV, a statistically significant correlation was observed for the Ac-Leu (p<0.001) and Ac-Ile (p<0.01). The proposed method is useful for the determination of Ac-Leu and Ac-Ile in the hairs of DP and HV. Human hair may serve as a noninvasive biosample for the diagnosis of diabetes. Crown Copyright © 2015. Published by Elsevier B.V. All rights

BAG3 (Bcl-2-Associated Athanogene-3) Coding Variant in Mice Determines Susceptibility to Ischemic Limb Muscle Myopathy by Directing Autophagy.

PubMed

McClung, Joseph M; McCord, Timothy J; Ryan, Terence E; Schmidt, Cameron A; Green, Tom D; Southerland, Kevin W; Reinardy, Jessica L; Mueller, Sarah B; Venkatraman, Talaignair N; Lascola, Christopher D; Keum, Sehoon; Marchuk, Douglas A; Spangenburg, Espen E; Dokun, Ayotunde; Annex, Brian H; Kontos, Christopher D

2017-07-18

Critical limb ischemia is a manifestation of peripheral artery disease that carries significant mortality and morbidity risk in humans, although its genetic determinants remain largely unknown. We previously discovered 2 overlapping quantitative trait loci in mice, Lsq-1 and Civq-1 , that affected limb muscle survival and stroke volume after femoral artery or middle cerebral artery ligation, respectively. Here, we report that a Bag3 variant (Ile81Met) segregates with tissue protection from hind-limb ischemia. We treated mice with either adeno-associated viruses encoding a control (green fluorescent protein) or 2 BAG3 (Bcl-2-associated athanogene-3) variants, namely Met81 or Ile81, and subjected the mice to hind-limb ischemia. We found that the BAG3 Ile81Met variant in the C57BL/6 (BL6) mouse background segregates with protection from tissue necrosis in a shorter congenic fragment of Lsq-1 (C.B6- Lsq1-3 ). BALB/c mice treated with adeno-associated virus encoding the BL6 BAG3 variant (Ile81; n=25) displayed reduced limb-tissue necrosis and increased limb tissue perfusion compared with Met81- (n=25) or green fluorescent protein- (n=29) expressing animals. BAG3 Ile81 , but not BAG3 Met81 , improved ischemic muscle myopathy and muscle precursor cell differentiation and improved muscle regeneration in a separate, toxin-induced model of injury. Systemic injection of adeno-associated virus-BAG3 Ile81 (n=9), but not BAG3 Met81 (n=10) or green fluorescent protein (n=5), improved ischemic limb blood flow and limb muscle histology and restored muscle function (force production). Compared with BAG3 Met81 , BAG3 Ile81 displayed improved binding to the small heat shock protein (HspB8) in ischemic skeletal muscle cells and enhanced ischemic muscle autophagic flux. Taken together, our data demonstrate that genetic variation in BAG3 plays an important role in the prevention of ischemic tissue necrosis. These results highlight a pathway that preserves tissue survival and muscle

Isoleucine epimerization and amino acid composition in molecular-weight separations of Pleistocene Genyornis eggshell

NASA Astrophysics Data System (ADS)

Kaufman, Darrell S.; Miller, Gifford H.

1995-07-01

This study explores the geochronological utility and analytical reproducibility of separating the high-molecular-weight fraction (HMW) from eggshells of the extinct late Pleistocene ratite, Genyornis, using disposable, prepacked gel-filtration columns. The superior integrity of ratite eggshell for the retention of amino acids indicates that this biomineral is better suited for this type of investigation than previously studied molluscan shell. To evaluate the reproducibility of the gel-filtration technique, we analyzed triplicate subsamples of three eggshells of different ages. The reproducibility, based on the average intrashell variation (coefficient of variation; CV) in the extent of isoleucine epimerization (aIle/Ile) in the HMW (enriched in molecules ca. >10,000 MW) is 3%, well within the range appropriate for geochronological purposes. The average intrashell variation in the total amino acid concentration (Σ[aa]) of the HMW is 5%, somewhat better than for the total acid hydrolysate (TOTAL) of the same samples (7%). To evaluate the relation between molecular weight and the rate of isoleucine epimerization, three molecular-weight fractions were separated using gel filtration, plus the naturally hydrolyzed free fraction (FREE), for each of four fossil eggshells. AIle/Ile increases with decreasing molecular weight in all shells, with a ca. sixfold to ninefold difference in ratios between the HMW andFREE, and a ca. fivefold difference between the HMW andTOTAL. Although linear correlations between aIle/Ile measured in each molecular-weight fraction and in theTOTAL are all highly significant (r ⩾ 0.951), the relation between the extent of epimerization in the HMW and in the TOTAL is best expressed as an exponential function (r = 0.951). This relation is consistent with the idea that, as the epimerization reaction approaches equilibrium in theTOTAL (ca. aIle/Ile > 1.1), its rate decreases beyond that of the HMW. The amino acid composition (relative percent of

New tRNA contacts facilitate ligand binding in a Mycobacterium smegmatis T box riboswitch.

PubMed

Sherwood, Anna V; Frandsen, Jane K; Grundy, Frank J; Henkin, Tina M

2018-04-10

T box riboswitches are RNA regulatory elements widely used by organisms in the phyla Firmicutes and Actinobacteria to regulate expression of amino acid-related genes. Expression of T box family genes is down-regulated by transcription attenuation or inhibition of translation initiation in response to increased charging of the cognate tRNA. Three direct contacts with tRNA have been described; however, one of these contacts is absent in a subclass of T box RNAs and the roles of several structural domains conserved in most T box RNAs are unknown. In this study, structural elements of a Mycobacterium smegmatis ileS T box riboswitch variant with an Ultrashort (US) Stem I were sequentially deleted, which resulted in a progressive decrease in binding affinity for the tRNA Ile ligand. Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) revealed structural changes in conserved riboswitch domains upon interaction with the tRNA ligand. Cross-linking and mutational analyses identified two interaction sites, one between the S-turn element in Stem II and the T arm of tRNA Ile and the other between the Stem IIA/B pseudoknot and the D loop of tRNA Ile These newly identified RNA contacts add information about tRNA recognition by the T box riboswitch and demonstrate a role for the S-turn and pseudoknot elements, which resemble structural elements that are common in many cellular RNAs.

Importance of Branched-Chain Amino Acid Utilization in Francisella Intracellular Adaptation

PubMed Central

Gesbert, Gael; Ramond, Elodie; Tros, Fabiola; Dairou, Julien; Frapy, Eric; Barel, Monique

2014-01-01

Intracellular bacterial pathogens have adapted their metabolism to optimally utilize the nutrients available in infected host cells. We recently reported the identification of an asparagine transporter required specifically for cytosolic multiplication of Francisella. In the present work, we characterized a new member of the major super family (MSF) of transporters, involved in isoleucine uptake. We show that this transporter (here designated IleP) plays a critical role in intracellular metabolic adaptation of Francisella. Inactivation of IleP severely impaired intracellular F. tularensis subsp. novicida multiplication in all cell types tested and reduced bacterial virulence in the mouse model. To further establish the importance of the ileP gene in F. tularensis pathogenesis, we constructed a chromosomal deletion mutant of ileP (ΔFTL_1803) in the F. tularensis subsp. holarctica live vaccine strain (LVS). Inactivation of IleP in the F. tularensis LVS provoked comparable intracellular growth defects, confirming the critical role of this transporter in isoleucine uptake. The data presented establish, for the first time, the importance of isoleucine utilization for efficient phagosomal escape and cytosolic multiplication of Francisella and suggest that virulent F. tularensis subspecies have lost their branched-chain amino acid biosynthetic pathways and rely exclusively on dedicated uptake systems. This loss of function is likely to reflect an evolution toward a predominantly intracellular life style of the pathogen. Amino acid transporters should be thus considered major players in the adaptation of intracellular pathogens. PMID:25332124

Glutathion-S-Transferase P1 polymorphisms association with broncopulmonary dysplasia in preterm infants

PubMed Central

Karagianni, P; Rallis, D; Fidani, L; Porpodi, M; Kalinderi, K; Tsakalidis, C; Nikolaidis, N

2013-01-01

Background: Oxidative stress, characterized by the excretion of pre-oxidative and anti-oxidative proteases, has a key role in the pathogenesis of bronchopulmonary dysplasia (BPD). One of the many host anti-oxidant enzymes is glutathione-S-transferase P1 (GSTP1), with three polymorphic alleles having been identified: homozygous ile, heterozygous ile/val and homozygous val isomorph. The aim of this study was to examine the genetic predisposition to BPD in the GSTP1 polymorphisms. Methods: A prospective case-control study was carried out in the 2nd Neonatal Intensive Care Unit of Aristotle University in Thessaloniki, Greece during 2008. The genetic polymorphisms of GSTP1 in 28 preterms <32 weeks gestational age (GA) with BPD compared to 74 controls (33 preterms without BPD and 41 healthy terms) were examined. Results: The homozygous ile isomorph was predominant in all groups (preterms with BPD: 82%, preterms without BPD: 70%, healthy terms: 78%), followed by the heterozygous ile/val (14%, 18% and 20% respectively) and the homozygous val isomorph (4%, 12% and 2% respectively). The homozygous ile isomorph was also identified in the majority of preterms with mild (80%), moderate (100%) and severe (73%) BPD. The GSTP1 genetic distribution did not differ between the groups and GSTP1 polymorphisms were not associated with the severity of BPD. Conclusions: This study could not confirm an association between GSTP1 polymorphisms and the development of BPD or the severity of the disease. PMID:25031518

Glutathion-S-Transferase P1 polymorphisms association with broncopulmonary dysplasia in preterm infants.

PubMed

Karagianni, P; Rallis, D; Fidani, L; Porpodi, M; Kalinderi, K; Tsakalidis, C; Nikolaidis, N

2013-10-01

Oxidative stress, characterized by the excretion of pre-oxidative and anti-oxidative proteases, has a key role in the pathogenesis of bronchopulmonary dysplasia (BPD). One of the many host anti-oxidant enzymes is glutathione-S-transferase P1 (GSTP1), with three polymorphic alleles having been identified: homozygous ile, heterozygous ile/val and homozygous val isomorph. The aim of this study was to examine the genetic predisposition to BPD in the GSTP1 polymorphisms. A prospective case-control study was carried out in the 2nd Neonatal Intensive Care Unit of Aristotle University in Thessaloniki, Greece during 2008. The genetic polymorphisms of GSTP1 in 28 preterms <32 weeks gestational age (GA) with BPD compared to 74 controls (33 preterms without BPD and 41 healthy terms) were examined. The homozygous ile isomorph was predominant in all groups (preterms with BPD: 82%, preterms without BPD: 70%, healthy terms: 78%), followed by the heterozygous ile/val (14%, 18% and 20% respectively) and the homozygous val isomorph (4%, 12% and 2% respectively). The homozygous ile isomorph was also identified in the majority of preterms with mild (80%), moderate (100%) and severe (73%) BPD. The GSTP1 genetic distribution did not differ between the groups and GSTP1 polymorphisms were not associated with the severity of BPD. This study could not confirm an association between GSTP1 polymorphisms and the development of BPD or the severity of the disease.

Gill structural integrity changes in fish deficient or excessive in dietary isoleucine: Towards the modulation of tight junction protein, inflammation, apoptosis and antioxidant defense via NF-κB, TOR and Nrf2 signaling pathways.

PubMed

Feng, Lin; Gan, Lu; Jiang, Wei-Dan; Wu, Pei; Liu, Yang; Jiang, Jun; Tang, Ling; Kuang, Sheng-Yao; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu

2017-04-01

This study firstly aimed to test the impact of dietary isoleucine (Ile) on tight junction protein, inflammation, apoptosis, antioxidant defense and related signaling molecule gene expression in the gill of fish. Young grass carp (Ctenopharyngodon idella) (weighing 256.8 ± 3.5 g) were fed six diets containing graded levels of Ile, namely, 3.8, 6.6, 9.3, 12.5, 15.2 and 18.5 g/kg diet for 8 weeks. The results firstly revealed that Ile deficiency down-regulated the mRNA expressions of claudin-3, claudin-b, claudin-c, occludin and zonula occludens-1 (ZO-1) and up-regulated the mRNA expression of claudin-12, which led to the intercellular structure damage of fish gill. These effects were partially ascribed to the up-regulation of pro-inflammatory cytokines [interleukin 1β (IL-1β), interleukin 8 (IL-8) and tumor necrosis factor-α (TNF-α)] mRNA expressions that referring to up-regulated nuclear factor κB P65 (NF-κB P65) mRNA expression and down-regulated inhibitor factor κBα (IκBα) mRNA expression, and the down-regulation of anti-inflammatory cytokines [interleukin 10 (IL-10) and transforming growth factor β1 (TGF-β1)] mRNA expressions that referring to the down-regulated TOR and S6K1 mRNA expression. Interestingly, no change in claudin 15 mRNA level was observed among every treatment. At the same time, the results firstly indicated that Ile deficiency also resulted in the cellular structure damage of fish gill: (1) DNA fragmentation partially due to the up-regulation of caspase-3, caspase-8 and caspase-9 mRNA expression; (2) increase in protein carbonyl (PC), malondialdehyde (MDA) and ROS contents, which may be partially attributed to the impaired antioxidant defense [indicated by decreased glutathione (GSH) level and depressed anti-superoxide anion (ASA), anti-hydroxyl radical (a-HR), copper/zinc superoxide dismutase (Cu/Zn-SOD), catalase (CAT) and glutathione peroxidase (GPx) activities] that referring to the down-regulation of corresponding antioxidant

What are the adverse effects associated with the combined use of intravenous lipid emulsion and extracorporeal membrane oxygenation in the poisoned patient?

PubMed

Lee, Hwee Min D; Archer, John R H; Dargan, Paul I; Wood, David M

2015-03-01

Intravenous lipid emulsion (ILE) and veno-arterial extracorporeal membrane oxygenation (VA-ECMO) are being used together or in close succession in the management of circulatory failure secondary to cardiotoxic drug poisoning. There have been reports of mechanical problems, including fat emulsion agglutination, clogging, increased blood clot formation and even cracking of parts of the machine, in patients concurrently receiving VA-ECMO and ILE as part of parenteral nutrition. To ascertain the adverse effects associated with the combined use of ILE and ECMO in the poisoned patient. PubMed and OVID (1966 to 9 June 2014) and EMBASE (1947 to 9 June 2014) were searched to identify publications relating to studies and/or case reports where ILE had been used at the same time when VA-ECMO was used - 7 were identified. In addition, the abstracts published between 2006 and 2013 inclusive of those from the North American Congress of Clinical Toxicology and the congresses of the European Association of Poisons Centres and Clinical Toxicologists were searched to identify additional cases and 2 were found. Finally all cases posted on lipidrescue.org were reviewed to determine if they related to the use of ILE with VA-ECMO and no new cases were identified. In vitro study. An in vitro study involving the continuous infusion of 20% ILE at 3 mL/h for 24 h demonstrated layering (separation of intact fat emulsion from blood) and agglutination (clumping resulting in little or no flow of fat emulsion through the circuit) in all circuits within 30 min of starting the fat emulsion infusion. An observational study based in 42 centres that regularly used 'fat emulsion' during VA-ECMO treatment reported cracking of stopcocks (the valve which restricts flow in the VA-ECMO tubing) (n = 10, 23.8%); fat emulsion agglutination (n = 11, 26.2%); clogging and associated malfunction of the membrane oxygenator (n = 2, 4.8%); and increased blood clot formation in the circuits (n = 2, 4.8%). In a

Renovating "Lycees" in Ile-de-France.

ERIC Educational Resources Information Center

PEB Exchange, 1992

1992-01-01

Laws that took effect in January 1986 transferred ownership of French upper secondary schools from central government to regional authorities. Describes the use of private, competitive contracts for public building projects in the renovation and maintenance work at one institution. (MLF)

Self-Assembly of MinE on the Membrane Underlies Formation of the MinE Ring to Sustain Function of the Escherichia coli Min System*

PubMed Central

Zheng, Min; Chiang, Ya-Ling; Lee, Hsiao-Lin; Kong, Lih-Ren; Hsu, Shang-Te Danny; Hwang, Ing-Shouh; Rothfield, Lawrence I.; Shih, Yu-Ling

2014-01-01

The pole-to-pole oscillation of the Min proteins in Escherichia coli results in the inhibition of aberrant polar division, thus facilitating placement of the division septum at the midcell. MinE of the Min system forms a ring-like structure that plays a critical role in triggering the oscillation cycle. However, the mechanism underlying the formation of the MinE ring remains unclear. This study demonstrates that MinE self-assembles into fibrillar structures on the supported lipid bilayer. The MinD-interacting domain of MinE shows amyloidogenic properties, providing a possible mechanism for self-assembly of MinE. Supporting the idea, mutations in residues Ile-24 and Ile-25 of the MinD-interacting domain affect fibril formation, membrane binding ability of MinE and MinD, and subcellular localization of three Min proteins. Additional mutations in residues Ile-72 and Ile-74 suggest a role of the C-terminal domain of MinE in regulating the folding propensity of the MinD-interacting domain for different molecular interactions. The study suggests a self-assembly mechanism that may underlie the ring-like structure formed by MinE-GFP observed in vivo. PMID:24914211

[Association between HRE-2 gene polymorphism at codon 655 and genetic susceptibility of colorectal cancer].

PubMed

Liang, Xia; Zhang, Yong-jing; Liu, Bing; Ni, Qin; Jin, Ming-juan; Ma, Xin-yuan; Yao, Kai-yan; Li, Qi-long; Chen, Kun

2009-06-01

To explore the distribution of HER-2 genetic polymorphism at codon 655 and its association with susceptibility of colorectal cancer in Chinese. A population-based case-control study was carried out. 292 patients with colorectal cancer and 842 healthy controls were interviewed. Meanwhile, the genetic polymorphism of HRE-2 was detected using polymerase chain reaction-restriction fragment length polymorphism. The frequencies of Ile/Val+Val/Val genotypes and Val allele were both higher in cases (25.34% and 13.36%) than those in controls (18.41% and 9.74%) (P<0.05). Compared with Ile/Ile genotype, Ile/Val+Val/Val genotypes were significantly associated with colorectal cancer [ORadjusted=1.54, 95% CI: 1.11-2.14]. The adjusted odds ratio of interactions between this polymorphism and smoking, alcohol drinking were 1.43 (95%CI: 0.88-2.30) and 1.29 (95%CI: 0.73-2.29), respectively. The present findings suggest that HER-2 genetic polymorphism at codon 655 may be associated with the risk of colorectal cancer in Chinese. In addition, there are no interactions between this polymorphism and smoking, alcohol drinking, respectively.

The self-assembly of redox active peptides: Synthesis and electrochemical capacitive behavior.

PubMed

Piccoli, Julia P; Santos, Adriano; Santos-Filho, Norival A; Lorenzón, Esteban N; Cilli, Eduardo M; Bueno, Paulo R

2016-05-01

The present work reports on the synthesis of a redox-tagged peptide with self-assembling capability aiming applications in electrochemically active capacitive surfaces (associated with the presence of the redox centers) generally useful in electroanalytical applications. Peptide containing ferrocene (fc) molecular (redox) group (Ac-Cys-Ile-Ile-Lys(fc)-Ile-Ile-COOH) was thus synthesized by solid phase peptide synthesis (SPPS). To obtain the electrochemically active capacitive interface, the side chain of the cysteine was covalently bound to the gold electrode (sulfur group) and the side chain of Lys was used to attach the ferrocene in the peptide chain. After obtaining the purified redox-tagged peptide, the self-assembly and redox capability was characterized by cyclic voltammetry (CV) and electrochemical impedance-based capacitance spectroscopy techniques. The obtained results confirmed that the redox-tagged peptide was successfully attached by forming an electroactive self-assembled monolayer onto gold electrode. The design of redox active self-assembly ferrocene-tagged peptide is predictably useful in the development of biosensor devices precisely to detect, in a label-free platform, those biomarkers of clinical relevance. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 357-367, 2016. © 2016 Wiley Periodicals, Inc.

PRKAG3 and CAST genetic polymorphisms and quality traits of dry-cured hams--I. Associations in Spanish dry-cured ham Jamón Serrano.

PubMed

Gou, P; Zhen, Z Y; Hortós, M; Arnau, J; Diestre, A; Robert, N; Claret, A; Čandek-Potokar, M; Santé-Lhoutellier, V

2012-12-01

The functional single polymorphisms identified in the calpastatin (CAST) gene have been related to the rate of meat tenderization and the protein turnover after slaughter, and the Ile199Val polymorphism identified in the coding region of the protein kinase AMP-activated (PRKAG3) gene has been proven to affect ultimate pH in muscle. The aim of the present study was to show the effects of these genetic polymorphisms on the quality traits of Spanish dry-cured ham Jamón Serrano. A tissue sample from 665 crossbreed pigs were genotyped for PRKAG3 Ile199Val, CAST Arg249Lys and CAST Ser638Arg polymorphisms, and a subsample of 120 dry cured hams was selected to perform physico-chemical, rheological, instrumental colour and sensory analyses. Associations between the polymorphisms and several quality traits of dry-cured ham, mainly related to flavour and texture, were found. The genotypes PRKAG3 Ile/Ile, CAST249 Arg/Arg and CAST638 Arg/Arg, and the haplotype CAST 249Arg-638Arg were the most favourable for Jamón Serrano production. Copyright © 2012 Elsevier Ltd. All rights reserved.

Passive smoking, Cyp1A1 gene polymorphism and dysmenorrhea

PubMed Central

Liu, Hong; Yang, Fan; Li, Zhiping; Chen, Changzhong; Fang, Zhian; Wang, Lihua; Hu, Yonghua; Chen, Dafang

2007-01-01

Objective This study investigated whether the association between passive smoking exposure and dysmenorrhea is modified by two susceptibility genes, CYP1A1MspI and CYP1A1HincII. Methods This report includes 1645 (1124 no dysmenorrhea, 521 dysmenorrhea) nonsmoking and nondrinking newly wed female workers at Anqing, China between June 1997 and June 2000. Multiple logistic regression models were used to estimate the associations of passive smoking exposure and genetic susceptibility with dysmenorrhea, adjusting for perceived stress. Results When stratified by women genotype, the adjusted OR of dysmenorrhea was 1.6 (95%CI=1.3-2.1) for passive smoking group with Ile/Ile462 genotype, and 1.5 (95%CI=1.1-2.1) with C/C6235 genotype, compared to non passive smoking group, respectively. The data further showed that there was a significant combined effect between passive smoking and the CYP1A1 Msp1 C/C6235 and HincII Ile/Ile462 genotype (OR=2.6, 95%CI=1.3-5.2). Conclusion CYP1A1 MspI and HincII genotypes modified the association between passive smoking and dysmenorrhea. PMID:17566695

Structure and biological activities of eumenine mastoparan-AF (EMP-AF), a new mast cell degranulating peptide in the venom of the solitary wasp (Anterhynchium flavomarginatum micado).

PubMed

Konno, K; Hisada, M; Naoki, H; Itagaki, Y; Kawai, N; Miwa, A; Yasuhara, T; Morimoto, Y; Nakata, Y

2000-11-01

A new mast cell degranulating peptide, eumenine mastoparan-AF (EMP-AF), was isolated from the venom of the solitary wasp Anterhynchium flavomarginatum micado, the most common eumenine wasp found in Japan. The structure was analyzed by FAB-MS/MS together with Edman degradation, which was corroborated by solid-phase synthesis. The sequence of EMP-AF, Ile-Asn-Leu-Leu-Lys-Ile-Ala-Lys-Gly-Ile-Ile-Lys-Ser-Leu-NH(2), was similar to that of mastoparan, a mast cell degranulating peptide from a hornet venom; tetradecapeptide with C-terminus amidated and rich in hydrophobic and basic amino acids. In fact, EMP-AF exhibited similar activity to mastoparan in stimulating degranulation from rat peritoneal mast cells and RBL-2H3 cells. It also showed significant hemolytic activity in human erythrocytes. Therefore, this is the first example that a mast cell degranulating peptide is found in the solitary wasp venom. Besides the degranulation and hemolytic activity, EMP-AF also affects on neuromuscular transmission in the lobster walking leg preparation. Three analogs EMP-AF-1 approximately 3 were snythesized and biologically tested together with EMP-AF, resulting in the importance of the C-terminal amide structure for biological activities.

Responsiveness of the ACTIVLIM-CP questionnaire measuring global activity performance in children with cerebral palsy.

PubMed

Paradis, Julie; Arnould, Carlyne; Thonnard, Jean-Louis; Houx, Laëtitia; Pons-Becmeur, Christelle; Renders, Anne; Brochard, Sylvain; Bleyenheuft, Yannick

2018-06-04

To investigate the responsiveness of the ACTIVLIM-CP questionnaire after two evidence-based interventions for children with cerebral palsy (CP). Seventy-five children with CP either participated in an intensive motor-skill learning intervention (hand-arm bimanual intensive therapy including lower extremities [HABIT-ILE], n=47) or received botulinum neurotoxin-A (BoNT-A) injection(s) into lower extremities combined with conventional physical therapy (n=28). All children were assessed three times: at baseline (T 0 ; before HABIT-ILE/the day of BoNT-A injection), at T 1 (last day of HABIT-ILE/6wks after BoNT-A injection), and at follow-up (T 2 ; 3-4mo after the beginning of intervention). Parents completed ACTIVLIM-CP and three other activity questionnaires. Responsiveness was analysed using group (based on intervention), subgroup (based on gross motor function level), and individual approaches. For the HABIT-ILE group, significant improvements in ACTIVLIM-CP were observed for the T 0 -T 1 period (p<0.001) but not for the T 1 -T 2 period. No significant changes were found in the BoNT-A group during assessments (p=0.84). In the subgroup analysis for the HABIT-ILE group (T 0 -T 1 ), greater changes were demonstrated for children in Gross Motor Function Classification System levels III and IV (p<0.001, effect size=1.36). The individual approach was congruent with the group approach. ACTIVLIM-CP demonstrated high responsiveness after HABIT-ILE, showing that this scale may be used to investigate global activity performance in clinical trials focusing on improving daily life activities. Good responsiveness of ACTIVLIM-CP questionnaire during intensive motor-skill learning intervention. Higher responsiveness for children in Gross Motor Function Classification System (GMFCS) levels III and IV versus I and II after intensive intervention. ACTIVLIM-CP is useful to identify children improving their performance after botulinum neurotoxin-A injection. © 2018 Mac Keith Press.

A randomized, controlled clinical trial of intravenous lipid emulsion as an adjunctive treatment for permethrin toxicosis in cats.

PubMed

Peacock, Rachel E; Hosgood, Giselle; Swindells, Katrin L; Smart, Lisa

2015-01-01

To assess for any clinical benefit of intravenous lipid emulsion (ILE) for permethrin toxicosis in cats by comparing the progression of clinical signs of cats before and after treatment with ILE to cats treated with a saline control. To accomplish this objective, a clinical staging system for cats with permethrin toxicosis was developed and validated. Prospective, multicenter, randomized, controlled clinical trial. University veterinary teaching hospital and 12 private veterinary emergency hospitals. Thirty-four client-owned cats with permethrin toxicosis. A clinical staging system was designed based on abnormalities found on physical examination of cats with permethrin toxicosis. The clinical staging system had 6 stages, ranging from Stage A for cats with no abnormalities to Stage F for cats with grand mal seizures. The system was validated for intraviewer and interviewer variability. Cats in the clinical trial were randomized to receive 15 mL/kg of either intravenous 0.9% saline (control) or 20% ILE over 60 minutes. For each cat, a clinical stage was recorded at set time points before and after the randomized treatment was administered. The distribution of clinical stage stratified over time was compared across treatment groups. The clinical staging system showed excellent repeatability (P = 1.0) and reliability (P = 1.0). In the clinical trial, there was a significant difference in the distribution of clinical stages over time (P < 0.001) and from presentation stage to Stage B (P = 0.006), with ILE-treated cats (n = 20) having lower clinical stages earlier than control cats (n = 14). There was no significant difference in signalment, body weight, or supportive treatment between the groups. The clinical staging system was repeatable and reliable. Clinical stages of permethrin toxicosis in ILE-treated cats improved earlier compared to control cats, suggesting ILE may be a useful adjunctive therapy in the treatment of permethrin toxicosis in cats. © Veterinary

Association of Aurora-A (STK15) Kinase Polymorphisms With Clinical Outcome of Esophageal Cancer Treated With Preoperative Chemoradiation

PubMed Central

Pan, Jennifer Y.; Ajani, Jaffer A.; Gu, Jian; Gong, Yubo; Quin, Angel; Hung, Maosheng; Wu, Xifeng; Izzo, Julie G.

2013-01-01

BACKGROUND: Aurora-A/STK15 is a serine/threonine kinase critical for regulated chromosome segregation and cytokinesis. We investigated the association between 2 nonsynonymous single nucleotide polymorphisms in the coding region of STK15, T91A (Phe31Ile) and G169A (Val57Ile), and clinical outcome of esophageal cancer treated with preoperative chemoradiation. METHODS: Genotypes at Phe31Ile and Val57Ile were assessed from peripheral blood lymphocytes of 190 esophageal cancer patients and were correlated to response to treatment, recurrence rate, risk of death, disease-free survival (DFS) and median survival time (MTS). RESULTS: All patients had resectable esophageal or gastroesophageal junction cancer and received preoperative chemoradiation followed by esophagectomy. The heterozygous variant Phe31/Ile variant was significantly associated with tumor recurrence (odds ratio [OR] = 4.39; 95% confidence interval [CI], 2.12-8.94; P < .001), shorter DFS (P = .0001), and shorter MTS (P = .012). For patients receiving cisplatin-based therapy, only the variant Phe31/Ile had an adverse effect on response (OR = 2.8; 95% CI, 1.01-5.17; P = .048) and MTS (P = .026). The variant 91A-169G haplotype carried a significant risk for lack of complete response (OR = 2.54; 95% CI, 1.15-5.54) and higher rate of recurrence (OR = 2.73; 95%CI, 1.00-7.29). The presence of at least 1 variant allele at each locus further increased the risk of recurrence (adjusted OR = 6.21; 95% CI, 2.28-17.11; P = <.001), and was associated significantly shorter DFS (P = .003). CONCLUSIONS: Our study shows that functional SNPs in the STK15 gene are associated with higher rate of recurrence, higher likelihood of chemoratiotherapy-resistance, shorter DFS, and shorter MTS. Confirmation of our data and understanding the mechanisms through which STK15 functional SNPs mediate resistance to chemoradiotherapy are warranted. PMID:22213102

Earth Observations taken by Expedition 30 crewmember

NASA Image and Video Library

2012-03-25

ISS030-E-193144 (25 March 2012) --- Wave clouds near Ile aux Cochons are featured in this image photographed by an Expedition 30 crew member on the International Space Station. This photograph illustrates the formation of wave clouds in the wake—or downwind side—of Ile aux Cochons (“Isle of Pigs”) located in the Southern Indian Ocean. The island is approximately located 3,000 kilometers southeast of the southern tip of the African continent and 2,300 kilometers northwest of Antarctica. The island itself, of which only a part of the eastern coastline is visible at center, is volcanic in origin with a summit elevation of 775 meters above sea level. According to scientists, the Ile aux Cochons stratovolcano is thought to have erupted within the last 12,000 years; however no historical activity has been recorded. The summit elevation is high enough for the land surface to interact with cloud layers and winds flowing past the island. Two major cloud layers are visible; a lower, more uniform layer consists of roughly parallel cloud “streets” that suggest a westerly flow pattern of air. When the air mass encounters the Ile aux Cochons, moisture-laden air rises and cools, causing more water vapor to condense into clouds. As the air mass passes over the summit of Ile aux Cochons and descends, it may encounter alternating moist and dry air layers, enabling the formation of the discontinuous chevron-shaped wave clouds in the wake of the island. While their appearance suggests that the clouds are forming in the wake of the island and moving eastwards, in fact it is the air mass that is moving, with clouds forming in regions of moist air and dissipating in dry regions. Ile aux Cochons is the westernmost of the islands that form the subantarctic Crozet Archipelago (part of the French Southern and Antarctic Lands). Accept for occasional research visits, the island is uninhabited. The island is an important breeding site for seabirds, including the world’s largest

Secure Learning and Learning for Security: Research in the Intersection

DTIC Science & Technology

2010-05-13

researchers to consider how Machine Learning and Statistics might be leveraged for constructing intelli - gent attacks. In a similar vein, security...Quantiles S am pl e Q ua nt ile s...8217 Residuals in Flow 144 Theoretical Quantiles S am pl e Q ua nt ile s 0 1 2 3 4 5 6 7 5. 0e + 07 1. 0e + 08 1. 5e + 08 Comparing Actual and Synthetic

Effect of lipid emulsion during resuscitation of a patient with cardiac arrest after overdose of chlorpromazine and mirtazapine.

PubMed

Matsumoto, Hisatake; Ohnishi, Mitsuo; Takegawa, Ryosuke; Hirose, Tomoya; Hattori, Yuji; Shimazu, Takeshi

2015-10-01

No specific treatment exists for poisoning with most fat-soluble drugs. Intravenous lipid emulsion (ILE) may be effective therapy against such drugs, but effects of ILE treatment are unclear. A 24-year-old woman with depression seen sleeping in the morning was found comatose in the evening, and an emerging lifesaving technologies service was called. After emerging lifesaving technologies departure to hospital, she stopped breathing, became pulseless, and cardiopulmonary life support was started immediately. Electrocardiographic monitoring showed asystole during resuscitation even after arrival at hospital. Empty packaging sheets of 60-tablet chlorpromazine (CPZ) (50 mg/tablet) and 66-tablet mirtazapine (MZP) (15 mg/tablet) found at the scene suggested drug-related cardiopulmonary arrest. Along with conventional administration of adrenaline (total dose, 5 mg), 20% Intralipid 100 mLwas given intravenously 8 minutes after hospital arrival and readministered 27 minutes after hospital arrival because of continued asystole. Return of spontaneous circulation occurred 29 minutes after arrival (70 minutes after cardiac arrest). The patient recovered without any major complications and was transferred to another hospital for psychiatric treatment 70 days after admission. Concentrations of CPZ and MZP were still high when return of spontaneous circulation was achieved with ILE. This case suggested the possible benefit of ILE in treating life threatening cardiotoxicity from CPZ and MZP overdose.

The use of high-dose insulin therapy and intravenous lipid emulsion to treat severe, refractory diltiazem toxicosis in a dog.

PubMed

Maton, Barbara L; Simmonds, Erin E; Lee, Justine A; Alwood, Amy J

2013-01-01

To describe the novel use of high-dose insulin (HDI) therapy and intravenous lipid emulsion (ILE) to treat refractory, severe diltiazem toxicosis in a dog. A 4-year-old Pomeranian was presented for treatment 2.5 hours following ingestion of a diltiazem extended-release capsule. Toxic ingestion was calculated at a maximum exposure of 79 mg/kg, with a reported canine LD50 of 50 mg/kg. Clinical signs of progressive hypotension and severe bradycardia with atrial standstill were observed, which persisted despite treatment with atropine, calcium, glucagon, and dopamine. The novel use of HDI and ILE as part of therapy for diltiazem toxicosis resulted in clinical resolution of life-threatening signs. Within 1 hour of initiating HDI therapy, the clinical signs improved, and with continued treatment, the patient remained normotensive and survived to discharge. To the authors' knowledge, this is the first reported clinical case describing the use of both HDI and ILE therapy in the treatment of severe refractory diltiazem toxicosis in veterinary medicine. No significant adverse effects were observed from the treatment. In veterinary patients with severe refractory calcium channel blocker toxicosis, the use of HDI and ILE should be considered for life-threatening clinical signs. © Veterinary Emergency and Critical Care Society 2013.

Implicit LES using adaptive filtering

NASA Astrophysics Data System (ADS)

Sun, Guangrui; Domaradzki, Julian A.

2018-04-01

In implicit large eddy simulations (ILES) numerical dissipation prevents buildup of small scale energy in a manner similar to the explicit subgrid scale (SGS) models. If spectral methods are used the numerical dissipation is negligible but it can be introduced by applying a low-pass filter in the physical space, resulting in an effective ILES. In the present work we provide a comprehensive analysis of the numerical dissipation produced by different filtering operations in a turbulent channel flow simulated using a non-dissipative, pseudo-spectral Navier-Stokes solver. The amount of numerical dissipation imparted by filtering can be easily adjusted by changing how often a filter is applied. We show that when the additional numerical dissipation is close to the subgrid-scale (SGS) dissipation of an explicit LES the overall accuracy of ILES is also comparable, indicating that periodic filtering can replace explicit SGS models. A new method is proposed, which does not require any prior knowledge of a flow, to determine the filtering period adaptively. Once an optimal filtering period is found, the accuracy of ILES is significantly improved at low implementation complexity and computational cost. The method is general, performing well for different Reynolds numbers, grid resolutions, and filter shapes.

Genotypic and phenotypic characterization of methicillin-resistant Staphylococcus aureus (MRSA) clones with high-level mupirocin resistance.

PubMed

González-Domínguez, María; Seral, Cristina; Potel, Carmen; Sáenz, Yolanda; Álvarez, Maximiliano; Torres, Carmen; Castillo, Francisco Javier

2016-06-01

A high proportion of methicillin-resistant Staphylococcus aureus isolates recovered in one year period showed high-level mupirocin-resistance (HLMUPR-MRSA) in our environment (27.2%). HLMUPR-MRSA isolates were mainly collected from skin and soft tissue samples, and diabetes was the main related comorbidity condition. These isolates were more frequently found in vascular surgery. HLMUPR-MRSA was more resistant to aminoglycosides than mupirocin-susceptible MRSA, linked to the presence of bifunctional and/or nucleotidyltransferase enzymes with/without macrolide resistance associated with the msr(A) gene. Most of HLMUPR-MRSA isolates belonged to ST125/t067. Nine IS257-ileS2 amplification patterns (p3 was the most frequent) were observed in HLMUPR-MRSA isolates, suggesting the presence of several mupirocin-resistance-carrying plasmids in our environment and promoting the emergence of mupirocin resistance. The presence of the same IS257-ileS2 amplification pattern p3 in 65% of HLMUPR-MRSA, all of them ST125/t067, suggests a clonal spread in our hospital and community environment which could explain the high prevalence of HLMUPR-MRSA during the study period. An outbreak situation or an increase in mupirocin consumption was not observed. Copyright © 2016 Elsevier Inc. All rights reserved.

Protection of hydrophobic amino acids against moisture-induced deterioration in the aerosolization performance of highly hygroscopic spray-dried powders.

PubMed

Yu, Jiaqi; Chan, Hak-Kim; Gengenbach, Thomas; Denman, John A

2017-10-01

Inhalable particles containing amorphous form of drugs or excipients may absorb atmospheric moisture, causing powder aggregation and recrystallization, adversely affecting powder dispersion and lung deposition. The present study aims to explore hydrophobic amino acids for protection against moisture in spray-dried amorphous powders, using disodium cromoglycate (DSCG) as a model drug. DSCG powders were produced by co-spray drying with isoleucine (Ile), valine (Val) and methionine (Met) in various concentrations (10, 20 and 40%w/w). Particle size distribution and morphology were measured by laser diffraction and scanning electron microscopy (SEM). Physiochemical properties of the powders were characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and dynamic vapor sorption (DVS). Particle surface chemistry was analyzed by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). In vitro aerosolization performance was evaluated by a next generation impactor (NGI) after the powders were stored at 60% or 75% relative humidity (RH) for one month and three months. Ile, Val and Met significantly reduced the deleterious effect of moisture on aerosol performance, depending on the amount of amino acids in the formulation. Formulations containing 10% or 20% of Ile, Val and Met showed notable deterioration in aerosol performance, with fine particle fraction (FPF) reduced by 6-15% after one-month storage at both 60% and 75% RH. However, 40% Ile was able to maintain the aerosol performance of DSCG stored at 75% RH for one month, while the FPF dropped by 7.5% after three months of storage. In contrast, 40% Val or Met were able to maintain the aerosol performance at 60% RH storage but not at 75% RH. At 40%w/w ratio, these formulations had particle surface coverage of 94.5% (molar percent) of Ile, 87.1% of Val and 84.6% of Met, respectively, which may explain their

Testing GSTP1 genotypes and haplotypes interactions in Slovenian post-/pre-menopausal women: novel involvement of glutathione S-transferases in bone remodeling process.

PubMed

Mlakar, Simona Jurkovic; Prezelj, Janez; Marc, Janja

2012-02-01

Osteoporosis (OP) is an age-related disease associated with increased production of reactive oxygen species (ROS) and a reduction in antioxidant defense system, such as low activity of glutathione S-transferase (GST) family. The enzyme activity of the member of GSTs, GSTP1, depends on gene polymorphisms such as: Ala114Val and Ile105Val. The aim of this study was to evaluate the association between genetic polymorphisms of the GSTP1 gene and BMD variation and biochemical bone remodeling markers in 523 Slovenian pre- and post-menopausal women. Observational pilot study in a representative cohort of Slovenian patients with adjustment for potential confounders (age, height, weight, years since menopause, smoking status and glucocorticoid use) using univariate one-way and two-way analyses. Ala114Val and Ile105Val polymorphisms genotypes of GSTP1 gene, bone mineral density (BMD) values of total hip (_th), femoral neck (_fn) and lumbar spine (_ls), plasma osteocalcin (OC), serum bone alkaline phosphatase (BALP), free soluble RANKL and serum osteoprotegerin (sOPG) concentrations were determined. Our results show that the Ala114Val heterozygotes are (borderline) significantly associated with higher concentrations of pOC (p=0.052) and decreased BMD_fn values (p=0.053) and the same trend is shown for BMD_th and BMD_ls values in osteopenic postmenopausal women. Furthermore, significantly higher concentrations of pOC were determined among Val allele carriers of Ile105Val gene polymorphism (p=0.037) and in carriers with the absent 114Ala-105Ile haplotype combination, again in osteopenic post-menopausal women. In addition, in pre-menopausal women the significant associations between sOPG and Ala114Val genotypes subgroups and between sBALP and Ile105Val genotypes subgroups, alone or in combination with Ala114Val, were determined (0.032, 0.026 and 0.008, respectively). Since significant associations existed in Ala114Val genotype and 114Ala-105Ile haplotype subgroups, these

The stereochemical effect of SMAP-29 and SMAP-18 on bacterial selectivity, membrane interaction and anti-inflammatory activity.

PubMed

Jacob, Binu; Rajasekaran, Ganesan; Kim, Eun Young; Park, Il-Seon; Bang, Jeong-Kyu; Shin, Song Yub

2016-05-01

Sheep myeloid antimicrobial peptide-29 (SMAP-29) is a cathelicidin-related antimicrobial peptide derived from sheep myeloid cells. In order to investigate the effects of L-to-D-amino acid substitution in SMAP-29 on bacterial selectivity, membrane interaction and anti-inflammatory activity, we synthesized its two D-enantiomeric peptides (SMAP-29-E1 and SMAP-29-E2 containing D-Ile and D-allo-Ile, respectively) and two diastereomeric peptides (SMAP-29-D1 and SMAP-29-D2). Additionally, in order to address the effect of L-to-D-amino acid substitution in the N-terminal helical peptide of SMAP-29 (named SMAP-18) on antimicrobial activity, we synthesized its two D-enantiomeric peptides (SMAP-18-E1 and SMAP-18-E2), which are composed of D-amino acids entirely. L-to-D-amino acid substitution in membrane-targeting AMP, SMAP-29 did not affect its antimicrobial activity. However, D-allo-Ile containing-SMAP-29-E2 and SMAP-29-D2 exhibited less hemolytic activity compared to D-Ile containing-SMAP-29-E1 and SMAP-29-D1, respectively. L-to-D-amino acid substitution in intracellular targeting-AMPs, SMAP-18 and buforin-2 improved antimicrobial activity by 2- to eightfold. The improved antimicrobial activity of the D-isomers of SMAP-18 and buforin-2 seems to be due to the stability against proteases inside bacterial cells. Membrane depolarization and dye leakage suggested that the membrane-disruptive mode of SMAP-29-D1 and SMAP-29-D2 is different from that of SMAP-29, SMAP-29-E1, and SMAP-29-E2. L-to-D-amino acid substitution in SMAP-29 improved anti-inflammatory activity in LPS-stimulated RAW 264.7 cells. In summary, we propose here that D-allo-Ile substitution is a more powerful strategy for increasing bacterial selectivity than D-Ile substitution in the design of D-enantiomeric and diastereomeric AMPs. SMAP-29-D1, and SMAP-29-D2 with improved bacterial selectivity and anti-inflammatory activity can serve as promising candidates for the development of anti-inflammatory and

Functional genetic variants in the vesicular monoamine transporter 1 modulate emotion processing.

PubMed

Lohoff, F W; Hodge, R; Narasimhan, S; Nall, A; Ferraro, T N; Mickey, B J; Heitzeg, M M; Langenecker, S A; Zubieta, J-K; Bogdan, R; Nikolova, Y S; Drabant, E; Hariri, A R; Bevilacqua, L; Goldman, D; Doyle, G A

2014-01-01

Emotional behavior is in part heritable and often disrupted in psychopathology. Identification of specific genetic variants that drive this heritability may provide important new insight into molecular and neurobiological mechanisms involved in emotionality. Our results demonstrate that the presynaptic vesicular monoamine transporter 1 (VMAT1) Thr136Ile (rs1390938) polymorphism is functional in vitro, with the Ile allele leading to increased monoamine transport into presynaptic vesicles. Moreover, we show that the Thr136Ile variant predicts differential responses in emotional brain circuits consistent with its effects in vitro. Lastly, deep sequencing of bipolar disorder (BPD) patients and controls identified several rare novel VMAT1 variants. The variant Phe84Ser was only present in individuals with BPD and leads to marked increase monoamine transport in vitro. Taken together, our data show that VMAT1 polymorphisms influence monoamine signaling, the functional response of emotional brain circuits and risk for psychopathology.

Genotype–phenotype correlation and course of transthyretin familial amyloid polyneuropathies in France

PubMed Central

Mariani, Louise‐Laure; Lozeron, Pierre; Théaudin, Marie; Mincheva, Zoia; Signate, Aissatou; Ducot, Beatrice; Algalarrondo, Vincent; Denier, Christian; Adam, Clovis; Nicolas, Guillaume; Samuel, Didier; Slama, Michel S.; Lacroix, Catherine; Misrahi, Micheline; Adams, David

2015-01-01

Objective To compare the natural history of familial transthyretin amyloid polyneuropathies (FAP) due to the Val30Met, Ser77Tyr, and Ile107Val mutations in France with the classical Portuguese Val30Met FAP. Methods We compared 84 French patients with a control group of 110 Portuguese patients carrying the Val30Met mutation also living in France, all referred to and followed at the French National FAP Reference Center from 1988 to 2010. Clinical examination, functional and walking disability scores, nerve conduction studies, and muscle biopsies are reported. We also conducted a comprehensive literature review to further determine the range of phenotypic expression. Results By comparison with Portuguese Val30Met FAP, French Ile107Val, Ser77Tyr, and LateVal30Met FAP showed more rapid and severe disease progression; onset of gait disorders was 3 times more rapid (p < 0.0001) and the rate of modified Norris test decline was up to 40 times faster in Ile107Val patients (p < 0.0001). Median survival was much shorter in Ile107Val and in Val30Met mutation with late onset (>50 years; LateMet30) FAP (p = 0.0005). Other distinctive features relative to the Portuguese patients included atypical clinical presentations, demyelination on nerve conduction studies (p = 0.0005), and difficult identification of amyloid deposits in nerve and muscle biopsies. Interpretation Ile107Val and LateMet30 mutations are associated with the most debilitating and severe FAP ever described, with rapid onset of tetraparesis and shorter median survival. It could be explained by frequent large‐fiber involvement and associated demyelination and more severe axonal loss. These findings have major implications for genetic counseling and patient management as new therapeutic options are being assessed in clinical trials (TTR gene silencing). Ann Neurol 2015;78:901–916 PMID:26369527

Functional Characterization of Rare RAB12 Variants and Their Role in Musician’s and Other Dystonias

PubMed Central

Hebert, Eva; Borngräber, Friederike; Schmidt, Alexander; Rakovic, Aleksandar; Brænne, Ingrid; Weissbach, Anne; Hampf, Jennie; Vollstedt, Eva-Juliane; Größer, Leopold; Schaake, Susen; Müller, Michaela; Manzoor, Humera; Jabusch, Hans-Christian; Alvarez-Fischer, Daniel; Kasten, Meike; Kostic, Vladimir S.; Gasser, Thomas; Zeuner, Kirsten E.; Kim, Han-Joon; Jeon, Beomseok; Bauer, Peter; Altenmüller, Eckart; Klein, Christine; Lohmann, Katja

2017-01-01

Mutations in RAB (member of the Ras superfamily) genes are increasingly recognized as cause of a variety of disorders including neurological conditions. While musician’s dystonia (MD) and writer’s dystonia (WD) are task-specific movement disorders, other dystonias persistently affect postures as in cervical dystonia. Little is known about the underlying etiology. Next-generation sequencing revealed a rare missense variant (c.586A>G; p.Ile196Val) in RAB12 in two of three MD/WD families. Next, we tested 916 additional dystonia patients; 512 Parkinson’s disease patients; and 461 healthy controls for RAB12 variants and identified 10 additional carriers of rare missense changes among dystonia patients (1.1%) but only one carrier in non-dystonic individuals (0.1%; p = 0.005). The detected variants among index patients comprised p.Ile196Val (n = 6); p.Ala174Thr (n = 3); p.Gly13Asp; p.Ala148Thr; and p.Arg181Gln in patients with MD; cervical dystonia; or WD. Two relatives of MD patients with WD also carried p.Ile196Val. The two variants identified in MD patients (p.Ile196Val; p.Gly13Asp) were characterized on endogenous levels in patient-derived fibroblasts and in two RAB12-overexpressing cell models. The ability to hydrolyze guanosine triphosphate (GTP), so called GTPase activity, was increased in mutants compared to wildtype. Furthermore, subcellular distribution of RAB12 in mutants was altered in fibroblasts. Soluble Transferrin receptor 1 levels were reduced in the blood of all three tested p.Ile196Val carriers. In conclusion, we demonstrate an enrichment of missense changes among dystonia patients. Functional characterization revealed altered enzyme activity and lysosomal distribution in mutants suggesting a contribution of RAB12 variants to MD and other dystonias. PMID:29057844

Functional Characterization of Rare RAB12 Variants and Their Role in Musician's and Other Dystonias.

PubMed

Hebert, Eva; Borngräber, Friederike; Schmidt, Alexander; Rakovic, Aleksandar; Brænne, Ingrid; Weissbach, Anne; Hampf, Jennie; Vollstedt, Eva-Juliane; Größer, Leopold; Schaake, Susen; Müller, Michaela; Manzoor, Humera; Jabusch, Hans-Christian; Alvarez-Fischer, Daniel; Kasten, Meike; Kostic, Vladimir S; Gasser, Thomas; Zeuner, Kirsten E; Kim, Han-Joon; Jeon, Beomseok; Bauer, Peter; Altenmüller, Eckart; Klein, Christine; Lohmann, Katja

2017-10-18

Mutations in RAB (member of the Ras superfamily) genes are increasingly recognized as cause of a variety of disorders including neurological conditions. While musician's dystonia (MD) and writer's dystonia (WD) are task-specific movement disorders, other dystonias persistently affect postures as in cervical dystonia. Little is known about the underlying etiology. Next-generation sequencing revealed a rare missense variant (c.586A>G; p.Ile196Val) in RAB12 in two of three MD/WD families. Next, we tested 916 additional dystonia patients; 512 Parkinson's disease patients; and 461 healthy controls for RAB12 variants and identified 10 additional carriers of rare missense changes among dystonia patients (1.1%) but only one carrier in non-dystonic individuals (0.1%; p = 0.005). The detected variants among index patients comprised p.Ile196Val ( n = 6); p.Ala174Thr ( n = 3); p.Gly13Asp; p.Ala148Thr; and p.Arg181Gln in patients with MD; cervical dystonia; or WD. Two relatives of MD patients with WD also carried p.Ile196Val. The two variants identified in MD patients (p.Ile196Val; p.Gly13Asp) were characterized on endogenous levels in patient-derived fibroblasts and in two RAB12-overexpressing cell models. The ability to hydrolyze guanosine triphosphate (GTP), so called GTPase activity, was increased in mutants compared to wildtype. Furthermore, subcellular distribution of RAB12 in mutants was altered in fibroblasts. Soluble Transferrin receptor 1 levels were reduced in the blood of all three tested p.Ile196Val carriers. In conclusion, we demonstrate an enrichment of missense changes among dystonia patients. Functional characterization revealed altered enzyme activity and lysosomal distribution in mutants suggesting a contribution of RAB12 variants to MD and other dystonias.

Insulin Signaling in Bupivacaine-induced Cardiac Toxicity: Sensitization during Recovery and Potentiation by Lipid Emulsion

PubMed Central

Fettiplace, Michael R.; Kowal, Katarzyna; Ripper, Richard; Young, Alexandria; Lis, Kinga; Rubinstein, Israel; Bonini, Marcelo; Minshall, Richard; Weinberg, Guy

2015-01-01

Background The impact of local anesthetics on regulation of glucose homeostasis by protein kinase B (Akt) and 5’-Adenosine monophosphate activated protein kinase (AMPK) is unclear but important because of the implications for both local anesthetic toxicity and its reversal by intravenous lipid emulsion (ILE). Methods Sprague-Dawley rats received 10mg/kg bupivacaine over 20 seconds followed by nothing or 10mL/kg ILE (or ILE without bupivacaine). At key time points, heart and kidney were excised. Glycogen content and phosphorylation levels of Akt, p70s6k, s6, IRS1, GSK-3β, AMPK, ACC, TSC2 were quantified. Three animals received Wortmannin to irreversibily inhibit phosphoinositide-3-kinase (Pi3k) signaling. Isolated heart studies were conducted with bupivacaine and LY294002—a reversible Pi3K inhibitor. Results Bupivacaine cardiotoxicity rapidly de-phosphorylated Akt at S473 to 63 ± 5% of baseline and phosphorylated AMPK to 151 ± 19%. AMPK activation inhibited targets downstream of mTORC1 via TSC2. Feedback dephosphorylation of IRS1 to 31 ± 8% of baseline sensitized Akt signaling in hearts resulting in hyper-phosphorylation of Akt at T308 and GSK-3β to 390 ± 64% and 293 ± 50% of baseline respectively. Glycogen accumulated to 142 ± 7% of baseline. Irreversible inhibition of Pi3k upstream of Akt exacerbated bupivacaine cardiotoxicity, while pretreating with a reversible inhibitor delayed onset of toxicity. ILE rapidly phosphorylated Akt at S473 and T308 to 150 ± 23% and 167 ± 10% of baseline, respectively but did not interfere with AMPK or targets of mTORC1. Conclusion Glucose handling by Akt and AMPK is integral to recovery from bupivacaine cardiotoxicity and modulation of these pathways by ILE contributes to lipid resuscitation. PMID:26646023

Meta- and Pooled Analysis of GSTP1 Polymorphism and Lung Cancer: A HuGE-GSEC Review

PubMed Central

Chen, Wei; Smith, Daryn W.; Benhamou, Simone; Bouchardy, Christine; Butkiewicz, Dorota; Fong, Kwun M.; Gené, Manuel; Hirvonen, Ari; Kiyohara, Chikako; Larsen, Jill E.; Lin, Pinpin; Raaschou-Nielsen, Ole; Povey, Andrew C.; Reszka, Edyta; Risch, Angela; Schneider, Joachim; Schwartz, Ann G.; Sorensen, Mette; To-Figueras, Jordi; Tokudome, Shinkan; Pu, Yuepu; Yang, Ping; Wenzlaff, Angela S.; Wikman, Harriet; Taioli, Emanuela

2009-01-01

Lung cancer is the most common cancer worldwide. Polymorphisms in genes associated with carcinogen metabolism may modulate risk of disease. Glutathione S-transferase pi (GSTP1) detoxifies polycyclic aromatic hydrocarbons found in cigarette smoke and is the most highly expressed glutathione S-transferase in lung tissue. A polymorphism in the GSTP1 gene, an A-to-G transition in exon 5 (Ile105Val, 313A → 313G), results in lower activity among individuals who carry the valine allele. The authors present a meta- and a pooled analysis of case-control studies that examined the association between this polymorphism in GSTP1 and lung cancer risk (27 studies, 8,322 cases and 8,844 controls and 15 studies, 4,282 cases and 5,032 controls, respectively). Overall, the meta-analysis found no significant association between lung cancer risk and the GSTP1 exon 5 polymorphism. In the pooled analysis, there was an overall association (odds ratio = 1.11, 95% confidence interval: 1.03, 1.21) between lung cancer and carriage of the GSTP1 Val/Val or Ile/Val genotype compared with those carrying the Ile/Ile genotype. Increased risk varied by histologic type in Asians. There appears to be evidence for interaction between amount of smoking, the GSTP1 exon 5 polymorphism, and risk of lung cancer in whites. PMID:19240225

Induced plant-defenses suppress herbivore reproduction but also constrain predation of their offspring.

PubMed

Ataide, Livia M S; Pappas, Maria L; Schimmel, Bernardus C J; Lopez-Orenes, Antonio; Alba, Juan M; Duarte, Marcus V A; Pallini, Angelo; Schuurink, Robert C; Kant, Merijn R

2016-11-01

Inducible anti-herbivore defenses in plants are predominantly regulated by jasmonic acid (JA). On tomato plants, most genotypes of the herbivorous generalist spider mite Tetranychus urticae induce JA defenses and perform poorly on it, whereas the Solanaceae specialist Tetranychus evansi, who suppresses JA defenses, performs well on it. We asked to which extent these spider mites and the predatory mite Phytoseiulus longipes preying on these spider mites eggs are affected by induced JA-defenses. By artificially inducing the JA-response of the tomato JA-biosynthesis mutant def-1 using exogenous JA and isoleucine (Ile), we first established the relationship between endogenous JA-Ile-levels and the reproductive performance of spider mites. For both mite species we observed that they produced more eggs when levels of JA-Ile were low. Subsequently, we allowed predatory mites to prey on spider mite-eggs derived from wild-type tomato plants, def-1 and JA-Ile-treated def-1 and observed that they preferred, and consumed more, eggs produced on tomato plants with weak JA defenses. However, predatory mite oviposition was similar across treatments. Our results show that induced JA-responses negatively affect spider mite performance, but positively affect the survival of their offspring by constraining egg-predation. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

BMI, RQ, Diabetes, and Sex Affect the Relationships Between Amino Acids and Clamp Measures of Insulin Action in Humans

PubMed Central

Thalacker-Mercer, Anna E.; Ingram, Katherine H.; Guo, Fangjian; Ilkayeva, Olga; Newgard, Christopher B.; Garvey, W. Timothy

2014-01-01

Previous studies have used indirect measures of insulin sensitivity to link circulating amino acids with insulin resistance and identify potential biomarkers of diabetes risk. Using direct measures (i.e., hyperinsulinemic-euglycemic clamps), we examined the relationships between the metabolomic amino acid profile and insulin action (i.e., glucose disposal rate [GDR]). Relationships between GDR and serum amino acids were determined among insulin-sensitive, insulin-resistant, and type 2 diabetic (T2DM) individuals. In all subjects, glycine (Gly) had the strongest correlation with GDR (positive association), followed by leucine/isoleucine (Leu/Ile) (negative association). These relationships were dramatically influenced by BMI, the resting respiratory quotient (RQ), T2DM, and sex. Gly had a strong positive correlation with GDR regardless of BMI, RQ, or sex but became nonsignificant in T2DM. In contrast, Leu/Ile was negatively associated with GDR in nonobese and T2DM subjects. Increased resting fat metabolism (i.e., low RQ) and obesity were observed to independently promote and negate the association between Leu/Ile and insulin resistance, respectively. Additionally, the relationship between Leu/Ile and GDR was magnified in T2DM males. Future studies are needed to determine whether Gly has a mechanistic role in glucose homeostasis and whether dietary Gly enrichment may be an effective intervention in diseases characterized by insulin resistance. PMID:24130332

Nontargeted LC-MS Metabolomics Approach for Metabolic Profiling of Plasma and Urine from Pigs Fed Branched Chain Amino Acids for Maximum Growth Performance.

PubMed

Soumeh, Elham A; Hedemann, Mette S; Poulsen, Hanne D; Corrent, Etienne; van Milgen, Jacob; Nørgaard, Jan V

2016-12-02

The metabolic response in plasma and urine of pigs when feeding an optimum level of branched chain amino acids (BCAAs) for best growth performance is unknown. The objective of the current study was to identify the metabolic phenotype associated with the BCAAs intake level that could be linked to the animal growth performance. Three dose-response studies were carried out to collect blood and urine samples from pigs fed increasing levels of Ile, Val, or Leu followed by a nontargeted LC-MS approach to characterize the metabolic profile of biofluids when dietary BCAAs are optimum for animal growth. Results showed that concentrations of plasma hypoxanthine and tyrosine (Tyr) were higher while concentrations of glycocholic acid, tauroursodeoxycholic acid, and taurocholic acid were lower when the dietary Ile was optimum. Plasma 3-methyl-2-oxovaleric acid and creatine were lower when dietary Leu was optimum. The optimum dietary Leu resulted in increased urinary excretion of ascorbic acid and choline and relatively decreased excretion of 2-aminoadipic acid, acetyl-dl-valine, Ile, 2-methylbutyrylglycine, and Tyr. In conclusion, plasma glycocholic acid and taurocholic acid were discriminating metabolites to the optimum dietary Ile. The optimum dietary Leu was associated with reduced plasma creatine and urinary 2-aminoadipic acid and elevated urinary excretion of ascorbic acid and choline. The optimum dietary Val had a less pronounced metabolic response reflected in plasma or urine than other BCAA.

[Suicide in Paris and Ile-de-France].

PubMed

Lecomte, D; Hatton, F; Jougla, E; Le Toullec, A

1995-01-01

A study carried out in collaboration between the Institute of Forensic Medicine of Paris and the INSERM (SC8) concerned all the suicide occurred in Paris region over 1990; 455 suicides in Paris and 1,229 in the suburbs of Paris (overall, 1,684 suicides observed in Paris area for the same period). For Paris city, the rate of suicide reaches 23.3 per 100,000 subjects. This frequency increases up to 40 years and falls after this age with a further rise between 75 and 85 years. Suicide represents 17% of the total mortality for adolescents and young adults living in Paris, with a large over-representation of males (277 males, 178 females). Suicide is more frequent before 45 years in Paris than in France but this tendency is reversed after 45 years. It represents the first cause of violent deaths among young population (15-34 years) living in Paris and is, after AIDS, the second cause of death. In Paris suburbs, it constitutes the second cause of mortality after traffic accidents. The mode of suicide in Paris is essentially poisoning, then hanging and jumping from high place. In contrast, outside Paris, the hanging is more frequently used than poisoning and firearms. The contribution of the Institute of Forensic Medicine of Paris is essential for the knowledge of these voluntary deaths, a large part of them being unknown in the National statistic of causes of death. This underestimation is extremely important: only 68% of the suicides are known by the Official Statistic in Paris region and 26% for Paris city.(ABSTRACT TRUNCATED AT 250 WORDS)

Ionic Liquids in Electro-active Devices (ILED)

DTIC Science & Technology

2013-12-12

Polyesters: Structure-Property Relationships in Thermal Behavior, Ionic Conductivity , and Morphology , Advanced Functional Materials, (01 2010...and Ionic Conductivities , Macromolecular Chemistry and Physics, (10 2011): . doi: M. Green, C. Schreiner, T. Long. Thermal , Rheological, and Ion...block giving thermal stability and ionic conductivity . Table 1 shows the molecular weight analysis of the triblock copolymers with increasing

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

PubMed

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

2001-02-01

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

Local Anesthetic Systemic Toxicity: A Review of Recent Case Reports and Registries.

PubMed

Gitman, Marina; Barrington, Michael J

2018-02-01

This review summarizes presenting features, management, and outcomes of local anesthetic systemic toxicity (LAST) from published cases and those submitted to online registries capturing use of intravenous lipid emulsion (ILE) therapy. The results of single-center and multicenter registries and epidemiologic studies complement this information. Between March 2014 and November 2016, 47 separate cases of LAST were described in 35 peer-reviewed articles. Local anesthetic systemic toxicity events occurred as a result of penile blocks (23%), local infiltration (17%), and upper/lower extremity, torso, and neuraxial blockade. Twenty-two patients (47%) were treated with ILE, and 2 patients (4.3%) died. During the same time period, 11 cases submitted to lipidrescue.org were treated with ILE and survived. The incidence of LAST reported in registries is 0.03% or 0.27 (95% confidence interval, 0.21-0.35) per 1000 peripheral nerve blocks (denominator of 251,325). Seizure (53% and 61% from case reports and registries, respectively) was the most common presenting feature.

On the properties of energy stable flux reconstruction schemes for implicit large eddy simulation

NASA Astrophysics Data System (ADS)

Vermeire, B. C.; Vincent, P. E.

2016-12-01

We begin by investigating the stability, order of accuracy, and dispersion and dissipation characteristics of the extended range of energy stable flux reconstruction (E-ESFR) schemes in the context of implicit large eddy simulation (ILES). We proceed to demonstrate that subsets of the E-ESFR schemes are more stable than collocation nodal discontinuous Galerkin methods recovered with the flux reconstruction approach (FRDG) for marginally-resolved ILES simulations of the Taylor-Green vortex. These schemes are shown to have reduced dissipation and dispersion errors relative to FRDG schemes of the same polynomial degree and, simultaneously, have increased Courant-Friedrichs-Lewy (CFL) limits. Finally, we simulate turbulent flow over an SD7003 aerofoil using two of the most stable E-ESFR schemes identified by the aforementioned Taylor-Green vortex experiments. Results demonstrate that subsets of E-ESFR schemes appear more stable than the commonly used FRDG method, have increased CFL limits, and are suitable for ILES of complex turbulent flows on unstructured grids.

New cytotoxic cyclic peptides and dianthramide from Dianthus superbus.

PubMed

Hsieh, Pei-Wen; Chang, Fang-Rong; Wu, Ching-Chung; Wu, Kuen-Yuh; Li, Chien-Ming; Chen, Su-Li; Wu, Yang-Chang

2004-09-01

Four new cyclic peptides, dianthins C-F (1-4), and a new dianthramide, 4-methoxydianthramide B (5), were isolated from the MeOH extract of the traditional Chinese medicinal plant Dianthus superbus. The sequences of cyclic peptides 1-4 were elucidated as cyclo(Gly(1)-Pro(2)-Phe(3)-Tyr(4)-Val(5)-Ile(6)-), cyclo(Gly(1)-Ser(2)-Leu(3)-Pro(4)-Pro(5)-Ile(6)-Phe(7)-), cyclo(Gly(1)-Pro(2)-Ile(3)-Ser(4)-Phe(5)-Val(6)-), and cyclo(Gly(1)-Pro(2)-Phe(3)-Val(4)-Phe(5)-) on the basis of ESI tandem mass fragmentation analysis, chemical evidence, and extensive 2D NMR methods. The conformation of compound 1 was established as an alpha-helix by CD analysis. Furthermore, compounds 3 and 5 showed cytotoxicities toward the Hep G2 cancer cell line with IC(50) values of 2.37 and 4.08, respectively.

RCWA and FDTD modeling of light emission from internally structured OLEDs.

PubMed

Callens, Michiel Koen; Marsman, Herman; Penninck, Lieven; Peeters, Patrick; de Groot, Harry; ter Meulen, Jan Matthijs; Neyts, Kristiaan

2014-05-05

We report on the fabrication and simulation of a green OLED with an Internal Light Extraction (ILE) layer. The optical behavior of these devices is simulated using both Rigorous Coupled Wave Analysis (RCWA) and Finite Difference Time-Domain (FDTD) methods. Results obtained using these two different techniques show excellent agreement and predict the experimental results with good precision. By verifying the validity of both simulation methods on the internal light extraction structure we pave the way to optimization of ILE layers using either of these methods.

Enhanced activity of human serotonin transporter variants associated with autism.

PubMed

Prasad, Harish C; Steiner, Jennifer A; Sutcliffe, James S; Blakely, Randy D

2009-01-27

Rare, functional, non-synonymous variants in the human serotonin (5-hydroxytryptamine, 5-HT) transporter (hSERT) gene (SLC6A4) have been identified in both autism and obsessive-compulsive disorder (OCD). Within autism, rare hSERT coding variants associate with rigid-compulsive traits, suggesting both phenotypic overlap with OCD and a shared relationship with disrupted 5-HT signalling. Here, we document functional perturbations of three of these variants: Ile425Leu; Phe465Leu; and Leu550Val. In transiently transfected HeLa cells, the three variants confer a gain of 5-HT transport phenotype. Specifically, enhanced SERT activity was also observed in lymphoblastoid lines derived from mutation carriers. In contrast to previously characterized Gly56Ala, where increased transport activity derives from catalytic activation, the three novel variants exhibit elevated surface density as revealed through both surface antagonist-binding and biotinylation studies. Unlike Gly56Ala, mutants Ile425Leu, Phe465Leu and Leu550Val retain a capacity for acute PKG and p38 MAPK regulation. However, both Gly56Ala and Ile425Leu demonstrate markedly reduced sensitivity to PP2A antagonists, suggesting that deficits in trafficking and catalytic modulation may derive from a common basis in perturbed phosphatase regulation. When expressed stably from the same genomic locus in CHO cells, both Gly56Ala and Ile425Leu display catalytic activation, accompanied by a striking loss of SERT protein.

Genetic diversity and population structure of an insular tree, Santalum austrocaledonicum in New Caledonian archipelago.

PubMed

Bottin, L; Verhaegen, D; Tassin, J; Olivieri, I; Vaillant, A; Bouvet, J M

2005-06-01

We present a study of the genetic diversity and structure of a tropical tree in an insular system. Santalum austrocaledonicum is endemic to the archipelago of New Caledonia and is exploited for oil extraction from heartwood. A total of 431 individuals over 17 populations were analysed for eight polymorphic microsatellite loci. The number of alleles per locus ranged from 3 to 33 and the observed heterozygosity per population ranged from 0.01 in Mare to 0.74 in Ile des Pins. The genetic diversity was lowest in the most recent islands, the Loyautes, and highest in the oldest island, Grande Terre, as well as the nearby small Ile des Pins. Significant departures from panmixia were observed for some loci-population combinations (per population FIS = 0-0.03 on Grande-Terre and Ile des Pins, and 0-0.67 on Loyautes). A strong genetic differentiation among all islands was observed (FST = 0.22), and the amount of differentiation increased with geographic distance in Iles Loyaute and in Grande Terre. At both population and island levels, island age and isolation seem to be the main factors influencing the amount of genetic diversity. In particular, populations from recent islands had large average FIS that could not be entirely explained by null alleles or a Wahlund effect. This result suggests that, at least in some populations, selfing occurred extensively. Conclusively, our results indicate a strong influence of insularity on the genetic diversity and structure of Santalum austrocaledonicum.

Analysis of glutathione S-transferase Pi isoform (GSTP1) single-nucleotide polymorphisms and macular telangiectasia type 2.

PubMed

Szental, Joshua A; Baird, Paul N; Richardson, Andrea J; Islam, F M Amirul; Scholl, Hendrik P N; Charbel Issa, Peter; Holz, Frank G; Gillies, Mark; Guymer, Robyn H

2010-12-01

Recent imaging studies have suggested that macular pigment is decreased centrally in macular telangiectasia type 2 (MT2). The uptake of xanthophyll pigment into the macula is thought to be facilitated by a xanthophyll-binding protein (XBP). The Pi isoform of glutathione S-transferase (GSTP1) represents one such XBP with high binding affinity. This case-control study aimed to determine whether two common single-nucleotide polymorphisms (SNPs) of GSTP1 were associated with MT2. DNA samples from 39 cases and 21 controls were collected. Two polymorphic sites of Ile105Val and Ala114Val in exons 5 and 6 respectively, of the GSTP1 gene were analysed. Comparison of alleles and genotypes between cases and controls indicated that there were no statistically significant differences for either the Ile105Val SNP (P=0.43) or the Ala114Val SNP (P=0.85), or for any combinations; however, the homozygous at-risk genotype (GG) of the Ile105Val SNP was present in 8% of cases but absent in controls. This study found no statistically significant association between two common GSTP1 SNPs and MT2; however, a trend towards a greater frequency of the GG genotype of the Ile105Val SNP in cases is of great interest. The biological plausibility of disturbed macular pigment uptake in MT2 makes GSTP1 an excellent candidate gene. Further investigation is warranted in future studies of MT2.

Tonic suppression of spontaneous baroreceptor reflex by endogenous angiotensins via AT(2) subtype receptors at nucleus reticularis ventrolateralis in the rat.

PubMed

Lin, K; Chan, S H; Chan, J Y

2001-04-01

We evaluated the role of endogenous angiotensins at the rostral nucleus reticularis ventrolateralis (NRVL) in the modulation of spontaneous baroreceptor reflex (BRR) response and the subtype of angiotensin receptors involved using rats anesthetized and maintained with pentobarbital sodium. Bilateral microinjection of angiotensin II (ANG II) or its active metabolite angiotensin III (ANG III) (5, 10, or 20 pmol) into the NRVL significantly suppressed the spontaneous BRR response, as represented by the magnitude of transfer function between systemic arterial pressure and heart rate signals. The inhibitory effect of ANG III (20 pmol) was discernibly reversed by coadministration with its peptide antagonist, [Ile(7)]ANG III (1.6 nmol), or the nonpeptide AT(2) receptor antagonist, PD-123319 (1.6 nmol), but not by the nonpeptide AT(1) receptor antagonist, losartan (1.6 nmol). On the other hand, the peptide antagonist, [Sar(1), Ile(8)]ANG II (1.6 nmol) or both non-peptide antagonists appreciably reversed the suppressive action of ANG II (20 pmol). Whereas losartan produced minimal effect, blocking the endogenous activity of the angiotensins by microinjection into the bilateral NRVL of PD-123319, [Sar(1), Ile(8)]ANG II or [Ile(7)]ANG III elicited significant enhancement of the spontaneous BRR response. We conclude that under physiologic conditions both endogenous ANG II and ANG III may exert a tonic inhibitory modulation on the spontaneous BRR response by acting selectively on the AT(2) subtype receptors at the NRVL. Copyright 2001 Wiley-Liss, Inc.

A single beta-amino acid substitution to angiotensin II confers AT2 receptor selectivity and vascular function.

PubMed

Jones, Emma S; Del Borgo, Mark P; Kirsch, Julian F; Clayton, Daniel; Bosnyak, Sanja; Welungoda, Iresha; Hausler, Nicholas; Unabia, Sharon; Perlmutter, Patrick; Thomas, Walter G; Aguilar, Marie-Isabel; Widdop, Robert E

2011-03-01

Novel AT(2)R ligands were designed by substituting individual β-amino acid in the sequence of the native ligand angiotensin II (Ang II). Relative ATR selectivity and functional vascular assays (in vitro AT(2)R-mediated vasorelaxation and in vivo vasodepressor action) were determined. In competition binding experiments using either AT(1)R- or AT(2)R- transfected HEK-293 cells, only β-Asp(1)-Ang II and Ang II fully displaced [(125)I]-Ang II from AT(1)R. In contrast, β-substitutions at each position of Ang II exhibited AT(2)R affinity, with β-Tyr(4)-Ang II and β-Ile(5)-Ang II exhibiting ≈ 1000-fold AT(2)R selectivity. In mouse aortic rings, β-Tyr(4)-Ang II and β-Ile(5)-Ang II evoked vasorelaxation that was sensitive to blockade by the AT(2)R antagonist PD123319 and the nitric oxide synthase inhibitor L-NAME. When tested with a low level of AT(1)R blockade, β-Ile(5)-Ang II (15 pmol/kg per minute IV for 4 hours) reduced blood pressure (BP) in conscious spontaneously hypertensive rats (β-Ile(5)-Ang II plus candesartan, -24 ± 4 mm Hg) to a greater extent than candesartan alone (-11 ± 3 mm Hg, n=7, P<0.05), an effect that was abolished by concomitant PD123319 infusion. However, in an identical experimental protocol, β-Tyr(4)-Ang II had no influence on BP (n=10), and it was less stable than β-Ile(5)-Ang II in plasma stability assays. Thus, this study demonstrated that a single β-amino acid substitution resulted in a compound that demonstrated both in vitro vasorelaxation and in vivo depressor activity via AT(2)R. This approach to the design and synthesis of novel AT(2)R-selective peptidomimetics shows great potential to provide insight into AT(2)R function.

Experience dans une classe d'immersion francaise aux Milles-Iles (An Experience in a French Immersion Class in Mille-Iles)

ERIC Educational Resources Information Center

Pariseau, Cecile

1978-01-01

A description of an immersion program for 6-year-old anglophone children modeled on "les classes d'accueil" for immigrant children. The program of intensive instruction in oral and written French is outlined. This school district has found this type of immersion superior to the usual kind. (The text is in French.) (AMH)

Lack of Association between ESR1 and CYP1A1 Gene Polymorphisms and Susceptibility to Uterine Leiomyoma in Female Patients of Iranian Descent.

PubMed

Taghizade Mortezaee, Fatemeh; Tabatabaiefar, Mohammad Amin; Hashemzadeh Chaleshtori, Morteza; Miraj, Sepideh

2014-01-01

Uterine leiomyoma (UL) is the most common benign smooth muscle cell tumor with as yet unknown etiology and pathogenesis. This study was carried out to investigate the association of ESR1-351 A>G, ESR1 -397 T>C and CYP1A1 (Ile462Val) polymorphisms with UL in female patients of Iranian origin. In this case-control study, 276 patients with UL and 156 healthy women were recruited. The genetic polymorphisms ESR1-351 A>G, ESR1-397 T>C and CYP1A1 (Ile462Val) were genotyped by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). No significant difference were found in frequencies of both genotypes and alleles of ESR1-351 A>G, ESR1-397 T>C and CYP1A1 (Ile462Val) polymorphisms between the two groups (p>0.05). Our findings indicated that these ESR1 and CYP1A1 polymorphisms were not associated with the development of UL in the cases reported here.

Specific formation of negative ions from leucine and isoleucine molecules

NASA Astrophysics Data System (ADS)

Papp, Peter; Shchukin, Pavel; Matejčík, Štefan

2010-01-01

Dissociative electron attachment (DEA) to gas phase leucine (Leu) and isoleucine (Ile) molecules was studied using experimental and quantum-chemical methods. The relative partial cross sections for DEA have been measured using crossed electron/molecular beams technique. Supporting ab initio calculations of the structure, energies of neutral molecules, fragments, and negative ions have been carried out at G3MP2 and B3LYP levels in order to interpret the experimental data. Leu and Ile exhibit several common features. The negative ionic fragments from both molecules are formed in the electron energy range from 0 to approximately 14 eV via three resonances (1.2, 5.5, and 8 eV). The relative partial cross sections for DEA Leu and Ile are very similar. The dominant negative ions formed were closed shell negative ions (M-H)- (m/z=130) formed preferentially via low electron energy resonance of 1.23 eV. Additional negative ions with m/z=115, 114, 113, 112, 84, 82, 74, 45, 26, and 17 have been detected.

Increasing the availability of threonine, isoleucine, valine, and leucine relative to lysine while maintaining an ideal ratio of lysine:methionine alters mammary cellular metabolites, mammalian target of rapamycin signaling, and gene transcription.

PubMed

Dong, X; Zhou, Z; Wang, L; Saremi, B; Helmbrecht, A; Wang, Z; Loor, J J

2018-06-01

Amino acids not only serve as precursors for protein synthesis but also function as signaling molecules that can regulate the mammalian target of rapamycin (mTOR) pathway. Methionine and Lys are the most-limiting AA for milk production and a ratio of ∼3:1 Lys:Met in the metabolizable protein has been determined to be ideal. Besides Met and Lys, recent studies have evaluated Ile, Leu, Val, and Thr as potentially limiting for milk protein synthesis. The objective of this experiment was to determine if varying the ratio of Lys:Thr, Lys:Ile, Lys:Val, and Lys:Leu while maintaining an ideal ratio of Lys:Met and fixed ratio of other essential AA (IPAA) elicits changes in intracellular metabolites, gene transcription related to protein synthesis, and phosphorylation status of mTOR pathway proteins. Immortalized bovine mammary epithelial cell line (MAC-T) cells were incubated for 12 h (n = 5 replicates/treatment) with IPAA (2.9:1 Lys:Met; 1.8:1 Lys:Thr; 2.38:1 Lys:His; 1.23:1 Lys:Val; 1.45:1 Lys:Ile; 0.85:1 Lys:Leu; 2.08:1 Lys:Arg) or IPAA supplemented with Thr, Ile, Val, and Leu to achieve a Lys:Thr 1.3:1 (LT1.3), Lys:Ile 1.29:1 (LI1.29), Lys:Val 1.12:1 (LV1.12), or Lys:Leu 0.78:1 (LL0.78). Compared with IPAA, metabolomics via gas chromatography-mass spectrometry revealed that increases in availability of Thr, Ile, Val, and Leu led to greater concentrations of essential AA (Leu, Ile, Thr), nonessential AA (Gly, Glu, Gln, Ser, Pro, Asp), and various metabolites including uric acid, phosphoric acid, N-acetylglutamic acid, and intermediates of glycolysis and the tricarboxylic acid cycle. Compared with other treatments, LV1.12 led to greater phosphorylation status of serine/threonine kinase B (Akt), mTORC1, and ribosomal protein S6 and lower phosphorylation of α subunit of eukaryotic translation initiation factor 2. In addition, LV1.12 upregulated abundance of CSN2 and both the abundance and promoter methylation of CSN1S1. Although LI1.29 led to the second highest response

A Quantitative Tool to Distinguish Isobaric Leucine and Isoleucine Residues for Mass Spectrometry-Based De Novo Monoclonal Antibody Sequencing

NASA Astrophysics Data System (ADS)

Poston, Chloe N.; Higgs, Richard E.; You, Jinsam; Gelfanova, Valentina; Hale, John E.; Knierman, Michael D.; Siegel, Robert; Gutierrez, Jesus A.

2014-07-01

De novo sequencing by mass spectrometry (MS) allows for the determination of the complete amino acid (AA) sequence of a given protein based on the mass difference of detected ions from MS/MS fragmentation spectra. The technique relies on obtaining specific masses that can be attributed to characteristic theoretical masses of AAs. A major limitation of de novo sequencing by MS is the inability to distinguish between the isobaric residues leucine (Leu) and isoleucine (Ile). Incorrect identification of Ile as Leu or vice versa often results in loss of activity in recombinant antibodies. This functional ambiguity is commonly resolved with costly and time-consuming AA mutation and peptide sequencing experiments. Here, we describe a set of orthogonal biochemical protocols, which experimentally determine the identity of Ile or Leu residues in monoclonal antibodies (mAb) based on the selectivity that leucine aminopeptidase shows for n-terminal Leu residues and the cleavage preference for Leu by chymotrypsin. The resulting observations are combined with germline frequencies and incorporated into a logistic regression model, called Predictor for Xle Sites (PXleS) to provide a statistical likelihood for the identity of Leu at an ambiguous site. We demonstrate that PXleS can generate a probability for an Xle site in mAbs with 96% accuracy. The implementation of PXleS precludes the expression of several possible sequences and, therefore, reduces the overall time and resources required to go from spectra generation to a biologically active sequence for a mAb when an Ile or Leu residue is in question.

Stretchable multichannel antennas in soft wireless optoelectronic implants for optogenetics.

PubMed

Park, Sung Il; Shin, Gunchul; McCall, Jordan G; Al-Hasani, Ream; Norris, Aaron; Xia, Li; Brenner, Daniel S; Noh, Kyung Nim; Bang, Sang Yun; Bhatti, Dionnet L; Jang, Kyung-In; Kang, Seung-Kyun; Mickle, Aaron D; Dussor, Gregory; Price, Theodore J; Gereau, Robert W; Bruchas, Michael R; Rogers, John A

2016-12-13

Optogenetic methods to modulate cells and signaling pathways via targeted expression and activation of light-sensitive proteins have greatly accelerated the process of mapping complex neural circuits and defining their roles in physiological and pathological contexts. Recently demonstrated technologies based on injectable, microscale inorganic light-emitting diodes (μ-ILEDs) with wireless control and power delivery strategies offer important functionality in such experiments, by eliminating the external tethers associated with traditional fiber optic approaches. Existing wireless μ-ILED embodiments allow, however, illumination only at a single targeted region of the brain with a single optical wavelength and over spatial ranges of operation that are constrained by the radio frequency power transmission hardware. Here we report stretchable, multiresonance antennas and battery-free schemes for multichannel wireless operation of independently addressable, multicolor μ-ILEDs with fully implantable, miniaturized platforms. This advance, as demonstrated through in vitro and in vivo studies using thin, mechanically soft systems that separately control as many as three different μ-ILEDs, relies on specially designed stretchable antennas in which parallel capacitive coupling circuits yield several independent, well-separated operating frequencies, as verified through experimental and modeling results. When used in combination with active motion-tracking antenna arrays, these devices enable multichannel optogenetic research on complex behavioral responses in groups of animals over large areas at low levels of radio frequency power (<1 W). Studies of the regions of the brain that are involved in sleep arousal (locus coeruleus) and preference/aversion (nucleus accumbens) demonstrate the unique capabilities of these technologies.

Successful treatment of a massive metoprolol overdose using intravenous lipid emulsion and hyperinsulinemia/euglycemia therapy.

PubMed

Barton, Cassie A; Johnson, Nathan B; Mah, Nathan D; Beauchamp, Gillian; Hendrickson, Robert

2015-05-01

Adrenergic β-antagonists, commonly known as β-blockers, are prescribed for many indications including hypertension, heart failure, arrhythmias, and migraines. Metoprolol is a moderately lipophilic β-blocker that in overdose causes direct myocardial depression leading to bradycardia, hypotension, and the potential for cardiovascular collapse. We describe the case of a 59-year-old man who intentionally ingested ~7.5 g of metoprolol tartrate. Initial treatment of bradycardia and hypotension included glucagon, atropine, dopamine, and norepinephrine. Despite these treatment modalities, the patient developed cardiac arrest. Intravenous lipid emulsion (ILE) and hyperinsulinemia/euglycemia (HIE) therapies were initiated during advanced cardiac life support and were immediately followed by return of spontaneous circulation. Further treatment included gastric lavage, activated charcoal, continued vasopressor therapy, and a repeat bolus of ILE. The patient was weaned off vasoactive infusions and was extubated within 24 hours. HIE therapy was continued for 36 hours after metoprolol ingestion. A urine β-blocker panel using mass spectrometry revealed a metoprolol concentration of 120 ng/ml and the absence of other β-blocking agents. To date, no clear treatment guidelines are available for β-blocker overdose, and the response to toxic concentrations is highly variable. In this case of a life-threatening single-agent metoprolol overdose, the patient was successfully treated with HIE and ILE therapy. Due to the increasing frequency with which ILE and HIE are being used for the treatment of β-blocker overdose, clinicians should be aware of their dosing strategies and indications. © 2015 Pharmacotherapy Publications, Inc.

Stretchable multichannel antennas in soft wireless optoelectronic implants for optogenetics

PubMed Central

Park, Sung Il; Shin, Gunchul; McCall, Jordan G.; Al-Hasani, Ream; Norris, Aaron; Xia, Li; Brenner, Daniel S.; Noh, Kyung Nim; Bang, Sang Yun; Bhatti, Dionnet L.; Jang, Kyung-In; Kang, Seung-Kyun; Mickle, Aaron D.; Dussor, Gregory; Price, Theodore J.; Gereau, Robert W.; Bruchas, Michael R.; Rogers, John A.

2016-01-01

Optogenetic methods to modulate cells and signaling pathways via targeted expression and activation of light-sensitive proteins have greatly accelerated the process of mapping complex neural circuits and defining their roles in physiological and pathological contexts. Recently demonstrated technologies based on injectable, microscale inorganic light-emitting diodes (μ-ILEDs) with wireless control and power delivery strategies offer important functionality in such experiments, by eliminating the external tethers associated with traditional fiber optic approaches. Existing wireless μ-ILED embodiments allow, however, illumination only at a single targeted region of the brain with a single optical wavelength and over spatial ranges of operation that are constrained by the radio frequency power transmission hardware. Here we report stretchable, multiresonance antennas and battery-free schemes for multichannel wireless operation of independently addressable, multicolor μ-ILEDs with fully implantable, miniaturized platforms. This advance, as demonstrated through in vitro and in vivo studies using thin, mechanically soft systems that separately control as many as three different μ-ILEDs, relies on specially designed stretchable antennas in which parallel capacitive coupling circuits yield several independent, well-separated operating frequencies, as verified through experimental and modeling results. When used in combination with active motion-tracking antenna arrays, these devices enable multichannel optogenetic research on complex behavioral responses in groups of animals over large areas at low levels of radio frequency power (<1 W). Studies of the regions of the brain that are involved in sleep arousal (locus coeruleus) and preference/aversion (nucleus accumbens) demonstrate the unique capabilities of these technologies. PMID:27911798

A quantitative tool to distinguish isobaric leucine and isoleucine residues for mass spectrometry-based de novo monoclonal antibody sequencing.

PubMed

Poston, Chloe N; Higgs, Richard E; You, Jinsam; Gelfanova, Valentina; Hale, John E; Knierman, Michael D; Siegel, Robert; Gutierrez, Jesus A

2014-07-01

De novo sequencing by mass spectrometry (MS) allows for the determination of the complete amino acid (AA) sequence of a given protein based on the mass difference of detected ions from MS/MS fragmentation spectra. The technique relies on obtaining specific masses that can be attributed to characteristic theoretical masses of AAs. A major limitation of de novo sequencing by MS is the inability to distinguish between the isobaric residues leucine (Leu) and isoleucine (Ile). Incorrect identification of Ile as Leu or vice versa often results in loss of activity in recombinant antibodies. This functional ambiguity is commonly resolved with costly and time-consuming AA mutation and peptide sequencing experiments. Here, we describe a set of orthogonal biochemical protocols, which experimentally determine the identity of Ile or Leu residues in monoclonal antibodies (mAb) based on the selectivity that leucine aminopeptidase shows for n-terminal Leu residues and the cleavage preference for Leu by chymotrypsin. The resulting observations are combined with germline frequencies and incorporated into a logistic regression model, called Predictor for Xle Sites (PXleS) to provide a statistical likelihood for the identity of Leu at an ambiguous site. We demonstrate that PXleS can generate a probability for an Xle site in mAbs with 96% accuracy. The implementation of PXleS precludes the expression of several possible sequences and, therefore, reduces the overall time and resources required to go from spectra generation to a biologically active sequence for a mAb when an Ile or Leu residue is in question.

Protein NMR Studies of Substrate Binding to Human Blood Group A and B Glycosyltransferases.

PubMed

Grimm, Lena Lisbeth; Weissbach, Sophie; Flügge, Friedemann; Begemann, Nora; Palcic, Monica M; Peters, Thomas

2017-07-04

Donor and acceptor substrate binding to human blood group A and B glycosyltransferases (GTA, GTB) has been studied by a variety of protein NMR experiments. Prior crystallographic studies had shown these enzymes to adopt an open conformation in the absence of substrates. Binding either of the donor substrate UDP-Gal or of UDP induces a semiclosed conformation. In the presence of both donor and acceptor substrates, the enzymes shift towards a closed conformation with ordering of an internal loop and the C-terminal residues, which then completely cover the donor-binding pocket. Chemical-shift titrations of uniformly 2 H, 15 N-labeled GTA or GTB with UDP affected about 20 % of all crosspeaks in 1 H, 15 N TROSY-HSQC spectra, reflecting substantial plasticity of the enzymes. On the other hand, it is this conformational flexibility that impedes NH backbone assignments. Chemical-shift-perturbation experiments with δ1-[ 13 C]methyl-Ile-labeled samples revealed two Ile residues-Ile123 at the bottom of the UDP binding pocket, and Ile192 as part of the internal loop-that were significantly disturbed upon stepwise addition of UDP and H-disaccharide, also revealing long-range perturbations. Finally, methyl TROSY-based relaxation dispersion experiments do not reveal micro- to millisecond timescale motions. Although this study reveals substantial conformational plasticity of GTA and GTB, the matter of how binding of substrates shifts the enzymes into catalytically competent states remains enigmatic. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Use of intravenous lipid emulsion to treat ivermectin toxicosis in a Border Collie.

PubMed

Clarke, Dana L; Lee, Justine A; Murphy, Lisa A; Reineke, Erica L

2011-11-15

A 2-year-old spayed female Border Collie was treated with IV lipid emulsion (ILE) after ingesting 6 mg/kg (2.73 mg/lb) of an equine ivermectin anthelmintic paste 8 hours prior to examination. On initial examination, the dog had stable cardiovascular signs but had diffuse muscle tremors and was hyperthermic. Neurologic evaluation revealed that the dog was ataxic and had mydriasis with bilaterally absent menace responses and pupillary light reflexes. The remaining physical examination findings were unremarkable. Results of CBC, serum biochemical analysis, venous blood gas analysis, and measurement of plasma lactate concentration were also within reference limits. The dog was treated with ILE in addition to supportive care with IV fluid therapy and cardiovascular, respiratory, and neurologic monitoring. The use of ILE treatment was initiated in this patient on the basis of previous clinical and experimental evidence supporting its use for toxicosis resulting from lipid-soluble agents. An initial bolus of 1.5 mL/kg (0.68 mL/lb) of a 20% sterile lipid solution was administered IV over 10 minutes, followed by a constant rate infusion of 0.25 mL/kg/min (0.11 mL/lb/min) over 60 minutes that was administered twice to treat clinical signs of ivermectin toxicosis. The dog was discharged from the hospital 48 hours after admission and was clinically normal within 4 days after ivermectin ingestion. Further diagnostic evaluation subsequently revealed that this dog was unaffected by the multidrug resistance gene (MDR-1) deletion, known as the ATP-binding cassette polymorphism. Ivermectin toxicosis in veterinary patients can result in death without aggressive treatment, and severe toxicosis often requires mechanical ventilation and intensive supportive care. This is particularly true in dogs affected by the ATP-binding cassette polymorphism. Novel ILE treatment has been shown to be effective in human patients with lipid-soluble drug toxicoses, although the exact mechanism is

Man and the chimaera. Selective versus neutral oxytocin evolution.

PubMed

Acher, R; Chauvet, J; Chauvet, M T

1995-01-01

The oxytocin/vasopressin superfamily encompasses vertebrate and invertebrate peptides and therefore the ancestral gene encoding the precursor protein antedates the divergence between the two groups, about 700 million years ago. The preserved nonapeptide pattern indicates that both the precursor structures and the processing enzymatic machinery were greatly conserved to ensure the building of a specific conformation. Substitutions, which may be neutral or selective, occurred in precise positions. Virtually all vertebrate species possess an oxytocin-like and a vasopressin-like peptide so that two evolutionary lineages can be traced. Because a single peptide, vasotocin ([Ile3]-vasopressin or [Arg8]-oxytocin) has been found in the most primitive Cyclostomata, a primordial gene duplication and subsequent mutations are assumed to have given rise to the two lineages. They started with vasotocin and isotocin ([Ser4,Ile8]-oxytocin) in bony fishes and culminated with vasopressin and oxytocin in placental mammals. Mesotocin ([Ile3]-oxytocin), found in lungfishes, amphibians, reptiles, birds and marsupials, appears as an evolutionary intermediate. The change from isotocin ([Ser4,Ile8]-oxytocin) into mesotocin ([Ile8]-oxytocin), can be observed in African and Australian lungfishes, species making the transition from bony fishes to land vertebrates. On the other hand the replacement of mesotocin by oxytocin can be detected in marsupials, particularly in the North-American opossum and the Australian Northern bandicoot that have both mesotocin and oxytocin whereas placental mammals possess only oxytocin. The invariability of this peptide in placentals can be explained by receptor-fitting selective pressure. In contrast to bony vertebrates in which neurohypophysial hormones revealed a remarkable structural stability, cartilaginous fishes displayed an unique oxytocin-like hormone evolution with variability and duality. Aside from vasotocin, in the subclass Selachii, rays have

Dating lacustrine episodes in the eastern Sahara by the epimerization of isoleucine in ostrich eggshells

USGS Publications Warehouse

Miller, G.H.; Wendorf, F.; Ernst, R.; Schild, R.; Close, A.E.; Friedman, I.; Schwarcz, H.P.

1991-01-01

The eggshell of the African ostrich, Struthio camelus, closely approximates a closed system for the retention of indigenous proteinaceous residues. Epimerization of the protein amino acid isoleucine follows linear first-order kinetics in laboratory simulations nearly to racemic equilibrium, and the variation in D/L ratio within a single fragment, or between fragments of the same age, is significantly less than in other carbonate systems. These observations suggest that the extent of isoleucine epimerization (aIle/Ile ratio) in ostrich eggshell offers the potential for high-resolution geochronology of Quaternary deposits. From the simulation experiments, and dated early Holocene samples for which we have in situ mean annual sediment temperature measurements, Arrhenius parameters have been calculated; the activation energy is 30.33 kcal mol-1, similar to that of other carbonate systems. We have measured the aIle/Ile ratio in ostrich eggshell associated with lacustrine episodes at Bir Tarfawi and Bir Sahara East, two depressions in what is currently the hyperarid eastern Sahara. The ratios can be used directly to indicate qualitatively the time represented by each series of lake sediment, and to correlate disjunct lacustrine deposits within and between the basins. Uranium-series disequilibrium dating of algal mats contained within some of the lake beds indicate that a major wet interval occurred about 130 ka ago. Using the U-series date for calibration, the amino acid ratios are used to date the most recent lacustrine interval to about 100 ka B.P., and two older intervals, one about 200 ?? 25 ka B.P., and an older interval that occurred prior to 250 ka ago. ?? 1991.

Changing molecular epidemiology and high rates of mupirocin resistance among meticillin-resistant Staphylococcus aureus in Singaporean hospitals.

PubMed

Hon, Pei Yun; Koh, Tse Hsien; Tan, Thean Yen; Krishnan, Prabha; Leong, Janice Wai-Yeng; Jureen, Roland; Chan, Joey; Tee, Nancy Wen-Sim; Murugesh, Jagadeesan; Chan, Kian Sing; Hsu, Li Yang

2014-03-01

A prospective cross-sectional study was performed to determine the continuing shift in the molecular epidemiology of meticillin-resistant Staphylococcus aureus (MRSA) in Singapore. In total, 666 MRSA isolates from screening cultures performed between 7 and 20 January 2013 were obtained from all seven public sector hospitals in Singapore and were subjected to molecular typing using multilocus variable-number tandem-repeat fingerprinting with confirmatory multilocus sequencing typing for clustered isolates. Isolates were also tested for the presence of the orfX-ACME insert and the high-level mupirocin resistance gene ileS-2. The major circulating clones in Singaporean hospitals were ST22 (63.2%), ST45 (18.9%) and ST239 (10.7%). The orfX-ACME insert was only found in ST239 isolates (31/71, 43.7%), but ileS-2 was found in 207 (31.1%) of the MRSA isolates, varying between 10.0% and 47.8% among the hospitals. In conclusion, the molecular epidemiology of MRSA in Singaporean hospitals has continued to change, with ST45 now replacing ST239 in addition to the ongoing replacement of the latter by ST22. Although a greater proportion of ST239 isolates carry the orfX-ACME insert, the actual clinical impact may be marginal as ST239 MRSA continues to decline. Finally, high-level mupirocin resistance rates are remarkably high in local healthcare-associated MRSA, with implications for MRSA decolonisation and infection prevention. Further surveillance is required to monitor the changing epidemiological trends. Copyright © 2013 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Molecular dynamics simulations on the conformational transitions from the GA 98 (GA 88) to GB 98 (GB 88) proteins.

PubMed

Song, Chunnian; Wang, Qing; Xue, Tuo; Wang, Yan; Chen, Guangju

2016-12-01

We performed conventional and targeted molecular dynamics simulations to address the dynamic transition mechanisms of the conformational transitions from the G A 98 protein with only 1 mutation of Leu45Tyr to G B 98 and from the G A 88 protein with 7 mutations of Gly24Ala, Ile25Thr, Ile30Phe, Ile33Tyr, Leu45Tyr, Ile49Thr, and Leu50Lys to G B 88. The results show that the conformational transition mechanism from the mutated 3α G A 98 (G A 88) state to the α+4β G B 98 (G B 88) state via several intermediate conformations involves the bending of loops at the N and C termini firstly, the unfolding of αA and αC, then the traversing of αB, and the formation of the 4β layer with the conversion of the hydrophobic core. The bending of loops at the N and C termini and the formation of the crucial transition conformation with the full unfolded structure are key factors in their transition processes. The communication of the interaction network, the bending directions of loops, and the traversing site of αB in the transition of G A 98 to G B 98 are markedly different from those in G A 88 to G B 88 because of the different mutated residues. The analysis of the correlations and the calculated mass center distances between some segments further supported their conformational transition mechanisms. These results could help people to better understand the Paracelsus challenge. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Transcription of detoxification genes following permethrin selection in the mosquito Aedes aegypti

PubMed Central

Saavedra-Rodriguez, Karla; Suarez, Adriana Flores; Salas, Ildefonso Fernandez; Strode, Clare; Ranson, Hilary; Hemingway, Janet; Black, William C.

2011-01-01

Changes in gene expression before, during and after five generations of permethrin laboratory selection were monitored in six strains of Aedes aegypti: five F2 – F3 collections from the Yucatán Peninsula of México and one F2 from Iquitos, Perú. Three biological replicate lines were generated for each strain. The response to selection was measured as changes in the lethal and knockdown permethrin concentrations (LC50, KC50) and in the frequency of the Ile1,016 substitution in the voltage gated sodium channel (para) gene. Changes in expression of 290 metabolic detoxification genes were measured using the “Aedes Detox” microarray. Selection simultaneously increased the LC50, KC50 and Ile1,016 frequency. There was an inverse relationship between Ile1,016 frequency and the numbers of differentially transcribed genes. The Iquitos strain lacked the Ile1,016 allele and 51 genes were differentially transcribed following selection as compared to 10–18 genes in the Mexican strains. Very few of the same genes were differentially transcribed among field strains but ten cytochrome P450 genes were upregulated in more than one strain. Laboratory adaptation to permethrin in Ae. aegypti is genetically complex and largely conditioned by geographic origin and preexisting target site insensitivity in the para gene. The lack of uniformity in the genes that responded to artificial selection as well as differences in the direction of their responses challenges the assumption that one or a few genes control permethrin metabolic resistance. Attempts to identify one or a few metabolic genes that are predictably associated with permethrin adaptation may be futile. PMID:22032702

The influence of cations on lithium ion coordination and transport in ionic liquid electrolytes: a MD simulation study.

PubMed

Lesch, Volker; Li, Zhe; Bedrov, Dmitry; Borodin, Oleg; Heuer, Andreas

2016-01-07

The dynamical and structural properties in two ionic liquid electrolytes (ILEs) based on 1-ethyl-3-methylimidazolium bis-(trifluoromethanesulfonyl)-imide ([emim][TFSI]) and N-methyl-N-propylpyrrolidinium bis-(trifluoromethanesulfonyl)imide([pyr13][TFSI]) were compared as a function of lithium bis-(trifluoromethanesulfonyl)-imide (LiTFSI) salt concentrations using atomistic molecular dynamics (MD) simulations. The many-body polarizable APPLE&P force field has been utilized. The influence of anion polarization on the structure of the first coordination shell of Li(+) was examined. In particular, the reduction of the oxygen of the TFSI anion (OTFSI) polarizability from 1.36 Å(3) to 1.00 Å(3) resulted in an increased fraction of the TFSI anion bidentate coordination to the Li(+). While the overall dynamics in [pyr13][TFSI]-based ILEs was slower than in [emim][TFSI]-based ILEs, the exchange of TFSI anions in and out of the first coordination shell of Li(+) was found to be faster in pyr13-based systems. The Li(+) ion transference number is higher for these systems as well. These trends can be related to the difference in interaction of TFSI with the IL cation which is stronger for pyr13 than for emim.

Disposed to distraction: Genetic variation in the cholinergic system influences distractibility but not time-on-task effects

PubMed Central

Berry, Anne S.; Demeter, Elise; Sabhapathy, Surya; English, Brett A.; Blakely, Randy D.; Sarter, Martin; Lustig, Cindy

2015-01-01

Both the passage of time and external distraction make it difficult to keep attention on the task at hand. We tested the hypothesis that time-on-task and external distraction pose independent challenges to attention, and that the brain’s cholinergic system selectively modulates our ability to resist distraction. Participants with a polymorphism limiting cholinergic capacity (Ile89Val variant (rs1013940) of the choline transporter gene SLC5A7) and matched controls completed self-report measures of attention and a laboratory task that measured decrements in sustained attention with and without distraction. We found evidence that distraction and time-on-task effects are independent and that the cholinergic system is strongly linked to greater vulnerability to distraction. Ile89Val participants reported more distraction during everyday life than controls, and their task performance was more severely impacted by the presence of an ecologically valid video distractor (similar to a television playing in the background). These results are the first to demonstrate a specific impairment in cognitive control associated with the Ile89Val polymorphism, and add to behavioral and cognitive neuroscience studies indicating the cholinergic system’s critical role in overcoming distraction. PMID:24666128

Implicit LES of Turbulent, Separated Flow: Wall-Mounted Hump Configuration

NASA Technical Reports Server (NTRS)

Sekhar, Susheel; Mansour, Nagi N.; Caubilla, David Higuera

2015-01-01

Direct simulations (ILES) of turbulent, separated flow over the wall-mounted hump configuration is conducted to investigate the physics of separated flows. A chord-based Reynolds number of Re(sub c) = 47,500 is set up, with a turbulent in flow of Re(sub theta) = 1,400 (theta/c = 3%). FDL3DI, a code that solves the compressible Navier-Stokes equations using high- order compact-difference scheme and filter, with the standard recycling/rescaling method of turbulence generation, is used. Two different configurations of the upper-wall are analyzed, and results are compared with both a higher Re(sub c) (= 936,000, Re(sub theta) = 7,200, theta/c = 0.77%) experiment for major flow features, and RANS (k-omega SST) results. A lower Rec allows for DNS-like mesh resolution, and an adequately wide span. Both ILES and RANS show delayed reattachment compared to experiment, and significantly higher skin friction in the forebody of the hump, as expected. The upper-wall shape influences the C(sub p) distribution only. Results from this study are being used to setup higher Rec (lower theta/c) ILES.

Application of liquid chromatography-tandem mass spectrometry in the diagnosis and follow-up of maple syrup urine disease in a Chinese population.

PubMed

Lin, Na; Ye, Jun; Qiu, Wenjuan; Han, Lianshu; Zhang, Huiwen; Gu, Xuefan

2013-01-01

Maple syrup urine disease (MSUD) is an inherited disorder caused by a deficiency of the mitochondrial branched-chain keto acid dehydrogenase complex. We investigated whether liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a more reliable and accurate method than MS/MS in the diagnosis and management of patients with MSUD in a Chinese population. A total of 370 dried blood spots (DBS) from healthy neonates, 44 DBS specimens from phenylketonuria neonates, and 38 DBS samples from 10 MSUD patients were retrospectively tested using the LC-MS/MS method. The results were compared with those obtained by the MS/MS method. The reference intervals of branched-chain amino acids (BCAAs) and alloiosleucine (Allo-Ile) were estimated for both sexes. In classic MSUD patients, Allo-Ile was markedly elevated (average of 136 μmol/L, which was significantly higher than the normal value, <5 μmol/L). The averages of BCAAs were also markedly elevated continually during the treatment. The application of the LC-MS/MS method in the measurement of Allo-Ile and BCAAs in DBS is more useful for diagnosing and managing classic MSUD than the MS/MS method.

Adverse Pregnancy Outcomes after Abnormal First Trimester Screening for Aneuploidy

PubMed Central

Goetzl, Laura

2010-01-01

Women with abnormal first trimester screening but with a normal karyotype are at risk for adverse pregnancy outcomes. A nuchal translucency >3.5mm is associated with an increased risk of subsequent pregnancy loss, fetal infection, fetal heart abnormalities and other structural abnormalities. Abnormal first trimester analytes are also associated with adverse pregnancy outcomes but the predictive value is less impressive. As a single marker, PAPP-A <1st%ile has a good predictive value for subsequent fetal growth restriction. Women with PAPP-A<5th%ile should undergo subsequent risk assessment with routine MSAFP screening with the possible addition of uterine artery PI assessment in the midtrimester. PMID:20638576

Kinetics of CO Recombination to the Heme in Geobacillus Stearothermophilus Nitric Oxide Synthase†

PubMed Central

Whited, Charlotte A.; Warren, Jeffrey J.; Lavoie, Katherine D.; Winkler, Jay R.; Gray, Harry B.

2012-01-01

We report the kinetics of CO rebinding to the heme in His134Ser, Ile223Val and His134Ser/Ile223Ser mutants of Geobacillus stearothermophilus nitric oxide synthase (gsNOS). The amplitudes of the two observed kinetics phases, which are insensitive to CO concentration, depend on enzyme concentration. We suggest that two forms of gsNOS are in equilibrium under the conditions employed (6.1–27 µM gsNOS with 20 or 100% CO atmosphere). The kinetics of CO rebinding to the heme do not depend on the identity of the NO-gate residues at positions 134 and 223. PMID:23976816

Çocuklarda Uyku Ölçeği’nin Geçerlik ve Güvenirliği

PubMed Central

Öner, Pınar; Barut, Yaşar; Öner, Özgür; Üneri, Özden Şükran; Bodur, Şahin; Turgut, Sevil; Munir, Kerim M

2017-01-01

Amaç Bu çalışmada çocuklarda uyku bozukluklarının değerlendirilmesinde kullanılan Çocuklarda Uyku Ölçeği (ÇUÖ)-uzun formunun Türkçe çevirisinin geçerlik ve güvenirliğinin belirlenmesi amaçlanmıştır. Bu ölçeğin kısaltılmış ve uzun olmak üzere 2 ayrı formu bulunmaktadır. Kısa olan form daha çok uykuya bağlı solunum problemleri ile ilişkili iken kapsamlı olan formunda, daha fazla uyku sorunu değerlendirilebilmektedir. Yöntem Ölçeğin Türkçe çevirisi ve geri-çeviri yapıldıktan sonra, 99 Dikkat Eksikliği Hiperaktivite Bozukluğu (DEHB) olgusu, 34 Üst Solunum yolu Direnci ve Horlaması olan (ÜSDH) olgu ve 42 sağlıklı kontrol değerlendirmeye alınmıştır. Güvenilirlik analizi için iç tutarlılık göstergesi olarak Cronbach alfa değerleri, madde-toplam puan korelasyonları ve test-tekrar test güvenirliği hesaplanmıştır. Faktörlerin belirlenmesi için ana bileşenler yöntemi ve varimax rotasyonu kullanılmıştır. Kesim noktaları, duyarlılık, özgüllük, negatif ve pozitif yordayıcı değerlerin hesaplanması için Alıcı İşlem Karakteristik Eğrileri kullanılmıştır. Bulgular Güvenirlik analizinde tüm ölçeğin Cronbach alfa katsayısı 0.77 olarak bulunmuştur. ÇUÖ’nin orijinal çalışmasındakine benzer bir şekilde dört faktörlü bir yapı ortaya çıkmıştır. Ancak, faktörlere farklı maddeler yüklendiği görülmüştür. Bulgular “Horlama,” “Davranış Sorunları” ve “Nefes Alma Sorunları” faktörlerinin gruplar arasında anlamlı farklar ve yeterli geçerlik ve güvenirlik gösterdiğini ancak “Diğer” faktörünün bu özellikleri sergilemediğini göstermektedir. “Nefes Alma Sorunları” DEHB grubunda kontrollerden; “Toplam Uyku Sorunları” da ÜSDH grubunda diğer iki gruptan fazla olarak saptanmıştır. Alıcı İşlem Karakteristik Eğrilerinden elde edilen kesim noktaları incelendiğinde, kesim noktası olarak ÇUÖ Toplam puanı 6 kabul

Incorporation of Tyrosine and Glutamine Residues into the Soluble Guanylate Cyclase Heme Distal Pocket Alters NO and O2 Binding*

PubMed Central

Derbyshire, Emily R.; Deng, Sarah; Marletta, Michael A.

2010-01-01

Nitric oxide (NO) is the physiologically relevant activator of the mammalian hemoprotein soluble guanylate cyclase (sGC). The heme cofactor of α1β1 sGC has a high affinity for NO but has never been observed to form a complex with oxygen. Introduction of a key tyrosine residue in the sGC heme binding domain β1(1–385) is sufficient to produce an oxygen-binding protein, but this mutation in the full-length enzyme did not alter oxygen affinity. To evaluate ligand binding specificity in full-length sGC we mutated several conserved distal heme pocket residues (β1 Val-5, Phe-74, Ile-145, and Ile-149) to introduce a hydrogen bond donor in proximity to the heme ligand. We found that the NO coordination state, NO dissociation, and enzyme activation were significantly affected by the presence of a tyrosine in the distal heme pocket; however, the stability of the reduced porphyrin and the proteins affinity for oxygen were unaltered. Recently, an atypical sGC from Drosophila, Gyc-88E, was shown to form a stable complex with oxygen. Sequence analysis of this protein identified two residues in the predicted heme pocket (tyrosine and glutamine) that may function to stabilize oxygen binding in the atypical cyclase. The introduction of these residues into the rat β1 distal heme pocket (Ile-145 → Tyr and Ile-149 → Gln) resulted in an sGC construct that oxidized via an intermediate with an absorbance maximum at 417 nm. This absorbance maximum is consistent with globin FeII-O2 complexes and is likely the first observation of a FeII-O2 complex in the full-length α1β1 protein. Additionally, these data suggest that atypical sGCs stabilize O2 binding by a hydrogen bonding network involving tyrosine and glutamine. PMID:20231286

Role of Metabolic Genes in Blood Aluminum Concentrations of Jamaican Children with and without Autism Spectrum Disorder

PubMed Central

Rahbar, Mohammad H.; Samms-Vaughan, Maureen; Pitcher, Meagan R.; Bressler, Jan; Hessabi, Manouchehr; Loveland, Katherine A.; Christian, MacKinsey A.; Grove, Megan L.; Shakespeare-Pellington, Sydonnie; Beecher, Compton; McLaughlin, Wayne; Boerwinkle, Eric

2016-01-01

Aluminum is a neurotoxic metal with known health effects in animals and humans. Glutathione-S-transferase (GST) genes and enzymes play a major role in detoxification of several heavy metals. Besides a direct relationship with oxidative stress; aluminum decreases GST enzyme activities. Using data from 116 Jamaican children; age 2–8 years; with Autism Spectrum Disorder (ASD) and 116 sex- and age-matched typically developing (TD) children; we investigated the association of polymorphisms in three GST genes (GSTP1; GSTM1; and GSTT1) with mean blood aluminum concentrations in children with and without ASD. Using log-transformed blood aluminum concentration as the dependent variable in a linear regression model; we assessed the additive and interactive effects of ASD status and polymorphisms in the three aforementioned GST genes in relation to blood aluminum concentrations. Although none of the additive effects were statistically significant (all p > 0.16); we observed a marginally significant interaction between GSTP1 Ile105Val (rs1695) and ASD status (p = 0.07); even after controlling for parental education level and consumption of avocado; root vegetables; and tuna (canned fish). Our findings indicate a significantly lower (p < 0.03) adjusted geometric mean blood aluminum concentration for TD children who had the Val/Val genotype (14.57 µg/L); compared with those with Ile/Ile or Ile/Val genotypes who had an adjusted geometric mean of 23.75 µg/L. However; this difference was not statistically significant among the ASD cases (p = 0.76). Our findings indicate that ASD status may be a potential effect modifier when assessing the association between GSTP1 rs1695 and blood aluminum concentrations among Jamaican children. These findings require replication in other populations. PMID:27834815

A conformational switch in the inhibitory gamma-subunit of PDE6 upon enzyme activation by transducin.

PubMed

Granovsky, A E; Artemyev, N O

2001-11-06

In response to light, a photoreceptor G protein, transducin, activates cGMP-phosphodiesterase (PDE6) by displacing the inhibitory gamma-subunits (Pgamma) from the enzyme's catalytic sites. Evidence suggests that the activation of PDE6 involves a conformational change of the key inhibitory C-terminal domain of Pgamma. In this study, the C-terminal region of Pgamma, Pgamma-73-85, has been targeted for Ala-scanning mutagenesis to identify the point-to-point interactions between Pgamma and the PDE6 catalytic subunits and to probe the nature of the conformational change. Pgamma mutants were tested for their ability to inhibit PDE6 and a chimeric PDE5-conePDE6 enzyme containing the Pgamma C-terminus-binding site of cone PDE. This analysis has revealed that in addition to previously characterized Ile86 and Ile87, important inhibitory contact residues of Pgamma include Asn74, His75, and Leu78. The patterns of mutant PDE5-conePDE6 enzyme inhibition suggest the interaction between the PgammaAsn74/His75 sequence and Met758 of the cone PDE6alpha' catalytic subunit. This interaction, and the interaction between the PgammaIle86/Ile87 and PDE6alpha'Phe777/Phe781 residues, is most consistent with an alpha-helical structure of the Pgamma C-terminus. The analysis of activation of PDE6 enzymes containing Pgamma mutants with Ala-substituted transducin-contact residues demonstrated the critical role of PgammaLeu76. Accordingly, we hypothesize that the initial step in PDE6 activation involves an interaction of transducin-alpha with PgammaLeu76. This interaction introduces a bend into the alpha-helical structure of the Pgamma C-terminus, allowing transducin-alpha to further twist the C-terminus thereby uncovering the catalytic pocket of PDE6.

An evaluation of transport mode shift policies on transport-related physical activity through simulations based on random forests.

PubMed

Brondeel, Ruben; Kestens, Yan; Chaix, Basile

2017-10-23

Physical inactivity is widely recognized as one of the leading causes of mortality, and transport accounts for a large part of people's daily physical activity. This study develops a simulation approach to evaluate the impact of the Ile-de-France Urban Mobility Plan (2010-2020) on physical activity, under the hypothesis that the intended transport mode shifts are realized. Based on the Global Transport Survey (2010, n = 21,332) and on the RECORD GPS Study (2012-2013, n = 229) from the French capital region of Paris (Ile-de-France), a simulation method was designed and tested. The simulation method used accelerometer data and random forest models to predict the impact of the transport mode shifts anticipated in the Mobility Plan on transport-related moderate-to-vigorous physical activity (T-MVPA). The transport mode shifts include less private motorized trips in favor of more public transport, walking, and biking trips. The simulation model indicated a mean predicted increase of 2 min per day of T-MVPA, in case the intended transport mode shifts in the Ile-de-France Urban Mobility Plan were realized. The positive effect of the transport mode shifts on T-MVPA would, however, be larger for people with a higher level of education. This heterogeneity in the positive effect would further increase the existing inequality in transport-related physical activity by educational level. The method presented in this paper showed a significant increase in transport-related physical activity in case the intended mode shifts in the Ile-de-France Urban Mobility Plan were realized. This simulation method could be applied on other important health outcomes, such as exposure to noise or air pollution, making it a useful tool to anticipate the health impact of transport interventions or policies.

Computational simulations assessment of mutations impact on streptokinase (SK) from a group G streptococci with enhanced activity - insights into the functional roles of structural dynamics flexibility of SK and stabilization of SK-μplasmin catalytic complex.

PubMed

Kazemi, Faegheh; Arab, Seyed Shahriar; Mohajel, Nasir; Keramati, Malihe; Niknam, Niloofar; Aslani, Mohammad Mehdi; Roohvand, Farzin

2018-05-28

Streptokinase (SK), a plasminogen activator (PA) that converts inactive plasminogen (Pg) to plasmin (Pm), is a protein secreted by groups A, C, and G streptococci (GAS, GCS, and GGS, respectively), with high sequence divergence and functional heterogeneity. While roles of some residual changes in altered SK functionality are shown, the underlying structural mechanisms are less known. Herein, using computational approaches, we analyzed the conformational basis for the increased activity of SK from a GGS (SKG132) isolate with four natural residual substitutions (Ile33Phe, Arg45Gln, Asn228Lys, Phe287Ile) compared to the standard GCS (SKC). Using the crystal structure of SK.Pm catalytic complex as main template SKC.μPm catalytic complex was modeled through homology modeling process and validated by several online validation servers. Subsequently, SKG132.μPm structure was constructed by altering the corresponding residual substitutions. Results of three independent MD simulations showed increased RMSF values for SKG132.μPm, indicating the enhanced structural flexibility compared to SKC.μPm, specially in 170 and 250 loops and three regions: R1 (149-161), R2 (182-215) and R3 (224-229). In parallel, the average number of Hydrogen bonds in 170 loop, R2 and R3 (especially for Asn228Lys) of SKG132 compared to that of the SKC was decreased. Accordingly, residue interaction networks (RINs) analyses indicated that Asn228Lys might induce more level of structural flexibility by generation of free Lys256, while Phe287Ile and Ile33Phe enhanced the stabilization of the SKG132.μPm catalytic complex. These results denoted the potential role of the optimal dynamic state and stabilized catalytic complex for increased PA potencies of SK as a thrombolytic drug.

Demonstration of isoleucine 199 as a structural determinant for the selective inhibition of human monoamine oxidase B by specific reversible inhibitors.

PubMed

Hubálek, Frantisek; Binda, Claudia; Khalil, Ashraf; Li, Min; Mattevi, Andrea; Castagnoli, Neal; Edmondson, Dale E

2005-04-22

Several reversible inhibitors selective for human monoamine oxidase B (MAO B) that do not inhibit MAO A have been described in the literature. The following compounds: 8-(3-chlorostyryl)caffeine, 1,4-diphenyl-2-butene, and trans,trans-farnesol are shown to inhibit competitively human, horse, rat, and mouse MAO B with K(i) values in the low micromolar range but are without effect on either bovine or sheep MAO B or human MAO A. In contrast, the reversible competitive inhibitor isatin binds to all known MAO B and MAO A with similar affinities. Sequence alignments and the crystal structures of human MAO B in complex with 1,4-diphenyl-2-butene or with trans,trans-farnesol provide molecular insights into these specificities. These inhibitors span the substrate and entrance cavities with the side chain of Ile-199 rotated out of its normal conformation suggesting that Ile-199 is gating the substrate cavity. Ile-199 is conserved in all known MAO B sequences except bovine MAO B, which has Phe in this position (the sequence of sheep MAO B is unknown). Phe is conserved in the analogous position in MAO A sequences. The human MAO B I199F mutant protein of MAO B binds to isatin (K(i) = 3 microM) but not to the three inhibitors listed above. The crystal structure of this mutant demonstrates that the side chain of Phe-199 interferes with the binding of those compounds. This suggests that the Ile-199 "gate" is a determinant for the specificity of these MAO B inhibitors and provides a molecular basis for the development of MAO B-specific reversible inhibitors without interference with MAO A function in neurotransmitter metabolism.

Role of neurotensin and opioid receptors in the cardiorespiratory effects of [Ile⁹]PK20, a novel antinociceptive chimeric peptide.

PubMed

Kaczyńska, Katarzyna; Szereda-Przestaszewska, Małgorzata; Kleczkowska, Patrycja; Lipkowski, Andrzej W

2014-10-15

Ile(9)PK20 is a novel hybrid of opioid-neurotensin peptides synthesized from the C-terminal hexapeptide of neurotensin and endomorphin-2 pharmacophore. This chimeric compound shows potent central and peripheral antinociceptive activity in experimental animals, however nothing is known about its influence on the respiratory and cardiovascular parameters. The present study was designed to determine the cardiorespiratory effects exerted by an intravenous injection (i.v.) of [Ile(9)]PK20. Share of the vagal afferentation and the contribution of NTS1 neurotensin and opioid receptors were tested. Intravenous injection of the hybrid at a dose of 100 μg/kg in the intact, anaesthetized rats provoked an increase in tidal volume preceded by a prompt short-lived decrease. Immediately after the end of injection brief acceleration of the respiratory rhythm appeared, and was ensued by the slowing down of breathing. Changes in respiration were concomitant with a bi-phasic response of the blood pressure: an immediate increase was followed by a sustained hypotension. Midcervical vagotomy eliminated the increase in tidal volume and respiratory rate responses. Antagonist of opioid receptors - naloxone hydrochloride eliminated only [Ile(9)]PK20-evoked decline in tidal volume response. Blockade of NTS1 receptors with an intravenous dose of SR 142,948, lessened the remaining cardiorespiratory effects. This study depicts that [Ile(9)]PK20 acting through neurotensin NTS1 receptors augments the tidal component of the breathing pattern and activates respiratory timing response through the vagal pathway. Blood pressure effects occur outside vagal afferentation and might result from activation of the central and peripheral vascular NTS1 receptors. In summary the respiratory effects of the hybrid appeared not to be profound, but they were accompanied with unfavourable prolonged hypotension. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluation of Glutathione-S-Transferase P1 Polymorphism and its Relation to Bone Mineral Density in Egyptian Children and Adolescents with Beta-Thalassemia Major

PubMed Central

Ragab, Seham M.; Badr, Eman A.; Ibrahim, Ahmed S.

2016-01-01

Background Osteoporosis is a major complication of beta thalassemia major (TM). Increased oxidative stress and its controlling genes were linked to osteoporosis. Ile105 Val variant is a functional polymorphism of Glutathione S-transferase P1 (GSTP1), with reduced anti-oxidative property. No data are available about this variant or its association with osteoporosis among thalassemia patients yet. Objectives To investigate Ile105Val polymorphism and its possible association with bone mineral density (BMD) values in a group of TM children. Methods Thirty five TM children and 30 age and sex matched healthy controls were included. Liver and renal functions, serum ferritin, calcium, phosphorous, alkaline phosphatase and osteocalcin were assayed. BMD was determined by DXA with calculation of Z-scores at lumbar spine (LS) and femoral neck (FN). Height for age Z- score (HAZ) adjusted BMD Z-scores were calculated. GSTP1 Ile105Val polymorphism was studied by polymerase chain reaction-restriction fragment length polymorphism. Results The relative frequency of 105 Val allele was significantly higher in TM patients than the controls (p<0.0001). Significant association between genotype subgroups and BMD parameters was detected. Compared to wild homozygotes, polymorphic homozygotes had lower LS-BMD (p =0.029), LS-BMD Z –score (p=0.008 ), LS- BMD haz - Z-score (p=0.011), FN- BMD (p= 0.001), FN- BMD Z –score (p=0.02) and FN-BMD haz - Z-score (p=0.001). They exhibited higher osteocalcin levels compared to heterozygotes and wild homozygotes (p=0.012, p=0.013, respectively). Conclusion Ile105Val polymorphism was frequent among TM patients and could increase their susceptibility to reduced BMD. Large sample studies are required to confirm these findings. PMID:26740865

Inventory and state of activity of rockglaciers in the Ile and Kungöy Ranges of Northern Tien Shan from satellite SAR interferometry

NASA Astrophysics Data System (ADS)

Strozzi, Tazio; Caduff, Rafael; Kääb, Andreas; Bolch, Tobias

2017-04-01

The best visual expression of mountain permafrost are rockglaciers, which, in contrast to the permafrost itself, can be mapped and monitored directly using remotely sensed data. Studies carried out in various parts of the European Alps have shown surface acceleration of rockglaciers and even destabilization of several such landforms over the two last decades, potentially related to the changing permafrost creep conditions. Changes in rockglacier motion are therefore believed to be the most indicative short- to medium-term response of rockglaciers to environmental changes and thus an indicator of mountain permafrost conditions in general. The ESA DUE GlobPermafrost project develops, validates and implements EO products to support research communities and international organizations in their work on better understanding permafrost characteristics and dynamics. Within this project we are building up a worldwide long-term monitoring network of active rockglacier motion investigated using remote sensing techniques. All sites are analysed through a uniform set of data and methods, and results are thus comparable. In order to quantify the rate of movement and the relative changes over time we consider two remote sensing methods: (i) matching of repeat optical data and (ii) satellite radar interferometry. In this contribution, we focus on the potential of recent high spatial resolution SAR data for the analysis of periglacial processes in mountain environments with special attention to the Ile and Kungöy Ranges of Northern Tien Shan at the border between Kazakhstan and Kyrgyzstan, an area which contains a high number of large and comparably fast (> 1m/yr) rockglaciers and is of interest as dry-season water resource and source of natural hazards. As demonstrated in the past with investigations conducted in the Swiss Alps, the visual analysis of differential SAR interferograms can be employed for the rough estimation of the surface deformation rates of rockglaciers and

What Is Enteral Nutrition?

MedlinePlus

... Solution Center NOVEL Project Parenteral Nutrition Resources Intravenous Lipid Emulsions (ILE) Video Series SmartPN Practice and Research Toolkits Publications & ASPEN Journals Journal of Parenteral and ...

Overweight in Latino Preschoolers: Do Parental Health Beliefs Matter?

PubMed Central

Kersey, Margaret; Lipton, Rebecca; Quinn, Michael T.; Lantos, John D.

2009-01-01

Objective To characterize the knowledge, attitudes, and beliefs (KAB) regarding childhood obesity among parents of Latino preschoolers. Methods Three hundred sixty-nine Mexican immigrant parents of children ages 2–5 were interviewed. Children were weighed and measured. Results Parents underestimated their own child’s weight status and had high levels of perceived control over their children’s eating and activity behaviors. Parents of overweight (≥95%ile-for-age-and-sex BMI) versus nonoverweight (<95%ile BMI) children did not differ in their beliefs about ideal child body size. Conclusion Latino parents of overweight children did not differ from parents of nonoverweight children with respect to their KAB about childhood obesity. PMID:20001191

A comparison of three approaches to compute the effective Reynolds number of the implicit large-eddy simulations

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

Zhou, Ye; Thornber, Ben

2016-04-12

Here, the implicit large-eddy simulation (ILES) has been utilized as an effective approach for calculating many complex flows at high Reynolds number flows. Richtmyer–Meshkov instability (RMI) induced flow can be viewed as a homogeneous decaying turbulence (HDT) after the passage of the shock. In this article, a critical evaluation of three methods for estimating the effective Reynolds number and the effective kinematic viscosity is undertaken utilizing high-resolution ILES data. Effective Reynolds numbers based on the vorticity and dissipation rate, or the integral and inner-viscous length scales, are found to be the most self-consistent when compared to the expected phenomenology andmore » wind tunnel experiments.« less

Chemical and structural changes of pretreated empty fruit bunch (EFB) in ionic liquid-cellulase compatible system for fermentability to bioethanol.

PubMed

Elgharbawy, Amal A; Alam, Md Zahangir; Moniruzzaman, Muhammad; Kabbashi, Nassereldeen Ahmad; Jamal, Parveen

2018-05-01

The pretreatment of empty fruit bunch (EFB) was conducted using an integrated system of IL and cellulases (IL-E), with simultaneous fermentation in one vessel. The cellulase mixture ( PKC-Cel ) was derived from Trichoderma reesei by solid-state fermentation. Choline acetate [Cho]OAc was utilized for the pretreatment due to its biocompatibility and biodegradability. The treated EFB and its hydrolysate were characterized by the Fourier transform infrared spectroscopy, scanning electron microscopy, and chemical analysis. The results showed that there were significant structural changes in EFB after the treatment in IL-E system. The sugar yield after enzymatic hydrolysis by the PKC-Cel was increased from 0.058 g/g of EFB in the crude sample (untreated) to 0.283 and 0.62 ± 06 g/g in IL-E system after 24 and 48 h of treatment, respectively. The EFB hydrolysate showed the eligibility for ethanol production without any supplements where ethanol yield was 0.275 g ethanol/g EFB in the presence of the IL, while lower yield obtained without IL-pretreatment. Moreover, it was demonstrated that furfural and phenolic compounds were not at the level of suppressing the fermentation process.

Intralipid therapy does not improve level of consciousness in overdoses with sedating drugs: a case series.

PubMed

Downes, Michael A; Calver, Leonie A; Isbister, Geoffrey K

2014-06-01

To assess the effect of intralipid emulsion therapy (ILE) in sedating drugs presenting to an urban emergency department. Following the introduction of a clinical protocol for the use of ILE a retrospective chart review was undertaken, which describes the use of ILE in treating sedating drug overdose in a facility with a tertiary referral level clinical toxicology unit. Demographic data as well as details of drug ingested, physiological parameters and disposition were extracted from the medical record. Over a 7 month period nine cases were treated with intralipid, of which two were male and the median age was 33 years (17-52 years). Endotracheal intubation was required in seven cases and of the other two, one required a nasopharyngeal airway for several hours while being observed in a critical care area. One patient was managed in the intensive care unit without intubation. The median duration of ventilation in the seven patients was 31 h (22-82 h), and median length of stay for all nine cases was 63 h (24-133 h). This study does not support any clinically significant effect of intralipid in sedating drug overdose. © 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Hypomorphic PCNA mutation underlies a human DNA repair disorder

PubMed Central

Baple, Emma L.; Chambers, Helen; Cross, Harold E.; Fawcett, Heather; Nakazawa, Yuka; Chioza, Barry A.; Harlalka, Gaurav V.; Mansour, Sahar; Sreekantan-Nair, Ajith; Patton, Michael A.; Muggenthaler, Martina; Rich, Phillip; Wagner, Karin; Coblentz, Roselyn; Stein, Constance K.; Last, James I.; Taylor, A. Malcolm R.; Jackson, Andrew P.; Ogi, Tomoo; Lehmann, Alan R.; Green, Catherine M.; Crosby, Andrew H.

2014-01-01

Numerous human disorders, including Cockayne syndrome, UV-sensitive syndrome, xeroderma pigmentosum, and trichothiodystrophy, result from the mutation of genes encoding molecules important for nucleotide excision repair. Here, we describe a syndrome in which the cardinal clinical features include short stature, hearing loss, premature aging, telangiectasia, neurodegeneration, and photosensitivity, resulting from a homozygous missense (p.Ser228Ile) sequence alteration of the proliferating cell nuclear antigen (PCNA). PCNA is a highly conserved sliding clamp protein essential for DNA replication and repair. Due to this fundamental role, mutations in PCNA that profoundly impair protein function would be incompatible with life. Interestingly, while the p.Ser228Ile alteration appeared to have no effect on protein levels or DNA replication, patient cells exhibited marked abnormalities in response to UV irradiation, displaying substantial reductions in both UV survival and RNA synthesis recovery. The p.Ser228Ile change also profoundly altered PCNA’s interaction with Flap endonuclease 1 and DNA Ligase 1, DNA metabolism enzymes. Together, our findings detail a mutation of PCNA in humans associated with a neurodegenerative phenotype, displaying clinical and molecular features common to other DNA repair disorders, which we showed to be attributable to a hypomorphic amino acid alteration. PMID:24911150

Evaluation of the association between the TAS1R2 and TAS1R3 variants and food intake and nutritional status in children

PubMed Central

Melo, Silvia V.; Agnes, Grasiela; Vitolo, Márcia R.; Mattevi, Vanessa S.; Campagnolo, Paula D.B.; Almeida, Silvana

2017-01-01

Abstract Taste perception plays a key role in determining individual food preferences and dietary habits and may influence nutritional status. This study aimed to investigate the association of TAS1R2 (Ile191Val - rs35874116) and TAS1R3 (-1266 C/T - rs35744813) variants with food intake and nutritional status in children followed from birth until 7.7 years old. The nutritional status and food intake data of 312 children were collected at three developmental stages (1, 3.9 and 7.7 years old). DNA was extracted from blood samples and the polymorphisms were analyzed by real-time polymerase chain reactions (qPCR) using hydrolysis probes as the detection method. Food intake and nutritional status were compared among individuals with different single nucleotide polymorphism (SNP) genotypes. At 3.9 years old, children homozygous (Val/Val) for the TAS1R2 Ile191Val polymorphism ingested less sugar and sugar-dense foods than children who were *Ile carriers. This finding demonstrated that a genetic variant of the T1R2 taste receptor is associated with the intake of different amounts of high sugar-content foods in childhood. This association may provide new perspectives for studying dietary patterns and nutritional status in childhood. PMID:28497839

Evaluation of the association between the TAS1R2 and TAS1R3 variants and food intake and nutritional status in children.

PubMed

Melo, Silvia V; Agnes, Grasiela; Vitolo, Márcia R; Mattevi, Vanessa S; Campagnolo, Paula D B; Almeida, Silvana

2017-01-01

Taste perception plays a key role in determining individual food preferences and dietary habits and may influence nutritional status. This study aimed to investigate the association of TAS1R2 (Ile191Val - rs35874116) and TAS1R3 (-1266 C/T - rs35744813) variants with food intake and nutritional status in children followed from birth until 7.7 years old. The nutritional status and food intake data of 312 children were collected at three developmental stages (1, 3.9 and 7.7 years old). DNA was extracted from blood samples and the polymorphisms were analyzed by real-time polymerase chain reactions (qPCR) using hydrolysis probes as the detection method. Food intake and nutritional status were compared among individuals with different single nucleotide polymorphism (SNP) genotypes. At 3.9 years old, children homozygous (Val/Val) for the TAS1R2 Ile191Val polymorphism ingested less sugar and sugar-dense foods than children who were *Ile carriers. This finding demonstrated that a genetic variant of the T1R2 taste receptor is associated with the intake of different amounts of high sugar-content foods in childhood. This association may provide new perspectives for studying dietary patterns and nutritional status in childhood.

Interactions between cycloguanil derivatives and wild type and resistance-associated mutant Plasmodium falciparum dihydrofolate reductases

NASA Astrophysics Data System (ADS)

Maitarad, Phornphimon; Kamchonwongpaisan, Sumalee; Vanichtanankul, Jarunee; Vilaivan, Tirayut; Yuthavong, Yongyuth; Hannongbua, Supa

2009-04-01

Comparative molecular field analysis (CoMFA) and quantum chemical calculations were performed on cycloguanil (Cyc) derivatives of the wild type and the quadruple mutant (Asn51Ile, Cys59Arg, Ser108Asn, Ile164Leu) of Plasmodium falciparum dihydrofolate reductase ( PfDHFR). The represented CoMFA models of wild type ( r_{{cv}}2 = 0.727 and r 2 = 0.985) and mutant type ( r_{{cv}}2 = 0.786 and r 2 = 0.979) can describe the differences of the Cyc structural requirements for the two types of PfDHFR enzymes and can be useful to guide the design of new inhibitors. Moreover, the obtained particular interaction energies between the Cyc and the surrounding residues in the binding pocket indicated that Asn108 of mutant enzyme was the cause of Cyc resistance by producing steric clash with p-Cl of Cyc. Consequently, comparing the energy contributions with the potent flexible WR99210 inhibitor, it was found that the key mutant residue, Asn108, demonstrates attractive interaction with this inhibitor and some residues, Leu46, Ile112, Pro113, Phe116, and Leu119, seem to perform as second binding site with WR99210. Therefore, quantum chemical calculations can be useful for investigating residue interactions to clarify the cause of drug resistance.

Isolation: analysis and properties of three bradykinin-potentiating peptides (BPP-II, BPP-III, and BPP-V) from Bothrops neuwiedi venom.

PubMed

Ferreira, L A; Galle, A; Raida, M; Schrader, M; Lebrun, I; Habermehl, G

1998-04-01

In the course of systematic investigations on low-molecular-weight compounds from the venom of Crotalidae and Viperidae, we have isolated and characterized at least three bradykinin-potentiating peptides (BPP-II, BPP-III, and BPP-V) from Bothrops neuwiedi venom by gel filtration on Sephadex G-25 M, Sephadex G-10 followed by HPLC. The peptides showed bradykinin-potentiating action on isolated guinea-pig ileum, for which the BPP-V was more active than of BPP-II, and BPP-III, rat arterial blood pressure, and a relevant angiotensin-converting enzyme (ACE) competitive inhibiting activity. The kinetic studies showed a Ki of the order of 9.7 x 10(-3) microM to BPP-II, 7 x 10(-3) microM to BPP-III, and 3.3 x 10(-3) microM to BPP-V. The amino acid sequence of the BPP-III has been determined to be pGlu-Gly-Gly-Trp-Pro-Arg-Pro-Gly-Pro-Glu-Ile-Pro-Pro, and the amino acid compositions of the BPP-II and BPP-V by amino acid analysis were 2Glu-2Gly-1Arg-4Pro-1Ile and 2Glu-2Gly-1Ser-3Pro-2Val-1Ile, with molecular weight of 1372, 1046, and 1078, respectively.

Growth requirements of hyperthermophilic sulfur-dependent heterotrophic archaea isolated from a shallow submarine geothermal system with reference to their essential amino acids.

PubMed Central

Hoaki, T; Nishijima, M; Kato, M; Adachi, K; Mizobuchi, S; Hanzawa, N; Maruyama, T

1994-01-01

Three hyperthermophilic sulfur-dependent heterotrophs were isolated from a shallow submarine hydrothermal system at an inlet of Kodakara-jima island, Kagoshima, Japan. The isolates grew at 60 to 97 degrees C, with the optimum temperatures at 85 to 90 degrees C. Sensitivity to rifampin and the existence of ether lipids indicated that the isolates are hyperthermophilic archaea. Partial sequencing of the genes coding for 16S rRNA showed that the three isolates are closely related to the genus Thermococcus. They grew on proteinaceous mixtures, such as yeast extract, Casamino Acids, and purified proteins (e.g., casein and gelatin), but not on carbohydrates or organic acids as sole carbon and energy sources. Nine amino acids were essential for growth of isolate KS-1 (Thr, Leu, Ile, Val, Met, Phe, His, Tyr, and Arg). Isolate KS-2 required Lys in addition to the nine amino acids, and KS-8 required Lys instead of Tyr. In comparative studies, it was shown that Thermococcus celer DSM 2476 required 10 amino acids (Thr, Leu, Ile, Val, Met, Phe, Tyr, Trp, Lys, and Arg) while Pyrococcus furiosus DSM 3638 required only Ile and Val. The hyperthermophilic fermentative eubacterium Thermotoga neapolitana DSM 4359 did not require any amino acids for growth. Images PMID:8085828

Lack of CHEK2 gene mutations in differentiated thyroid carcinoma patients using high resolution melting analysis.

PubMed

Fayaz, Shima; Fard-Esfahani, Pezhman; Torbati, Peyman Mohammadi

2014-01-01

Recently, mutations in the genes involved in cell cycle control, including CHEK2, are being considered as etiological factors in different kinds of cancers. The CHEK2 protein plays an important role in protecting damaged DNA from entering mitosis. In this study the potential effects of two common mutations IVS2+1G?A and Ile157Thr of CHEK2 gene in differentiated thyroid carcinoma (DTC) were evaluated. A total of 100 patients admitted to the Research Institute for Nuclear Medicine were diagnosed with DTC based on pathology reports of surgery samples. An additional 100 people were selected as a control group with no cancer history. PCR-HRM (high resolution melting) analysis was performed to deal with each of mutations in all case and control samples separately. During the analysis of IVS2+1G?A and Ile157Thr mutations of CHEK2 gene in the case and control groups, all the samples were identified as wild homozygote type. The finding suggests that IVS2+1G?A and Ile157Thr mutations of CHEK2 gene do not constitute a risk factor for DTC in the Iranian population. However, further studies with a larger population are required to confirm the outcome.

Dipeptidyl-peptidase IV inhibitory activity of peptides derived from tuna cooking juice hydrolysates.

PubMed

Huang, Shih-Li; Jao, Chia-Ling; Ho, Kit-Pan; Hsu, Kuo-Chiang

2012-05-01

The in vitro DPP-IV inhibitory activity of isolated peptides from of tuna cooking juice hydrolyzed by Protease XXIII (PR) and orientase (OR) was determined. The results showed that the peptide fractions with the molecular weight over 1,422 Da possessed the greatest DPP-IV inhibitory activity. The amino acid sequences of the three peptides isolated from PR and OR hydrolysates were identified by MALDI-TOF/TOF MS/MS, and they were Pro-Gly-Val-Gly-Gly-Pro-Leu-Gly-Pro-Ile-Gly-Pro-Cys-Tyr-Glu (1412.7 Da), Cys-Ala-Tyr-Gln-Trp-Gln-Arg-Pro-Val-Asp-Arg-Ile-Arg (1690.8 Da) and Pro-Ala-Cys-Gly-Gly-Phe-Try-Ile-Ser-Gly-Arg-Pro-Gly (1304.6 Da), while they showed the dose-dependent inhibition effect of DPP-IV with IC(50) values of 116.1, 78.0 and 96.4 μM, respectively. In vitro simulated gastrointestinal digestion retained or even improved the DPP-IV inhibitory activities of the three peptides. The results suggest that tuna cooking juice would be a good precursor of DPP-IV inhibitor, and the DPP-IV inhibitory peptides can successfully passed through the digestive tract. Copyright © 2012 Elsevier Inc. All rights reserved.

Popular Ideas, Attitudes, and Value Patterns Affecting Participation in Adult Literacy Programs in Slum Communities of Turkey: The Case of Nato Yolu Neighborhood

ERIC Educational Resources Information Center

Yildiz, Ahmet

2008-01-01

Despite the fact that there are nationwide literacy programs in Turkey in order to raise the literacy rate, the participation of illiterate individuals in these programs is not at a satisfactory level. This article is a study into the popular ideas, attitudes, and value patterns that negatively affect participation in literacy programs in a slum…

[Retrospective study of clozapine use in Ile-de-France].

PubMed

Hiltgen, S; Mantelet, S; Pinabel, F; Enjaume, F

2006-10-01

Clozapine, synthesized in the sixties, is an atypical antipsychotic drug whose history has been marked by its haematological toxicity. The purpose of this study was, ten years after it had been replaced at French psychiatrists' disposal, to gather data on the prescription modalities of clozapine, assess whether some factors could affect its efficacy, and describe the population of schizophrenic patients concerned. Psychiatrists in the Paris region were asked to answer a questionnaire about their patients treated with clozapine. The information collected was about socio-demographic data, history of psychiatric disorder and the way clozapine was used. It was a retrospective study concerning 98 patients. Subjects were 57 men and 41 women, with a mean age of 38 years. The majority of patients came from metropolitan France. Patients suffered from various clinical subtypes of schizophrenia, as assessed according to DSM IV criteria. Predominant symptomatology during lifetime was most often auditory hallucinations (41%). Mean duration of lifetime neuroleptic treatment was 10.3 years and breaks in follow-up were rare. Mean number of hospitalisations was 6.9 and a little less than half of the patients had been committed involuntarily. Lastly, 38% of patients had attempted suicide at least once and 35% had expressed hetero-agressive behavior. Main indication of clozapine was resistant schizophrenia (88.5% of patients) and mean duration of treatment was 2 years and 4 months. Treatment efficacy was assessed as good or medium in 77.9% of patients, at mean doses (322 mg per day) in keeping with data from the literature. Tolerance was considered on the whole as satisfactory by half of the clinicians. Among the 98 patients of the study, 21.6% had stopped taking clozapine. The reasons for withdrawal were: inefficacy (6.2%), granulopenia (5.2%), epilepsy (1%) and 8.2% for various reasons (half of these cases being non-compliance with treatment). The study of the 5 cases of granulopenia showed that 3 patients had another associated psychotropic medication: 1 patient received only clozapine as monotherapy, 1 data was missing. Two thirds of all patients were receiving another psychotropic drug in association with clozapine, mainly benzodiazepines (18.4%), antidepressants (15.3%) or mood stabilizers (7.1%). The "therapeutic efficacy" variable was compared with some variables in order to isolate factors possibly associated with a better efficacy of clozapine or, on the contrary, with a population of patients poorly responding to treatment. However, no statistically significant difference appeared according to the variables studied, such as gender or lifetime duration of neuroleptic treatment. Moreover, there was no statistically significant difference in efficacy according to schizophrenia subtype, main symptomatology during the course of illness or substance abuse. We studied whether any factor could affect the occurrence of granulopenia. No statistically significant difference was found. The mean age of patients having stopped the treatment because of granulopenia was higher than in the group with other reasons for interruption, but did not reach statistical significance. A trend also appeared towards female predominance (60% of women in the granulopenia group) and 3/4 of patients who had stopped their treatment because of agranulocytosis received another psychotropic drug in association with clozapine. As expected, the main indication for prescribing clozapine was resistant schizophrenia, but contrary to data from the international literature, the efficacy profile was the same whatever the clinical subtype of schizophrenia. The tolerance to clozapine was considered on the whole as satisfactory, but the high proportion of granulopenias leading to treatment withdrawal (5.2% of patients) confirms the need to remain cautious and stresses the importance of regular haematological monitoring. Furthermore, the study of the prescription modalities of clozapine shows that contrary to the guidelines, clozapine is often associated with other psychotropic drugs. In this study, it is striking to note that 75% of granulopenias occurred in a coprescription situation.

Design of an α-helical antimicrobial peptide with improved cell-selective and potent anti-biofilm activity

PubMed Central

Zhang, Shi-Kun; Song, Jin-wen; Gong, Feng; Li, Su-Bo; Chang, Hong-Yu; Xie, Hui-Min; Gao, Hong-Wei; Tan, Ying-Xia; Ji, Shou-Ping

2016-01-01

AR-23 is a melittin-related peptide with 23 residues. Like melittin, its high α-helical amphipathic structure results in strong bactericidal activity and cytotoxicity. In this study, a series of AR-23 analogues with low amphipathicity were designed by substitution of Ala1, Ala8 and Ile17 with positively charged residues (Arg or Lys) to study the effect of positively charged residue distribution on the biological viability of the antimicrobial peptide. Substitution of Ile17 on the nonpolar face with positively charged Lys dramatically altered the hydrophobicity, amphipathicity, helicity and the membrane-penetrating activity against human cells as well as the haemolytic activity of the peptide. However, substitution on the polar face only slightly affected the peptide biophysical properties and biological activity. The results indicate that the position rather than the number of positively charged residue affects the biophysical properties and selectivity of the peptide. Of all the analogues, A(A1R, A8R, I17K), a peptide with Ala1-Arg, Ala8-Arg and Ile17-Lys substitutions, exhibited similar bactericidal activity and anti-biofilm activity to AR-23 but had much lower haemolytic activity and cytotoxicity against mammalian cells compared with AR-23. Therefore, the findings reported here provide a rationalization for peptide design and optimization, which will be useful for the future development of antimicrobial agents. PMID:27271216

The dominant role of side chains in supramolecular double helical organisation in synthetic tripeptides

NASA Astrophysics Data System (ADS)

Sharma, Ankita; Tiwari, Priyanka; Dutt Konar, Anita

2018-06-01

Peptide self-assembled nanostructures have attracted attention recently owing to their promising applications in diversified avenues. To validate the importance of sidechains in supramolecular architectural stabilization, herein this report describes the self-assembly propensities involving weak interactions in a series of model tripeptides Boc-Xaa-Aib-Yaa-OMe I-IV, (where Xaa = 4-F-Phe/NMeSer/Ile & Yaa = Tyr in peptide I-III respectively and Xaa = 4-F-Phe & Yaa = Ile in peptide IV) differing in terminal side chains. The solid state structural analysis reveals that tripeptide (I) displays supramolecular preference for double helical architecture. However, when slight modification has been introduced in the N-terminal side chains disfavour the double helical organisation (Peptide II and III). Indeed the peptides display sheet like ensemble within the framework. Besides replacement of C-terminal Tyr by Ile in peptide I even do not promote the architecture, emphasizing the dominant role of balance of side chains in stabilizing double helical organisation. The CD measurements, concentration dependant studies, NMR titrations and ROESY spectra are well in agreement with the solid state conformational investigation. Moreover the morphological experiments utilizing FE-SEM, support the heterogeneity present in the peptides. Thus this work may not only hold future promise in understanding the structure and function of neurodegenerative diseases but also assist in rational design of protein modification in biologically active peptides.

Naturally fractured tight gas reservoir detection optimization. Quarterly report, April--June 1994

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

Not Available

1994-07-01

Geologic assessment of the basin during the third quarter possessed several major objectives. The first task was to test the validity of the gas-centered basin model for the Piceance Basin. The second objective was to define the location and variability of gas-saturated zones within the Williams Fork and Iles Formation reservoir horizons. A third objective was to prepare an updated structure map of the Piceance Basin on the top of the Iles Formation (Rollins Sandstone) to take advantage of new data provided by ten years of drilling activity throughout the basin. The first two objectives formed the core of themore » ARI poster session presented at the AAPG annual meeting in Denver. The delineation of the gas and water-saturated zone geometries for the Williams Fork and Iles Formations in the basin was presented in the form of a poster session at the AAPG Annual meeting held in Denver in mid-June. The poster session outlined the nature of the gas-centered basin geometry and demonstrated the gas and water-saturated conditions for the Williams Fork, Cozzette and Corcoran reservoir horizons throughout the basin. Initial and cumulative production data indicate that these reservoir horizons are gas-saturated in most of the south-central and eastern basin. The attached report summarizes the data and conclusions of the poster session.« less

Identification of dipeptidyl peptidase-IV inhibitory peptides from mare whey protein hydrolysates.

PubMed

Song, J J; Wang, Q; Du, M; Ji, X M; Mao, X Y

2017-09-01

Inhibition of dipeptidyl peptidase-IV (DPP-IV) activity is a promising strategy for treatment of type 2 diabetes. In the current study, DPP-IV inhibitory peptides were identified from mare whey protein hydrolysates obtained by papain. The results showed that all the mare whey protein hydrolysates obtained at various hydrolysis durations possessed more potent DPP-IV inhibitory activity compared with intact whey protein. The 4-h hydrolysates showed the greatest DPP-IV inhibitory activity with half-maximal inhibitory concentration of 0.18 mg/mL. The 2 novel peptides from 4-h hydrolysate fractions separated by successive chromatographic steps were characterized by liquid chromatography-electrospray ionization tandem mass spectrometry. The novel peptides Asn-Leu-Glu-Ile-Ile-Leu-Arg and Thr-Gln-Met-Val-Asp-Glu-Glu-Ile-Met-Glu-Lys-Phe-Arg, which corresponded to β-lactoglobulin 1 f(71-77) and β-lactoglobulin 1 f(143-155), demonstrated DPP-IV inhibitory activity with half-maximal inhibitory concentrations of 86.34 and 69.84 μM, respectively. The DPP-IV inhibitory activity of the 2 peptides was retained or even improved after simulated gastrointestinal digestion in vitro. Our findings indicate that mare whey protein-derived peptides may possess potential as functional food ingredients in the management of type 2 diabetes. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Ranalexin. A novel antimicrobial peptide from bullfrog (Rana catesbeiana) skin, structurally related to the bacterial antibiotic, polymyxin.

PubMed

Clark, D P; Durell, S; Maloy, W L; Zasloff, M

1994-04-08

Antimicrobial peptides comprise a diverse class of molecules used in host defense by plants, insects, and animals. In this study we have isolated a novel antimicrobial peptide from the skin of the bullfrog, Rana catesbeiana. This 20 amino acid peptide, which we have termed Ranalexin, has the amino acid sequence: NH2-Phe-Leu-Gly-Gly-Leu-Ile-Lys-Ile-Val-Pro-Ala-Met-Ile-Cys-Ala-Val-Thr- Lys-Lys - Cys-COOH, and it contains a single intramolecular disulfide bond which forms a heptapeptide ring within the molecule. Structurally, Ranalexin resembles the bacterial antibiotic, polymyxin, which contains a similar heptapeptide ring. We have also cloned the cDNA for Ranalexin from a metamorphic R. catesbeiana tadpole cDNA library. Based on the cDNA sequence, it appears that Ranalexin is initially synthesized as a propeptide with a putative signal sequence and an acidic amino acid-rich region at its amino-terminal end. Interestingly, the putative signal sequence of the Ranalexin cDNA is strikingly similar to the signal sequence of opioid peptide precursors isolated from the skin of the South American frogs Phyllomedusa sauvagei and Phyllomedusa bicolor. Northern blot analysis and in situ hybridization experiments demonstrated that Ranalexin mRNA is first expressed in R. catesbeiana skin at metamorphosis and continues to be expressed into adulthood.

Association of polymorphisms in glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) with idiopathic azoospermia or oligospermia in Sichuan, China.

PubMed

Xiong, Da-Ke; Chen, Hong-Han; Ding, Xian-Ping; Zhang, Shao-Hong; Zhang, Jian-Hui

2015-01-01

The reported effects of the glutathione S-transferase (GSTs) genes (GSTM1, GSTT1, and GSTP1) on male factor infertility have been inconsistent and even contradictory. Here, we conducted a case-control study to investigate the association between functionally important polymorphisms in GST genes and idiopathic male infertility. The study group consisted of 361 men with idiopathic azoospermia, 118 men with idiopathic oligospermia, and 234 age-matched healthy fertile male controls. Genomic DNA was extracted from the peripheral blood, and analyzed by polymerase chain reaction and restriction fragment length polymorphism analysis. There was a significant association between the GSTP1 variant genotype (Ile/Val + Val/Val) with idiopathic infertility risk (odds ratio [OR]: 1.53; 95% confidence interval [CI]: 1.11-2.11; P = 0.009). Similarly, a higher risk of infertility was noted in individuals carrying a genotype combination of GSTT1-null and GSTP1 (Ile/Val + Val/Val) (OR: 2.17; 95% CI: 1.43-3.31; P = 0.0002). These results suggest an increased risk of the GSTP1 variant genotype (Ile/Val + Val/Val) for developing male factor infertility. Our findings also underrate the significance of the effect of GSTM1 and/or GSTT1 (especially the former) in modulating the risk of male infertility in males from Sichuan, Southwest China.

Glutathione S-transferase polymorphisms (GSTM1, GSTT1, GSTP1) and male factor infertility risk: a pooled analysis of studies.

PubMed

Safarinejad, Mohammad Reza; Dadkhah, Farid; Ali Asgari, Majid; Hosseini, Seyed Yousef; Kolahi, Ali Asgar; Iran-Pour, Elham

2012-01-01

To determine the role of glutathione S-transferases (GSTs; GSTM1, GSTT1, and GSTP1) gene polymorphisms in susceptibility to male factor infertility. We report a pooled analysis of 11 studies on the association of GSTM1, GSTT1, and GSTP1 polymorphisms and male factor infertility, including 1323 cases and 1054 controls. An overall significant association was determined between the GSTM1 null genotype [odds ratio (OR), 2.74; 95% confidence interval (CI), 1.72 to 3.84; P = .003], GSTT1 null genotype (OR, 1.54; 95% CI, 1.43 to 3.47; P = .02), and male factor infertility. The GSTP1 Ile/Val genotype had overall protective effect against development of infertility (OR, 0.48; 95% CI, 0.27 to 0.77), while there was significant heterogeneity between studies. In sensitivity analysis, two studies were excluded; the association and direction between GSTM1 and GSTT1 null genotypes and GSTP1 Ile/Val genotype and male infertility remained unchanged. There was no significant interaction between smoking status and studied genotypes on male infertility risk (P = .26). These results demonstrated that amongst populations studied to date, GSTM1 and GSTT1 null genotypes are associated with strong and modest increase in the risk of male infertility, respectively. On the contrary, GSTP1 Ile/Val genotype has protective effect.

Monet's Painting under the Microscope

NASA Astrophysics Data System (ADS)

Dredge, Paula; Wuhrer, Richard; Phillips, Matthew R.

2003-04-01

An oil painting by Claude Monet, Port-Goulphar, Belle-Ile 1887 (collection of the Art Gallery of New South Wales), was examined to determine both the identity of the pigments used by the artist in this painting and his technique of mixing colors and laying paint on the canvas. The extremely complex construction of the painting was revealed by optical microscopy, scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDS), and X-ray mapping (XRM) analysis of cross sections of paint flakes excised from damaged regions of Port-Goulphar, Belle-Ile. Nine different pigments were found on the painting. Many of the identified colors were modern pigments that became available only late in the 19th century as a result of scientific advances in pigment chemistry. Although similar colors were available in a natural mineral form, they lacked the vivid color of their manufactured counterparts. The use of these new synthetic metallic oxide colors by Monet accounts for the brilliance of his paintings. In addition, a separation between successive paint layers was observed in some areas of paint chip cross sections, indicating that oil-based paint was applied to paint that had dried, and consequently, Port-Goulphar, Belle-Ile was painted over a long period of time. This observation is contrary to the general perception of Monet's technique of painting freely and quickly.

Effect of Genetic Polymorphisms and Long-Term Tobacco Exposure on the Risk of Breast Cancer.

PubMed

Verde, Zoraida; Santiago, Catalina; Chicharro, Luis Miguel; Reinoso-Barbero, Luis; Tejerina, Alejandro; Bandrés, Fernando; Gómez-Gallego, Félix

2016-10-14

Tobacco smoke contains many potentially harmful compounds that may act differently and at different stages in breast cancer development. The focus of this work was to assess the possible role of cigarette smoking (status, dose, duration or age at initiation) and polymorphisms in genes coding for enzymes involved in tobacco carcinogen metabolism ( CYP1A1 , CYP2A6 ) or in DNA repair ( XRCC1 , APEX1 , XRCC3 and XPD ) in breast cancer development. We designed a case control study with 297 patients, 217 histologically verified breast cancers (141 smokers and 76 non-smokers) and 80 healthy smokers in a cohort of Spanish women. We found an association between smoking status and early age at diagnosis of breast cancer. Among smokers, invasive carcinoma subtype incidence increased with intensity and duration of smoking (all P trend < 0.05). When smokers were stratified by smoking duration, we only observed differences in long-term smokers, and the CYP1A1 Ile462Ile genotype was associated with increased risk of breast cancer (OR = 7.12 (1.98-25.59)). Our results support the main effect of CYP1A1 in estrogenic metabolism rather than in tobacco carcinogen activation in breast cancer patients and also confirmed the hypothesis that CYP1A1 Ile462Val , in association with long periods of active smoking, could be a breast cancer risk factor.

Mapping of the Localization of Type 1 Angiotensin Receptor in Membrane Microdomains Using Bioluminescence Resonance Energy Transfer-based Sensors*

PubMed Central

Balla, András; Tóth, Dániel J.; Soltész-Katona, Eszter; Szakadáti, Gyöngyi; Erdélyi, László Sándor; Várnai, Péter; Hunyady, László

2012-01-01

Initiation and termination of signaling of the type I angiotensin receptor (AT1-R) can lead to dynamic changes in its localization in plasma membrane microdomains. Several markers were recently developed to investigate membrane microdomains. Here, we used several YFP-labeled fusion constructs (i.e. raft or non-raft plasma membrane markers) to analyze the agonist-induced changes in compartmentalization of AT1-R, including internalization or lateral movement between plasma membrane compartments in response to stimulation using bioluminescence resonance energy transfer measurements. Our data demonstrate that angiotensin II (AngII) stimulus changes the microdomain localization of wild type or mutated (DRY → AAY or TSTS → AAAA) AT1-Rs co-expressed with the fluorescent probes in HEK293 cells. The comparison of the trafficking of AT1-R upon AngII stimulus with those of [Sar1,Ile8]AngII or [Sar1,Ile4,Ile8]AngII stimulus revealed different types of changes, depending on the nature of the ligand. The observed changes in receptor compartmentalization of the AT1-R are strikingly different from those of 5HT-2C and EGF receptors, which demonstrate the usefulness of the bioluminescence resonance energy transfer-based measurements in the investigation of receptor trafficking in the plasma membrane in living cell experiments. PMID:22291018

Monet's painting under the microscope.

PubMed

Dredge, Paula; Wuhrer, Richard; Phillips, Matthew R

2003-04-01

An oil painting by Claude Monet, Port-Goulphar, Belle-Ile 1887 (collection of the Art Gallery of New South Wales), was examined to determine both the identity of the pigments used by the artist in this painting and his technique of mixing colors and laying paint on the canvas. The extremely complex construction of the painting was revealed by optical microscopy, scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDS), and X-ray mapping (XRM) analysis of cross sections of paint flakes excised from damaged regions of Port-Goulphar, Belle-Ile. Nine different pigments were found on the painting. Many of the identified colors were modern pigments that became available only late in the 19th century as a result of scientific advances in pigment chemistry. Although similar colors were available in a natural mineral form, they lacked the vivid color of their manufactured counterparts. The use of these new synthetic metallic oxide colors by Monet accounts for the brilliance of his paintings. In addition, a separation between successive paint layers was observed in some areas of paint chip cross sections, indicating that oil-based paint was applied to paint that had dried, and consequently, Port-Goulphar, Belle-Ile was painted over a long period of time. This observation is contrary to the general perception of Monet's technique of painting freely and quickly.

3-Hydroxyisobutyrate Dehydrogenase Is Involved in Both, Valine and Isoleucine Degradation in Arabidopsis thaliana.

PubMed

Schertl, Peter; Danne, Lennart; Braun, Hans-Peter

2017-09-01

In plants, amino acid catabolism is especially relevant in metabolic stress situations (e.g. limited carbohydrate availability during extended darkness). Under these conditions, amino acids are used as alternative substrates for respiration. Complete oxidation of the branched-chain amino acids (BCAAs) leucine, isoleucine (Ile), and valine (Val) in the mitochondria efficiently allows the formation of ATP by oxidative phosphorylation. However, the metabolic pathways for BCAA breakdown are largely unknown so far in plants. A systematic search for Arabidopsis ( Arabidopsis thaliana ) genes encoding proteins resembling enzymes involved in BCAA catabolism in animals, fungi, and bacteria as well as proteomic analyses of mitochondrial fractions from Arabidopsis allowed the identification of a putative 3-hydroxyisobutyrate dehydrogenase, AtHDH1 (At4g20930), involved in Val degradation. Systematic substrate screening analyses revealed that the protein uses 3-hydroxyisobutyrate but additionally 3-hydroxypropionate as substrates. This points to a role of the enzyme not only in Val but possibly also in Ile metabolism. At4g20930 knockdown plants were characterized to test this conclusion. Root toxicity assays revealed increased root growth inhibition of the mutants if cultivated in the presence of Val or Ile but not in the presence of leucine. We conclude that AtHDH1 has a dual role in BCAA metabolism in plants. © 2017 American Society of Plant Biologists. All Rights Reserved.

Comparison of V-4 and V-5 Exercise/Oxygen Prebreathe Protocols to Support Extravehicular Activity in Microgravity

NASA Technical Reports Server (NTRS)

Pollock, N. W.; Natoli, M. J.; Vann, R. D.; Gernhardt, M. L.; Conkin, Johnny

2007-01-01

The Prebreathe Reduction Program (PRP) used exercise during oxygen prebreathe to reduce necessary prebreathe time prior to depressurizing to work in a 4.3 psi suit during extravehicular activity (EVA). Initial testing produced a two-hour protocol incorporating ergometry exercise and a 30 min cycle of depress/repress to 10.2 psi where subjects breathed 26.5% oxygen/balance nitrogen (Phase II - 10 min at 75% peak oxygen consumption [VO2 peak] followed by 40 min intermittent light exercise [ILE] [approx. 5.8 mL-per kilogram- per minute], then 50 min of rest). The Phase II protocol (0/45 DCS) was approved for operations and has been used on 40 EVAs, providing significant time savings compared to the standard 4 h resting oxygen prebreathe. The Phase V effort focused on performing all light in-suit exercise. Two oxygen prebreathe protocols were tested sequentially: V-4) 160 min prebreathe with 150 min of continuous ILE. The entire protocol was completed at 14.7 psi. All exercise involved upper body effort. Exercise continued until decompression. V-5) 160 min prebreathe with 140 min of ILE - first 40 min at 14.7 psi, then 30 min at 10.2 psi (breathing 26.5% oxygen) after a 20 min depress, simulating a suit donning period. Subjects were then repressed to 14.7 psi and performed another 50 min of lower body ILE, followed by 50 min rest before decompression. The V-4 protocol was rejected with 3 DCS/6 person-exposures. Initial V-5 testing has produced 0 DCS/11 person-exposures (ongoing trials). The difference in DCS rate was significant (Fisher Exact p=0.029). The observations of DCS were significantly lower in early V-5 trials than in V-4 trials. Additional studies are required to evaluate the relative contribution of the variables in exercise distribution, the 10.2 psi depress/repress component, pre-decompression rest, or possible variation in total oxygen consumption.

The topology of metabolic isotope labeling networks.

PubMed

Weitzel, Michael; Wiechert, Wolfgang; Nöh, Katharina

2007-08-29

Metabolic Flux Analysis (MFA) based on isotope labeling experiments (ILEs) is a widely established tool for determining fluxes in metabolic pathways. Isotope labeling networks (ILNs) contain all essential information required to describe the flow of labeled material in an ILE. Whereas recent experimental progress paves the way for high-throughput MFA, large network investigations and exact statistical methods, these developments are still limited by the poor performance of computational routines used for the evaluation and design of ILEs. In this context, the global analysis of ILN topology turns out to be a clue for realizing large speedup factors in all required computational procedures. With a strong focus on the speedup of algorithms the topology of ILNs is investigated using graph theoretic concepts and algorithms. A rigorous determination of all cyclic and isomorphic subnetworks, accompanied by the global analysis of ILN connectivity is performed. Particularly, it is proven that ILNs always brake up into a large number of small strongly connected components (SCCs) and, moreover, there are natural isomorphisms between many of these SCCs. All presented techniques are universal, i.e. they do not require special assumptions on the network structure, bidirectionality of fluxes, measurement configuration, or label input. The general results are exemplified with a practically relevant metabolic network which describes the central metabolism of E. coli comprising 10390 isotopomer pools. Exploiting the topological features of ILNs leads to a significant speedup of all universal algorithms for ILE evaluation. It is proven in theory and exemplified with the E. coli example that a speedup factor of about 1000 compared to standard algorithms is achieved. This widely opens the door for new high performance algorithms suitable for high throughput applications and large ILNs. Moreover, for the first time the global topological analysis of ILNs allows to comprehensively

Jasmonic acid-amino acid conjugation enzyme assays.

PubMed

Rowe, Martha L; Staswick, Paul E

2013-01-01

Jasmonic acid (JA) is activated for signaling by its conjugation to isoleucine (Ile) through an amide linkage. The Arabidopsis thaliana JASMONIC ACID RESISTANT1 (JAR1) enzyme carries out this Mg-ATP-dependent reaction in two steps, adenylation of the free carboxyl of JA, followed by condensation of the activated group to Ile. This chapter details the protocols used to detect and quantify the enzymatic activity obtained from a glutathione-S-transferase:JAR1 fusion protein produced in Escherichia coli, including an isotope exchange assay for the adenylation step and assays for the complete reaction that involve the high-performance liquid chromatography quantitation of adenosine monophosphate, a stoichiometric by-product of the reaction, and detection of the conjugation product by thin-layer chromatography or gas -chromatography/mass spectrometry.

Purification and structural characterization of vasoactive intestinal polypeptide from the trout and bowfin.

PubMed

Wang, Y; Conlon, J M

1995-04-01

Vasoactive intestinal polypeptide (VIP) was purified from extracts of the stomachs of the rainbow trout, Oncorhynchus mykiss, and the bowfin, Amia calva. The primary structure of VIP from both species was the same: His-Ser-Asp-Ala-Ile-Phe-Thr-Asp-Asn-Tyr10- Ser-Arg-Phe-Arg-Lys-Gln-Met-Ala-Val-Lys20-Lys-Tyr-Leu-Asn-Ser-Val- Leu-Thr. This amino acid sequence shows only one amino acid substitution (Val5-->Ile) compared with the common sequence of VIP from the chicken, alligator, and European green frog. The structural identity of VIP from the trout and bowfin is consistent with the close phylogenetic relationship between the Salmoniformes and the Amiiformes and the data indicate that pressure to conserve the complete primary structure of VIP during vertebrate evolution has been very strong.

Fragile X Mental Retardation Syndrome: Structure of the KH1-KH2 Domains of Fragile X Mental Retardation Protein

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

Valverde,R.; Poznyakova, I.; Kajander, T.

Fragile X syndrome is the most common form of inherited mental retardation in humans, with an estimated prevalence of about 1 in 4000 males. Although several observations indicate that the absence of functional Fragile X Mental Retardation Protein (FMRP) is the underlying basis of Fragile X syndrome, the structure and function of FMRP are currently unknown. Here, we present an X-ray crystal structure of the tandem KH domains of human FMRP, which reveals the relative orientation of the KH1 and KH2 domains and the location of residue Ile304, whose mutation to Asn is associated with a particularly severe incidence ofmore » Fragile X syndrome. We show that the Ile304Asn mutation both perturbs the structure and destabilizes the protein.« less

Epitope Mapping of Monoclonal Antibody PMab-48 Against Dog Podoplanin.

PubMed

Yamada, Shinji; Kaneko, Mika K; Itai, Shunsuke; Chang, Yao-Wen; Nakamura, Takuro; Yanaka, Miyuki; Ogasawara, Satoshi; Murata, Takeshi; Uchida, Hiroaki; Tahara, Hideaki; Harada, Hiroyuki; Kato, Yukinari

2018-04-02

Podoplanin (PDPN), a type I transmembrane sialoglycoprotein, is expressed on normal renal podocytes, pulmonary type I alveolar cells, and lymphatic endothelial cells. Increased expression of PDPN in cancers is associated with poor prognosis and hematogenous metastasis through interactions with C-type lectin-like receptor 2 (CLEC-2) on platelets. We previously reported a novel PMab-48 antibody, which is an anti-dog PDPN (dPDPN) monoclonal antibody (mAb) recognizing PDPN expressed in lymphatic endothelial cells. However, the binding epitope of PMab-48 is yet to be clarified. In this study, an enzyme-linked immunosorbent assay and flow cytometry were used to investigate epitopes of PMab-48. The results revealed that the critical epitope of PMab-48 comprises Asp29, Asp30, Ile31, Ile32, and Pro33 of dPDPN.

Isolation and structural analysis of antihypertensive peptides that exist naturally in Gouda cheese.

PubMed

Saito, T; Nakamura, T; Kitazawa, H; Kawai, Y; Itoh, T

2000-07-01

Seven kinds of ripened cheeses (8-mo-aged and 24-mo-aged Gouda, Emmental, Blue, Camembert, Edam, and Havarti) were homogenized with distilled water, and water-soluble peptides were prepared by C-18 hydrophobic chromatography. The inhibitory activity to angiotensin I-converting enzyme and decrease in the systolic blood pressure in spontaneously hypertensive rats were measured before and after oral administration of each peptide sample. The strongest depressive effect in the systolic blood pressure (-24.7 mm Hg) and intensive inhibitory activity to angiotensin I-converting enzyme (75.7%) were detected in the peptides from 8-mo-aged Gouda cheese. Four peptides were isolated by HPLC with reverse-phase and gel filtration modes. Their chemical structures and origins, clarified by combination analyses of protein sequencing, amino acid composition, and mass spectrometry, were as follows: peptide A, Arg-Pro-Lys-His-Pro-Ile-Lys-His-Gln [alpha(s1)-casein (CN), B-8P; f 1-9]; peptide B, Arg-Pro-Lys-His-Pro-Ile-Lys-His-Gln-Gly-Leu-Pro-Gln (alpha(s1)-CN, B-8P; f 1-13); peptide F, Tyr-Pro-Phe-Pro-Gly-Pro-Ile-Pro-Asn (beta-CN, A2-5P; f 60-68); and peptide G, Met-Pro-Phe-Pro-Lys-Tyr-Pro-Val-Gln-Pro-Phe (beta-CN, A2-5P; f 109-119). Peptides A and F, which were chemically synthesized, showed potent angiotensin I-converting enzyme inhibitory activity with little antihypertensive effects.

Combinatorial interactions of two amino acids with a single base pair define target site specificity in plant dimeric homeodomain proteins

PubMed Central

Tron, Adriana E.; Bertoncini, Carlos W.; Palena, Claudia M.; Chan, Raquel L.; Gonzalez, Daniel H.

2001-01-01

Four groups of plant homeodomain proteins contain a dimerization motif closely linked to the homeodomain. We here show that two sunflower homeodomain proteins, Hahb-4 and HAHR1, which belong to the Hd-Zip I and GL2/Hd-Zip IV groups, respectively, show different binding preferences at a defined position of a pseudopalindromic DNA-binding site used as a target. HAHR1 shows a preference for the sequence 5′-CATT(A/T)AATG-3′, rather than 5′-CAAT(A/T)ATTG-3′, recognized by Hahb-4. To analyze the molecular basis of this behavior, we have constructed a set of mutants with exchanged residues (Phe→Ile and Ile→Phe) at position 47 of the homeodomain, together with chimeric proteins between HAHR1 and Hahb-4. The results obtained indicate that Phe47, but not Ile47, allows binding to 5′-CATT(A/T)AATG-3′. However, the preference for this sequence is determined, in addition, by amino acids located C-terminal to residue 53 of the HAHR1 homeodomain. A double mutant of Hahb-4 (Ile47→Phe/Ala54→Thr) shows the same binding behavior as HAHR1, suggesting that combinatorial interactions of amino acid residues at positions 47 and 54 of the homeodomain are involved in establishing the affinity and selectivity of plant dimeric homeodomain proteins with different DNA target sequences. PMID:11726696

Effect of Genetic Polymorphisms and Long-Term Tobacco Exposure on the Risk of Breast Cancer

PubMed Central

Verde, Zoraida; Santiago, Catalina; Chicharro, Luis Miguel; Reinoso-Barbero, Luis; Tejerina, Alejandro; Bandrés, Fernando; Gómez-Gallego, Félix

2016-01-01

Introduction: Tobacco smoke contains many potentially harmful compounds that may act differently and at different stages in breast cancer development. The focus of this work was to assess the possible role of cigarette smoking (status, dose, duration or age at initiation) and polymorphisms in genes coding for enzymes involved in tobacco carcinogen metabolism (CYP1A1, CYP2A6) or in DNA repair (XRCC1, APEX1, XRCC3 and XPD) in breast cancer development. Methods: We designed a case control study with 297 patients, 217 histologically verified breast cancers (141 smokers and 76 non-smokers) and 80 healthy smokers in a cohort of Spanish women. Results: We found an association between smoking status and early age at diagnosis of breast cancer. Among smokers, invasive carcinoma subtype incidence increased with intensity and duration of smoking (all Ptrend < 0.05). When smokers were stratified by smoking duration, we only observed differences in long-term smokers, and the CYP1A1 Ile462Ile genotype was associated with increased risk of breast cancer (OR = 7.12 (1.98–25.59)). Conclusions: Our results support the main effect of CYP1A1 in estrogenic metabolism rather than in tobacco carcinogen activation in breast cancer patients and also confirmed the hypothesis that CYP1A1 Ile462Val, in association with long periods of active smoking, could be a breast cancer risk factor. PMID:27754415

Structural basis for drug and substrate specificity exhibited by FIV encoding a chimeric FIV/HIV protease

PubMed Central

Lin, Ying-Chuan; Perryman, Alexander L.; Olson, Arthur J.; Torbett, Bruce E.; Elder, John H.; Stout, C. David

2011-01-01

A chimeric feline immunodeficiency virus (FIV) protease (PR) has been engineered that supports infectivity but confers sensitivity to the human immunodeficiency virus (HIV) PR inhibitors darunavir (DRV) and lopinavir (LPV). The 6s-98S PR has five replacements mimicking homologous residues in HIV PR and a sixth which mutated from Pro to Ser during selection. Crystal structures of the 6s-98S FIV PR chimera with DRV and LPV bound have been determined at 1.7 and 1.8 Å resolution, respectively. The structures reveal the role of a flexible 90s loop and residue 98 in supporting Gag processing and infectivity and the roles of residue 37 in the active site and residues 55, 57 and 59 in the flap in conferring the ability to specifically recognize HIV PR drugs. Specifically, Ile37Val preserves tertiary structure but prevents steric clashes with DRV and LPV. Asn55Met and Val59Ile induce a distinct kink in the flap and a new hydrogen bond to DRV. Ile98Pro→Ser and Pro100Asn increase 90s loop flexibility, Gln99Val contributes hydrophobic contacts to DRV and LPV, and Pro100Asn forms compensatory hydrogen bonds. The chimeric PR exhibits a comparable number of hydrogen bonds, electrostatic interactions and hydrophobic contacts with DRV and LPV as in the corresponding HIV PR complexes, consistent with IC50 values in the nanomolar range. PMID:21636894

Large eddy simulation study of turbulent kinetic energy and scalar variance budgets and turbulent/non-turbulent interface in planar jets

NASA Astrophysics Data System (ADS)

Watanabe, Tomoaki; Sakai, Yasuhiko; Nagata, Koji; Ito, Yasumasa

2016-04-01

Spatially developing planar jets with passive scalar transports are simulated for various Reynolds (Re = 2200, 7000, and 22 000) and Schmidt numbers (Sc = 1, 4, 16, 64, and 128) by the implicit large eddy simulation (ILES) using low-pass filtering as an implicit subgrid-scale model. The budgets of resolved turbulent kinetic energy k and scalar variance < {φ }\\prime 2> are explicitly evaluated from the ILES data except for the dissipation terms, which are obtained from the balance in the transport equations. The budgets of k and < {φ }\\prime 2> in the ILES agree well with the DNS and experiments for both high and low Re cases. The streamwise decay of the mean turbulent kinetic energy dissipation rate obeys the power low obtained by the scaling argument. The mechanical-to-scalar timescale ratio C ϕ is evaluated in the self-similar region. For the high Re case, C ϕ is close to the isotropic value (C ϕ = 2) near the jet centerline. However, when Re is not large, C ϕ is smaller than 2 and depends on the Schmidt number. The T/NT interface is also investigated by using the scalar isosurface. The velocity and scalar fields near the interface depend on the interface orientation for all Re. The velocity toward the interface is observed near the interface facing in the streamwise, cross-streamwise, and spanwise directions in the planar jet in the resolved velocity field.

St. Lawrence Seaway, Quebec, Canada

NASA Image and Video Library

1991-05-06

STS039-83-059 (28 April-6 May 1991) --- This high oblique view taken from over southeastern Quebec, looking to the southwest down the estuary of the St. Lawrence River (Fleuve Saint-Laurent). The primary road on the north side of the river (right) runs from Quebec, at the end of the estuary behind Ile D'Orleans, northeast to its terminus at Sept-Iles (near nadir, and not visible in this scene). The St. Lawrence disappears underneath the cloud bank over western New York and Ontario just to the west of Montreal. The light snow cover enhances the area of forests (dark) and non-forest (white). In this view, most of the irregular areas of white on the right side of the St. Lawrence River are previously forested areas that were burned over during the extraordinary Canadian forest fires of 1989.

Intellectual impairment in patients with epilepsy in Ile-Ife, Nigeria.

PubMed

Sunmonu, T A; Komolafe, M A; Ogunrin, A O; Oladimeji, B Y; Ogunniyi, A

2008-12-01

Epilepsy is the most common non-infectious neurologic disease in developing countries such as Africa, including Nigeria. This study was designed to assess the intellectual performance of patients with epilepsy (PWE) in Nigeria hoping that the result will serve as the basis for educational, vocational, and social counseling. Forty-one PWE were studied along with 41 age-, sex- and education-matched healthy controls. A questionnaire was developed and applied to all subjects and history was taken from patients and eyewitness. The intellectual function of each subject was assessed with the aid of Wechsler Adult Intelligence Scale adapted for Nigerians. All patients subsequently had electroencephalography (EEG) performed and the EEG findings were noted. SPSS statistical package was used to analyze the data. The PWE performed poorly on the verbal IQ, performance IQ, and full scale IQ scores when compared with controls (P < 0.05) and 20% of PWE had mental retardation. Long duration of epilepsy, long duration of antiepileptic drug therapy, younger age at onset of epilepsy, increased frequency of seizures, and low educational status were found to have negative impacts on intellectual performance in PWE (P < 0.05) while seizure types and type of antiepileptic drugs (carbamazepine or phenytoin) did not influence intellectual performance. This study shows that PWE had significant intellectual impairment when compared with controls. In addition, long duration of epilepsy, long duration of AED therapy, earlier age of onset, increased seizure frequency, and low educational status had a negative impact on intellectual functioning in PWE.

Genotype-phenotype correlation and functional studies in patients with cystic fibrosis bearing CFTR complex alleles.

PubMed

Terlizzi, Vito; Castaldo, Giuseppe; Salvatore, Donatello; Lucarelli, Marco; Raia, Valeria; Angioni, Adriano; Carnovale, Vincenzo; Cirilli, Natalia; Casciaro, Rosaria; Colombo, Carla; Di Lullo, Antonella Miriam; Elce, Ausilia; Iacotucci, Paola; Comegna, Marika; Scorza, Manuela; Lucidi, Vincenzina; Perfetti, Anna; Cimino, Roberta; Quattrucci, Serena; Seia, Manuela; Sofia, Valentina Maria; Zarrilli, Federica; Amato, Felice

2017-04-01

The effect of complex alleles in cystic fibrosis (CF) is poorly defined for the lack of functional studies. To describe the genotype-phenotype correlation and the results of either in vitro and ex vivo studies performed on nasal epithelial cells (NEC) in a cohort of patients with CF carrying cystic fibrosis transmembrane conductance regulator ( CFTR ) complex alleles. We studied 70 homozygous, compound heterozygous or heterozygous for CFTR mutations: p.[Arg74Trp;Val201Met;Asp1270Asn], n=8; p.[Ile148Thr;Ile1023_Val1024del], n=5; p.[Arg117Leu;Leu997Phe], n=6; c.[1210-34TG[12];1210-12T[5];2930C>T], n=3; p.[Arg74Trp;Asp1270Asn], n=4; p.Asp1270Asn, n=2; p.Ile148Thr, n=6; p.Leu997Phe, n=36. In 39 patients, we analysed the CFTR gating activity on NEC in comparison with patients with CF (n=8) and carriers (n=4). Finally, we analysed in vitro the p.[Arg74Trp;Val201Met;Asp1270Asn] complex allele. The p.[Ile148Thr;Ile1023_Val1024del] caused severe CF in five compound heterozygous with a class I-II mutation. Their CFTR activity on NEC was comparable with patients with two class I-II mutations (mean 7.3% vs 6.9%). The p.[Arg74Trp;Asp1270Asn] and the p.Asp1270Asn have scarce functional effects, while p.[Arg74Trp;Val201Met;Asp1270Asn] caused mild CF in four of five subjects carrying a class I-II mutation in trans , or CFTR-related disorders (CFTR-RD) in three having in trans a class IV-V mutation. The p.[Arg74Trp;Val201Met;Asp1270Asn] causes significantly (p<0.001) higher CFTR activity compared with compound heterozygous for class I-II mutations. Furthermore, five of six compounds heterozygous with the p.[Arg117Leu;Leu997Phe] had mild CF, whereas the p.Leu997Phe, in trans with a class I-II CFTR mutation, caused CFTR-RD or a healthy status (CFTR activity: 21.3-36.9%). Finally, compounds heterozygous for the c.[1210-34TG[12];1210-12T[5];2930C>T] and a class I-II mutation had mild CF or CFTR-RD (gating activity: 18.5-19.0%). The effect of complex alleles partially depends on the

Enhancement of the thermostability of Hydrogenobacter thermophilus cytochrome c(552) through introduction of an extra methylene group into its hydrophobic protein interior.

PubMed

Tai, Hulin; Irie, Kiyofumi; Mikami, Shin-ichi; Yamamoto, Yasuhiko

2011-04-19

Careful scrutiny of the protein interior of Hydrogenobacter thermophilus cytochrome c(552) (HT) on the basis of its X-ray structure [Travaglini-Allocatelli, C., Gianni, S., Dubey, V. K., Borgia, A., Di Matteo, A., Bonivento, D., Cutruzzola, F., Bren, K. L., and Brunori, M. (2005) J. Biol. Chem. 280, 25729-25734] indicated that a void space, which is large enough to accommodate a methyl group, exists in the hydrophobic protein interior near the heme. We tried to reduce the void space through the replacement of a Val by Ile or Leu (Val/Ile or Val/Leu mutation), and then the structural and functional consequences of these two mutations were characterized in order to elucidate the relationship between the nature of the packing of hydrophobic residues and the functional properties of the protein. The study demonstrated striking differences in the structural and functional consequences between the two mutations. The Val/Ile mutation was found to cause further enhancement of the thermostability of the oxidized HT, as reflected in the increase of the denaturation temperature (T(m)) value by ∼ 3 deg, whereas the thermostability of the reduced form was essentially unaffected. As a result, the redox potential (E(m)) of the Val/Ile mutant exhibited a negative shift of ∼ 50 mV relative to that of the wild-type protein in an enthalpic manner, this being consistent with our previous finding that a protein with higher stability in its oxidized form exhibits a lower E(m) value [Terui, N., Tachiiri, N., Matsuo, H., Hasegawa, J., Uchiyama, S., Kobayashi, Y., Igarashi, Y., Sambongi, Y., and Yamamoto, Y. (2003) J. Am. Chem. Soc. 125, 13650-13651]. In contrast, the Val/Leu mutation led to a decrease in thermostability of both the redox forms of the protein, as reflected in the decreases of the T(m) values of the oxidized and reduced proteins by ∼ 3 and ∼ 5 deg, respectively, and the E(m) value of the Val/Leu mutant happened to be similar to that of the Val/Ile one. The E

A Population-Based Study of Long-term Outcomes of Cryptogenic Focal Epilepsy in Childhood: Cryptogenic Epilepsy is NOT Probably Symptomatic Epilepsy

PubMed Central

Wirrell, Elaine C; Grossardt, Brandon R; So, Elson L; Nickels, Katherine C

2011-01-01

Purpose To compare long-term outcome in a population-based group of children with cryptogenic vs symptomatic focal epilepsy diagnosed from 1980–2004 and to define the course of epilepsy in the cryptogenic group. Methods We identified all children residing in Olmsted County, MN, 1 month through 17 years with newly diagnosed, non-idiopathic focal epilepsy from 1980–2004. Children with idiopathic partial epilepsy syndromes were excluded. Medical records were reviewed to determine etiology, results of imaging and EEG studies, treatments used, and long-term outcome. Children were defined as having symptomatic epilepsy if they had a known genetic or structural/metabolic etiology, and as cryptogenic if they did not. Key Findings Of 359 children with newly-diagnosed epilepsy, 215 (60%) had non-idiopathic focal epilepsy. Of these, 206 (96%) were followed for more than 12 months. Ninety five children (46%) were classified as symptomatic. Median follow-up from diagnosis was similar in both groups, being 157 months (25%ile, 75%ile 89, 233) in the cryptogenic group vs 134 months (25%ile, 75%ile 78, 220) in the symptomatic group (p=0.26). Of 111 cryptogenic cases, 66% had normal cognition. Long-term outcome was significantly better in those with cryptogenic vs symptomatic etiology (intractable epilepsy at last follow-up, 7% vs 40%, p<0.001; seizure-freedom at last follow-up, 81% vs 55%, p<0.001). Of those who achieved seizure-freedom at final follow-up, 68% of the cryptogenic group versus only 46% of the symptomatic group were off antiepileptic medications (p=0.01). One third of the cryptogenic group had a remarkably benign disorder, with no seizures seen after initiation of medication, or in those who were untreated, after the second afebrile seizure. A further 5% had seizures within the first year but remained seizure-free thereafter. With the exception of perinatal complications, which predicted against seizure remission, no other factors were found to significantly

MODEL VERSION CONTROL FOR GREAT LAKES MODELS ON UNIX SYSTEMS

EPA Science Inventory

Scientific results of the Lake Michigan Mass Balance Project were provided where atrazine was measured and modeled. The presentation also provided the model version control system which has been used for models at Grosse Ile for approximately a decade and contains various version...

York Papers in Linguistics, Volume 17.

ERIC Educational Resources Information Center

Local, J. K., Ed.; Warner, A. R., Ed.

1996-01-01

These 14 articles on aspects of linguistics include the following: "Economy and Optionality: Interpretations of Subjects in Italian" (David Adger); "Collaborative Repair in EFL Classroom Talk" (Zara Iles); "A Timing Model for Fast French" (Eric Keller, Brigitte Zellner); "Another Travesty of Representation:…

Evaluation of human epidermal growth factor receptor 2 (HER2) single nucleotide polymorphisms (SNPs) in normal and breast tumor tissues and their link with breast cancer prognostic factors.

PubMed

Furrer, Daniela; Lemieux, Julie; Côté, Marc-André; Provencher, Louise; Laflamme, Christian; Barabé, Frédéric; Jacob, Simon; Michaud, Annick; Diorio, Caroline

2016-12-01

Amplification of the human epidermal growth factor receptor 2 (HER2) gene is associated with worse prognosis and decreased overall survival in breast cancer patients. The HER2 gene contains several polymorphisms; two of the best-characterized HER2 polymorphisms are Ile655Val and Ala1170Pro. The aim of this study was to evaluate the association between these two HER2 polymorphisms in normal breast and breast cancer tissues and known breast cancer prognostic factors in a retrospective cohort study of 73 women with non-metastatic HER2-positive breast cancer. HER2 polymorphisms were assessed in breast cancer tissue and normal breast tissue using TaqMan assay. Ala1170Pro polymorphism in normal breast tissue was associated with age at diagnosis (p = 0.007), tumor size (p = 0.004) and lymphovascular invasion (p = 0.06). Similar significant associations in cancer tissues were observed. No association between the Ile655Val polymorphism and prognostic factors were observed. However, we found significant differences in the distribution of Ile655Val (p = 0.03) and Ala1170Pro (p = 0.01) genotypes between normal breast and breast tumor tissues. This study demonstrates that only the Ala1170Pro polymorphism is associated with prognostic factors in HER2-positive breast cancer patients. Moreover, our results suggest that both HER2 polymorphisms could play a significant role in carcinogenesis in non-metastatic HER2-positive breast cancer women. Copyright © 2016 Elsevier Ltd. All rights reserved.

PAN and O3 enhancement at Taehwa Research Forest in Korea

NASA Astrophysics Data System (ADS)

Gil, J.; Lee, M.; Rhee, H.; Lee, Y.; Park, H.; Kim, S.

2017-12-01

PAN (Peroxyacetyl Nitrate) is one of the most important secondary pollutant produced by the reaction of NOx (= NO + NO2) and oxygenated VOCs (Volatile Organic Compounds). It is considered more reliable indicator of photochemical pollution than O3 in urban area. To observe the evolution of biogenic emission being mixed with urban pollutants, measurement was conducted at TRF (Taehwa Research Forest) near SMA (Seoul Metropolitan Area) in Korea during 2012, and 2013. PAN with reactive gases (O3, NOx, CO, SO2) were measured at six heights (4.1, 9.5, 15, 20, 31, 39 m) of a 41m tower along with BVOCs (Biogenic Volatile Organic Compounds). PAN was measured using a fast GC-LCD (Gas Chromatography with Luminol-based Chemiluminescence Detection). For PAN and O3, the 5%ile, 50%ile, and 95%ile were 0.12 ppbv, 0.46 ppbv, and 2.09 ppbv, and 18.4 ppbv, 44.7 ppbv, and 66.6 ppbv respectively. PAN was visibly higher during warm seasons (0.69 ppbv) than cold seasons (0.35 ppbv) and their monthly mean concentrations were the highest in June. The PAN maxima (7.78 ppbv) was observed in August 2013 with the elevation of O3 and NOx. It is noteworthy that there were enhancement of PAN and O3 around 6 PM, along with isoprene emission and a sudden increase of NO2 near the time for enhancement. A F0AM (Framework for 0-D Atmospheric Modeling) was used to identify the contribution of BVOCs and NOx to PAN and O3 enhancement.

Quantitation of underivatized branched-chain amino acids in sport nutritional supplements by capillary electrophoresis with direct or indirect UV absorbance detection.

PubMed

Qiu, Jun; Wang, Jinhao; Xu, Zhongqi; Liu, Huiqing; Ren, Jie

2017-01-01

The branched-chain amino acids (BCAAs) including leucine (Leu), isoleucine (Ile) and valine (Val) play a pivotal role in the human body. Herein, we developed capillary electrophoresis (CE) coupled with conventional UV detector to quantify underivatized BCAAs in two kinds of sport nutritional supplements. For direct UV detection at 195 nm, the BCAAs (Leu, two enantiomers of Ile and Val) were separated in a background electrolyte (BGE) consisting of 40.0 mmol/L sodium tetraborate, and 40.0 mmol/L β-cyclodextrin (β-CD) at pH 10.2. In addition, the indirect UV detection at 264 nm was achieved in a BGE of 2.0 mmol/L Na2HPO4, 10.0 mmol/L p-aminosalicylic acid (PAS) as UV absorbing probe, and 40.0 mmol/L β-CD at pH 12.2. The β-CD significantly benefited the isomeric separation of Leu, L- and D-Ile. The optimal conditions allowed the LODs (limit of detections) of direct and indirect UV absorption detection to be tens μmol/L level, which was comparable to the reported CE inline derivatization method. The RSDs (relative standard deviations) of migration time and peak area were less than 0.91% and 3.66% (n = 6). Finally, CE with indirect UV detection method was applied for the quantitation of BCAAs in two commercial sport nutritional supplements, and good recovery and precision were obtained. Such simple CE method without tedious derivatization process is feasible of quality control and efficacy evaluation of the supplemental proteins.

Quantitation of underivatized branched-chain amino acids in sport nutritional supplements by capillary electrophoresis with direct or indirect UV absorbance detection

PubMed Central

Liu, Huiqing; Ren, Jie

2017-01-01

The branched-chain amino acids (BCAAs) including leucine (Leu), isoleucine (Ile) and valine (Val) play a pivotal role in the human body. Herein, we developed capillary electrophoresis (CE) coupled with conventional UV detector to quantify underivatized BCAAs in two kinds of sport nutritional supplements. For direct UV detection at 195 nm, the BCAAs (Leu, two enantiomers of Ile and Val) were separated in a background electrolyte (BGE) consisting of 40.0 mmol/L sodium tetraborate, and 40.0 mmol/L β-cyclodextrin (β-CD) at pH 10.2. In addition, the indirect UV detection at 264 nm was achieved in a BGE of 2.0 mmol/L Na2HPO4, 10.0 mmol/L p-aminosalicylic acid (PAS) as UV absorbing probe, and 40.0 mmol/L β-CD at pH 12.2. The β-CD significantly benefited the isomeric separation of Leu, L- and D-Ile. The optimal conditions allowed the LODs (limit of detections) of direct and indirect UV absorption detection to be tens μmol/L level, which was comparable to the reported CE inline derivatization method. The RSDs (relative standard deviations) of migration time and peak area were less than 0.91% and 3.66% (n = 6). Finally, CE with indirect UV detection method was applied for the quantitation of BCAAs in two commercial sport nutritional supplements, and good recovery and precision were obtained. Such simple CE method without tedious derivatization process is feasible of quality control and efficacy evaluation of the supplemental proteins. PMID:28640882

Combined effect of ADH1B RS1229984, RS2066702 and ADH1C RS1693482/ RS698 alleles on alcoholism and chronic liver diseases.

PubMed

Tóth, Réka; Fiatal, Szilvia; Petrovski, Beáta; McKee, Martin; Adány, Róza

2011-01-01

The aim of this study was to analyze the combined effect of the most frequent alcohol dehydrogenase polymorphisms (Arg48His and Arg370Cys in ADH1B, Arg272Gln and Ile350Val in ADH1C) on the alcohol use habits, alcohol dependence and chronic liver diseases in Hungary. The study included men, aged 45-64 years. Altogether, 241 cases with chronic liver disease (CLD) and 666 randomly selected controls without CLD were analysed for all four polymorphisms. Associations between the polymorphisms, individually, and in combination, and excessive and problem drinking and CLD, were assessed using logistic regression. In this study we have identified a novel mutation, called ADH1B Arg370His. The ADH1C Arg272Gln and Ile350Val showed almost complete linkage. The 272Gln/35Val allele increased the risk of excessive and problem drinking in homozygous form (OR=1.582, p=0.035, CI=1.034-2.421, OR=1.780, p=0.016, CI=1.113-2.848, respectively). The joint analysis showed that when combined with the wild type ADH1C Arg272/Ile350 allele, the ADH1B 48His is protective against CLD (OR=0.368, p=0.019, CI=0.159-0.851). The results obtained in the study help not only to clarify the effects of different ADH SNPs but to better understand how these polymorphisms modify each other's effects in the development of alcoholism and related diseases.

Identification of a novel amino acid racemase from a hyperthermophilic archaeon Pyrococcus horikoshii OT-3 induced by D-amino acids.

PubMed

Kawakami, Ryushi; Ohmori, Taketo; Sakuraba, Haruhiko; Ohshima, Toshihisa

2015-08-01

To date, there have been few reports analyzing the amino acid requirement for growth of hyperthermophilic archaea. We here found that the hyperthermophilic archaeon Pyrococcus horikoshii OT-3 requires Thr, Leu, Val, Phe, Tyr, Trp, His and Arg in the medium for growth, and shows slow growth in medium lacking Met or Ile. This largely corresponds to the presence, or absence, of genes related to amino acid biosynthesis in its genome, though there are exceptions. The amino acid requirements were dramatically lost by addition of D-isomers of Met, Leu, Val, allo-Ile, Phe, Tyr, Trp and Arg. Tracer analysis using (14)C-labeled D-Trp showed that D-Trp in the medium was used as a protein component in the cells, suggesting the presence of D-amino acid metabolic enzymes. Pyridoxal 5'-phosphate (PLP)-dependent racemase activity toward Met, Leu and Phe was detected in crude extract of P. horikoshii and was enhanced in cells grown in the medium supplemented with D-amino acids, especially D-allo-Ile. The gene encoding the racemase was narrowed down to one open reading frame on the basis of enzyme purification from P. horikoshii cells, and the recombinant enzyme exhibited PLP-dependent racemase activity toward several amino acids, including Met, Leu and Phe, but not Pro, Asp or Glu. This is the first report showing the presence in a hyperthermophilic archaeon of a PLP-dependent amino acid racemase with broad substrate specificity that is likely responsible for utilization of D-amino acids for growth.

A diurnal component to the variation in sieve tube amino acid content in wheat.

PubMed

Gattolin, Stefano; Newbury, H John; Bale, Jeffrey S; Tseng, Hua-Ming; Barrett, David A; Pritchard, Jeremy

2008-06-01

We have used high-sensitivity capillary electrophoresis coupled to a laser-induced fluorescence detection method to quantify 16 amino acids in wheat (Triticum aestivum) sieve tube (ST) samples as small as 2 nL collected by severing the stylets of feeding aphids. The sensitivity of the method was sufficient to determine a quantitative amino acid profile of individual STs without the need to bulk samples to produce larger volumes for analysis. This allowed the observation of the full range of variation that exists in individual STs. Some of the total concentrations of amino acids recorded are higher than those reported previously. The results obtained show variation in the concentrations of phenylalanine (Phe), histidine/valine (His/Val), leucine/isoleucine (Leu/Ile), arginine, asparagine, glutamine, tyrosine (Tyr), and lysine (Lys) across the ST samples. These could not be explained by plant-to-plant variation. Statistical analyses revealed five analytes (Tyr, Lys, Phe, His/Val, and Leu/Ile) that showed striking covariation in their concentrations across ST samples. A regression analysis revealed a significant relationship between the concentrations of Tyr, Lys, Phe, Leu/Ile, His/Val, asparagine, arginine, and proline and the time of collection of ST samples, with these amino acids increasing in concentration during the afternoon. This increase was confirmed to occur in individual STs by analyzing samples obtained from stylet bundles exuding for many hours. Finally, an apparent relationship between the exudation rate of ST sap and its total amino acid concentration was observed: samples containing higher total amino acid concentrations were observed to exude from the severed stylet bundles more slowly.

AGXT Gene Mutations and Prevalence of Primary Hyperoxaluria Type 1 in Moroccan Population.

PubMed

Boualla, Lamiae; Tajir, Mariam; Oulahiane, Najat; Lyahyai, Jaber; Laarabi, Fatima Zahra; Chafai Elalaoui, Siham; Soulami, Kenza; Ait Ouamar, Hassan; Sefiani, Abdelaziz

2015-11-01

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder caused by deficiency of alanine glyoxylate aminotransferase, due to a defect in the AGXT gene. Several mutations in this gene have been reported and some of them have been observed in multiple populations. The aim of our study was to analyze the mutations causing PH1 in the Moroccan population and to estimate its prevalence in Morocco. Molecular studies of 29 unrelated Moroccan patients with PH were performed by direct sequencing of all exons of the AGXT gene. In addition, to estimate the prevalence of PH1, we screened for the recurrent p.Ile244Thr mutation in 250 unrelated Moroccan newborns using real-time polymerase chain reaction. Four pathogenic mutations were detected in 25 unrelated patients. The c.731T>C (p.Ile244Thr) was the most frequent mutation with a frequency of 84%. The other three mutations were c.33delC, c.976delG, and c.331C>T. The prevalence of the PH1 mutation among Moroccans was then estimated to range from 1/7267 to 1/6264. PH1 is one of the most prevalent genetic diseases in the Moroccan population and is probably underdiagnosed. Front line genetic testing for PH1 in Morocco should be initiated using an assay for the recurrent p.Ile244Thr mutation. This strategy would provide a useful tool for precocious diagnosis of presymptomatic individuals and to prevent their rapid progression to renal failure.

How Can Innovative Learning Environments Promote the Diffusion of Innovation?

ERIC Educational Resources Information Center

Osborne, Mark

2016-01-01

Schools implementing innovative learning environments (ILEs) face many challenges, including the need to discard previously cherished practices and behaviours, adjust mindsets, and invent successful new ways of operating. Leaders can support these processes by implementing structures that: i) support ongoing, distributed, participatory innovation;…

75 FR 6362 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-09

..., Department of Defense. NM01500-9 SYSTEM NAME: Integrated Learning Environment (ILE) Classes (September 19... personal identifier number assigned to individual, pay plan/grade, rank, occupation, Unit Identification... register to take classes offered under Navy eLearning.'' AUTHORITY FOR MAINTENANCE OF THE SYSTEM: Delete...

U.S. EPA, Pesticide Product Label, , 07/17/1984

EPA Pesticide Factsheets

2011-04-14

... ff~(;t bcgirullng \\I;hen qta!":~ reSU:',C'5 gro'wo't.h ill t.ile G!'ring (t"~~rcb-;\\} rll}. Rcpelit. at 7 to 10 day ... 1 : .I 1 L t "rll~lt l Iy l! ~ I '" I ' , • , ,t '.; r • ',.r ...

s09-48-3139

NASA Image and Video Library

2009-06-25

STS009-48-3139 (28 Nov-8 Dec 1983) --- Canada (Quebec) the contrast between forest, water, and snow make the Manicouagane impact formation stand out. Location: 150 miles (250 Km) NNW of Sept Iles or 500 miles (800 Km) NNE of Montreal on the Canadian Shield.

Evaluation of Imagine Learning English, a Computer-Assisted Instruction of Language and Literacy for Kindergarten Students

ERIC Educational Resources Information Center

Longberg, Pauline Oliphant

2012-01-01

As computer assisted instruction (CAI) becomes increasingly sophisticated, its appeal as a viable method of literacy intervention with young children continues despite limited evidence of effectiveness. The present study sought to assess the impact of one such CAI program, "Imagine Learning English" (ILE), on both the receptive…

United States Coast Guard Antisubmarine Warfare (ASW) in the Maritime Defense Zone (MDZ) - A Strategic Approach

DTIC Science & Technology

1989-03-01

RIC ILE COPY AIR WAR COLLGE REEAC R~pCR UNITED STATES COAST GUARD ANTISUBMARINE WARFARE (ASW) IN THE MARITIME DEFENSE ZONE (MDZ) -A STRATEGIC...going to perform in these MDZs. Those tasks identified so far include: port and coastal physical security & preventive safety, mine warfare

Trace mineral absorption status in infants with ileostomies

USDA-ARS?s Scientific Manuscript database

Infants with ileostomies are often supplemented with zinc and limited in copper, because of potential increased bilious zinc loss and increased cholestasis due to reduced copper excretion. However, no data exist on zinc or copper balance in infants with ileostomies. To determine the effect of an ile...

Schooling Redesigned: Towards Innovative Learning Systems

ERIC Educational Resources Information Center

Istance, David

2015-01-01

What does redesigning schools and schooling through innovation mean in practice? How might it be brought about? These questions have inspired an influential international reflection on "Innovative Learning Environments" (ILE) led by the OECD. This reflection has already resulted in publications on core design principles and frameworks…

Brain response to taste in overweight children: A pilot feasibility study.

PubMed

Bohon, Cara

2017-01-01

Understanding the neural response to food and food cues during early stages of weight gain in childhood may help us determine the drive processes involved in unhealthy eating behavior and risk for obesity. Healthy weight and overweight children ages 6-8 (N = 18; 10 with BMI between 5th and 85th %ile and 8 with BMI >85th %ile) underwent fMRI scans while anticipating and receiving tastes of chocolate milkshake. Parents completed a Children's Eating Behaviour Questionnaire. Results reveal greater response to milkshake taste receipt in overweight children in the right insula, operculum, precentral gyrus, and angular gyrus, and bilateral precuneus and posterior cingulate. No group differences were found for brain response to a visual food cue. Exploratory analyses revealed interactions between self-report measures of eating behavior and weight status on brain response to taste. This pilot study provides preliminary evidence of feasibility of studying young children's taste processing and suggests a possible developmental shift in brain response to taste.

Synthesis, screening, and nanocrystals preparation of rhein amide derivatives.

PubMed

Chen, Lijiang; Zhang, Jinfeng; Rong, Jinghong; Liu, Yu; Zhao, Jinhua; Cui, Qingguo; Wang, Xin; Liang, Xiao; Pan, Hao; Liu, Hongsheng

2018-04-23

Rhein (RH) have many bioactivities, but the application was limited of its poor solubility. The present study aimed to establish an efficient method for the synthesis of rhein amide derivatives (RAD) to increase the solubility and anti-tumor activity. RAD exhibited stronger anti-tumor activity than RH in MTT assay. The solubility and oil/water partition coefficient results indicated that rhein-phenylalanine and rhein-isoleucine have better absorption effect, which was consolidated in pharmacokinetic study. Then, rhein-phenylalanine and rhein-isoleucine were prepared into nanocrystals via the precipitation-high pressure homogenization method. Additionally, the nanocrystals both displayed much higher dissolution profiles than the bulk drugs. Pharmacokinetics study indicated that the AUC 0-∞ and C max of nanocrystals increased markedly (p < 0.01). However, the concentration of RH-Phe-NC was far less than RH-Ile-NC in plasma. Consequently, RH-Ile-NC was validated to be an applicable way to improve the bioavailability of RH, which owns a promising future in clinical application.

Identification of striated muscle activator of Rho signaling (STARS) as a novel calmodulin target by a newly developed genome-wide screen.

PubMed

Furuya, Yusui; Denda, Miwako; Sakane, Kyohei; Ogusu, Tomoko; Takahashi, Sumio; Magari, Masaki; Kanayama, Naoki; Morishita, Ryo; Tokumitsu, Hiroshi

2016-07-01

To search for novel target(s) of the Ca(2+)-signaling transducer, calmodulin (CaM), we performed a newly developed genome-wide CaM interaction screening of 19,676 GST-fused proteins expressed in human. We identified striated muscle activator of Rho signaling (STARS) as a novel CaM target and characterized its CaM binding ability and found that the Ca(2+)/CaM complex interacted stoichiometrically with the N-terminal region (Ala13-Gln35) of STARS in vitro as well as in living cells. Mutagenesis studies identified Ile20 and Trp33 as the essential hydrophobic residues in CaM anchoring. Furthermore, the CaM binding deficient mutant (Ile20Ala, Trp33Ala) of STARS further enhanced its stimulatory effect on SRF-dependent transcriptional activation. These results suggest a connection between Ca(2+)-signaling via excitation-contraction coupling and the regulation of STARS-mediated gene expression in muscles. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lead Optimization Studies on FimH Antagonists: Discovery of Potent and Orally Bioavailable Ortho-substituted Biphenyl Mannosides

PubMed Central

Han, Zhenfu; Pinkner, Jerome S.; Ford, Bradley; Chorell, Erik; Crowley, Jan M.; Cusumano, Corinne K.; Campbell, Scott; Henderson, Jeffrey P.; Hultgren, Scott J.; Janetka, James W.

2012-01-01

Herein, we describe the X-ray structure-based design and optimization of biaryl mannoside FimH inhibitors. Diverse modifications to the biaryl ring to improve drug-like physical and pharmacokinetic properties of mannosides were assessed for FimH binding affinity based on their effects on hemagglutination and biofilm formation along with direct FimH binding assays. Substitution on the mannoside phenyl ring ortho to the glycosidic bond results in large potency enhancements of several-fold higher than corresponding unsubstituted matched pairs and can be rationalized from increased hydrophobic interactions with the FimH hydrophobic ridge (Ile13) or “tyrosine gate” (Tyr137 and Tyr48) also lined by Ile52. The lead mannosides have increased metabolic stability and oral bioavailability as determined from in vitro PAMPA predictive model of cellular permeability and in vivo pharmacokinetic studies in mice, thereby representing advanced preclinical candidates with promising potential as novel therapeutics for the clinical treatment and prevention of recurring urinary tract infections. PMID:22449031

An investigation of implicit turbulence modeling for laminar-turbulent transition in natural convection

NASA Astrophysics Data System (ADS)

Li, Chunggang; Tsubokura, Makoto; Wang, Weihsiang

2017-11-01

The automatic dissipation adjustment (ADA) model based on truncated Navier-Stokes equations is utilized to investigate the feasibility of using implicit large eddy simulation (ILES) with ADA model on the transition in natural convection. Due to the high Rayleigh number coming from the larger temperature difference (300K), Roe scheme modified for low Mach numbers coordinating ADA model is used to resolve the complicated flow field. Based on the qualitative agreement of the comparisons with DNS and experimental results and the capability of numerically predicating a -3 decay law for the temporal power spectrum of the temperature fluctuation, this study thus validates the feasibility of ILES with ADA model on turbulent natural convection. With the advantages of ease of implementation because no explicit modeling terms are needed and nearly free of tuning parameters, ADA model offers to become a promising tool for turbulent thermal convection. Part of the results is obtained using the K computer at the RIKEN Advanced Institute for Computational Science (Proposal number hp160232).

Isolation and characterization of a novel bradykinin potentiating peptide (BPP) from the skin secretion of Phyllomedusa hypochondrialis.

PubMed

Conceição, Katia; Konno, Katsuhiro; de Melo, Robson Lopes; Antoniazzi, Marta M; Jared, Carlos; Sciani, Juliana M; Conceição, Isaltino M; Prezoto, Benedito C; de Camargo, Antônio Carlos Martins; Pimenta, Daniel C

2007-03-01

Bradykinin potentiating peptides (BPPs) from Bothrops jararaca venom were first described in the middle of 1960s and were the first natural inhibitors of the angiotensin-converting enzyme (ACE). BPPs present a classical motif and can be recognized by their typical pyroglutamyl (Pyr)/proline rich sequences presenting, invariably, a proline residue at the C-terminus. In the present study, we describe the isolation and biological characterization of a novel BPP isolated from the skin secretion of the Brazilian tree-frog Phyllomedusa hypochondrialis. This new BPP, named Phypo Xa presents the sequence Pyr-Phe-Arg-Pro-Ser-Tyr-Gln-Ile-Pro-Pro and is able to potentiate bradykinin activities in vivo and in vitro, as well as efficiently and competitively inhibit ACE. This is the first canonical BPP (i.e. Pyr-Aaa(n)-Gln-Ile-Pro-Pro) to be found not only in the frog skin but also in any other natural source other than the snake venoms.

Mutations of the RTEL1 Helicase in a Hoyeraal-Hreidarsson Syndrome Patient Highlight the Importance of the ARCH Domain.

PubMed

Jullien, Laurent; Kannengiesser, Caroline; Kermasson, Laetitia; Cormier-Daire, Valérie; Leblanc, Thierry; Soulier, Jean; Londono-Vallejo, Arturo; de Villartay, Jean-Pierre; Callebaut, Isabelle; Revy, Patrick

2016-05-01

The DNA helicase RTEL1 participates in telomere maintenance and genome stability. Biallelic mutations in the RTEL1 gene account for the severe telomere biology disorder characteristic of the Hoyeraal-Hreidarsson syndrome (HH). Here, we report a HH patient (P4) carrying two novel compound heterozygous mutations in RTEL1: a premature stop codon (c.949A>T, p.Lys317*) and an intronic deletion leading to an exon skipping and an in-frame deletion of 25 amino-acids (p.Ile398_Lys422). P4's cells exhibit short and dysfunctional telomeres similarly to other RTEL1-deficient patients. 3D structure predictions indicated that the p.Ile398_Lys422 deletion affects a part of the helicase ARCH domain, which lines the pore formed with the core HD and the iron-sulfur cluster domains and is highly specific of sequences from the eukaryotic XPD family members. © 2016 WILEY PERIODICALS, INC.

Design, synthesis and biological evaluation of indole derivatives as Vif inhibitors.

PubMed

Pu, Chunlan; Luo, Rong-Hua; Zhang, Mengqi; Hou, Xueyan; Yan, Guoyi; Luo, Jiang; Zheng, Yong-Tang; Li, Rui

2017-09-01

The crystal structure of viral infectivity factor (Vif) was reported recently, which makes it possible to design new inhibitors against Vif by structure-based drug design. Through analysis of the protein surface of Vif, the C2 pocket located in the N-terminal was found, which is suit for developing small molecular inhibitors. Then, in our article, fragment-based virtual screening (FBVS) was conducted and a series of fragments was obtained, among which, Zif-1 bearing indole scaffold and pyridine ring can form H-bonds with Tyr148 and Ile155. Subsequently, 19 derivatives of Zif-1 were synthesized. Through the immune-fluorescence staining and Western blot assays, Zif-15 shows potent activity in inhibiting Vif-mediated A3G degradation. Further docking experiment shows that Zif-15 form H-bond interactions with residues His139, Tyr148 and Ile155. Therefore, Zif-15 is a promising lead compound against Vif that can be used to treat AIDS. Copyright © 2017. Published by Elsevier Ltd.

Multiple Pathways to Learning: An Examination of Universal Design and Online Strategic Learning in Higher Education

ERIC Educational Resources Information Center

Hicks, Maryruth Wilks

2010-01-01

The purpose of this study was to examine the effectiveness of universally designed (UD) instruction on strategic learning in an online, interactive learning environment (ILE). The research focused on the premise that the customizable, media-based framework of UD instruction might influence diverse online learning strategies. This study…

Waterborne Commerce of the United States Calendar Year 1987. Part 1. Waterways and Harbors Atlantic Coast

DTIC Science & Technology

1989-05-31

Finished Tensile Group 09-Prel, Pith and Other Marine -utttdigKt Products 2311 Apparel and other fini.iled teni prodats.. .9il F .. h fsh.-pt .L~f...1,072,358 241,901 84,000 5,424 3.040 132,42. 429,00 276,765 0101 COTON , RA -.............................. 92

An Analysis of Student Model Portability

ERIC Educational Resources Information Center

Valdés Aguirre, Benjamín; Ramírez Uresti, Jorge A.; du Boulay, Benedict

2016-01-01

Sharing user information between systems is an area of interest for every field involving personalization. Recommender Systems are more advanced in this aspect than Intelligent Tutoring Systems (ITSs) and Intelligent Learning Environments (ILEs). A reason for this is that the user models of Intelligent Tutoring Systems and Intelligent Learning…

Analysis of Critical Success Factors of Online International Learning Exchange of Korean School Pupils with English-Speaking Counterparts

ERIC Educational Resources Information Center

Lee, Jong-Yeon; Park, Sanghoon

2017-01-01

This study identifies the factors influencing the success of online international learning exchange (ILE) among Korean school pupils who partnered with American and Australian pupils. In particular, it examined the effects of self-efficacy (SE), exchange infrastructure (EI) and quality of exchange activities (QEA) on the students' learning…

Impacts and Characteristics of Computer-Based Science Inquiry Learning Environments for Precollege Students

ERIC Educational Resources Information Center

Donnelly, Dermot F.; Linn, Marcia C.; Ludvigsen, Sten

2014-01-01

The National Science Foundation-sponsored report "Fostering Learning in the Networked World" called for "a common, open platform to support communities of developers and learners in ways that enable both to take advantage of advances in the learning sciences." We review research on science inquiry learning environments (ILEs)…

Teaching Content Area Literacy in Informal Learning Environments

ERIC Educational Resources Information Center

Kenny, Heather A.

2015-01-01

In the United States, visits to informal learning environments [ILEs] such as zoos, have historically been considered to be important educational experiences that promote increased student achievement in content-area subjects. Recently, however, funds are more likely to be diverted away from field trip experiences, depriving less-privileged…

Salt-tolerant and -sensitive alfalfa (Medicago sativa) cultivars have large variations in defense responses to the lepidopteran insect Spodoptera litura under normal and salt stress condition

PubMed Central

Lei, Yunting; Liu, Qing; Hettenhausen, Christian; Cao, Guoyan; Tan, Qing; Zhao, Weiye; Lin, Honghui

2017-01-01

In nature, plants are often exposed to multiple stress factors at the same time. Yet, little is known about how plants modulate their physiology to counteract simultaneous abiotic and biotic stresses, such as soil salinity and insect herbivory. In this study, insect performance bioassays, phytohormone measurements, quantification of transcripts, and protein determination were employed to study the phenotypic variations of two alfalfa (Medicago sativa) cultivars in response to insect Spodoptera litura feeding under normal and salt stress condition. When being cultivated in normal soil, the salt-tolerant alfalfa cultivar Zhongmu-1 exhibited lower insect resistance than did the salt-sensitive cultivar Xinjiang Daye. Under salinity stress, the defense responses of Xinjiang Daye were repressed, whereas Zhongmu-1 did not show changes in resistance levels. It is likely that salinity influenced the resistance of Xinjiang Daye through suppressing the accumulation of jasmonic acid-isoleucine (JA-Ile), which is the bioactive hormone inducing herbivore defense responses, leading to attenuated trypsin proteinase inhibitor (TPI) activity. Furthermore, exogenous ABA supplementation suppressed the insect herbivory-induced JA/JA-Ile accumulation and levels of JAR1 (jasmonate resistant 1) and TPI, and further decreased the resistance of Xinjiang Daye, whereas Zhongmu-1 showed very little response to the increased ABA level. We propose a mechanism, in which high levels of abscisic acid induced by salt treatment may affect the expression levels of JAR1 and consequently decrease JA-Ile accumulation and thus partly suppress the defense of Xinjiang Daye against insects under salt stress. This study provides new insight into the mechanism by which alfalfa responds to concurrent abiotic and biotic stresses. PMID:28719628

Salt-tolerant and -sensitive alfalfa (Medicago sativa) cultivars have large variations in defense responses to the lepidopteran insect Spodoptera litura under normal and salt stress condition.

PubMed

Lei, Yunting; Liu, Qing; Hettenhausen, Christian; Cao, Guoyan; Tan, Qing; Zhao, Weiye; Lin, Honghui; Wu, Jianqiang

2017-01-01

In nature, plants are often exposed to multiple stress factors at the same time. Yet, little is known about how plants modulate their physiology to counteract simultaneous abiotic and biotic stresses, such as soil salinity and insect herbivory. In this study, insect performance bioassays, phytohormone measurements, quantification of transcripts, and protein determination were employed to study the phenotypic variations of two alfalfa (Medicago sativa) cultivars in response to insect Spodoptera litura feeding under normal and salt stress condition. When being cultivated in normal soil, the salt-tolerant alfalfa cultivar Zhongmu-1 exhibited lower insect resistance than did the salt-sensitive cultivar Xinjiang Daye. Under salinity stress, the defense responses of Xinjiang Daye were repressed, whereas Zhongmu-1 did not show changes in resistance levels. It is likely that salinity influenced the resistance of Xinjiang Daye through suppressing the accumulation of jasmonic acid-isoleucine (JA-Ile), which is the bioactive hormone inducing herbivore defense responses, leading to attenuated trypsin proteinase inhibitor (TPI) activity. Furthermore, exogenous ABA supplementation suppressed the insect herbivory-induced JA/JA-Ile accumulation and levels of JAR1 (jasmonate resistant 1) and TPI, and further decreased the resistance of Xinjiang Daye, whereas Zhongmu-1 showed very little response to the increased ABA level. We propose a mechanism, in which high levels of abscisic acid induced by salt treatment may affect the expression levels of JAR1 and consequently decrease JA-Ile accumulation and thus partly suppress the defense of Xinjiang Daye against insects under salt stress. This study provides new insight into the mechanism by which alfalfa responds to concurrent abiotic and biotic stresses.

Purification and structural characterization of insulin and glucagon from the bichir Polypterus senegalis (Actinopterygii: Polypteriformes).

PubMed

Conlon, J M; Fan, H; Fritzsch, B

1998-01-01

The Polypteriformes (bichirs and reedfish) are a family of ray-finned fishes of ancient lineage. Insulin has been isolated from an extract of the pancreas and upper gastrointestinal tract of the bichir Polypterus senegalis and its primary structure established as A-chain: Gly-Ile-Val-Glu-Gln-Cys-Cys-Asp-Thr-Pro10-Cys-Ser- Leu-Tyr-Asp-Leu-Glu-Asn-Tyr-Cys20-Asn: B-chain: Ala-Ala-Asn-Arg-His-Leu-Cys-Gly-Ser-His10-Leu-Val- Glu-Ala-Leu-Tyr-Leu-Val-Cys-Gly20-Asn-Arg-Gly-Phe- Phe-Tyr-Ile-Pro-Ser-Lys30-Met. Despite the fact that Polypterus insulin contains several unusual structural features that are not found in insulins from other jawed fish (Asp at A-8, Thr at A-9, Arg at B-4, Asn at B-21, Ile at B-27, Met at B-31), all the residues in human insulin that are involved in receptor binding, dimerization, and hexamerization have been conserved. A comparison of the structures of insulins from a range of species indicates that Polypterus insulin most closely resembles paddlefish insulin II (seven amino acid substitutions). In contrast, Polypterus glucagon (His-Ser- Gln-Gly-Thr-Phe-Thr-Asn-Asp-Tyr10-Thr-Lys-Tyr- Gln-Asp-Ser-Arg-Arg-Ala-Gln20-Asp-Phe-Val-Gln- Trp-Leu-Met-Ser-Asn) most closely resembles the glucagons from the gar Lepisosteus spatula and the bowfin Amia calva (four amino acid substitutions). The data are consistent with the conclusion based on comparison of morphological characteristics that the Polypterids are the most basal living group of the Actinopterygians with evolutionary connections to both the Acipenserids and the Neopterygians.

Structural basis for drug and substrate specificity exhibited by FIV encoding a chimeric FIV/HIV protease

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

Lin, Ying-Chuan; Perryman, Alexander L.; Olson, Arthur J.

2011-06-01

Crystal structures of the 6s-98S FIV protease chimera with darunavir and lopinavir bound have been determined at 1.7 and 1.8 Å resolution, respectively. A chimeric feline immunodeficiency virus (FIV) protease (PR) has been engineered that supports infectivity but confers sensitivity to the human immunodeficiency virus (HIV) PR inhibitors darunavir (DRV) and lopinavir (LPV). The 6s-98S PR has five replacements mimicking homologous residues in HIV PR and a sixth which mutated from Pro to Ser during selection. Crystal structures of the 6s-98S FIV PR chimera with DRV and LPV bound have been determined at 1.7 and 1.8 Å resolution, respectively. Themore » structures reveal the role of a flexible 90s loop and residue 98 in supporting Gag processing and infectivity and the roles of residue 37 in the active site and residues 55, 57 and 59 in the flap in conferring the ability to specifically recognize HIV PR drugs. Specifically, Ile37Val preserves tertiary structure but prevents steric clashes with DRV and LPV. Asn55Met and Val59Ile induce a distinct kink in the flap and a new hydrogen bond to DRV. Ile98Pro→Ser and Pro100Asn increase 90s loop flexibility, Gln99Val contributes hydrophobic contacts to DRV and LPV, and Pro100Asn forms compensatory hydrogen bonds. The chimeric PR exhibits a comparable number of hydrogen bonds, electrostatic interactions and hydrophobic contacts with DRV and LPV as in the corresponding HIV PR complexes, consistent with IC{sub 50} values in the nanomolar range.« less

Analysis of plant hormone profiles in response to moderate dehydration stress.

PubMed

Urano, Kaoru; Maruyama, Kyonoshin; Jikumaru, Yusuke; Kamiya, Yuji; Yamaguchi-Shinozaki, Kazuko; Shinozaki, Kazuo

2017-04-01

Plant responses to dehydration stress are mediated by highly complex molecular systems involving hormone signaling and metabolism, particularly the major stress hormone abscisic acid (ABA) and ABA-dependent gene expression. To understand the roles of plant hormones and their interactions during dehydration, we analyzed the plant hormone profiles with respect to dehydration responses in Arabidopsis thaliana wild-type (WT) plants and ABA biosynthesis mutants (nced3-2). We developed a procedure for moderate dehydration stress, and then investigated temporal changes in the profiles of ABA, jasmonic acid isoleucine (JA-Ile), salicylic acid (SA), cytokinin (trans-zeatin, tZ), auxin (indole-acetic acid, IAA), and gibberellin (GA 4 ), along with temporal changes in the expression of key genes involved in hormone biosynthesis. ABA levels increased in a bi-phasic pattern (at the early and late phases) in response to moderate dehydration stress. JA-Ile levels increased slightly in WT plants and strongly increased in nced3-2 mutant plants at 72 h after the onset of dehydration. The expression profiles of dehydration-inducible genes displayed temporal responses in an ABA-dependent manner. The early phase of ABA accumulation correlated with the expression of touch-inducible genes and was independent of factors involved in the major ABA regulatory pathway, including the ABA-responsive element-binding (AREB/ABF) transcription factor. JA-Ile, SA, and tZ were negatively regulated during the late dehydration response phase. Transcriptome analysis revealed important roles for hormone-related genes in metabolism and signaling during dehydration-induced plant responses. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Simple and rapid analytical method for detection of amino acids in blood using blood spot on filter paper, fast-GC/MS and isotope dilution technique.

PubMed

Kawana, Shuichi; Nakagawa, Katsuhiro; Hasegawa, Yuki; Yamaguchi, Seiji

2010-11-15

A simple and rapid method for quantitative analysis of amino acids, including valine (Val), leucine (Leu), isoleucine (Ile), methionine (Met) and phenylalanine (Phe), in whole blood has been developed using GC/MS. In this method, whole blood was collected using a filter paper technique, and a 1/8 in. blood spot punch was used for sample preparation. Amino acids were extracted from the sample, and the extracts were purified using cation-exchange resins. The isotope dilution method using ²H₈-Val, ²H₃-Leu, ²H₃-Met and ²H₅-Phe as internal standards was applied. Following propyl chloroformate derivatization, the derivatives were analyzed using fast-GC/MS. The extraction recoveries using these techniques ranged from 69.8% to 87.9%, and analysis time for each sample was approximately 26 min. Calibration curves at concentrations from 0.0 to 1666.7 μmol/l for Val, Leu, Ile and Phe and from 0.0 to 333.3 μmol/l for Met showed good linearity with regression coefficients=1. The method detection limits for Val, Leu, Ile, Met and Phe were 24.2, 16.7, 8.7, 1.5 and 12.9 μmol/l, respectively. This method was applied to blood spot samples obtained from patients with phenylketonuria (PKU), maple syrup urine disease (MSUD), hypermethionine and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), and the analysis results showed that the concentrations of amino acids that characterize these diseases were increased. These results indicate that this method provides a simple and rapid procedure for precise determination of amino acids in whole blood. Copyright © 2010 Elsevier B.V. All rights reserved.

Streptococcal phosphoenolpyruvate-sugar phosphotransferase system: amino acid sequence and site of ATP-dependent phosphorylation of HPr

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

Deutscher, J.; Pevec, B.; Beyreuther, K.

1986-10-21

The amino acid sequence of histidine-containing protein (HPr) from Streptococcus faecalis has been determined by direct Edman degradation of intact HPr and by amino acid sequence analysis of tryptic peptides, V8 proteolyptic peptides, thermolytic peptides, and cyanogen bromide cleavage products. HPr from S. faecalis was found to contain 89 amino acid residues, corresponding to a molecular weight of 9438. The amino acid sequence of HPr from S. faecalis shows extended homology to the primary structure of HPr proteins from other bacteria. Besides the phosphoenolpyruvate-dependent phosphorylation of a histidyl residue in HPr, catalyzed by enzyme I of the bacterial phosphotransferase system,more » HPr was also found to be phosphorylated at a seryl residue in an ATP-dependent protein kinase catalyzed reaction. The site of ATP-dependent phosphorylation in HPr of S faecalis has now been determined. (/sup 32/P)P-Ser-HPr was digested with three different proteases, and in each case, a single labeled peptide was isolated. Following digestion with subtilisin, they obtained a peptide with the sequence -(P)Ser-Ile-Met-. Using chymotrypsin, they isolated a peptide with the sequence -Ser-Val-Asn-Leu-Lys-(P)Ser-Ile-Met-Gly-Val-Met-. The longest labeled peptide was obtained with V8 staphylococcal protease. According to amino acid analysis, this peptide contained 36 out of the 89 amino acid residues of HPr. The following sequence of 12 amino acid residues of the V8 peptide was determined: -Tyr-Lys-Gly-Lys-Ser-Val-Asn-Leu-Lys-(P)Ser-Ile-Met-. Thus, the site of ATP-dependent phosphorylation was determined to be Ser-46 within the primary structure of HPr.« less

Assessment of cumulative evidence for the association between glutathione S-transferase polymorphisms and lung cancer: application of the Venice interim guidelines

PubMed Central

Langevin, Scott M.; Ioannidis, John P.A.; Vineis, Paolo; Taioli, Emanuela

2010-01-01

There is an overwhelming abundance of genetic association studies available in the literature, which often can be collectively difficult to interpret. To address this issue, the Venice interim guidelines were established for determining the credibility of the cumulative evidence. The objective of this report is to evaluate the literature on the association of common GST variants (GSTM1 null, GSTT1 null and GSTP1 Ile105Val polymorphism) and lung cancer, and to assess the credibility of the associations using the newly proposed cumulative evidence guidelines. Information from the literature was enriched with an updated meta-analysis and a pooled analysis using data from the Genetic Susceptibility to Environmental Carcinogens (GSEC) database. There was a significant association between GSTM1 null and lung cancer for the meta- (meta OR = 1.17, 95% CI: 1.10–1.25) and pooled analysis (adjusted OR = 1.10, 95% CI: 1.04–1.16), although substantial heterogeneity was present. No overall association between lung cancer and GSTT1 null or GSTP1 Ile105Val was found. When the Venice criteria was applied, cumulative evidence for all associations were considered “weak”, with the exception of East Asian carriers of the G allele of GSTP1 Ile105Val, which was graded as “moderate” evidence. In spite of large amounts of studies, and several statistically significant summary estimates produced by meta-analyses, the application of the Venice criteria suggests extensive heterogeneity and susceptibility to bias for the studies on association of common genetic polymorphisms, such as with GST variants and lung cancer. PMID:20729793

Substrate specificity of platypus venom L-to-D-peptide isomerase.

PubMed

Bansal, Paramjit S; Torres, Allan M; Crossett, Ben; Wong, Karen K Y; Koh, Jennifer M S; Geraghty, Dominic P; Vandenberg, Jamie I; Kuchel, Philip W

2008-04-04

The L-to-D-peptide isomerase from the venom of the platypus (Ornithorhyncus anatinus) is the first such enzyme to be reported for a mammal. In delineating its catalytic mechanism and broader roles in the animal, its substrate specificity was explored. We used N-terminal segments of defensin-like peptides DLP-2 and DLP-4 and natriuretic peptide OvCNP from the venom as substrates. The DLP analogues IMFsrs and ImFsrs (srs is a solubilizing chain; lowercase letters denote D-amino acid) were effective substrates for the isomerase; it appears to recognize the N-terminal tripeptide sequence Ile-Xaa-Phe-. A suite of 26 mutants of these hexapeptides was synthesized by replacing the second residue (Met) with another amino acid, viz. Ala, alpha-aminobutyric acid, Ile, Leu, Lys, norleucine, Phe, Tyr, and Val. It was shown that mutant peptides incorporating norleucine and Phe are substrates and exhibit L- or D-amino acid isomerization, but mutant peptides that contain residues with shorter, beta-branched or long side chains with polar terminal groups, viz. Ala, alpha-aminobutyric acid, Ile, Val, Leu, Lys, and Tyr, respectively, are not substrates. It was demonstrated that at least three N-terminal amino acid residues are absolutely essential for L-to-D-isomerization; furthermore, the third amino acid must be a Phe residue. None of the hexapeptides based on LLH, the first three residues of OvCNP, were substrates. A consistent 2-base mechanism is proposed for the isomerization; abstraction of a proton by 1 base is concomitant with delivery of a proton by the conjugate acid of a second base.

Unraveling Brazilian Indian population prostate good health: clinical, anthropometric and genetic features

PubMed Central

de Lima, Mario M.; Reis, Leonardo O.; Ferreira, Ubirajara; Cardoso, Ulieme Oliveira; Barbieri, Raquel Bueno; de Mendonça, Gustavo B.; Ward, Laura S.

2015-01-01

Purpose To compare dietary, lifestyle, clinical, anthropometric, genetic and prostatic features of Brazilian Indians and non-Indians (Amazon). Methods 315 men, 228 Indians and 89 non-Indians, ≥40 years old were submitted to digital rectal examination, serum prostate specific antigen (PSA), testosterone, TP53 and GSTP1 genotyping, anthropometric, lifestyle, dietary, personal and familial medical history. Prostatic symptoms were evaluated with the International Prostate Symptom Score (IPSS). Results Macuxis and Yanomamis represented 43.6% and 14.5% of Indians respectively who spontaneously referred no prostate symptoms. Mean IPSS was 7, range 3-19, with only 15% of moderate symptoms (score 8-19); Mean age was 54.7 years, waist circumference 86.6 cm, BMI 23.9 kg/m2. Yanomamis presented both lower BMI (21.4 versus 24.8 and 23.3, p=0,001) and prostate volume than Macuxis and “other ethnic groups” (15 versus 20, p=0.001). Testosterone (414 versus 502 and 512, p=0.207) and PSA (0.48 versus 0.6 and 0.41, p=0.349) were similar with progressive PSA increase with aging. Val/Val correlated with lower PSA (p=0.0361). Indians compared to control population presented: - TP53 super representation of Arg/Arg haplotype, 74.5% versus 42.5%, p<0.0001. -GSTP1 Ile/Ile 35.3% versus 60.9%; Ile/Val 45.9% versus 28.7%; Val/Val 18.8% versus 10.3%; p=0.0003. Conclusions Observed specific dietary, lifestyle, anthropometric and genetic profile for TP53 and GSTP1 may contribute to Brazilian Indian population prostate good health. PMID:26005978

A major cathepsin B protease from the liver fluke Fasciola hepatica has atypical active site features and a potential role in the digestive tract of newly excysted juvenile parasites

PubMed Central

Beckham, Simone A.; Piedrafita, David; Phillips, Carolyn I.; Samarawickrema, Nirma; Law, Ruby H.P.; Smooker, Peter M.; Quinsey, Noelene S.; Irving, James A.; Greenwood, Deanne; Verhelst, Steven H. L.; Bogyo, Matthew; Turk, Boris; Coetzer, Theresa H.; Wijeyewickrema, Lakshmi C.; Spithill, Terry W.; Pike, Robert N.

2012-01-01

The newly excysted juvenile (NEJ) stage of the Fasciola hepatica lifecycle occurs just prior to invasion into the wall of the gut of the host, rendering it an important target for drug development. The cathepsin B enzymes from NEJ flukes have recently been demonstrated to be crucial to invasion and migration by the parasite. Here we characterize one of the cathepsin B enzymes (recombinant FhcatB1) from NEJ flukes. FhcatB1 has biochemical properties distinct from mammalian cathepsin B enzymes, with an atypical preference for Ile over Leu or Arg residues at the P2 substrate position and an inability to act as an exopeptidase. FhcatB1 was active across a broad pH range (optimal activity at pH 5.5–7.0) and resistant to inhibition by cystatin family inhibitors from sheep and humans, suggesting that this enzyme would be able to function in extracellular environments in its mammalian hosts. It appears, however, that the FhcatB1 protease functions largely as a digestive enzyme in the gut of the parasite, due to the localization of a specific, fluorescently labeled inhibitor with an Ile at the P2 position. Molecular modelling and dynamics were used to predict the basis for the unusual substrate specificity: a P2 Ile residue positions the substrate optimally for interaction with catalytic residues of the enzyme, and the enzyme lacks an occluding loop His residue crucial for exopeptidase activity. The unique features of the enzyme, particularly with regard to its specificity and likely importance to a vital stage of the parasite’s life cycle, make it an excellent target for therapeutic inhibitors or vaccination. PMID:19401154

Functional and pharmacological evaluation of novel GLA variants in Fabry disease identifies six (two de novo) causative mutations and two amenable variants to the chaperone DGJ.

PubMed

Ferri, Lorenzo; Malesci, Duccio; Fioravanti, Antonella; Bagordo, Gaia; Filippini, Armando; Ficcadenti, Anna; Manna, Raffaele; Antuzzi, Daniela; Verrecchia, Elena; Donati, Ilaria; Mignani, Renzo; Cavicchi, Catia; Guerrini, Renzo; Morrone, Amelia

2018-06-01

Allelic heterogeneity is an important feature of the GLA gene for which almost 900 known genetic variants have been discovered so far. Pathogenetic GLA variants cause alpha-galactosidase A (α-Gal A) enzyme deficiency leading to the X-linked lysosomal storage disorder Fabry disease (FD). Benign GLA intronic and exonic variants (e.g. pseudodeficient p.Asp313Tyr) have also been described. Some GLA missense variants, previously deemed to be pathogenetic (e.g. p.Glu66Gln and p.Arg118Cys), they have been reclassified as benign after re-evaluation by functional and population studies. Hence, the functional role of novel GLA variants should be investigated to assess their clinical relevance. We identified six GLA variants in 4 males and 2 females who exhibited symptoms of FD: c.159C>G p.(Asn53Lys), c.400T>C p.(Tyr134His), c.680G>C (p.Arg227Pro), c.815A>T p.(Asn272Ile), c.907A>T p.(Ile303Phe) and c.1163_1165delTCC (p.Leu388del). We evaluated their impact on the α-Gal A protein by bioinformatic analysis and homology modelling, by analysis of the GLA mRNA, and by site-directed mutagenesis and in vitro expression studies. We also measured their responsiveness to the pharmacological chaperone DGJ. The six detected GLA variants cause deficient α-Gal A activity and impairment or loss of the protein wild-type structure. We found p.Asn53Lys and p.Ile303Phe variants to be susceptible to DGJ. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Maternal BMI and migration status as predictors of childhood obesity in Mexico.

PubMed

Jiménez-Cruz, A; Wojcicki, J M; Bacardí-Gascón, M; Castellón-Zaragoza, A; García-Gallardo, J L; Schwartz, N; Heyman, M B

2011-01-01

To assess the association of maternal migration to Baja California, body mass index (BMI) status, children's perceived food insecurity, and childhood lifestyle behaviors with overweight (BMI > 85% ile), obesity (BMI > 95% ile) and abdominal obesity (Waist Circumference > 90% ile). Convenience sampling methods were used to recruit a cross-sectional sample of 4th, 5th and 6th grade children and their parents at Tijuana and Tecate Public Schools. Children's and parents' weights and heights were measured. Children were considered to have migrant parents if parents were not born in Baja California. One hundred and twenty-two children and their parents were recruited. The mean age of the children was 10.1 ± 1.0 years. Forty nine per cent of children were overweight or obese. Children with obese parents (BMI > 30) had greater odds of being obese, Odds Ratio (OR) 4.9 (95% Confidence Interval (CI), 1.2-19, p = 0.03). Children with migrant parents had greater odds of being obese, OR= 3.7 (95% CI, 1.6-8.3), p = 0.01) and of having abdominal obesity, OR = 3.2 (95% CI, 1.4-7.1, p = 0.01). Children from migrant parents have greater risk of higher consumption of potato chips, OR = 8.0 (95% CI, 2.1-29.1, p = 0.01). Children from non-migrant parents had greater odds of being at risk of hunger. Parental obesity and migration are associated with increased risk of obesity among Mexican children. Children whose parents were born in Baja California have greater odds of being at risk of hunger. Further studies should evaluate the role of migration on risk for childhood obesity.

Ocular toxoplasmosis: susceptibility in respect to the genes encoding the KIR receptors and their HLA class I ligands.

PubMed

Ayo, Christiane Maria; Frederico, Fábio Batista; Siqueira, Rubens Camargo; Brandão de Mattos, Cinara de Cássia; Previato, Mariana; Barbosa, Amanda Pires; Murata, Fernando Henrique Antunes; Silveira-Carvalho, Aparecida Perpétuo; de Mattos, Luiz Carlos

2016-11-09

The objective of this study was to investigate the influence of the genes encoding the KIR receptors and their HLA ligands in the susceptibility of ocular toxoplasmosis. A total of 297 patients serologically-diagnosed with toxoplasmosis were selected and stratified according to the presence (n = 148) or absence (n = 149) of ocular scars/lesions due to toxoplasmosis. The group of patients with scars/lesions was further subdivided into two groups according to the type of ocular manifestation observed: primary (n = 120) or recurrent (n = 28). Genotyping was performed by PCR-SSOP. Statistical analyses were conducted using the Chi-square test, and odds ratio with a 95% confidence interval was also calculated to evaluate the risk association. The activating KIR3DS1 gene was associated with increased susceptibility for ocular toxoplasmosis. The activating KIR together with their HLA ligands (KIR3DS1-Bw4-80Ile and KIR2DS1 + /C2 ++ KIR3DS1 + /Bw4-80Ile + ) were associated with increased susceptibility for ocular toxoplasmosis and its clinical manifestations. KIR-HLA inhibitory pairs -KIR2DL3/2DL3-C1/C1 and KIR2DL3/2DL3-C1- were associated with decreased susceptibility for ocular toxoplasmosis and its clinical forms, while the KIR3DS1 - /KIR3DL1 + /Bw4-80Ile + combination was associated as a protective factor against the development of ocular toxoplasmosis and, in particular, against recurrent manifestations. Our data demonstrate that activating and inhibitory KIR genes may influence the development of ocular toxoplasmosis.

Assessment of cumulative evidence for the association between glutathione S-transferase polymorphisms and lung cancer: application of the Venice interim guidelines.

PubMed

Langevin, Scott M; Ioannidis, John P A; Vineis, Paolo; Taioli, Emanuela

2010-10-01

There is an overwhelming abundance of genetic association studies available in the literature, which can often be collectively difficult to interpret. To address this issue, the Venice interim guidelines were established for determining the credibility of the cumulative evidence. The objective of this report is to evaluate the literature on the association of common glutathione S-transferase (GST) variants (GSTM1 null, GSTT1 null and GSTP1 Ile105Val polymorphism) and lung cancer, and to assess the credibility of the associations using the newly proposed cumulative evidence guidelines. Information from the literature was enriched with an updated meta-analysis and a pooled analysis using data from the Genetic Susceptibility to Environmental Carcinogens database. There was a significant association between GSTM1 null and lung cancer for the meta-analysis (meta odds ratio=1.17, 95% confidence interval: 1.10-1.25) and pooled analysis (adjusted odds ratio=1.10, 95% confidence interval: 1.04-1.16), although substantial heterogeneity was present. No overall association between lung cancer and GSTT1 null or GSTP1 Ile105Val was found. When the Venice criteria was applied, cumulative evidence for all associations were considered 'weak', with the exception of East Asian carriers of the G allele of GSTP1 Ile105Val, which was graded as 'moderate' evidence. Despite the large amounts of studies, and several statistically significant summary estimates produced by meta-analyses, the application of the Venice criteria suggests extensive heterogeneity and susceptibility to bias for the studies on association of common genetic polymorphisms, such as with GST variants and lung cancer.

Ocular toxoplasmosis: susceptibility in respect to the genes encoding the KIR receptors and their HLA class I ligands

PubMed Central

Ayo, Christiane Maria; Frederico, Fábio Batista; Siqueira, Rubens Camargo; Brandão de Mattos, Cinara de Cássia; Previato, Mariana; Barbosa, Amanda Pires; Murata, Fernando Henrique Antunes; Silveira-Carvalho, Aparecida Perpétuo; de Mattos, Luiz Carlos

2016-01-01

The objective of this study was to investigate the influence of the genes encoding the KIR receptors and their HLA ligands in the susceptibility of ocular toxoplasmosis. A total of 297 patients serologically-diagnosed with toxoplasmosis were selected and stratified according to the presence (n = 148) or absence (n = 149) of ocular scars/lesions due to toxoplasmosis. The group of patients with scars/lesions was further subdivided into two groups according to the type of ocular manifestation observed: primary (n = 120) or recurrent (n = 28). Genotyping was performed by PCR-SSOP. Statistical analyses were conducted using the Chi-square test, and odds ratio with a 95% confidence interval was also calculated to evaluate the risk association. The activating KIR3DS1 gene was associated with increased susceptibility for ocular toxoplasmosis. The activating KIR together with their HLA ligands (KIR3DS1-Bw4-80Ile and KIR2DS1+/C2++ KIR3DS1+/Bw4-80Ile+) were associated with increased susceptibility for ocular toxoplasmosis and its clinical manifestations. KIR-HLA inhibitory pairs -KIR2DL3/2DL3-C1/C1 and KIR2DL3/2DL3-C1- were associated with decreased susceptibility for ocular toxoplasmosis and its clinical forms, while the KIR3DS1−/KIR3DL1+/Bw4-80Ile+ combination was associated as a protective factor against the development of ocular toxoplasmosis and, in particular, against recurrent manifestations. Our data demonstrate that activating and inhibitory KIR genes may influence the development of ocular toxoplasmosis. PMID:27827450

Earth Observations taken by Expedition 38 crewmember

NASA Image and Video Library

2014-01-28

ISS038-E-036501 (28 Jan. 2014) --- This wide field-of-view image photographed by an Expedition 38 crew member on the International Space Station shows an east-west swath of the southwestern Indian Ocean. Two remote islands, part of the French Southern and Antarctic Lands, appear in the center of the image. Possession Island (right center) and East Island (center) are both only 18 kilometers long. A smaller island, Ile aux Cochons (Pigs Island), lies 100 kilometers to the west. Each island has set up V-shaped trains of waves, like bow waves, as the air flows over the islands from the west (right to left). The bow-wave patterns are overlaid on the low regional stratus (blanket) cloud that is so common in the southern Indian Ocean at 50 degrees south latitude. This view was taken from more than 400 kilometers above the sea surface and reveals relationships that could not be readily understood by someone standing on one of the islands. For example, larger and higher islands produce larger waves. So the largest are being generated by Possession Island (934 meters above sea level at the highest point), and East Island, versus much smaller waves developed downwind of the tiny Ile de Pingouins (340 meters above sea level high, invisible below the cloud deck). Other patterns also can be detected. Waves in an upper layer can be seen casting shadows onto a lower layer (lower left). In the top half of the image the waves are making thicker and thinner zones in the clouds of the lower layer. Wave trains from Possession Island and Ile aux Cochons are interacting in a cross-hatch pattern (center).

Mutations within Four Distinct Gag Proteins Are Required To Restore Replication of Human Immunodeficiency Virus Type 1 after Deletion Mutagenesis within the Dimerization Initiation Site

PubMed Central

Liang, Chen; Rong, Liwei; Quan, Yudong; Laughrea, Michael; Kleiman, Lawrence; Wainberg, Mark A.

1999-01-01

Human immunodeficiency virus type 1 (HIV-1) genomic RNA segments at nucleotide (nt) positions +240 to +274 are thought to form a stem-loop secondary structure, termed SL1, that serves as a dimerization initiation site for viral genomic RNA. We have generated two distinct deletion mutations within this region, termed BH10-LD3 and BH10-LD4, involving nt positions +238 to +253 and +261 to +274, respectively, and have shown that each of these resulted in significant diminutions in levels of viral infectiousness. However, long-term culture of each of these viruses in MT-2 cells resulted in a restoration of infectiousness, due to a series of compensatory point mutations within four distinct proteins that are normally cleaved from the Gag precursor. In the case of BH10-LD3, these four mutations were MA1, CA1, MP2, and MNC, and they involved changes of amino acid Val-35 to Ile within the matrix protein (MA), Ile-91 to Thr within the capsid (CA), Thr-12 to Ile within p2, and Thr-24 to Ile within the nucleocapsid (NC). The order in which these mutations were acquired by the mutated BH10-LD3 was MNC > CA1 > MP2 > MA1. The results of site-directed mutagenesis studies confirmed that each of these four substitutions contributed to the increased viability of the mutated BH10-LD3 viruses and that the MNC substitution, which was acquired first, played the most important role in this regard. Three point mutations, MP2, MNC, and MA2, were also shown to be sequentially acquired by viruses that had emerged in culture from the BH10-LD4 deletion. The first two of these were identical to those described above, while the last involved a change of Val-35 to Leu. All three of these substitutions were necessary to restore the infectiousness of mutated BH10-LD4 viruses to wild-type levels, although the MP2 mutation alone, but neither of the other two substitutions, was able to confer some viability on BH10-LD4 viruses. Studies of viral RNA packaging showed that the BH10-LD4 deletion only

Association of genetic polymorphism of glutathione S-transferase (GSTM1, GSTT1, GSTP1) with bladder cancer susceptibility.

PubMed

Safarinejad, Mohammad Reza; Safarinejad, Saba; Shafiei, Nayyer; Safarinejad, Shiva

2013-10-01

The glutathione-S-transferases (GSTs) comprise a class of enzymes that detoxify carcinogenic compounds by conjugating glutathione to facilitate their removal. Polymorphisms in GSTM1, GSTT1, and GSTP1 genes have been related to risk for bladder cancer. Studies focusing on GSTs gene variants relationship with the risk of bladder cancer have produced conflicting and inconsistent results. We examine the association between genetic polymorphism of glutathione S-transferase P1, GSTM1, GSTT1 genes and development of bladder transitional cell carcinoma (TCC). The study population consisted of 166 histologically confirmed male bladder TCC cases and 332 healthy male controls. Genotyping was done using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method and also investigated combined gene interactions. The GSTP1 Val/Val genotype was significantly associated with bladder cancer (OR = 4.32, 95% CI: 2.64-6.34), whereas the association observed for GSTM1 null (OR = 1.32, 95% CI: 0.82-2.62; P = 0.67) and GSTT1 null genotype (OR = 1.18, 95% CI: 0.79-1.67; P = 0.74) did not reach statistical significance. There was a significant multiple interaction between GSTM1, GSTT1, and GSTP1 genotypes in risk of bladder cancer (P for interaction = 0.02). The risk associated with the concurrent presence of GSTM1 positive and GSTP1 Ile/Val or Val/Val (OR = 3.71, 95% CI: 2.34-5.54) and GSTT1 positive and GSTP1 Ile/Val or Val/Val (OR = 2.66, 95% CI: 1.54-4.72) was statistically significant. Patients carrying GSTP1 Val/Val genotype were at increased risk for developing high-grade (OR = 7.68, 95% CI: 4.73-19.25) and muscle invasive (OR = 10.67, 95% CI: 6.34-21.75) bladder cancer. High risk for bladder TCC also was observed with respect to combined GSTT1 null/GSTP1 Ile/Val or Val/Val (OR = 4.76, 95% CI: 2.68-18.72) and GSTM1 null/GSTT1 null/GSTP1 Ile/Val or Val/Val (OR = 6.42, 95% CI: 4.76-14.72) genotype variant. This study suggests that the GSTP1 polymorphism

Interaction of human platelets with laminin and identification of the 67 kDa laminin receptor on platelets.

PubMed Central

Tandon, N N; Holland, E A; Kralisz, U; Kleinman, H K; Robey, F A; Jamieson, G A

1991-01-01

A microtitre adhesion assay has been developed to define parameters affecting the adherence of washed platelets to laminin. Adherence was optimally supported by Mg2+ and was inhibited by Ca2+ and by anti-laminin Fab fragments, but significant adhesion (75-90% of control) was found both in heparinized plasma containing physiological levels of bivalent cations and in plasma anti-coagulated with EGTA. Adherence was unaffected by platelet activation with ADP but was decreased by 50% by treatment with alpha-thrombin (1 unit/ml, 5 min). Adherence was unaffected by monospecific polyclonal antibodies to glycoprotein (GP) Ib and GPIV, and was normal with platelets from two patients with Glanzmann's thrombasthaenia, indicating that GPIb, the GPIIb/IIIa complex and GPIV are not involved in platelet-laminin interaction. Affinity chromatography of Triton-solubilized membranes on laminin-Sepharose followed by elution with 0.2 M-glycine/HCl (pH 2.85) identified a major band with a molecular mass of 67 kDa in the reduced and of 53 kDa in the unreduced form. This protein gave a positive reaction on Western blotting with a monospecific polyclonal antibody raised against the high-affinity laminin receptor isolated from human breast carcinoma tissue. The adhesion of platelets to laminin was inhibited by two monoclonal IgM antibodies specific to the LR-1 domain of the 67 kDa receptor. The binding protein was surface-oriented, as shown by flow cytofluorimetry and by the fact that it could be iodinated in intact platelets, but it was not labelled by the periodate-borotritide procedure, suggesting that it did not contain terminal sialic acid. The laminin-derived peptides Tyr-Ile-Gly-Ser-Arg and Cys-Asp-Pro-Gly-Tyr-Ile-Gly-Ser-Arg-NH2, which constitute a complementary binding domain in laminin for the 67 kDa receptor, themselves supported platelet adhesion, bound to the receptor and inhibited the adhesion of platelets to laminin. In addition, Fab fragments of anti-Tyr-Ile

Origin and applicability of tetraether membrane lipids as temperature proxies in French peri-urban lakes

NASA Astrophysics Data System (ADS)

Mainié, François; Huguet, Arnaud; Breban, Alice; Lacroix, Gérard; Anquetil, Christelle; Derenne, Sylvie

2015-04-01

The Ile-de-France region is the most populated area in France, with ca. 12 million inhabitants, i.e. about 20 % of French population. The peri-urban aquatic ecosystems of this region are impacted by a large variety of environmental stressors, and especially high anthropogenic pressures (agricultural, industrial and urban pollutants), leading to the increased eutrophication of these water systems. The Ile-de-France lakes are therefore highly vulnerable ecosystems. Over the last years, several environmental markers have been developed to better understand the functioning of aquatic ecosystems, including the so-called GDGTs (glycerol dialkyl glycerol tetraethers). GDGTs are membrane lipids produced by archaea and some unknown bacteria, which are increasingly used to reconstruct mean annual air and surface water temperature as well as pH. These compounds are ubiquitous in terrestrial and aquatic environments, but their origin and applicability as temperature and pH proxies in lakes, especially highly polluted ones, need further investigation. In this study, GDGTs were analysed in 33 lakes from the Ile-de-France region, representing the diversity of the regional landscape and characterised by different levels of eutrophication. The abundance and distribution of GDGTs in lacustrine sediments and surrounding soils were compared. Bacterial GDGTs were systematically much more abundant in sediments than in soils and displayed different distributions in the two types of environments, showing that they are mainly produced in situ in lakes, in the water column and/or sediment. Similarly, the concentration in archaeal GDGTs was much higher in sediments than in soils and the distribution of these compounds differed between soils and sediments, implying that the predominant archaeal communities are not the same in the two environments. When the lakes are distinguished by their eutrophication level, the latter was shown for the first time to have an impact on the microorganisms

Innovative Learning Environments and New Materialism: A Conjunctural Analysis of Pedagogic Spaces

ERIC Educational Resources Information Center

Charteris, Jennifer; Smardon, Dianne; Nelson, Emily

2017-01-01

An Organisation for Economic Cooperation and Development research priority, innovative learning environments (ILEs) have been translated into policy and practice in 25 countries around the world. In Aotearoa/New Zealand, learning spaces are being reconceptualised in relation to this policy work by school leaders who are confronted by an impetus to…

U.S. EPA, Pesticide Product Label, , 03/11/1980

EPA Pesticide Factsheets

2011-04-14

... ns per .c,e. Do n")t mill' I<.ERS'with 1:ny '''luv.nl$ (,of ... "." oil' JI, S .t:.l,·#'·1 .it 'v'" ~.1"l. ''1!','j', ~.! 1ll"I:;' ·h ... pc, t ·c.ted .cre on t .... o 5 Inert 1''''oIled o.nds ...

Repositioning Guidance and Counselling and Curriculum Innovation in Higher Education in Nigeria

ERIC Educational Resources Information Center

Onyilofor, Florence N. C.

2013-01-01

This study focuses on repositioning guidance and counseling and curriculum innovation in higher education in Nigeria. Descriptive survey research design was employed in the study. The study covered four Federal universities in the South-West Geopolitical zone of Nigeria, namely University of Ibadan in Oyo State; Obafemi Awolowo University, Ile-Ife…

77 FR 66785 - Proposed Flood Elevation Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-07

... Lafayette Parish. Approximately 1.27 +30 +29 miles upstream of Ridge Road. Coulee Ile Des Cannes--Lateral 3.... SUMMARY: On January 24, 2008, September 27, 2010, and August 3, 2011, FEMA published proposed rules in the Federal Register. The August 3, 2011 proposed rule contained an erroneous table. This notice provides...

Commentary on: "Toward Computer-Based Support of Metacognitive Skills: A Computational Framework to Coach Self Explanation"

ERIC Educational Resources Information Center

Conati, Cristina

2016-01-01

This paper is a commentary on "Toward Computer-Based Support of Meta-Cognitive Skills: a Computational Framework to Coach Self-Explanation", by Cristina Conati and Kurt Vanlehn, published in the "IJAED" in 2000 (Conati and VanLehn 2010). This work was one of the first examples of Intelligent Learning Environments (ILE) that…

Religious Tolerance and Understanding in the French Education System

ERIC Educational Resources Information Center

Ferrara, Carol

2012-01-01

This research is based on an interview and survey-based case study of an Islamic "lycee", a Catholic "lycee", and two public "lycees" in the Ile-de-France region of France. The study investigated whether students in private schools receiving some form of education about religion tend to be more tolerant and…

New Estimates of the Effect of Unemployment on Enlisted Retention

DTIC Science & Technology

1985-07-01

S14cw’tity lafication) New Estimates of the Effect of Umemployment on Enlisted Retention 12. PERSONAL AUTHOR(S) Ile, TYPE OF REPORT 3b~. TIME COVERED...wider swings in the umemployment rate during recent years, relative military pay has played at least as important a role as the unemployment rate in

Differentiating founder and chronic HIV envelope sequences

PubMed Central

Maher, Stephen; Mota, Talia; Suzuki, Kazuo; Kelleher, Anthony D.

2017-01-01

Significant progress has been made in characterizing broadly neutralizing antibodies against the HIV envelope glycoprotein Env, but an effective vaccine has proven elusive. Vaccine development would be facilitated if common features of early founder virus required for transmission could be identified. Here we employ a combination of bioinformatic and operations research methods to determine the most prevalent features that distinguish 78 subtype B and 55 subtype C founder Env sequences from an equal number of chronic sequences. There were a number of equivalent optimal networks (based on the fewest covarying amino acid (AA) pairs or a measure of maximal covariance) that separated founders from chronics: 13 pairs for subtype B and 75 for subtype C. Every subtype B optimal solution contained the founder pairs 178–346 Asn-Val, 232–236 Thr-Ser, 240–340 Lys-Lys, 279–315 Asp-Lys, 291–792 Ala-Ile, 322–347 Asp-Thr, 535–620 Leu-Asp, 742–837 Arg-Phe, and 750–836 Asp-Ile; the most common optimal pairs for subtype C were 644–781 Lys-Ala (74 of 75 networks), 133–287 Ala-Gln (73/75) and 307–337 Ile-Gln (73/75). No pair was present in all optimal subtype C solutions highlighting the difficulty in targeting transmission with a single vaccine strain. Relative to the size of its domain (0.35% of Env), the α4β7 binding site occurred most frequently among optimal pairs, especially for subtype C: 4.2% of optimal pairs (1.2% for subtype B). Early sequences from 5 subtype B pre-seroconverters each exhibited at least one clone containing an optimal feature 553–624 (Ser-Asn), 724–747 (Arg-Arg), or 46–293 (Arg-Glu). PMID:28187204

Case Report: Nodule Development From Subcapsular Aldosterone-Producing Cell Clusters Causes Hyperaldosteronism.

PubMed

Nishimoto, Koshiro; Seki, Tsugio; Kurihara, Isao; Yokota, Kenichi; Omura, Masao; Nishikawa, Tetsuo; Shibata, Hirotaka; Kosaka, Takeo; Oya, Mototsugu; Suematsu, Makoto; Mukai, Kuniaki

2016-01-01

We previously reported that the human adrenal cortex remodels to form subcapsular aldosterone-producing cell clusters (APCCs). Some APCCs were recently found to carry aldosterone-producing adenoma (APA)-associated somatic mutations in ion channel/pump genes, which implied that APCCs produce aldosterone autonomously and are an origin of APA. However, there has been no report describing an APCC-to-APA transitional lesion. A histological examination revealed unilateral multiple adrenocortical micronodules in the adrenals of two patients with primary aldosteronism (PA). Based on immunohistochemistry for aldosterone synthase, some of the micronodules were identified as possible APCC-to-APA transitional lesions (pAATLs; a tentative term used in this manuscript), which consisted of a subcapsular APCC-like portion and an inner micro-APA-like (mAPA-like) portion without an apparent histological border. Genomic DNA samples prepared from pAATL histological sections were analyzed by next-generation sequencing for the known APA-associated mutations. The mAPA-like portions from two of the three large pAATLs examined harbored mutations (KCNJ5 [p.G151R] in pAATL 3 and ATP1A1 [p.L337M] in pAATL 7), whereas their corresponding APCC-like portions did not, suggesting their role in the formation of mAPA. Another lesion carried novel mutations in ATP1A1 (p.Ile322_Ile325del and p.Ile327Ser) in both the mAPA-like and APCC-like portions, thereby supporting these portions having a clonal origin. A novel aldosterone-producing pathology, pAATL that causes unilateral PA, was detected in the adrenals of two patients. Next-generation sequencing analyses of the large pAATLs suggested that the introduction of APA-associated mutations in the ion channel/pump genes may be involved in the development of mAPA from existing APCCs.

Genetic polymorphisms in glutathione S-transferase (GST) superfamily and arsenic metabolism in residents of the Red River Delta, Vietnam

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

Agusa, Tetsuro; Center for Marine Environmental Studies; Iwata, Hisato, E-mail: iwatah@agr.ehime-u.ac.j

To elucidate the role of genetic factors in arsenic metabolism, we investigated associations of genetic polymorphisms in the members of glutathione S-transferase (GST) superfamily with the arsenic concentrations in hair and urine, and urinary arsenic profile in residents in the Red River Delta, Vietnam. Genotyping was conducted for GST omega1 (GSTO1) Ala140Asp, Glu155del, Glu208Lys, Thr217Asn, and Ala236Val, GST omega2 (GSTO2) Asn142Asp, GST pi1 (GSTP1) Ile105Val, GST mu1 (GSTM1) wild/null, and GST theta1 (GSTT1) wild/null. There were no mutation alleles for GSTO1 Glu208Lys, Thr217Asn, and Ala236Val in this population. GSTO1 Glu155del hetero type showed higher urinary concentration of As{sup V} thanmore » the wild homo type. Higher percentage of DMA{sup V} in urine of GSTM1 wild type was observed compared with that of the null type. Strong correlations between GSTP1 Ile105Val and arsenic exposure level and profile were observed in this study. Especially, heterozygote of GSTP1 Ile105Val had a higher metabolic capacity from inorganic arsenic to monomethyl arsenic, while the opposite trend was observed for ability of metabolism from As{sup V} to As{sup III}. Furthermore, other factors including sex, age, body mass index, arsenic level in drinking water, and genotypes of As (+ 3 oxidation state) methyltransferase (AS3MT) were also significantly co-associated with arsenic level and profile in the Vietnamese. To our knowledge, this is the first study indicating the associations of genetic factors of GST superfamily with arsenic metabolism in a Vietnamese population.« less

Effects of genetic polymorphisms of metabolic enzymes on cytokinesis-block micronucleus in peripheral blood lymphocyte among coke-oven workers

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

Shuguang Leng; Yufei Dai; Yong Niu

Exploring the associations between genetic polymorphisms of metabolic enzymes and susceptibility to polycyclic aromatic hydrocarbon (PAH)-induced chromosomal damage is of great significance for understanding PAH carcinogenesis. Cytochrome P450, glutathione S-transferase, microsomal epoxide hydrolase, NAD(P)H:quinone oxidoreductase, and N-acetyltransferase are PAH-metabolizing enzymes. In this study, we genotyped for the polymorphisms of these genes and assessed their effects on cytokinesis-block micronucleus (CBMN) frequencies in peripheral blood lymphocytes among 141 coke-oven workers and 66 non-coke-oven worker controls. The geometric means of urinary 1-hydroxypyrene levels in coke-oven workers and the controls were 12.0 and 0.7 {mu}mol/mol creatinine, respectively. The CBMN frequency (number of micronuclei permore » 1,000 binucleated lymphocytes) was significantly higher in coke-oven workers (9.5 {+-} 6.6) than in the controls. Among the coke-oven workers, age was positively associated with CBMN frequency; the mEH His{sup 113} variant genotype exhibited significantly lower CBMN frequency than did the Tyr{sup 113}/Tyr{sup 113} genotype; the low mEH activity phenotype exhibited a lower CBMN frequency than did the high mEH activity phenotype; the GSTP1 Val{sup 105}/Val{sup 105} genotype exhibited a higher CBMN frequency than did the GSTP1 Ile{sup 105}/Ile{sup 105} or Ile{sup 105}/Val{sup 105} genotypes; the joint effect of high mEH activity phenotype and GSTM1 null genotype on CBMN frequencies was also found. Gene-environment interactions between occupational PAH exposure and polymorphisms of mEH and/or GSTM1 were also evident. These results indicate that the mEH, GSTP1, and GSTM1 polymorphisms may play a role in sensitivity or genetic susceptibility to the genotoxic effects of PAH exposure in the coke-oven workers.« less

Common genetic variants of the ion channel transient receptor potential membrane melastatin 6 and 7 (TRPM6 and TRPM7), magnesium intake, and risk of type 2 diabetes in women.

PubMed

Song, Yiqing; Hsu, Yi-Hsiang; Niu, Tianhua; Manson, Joann E; Buring, Julie E; Liu, Simin

2009-01-17

Ion channel transient receptor potential membrane melastatin 6 and 7 (TRPM6 and TRPM7) play a central role in magnesium homeostasis, which is critical for maintaining glucose and insulin metabolism. However, it is unclear whether common genetic variation in TRPM6 and TRPM7 contributes to risk of type 2 diabetes. We conducted a nested case-control study in the Women's Health Study. During a median of 10 years of follow-up, 359 incident diabetes cases were diagnosed and matched by age and ethnicity with 359 controls. We analyzed 20 haplotype-tagging single nucleotide polymorphisms (SNPs) in TRPM6 and 5 common SNPs in TRPM7 for their association with diabetes risk. Overall, there was no robust and significant association between any single SNP and diabetes risk. Neither was there any evidence of association between common TRPM6 and TRPM7 haplotypes and diabetes risk. Our haplotype analyses suggested a significant risk of type 2 diabetes among carriers of both the rare alleles from two non-synomous SNPs in TRPM6 (Val1393Ile in exon 26 [rs3750425] and Lys1584Glu in exon 27 [rs2274924]) when their magnesium intake was lower than 250 mg per day. Compared with non-carriers, women who were carriers of the haplotype 1393Ile-1584Glu had an increased risk of type 2 diabetes (OR, 4.92, 95% CI, 1.05-23.0) only when they had low magnesium intake (<250 mg/day). Our results provide suggestive evidence that two common non-synonymous TRPM6 coding region variants, Ile1393Val and Lys1584Glu polymorphisms, might confer susceptibility to type 2 diabetes in women with low magnesium intake. Further replication in large-scale studies is warranted.

Differences in N-linked glycosylation between human surfactant protein-B variants of the C or T allele at the single-nucleotide polymorphism at position 1580: implications for disease.

PubMed Central

Wang, Guirong; Christensen, Neil D; Wigdahl, Brian; Guttentag, Susan H; Floros, Joanna

2003-01-01

Human surfactant protein-B (SP-B), a hydrophobic protein, is essential for normal lung function. SP-B is expressed and secreted by specific lung cell types, i.e. alveolar type II and Clara cells, of the respiratory epithelium. The SP-B precursor (42 kDa) undergoes post-translational processing to generate an 8 kDa mature SP-B. A single-nucleotide polymorphism (SNP) at nucleotide 1580 (C/T) in exon 4 of SP-B that changes amino acid 131 from threonine to isoleucine (Thr131-->Ile) is associated with several pulmonary diseases. The Thr131-->Ile substitution can eliminate a potential N-linked glycosylation site, Asn129-Gln-Thr131, which is present in the SP-B variant of the C allele (ACT/Thr) but not in that of the T allele (ATT/Ile). To determine whether the C allele SP-B variant is indeed glycosylated at Asn(129)-Gln-Thr131, we first generated stably transfected Chinese hamster ovary cell lines that expressed each version of SP-B, and developed specific SP-B polyclonal anti-peptide antibodies. Using both the stably transfected cell lines and fetal lung explants, we observed that the C allele variant is indeed glycosylated at the Asn129-Gln-Thr131 site, whereas the T allele variant, which served as a control, is not. In addition, we also confirmed that both SP-B variants contain another N-linked glycosylation site, Asn311-Ser-Ser313. Given its association with several pulmonary diseases, this finding provides useful information for future studies in disease systems associated with this SNP. Further, we speculate that, given the fact that this SNP is found frequently in the general population, N-linked glycosylation at residue Asn129 interferes with SP-B processing, secretion and folding under certain disease conditions. PMID:12356334

Energy requirements of Texel crossbred lambs.

PubMed

Galvani, D B; Pires, C C; Kozloski, G V; Wommer, T P

2008-12-01

Two trials were conducted to determine the energy requirements of feedlot Texel crossbred lambs. In a comparative slaughter trial, thirty 11/16 Texel x 5/16 Ile de France crossbred noncastrated male lambs, weaned at 42 d of age (16.2 +/- 2.1 kg of shrunk BW; SBW), were used. Five lambs were randomly chosen and slaughtered after 10 d of experimental management and diet adaptation (baseline group). Fifteen lambs then were fed for ad libitum intake and slaughtered at 25, 30, or 35 kg of SBW. The remaining 10 lambs were randomly assigned to 2 levels of DMI, either 70 or 55% of the ad libitum intake, and were slaughtered concomitantly with lambs of the 35 kg of SBW group. Total body N, fat, and energy contents were determined. In a digestibility trial, 6 Texel x Ile de France crossbred lambs (30.4 +/- 2.6 kg of SBW) were housed in metabolic cages and used in a replicated 3 x 3 Latin square experiment to evaluate the energetic value of the diet at different feed intake levels. Net and ME requirements for maintenance were 58.6 and 91 kcal/kg(0.75) of SBW, respectively. Consequently, partial efficiency of energy use for maintenance was 0.64. Body fat content varied from 72.7 to 125.9 g/kg of empty BW, respectively, for 13.1 and 28.2 kg of empty BW. Net energy requirements for growth of lambs at 15 and 35 kg of SBW at an ADG of 250 g were 424 and 553 kcal/d, respectively. Partial efficiency of energy use for growth was 0.47. Texel x Ile de France crossbred growing lambs used in this study showed decreased nutritional requirements than those reported by most nutritional systems.

Replacement of two amino acids of 9R-dioxygenase-allene oxide synthase of Aspergillus niger inverts the chirality of the hydroperoxide and the allene oxide.

PubMed

Sooman, Linda; Wennman, Anneli; Hamberg, Mats; Hoffmann, Inga; Oliw, Ernst H

2016-02-01

The genome of Aspergillus niger codes for a fusion protein (EHA25900), which can be aligned with ~50% sequence identity to 9S-dioxygenase (DOX)-allene oxide synthase (AOS) of Fusarium oxysporum, homologues of the Fusarium and Colletotrichum complexes and with over 62% sequence identity to homologues of Aspergilli, including (DOX)-9R-AOS of Aspergillus terreus. The aims were to characterize the enzymatic activities of EHA25900 and to identify crucial amino acids for the stereospecificity. Recombinant EHA25900 oxidized 18:2n-6 sequentially to 9R-hydroperoxy-10(E),12(Z)-octadecadienoic acid (9R-HPODE) and to a 9R(10)-allene oxide. 9S- and 9R-DOX-AOS catalyze abstraction of the pro-R hydrogen at C-11, but the direction of oxygen insertion differs. A comparison between twelve 9-DOX domains of 9S- and 9R-DOX-AOS revealed conserved amino acid differences, which could contribute to the chirality of products. The Gly616Ile replacement of 9R-DOX-AOS (A. niger) increased the biosynthesis of 9S-HPODE and the 9S(10)-allene oxide, whereas the Phe627Leu replacement led to biosynthesis of 9S-HPODE and the 9S(10)-allene oxide as main products. The double mutant (Gly616Ile, Phe627Leu) formed over 90% of the 9S stereoisomer of HPODE. 9S-HPODE was formed by antarafacial hydrogen abstraction and oxygen insertion, i.e., the original H-abstraction was retained but the product chirality was altered. We conclude that 9R-DOX-AOS can be altered to 9S-DOX-AOS by replacement of two amino acids (Gly616Ile, Phe627Leu) in the DOX domain. Copyright © 2015 Elsevier B.V. All rights reserved.

Critical Roles of Two Hydrophobic Residues within Human Glucose Transporter 9 (hSLC2A9) in Substrate Selectivity and Urate Transport*

PubMed Central

Long, Wentong; Panwar, Pankaj; Witkowska, Kate; Wong, Kenneth; O'Neill, Debbie; Chen, Xing-Zhen; Lemieux, M. Joanne; Cheeseman, Chris I.

2015-01-01

High blood urate levels (hyperuricemia) have been found to be a significant risk factor for cardiovascular diseases and inflammatory arthritis, such as hypertension and gout. Human glucose transporter 9 (hSLC2A9) is an essential protein that mainly regulates urate/hexose homeostasis in human kidney and liver. hSLC2A9 is a high affinity-low capacity hexose transporter and a high capacity urate transporter. Our previous studies identified a single hydrophobic residue in trans-membrane domain 7 of class II glucose transporters as a determinant of fructose transport. A mutation of isoleucine 335 to valine (I355V) in hSLC2A9 can reduce fructose transport while not affecting glucose fluxes. This current study demonstrates that the I335V mutant transports urate similarly to the wild type hSLC2A9; however, Ile-335 is necessary for urate/fructose trans-acceleration exchange to occur. Furthermore, Trp-110 is a critical site for urate transport. Two structural models of the class II glucose transporters, hSLC2A9 and hSLC2A5, based on the crystal structure of hSLC2A1 (GLUT1), reveal that Ile-335 (or the homologous Ile-296 in hSLC2A5) is a key component for protein conformational changes when the protein translocates substrates. The hSLC2A9 model also predicted that Trp-110 is a crucial site that could directly interact with urate during transport. Together, these studies confirm that hSLC2A9 transports both urate and fructose, but it interacts with them in different ways. Therefore, this study advances our understanding of how hSLC2A9 mediates urate and fructose transport, providing further information for developing pharmacological agents to treat hyperuricemia and related diseases, such as gout, hypertension, and diabetes. PMID:25922070

Genetic polymorphisms in glutathione S-transferase (GST) superfamily and arsenic metabolism in residents of the Red River Delta, Vietnam.

PubMed

Agusa, Tetsuro; Iwata, Hisato; Fujihara, Junko; Kunito, Takashi; Takeshita, Haruo; Minh, Tu Binh; Trang, Pham Thi Kim; Viet, Pham Hung; Tanabe, Shinsuke

2010-02-01

To elucidate the role of genetic factors in arsenic metabolism, we investigated associations of genetic polymorphisms in the members of glutathione S-transferase (GST) superfamily with the arsenic concentrations in hair and urine, and urinary arsenic profile in residents in the Red River Delta, Vietnam. Genotyping was conducted for GST omega1 (GSTO1) Ala140Asp, Glu155del, Glu208Lys, Thr217Asn, and Ala236Val, GST omega2 (GSTO2) Asn142Asp, GST pi1 (GSTP1) Ile105Val, GST mu1 (GSTM1) wild/null, and GST theta1 (GSTT1) wild/null. There were no mutation alleles for GSTO1 Glu208Lys, Thr217Asn, and Ala236Val in this population. GSTO1 Glu155del hetero type showed higher urinary concentration of As(V) than the wild homo type. Higher percentage of DMA(V) in urine of GSTM1 wild type was observed compared with that of the null type. Strong correlations between GSTP1 Ile105Val and arsenic exposure level and profile were observed in this study. Especially, heterozygote of GSTP1 Ile105Val had a higher metabolic capacity from inorganic arsenic to monomethyl arsenic, while the opposite trend was observed for ability of metabolism from As(V) to As(III). Furthermore, other factors including sex, age, body mass index, arsenic level in drinking water, and genotypes of As (+3 oxidation state) methyltransferase (AS3MT) were also significantly co-associated with arsenic level and profile in the Vietnamese. To our knowledge, this is the first study indicating the associations of genetic factors of GST superfamily with arsenic metabolism in a Vietnamese population. Copyright 2009 Elsevier Inc. All rights reserved.

Evaluation of the detection of Toll-like receptors (TLRs) in cancer development and progression in patients with colorectal cancer.

PubMed

Messaritakis, Ippokratis; Stogiannitsi, Maria; Koulouridi, Asimina; Sfakianaki, Maria; Voutsina, Alexandra; Sotiriou, Afroditi; Athanasakis, Elias; Xynos, Evangelos; Mavroudis, Dimitris; Tzardi, Maria; Souglakos, John

2018-01-01

Toll-like receptors (TLRs) play essential role in innate and acquired immunity, are expressed in various cell types, and are associated with altered susceptibility to many diseases, and cancers. The aim of this study was to investigate TLR2 (-196 to-174del), TLR4 (Asp299Gly and Thr399Ile) and TLR9 (T1237C and T1486C) gene polymorphisms at risk of colorectal cancer (CRC) development and progression. Peripheral blood was obtained from 397 patients with adjuvant (stage II/III, n = 202) and metastatic (n = 195) CRC. Moreover, blood samples from 50 healthy volunteers and 40 patients with adenomatous polyps were also included as control groups. DNA from patients and controls was analyzed using PCR and PCR-RFLP for genotyping functional polymorphism within TLR2, TLR4 and TLR9 genotypes. TLR2-196 to-174del/del genotype was detected in 76.6% of the patients and was significantly higher that the controls groups (p<0.001). TLR4 Asp299Gly, TLR4 Thr399Ile, TLR9 T1237C and T1486C homozygous genotypes were detected in 70.5%, 70.5%, 61.5% and 61.5% of the patients respectively, and were also significantly higher than that in the control groups (p<0.001). All polymorphisms detected were also significantly associated with the metastatic disease (p<0.001) leading to shorter overall survival (p<0.001); whereas, TLR4 Asp299Gly and Thr399Ile polymorphisms were significantly associated with KRAS mutations. The detection of higher frequencies of the TLR2, TLR4 and/or TLR9 polymorphisms in CRC patients compared with the control groups highlight the role of these polymorphism in CRC development and cancer progression.

Maternal BMI and migration status as predictors of childhood obesity in Mexico

PubMed Central

Jiménez-Cruz, A.; Wojcicki, J. M.; Bacardí-Gascón, M.; Castellón-Zaragoza, A.; García-Gallardo, J. L.; Schwartz, N.; Heyman, M. B.

2011-01-01

Objective To assess the association of maternal migration to Baja California, body mass index (BMI) status, children’s perceived food insecurity, and childhood lifestyle behaviors with overweight (BMI > 85% ile), obesity (BMI > 95% ile) and abdominal obesity (Waist Circumference > 90% ile). Methods Convenience sampling methods were used to recruit a cross-sectional sample of 4th, 5th and 6th grade children and their parents at Tijuana and Tecate Public Schools. Children‘s and parents’ weights and heights were measured. Children were considered to have migrant parents if parents were not born in Baja California. Results One hundred and twenty-two children and their parents were recruited. The mean age of the children was 10.1 ± 1.0 years. Forty nine per cent of children were overweight or obese. Children with obese parents (BMI > 30) had greater odds of being obese, Odds Ratio (OR) 4.9 (95% Confidence Interval (CI), 1.2–19, p = 0.03). Children with migrant parents had greater odds of being obese, OR= 3.7 (95% CI, 1.6–8.3), p = 0.01) and of having abdominal obesity, OR = 3.2 (95% CI, 1.4–7.1, p = 0.01). Children from migrant parents have greater risk of higher consumption of potato chips, OR = 8.0 (95% CI, 2.1–29.1, p = 0.01). Children from non-migrant parents had greater odds of being at risk of hunger. Conclusions Parental obesity and migration are associated with increased risk of obesity among Mexican children. Children whose parents were born in Baja California have greater odds of being at risk of hunger. Further studies should evaluate the role of migration on risk for childhood obesity. PMID:21519746

Clinicopathologic and molecular spectrum of RNASEH1-related mitochondrial disease

PubMed Central

Bugiardini, Enrico; Poole, Olivia V.; Manole, Andreea; Pittman, Alan M.; Horga, Alejandro; Hargreaves, Iain; Woodward, Cathy E.; Sweeney, Mary G.; Holton, Janice L.; Taanman, Jan-Willem; Plant, Gordon T.; Poulton, Joanna; Zeviani, Massimo; Ghezzi, Daniele; Taylor, John; Smith, Conrad; Fratter, Carl; Kanikannan, Meena A.; Paramasivam, Arumugam; Thangaraj, Kumarasamy; Spinazzola, Antonella; Holt, Ian J.; Houlden, Henry; Hanna, Michael G.

2017-01-01

Objective: Pathologic ribonuclease H1 (RNase H1) causes aberrant mitochondrial DNA (mtDNA) segregation and is associated with multiple mtDNA deletions. We aimed to determine the prevalence of RNase H1 gene (RNASEH1) mutations among patients with mitochondrial disease and establish clinically meaningful genotype-phenotype correlations. Methods: RNASEH1 was analyzed in patients with (1) multiple deletions/depletion of muscle mtDNA and (2) mendelian progressive external ophthalmoplegia (PEO) with neuropathologic evidence of mitochondrial dysfunction, but no detectable multiple deletions/depletion of muscle mtDNA. Clinicopathologic and molecular evaluation of the newly identified and previously reported patients harboring RNASEH1 mutations was subsequently undertaken. Results: Pathogenic c.424G>A p.Val142Ile RNASEH1 mutations were detected in 3 pedigrees among the 74 probands screened. Given that all 3 families had Indian ancestry, RNASEH1 genetic analysis was undertaken in 50 additional Indian probands with variable clinical presentations associated with multiple mtDNA deletions, but no further RNASEH1 mutations were confirmed. RNASEH1-related mitochondrial disease was characterized by PEO (100%), cerebellar ataxia (57%), and dysphagia (50%). The ataxia neuropathy spectrum phenotype was observed in 1 patient. Although the c.424G>A p.Val142Ile mutation underpins all reported RNASEH1-related mitochondrial disease, haplotype analysis suggested an independent origin, rather than a founder event, for the variant in our families. Conclusions: In our cohort, RNASEH1 mutations represent the fourth most common cause of adult mendelian PEO associated with multiple mtDNA deletions, following mutations in POLG, RRM2B, and TWNK. RNASEH1 genetic analysis should also be considered in all patients with POLG-negative ataxia neuropathy spectrum. The pathophysiologic mechanisms by which the c.424G>A p.Val142Ile mutation impairs human RNase H1 warrant further investigation. PMID:28508084

Remote Exosites of the Catalytic Domain of Matrix Metalloproteinase-12 Enhance Elastin Degradation┼

PubMed Central

Fulcher, Yan G.; Van Doren, Steven R.

2011-01-01

How does matrix metalloproteinase-12 (MMP-12 or metalloelastase) degrade elastin with high specific activity? NMR suggested soluble elastin to cover surfaces of MMP-12 far from its active site. Two of these surfaces have been found, by mutagenesis guided by the BINDSIght approach, to affect degradation and affinity for elastin substrates but not a small peptide substrate. Main exosite 1 has been extended out to Asp124 that binds calcium. Novel exosite 2 comprises residues from the II–III loop and β-strand I near the back of the catalytic domain. The high exposure of these distal exosites may make them accessible to elastin made more flexible by partial hydrolysis. Importantly, combination of a lesion at each of exosites 1 and 2 and active site decreased catalytic competence towards soluble elastin by 13- to 18-fold to the level of MMP-3, homologue and poor elastase. Double mutant cycle analysis of conservative mutations of Met156 (exosite 2) and either Asp124 (exosite 1) or Ile180 (active site) had additive effects. Compared to polar substitutions observed in other MMPs, Met156 enhanced affinity and Ile180 kcat for soluble elastin. Both residues detracted from the higher folding stability with polar mutations. This resembles the trend in enzymes of an inverse relationship between folding stability and activity. Restoring Asp124 from combination mutants enhanced kcat for soluble elastin. In elastin degradation, exosites 1 and 2 contributed independently of each other and Ile180 at the active site, but with partial coupling to Ala182 near the active site. The concept of weak, separated interactions coalescing somewhat independently can be extended to this proteolytic digestion of a protein from fibrils. PMID:21967233

Degradation of neurotensin by rat brain synaptic membranes: involvement of a thermolysin-like metalloendopeptidase (enkephalinase), angiotensin-converting enzyme, and other unidentified peptidases.

PubMed

Checler, F; Vincent, J P; Kitabgi, P

1983-08-01

Neurotensin was inactivated by membrane-bound and soluble degrading activities present in purified preparations of rat brain synaptic membranes. Degradation products were identified by HPLC and amino acid analysis. The major points of cleavage of neurotensin were the Arg8-Arg9, Pro10-Tyr11, and Tyr11-Ile12 peptide bonds with the membrane-bound activity and the Arg8-Arg9 and Pro10-Tyr11 bonds with the soluble activity. Several lines of evidence indicated that the cleavage of the Arg8-Arg9 bond by the membrane-bound activity resulted mainly from the conversion of neurotensin1-10 to neurotensin1-8 by a dipeptidyl carboxypeptidase. In particular, captopril inhibited this cleavage with an IC50 (5.7 nM) close to its K1 (7 nM) for angiotensin-converting enzyme. Thiorphan inhibited the cleavage at the Tyr11-Ile12 bond by the membrane-bound activity with an IC50 (17 nM) similar to its K1 (4.7 nM) for enkephalinase. Both cleavages were inhibited by 1,10-phenanthroline. These and other data suggested that angiotensin-converting enzyme and a thermolysin-like metalloendopeptidase (enkephalinase) were the membrane-bound peptidases responsible for cleavages at the Arg8-Arg9 and Tyr11-Ile12 bonds, respectively. In contrast, captopril had no effect on the cleavage at the Arg8-Arg9 bond by the soluble activity, indicating that the enzyme responsible for this cleavage was different from angiotensin-converting enzyme. The cleavage at the Pro10-Tyr11 bond by both the membrane-bound and the soluble activities appeared to be catalyzed by an endopeptidase different from known brain proline endopeptidases. The possibility is discussed that the enzymes described here participate in physiological mechanisms of neurotensin inactivation at the synaptic level.

Association between TLR2 and TLR4 Gene Polymorphisms and the Susceptibility to Inflammatory Bowel Disease: A Meta-Analysis.

PubMed

Cheng, Yang; Zhu, Yun; Huang, Xiuping; Zhang, Wei; Han, Zelong; Liu, Side

2015-01-01

The associations between toll-like receptor 2 (TLR2) and toll-like receptor 4(TLR4) polymorphisms and inflammatory bowel disease (IBD) susceptibility remain controversial. A meta-analysis was performed to assess these associations. A systematic search was performed to identify all relevant studies relating TLR2 and TLR4 polymorphisms and IBD susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed by ethnicity and publication quality. Thirty-eight eligible studies, assessing 10970 cases and 7061 controls were included. No TLR2 Arg677Trp polymorphism was found. No significant association was observed between TLR2 Arg753Gln polymorphism and Crohn's disease (CD) or ulcerative colitis (UC) in all genetic models. Interestingly, TLR4 Asp299Gly polymorphism was significantly associated with increased risk of CD and UC in all genetic models, except for the additive one in CD. In addition, a statistically significant association between TLR4 Asp299Gly polymorphism and IBD was observed among high quality studies evaluating Caucasians, but not Asians. Associations between TLR4 Thr399Ile polymorphisms and CD risk were found only in the allele and dominant models. The TLR4 Thr399Ile polymorphism was associated with UC risk in pooled results as well as subgroup analysis of high quality publications assessing Caucasians, in allele and dominant models. The meta-analysis provides evidence that TLR2 Arg753Gln is not associated with CD and UC susceptibility in Asians; TLR4 Asp299Gly is associated with CD and UC susceptibility in Caucasians, but not Asians. TLR4 Thr399Ile may be associated with IBD susceptibility in Caucasians only. Additional well-powered studies of Asp299Gly and other TLR4 variants are warranted.

Association between TLR2 and TLR4 Gene Polymorphisms and the Susceptibility to Inflammatory Bowel Disease: A Meta-Analysis

PubMed Central

Huang, Xiuping; Zhang, Wei; Han, Zelong; Liu, Side

2015-01-01

Background The associations between toll-like receptor 2 (TLR2) and toll-like receptor 4(TLR4) polymorphisms and inflammatory bowel disease (IBD) susceptibility remain controversial. A meta-analysis was performed to assess these associations. Methods A systematic search was performed to identify all relevant studies relating TLR2 and TLR4 polymorphisms and IBD susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed by ethnicity and publication quality. Results Thirty-eight eligible studies, assessing 10970 cases and 7061 controls were included. No TLR2 Arg677Trp polymorphism was found. No significant association was observed between TLR2 Arg753Gln polymorphism and Crohn’s disease (CD) or ulcerative colitis (UC) in all genetic models. Interestingly, TLR4 Asp299Gly polymorphism was significantly associated with increased risk of CD and UC in all genetic models, except for the additive one in CD. In addition, a statistically significant association between TLR4 Asp299Gly polymorphism and IBD was observed among high quality studies evaluating Caucasians, but not Asians. Associations between TLR4 Thr399Ile polymorphisms and CD risk were found only in the allele and dominant models. The TLR4 Thr399Ile polymorphism was associated with UC risk in pooled results as well as subgroup analysis of high quality publications assessing Caucasians, in allele and dominant models. Conclusions The meta-analysis provides evidence that TLR2 Arg753Gln is not associated with CD and UC susceptibility in Asians; TLR4 Asp299Gly is associated with CD and UC susceptibility in Caucasians, but not Asians. TLR4 Thr399Ile may be associated with IBD susceptibility in Caucasians only. Additional well-powered studies of Asp299Gly and other TLR4 variants are warranted. PMID:26023918

CARCINOGEN METABOLISM GENES, RED MEAT AND POULTRY INTAKE, AND COLORECTAL CANCER RISK

PubMed Central

Wang, Jun; Joshi, Amit D.; Corral, Román; Siegmund, Kimberly D.; Le Marchand, Loïc; Martinez, Maria Elena; Haile, Robert W.; Ahnen, Dennis J.; Sandler, Robert S.; Lance, Peter; Stern, Mariana C.

2011-01-01

Diets high in red meat are established risk factors for colorectal cancer (CRC). Carcinogenic compounds generated during meat cooking have been implicated as causal agents. We conducted a family-based case-control study to investigate the association between polymorphisms in carcinogen metabolism genes (CYP1A2 -154A>C, CYP1B1 Leu432Val, CYP2E1 -1054C>T, GSTP1 Ile105Val, PTGS2 5UTR -765, EPHX1 Tyr113His, NAT2 Ile114Thr, NAT2 Arg197Gln and NAT2 Gly286Glu) and CRC risk. We tested for gene-environment interactions using case-only analyses (N = 577) and compared statistically significant results to those obtained using case-unaffected sibling comparisons (N = 307 sibships). Our results suggested that CYP1A2 -154A>C might modify the association between intake of red meat cooked using high temperature methods and well done on the inside and CRC risk (case-only interaction OR = 1.53; 95% CI = 1.19-1.97; p = 0.0008) and the association between intake of red meat heavily browned on the outside and rectal cancer risk (case-only interaction OR = 0.65; 95% CI = 0.48-0.86; p = 0.003). We also found that GSTP1 Ile105Val might modify the association between intake of poultry cooked with high temperature methods and CRC risk (p = 0.0035), a finding that was stronger among rectal cancer cases. Our results support a role for heterocyclic amines that form in red meat as a potential explanation for the observed association between diets high in red meat and CRC. Our findings also suggest a possible role for diets high in poultry cooked at high temperatures in CRC risk. PMID:21618522

Structure of the Branched-chain Amino Acid and GTP-sensing Global Regulator, CodY, from Bacillus subtilis.

PubMed

Levdikov, Vladimir M; Blagova, Elena; Young, Vicki L; Belitsky, Boris R; Lebedev, Andrey; Sonenshein, Abraham L; Wilkinson, Anthony J

2017-02-17

CodY is a branched-chain amino acid (BCAA) and GTP sensor and a global regulator of transcription in low G + C Gram-positive bacteria. It controls the expression of over 100 genes and operons, principally by repressing during growth genes whose products are required for adaptations to nutrient limitation. However, the mechanism by which BCAA binding regulates transcriptional changes is not clear. It is known that CodY consists of a GAF (c G MP-stimulated phosphodiesterases, a denylate cyclases, F hlA) domain that binds BCAAs and a winged helix-turn-helix (wHTH) domain that binds to DNA, but the way in which these domains interact and the structural basis of the BCAA dependence of this interaction are unknown. To gain new insights, we determined the crystal structure of unliganded CodY from Bacillus subtilis revealing a 10-turn α-helix linking otherwise discrete GAF and wHTH domains. The structure of CodY in complex with isoleucine revealed a reorganized GAF domain. In both complexes CodY was tetrameric. Size exclusion chromatography with multiangle laser light scattering (SEC-MALLS) experiments showed that CodY is a dimer at concentrations found in bacterial cells. Comparison of structures of dimers of unliganded CodY and CodY-Ile derived from the tetramers showed a splaying of the wHTH domains when Ile was bound; splaying is likely to account for the increased affinity of Ile-bound CodY for DNA. Electrophoretic mobility shift and SEC-MALLS analyses of CodY binding to 19-36-bp operator fragments are consistent with isoleucine-dependent binding of two CodY dimers per duplex. The implications of these observations for effector control of CodY activity are discussed. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Definition of the binding mode of phosphoinositide 3-kinase α-selective inhibitor A-66S through molecular dynamics simulation.

PubMed

Bian, Xiaoli; Dong, Wangqing; Zhao, Yang; Sun, Rui; Kong, Wanjun; Li, Yiping

2014-04-01

Activation of the phosphatidylinositol 3-kinase α (PI3Kα) is commonly observed in human cancer and is critical for tumor progression, which has made PI3Kα an attractive target for anticancer drug discovery. To systematically investigate the binding mode of A-66S, a new selective PI3Kα inhibitor for PI3Kα, molecular docking, molecular dynamics simulation and ensuing energetic analysis were performed. The binding free energy between PI3Kα and A-66S is -11.27 kcal•mol⁻¹ using MMPBSA method, while -14.67 kcal•mol⁻¹ using MMGBSA method, which is beneficial for the binding, and the van der Waals/hydrophobic and electrostatic interactions are critical for the binding. The conserved hydrophobic adenine region of PI3Kα made up of Met772, Pro778, Ile800, Tyr836, Ile848, Val850, Val851, Met922, Phe930 and Ile932 accommodates the flat 2-tert-butyl-4'-methyl-4,5'-bithiazol moiety of A-66S, and the NH of Val851 forms a hydrogen with the nitrogen atom embedded in the aminothiazole ring of A-66S. The (S)-pyrrolidine carboxamide urea moiety especially extends toward the region of the binding site wall (Ser854-Gln859) defined by the C-terminal lobe, and has three hydrogen-bond arms with the backbone of Ser854 and the side chain of Gln859. Notably the interaction between the non-conserved residue Gln859 and A-66S is responsible for the selectivity profile of A-66S. The binding mode of A-66S for PI3Kα presented in this study should aid in the design of a new highly selective PI3Kα inhibitor.

Approaches to supporting lactation and breastfeeding for very preterm infants in the NICU: a qualitative study in three European regions

PubMed Central

Bonet, Mercedes; Forcella, Emanuela; Blondel, Béatrice; Draper, Elizabeth S; Agostino, Rocco; Cuttini, Marina; Zeitlin, Jennifer

2015-01-01

Objectives To explore differences in approaches to supporting lactation and breastfeeding for very preterm infants in neonatal intensive care units (NICU) in 3 European regions. Design Qualitative cross-sectional study carried out by means of face-to-face semistructured interviews. Verbatim transcripts were coded using a theoretical framework derived from the literature and supplemented by data-driven concepts and codes. Setting 4 purposively selected NICUs in each of 3 European regions in 2010 (Ile-de-France in France, Lazio in Italy, and the former Trent region in the UK). Participants NICU staff members (n=22). Results Policies and practices for managing mother's own milk for very preterm babies differed between regions, and were much more complex in Ile-de-France than in the Trent or Lazio regions. Staff approaches to mothers to initiate lactation differed by region, with an emphasis on the nutritional and immunological value of human milk in the Trent region and on the ‘normalising’ effect of breastfeeding on the mother-child relationship in Lazio. French and English staff expressed conflicting opinions about the use of bottles, which was routine in Italy. Italian informants stressed the importance of early maternal milk expression and feeding, but also mentioned discharging infants home before feeding at the breast was established. In Ile-de-France and Trent, successful feeding from the breast was achieved before discharge, although this was seen as a factor that could prolong hospitalisation and discourage continued breastfeeding for some women. Conclusions Targeted health promotion policies in the NICU are necessary to increase the number of infants receiving their mother's milk and to support mothers with transfer of the infant to the breast. Integrating knowledge about the different approaches to lactation and breastfeeding in European NICUs could improve the relevance of recommendations in multiple cultural settings. PMID:26129632

Structural insights into alternative splicing-mediated desensitization of jasmonate signaling.

PubMed

Zhang, Feng; Ke, Jiyuan; Zhang, Li; Chen, Rongzhi; Sugimoto, Koichi; Howe, Gregg A; Xu, H Eric; Zhou, Mingguo; He, Sheng Yang; Melcher, Karsten

2017-02-14

Jasmonate ZIM-domain (JAZ) transcriptional repressors play a key role in regulating jasmonate (JA) signaling in plants. Below a threshold concentration of jasmonoyl isoleucine (JA-Ile), the active form of JA, the C-terminal Jas motif of JAZ proteins binds MYC transcription factors to repress JA signaling. With increasing JA-Ile concentration, the Jas motif binds to JA-Ile and the COI1 subunit of the SCF COI1 E3 ligase, which mediates ubiquitination and proteasomal degradation of JAZ repressors, resulting in derepression of MYC transcription factors. JA signaling subsequently becomes desensitized, in part by feedback induction of JAZ splice variants that lack the C-terminal Jas motif but include an N-terminal cryptic MYC-interaction domain (CMID). The CMID sequence is dissimilar to the Jas motif and is incapable of recruiting SCF COI1 , allowing CMID-containing JAZ splice variants to accumulate in the presence of JA and to re-repress MYC transcription factors as an integral part of reestablishing signal homeostasis. The mechanism by which the CMID represses MYC transcription factors remains elusive. Here we describe the crystal structure of the MYC3-CMID JAZ10 complex. In contrast to the Jas motif, which forms a single continuous helix when bound to MYC3, the CMID adopts a loop-helix-loop-helix architecture with modular interactions with both the Jas-binding groove and the backside of the Jas-interaction domain of MYC3. This clamp-like interaction allows the CMID to bind MYC3 tightly and block access of MED25 (a subunit of the Mediator coactivator complex) to the MYC3 transcriptional activation domain, shedding light on the enigmatic mechanism by which JAZ splice variants desensitize JA signaling.

Hydrolysis of substance p and neurotensin by converting enzyme and neutral endopeptidase.

PubMed

Skidgel, R A; Engelbrecht, S; Johnson, A R; Erdös, E G

1984-01-01

Angiotensin I converting enzyme (ACE) and neutral endopeptidase ("enkephalinase"; NEP), were purified to homogeneity from human kidney. NEP cleaved substance P (SP) at Gln6-Phe7,-Phe8, and Gly9-Leu10 and neurotensin (NT) at Pro10-Tyr11 and Tyr11-Ile12. NEP hydrolyzed 0.1 mM SP, NT and their C-terminal fragments at the following rates (mumol/min/mg): SP1-11 = 7.8, SP4-11 = 11.7, SP5-11 = 15.4, SP6-11 = 15.6, SP8-11 = 6.7, NT1-13 = 2.9, and NT8-13 = 4.0. Purified ACE rapidly inactivated SP as measured in bioassay. HPLC analysis showed that ACE cleaved SP at Phe8-Gly9 and Gly9-Leu10 to release C-terminal tri- and dipeptide (ratio = 4:1). The hydrolysis was Cl- dependent and inhibited by captopril. ACE released mainly C-terminal tripeptide from SP methyl ester, but only dipeptide from SP free acid. Modification of arginine residues in ACE with cyclohexanedione or butanedione similarly inhibited hydrolysis of SP, bradykinin and Bz-Gly-Phe-Arg (80-93%) indicating an active site arginine is required for hydrolysis of SP. ACE hydrolyzed NT at Tyr11-Ile12 to release Ile12-Leu13. SP, NT and their derivatives (0.1 mM) were cleaved by ACE at the following rates (mumol/min/mg): SP1-11 = 1.2, SP methyl ester = 0.7, SP free acid = 8.5, SP4-11 = 2.4, SP5-11 = 0.9, SP6-11 = 1.4, SP8-11 = 0, NT1-13 = 0.2, and NT8-13 = 1.3. Peptide substrates were used as inhibitors of ACE (substrate = FA-Phe-Gly-Gly) and NEP (substrate = Leu5-enkephalin).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical implications of mutation analysis in primary hyperoxaluria type 1.

PubMed

van Woerden, Christiaan S; Groothoff, Jaap W; Wijburg, Frits A; Annink, Carla; Wanders, Ronald J A; Waterham, Hans R

2004-08-01

Primary hyperoxaluria type 1 (PH1) is an inborn error of glyoxylate metabolism with an extensive clinical and genetic heterogeneity. Although over 50 disease-causing mutations have been identified, the relationship between genotype and clinical outcome remains unclear. The aim of this study was to determine this association in order to find clues for improvement of patient care. AGXT mutation analysis and assessment of biochemical characteristics and clinical outcome were performed on patients from a Dutch PH1 cohort. Thirty-three of a cohort of 57 PH1 patients, identified in The Netherlands over a period of 30 years, were analyzed. Ten different mutations were found. The most common mutations were the Gly170Arg, Phe152Ile, and the 33insC mutations, with an allele frequency of 43%, 19%, and 15%, respectively. Homozygous Gly170Arg and Phe152Ile mutations were associated with pyridoxine responsiveness and a preserved renal function over time when treatment was timely initiated. All patients homozygous for the 33insC mutation had end-stage renal disease (ESRD) before the first year of age. In two unrelated patients, a new Val336Asp mutation was found coupled with the Gly170Arg mutation on the minor allele. We also found 3 patients homozygous for a novel Gly82Arg mutation with adverse outcome in 2 of them. Early detection of Gly170Arg and Phe152Ile mutations in PH1 has important clinical implications because of their association with pyridoxine responsiveness and clinical outcome. The association of a homozygous 33insC mutation with severe infantile ESRD, resulting in early deaths in 2 out of 3 cases, warrants a choice for prenatal diagnostics in affected families.

Readressing the role of Toll-like receptor-4 alleles in inflammatory bowel disease: colitis, smoking, and seroreactivity.

PubMed

Manolakis, Anastassios C; Kapsoritakis, Andreas N; Kapsoritaki, Anastasia; Tiaka, Elisavet K; Oikonomou, Konstantinos A; Lotis, Vassilis; Vamvakopoulou, Dimitra; Davidi, Ioanna; Vamvakopoulos, Nikolaos; Potamianos, Spyros P

2013-02-01

Toll-like receptor (TLR) polymorphisms, and especially TLR-4 Asp299Gly and TLR-4 Thr399Ile, have been linked with Crohn's disease (CD) and to a lesser extent with ulcerative colitis (UC), CD behavior, and compromised seroreactivity to microbial antigens. Available data, however, are conflicting. To address these issues, the distribution of TLR-4 polymorphic alleles was assessed in patients with UC, CD, and healthy controls (HC), considering patient and disease characteristics as well as related serological markers. TLR-4 Asp299Gly and TLR-4 Thr399Ile polymorphisms were determined in 187 UC and 163 CD patients and 274 randomly selected HC. C reactive protein, anti-Saccharomyces cerevisiae mannan antibodies, anti-mannobioside carbohydrate antibodies, anti-laminariobioside carbohydrate antibodies IgG, and anti-chitobioside carbohydrate antibodies (ACCA) IgA levels were also assessed. UC and especially pancolitis patients carried the mutant alleles more frequently compared to CD patients and HC or UC patients with different disease extents (P = 0.002 and P < 0.0001, respectively). Involvement of the colon was more frequent in CD patients with mutant TLR-4 compared to those with wild-type alleles (P = 0.004). Levels and positivity rates of ACCA IgA were lower in inflammatory bowel disease (IBD) patients carrying the mutant compared to those with wild-type alleles (0.075 < P < 0.05). Despite the mutant TLR-4 predisposition for UC pancolitis, smoking was associated with more limited disease (P < 0.001). The presence of TLR-4 Asp299Gly and TLR-4 Thr399Ile polymorphisms is related to UC pancolitis, involvement of the colon in CD, and lower ACCA IgA levels. Smoking reduces the extent of UC, even in the presence of mutant alleles.

In silico approaches to predict the potential of milk protein-derived peptides as dipeptidyl peptidase IV (DPP-IV) inhibitors.

PubMed

Nongonierma, Alice B; Mooney, Catherine; Shields, Denis C; FitzGerald, Richard J

2014-07-01

Molecular docking of a library of all 8000 possible tripeptides to the active site of DPP-IV was used to determine their binding potential. A number of tripeptides were selected for experimental testing, however, there was no direct correlation between the Vina score and their in vitro DPP-IV inhibitory properties. While Trp-Trp-Trp, the peptide with the best docking score, was a moderate DPP-IV inhibitor (IC50 216μM), Lineweaver and Burk analysis revealed its action to be non-competitive. This suggested that it may not bind to the active site of DPP-IV as assumed in the docking prediction. Furthermore, there was no significant link between DPP-IV inhibition and the physicochemical properties of the peptides (molecular mass, hydrophobicity, hydrophobic moment (μH), isoelectric point (pI) and charge). LIGPLOTs indicated that competitive inhibitory peptides were predicted to have both hydrophobic and hydrogen bond interactions with the active site of DPP-IV. DPP-IV inhibitory peptides generally had a hydrophobic or aromatic amino acid at the N-terminus, preferentially a Trp for non-competitive inhibitors and a broader range of residues for competitive inhibitors (Ile, Leu, Val, Phe, Trp or Tyr). Two of the potent DPP-IV inhibitors, Ile-Pro-Ile and Trp-Pro (IC50 values of 3.5 and 44.2μM, respectively), were predicted to be gastrointestinally/intestinally stable. This work highlights the needs to test the assumptions (i.e. competitive binding) of any integrated strategy of computational and experimental screening, in optimizing screening. Future strategies targeting allosteric mechanisms may need to rely more on structure-activity relationship modeling, rather than on docking, in computationally selecting peptides for screening. Copyright © 2014 Elsevier Inc. All rights reserved.

The Micropolitics of School Principals' Decision Making in Nigeria: Principals' Perspective

ERIC Educational Resources Information Center

Olayiwola, Shina; Alabi, Kingsley

2015-01-01

This study depicted a micropolitical analysis of school principals' decision making as regards the influence of formal and informal groups on school administrative processes from the point of view of principals. It was based on descriptive survey study of all 24 public secondary schools within Ile-Ife community, Osun State, Nigeria, out of which a…

Selective Attentional Effects of Adjunct Study Questions on Achievement in Nigerian Secondary School Science

ERIC Educational Resources Information Center

Okoye, Nnamdi S.

2008-01-01

The study investigated the selective attentional effects of adjunct study questions inserted before or after the presentation of science flow diagrams. The basic design for the study was a post-test only control group design involving a total of 252 students randomly selected from six secondary schools in Ile-Ife, Oshun State Nigeria. These were…

Prospects and Challenges of Online Guidance and Counselling Services in a Nigerian University

ERIC Educational Resources Information Center

Adebowale, Olusegun F.; Popoola, Bayode I.

2011-01-01

This study examined the prospects and challenges of online guidance and counselling services at the Obafemi Awolowo University, Ile-Ife, Nigeria. It considered students' views on the nature of and preferences for online services, and the problems that might potentially be presented in that context. It also surveyed staff in regard to assessing the…

Prevalence of Obesity-Related Chronic Health Conditions in Overweight Adolescents with Disabilities

ERIC Educational Resources Information Center

Yamaki, Kiyoshi; Rimmer, James H.; Lowry, Brienne D.; Vogel, Lawrence C.

2011-01-01

The prevalence of 15 common obesity-related chronic health conditions was examined in a convenience sample of adolescents, ages 12-18 years old, with mobility and non-mobility limitations (n=208 and 435, respectively). In both groups, overweight adolescents (BMI[greater than or equal to] 85th %ile) had a significantly higher number of…

A System Status Monitor for the National Aerospace Plane.

DTIC Science & Technology

1987-12-01

12 4.5 Remediation Function .. 17 V. Results .. .. . .. . . .. . . .. . . . . ... .... . 5.1 Test IA...5.2 Test IlB.... .. .. .. .. .. .............. .G2 . 5.3 Test IC . . . . . . ..... 5.5 Te.st ILE . 71 -N IVI ,. .**,*, 𔃻’ d* *-*-’ . d...8217*?~~** ~ % ~~ *~*%’** ~ %?, P age 5.6 Test 2A .. .. .... .... ... .... .... .... .... .... .... 73 5.7 Test213. .. ... .... .... .... ... .... .... .... ..... 7

Downscaled rainfall projections in south Florida using self-organizing maps.

PubMed

Sinha, Palash; Mann, Michael E; Fuentes, Jose D; Mejia, Alfonso; Ning, Liang; Sun, Weiyi; He, Tao; Obeysekera, Jayantha

2018-04-20

We make future projections of seasonal precipitation characteristics in southern Florida using a statistical downscaling approach based on Self Organized Maps. Our approach is applied separately to each three-month season: September-November; December-February; March-May; and June-August. We make use of 19 different simulations from the Coupled Model Inter-comparison Project, phase 5 (CMIP5) and generate an ensemble of 1500 independent daily precipitation surrogates for each model simulation, yielding a grand ensemble of 28,500 total realizations for each season. The center and moments (25%ile and 75%ile) of this distribution are used to characterize most likely scenarios and their associated uncertainties. This approach is applied to 30-year windows of daily mean precipitation for both the CMIP5 historical simulations (1976-2005) and the CMIP5 future (RCP 4.5) projections. For the latter case, we examine both the "near future" (2021-2050) and "far future" (2071-2100) periods for three scenarios (RCP2.6, RCP4.5, and RCP8.5). Copyright © 2018 Elsevier B.V. All rights reserved.

Brain response to taste in overweight children: A pilot feasibility study

PubMed Central

Bohon, Cara

2017-01-01

Understanding the neural response to food and food cues during early stages of weight gain in childhood may help us determine the drive processes involved in unhealthy eating behavior and risk for obesity. Healthy weight and overweight children ages 6–8 (N = 18; 10 with BMI between 5th and 85th %ile and 8 with BMI >85th %ile) underwent fMRI scans while anticipating and receiving tastes of chocolate milkshake. Parents completed a Children’s Eating Behaviour Questionnaire. Results reveal greater response to milkshake taste receipt in overweight children in the right insula, operculum, precentral gyrus, and angular gyrus, and bilateral precuneus and posterior cingulate. No group differences were found for brain response to a visual food cue. Exploratory analyses revealed interactions between self-report measures of eating behavior and weight status on brain response to taste. This pilot study provides preliminary evidence of feasibility of studying young children’s taste processing and suggests a possible developmental shift in brain response to taste. PMID:28235080

Timing generator of scientific grade CCD camera and its implementation based on FPGA technology

NASA Astrophysics Data System (ADS)

Si, Guoliang; Li, Yunfei; Guo, Yongfei

2010-10-01

The Timing Generator's functions of Scientific Grade CCD Camera is briefly presented: it generates various kinds of impulse sequence for the TDI-CCD, video processor and imaging data output, acting as the synchronous coordinator for time in the CCD imaging unit. The IL-E2TDI-CCD sensor produced by DALSA Co.Ltd. use in the Scientific Grade CCD Camera. Driving schedules of IL-E2 TDI-CCD sensor has been examined in detail, the timing generator has been designed for Scientific Grade CCD Camera. FPGA is chosen as the hardware design platform, schedule generator is described with VHDL. The designed generator has been successfully fulfilled function simulation with EDA software and fitted into XC2VP20-FF1152 (a kind of FPGA products made by XILINX). The experiments indicate that the new method improves the integrated level of the system. The Scientific Grade CCD camera system's high reliability, stability and low power supply are achieved. At the same time, the period of design and experiment is sharply shorted.

Structure and receptor-binding activity of insulin from a holostean fish, the bowfin (Amia calva).

PubMed

Conlon, J M; Youson, J H; Whittaker, J

1991-05-15

The holostean fishes are the extant representatives of the primitive ray-finned fishes from which the present-day teleosts may have evolved. The primary structure of insulin from a holostean fish, the bowfin (Amia calva), was established as: A-chain: Gly-Ile-Val-Glu-Gln-Cys-Cys-Leu-Lys-Pro-Cys-Thr-Ile-Tyr-Glu-Met-Glu- Lys-Tyr-Cys-Asn B-chain: Ala-Ala-Ser-Gln-His-Leu-Cys-Gly-Ser-His-Leu-Val-Glu-Ala-Leu-Phe-Leu- Val-Cys-Gly-Glu-Ser-Gly-Phe-Phe-Tyr-Asn-Pro-Asn-Lys-Ser This amino acid sequence contains several substitutions (methionine at A16, phenylalanine at B16 and serine at B22) at sites that have been strongly conserved in other vertebrate species and that may be expected to influence biological activity. Consistent with this prediction, bowfin insulin was approx. 14-fold less potent than pig insulin in inhibiting the binding of [125I-Tyr-A14](human insulin) to transfected mouse NIH 3T3 cells expressing the human insulin receptor.

Structure and receptor-binding activity of insulin from a holostean fish, the bowfin (Amia calva).

PubMed Central

Conlon, J M; Youson, J H; Whittaker, J

1991-01-01

The holostean fishes are the extant representatives of the primitive ray-finned fishes from which the present-day teleosts may have evolved. The primary structure of insulin from a holostean fish, the bowfin (Amia calva), was established as: A-chain: Gly-Ile-Val-Glu-Gln-Cys-Cys-Leu-Lys-Pro-Cys-Thr-Ile-Tyr-Glu-Met-Glu- Lys-Tyr-Cys-Asn B-chain: Ala-Ala-Ser-Gln-His-Leu-Cys-Gly-Ser-His-Leu-Val-Glu-Ala-Leu-Phe-Leu- Val-Cys-Gly-Glu-Ser-Gly-Phe-Phe-Tyr-Asn-Pro-Asn-Lys-Ser This amino acid sequence contains several substitutions (methionine at A16, phenylalanine at B16 and serine at B22) at sites that have been strongly conserved in other vertebrate species and that may be expected to influence biological activity. Consistent with this prediction, bowfin insulin was approx. 14-fold less potent than pig insulin in inhibiting the binding of [125I-Tyr-A14](human insulin) to transfected mouse NIH 3T3 cells expressing the human insulin receptor. PMID:2039477

Characterization of Lipopeptide Biosurfactants Produced by Bacillus licheniformis MB01 from Marine Sediments

PubMed Central

Chen, Yulin; Liu, Shiliang A.; Mou, Haijin; Ma, Yunxiao; Li, Meng; Hu, Xiaoke

2017-01-01

Antibiotic resistance has become one of the world’s most severe problems because of the overuse of antibiotics. Antibiotic-resistant bacteria are more difficult to kill and more expensive to treat. Researchers have been studied on antibiotic alternatives such as antimicrobial peptides and lipopeptides. A functional bacteria MB01 producing lipopeptides which can be used as bacteriostat was isolated from the Bohai Sea sediments, which had been identified as Bacillus licheniformis by the morphological, physiological, and biochemical identification and 16s rDNA sequence. The lipopeptides produced by MB01 were determined to be cyclic surfactin homologs by LC-ESI-MS structural identification after crude extraction and LH-20 chromatography. [M+H]+ m/z 994, 1008, 1022, and 1036 were all the characteristic molecular weight of surfactin homologs. CID analysis revealed that the molecular structure of the lipopeptides was Rn-Glu1-Leu/Ile2-Leu3-Val4-Asp5-Leu6-Leu/Ile7. The lipopeptides showed well resistance to UV light and the change of pH and temperature. PMID:28559889

Formation of vesicles through solvent assisted self-assembly of hydrophobic pentapeptides: encapsulation and pH responsive release of dyes by the vesicles.

PubMed

Kar, Sudeshna; Drew, Michael G B; Pramanik, Animesh

2011-09-01

In the biomimetic design two hydrophobic pentapetides Boc-Ile-Aib-Leu-Phe-Ala-OMe (I) and Boc-Gly-Ile-Aib-Leu-Phe-OMe (II) (Aib: α-aminoisobutyric acid) containing one Aib each are found to undergo solvent assisted self-assembly in methanol/water to form vesicular structures, which can be disrupted by simple addition of acid. The nanovesicles are found to encapsulate dye molecules that can be released by the addition of acid as confirmed by fluorescence microscopy and UV studies. The influence of solvent polarity on the morphology of the materials generated from the peptides has been examined systematically, and shows that fibrillar structures are formed in less polar chloroform/petroleum ether mixture and vesicular structures are formed in more polar methanol/water. Single crystal X-ray diffraction studies reveal that while β-sheet mediated self-assembly leads to the formation of fibrillar structures, the solvated β-sheet structure leads to the formation of vesicular structures. The results demonstrate that even hydrophobic peptides can generate vesicular structures from polar solvent which may be employed in model studies of complex biological phenomena.

Proteomic profile of dry-cured ham relative to PRKAG3 or CAST genotype, level of salt and pastiness.

PubMed

Skrlep, Martin; Candek-Potokar, Marjeta; Mandelc, Stanislav; Javornik, Branka; Gou, Pere; Chambon, Christophe; Santé-Lhoutellier, Véronique

2011-08-01

Two-dimensional electrophoresis was used to compare dry-cured biceps femoris insoluble protein fraction according to genotype (PRKAG3Ile199Val and CASTLys249Arg/Ser638Arg) as well as salt and pastiness level. The PRKAG3 affected mainly muscle metabolic enzymes, indicating its possible influence on muscle metabolism with heterozygotes Ile/Val appearing different from both homozygous genotypes. The effect of CAST was smaller, affecting the quantity of one actin fragment. Dry-cured ham salt and pastiness level affected a wide variety of protein spots including metabolic enzymes, plasma proteins, chaperones and myofibrillar proteins, including protein fragments, indicating the connection with proteolysis. Pastiness was associated with salt content, reflected also by the fact that many spots were affected by both factors. Despite the absence of extreme pastiness (or low salt samples), some protein spots (actin, MHC fragment, desmin fragment) exhibited important differences in intensity according to pastiness (and salt level) suggesting they could be used as potential quality markers. Copyright © 2011 Elsevier Ltd. All rights reserved.

Refuge-effect hypothesis and the demise of the Dodo.

PubMed

Roberts, David L

2013-12-01

The Dodo was last sighted on the inshore island of Ile d'Ambre in 1662, nearly 25 years after the previous sighting on the mainland of Mauritius. It has been suggested that its survival on the inshore island is representative of the refuge effect. Understanding what constitutes significant persistence is fundamental to conservation. I tested the refuge-effect hypothesis for the persistence of the Dodo (Raphus cucullatus) on an inshore island beyond that of the mainland population. For a location to be considered a refuge, most current definitions suggest that both spatial and temporal isolation from the cause of disturbance are required. These results suggest the island was not a refuge for the Dodo because the sighting in 1662 was not temporally isolated from that of the mainland sightings. Furthermore, with only approximately 350 m separating Ile d'Ambre from the mainland of Mauritius, it is unlikely this population of Dodos was spatially isolated. Hipótesis del Efecto Refugio y la Desaparición del Dodo. © 2013 Society for Conservation Biology.

A mutation in the gamma actin 1 (ACTG1) gene causes autosomal dominant hearing loss (DFNA20/26)

PubMed Central

van Wijk, E; Krieger, E; Kemperman, M; De Leenheer, E M R; Huygen, P; Cremers, C; Cremers, F; Kremer, H

2003-01-01

Linkage analysis in a multigenerational family with autosomal dominant hearing loss yielded a chromosomal localisation of the underlying genetic defect in the DFNA20/26 locus at 17q25-qter. The 6-cM critical region harboured the γ-1-actin (ACTG1) gene, which was considered an attractive candidate gene because actins are important structural elements of the inner ear hair cells. In this study, a Thr278Ile mutation was identified in helix 9 of the modelled protein structure. The alteration of residue Thr278 is predicted to have a small but significant effect on the γ 1 actin structure owing to its close proximity to a methionine residue at position 313 in helix 11. Met313 has no space in the structure to move away. Moreover, the Thr278 residue is highly conserved throughout eukaryotic evolution. Using a known actin structure the mutation could be predicted to impair actin polymerisation. These findings strongly suggest that the Thr278Ile mutation in ACTG1 represents the first disease causing germline mutation in a cytoplasmic actin isoform. PMID:14684684

Natural killer cell-mediated innate sieve effect on HIV-1: the impact of KIR/HLA polymorphism on HIV-1 subtype-specific acquisition in east Africa.

PubMed

Koehler, Rebecca N; Alter, Galit; Tovanabutra, Sodsai; Saathoff, Elmar; Arroyo, Miguel A; Walsh, Anne M; Sanders-Buell, Eric E; Maboko, Leonard; Hoelscher, Michael; Robb, Merlin L; Michael, Nelson L; McCutchan, Francine E; Kim, Jerome H; Kijak, Gustavo H

2013-10-15

Here we explore the association between killer cell immunoglobulin-like receptor (KIR)/HLA and human immunodeficiency virus type 1 (HIV-1) acquisition with different viral subtypes circulating in East Africa. In the prospective Cohort Development (CODE) cohort (Mbeya, Tanzania), carriers of KIR3DS1 and its putative ligand (HLA-A or HLA-B Bw4-80Ile alleles) showed increased HIV-1 acquisition risk (odds ratio [OR] = 3.46; 95% confidence interval [CI], 1.12-10.63; P = .04) and a trend for enrichment for subtype A and A-containing recombinants (78% vs. 46%; OR = 4.05; 95% CI, .91-28.30; P = .09) at the expense of subtype C (11% vs. 43%; OR = 0.17; 95% CI, .01-.97; P = .08). In vitro, only natural killer cells from KIR3DS1(+)/HLA-Bw4-80Ile(+) healthy donors showed a 2-fold increased capacity to inhibit replication of subtype C vs subtype A viruses (P = .01). These findings suggest the presence of an innate sieve effect and may inform HIV-1 vaccine development.

Determining English Language Learners' Response to Intervention: Questions and Some Answers

ERIC Educational Resources Information Center

Linan-Thompson, Sylvia; Cirino, Paul T.; Vaughn, Sharon

2007-01-01

Using an extant database, we examined three grade 1 criteria for identifying response to intervention (RTI) in English language learners (ELLs): (a) set benchmark criteria with a standard score above 95 (37th %ile) on both decoding and comprehension measures and a raw score of 40 or more correct words per minute (CWPM) on oral reading fluency; (b)…

The Presence of the British Education Model in Spain: Reception through the Institución Libre De Enseñanza

ERIC Educational Resources Information Center

Fernández-Soria, Juan Manuel

2014-01-01

Spain suffered a severe political and moral crisis in the final years of the nineteenth century and the first third of the twentieth. Pedagogues and politicians belonging to the "Institución Libre de Enseñanza" (ILE), or those close to it, did not consider it possible to regenerate the country without attending to education and Britain…

Bibliography of In-House and Contract Reports. Supplement 9.

DTIC Science & Technology

1981-02-01

11;il CasCil roads andl ril roads would significantlN rcduLcc tlic ~anIual labor IMnOls d III V, i 1111111 d il.1 . graphic data bascs. ile effort...GUIDE FOR CLIMA TE (Rpt. No. 5 in the ETL Series on Guides for Army Terrain Analysts) September 1980 Keywords: Climatic Analysis, Factor Mapping

The Development and Initial Evaluation of the Human Readiness Level Framework

DTIC Science & Technology

2010-06-01

View ICD Initial Capabilities Document ICW Interactive Course Ware ILE Interactive Learning Environment ILT Instructor Led Training IOC...Programmatic Environmental Safety and Health Evaluation PHA Preliminary Hazard Analysis PHL Preliminary Hazard List xiv PM Program Manager PQS...Occupational Health SOW Statement of Work SRD System Requirements Document SPS System Performance Specification SRR System Requirements Review SVR

Army Reserve Instructors' Perceptions regarding the Effectiveness of the Experiential Learning Model in Teaching Mid-Level Army Reserve Officers

ERIC Educational Resources Information Center

Meyer, Robert S.

2010-01-01

The Command and General Staff College (CGSC) at Ft. Leavenworth is a fully accredited graduate school. The primary professional development program at CGSC has been for mid-level officers. This program is referred to as ILE (Intermediate Level Education) and is taught in small cohort groups of 12 to 18 students. CGSC has embraced the principles of…

Finding the Sweet Spot: Bridging X3D, S1000D, and SCORM for Embedded Performance Assessment and Life Cycle Training Content Management

DTIC Science & Technology

2010-07-14

f\\11 eL1&iled.i’m:COilPI: Io) d< olt <llllllt e\\’CDI: re<ci\\oifi’Om XJD KCD!: f71 10Ucl!C«~~~:ItttO nl’liTOIIdledAI (I’R.ooicnRes>ocl t\\’t:U r«d\\’ed

Hybrid E-Textbooks as Comprehensive Interactive Learning Environments

ERIC Educational Resources Information Center

Ghaem Sigarchian, Hajar; Logghe, Sara; Verborgh, Ruben; de Neve, Wesley; Salliau, Frank; Mannens, Erik; Van de Walle, Rik; Schuurman, Dimitri

2018-01-01

An e-TextBook can serve as an interactive learning environment (ILE), facilitating more effective teaching and learning processes. In this paper, we propose the novel concept of an EPUB 3-based Hybrid e-TextBook, which allows for interaction between the digital and the physical world. In that regard, we first investigated the gap between the…

International Conference on Case Histories in Geotechnical Engineering (2nd) Held in Rolla, Missouri on 1-5 June 1988. Volume 2

DTIC Science & Technology

1989-06-30

Wright (USA) AAV. Shroff Epoxy Resin (rout System for Solutions to Traditional D.P. Am in (;eotechnical Problems. 5.66...echate Containment System -(eotechnical (U SA ) Considerations . .......................................................... 1577 W D .I. Finn Case...girders were set in place in the formed under co er of tne above ra iling system . clayey overburden by low-frequency vibro-driving methoo, then

Protective effects of diketopiperazines from Moslae Herba against influenza A virus-induced pulmonary inflammation via inhibition of viral replication and platelets aggregation.

PubMed

Zhang, Huan-Huan; Yu, Wen-Ying; Li, Lan; Wu, Fang; Chen, Qin; Yang, Yang; Yu, Chen-Huan

2018-04-06

Moslae Herba (MH) is broadly used as an antiviral, antipyretic and anticoagulant drug which effectively treats respiratory diseases including cough, asthma, throat, cold and flu. The excessive inflammation of the lungs is the hallmark of severe influenza A virus (IAV) infection, while platelet aggregation and its subsequent microvascular thrombosis can exacerbate IAV-induced lung injury. Thus, inhibition of platelet aggregation can be a potential target for IAV treatment. Previous studies focus on the flavonoids from MH and their anti-inflammatory activities, but the anticoagulant compounds and potential molecular mechanism of MH remains unclear. This study was to isolate and characterize diketopiperazines (DKPs) from MH and to explore the underlying anticoagulant mechanism on IAV infection models. EtOAc sub-extract separated from MH ethanolic extract was subjected to fractionation through column chromatography. The chemical structures of pure compounds were characterized by the spectral analysis. Antiviral activities of DKPs were assayed in IAV-infected Madin-Darby canine kidney (MDCK) cells and mice. Anticoagulant effects of DKPs were investigated on adenosine 5'-diphosphate (ADP)-induced acute pulmonary embolism and IAV-induced lung injury in vivo, as well as the inhibition on platelet activating factor (PAF), arachidonic acid (AA) and ADP-induced platelet aggregation in vitro. The serum levels of thromboxane B 2 (TXB 2 ) and 6-keto-PGF 1α were detected by ELISA. The expressions of key proteins in CD41-mediated PI3K/AKT pathways were determined by western blotting analysis. Six DKPs were, for the first time, isolated from MH and identified as cyclo(Tyr-Leu) (1), cyclo(Phe-Phe) (2), cyclo(Phe-Tyr) (3), cyclo(Ala-Ile) (4), cyclo(Ala-Leu) (5) and Bz-Phe-Phe-OMe (6). Among these DKPs, cyclo(Ala-Ile) and Bz-Phe-Phe-OMe possessed low cytotoxicities and significant inhibition against cytopathic effects induced by IAV (H1N1 and H3N2) replication in MDCK cells

Kinin B1 receptor antagonists containing alpha-methyl-L-phenylalanine: in vitro and in vivo antagonistic activities.

PubMed

Gobeil, F; Charland, S; Filteau, C; Perron, S I; Neugebauer, W; Regoli, D

1999-03-01

-To protect from metabolism and to improve potency of the AcLys-[D-betaNal7,Ile8]desArg9-bradykinin (BK) (R 715), we prepared and tested 3 analogues containing alpha-methyl-L-Phe ([alphaMe]Phe) in position 5: these are the AcLys-[(alphaMe)Phe5,D-betaNal7, Ile8]desArg9BK (R 892), Lys-Lys-[(alphaMe)Phe5,D-betaNal7, Ile8]desArg9BK (R 913), and AcLys-Lys-[(alphaMe)Phe5,D-betaNal7, Ile8]desArg9BK (R 914). The new compounds were tested against the contractile effect induced by desArg9BK on 2 B1 receptor bioassays, the human umbilical vein, and the rabbit aorta. Their antagonistic activities were compared with those of the early prototypes (Lys-[Leu8]desArg9BK and [Leu8]desArg9BK) and with other recently described peptide antagonists. The 3 (alphaMe)Phe analogues showed high antagonistic potencies (pA2) at both the human (8.8, 7.7, and 8. 7, respectively) and rabbit (8.6, 7.8, and 8.6, respectively) B1 receptors. No antagonistic effects (pA2<5) were observed on the B2 receptors that mediate the contractile effects of BK on the human umbilical vein, the rabbit jugular vein, and the guinea pig ileum. Moreover, these new B1 antagonists were found to be resistant to in vitro degradation by purified angiotensin-converting enzyme from rabbit lung. The Nalpha-acetylated forms, R 892 and R 914, were resistant to aminopeptidases from human plasma. In vivo antagonistic potencies (ID50) of B1 receptor antagonists were evaluated in anesthetized lipopolysaccharide-treated (for B1 receptor) and nontreated (for B2 receptor) rabbits against the hypotensive effects of exogenous desArg9BK and BK. R 892 efficiently inhibited (ID50 2.8 nmol/kg IV) hypotension induced by desArg9BK without affecting that evoked by BK (ID50 >600 nmol/kg IV). Conversely, the peptide antagonists Lys-Lys-[Hyp3,Igl5,D-Igl7,Oic8]desArg9BK (B 9858) and DArg-[Hyp3,Thi5,D-Tic7,Oic8] desArg9BK (S 0765) showed dual B1/B2 receptor antagonism in vitro and in vivo. It is concluded that R 892 and congeners provide selective

Central nervous system bleeding in pediatric patients with factor XIII deficiency: a study on 23 new cases.

PubMed

Naderi, Majid; Alizadeh, Shaban; Kazemi, Ahmad; Tabibian, Shadi; Zaker, Farhad; Bamedi, Taregh; Kashani Khatib, Zahra; Dorgalaleh, Akbar

2015-03-01

Factor XIII (FXIII) deficiency is an extremely rare bleeding disorder, which has the highest incidence in Sistan and Baluchistan Province in Iran, compared to its overall incidence around the world. This disorder has different clinical manifestations ranging from mild bleeding tendency to lethal bleeding episodes including central nervous system (CNS) hemorrhage. The aim of this study was to evaluate the demographic data, pattern of CNS bleeding, and the role of plasminogen activator inhibitor-1 (PAI-1) (PAI-1) 4G/5G and thrombin activatable fibrinolysis inhibitor (TAFI) Thr325Ile polymorphisms in intracranial and extracranial hemorrhages in 23 new cases of FXIII-deficient subjects. This case-control study was conducted on 23 FXIII-deficient patients with CNS bleeding episodes and 23 patients as the control group with FXIII deficiency but without any history of CNS bleeding. Initially, to confirm the molecular defect, both groups were evaluated for the most frequently reported mutation of FXIII (Trp187Arg mutation) in a previous study in Sistan and Baluchistan Province. Then, demographic data, clinical manifestations, and pattern of CNS bleeding were determined. Eventually, the patients were assessed for PAI-14G/5G and TAFI Thr325Ile polymorphisms. The results of this study revealed that all the subjects (including the case and control groups) were homozygous for Trp187Arg mutation. Nineteen patients (82.6%) had intracranial hemorrhage (ICH) and four patients (17.4%) had extracranial hemorrhage (ECH). Intraparenchymal hemorrhage was the most common form of ICH (89.5%), and epidural hemorrhage was observed in two patients (10.5%). Anatomic regions in patients with intraparenchymal hemorrhage were temporal in six (35.3%), occipital in four (23.5%), diffused intraparenchymal in four (23.5%), temporal-occipital in two (11.8%), and subdural with temporal in one (5.9%) patient. We found that in the case group, 14 patients (60.8%) were homozygous for TAFI Thr325Ile

[A four year study of the personal and interpersonal value systems of freshman nursing students at Yonsei University].

PubMed

Choi, Y S

1991-01-01

The purpose of this study was to determine the values of freshman nursing students and to determine changes each year over the four years of the study and to provide base data for curriculum and student guidance. The sample consisted of the freshman students who entered college of nursing from 1988 through 1991. The total sample was 358 students and data were collected during March of each of the four years. The data were analyzed using t-test, ANOVA and Pearson Correlation to examine the relationship between the subcategories of values and Duncan multiple range test to examine the relationship between the scores for each year and the demographic data. The instrument used in this study was the Survey of Personal Values and Interpersonal Values modified by UngYun Hwang and KyungHae Lee in accordance with L.V. Gordon's instrument. This tool provides scores on practical mindedness, achievement, variety, decisiveness, orderliness, goal orientation, support, conformity, recognition, independence, benevolence and leadership. The results of the study were as follows: 1. The nursing freshman students surveyed had the highest score for goal orientation (21.44) and the lowest for variety (17.13) on the SPV (Survey of Personal Values) and the highest score for benevolence (21.19) and lowest for leadership (17.00) on the SIV (Survey of Interpersonal Values). In accordance with the standardized scores for Gordon's SPV for other woman college students, the students in the study were between the 78%ile-97%ile and were in the 72%ile-97%ile for the SIV. 2. When t-test scores were compared, no significant variation was found between the years for each of the values (P less than .05). 3. A significant variation was found on variety, between 1989 and 1991 (P less than .05), and between 1988 and 1991. The highest score was in 1991 in both comparisons. Supporting was also higher for 1991 than for 1988 (P less than .05). 4. Religion and occupation of father did not show any significant

Popular Culture Images of Gender as Reflected through Young Children's Story.

ERIC Educational Resources Information Center

Clark, Elaine

A study investigated the impact of popular culture on young children's conception of gender, as revealed through the stories they write and tell. The research was conducted at Grosse Ile High School on the remote Magdalen Islands in the Gulf of Saint Lawrence, Quebec, Canada, from 1991-1994 with 46 students ages 6-7 years old. The concept of the…

Determination of the Chronic Mammalian Toxicological Effects of TNT (twenty-Four Month Chronic Toxicity/Carcinogenicity Study of Trinitrotoluene (TNT) in the Fischer 344 Rat). Volume 1

DTIC Science & Technology

1984-12-01

the study were also analyzed for nitrate, nitrite and mercury content by TEl. 200 Fischer 344 rats, obtained from Harlan Sprague-Dawley, Madison , WI...Iles Pancreas Pituitary gland Prostate Rectum Salivary gland Sciatic nerve Seminal vesicles Skin, abdominal Spinal cord (cervical, thoracic, lumbar ...Skin, abdominal Spinal cord (cervical, thoracic and lumbar ) Sp I een Sternum Including bone marrow Stomach TIssue masses Thyroids (parathyrolds

Potential Side Effect of Inadvertent Intravascular Administration of Liposomal Bupivacaine

DTIC Science & Technology

2017-06-01

treat and is potentially fatal. LAST can impair function of the central nervous system and cause cardiovascular collapse, with potentially...in the reversal of cardiovascular and central nervous system symptoms of local anesthetic and other lipophilic drug overdoses. ILE is gaining...to the sites of toxic action in the central nervous system and the heart. However, liposomal formulations of local anesthetics (EXPAREL in

Analysis of Liquid Rocket Tankage

DTIC Science & Technology

1975-04-01

pitting and essencially no attack of’ the base metal. The internal surfacees showed some shallow pitting and discoloration which 28 were less severe than...301 STAINLESS STEEL. spoIclus Cur FROM PARENT KETAL AND W=O JOINTS Oil A2IDE CRYOPORMNT OLTIATZ 0’ .% OFFSET TOS ILE YI AID 5 LOCATION"UNDOU S?1C1M N

Anti-Exposure Technology Identification for Mission Specific Operational Requirements

DTIC Science & Technology

1981-08-08

APPENDIX A- ANTHROPOMETRY MEASUREMENT PROCEDURES A-1 APPENDIX B - MOBILITY AND REACH MEASUREMENT PROCEDURES B-1 APPENDIX C - MOBILITY REDUCTION DATA...Anti-Exposure Configurations Studied 12 IV Garments/Flight Gear Worn With Each Configuration and Donning Sequence 18 V Subject Anthropometry (% ILE...body anthropometry . The following measurements were made according to the procedures described in Appendix A. Weight Stature (Height) Crotch Height

Basic Research in Computer Science

DTIC Science & Technology

1993-10-01

No 0704-0188 _7 7 , - -s ,,, - .’ . .. ..... _" r oI N tp o .. ,o - Ile *, nhe’ asect of 1. AGENCY USE ONLY :leave b/in,) 2 REPORT DATE 7 REPORT TYPE...Parallel Programming. ACM, April, 1991. 116 [Laird et al. 90] Laird, J.E., C.B. Congdon , C.B. Altmann, and K. Swedlow. Soar User’s Manual: Version 5.2

Effects of Stimulated Raman Scattering on Light Beam Properties During High-Power Laser Beam Long-Path Propagation

DTIC Science & Technology

1993-11-03

GebhardtFG. Appl Optics, 1976, IS: 1479. (51 Loy MT, Shen MA. IEEE J Q E. 1973, QW-9: 409. [6] ArecchiFT et al. Laser Handbook, North- Holand 1972. (71 ’ Carman...AFIT/ILE 1 P090 NSA/CDB 1 2206 FSL 1 microfkice N~br: F1 ’D93CO000626 FrD-ID(RS) T-0100-93

Stabilization of an immunoglobulin fold domain by an engineered disulfide bond at the buried hydrophobic region.

PubMed

Hagihara, Yoshihisa; Mine, Shouhei; Uegaki, Koichi

2007-12-14

We report for the first time the stabilization of an immunoglobulin fold domain by an engineered disulfide bond. In the llama single-domain antibody, which has human chorionic gonadotropin as its specific antigen, Ala49 and Ile70 are buried in the structure. A mutant with an artificial disulfide bond at this position showed a 10 degrees C higher midpoint temperature of thermal unfolding than that without the extra disulfide bond. The modified domains exhibited an antigen binding affinity comparable with that of the wild-type domain. Ala49 and Ile70 are conserved in camel and llama single-domain antibody frameworks. Therefore, domains against different antigens are expected to be stabilized by the engineered disulfide bond examined here. In addition to the effect of the loop constraints in the unfolded state, thermodynamic analysis indicated that internal interaction and hydration also control the stability of domains with disulfide bonds. The change in physical properties resulting from mutation often causes unpredictable and destabilizing effects on these interactions. The introduction of a hydrophobic cystine into the hydrophobic region maintains the hydrophobicity of the protein and is expected to minimize the unfavorable mutational effects.

Active-site protein dynamics and solvent accessibility in native Achromobacter cycloclastes copper nitrite reductase.

PubMed

Sen, Kakali; Horrell, Sam; Kekilli, Demet; Yong, Chin W; Keal, Thomas W; Atakisi, Hakan; Moreau, David W; Thorne, Robert E; Hough, Michael A; Strange, Richard W

2017-07-01

Microbial nitrite reductases are denitrifying enzymes that are a major component of the global nitrogen cycle. Multiple structures measured from one crystal (MSOX data) of copper nitrite reductase at 240 K, together with molecular-dynamics simulations, have revealed protein dynamics at the type 2 copper site that are significant for its catalytic properties and for the entry and exit of solvent or ligands to and from the active site. Molecular-dynamics simulations were performed using different protonation states of the key catalytic residues (Asp CAT and His CAT ) involved in the nitrite-reduction mechanism of this enzyme. Taken together, the crystal structures and simulations show that the Asp CAT protonation state strongly influences the active-site solvent accessibility, while the dynamics of the active-site 'capping residue' (Ile CAT ), a determinant of ligand binding, are influenced both by temperature and by the protonation state of Asp CAT . A previously unobserved conformation of Ile CAT is seen in the elevated temperature series compared with 100 K structures. DFT calculations also show that the loss of a bound water ligand at the active site during the MSOX series is consistent with reduction of the type 2 Cu atom.

Impact of microencapsulated peptidase (Aspergillus oryzae) on cheddar cheese proteolysis and its biologically active peptide profile.

PubMed

Seneweera, Saman; Kailasapathy, Kaila

2011-07-01

We investigated the delivery of calcium-alginate encapsulated peptidase (Flavourzyme(®), Aspergillus oryzae) on proteolysis of Cheddar cheese. Physical and chemical characteristics such as moisture, pH and fat content were measured, and no differences were found between control and experimental cheese at day 0. SDS-PAGE analysis clearly showed that proteolysis of α and k casein was significantly accelerated after three months of maturity in the experimental cheese. A large number of low molecular weight peptides were found in the water soluble fraction of the experimental cheeses and some of these peptides were new. N-terminal amino acid sequence analysis identified these as P(1), Leu-Thu-Glu; P(3), Asp-Val-Pro-Ser-Glu) and relatively abundant stable peptides P(2), P(4), Arg-Pro-Lys-His-Pro-Ile; P(5), Arg-Pro-Lys-His-Pro-Ile-Lys and P(6). These peptides were mainly originated from αs1-CN and β-CN. Three of the identified peptides (P(1), P(2), P(3) and P(4)) are known to biologically active and P(1) and P(3) were only present in experimental cheese suggesting that experimental cheese has improved health benefits.

Genotoxicity testing of a fenugreek extract.

PubMed

Flammang, A M; Cifone, M A; Erexson, G L; Stankowski, L F

2004-11-01

Fenugreek seeds have been used in traditional medicines as a remedy for diabetes. Rich in protein, fenugreek seeds contain the unique major free amino acid 4-hydroxyisoleucine (4-OH-Ile), which has been characterized as one of the active ingredients for blood glucose control. Current use of fenugreek in foodstuff has been limited to its role as a flavoring agent, and not as an ingredient to help mitigate the blood glucose response for people with diabetes. As part of a safety evaluation of novel ingredients for use in blood glucose control, the potential genotoxicity of a fenugreek seed extract (THL), containing a minimum of 40% 4-OH-ILE, was evaluated using the standard battery of tests (reverse mutation assay; mouse lymphoma forward mutation assay; mouse micronucleus assay) recommended by US Food and Drug Administration (FDA) for food ingredients. THL was determined not to be genotoxic under the conditions of the tested genetic toxicity battery. The negative assay results provide support that addition of THL to foodstuffs formulated for people with diabetes is expected to be safe. A wide safety margin is established, as anticipated doses are small compared to the doses administered in the assays.

Characteristics of the mixing volume model with the interactions among spatially distributed particles for Lagrangian simulations of turbulent mixing

NASA Astrophysics Data System (ADS)

Watanabe, Tomoaki; Nagata, Koji

2016-11-01

The mixing volume model (MVM), which is a mixing model for molecular diffusion in Lagrangian simulations of turbulent mixing problems, is proposed based on the interactions among spatially distributed particles in a finite volume. The mixing timescale in the MVM is derived by comparison between the model and the subgrid scale scalar variance equation. A-priori test of the MVM is conducted based on the direct numerical simulations of planar jets. The MVM is shown to predict well the mean effects of the molecular diffusion under various conditions. However, a predicted value of the molecular diffusion term is positively correlated to the exact value in the DNS only when the number of the mixing particles is larger than two. Furthermore, the MVM is tested in the hybrid implicit large-eddy-simulation/Lagrangian-particle-simulation (ILES/LPS). The ILES/LPS with the present mixing model predicts well the decay of the scalar variance in planar jets. This work was supported by JSPS KAKENHI Nos. 25289030 and 16K18013. The numerical simulations presented in this manuscript were carried out on the high performance computing system (NEC SX-ACE) in the Japan Agency for Marine-Earth Science and Technology.

The role of innate immunity in acute allograft rejection after lung transplantation.

PubMed

Palmer, Scott M; Burch, Lauranell H; Davis, R Duane; Herczyk, Walter F; Howell, David N; Reinsmoen, Nancy L; Schwartz, David A

2003-09-15

Although innate immunity is crucial to pulmonary host defense and can initiate immune and inflammatory responses independent of adaptive immunity, it remains unstudied in the context of transplant rejection. To investigate the role of innate immunity in the development of allograft rejection, we assessed the impact of two functional polymorphisms in the toll-like receptor 4 (TLR4) associated with endotoxin hyporesponsiveness on the development of acute rejection after human lung transplantation. Patients and donors were screened for the TLR4 Asp299Gly and Thr399Ile polymorphisms by polymerase chain reaction using sequence-specific primers. The rate of acute rejection at 6 months was significantly reduced in recipients, but not in donors, with the Asp299Gly or Thr399Ile alleles as compared with wild type (29 vs. 56%, respectively, p = 0.05). This association was confirmed in Cox proportional hazards and multivariate logistic regression models. Our results suggest activation of innate immunity in lung transplant recipients through TLR4 contributes to the development acute rejection after lung transplantation. Therapies directed at inhibition of innate immune responses mediated by TLR4 may represent a novel and effective means to prevent acute rejection after lung transplantation.

Providencia thailandensis sp. nov., isolated from seafood processing wastewater.

PubMed

Khunthongpan, Suwannee; Sumpavapol, Punnanee; Tanasupawat, Somboon; Benjakul, Soottawat; H-Kittikun, Aran

2013-01-01

The bacterial strain C1112(T) was isolated from seafood processing wastewater collected from a treatment pond of the seafood factory in Songkhla Province, Thailand. Phylogenetic analysis based on concatenated sequences from the 16S rRNA gene and five housekeeping genes, fusA, lepA, leuS, gyrB and ileS respectively showed that the strain C1112(T) belonged to the genus Providencia, and share 91.75% similarity with P. stuartii DSM 4539(T). DNA-DNA hybridization between the strain C1112(T) and P. stuartii KCTC 2568(T) was 48.1% relatedness. Moreover, some results from biochemical properties indicated that the strain C1112(T) was distinguished from the phylogenetically closest relatives. The major fatty acids of the strain C1112(T) were C16:0, iso-C15:0, C14:0 and C17:0 cyclo and the DNA G+C content was 41 mol%. Based on the genotypic and phenotypic considerations, it should be classified as a novel species of the genus Providencia for which the name Providencia thailandensis sp. nov. is proposed. The type strain is C1112(T) (= KCTC 23281(T) =NBRC 106720(T)).

Directed Evolution of Carbonyl Reductase from Rhodosporidium toruloides and Its Application in Stereoselective Synthesis of tert-Butyl (3R,5S)-6-Chloro-3,5-dihydroxyhexanoate.

PubMed

Liu, Zhi-Qiang; Wu, Lin; Zhang, Xiao-Jian; Xue, Ya-Ping; Zheng, Yu-Guo

2017-05-10

tert-Butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate ((3R,5S)-CDHH) is a key intermediate of atorvastatin and rosuvastatin synthesis. Carbonyl reductase RtSCR9 from Rhodosporidium toruloides exhibited excellent activity toward tert-butyl (S)-6-chloro-5-hydroxy-3-oxohexanoate ((S)-CHOH). For the activity of RtSCR9 to be improved, random mutagenesis and site-saturation mutagenesis were performed. Three positive mutants were obtained (mut-Gln95Asp, mut-Ile144Lys, and mut-Phe156Gln). These mutants exhibited 1.94-, 3.03-, and 1.61-fold and 1.93-, 3.15-, and 1.97-fold improvement in the specific activity and k cat /K m , respectively. Asymmetric reduction of (S)-CHOH by mut-Ile144Lys coupled with glucose dehydrogenase was conducted. The yield and enantiomeric excess of (3R,5S)-CDHH reached 98 and 99%, respectively, after 8 h bioconversion in a single batch reaction with 1 M (S)-CHOH, and the space-time yield reached 542.83 mmol L -1 h -1 g -1 wet cell weight. This study presents a new carbonyl reductase for efficient synthesis of (3R,5S)-CDHH.

Purification and characterization of a fibrinolytic enzyme produced from Bacillus sp. strain CK 11-4 screened from Chungkook-Jang.

PubMed Central

Kim, W; Choi, K; Kim, Y; Park, H; Choi, J; Lee, Y; Oh, H; Kwon, I; Lee, S

1996-01-01

Bacillus sp. strain CK 11-4, which produces a strongly fibrinolytic enzyme, was screened from Chungkook-Jang, a traditional Korean fermented-soybean sauce. The fibrinolytic enzyme (CK) was purified from supernatant of Bacillus sp. strain CK 11-4 culture broth and showed thermophilic, hydrophilic, and strong fibrinolytic activity. The optimum temperature and pH were 70 degrees C and 10.5, respectively, and the molecular weight was 28,200 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The first 14 amino acids of the N-terminal sequence of CK are Ala-Gin-Thr-Val-Pro-Tyr-Gly-Ile-Pro-Leu-Ile-Lys-Ala-Asp. This sequence is identical to that of subtilisin Carlsberg and different from that of nattokinase, but CK showed a level of fibrinolytic activity that was about eight times higher than that of subtilisin Carlsberg. The amidolytic activity of CK increased about twofold at the initial state of the reaction when CK enzyme was added to a mixture of plasminogen and substrate (H-D-Val-Leu-Lys-pNA). A similar result was also obtained from fibrin plate analysis. PMID:8779587

Neurotensin-metabolizing peptidases in rat fundus plasma membranes.

PubMed

Checler, F; Barelli, H; Kwan, C Y; Kitabgi, P; Vincent, J P

1987-08-01

The mechanisms by which neurotensin (NT) was inactivated by rat fundus plasma membranes were characterized. Primary inactivating cleavages occurred at the Arg8-Arg9, Pro10-Tyr11, and Ile12-Leu13 peptidyl bonds. Hydrolysis at the Arg8-Arg9 bond was fully abolished by the use of N-[1(R,S)-carboxy-2-phenylethyl]-alanyl-alanyl-phenylalanine-p- aminobenzoate, a result indicating the involvement at this site of a recently purified soluble metallopeptidase. Hydrolysis of the Pro10-Tyr11 bond was totally resistant to N-benzyloxycarbonyl-prolyl-prolinal and thiorphan, an observation suggesting that the peptidase responsible for this cleavage was different from proline endopeptidase and endopeptidase 24.11 and might correspond to a NT-degrading neutral metallopeptidase recently isolated from rat brain synaptic membranes. The enzyme acting at the Ile12-Leu13 bond has not yet been identified. Secondary cleavages occurring on NT degradation products were mainly generated by bestatin-sensitive aminopeptidases and post-proline dipeptidyl aminopeptidase. The content in NT-metabolizing peptidases present in rat fundus plasma membranes is compared with that previously established for purified rat brain synaptic membranes.

Simultaneous determination of leucine, isoleucine and valine in Beagle dog plasma by HPLC-MS/MS and its application to a pharmacokinetic study.

PubMed

Wang, Ting; Xie, Huiru; Chen, Xu; Jiang, Xuehua; Wang, Ling

2015-10-10

Leucine (Leu), isoleucine (Ile) and valine (Val) are three branched-chain amino acids (BCAAs), which have been widely used as dietary supplements for professional athletes and patients with liver failure or catabolic diseases. To date, no pharmacokinetic studies of BCAAs in vivo useful for the assessment of clinical effect following daily intake has been reported. Thus in this study, an HPLC-MS/MS method for simultaneous determination of Leu, Ile and Val in Beagle dog plasma using homoarginine as the internal standard was developed and validated in terms of specificity, linearity, precision, accuracy, and stability. This assay method was then applied to a pharmacokinetic study of BCAAs in dogs following oral administration of 0.25 g/kg and 0.50 g/kg BCAAs. The HPLC-MS/MS method was found to be sensitive and reproducible for quantification of BCAAs in dog plasma and successfully applied to the pharmacokinetic study. All these BCAAs were well absorbed with a substantial increase in the plasma concentration after a baseline modification. No statistical significance was identified in different gender group and no drug accumulation was observed following multiple doses. Copyright © 2015 Elsevier B.V. All rights reserved.

Structural Determinants of the 5′-Methylthioinosine Specificity of Plasmodium Purine Nucleoside Phosphorylase

PubMed Central

Donaldson, Teraya M.; Ting, Li-Min; Zhan, Chenyang; Shi, Wuxian; Zheng, Renjian; Almo, Steven C.; Kim, Kami

2014-01-01

Plasmodium parasites rely upon purine salvage for survival. Plasmodium purine nucleoside phosphorylase is part of the streamlined Plasmodium purine salvage pathway that leads to the phosphorylysis of both purines and 5′-methylthiopurines, byproducts of polyamine synthesis. We have explored structural features in Plasmodium falciparum purine nucleoside phosphorylase (PfPNP) that affect efficiency of catalysis as well as those that make it suitable for dual specificity. We used site directed mutagenesis to identify residues critical for PfPNP catalytic activity as well as critical residues within a hydrophobic pocket required for accommodation of the 5′-methylthio group. Kinetic analysis data shows that several mutants had disrupted binding of the 5′-methylthio group while retaining activity for inosine. A triple PfPNP mutant that mimics Toxoplasma gondii PNP had significant loss of 5′-methylthio activity with retention of inosine activity. Crystallographic investigation of the triple mutant PfPNP with Tyr160Phe, Val66Ile, andVal73Ile in complex with the transition state inhibitor immucillin H reveals fewer hydrogen bond interactions for the inhibitor in the hydrophobic pocket. PMID:24416224

Preconceptional identification of cystic fibrosis carriers in the Sardinian population: A pilot screening program.

PubMed

Coiana, Alessandra; Faa', Valeria; Carta, Daniela; Puddu, Rosalba; Cao, Antonio; Rosatelli, Maria Cristina

2011-05-01

In Sardinia the mutational spectrum of CFTR gene is well defined. A mutation detection rate of 94% can be achieved by screening for 15 CFTR mutations with a frequency higher than 0.5%. The efficiency of this molecular test suggests that Sardinians may represent a suitable population for a preconceptional screening. Five hundred couples of Sardinia descent were screened for 38 mutations using a semi-automated reverse-dot blot and PCR-gel electrophoresis assays. This mutation panel included the 15 most frequent CF alleles in Sardinia. We identified 38 CF carriers, revealing an overall frequency of 1/25 (4%). The most common CF allele was the p.Thr338Ile (T338I) (65%), followed by the p.Phe508del (F508del) (22.5%). We also identified one couple at risk and an asymptomatic female homozygote for the p.Thr338Ile allele. In spite of the low number of the couples tested, the results herein reported demonstrate the efficacy and efficiency of the preconceptional screening program and the high participation rate of the Sardinian population (99%). Copyright © 2010 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Hexanoic acid is a resistance inducer that protects tomato plants against Pseudomonas syringae by priming the jasmonic acid and salicylic acid pathways.

PubMed

Scalschi, Loredana; Vicedo, Begonya; Camañes, Gemma; Fernandez-Crespo, Emma; Lapeña, Leonor; González-Bosch, Carmen; García-Agustín, Pilar

2013-05-01

Hexanoic acid-induced resistance (Hx-IR) is effective against several pathogens in tomato plants. Our study of the mechanisms implicated in Hx-IR against Pseudomonas syringae pv. tomato DC3000 suggests that hexanoic acid (Hx) treatment counteracts the negative effect of coronatine (COR) and jasmonyl-isoleucine (JA-Ile) on the salicylic acid (SA) pathway. In Hx-treated plants, an increase in the expression of jasmonic acid carboxyl methyltransferase (JMT) and the SA marker genes PR1 and PR5 indicates a boost in this signalling pathway at the expense of a decrease in JA-Ile. Moreover, Hx treatment potentiates 12-oxo-phytodienoic acid accumulation, which suggests that this molecule might play a role per se in Hx-IR. These results support a positive relationship between the SA and JA pathways in Hx-primed plants. Furthermore, one of the mechanisms of virulence mediated by COR is stomatal re-opening on infection with P. syringae. In this work, we observed that Hx seems to inhibit stomatal opening in planta in the presence of COR, which suggests that, on infection in tomato, this treatment suppresses effector action to prevent bacterial entry into the mesophyll. © 2012 BSPP AND BLACKWELL PUBLISHING LTD.

T box riboswitches in Actinobacteria: Translational regulation via novel tRNA interactions

PubMed Central

Sherwood, Anna V.; Grundy, Frank J.; Henkin, Tina M.

2015-01-01

The T box riboswitch regulates many amino acid-related genes in Gram-positive bacteria. T box riboswitch-mediated gene regulation was shown previously to occur at the level of transcription attenuation via structural rearrangements in the 5′ untranslated (leader) region of the mRNA in response to binding of a specific uncharged tRNA. In this study, a novel group of isoleucyl-tRNA synthetase gene (ileS) T box leader sequences found in organisms of the phylum Actinobacteria was investigated. The Stem I domains of these RNAs lack several highly conserved elements that are essential for interaction with the tRNA ligand in other T box RNAs. Many of these RNAs were predicted to regulate gene expression at the level of translation initiation through tRNA-dependent stabilization of a helix that sequesters a sequence complementary to the Shine–Dalgarno (SD) sequence, thus freeing the SD sequence for ribosome binding and translation initiation. We demonstrated specific binding to the cognate tRNAIle and tRNAIle-dependent structural rearrangements consistent with regulation at the level of translation initiation, providing the first biochemical demonstration, to our knowledge, of translational regulation in a T box riboswitch. PMID:25583497

Operation JOSS, Offensive, Deliberate Assault, Amphibious, 10-16 July 1943

DTIC Science & Technology

1984-05-01

German) S-4 •-i-Ile 16 July 1943 ’.-- Prepared by: Staff Group B/Section 3 Staff Group Leader: MAJ (P) Richard M. Colbert , MP MAJ Joseph W. BowabU TC MAJ...US Amy , 49th Siotal Intelliprr Str-ite, .btv’qj.L& Histz, o . iit 49th Signal loeiliunce §Irvice , dated 27 JWy j045. - Page 61 - I.III compromising

The 1980-81 AFOSR (Air Force Office of Scientific Research)-HTTM (Heat Transfer and Turbulence Mechanics)-Stanford Conference on Complex Turbulent Flows: Comparison of Computation and Experiment. Volume 3. Comparison of Computation with Experiment, and Computors’ Summary Report.

DTIC Science & Technology

1981-09-01

organized the paperwork system , including finances, travel, k, , f iling, and programs in a highly independent and responsible fashion. Thanks are also due...three-dimensional transformation procedure for arbitrary non-orthogonal coordinate systems , for the purpose of the three-dimensional turbulent...transformation procedure for arbitrary non-orthogonal coordinate systems so as to acquire the generality in the application for elliptic flows (for the square

33 CFR 117.631 - Detroit River (Trenton Channel).

Code of Federal Regulations, 2010 CFR

2010-07-01

... as follows: (1) Between the hours of 7 a.m. and 11 p.m., seven days a week and holidays, the draw... Ile, shall operate as follows: (1) From March 16 through December 14— (i) Between the hours of 7 a.m...:45 a.m., 8:45 a.m., 4:15 p.m. and 5:15 p.m., Monday through Friday, except holidays; for commercial...

33 CFR 117.631 - Detroit River (Trenton Channel).

Code of Federal Regulations, 2011 CFR

2011-07-01

... as follows: (1) Between the hours of 7 a.m. and 11 p.m., seven days a week and holidays, the draw... Ile, shall operate as follows: (1) From March 16 through December 14— (i) Between the hours of 7 a.m...:45 a.m., 8:45 a.m., 4:15 p.m. and 5:15 p.m., Monday through Friday, except holidays; for commercial...

33 CFR 117.631 - Detroit River (Trenton Channel).

Code of Federal Regulations, 2014 CFR

2014-07-01

... as follows: (1) Between the hours of 7 a.m. and 11 p.m., seven days a week and holidays, the draw... Ile, shall operate as follows: (1) From March 16 through December 14— (i) Between the hours of 7 a.m...:45 a.m., 8:45 a.m., 4:15 p.m. and 5:15 p.m., Monday through Friday, except holidays; for commercial...

33 CFR 117.631 - Detroit River (Trenton Channel).

Code of Federal Regulations, 2012 CFR

2012-07-01

... as follows: (1) Between the hours of 7 a.m. and 11 p.m., seven days a week and holidays, the draw... Ile, shall operate as follows: (1) From March 16 through December 14— (i) Between the hours of 7 a.m...:45 a.m., 8:45 a.m., 4:15 p.m. and 5:15 p.m., Monday through Friday, except holidays; for commercial...

33 CFR 117.631 - Detroit River (Trenton Channel).

Code of Federal Regulations, 2013 CFR

2013-07-01

... as follows: (1) Between the hours of 7 a.m. and 11 p.m., seven days a week and holidays, the draw... Ile, shall operate as follows: (1) From March 16 through December 14— (i) Between the hours of 7 a.m...:45 a.m., 8:45 a.m., 4:15 p.m. and 5:15 p.m., Monday through Friday, except holidays; for commercial...

Digital Flight Control System Validation.

DTIC Science & Technology

1982-06-01

dastia Lfe syal. an ideatIled in figure I sad table 3. -Fm. sad~~b~ vaw." Tomm abm occu I A Pas sr be eveated, the Structue built upon it r must be...to base the Kseetles faiuLte pruiletles ad Specifi sytem . falue. prob- ability forat lo MoSigt will be 10 bue IMPeLASt Is the requiminas fog mnds

Power Plant Discharge Structure, Delta Stabilization Dike, and On-Land Taconite Tailings Disposal, Reserve Mining Company, Silver Bay, Lake County, Minnesota.

DTIC Science & Technology

1977-03-01

preserved in 70% ethanol for future reference. Periphyton (Attached Algae ): Periphyton from the rivers are being collected and periphyton from bear...most abundant of phytoplankton include: Asterionella formosa, Tabellaria fenestrata, Melosica granulata, Dinobryon sp., Synedra acus, and Cyclotella sp...listed in table 5 below: TABLE 5 Aquatic Habitats - :4ile Post 7 Site Classif- Species of Major Major Benthic Water Body ication Importance Substrates

Learning Management Systems: Practical Considerations for the Selection and Implementation of an E-learning Platform for the Navy

DTIC Science & Technology

2007-01-28

is interested in B2B and B2C e-commerce, enterprise resource planning, e-procurement, supply-chain management, data mining, and knowledge discovery... social networking tools, collaborative spaces, knowledge management, “connecting-enabling” protocols like RSS, and other tools. The intent of the ILE...delivered to them, what learning pedagogy is appropriate for them, the optimal level of social interaction for learning, and available resources

Hypersonic Flight: Time To Go Operational

DTIC Science & Technology

2013-02-14

and turbojet /turbofan driven aircraft both individually and combined with the latter taking over fighter propulsion in 1945-1948 and quickly...2000 2020 Early Turbojet / Turbofan Piston Aircraft Late Turbojet / Turbofan Year Deployed M ile s pe r H ou 6 ensure the...threaten aircraft , airbases, and naval assets, especially aircraft carrier battle groups. The future is uncertain and the preceding vision of the

The role of d-allo-isoleucine in the deposition of the anti-Leishmania peptide bombinin H4 as revealed by 31P solid-state NMR, VCD spectroscopy, and MD simulation.

PubMed

Mijiddorj, Batsaikhan; Kaneda, Shiho; Sato, Hisako; Kitahashi, Yuki; Javkhlantugs, Namsrai; Naito, Akira; Ueda, Kazuyoshi; Kawamura, Izuru

2018-07-01

Bombinin H4 is an antimicrobial peptide that was isolated from the toad Bombina variegata. Bombinin H family peptides are active against gram-positive, gram-negative bacteria, and fungi as well as the parasite Leishmania. Among them, bombinin H4 (H4), which contains d-allo-isoleucine (d-allo-Ile) as the second residue in its sequence, is the most active, and its l-isomer is bombinin H2 (H2). H4 has a significantly lower LC50 than H2 against Leishmania. However, the atomic-level mechanism of the membrane interaction and higher activity of H4 has not been clarified. In this work, we investigated the behavior of the conformations and interactions of H2 and H4 with the Leishmania membrane using 31 P solid-state nuclear magnetic resonance (NMR), vibrational circular dichroism (VCD) spectroscopy, and molecular dynamics (MD) simulations. The generation of isotropic 31 P NMR signals depending on the peptide concentration indicated the abilities of H2 and H4 to exert antimicrobial activity via membrane disruption. The VCD experiment and density functional theory calculation confirmed the different stability and conformations of the N-termini of H2 and H4. MD simulations revealed that the N-terminus of H4 is more stable than that of H2 in the membrane, in line with the VCD experiment data. VCD and MD analyses demonstrated that the first l-Ile and second d-allo-Ile of H4 tend to take a cis conformation. These residues function as an anchor and facilitate the easy winding of the helical conformation of H4 in the membrane. It may assist to quickly reach to the threshold concentration of H4 on the Leishmania membrane. This article is part of a Special Issue entitled: d-Amino acids: biology in the mirror, edited by Dr. Loredano Pollegioni, Dr. Jean-Pierre Mothet and Dr. Molla Gianluca. Copyright © 2018 Elsevier B.V. All rights reserved.

Mutation spectrum of NDP, FZD4 and TSPAN12 genes in Indian patients with retinopathy of prematurity.

PubMed

Rathi, Sonika; Jalali, Subhadra; Musada, Ganeswara Rao; Patnaik, Satish; Balakrishnan, Divya; Hussain, Anjli; Kaur, Inderjeet

2018-02-01

Retinopathy of prematurity (ROP) is a vasoproliferative eye disease in preterm infants. Based on its phenotypic similarities with familial exudative vitreo retinopathy (FEVR), the present study was conducted to screen the Norrin signalling pathway genes (already been implicated in FEVR) for understanding their involvement among Indian patients with ROP. The study cohort consisted of patients with ROP (n=246) and controls (n=300) that included full term (n=110) and preterm babies devoid of ROP (n=190). Screening of the NDP, FZD4, TSPAN12 genes were accomplished by resequencing the entire coding and untranslated regions (UTR). The genotype data of the patients with ROP were analysed in the background of their clinical manifestations and further analysed in conjunction with other available data on these genes worldwide. Two novel variants in intron 1 (IVS1 +16A>G) and 3'UTR (c.5 22T>C) along with a previously reported change in the 5'UTR (c.395_409del14bp) were observed in the NDP gene in three patients with ROP. Screening of the FZD4 revealed four heterozygous variants, p.(Pro33Ser), p.(Pro168Ser), p.(Ile192Ile) and p.(Ile360Val), a compound heterozygous (p.(Pro33Ser)/p.(Pro168Ser)) and a 3'UTR (c*G>T) variants in the study cohort. Variants p.(Pro33Ser) and p.(Pro168Ser) were found to be significantly associated with ROP. A heterozygous variant p.(Leu119Arg) in TSPAN12 gene was observed in a patient with threshold ROP. However, a formal genotype-phenotype correlation could not be established due to the low frequencies of the variant alleles in these genes. This is a first study that revealed association of few variants in Norrin signalling genes among Indian patients with ROP that warrants further detailed investigation worldwide. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Turning Saccharomyces cerevisiae into a Frataxin-Independent Organism

PubMed Central

Yoon, Heeyong; Knight, Simon A. B.; Pandey, Alok; Pain, Jayashree; Turkarslan, Serdar; Pain, Debkumar; Dancis, Andrew

2015-01-01

Frataxin (Yfh1 in yeast) is a conserved protein and deficiency leads to the neurodegenerative disease Friedreich’s ataxia. Frataxin is a critical protein for Fe-S cluster assembly in mitochondria, interacting with other components of the Fe-S cluster machinery, including cysteine desulfurase Nfs1, Isd11 and the Isu1 scaffold protein. Yeast Isu1 with the methionine to isoleucine substitution (M141I), in which the E. coli amino acid is inserted at this position, corrected most of the phenotypes that result from lack of Yfh1 in yeast. This suppressor Isu1 behaved as a genetic dominant. Furthermore frataxin-bypass activity required a completely functional Nfs1 and correlated with the presence of efficient scaffold function. A screen of random Isu1 mutations for frataxin-bypass activity identified only M141 substitutions, including Ile, Cys, Leu, or Val. In each case, mitochondrial Nfs1 persulfide formation was enhanced, and mitochondrial Fe-S cluster assembly was improved in the absence of frataxin. Direct targeting of the entire E. coli IscU to ∆yfh1 mitochondria also ameliorated the mutant phenotypes. In contrast, expression of IscU with the reverse substitution i.e. IscU with Ile to Met change led to worsening of the ∆yfh1 phenotypes, including severely compromised growth, increased sensitivity to oxygen, deficiency in Fe-S clusters and heme, and impaired iron homeostasis. A bioinformatic survey of eukaryotic Isu1/prokaryotic IscU database entries sorted on the amino acid utilized at the M141 position identified unique groupings, with virtually all of the eukaryotic scaffolds using Met, and the preponderance of prokaryotic scaffolds using other amino acids. The frataxin-bypassing amino acids Cys, Ile, Leu, or Val, were found predominantly in prokaryotes. This amino acid position 141 is unique in Isu1, and the frataxin-bypass effect likely mimics a conserved and ancient feature of the prokaryotic Fe-S cluster assembly machinery. PMID:25996596

Ferrobasalt-rhyolite immiscibility in tholeiitic volcanic and plutonic series (Invited)

NASA Astrophysics Data System (ADS)

Charlier, B.; Namur, O.; Kamenetsky, V. S.; Grove, T. L.

2013-12-01

One atmosphere experiments show that silicate liquid immiscibility develops between Fe-rich and Si-rich melts below 1000-1020°C in compositionally diverse lavas that represent classical tholeiitic trends, such as Mull, Iceland, Snake River Plain and Sept Iles. Extreme iron enrichment along the evolution trend is not necessary; immiscibility also develops during iron depletion and silica enrichment after Fe-Ti oxide saturation. Natural liquid lines of descent for major tholeiitic series also approach or intersect the experimentally-defined compositional space of immiscibility. The importance of ferrobasalt-rhyolite unmixing in both volcanic and plutonic environments is supported by worldwide occurrence of immiscible globules in the mesostasis of erupted basalts, and by unmixed melt inclusions in cumulus phases of major layered intrusions such as Sept Iles, Skaergaard and Sudbury. A clear case of liquid immiscibility is also recorded in intrusive tholeiitic gabbros from the Siberian Large Igneous Province and is evidenced by textures and compositions of millimeter-sized silicate melt pools trapped in native iron. An important implication of immiscibility in natural ferrobasaltic provinces is the development of a compositional gap characterized by the absence of intermediate compositions, a major feature observed in many tholeiitic provinces and referred to as the Daly gap. The compositions of experimental silica-rich immiscible melts coincide with those of natural rhyolites with high FeOtot and low Al2O3, which suggests a potential role for large-scale immiscibility in the petrogenesis of late-stage ferroan silicic melts. No evidence for the paired ferrobasaltic melt is observed in volcanic provinces, probably because of its uneruptable characteristics. Instead, Fe-Ti×P-rich gabbros crystallized at depth and are the cumulate products of immiscible Fe-rich melts in plutonic settings, a feature clearly evidenced in the Sept Iles intrusion. The production of

CO2-MEGAPARIS: Quantification of CO2 emissions from Paris megacity and their spread out to the neightbouring Centre region. (Invited)

NASA Astrophysics Data System (ADS)

Xueref-Remy, I.

2010-12-01

Atmospheric CO2 concentration has been increasing of more than 30% since the pre-industrial era due to human activities, and is very likely involved in the recent global temperature increase [IPCC, 2007]. Although we have good estimates of the CO2 fluxes on a global basis, and have a relatively well-established system to detect the large-scale trends, regional information (10-500km) is needed if society is ever to manage or verify carbon emissions. We must improve our understanding of regional variations in the sources and sinks of CO2 because they help identify possible sequestration or emission management options. New programs are needed to improve our understanding of meso-scale carbon fluxes, and to discriminate between the anthropogenic and biospheric sources which are very strongly overlapped in European countries. In this context we need to monitor the emissions originating from the megalopolis such as Paris and its agglomeration, and the way they are spreading in the background atmosphere. Nowadays, inventories (CITEPA, AIRPARIF) based on statistical information provide CO2 emissions from Ile de France and all others regions of France, but no independent verification based on CO2 measurements has been done yet. Atmospheric measurements coupled to a meso-scale model can be used to provide such verification, especially to detect the interannual and decadal trends which could result from regional management strategy. The CO2-MEGAPARIS project (2009-2012) objective is to develop four independent methods to verify the emission inventories, and to monitor the daily to monthly CO2 emissions from Ile de France as well as their spreading to neighbouring regions with a scale up to 2x2 km2. The first method consists in developing a synergy between a mesoscale model (CHIMERE/MM5), inventories and observations using a top-down approach based on an inversion technique to retrieve surface fluxes (3 new observing stations are developed among which the top of the Eiffel

National Dam Safety Program. Patterson, Brixius, Grey Creek Watershed Project, Site 1 (Inventory Number NY698), Susquehanna River Basin, Broome County, New York. Phase I Inspection Report

DTIC Science & Technology

1980-08-01

km., -s . 4t ts Wut - fie- mu sekbdisgnr - -- o - atslowly !.rsabl - Slsnghatt $3, o$Ic Porn -lr -hSconsla. are, Un0dM4:s. Tube satorotei -Slowly...denses t- wrsy iss -Sa ilL ____-_____________ 4OC 7 drL 30. di. s - Iso-gsoa il.E This pit dog under 1920, the of"re I te OIL U.to 991. Acurately. am39O

Evaluation of (1-Sarcosine, 8-Isoleucine) Angiotensin II as a Therapeutic Agent for OLEIC Acid-Induced Pulmonary Edema

DTIC Science & Technology

1986-02-01

during continuous intravenous infusion of the drug. No for angiotensinogenic hypertension . Clinical trials indi- changes were detected in systemic or...results suggest that (1-Sar, 8-Ile) A II may have of synthetic angiotensin 11 analogue. Jpn Circ J 38:997.1003, some desirable effects on the systemic ...Hata T, sive Kumahara Y: Changes of blood pressure, plasma renin activity pressure and peripheral resistance without changing and plasma aldosterone

The Preliminary Pollutant Limit Value Approach: Procedures and Data Base.

DTIC Science & Technology

1984-06-01

IIllfllfflfflffllfllf IIIIIIIIIIIEI 41. ILE. 1 . 0 * n I s . 8c .5 11111 * 1 .6 flu IL MICROCOPY RESOLUTION TEST CHART NATIONAL BUREAU OF STANDARDS...AMEW,&A PROMS wD VE.OIWT coWma PAWIKIOK MARYAI 21701 *. ~~0 1 U..... .~-N:\\W-***- NOTICE * Disclaimer The findings in this report are not to be...APPENDIX HI: NOTATION. .. . .. ...................................... 106.- FIGURE S 1 . Model to derive SPPPLV for pathway 7 (meat consumption

The Design of a Secure File Storage System

DTIC Science & Technology

1979-12-01

ERROR _CODE (Przi SUCO COPE) !01ile not found; write access to dtrectorv not permitted I t := GATEKEFPER?.TICKFT ’MAIL BOX, 0) G ATE KF YP F I ~D iNC...BOX.MS’T.SUCC CODE F’OF COD? (DIOR SUCO CODE) Ifile_ not found.; Fead acceLss to directoryv file t ~TRKEPE.TIKFT MIT BOX C) GATHYP~PE-I.AWAIT (MAILBOX, C. (t+2